A long-term study of the elderly has revealed that their average rate of weight loss doubles in the year before symptoms of Alzheimer's-type dementia first become detectable. The finding may be useful to researchers seeking ways to detect and treat Alzheimer's before it causes irreversible brain damage.
The study is the first to confirm in precise detail a link between weight loss and dementia tentatively identified a decade ago. Researchers report in the September 2006 Archives of Neurology that one year before study volunteers were diagnosed with very mild dementia, their rate of weight loss doubled from 0.6 pounds per year to 1.2 pounds per year. The analysis used data from the Memory and Aging Project at the Alzheimer's Disease Research Center (ADRC) of Washington University School of Medicine in St. Louis.
Alzheimer's researchers are working hard to find biomarkers, indicators that can be used to detect the presence of Alzheimer's before clinical symptoms become obvious. Studies at the ADRC and elsewhere have strongly suggested that if Alzheimer's treatments will ever prevent lasting cognitive damage, they may have to be given to patients before memory loss and other disruptions caused by the disorder are evident.
When you read claims that being overweight is not correlated with shorter lifespans keep in mind that a number of illnesses cause weight loss before the illnesses are diagnosed. Cancer can cause weight loss. Unexpected weight loss is sometimes the reason people with undiagnosed cancer go to a doctor and end up with a cancer diagnosis. But cancer is not the only major disease common in old age that causes weight loss. As reported above, even Alzheimer's causes weight loss before diagnosis.
Botton line: People who keep their weight down as a conscious choice are mixed in with people who have lost weight due to illness. So reports which show similar risk of death in the overweight and regular weight are misleading unless they are carefully crafted to control for illness as a cause of weight loss.
A couple of recent studies did attempt to control for illness as a cause of weight loss. They used weight of their subjects before the subjects reached old age. This allowed them to reduce the bias caused by weight loss due to undiagnosed illnesses. They found that being overweight really does shorten life expectancy. See my post Two Studies Find Being Overweight Shortens Life Expectancy for the details.
In Milan (or as the Italians say, Milano) Italy some people have a mutation of high density lipoprotein (HDL) cholesterol called Apolipoprotein A-I Milano which is suspected of reducing the risk of heart and cardiovascular disease. In order to investigate whether Apo A-I Milano really does reduce risk of cardiovascular diseases researchers at Cedars-Sinai put human variations of HDL choelsterol into mice and then measured the resulting mice. While normal human HDL cholesterol reduced plaque build-up by 25% the Apo A-I Milano version of the gene reduces plaque build-up by 65%.
LOS ANGELES - Transfer of a gene that produces a mutant form of good cholesterol provides significantly better anti-plaque and anti-inflammation benefits than therapy using the "normal" HDL gene, according to a mouse study conducted by cardiology researchers at Cedars-Sinai Medical Center and reported in the Oct. 3 issue of the Journal of the American College of Cardiology.
Apolipoprotein A-I is a naturally occurring component of normal HDL (high-density lipoprotein), the "good" cholesterol that circulates in the blood stream. Apolipoprotein A-I Milano is a mutant form, which was originally found in a small number of individuals in Italy who appear to be protected from cholesterol-related heart disease. Researchers are studying the possibility of treating vascular inflammation and plaque buildup through the transfer of protective genes.
"There has been uncertainty and controversy about whether apo A-I Milano is a better form of HDL than the "wild type" (regular) apo A-I in terms of protective effect against atherosclerosis and vascular inflammation, which are tied together," said Prediman K. Shah, M.D., director of the Division of Cardiology and the Atherosclerosis Research Center at Cedars-Sinai.
"We used a unique approach to do a head-to-head comparison, which allowed us to conclusively ascertain the differences between the two genes. Our study demonstrated that A-I Milano gene transfer is much more effective in reducing plaque and vascular inflammation than the normal (wild type) form of apo A-I," said Shah, the article's senior author.
Compared to control, wild type apo A-I gene transfer led to about a 25 percent decrease in the amount of plaque buildup in the animals' aortas and other vessels. Apo A-I Milano gene transfer resulted in a 65 percent reduction. The amount of gene product (protein) produced by each gene was identical, measured in the blood and in the plaque.
A gene therapy that converted our livers to make Apo A-I Milano HDL cholesterol would likely reduce both inflammation and the rate of accumulation of damage from oxidation and plaque build-up in the circulatory system. My guess is such a treatment would reduce the amount of free radicals in the blood and therefore also reduce the rate of brain aging.
Drugs that raise the concentration of HDL cholesterol will hit the market many years before a gene therapy that converts our bodies to make Apo A-I Milano HDL. We might also see clinical use of intravenous administration of Apo A-I Milano HDL as a way to get a bigger and quicker benefit, especially for those suffering angina. Also see my post Synthetic HDL Cholesterol Reduces Artery Clogging In 6 Weeks.
The completion of the Allen Institute for Brain Science's inaugural project signals a remarkable leap forward in one of the last frontiers of medical science -- the brain.
The Institute today announced the completion of the groundbreaking Allen Brain Atlas, a Web-based, three-dimensional map of gene expression in the mouse brain. Detailing more than 21,000 genes at the cellular level, the Atlas provides scientists with a level of data previously not available.
Since humans share more than 90 percent of their genes with mice, the Atlas offers profound opportunity to further understanding of human disorders and diseases such as Alzheimer's, Parkinson's, epilepsy, schizophrenia, autism and addiction. About 26 percent of American adults -- close to 58 million people -- suffer from a diagnosable mental disorder in a given year.
Many human brain diseases have mouse equivalents developed using genetic engineering on lab mice. As the cost of measuring gene activity drops a logical next step would be to repeat this work using mice which have a variety of brain disorders.
You can access the Brain Atlas for free online.
"This project is an unprecedented union of neuroscience and genomics," said philanthropist and Microsoft co-founder Paul G. Allen, who provided $100 million in seed money to launch the Allen Institute for Brain Science and its first project, the Allen Brain Atlas, in 2003. "The comprehensive information provided by the Atlas will help lead scientists to new insights and propel the field of neuroscience forward dramatically."
Publicly available at no cost, the map shows which genes are active -- or "expressed" -- within the brain and which regions and cells they are expressed in, thereby linking them to particular brain functions.
The brain uses most of the genome.
The project has already led to several significant new findings about the brain. It reveals that 80 percent of genes are turned on in the brain, much higher than the 60 to 70 percent scientists previously believed.
It indicates that very few genes are turned on in only one region of the brain -- paving the way for additional insight about the benefits and potential side effects of drug treatments. And it shows the location of genes associated with specific functions, providing scientists with valuable information about regional brain activity.
Many brain scientists use the Atlas.
Even before its announced completion, the Atlas was receiving more than 4 million hits monthly and being accessed by approximately 250 scientists on any given work day. Users are not required to provide information about their work, but anecdotal evidence indicates that the Atlas is already assisting research projects.
"I use it around the clock, night and day. My whole lab does," said Stanford University neurobiology professor Ben A. Barres, who is using the Atlas to confirm his team's findings about glial cells, a type of non-neuronal cell within the nervous system.
"It's completely essential. It's saved us years and years of work, maybe decades. We could never have done all this, either financially or in terms of the amount of labor and time. It was just so incredibly generous of Mr. Allen to do this, and I think it's hard to even overstate what the payoff is going to be for research."
Researchers at the Allen Institute created the database using a process known as in-situ hybridization. A mouse brain is sliced into thin layers and then labeled with a DNA "probe" that binds only to a single gene, highlighting the expression pattern for that gene.
In-situ maps were made for every gene in the mouse genome, then loaded into a massive database. To complete the entire database, researchers processed 170 genes per day, and produced some 1,000 gigabytes of data each day. The finished atlas cost about $41 million to produce.
The development of gene array chips and other technologies for measuring many parts of a biological system at once look set to continue to accelerate the rate at which scientists can collect information from cells and organisms. The Brain Atlas couldn't have been developed 10 years ago. 10 years from now we'll have still more orders of magnitude improvement in the ability to measure and collect data on the activites inside cells and organisms.
The next project, Jones said, will be to develop a digital, three-dimensional, interactive map of the genes at work in a human brain's neocortex, the outer layer that is the seat of higher thought and emotion, using brains from cadavers as well as tissue removed during brain surgeries.
We are coming to the end of the dark ages of how the human brain works.
Methyl groups (a carbon and 3 hydrogens attached to a larger molecule) get placed on outsides of DNA double helixes in order to control gene expression. A group of scientists has found that embryonic cell type have unqiue patterns of methyl group attachment (methylation) that make them different from other cell types.
San Diego, Calif. -- Scientists from the Burnham Institute for Medical Research (BIMR) and Illumina Inc., in collaboration with stem cell researchers around the world, have found that the DNA of human embryonic stem cells is chemically modified in a characteristic, predictable pattern. This pattern distinguishes human embryonic stem cells from normal adult cells and cell lines, including cancer cells. The study, which appears online today in Genome Research, should help researchers understand how epigenetic factors contribute to self-renewal and developmental pluripotence, unique characteristics of human embryonic stem cells that may one day allow them to be used to replace diseased or damaged cells with healthy ones in a process called therapeutic cloning.
Embryonic stem cells are derived from embryos that are undergoing a period of intense cellular activity, including the chemical addition of methyl groups to specific DNA sequences in a process known as DNA methylation. The methylation and demethylation of particular DNA sequences in the genome are known to have profound effects on cellular behavior and differentiation. For example, DNA methylation is one of the critical epigenetic events leading to the inactivation of one X chromosome in female cells. Failure to establish a normal pattern of DNA methylation during embryogenesis can cause immunological deficiencies, mental retardation and other abnormalities such as Rett, Prader-Willi, Angelman and Beckwith-Wiedemann syndromes.
This result is entirely unsurprising. Methylation is an expected way that cells get controlled to act like one cell type rather than other cell types. For example, methyl groups can prevent proteins from binding to a section of DNA and thereby prevent cellular machnery from reading specific genes that have been methylated.
The way more exciting result here is the development of technology for measuring methylation of hundreds of sites on DNA at a time.
Until recently, DNA methylation could only be studied one gene at a time. But a new microarray-based technique developed at Illumina enabled the scientists conducting this new study to simultaneously examine hundreds of potential methylation sites, thereby revealing global patterns. "Analyzing the DNA methylation pattern of hundreds of genes at a time opens a new window for epigenetic research," says Dr. Jian-Bing Fan, director of molecular biology at Illumina. "Exciting insights into development, aging, and cancer should come quickly from understanding global patterns of DNA methylation."
The ability to rapidly read large amounts of epigenetic information is more important than the results from any one set of experiments that collect epigenetic data.
This report provides yet another illustration of how advances in instrumentation for biological systems are accelerating the rate of advance of biological science and technology.
To examine global DNA methylation patterns in human embryonic stem cells, the researchers analyzed 14 human embryonic stem cell lines from diverse ethnic origins, derived in several different labs, and maintained for various times in culture. They tested over 1500 potential methylation sites in the DNA of these cells and in other cell types and found that the embryonic stem cells shared essentially identical methylation patterns in a large number of gene regions. Furthermore, these methylation patterns were distinct from those in adult stem cells, differentiated cells, and cancer cells.
"Our results suggest that therapeutic cloning of patient-specific human embryonic stem cells will be an enormous challenge, as nuclei from adult cells will have to be epigenetically reprogrammed to reflect the specific DNA methylation signature of normal human embryonic stem cells," explains Dr. Jeanne Loring, co-director of the stem cell center at BIMR. "This reinforces the need for basic research directed at understanding the fundamental biology of human embryonic stem cells before therapeutic uses can be considered."
Some day techniques to change methylation patterns on the genome will be found. Those techniques will make it much easier to change cells into any desired cell type for therapeutic purposes. The ability to rapidly read methylation patterns will make it easier to test techniques tin the development of ways to change methylation patterns. So advances in reading methylation patterns will lead to advances for growing replacement organs and for creating stem cell therapies.
Another point: The increase in ability to read methylation patterns sounds like it was of orders of magnitude. Some people argue that anti-aging therapies are a distant prospect because even at Moore's Law (which is a doubling time for computer power of about 18 to 24 months) rates of advance it will take a long time before biotechnology cna reverse full body aging. But the advance reported above for reading methylation patterns sounds like it was much faster than the rate of Moore's Law. But biotechnology can advance more rapidly than computer technology did because biotechnology is in the process of harnessing techniques first developed for the computer industry over a period of decades.
Think of it this way: The move to put biochemical tests and sensors on chips amounts to jumping biotechnology over onto computer semiconductor technology. But that semiconductor technology took decades to develop and now biotechnology is starting to get moved over onto semiconductor devices. This allows biotech to capture in a relatively short period of time the gains of decades of semiconductor technology. So I'm not surprised to read about sudden orders of magnitude increases in the ability to do biological experiments using silicon chips.
Providence, RI – Stimulation of a receptor in the brain that controls insulin responses has been shown to halt or diminish the neurodegeneration of Alzheimer's disease, providing evidence that the disease can be treated in its early stages, according to a study by researchers at Rhode Island Hospital and Brown Medical School.
Researchers have found that peroxisome-proliferator activated receptor (PPAR) agonists prevent several components of neurodegeneration and preserve learning and memory in rats with induced Alzheimer's disease (AD). They found that an agonist for PPAR delta, a receptor that is abundant in the brain, had the most overall benefit.
"This raises the possibility that you can treat patients with mild cognitive impairment who have possible or probable Alzheimer's disease. This is really amazing because right now, there's just no treatment that works," says lead author Suzanne M. de la Monte, MD, MPH, a neuropathologist at Rhode Island Hospital and a professor of pathology and clinical neuroscience at Brown Medical School in Providence, RI.
The study appears in the September issue (Volume 10, Issue 1) of the Journal of Alzheimer's Disease (www.j-alz.com).
Alzheimer's looks to be a type of diabetes that is specific to the brain.
In previous studies, the researchers demonstrated that Alzheimer's is a brain-specific neuroendocrine disorder, or a Type 3 diabetes, distinct from other types of diabetes. They showed that insulin and IGF-I receptors are produced separately in the brain, and begin to disappear early in Alzheimer's and continue to decline as the disease progresses. As insulin signaling breaks down, it leads to increased oxidative stress, impaired metabolism and cell death – all causing neurodegeneration.
Scientists were also previously able to replicate Alzheimer's in rats with Streptozotocin (STZ), a compound that is known to destroy insulin producing cells in the pancreas and cause diabetes. When injected into the brains of rats, the compound mimicked the neurodegeneration of Alzheimer's disease – plaque deposits, neurofibrillary tangles, diminished brain size, impaired cognitive function, cell loss and overall brain deterioration.
Since PPAR gamma is already approved as a treatment for Type 2 (insulin resistant) diabetes in humans it would be pretty easy to try it out in early stage Alzheimer's patients. PPAR alpha and PPAR delta would also be useful against Alzheimer's.
Having created an animal model for Alzheimer's, researchers in this study induced Alzheimer's with STZ and then administered treatment with three classes of PPAR agonists – alpha, gamma and delta. All are found in various tissues and organs in the body, including the brain, and PPAR gamma is already FDA approved as a treatment for Type 2 diabetes, or adult-onset diabetes. The two other classes of PPAR agonists have not yet been approved for clinical use.
