Health,Stem Cells, and Technology

Thursday, December 30, 2010

Nutrition In Early Life Affects Fertility

Reproductive success of men and women is influenced by their nutitional status in early life, according to new research by Dr Ian Rickard from the Department of Animal and Plant Sciences the the University of Sheffield.

The research was published in the journal Ecology, and is the first study of its kind to show that what you eat as a child, and the nutrition you receive as a fetus, can have a serious influence on your life-long fertility.

Professor Ian Rickard's team used a combination of church record data on births in 18th century Finland and agricultural data on crop yields of rye and barley from the same time and place.

The study showed that in men and women who were born into poor families, food in very early life was related to the probability of reproducing. About half of the poor people who were born in a year in which both rye and barley yields were low would not have any children during their entire lives. However almost everyone from a poor family born in bumper harvest years would reproduce at least once in their life.

These results suggests that food received during prenatal or early postnatal life may regulate the development of the reproductive system, and present lifelong consequences. Thus malnourishment early in life leads to many consequences, including a possible lifelong inability to procreate.

Monday, December 27, 2010

TA-65 Anti-Aging Hype : Telomerase Activator Fails To Increase Telomere Length, But Exercise Does!

A Sept 2010 publication in Rejuvenation Research demonstrates the failure of TA-65 to lengthen telomeres. In a poorly controlled study, the authors do report a minor increase in telomerase in human keratinocytes, fibroblasts, and immune cells in culture, but observe no change in mean telomere length. Although a minor effect was observed in telomerase, but not telomere length, one can possibly attribute the telomerase activity to uncontrolled variables in the study.

Telomeres are like anglets at the end of shoestring, and like the anglet protecting the shoestring from unraveling, help protect the chromosomes (DNA) from unraveling or mutating. As the telomeres shorten with each cell division as we age, the likelihood of mutations increases. Here's the hype: TA-65 is falsely claimed to lengthen the telomeres, thus reducing your chances of experiencing mutated DNA and leading to a healthier life. Unfortunately, science does not back the hype. TA-65 does not work to lengthen telomeres.

TA-65 was originally discovered/invented by Geron in Menlo Park, CA. The product was then sold (licensed) to a sales/marketing company. The sales and marketing company will sell you a year's supply of TA-65 for about $2,500 to $8,000, depending on dosing. If TA-65 is a revolutionary means for "anti-aging," or improving health, or for life-extension as the sales people claim, why did Geron choose not to develop this product, but instead sold (licensed) the product to another company?  In other words, if Geron had something great, why did they give it away?

Furthermore, if indeed it were true that TA-65 can extend telomere length in human cells, then the long-term expression of telomerase throughout the body could present an unsafe risk of cancer. Many studies suggest that the adult human body has many uncontrolled cells (pre-malignant) and "mortal cancer cells" possessing activated oncogenes and inactivated tumor suppressor genes, but have stalled growth patterns because of their mortal state. Examples of such pre-malignant tumors would be skin growths (Actinic Keratosis), colon polyps, growing prostates, or large growing moles. Mortal cancer cells would include the "non-aggressive" subset of cancer cells in the mouth associated with smoking that are more easily controlled by cancer therapeutics than the aggressive, non-mortal types of cancer cells. A regimen to reset cellular growth to benefit human health during aging will require careful design and years of proper laboratory and clinical testing in order to possibly increase the probability of human longevity without exposing people to the unnecessary risk of cancer, or other possible safety issues.

In May 2010, Dr. Elizabeth Blackburn, professor of biochemistry and biophysics at UCSF, best known for her Nobel Prize winning studies of the nature of telomeres, and co-discovery of the enzyme telomerase, co-authored a paper "The power of exercise: buffering the effect of chronic stress on telomere length ." The paper showed that vigorous physical activity appears to protect those experiencing high stress by buffering the relationship of stress to telomere length. Thus exercise is a key to lengthening telomeres, and unlike the $8,000 TA-65, is proven to be safe, and costs no more than some running shoes, shorts and a shirt. Telomerase activity was not measured in this study, so whether the mechanisms underlying telomere lengthening due to excersie in this study involved the activation of telomerase cannot be stated (although recent studies in Germany suggest this to be the true).
At this point no significant scientific evidence of efficacy has been shown to warrant the use of TA-65, no longitudinal or other significant studies of safety reported, and therefore any use of TA-65 in medicine is unjustified.

As I continually point out, biology is complicated and works as a system, and not in a reductionist manner as some would like to believe. Ingesting one compound, such as TA-65, and doing so at high levels using a refined product is at best likely to do little, and at worst, likely to be harmful, possibly inducing cancer. If you want a safe proven way to lengthen your telomeres and promote better health you must work at it. That work requires exercise, good diet, and a proper lifestyle, and provides a "systems-biology' based means instead of a reductionist means for attaining good health.

