Our Genes Are Not Yet Ready For So Many Wheat-Based Products

According to an expert in digestive disorders, the current rise in dietary problems related to gluten could be due to over reliance on wheat-based products.Sanders explains that up to 6% of the world's population could be sensitive to gluten, making it the second leading gluten-related disorder after celiac disease.

PLoS Pathogens: How Do Viruses Interact with Stress-Associated RNA Granules?

See Stress Granules and Neurodegenerative Disease—What’s the Scoop?Alzforum

PLoS Genetics: Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis

IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10−32–3×10−10), with heterogeneity detected only at the PSMB9/TAP1 locus (I2 = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10−4). A seven–SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10−128). This model paralleled the known East–West gradient in disease risk. Moreover, the prediction of a South–North axis was confirmed by registry data showing that the prevalence of IgAN–attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.

The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis.

Epstein-Barr virus (EBV) infection is widely considered to be a risk factor for multiple sclerosis (MS). A previous meta-analysis estimated an odds ratio (OR) for MS in individuals seronegative for EBV of 0.06. Given the potential importance of this finding, we aimed to establish a more precise OR for adult and paediatric onset MS in EBV seronegative individuals METHODS: PubMed and EMBASE searches were undertaken to identify studies investigating the association between MS and EBV. Twenty-two adult and three paediatric studies were included. ORs were calculated using a fixed effects model. A sub-group analysis based on the method of EBV detection was performed.RESULTS: The OR for developing adult MS in EBV seronegatives was 0.18 (95% confidence interval (CI) 0.13-0.26)) and for paediatric MS was 0.18 (95% CI 0.11-0.30). Sub-group analysis on EBV detection method showed that studies which used immunofluoresence generated an OR=0.07 (95% CI 0.03-0.16); for those that used enzyme-linked immunosorbent assay (ELISA) OR=0.33 (95% CI 0.22-0.50) and for studies which used ELISA and immunofluoresence OR=0.00 (95% CI 0-0.43).

CONCLUSION: The sensitivity and specificity of the assay used to measure EBV antibody titres have an influence on the association between MS and EBV. Looking at studies where two independent methods are used and therefore are likely to be the most robust, EBV appears to be present in 100% of MS patients. This has implications for future studies of EBV in MS. MS patients without EBV infection, if they truly exist, should be studied in more detail.

Flu immunity is affected by how many viruses actually cause the infection

Not only does the type of flu virus affect a patient's outcome, but a new research report appearing in the Journal of Leukocyte Biology suggests that the number of viruses involved in the initial infection may be important too. Scientists from Canada found that when mice were infected by relatively high concentrations of the flu virus, they not only developed immunity against the virus that infected them, but this also promoted the generation of a type of immune cell in the lungs poised to rapidly react against infections with other strains of the flu, as well. Mice that were infected with a relatively low concentration of the virus developed weaker immunity against the strain that infected them, did not build up this crucial population of immune cells in the lungs, and showed only delayed immunity toward other flu strains. This discovery could pave the way for new prophylactic strategies to fight flu infections and provides a novel basis for vaccine design.

New animal model for rheumatoid arthritis

Researchers at Northwestern University Feinberg School of Medicine have created the first animal model that spontaneously develops rheumatoid arthritis (RA) and is predisposed towards atherosclerosis, or hardening of the arteries.

Junk-food diets spur inflammation more than saturated fats alone

(Medical Xpress) -- A diet based on American junk food could lead to more obesity-induced inflammation than a diet high in animal fat, according to a new study by researchers at the University of North Carolina at Chapel Hill.
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DISC1 localisation in the pineal gland: Gene Report | BioGPS

PLoS Biology: Circadian-Related Heteromerization of Adrenergic and Dopamine D4 Receptors Modulates Melatonin Synthesis and Release in the Pineal Gland

The role of the pineal gland is to translate the rhythmic cycles of night and day encoded by the retina into hormonal signals that are transmitted to the rest of the neuronal system in the form of serotonin and melatonin synthesis and release. Here we describe that the production of both melatonin and serotonin by the pineal gland is regulated by a circadian-related heteromerization of adrenergic and dopamine D4 receptors. Through α1B-D4 and β1-D4 receptor heteromers dopamine inhibits adrenergic receptor signaling and blocks the synthesis of melatonin induced by adrenergic receptor ligands. This inhibition was not observed at hours of the day when D4 was not expressed. These data provide a new perspective on dopamine function and constitute the first example of a circadian-controlled receptor heteromer. The unanticipated heteromerization between adrenergic and dopamine D4 receptors provides a feedback mechanism for the neuronal hormone system in the form of dopamine to control circadian inputs.

Alzheimer's blood test moves closer - FierceBiomarkers

The team of researchers followed up older people from the Sydney Memory and Aging Study, including healthy people and people with mild cognitive impairment, over two years, and measured their apolipoprotein levels. They found that the levels of the proteins were altered in people with cognitive impairment, and that, in people with normal cognition, lower levels of ApoA1, ApoH and ApoJ (clusterin) predicted a decline in cognitive impairment, the early stages of Alzheimer's disease. The results were published in PLoS One.

Immune response to heart attack worsens atherosclerosis, increases future risk

A heart attack doesn't just damage heart muscle tissue by cutting off its blood supply, it also sets off an inflammatory cascade that worsens underlying atherosclerosis, actively increasing the risk for a future heart attack. These findings from a study receiving advance online publication in Nature suggest an important new therapeutic strategy for preventing heart attacks and strokes, both of which are caused when atherosclerotic plaques rupture and block important blood vessels.

Specific solvents may increase risk of Parkinson's disease

he researchers found that exposure to trichloroethylene (TCE) correlated with a significantly increased risk of Parkinson's disease (odds ratio [OR], 6.1; P = 0.034). There was a trend toward significance for exposure to perchloroethylene (PERC; OR, 10.5; P = 0.053) and carbon tetrachloride (CCl4; OR, 2.3; P = 0.088).

Regulation of Neuronal Proapoptotic Potassium Currents by the Hepatitis C Virus Nonstructural Protein 5A

Apoptosis-enabling neuronal potassium efflux is mediated by an enhancement of K+ currents. In cortical neurons, increased currents are triggered by dual phosphorylation of Kv2.1 by Src and p38 at channel residues Y124 and S800. It was recently shown that a K+ current surge is also present in hepatocytes undergoing apoptosis, and that the hepatitis C virus (HCV) nonstructural protein 5A (NS5A) could inhibit Kv2.1-mediated currents and block cell death. Here, we show that NS5A1b (from HCV genotype 1b) expression in rat neurons depresses delayed rectifier potassium currents, limits the magnitude of the K+ current surge following exposure to activated microglia, and is neuroprotective. In a non-neuronal recombinant expression system, cells expressing Kv2.1 mutated at residue Y124, but not S800 mutants, are insensitive to NS5A1b-mediated current inhibition. Accordingly, NS5A1b coexpression prevents phosphorylation of wild-type Kv2.1 by Src at Y124, but is unable to inhibit p38 phosphorylation of the channel at S800. The actions of the viral protein are genotype-selective, as NS5A1a does not depress neuronal potassium currents nor inhibit Src phosphorylation of Kv2.1. Our results indicate that NS5A1b limits K+ currents following injury, leading to increased neuronal viability. NS5A1b may thus serve as a model for a new generation of neuroprotective agents.

Pollutants may contribute to illness and becoming overweight

Lack of physical activity and poor diet alone cannot explain the dramatic rise in obesity and diabetes occurring in many countries, believe some researchers. It is time to face the possibility that hazardous chemicals may also share part of the blame.

New role for RNAi discovered: Epigenetic memory may pass RNA silencing from one generation to the next

UMass Medical School researchers have identified a mechanism related to RNAi that scans for intruders not by recognizing dsRNA or some other aberrant feature of the foreign sequence, but rather by comparing the foreign sequences to a memory of previously expressed native RNA. Once identified, an "epigenetic memory" of the foreign DNA fragments is created and can be passed on from one generation to the next, permanently silencing the gene.

Even after Lyme disease is gone, its remains may perpetuate inflammation

(Medical Xpress) -- Non-infectious proteins of the species of bacteria that causes Lyme disease can remain in the body for a long time after antibiotic therapy, and are capable of causing an inflammatory immune reaction that could contribute to the development of antibiotic-resistant arthritis, Yale researchers have found. The study appears in the online Journal of Clinical Investigation.

serum phthalate levels higher in obese children

Serum levels of di(2-ethylhexyl) phthalate (DEHP) are increased in obese versus nonobese children, according to a study presented at the annual meeting of The Endocrine Society, held from June 23 to 26 in Houston.