Following treatment, many of the abnormalities associated with Alzheimer's were reduced or nearly disappeared. The agonists affected different regions of the brain, with PPAR delta producing the most striking effect in preserving the hypothalamus and temporal lobes, areas of the brain responsible for memory, learning, and behavior. In these brain regions, PPAR alpha and PPAR gamma were effective in reducing amyloid gene expression. PPAR delta had the most benefit for reducing oxidative stress and improving learning and memory.
"That was the most spectacular," de la Monte says, "because everybody wants something for cognitive impairment, and that was the most improved with the PPAR delta agonist."
Researchers were not able to stop the deterioration of insulin and its receptors. However, by administering PPAR, they were able to bypass the defects in insulin signaling and preserve the cells that need insulin to thrive. PPAR molecules go directly to the nucleus of cells and tell DNA to turn on or off genes that are normally regulated by insulin, thus preventing them from dying and allowing them to communicate with each other. The major effects of the PPAR treatments were to increase brain size, preserve insulin and IGF-II receptor bearing neurons, and preserve learning and memory.
"The trigger for dementia is the loss of insulin and IGF producing cells. The cells that need those growth factors subsequently die. This study shows you can block the second phase, which is responsible for dementia. This is great news for patients since you treat early stages of disease," de la Monte says.
Another promising result for Alzheimer's patients is that these drugs could be given in the form of a pill, de la Monte says. In the study, the drugs were injected to control the amounts administered.
"One of the most exciting findings was that peripheral (intraperitoneal) injection of the PPAR agonists either partially or completely rescued the brains from neurodegeneration," the authors write.
Alzheimer's appears to be caused by parallel abnormalities – impaired insulin signaling and oxidative stress, which is regulated by the genes NOS and NOX. The PPAR agonists treatments target both problems. They preserve the cells regulated by insulin and IGF, and they decrease oxidative stress, resulting in fewer lesions in the brain.
"If the diagnosis is suspected or patients are in the early phases of AD, there's a good possibility they could get treatment that will help them. It's possible that in the moderate phase, treatment will also help, but more work needs to be done to show that," de la Monte says.
Treatment is not likely to work in the late stages of the disease, she says, because the cells have already died.
All the reports lately about much earlier stage tests for Alzheimer's will turn out to be very useful because periodic testing as we age might be used to determine when to start treatment for type 3 diabetes.
These results remind me of other studies on brain aging. As we age glucose concentrations drop more rapidly and rise more slowly when we do mental work. Basically, our brains can not get enough glucose for sustained concentration. Is the brain glucose shortage seen in normal aging just a milder manifestation of the Type 3 diabetes that these reseachers claim is the cause of Alzheimer's? As we age would we be better able to maintain sustained concentration by taking drugs developed to stimulate insulin receptors in the brain?
Also, is Alzheimer's caused by a glucose shortage that robs the neurons of enough energy to remove the junk (e.g. beta amyloid plaque) that accumulates? Or does the lack of stimulation of the insulin receptors reduce the signalling that tells intracellular machinery to break down the accumulated junk?
Thanks to Lou Pagnucco for the heads up.
Embryonic stem cells can serve as a renewable source of replacement tissue to rescue visual function in rats with degenerative eye disease similar to age-related macular degeneration, a leading cause of blindness in humans, according to a report to be published in the Fall 2006 (Volume 8, Number 3) issue of Cloning and Stem Cells, a peer-reviewed journal published by Mary Ann Liebert, Inc. The paper is available online ahead of print at www.liebertpub.com/clo
Robert Lanza, M.D. and Irina Klimanskaya, Ph.D. at Advanced Cell Technology (Worcester, MA), and Raymond Lund, Ph.D. and colleagues at the University of Utah Health Science Center (Salt Lake City) generated retinal pigment epithelium (RPE)--the cells that support photoreceptor function in the eye--from human embryonic stem cell lines grown in culture in the laboratory. They transplanted the engineered tissue into the eyes of rats that had a defect in their RPE. This defect results in the loss of photoreceptors and visual function.
The authors reported 100% improvement in visual performance (spatial acuity) in treated animals compared to an untreated control group, and the transplanted RPE cells did not cause any pathology. In the treated rats, spatial acuity, or the ability to see fine detail, was approximately 70% that of normal rats (that had no RPE defect).
"These observations are very exciting as they show that one day it will be possible to treat diseases of human eyes with cells," says Ian Wilmut, Ph.D., Editor-In-Chief of Cloning and Stem Cells and director of the Centre for Regenerative Medicine, in Edinburgh, Scotland. "They also emphasize the great potential benefit of research with human embryo stem cells, in this case for cell therapy."
Macular degeneration is the leading cause of blindness in persons over age 60 in the United States and affects more than 30 million people worldwide. Embryonic stem cells would offer a readily available, safe, and reproducible source of replacement tissue to restore photoreceptors damaged or destroyed by disease and to restore a range of visual functions.
"One important advantage offered by hES-derived cells over other cells developed to mimic or replace lost retinal pigment epithelium is that they more closely resemble primary human RPEs," stated Raymond D. Lund, Ph.D., Professor at the Moran Eye Center, University of Utah Health Science Center, Salt Lake City and the study's lead author. "Another significant advantage of using these cells is that a range of lines can be derived allowing the opportunity to 'tissue match' donor cells with recipient, a real advantage given that RPE cells are highly immunogenic and susceptible to rejection without some form of immunosuppression."
"Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement cells for clinical studies," stated Robert Lanza, M.D., Vice President of Research & Scientific Development at ACTC and senior author of the paper. "All 18 human embryonic stem cell lines we studied reliably produced retinal cells that could potentially be used to treat retinal degenerative diseases, such as macular degeneration. We showed that these cells have the capacity to rescue visual function in animals that otherwise would have gone blind. Importantly, the cells did not appear to cause any unwanted pathological responses in the animals following transplantation."
Once useful human therapies are available which have been created using hESC the people making ethical arguments against the use of hESC are going to face much more opposition than they do today. The hypothetical future promise of hESC doesn't today motivate people to support hESC research as much as the availability of real treatments will.
The opponents of the use of hESC really ought to push harder to increase funding to develop other methods to create flexible and youthful stem cells. If they fail to do that they will find they are fighitng for a losing cause.
In a move that might provide a away around ethical objections to other ways to create human embryonic stem cells scientists were able to extract human embryonic stem cells from embryos that had ceased to grow
The journal STEM CELLS(R) today announced that scientists were able, for the first time, to derive pluripotent human embryonic stem cells (hESCs) from non-viable early human embryos.
The team, led by Professor Miodrag Stojkovic, derived hESCs using surplus and donated embryos that had stopped their cleavage. The scientists demonstrated that these non-viable embryos could be used under suitable laboratory conditions for derivation of hESCs and for study of early human development.
This progress, published in STEM CELLS(R), encourages other scientists to perform hESC research using both viable and non-viable pre-implantation embryos in their attempt to understand and fight debilitating diseases.
'This should get round opposition to stem cell science because live embryos will no longer need to be used in all experiments,' said Professor Miodrag Stojkovic, the researcher who carried out the experiments at the Centre for Stem Cell Biology at Newcastle University last year.
The embryos used were from attempts at in vitro fertilization where the embryos stopped growing even before implantation.
Stojkovic's experiments were carried out while he was working at the Centre for Stem Cell Biology at Newcastle last year. In a paper, published last week online on the website of the journal Stem Cells, Stojkovic reveals he and his colleagues took 13 embryos, created by IVF. All 13 had stopped developing a few days after conception. 'They were in a very early stage of development,' said Stojkovic, now head of Sintocell, the Serbian medical research centre.
The team then waited 24 hours to check that the embryos were no longer dividing before beginning their experiments.
But other stem cell scientists and ethicists quickly raised a host of reasons that the advance may have little practical impact on the stormy research field. Among them are concerns that cells from dead embryos may be genetically abnormal, and the lack of a definitive test for proving that an embryo has no lingering potential for life.
How to get around the genetic abormality problem? In theory doctors could take embryos from pregnant women who die from trauma such as from car accidents. The removal of cells from embryos to use for therapy development would be analogous to using organs. But I'm guessing that the early stage pregnancies where the embryos still have pluripotent (highly flexible) stem cells aren't going to be recognized either by the mother or by emergency room workers.
It could turn out that some of the IVF embryos stop dividing for epigenetic (chemical state around the genes rather than the genes themselves) reasons. If that turns out to be the case then some stem cells extracted using this technique might turn out to be in good genetic shape.
The full paper is available with free access.Here's the abstract excerpted from the paper (PDF format).
Human embryonic stem cells (hESC) hold huge promise in modern regenerative medicine, drug discovery, and as a model for studying early human development. However, usage of embryos and derivation of hESC for research and potential medical application has resulted in polarised ethical debates since the process involves destruction of viable developing human embryos. Here we describe that not only developing embryos (morulae and blastocysts) of both good and poor quality but also arrested embryos could be used for the derivation of hESC. Analysis of arrested embryos demonstrated that these embryos express pluripotency marker genes such OCT4, NANOG and REX1. Derived hESC lines also expressed specific pluripotency markers (TRA-1-60, TRA-1-81, SSEA4, alkaline phosphatase, OCT4, NANOG, TERT and REX1) and differentiated under in vitro and in vivo conditions into derivates of all three germ layers. All the new lines including line derived from late arrested embryo have normal karyotype. These results demonstrate that arrested embryos are additional valuable resources to surplus and donated developing embryos and should be used to study early human development or derive pluripotent hESC.
Washington, D.C.— Plug-in hybrid vehicles could contribute greatly to reducing automobile oil consumption and emissions, but reaching those goals requires major progress in key areas. According to a report released today by the American Council for an Energy-Efficient Economy, the environmental and economic appeal of plug-in hybrid vehicles will depend heavily upon cleaner power sources and further battery advances. The report, Plug-In Hybrids: An Environmental and Economic Outlook, examines the benefits of plug-ins relative to today’s hybrids. It finds that greenhouse gas emissions reductions associated with a plug-in powered by today’s electric grid would be about 15% on average across the nation, ranging from 32% using California electricity to zero using Upper Midwest electricity.
Note the lack of mention of particulates or mercury from coal burning electric plants.
Plug-ins’ oil savings could be quite large. Battery size and cost rise steeply with the amount of fuel savings, however, suggesting that plug-ins with modest electric-only range will appear first. According to report co-author James Kliesch, the “electric-then-gasoline” depiction of plug-in operation is not realistic and has contributed to overstatements of the fuel savings potential of plug-ins in the popular media. “Achieving adequate battery lifetimes and minimizing battery costs will require a vehicle control logic that turns on the internal combustion engine when extra power is needed, even within the ‘electric-only’ range of the vehicle,” said Kliesch. The ACEEE report estimates fuel savings relative to today’s hybrids of 30% for a plug-in with a 20-mile electric-only range and 50% for a 40-mile range.
We need better battery technology to make plug-ins cost effective.
For a plug-in owner in California, where most electricity on the grid is generated by low-pollution facilities, driving a PHEV might cut emissions of carbon dioxide by one-third compared with driving a regular hybrid.
But if the same PHEV were charged in the Midwest, where coal-fired power plants supply the electricity, reduction of CO2 emissions would be nil. Nitrous-oxide emissions (which form smog) would fall slightly, but sulfur-dioxide emissions (which contribute to acid rain) would quadruple.
Still, environmental gains are possible.
Plug-ins would chop CO2 emissions by 15 percent on a national average, compared with conventional hybrid cars, the ACEEE report found. At the same time, the plug-in would emit 157 percent more sulfur-dioxide pollution. The need, plug-in proponents say, is for policies that would clean up the electricity grid so that PHEV technology supplies cleaner skies along with energy independence.
This report overstates the environmental benefits of plug-in hybrids. Anyone see the reason why? Hint: large scale use of plug-ins would require construction of new power plants. What about those plants would make things worse?
Answer: New electric power plants will be more heavily weighted toward coal burners than the existing fleet. Natural gas has become too expensive. Hydro power is all tapped out with limited potential for expansion and environmentalists want to see some existing dams dismantled. Nuclear power has fallen out of fashion. Coal looks set to become a larger percentage of total electric generating capacity. Not only would the coal put out more sulfur but also particulates, mercury and other bad stuff.
In California coal faces big regulatory obstacles and the politicians are forcing a big push into renewables. So a shift toward plug-ins here would probably improve air quality. But the cost in electricity will be higher. In the last year nationally electric power costs rose on average from 9.08 cents to 10.15 cents per kilowatt-hour (kwh) or 11.8%. But in California the cost rose from 11.82 cents to 13.84 cents for a 17% increase. New electric power capacity in California (e.g. wind mills) is much more expensive than existing capacity. So the demand for electric power to run cars will drive up average electric prices for all uses.
We could have regulations that require cleaner coal generators nationally. But that too would raise average electric prices. Plus, as demand grows the percentage of total electric power that comes from cheaper hydro-electric dams will decline and the average cost will rise for that reason as well.
If new electric power capacity came from nuclear plants then shifting to plug-in hybrids would deliver a clear and quite substantial environmental benefit. The same will hold some day when photovoltaics become much cheaper. But right now higher electric power demand translates into higher coal burning electric plant construction in most parts of the United States and in other parts it translates into higher electric power prices.
A new study out in the Journal of the American Medical Association provides more reason to eat fatty fish. Vitamin D and/or omega 3 fatty acids are probably involved in the protective effect of eating fatty fish.
Preliminary research suggests that higher consumption of fatty fish in women is linked with a lower risk of renal cell carcinoma, a common form of kidney cancer, according to a study in the September 20 issue of JAMA.
Renal cell carcinoma (RCC) involving the renal parenchyma (the functional tissue of the kidney) accounts for more than 80 percent of all kidney cancers. Renal cell carcinoma incidence rates in the United States had been increasing in 1970-1990s, especially among black women and men; more recent data suggest a leveling off in this trend for most racial groups. The evidence that fish consumption, especially fatty fish, may be associated with lower risk of several cancers has not been consistent, according to background information in the article.
By differentiating between consumption of fish with differing levels of omega 3 fatty acids the researchers were able to discover a stronger relationship between fish consumption and reduced cancer risk.
Previous studies have analyzed total fish consumption and have not taken into account that there are large differences between fatty fish and lean fish in the content of omega-3 fatty acids and vitamin D. Marine omega-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaneoic acid, which are present in significant amounts in fatty cold-water fish (up to 20-30 times higher content than in lean fish), have been reported to slow the development of cancer. Fatty fish has 3 to 5 times higher content of vitamin D than lean fish, and lower serum vitamin D levels have been associated with development and progression of RCC.
Alicja Wolk, D.M.Sc., of the Karolinska Institutet, Stockholm, Sweden and colleagues investigated the association between fatty fish and lean fish consumption and the risk for development of RCC in a population with a relatively high consumption of fatty fish. The participants, from the Swedish Mammography Cohort, included 61,433 women age 40 to 76 years without previous diagnosis of cancer at baseline (March 1987 to December 1990). Participants filled in a food frequency questionnaire at baseline and in September 1997. The researchers considered fatty fish to include salmon, herring, sardines, and mackerel; lean fish included cod, tuna, and sweet water fish; and other seafood included shrimp, lobster, and crayfish.
During an average of 15.3 years of follow-up between 1987 and 2004, 150 RCC cases were diagnosed. After adjustment for potential confounders, an inverse association of fatty fish consumption with the risk of RCC was found, while no association was found with the consumption of lean fish or other seafood.
Want to cut your kidney cancer risk by about 3/4ths?