Sunday, December 26, 2010

Cancer Mechanism? New Cell Biological Mechanism That Regulates Protein Stability In Cells Discovered At UCLA

Multivesicular bodies (MVBs) comprise an essential step in the trafficking of cell surface receptors for degradation. In the Dec. 23, 2010, issue of Cell, Taelman et al. show that during Wnt signaling the enzyme Glycogen Synthase Kinase 3 (designated in red below) is bound by the Wnt receptor complex, becoming sequestered from the cytoplasm inside MVBs. Through this pathway the Wnt growth factor inhibits GSK3 activity, causing the stabilization of many proteins. This “enzyme incarceration” mechanism links the basic intracellular membrane trafficking machinery to cell signaling. The finding is important because sequestering the enzyme, Glycogen Synthase Kinase 3 (GSK3), results in the stabilization of proteins in the cell, at least one of which is known to be a key player in cancer.

Dr. De Robertis, the lead author, and professor in the Dept. of Biological Chemistry, hypothesizes that one of the functions of Wnt may be to stabilize certain cell functions and it may be that cancer cells need higher stability than other cells, which is why increased Wnt signaling if found in so many cancers. These findings may lead to new therapeutic targets for preventing sequestrations inside these membranes, which would decrease Wnt signaling, and hence lead to down regulation of cancerous cell growth.

Friday, December 24, 2010

Obesity Is Reduced With Recombinant Probiotics

Genetically engineered probiotics can modulate the physiology of host fat cells according to a new study in Microbiology. The findings could lead to specialised probiotics that have a role in the prevention or treatment of conditions such as obesity.

Dr Catherine Stanton and team from the Alimentary Pharmabiotic Centre (APC), Cork, University College Cork and Teagasc, in Ireland engineered a strain of the bacterium Lactobacillus to produce a fatty acid molecule called conjugated linoleic acid (CLA). When this engineered bacterial strain was fed to mice, the researchers observed that the composition of the mice's fat tissue was significantly changed, demonstrating that ingesting active bacteria can influence metabolism at remote sites in the body.
CLA is a fatty acid that is produced in different versions by different types of bacteria. One type, called t10, c12 CLA, is associated with decreased body fat in humans and other animals. t10, c12 CLA also has the ability to inhibit the growth of colon cancer cells and induce their death. However, this type of CLA is only produced by certain types of bacteria including Propionibacterium acnes - a skin bacterium that can cause acne.

The present study used an enzyme-encoding gene from P. acnes that was transferred to the Lactobacillus strain allowing it to produce t10, c12 CLA. Lactobacillus strains are common inhabitants of the gut flora and are often found in probiotic products. The researchers found that the level of t10, c12 CLA in the mice's fat tissue quadrupled when they were fed this recombinant probiotic. Thus, this study demonstrates that gut microbes have an impact on host metabolism, and in particular fat composition.

CLA has previously been shown to alleviate non-alcoholic fatty liver disease that often accompanies obesity. Therefore, increasing levels of CLA in the liver by ingestion of a probiotic is of therapeutic relevance. Because fat is not an inert layer around our bodies, but is an active signaling system and is proinflammatory and a risk factor for many diseases, including cancers, these data demonstrate the potential to influence the disease-causing fat signaling system through diet-microbe-host interactions in the gut.

Tuesday, December 21, 2010

Cancer Clusters Across the U.S. Need Investigation

Across the US cancer statistics are alarming.  According to the CDC and National Center for Disease Control, 46 children per day (two classrooms a day) are being diagnosed with cancers unrelated to genetics or family history. In contrast, recent studies by British scientist show that the ancient Egytians, whose society had few or none of the toxic chemicals associated with modern day socities, experienced few or no tumors.
Senator Barbara Boxer (D-CA) has filed a new bill "Strengthening Protection For Children and Communities From Disease Clusters Act," or "Trevor's Law," that calls for an improved, streamlined process to investigate and address disease clusters across the U.S. by:

1. Strengthening federal agency coordination and accountability when investigating and helping to address potential disease clusters;
2. Increasing resources to communities who may be impacted by potential disease clusters, including by providing for community-based committees that play an integral role in actions to investigate and help address such clusters; and
3. Enhancing federal, state and academic capacity to investigate and help address such clusters, including through partnerships and grants and by developing new pollution and disease tracking tools to facilitate investigation and actions to address clusters.

Sen. Boxer's legislation was named for Trevor Schaefer, a young cancer survivor and advocate who was diagnosed with brain cancer seven years ago at the age of thirteen. There were other children and young adults with brain cancer in his small town in Idaho at the time of his diagnosis.  Trevor and his mother became aware that environmental contamination might have played a part in these illnesses.  Yet authorities did not seem to care.  Trevor's mission is to be a champion for the protection of children and small communities from environmental contamination, and he wants to help them from slipping through the cracks of environmental regulation.  Similar to laws in Europe, the bill hopes to hold companies accountable for proper disposal of toxins and to make sure that other children will not have to experience what Trevor did. 

Nearly every state has reported cancer clusters, and some of the more notable include: Moreland, ID; Fallon, NV; The Acreage, FL; Sierra Vista, AZ; Carlsbad, CA; Santa Susana, CA; Kettleman City, CA; and Victor, NY.  According to the National Disease Cluster Alliance (NDCA), state epidemiologists are charged with investigating an average of 1,000 suspected cancer clusters every year.