Fungicide used on farm crops linked to insulin resistance

A fungicide used on farm crops can induce insulin resistance, a new tissue-culture study finds, providing another piece of evidence linking environmental pollutants to diabetes. The results will be presented at The Endocrine Society's 94th Annual Meeting in Houston.
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Intrinsically Unstructured Domain 3 of Hepatitis C Virus NS5A Forms a "Fuzzy Complex" with VAPB-MSP Domain Which Carries ALS-Causing Mutations.

Hepatitis C virus (HCV) affects nearly 200 million people worldwide and is a leading factor for serious chronic liver diseases. For replicating HCV genome, the membrane-associated replication machinery needs to be formed by both HCV non-structural proteins including NS5A and human host factors. Recently NS5A has been identified to bind ER-anchored human VAP proteins and consequently this interaction may serve as a novel target for design of anti-HCV drugs. So far no biophysical characterization of this interaction has been reported. Here, we dissected the 243-residue VAPB into 4 and 447-residue NS5A into 10 fragments, followed by CD and NMR characterization of their structural properties. Subsequently, binding interactions between these fragments have been extensively assessed by NMR HSQC titration which is very powerful in detecting even very weak binding. The studies lead to three important findings: 1). a "fuzzy complex" is formed between the intrinsically-unstructured third domain (D3) of NS5A and the well-structured MSP domain of VAPB, with an average dissociation constant (Kd) of ∼5 µM. 2). The binding-important residues on both NS5A-D3 and VAPB-MSP have been successfully mapped out, which provided experimental constraints for constructing the complex structure. In the complex, unstructured D3 binds to three surface pockets on one side of the MSP structure. Interestingly, two ALS-causing mutations T46I and P56S are also located on the D3-MSP interface. Moreover, NS5A-D3, FFAT-containing proteins and EphA4 appear to have overlapped binding interfaces on the MSP domain. 3). NS5A-D3 has been experimentally confirmed to competes with EphA4 in binding to the MSP domain, and T46I mutation of MSP dramatically abolishes its binding ability to D3. Our study not only provides essential foundation for further deciphering structure and function of the HCV replication machinery, but may also shed light on rationalizing a recent observation that a chronic HCV patient surprisingly developed ALS-like syndrome.

Natural Antidepressant Discovered | The Scientist

Researchers have identified a nerve growth factor that regulates synaptic plasticity and appears to have antidepressant effects. In new research, published today (June 25) in Proceedings of the National Academy of Sciences, scientists show that neuritin, which increases synaptic connections in the hippocampus, can alleviate stress-induced depressive symptoms.

Treating vitamin D deficiency may improve depression

Women with moderate to severe depression had substantial improvement in their symptoms of depression after they received treatment for their vitamin D deficiency, a new study finds.

How Germs Control Your Brain

Huntington's Disease Symptoms May Be Reversed By Proposed Drug: Single Treatment Produces Long-Term Improvement In Animal Models

Don W. Cleveland, PhD, professor and chair of the UC San Diego Department of Cellular and Molecular Medicine and head of the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research, and colleagues infused mouse and primate models of Huntington's disease with one-time injections of an identified DNA drug based on antisense oligonucleotides (ASOs). These ASOs selectively bind to and destroy the mutant gene's molecular instructions for making the toxic huntingtin protein.

The treatment produced rapid results. Treated animals began moving better within one month and achieved normal motor function within two. More remarkably, the benefits persisted, lasting nine months, well after the drug had disappeared and production of the toxic proteins had resumed.

Neurons that control overeating also drive appetite for cocaine

Infection biology: The elusive third factor

LMU researchers have identified an enzyme that is involved in a modification pathway that is essential for bacterial pathogenicity. Because it shows no similarity to other known proteins, it may be an ideal target for development of novel antimicrobial drugs.

New approach to diagnosing and treating dementia: Immunosuppression

Scientists at Charité -- Universitätsmedizin Berlin have succeeded in recommending a new type of therapeutic approach to dementia. The study published in the journal Neurology shows that immune reactions against the body's own nerve cells can be the cause of advanced dementia and an appropriate immune suppressive therapy can develop with significant effectiveness.
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New study explains how stress can boost immune system

A study spearheaded by a Stanford University School of Medicine scientist has tracked the trajectories of key immune cells in response to short-term stress and traced, in great detail, how hormones triggered by such stress enhance immune readiness. The study, conducted in rats, adds weight to evidence that immune responsiveness is heightened, rather than suppressed as many believe, by the so-called "fight-or-flight" response.

Danish scientists detect new immune alert signal

Researchers from Aarhus University have now located the place in the human body where the earliest virus alert signal triggers the human immune system. They have also discovered a new alarm signal, which is activated at the very first sign of a virus attack.

Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING Nature Immunology

Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10(-/-) mice.

The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia. This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(-/-), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(-/-) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.

Allergies Become Epidemic: Food Allergy Sufferers Double In The Last 10 Years

This week the European Academy of Allergy and Clinical Immunology (EAACI) launched its Food Allergy Campaign. The purpose of the campaign is to raise awareness of the sharp increase of anaphylaxis in children, an allergic reaction that is severe and potentially life-threatening. It aims at educating the public to recognise the symptoms and its triggers, and to teach methods of how to react in case of emergency, e.g. by using an adrenaline pen.

Don't Hog the Data | The Daily Scan | GenomeWeb

The UK Royal Society says that for science to work, it has to be as open as possible, reports Richard Van Noorden at the Nature News blog. In a new report, the society says that researchers who hog their data are presenting a "serious impediment" to scientific process, adding that "science is an open enterprise." Furthermore, the report adds, it's not enough for researchers to allow access to their data. What's needed is the kind of openness where researchers talk to each other about data, especially when speaking to researcherswho are specialists in other fields who might be able to use that data in their own work, Van Noorden says. "Many scientists already appreciate the value of sharing data sets in organized public databases, simply because it provides more efficient and creative ways to do research," he adds. "But some still cling possessively to their data, and top-down constraints, such as the lack of recognition for generating and communicating data, also blunt the urge to share." The report adds that researchers have to learn to adjust to the large volumes of data that are common today, and invest in good data management tools and training.
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Immune system molecule weaves cobweb-like nanonets to snag intestinal microbes / UCLA Newsroom

A multidisciplinary team of researchers has found that human alpha-defensin 6 (HD6) — a key component of the body's innate defense system — binds to microbial surfaces and forms "nanonets" that surround, entangle and disable microbes, preventing bacteria from attaching to or invading intestinal cells.

An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration.

Previous studies have shown that Toll-like receptors on neurons and glia can cause CNS damage through mechanisms that are not pathogen-induced, but the identity of these alternative triggers remained elusive. Lehnardt and colleagues now show that the microRNA (miRNA) let-7 can act as a potent activator of TLR7 signalling in neurons and that this activation can induce neurodegeneration, thus also revealing a new role of miRNAs beyond their function as regulators of gene expression.

An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration

Antibacterials in personal-care products linked to allergy risk in children

(Medical Xpress) -- Exposure to common antibacterial chemicals and preservatives found in soap, toothpaste, mouthwash and other personal-care products may make children more prone to a wide range of food and environmental allergies, according to new research from Johns Hopkins Children’s Center.The investigators say their findings are also consistent with the so-called hygiene hypothesis, which has recently gained traction as one possible explanation behind the growing rates of food and environmental allergies in the developed world.
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MicrobeWorld - Intestinal bacteria produce neurotransmitter (GABA), could play role in inflammation

We identified, to our knowledge, the first bifidobacterial strain, Bifidobacterium dentium, that is capable of secreting large amounts of gamma-aminobutyric acid (GABA). This molecule is a major inhibitory neurotransmitter in the central and enteric nervous systems, says Karina Pokusaeva, a researcher on the study and a member of the laboratory of James Versalovic.
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Brothers in arms: Commensal bacteria help fight viruses

Healthy humans harbor an enormous and diverse group of bacteria and other bugs that live within their intestines. These microbial partners provide beneficial aid in multiple ways – from helping digest food to the development of a healthy immune system. In a new study published online in the journal Immunity, David Artis, PhD, associate professor of Microbiology, and Michael Abt, PhD, a postdoctoral researcher in the Artis lab, Perelman School of Medicine, University of Pennsylvania, show that commensal bacteria are also essential to fight off viral infections.

