To spread, nervous system viruses sabotage cell, hijack transportation

Herpes and other viruses that attack the nervous system may thrive by disrupting cell function in order to hijack a neuron's internal transportation network and spread to other cells.

Ketamine improved bipolar depression within minutes

A group of researchers at the National Institute of Mental Health, led by Dr. Carlos Zarate, previously found that a single dose of ketamine produced rapid antidepressant effects in depressed patients with bipolar disorder. They have now replicated that finding in an independent group of depressed patients, also with bipolar disorder. Replication is an important component of the scientific method, as it helps ensure that the initial finding wasn't accidental and can be repeated.

Researchers complete the first epigenome in Europe

A study led by Manel Esteller, director of the Epigenetics and Cancer Biology Program at the Bellvitge Biomedical Research Institute (IDIBELL), professor of genetics at the University of Barcelona and ICREA researcher, has completed the first epigenome in Europe. The finding is published in the latest issue of the international scientific journal Epigenetics.

Too much vitamin D can be as unhealthy as too little, study suggests

Scientists know that Vitamin D deficiency is not healthy. However, new research from the University of Copenhagen now indicates that too high a level of the essential vitamin is not good either. The study is based on blood samples from 247,574 Copenhageners. The results have just been published in the reputed scientific Journal of Clinical Endocrinology and Metabolism.

Immune self-reactivity triggered by drug-modified HLA-peptide repertoire : Nature : Nature Publishing Group

Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to Tcells. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes. A growing number of immunologically based drug reactions, including abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens–Johnson syndrome (SJS), are associated with specific HLA alleles However, little is known about the underlying mechanisms of these associations, including AHS, a prototypical HLA-associated drug reaction occurring exclusively in individuals with the common histocompatibility allele HLA-B*57:01, and with a relative risk of more than 1,000 . We show that unmodified abacavir binds non-covalently to HLA-B*57:01, lying across the bottom of the antigen-binding cleft and reaching into the F-pocket, where a carboxy-terminal tryptophan typically anchors peptides bound to HLA-B*57:01. Abacavir binds with exquisite specificity to HLA-B*57:01, changing the shape and chemistry of the antigen-binding cleft, thereby altering the repertoire of endogenous peptides that can bind HLA-B*57:01. In this way, abacavir guides the selection of new endogenous peptides, inducing a marked alteration in ‘immunological self’. The resultant peptide-centric ‘altered self’ activates abacavir-specific T-cells, thereby driving polyclonal CD8 T-cell activation and a systemic reaction manifesting as AHS. We also show that carbamazepine, a widely used anti-epileptic drug associated with hypersensitivity reactions in HLA-B*15:02 individuals, binds to this allotype, producing alterations in the repertoire of presented self peptides. Our findings simultaneously highlight the importance of HLA polymorphism in the evolution of pharmacogenomics and provide a general mechanism for some of the growing number of HLA-linked hypersensitivities that involve small-molecule drugs.

Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling

Dietary fish oil containing ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit cardioprotective and anti-inflammatory effects through unresolved mechanisms that may involve competition and inhibition at multiple levels. Here, we report the effects of arachidonic acid (AA), EPA, and DHA supplementation on membrane incorporation, phospholipase A2 catalyzed release, and eicosanoid production in RAW264.7 macrophages. Using a targeted lipidomics approach, we observed that Toll-like receptor 4 and purinergic receptor activation of supplemented cells leads to the release of 22-carbon fatty acids that potently inhibit cyclooxygenase pathways. This inhibition was able to shunt metabolism of AA to lipoxygenase pathways, augmenting leukotriene and other lipoxygenase mediator synthesis. In resident peritoneal macrophages, docosapentaenoic acid (DPA) was responsible for cyclooxygenase inhibition after EPA supplementation, offering fresh insights into how EPA exerts anti-inflammatory effects indirectly through elongation to 22-carbon DPA.

Cancer Exosomes Promote Metastasis | The Scientist

Exosomes, small membrane vesicles once thought to do little more than clean up a cell’s trash, have recently been recognized for their ability to carry diverse and complex messages around the body.A new study published this week (May 27) in Nature Medicine demonstrates the importance of exosomes in promoting melanoma metastasis

Parkinson's Risk Prediction From Colonic Tissue Samples

Colonic tissue samples taken during flexible sigmoidoscopy or colonoscopy can be used to predict whether or not a patient will develop Parkinson's disease, researchers from Rush University Medical Center reported. The scientists reported findings from two studies in Movement Disorders.

Treatment for Helicobacter pylori infection and risk of parkinson's disease in Denmark.

It has been speculated that gastrointestinal infection with Helicobacter pylori (HP) contributes to the development of Parkinson'sdisease (PD). We used nationwide Danish registers to investigate this hypothesis. Methods:  We identified 4484 patients with a first time PD diagnosis between 2001 and 2008 from the Danish National Patient Register (DNPR) and 22 416 population controls from the Danish Civil Registration System (CRS). Information on drug use was obtained from the National Prescription Registry (NPR). We used logistic regression to compute odds ratios (OR) for the association between treatment for HP and risk of PD. Results:  Prescriptions for HP-eradication drugs and proton pump inhibitors (PPI) 5 or more years prior to the diagnosis of PD were associated with a 45% and 23% increase in PD risk, respectively. Hospitalizations and outpatient visits for gastritis and peptic/duodenal ulcers, however, were not associated with PD. Conclusions:  Our population-based study suggests that chronic HP infections and/or gastritis contribute to PD or that these are PD-related pathologies that precede motor symptoms.

MicrobeWorld - How Curry Spice Helps The Immune System Kill Bacteria

American and Danish scientists have found curcumin increases levels of a protein called (cathelicidin antimicrobial peptide or  CAMP)  that helps the immune system to fight off bacteria, viruses and fungi the first time they try to attack
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T cells 'hunt' parasites like animal predators seek prey, study shows

By pairing an intimate knowledge of immune-system function with a deep understanding of statistical physics, a cross-disciplinary team at the University of Pennsylvania has arrived at a surprising finding: T cells use a movement strategy to track down parasites that is similar to strategies that predators such as monkeys, sharks and blue-fin tuna use to hunt their prey.

Scientists unravel mechanism that causes liver cancer

 Scientists at the Genome Institute of Singapore (GIS) have unraveled the mechanism that causes liver cancer (hepatocellular carcinoma, HCC), one of the most common solid tumors worldwide. Essentially, the Hepatitis B virus (HBV) integrates its own DNA into human genes: Their analyses revealed that the incidences of HBV integrations were high – 76 of the 88 patients had HBV integration. Specifically, they discovered that the HBV will integrate into genes CCNE1, SENP5 and ROCK1, causing an increase in the expression levels in these genes, and subsequently enhancing the tumor growth. This discovery is in addition to the previously reported integration into the TERT and MLL4 genes.