“In this large population-based cohort with data on long-term diet, we found that women who consumed one or more servings of fatty fish per week had a statistically significant 44 percent decreased risk of RCC compared with women who did not consume any fish. Women who reported consistent long-term consumption of fatty fish at baseline and 10 years later had a statistically significant 74 percent lower risk,” the authors write.
“Our results support the hypothesis that frequent consumption of fatty fish may lower the risk of RCC possibly due to increased intake of fish oil rich in eicosapentaenoic acid and docosahexaneoic acid as well as vitamin D,” they write. “Our results, however, require confirmation because this is the first epidemiological study addressing this issue.” (JAMA. 2006;296:1371-1376)
The reducting in kidney cancer risk is probably also being accompanied by a reduction in risk of other types of cancer. The vitamin D in the fish has already been linked to reduction of risk for other cancers. See my posts Vitamin D Could Decrease Overall Cancer Risk 30%, Vitamin D Reduces Risk Of Pancreatic Cancer, and Vitamin D Reduces Breast Cancer Risk. Also, omega 3 fatty acids as contributors to reduced kidney cancer risk seem quite plausible. See my post Omega 3 Fatty Acids Cut Rat Prostate Cancer.
I'm having salmon for dinner.
Chronic inflammation is now widely seen as a contributing factor to many diseases of old age. Any dietary or lifestyle choices that increase the amount of inflammation in your body is probably going to accelerate your aging and make you more prone to not just infections but chronic degenerative illnesses such as heart disease and arthritis. With that thought in mind consider that skimping on sleep increases the amount of inflammation in the body.
Researchers at UCLA are the first to show how sleep loss affects the immune system's inflammatory response and suggest sleep interventions as a possible way to address problems associated with inflammation and autoimmune disorders.
Reporting in the Sept. 6 edition of the peer-reviewed journal Archives of Internal Medicine, the research team finds that even modest sleep loss triggers cellular and genetic processes involved in the immune system's inflammatory response to disease and injury.
The findings increase understanding of sleep's role in altering immune cell physiology and suggest sleep interventions as a possible way to address inflammation associated with risk of cardiovascular disease, arthritis, diabetes and other autoimmune disorders.
"This study shows that even a modest loss of sleep for a single night increases inflammation, which is a key factor in the onset of cardiovascular disease and autoimmune disorders such as rheumatoid arthritis." said Dr. Michael Irwin, professor and director of the Cousins Center for Psychoneuroimmunology at the Semel Institute for Neuroscience and Human Behavior at UCLA.
About one-third of the people in the United States have trouble getting a good night's sleep. The problem is more prevalent among people with chronic inflammatory disorders, including heart disease. Epidemiology studies link poor sleep with risk of chronic disease in some people.
Inflammation, with its accompanying redness and swelling, occurs when the immune system floods a diseased or damaged portion of the body with infection-fighting white blood cells that promote healing. However, a variety of immune system disorders can cause the body to turn on itself, sometimes causing inflammation that can damage healthy organs and tissues.
The UCLA research team conducted blood and DNA analyses of 30 healthy adults drawn during the day across three baseline periods and after partial night sleep deprivation. The results show white blood cells called monocytes produce significantly greater amounts of two disease-fighting proteins after a night of sleep loss, compared with amounts found after a night of uninterrupted sleep.
So the dog who insisted I let him out at 4 AM this morning helped accelerate aging. I explained this to him and he was complelely indifferent.
If you can see small changes you can make to your life to up the amount of sleep you get to an adequate amount then make those changes. You'll be better off in the long run.
Update: Does anyone know of scientific research into factors that increase or decrease your need for sleep? For example, if you are doing a lot of mental work and learning during the day does that increase the need for sleep because the mind needs to spend more time processing to form lasting memories of what it learned that day? Or do high fat diets increase the need for sleep as compared to low fat diets? Or does a diet high in vegetables decrease the need for sleep?
Nicotinamide (aka niacinamide as distinct from niacin) is the form of vitamin B3 that does not cause flushing in your skin. Nicotinamide injected into mice provided protection to nerve cells from a mouse disease that is very similar to multiple sclerosis.
A team led by Shinjiro Kaneko, MD, a research fellow at Children's, and senior investigator Zhigang He, PhD, also from Children's, worked with mice that had an MS-like disease called experimental autoimmune encephalitis (EAE). Through careful experiments, they showed that nicotinamide protected the animals' axons from degeneration - not only preventing axon inflammation and myelin loss, but also protecting axons that had already lost their myelin from further degradation.
Intriguingly, mice with EAE who received daily nicotinamide injections under their skin had a delayed onset of neurologic disability, and the severity of their deficits was reduced for at least eight weeks after treatment. The greater the dose of nicotinamide, the greater the protective effect.
This is great news because nicotinamide has very low toxicity, is cheap, and is easy to administer. Just taking large doses in pills might be enough to greatly slow the progress of MS.
The highest nicotinamide doses provided the biggest benefit.
On a scale of 1 to 5 (1 indicating mild weakness only in the tail, 4 indicating paralysis involving all four limbs, and 5, death from the disease), mice receiving the highest doses of nicotinamide had neurologic scores between 1 and 2, while control mice had scores between 3 and 4. All differences between treated groups and controls were statistically significant.
Mice with the greatest neurologic deficits had the lowest levels of NAD in their spinal cord, and those with the mildest deficits had the highest NAD levels. Mice that had higher levels of an enzyme that converts nicotinamide to NAD (known as Wlds mice) responded best to treatment.
Moreover, nicotinamide significantly reduced neurologic deficits even when treatment was delayed until 10 days after the induction of EAE, raising hope that it will also be effective in the later stages of MS. 'The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the chronic stage,' says Kaneko.
In other experiments, the researchers demonstrated that nicotinamide works by increasing levels of NAD in the spinal cord and that NAD levels decrease when axons degenerate. Finally, they showed that giving NAD directly also prevented axon degeneration.
NAD is used extensively by cells to produce energy through the breakdown of carbohydrates.
Perhaps nicotinamide works by boosting energy output so that damaged nerve cells can repair themselves faster and thereby avoid too much accumulated damage.
As much as I like high technology I even more like low tech solutions that can be put into practice immediately.
If you are wondering about dosing: The doses were 125 mg per kg and 500 mg per kg. A kilogram is 2.2 pounds. I have no idea whether the human doses would need to scale by those ratios.
CHAPEL HILL - Scientists from the University of North Carolina at Chapel Hill have established how statins -- cholesterol-lowering drugs -- inhibit inflammation and nerve cell damage caused by multiple sclerosis.
Preliminary research has shown that multiple sclerosis (MS) patients taking statins with their standard drug regimen develop less nerve cell damage over time than MS patients on standard therapy. Understanding the precise mechanisms by which statins fight multiple sclerosis is an important step toward approving the commonly used drugs for MS treatment, said Dr. Silva Markovic-Plese, associate professor of neurology, immunology and microbiology in the UNC School of Medicine.
In tests performed on blood samples from people with relapse-remitting MS, statins shut down several inflammatory processes. The statins inhibited the formation of immune-system cells called lymphocytes and monocytes, which cause inflammation by attacking the body's nerve cells.
"When we compared the effects of statins to well-understood MS therapies such as interferon, an anti-inflammatory, statins were equal if not stronger in some aspects," Markovic-Plese said. The researchers also examined blood samples from healthy people.
People suffering from MS ought to consider taking one of the statin drugs such as Crestor (Rosuvastatin), Lipitor (Atorvastatin), Zocor (Simvastatin), Mevacor (Lovastatin), Pravachol (Pravastatin), or Lescol (Fluvastatin).
An article in MIT's Technology Review reports on the potential of thin film batteries to replace lithium ion batteries and to make electric cars feasible.
These new batteries replace the liquid or gel electrolyte with thin layers of solid glass-like or polymer materials, which are more stable. "Nothing can leak, nothing can freeze, nothing can boil, rupture, or explode," says Tim Bradow, vice president of business development at Infinite Power Solutions of Golden, CO, a leading developer of thin-film batteries.
All those recent exploding and burning laptop battery stories do not mean we've hit a technological limit in battery development. Thin film batteries will lower costs, increase safety, and increase capacity all at the same time.
MIT battery researcher Donald Sadoway says the use of solid electrolytes allows the use of pure lithium in the battery anode and this maximizes the amount of electricity that can be stored. Plus, this approach is amenable to use of a much lower cost manufacturing process.
In contrast to the glass-like electrolyte used by Infinite Power Solutions and others, Sadoway has developed a solid-polymer electrolyte (today's lithium-ion polymer batteries use a gel) for use in thin-film batteries. This electrolyte, he says, could be processed in rolls like newspaper, or some other high-throughput process. Such a process for thin-film batteries, although not now being developed by industry, could bring down costs, he says, while innovative ways of packaging electrodes could reduce size. "We've made batteries in the laboratory that are 300 watt-hours per kilogram," he says. "That's two times the best lithium-ion [battery] on the market today."
Low cost and high capacity could open the door to electric cars. Electric cars could end our dependence on liquid fuels for ground transportation. This would allow nuclear, coal, solar, and wind to compete directly oil, gasoline, and diesel fuel.
Note that battery energy storage capacity does not have to equal the energy content of gasoline or even of ethanol in order to make electric cars that will go as far on a charge as a car can go on a tank of gasoline. A shift to pure electric vehicles would allow the elimination of a heavy engine and a heavy transmission. Some of the weight budget currently allocated to the drivetrain could instead go to batteries. Then the car could be powered by electric motors located in each wheel.No need for a transmission and axle to turn the wheels.
“It is getting harder and harder for American farmers to say they feed the world,” said Ken Cook, president of the Environmental Working Group, an environmental research group based in Washington. “Instead, they feed S.U.V.’s.”
The decline of wheat and the broad relandscaping of America’s farmland have come about for several reasons. Better seed technology has given corn and soybeans a widening edge over wheat, and more favorable subsidies have encouraged farmers to abandon wheat. Changing consumer tastes and food packaging advancements have slowed American wheat demand.
But the growing biofuels industry is creating the strongest drag on wheat lately, as corn and soybeans are increasingly favored for their use in ethanol and biodiesel.
Fears of genetically engineered foods in major export markets have kept US farmers from shifting to genetically engineered wheat. So seed suppliers invest less in genetic engineering of new wheat strains. Whereas corn is used more for animal feed and so consumer fears of genetically modified food crops do not have as much impact. Therefore the gap between corn and wheat production costs gradually shifts in favor of corn.
Corn needs more energy and water inputs.
Corn yields are rising faster than wheat yields.
American corn yields rose by 30 percent from 1995 to 2005, while wheat yields grew by only 17 percent. In recent years corn has pulled further ahead, with an annual growth rate in yield that is four times that of wheat.
Lester Brown, president of the Earth Policy Institute, argues that the increasing demand for biomass to make ethanol and biodiesel will bring the demand for energy into competition with the demand for food.
With so many distilleries being built, livestock producers fear there may not be enough corn to feed animals, possibly leading to shortages in milk, eggs, beef, pork and poultry. And because the United States supplies 70 percent of world corn exports, importing countries — such as Egypt, Japan and Mexico — should be worried, too.
In agricultural terms, our appetite for automotive fuel is insatiable: The grain required to fill a 25-gallon SUV gas tank with ethanol would feed one person for a full year. If the United States converted its entire grain harvest into ethanol, it would satisfy less than 16 percent of its auto fuel needs.
Since I see the growth of demand for biomass ethanol and biodiesel as inevitable I tend toward favoring even more rapid development of biomass energy technologies. Sufficient advances in genetic engineering and chemical plant engineering to make ethanol and biodiesel might reduce the amount of land diverted to produce biomass energy.
Though I'd much rather see a bigger push to accelerate the development of photovoltaics and nuclear power as alternatives to turning huge amounts of land into energy production farms. Photovoltaics and nuclear power would use much less land to produce the same amount of usable energy.
A Purdue University team led by professor Li-fu Chen and research assistant Qin Xu, both from the Purdue food science department, discovered a new method to create ethanol from corn. The method also produces biodegradable byproducts that could be safely eaten.
Existing methods of corn-to-ethanol conversion produce as much as 2.6 gallons of ethanol per bushel. The new Chen-Xu method produces 2.85 gallons for a 9.6% improvement. But this method also reduces energy use in the conversion process and produces less waste.
The Chen-Xu Method produces about 2.85 gallons of ethanol for every bushel of corn processed. That output is slightly higher than current methods, but the same process that creates the ethanol also creates other marketable products. Chen said the method also meets federal Clean Air Act standards, eliminating costs that other methods incur in meeting environmental regulations.
"One of the common methods of manufacturing ethanol, called dry milling, is often the cause of air pollutants by drying and storage of DDG, a byproduct of the process," Chen said. "Another method - wet milling - produces an odor because it requires the input of sulfur dioxide. The Chen-Xu Method eliminates both issues, and the only odor comes from the smell of the corn and yeast fermentation."
Using a machine originally designed to make plastics, the Chen-Xu Method grinds corn kernels and liquefies starch with high temperatures. The water input required by wet milling is reduced by 90 percent, Chen said. Wastewater output is cut by 95 percent, and electricity use is reduced by 47 percent.
"The total operating cost of a Chen-Xu Method ethanol plant should be much less than that of a wet-milling plant, and total equipment investment is less than half," Chen said. "And with proper planning and management, total equipment investment should be less than that of a dry-milling plant."
Lower capital costs, lower operating costs, more ethanol output for with less corn, less electricity, less waste. What's not to like?
Biomass energy technologies are going to keep dropping in cost and increasing in net energy efficiency. Gasoline currently costs more to make than ethanol even after adjusting for the lower energy content of a gallon of ethanol as compared to a gallon of gasoline. The price of oil may drop further. But the cost of converting biomass to ethanol will continue to drop in the coming years.
Peter A. Thiel, co-founder and former CEO of online payments system PayPal, and Founder and Managing Member of Clarium Capital Management, a San Francisco-based hedge fund, today announced his pledge of $3.5 Million to support scientific research into the alleviation and eventual reversal of the debilities caused by aging, to be conducted under the auspices of the Methuselah Foundation, a charity co-founded and Chaired by Dr. Aubrey de Grey.
Mr. Thiel commented, "Rapid advances in biological science foretell of a treasure trove of discoveries this century, including dramatically improved health and longevity for all. I'm backing Dr. de Grey, because I believe that his revolutionary approach to aging research will accelerate this process, allowing many people alive today to enjoy radically longer and healthier lives for themselves and their loved ones."
Mr. Thiel will donate a total of $500,000 over the next three years to fund pilot research projects intended to deliver early stage validation of the "SENS" approach to combating the debilitation caused by aging.
Additionally, from now until the end of 2009, Mr. Thiel promises to match every Dollar donated to the Methuselah Foundation for SENS research with a 50 cent matching contribution from himself, up to a maximum of $3 Million of matching funds.
Dr. de Grey said, "I am extremely grateful to Peter for his bold and visionary initiative. I have been working with leading biologists and biochemists around the world in identifying promising research projects, and with this generous donation we will go to work straightaway."
SENS (Strategies for Engineered Negligible Senescence) is a set of approaches to repair the body and reverse the aging process to make bodies fully young again. Click through on one of the SENS links and read all about it if the term is new to you.
I expect Thiel's donations to be the first of many very large donations aimed at reversing the aging process. The large number of multi-millionaires are very sharp people who know they really can't take their money with them when they die. So why not use a piece of their wealth to take a stab at making their bodies young again?