Senator Boxer's bill would set up an objective, transparent process for conducting investigations and provide for the prominent involvement of concerned community members

Saturday, December 18, 2010

Neuroprotection Against Stroke And Brain Injury From Curry Spice

Once again the curry spice turmeric, or in this case a synthetic derivative of turmeric, made by scientists at the Salk Institute for Biological Studies in San Diego, CA, dramatically improves the behavioral and molecular deficits seen in animal models of ischemic stroke and traumatic brain injury (TBI). Two new studies suggest that the novel compound may have clinical promise for these conditions, which currently lack significant therapies.

Ischemic stroke is the leading cause of disability and the third leading cause of death of the aged in the United States, while TBI is the leading cause of death and disability in civilians and military personnel under the age of 45. In particular, TBI is the major cause of disability in veterans returning from Iraq and Afghanistan. In both conditions, those who survive frequently have serious behavioral and memory deficits. The only FDA-approved treatment for stroke is tissue plasminogen activator (TPA), a biotechnology product made with recombinant technology, which is effective only in about 20 percent of cases. There is no effective documented treatment for TBI.

Previous studies by David R. Schubert. Ph.D., and Pamela Maher, Ph.D. at the Salk Institute had developed a series of new compounds using a novel drug discovery paradigm that starts with natural products derived from plants. The procedure then selects synthetic derivatives that show efficacy in multiple assays testing for protection against various aspects of the nerve cell damage and death that occur in brain injuries and in age related neurodegenerative diseases. One compound, called CNB-001, derived from curcumin, the active ingredient in the spice turmeric, proved highly neuroprotective in all of the assays and also enhanced memory in normal animals.

Thus Drs. Schubert and Maher once again provide data showing the positive effects of tumeric, or tumeric-like compounds, in treating or preventing inflammatory conditions associated with disease and trauma. Years ago the observation that the diet of Indians, whose level of age related dementia, including Alzeheimer's, is much lower than that of those living in he USA, was one of the observations that led to the beginnings of rigorous scientific investigation of turmeric and other plant based compounds used in Ayurvedic practices, i.e. native Indian medicine.

Note: see Scientific Basis for Ayurvedic Therapies (2003) edited by Lakshmi C. Mishra

Friday, December 17, 2010

Physicists At UC Santa Barbara Observe Quantum Mechanics At The Macroscopic Level: The World's First Quantum Machine

Dr. Andrew Cleland and John Martinis, professors at UCSB, along with their team of scientists have observed, for the first time, quantum mechanics at the macroscopic level. In their Nature paper entitled, "Quantum ground state and single-phonon control of a mechanical resonator" they describe building a device that cools materials to their ground state so that a baseline measurement without vibration is achieved. The researchers demonstrated that, once cooled, the mechanical resonator followed the laws of quantum mechanics; observing the so-called phonons. While exchanging this energy in their sensing device, the transduction of the quantum to the macroscopic become "quantum entangled," such that the act of measuring the transduction then forces the mechanical resonator to "choose" the vibrational state in which it should remain. In a related experiment, the UCSB group placed the mechanical resonator in a quantum superposition, a state in which the resonator simultaneously had zero and one quantum of excitation. This is one of those quantum mechanical oddities that we all discuss, and can be thought of as the energetic equivalent of an object being in two places at the same time. The researchers showed in these studies that the resonator behaved as expected by quantum theory.

The authors abstract: Quantum mechanics provides a highly accurate description of a wide variety of physical systems. However, a demonstration that quantum mechanics applies equally to macroscopic mechanical systems has been a long-standing challenge, hindered by the difficulty of cooling a mechanical mode to its quantum ground state. The temperatures required are typically far below those attainable with standard cryogenic methods, so significant effort has been devoted to developing alternative cooling techniques. Once in the ground state, quantum-limited measurements must then be demonstrated. Here, using conventional cryogenic refrigeration, we show that we can cool a mechanical mode to its quantum ground state by using a microwave-frequency mechanical oscillator—a ‘quantum drum’—coupled to a quantum bit, which is used to measure the quantum state of the resonator. We further show that we can controllably create single quantum excitations (phonons) in the resonator, thus taking the first steps to complete quantum control of a mechanical system.

The principles developed here may lead to further designs in quantum information processing, where signal mixing of microwaves and visible or IR radiation, for example, may be implemented for industrial applications.

Monday, December 13, 2010

Sperm Stem Cells Transformed Into Insulin-Producing Cells

Dr G. Ian Gallicano, an associate professor in the Department of Cell Biology at Georgetown University Medical Center (GUMC) in Washington DC told delegates at the 50th Annual Meeting of American Society for Cell Biology in Philadelphia, that his lab has shown proof of principle in an animal study that it is possible to extract human spermatogonial stem cells (SSCs) from testicular tissue and change them into insulin-secreting beta islet cells that are normally found in the pancreas.

