Aspirin Tied To Lower Risk For Liver Cancer And Death From Liver Disease

A new study from the US finds that use of aspirin is tied to a reduced risk for hepatocellular carcinoma, the most common type of primary liver cancer, and also to a reduced risk of death from chronic liver disease.

Controversial chelation treatment for autism may do more harm than good, researchers find

A controversial treatment for autism spectrum disorder (ASD) is not only ineffective but may be harmful, according to a study conducted by Baylor University researchers.

Read more at: http://medicalxpress.com/news/2012-11-controversial-treatment-autism-good.html#jCp

Promising drug slows down advance of Parkinson's disease and improves symptoms

Treating Parkinson's disease patients with the experimental drug GM1 ganglioside improved symptoms and slowed their progression during a two and a half-year trial, Thomas Jefferson University researchers report in a new study published online November 28 in the Journal of the Neurological Sciences.

Read more at: http://medicalxpress.com/news/2012-11-drug-advance-parkinson-disease-symptoms.html#jCp

Molecular root of 'exhausted' T cells in chronic viral infection

When you get an acute infection, such as influenza, the body generally responds with a coordinated response of immune-cell proliferation and attack that rapidly clears the pathogen. Then, their mission done, the immune system stands down, leaving a population of sentinel memory cells to rapidly redeploy the immune system in the event of reinfection.But what about chronic infection? In the case of such pathogens as hepatitis C, HIV, and malaria, the body and the pathogen essentially fight to a prolonged stalemate, neither able to gain an advantage. Over time, however, the cells become "exhausted" and the immune system can collapse, giving the pathogen the edge.

Read more at: http://medicalxpress.com/news/2012-11-molecular-root-exhausted-cells-chronic.html#jCp

Increased 3-Hydroxykynurenine serum concentrations differentiate Alzheimer's disease patients from controls.

Increased degradation of tryptophan (TRP) through the kynurenine (KYN) pathway (KP) is known to be involved in the molecular mechanisms resulting in the neuropathogenesis of Alzheimer's disease (AD). Activation of the KP leads to the production of neurotoxic metabolites 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) by immune cells and neuroprotective derivates kynurenic acid (KYNA) and picolinic acid (PIC) by astrocytes and neurons. We therefore investigated whether an imbalance between neurotoxic and neuroprotective kynurenine metabolites could be detected in patients with AD. We measured serum levels of TRP, KYNA, 3-HK, PIC and QUIN in 20 patients with AD and for comparison in 20 patients with major depression, and 19 subjectively cognitive impaired subjects. Serum levels of 3-HK were markedly increased in AD patients compared to the comparison groups (p < .0001). Serum levels of the other KP metabolites were not significantly different between groups. Our data indicate an increased production of the neurotoxic KP metabolite 3-HK in AD. In contrast to its downstream metabolites QUIN and PIC, 3-HK can cross the blood-brain barrier via an active transport process. Our data therefore indicate an enhanced availability of 3-HK in the brain of AD patients, which may be related to the previously reported higher production of QUIN in AD brains.

Women 16-49 at risk of multiple pollutants, which could harm brain development of fetuses and babies

In a recent study, more than half of women of childbearing age had median or higher levels of at least two of three pollutants that could harm brain development. Nearly 23 percent of American women of childbearing age met or exceeded the median blood levels for all three environmental chemical pollutants -- lead, mercury, and PCBs -- tracked in an analysis of data on thousands of women by Brown University researchers. All but 17.3 percent of the women aged 16 to 49 were at or above the median blood level for one or more of these chemicals, which are passed to fetuses through the placenta and to babies through breast milk.

1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients.

As immune defects in amyloid-β (Aβ) phagocytosis and degradation underlie Aβ deposition and inflammation in Alzheimer's disease (AD) brain, better understanding of the relation between Aβ phagocytosis and inflammation could lead to promising preventive strategies. We tested two immune modulators in peripheral blood mononuclear cells (PBMCs) of AD patients and controls: 1α,25(OH)2-vitamin D3 (1,25D3) and resolvin D1 (RvD1). Both 1,25D3 and RvD1 improved phagocytosis of FAM-Aβ by AD macrophages and inhibited fibrillar Aβ-induced apoptosis. The action of 1,25D3 depended on the nuclear vitamin D and the protein disulfide isomerase A3 receptors, whereas RvD1 required the chemokine receptor, GPR32. The activities of 1,25D3 and RvD1 commonly required intracellular calcium, MEK1/2, PKA, and PI3K signaling; however, the effect of RvD1 was more sensitive to pertussis toxin. In this case study, the AD patients: a) showed significant transcriptional up regulation of IL1RN, ITGB2, and NFκB; and b) revealed two distinct groups when compared to controls: group 1 decreased and group 2 increased transcription of TLRs, IL-1, IL1R1 and chemokines. In the PBMCs/macrophages of both groups, soluble Aβ (sAβ) increased the transcription/secretion of cytokines (e.g., IL1 and IL6) and chemokines (e.g., CCLs and CXCLs) and 1,25D3/RvD1 reversed most of the sAβ effects. However, they both further increased the expression of IL1 in the group 1, sβ-treated cells. We conclude that in vitro, 1,25D3 and RvD1 rebalance inflammation to promote Aβ phagocytosis, and suggest that low vitamin D3 and docosahexaenoic acid intake and/or poor anabolic production of 1,25D3/RvD1 in PBMCs could contribute to AD onset/pathology.

