Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus

Despite major advances in our understanding of many aspects of human papillomavirus (HPV) biology, HPV entry is poorly understood. To identify cellular genes required for HPV entry, we conducted a genome-wide screen for siRNAs that inhibited infection of HeLa cells by HPV16 pseudovirus. Many retrograde transport factors were required for efficient infection, including multiple subunits of the retromer, which initiates retrograde transport from the endosome to the trans-Golgi network (TGN). The retromer has not been previously implicated in virus entry. Furthermore, HPV16 capsid proteins arrive in the TGN/Golgi in a retromer-dependent fashion during entry, and incoming HPV proteins form a stable complex with retromer subunits. We propose that HPV16 directly engages the retromer at the early or late endosome and traffics to the TGN/Golgi via the retrograde pathway during cell entry. These results provide important insights into HPV entry, identify numerous potential antiviral targets, and suggest that the role of the retromer in infection by other viruses should be assessed.

Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development

Hypoxia, or low oxygen tension, is a major regulator of tumor development and aggressiveness. However, how cancer cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Here, we show that secreted vesicles with exosome characteristics mediate hypoxia-dependent intercellular signaling of the highly malignant brain tumor glioblastoma multiforme (GBM). In vitro hypoxia experiments with glioma cells and studies with patient materials reveal the enrichment in exosomes of hypoxia-regulated mRNAs and proteins (e.g., matrix metalloproteinases, IL-8, PDGFs, caveolin 1, and lysyl oxidase), several of which were associated with poor glioma patient prognosis. We show that exosomes derived from GBM cells grown at hypoxic compared with normoxic conditions are potent inducers of angiogenesis ex vivo and in vitro through phenotypic modulation of endothelial cells. Interestingly, endothelial cells were programmed by GBM cell-derived hypoxic exosomes to secrete several potent growth factors and cytokines and to stimulate pericyte PI3K/AKT signaling activation and migration. Moreover, exosomes derived from hypoxic compared with normoxic conditions showed increased autocrine, promigratory activation of GBM cells. These findings were correlated with significantly enhanced induction by hypoxic compared with normoxic exosomes of tumor vascularization, pericyte vessel coverage, GBM cell proliferation, as well as decreased tumor hypoxia in a mouse xenograft model. We conclude that the proteome and mRNA profiles of exosome vesicles closely reflect the oxygenation status of donor glioma cells and patient tumors, and that the exosomal pathway constitutes a potentially targetable driver of hypoxia-dependent intercellular signaling during tumor development.

LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus

Vesicular stomatitis virus (VSV) exhibits a remarkably robust and pantropic infectivity, mediated by its coat protein, VSV-G. Using this property, recombinant forms of VSV and VSV-G-pseudotyped viral vectors are being developed for gene therapy, vaccination, and viral oncolysis and are extensively used for gene transduction in vivo and in vitro. The broad tropism of VSV suggests that it enters cells through a highly ubiquitous receptor, whose identity has so far remained elusive. Here we show that the LDL receptor (LDLR) serves as the major entry port of VSV and of VSV-G-pseudotyped lentiviral vectors in human and mouse cells, whereas other LDLR family members serve as alternative receptors. The widespread expression of LDLR family members accounts for the pantropism of VSV and for the broad applicability of VSV-G-pseudotyped viral vectors for gene transduction.

Neurobiology of Disease - MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients

Schizophrenia is a common neuropsychiatric disorder that has a strong genetic component. MicroRNAs (miRNAs) have been implicated in neurodevelopmental and psychiatric disorders including schizophrenia, as indicated by their dysregulation in post-mortem brain tissues and in peripheral blood of schizophrenia patients. The olfactory epithelium (OE) is one of the few accessible neural tissues that contain neurons and their stem cells. Previous studies showed that OE-derived tissues and cells can be safely and easily collected from live human subjects and may provide a “window” into neuronal processes involved in disorders such as schizophrenia, while avoiding the limitations of using postmortem brain samples or non-neuronal tissues. In this study, we found that the brain-enriched miR-382 (miR-382-5p) expression was elevated in in vitro cultured olfactory cells, in a cohort of seven schizophrenia patients compared with seven non-schizophrenic controls. MiR-382 elevation was further confirmed in laser-capture microdissected OE neuronal tissue (LCM-OE), enriched for mature olfactory neurons, in a cohort of 18 schizophrenia patients and 18 non-schizophrenic controls. In sharp contrast, miR-382 expression could not be detected in lymphoblastoid cell lines generated from schizophrenic or non-schizophrenic individuals. We further found that miR-382 directly regulates the expression of two genes, FGFR1 and SPRY4, which are downregulated in both the cultured olfactory cells and LCM-OE derived from schizophrenia patients. These genes are involved in the fibroblast growth factor (FGF) signaling pathway, while impairment of this pathway may underlie abnormal brain development and function associated with schizophrenia. Our data suggest that miR-382 elevation detected in patients' OE-derived samples might serve to strengthen current biomarker studies in schizophrenia. This study also illustrates the potential utility of OE-derived tissues and cells as surrogate samples for the brain.