MicrobeWorld - Garlic Constituent Blocks Biofilm Formation, Could Benefit Cystic Fibrosis Patients and Others

Bacterial biofilms are far more resistant than individual bacteria to the armories of antibiotics we have devised to combat them. Now Tim Holm Jakobsen and Michael Givskov of the University of Copenhagen, and their many collaborators have pinpointed a constituent of garlic that attacks a key step in the development of biofilms

IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and depression are considered to be neuro-immune disorders (Maes and Twisk, BMC Medicine 8:35, 2010). There is also evidence that depression and ME/CFS are accompanied by oxidative and nitrosative stress (O&NS) and by increased autoantibodies to a number of self-epitopes some of which have become immunogenic due to damage by O&NS. The aim of this study is to examine IgM-mediated autoimmune responses to different self-epitopes in ME/CFS versus depression. We examined serum IgM antibodies to three anchorage molecules (palmitic and myristic acid and S-farnesyl-L-cysteine); acetylcholine; and conjugated NO-modified adducts in 26 patients with major depression; 16 patients with ME/CFS, 15 with chronic fatigue; and 17 normal controls. Severity of fatigue and physio-somatic (F&S) symptoms was measured with the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale. Serum IgM antibodies to the three anchorage molecules and NO-phenylalanine were significantly higher in ME/CFS than in depression. The autoimmune responses to oxidatively, but not nitrosatively, modified self-epitopes were significantly higher in ME/CFS than in depression and were associated with F&S symptoms. The autoimmune activity directed against conjugated acetylcholine did not differ significantly between ME/CFS and depression, but was greater in the patients than controls. Partially overlapping pathways, i.e. increased IgM antibodies to a multitude of neo-epitopes, underpin both ME/CFS and depression, while greater autoimmune responses directed against anchorage molecules and oxidatively modified neo-epitopes discriminate patients with ME/CFS from those with depression. These autoimmune responses directed against neoantigenic determinants may play a role in the dysregulation of key cellular functions in both disorders, e.g. intracellular signal transduction, cellular differentiation and apoptosis, but their impact may be more important in ME/CFS than in depression.

International Symposium on HIV & Emerging Infectious Diseases (Open access abstracts)

The Abstracts of the International Symposium on HIV & Emerging Infectious Diseases held May 23-25 in Marseilles, France are available online. They are published on as individual articles and a PDF file of 54 pages. You can go and have a look at them on the website of this top quality open access journal that have an impact factor of 5.24:

Diabetes Treatment - Potential New Target ( APOA4)

The online edition of Proceedings of the National Academy of Sciences reports that Cincinnati University (UC) researchers have discovered that apolipoprotein A-IV (apoA-IV), a naturally produced protein that has the ability to reduce blood sugar levels and enhance insulin secretion, could be a potential target for a new diabetes treatment.

Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers

Ihe objective was to evaluate the effect of a moderate intake of red wine polyphenols on select gut microbial groups implicated in host health benefits.
Design: Ten healthy male volunteers underwent a randomized, crossover, controlled intervention study. After a washout period, all of the subjects received red wine, the equivalent amount of de-alcoholized red wine, or gin for 20 d each. Total fecal DNA was submitted to polymerase chain reaction(PCR)–denaturing gradient gel electrophoresis and real-time quantitative PCR to monitor and quantify changes in fecal microbiota. Several biochemical markers were measured.
Results: The dominant bacterial composition did not remain constant over the different intake periods. Compared with baseline, the daily consumption of red wine polyphenol for 4 wk significantly increased the number of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides–Eubacterium rectale groups (P < 0.05). In parallel, systolic and diastolic blood pressures and triglyceride, total cholesterol, HDL cholesterol, and C-reactive protein concentrations decreased significantly (P < 0.05). Moreover, changes in cholesterol and C-reactive protein concentrations were linked to changes in the bifidobacteria number.
Conclusion: This study showed that red wine consumption can significantly modulate the growth of select gut microbiota in humans, which suggests possible prebiotic benefits associated with the inclusion of red wine polyphenols in the diet.

Cystic fibrosis breakthrough reveals why females fare worse than males

Researchers from the Respiratory Research Division of the Department of Medicine, Royal College of Surgeons in Ireland (RCSI) have published a study which represents a major breakthrough in understanding why females with cystic fibrosis do worse than males. The study is the first to show that the female hormone estrogen promotes the presence of a particular form of bacteria ( Pseudomonas aeruginosa) which results in more severe symptoms for female cystic fibrosis patients. In addition, females who were taking the oral contraceptive pill, which decreases the amount of naturally occurring estrogen in their bodies, were found to have lower levels of the problematic bacteria.

First study to suggest that the immune system may protect against Alzheimer's changes in humans

Recent work in mice suggested that the immune system is involved in removing beta-amyloid, the main Alzheimer's-causing substance in the brain. Researchers have now shown for the first time that this may apply in humans.
Leukocyte ccr2 expression is associated with mini-mental state examination (MMSE) score in older adults. Rejuvenation Research 2012

Physicians definitively links irritable bowel syndrome and bacteria in gut

An overgrowth of bacteria in the gut has been definitively linked to Irritable Bowel Syndrome in the results of a new Cedars-Sinai study which used cultures from the small intestine. This is the first study to use this "gold standard" method of connecting bacteria to the cause of the disease that affects an estimated 30 million people in the United States.

Dietary supplementation with S-adenosyl methionine delayed amyloid-β and tau pathology in 3xTg-AD mice.

S-adenosyl methionine (SAM) contributes to multiple pathways in neuronal homeostasis, several of which are compromised in age-related neurodegeneration and Alzheimer's disease. Dietary supplementation of transgenic mice with SAM maintained acetylcholine levels, cognitive performance, oxidative buffering capacity, and phosphatase activity, and reduced aggression, calcium influx, endogenous PS-1 expression, γ-secretase activity, and levels of amyloid-β (Aβ) and phospho-tau. Herein, we examined whether or not SAM could delay neuropathology in 3xTg-AD mice, which harbor mutant genes for human AβPP, PS-1 and tau. Mice received a standard AIN-76 diet with or without SAM (100 mg/kg diet) for 1 month commencing at 10 months of age or for 3 months commencing at 12.5 months of age; mice were sacrificed and examined for Aβ and tau neuropathology at 11 and 15.5 months of age, respectively. SAM supplementation reduced hippocampal intracellular AβPP/Aβ and phospho-tau immunoreactivity to a similar extent at both sampling intervals. Supplementation reduced the number of extracellular Aβ deposits by 80% (p < 0.01) at 11 months of age after 1 month of treatment but only by 24% (p < 0.34) at 15.5 months of age after 3 months of treatment. As anticipated, neurofibrillary tangles were not observed in mice at these young ages; however, supplementation reduced levels of phospho-tau and caspase-cleaved tau within Sarkosyl-insoluble preparations in mice at 15.5 months of age. These limited analyses indicate that SAM can modulate the time course of AD neuropathology, and support further long-term analyses.

The Aging and Inflammation Link | The Scientist

Scientists studying mice genetically engineered to lack an anti-inflammatory factor have stumbled upon an unexpected secondary function for the protein—it slows down aging. The surprising discovery, which is reported online today (May 24) in Molecular Cell, has implications for inflammatory and age-related diseases, but also for cancer.

Research team uncovers mechanism behind drugs that cause altered immunity

(Medical Xpress) -- An Australian research team has opened the door to understanding why certain drugs cause a so called altered immunity response when offered as treatment for certain specific ailments. In their paper published in the journal Nature, the team explains how they’ve uncovered the mechanism that causes an HIV treatment drug to lead to hypersensitivity syndrome.