Excessive Extracellular Volume Reveals a Neurodegenerative Pattern in Schizophrenia Onset


Diffusion MRI has been successful in identifying the existence of white matter abnormalities in schizophrenia in vivo. However, the role of these abnormalities in the etiology of schizophrenia is not well understood. Accumulating evidence from imaging, histological, genetic, and immunochemical studies support the involvement of axonal degeneration and neuroinflammation—ubiquitous components of neurodegenerative disorders—as the underlying pathologies of these abnormalities. Nevertheless, the current imaging modalities cannot distinguish neuroinflammation from axonal degeneration, and therefore provide little specificity with respect to the pathophysiology progression and whether it is related to a neurodegenerative process. Free-water imaging is a new methodology that is sensitive to water molecules diffusing in the extracellular space. Excessive extracellular volume is a surrogate biomarker for neuroinflammation and can be separated out to reveal abnormalities such as axonal degeneration that affect diffusion characteristics in the tissue. We applied free-water imaging on diffusion MRI data acquired from schizophrenia-diagnosed human subjects with a first psychotic episode. We found a significant increase in the extracellular volume in both white and gray matter. In contrast, significant signs of axonal degeneration were limited to focal areas in the frontal lobe white matter. Our findings demonstrate that neuroinflammation is more prominent than axonal degeneration in the early stage of schizophrenia, revealing a pattern shared by many neurodegenerative disorders, in which prolonged inflammation leads to axonal degeneration. These findings promote anti-inflammatory treatment for early diagnosed schizophrenia patients.

Can Worms Alleviate Autism? | The Scientist Magazine®

A growing body of evidence suggests that in some patients, increased inflammation contributes to autistic behaviors. Now, a Phase I clinical trial is under way to measure the effects of infecting autistic patients with a non-pathogenic parasitic worm. Scientists at Montefiore Medical Center at the Albert Einstein College of Medicine in New York and biotech company Coronado Bioscienceswill test the hypothesis that treating these patients with Trichuris suis, a non-pathogenic parasitic pig whipworm, will dampen their immune responses and ameliorate repetitive and irritable behaviors.

Lipid and protein oxidation in female patients with chronic fatigue syndrome.


Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS.

MATERIAL AND METHODS:

Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined.

RESULTS:

The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol.

CONCLUSIONS:

The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.

Genetic risk score predicting accelerated progression from mild cognitive impairment to Alzheimer's disease.

Aside from APOE, the genetic factors that influence the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) remain largely unknown. We assessed whether a genetic risk score (GRS), based on eight non-APOE genetic variants previously associated with AD risk in genome-wide association studies, is associated with either risk of conversion or with rapid progression from MCI to AD. Among 288 subjects with MCI, follow-up (mean 26.3 months) identified 118 MCI-converters to AD and 170 MCI-nonconverters. We genotyped ABCA7 rs3764650, BIN1 rs744373, CD2AP rs9296559, CLU rs1113600, CR1 rs1408077, MS4A4E rs670139, MS4A6A rs610932, and PICALM rs3851179. For each subject we calculated a cumulative GRS, defined as the number of risk alleles (range 0-16) with each allele weighted by the AD risk odds ratio. GRS was not associated with risk of conversion from MCI to AD. However, MCI-converters to AD harboring six or more risk alleles (second and third GRS tertiles) progressed twofold more rapidly to AD when compared with those with less than six risk alleles (first GRS tertile). Our GRS is a first step toward development of prediction models for conversion from MCI to AD that incorporate aggregate genetic factors.

Valine, a branched-chain amino Acid, reduced HCV viral load and led to eradication of HCV by interferon therapy in a decompensated cirrhotic patient.

A decreased serum level of branched-chain amino acid (BCAA) is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV) load has never been reported. Here, we first describe a case of HCV-related advanced liver cirrhosis that was treated by an oral valine agent. The administration of valine resulted in an improvement of fatigue and a reduction in hepatic fibrosis indexes as well as serum α-fetoprotein level. Furthermore, a marked reduction in HCV RNA levels was seen after valine treatment. The patient was then treated by interferon β, resulting in the successful eradication of chronic HCV infection. Thus, valine may be involved in the reduction of HCV viral load and could support a sustained virologic response to interferon therapy.
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Researchers show possible trigger for MS nerve damage

High-resolution real-time images show in mice how nerves may be damaged during the earliest stages of multiple sclerosis. The results suggest that the critical step happens when fibrinogen, a blood-clotting protein, leaks into the central nervous system and activates immune cells called microglia.

Read more at: http://medicalxpress.com/news/2012-11-trigger-ms-nerve.html#jCp

Protein injection points to muscular dystrophy treatment

Scientists have discovered that injecting a novel human protein into muscle affected by Duchenne muscular dystrophy significantly increases its size and strength, findings that could lead to a therapy akin to the use of insulin by diabetics. These results were published today in the Proceedings of the National Academy of Sciences by Dr. Julia von Maltzahn and Dr. Michael Rudnicki, the Ottawa scientist who discovered muscle stem cells in adults.