The study observed that once you remove the SSCs from the testes niche, the stem cells receive new signals from the new niche, and will form all three germ layers within several weeks. He and his team are hopeful that their study means men with type 1 diabetes may be able to grow their own insulin-producing beta-islet cells from their testicular tissue. Also, in principle there is no reason why this new method of differentiating and grafting beta-islet cells should not also work with the female equivalent, the oocyte cells that become mature eggs in the ovaries.

Beta-islet cells are the cells in the pancreas that produce insulin. People with type 1 diabetes mellitus, sometimes referred to as juvenile or early onset diabetes, loose these cells because their immune system destroys them, resulting in too much glucose in their blood and urine.

Future treatments based on their research could use an autologous procedure, where cells are taken from the patient's own testicular tissue, so the immune system would recognize the cells as "self" and not attack them, thus removing the risk of rejection.

Sunday, December 12, 2010

Breakfast With David Dodge At Grateful Bread: The Benefits Of Freshly Milled Organic Whole Grains

While visiting Miami on one of those rare beautiful mornings in South Florida, with cool crisp air and plenty of sunshine, we enhanced our experience with a breakfast at the Grateful Bread bakery and restaurant. Greeted by the owner, David Dodge, we quickly learned that David's bread products are made entirely with organic, whole grains sourced from the north of Montana; importantly David mills all of the grains on site at Grateful Bread to produce the flour for all his baked goods. Our breakfast, including incredible blueberry pancakes and whole grain toast was inspiring; inspiring to such an extent that I write this blog as I digest my food.

David and I had a wonderful exchange on the benefits of healthy foods in general, and organic, freshly milled whole grains in particular. David's knowledge extends back to a wonderfully obscure correspondence from 1947 in the British Medical Journal discussing whole grains in the diet, and lack therof leading to canine hysteria. So to David, thank you for the best breakfast I've ever had in Miami, and for the inspiration to write this morning. In honor of David Dodge this morning, a few notes (from many) taken directly from the literature on whole grains from recently published literature:

de Munter JS, et al. PLoS Med. 2007 Aug;4(8):e261. Whole grain intake is inversely associated with risk of type 2 diabetes, and this association is stronger for bran than for germ. Findings from prospective cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes.

Jensen MK, et al. Am J Clin Nutr. 2004 Dec;80(6):1492-9. This study supports the reported beneficial association of whole-grain intake with CHD (prevention of chronic heart disease, eds note) and suggests that the bran component of whole grains could be a key factor in this relation

Landberg R et al. J Nutr. 2010 Dec;140(12):2180-6. Epub 2010 Oct 27. We conclude that whole grain and bran from rye resulted in significantly lower plasma PSA compared with a cellulose-supplemented refined wheat diet in patients with prostate cancer. The effect may be related to inhibition of prostate cancer progression caused by decreased exposure to insulin, as indicated by plasma insulin and urinary C-peptide excretion.

McIntosh GH, et al. Am J Clin Nutr. 2003 Apr;77(4):967-74. High-fiber rye and wheat food consumption improved several markers of bowel and metabolic health relative to that of low-fiber food. Fiber from rye appears more effective than that from wheat in overall improvement of biomarkers of bowel health

Saturday, December 11, 2010

Duchenne Muscular Dystrophy Data Implicates Lack Of Stem Cell Availability

Dr. Helen Blau, professor at Stanford University, has new data that help to understand why children with Duchenne muscular dystrophy experience severe muscle wasting and eventual death. Previous studies have shown that laboratory mice with the same mutation that causes the disease in humans display only a slight weakness. Professor Blau's work uses a new animal model of the disease that her team developed, demonstrating the inability of stem cells within the human muscle (hMuSCs), unlike those in the animal model, to heal the ongoing damage caused by the disorder. The disorder affects about one of every 3,500 boys in the United States, whereas girls are spared because the gene lies on the X-chromosome.

Mechanistically, the difference is caused by mice having significantly longer protective caps on the ends of their chromosomes. The caps, called telomeres, are like the aglets at the end of a shoestring, protecting the cells and allowing them to continue to divide and replenish the damaged muscle long after the human cells have reached their capacity for division.

The research marks the first time that muscular dystrophy has been shown definitively to be a stem-cell-based disorder, and suggest that treatments directed solely at the muscle fiber will not suffice and could even exacerbate the disease. Thus, stem cells will need to be added, or the stem cell niche enhanced, or both in order to treat this disease in humans.