New test shows potential for detecting active cases of Lyme disease

George Mason University researchers can find out if a tick bite means Lyme disease well before the bite victim begins to show symptoms.

Newly discovered breast milk antibodies help neutralize HIV

Antibodies that help to stop the HIV virus have been found in breast milk. Researchers at Duke University Medical Center isolated the antibodies from immune cells called B cells in the breast milk of infected mothers in Malawi, and showed that the B cells in breast milk can generate neutralizing antibodies that may inhibit the virus that causes AIDS.

Possible role of autoantibodies in Alzheimer’s

New research by scientists at the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine (UMDNJ-SOM) demonstrates how dying or damaged brain cells release debris into the bloodstream and give rise to specific autoantibodies that appear to be reliable biomarkers for early diagnosis of Alzheimer's and other neurodegenerative diseases. The researchers also identify a key mechanism in the development of Alzheimer's that mirrors a process that is common in such autoimmune disorders as rheumatoid arthritis.

Fever during pregnancy more than doubles the risk of autism or developmental delay

A team of UC Davis researchers has found that mothers who had fevers during their pregnancies were more than twice as likely to have a child with autism or developmental delay than were mothers of typically developing children, and that taking medication to treat fever countered its effect.

Caesarean section delivery may double risk of childhood obesity: May be due to different gut bacteria

Caesarean section delivery has already been linked to an increased risk of subsequent childhood asthma and allergic rhinitis, and around one in three babies born in the US is delivered this way.

Fungicide Linked to Anxiety, Obesity and Autistic Traits in Rats | Psych Central News

Rats who were exposed to fungicide had babies, grandbabies, and even great grandbabies with an increasing amount of anxiety, stress, autism and obesity, according to a study published in the Proceedings of the National Academy of Sciences.

Reverse engineering epilepsy's 'miracle' diet

For decades, neurologists have known that a diet high in fat and extremely low in carbohydrates can reduce epileptic seizures that resist drug therapy. But how the diet worked, and why, was a mystery—so much so that in 2010, The New York Times Magazine called it "Epilepsy's Big, Fat Miracle."

Hormone plays surprise role in fighting skin infections

Antimicrobial peptides (AMPs) are molecules produced in the skin to fend off infection-causing microbes. Vitamin D has been credited with a role in their production and in the body's overall immune response, but scientists at the University of California, San Diego School of Medicine say a hormone previously associated only with maintaining calcium homeostasis and bone health is also critical, boosting AMP expression when dietary vitamin D levels are inadequate.
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Children's body fat linked to Vitamin D insufficiency in mothers

Children are more likely to have more body fat during childhood if their mother has low levels of Vitamin D during pregnancy, according to scientists at the Medical Research Council Lifecourse Epidemiology Unit (MRC LEU), University of Southampton.

Phthalates in PVC floors taken up by the body in infants

A new study at Karlstad University in Sweden shows that phthalates from PVC flooring materials is taken up by our bodies. Phthalates are substances suspected to cause asthma and allergies, as well as other chronic diseases in children. The study shows that children can ingest these softening agents with food but also by breathing and through the skin.

Epstein-Barr virus latent membrane protein 2A exacerbates experimental autoimmune encephalomyelitis and enhances antigen presentation function.

Multiple sclerosis (MS) is an inflammatory, autoimmune disease of the central nervous system. The cause of MS is still unknown but epidemiological and immunological studies have implicated Epstein-Barr virus (EBV), which infects B cells, as a possible etiological agent involved in disease. Of particular interest is EBV latent membrane protein 2A (LMP2A) because previous studies have demonstrated that LMP2A enhances the expansion and differentiation of B cells upon antigen stimulation, revealing a potential contribution of this protein in autoimmunity. Since B cells are thought to contribute to MS, we examined the role of LMP2A in the animal model experimental autoimmune encephalomyelitis (EAE). In this model, transgenic mice in which B cells express LMP2A show increased severity and incidence of disease. This difference was not due to lymphocyte recruitment into the CNS or differences in T cell activation, rather, we show that LMP2A enhances antigen presentation function.

NIH-supported study shows how immune cells change wiring of the developing mouse brain, May 23, 2012 News Release - National Institutes of Health (NIH)

Researchers have shown in mice how immune cells in the brain target and remove unused connections between brain cells during normal development. This research, supported by the National Institutes of Health, sheds light on how brain activity influences brain development, and highlights the newly found importance of the immune system in how the brain is wired, as well as how the brain forms new connections throughout life in response to change.
Disease-fighting cells in the brain, known as microglia, can prune the billions of tiny connections (or synapses) between neurons, the brain cells that transmit information through electric and chemical signals.
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Nature: Peroxiredoxins are conserved markers of circadian rhythms : Nature : Nature Publishing Group

Cellular life emerged ~3.7billion years ago. With scant exception, terrestrial organisms have evolved under predictable daily cycles owing to the Earth’s rotation. The advantage conferred on organisms that anticipate such environmental cycles has driven the evolution of endogenous circadian rhythms that tune internal physiology to external conditions. The molecular phylogeny of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins are not conserved across the domains of life: Bacteria, Archaea and Eukaryota. Here we show that oxidation–reduction cycles of peroxiredoxin proteins constitute a universal marker for circadian rhythms in all domains of life, by characterizing their oscillations in a variety of model organisms. Furthermore, we explore the interconnectivity between these metabolic cycles and transcription–translation feedback loops of the clockwork in each system. Our results suggest an intimate co-evolution of cellular timekeeping with redox homeostatic mechanisms after the Great Oxidation Event ~2.5billion years ago.

Flu shot during pregnancy shows unexpected benefits in large study

Getting a flu shot during pregnancy provides unanticipated benefits to the baby, according to the authors of a large population-based study examining the issue. Specifically, the study showed that H1N1 vaccination during the pandemic was associated with a significantly reduced risk of stillbirth, preterm birth and extremely small babies at birth.

Rapid DNA sequencing may soon be routine part of each patient's medical record

While the first sequencing of the human genome took researchers 13 years and $3 billion to achieve, under the auspicies of the Human Genome Project , the feat may soon be accomplished at the blinding rate of 6 billion nucleotide bases every 6 hours at a cost of $900. At least that is the extravagant claim being made by Oxford Nanopore Technologies, one of the pioneering companies driving new sequencing developments.

Researchers unravel the relation between DNA methylomes and obesity

In a highlighted paper published online in Nature Communications, researchers from Sichuan Agricultural University and BGI reported the atlas of DNA methylomes in porcine adipose and muscle tissues, providing a valuable epigenomic source for obesity prediction and prevention as well as boosting the further development of pig as a model animal for human obesity research.

Today's environment influences behavior generations later: Chemical exposure raises descendants' sensitivity to stress

Researchers at The University of Texas at Austin and Washington State University have seen an increased reaction to stress in animals whose ancestors were exposed to an environmental compound (vinclozolin, a popular fruit and vegetable fungicide) generations earlier.

Surgical removal of abdominal fat reduces skin cancer in mice

In animal studies, Rutgers scientists have found that surgical removal of abdominal fat from mice fed a high-fat diet reduces the risk of ultraviolet-light induced skin cancer -- the most prevalent cancer in the United States with more than 2 million new cases each year.

Lifecourse infectious origins of sexual inequalities in central adiposity.