Read more at: http://medicalxpress.com/news/2012-11-protein-muscular-dystrophy-treatment.html#jCp

New study shows need for caution, as drugs like Prozac can have some adverse effects on babies

(Medical Xpress)—Depression—one of the most crippling and costly illnesses in the United States—is the leading cause of disability among people ages 15 to 44. Since Prozac hit the market in 1987, many Americans have relied on antidepressant medications to control their symptoms. One in 10 of us takes antidepressants, making them the third most common prescription drug, after painkillers and high blood pressure pills, according to a 2011 report from the National Center for Health Statistics.The researchers also found studies linking fetal exposure to the antidepressants with cardiac and respiratory problems, growth and developmental delays—and even autism.

Read more at: http://medicalxpress.com/news/2012-11-caution-drugs-prozac-adverse-effects.html#jCp


Global High Fructose Corn Syrup Use May Be Fueling Diabetes Increase | Observations, Scientific American Blog Network

A new study of 43 countries in Global Public Health, published online November 27, found that adult type-2 diabetes is 20 percent higher in countries that consume large quantities of high fructose corn syrup. “The study adds to a growing body of scientific literature that indicates HFCS consumption may result in negative health consequences distinct from and more deleterious than natural sugar,” Michael Goran, of the University of Southern California Department of Preventive Medicine and co-author of the new study, said in a prepared statement.

Scientists Identify Unknown Proteins Of The Herpesvirus

The genome encodes the complete information needed by an organism, including that required for protein production. Viruses, which are up to a thousand times smaller than human cells, have considerably smaller genomes. Using a type of herpesvirus as a model system, the scientists of the Max Planck Institute of Biochemistry in Martinsried near Munich and their collaboration partners at the University of California in San Francisco have shown that the genome of this virus contains much more information than previously assumed. The researchers identified several hundred novel proteins, many of which were surprisingly small. 

Chemical soup clouds connection between toxins and poor health : Nature News & Comment

From plastics to flame retardants, the ubiquitous chemicals of our daily lives have raised public health concerns like never before. Inside the Beltway, however, data-crunching scientists are often no match for industry lobbyists and corporate lawyers. The exception, no doubt, is Linda Birnbaum, the toxicologist who leads, two little-known scientific agencies, the National Institute of Environmental Health Services (NIEHS) and the National Toxicology Program .

Researchers find chemical 'switches' for neurodegenerative diseases

Dr. Parker's team found that deleting the TDP-43 and FUS genes, which produce the proteins of the same name, reduced neurodegeneration caused by mutant huntingtin. They then confirmed their findings in the cell of a mammal cell, again by using models. The next step was then to determining how neuroprotection works. TDP-43 targets a chemical called progranulin, a protein linked to dementia. "We demonstrated that removing progranulin from either worms or cells enhanced huntingtin toxicity, but increasing progranulin reduced cell death in mammalian neurons. This points towards progranulin as a potent neuroprotective agent against mutant huntingtin neurodegeneration," Dr. Parker said. The researchers will need to do further testing this in more complex biological models to determine if the same chemical switches work in all mammals. If they do, then progranulin treatment may slow disease onset or progression in Huntington's disease patients

JAMA Network | Archives of General Psychiatry | Microglial Activation in Young Adults With Autism Spectrum DisorderMicroglia in Young Adults With ASD

A growing body of evidence suggests that aberrant immunologic systems underlie the pathophysiologic characteristics of autism spectrum disorder (ASD). However, to our knowledge, no information is available on the patterns of distribution of microglial activation in the brain in ASD.
Objectives  To identify brain regions associated with excessively activated microglia in the whole brain, and to examine similarities in the pattern of distribution of activated microglia in subjects with ASD and control subjects.
Design  Case-control study using positron emission tomography and a radiotracer for microglia—[11C](R)-(1-[2-chrorophynyl]- N-methyl- N-[1-methylpropyl]-3 isoquinoline carboxamide) ([11C](R)-PK11195).
Setting  Subjects recruited from the community.
Participants  Twenty men with ASD (age range, 18-31 years; mean [SD] IQ, 95.9 [16.7]) and 20 age- and IQ-matched healthy men as controls. Diagnosis of ASD was made in accordance with the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised.
Main Outcome Measures  Regional brain [11C](R)-PK11195 binding potential as a representative measure of microglial activation.
Results  The [11C](R)-PK11195 binding potential values were significantly higher in multiple brain regions in young adults with ASD compared with those of controls (P < .05, corrected). Brain regions with increased binding potentials included the cerebellum, midbrain, pons, fusiform gyri, and the anterior cingulate and orbitofrontal cortices. The most prominent increase was observed in the cerebellum. The pattern of distribution of [11C](R)-PK11195 binding potential values in these brain regions of ASD and control subjects was similar, whereas the magnitude of the [11C](R)-PK11195 binding potential in the ASD group was greater than that of controls in all regions.
Conclusions  Our results indicate excessive microglial activation in multiple brain regions in young adult subjects with ASD. The similar distribution pattern of regional microglial activity in the ASD and control groups may indicate augmented but not altered microglial activation in the brain in the subjects with ASD.