The full reversal of the aging process is an achievable goal. We will develop the biotechnologies to grow replacement parts, to do gene therapy, to send in stem cells to do repairs, and to remove the junk that accumulates in cells and between cells as we age. Daily announcements from biological resesarch labs demonstrate progress toward many of the technologies needed to reverse the aging process. Some people who are alive today will live to see the conquest of aging and the end of death from old age.
Semiconductor technology advances are mostly funded by sales of computer processors, memory, and other digital computer parts. Those advances have created capabilities to manipulate small scale devices for a variety of other purposes including microfluidic devices that function as biological and chemical labs on a chip. Another application being pursued at MIT is the development of extremely small gas turbines for generation of electricity. MIT researchers expect their miniature gas turbine to eventually compete with very large natural gas burning electric generator plants in efficiency.
MIT researchers are putting a tiny gas-turbine engine inside a silicon chip about the size of a quarter. The resulting device could run 10 times longer than a battery of the same weight can, powering laptops, cell phones, radios and other electronic devices.
It could also dramatically lighten the load for people who can't connect to a power grid, including soldiers who now must carry many pounds of batteries for a three-day mission -- all at a reasonable price.
The researchers say that in the long term, mass-production could bring the per-unit cost of power from microengines close to that for power from today's large gas-turbine power plants.
Making things tiny is all the rage. The field -- called microelectromechanical systems, or MEMS -- grew out of the computer industry's stunning success in developing and using micro technologies. "Forty years ago, a computer filled up a whole building," said Professor Alan Epstein of the Department of Aeronautics and Astronautics. "Now we all have microcomputers on our desks and inside our thermostats and our watches."
Cheap mass manufactured miniature electric generators could eliminate the need to connect to the electric grid, thereby reducing vulnerability from central system failures. Distributed generation would also cut transmission line losses of electricity due to resistance in cables.. However, large electric generator plants have one really big advantage: Their emissions can be rmonitored, regulated, and controlled.
A pair of reports make the potential losses from a killer bird H5N1 flu pandemic look a lot smaller. First off, at the US military's Uniformed Services University of the Health Sciences some researchers have discovered that plasma taken from recovered flu victims in 1918 reduced the fatality rate of others infected by the killer 1918 flu.
USU faculty have discovered that a treatment for the Spanish Influenza pandemic may also be effective for current Avian Influenza patients. Navy Capt. Edward Kilbane, Army Col. Jeffrey Jackson and Navy Lt. Cmdr. Thomas Luke, are all alumni and faculty of the Uniformed Services University of the Health Sciences (USU). They, along with retired Navy physician, Capt. Stephen Hoffman, published their research Tuesday, Aug. 29, in the online edition of the Annals of Internal Medicine.
The four researchers analyzed medical literature reported during the Spanish Flu pandemic of 1918 to 1920. They found that transfusions with blood products from Spanish Flu survivors may have reduced the risk of death in seriously ill Spanish Flu patients.
The meta-analysis of these data show that treatment of patients in 1918 with convalescent whole blood, plasma or serum obtained from humans who had recovered from Spanish Influenza resulted in a reduced mortality of seriously ill patients by 50 percent.
If antibodies extracted from patients who recover from H5N1 avian flu would work against H5N1 in other people then each infected person who recovers could produce enough antibodies each week to help several people.
Another report argues that by switching to use of cell cultures to grow pandemic flu vaccine enough vaccine could be produced in the United States to treat the entire population of the US in a few months.
In a study led by University of Michigan professor of chemical and biomedical engineering Henry Wang and doctoral student Lyle Lash, researchers examined the economics of producing egg versus cell culture vaccines in the event of a flu pandemic. They found that training personnel to make cell culture vaccines in existing facilities is the only way to make enough doses to cover the United States in a short time without requiring huge capital investments to build new dedicated flu vaccine cell culture facilities.
The reasons to shift from egg to cell culture production are time and capacity, both of which are critical factors in responding to a pandemic, researchers said. It takes much longer to compile millions of hen eggs than it would to grow up existing cell lines from frozen vials, Lash said. While cell culture has a lower yield than egg culture, there is more existing capacity for cell culture than for inoculating and processing eggs.
"Based on existing dosages, we'd have enough doses in about 3 to 4 months to cover the U.S. with the system we propose," Lash said. Currently, it would take six months to make 250 to 300 million doses of pandemic flu vaccine for the United States. "What we're proposing could make 600 million doses in four months."
If you could manage to isolate yourself and your family for a few months starting at the very beginning of a pandemic then you could come out after those few months and get vaccinated. Also, plasma treatments would become available.
This all reminds me that I've yet to stockpile N95 and N100 face masks. They'd be helpful for occasional trips to the store. Otherwise I'll totally isolate myself if a killer pandemic hits.
Every time a piece of safety equipment becomes fairly cheap the United States government and governments of other highly industrialized nations have moved to require the use of that equipment. When automated operation of cars by embedded computers becomes safer than human driving will governments move to require installation of such artificially intelligent (AI) computer systems in all new cars? Will governments eventually go even further and some day even ban the operation of cars and trucks by humans?
The US government is going to mandate computer-controlled features to help maintain vehicle control. Electronic anti-lock brakes (ABS) and other computer-controlled means to keep tire traction on the road will become mandatory in the United States for all new cars.
The National Highway Traffic Safety Administration is set to announce a preliminary regulation requiring electronic stability control technology on all new vehicles.
I predict the US government will require all new cars be constructed to support fully automated operation within 20 to 30 years.
Auto companies think automated systems for avoiding loss of driving control are more important than air bags for reducing accidents, injuries, and deaths.
The Insurance Institute for Highway Safety estimated in a report in June that as many as 10,000 deaths a year could be prevented if all vehicles were equipped with the feature. Auto companies have said the systems are more critical in preventing deaths than air bags, which are credited with saving 1,200 lives per year.
Many computer-assisted driving technologies are hitting the market. All these technologies will become more advanced and lower in cost in coming decades. Toyota is moving from radar to optical (i.e. light-based) sensors to detect and automatically try to avoid crashes into road obstacles such as pedestrians.
Toyota Motor Corp. and Denso Corp. collaborated with NEC to implement the chip in autos. It was adopted as an image-processing unit for a pre-crash safety system for Toyota's Lexus LS460 to be introduced in the fall. Toyota already offered a pre-crash safety system that employs milliwave radar.
The new Lexus LS460 with the image processors will automatically slam on the brakes a split second before hitting a pedestrian or vehicle and prevent a collision or reduce impact.
Systems that monitor driver wakefulness and attention are also starting to hit the market. Cameras aimed at drivers try to alert drivers when they are not paying attention and an obstacle looms.
And if all the coddling means your attention wanders, there is a camera checking the driver's eyes are on the road.
Lexus' Pedro Pacheco says: "In the event that there is an obstacle in front of the car and the driver is at the same time looking at the side of the road, the system will sound a warning to alert the driver.
I've also read proposals to have cars automatically detect whether a person has been drinking alcohol and is too drunk to operate a car.
Dr. Grace, a former Carnegie Mellon University professor, is CEO of Attention Technologies Inc., which just started marketing a Driver Fatigue Monitor -- a dashboard-mounted camera that measures how often a sleepy driver's eyes close at night and then sets off a warning alarm.
Attention Technologies is one of two local companies that have developed anti-drowsiness monitors.
The other is AssistWare Technology Inc., another Carnegie Mellon spinoff that is selling a forward-mounted camera that sets off an alarm when a vehicle veers out of its lane or wanders erratically within the lane.
GÖTEBORG, Sweden (November 30, 2005) – Volvo Car Corporation is taking a decisive new step toward helping drivers avoid vehicle collisions with its new Volvo Driver Alert system, technology designed to monitor a vehicle's progress on the road and alert the driver if it detects signs of fatigue or distraction. The system helps drivers make the right decision, rather than taking control of the vehicle.
The company intends to patent the Driver Alert technology and plans to make the system available in Volvo vehicles within two years.
Driver fatigue is a major traffic safety problem around the world. According to the U.S. National Highway Traffic Safety Administration (NHTSA), approximately 100,000 collisions are caused every year on American highways by drivers who fall asleep. Fifteen hundred of the collisions result in fatalities and a further 71,000 lead to physical injuries. In Europe, the situation is very similar: the German Insurance Association – GDV (Gesamtverband der Deutschen Versicherungswirtschaft e.V.) – estimates that 25 per cent of all fatal collisions on German roads are caused by fatigue.
Safe motoring in style means maintaining maximum attention also on long distances. And this is precisely why BMW Group engineers have developed an assistance system helping the driver to avoid situations where they begin to lose their attention and awareness. Lane Departure Warning therefore informs the driver in good time of any unattended deviation from the car’s proper course, telling the driver through clear signals to countersteer and move back in the desired direction. This serves to avoid driving errors resulting from lack of concentration on traffic conditions.
Adaptive Cruise Control is a new technology that automatically adjusts vehicle speed to maintain a driver-selected distance from the vehicle ahead in the same lane. This next generation of cruise control uses forward-looking radar, installed behind the grill of a vehicle, to detect the speed and distance of the vehicle ahead of it, and then automatically adjusts your speed accordingly.
How does it work? The radar headway sensor sends information to a digital signal processor, which in turn translates the speed and distance information for a longitudinal controller. The result? If the lead vehicle slows down, or if another object is detected, the system sends a signal to the engine or braking system to decelerate. Then, when the road is clear, the system will re-accelerate the vehicle back to the set speed.
BMW AG, DaimlerChrysler AG and Toyota Motor Corp. are among the makers of premium models that are starting to market cars that automate many parts of the driving experience: self-parking cars (with the driver inside or out); parking guidance systems (for the less-lazy driver); enhanced cruise-control systems that work in stop-and-go-traffic and maintain a safe distance between cars; and warning systems that tell you when you've strayed from your lane.
Brakes and gas pedals are not the only parts of cars which are coming under partial computer car. Automotive engineers are also targetting control of the steering wheel. Mercedes has just introduced a radar-based parking assistance technology as an option in their CL-class cars.
First, the parking guidance system automatically uses side mounted radar sensors to monitor whether the space on either the driver or passenger side is adequate to park the vehicle. If it is, the dashboard displays a "P" icon, alerting the driver to the fact a suitable space is available.
Once the driver stops the vehicle and changes to reverse gear, the instrument cluster then displays a bird's eye view of the parking situation along with guide lines showing how best to park. Red lines indicate the current steering angle, while yellow lines show the steering angle needed. As the driver turns the steering wheel and the two lines coincide, they then combine to form green lines, alerting the driver that he is now in the appropriate angle to reverse.
Finally, as the driver is reversing, an audible signal gives notice when it's time to countersteer, perfectly situating them and their new coupe in that ordinarily too-tight-to-fit-in parking space.
You can see where all this is going. As optical and radar sensors and computers drop in price and become more powerful and as software algorithms become more sophisticated computers are going to gradually take over more driving tasks from truck and car drivers. Computers will become better than drivers and computer-operated cars will become safer than human-operated cars.
Biogerontologist Aubrey de Grey foresees a human future where biotechnologies allow us to live in eternal youth and never grow old. Once we reach that future accidents, murder, and suicide will become the major causes of death. Aubrey expects political movements will successfuly bring about a ban on cars in order to reduce death from accidents. I do not think most governments and polities will go down that path. More likely computers will make car operation so incredibly safe and accidents so rare that cars will not have much impact on average longevity.
Update: Skepticism about the feasibility of computer-operated vehicles became harder to maintain when the Defense Advanced Research Project Agency's Grand Challenge periodic contest for autonomous driverless vehicles finally produced winners in October 2005.
A robotic Volkswagen called “Stanley”, developed by a team from Stanford University in Palo Alto, California, won a $2 million prize on Sunday for winning a tough desert race of driverless vehicles.
And in a stunning improvement on 2004’s Grand Challenge, when no car completed more than 5% of the course, four other vehicles also finished. The 212-kilometre race across the Nevada desert is set by the US Defense Advanced Research Projects Agency (DARPA).
It says something about the rate of advance of the underlying technologies that so many contestants could all suddenly achieve the needed capability in the same year.
The Defense Advanced Research Projects Agency (DARPA) today announced plans to hold its third Grand Challenge competition on November 3, 2007.
The DARPA Urban Challenge will feature autonomous ground vehicles executing simulated military supply missions safely and effectively in a mock urban area. Safe operation in traffic is essential to U.S. military plans to use autonomous ground vehicles to conduct important missions.
DARPA will award prizes for the top three autonomous ground vehicles that compete in a final event where they must safely complete a 60-mile urban area course in fewer than six hours. First prize is $2 million, second prize is $500,000 and third prize is $250,000. To succeed, vehicles must autonomously obey traffic laws while merging into moving traffic, navigating traffic circles, negotiating busy intersections and avoiding obstacles.
Does anyone doubt this challenge will be conquered within 5 years?
If the findings of a British researcher are correct then obsessive compulsive mobile cell phone users have a substance abuse problem where the substance is a cell phone.
Psychologist Dr David Sheffield asked to group of students to fill in a survey based on one used to diagnose gambling addiction.
The volunteers, who were aged between 18 and 25, were asked questions such as whether relatives had ever asked them to cut down on their mobile use and if they became bad tempered when denied access to their phone.
Analysis of the results showed one in seven became restless and irritable when they couldn't make phone calls and had no qualms about would lying to cover up the amount of time they spent on their handset.
Ninety per cent said they took their mobiles wherever they went and third used phone calls to lift their mood. Seven per cent even said they would rather lose a job or relationship than give up their mobile.
They have to have their mobile cell phone fixes.
People are becoming addicted to mobile phones, causing them to become stressed and irritable, work suggests.
Dr David Sheffield, of the University of Staffordshire, found problem behaviour linked to using a mobile in 16% of 106 users who were studied.
In a separate study, to be presented at a conference in Essex later, he found blood pressure was lower in those who had given up using mobile phones.
I know people who excessively use their cell phones. So this report rings true. Humans are not evolved to live in the technological societies we've created. They are not adapted to use the technologies they encounter in their environments.
(Philadelphia, PA) - Building on previous work, researchers at the University of Pennsylvania School of Medicine have found that deleting an inflammation enzyme in a mouse model of heart disease slowed the development of atherosclerosis. What's more, the composition of the animals' blood vessels showed that the disease process had not only slowed, but also stabilized. This study points to the possibility of a new class of nonsteroidal anti-inflammatory drugs (NSAIDs) that steer clear of heart-disease risk and work to reduce it.
Drugs that block the same gene (or its protein product) that was knocked out in these mice might also stop the development of arterial plaque that clogs up our circulatory systems. Mouse knock-out experiments once again deliver the goods.
Senior author Garret FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at Penn, and colleagues report their findings this week in the online edition of the Proceedings of the National Academy of Sciences.
NSAIDs like ibuprofen (Advil) and naproxen (Naprosyn) relieve pain and inflammation by blocking the cyclooxygenases, or COX enzymes (COX-1 and COX-2). These enzymes help make fats called prostaglandins. COX-2 is the most important source of the two prostaglandins - PGE2 and prostacyclin - that mediate pain and inflammation. However, COX-2-derived PGE2 and prostacyclin may also protect the heart, and loss of this function - particularly suppression of prostacyclin - explains the risk of heart attacks from NSAIDs that inhibit COX-2, such as rofecoxib (Vioxx), valdecoxib (Bextra), and celecoxib (Celebrex).