Fast, Inexpensive Semiconductor-Based DNA Sequencing

A semiconductor chip that reads the sequence of DNA could bring the power of sequencing to a much broader user base in the science and diagnostics world. The desktop machine, developed by the emerging biotech called Ion Torrent, based in Connecticut and California, is now on sale  and will cost about $50,000, approximately one-tenth of the cost of other sequencing machines on the market.
Basically the chip is a massively parallel micro pH meter. When a nucleotide is incorporated into a strand of DNA by a polymerase thus liberating a hydrogen ion, that hydrogen ion is measured as a digital electronic event. Reactions take place in a massively parallel manner where each reaction is measured using a specific DNA template. During the process of nucleotide incorporation, a hydrogen ion is liberated and sensed by the chip. Each of the massively parallel wells holds a different DNA template, and therefore each well provides one piece of the sequence puzzle. Thus each electronic event is measuring a ph change associated with a specific portion of the DNA sequence.
The biggest advantages of the new technology are its speed and costs; the Ion Torrent machine can sequence a sample of DNA in a couple of hours, rather than the week or more required by most of the machines now on the market. That could make the technology particularly useful for genetic diagnostics, which require a quick turnaround. Although Ion Torrent's machines are inexpensive, the cost of sequencing per base pair is higher than for other instruments because each chip can only be used once, and the disposable chip currently costs about $250. However, as the machine commands more market share, the price per chip should likely drop as economy by scale is realized.
Life Technologies, of Carlsbad, CA, purchased Ion Torrent in late 2010

Friday, December 10, 2010

Reduced Clearance Of Beta-Amyloid In Alzeheimer's Demonstrated By Tracer-Based Metabolomics

Alzheimer’s disease is hypothesized to be caused by an imbalance between β-amyloid (Aβ) production and clearance leading to Aβ accumulation in the central nervous system. A study published in Science by Dr. Randall Bateman and colleagues shows that Alzheimer's disease is linked to the brain's poor elimination of a plaque component, beta-amyloid protein. Studies had previously shown that beta-amyloid protein accumulation occurs in Alzheimer's patients, but this study reveals something previously unknown, that it is the poor clearance of the protein causing the accumulation.

Using a form of stable-isotope dynamic metabolic profiling, sometimes called SIDMAP in the literature (Maguire et al, 2006, SiDMAP- A Metabolomics Approach to Assess The Effects Of Drug Candidates On The Dynamic Properties Of Biochemical Pathways. Expert Opinion in Drug Discovery, 1: 351-359; Maguire, et al 2007,  An Overview of Metabolomics: Implications for the Pharmaceutical Industry. International Journal of Pharmaceutical Medicine. 21(3):217-224), leucine is labeled with a "heavy carbon tracer"  and incorporated into the new copies of a-beta proteins. Over a period of a few hours, periodic samples of the patients' cerebrospinal fluid were taken through a lumbar catheter. They purified the a-beta from the samples and could determine how much of it included labeled leucine. The scientists were eventually able to measure the individual's a-beta production rate. What the scientist measure using mass-spec instrumentation is the amount of  "heavy carbon label" in the a-beta samples taken from the patients.

As soon as the percentage of a-beta containing labeled leucine peaked, the scientists stopped introducing the labeled leucine and acquired periodic samples of the participants cerebrospinal fluid. In this manner scientists measure how quickly the patient's nervous systems eliminated the labeled a-beta. In other words, the technique describes how efficiently the brain was clearing out the a-beta protein.

Not only are these data important for understanding the mechanisms of Alzeheimer's, but development of this technique may provide a future biomarker for Alzeheimer's, serving as a quantitative measure of the disease. And this biomarker may prove to be an early indicator, that is the reduced clearance of a-beta protein can be measured before the clinical/behavioral manifestations of the disease are observable.

Thursday, December 9, 2010

NIH Proposes To Create Translational Science Center

National Institutes of Health (NIH) Director Francis Collins said that he is moving ahead with his biggest initiative yet - a plan to create a new center focused on translational science. The center could be running a year from now, despite the concerns of many that it may mean dismantling another NIH center.

Debate over the proposal flared at an NIH advisory board meeting. Nearly 20 groups and investigators supported by the National Center for Research Resources, which would be partly absorbed by the new center, sent letters or gave testimony expressing concern that existing NCRR programs might be lost. The proposed center is very large organization being implemented on a very fast time scale, and the community that will be affected is arguing for more time to provide input. NCRR Director Barbara Alving urged the board instead to expand NCRR into the new translational center.

Despite such concerns, the board voted 12-1 to create the new center. Only Jeremy Berg, director of the National Institute of General Medical Sciences, voted no given his concern that the implications for the rest of NIH hadn't been adequately discussed.

Collins called the decision to go ahead "a momentous occasion" because the center is being created "on the basis of scientific arguments" and not politics, which has "rarely" happened at NIH. The proposal was made by the Scientific Management Review Board (SMRB), a panel of outside scientists and NIH institute directors whose task is to find ways to streamline and improve NIH's structure. An SMRB working group on translational medicine and therapeutics concluded in a draft summary in November that NIH needs to do more work in this area.

The center would house several existing programs at NIH, including the $113 million Molecular Libraries screening program, a $25 million effort called Therapeutics for Rare and Neglected Diseases, and NCRR's Clinical and Translational Science Awards (CTSA). It would also fold in the Cures Acceleration Network, a drug-development program created by the health care reform bill but not yet funded.