JAMA Network | Archives of General Psychiatry | Traffic-Related Air Pollution, Particulate Matter, and AutismAir Pollution, Particulate Matter, and Autism

Autism is a heterogeneous disorder with genetic and environmental factors likely contributing to its origins. Examination of hazardous pollutants has suggested the importance of air toxics in the etiology of autism, yet little research has examined its association with local levels of air pollution using residence-specific exposure assignments.
Objective  To examine the relationship between traffic-related air pollution, air quality, and autism.
Design  This population-based case-control study includes data obtained from children with autism and control children with typical development who were enrolled in the Childhood Autism Risks from Genetics and the Environment study in California. The mother's address from the birth certificate and addresses reported from a residential history questionnaire were used to estimate exposure for each trimester of pregnancy and first year of life. Traffic-related air pollution was assigned to each location using a line-source air-quality dispersion model. Regional air pollutant measures were based on the Environmental Protection Agency's Air Quality System data. Logistic regression models compared estimated and measured pollutant levels for children with autism and for control children with typical development.
Setting  Case-control study from California.
Participants  A total of 279 children with autism and a total of 245 control children with typical development.
Main Outcome Measures  Crude and multivariable adjusted odds ratios (AORs) for autism.
Results  Children with autism were more likely to live at residences that had the highest quartile of exposure to traffic-related air pollution, during gestation (AOR, 1.98 [95% CI, 1.20-3.31]) and during the first year of life (AOR, 3.10 [95% CI, 1.76-5.57]), compared with control children. Regional exposure measures of nitrogen dioxide and particulate matter less than 2.5 and 10 μm in diameter (PM2.5 and PM10) were also associated with autism during gestation (exposure to nitrogen dioxide: AOR, 1.81 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.08 [95% CI, 1.93-2.25]; exposure to PM10: AOR, 2.17 [95% CI, 1.49-3.16) and during the first year of life (exposure to nitrogen dioxide: AOR, 2.06 [95% CI, 1.37-3.09]; exposure to PM2.5: AOR, 2.12 [95% CI, 1.45-3.10]; exposure to PM10: AOR, 2.14 [95% CI, 1.46-3.12]). All regional pollutant estimates were scaled to twice the standard deviation of the distribution for all pregnancy estimates.
Conclusions  Exposure to traffic-related air pollution, nitrogen dioxide, PM2.5, and PM10 during pregnancy and during the first year of life was associated with autism. Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal.

Lack of nutrients and metabolic syndrome linked to different subtypes of depression

A low intake of folate and vitamin B12 increases the risk of melancholic depressive symptoms, according to a study among nearly 3,000 middle-aged and elderly Finnish subjects. On the other hand, non-melancholic depressive symptoms are associated with an increased risk for the metabolic syndrome. Based on these new observations, melancholic and non-melancholic depression may be separate depressive subtypes with different etiologies in terms of proinflammation and diet. The study was the first to look at these depressive sub-types separately.

Read more at: http://medicalxpress.com/news/2012-11-lack-nutrients-metabolic-syndrome-linked.html#jCp

Combination of two pharmaceuticals proves effective in the treatment of multiple sclerosis

The Cyclosporine and FK506 (tacrolimus)-series have been utilized in a chemically slightly altered form as immunosuppressant medications for a long time. Both suppress the cellular immune defenses. This effect is necessary in conjunction with organ transplants, but otherwise problematic for the organism. The specific combination of the two substances amplifies the protective effect on the nerve cells thanks to different but synergistic efficacy mechanisms. The impact on the immune defense is reduced at the same time, which results in fewer side effects

Read more at: http://medicalxpress.com/news/2012-11-combination-pharmaceuticals-effective-treatment-multiple.html#jCp

Previously Discarded, Human-Specific 'Junk' DNA Represents Untapped Resource In The Study Of Diseases Like Alzheimer's And Autism

Short snippets of DNA found in human brain tissue provide new insight into human cognitive function and risk for developing certain neurological diseases, according to researchers from the Departments of Psychiatry and Neuroscience at Mount Sinai School of Medicine. The findings are published in PLoS Biology

Alzheimer's disease in mice alleviated promising therapeutic approach for humans

Pathological changes typical of Alzheimer's disease were significantly reduced in mice by blockade of an immune system transmitter. A research team from Charité - Universitätsmedizin Berlin and the University of Zurich has just published a new therapeutic approach in fighting Alzheimer's disease in the current issue of Nature Medicine. This approach promises potential in prevention, as well as in cases where the disease has already set in.The strongest effects were demonstrated after reducing amyloid-ß by approximately 65 percent, when the immune molecule p40 was affected, which is a component of signalling for the cytokines interleukin IL12 and IL23.

Read more at: http://medicalxpress.com/news/2012-11-alzheimer-disease-mice-alleviated-therapeutic.html#jCp

MicrobeWorld - Human gut may engineer its bacterial environment via secretions

The human gut may help control the bacterial populations that live within it via secretions that kill some bacteria while supporting others, according to a study published Tuesday in the journal PLoS Biology.

The gut is an enormously complex environment inhabited not only by human cells but also by trillions of bacteria. Some of those bacteria actively aid us by improving digestion (hence the term "probiotic"), producing useful compounds like vitamins, or providing resistance against pathogens.

Short DNA strands in genome may be key to understanding human cognition and diseases

ScienceDaily (Nov. 21, 2012) — Short snippets of DNA found in human brain tissue provide new insight into human cognitive function and risk for developing certain neurological diseases, according to researchers from the Departments of Psychiatry and Neuroscience at Mount Sinai School of Medicine.