Nanoparticle Exposure Linked To Rheumatoid Arthritis And Other Autoimmune Diseases

Medical News Today: According to a study published in the journal Nanomedicine, researchers have found an association between exposure to nanoparticles and rheumatoid arthritis and the development of other serious autoimmune disease. In addition, the team discovered new cellular targets for developing potential drug therapies to treat autoimmune diseases. The process involves citrullination, the transformation of arginine into citrulline, which can trigger autoimmune diseases.
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The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol.

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). Epidemiological studies revealed that consumption of docosahexaenoic acid (DHA: 22 : 6 (ω3)), a major brain polyunsaturated fatty acid, is protective for AD and that elevated cholesterol levels are an AD risk factor. We presently investigated the extent to which the pathological effects of apoE4 in vivo can be prevented by consuming fish oil (DHA) or can be modified by cholesterol. Accordingly, apoE3- and apoE4-targeted replacement mice were subjected, following weaning, to a fish oil diet enriched in DHA and to a cholesterol-containing diet under regular and enriched environments. Cholesterol metabolism in the hippocampus and the corresponding phospholipid and fatty acid levels were affected by fish oil (DHA) and cholesterol diets and by environmental stimulation. Importantly, cholesterol metabolism and the fatty acid levels were not affected by apoE4. The phospholipid levels were, however, affected by apoE4. This effect was most pronounced in the cholesterol-fed mice and was abolished by the fish oil (DHA) diet. ApoE4 elevated hippocampal intraneuronal amyloid-β levels under regular conditions and lowered them following environmental stimulation, relative to those of the apoE3 mice. ApoE4 also elevated the levels of the presynaptic transporters Vglut and Vgat, and decreased behavioral performance in an object recognition test. Importantly, all of these apoE4 phenotypes were abolished by the fish oil (DHA) diet, whereas the cholesterol diet modified them. These findings suggest that a fish oil (DHA) diet could be used to attenuate the effects of apoE4 in AD.

Probucol suppresses enterocytic accumulation of amyloid-β induced by saturated fat and cholesterol feeding.

Amyloid-β (Aβ) is secreted from lipogenic organs such as intestine and liver as an apolipoprotein of nascent triacylglycerol rich lipoproteins. Chronically elevated plasma Aβ may compromise cerebrovascular integrity and exacerbate amyloidosis--a hallmark feature of Alzheimer's disease (AD). Probucol is a hypocholesterolemic agent that reduces amyloid burden in transgenic amyloid mice, but the mechanisms for this effect are presently unclear. In this study, the effect of Probucol on intestinal lipoprotein-Aβ homeostasis was explored. Wild-type mice were fed a control low-fat diet and enterocytic Aβ was stimulated by high-fat (HF) diet enriched in 10% (w/w) saturated fat and 1% (w/w) cholesterol for the duration of 1 month. Mice treated with Probucol had the drug incorporated into the chow at 1% (w/w). Quantitative immunofluorescence was utilised to determine intestinal apolipoprotein B (apo B) and Aβ abundance. We found apo B in both the perinuclear region of the enterocytes and the lacteals in all groups. However, HF feeding and Probucol treatment increased secretion of apo B into the lacteals without any change in net villi abundance. On the other hand, HF-induced enterocytic perinuclear Aβ was significantly attenuated by Probucol. No significant changes in Aβ were observed within the lacteals. The findings of this study support the notion that Probucol suppresses dietary fat induced stimulation of Aβ biosynthesis and attenuate availability of apo B lipoprotein-Aβ for secretion.

J Neurol Neurosurg Psychiatry 2012;83:638-645 doi:10.1136/jnnp-2011-301237 Neuro-immunology Review Central nervous system neuronal surface antibody associated syndromes:

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.

ASM meeting Live: American society for microbiology videos

saccharin and other sweeteners may paradoxically foster overeating.

At some level, the brain can sense a difference between sugar and no-calorie sweeteners, several studies have demonstrated. Using brain imaging, San Diego researchers now show that the brain processes sweet flavors differently depending on whether a person regularly consumes diet soft drinks.The new findings may help explain an oft-observed association between diet soda consumption and weight gain, the researchers say. Once fooled, the brain’s sweet sensors can no longer provide a reliable gauge of energy consumption.
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Lipid metabolite profiling identifies desmosterol metabolism as a new antiviral target for hepatitis C virus.

Hepatitis C virus (HCV) infection has been clinically associated with serum lipid abnormalities, yet our understanding of the effects of HCV on host lipid metabolism and conversely the function of individual lipids in HCV replication remains incomplete. Using liquid chromatography-mass spectrometry metabolite profiling of the HCV JFH1 cell culture infection model, we identified a significant steady-state accumulation of desmosterol, an immediate precursor to cholesterol. Pharmacological inhibition or RNAi-mediated depletion of DHCR7 significantly reduced steady-state HCV protein expression and viral genomic RNA. Moreover, this effect was reversed when cultures were supplemented with exogenous desmosterol. Together, these observations suggest an intimate connection between HCV replication and desmosterol homeostasis and that the enzymes responsible for synthesis of desmosterol may be novel targets for antiviral design.

Multiple Sclerosis Discovery Forum

An online community and information portal that aims to inspire connections and clinical advances

Psoriasis tied to 14 other autoimmune diseases

Patients with psoriasis have significantly higher odds for having at least one of 14 other autoimmune diseases, according to a study published online June 4 in the Journal of the American Academy of Dermatology.

Bisphenol A exposure effects may last for generations

Exposure to low doses of Bisphenol A (BPA) during gestation had immediate and long-lasting, trans-generational effects on the brain and social behaviors in mice, according to a recent study accepted for publication in the journal Endocrinology, a publication of The Endocrine Society.

PLoS Genetics: Diverse CRISPRs Evolving in Human Microbiomes

Secondary structure image for CRISPR-DR6 (RF01...
Secondary structure image for CRISPR-DR6 (RF01319). Nucleotide colouring indicates sequence conservation between the members of this family, with the red end of the spectrum labelling highest conservation. (Photo credit: Wikipedia)
Human bodies are complex ecological systems in which various microbial organisms and viruses interact with each other and with the human host. The Human Microbiome Project (HMP) has resulted in >700 datasets of shotgun metagenomic sequences, from which we can learn about the compositions and functions of human-associated microbial communities. CRISPR/Cas systems are a widespread class of adaptive immune systems in bacteria and archaea, providing acquired immunity against foreign nucleic acids: CRISPR/Cas defense pathways involve integration of viral- or plasmid-derived DNA segments into CRISPR arrays (forming spacers between repeated structural sequences), and expression of short crRNAs from these single repeat-spacer units, to generate interference to future invading foreign genomes. Powered by an effective computational approach (the targeted assembly approach for CRISPR), our analysis of CRISPR arrays in the HMP datasets provides the very first global view of bacterial immunity systems in human-associated microbial communities. The great diversity of CRISPR spacers we observed among different body sites, in different individuals, and in single individuals over time, indicates the impact of subtle niche differences on the evolution of CRISPR defenses and indicates the key role of bacteriophage (and plasmids) in shaping human microbial communities.
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A cholesterol and actinide dependent shadow biosphere of archaea and viroids in autoimmune diseases.

Endogenous digoxin has been related to the pathogenesis of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis. The possibility of endogenous digoxin synthesis by archaea with a mevalonate pathway and cholesterol catabolism was considered. 10 cases each of multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis before starting treatment and 10 age and sex matched healthy controls from general population were chosen for the study. Cholesterol substrate was added to the plasma of the patients and the generation of cytochrome F420, free RNA, free DNA, polycyclic aromatic hydrocarbon, hydrogen peroxide, serotonin, pyruvate, ammonia, glutamate, cytochrome C, hexokinase, ATP synthase, HMG CoA reductase, digoxin and bile acids were studied. The changes with the addition of antibiotics and cerium to the patient's plasma were also studied. The statistical analysis was done by ANOVA. The parameters mentioned above were increased the patient's plasma with addition of cholesterol substrate. The addition of antibiotics to the patient's plasma caused a decrease in all the parameters while addition of cerium increased their levels. An actinide dependent shadow biosphere of archaea and viroids is described in multiple sclerosis and other autoimmune diseases like systemic lupus erythematosis and rheumatoid arthritis contributing to their pathogenesis.

Breast milk kills HIV and blocks its oral transmission in humanized mouse

More than 15 percent of new HIV infections occur in children. Without treatment, only 65 percent of HIV-infected children will live until their first birthday, and fewer than half will make it to the age of two. Although breastfeeding is attributed to a significant number of these infections, most breastfed infants are not infected with HIV, despite prolonged and repeated exposure.