HealthMap: Global Mapping of infectious diseases

 "HealthMap, a team of researchers, epidemiologists and software developers at Boston Children's Hospital founded in 2006, is an established global leader in utilizing online informal sources for disease outbreak monitoring and real-time surveillance of emerging public health threats. The freely available Web site 'healthmap.org' and mobile app 'Outbreaks Near Me' deliver real-time intelligence on a broad range of emerging infectious diseases for a diverse audience including libraries, local health departments, governments, and international travelers. HealthMap brings together disparate data sources, including online news aggregators, eyewitness reports, expert-curated discussions and validated official reports, to achieve a unified and comprehensive view of the current global state of infectious diseases and their effect on human and animal health. Through an automated process, updating 24/7/365, the system monitors, organizes, integrates, filters, visualizes and disseminates online information about emerging diseases in nine languages, facilitating early detection of global public health threats."

Molecular Psychiatry - Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism.

Boosting the Powers of Genomic Science GWAS

With two new methods, UC San Diego scientists hope to improve genome-wide association studies: As scientists probe and parse the genetic bases of what makes a human a human (or one human different from another), and vigorously push for greater use of whole genome sequencing, they find themselves increasingly threatened by the unthinkable: Too much data to make full sense of. 

In a pair of papers published in the April 25, 2013 issue of PLOS Genetics, two diverse teams of scientists, both headed by researchers at the University of California, San Diego School of Medicine, describe novel statistical models that more broadly and deeply identify associations between bits of sequenced DNA called single nucleotide polymorphisms or SNPs and say lead to a more complete and accurate understanding of the genetic underpinnings of many diseases and how best to treat them.    

As CO2 Reaches Symbolic Milestone, Scripps Launches Daily Keeling Curve Update

For the first time in human history, concentrations of the greenhouse gas carbon dioxide (CO₂) could rise above 400 parts per million (ppm) for sustained lengths of time throughout much of the Northern Hemisphere as soon as May 2013.

Treatment-resistant Depression | Glutamate, Stress Hormones, and their Role in the Regeneration of NeuronsThe New York Academy of Sciences

The standard of care for clinical depression has significant limitations: traditional drugs that focus on monoamine neurotransmitters can take several weeks to be effective, and many patients never respond to any form of treatment. Several clinical trials have demonstrated strikingly better outcomes using the anesthetic ketamine to treat depression. Notably, a single application can have rapid and lasting antidepressant effects in patients who do not respond to other treatments. Because ketamine is an antagonist of NMDA-type glutamate receptors, research is focused on the role of glutamate neurotransmission in depression and on drug development that targets the glutamatergic system. The March 25, 2013, meeting of the Academy's Biochemical Pharmacology Discussion Group, Treatment-resistant Depression: Glutamate, Stress Hormones, and their Role in the Regeneration of Neurons, presented this new research and the avenues it is opening for the treatment of depression.

Can Network Analysis Identify Pathological Pathways in Alzheimer’s - AlzForum Alzheimer Research Live Discussions

: "In the April 25 Cell, Valur Emilsson at the Icelandic Heart Association and Eric Schadt at Icahn School of Medicine at Mount Sinai, New York, report that they have identified molecular networks that are perturbed in Alzheimer’s disease patients compared to normal, age-matched controls. Several of these networks comprise genes previously linked to AD, including TREM2 and CD33. The scientists also identified a new player, TYROBP, as a master regulator of these molecular modules. Meanwhile, in the April 25 Neuron, researchers led by Rudy Tanzi and Ana Griciuc at Massachusetts General Hospital, Charlestown, report that microglia in the AD brain overproduce CD33, which seems to prevent these cells from binding to and degrading amyloid-β. Together, these findings tighten the link between AD pathology and microglial dysfunction."