Social disparities in obesity are often more marked among women than men, possibly due to social factors. Taking a life-history perspective, we hypothesized that childhood infections could be relevant via sex-specific effects of immune system activation on sexual development and, hence, body shape.
METHODS: We used multivariable linear regression to assess the sex-specific, adjusted associations of 'childhood' pathogens [0 (n = 1002), 1 (n = 2199), 2 (n = 3442) or 3 (n = 4833) of HSV1, CMV and hepatitis A antibodies] and 'adult' pathogens [0 (n = 5836), 1 (n = 3018) or ≥ 2 (n = 720) of HSV2, HHV8 and hepatitis B or C) with waist-hip ratio (WHR) and body mass index (BMI) standard deviations (SDs) using NHANES III (1988-94). As validation, we assessed
associations with height.
RESULTS: 'Childhood' pathogens were positively associated with WHR among women [0.18 SD, 95% confidence interval (95% CI) 0.04-0.32 for 3, compared with 0], but not men (-0.04 SD, 95% CI -0.15 to 0.08), adjusted for age, education, race/ethnicity, smoking and alcohol. Further adjustments for leg length barely changed the estimates. There were no such sex-specific associations for BMI or for adult pathogens. 'Childhood', but not 'adult', pathogens were negatively associated with height, adjusted for age, sex, education and race/ethnicity. CONCLUSIONS: These observations are consistent with the lifecourse hypothesis that early exposure to infections makes women vulnerable to central obesity. This
hypothesis potentially sheds new light on the developmental origins of obesity, and is consistent with the generally higher levels of central obesity among women than men in developing populations.

Hitting parasites where they hurt: New research shows promise in the fight against Toxoplasmosis

Toxoplasmosis, a disease caused by the parasite Toxoplasma gondii, is one of the most common parasitic infections in the world. In the U.S. it is estimated that more than 22 percent of the population 12 years and older have been infected with toxoplasma, according to the Centers for Disease Control and Prevention.
The parasite has also been implicated in a number of psychiatric disorders  (see posts )
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Shocking Risk Figures For Teens Developing Diabetes And Heart Problems

With around one third of all adolescents either over-weight or obese, risk factors for heart disease, another long term health problem that puts a tremendous burden on healthcare providers, look just as bad. Half of overweight and nearly two thirds of obese teens are already showing risk factors for heart disease, such as high blood pressure, high cholesterol, or diabetes risks; by way of comparison, researchers cite figures showing around one third of regular teens show minor risks, of heart problems.

.........................When are we going to see the first teenager with Alzheimer's disease because of the obesity scandal ?

Prenatal exposure to perfluorooctanoate and risk of overweight at 20 years of age: a prospective cohort study.

Perfluoroalkyl acids are persistent compounds used in various
industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is
currently detected in humans worldwide. A recent study on low-dose developmental
exposure to PFOA in mice reported increased weight and elevated biomarkers of
adiposity in postpubertal female offspring.Objective: We examined whether the
findings of increased weight in postpubertal female mice could be replicated in
humans.Methods: A prospective cohort of 665 Danish pregnant women was recruited
in 1988-1989 with offspring follow-up at 20 years. PFOA was measured in serum
from gestational week 30. Offspring body mass index (BMI) and waist circumference
were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified
in a subset (n = 422) of participants.Results: After adjusting for covariates,
including maternal pre-pregnancy BMI, smoking, education, and birth weight, in
utero exposure to PFOA was positively associated with anthropometry at 20 years
in female but not male offspring. Adjusted relative risks comparing the highest
with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration
were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥
25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female
offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6,
2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference,
respectively. In addition, maternal PFOA concentrations were positively
associated with serum insulin and leptin levels and inversely associated with
adiponectin levels in female offspring. Similar associations were observed for
males, although point estimates were less precise because of fewer observations.
Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA),
and perfluorononanoate (PFNA) concentrations were not independently associated
with offspring anthropometry at 20 years.Conclusions: Our findings on the effects
of low-dose developmental exposures to PFOA are in line with experimental results
suggesting obesogenic effects in female offspring at 20 years of age.

Epigenetic reprogramming of host genes in viral and microbial pathogenesis.

This review showed that host epigenetic changes have been associated with a number of viruses and also with bacterial infections. 
One of the key questions in the study of mammalian gene regulation is how epigenetic methylation patterns on histones and DNA are initiated and established. These stable, heritable, covalent modifications are largely associated with the repression or silencing of gene transcription, and when deregulated can be involved in the development of human diseases such as cancer. This article reviews examples of viruses and bacteria known or thought to induce epigenetic changes in host cells, and how this might contribute to disease. The heritable nature of these processes in gene regulation suggests that they could play important roles in chronic diseases associated with microbial persistence; they might also explain so-called 'hit-and-run' phenomena in infectious disease pathogenesis.

Tobacco virus may help prevent Parkinson's | The Poughkeepsie Journal |

The Tobacco mosaic virus apparently generates  an antibody response  that “may be protective against Parkinson’s disease, perhaps explaining an inverse association between smoking and Parkinson's disease.

Human cytomegalovirus infection is sensitive to the host cell DNA methylation state and alters global DNA methylation capacity.

Epigenetics and gene methylation play an important role in many disorders. This study showed that cytomegalovirus infection has marked effect on host gene methylation. How many other viruses produce similar effects ?
Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects and establishes latency in the majority of the human population and may cause fatal infections in immunocompromised patients. Recent data implies a close interaction between HCMV encoded proteins and cellular epigenetic mechanisms such as histone acetylation and deacetylation. In this study, we investigated the interactions between HCMV infection and the DNA methylation machinery in different host cells using several approaches. We found that colon cancer cell line HCT-116 lacking the DNMT1 and DNMT3b methyltransferases was susceptible to HCMV-AD169 infection, while wild-type cells were non-susceptible. Treatment of wild-type HCT-116 cells with 5-azacytidine rendered them susceptible to infection. Further investigation of HCMV infected MRC-5 fibroblasts demonstrated significant global hypomethylation, a phenomenon that was virus strain-specific and associated with the re-localization of DNMT1 and DNMT3b from the nucleus to the cytoplasm. The cytoplasmic accumulation of DNMT1 was also evident in in vitro infected macrophages and in epithelial cells in tissue samples from patients with inflammatory bowel disease and concomitant HCMV infection. Foscavir treatment of virus infected fibroblasts did not affect the majority of the virus induced nuclear exclusion of DNMT1, which suggest that it is dependent on viral IE gene products. In conclusion, HCMV infection results in profound effects on the host cell DNA methylation machinery and is associated with inflammation in vivo. Our results improve the understanding of cytomegalovirus pathogenesis and open the search for new antiviral therapy targets. These findings may also contribute to the further understanding of mechanisms involved in DNA methylation abnormalities in physiological and pathological conditions.

KEGG pathway analysis of the genes implicated in chronic fatigue syndrome

There are relatively few genetic studies on chronic fatigue syndrome /fibromyalgia compared to other disorders, and a systems biology approach is necessarily limited. The main thrust so far seems to be related to neurotransmitter systems,(dopamine/ glutamate and serotonin) but also to the immune network and viral and pathogen related pathways.