Environmental factors spread obesity, study reports

An international team of researchers' study of the spatial patterns of the spread of obesity suggests America's bulging waistlines may have more to do with collective behavior than genetics or individual choices. The team, led by City College of New York physicist Hernán Makse, found correlations between the epidemic's geography and food marketing and distribution patterns.

Link between metabolic disorders and Alzheimer's disease examined

No effective treatments are currently available for the prevention or cure of Alzheimer's disease (AD), the most frequent form of dementia in the elderly. The most recognized risk factors, advancing age and having the apolipoprotein E Ɛ4 gene, cannot be modified or treated. Increasingly, scientists are looking toward other risk factors to identify preventive and therapeutic strategies. Much attention recently has focused on the metabolic syndrome (MetS), with a strong and growing body of research suggesting that metabolic disorders and obesity may play a role in the development of dementia.

Folic acid intake associated with reduced risk of autism: study

(Medical Xpress) -- A new study by researchers at the UC Davis MIND Institute suggests that women who consume the recommended daily dosage of folic acid, the synthetic form of folate or vitamin B-9, during the first month of pregnancy may have a reduced risk of having a child with autism.

Childhood virus infection linked to prolonged seizures with fever

New research shows that human herpesviruses (HHV)-6B and HHV-7, commonly know as roseola virus), account for one third of febrile status epilepticus (FSE) cases. Results of the FEBSTAT prospective study now available in Epilepsia, a journal published by Wiley-Blackwell on behalf of the International League Against Epilepsy (ILAE), suggest that HHV-6B may be involved in the development of epilepsy and further research is urgently needed.

Effect of the oral intake of yogurt containing Bifidobacterium longum BB536 on the cell numbers of enterotoxigenic Bacteroides fragilis in microbiota.

Enterotoxigenic Bacteroides fragilis (ETBF) strains have been suggested to be associated with acute and persistent diarrheal disease, inflammatory bowel disease and colorectal cancer, although further epidemiological studies are needed for clarification. Here, a pilot study was performed to examine the effect of the oral administration of yogurt supplemented with a probiotic strain on the cell numbers of fecal ETBF in a healthy population. Among 420 healthy adults, 38 subjects were found to be ETBF carriers, giving a prevalence of approximately 9%. Among them, 32 subjects were enrolled in an open, randomized, parallel-group study to ingest yogurt supplemented with a probiotic strain, Bifidobacterium longum BB536 (BB536Y group), for 8 weeks, with milk provided to the control group (milk group). The cell numbers of ETBF and the dominant species of the B. fragilis group were measured by a quantitative PCR method. Compared with the baseline values, there was a significant decrease in the cell number of ETBF at week 8 in the BB536Y group but not in the milk group. Linear mixed models analysis for longitudinal data revealed a significant difference in the changes of ETBF cell number between the two groups during the intervention phase. These results imply the potential of probiotic yogurt for eliminating ETBF in the microbiota, but its clinical significance needs to be evaluated in the future. This is the first report of a possible effect of probiotic intake on ETBF in the microbiota.
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Therapeutic Potential of the Endocannabinoid system - Free issue: ACS Chemical Neuroscience

The cannabinoid system has many therapeutic applications in relation to analgesia, psychiatry and immunology as featured in this series of open access reviews.

Timing, duration of biochemical bugle call critical for fighting viruses

Scientists at Washington University School of Medicine in St. Louis have shown that a key molecule, MDA5, is essential for producing enough interferon (the bugle call) to rally virus-fighting cells during certain viral infections. In mice, the lack of MDA5 forces the immune system to rely on less effective defenders, which may give the virus opportunities to establish or expand a chronic infection.

Lack of single protein (Toll receptor TLR7) results in persistent viral infection

Scientists from The Scripps Research Institute have shown a single protein can make the difference between an infection clearing out of the body or persisting for life. The results also show where the defects occur in the immune system without the protein and offer the possibility that targeting this signaling pathway could be beneficial for treatment of persistent viral infections in humans. Currently hundreds of millions of people around the world are afflicted with persistent viral infections such as HIV, HCV, and HBV.

Western diet changes gut bacteria and triggers colitis in those at risk

Certain saturated fats that are common in the modern Western diet can initiate a chain of events leading to complex immune disorders such as inflammatory bowel diseases (IBD) in people with a genetic predisposition, according to a study to be published early online in the journal Nature.

Herpes simplex virus 1 induces cytoplasmic accumulation of TIA-1/TIAR and both synthesis and cytoplasmic accumulation of tristetraprolin, two cellular proteins that bind and destabilize AU-rich RNAs.

Herpes simplex virus 1 causes a shutoff of cellular protein synthesis through the degradation of RNA that is mediated by the virion host shutoff (Vhs) protein encoded by the U(L)41 gene. We reported elsewhere that the Vhs-dependent degradation of RNA is selective, and we identified RNAs containing AU-rich elements (AREs) that were upregulated after infection but degraded by deadenylation and progressive 3'-to-5' degradation. We also identified upregulated RNAs that were not subject to Vhs-dependent degradation (A. Esclatine, B. Taddeo, L. Evans, and B. Roizman, Proc. Natl. Acad. Sci. USA 101:3603-3608, 2004). Among the latter was the RNA encoding tristetraprolin, a protein that binds AREs and is known to be associated with the degradation of RNAs containing AREs. Prompted by this observation, we examined the status of the ARE binding proteins tristetraprolin and TIA-1/TIAR in infected cells. We report that tristetraprolin was made and accumulated in the cytoplasm of wild-type virus-infected human foreskin fibroblasts as early as 2 h and in HEp-2 cells as early as 6 h after infection. The amounts of tristetraprolin that accumulated in the cytoplasm of cells infected with a mutant virus lacking U(L)41 were significantly lower than those in wild-type virus-infected cells. The localization of tristetraprolin was not modified in cells infected with a mutant lacking the gene encoding infected cell protein 4 (ICP4). TIA-1 and TIAR are two other proteins that are associated with the regulation of ARE-containing RNAs and that normally reside in nuclei. In infected cells, they started to accumulate in the cytoplasm after 6 h of infection. In cells infected with the mutant virus lacking U(L)41, TIA-1/TIAR accumulated in the cytoplasm in granular structures reminiscent of stress granules in a significant percentage of the cells. In addition, an antibody to tristetraprolin coprecipitated the Vhs protein from lysates of cells late in infection. The results indicate that the Vhs-dependent degradation of ARE-containing RNAs correlates with the transactivation, cytoplasmic accumulation, and persistence of tristetraprolin in infected cells.

Researchers identify new group of proteins in the brains of Alzheimer's patients

The researchers identified a new group of proteins, termed RNA-binding proteins, which accumulate in the brains of patients with Alzheimer's disease, and are present at much lower levels in subjects who are cognitively intact. The group found two different proteins, both of which show striking patterns of accumulation. "Proteins such as TIA-1 and TTP, accumulate in neurons that accumulate tau protein, and co-localize with neurofibrillary tangles. These proteins are a component off stress granules.

Mutant gut bacteria reverse colon cancer in lab models

(Medical Xpress) -- A mutant form of a meek microbe deals a gutsy blow to colon cancer, University of Florida scientists have discovered. The special bacteria halted abnormal inflammation, reduced precancerous growths and reversed progression of severe cancerous lesions in the large intestines of mice. The findings appear June 11 in the Proceedings of the National Academy of Sciences.

Researchers find success with new immune approach to fighting some cancers

A national research collaboration of senior researchers, including a researcher from Moffitt Cancer Center, has found that 20 to 25 percent of "heavily pre-treated" patients with a variety of cancers who enrolled in a clinical trial had "objective and durable" responses to a treatment with BMS-936558, an antibody that specifically blocks programmed cell death 1 (PD-1). PD-1 is a key immune "checkpoint" receptor expressed by activated immune cells (T-cells) and is involved in the suppression of immunity.

NIH Human Microbiome Project defines normal bacterial makeup of the body, June 13, 2012 News Release - National Institutes of Health (NIH)

Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for human survival. For the first time, a consortium of researchers organized by the National Institutes of Health has mapped the normal microbial makeup of healthy humans, producing numerous insights and even a few surprises.

See the Human Microbiome project site for details and PLOS and Nature papers

How infection can lead to cancer

One of the biggest risk factors for liver, colon or stomach cancer is chronic inflammation of those organs, often caused by viral or bacterial infections. A new study from MIT offers the most comprehensive look yet at how such infections provoke tissues into becoming cancerous.