A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models.

Multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus, are associated with an allelic variant of protein tyrosine phosphatase nonreceptor 22 (PTPN22), which encodes the protein LYP. To model the human disease-linked variant LYP-R620W, we generated knockin mice expressing the analogous mutation, R619W, in the murine ortholog PEST domain phosphatase (PEP). In contrast with a previous report, we found that this variant exhibits normal protein stability, but significantly alters lymphocyte function. Aged knockin mice exhibited effector T cell expansion and transitional, germinal center, and age-related B cell expansion as well as the development of autoantibodies and systemic autoimmunity. Further, PEP-R619W affected B cell selection and B lineage-restricted variant expression and was sufficient to promote autoimmunity. Consistent with these features, PEP-R619W lymphocytes were hyperresponsive to antigen-receptor engagement with a distinct profile of tyrosine-phosphorylated substrates. Thus, PEP-R619W uniquely modulates T and B cell homeostasis, leading to a loss in tolerance and autoimmunity.

Hitting 'reset' in protein synthesis restores myelination: Suggests new treatment for misfolded protein diseases such as Alzheimer's

A potential new treatment strategy for patients with Charcot-Marie-Tooth disease is on the horizon, thanks to research by neuroscientists now at the University at Buffalo's Hunter James Kelly Research Institute and their colleagues in Italy and England.

Air Pollution Tied To Hardening Of Arteries

MNT:  "Over time, increased exposure to air pollution is linked to faster "hardening" of the arteries, or atherosclerosis, a leading cause of heart attacks and strokes. Conversely, exposure to reduced levels of air pollution is linked to slowed progression of atherosclerosis. These are the findings of a new study from the US published this week in PLOS Medicine. "

Autism risk spotted at birth in abnormal placentas

 "Researchers at the Yale School of Medicine have figured out how to measure an infant's risk of developing autism by looking for abnormalities in his/her placenta at birth, allowing for earlier diagnosis and treatment for the developmental disorder. The findings are reported in the April 25 online issue of Biological Psychiatry."

Roundworm quells obesity and related metabolic disorders

"Researchers at the University of Maryland School of Medicine, Baltimore, have shown in a mouse model that infection with nematodes (also known as roundworms) can not only combat obesity but ameliorate related metabolic disorders. Their research is published ahead of print online in the journal Infection and Immunity."

Team finds melatonin delays ALS symptom onset and death in mice

 "Melatonin injections delayed symptom onset and reduced mortality in a mouse model of the neurodegenerative condition amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, according to a new study by researchers at the University of Pittsburgh School of Medicine. In a report published online ahead of print in the journal Neurobiology of Disease, the team revealed that receptors for melatonin are found in the nerve cells, a finding that could launch novel therapeutic approaches."

Potential diabetes breakthrough: Researchers discover new hormone spurring beta cell production

 "The hormone, called betatrophin, causes mice to produce insulin-secreting pancreatic beta cells at up to 30 times the normal rate. The new beta cells only produce insulin when called for by the body, offering the potential for the natural regulation of insulin and a great reduction in the complications associated with diabetes, the leading medical cause of amputations and non-genetic loss of vision."

#Probiotics found to reduce hepatic encephalopathy | BreakThrough Digest Medical News

Update: Risk Factors | Multiple Sclerosis Discovery Forum

American Academy of Neurology meeting report

STEPHANI SUTHERLAND

SAN DIEGO—Life in the Western world has changed dramatically over the past 50 years. We spend more time indoors, eat more processed foods, have children later, and, unfortunately, fall prey to more autoimmune diseases than ever before. Could the changes in our lifestyle be contributing to the higher disease rate? At last month’s meeting of the American Academy of Neurology, researchers presented work that provided an update on risk factors for MS and indicated how these risk factors might help inform future therapies for MS.