The problems with COX-2 inhibitors have prompted the search for alternative drug targets that suppress pain and inflammation yet are safe for the cardiovascular system. One possibility is an enzyme called mPGES-1, which converts PGH2 (a chemical product of COX-2) into PGE2. Previous studies at other institutions in mice lacking mPGES-1 suggest that inhibitors of this enzyme might retain much of the effectiveness of NSAIDs in combating pain and inflammation. However, unlike COX-2 inhibition or deletion, the Penn researchers had found that mPGES-1 deletion did not elevate blood pressure or predispose the mice to thrombosis. This work began to raise the possibility that mPGES-1 inhibitors might even benefit the heart.
In the PNAS study, the researchers studied the impact of deleting the mPGES-1 gene in mice predisposed to hardening of the arteries. Removing the enzyme had a dramatic effect on the development of the disease. "Both male and female mice slowed their development of atherosclerosis," explains first author Miao Wang, PhD, a postdoctoral fellow in the Penn Institute.
The composition of the blood vessels of the transgenic mice suggested that the disease process had not only slowed, but also stabilized. Collaborators Ellen Pure and Alicia Zukas at the Wistar Institute examined the detailed structure of the diseased arteries. Deleting mPGES-1 resulted in a dramatic change in the cellular constituents of the atherosclerotic plaques seen in the transgenic mice. In the absence of the enzyme, the diseased vessels were depleted of immune cells called macrophages, which led to the predominance of vascular smooth muscle cells in blood vessel walls. In turn, this led to a switch in the form of collagen - a fibrous structure that contributes to the fabric of plaques - to a more stable and benign form.
"It seems that it is the complete reverse of the mechanism that creates problems for COX-2 inhibitors," says FitzGerald. Mice lacking mPGES-1 boost their production of prostacyclin, the major heart-protecting fat produced by COX-2. They do this by redirecting prostacylcin to vascular smooth muscle cells. The same mechanism explains the group's earlier findings on blood pressure and thrombosis.
"It remains to be determined whether specific inhibitors of mPGES-1 can replicate the consequences of removing the gene" explains FitzGerald, "And if so, whether these results will translate from mice to humans."
In the meantime, these results, say the investigators, will fuel interest in the possibility of a new class of "super NSAIDs," which may not just avoid the risk of heart disease, but also actually work to diminish it.
The build-up of artery plaque is going to become totally preventable and in short order. Diet alone already can reduce the risk enormously. Eat the ape diet if you want to lower your risk of heart disease, stroke and other diseases..
University of California, Davis researchers have shown that statins not only improve cholesterol levels, but also dramatically reduce disease-causing inflammation in patients with metabolic syndrome -- a condition defined by symptoms that include abdominal obesity and high blood pressure.
The UC Davis team conducted a double-blind, randomized, placebo-controlled study in which they gave a standard daily dose of a statin (Simvastatin or placebo) to 50 patients with metabolic syndrome. After eight weeks, they measured cholesterol levels, as well as biomarkers of inflammation in the circulation, but more importantly, in cells pivotal in all stages of plaque formation, the monocytes. They found, as expected, that statin lowered low-density-lipoprotein- cholesterol and non-high-density-lipoprotein-cholesterol levels, both of which the American Heart Association guidelines target for treatment of metabolic syndrome.
Jialal and his colleagues also found marked reductions in two pivotal biomarkers of inflammation: C-reactive protein (CRP) and interleukin-6. While these markers are typically elevated in insulin resistance, a condition that precedes the development of diabetes, statin therapy reduced these levels by 36 percent and 44 percent, respectively.
Chronic inflammation is harmful and widespread.
As for people who have a need to take one of the existing NSAIDs, a recent pair of papers in the Journal of the American Medical Association found that Celebrex does not pose as large of a heart risk as Vioxx.
In one paper, three researchers at Harvard examined 114 clinical trials of Vioxx and other drugs and found that Vioxx was linked to substantially higher rates of increased blood pressure than was Celebrex, a similar painkiller, which is still sold.
In the other paper, two Australian researchers found that Vioxx appeared more dangerous than Celebrex or several older painkillers in observational studies, which examine the safety and effectiveness of drugs in real-world settings after they are approved.
David Graham of the FDA, writing as a private citizen, argues in JAMA that naproxen appears safest out of all the NSAIDs and probably is neutral in terms of risk of heart attack (MI or myocardial infarction).
Some people spend their whole lives in search of happiness and escape from a feeling of hopelessness and ennui. They lack the technology that would grant them immediate satisfaction. Knock out a gene and be happy.
A new breed of permanently 'cheerful' mouse is providing hope of a new treatment for clinical depression. TREK-1 is a gene that can affect transmission of serotonin in the brain. Serotonin is known to play an important role in mood, sleep and sexuality. By breeding mice with an absence of TREK-1, researchers were able create a depression-resistant strain. The details of this research, which involved an international collaboration with scientists from the University of Nice, France, are published in Nature Neuroscience this week.
"Depression is a devastating illness, which affects around 10 percent of people at some point in their life," says Dr. Guy Debonnel an MUHC psychiatrist, professor in the Department of Psychiatry at McGill University, and principal author of the new research. "Current medications for clinical depression are ineffective for a third of patients, which is why the development of alternate treatments is so important."
Mice without the TREK-1 gene ("knock-out" mice) were created and bred in collaboration with Dr. Michel Lazdunski, co-author of the research, in his laboratory at the University of Nice, France. "These 'knock-out' mice were then tested using separate behavioral, electrophysiological and biochemical measures known to gauge 'depression' in animals," says Dr. Debonnel. "The results really surprised us; our 'knock-out' mice acted as if they had been treated with antidepressants for at least three weeks."
One of the reasons I watch for mouse gene knock-out studies is that they are a glimpse into the choices prospective parents (and domineering governments) will face when it becomes possible to tinker with the DNA of eggs, sperm, and embryos. In the future some people will opt for offspring genetic engineering to make their kids congenitally happy uncurable optimists. Other people will genetically engineer their kids to be highly objective analytical realists. Not a few of the latter will want to come up with ways to infect the obnoxiously optimistic with viruses that will reprogram them for more realism and less optimism.
Other future parents will opt for drugs instead of genetic engineering to make their kids happy, calm, content, and confident. Make Johnny and Jill grow up as joyful kids but then tell them at age 18 they just have to stop taking the pills and they'll be able to suffer all the doubts, depression, and sadness that the older generations experienced.
Gene knock-out studies also provide glimpses into just how little free will we have (if we even have any at all).
The discoveries from gene knock-out studies will become a torrent when efforts to create mice with gene knock-outs for each mouse gene achieve their goals.
Adults in Japan who consumed higher amounts of green tea had a lower risk of death due to all causes and due to cardiovascular disease, according to a study in the September 13 issue of JAMA. But there was no link between green tea consumption and a reduced risk of death due to cancer.
Tea is the most consumed beverage in the world aside from water. Three billion kilograms of tea are produced each year worldwide, according to background information in the article. Because of the high rates of tea consumption in the global population, even small effects in humans could have large implications for public health. Among teas, green tea polyphenols have been extensively studied as cardiovascular disease (CVD) and cancer chemopreventive agents. Although substantial evidence from in vitro and animal studies indicates that green tea preparations may impede CVD and carcinogenic processes, the possible protective role of green tea consumption against these diseases in humans remains unclear.
Shinichi Kuriyama, M.D., Ph.D., of the Tohoku University School of Public Policy, Sendai, Japan, and colleagues examined the association between green tea consumption and mortality (death rate) due to all causes, CVD, and cancer within a large population. The study, initiated in 1994, included 40,530 adults (age 40 to 79 years) in northeastern Japan, where green tea is widely consumed. Within this region, 80 percent of the population drinks green tea and more than half of them consume 3 or more cups and day. The participants, who had no history of stroke, coronary heart disease, or cancer at baseline, were followed for up to 11 years (1995-2005) for all-cause death and for up to 7 years (1995-2001) for cause-specific death.
Over 11 years of follow-up, 4,209 participants died, and over 7 years of follow-up, 892 participants died of cardiovascular disease and 1,134 participants died of cancer. The researchers found that green tea consumption was inversely associated with death due to all causes and due to cardiovascular disease. Compared with participants who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a risk of all-cause mortality and CVD mortality that was 16 percent lower (during 11 years of follow-up) and 26 percent lower (during 7 years of follow-up), respectively.
These inverse associations of all-cause and CVD mortality were stronger among women, although the inverse association for green tea consumption was observed in both sexes. In women, compared with those who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a 31 percent lower risk of CVD death.
Actuarial Escape Velocity (AEV) is the point where the rate of advance in the development of rejuvenating medical therapies becomes faster than the rate of aging. Bodies will become rejuvenated faster than they age. Your odds of living to the day when AEV is reached depends on a couple of factors that are under your control. First off, you can help speed up the rate of biomedical advance by supporting efforts like the Methuselah Mouse Prize to provide scientists with more incentives to work on rejuvenation therapies. You can also let your elected officials know that you want to see governments aggressively fund the development of Strategies for Engineered Negligible Senescence (SENS) to develop the technologies that will make it possible to repair the accumulation of damage which is aging.
Of course, even if you do all you can to support biotechnological advances needed to conquer aging you still are at risk of dying before the SENS treatments become available. So what to do about that? Eat better. Drink better too. Get exercise too.
For a larger discussion of polyphenols, flavonoids, and other chemicals in foods that lower disease risk see my post Fruit And Vegetable Juices Make Big Cut In Alzheimers Risk.
Cell phones can report where they are because they have GPS (global positioning system) circuitry that allows them to query satellites to determine their locations. By watching the reported changing positions of cell phones it is possible to figure out which ones are in vehicles and determine traffic speeds on roads and highways.
Engineers have developed a system for taking anonymous cell-phone location information and turning it into an illuminated traffic map that identifies congestion in real time.The system takes advantage of the steady stream of positioning cues--untraced signals all cell phones produce, whether in use or not, as they seek towers with the strongest signals. It is the first traffic-solution technology that monitors patterns on rural roads and city streets as easily as on highways.
Developed by IntelliOne of Atlanta, Ga., the TrafficAid system could not only help guide drivers around tie-ups, but also tell emergency responders where accidents are or how effectively an evacuation is unfolding by pinpointing clusters of cell phones.
"Unlike sensors and other equipment along major freeways that is expensive and takes years to deploy, our system takes advantage of existing cellular networks in which wireless carriers have already invested billions of dollars," said National Science Foundation (NSF) awardee and IntelliOne CEO Ron Herman, a former engineer and computer scientist.
Herman was inspired by a friend's demonstration several years ago of a proof-of-concept Palm Pilot software that used real-time California Department of Transportation travel-time data to route the drivers around traffic snarls."I was completely sold," said Herman. "I believed then the next 'killer app' for mobile would demand live traffic data for every road--not just select highways equipped with speed sensors--and set out to make it happen."
There's a bigger pattern here: Data collected for one purpose gets aggregated, analyzed, and used for other purposes. Devices that can get queried to report information automatically without human involvement are becoming ubiquitous. Devices that would cost too much to deploy for some reason (e.g. traffic flow tracking) can get deployed for other reasons (e.g. mobile telephones) and then reused for other less economically valuable purposes.
The continued rapid increase in speed of computers is a well known phenomenon. I think the steadily falling costs of communications and data collection will have an even more profound effect. We are going to increasingly live in societies which are extremely measured and monitored. More nooks and crannies of life will have sensors and communications devices attached to them.
PHILADELPHIA -- Consumption of Vitamin D tablets was found to cut the risk of pancreatic cancer nearly in half, according to a study led by researchers at Northwestern and Harvard universities.
The findings point to Vitamin D's potential to prevent the disease, and is one of the first known studies to use a large-scale epidemiological survey to examine the relationship between the nutrient and cancer of the pancreas. The study, led by Halcyon Skinner, Ph.D., of Northwestern, appears in the September issue of Cancer Epidemiology Biomarkers & Prevention.
The study examined data from two large, long-term health surveys and found that taking the U.S. Recommended Daily Allowance of Vitamin D (400 IU/day) reduced the risk of pancreatic cancer by 43 percent. By comparison, those who consumed less than 150 IUs per day experienced a 22 percent reduced risk of cancer. Increased consumption of the vitamin beyond 400 IUs per day resulted in no significant increased benefit.
The conclusions were reached by analysis of two prospective studies.
Skinner, currently in the Department of Population Health Sciences at the University of Wisconsin School of Medicine and Public Health, and his colleagues analyzed data from two long-term studies of health and diet practices, conducted at Harvard University. They looked at data on 46,771 men aged 40 to 75 years who took part in the Health Professionals Follow-up Study, and 75,427 women aged 38 to 65 years who participated in the Nurses' Health Study. Between the two studies, they identified 365 cases of pancreatic cancer. The surveys are considered valuable for their prospective design, following health trends instead of looking at purely historical information, high follow-up rates and the ability to enable researchers like Skinner to incorporate data from two independent studies.
If you get pancreatic cancer you die.
Pancreatic cancer is a rapidly fatal disease and the fourth-leading cause of death from cancer in the United States. This year, the American Cancer Society estimates that 32,000 new cases of cancer will be diagnosed. About the same number of people will die this year from the disease. It has no known cure, and surgical treatments are not often effective. Except for cigarette smoking, no environmental factors or dietary practices have been linked to the disease.
Vitamin D is probably the best supplement to take to reduce the risk of a wide range of cancers.
In the first large-scale screen of genetic changes in cancer cells, researchers have found that a typical breast or colorectal tumor results from mutations in about 90 genes, with different sets of mutations producing the same type of cancer. But the many different genetic routes to malignancy share common features that point toward new means of cancer prevention, diagnosis, and treatment.
Previous genetic studies of cancer have concentrated on specific genes or on chromosomal regions. In the September 8, 2006, issue of Science, Howard Hughes Medical Institute (HHMI) investigators Bert Vogelstein at Johns Hopkins University and Sanford D. Markowitz at Case Western Reserve University School of Medicine, together with a team of researchers from The Kimmel Cancer Center at Johns Hopkins and other institutions, report on a radically new way of identifying genes involved in cancer.
They analyzed 13,000 genes in 11 breast cancer tumors and 11 colorectal tumors to come up with the 90 genes of interest in cancer. One obvious next step would be to repeat this process for more types of cancer and more instances of each type.
While many mutations and genes are involved they fit into a smaller number of pathways that are crucial for the development of cancers. While not mentioned here I'm guessing genes which are involved in producing signals for angiogenesis (growth of new blood vessels) are in their set of 90 genes.
Despite the complexity of the results, a closer examination of the data has started to reveal an underlying order. Many of the genes that are mutated are involved in pathways thought to be important in cancer, such as cell adhesion, movement, and signaling. Each of these pathways relies on multiple genes, and flaws in any of the genes in a pathway may have similar consequences.
“By taking a systems biology approach to connect these genes, we suspect that the complexity will be less than it appears at first sight,” said Vogelstein. “The same 10 or 20 pathways may be altered in every cancer, though the particular mutated genes in these pathways will be different. The picture will become much clearer as the function of these genes and the ways they interact are better worked out.”
They've identified 90 genes involved in cancer. But they do not know what the proteins do which are made by some of these genes. But they now have identified many genes whose proteins can be studied by cancer research labs.
Technological advances only recently made possible the collection of the data which produced these results.