Oxytocin improves brain function in children with autism

Preliminary results from an ongoing, large-scale study by Yale School of Medicine researchers shows that oxytocin -- a naturally occurring substance produced in the brain and throughout the body -- increased brain function in regions that are known to process social information in children and adolescents with autism spectrum disorders (ASD).

Treatment of Chronic Fatigue Syndrome as an Immunological Disorder - Autoimmunity Network

At the 2012 International Congress on Autoimmunity, in Granada, Spain, Inge Lindseth, from Oslo, Norway, presented a case series of 63 Chronic Fatigue Syndrome ( CFS/ME ) patients from Canada and Norway, who, in general, are responding well to an immunostimulatory therapy.

Prof Trevor Marshall - Video: How Microbes cause Chronic Disease on Vimeo

Prof. Trevor Marshall addressed the issue of biological complexity in his presentation at the 5th Asian Congress on Autoimmunity, in Singapore, on 19 November 2011. He explored how the Human Microbiome leads to a semi-infinite Interactome, and how the combined metagenomes from the microbes living in and on the human body accumulate to cause chronic disease, including Autoimmune Disease.

Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort.

To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS:This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010. RESULTS:Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML. CONCLUSIONS:These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.
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RNA modification influences thousands of genes: Revolutionizes understanding of gene expression

Over the past decade, research in the field of epigenetics has revealed that chemically modified bases are abundant components of the human genome and has forced us to abandon the notion we've had since high school genetics that DNA consists of only four bases.Now, researchers at Weill Cornell Medical College have made a discovery that once again forces us to rewrite our textbooks. This time, however, the findings pertain to RNA, which like DNA carries information about our genes and how they are expressed. The researchers have identified a novel base modification in RNA which they say will revolutionize our understanding of gene expression.

Subchronic polychlorinated biphenyl (Aroclor 1254) exposure produces oxidative damage and neuronal death of ventral midbrain dopaminergic systems.

Recent epidemiologic studies have demonstrated a link between organochlorine and pesticide exposure to an enhanced risk for neurodegenerative disorders such as Parkinson's disease (PD). A common biological phenomenon underlying cell injury associated with both polychlorinated biphenyl (PCB) exposure and dopaminergic neurodegeneration during aging is oxidative stress (OS). In this study, we tested the hypothesis that oral PCB exposure, via food ingestion, impairs dopamine systems in the adult murine brain. We determined whether PCB exposure was associated with OS in dopaminergic neurons, a population of cells that selectively degenerate in PD. After 4 weeks of oral exposure to the PCB mixture Aroclor 1254, several congeners, mostly ortho substituted, accumulated throughout the brain. Significant increases in locomotor activity were observed within 2 weeks, which persisted after cessation of PCB exposure. Stereologic analyses revealed a significant loss of dopaminergic neurons within the substantia nigra and ventral tegmental area. However, striatal dopamine levels were elevated, suggesting that compensatory mechanisms exist to maintain dopamine homeostasis, which could contribute to the observed increases in locomotor activity following PCB exposure. Biochemical experiments revealed alterations in OS markers, including increases in SOD and HO-1 levels and the presence of oxidatively modified lipids and proteins. These findings were accompanied by elevated iron levels within the striatal and midbrain regions, perhaps due to the observed dysregulation of transferrin receptors and ferritin levels following PCB exposure. In this study, we suggest that both OS and the uncoupling of iron regulation contribute to dopamine neuron degeneration and hyperactivity following PCB exposure.
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'Rare' genetic variants are surprisingly common, life scientists report / UCLA Newsroom

A large survey of human genetic variation, published today in the online version of the journal Science, shows that rare genetic variants are not so rare after all and offers insights into human diseases.

PLoS Pathogens: Influence of Microbiota on Viral Infections

With the advent of the Human Microbiome Project, we are now aware of the number and diversity of microbes that make the human body their primary place of residence. Consequently, the microbiota can no longer be ignored when studying host–pathogen interactions. The influences of microbiota on virus infections could be either protective or detrimental for the host. Whereas the microbiota positively regulate adaptive immune responses against influenza, they suppress antivirus adaptive responses against MMTV and facilitate replication of poliovirus and reovirus by enhancing virus attachment to target cells. Thus, microbiota play a dual role in virus–host interactions. An open question that currently drives research related to microbiota is how the microbiota can be manipulated so that the host is protected from deleterious infections. In the case of pathogens that take advantage of the microbiota, one can hope to find a way to ablate these interactions, thus preventing pathogen spread/propagation. This could be done either by manipulating the composition of the microbiota (ablation of a specific microbe exploited by a virus) or by blocking interactions between the viral pathogen and specific bacterial compounds that benefit the pathogen. Future discoveries in the area of microbiota–pathogen interactions will undoubtedly unveil new opportunities for therapeutic interventions in infectious disease.

When you eat matters: Study offers drug-free intervention to prevent obesity, diabetes

When we eat may be as important as what we eat. Scientists at the Salk Institute for Biological Studies have found that regular eating times and extending the daily fasting period may override the adverse health effects of a high-fat diet and prevent obesity, diabetes and liver disease in mice.

TSRI At The Forefront: Modulating the body's internal clock to prompt weight loss

Drugs that affect circadian rhythms – the brain's biological clock – may help counter a host of problems, from obesity and diabetes to jet lag, according to new research from Scripps Florida.
Circadian rhythms play a key role in metabolism, revving it up in the morning and slowing it down at night.

Chef Jamie Oliver, UCLA Health System bring life-changing cooking lessons to L.A. youth / UCLA Newsroom

Jamie Oliver's Food Revolution
Jamie Oliver's Food Revolution (Photo credit: Wikipedia)
Celebrity chef Oliver is teaming with the UCLA Health System — an institution also dedicated to healthy eating and living — for a day of events bringing together foodies, chefs, parents, educators, companies, activists and celebrities to arm people with the knowledge and tools to make healthier food choices.
See also:  Childhood obesity risk factors
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ACMA | Abstract | Antibacterial activity of statins: a comparative study of Atorvastatin, Simvastatin, and Rosuvastatin

Statins have several effects beyond their well-known antihyperlipidemic activity, which include immunomodulatory, antioxidative and anticoagulant effects. In this study, we have tested the possible antimicrobial activity of statins against a range of standard bacterial strains and bacterial clinical isolates.
It was revealed that statins are able to induce variable degrees of antibacterial activity with atorvastatin, and simvastatin being the more potent than rosuvastatin. Methicillin-sensitive staphylococcus aureus (MSSA), methicillin-resistant staphylococcus aureus (MRSA), vancomycin-susceptible enterococci (VSE), vancomycin-resistant enterococcus (VRE), acinetobacter baumannii, staphylococcus epidermidis, and enterobacter aerogenes, were more sensitive to both atorvastatin, and simvastatin compared to rosuvastatin. On the other hand, escherichia coli, proteus mirabilis, and enterobacter cloacae were more sensitive to atorvastatin compared to both simvastatin and rosuvastatin. Furthermore, most clinical isolates were less sensitive to statins compared to their corresponding standard strains.


Our findings might raise the possibility of a potentially important antibacterial class effect for statins especially, atorvastatin and simvastatin.