Cell - Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease

The genetics of complex disease produce alterations in the molecular interactions of cellular pathways whose collective effect may become clear through the organized structure of molecular networks. To characterize molecular systems associated with late-onset Alzheimer’s disease (LOAD), we constructed gene-regulatory networks in 1,647 postmortem brain tissues from LOAD patients and nondemented subjects, and we demonstrate that LOAD reconfigures specific portions of the molecular interaction structure. Through an integrative network-based approach, we rank-ordered these network structures for relevance to LOAD pathology, highlighting an immune- and microglia-specific module that is dominated by genes involved in pathogen phagocytosis, contains TYROBP as a key regulator, and is upregulated in LOAD. Mouse microglia cells overexpressing intact or truncated TYROBP revealed expression changes that significantly overlapped the human brain TYROBP network. Thus the causal network structure is a useful predictor of response to gene perturbations and presents a framework to test models of disease mechanisms underlying LOAD.

NIMH · Suppressing CD33 Protein May Stem Alzheimer’s Disease Process

Too much CD33 activity appears to promote late-onset Alzheimer’s by preventing support cells from clearing out toxic plaques, key risk factors for the disease,” explained Rudolph Tanzi, Ph.D., of Massachusetts General Hospital and Harvard University, a grantee of the NIH’s National Institute of Mental Health (NIMH) and National Institute on Aging (NIA). “Future medications that impede CD33 activity in the brain might help prevent or treat the disorder.”

Tanzi and colleagues report on their findings April 25, 2013 in the journal Neuron.

Lamarck and the Missing Lnc | The Scientist Magazine®

Although biologists have generally considered Lamarck’s ideas to contain as much truth as Kipling’s fables, the burgeoning field of epigenetics has made some of us reconsider our ridicule. While no biologist believes that organisms can willfully change their physiology in response to their environment and pass those changes on to their offspring, some evidence suggests that the environment can make lasting changes to the genome via epigenetic mechanisms—changes that may be passed on to future generations.

NMDA Receptor Blockade by Ketamine Abrogates Lipopolysaccharide-Induced Depressive-Like Behavior in C57BL/6J Mice.

We have previously demonstrated that lipopolysaccharide (LPS) induces depressive-like behavior by activating indoleamine 2,3 dioxygenase (IDO; O'Connor et al, 2009c). IDO degrades tryptophan along the kynurenine pathway. Using mass-spectrometry (LC-MS) analysis of kynurenine metabolites in the brain of mice injected at the periphery with 1 mg/kg LPS, we show that LPS activates the kynurenine 3-monooxygenase pathway that ultimately degrades kynurenine into quinolinic acid. As quinolinic acid acts as an N-methyl-D-aspartate (NMDA) receptor agonist, we used the NMDA receptor antagonist ketamine to assess the role of NMDA receptor activation in LPS-induced depressive-like behavior. Here, we report that a low dose of ketamine (6 mg/kg, intraperitoneally) immediately before administration of LPS (0.83 mg/kg, intraperitoneally) in C57Bl/6 J mice abrogated the development of LPS-induced depressive-like behavior, without altering LPS-induced sickness measured by body weight loss, decreased motor activity, and reduced food intake. Depressive-like behavior was measured 24 h after LPS by decreased sucrose preference and increased immobility in the forced swim test (FST). Ketamine had no effect on LPS-induced cytokineexpression in the liver and brain, IDO activation, and brain-derived neurotrophic factor (BDNF) transcripts. The ability of ketamine to abrogate LPS-induced depressive-like behavior independently of a possible interference with LPS-induced inflammatory signaling was confirmed when ketamine was administered 10 h after LPS instead of immediately before LPS. In contrast, ketamine had no effect when administered 24 h before LPS. To confirm that NMDA receptor antagonism by ketamine mediates the antidepressant-like activity of this compound in LPS-treated mice, mice were pretreated with the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione (NBQX) to block enhanced AMPA receptor glutamatergic neurotransmission after NMDA receptor antagonism by ketamine. NBQX administered at the dose of 10 mg/kg intraperitoneally 15 min before ketamine in mice treated with LPS 24 h earlier restored LPS-induced decreased sucrose preference. These findings indicate that LPS-induced depressive-like behavior is mediated by NMDA receptor activation, probably as a consequence of formation of quinolinic acid.

Nasal lining used to breach blood/brain barrier

Study shows gut bacteria byproduct predicts heart attack and stroke

A microbial byproduct of intestinal bacteria contributes to heart disease and serves as an accurate screening tool for predicting future risks of heart attack, stroke and death in persons not otherwise identified by traditional risk factors and blood tests, according to Cleveland Clinic research published today in The New England Journal of Medicine."The current study is an extension of Dr. Hazen's previous work, in which he found that a chemical byproduct called trimethylamine N-oxide (TMAO) is produced when intestinal bacteria digest the nutrient phosphatidylcholine, commonly known as lecithin. The prior research showed that TMAO levels in the blood were associated with heart disease. Dr. Hazen and colleagues have now confirmed that gut flora are essential in forming TMAO in humans and demonstrated a relationship between TMAO levels and future cardiac events like heart attack, stroke, and death—even in those with no prior evidence of cardiac disease risk.