This kind of study could not have been done a few years ago, said Tobias Sjöblom, an HHMI research associate in Vogelstein's lab, who is the lead author of the Science article. But the availability of the human genome sequence and improvements in sequencing and bioinformatics technologies have made it possible to examine the genome of cancer cells in a comprehensive and unbiased manner, he said.
The rate of biotechnological advance is not slowing. Successively better generations of test equipment and software are both accelerating the rate at which genetic and other biological information can be collected and analysed. The rate of advance in understanding of how cancer works was a snail's pace 30 or 40 years ago. The pace now is much faster. 10 years from now with all the instrumentation and software advances that'll happen in the meantime the rate of advance will be blazing. 20 years from now death from cancer should become rare.
Dr Sarah-Jayne Blakemore of the University College London Institute of Cognitive Neuroscience has found from brain scans that when compared to adults kids from age 8 through the teen years use less of an area of the brain involved in empathy and emotional evaluation when making decisions about the reactions of themselves and others to future hypothetical situations.
Teenagers take less account than adults of people's feelings and, often, even fail to think about their own, according to a UCL neuroscientist. The results, presented at the BA Festival of Science today, show that teenagers hardly use the area of the brain that is involved in thinking about other people's emotions and thoughts, when considering a course of action.
Many areas of the brain alter dramatically during adolescence. One area in development well beyond the teenage years is the medial prefrontal cortex, a large region at the front of the brain associated with higher-level thinking, empathy, guilt and understanding other people's motivations. Scientists have now found that, when making decisions about what action to take, the medial prefrontal cortex is under-used by teenagers. Instead, a posterior area of the brain, involved in perceiving and imagining actions, takes over.
Kids are deficient in empathy and guilt because they haven't yet developed the brain areas needed to fully consider the effects of their actions on others.
Functional Magnetic Resonance Imaging (fMRI) brain scans done while adults and teenagers were asked the same questions showed a different pattern of brain activation in teenagers versus adults.
In the study, teenagers and adults were asked questions about the actions they would take in a given situation while their brains were being scanned using fMRI. For example, 'You are at the cinema and have trouble seeing the screen. Do you move to another seat?' A second set of questions asked what they would expect to happen as a result of a natural event eg. 'A huge tree comes crashing down in a forest. Does it make a loud noise?'
Although teenagers and adults chose similar responses, the medial pre-frontal cortex was significantly more active in adults than in teenagers when questioned about their intended actions. Teenagers, on the other hand, activated the posterior area of the brain known as the superior temporal sulcus – an area that's involved in predicting future actions based on past actions.
Adults can imagine emotional reactions more rapidly than teenagers can.
Participants aged eight to 36 years were asked how they would feel and how they would expect someone else to feel in a series of situations. Adults were far quicker than teenagers at judging emotional reactions – both how they would feel and how a third party might feel in a given situation. For example, "How would you feel if you were not allowed to go to your best friend's party?" or 'A girl has just had an argument with her best friend. How does she feel?"
Brains of kids undergo sharp growth spurts. Therefore the brain undergoes distinct stages of development.
"Whatever the reasons, it is clear that teenagers are dealing with, not only massive hormonal shifts, but also substantial neural changes. These changes do not happen gradually and steadily between the ages of 0–18. They come on in great spurts and puberty is one of the most dramatic developmental stages."
I'd like to see various types of criminals compared to a general adult population. Do some criminals lack fully developed medial prefrontal cortexes? Could neural growth hormones delivered in adolescence to juvenile delinquents steer them away from a life of crime?
"The superior temporal sulcus is usually used in making simple actions, or watching other people make actions," said Dr Blakemore. "We think adolescents are performing this task by simply thinking about the action they're going to take.
"The part of the brain that the adults are using more is involved in much higher level thinking, such as thinking about the consequences of your actions in terms of other peoples' emotions and feelings."
Basically, adults run more complex models of the world that take into account more factors. They also experience feelings resulting from their internal mental simulations of the world and those feelings temper their actions.
Blakemore thinks the law should take into account differences in stages of brain development (and FuturePundit agrees).
The work has implications for the types of responsibility given to adolescents, Blakemore says: “Teenager’s brains are a work in progress and profoundly different from adults. If you’re making decisions about how to treat teenagers in terms of the law, you need to take this new research into account.”
Brains go through quite a transformation in the adolescent years. Kids are not just surly, sullen, rude, cruel, unhappy, and insensitive because they are sexually frustrated or resentful of their low status. Their ability to read the emotions in the faces of others even dips sharply starting around the age of 11. See my post Adolescence Is Tough On The Brain.
Why do we age? Why don't our stem cells continue to divide to produce cells needed to repair and maintain the body? Three research groups at Harvard, University of North Carolina at Chapel Hill, and at University of Michican have found very strong evidence that as cells age they make more of a protein that slows down cells in order to reduce the risk of cancer.
ANN ARBOR, Mich.—The natural consequences of growing old include slower wound-healing and a brain that makes fewer new neurons because old tissues have less regenerative capacity. What has not been clear is why. A trio of papers published on-line Sept. 6 in the journal Nature shows that old stem cells don’t simply wear out, they actively shut themselves down, probably as a defense against becoming cancerous from genetic defects that accumulate with age.
"The good news is that we can get older before we get cancer," said Sean Morrison, director of the Center for Stem Cell Biology at the University of Michigan, and lead author on one of the three papers. "The bad news is that our tissues can’t repair themselves as well."
Though science has long known about the reduced regenerative capacity in aging tissues, the actual mechanisms are only now coming to light. What Morrison and his colleagues at Harvard University and the University of North Carolina have found is that a gene called Ink4a actively interferes with the ability of stem cells to divide in several different types of tissue, including the brain, the pancreas, and the blood-forming system of the bone marrow.
This important discovery came as a result of the development of a mouse with a gene knockout for Ink4a.
Though mice with Ink4a deleted had more regenerative capacity in tissues like the brain and the pancreas as they aged, they started dying of a wide variety of cancers at one year of age. So it can’t really be said that losing the gene helped them live longer.
"If you had a drug that could inhibit Ink4a function, you’d potentially have a therapy against degenerative diseases," Morrison said. "But you’d have to watch patients carefully for cancers. By the same token, drugs that mimic Ink4a function could be used to fight cancer." Ink4a was known to be a tumor suppressor gene that becomes more highly expressed with age, eventually triggering the cell to shut down replication. Sharpless was investigating cancer genes when he developed a mouse without Ink4a six years ago, while working at Harvard, but he also became intrigued by its 10- to 100-fold increase in expression with age.
I find these results thoroughly unsurprising. Biogerontologists have speculated that natural selection has selected for a trade-off where cells in older bodies become less able to divide in order to reduce the risk of cancer. The reduced cancer risk comes at the expensive of gradually losing the ability to do repairs. These results show a mechanism for how this works.
The researchers found that reducing the accumulation of p16INK4a in haematopoietic stem cells (blood stem cells) reduces cell death as well as defects in the ability of the cells to repopulate.
"There are two things about this that are important," Scadden said. "It shows that specific properties of aging stem cells directly contribute to the reduced healing that occurs with aging; and it indicates that one might be able to modify a single gene product and improve the function of aging stem cells and repair of aging tissue - and that is very encouraging. This may mean that there are opportunities to target this gene product with medication and potentially decrease the impact of aging.
"However," Scadden noted, "p16INK4a is also known to suppress tumor formation, so a judicious balance must be struck between reduced p16INK4a when needed for repair and sufficient p16INK4a to prevent emergence of malignant stem cells."
One obstacle to the use of stem cells as rejuvenation therapies is that the stem cells could become cancerous.
The UNC study focused on p16INK4a effects on the function of pancreatic islet cells. Islet cells are responsible for insulin production and secretion. Because p16INK4a stops cancer cells from dividing and demonstrates increased expression with age, the scientists suspected the gene played a similar role in aging. The researchers developed strains of mice that were either deficient in p16INK4a (the gene was deleted, or 'knocked out") or genetically altered to have an excess of the protein to a degree seen in aging.
According to Sharpless, islet proliferation persisted in p16INK4a -deficient animals as they aged, "almost as if they were younger animals." In mice with an excess of p16INK4a, "islet cells aged prematurely; they stopped dividing early."
"This suggests that if we could attenuate p16INK4a expression in some way in humans, it could lead to enhanced islet re-growth in adults and a possible new treatment for diabetes," Sharpless said.
Similar results were found in the other studies, which focused on brain stem cells and blood stem cells.
Diabetics experience accelerated aging. So use of a drug to temporarily suppress the INK4a gene that allowed pancreatic islet cells to repopulate would probably good trade-off on risks and benefits.
Sharpless cautions that any promise of a potential new aging treatment based on p16INK4a should include two important caveats. "First, even though old mice lacking p16INK4a show enhanced stem cell function, they do not live longer. This is because p16INK4a is an important cancer-suppressor gene, and mice lacking p16INK4a develop more cancers than old, normal mice," he said.
"Secondly, in all three studies, p16INK4a loss was associated with an improvement in some but not all of the consequences of aging. There are clearly things in addition to p16INK4a that contribute to aging. We don't yet know what they are."
However, the gene may prove immediately useful as a biomarker for studies of aging, Sharpless said. "If you were going to calorically restrict yourself or take green tea or resveratrol every day for years in an effort to prevent aging, wouldn't you like some evidence that these not entirely benign things were having a beneficial effect? Now we have a biomarker that can directly test the effects of such things," he said.
One really big question: Is the INK4a gene upregulated in older cells due to factors floating around in entire old bodies? Or is the gene upregulated by changes that happen in each cell? If the answer is the former possibility then even introduction of youthful stem cells into an old body will not help the old body rejuvenate very much. If compounds in circulation in old bodies can cause injected youthful stem cells to slow down and do less repair work then that makes rejuvenation much harder. I'm pessimistic on that score and my pessimism predates this latest report. See my previous post Young Mice Blood Turns On Regenerative Ability Of Old Mice Muscle.
Once we have highly effective and low general toxicity cures for cancer (i.e. cancer cures that only damage cancer cells) then drugs that turn down the activity of INK4a could be developed and used to safely make stem cells do more repair work. We need cures for cancer in any case. But cancer cures will also make possible more aggressive and risky uses of stem cell therapies.
Even without great cancer cures drugs that block INK4a would still be useful for people who are at very high risk of death from heart disease. Someone who has a great risk of death from heart disease probably would reduce their total risk of death even if they took an INK4a suppressor that increased their risk of cancer.
We need stem cells that do not have any mutations that increase the risk of cancer. We also need to prevent those stem cells from being suppressed by the INK4a gene. We also need gene therapies that will repair cells in the body so that their accumulated damage will not cause them or other cells to make INK4a.
Stem cell therapies are not the only method possible for replacing aged and damaged cells. Stem cells will also be used to grow replacement organs outside the human body for transplant. Those transplant organs will replace much larger chunks of aged cells. But replacement organs are not practical for all parts of the body - especially not for the central and peripheral nervous systems.
Morrison and his colleagues also found evidence that the gene does not play the same role in other neural tissues. “There are different kinds of stem cells in different regions of the brain, and some of those stem cells are more sensitive to factors like p16INK4a than others,” said Morrison. p16INK4a deficiency did not prevent the atrophy of the cortex that normally occurs with aging, they found. Nor did the deficiency prevent loss of function in another brain region, the hippocampus, that is also a center for neurogenesis in adults. The researchers also analyzed peripheral nerve cells in the gut and found that p16INK4a did not prevent loss of stem cell function there. “There are probably other factors that are important for aging of the hippocampus and the peripheral nervous system,” Morrison noted.
Nevertheless, he said, the discovery of the central role of p16INK4a is highly significant. “I think if you asked before these studies whether you could delete a single gene and rescue stem cell function in multiple tissues, and neurogenesis in an old brain, many people would have said that aging is such a complex phenomenon that you would not get a significant effect,” he said.
Morrison theorized that p16INK4a is a suppressor of stem cell function that evolved as part of the regulatory machinery that also includes proto-oncogenes that encourage cell proliferation. “We are all evolutionarily selected to, on the one hand, maintain regenerative capacity of our tissues through adult life so that we can repair our cells and survive injuries — while on the other hand, limit proliferation in our tissues with age, so cells don't divide out of control, causing cancers,” he said. “And the way that we achieve that balance is by having proto-oncogenes that promote proliferation come into balance with tumor suppressor genes that inhibit proliferation. This work shows one way that this balance changes with age.
What causes these other stem cells to slow down with age?
Stem cells that slow down due to internal damage or due to genetic clocks internal to each stem cell do not pose much of a problem for the development of rejuvenation therapies. Once scientists develop the ability to create replacement stem cells of each desired type then existing stem cell reservoirs in the body can be reseeded with younger and more vigorous stem cells
More systemic body-wide signals that tell cells throughout the body to slow down strike me as much more problematic for the development of rejuvenating stem cell therapies. I see two strategies for dealing with these signals. First, develop such great cancer treatments that it becomes very low risk to neutralize the hormones or other compounds that travel through the bloodstream to tell cells throughout the body to slow with age. A second approach would be to genetically program replacement stem cells to be less sensitive to the body-wide stem cell suppressor signals. The genetic programming of youthful stem cells could be done in a way that allowed those cells to ignore suppressor signals for a few decades. Basically give them a genetic clock that allowed them to divide even though the body has stem cell suppressor chemicals circulating in it that are the result of aging.
Efforts to collect information about gene, cell, and organism function are becoming increasingly systematic and comprehensive. For example, complete genetic sequencing is being done on an ever increasing list of species. Activity levels of thousands of genes get measured simultaneously using gene array chips. As costs fall and gene array chips become more powerful gene expression gets measured in more tissue types and under more conditions (e.g. at different ages and in the presence of different kinds of illnesses). New techiniques allow quick measuring for the presence of many proteins and other compounds at the same time.
Efforts to develop lab animal strains are similarly becoming more ambitious. For many years scientists have created mouse breeds in which specific genes are deactivated. This allows scientists to more easily discover what purposes each gene serves in cells and organisms. The US National Institutes of Health are joining 2 other efforts to an ambitious effort produce gene knockout mouse strains for each of the genes found in mice.
BETHESDA, Md., Thurs., Sept. 7, 2006 – The National Institutes of Health (NIH) today awarded a set of cooperative agreements, totaling up to $52 million over five years, to launch the Knockout Mouse Project. The goal of this program is to build a comprehensive and publicly available resource of knockout mutations in the mouse genome. The knockout mice produced from this resource will be extremely useful for the study of human disease.
Some knockouts will be fatal. Embryos will fail to develop without some key genes. But discovering which genes are absolutely essential is itself quite useful knowledge. Also, once each gene has been knocked out knocking out pairs of genes in the same mouse can yield yet more useful knowledge. What is harder and done less often: Create mice that express too much of each gene. Also, genes can be created which can be turned on and off by administered drugs.
The NIH effort joins two other efforts already underway.
The NIH Knockout Mouse Project will work closely with other large-scale efforts to produce knockouts that are underway in Canada, called the North American Conditional Mouse Mutagenesis Project (NorCOMM), and in Europe, called the European Conditional Mouse Mutagenesis Program (EUCOMM). The objective of all these programs is to create a mutation in each of the approximately 20,000 protein-coding genes in the mouse genome.
"Knockout mice are powerful tools for exploring the function of genes and creating animal models of human disease. By enabling more researchers to study these knockouts, this trans-NIH initiative will accelerate our efforts to translate basic research findings into new strategies for improving human health," said NIH Director Elias A. Zerhouni, M.D. "It is exciting that so many components of NIH have joined together to support this project, and that the NIH Knockout Mouse Project will be working hand-in-hand with other international efforts. This is scientific teamwork at its best."