PUFAs At Work | The Scientist Magazine® Poster

Polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), function in both enzymatic and nonenzymatic pathways to regulate gene expression.

Scientists report a potential new treatment to prevent strokes

(Medical Xpress)—Scientists may have discovered a new way to prevent strokes in high risk patients, according to research from the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW).

Read more at: http://medicalxpress.com/news/2012-11-scientists-potential-treatment.html#jCp

Genetic Influences on Disease Remain Hidden

The quest to find genes that strongly influence whether people will develop common diseases is turning out to be even more difficult than some researchers had expected. At the annual meeting of the American Society of Human Genetics, several huge DNA sequencing studies aimed at ferreting out genetic variants behind diseases such as diabetes and heart disease reported initial findings. This work shows that a popular hypothesis in the field—that the general population carries somewhat rare variants that greatly increase or decrease a person's disease risk—is not yet panning out.
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Taste in the Mouth, Gut, and Airways | The Scientist Magazine®

Taste-bud receptors, primarily on the tongue, sense the qualities of salty, sour, bitter, sweet, and umami (the taste of glutamate). While sweet, umami, and salty foods provide pleasurable sensations that drive the intake of carbohydrates, amino acids, and sodium, the tastes of bitter and sour inhibit intake of potentially toxic substances and strong acids.
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New Epilepsy Drug From Fatty Acids

Scientists in London have identified specific fatty acids that could form the basis of new drugs to treat epilepsy in children and adults. They suggest drugs based on them could provide similar epilepsy control as a ketogenic diet, a treatment often prescribed for children with severe drug-resistant epilepsy and which mimics aspects of starvation but with troubling side effects.

Methylome modifications offer new measure of our 'biological' age

In a new study of DNA methylation,  researchers at the University of California, San Diego School of Medicine, with colleagues elsewhere, describe markers and a model that quantify how aging occurs at the level of genes and molecules, providing not just a more precise way to determine how old someone is, but also perhaps anticipate or treat ailments and diseases that come with the passage of time.

Read more at: http://medicalxpress.com/news/2012-11-methylome-modifications-biological-age.html#jCp

Molecular Psychiatry - An environmental analysis of genes associated with schizophrenia: hypoxia and vascular factors as interacting elements in the neurodevelopmental model

Investigating and understanding gene–environment interaction (G × E) in a neurodevelopmentally and biologically plausible manner is a major challenge for schizophrenia research. Hypoxia during neurodevelopment is one of several environmental factors related to the risk of schizophrenia, and links between schizophrenia candidate genes and hypoxia regulation or vascular expression have been proposed. Given the availability of a wealth of complex genetic information on schizophrenia in the literature without knowledge on the connections to environmental factors, we now systematically collected genes from candidate studies (using SzGene), genome-wide association studies (GWAS) and copy number variation (CNV) analyses, and then applied four criteria to test for a (theoretical) link to ischemia–hypoxia and/or vascular factors. In all, 55% of the schizophrenia candidate genes (n=42 genes) met the criteria for a link to ischemia–hypoxia and/or vascular factors. Genes associated with schizophrenia showed a significant, threefold enrichment among genes that were derived from microarray studies of the ischemia–hypoxia response (IHR) in the brain. Thus, the finding of a considerable match between genes associated with the risk of schizophrenia and IHR and/or vascular factors is reproducible. An additional survey of genes identified by GWAS and CNV analyses suggested novel genes that match the criteria. Findings for interactions between specific variants of genes proposed to be IHR and/or vascular factors with obstetric complications in patients with schizophrenia have been reported in the literature. Therefore, the extended gene set defined here may form a reasonable and evidence-based starting point for hypothesis-based testing of G × E interactions in clinical genetic and translational neuroscience studies.

Beneficial microbes are 'selected and nurtured' in the human gut

ScienceDaily (Nov. 20, 2012) — Animals, including humans, actively select the gut microbes that are the best partners and nurture them with nutritious secretions, suggests a new study led by Oxford University, and published November 20 in the open-access journal PLOS Biology.

Autism-like behaviors reversed in mice: New hope for understanding autism

English: diagram showing how the translation o...
English: diagram showing how the translation of the mRNA and the synthesis of proteins is made by ribosomes. Français : Diagramme montrant comment la traduction de l'ARN messager et la synthèse protéique se font dans les ribosomes. Légendes en anglais. (Photo credit: Wikipedia)
Regulation of protein synthesis, also termed mRNA translation, is the process by which cells manufacture proteins. This mechanism is involved in all aspects of cell and organism function. A new study in mice has found that abnormally high synthesis of a group of neuronal proteins called neuroligins results in symptoms similar to those diagnosed in ASD. The study also reveals that autism-like behaviors can be rectified in adult mice with compounds inhibiting protein synthesis, or with gene-therapy targeting neuroligins. Their results are published in the journal Nature.
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Aberrant light directly impairs mood and learning through melanopsin-expressing neurons : Nature : Nature Publishing Group

The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep–wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.
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"Obese But Happy" Gene Discovered By Scientists

MNT: Why are some people happier than others? The gene FTO, which is a significant gene associated with obesity, is also linked to an 8% decrease in a person's chances of developing depression, according to researchers from McMaster University in their recent study published in Molecular Psychiatry

Scientists identify inhibitor of myelin formation in the central nervous system

Scientists at the Mainz University Medical Center have discovered another molecule that plays an important role in regulating myelin formation in the central nervous system. Myelin promotes the conduction of nerve cell impulses by forming a sheath around their projections, the so-called axons, at specific locations – acting like the plastic insulation around a power cord. The research team, led by Dr. Robin White of the Institute of Physiology and Pathophysiology at the University Medical Center of Johannes Gutenberg University Mainz, recently published their findings in the prestigious journal EMBO Reports.