Drinking one 12oz sugar-sweetened soft drink a day can increase the risk of type 2 diabetes by 22 percent

"Drinking one (or one extra)* 12oz serving size of sugar-sweetened soft drink a day can be enough to increase the risk of developing type 2 diabetes by 22%, a new study suggests. The research is published in Diabetologia (the journal of the European Association for the Study of Diabetes) and comes from data in the InterAct consortium**. The research is by Dr Dora Romaguera, Dr Petra Wark and Dr Teresa Norat, Imperial College London, UK, and colleagues."

Guelph scientists develop first vaccine to help control autism symptoms | BreakThrough Digest Medical News

They developed a carbohydrate-based vaccine against the gut bug, Clostridium bolteae.

C. bolteae is known to play a role in gastrointestinal disorders, and it often shows up in higher numbers in the GI tracts of autistic children than in those of healthy kids.More than 90 per cent of children with autism spectrum disorders suffer from chronic, severe gastrointestinal symptoms. Of those, about 75 per cent suffer from diarrhea, according to current literature.“Little is known about the factors that predispose autistic children to C. bolteae,” said Monteiro. Although most infections are handled by some antibiotics, he said, a vaccine would improve current treatment.This is the first vaccine designed to control constipation and diarrhea caused by C. bolteae and perhaps control autism-related symptoms associated with this microbe,” he said.

Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study.

OBJECTIVE:To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.
DESIGN:Population based nested case-control study.
SETTING:Stockholm County, Sweden, 2001-07.
PARTICIPANTS:4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years.
MAIN OUTCOME MEASURE:A diagnosis of autism spectrum disorder, with or without intellectual disability. EXPOSURES: Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.
RESULTS:A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.
CONCLUSIONS:In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.

Vets and medical doctors should team up to tackle diseases transmitted from animals to humans #zoonoses

Use of anti-epileptic drug during pregnancy associated with increased risk of autism

 "Maternal use of valproate (a drug used for the treatment of epilepsy and other neuropsychological disorders) during pregnancy was associated with a significantly increased risk of autism in offspring, according to a study in the April 24 issue of JAMA. The authors caution that these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control."

New research examines connection between inflammatory stimulus and Parkinson's disease

 "The precise cause or causes of PD is unknown, but there is a consensus that an inflammatory event or episode is involved in the initiation of neurodegeneration, and that chronic neuroinflammation is a sustaining and exacerbating reason for the loss of the dopaminergic neurons. A new study conducted by a team of Texas researchers brings the understanding of inflammation's role a step further. They have found that a single, high-dose exposure of an experimental inflammatory agent in an animal model causes changes in brain tissue that are similar to those associated with the development of the disease."

Research shows oral supplement (glutathione) increases body's storage of antioxidant

"Oral supplementation of glutathione is effective in increasing the body's stores of the antioxidant, said Penn State College of Medicine researchers in study results presented at a conference today (April 22)."

Epigenetic changes shed light on biological mechanism of autism

"Scientists from King's College London have identified patterns of epigenetic changes involved in autism spectrum disorder (ASD) by studying genetically identical twins who differ in autism traits. The study, published in Molecular Psychiatry, is the largest of its kind and may shed light on the biological mechanism by which environmental influences regulate the activity of certain genes and in turn contribute to the development of ASD and related behaviour traits."

Thalamic Atrophy in key region of brain associated with multiple sclerosis

"Magnetic resonance imaging (MRI) measurements of atrophy in an important area of the brain are an accurate predictor of multiple sclerosis (MS), according to a new study published online in the journal Radiology. According to the researchers, these atrophy measurements offer an improvement over current methods for evaluating patients at risk for MS."