This ambitious project has become possible due to technological advances in methods to manipulate DNA.
Knockout mice are lines of mice in which specific genes have been completely disrupted, or "knocked out." Systematic disruption of each of the 20,000 genes in the mouse genome will allow researchers to determine the role of each gene in normal physiology and development. Even more importantly, researchers will use knockout mice to develop better models of inherited human diseases such as cancer, heart disease, neurological disorders, diabetes and obesity. Recent advances in recombinant DNA technologies, as well as completion of the mouse genome sequence, now make this project feasible.
The technological advances in tools will continue to keep happening. Advances in science do not come from a simple constant rate accumulation of knowledge. Advances in science and technology produce techniques and tools that accelerate the rate at which experiments can be done and make it possible to do new kinds of experiments and measure and manipulate more kinds of systems and phenomena.
Three quarters of the genes in mice do not yet have knockout versions.
To date, academic researchers around the world have created mouse knockouts of about 4,000 genes. In addition, a random disruption strategy has been used by the International Gene Trap Consortium to mutate 8,000 mouse genes. Due to some overlap between these efforts, about 15,000 genes remain to be knocked out in the mouse genome.
Genetic similarities between species mean the identification of purposes for mouse genes will yield insights into corresponding genes in humans and other organisms. We will learn the purposes of human genes much sooner due to the ability of scientists to knock out genes in mice.
The well-educated are significantly more open to the idea of "designing" babies than the poorly educated, according to a new study by psychologists at the University of East Anglia.
Here's a summary of some of the findings of this research group:
Once genetic engineering of embryos allows prospective parents to make their kids smarter, better looking, higher athletic performers, and with more desired personality traits all the reticence about genetic engineering for non-medical reasons will go out the window. I'm expecting a stampede toward offspring genetic engineering once it becomes possible.
Higher education is a proxy for higher intelligence. The correlation is not exactly 1 but it is very high. The more highly educated and smarter people will more rapidly and deeply develop a grasp of what offspring genetic engineering can deliver. Also, since the smarter have higher incomes on average they will be better able to pay for genetic tinkering than will poor people.
With the cognitive elite stampeding to make their kids have 150 IQs the less bright and downright dim will be left in the dust. Society will become even more divided by intellectual ability than it already is.
Offspring genetic engineering will also create inter-generational rifts as younger smarter people find less in common with older less bright people.
I am expecting a portion of the cognitive elite to demand that governments pay for free genetic engineering for anyone who plans to have a baby. But if the less bright are left to choose which genetic enhancements to give to their developing fetuses will they place a high value on raising intelligence?
The UW-Madison scientists found that two key regions of the brain - the amygdala and the hippocampus - become activated when a person is anticipating a difficult situation. Scientists think the amygdala is associated with the formation of emotional memories, while the hippocampus helps the brain form long-term recollections, Nitschke says.
The researchers studied the brain activity of 36 healthy volunteers using a technique known as functional magnetic resonance imaging, which produces high-contrast images of human tissue. They began by showing the volunteers two kinds of signals. One was neutral, but the other indicated that some type of gruesome picture was soon to follow, such as explicit photos of bloody, mutilated bodies. Thirty minutes after the researchers had shown dozens of violent images, they quizzed study participants on how well they remembered the pictures they had just seen.
"We found that the more activated the amygdala and hippocampus had been during the anticipation [of the pictures], the more likely it was that a person would remember more of them right away," says Nitschke.
Two weeks after the experiment, scientists met with the study subjects again to measure how well they remembered the same disturbing images. This time, they found that people who best remembered them had shown the greatest amygdala and hippocampus activity during the picture-viewing exercise two weeks before. That suggested that those subjects' brains had already started converting short-term memories of the images into longer-lasting ones.
Mackiewicz says the anticipation of an uncomfortable situation probably kick-starts a kind of "arousal or fear circuitry" in the brain, which in turn helps to reinforce old memories.
"In the future, we could look for ways to dampen that arousal response in patients so that they do not evoke negative memories so easily," she adds.
We need drugs that'll turn on the amygdala and hippocampus so that we can form better memories.
Nobody knows what it does yet but a section of DNA that codes for DUF1220 has become heavily duplicated in humans as compared to other species.
The team compared the DNA sequences of humans, chimpanzees and monkeys, and looked for genes that were repeated more often in human DNA than in the other primate genomes. One gene that codes for a piece of protein called DUF1220 stood out. Humans carry 212 copies of DUF1220, whereas chimps have 37 copies, and monkeys have only 30 copies, the researchers found. Mice and rats each had a paltry single copy of the protein-coding region. When the team looked for the protein in the human body, they found it in many places, including in neurons in the brain.
It probably does stuff in the brain and we probably became smarter as a result of having many DUF1220 segments in the human genome.
Extreme gene duplication is a major source of evolutionary novelty. A genome-wide survey of gene copy number variation among human and great ape lineages revealed that the most striking human lineage–specific amplification was due to an unknown gene, MGC8902, which is predicted to encode multiple copies of a protein domain of unknown function (DUF1220). Sequences encoding these domains are virtually all primate-specific, show signs of positive selection, and are increasingly amplified generally as a function of a species' evolutionary proximity to humans, where the greatest number of copies (212) is found. DUF1220 domains are highly expressed in brain regions associated with higher cognitive function, and in brain show neuron-specific expression preferentially in cell bodies and dendrites.
Do humans differ in how many copies of MGC8902 and DUF1220 we have?
So there are two stories here. One is about the multiple duplication of MGC8902 on the human lineage. The draft human genome has 49 copies of it, chimpanzees have only 10.
A seperate story is about the proliferation of this DUF1220 domain, which occurs in many proteins. This domain increased in copy number on the human lineage compared to chimpanzees, the African ape lineage compared to orangutans, and primates compared to other mammals.
To me the DUF1220 story is the fascinating part. Not only one gene, but apparently many genes that contain this domain have been proliferating; additionally some genes apparently have acquired this domain during human evolution. In at least one gene, the DUF1220 domain shows evidence of positive selection, but the rest of the coding sequence doesn't.
In the next 10 years we will learn the identity of most of the genes that make us smarter than other specices. We will also learn which genetic variations make some humans smarter than others.
Sustained inflammation response contributes the development of a variety of diseases. The bodies of depressed people respond to stresses with a larger inflammation response than non-depressed people experience.
ATLANTA--Individuals with major depression have an exaggerated inflammatory response to psychological stress compared to those who do not suffer from depression, according to a study by researchers at Emory University School of Medicine. Because an overactive inflammatory response may contribute to a number of medical disorders as well as to depression, the findings suggest that increased inflammatory responses to stress in depressed patients may be a link between depression and other diseases, including heart disease, as well as contributing to depression itself.
Results of the study, led by Andrew Miller, MD, and Christine Heim, PhD, of Emory's Department of Psychiatry and Behavioral Sciences, are published in the Sept. 1 issue of the American Journal of Psychiatry.
"Several examples of increased resting inflammation in depressed patients already exist in the literature, but this is the first time anyone has shown evidence to suggest that the inflammatory response to stress may be greater in depressed people," says Dr. Miller.
The study included 28 medically healthy male participants, half of whom were diagnosed with major depression and half of whom were not depressed. The participants were exposed to two moderately stressful situations during a 20-minute time period. Blood was collected every 15 minutes starting immediately before and then up to an hour and a half after the test to check for key indicators of inflammation. The researchers measured levels of a pro-inflammatory cytokine (a regulatory protein secreted by the immune system) called interleukin-6, and the activity of a pro-inflammatory signaling molecule in white blood cells called nuclear factor-kB.
While at rest (before the stress challenge), the depressed patients had increased inflammation relative to the control group. Both the depressed and the healthy groups showed an inflammatory response to the stress challenge, but people who were currently depressed exhibited the greatest increases of interleukin-6 and nuclear factor-kB.
Inflammation damages the body and basically accelerates aging.
"While inflammation is essential for us to fight bacterial and viral infections, too much inflammation can cause harm," says Dr. Miller. "There's always some collateral damage when the immune system gets fired up, and we now believe that too much inflammation, either at rest or during stress, may predispose people to become depressed or stay depressed." In addition, medical research over the last decade has shown that runaway inflammation may play a role in a number of disorders, including heart disease, cancer, and diabetes, all of which have been associated with depression.
If you are depressed and can not find an effective drug to treat your condition then consider diet and exercise as methods to decrease inflammation. Eat some fish for omega 3 fatty acids for starters. Eat lots of vegetables and fruits too.
If you are not depressed but know depressed people treat them kindly. They can not handle stress as well as you can.
Sometimes scientists discover amazingly useful things by accident. Nava Dekel, a professor at the Weizmann Institute in Rehovot Israel, was part of a team examining a protein's role in allowing a fertilized egg to implant in a woman's uterus. The team did biopsies on a dozen women who were having problems starting pregnancies and 11 of the 12 became pregnant. The team suspected that biopsy increases fertility and so did a study of biopsy's effect on larger number of women. They discovered that biopsy (presumably of the uterus) doubles the success rate of implanting embryos created by in vitro fertilization (IVF).
"We decided to conduct a larger study of this phenomenon, and enlarged the group to 140 women. We explained the goals of the study, and 50 of them volunteered to have the biopsies. The rest were used as a control group," she said.
The results showed that the women who underwent the biopsies had a success rate of pregnancy double than the women who underwent the standard IVF treatment without biopsy. In other words, having a biopsy doubled a woman's chances of becoming pregnant.
Three Israeli institutions now use biopsy as a standard way to increase fertility and Professor Dekel expects American fertility clinics to soon copy this practice. This one practice could cause a large increase in the number of babies created by IVF. If the technique boosts the success rate it will also greatly reduce the cost of IVF because it will reduce the number of repeat attempts necessary to start a pregnancy.
Another Israeli study mentioned in the same article found that immune cells play a key role in releasing a compound that causes placental growth. So one cause of infertility might be immune system malfunction.
Methods to increase the reliability of IVF will increase IVF's use both with a female's own eggs and also with egg donation. So I expect this advance will increase the demand for donor eggs. In legal jurisdictions where compensation of egg donors is legal this advance might raise the prices for donor eggs.
IVF is going to become cheaper and more reliable. At the same time, an accelerating rate of discovery of the significance of genetic variations will produce a wealth of knowledge of genetic variations to test for before implantation. This will result in the greater use of Pre-implantation Genetic Diagnosis (PGD or PIGD) used in conjunction with IVF to choose embryos to implant. Cheap IVF and cheap and powerful PGD will increase the attractiveness of IVF as the method to use to start pregnancies. That will lead to an acceleration in the artificial (i.e. by conscious human choice) selection of genes as opposed to natural selection. What would Charles Darwin make of this development?
The New York Times reports couple using in vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD or PIGD) are screening for genes that affect cancer risk in order to select against embryos that have a higher risk of cancer.
Prospective parents have been using the procedure, known as preimplantation genetic diagnosis, or P.G.D., for more than a decade to screen for genes certain to cause childhood diseases that are severe and largely untreatable.
Now a growing number of couples like the Kingsburys are crossing a new threshold for parental intervention in the genetic makeup of their offspring: They are using P.G.D. to detect a predisposition to cancers that may or may not develop later in life, and are often treatable if they do.
For most parents who have used preimplantation diagnosis, the burden of playing God has been trumped by the near certainty that diseases like cystic fibrosis and sickle cell anemia will afflict the children who carry the genetic mutation that causes them. The procedure has also been used to avoid passing on Huntington’s disease, a severe neurological disease that typically does not surface until middle age but spares no one who carries the mutation that causes it.
I suspect as meaning of more genetic variations get identified that selection to lower cancer risk will eventually lose out to selection for other qualities. This will happen in part as a result of the development of better treatments for cancer. Also, as the significance of more genetic variations become known people will weigh cancer risk against advantages and disadvantages of other genetic variations found in each embryo.
Australian fertility clinics that do IVF (in vitro fertilization) also are now offering tests for genetic variations that increase cancer risks.
The tests pick up mutations in the BRCA1 and BRCA2 genes, Dr Leeanda Wilton, head of the Genetic and Molecular Research Lab at Melbourne IVF, told a recent international conference in Brisbane.
This technique can also detect mutations in the BRCA genes, which confer an estimated 65-85% risk of the carrier developing breast cancer by the age of 70.
Suppose a gene therapy to breasts to correct the BRCA gene only in breast tissue is developed 10 or 20 years after an IVF baby is born. Well, selecting against BRCA variants for breast cancer risk reduction will turn out to be unnecessary.
I suspect the people who are selecting against BRCA1 and BRCA2 in their offspring are making a poor trade-off without even being aware they are making a trade-off. If Greg Cochran and Henry Harpending are correct the genetic variations that occur at higher rates in Ashkenazi Jews which cause health problems (including BRCA1 and BRCA2) are there due to selection for higher intelligence during the Middle Ages. Then selecting out BRCA1 and BRCA2 mutations using PGID and IVF will result in dumber offspring. Henry Harpending explains that BRCA1 probably accelerates early central nervous system (CNS) development at the expense of higher breast cancer risk later on:
Re mechanism: The argument (well known to breeders where there is no argument) goes like this: In a drastic new environment there is big fitness payoff to IQ. In this new environment there is a payoff to "turning down" BRCA1 to free up early CNS development but at the cost of higher cancer rates later in life. Eventually, especially in a big population, a BRCA1 variant with the optimum activity will show up. Meanwhile carriers of one normal and one broken BRCA1 gene have a big fitness advantage because they have, say, 90% of normal suppression of early CNS development. So the broken BRCA1 allele is favored by selection even though homozygotes for it die. After a long time it would be replaced by the optimum allele but it takes a long time for that optimum allele to show up.
But if biomedical advances will produce cures for cancer within 20 years (and I'd be very very surprised if they didn't) then for the BRCA variations the trade-off for getting lower cancer risk at the expense of lower intelligence is a bad choice to make today. Better to boost the risk of a disease that will become easy curable before the disease is likely to develop and give your daughter higher IQ. The higher IQ will be a tremendous asset throughout life. The cancer problem will be fixable. If you believe as I do that the rate of biotechnological advance is accelerating so rapidly that cancer will become curable before babies born today reach their 30s then the risk of increased breast cancer is a price worth paying in order to give your daughter a smarter brain.
I predict most of us will live to see the day that donor egg banks offer eggs with the BRCA1 and BRCA2 mutations as selling points.
Toshihiko Komatsu, a functional anatomist at Osaka University in Japan, found in a study of dissection results that where most humans have 2 muscles as upper arm biceps some people have 3 or even 4 bicep muscles. (triceps? quadraceps?)
However, in Komatsu's research, 14 to 20 percent of people were found to have three muscles and 1 to 4 percent were found to have four muscles in their biceps.
People with more than the usual two muscles also tended to have more muscles than normal in other parts of their body, such as their elbows or fingers.
Do some people have genetic variations that code for more muscles? Or does noise in the system cause some small fraction of developing embryos to grow extra muscles in assorted places?
If people who have extra muscles are symmetric in their muscle counts (e.g. 3 muscles on upper arms on both arms) then that tends to suggest genetic variations coding for this result.