Read more at: http://medicalxpress.com/news/2012-11-scientists-inhibitor-myelin-formation-central.html#jCp

Futurity.org – Flame retardants linked to delays in kids

Experts report a link between exposure to a common flame retardant and deficits in motor and cognitive development among school-aged children.The findings add to growing health concerns over this class of endocrine-disrupting compounds, which are commonly found in US households. PBDEs, or polybrominated diphenyl ethers, are used in foam furniture, electronics, carpets, upholstery, and other consumer products. The chemicals easily leach out into the environment, are inhaled or ingested through dust, and then accumulate in human fat cells.
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Pathways Of Motivation Through Brain Illuminated By Optogenetics

Optogenetics was used to analyse pathways from the prefrontal contex to brainstem areas such as the raphe and habenula which seem to be able to control motivational behaviour: This is severely disrupted in depression.

JCI - Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.

B cell exchange across the blood-brain barrier in multiple sclerosis.

In multiple sclerosis (MS) pathogenic B cells likely act on both sides of the blood-brain barrier (BBB). However, it is unclear whether antigen-experienced B cells are shared between the CNS and the peripheral blood (PB) compartments. We applied deep repertoire sequencing of IgG heavy chain variable region genes (IgG-VH) in paired cerebrospinal fluid and PB samples from patients with MS and other neurological diseases to identify related B cells that are common to both compartments. For the first time to our knowledge, we found that a restricted pool of clonally related B cells participated in robust bidirectional exchange across the BBB. Some clusters of related IgG-VH appeared to have undergone active diversification primarily in the CNS, while others have undergone active diversification in the periphery or in both compartments in parallel. B cells are strong candidates for autoimmune effector cells in MS, and these findings suggest that CNS-directed autoimmunity may be triggered and supported on both sides of the BBB. These data also provide a powerful approach to identify and monitor B cells in the PB that correspond to clonally amplified populations in the CNS in MS and other inflammatory states.

Study identifies a potential cause of Parkinson's disease

Conti and his team were looking for biological pathways that could connect the immune system's inflammatory response to the damage seen in dopaminergic neurons. After searching human genomics databases, the team's attention was caught by a gene encoding a protein known as interleukin-13 receptor alpha 1 chain (IL-13Ra1), as it is located in the PARK12 locus, which has been linked to Parkinson's. IL-13rα1 is a receptor chain mediating the action of interleukin 13 (IL-13) and interleukin 4 (IL-4), two cytokines investigated for their role as mediators of allergic reactions and for their anti-inflammatory action.

Read more at: http://medicalxpress.com/news/2012-11-potential-parkinson-disease.html#jCp

Multiple sclerosis 'immune exchange' between brain and blood is uncovered

The cells in question, obtained from spinal fluid and blood samples, are called B cells, which normally help to clear foreign infections from the body but sometimes react strongly with the body itself. One of the current theories of multiple sclerosis, which strikes hundreds of thousands of Americans and millions more worldwide, holds that the disease manifests when self-reactive B cells in the brain become activated and cause inflammation there. The apparent exchange of the cells between the brain and the blood may be a key to unlocking better treatments and diagnostics, because the activated B cells causing problems in the brain may be accessible when they move from the brain to the periphery.

Read more at: http://medicalxpress.com/news/2012-11-multiple-sclerosis-immune-exchange-brain.html#jCp

Brain displays an intrinsic mechanism for fighting infection

(Medical Xpress)—White blood cells have long reigned as the heroes of the immune system. When an infection strikes, the cells, produced in bone marrow, race through the blood to fight off the pathogen. But new research is emerging that individual organs can also play a role in immune system defense, essentially being their own hero. In a study examining a rare and deadly brain infection, scientists at The Rockefeller University have found that the brain cells of healthy people likely produce their own immune system molecules, demonstrating an "intrinsic immunity" that is crucial for stopping an infection.

Read more at: http://medicalxpress.com/news/2012-11-brain-intrinsic-mechanism-infection.html#jCp

Nanoparticles Stop Multiple Sclerosis In Mice

A breakthrough new experimental treatment that uses nanoparticles covered with proteins to trick the immune system, managed to stop it attacking myelin and halt disease progression in mice with relapsing remitting multiple sclerosis (MS). The researchers say the approach may also be applicable to other auto-immune diseases such as asthma and type 1 diabetes. 

Month of birth effect: Give pregnant women vitamin D supplements to ward off multiple sclerosis, say researchers

ScienceDaily (Nov. 14, 2012) — The risk of developing multiple sclerosis (MS) is highest in the month of April, and lowest in October, indicates an analysis of the available evidence, published online in the Journal of Neurology Neurosurgery and Psychiatry.The findings, which include several populations at latitudes greater than 52 degrees from the equator for the first time, strongly implicate maternal exposure to vitamin D during pregnancy.