Molecular Psychiatry - Pathogenic disruption of DISC1-serine racemase binding elicits schizophrenia-like behavior via D-serine depletion

Perturbation of Disrupted-In-Schizophrenia-1 (DISC1) and d-serine/NMDA receptor hypofunction have both been implicated in the pathophysiology of schizophrenia and other psychiatric disorders. In the present study, we demonstrate that these two pathways intersect with behavioral consequences. DISC1 binds to and stabilizes serine racemase (SR), the enzyme that generates d-serine, an endogenous co-agonist of the NMDA receptor. Mutant DISC1 fails to bind to SR, facilitating ubiquitination and degradation of SR and a decrease in d-serine production. To elucidate DISC1–SR interactions in vivo, we generated a mouse model of selective and inducible expression of mutant DISC1 in astrocytes, the main source ofd-serine in the brain. Expression of mutant DISC1 downregulates endogenous DISC1 and decreases protein but not mRNA levels of SR, resulting in diminished production of d-serine. In contrast, mutant DISC1 does not alter levels of ALDH1L1, connexins, GLT-1 or binding partners of DISC1 and SR, LIS1 or PICK1. Adult male and female mice with lifelong expression of mutant DISC1 exhibit behavioral abnormalities consistent with hypofunction of NMDA neurotransmission. Specifically, mutant mice display greater responses to an NMDA antagonist, MK-801, in open field and pre-pulse inhibition of the acoustic startle tests and are significantly more sensitive to the ameliorative effects of d-serine. These findings support a model wherein mutant DISC1 leads to SR degradation via dominant negative effects, resulting in d-serine deficiency that diminishes NMDA neurotransmission thus linking DISC1 and NMDA pathophysiological mechanisms in mental illness.

Mercury, APOE, and children's neurodevelopment.

The benefit of the nutritious elements in fish is insufficient for explaining the controversial finding regarding prenatal mercury (Hg) exposure and neurodevelopment; the varying frequency of susceptible genes among these populations may shed light on these observations. However, limited studies have been reported on the association between genetic susceptibility, of prenatal Hg exposure and child development. Apolipoprotein E (APOE, protein; Apoe, gene) is a major protein transporter expressed in the brain. The Apoe epsilon 4 (ɛ4) allele is associated with poor neural repair function and is a risk factor associated with Alzheimer disease. We conducted a prospective cohort study in 2004 and 2005. In this study, 168 subjects were recruited at delivery and followed up at two years of age, and genetic polymorphisms of Apoe were included to assess genetic susceptibility and to determine the relationship between Hg concentrations in cord blood and neurodevelopment. The results showed that adverse effects on neurodevelopment were consistently associated with prenatal Hg exposure in all subtests of Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) among ɛ4 carriers as assessed by both simple linear and multiple linear regression models. After controlling for confounding factors, statistical significance was found in the subtests of cognition tests (β = -8.47, 95% confidence interval (CI) = -16.10 to -0.84), social tests (β = -11.02, 95% CI = -20.85 to -1.19) and the whole test of CDIIT (β = -10.45, 95% CI = -17.36 to -3.54) in a multiple linear regression model. Additionally, the interaction effect between gene polymorphisms of Apoe and Hg levels was significant in the whole test CDIIT and subtests of cognition, language and fine motor tests. In conclusion, Apoe modifies the adverse effects of cord blood Hg on neurodevelopment at the age of two years.

Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes.

BACKGROUND:

Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries.

METHODS:

We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS) for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS) and the average publication rate for each disease.

RESULTS:

For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r(2)=0.3198) and that the vast majority of disease pairs (89.56%) never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25%) of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r(2)=0.7931), and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r(2)=0.8585). These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research.

CONCLUSIONS:

Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better understanding of the taxonomy of human diseases, cross-disease research approaches should become the rule rather than the exception.

New light shed on early stage Alzheimer's disease

: "The disrupted metabolism of sugar, fat and calcium is part of the process that causes the death of neurons in Alzheimer's disease. Researchers from Karolinska Institutet in Sweden have now shown, for the first time, how important parts of the nerve cell that are involved in the cell's energy metabolism operate in the early stages of the disease. These somewhat surprising results shed new light on how neuronal metabolism relates to the development of the disease."

New immune cells hint at eczema cause

"(Medical Xpress)—University of Sydney researchers have discovered a new type of immune cell in skin that plays a role in fighting off parasitic invaders such as ticks, mites, and worms, and could be linked to eczema and allergic skin diseases. The findings have been published today in the journal Nature Immunology."