The most controversial issue seems to be the fate of NCRR programs. The CTSA grants cost $490 million a year, about 40% of NCRR's $1.2 billion budget. It's not clear what would happen to the rest of NCRR's portfolio, which includes support for construction and instrumentation, primate centers and other model animal resources, and grants for minority institutions and states that don't have much NIH funding.
SMRB agreed that a working group of NIH staff members will report back in 3 months on NCRR programs.

Dr. Collins will send his recommendation for the new translational center to Health and Human Services Secretary Kathleen Sebelius, who will forward it to legislators. Congress will have 180 days to object; otherwise, the new institute will move forward.

Wednesday, December 8, 2010

Decreased Biodiversity May Increase The Prevalence Of Infectious Diseases

Current unprecedented declines in biodiversity reduce the ability of ecological communities to provide many fundamental ecosystem services, including, according to a study in Nature, limitations on the transmission of infectious diseases. The study suggests that loss of species from an environment could have dangerous consequences for the spread and incidence of infections, including those that affect humans.

Dr. Felicia Keesing, a NSF funded professor of biology at Bard College in Annandale, New York, and her colleagues reviewed several dozen studies published in the past five years and found that the link holds true across various ecosystems, pathogens, and hosts. Thus a disctinct pattern has emerged showing that biodiversity loss increases disease transmission.

The underlying mechanisms for the observed relationship between biodiversity loss and increased disease transmission is not yet known. However, Dr. Keesing speculates that some species are better at buffering disease transmission. For example, because some species have low rates of reproduction or invest heavily in immunity, that species may tend to become extinct first when diversity declines, whereas species that have high rates of reproduction or invest less in immunity, and thus are more likely to be disease hosts, survive for longer.

Regardless of the underlying mechanisms, the implication for the observation is clear: increased biodiversity results in fewer diseases for mankind. Biodiversity serves mankind in many ways that we'll probably never understand, but we can think of many......I'm thinking of my PCR experiments, or crime scene PCR diagnostics that use taq polymerase from the bacterium Thermus aquaticus dwelling in hot water enviornments.

Tuesday, December 7, 2010

Spontaneous Healing Of CNS: Beginning A Genetic Database

Dr. Robin J M Franklin, professor of neuroscience at the University of Cambridge in England, and team have generated a transcriptional database of genes that are differentially expressed in association with spontaneous CNS remyelination after nerve damage. This transcriptome of remyelination is the beginning of a useful resource that should allow scientists to better understand the systems biology of endogenous repair mechanisms in the injured brain, as well as how normally expressed genes and signaling pathways in the white matter might be affected in pathologies of CNS demyelination or failed myelin regeneration. Transcriptonomics is one important aspect of understanding the systems biology of normal and damaged tissues, and is helpful in understanding the expression of those factors, such as proteins, in the role of, in this case, the spontaneous healing mechanisms involved in the repair of nerve myelination.

The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. Franklin's group at Cambridge generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts encoding for the retinoid acid receptor RXR-γ were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-γ in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Removal, termed "knockdown" of RXR-γ by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-γ, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Mimicing RXR activity by applying a RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Dr. Franklin's studies indicate that RXR-γ is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target, probably one of many targets, required for regenerative therapy in the CNS. This study is a beautiful beginning to understanding spontaneous healing at the molecular level, and utilized an Illumina chip array with over 22,000 genes, but I suspect we have a long way to go before we understand the system of spontaneous healing in remyelination.

Monday, December 6, 2010

Simple, Inexpensive Biomicroscopes Invented At CalTech And UCLA

Using a $1.50 digital camera sensor, Dr.  Changhuei Yang, a professor of engineering at Caltech, and his team have created the simplest and least expensive lens-free microscope yet. The device uses microfluidics and could have many applications, including helping diagnose disease in the developing world, and enabling rapid screening of new drug candidates.

The best current means to diagnose malaria uses a skilled technician to examine blood samples with a conventional optical microscope. But this is impractical in parts of the developing world where malaria is common. A simple lens-free imaging device connected to a smart phone or other mobile communications device could automatically diagnose disease, obviating the need for a costly microscope and technician in the field.  A lensless microscope could also be used for rapid cancer or drug screening, with dozens or hundreds of microscopes working in parallel.

The Caltech device is remarkably simple. A system of microscopic channels called microfluidics lead a sample across the light-sensing chip that snaps images in rapid succession as the sample passes across the sensor. There are no other parts. Earlier versions featured pinhole apertures and an electrokinetic drive for moving cells in a fixed orientation with an electric field. In the new device, this complexity is eliminated thanks to further refinements in design and more sophisticated software algorithms. Samples flow through the channel because of a tiny difference in pressure from one end of the chip to the other. The inventors call it a subpixel resolving optofluidic microscope, or SROFM.