Nature or nurture? It may depend on where you live

In a study published June 12 in the journal Molecular Psychiatry, researchers from the Twins Early Development Study at King's College London's Institute of Psychiatry studied data from more than 6700 families relating to 45 childhood characteristics, from IQ and hyperactivity to height and weight. They found that genetic and environmental contributions to these characteristics vary geographically in the UK and have published their results online as a series of nature-nurture maps.
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Early gut bacteria regulate brain serotonin and happiness

This research shows that normal adult brain and serotonin function depends on the presence of gut microbes during development. Serotonin, the major chemical involved in the regulation of mood and emotion, is altered in times of stress, anxiety and depression and most clinically effective antidepressant drugs work by targeting this neurochemical.

Nature Outlook : Diabetes: Free supplement

About 350 million people — 5% of the world’s population — are afflicted by either type 1 diabetes, an autoimmune disorder, or type 2 diabetes, largely linked to lifestyle. Nature Outlook: Diabetes examines the latest research into the causes, therapy, prevention and impact of these devastating diseases.

Cyanobacteria blooms produce teratogenic retinoic acids: PNAS

Deformed amphibians have been observed in eutrophic habitats, and some clues point to the retinoic acids (RAs) or RA mimics. However, RAs are generally thought of as vertebrate-specific hormones, and there was no evidence that RAs exist in cyanobacteria or algae blooms. By analyzing RAs and their analogs 4-oxo-RAs in natural cyanobacteria blooms and cultures of cyanobacteria and algae, we showed that cyanobacteria blooms could produce RAs, which were powerful animal teratogens. Intracellular RAs and 4-oxo-RAs with concentrations between 0.4 and 4.2 × 102 ng/L were detected in all bloom materials, and extracellular concentrations measured in water from Taihu Lake, China, were as great as 2.0 × 10 ng/L, which might pose a risk to wildlife through chronic exposure. Further examination of 39 cyanobacteria and algae species revealed that 32 species could produce RAs and 4-oxo-RAs (1.6–1.4 × 103 ng/g dry weight), and the dominant cyanobacteria species in Taihu Lake, Microcystis flos-aquae and Microcystis aeruginosa, produced high amounts of RAs and 4-oxo-RAs with concentrations of 1.4 × 103 and 3.7 × 102 ng/g dry weight, respectively. Most genera of cyanobacteria that could produce RAs and 4-oxo-RAs, such as Microcystis, Anabaena, and Aphanizomenon, often occur dominantly in blooms. Production of RAs and 4-oxo-RAs by cyanobacteria was associated with species, origin location, and growth stage. These results represent a conclusive demonstration of endogenous production of RAs in freshwater cyanobacteria blooms. The observation of teratogenic RAs in cyanobacteria is evolutionarily and ecologically significant because RAs are vertebrate-specific hormones, and cyanobacteria form extensive and highly visible blooms in many aquatic ecosystems.
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DNA Methylation Declines with Age | The Scientist

Aging is associated with loss of an epigenetic marker that helps control gene expression, according to new research published in Proceedings of the National Academy of Sciences, with a centenarian carrying some 7 percent fewer methylated DNA bases than a newborn. Researchers posit that reductions in methylation may be one of the mechanisms underlying the aging process.

Synthetic Food Colors and Neurobehavioral Hazards: The View from Environmental Health Research

.............."The FDA has had 35 years since the Feingold book (Feingold 1975) and 37 years since the GRAS report (Siu et al. 1977) to address the neurobehavioral toxicity of food colors. However, the British Food Standards Agency has advised parents to consider eliminating artificial food colors from the diet, and the European Union has called for eliminating six colors or listing on the label the warning that “[the color] may have an adverse effect on activity and attention in children” (Food Standards Agency 2011)."
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Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active multiple sclerosis.

Multiple sclerosis (MS) is considered to be an autoimmune disease with an unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS. Human endogenous retroviruses (HERVs) constitute 5 to 8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS. We studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in peripheral blood mononuclear cells (PBMCs) from healthy controls and from MS patients with nonactive or active disease. There was a significant increase in HERV-H/F Gag expression in CD4(+) (P < 0.001) and CD8(+) (P < 0.001) T lymphocytes and in monocytes (P = 0.0356) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute quantitative PCR (Q-PCR) evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We found a 4-fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS compared with healthy controls (P < 0.001). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expression levels will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.

Prenatal activation of Toll-like receptors-3 by administration of the viral mimetic poly(I:C) changes synaptic proteins, N-methyl-D-aspartate receptors and neurogenesis markers in offspring.

There is mounting evidence for a neurodevelopmental basis for disorders such as autism and schizophrenia, in which prenatal or early postnatal events may influence brain development and predispose the young to develop these and related disorders. We have now investigated the effect of a prenatal immune challenge on brain development in the offspring. Pregnant rats were treated with the double-stranded RNA polyinosinic:polycytidylic acid (poly(I:C); 10mg/kg) which mimics immune activation occurring after activation of Toll-like receptors-3 (TLR3) by viral infection. Injections were made in late gestation (embryonic days E14, E16 and E18), after which parturition proceeded naturally and the young were allowed to develop up to the time of weaning at postnatal day 21 (P21). The brains of these animals were then removed to assess the expression of 13 different neurodevelopmental molecules by immunoblotting.

RESULTS:

Measurement of cytokine levels in the maternal blood 5 hours after an injection of poly(I:C) showed significantly increased levels of monocyte chemoattractant protein-1 (MCP-1), confirming immune activation. In the P21 offspring, significant changes were detected in the expression of GluN1 subunits of NMDA receptors, with no difference in GluN2A or GluN2B subunits or the postsynaptic density protein PSD-95 and no change in the levels of the related small GTPases RhoA or RhoB, or the NMDA receptor modulator EphA4. Among presynaptic molecules, a significant increase in Vesicle Associated Membrane Protein-1 (VAMP-1; synaptobrevin) was seen, with no change in synaptophysin or synaptotagmin. Proliferating Cell Nuclear Antigen (PCNA), as well as the neurogenesis marker doublecortin were unchanged, although Sox-2 levels were increased, suggesting possible changes in the rate of new cell differentiation.

CONCLUSIONS:

The results reveal the induction by prenatal poly(I:C) of selective molecular changes in the brains of P21 offspring, affecting primarily molecules associated with neuronal development and synaptic transmission. These changes may contribute to the behavioural abnormalities that have been reported in adult animals after exposure to poly(I:C) and which resemble symptoms seen in schizophrenia and related disorders.

Scientists develop new tools to unveil mystery of the ‘Glycome’

Scientists at The Scripps Research Institute have developed chemical compounds that can make key modifications to common sugar molecules ("glycans"), which are found on the surface of all cells in our body. The new study presents powerful new tools for studying these molecules' function, for example in cell signaling and immunity, and for investigating new treatments for chronic inflammation, autoimmune diseases, cancer metastasis, and related conditions.
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Nanoparticles in polluted air, smoke & nanotechnology products have serious impact on health

New groundbreaking research by scientists at Trinity College Dublin has found that exposure to nanoparticles can have a serious impact on health, linking it to rheumatoid arthritis and the development of other serious autoimmune diseases.

Lessons from epigenome evolution

he sequencing of the human genome has provided a wealth of genetic information, yet the goal of understanding the function of every gene remains outstanding. New research from the University of Illinois published in Cell suggests determining the purpose of genes through a new method they call "comparative epigenomics."

Long-ignored enzyme turns out to be key to killing infectious bacteria

Ohio State University scientists have determined that caspase-11 in mice, enables components in immune cells to fuse and degrade the bacteria that cause Legionnaires' disease, a type of pneumonia. Without that fusion and degradation, these bacteria thrive, grow or replicate and cause illness. Whether the effect is the same in other bacteria remains unknown.
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Sick from your stomach: Bacterial changes may trigger diseases like rheumatoid arthritis

The billions of bugs in our guts have a newfound role: regulating the immune system and related autoimmune diseases such as rheumatoid arthritis, according to researchers at Mayo Clinic and the University of Illinois at Urbana-Champaign.

Futurity.org – Kids’ body fat linked to low vitamin D in moms

Immune cells in the gut may improve control of HIV growth

The findings of a new study in monkeys may help clarify why some people infected with HIV are better able to control the virus. They also may pinpoint a target for treatment during early HIV infection aimed at increasing the supply of certain immune cells in the gut, which the study shows could be an important factor in limiting HIV growth in cells throughout the body.

Receptor may hold key to multiple sclerosis treatment

(Medical Xpress) -- A receptor (the A2A adenosine receptor) recently discovered to control the movement of immune cells across central nervous system barriers (including the blood-brain barrier) may hold the key to treating multiple sclerosis (MS), a neuroinflammatory disease of the central nervous system.