Schizophrenia Research Forum: SIRS 2012—Immunology Takes Center Stage

CHORI Bar Improves Cognitive and Metabolic Benefits In Just 2 Weeks

National Medal of Science winner Bruce N. Ames, PhD, led a team of scientists at the Children's Hospital Oakland Research Institute's (CHORI) Nutrition & Metabolism Center to develop the CHORI bar, a low-calorie fruit based vitamin and mineral nutrition bar that is designed to help restore optimal nutritional balance in those with poor eating habits and to assist them in adopting a healthier diet.

NIH-funded research provides new clues on how ApoE4 affects Alzheimer's risk, May 16, 2012 News Release - National Institutes of Health (NIH)

Common variants of the ApoE gene are strongly associated with the risk of developing late-onset Alzheimer's disease, but the gene's role in the disease has been unclear. Now, researchers funded by the National Institutes of Health have found that in mice, having the most risky variant of ApoE damages the blood vessels that feed the brain.
The researchers found that the high-risk variant, ApoE4, triggers an inflammatory reaction that weakens the blood-brain barrier, a network of cells and other components that lines brain's brain vessels. Normally, this barrier allows nutrients into the brain and keeps harmful substances out.

MicrobeWorld - Commensal bacteria are necessary to clear pathogenic bacteria from intestinal infections

Explore the Human Microbiome [Interactive]: Scientific American

The body contains 10 times more bacteria, fungi and other micro-organisms than human cells. Most of these species are harmless—although they can still cause illness if they wind up in the wrong place. In addition, researchers are beginning to learn exactly how some microbial species in the body help digestion and contribute to regulation of appetite and the immune system.

Mixed Chimerism and Growth Factors Augment β Cell Regeneration and Reverse Late-Stage Type 1 Diabetes

Type 1 diabetes (T1D) results from an autoimmune destruction of insulin-producing β cells. Currently, islet transplantation is the only curative therapy for late-stage T1D, but the beneficial effect is limited in its duration, even under chronic immunosuppression, because of the chronic graft rejection mediated by both auto- and alloimmunity. Clinical islet transplantation is also restricted by a severe shortage of donor islets. Induction of mixed chimerism reverses autoimmunity, eliminates insulitis, and reverses new-onset but not late-stage disease in the nonobese diabetic (NOD) mouse model of T1D. Administration of gastrin and epidermal growth factor (EGF) also reverses new-onset but not late-stage T1D in this animal model. Here, we showed that combination therapy of induced mixed chimerism under a radiation-free nontoxic anti-CD3/CD8 conditioning regimen and administration of gastrin/EGF augments both β cell neogenesis and replication, resulting in reversal of late-stage T1D in NOD mice. If successfully translated into humans, this combination therapy could replace islet transplantation as a long-term curative therapy for T1D.

Sugar makes you stupid: Study shows high-fructose diet sabotages learning, memory

A new UCLA rat study is the first to show how a diet steadily high in fructose slows the brain, hampering memory and learning — and how omega-3 fatty acids can counteract the disruption. The peer-reviewed Journal of Physiology publishes the findings in its May 15 edition.
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Why omega-3 oils help at the cellular level: Findings suggest possibility of boosting their health benefit

After supplementing mouse macrophages with fatty acids, the scientists stimulated them to produce an inflammatory response. They discovered that omega-3 fatty acids inhibit an enzyme called cyclooxygenase (COX), which produces the prostaglandin hormones that spark inflammation. The action is similar to what happens when one takes an aspirin, which disrupts the COX-2 signaling pathway, thus reducing inflammation and pain.

Researchers identify key genes and prototype predictive test for schizophrenia - IU Communications - School of Medicine

We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein–coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. We also show, in three independent cohorts, two European American and one African American, increasing overlap, reproducibility and consistency of findings from single-nucleotide polymorphisms to genes, then genes prioritized by CFG, and ultimately at the level of biological pathways and mechanisms. Finally, we compared our top candidate genes for schizophrenia from this analysis with top candidate genes for bipolar disorder and anxiety disorders from previous CFG analyses conducted by us, as well as findings from the fields of autism and Alzheimer. Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics and therapeutics. It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology.

Dietary supplements increase cancer risk

Beta-carotene, selenium and folic acid – taken up to three times their recommended daily allowance, these supplements are probably harmless. But taken at much higher levels as some supplement manufacturers suggest, these three supplements have now been proven to increase the risk of developing a host of cancers.
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PNAS: Brain anomalies in children exposed prenatally to a common organophosphate pesticide

Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9–11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure × IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose–response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.
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Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency.

Human UBIAD1 localizes to mitochondria and converts vitamin K(1) to vitamin K(2). Vitamin K(2) is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K(2) exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson's disease that affects mitochondrial function. Here, we found that vitamin K(2) was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K(2), and, similar to ubiquinone, vitamin K(2) transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K(2) that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.

Some Symptoms Of Multiple Sclerosis Respond To Smoked Cannabis

A clinical study of 30 adult patients with multiple sclerosis at the University of California, San Diego School of Medicine has shown that smoked cannabis may be an effective treatment for spasticity - a common and disabling symptom of this neurological disease.

Gastrointestinal inflammation and associated immune activation in schizophrenia.

Immune factors are implicated in normal brain development and in brain disorder
pathogenesis. Pathogen infection and food antigen penetration across
gastrointestinal barriers are means by which environmental factors might affect
immune-related neurodevelopment. Here, we test if gastrointestinal inflammation
is associated with schizophrenia and therefore, might contribute to bloodstream
entry of potentially neurotropic milk and gluten exorphins and/or immune
activation by food antigens. IgG antibodies to Saccharomyces cerevisiae (ASCA, a
marker of intestinal inflammation), bovine milk casein, wheat-derived gluten, and
6 infectious agents were assayed. Cohort 1 included 193 with non-recent onset
schizophrenia, 67 with recent onset schizophrenia and 207 non-psychiatric
controls. Cohort 2 included 103 with first episode schizophrenia, 40 of whom were
antipsychotic-naïve. ASCA markers were significantly elevated and correlated with
food antigen antibodies in recent onset and non-recent onset schizophrenia
compared to controls (p≤0.00001-0.004) and in unmedicated individuals with first
episode schizophrenia compared to those receiving antipsychotics (p≤0.05-0.01).
Elevated ASCA levels were especially evident in non-recent onset females
(p≤0.009), recent onset males (p≤0.01) and in antipsychotic-naïve males (p≤0.03).
Anti-food antigen antibodies were correlated to antibodies against Toxoplasma
gondii, an intestinally-infectious pathogen, particularly in males with recent
onset schizophrenia (p≤0.002). In conclusion, gastrointestinal inflammation is a
relevant pathology in schizophrenia, appears to occur in the absence of but may
be modified by antipsychotics, and may link food antigen sensitivity and
microbial infection as sources of immune activation in mental illness.
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Scientists uncover potential treatment for painful side effect of diabetes

Why diabetics suffer from increased pain and temperature sensitivity is a step closer to being understood and effectively treated. The methylglyoxalproduced in diabetes modifies a sodium channel Nav 1.8 (SCN10A)  causing nerves to become super-sensitive to pain and extremes of temperature.
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Genes May Influence Body's Bacteria - Science News

51 different human genetic variants are associated with the relative abundance of certain bacteria living in or on 15 body sites. Some of those genetic variants and the microbes they were associated with have also been linked to diseases. People with a genetic variant near the PCSK2 gene, which is involved in producing insulin, have more Bacteroides bacteria in their intestines, Blekhman reported May 9 at the Biology of Genomes meeting. That same genetic variant has been linked to type 2 diabetes. So has an overabundance of Bacteroides.