Dr Aydogan Ozcan, a professor at UCLA, uses a different approach incorporating wide-field fluorescent and darkfield imaging on a cell-phone with compact, light-weight and cost-effective optical components that are mechanically attached to the existing camera unit of the cell-phone. They used battery powered light-emitting diodes (LEDs) to pump the sample of interest from the side using butt-coupling, where the pump light was guided within the sample cuvette to uniformly excite the specimen. The fluorescent emission from the sample was then imaged using an additional lens that was positioned right in front of the existing lens of the cell-phone camera. Because the excitation occurs through guided waves that propagate perpendicular to our detection path, an inexpensive plastic colour filter was sufficient to create the dark-field background required for fluorescent imaging, without the need for a thin-film interference filter. The scientists validated the performance of this platform by imaging various fluorescent micro-objects in 2 colours (i.e., red and green) over a large field-of-view (FOV) of similar81 mm2 with a raw spatial resolution of similar20 μm. With additional digital processing of the captured cell-phone images, through the use of compressive sampling theory, we demonstrate similar2 fold improvement in our resolving power, achieving similar10 μm resolution without a trade-off in our FOV. They also demonstrated darkfield imaging of non-fluorescent specimen using the same interface, where this time the scattered light from the objects is detected without the use of any filters. The capability of imaging a wide FOV would be exceedingly important to probe large sample volumes (e.g., >0.1 mL) of e.g., blood, urine, sputum or water, and for this end we also demonstrate fluorescent imaging of labeled white-blood cells from whole blood samples, as well as water-borne pathogenic protozoan parasites such as Giardia Lamblia cysts. Weighing only similar28 g (similar1 ounce), this compact and cost-effective fluorescent imaging platform attached to a cell-phone could be quite useful especially for resource-limited settings, and might provide an important tool for wide-field imaging and quantification of various lab-on-a-chip assays developed for global health applications, such as monitoring of HIV+ patients for CD4 counts or viral load measurements.

Secret Space Plane Returns To California's Vandenberg Air Force Base From Space Orbit

After 225 days in orbit the Air Force’s secretive X-37B space plane touched down Friday at 1:16 a.m. local time at California’s Vandenberg Air Force Base. This flight was only the second fully automated re-entry and runway landing in the history of space flight. The Soviets achieved the first in 1988 with the robotic prototype of their Buran Space Shuttle clone. The Air Force has been consistently vague about what that mission really was. For a while, military personnel claimed they didn’t even know when the X-37B was coming back to Earth.

With a payload bay roughly the size of a pickup-truck bed, the 29-foot-long robot can carry sensors or even weapons. The vehicle is highly maneuverable and can used to intersect satellites, both friend and foe, as needed, or used as a flying laboratory. The design is for a quick turnaround time betwen launches, which is now being tested.

Saturday, December 4, 2010

FDA Approves Clinical Trial To Treat Macular Degeneration With Embryonic Stem Cells

FDA has lifted a hold on a clinical trial using retinal cells derived from human embryonic stem cells to treat patients with SMD (Stargardt's Macula Dystrophy), a common form of macular degeneration that affects young people.

Stargardt's Macular Dystrophy, sometimes called Juvenile Macular Dystrophy, is an inherited condition affecting the macula, which is the central area of the retina responsible for focused, high resolution sight. That is, the macula is responsible for what we see directly in front of us, the vision required for detailed activities, such as writing and reading, and the detection and appreciation of color. Other parts of the retina, the more peripheral retina, are involved in orienting our vision, or the initial detection of things of interest. SMD tends to first appear when the patient is aged between ten and twenty years, at which time some of the macula cells stop working, resulting in problems with central vision, detailed vision, and possibly color perception. The disease causes cells of the pigmented layer of the retina, called the retinal pigment epithelium (RPE), to deteriorate and die, and is a progressive disease that eventually leads to blindness.

There is currently no treatment for Stargardt's disease. In this study stem cells are used to supply RPE cells, which are the first cells to die off in SMD and other forms of macular degeneration. Animal models of this eye disease showed a 100% improvement in visual performance over untreated animals without any adverse effects. The studies showed that the cells were capable of extensive rescue of photoreceptors in animals that otherwise would have gone blind. Near-normal function was also achieved in a mouse model of Stargardt's disease. Researchers at Advanced Cell Technologies hope to see a similar benefit in patients with various forms of macular degeneration.

Friday, December 3, 2010

You Are What Your Mother Ate : Odors In Womb Sensitize Fetus

A new study (Dec. 1, 2010 in the Proceedings of the Royal Society B.)
shows that a pregnant mother's diet not only sensitizes the fetus to those smells and flavors, but physically changes the brain directly impacting what the infant eats and drinks in the future.

This highlights the importance of eating a healthy diet and refraining from drinking alcohol during pregnancy and nursing. If the mother drinks alcohol, her child may be more attracted to alcohol because the developing fetus "expects" that whatever comes from the mother must be safe. If she eats healthy food, the child will prefer healthy food.

Researchers studying mice found that the pups' sense of smell is changed by what their mothers eat, teaching them to like the flavors in her diet. At the same time, they found significant changes in the structure of the brain's olfactory glomeruli, which processes smells, because odors in the amniotic fluid affect how this system develops.

What an expectant mother chooses to eat and drink has long-term effects, for better or worse, on her child's sensory anatomy, that is the child's brain structure, and on the child's odor memory and food preferences in the future. How long these changes and preferences last is unclear, but that is currently being investigated. If your planning a diet of chips, fries, pastries, and soda during pregnancy, you may be setting your child on a course of lifelong eating disorders.