Fighting cancer with the immune system

The human immune system has a natural ability to identify and attack tumor cells. Natural killer (NK) cells are innate immune cells that are particularly effective at killing tumor cells due to their ability to secrete cytotoxic enzymes. However, mutations have allowed many types of tumors to develop a resistance to NK-mediated killing through ill-defined mechanisms.
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Peroxiredoxin sets the brain on fire after stroke : Nature Medicine : Nature Publishing Group

How blood-borne inflammatory cells cause tissue damage in the brain after ischemic stroke remains elusive. Peroxiredoxins, cytosolic antioxidant proteins vital for redox balance, are released extracellularly from ischemic cells, acting as potent 'danger signals' that activate macrophages and lead to a harmful cytokine response, a new study shows. The findings unveil a new culprit in the delayed phase of ischemic injury and suggest new therapeutic approaches (pages 911–917).

Revealed: Secret of HIV's natural born killers

Only about one person in 300 has the ability to control the human immunodeficiency virus (HIV) without drugs, using a strain of "killer" cells called cytotoxic T lymphocyte (CTL) cells, previous research has found.Taking that discovery further, scientists from the United States, Canada, Japan and Germany reported that the strain has molecules called receptors that are better able to identify HIV-infected white blood cells for attack.
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BCG bacteria to treat Bladder Cancer | The Scientist

Bacillus Calmette-Guérin (BCG) is a puny cousin of the bacteria that causes tuberculosis, and as such serves as an excellent vaccine against the disease. But BCG is also used to treat bladder cancer. Research published today (June 5) in Science Translational Medicine reveals how BCG achieves its cancer-fighting performance, and suggests the bug has a better chance of winning if the patient has a prior BCG vaccination.
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Pregnancy: Why mother's immune system does not reject developing fetus as foreign tissue

Researchers at NYU School of Medicine have made an important discovery that partially answers the long-standing question of why a mother's immune system does not reject a developing fetus as foreign tissue.The researchers discovered that embryo implantation sets off a process that ultimately turns off a key pathway required for the immune system to attack foreign bodies. As a result, immune cells are never recruited to the site of implantation and therefore cannot harm the developing fetus.
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McGill discovery: Alzheimer's drugs make bones stronger

(Medical Xpress) -- The drugs commonly used to treat memory loss in Alzheimer’s patients can make bones stronger, according to a recent study led by Faleh Tamimi, assistant professor at McGill University's Faculty of Dentistry.  The findings, published in Journal of Bone and Mineral Research and highlighted in Nature Reviews: Endocrinology, could help further research into the idea that bone strength is controlled centrally within the brain.
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Identifying the Real Culprit Behind Killer Vascular Diseases

Within the walls of blood vessels are smooth muscle cells and newly discovered vascular stem cells. The stem cells are multipotent and are not only able to differentiate into smooth muscle cells, but also into fat, cartilage and bone cells. UC Berkeley researchers provide evidence that the stem cells are contributing to clogged and hardened arteries.

The Lancet Neurology - Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study

In this promising Phase 1 safety study, the  findings suggest that CAD106 ( see Alzforum) has a favourable safety profile and acceptable antibody response in patients with Alzheimer's disease. Larger trials with additional dose investigations are needed to confirm the safety and establish the efficacy of CAD106.

Science: Special issue on the microbiome.

Innate Lymphoid Cells Promote Anatomical Containment of Lymphoid-Resident Commensal Bacteria

The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)–producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn’s disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.
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Live Chat: The Bugs Inside of Us - ScienceNOW

Our bodies, inside and out, are teeming with trillions of microbes. Most of them are our friends, helping us to digest food, strengthening our immune systems, and keeping dangerous enemy pathogens from invading our tissues and organs. Evidence is building that this resident community of microbes, called the microbiome, plays a major role in health and disease. Disorders as diverse as cancer, obesity, inflammatory bowel disease, psoriasis, asthma, and possibly even autism may be influenced by the microbiome when its normal composition is thrown off balance. How similar are the microbial communities of different people? How are scientists establishing links between microbes and health? And what might be done to alter the microbiome to prevent disease?
Join us for a live chat at 3 p.m. EDT on Thursday, 7 June, on this page. You can leave your questions in the comment box below before the chat starts. The full text of the chat will be archived on this page

Complex world of gut microbes fine-tune body weight

Microorganisms in the human gastrointestinal tract form an intricate, living fabric made up of some 500 to 1000 distinct bacterial species, (in addition to other microbes). Recently, researchers have begun to untangle the subtle role these diverse life forms play in maintaining health and regulating weight.

Gut immune cells keep beneficial microbes in their place

The healthy human intestine is colonized with over 100 trillion beneficial, or commensal, bacteria of many different species. In healthy people, these bacteria are limited to the intestinal tissues and have a number of helpful properties, including aiding in the digestion of food and promoting a healthy immune system.

Three types of fetal cells can migrate into maternal organs during pregnancy: Some mothers literally carry pieces of their children in their bodies

A pregnant woman's blood stream contains not only her own cells, but a small number of her child's, as well, and some of them remain in her internal organs long after the baby is born. Understanding the origin and identity of these cells is vital to understanding their potential effects on a mother's long-term health. For example, fetal cells have been found at tumor sites in mothers, but it is unknown whether the cells are helping to destroy the tumor or to speed its growth.
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Cedars-Sinai researchers explore role of fungus in digestive disorders

Cedars-Sinai researchers say their examination of the fungi in the intestines suggests an important link between these microbes and inflammatory diseases such as ulcerative colitis.
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Spreading of Alzheimer's disease inflammatory signaling through soluble micro-RNA.

Alzheimer's disease is a progressive, neurodegenerative disorder that develops within the limbic system, spreading radially into anatomically linked brain association areas as the disease progresses. Analysis of temporal-lobe association of neocortex-derived extracellular fluid and cerebrospinal fluid from Alzheimer's disease patients shows an abundant presence of micro-RNA (miRNA),
including the proinflammatory miRNA-146a and miRNA-155. Using a novel and highly sensitive LED-Northern dot-blot focusing technique, we detected the secretion of potentially pathogenic amounts of miRNA-146a and miRNA-155 from stressed human primary neural cells. A conditioned medium containing miRNA-146a and miRNA-155 was found to induce Alzheimer-type gene expression changes in control brain cells. These included downregulation in the expression of an important repressor of the innate immune response, complement factor H (CFH). These effects were
neutralized using anti-miRNA strategies. Anti-miRNA-based therapeutics may provide a novel and efficacious treatment to stem the miRNA-mediated spreading of inflammatory signaling involved in Alzheimer's disease.

Researchers ID cluster of genes in blood that predict Parkinson's

Because there is currently no laboratory test that can diagnose Parkinson's disease, it is practically impossible to detect those individuals who are in the earliest stages of the disease. As a result, Parkinson's disease can only be diagnosed by a clinical neurological examination based on findings suggestive of the disease.

Study: How immune system, inflammation may play role in Lou Gehrig's disease / UCLA Newsroom

In an early study, UCLA researchers found that the immune cells of patients with amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, may play a role in damaging the neurons in the spinal cord. ALS is a disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement.

Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis.

B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS). A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR). Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs) of MRZR with magnetic resonance imaging (MRI) findings in patients with first MS diagnosis.

METHODS/RESULTS:

MRZR was determined in 68 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting MS (RRMS). Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI) and cMRI combined with spinal MRI (sMRI). Measles virus AI correlated significantly with T2 lesion load on cMRI (p = 0.0312, Mann-Whitney U test) and the sum of lesions on cMRI and sMRI (p = 0.0413). Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p = 0.2893).

CONCLUSION:

The results confirm MRZR as part of the polyspecific immune reaction in MS with possible prognostic impact on MRI and clinical parameters. Furthermore, the data indicate that intrathecal measles virus IgG production correlates with disease activity on cMRI and sMRI in patients with early MS.

Dr.VIS Human Disease-Related Viral Integration Sites Database

Dr.VIS collects and locates human disease-related viral integration sites. So far, about 600 sites covering 5 virus organisms and 11 human diseases are available. Integration sites in Dr.VIS are located against chromesome, cytoband, gene and refseq position as specific as possible. Viral-cellular junction sequences are extracted from papers and nucleotide databases, and linked to cooresponding integration sites Graphic views summarizing distribution of viral integration sites are generated according to chromosome maps. It is free to browse and download data in Dr.VIS.

Inhibition of multiplication of herpes simplex virus by caffeic acid.