Infections Cause Many Cancers Globally

A new study published Online First in The Lancet Oncology reveals that from 7.5 million cancer deaths in 2008, about 1.5 million were due to infections that could have either been prevented or treated.
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Scientists discover 'switch' to boost anti-viral response to fight infectious diseases

Singapore scientists from Bioprocessing Technology Institute (BTI) under the Agency of Science, Technology and Research have for the first time, identified the molecular ‘switch’ that directly triggers the body’s first line of defence against pathogens, more accurately known as the body’s “innate immunity”. The scientists found that this ‘switch’ called Bruton’s tyrosine kinase (BTK) when turned on, activates the production of interferons - a potent class of virus killers that enables the body to fight harmful pathogens such as dengue and influenza viruses.
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Vitamin K2: New hope for Parkinson's patients?

Neuroscientist Patrik Verstreken, associated with VIB and KU Leuven, succeeded in undoing the effect of one of the genetic defects that leads to Parkinson's using vitamin K2. His discovery gives hope to Parkinson's patients. This research was done in collaboration with colleagues from Northern Illinois University (US) and will be published in  Science. Vitamin K2 plays a role in the energy production of defective mitochondria. Because defective mitochondria are also found in Parkinson's patients with a PINK1 or Parkin mutation, vitamin K2 potentially offers hope for a new treatment for Parkinson's.
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Stay happy by avoiding junk food, says study - Yahoo! News

Feeling blue? Drop the burger and donuts. While junk food and processed foods may provide a dose of instant gratification, Spanish researchers say they’ve found a direct link between the consumption of fast food and depression.
After observing 8,964 participants over six months, scientists found that consumers of fast food were 51 percent more likely to develop depression. And the more they ate, the greater the risk.
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Toxoplasma gondii infection inhibits Th17-mediated spontaneous development of arthritis in interleukin-1 receptor antagonist-deficient mice.

Interleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection with Toxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed in T. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c(+) cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c(+) cells also produced IL-10, IL-1β, and IL-6, CD4(+) T cells from T. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of the T. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.

Life Science Technologies: Spot-On Protein Microarrays: An Old Proteomics Tool

When it comes to 'omics-inspired bioscience tools, next-gen DNA sequencing is the undisputed king. The previous champ was the DNA microarray, with the protein array its logical successor. Yet while DNA arrays achieved their potential, protein arrays never really took off, owing largely to the fact that, while every DNA oligo behaves more or less identically, the same cannot be said of proteins. They're also harder to synthesize, purify, and stabilize. Still, to paraphrase Mark Twain, the rumor of protein array's death has been greatly exaggerated. Today, new array formats and strategies have made the protein microarray a viable and growing tool for biomarker discovery, interactome research, functional genomics, and more.
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Rare Alleles Rise with Population | The Scientist

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis.

Chronic fatigue / Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time. This study investigates Natural Killer (NK) cell cytotoxic activity, NK cell subsets (CD56brightCD16- and CD56dimCD16+) and cytokines, over the course of a12 month period in patients with CFS/ME.

METHODS:The participants in the study comprised 65 (47.2+/-11.5 years) CFS/ME participants and 21 (45.2 +/-9.3 years) non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1), 6 (T2) and 12 months (T3). Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells.

RESULTS: NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16- NK cells at both T1 and T2. Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-gamma and TNF-alpha at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non- fatigued controls. Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56brightCD16- NK cells were much lower at T2 compared to the T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to the T1 and T3.


These results confirm decreases in immune  function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore NK cytotoxic activity may be a suitable biomarker for diagnosing CFS/ME as it was consistently decreased during the course of the 12 months study.
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T cells Reacting to changing circumstances - Immune Research Highlights - RIKEN RESEARCH

An analysis of a subset of immune cells reveals how these cells rally defenses against infection while keeping potentially harmful inflammatory reactions in check
T cells represent a significant component of the ‘muscle’ in the immune system, promoting aggressive action against perceived threats or restraining fellow immune cells from launching an unhealthy autoimmune response.  Dendritic cells help to manage these cells, presenting bits of antigen to T cells in a context that allows them to react appropriately.

Gut-throat competition: Native bacteria fend off invaders, suggesting new way to stop dangerous forms of E. coli

The bacteria that usually live in our digestive tracts compete against invading bacteria such as E. coli to help our bodies fend them off. The researchers also show that the invaders depend on certain genes to gain a temporary upper hand in that battle -- just long enough to reproduce and cause the symptoms that expel their offspring from the body so they can find a new host.

Maternal antibodies to gluten linked to schizophrenia risk in children

Babies born to women with sensitivity to gluten appear to be at increased risk for certain psychiatric disorders later in life, according to research by scientists at Karolinska Institutet in Sweden and Johns Hopkins Children's Center in Baltimore.

Gut bugs might influence child's odds for obesity

Overweight and obese children had different proportions of various gut bacteria than normal weight children. The ratio of Bacteroides fragilis to Bacteroides vulgatus was 3:1 in overweight and obese children, while this ratio was reversed in normal weight children, the investigators found.

Blood test could show women at risk of Postnatal Depression

(Medical Xpress) -- Researchers at Warwick Medical School have discovered a way of identifying which women are most at risk of postnatal depression (PND) by checking for specific genetic variants. The findings could lead to the development of a simple, accurate blood test which checks for the likelihood of developing the condition.

What Are The Top 10 Healthy Foods? Medical News Today

Apples, almonds, broccoli, blueberries, oily fish, leafy greens, sweet potatoes, wheat germ, avocados and oatmeal figure among the top foods thought to play a role in disease prevention
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Biology of Genomes Presentation Describes Hunt for Microbiome-Related Host Genes | GenomeWeb Daily News | Sequencing | GenomeWeb

COLD SPRING HARBOR, NY (GenomeWeb News) – Researchers are using human reads from metagenomic sequencing studies to begin looking at how host genetics influence microbial communities on and in the human body.

Human gut microbiome viewed across age and geography : Nature : Nature Publishing Group

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.
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Study Says Predictive Whole-Genome Sequencing Is Probably Not Very Useful | Genome Technology | Sequencing | GenomeWeb

Vogelstein also referenced a recent review article by Colditz et al. in Science Translational Medicine, which suggested that US cancer deaths could be halved every year if people applied what was already known about cancer prevention and took steps like quitting smoking, losing weight, or getting vaccinated against HPV and hepatitis. See : Applying what we know to accelerate cancer prevention.

Unveiling the mechanisms for decreased glutathione in individuals with HIV infection.