Thursday, December 2, 2010

21St Century Initiative in California Defines Roadmap for Sustainable Transportation

Better Place, with support from the U.S. Department of Transportation through the Metropolitan Transportation Commission, announced in October 2010 a commitment to bring a switchable battery, electric taxi program to the Bay Area in partnership with the cities of San Francisco and San Jose to further cement the region’s position as the EV Capital of the U.S.

In 2008 Governor Arnold Schwarzenegger, along with the Mayors of San Francisco, San Jose, and Oakland, joined together with the Bay Area Council, the Silicon Valley Leadership Group, and Better Place, a privately held company in Palo Alto, CA, to announce a sweeping plan to reinvigorate the state’s competitive advantage in innovative technology through public-private investments in electric vehicles and other types of ‘green’ infrastructure. Instead of the conventional assumptions that economic and environmental recovery are at odds with each other, this new approach aligns the two.

The group defined a vision for encouraging investment in green infrastructure as a means for boosting the state’s competitive advantage while reducing its dependence on oil for transportation and reducing greenhouse gas emissions. The group believes that the move to a sustainable mobility model of electric vehicles fueled by renewable energy, beginning in the Bay area, will serve as an economic and environmental stimulus blueprint for the entire US, particularly the nation’s lagging automotive sector.

Estimates suggest that transportation accounts for about 40% of California’s greenhouse gas emissions, and is globally forecast to consume over half of all oil in the coming decades. The initiative will enable the Bay Area as the leader in developing the science, engineering, and public policy innovations that simultaneously reduce greenhouse gas emissions and lead us to the next economic boom - the clean energy century. The Bay Area will serve as the first region of California to make the switch from carbon-based transportation to sustainable mobility.

Better Place, led by CEO and Founder Shai Agassi, is the world’s leading sustainability mobility operator, providing a network of battery charging and switching stations, announced that it would enter the US market with California as its first state, beginning in the Bay Area. Better Place will work a similar infrastructure investment model as it has in Israel, Denmark, and Australia. Network planning and permitting will begin in January 2009 with infrastructure deployment beginning in 2010. Better Place has already signed an alliance with Renault-Nissan to bring an electric car network to Isreal. Better Place esentially provides a network of standardized charging stations and battery switching stations so that electric cars can stop at station, reenergize by switching their batteries in about 60 seconds, and continue to their destination.

Mass market availability of electric cars is targeted for 2012, and Better Place estimates the network investment in the Bay Area will total $1 billion when the system is fully deployed. The Better Place model is an open network model built on industry standards, allowing for fixed battery and battery exchange electric vehicles to operate on the network.
The Silicon Valley Leadership Group is strongly committed to accelerating action on climate change and views commercialization of the EV technology and affordable solar energy solutions as necessary to meet the growing demand for clean energy.

California’s leadership in clean energy began in the 1970s under the leadership of Governor Jerry Brown, has seen mixed support in the 1980s and 1990s, but has been revived under the leadership of Governor Arnold Schwarznegger, and will likely see ever increasing support when Jerry Brown once again returns to the State’s helm. As Europe and China make great gains in clean energy and position their economies for the future, California must once again embrace a leadership role for the development of “green industry” in the USA. Kudos to the government, NGO, and business leaders in California, especially San Francisco, who have a positive vision of our future.

Wednesday, December 1, 2010

Squandered Taxpayer's Dollars Pay For Noah's Ark Fantasyland In Kentucky

Ark Encounter LLC announced today the planned construction of a full-scale Noah’s Ark tourist attraction in northern Kentucky. Partnering with the Ark Encounter is the non-profit Answers in Genesis, which is most widely known for its high-tech and popular Creation Museum in Petersburg, Ky. According to the Louisville Courier-Journal, the Ark Encounter project is likely to receive $37.5 million in government incentives.

Partnering with Answers in Genesis tells us about what tax payer dollars will support given that the Answers in Genesis Museum teaches anti-intellectual and unscientific notions such as:

1. Earth is barely 6,000 years old, dinosaurs were created on the sixth day, and Jesus is the savior who will one day repair the trauma of man’s fall.

2. Fossils are no older than Noah’s flood and dinosaurs were on the ark.

3. The eruption of Mount St. Helens in 1980 reveals how plausible it is that the waters of Noah’s flood could have carved out the Grand Canyon within days.

4. Scientific activity presumes that the material world is organized according to unchanging laws, while biblical fundamentalism presumes that those laws are themselves subject to disruption and miracle.

In these troubled times when the USA is falling fast economically, and our scientific, engineering, and teaching institutions are receiving fewer and fewer tax dollars, to spend taxpayer’s dollars on a fantasyland that is diametrically opposed to science and reason will surely contribute to the continued slide of the USA. Let us all rejoice in such places as California, where taxpayer’s dollars are being used to build a series of stem cell research institutes stretching from San Diego to San Francisco.