Hot water extracts of coffee grinds and commercial instant coffee solutions have been shown to exhibit marked antiviral and virucidal activities against herpes simplex virus type 1 (HSV-1). Specifically, it has been shown that caffeine and N-methyl-pyridinium formate inhibit the multiplication of HSV-1 in HEp-2 cells. The present study examined the virological properties and the antiviral activity of caffeic acid against HSV-1. Caffeic acid inhibited the multiplication of HSV-1 in vitro, while chlorogenic acid, a caffeic acid ester with quinic acid, did not. These reagents did not have a direct virucidal effect. The one-step growth curve of HSV-1 showed that the addition of caffeic acid at 8 h post infection (h p.i.) did not significantly affect the formation of progeny viruses. An analysis of the influence of the time of caffeic acid addition, revealed that addition at an early time post infection remarkably inhibited the formation of progeny infectious virus in the infected cells, but its addition after 6 h p.i. (i.e., the time of the completion of viral genome replication) did not efficiently inhibit this process. These results indicate that caffeic acid inhibits HSV-1 multiplication mainly before the completion of viral DNA replication, but not thereafter. Although caffeic acid showed some cytotoxicity by prolonged incubation, the observed antiviral activity is likely not the secondary result of the cytotoxic effect of the reagent, because the inhibition of the virus multiplication was observed before appearance of the notable cytotoxicity.

High blood caffeine levels in older adults linked to avoidance of Alzheimer’s disease

This was linked to the caffeine in coffee rather than tea, and suggested that caffeine intake might be able to delay the onset of Alzheimer's disease in individuals with mild cognitive impairment.Cao et al, 2012


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How infectious disease may have shaped human origins

Mutations in immune-related genes resulting in increased resistance to pathogens may have shaped human evolution, promulgating the explosion and expansion of the human population 100, 000 years ago. 
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Healthy habits can prevent disease

Five new studies provide evidence to support simple steps we can take to prevent illness and improve our overall health. In the June issue of The American Journal of Medicine, researchers report on fish consumption to reduce the risk of colon cancer; the effectiveness of hypnotherapy and acupuncture for smoking cessation; regular teeth cleaning to improve cardiovascular health; the effectiveness of primary care physicians in weight loss programs; and the use of low-dose aspirin to reduce cancer risk.
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Study IDs immune system glitch tied to fourfold higher likelihood of death

Mayo Clinic researchers have identified an immune system deficiency whose presence shows someone is up to four times likelier to die than a person without it. The glitch involves an antibody molecule called a free light chain; people whose immune systems produce too much of the molecule are far more likely to die of a life-threatening illness such as cancer, diabetes and cardiac and respiratory disease than those whose bodies make normal levels. The study is published in the June issue of Mayo Clinic Proceedings.

For advanced prostate cancer, new drug slows disease

A new medication (abiraterone acetate) proved effective in slowing the spread of metastatic prostate cancer, while helping to maintain the quality of life, in patients with advanced disease. The phase 3 study was unblinded midway, allowing patients receiving the placebo to instead take the drug because of the favorable results.

The road not taken: life experiences in monozygotic twin pairs discordant for major depression.

In an effort to understand how environmental experiences contribute to risk for major depression (MD), we conducted joint autobiographical interviews with 14 pairs of monozygotic twins (mean age 51.2) rigorously discordant for a lifetime history of MD. Twelve of the pairs could be sorted into four broad categories. In two pairs, discordance was associated with a single traumatic event occurring to the affected twin. In seven pairs, the well twin had one stable, long-term, successful romantic relationship, whereas the affected co-twin had romantic reversals one or more of which precipitated depressive episodes. These pairs varied in the degree to which the romantic problems seemed to arise from bad luck or poor choices. In one pair, occupational difficulties were strongly related to discordance in experiences with MD. In two pairs, several mechanisms seemed to be at work. Discordance in the quality of intimate love relationships was the most common etiological factor revealed by interview in these discordant pairs, with single dramatic events and occupational problems being considerably rarer. Even in this best of natural experiments, the causal interrelationship between personality, environment and depressive episodes was not always clear. Many pairs illustrated the protective effects of planfulness and the malignant effect of cumulative continuity where early difficulties in relationships shaped the subsequent life course. These results speak both to the importance of environmental influences on human well-being and psychopathology, and the complexity of the causal paths underlying their effects.
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Harpagoside attenuates MPTP/MPP⁺ induced dopaminergic neurodegeneration and movement disorder via elevating glial cell line-derived neurotrophic factor.

Parkinson's disease is a chronic neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. New therapeutic approaches aiming at delaying or reversing the neurodegenerative process are under active investigations. In this work, we found that harpagoside, an iridoid purified from the Chinese medicinal herb Scrophularia ningpoensis, could not only prevent but also rescue the dopaminergic neurodegeneration in MPTP/MPP(+) intoxication with promising efficacy. Firstly, in cultured mesencephalic neurons, harpagoside significantly attenuated the loss of TH-positive neuron numbers and the shortening of axonal length. Secondly, in a chronic MPTP mouse model, harpagoside dose-dependently improved the loco-motor ability (rotarod test), increased the TH-positive neuron numbers in the substantia nigra pars compacta (unbiased stereological counting) and increased the striatal DAT density ((125) I-FP-CIT autoradiography). Thirdly, harpagoside markedly elevated the GDNF mRNA and GDNF protein levels in MPTP/MPP(+) lesioned models. However, the protecting effect of harpagoside on the dopaminergic degeneration disappeared when the intrinsic GDNF action was blocked by either the Ret inhibitor PP1 or the neutralizing anti-GDNF antibody. Taken together, we conclude that harpagoside attenuates the dopaminergic neurodegeneration and movement disorder mainly through elevating glial cell line-derived neurotrophic factor.

A molecular signature in blood identifies early Parkinson's disease.

The search for biomarkers in Parkinson's disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.

RESULTS:

The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60-0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08-1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75-0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60-0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14-1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. The performance of the five-gene classifier on the de novo PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22)), suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer's disease (n = 29).

CONCLUSIONS:

The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.

Influence of antipsychotic drugs (valproate) on human endogenous retrovirus (HERV) transcription in brain cells.

Human endogenous retroviruses (HERVs) have been associated with various neurological and neuropsychiatric disorders. Transcripts and proteins of at least three HERV groups, HERV-W, ERV9 and HERV-K(HML-2) have been detected repeatedly in brain samples or cerebrospinal fluid of patients with schizophrenia suggesting that alterations in HERV activity may play a role in etiopathogenesis. Current therapies otherwise include neuroleptics and/or antidepressants that may induce epigenetic alterations and thus influence HERV expression. To investigate the effects of these drugs on HERV transcriptional activity, HERV expression profiles of a broad range of human brain cell lines treated with valproic acid (VPA), haloperidol, risperidone, and clozapine were analyzed using a retrovirus-specific microarray and qRT-PCR. Investigation of 52 HERV subgroups revealed upregulation of several class I and class II HERV elements by VPA in a dose-dependent manner. The strongest effect was observed on HERV-W and ERV9 groups in the human glioblastoma cell lines SK-N-SH and SK-N-MC, respectively. The transcript level of HERV-K(HML-2) elements was not influenced. Transcription of HERV-W, ERV9 and HERV-K(HML-2) taxa was further quantified in postmortem brain samples of patients with schizophrenia, bipolar disorders and a healthy control group with regard to their medication. Patients with schizophrenia showed a significantly higher HERV-W transcription associated with VPA treatment. However in case of ERV9, enhanced transcript levels could not be explained solely by VPA treatment, since a slight increase was also found in untreated patients compared to healthy controls. HERV-K(HML-2) elements appeared to be upregulated in some patients with bipolar disorders independent from medication. In conclusion, these results suggest that antipsychotic medication may contribute to increased expression of distinct HERV taxa in patients with neuropsychiatric diseases.

The influence of DHEA pretreatment on prepulse inhibition and the HPA-axis stress response in rat offspring exposed prenatally to polyriboinosinic-polyribocytidylic-acid

Prenatal exposure to maternal infection may be associated with the development of neurodevelopmental disorders as well as increased susceptibility to the development of schizophrenia. Prenatal administration of polyriboinosinic-polyribocytidilic-acid, mimicking RNA virus exposure, has been shown to induce schizophrenia-like behavioral, neurochemical and neuorophysiological abnormalities in rodent offspring. In the present study PIC prenatal administration at gestation day 15 was associated with alterations in the acoustic-startle-response/prepulse-inhibition [ASR/PPI] and the HPA-axis stress response in rat offspring on day 90. We show that pretreatment with dehydroepiandrosterone (DHEA) reverses PIC-related ASR/PPI disruption in female rats and normalizes HPA-axis stress response in a united group of male and female rats. Further research in both animal and human studies is recommended in order to confirm these preliminary findings and their application to the understanding and management of schizophrenia and related conditions.