We examined the causes for decreased glutathione (GSH) in individuals with HIV infection. We observed lower levels of intracellular GSH in macrophages from individuals with HIV compared to healthy subjects. Further, the GSH composition found in macrophages from HIV(+) subjects heavily favors oxidized glutathione (GSSG) which lacks antioxidant activity, over free GSH which is responsible for GSH's antioxidant activity. This decrease correlated with an increase in the growth of Mycobacterium tuberculosis (M. tb) in macrophages from HIV(+) individuals. In addition, we observed increased levels of free radicals, interleukin-1 (IL-1), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in plasma samples derived from HIV(+) individuals compared to healthy subjects. We observed decreased expression of the genes coding for enzymes responsible for de novo synthesis of GSH in macrophages derived from HIV(+) subjects using quantitative PCR (qPCR). Our results indicate that overproduction of proinflammatory cytokines in HIV(+) individuals lead to increased production of free radicals. This combined with the decreased expression of GSH synthesis enzymes leads to a depletion of free GSH and may lead in part to the loss of immune function observed in HIV patients.
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A CB(1)/CB(2) receptor agonist, WIN 55,212... [Neuropharmacology. 2012] - PubMed - NCBI

Infection of mice with Theiler's murine encephalomyelitis virus (TMEV) leads to the development of TMEV-induced demyelinating disease (TMEV-IDD), an autoimmune, demyelinating and neurodegenerative pathology that serves as a model of multiple sclerosis. Activation of endogenous CB(1)/CB(2) cannabinoid receptors inhibits inflammation and improves the clinical status of TMEV-IDD animals. In the present study, mice with established TMEV-IDD were treated with the CB(1)/CB(2) receptor agonist WIN 55,212-2 (WIN), which restored self-tolerance to a myelin self-antigen while ameliorating the disease in a long-term manner. Accordingly, disruption of self-tolerance with cyclophosphamide provoked chronic relapse. Furthermore, transfer of splenocytes from WIN-treated TMEV-IDD mice to TMEV-infected mice at disease onset prevented the autoimmune inflammatory response and motor impairment. The therapeutic effect of WIN correlated with a decrease in the activation of CD4(+)CD25(+)Foxp3(-) T cells and an increase in regulatory CD4(+)CD25(+)Foxp3(+) T cells in the CNS, along with alterations in the cytokine and chemokine milieu. These findings demonstrate for the first time that the suppression of autoimmune responses to myelin antigens underlies the therapeutic effect of CB(1)/CB(2) cannabinoid agonists in the treatment of multiple sclerosis.
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Frontiers | Whole Genome Sequences of a Male and Female Supercentenarian, Ages Greater than 114 Years | Frontiers in Genetics of Aging

Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age of 100 and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals’ DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to-date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for coding variants near longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity-associated variants that may counter the effects of disease-predisposing variants and extend lifespan. The continued analysis of the genomes of these and other rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme aging.
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Psychiatric medications' effect on brain structure varies

It is increasingly recognized that chronic psychotropic drug treatment may lead to structural remodeling of the brain. Indeed, clinical studies in humans present an intriguing picture: antipsychotics, used for the treatment of schizophrenia and psychosis, may contribute to cortical gray matter loss in patients, whereas lithium, used for the treatment of bipolar disorder and mania, may preserve gray matter in patients.
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In Infants, Gut Flora Affects Maturation Of B Cells

Infants whose gut is colonised by E. coli bacteria early in life have a higher number of memory B cells in their blood, reveals a study of infants carried out at the Sahlgrenska Academy at the University of Gothenburg, Sweden. The bacteria in our gut outnumber the cells in our bodies by a factor of ten and are extremely important for our health because they stimulate the maturation of the immune system. The normal bacterial flora in the gut is established at the very beginning of our lives, but an increasingly hygienic lifestyle has led to changes in this flora.
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Regulatory immune cell diversity tempers autoimmunity in rheumatoid arthritis

Untangling the root cause of rheumatoid arthritis has been a difficult task for immunologists, as decades of research has pointed to multiple culprits in our immune system, with contradictory lines of evidence. Now, researchers at The Wistar Institute announce that it takes a diverse array of regulatory T cells (a specialized subset of white blood cells) to prevent the immune system from generating the tissue-specific inflammation that is a hallmark of the disease. Regulatory T cell diversity, the researchers say, provides a cumulative protective effect against rheumatoid arthritis. When that diversity is not present, it allows the immune system to attack joints.
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Killer T-cells found to counter obesity-related diabetes

(Medical Xpress) -- For years, researchers have known that obesity, type 2 diabetes and low-level inflammation are linked, but how they are connected has not been well understood.A recent Cornell-led study has found that a type of immune cells -- called natural killer T (NKT) cells -- is an important part of the puzzle.

Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition -- Zuliani et al. 83 (6): 638 -- Journal of Neurology, Neurosurgery & Psychiatry

The concept of antibody mediated CNS disorders is relatively recent. The classical CNS paraneoplastic neurological syndromes are thought to be T cell mediated, and the onconeural antibodies merely biomarkers for the presence of the tumour. Thus it was thought that antibodies rarely, if ever, cause CNS disease. Over the past 10 years, identification of autoimmune forms of encephalitis with antibodies against neuronal surface antigens, particularly the voltage gated potassium channel complex proteins or the glutamate N-methyl-D-aspartate receptor, have shown that CNS disorders, often without associated tumours, can be antibody mediated and benefit from immunomodulatory therapies. The clinical spectrum of these diseases is not yet fully explored, there may be others yet to be discovered and some types of more common disorders (eg, epilepsy or psychosis) may prove to have an autoimmune basis. Here, the known conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of further disorders are suggested.

Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes
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MicrobeWorld - Fed fiber, killer cells may ward off cancer

Defective carnitine metabolism may play role in autism

The deletion of part of a gene that plays a role in the synthesis of carnitine -- an amino acid derivative that helps the body use fat for energy -- may play a role in milder forms of autism, said a group of researchers led by those at Baylor College of Medicine and Texas Children's Hospital.

Death risks higher for heart attack survivors living near major roadways

Heart attack survivors who live about 100 meters (328 feet) or less from a major U.S. roadway face increased risk of death from all causes, according to new research in the American Heart Association's journal Circulation.

Deep brain stimulation may hold promise for mild Alzheimer's disease

A study on a handful of people with suspected mild Alzheimer's disease (AD) suggests that a device that sends continuous electrical impulses to specific "memory" regions of the brain appears to increase neuronal activity. Results of the study using deep brain stimulation, a therapy already used in some patients with Parkinson's disease and depression, may offer hope for at least some with AD, an intractable disease with no cure.
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Lifelong depression may increase risk of vascular dementia

Depressive symptoms that occur in both midlife and late life are associated with an increased risk of developing vascular dementia, while symptoms that occur in late life only are more likely to be early signs of Alzheimer's disease, according to University of California at San Francisco and Kaiser Permanente researchers.
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Scientists show how memory B cells stay 'in class' to fight different infections

Scientists at The Scripps Research Institute have made an important discovery about the internal programming of B cells, the immune cells that make antibodies against infections. The finding opens the way for the development of vaccines that can work more efficiently and hints at therapies for conditions in which B cells cause harm—such as the autoimmune disease lupus erythymatosus, severe allergies, and B-cell lymphomas.
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The influence of the mother: Maternal epigenetic inheritance

(Medical Xpress) -- A study published in Genes and Development from scientists at the Friedrich Miescher Institute for Biomedical Research pinpoints the importance of maternal epigenetic influences during early embryogenesis in mammals. A chromatin regulatory complex in the oocyte ensures that the proper luggage of maternal transcripts and chromatin structures control the first steps in the formation of an embryo. In the absence of this epigenetic regulator the embryo fails to develop correctly.
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