Social stress and the inflamed brain: relevance to depression

 "The study, conducted in male rats, compared expression of 88 genes involved in signaling within the brain between socially stressed and non-stressed rats. It revealed more than 35 genes in stressed rats that had altered expression compared with non-stressed controls. Many of the genes that were differentially expressed were related to inflammation. Follow-up studies measuring protein levels revealed that Interleukin-1β and Monocyte chemotactic protein-1, inflammatory markers known to play a role in depression and heart disease, were suppressed in the brains of the resilient subset of rats and Interleukin-1β was increased in the vulnerable group. Dr. Wood measured the gene and protein levels under resting conditions 24 hours after just 5 daily 30-minute exposures to social stress."

Low-dose aspirin stymies proliferation of two breast cancer lines

"The study found that aspirin slowed the growth of breast cancer cell lines in the lab and significantly reduced the growth of tumors in mice. The age-old headache remedy also exhibits the ability to prevent tumor cells from spreading."

Vital Clues About Brain Tumors Provided By Virus-Like Particles (exosomes)

MNT: Exosomes are small vesicles of only 30 nm. They are produced inside cells and act as "transport vehicles" of genetic material that can be transferred to surrounding cells. Since their first discovery, exosomes have been found in blood, saliva, urine, breast milk and other body fluids.

Futurity.org – Are those tiny gold nanoparticles bad for you?

 "Pure gold nanoparticles found in everyday items such as personal care products can inhibit fat storage, slow wound healing, and accelerate wrinkling"

Study suggests reduced risk of dementia

A new Swedish study published in the journal Neurology shows that the risk of developing dementia may have declined over the past 20 years, in direct contrast to what many previously assumed. The result is based on data from SNAC-K, an ongoing study on aging and health that started in 1987.The overall risk of developing dementia must have declined during the period, possibly thanks to prevention and better treatment of cardiovascular disease.

Diabetes Risk Linked To Melatonin Secretion During Sleep

MNT  "Despite the fact every year millions of people discover they have type 2 diabetes, we still don't know exactly what causes the disease. Now researchers in the US suggest it may be linked to the amount of melatonin a person secretes: in a JAMA study published online this month they show participants who secreted the least melatonin into the bloodstream during sleep had double the risk of developing type 2 diabetes."

Humans Share Microbiomes With Their Dogs, Study Finds | Popular Science

Researchers abuzz over caffeine as 'cancer-cell killer'

"Researchers from the University of Alberta are abuzz after using fruit flies to find new ways of taking advantage of caffeine's lethal effects on cancer cells -- results that could one day be used to advance cancer therapies for people."

New understanding of asthma development: Transmission of respiratory viruses in utero

 "The most common cause of lower respiratory tract infections in infants and young children, respiratory syncytial virus (RSV), can be transferred during pregnancy to an unborn baby, according to Cleveland Clinic Children's Hospital research published online this week in the journal PLOS ONE."

High levels of glutamate in brain may kick-start schizophrenia

"An excess of the brain neurotransmitter glutamate may cause a transition to psychosis in people who are at risk for schizophrenia, reports a study from investigators at Columbia University Medical Center (CUMC) published in the current issue of Neuron."

High-salt diet and ulcer bug combine to increase risk of cancer

 "Numerous epidemiologic studies have shown that a diet high in salt is associated with an increased risk of gastric cancer. Now Timothy L. Cover and colleagues of Vanderbilt University show that high dietary salt combined with infection by the ulcer-causing bacterium Helicobacter pylori greatly increases the risk of cancer. The study was published ahead of print in the journal Infection and Immunity."

Why does smallpox vaccine shield some, not others? It's in the genes, study finds

"How well people are protected by the smallpox vaccine depends on more than the quality of the vaccination: individual genes can alter their response, Mayo Clinic research shows. The findings, gathered using sophisticated genomic screening, appear in today's online issue of the journal Genes and Immunity."

Futurity.org – To harness HIV, make it get ‘naked’

"EMORY (US) — A new understanding of how HIV “gets dressed” in the human cells it has taken over could lead to new antiretroviral drugs, researchers say."