Intracerebral propagation of Alzheimer’s disease: Strengthening evidence of a herpes simplex virus etiology

A faulty human protein, abnormally phosphorylated tau, was recently publicized to spread “like a virus” from neuron to neuron in Alzheimer’s patients’ brains. For several decades, we have been amassing arguments showing that herpes simplex virus type 1 (HSV-1), not p-tau, propagates this interneuronal, transsynaptic pathologic cascade.

Methods

We reiterate convincing data from our own (and other) laboratories, reviewing the first anatomic foothold neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic immunosurveillance cellularity of the trigeminal ganglia wherein HSV-1 awakens from latency to reactivate; the inabilities of p-tau protein's physical properties to promote it to jump synapses; the amino acid homology between human p-tau and VP22, a key target for phosphorylation by HSV serine/threonine–protein kinase UL13; and the exosomic secretion of HSV-1–infected cells’ L-particles, attesting to the cell-to-cell passage of microRNAs of herpesviruses.

Results

The now-maturing construct that reactivated HSV-1 best accounts for the intracerebral propagation of AD changes in the human brain should at last seem highly attractive. This hypothesis might even explain statins' apparent mechanism in some studies for lowering AD incidence.

Conclusion

Provided that funding agencies will quickly ignite a new realm of investigation, the rejuvenated enthusiasm for testing this optimistic construct holds incalculable potential for rapid, efficacious clinical application, through already available and relatively safe antiviral therapeutics.

GEN | News Highlights:Gene Predicts Time of Death


A common variant in the perion gene PER1 separates early birds from night owls, and can even predict someone’s hour of death.
The findings—published in the November issue of the journal Annals of Neurology—could help people schedule anything from work to medical treatments, while offering clues to the conditions of vulnerable patients.

Complement Receptor 1 Variants Confer Protection from Severe Malaria in Odisha, India.


In Plasmodium falciparum infection, complement receptor-1 (CR1) on erythrocyte's surface and ABO blood group play important roles in formation of rosettes which are presumed to be contributory in the pathogenesis of severe malaria. Although several studies have attempted to determine the association of CR1 polymorphisms with severe malaria, observations remain inconsistent. Therefore, a case control study and meta-analysis was performed to address this issue.

METHODS:

Common CR1 polymorphisms (intron 27 and exon 22) and blood group were typed in 353 cases of severe malaria (SM) [97 cerebral malaria (CM), 129 multi-organ dysfunction (MOD), 127 non-cerebral severe malaria (NCSM)], 141 un-complicated malaria and 100 healthy controls from an endemic region of Odisha, India. Relevant publications for meta-analysis were searched from the database.

RESULTS:

The homozygous polymorphisms of CR1 intron 27 and exon 22 (TT and GG) and alleles (T and G) that are associated with low expression of CR1 on red blood cells, conferred significant protection against CM, MOD and malaria deaths. Combined analysis showed significant association of blood group B/intron 27-AA/exon 22-AA with susceptibility to SM (CM and MOD). Meta-analysis revealed that the CR1 exon 22 low expression polymorphism is significantly associated with protection against severe malaria.

CONCLUSIONS:

The results of the present study demonstrate that common CR1 variants significantly protect against severe malaria in an endemic area.

Chronic fatigue syndrome: System under stress

"ScienceDaily (Nov. 14, 2012) — Australian researchers have discovered for the first time that reduced heart rate variability -- or changes in heart beat timing -- best predicts cognitive disturbances, such as concentration difficulties commonly reported by people with chronic fatigue syndrome (CFS). This adds to the growing body of evidence linking autonomic nervous system imbalance to symptoms of this poorly understood disorder."

'via Blog this'

Vitamin D deficiency linked to type 1 diabetes

ScienceDaily (Nov. 15, 2012) — A study led by researchers from the University of California, San Diego School of Medicine has found a correlation between vitamin D3 serum levels and subsequent incidence of Type 1 diabetes. The six-year study of blood levels of nearly 2,000 individuals suggests a preventive role for vitamin D3 in this disease. The research appears the December issue ofDiabetologia, a publication of the European Association for the Study of Diabetes (EASD).

Probiotic worm treatment may improve symptoms of colitis by restoring gut bacteria to healthy state

Probiotic worm treatment may improve symptoms of colitis by restoring gut bacteria to healthy state:

'via Blog this'

Influenza curbs part of the immune system and abets bacterial infections

When infected with influenza, the body becomes an easy target for bacteria. The flu virus alters the host's immune system and compromises its capacity to effectively fight off bacterial infections. Now, a team of immunologists at the Helmholtz Centre for Infection Research (HZI) and cooperation partners has discovered that an immune system molecule called TLR7 is partly to blame. The molecule recognizes the viral genome – and then signals scavenger cells of the immune system to ingest fewer bacteria. The researchers published their findings in the Journal of Innate Immunity.

Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome.

Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host-virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.

TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria.