Any time you read about people who deviate from the biological norm for some quality of their bodies keep in mind that anything that can happen naturally will some day become selectable using biotechnology. If the people who have extra muscles gain some performance advantage then expect some parents in the future to opt for genetic engineering to give their kids the extra muscles on purpose.
Adding extra muscles to adults will become possible when advances in stem cell research and tissue engineering provide the ability to grow replacement muscles either inside or outside the body. But making those muscles useful might be much harder because wiring up neurons to the muscles and then training the brain to control them appropriately could turn out to be quite difficult.
A team of researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, has demonstrated sustained regression of advanced melanoma in a study of 17 patients by genetically engineering patients' own white blood cells to recognize and attack cancer cells. The study appears in the online edition of the journal Science on August 31, 2006*.
"These results represent the first time gene therapy has been used successfully to treat cancer. Moreover, we hope it will be applicable not only to melanoma, but also for a broad range of common cancers, such as breast and lung cancer," said NIH Director Elias A. Zerhouni, M.D.
Immunotherapies that are specific to cancer cells are much preferred over chemotherapies and radiation therapies that also trash normal cells throughout the body. Gene therapy that programs immune cells to attack only cancer cells will cause far fewer harmful side effects. If scientists can find surface protein features specific to all cancers (and it is not clear to me that this is possible) then genetically engineered immunotherapies will eventually cure all cancers.
Not all patients benefitted but it looks like a cure for 2 of them.
Thus, NCI researchers, led by Steven A. Rosenberg, M.D., Ph.D., sought an effective way to convert normal lymphocytes in the lab into cancer-fighting cells. To do this, they drew a small sample of blood that contained normal lymphocytes from individual patients and infected the cells with a retrovirus in the laboratory. The retrovirus acts like a carrier pigeon to deliver genes that encode specific proteins, called T cell receptors (TCRs), into cells. When the genes are turned on, TCRs are made and these receptor proteins decorate the outer surface of the lymphocytes. The TCRs act as homing devices in that they recognize and bind to certain molecules found on the surface of tumor cells. The TCRs then activate the lymphocytes to destroy the cancer cells.
In this study, newly engineered lymphocytes were infused into 17 patients with advanced metastatic melanoma. There were three groups of patients in this study. The first group consisted of three patients who showed no delay in the progression of their disease. As the study evolved, the researchers improved the treatment of lymphocytes in the lab so that the cells could be administered in their most active growth phase. In the remaining two groups, patients received the improved treatments. Two patients experienced cancer regression, had sustained high levels of genetically altered lymphocytes, and remained disease-free over one year. One month after receiving gene therapy, all patients in the last two groups still had 9 percent to 56 percent of their TCR-expressing lymphocytes. There were no toxic side effects attributed to the genetically modified cells in any patient.
So 2 out of the 14 patients who received better optimized later rounds of therapy are cancer-free over a year later.
This team is trying various ways to enhance the treatment. They are also creating lymphocytes to target breast, lung, and other cancers.
"We are currently treating advanced melanoma patients using adoptive transfer of genetically altered lymphocytes, and we have now expressed other lymphocyte receptors that recognize breast, lung, and other cancers," said Rosenberg.
Developing the new treatment involved first investigating the chemical markers on the outside of cancer cells that the body's natural immune system recognises. The team honed in on chemical markers unique to melanoma cells, such as one called "MART-1".
As more is learned about various types of cancer and as instrumentation for detecting and measuring proteins on the surfaces of cells become more sensitive the scientists will gain more targets on cancer cells to aim immune cells at.
The fact that only two out of the seventeen patients in this trial responded is disappointing, says Davis. The researchers suspect the problem was that their technique did not always alter the T cells in the desired way; they say they have improved their technique in the months since this trial was done, so future remission rates should be higher.
This therapy will only get better. Development of better ways to deliver gene therapy will enhance the effectiveness of this therapy by providing scientists with a way to convert a larger fraction of T cells into cancer killers.
Cancer is curable. Most of us are going to live to see it cured.
Other researchers are working on similar strategies. Hwu, of M.D. Anderson, is engineering lymphocytes that have receptors for substances called chemokines that some tumors put out. This will help the lymphocytes home in on the cancer.
"We need to figure out how to get the T cells to migrate into the tumor more efficiently," he said. "If the T cells are able to recognize the cancer but are circulating in the bloodstream, then they are not on the battlefield where they need to be."
One problem that immunotherapies need to address comes from compounds which some cancer cells secrete that basically discourage immune cells from approaching. These compounds are one reason cancer vaccines have not achieved great success. A combination of immune cells aimed at cancer cells with monoclonal antibodies or other approaches that aim at the immune system damping compounds would be more potent.
The New York Times has an excellent article surveying what is known about the role genetic inheritence in determining life expectancy and mortality. Recent studies on twins point toward a much smaller than expected role for genetics in determing life expectancy.
His solution, a classic one in science, was to study twins. The idea was to compare identical twins, who share all their genes, with fraternal twins, who share some of them. To do this, Dr. Christensen and his colleagues took advantage of detailed registries that included all the twins in Denmark, Finland and Switzerland born from 1870 to 1910. That study followed the twins until 2004 to 2005, when nearly all had died.
Now, Dr. Christensen and his colleagues have analyzed the data. They restricted themselves to twins of the same sex, which obviated the problem that women tend to live longer than men. That left them with 10,251 pairs of same-sex twins, identical or fraternal. And that was enough for meaningful analyses even at the highest ages. “We were able to disentangle the genetic component,” Dr. Christensen said.
But the genetic influence was much smaller than most people, even most scientists, had assumed. The researchers reported their findings in a recent paper published in Human Genetics. Identical twins were slightly closer in age when they died than were fraternal twins.
But, Dr. Christensen said, even with identical twins, “the vast majority die years apart.”
On average identical twins die over 10 years apart. I would not have expected that result.
Even the role for genetic inheritance for cancer risk differences is seen as fairly small.
In a paper in The New England Journal of Medicine in 2000, Dr. Paul Lichtenstein of the Karolinska Institute in Stockholm and his colleagues analyzed cancer rates in 44,788 pairs of Nordic twins. They found that only a few cancers — breast, prostate and colorectal — had a noticeable genetic component. And it was not much. If one identical twin got one of those cancers, the chance that the other twin would get it was generally less than 15 percent, about five times the risk for the average person but not a very big risk over all.
Of course there are people who have genetic variations which put them at very high risk of cancer.
Alzheimer's risk has a larger genetic component.
Dr. Gatz and Dr. Pedersen analyzed data from a study of identical and fraternal Swedish twins 65 and older. If one of a pair of identical twins developed Alzheimer’s disease, the other had a 60 percent chance of getting it. If one of a pair of fraternal twins, who are related like other brothers and sisters, got Alzheimer’s, the other had a 30 percent chance of getting it.
But, Dr. Pedersen noted, Alzheimer’s is so common in the elderly that it occurs in 35 percent of people age 80 and older.
Note there are some complicating factors here. Most notably, some genetic variations put you at risk for some disease only if you do or do not do some certain thing. For example, a genetic variation for apolipoprotein E increases risk of Alzheimer's but if you have that apoliprotein E allele then diet can greatly reduce the risk. So if you live in a culture where the customary foods cancel out the genetic risk you aren't going to be at much greater risk from that genetic allele. But if you live in a culture where you eat customary foods which do not provide compensating protections then carrying that genetic allele will put you at much greater risk of Alzheimer's.
One theory of aging and longevity is that we randomly collect defects and damage during development and also during aging. Given that the process of collecting those defects is random their distribution is random. If you are lucky your defects will accumulate with a fairly even distribution throughout the body. That way it will take longer for one organ to collect enough defects to fail entirely. But if you are unlucky then by chance many of your defects will accumulate in one organ or one part of an organ (e.g. in a heart valve) or in one cell (e.g. a set of mutations that make the cell become cancerous) to the point of failure and then you'll die sooner. Twins won't live the same amount of time because they each will accumulate defects in a different random distribution.
So what's the take-away lesson from this article? There's no reason for complacency about your life expectancy. Say your parents or grandparents lived a long time. So what. That's no guarantee you won't get cancer tomorrow or have a heart attack next week. Your defects are accumulating randomly. You might be accumulating a cluster somewhere that is going to kill you years before other family members die. If you want to live a very long time then support SENS research. Anything short of SENS technologies can't save you from the damage building up within.
The whole article is worth reading.
In a large epidemiological study, researchers found that people who drank three or more servings of fruit and vegetable juices per week had a 76 percent lower risk of developing Alzheimer’s disease than those who drank juice less than once per week.
The study by Qi Dai, M.D., Ph.D., assistant professor of Medicine, and colleagues appears in the September issue of The American Journal of Medicine.
The researchers followed a subset of subjects from a large cross-cultural study of dementia, called the Ni-Hon-Sea Project, which investigated Alzheimer’s disease and vascular dementia in older Japanese populations living in Japan, Hawaii and Seattle, Wash.
For the current study, called the Kame Project, the researchers identified 1,836 dementia-free subjects in the Seattle population and collected information on their dietary consumption of fruit and vegetable juices. They then assessed cognitive function every two years for up to 10 years.
After controlling for possible confounding factors like smoking, education, physical activity and fat intake, the researchers found that those who reported drinking juices three or more times per week were 76 percent less likely to develop signs of Alzheimer’s disease than those who drank less than one serving per week.
The benefit appeared particularly enhanced in subjects who carry the apolipoprotein E ÿ-4 allele, a genetic marker linked to late-onset Alzheimer’s disease – the most common form of the disease, which typically occurs after the age of 65.
A diet that cuts Alzheimer's risk probably cuts stroke and heart disease risk as well.
Researchers have found that vitamins C, E, and beta carotene do not provide a neuroprotective effect against Alzheimer's. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) also have been found to provide little or no benefit. The researchers behind this study suspected that perhaps polyphenols in foods provide benefit.
Dai began to suspect that another class of antioxidant chemicals, known as polyphenols, could play a role. Polyphenols are non-vitamin antioxidants common in the diet and particularly abundant in teas, juices and wines. Most polyphenols exist primarily in the skins and peels of fruits and vegetables. Recent studies have shown that polyphenols (like resveratrol in wine) extend maximum lifespan by 59 percent and delay age-dependent decay of cognitive performance in animal models.
"Also, animal studies and cell culture studies confirmed that some polyphenols from juices showed a stronger neuroprotective effect than antioxidant vitamins. So we are now looking at polyphenols," Dai said.
The researchers intend to check blood polyphenol levels to see if high polyphenols correlate with low Alzheimer's risk.
The nomenclature here may seem confusing. Catechins in tea are both polyphenols and flavonoids. Polyphenols are a larger set of chemical compounds which includes flavonoids as a subset. Then within the subset called flavonoids exists the smaller subset catechins. Fruits have flavonoids called anthocyanins. Tea and wine (and presumably dark grape juice) contain flavonoids called catechins.
Obvious question: Was the protective effect against Alzheimer's seen in this study due to catechins from tea and grape juice or from anthocyanins found in fruits? Or perhaps from other flavonoids called flavones and flavonols? Or other polyphenols? Or some combination of the above? I'm sorry I do not have an answer for you.
One obvious question: Drink the juice or eat whole fruits and vegetables? Well, juices appear to work (see above) and are quicker to consume. But perhaps the people who consume more fruit and vegetable juices also eat more fruits and vegetables. It is not clear what confounding factors these researchers controlled for.
Writing in the article, Qi Dai, MD, PhD, states, “We found that frequent drinking of fruit and vegetable juices was associated with a substantially decreased risk of Alzheimer’s disease. This inverse association was stronger after adjustments for potential confounding factors, and the association was evident in all strata of selected variables. These findings are new and suggest that fruit and vegetable juices may play an important role in delaying the onset of Alzheimer’s disease”.
I find it really surprising that these researchers could find an influence from juices above the background of all the other factors that will influence polyphenol content of diet.
Enormous amounts of other research has been done on the health benefits of polyphenols including flavonoids. Green tea catechins might reduce the risk of prostate cancer.
Anaheim, Calif. – After a year's oral administration of green tea catechins (GTCs), only one man in a group of 32 at high risk for prostate cancer developed the disease, compared to nine out of 30 in a control, according to a team of Italian researchers from the University of Parma and University of Modena and Reggio Emilia led by Saverio Bettuzzi, Ph.D.
The 600 mg-per-day dosage of caffeine-free, total catechins (50 percent of which is EGCG) given to participants in the Italian study is one or two times the amount of green tea consumed daily in China, where ten to 20 cups a day is normal.
I do not want to drink 10, let alone 20, cups of green tea a day. I'd rather take some caffeine-free catechin capsules. Better yet, I'd rather figure out which fruits and vegetables would deliver the same benefits and eat them instead.
Green tea is very popular in Japan and its consumption there might be the cause of lower Alzheimer's in Japanese in Japan as compared to Japanese in America.
Another paper which reported a reduction in blood plasma peroxide free radicals with green tea extract found a higher concentration of catechin polyphenols per cup of green tea.
"We believe we have shown for the first time the course change of both green tea catechin levels in human plasma as well as human plasma lipid peroxide levels after oral green tea catechin supplementation, " said Teruo Miyazawa, Ph.D., biodynamic chemistry professor at the Tohoku University Graduate School of Life Science and Agriculture and the study's principal investigator.
In the study, 18 healthy male subjects between the ages of 23 and 41 ingested green tea extracts in tablet form (including 254 milligrams of catechins per subject - one cup of green tea contains about 100 to 150 milligrams of catechin). All of the subjects avoided tea and tea-related beverages for 12 hours prior to the testing. Blood samples were taken one hour before and after the catechin ingestion.
I'd love to see a massive comparison study of a wide range of fruits and vegetables, juices, teas, and cocoa (which also contains catechins) where the effects of each food on blood plasma peroxides, blood pressure, and other indicators were compared. What are the most potent foods to eat?
The 806 male participants, averaging age 71 in 1985, were followed until 1995, with complete dietary and medical examinations in 1985 and 1990. Epidemiological evaluation of the health effects of catechins has previously been difficult due to the lack of information on the exact catechin composition of foods. For this study, the authors measured the catechin content of 120 frequently consumed plant foods, using the data to divide the subjects into low, medium and high quintiles of catechin consumption.Among the men in the highest quintile, 87% of catechins in the diet came from black tea; whereas those in lower quintiles ate more foods in which catechins were less concentrated. High catechin intake was associated with other practices characteristic of a healthy lifestyle, such as refraining from smoking, eating more fruits and vegetables, and increased activity levels.
For examples of more on the health benefits of tea see these research reports: Tea Intake Is Inversely Related to Blood Pressure in Older Women and Black and Green Tea Polyphenols Attenuate Blood Pressure Increases in Stroke-Prone Spontaneously Hypertensive Rats.
Green tea is hardly the only food that can improve blood flow and reduce blood free radicals. For example, see the research paper: Wine Polyphenols Decrease Blood Pressure, Improve NO Vasodilatation, and Induce Gene Expression. The "NO" in the title refers to Nitric Oxide which is a naturally occurring vasodilator (i.e. it makes blood vessels widen which lowers blood pressure). Nitric oxide deficiency is, in all likelihood, a cause of high blood pressure. Some drugs release NO as their mechanism of action. Viagra and Cialis work by releasing NO to cause blood to flow in the right places for male sexual function. Minoxidil, the anti-hair loss drug, has the "nox" in its name because it too is an NO releaser. But better to raise your vascular NO by diet before resorting to drug use. The foods that'll improve NO will also deliver other benefits.