MicrobeWorld - TEDMED talk on the human microbiome

Elevated interleukin-18 serum levels in chronic schizophrenia: Association with psychopathology.

Schizophrenia is associated with various abnormalities in the immune system including elevated levels of Interleukin-18 (IL-18), a potent inflammatory cytokine in T-helper 1 (Th1) responses. The aim of this study was to assess the clinical significance of serum IL-18 levels in various stages of schizophrenia.

We measured serum IL-18 levels using a sandwich enzyme-linked immunosorbent assay (ELISA) from 78 never-medicated first-episode schizophrenia, 79 medicated chronic schizophrenia and 78 healthy control subjects. The symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS).

The chronic patients had significantly greater serum IL-18 levels than both first-episode patients and controls. Serum IL-18 was also positively correlated with the PANSS general psychopathology subscore in chronic schizophrenic patients
Our results showed elevated IL-18 pathway activity may be involved in the psychopathology of schizophrenia.

Early atherosclerotic plaques show evidence of infection by Chlamydia pneumoniae

Chlamydia pneumoniae (Cpn) could play an important role in the development of atherosclerosis. Cpn interferes with HIF-1alpha regulation in infected host cells during intracellular replication in hypoxia. We obtained carotid artery specimens with low (n=38), high (n=25) levels of stenosis and 10 middle cerebral arteries. Fifty eight percent of the carotids with low levels of stenosis showed evidence of the viable organism. Ninety one percent of the positive results were derived from pre-atheromatous lesions. Only 12 percent of plaques removed at endarterectomy showed the presence of Cpn DNA. All middle cerebral arteries failed to show evidence of live Chlamydia. Ninety one percent of sera from 22 endarterectomy patients failed to show the presence of Cpn antibodies. Immunohistology of carotid arteries with low levels of stenosis was used to confirm the presence of HIF-1alpha in infected specimens and showed a correlation between the over-expression of HIF-1alpha and Cpn in the plaque (p less than 0.05). Cpn might play an important role in activation and development of the initial stages of atherosclerotic lesions.

Caprospinol: discovery of a steroid drug candidate to treat Alzheimer's disease based on 22R-hydroxycholesterol structure and properties.

The overall ability of the brain to synthesise neuroactive steroids led us to the identification of compounds that would reproduce aspects of neurosteroid pharmacology. The rate-determining step in neurosteroid biosynthesis is the import of the substrate cholesterol into the mitochondria, where it is metabolised into pregnenolone via the intermediate 22R-hydroxycholesterol. The levels of translocator protein 18-kDa, mediating the import of cholesterol into mitochondria, correlated with increased pregnenolone formation and reduced levels of 22R-hydroxycholesterol in biopsies from Alzheimer's disease (AD), but not age-matched control, brains. 22R-hydroxycholesterol was shown to protect against β-amyloid (Aβ(42) )-induced neurotoxicity. In search of 22R-hydroxycholesterol stable analogues, we identified the naturally occurring heterospirostenol, (22R,25R)-20α-spirost-5-en-3β-yl hexanoate (caprospinol) and derivatives that protect neuronal cells against Aβ(1-42) neurotoxicity. The neuroprotective effect of caprospinol is the result of a combination of overlapping properties, including: (i) the ability to bind to Aβ(42) and reduce plaque formation in the brain in vivo; (ii) interaction with components of the mitochondria respiratory chain resulting in an anti-uncoupling effect; (iii) the capacity to scavenge Aβ(42) monomers present in mitochondria; and (iv) the property of being a sigma-1 receptor ligand. In vivo, caprospinol crosses the blood-brain barrier, accumulates in the brain, and restores cognitive impairment in a pharmacological rat model of AD. Caprospinol is stable, does not bind to known steroid receptors, is devoid of mutagenic and genotoxic properties, and is devoid of acute toxicity in rodents. The pharmacokinetics and pharmacodynamics of caprospinol were studied, and long-term toxicity studies are under investigation, aiming to develop this compound as a disease-modifying drug for the treatment of AD.

Preteen food choices may help predict eating disorders later

The study, presented recently at the International Conference on Eating Disorders in Austin, Texas, found the percentage of carbohydrates and fats girls ate at around the age of 11 helped to predict increasing dissatisfaction with the body by the age of 14. The researchers noted 15-year-old girls who ate little fat and a lot of carbohydrates were more likely to have erratic eating habits by age 19. This was particularly true for girls who were considered perfectionists.

PLoS Pathogens: Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis

Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases.

Intestinal microbiota determine severity of myocardial infarction in rats.

Signals from the intestinal microbiota are important for normal host physiology; alteration of the microbiota (dysbiosis) is associated with multiple disease states. We determined the effect of antibiotic-induced intestinal dysbiosis on circulating cytokine levels and severity of ischemia/reperfusion injury in the heart. Treatment of Dahl S rats with a minimally absorbed antibiotic vancomycin, in the drinking water, decreased circulating leptin levels by 38%, resulted in smaller myocardial infarcts (27% reduction), and improved recovery of postischemic mechanical function (35%) as compared with untreated controls. Vancomycin altered the abundance of intestinal bacteria and fungi, measured by 16S and 18S ribosomal DNA quantity. Pretreatment with leptin (0.12 μg/kg i.v.) 24 h before ischemia/reperfusion abolished cardioprotection produced by vancomycin treatment. Dahl S rats fed the commercially available probiotic product Goodbelly, which contains the leptin-suppressing bacteria Lactobacillus plantarum 299v, also resulted in decreased circulating leptin levels by 41%, smaller myocardial infarcts (29% reduction), and greater recovery of postischemic mechanical function (23%). Pretreatment with leptin (0.12 μg/kg i.v.) abolished cardioprotection produced by Goodbelly. This proof-of-concept study is the first to identify a mechanistic link between changes in intestinal microbiota and myocardial infarction and demonstrates that a probiotic supplement can reduce myocardial infarct size.
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Autoantibodies to αS1-casein are induced by breast-feeding.

The generation of antibodies is impaired in newborns due to an immature immune system and reduced exposure to pathogens due to maternally derived antibodies and placental functions. During nursing, the immune system of newborns is challenged with multiple milk-derived proteins. Amongst them, caseins are the main constituent. In particular, human αS1-casein (CSN1S1) was recently shown to possess immunomodulatory properties. We were thus interested to determine if auto-antibodies to CSN1S1 are induced by breast-feeding and may be sustained into adulthood.

62 sera of healthy adult individuals who were (n = 37) or were not (n = 25) breast-fed against human CSN1S1 were investigated by a new SD (surface display)-ELISA. For cross-checking, these sera were tested for anti Epstein-Barr virus (EBV) antibodies.
IgG-antibodies were predominantly detected in individuals who had been nursed. At a cut-off value of 0.4, the SD-ELISA identified individuals with a history of having been breast-fed with a sensitivity of 80% and a specificity of 92%. Under these conditions, 35 out of 37 sera from healthy donors, who where breast-fed, reacted positively but only 5 sera of the 25 donors who were not breast-fed. The duration of breast-feeding was of no consequence to the antibody reaction as some healthy donors were only short term breast-fed (5 days minimum until 6 weeks maximum), but exhibited significant serum reaction against human CSN1S1 nonetheless.

CONCLUSION:

We postulate that human CSN1S1 is an autoantigen> The antigenicity is orally determined, caused by breast-feeding, and sustained into adulthood.

Certain Features Of Autism May Be Improved By Antioxidant (N-acetyl cysteine)

The antioxidant, N-Acetylcysteine, or NAC, lowered irritability in children with autism as well as reducing the children's repetitive behaviors. The researchers emphasized that the findings must be confirmed in a larger trial before NAC can be recommended for children with autism.

Injection offers hope for treating auto-immune disease

Australian researchers have uncovered a potential new way to regulate the body’s natural immune response, offering hope of a simple and effective treatment for auto-immune diseases.The new approach involves increasing good regulating cells in the body, unlike most current research which focuses on stopping “bad” or “effector” cells, says lead researcher Dr. Suzanne Hodgkinson, from UNSW’s Faculty of Medicine and Liverpool Hospital.
The researchers induced the body’s T-cell front-line defences by injecting cell-signalling proteins called cytokines, in particular cytokine Interleukin-5 (II-5 cytokine).