Phagocytosis, which is essential for the immune response to pathogens, is
initiated by specific interactions between pathogens and cell surface receptors
expressed by phagocytes. This study identifies triggering receptor expressed on
myeloid cells 2 (TREM-2) and its signaling counterpart DAP12 as a molecular
complex that promotes phagocytosis of bacteria. Expression of TREM-2-DAP12
enables nonphagocytic Chinese hamster ovary cells to internalize bacteria. This
function depends on actin cytoskeleton dynamics and the activity of the small
guanosine triphosphatases Rac and Cdc42. Internalization also requires src kinase
activity and tyrosine phosphorylation. In bone marrow-derived macrophages,
phagocytosis is decreased in the absence of DAP12 and can be restored by
expression of TREM-2-DAP12. Depletion of TREM-2 inhibits both binding and uptake
of bacteria. Finally, TREM-2-dependent phagocytosis is impaired in Syk-deficient
macrophages. This study highlights a novel role for TREM-2-DAP12 in the immune
response to bacterial pathogens.

Bright light At Night Can Cause Depression

"Basically, what we found is that chronic exposure to bright light - even the kind of light you experience in your own living room at home or in the workplace at night if you are a shift worker - elevates levels of a certain stress hormone in the body, which results in depression and lowers cognitive function."

Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study.

:Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelopment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of antibiotics reported by the mother during pregnancy and the risk for autism spectrum disorder (ASD) and infantile autism in the offspring.METHODS:We used a population-based cohort consisting of 96 736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD.RESULTS:Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism.CONCLUSIONS:Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism. The results may be due to multiple testing; the few positive findings are potential chance findings.

Rare genetic mutation triples Alzheimer's risk

A gene so powerful it nearly triples the risk of Alzheimer's disease has been discovered by an international team including researchers from Mayo Clinic. It is the most potent genetic risk factor for Alzheimer's identified in the past 20 years. The findings were reported Wednesday in the online edition of the New England Journal of Medicine. 

The gene is TREM2  The encoded protein may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines (NCBI)

Read more at: http://medicalxpress.com/news/2012-11-rare-genetic-mutation-triples-alzheimer.html#jCp

Could poor sleep contribute to symptoms of schizophrenia?

Neuroscientists studying the link between poor sleep and schizophrenia have found that irregular sleep patterns and desynchronised brain activity during sleep could trigger some of the disease's symptoms. The findings, published in the journal Neuron, suggest that these prolonged disturbances might be a cause and not just a consequence of the disorder's debilitating effects.

Read more at: http://medicalxpress.com/news/2012-11-poor-contribute-symptoms-schizophrenia.html#jCp

Discovery could lead to faster diagnosis for some chronic fatigue syndrome cases

In a pilot study of six patients, scientists detected specific antibodies linked to latent Epstein-Barr virus reactivation in blood samples from people who had experienced classic CFS symptoms and responded to antiviral treatment. Control blood samples from 20 healthy people showed no such antibodies.

Read more at: http://medicalxpress.com/news/2012-11-discovery-faster-diagnosis-chronic-fatigue.html#jCp

BPA shown to disrupt thyroid function in pregnant animals and offspring

In utero exposure to bisphenol A (BPA) can be associated with decreased thyroid function in newborn sheep, according to a recent study accepted for publication in Endocrinology. Hypothyroidism is characterized by poor mental and physical performance in human adults and in children can result in cognitive impairment and failure to grow normally.

Read more at: http://medicalxpress.com/news/2012-11-bpa-shown-disrupt-thyroid-function.html#jCp
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Type 1 Diabetes Stem Cell Breakthrough Moves Toward Cure


In a breakthrough that signifies a move toward a cure for type 1 diabetes, researchers in Australia have identified stem cells in the pancreas that can be turned into insulin-producing cells. The finding promises to bring closer the day when people with type 1 diabetes will be able to produce their own insulin in their own regenerated insulin-producing pancreatic cells.

Autism treatment: Metal-binding agent applied to the skin is not absorbed and is therefore ineffective

ScienceDaily (Nov. 13, 2012) — Metal-binding agents rubbed into the skin, prescribed by some alternative practitioners for the treatment of autism, are not absorbed and therefore are unlikely to be effective at helping the body excrete excess mercury, a new study finds. The study by Jennifer Cohen and Michelle Ruha from Banner Good Samaritan Medical Center in the US, and their colleagues, provides evidence against the use of these treatments in children with autism.

New type of bacterial protection found within cells: Novel immune system response to infections discovered

ScienceDaily (Nov. 13, 2012) — UC Irvine biologists have discovered that fats within cells store a class of proteins ( histone proteins) with potent antibacterial activity, revealing a previously unknown type of immune system response that targets and kills bacterial infections.

Genetic variation may modify associations between low vitamin D levels and adverse health outcomes

ScienceDaily (Nov. 13, 2012) — Findings from a study suggest that certain variations in vitamin D metabolism genes may modify the association of low serum 25-hydroxyvitamin D concentrations with health outcomes such as hip fracture, heart attack, cancer, and death, according to a study appearing in the November 14 issue of JAMA.

Glutamate neurotransmission system may be involved with depression risk

Researchers using a new approach to identifying genes associated with depression have found that variants in a group of genes involved in transmission of signals by the neurotransmitter glutamate appear to increase the risk of depression. The report published in the journal Translational Psychiatry suggests that drugs targeting the glutamate system may help improve the limited success of treatment with current antidepressant drugs.

Read more at: http://medicalxpress.com/news/2012-11-glutamate-neurotransmission-involved-depression.html#jCp
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