Rab11-FIP1C and Rab14 Direct Plasma Membrane Sorting and Particle Incorporation of the HIV-1 Envelope Glycoprotein Complex PLOS PATHOGENS

New Technique For Making Myelinating Cells Holds Promise For The Treatment Of Multiple Sclerosis And Cerebral Palsy

MNT: This breakthrough now enables "on demand" production of myelinating cells, which provide a vital sheath of insulation that protects neurons and enables the delivery of brain impulses to the rest of the body. In patients with multiple sclerosis (MS), cerebral palsy (CP), and rare genetic disorders called leukodystrophies, myelinating cells are destroyed and cannot be replaced. "

Common Pregnancy Conditions Increase Risk Of Diabetes

Two common conditions in pregnancy, preeclampsia and gestational hypertension, may increase the risk of future diabetes, according to a study of more than one million women.

Study reveals natural process related to endosomal cholesterol that blocks viruses

 "The human body has the ability to ward off viruses by activating a naturally occurring protein ( IFITM3) at the cellular level, setting off a chain reaction that disrupts the levels of cholesterol required in cell membranes to enable viruses to enter cells. The findings, discovered by researchers in molecular microbiology and immunology at the Keck School of Medicine of USC, hold promise for the development of therapies to fight a variety of viral infections."

Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter.

Bisphenol A (BPA) is a ubiquitous compound that is emerging as a possible toxicant during embryonic development. BPA has been shown to epigenetically affect the developing nervous system, but the molecular mechanisms are not clear. Here we demonstrate that BPA exposure in culture led to delay in the perinatal chloride shift caused by significant decrease in potassium chloride cotransporter 2 (Kcc2) mRNA expression in developing rat, mouse, and human cortical neurons. Neuronal chloride increased correspondingly. Treatment with epigenetic compounds decitabine and trichostatin A rescued the BPA effects as did knockdown of histone deacetylase 1 and combined knockdown histone deacetylase 1 and 2. Furthermore, BPA evoked increase in tangential interneuron migration and increased chloride in migrating neurons. Interestingly, BPA exerted its effect in a sexually dimorphic manner, with a more accentuated effect in females than males. By chromatin immunoprecipitation, we found a significant increase in binding of methyl-CpG binding protein 2 to the "cytosine-phosphate-guanine shores" of the Kcc2 promoter, and decrease in binding of acetylated histone H3K9 surrounding the transcriptional start site. Methyl-CpG binding protein 2-expressing neurons were more abundant resulting from BPA exposure. The sexually dimorphic effect of BPA on Kcc2 expression was also demonstrated in cortical neurons cultured from the offspring of BPA-fed mouse dams. In these neurons and in cortical slices, decitabine was found to rescue the effect of BPA on Kcc2 expression. Overall, our results indicate that BPA can disrupt Kcc2 gene expression through epigenetic mechanisms. Beyond increase in basic understanding, our findings have relevance for identifying unique neurodevelopmental toxicity mechanisms of BPA, which could possibly play a role in pathogenesis of human neurodevelopmental disorders.

Large-scale study of preventive antibiotic usage against Lyme disease

 "Today, at the start of the "Tick Week", the National Institute for Public Health and the Environment (RIVM) and Wageningen University are commencing a large-scale study to discover whether preventive use of antibiotics can stop Lyme disease developing after a tick bite. Of the more than 3400 ticks that were sent to RIVM via Tekenradar.nl (Tick radar) last year, more than 20% turned out to be infected with the Borrelia bacteria which can cause Lyme disease. Around 3% of the people bitten by ticks developed Lyme disease."

Breakthrough Study Shows Benefits Of Adjunctive L-Methylfolate In The Treatment Of SSRI-Resistant Major Depressive Disorder

MNT: "New research shows that patients with SSRI-resistant depression can benefit from augmentation therapy with the medical food L-methylfolate. The study, published in the American Journal of Psychiatry, demonstrates the safety superior response and tolerability of L-methylfolate, (available by prescription in the U.S. under the brand name Deplin®) in patients with Major Depressive Disorder (MDD). Approximately two thirds of people living with depression will be unsuccessful with their first round of antidepressant monotherapy. Yet, many are unaware that certain metabolic imbalances inhibit adequate response to treatment with traditional serotonin reuptake inhibitors (SSRI's) alone. "

Popular Pesticides May Hurt Birds | The Scientist Magazine®

A commonly used class of pesticides, known as neonicotinoids or neonics, may be more harmful to birds than previously thought, according to a new report by the American Bird Conservancy (ABC). Neonics have been suspected to harm bees and other pollinating insects as well. The ABC is calling for a ban on treating seeds with the pesticides and for other uses of the pesticide to be suspended until their effects have been independently reviewed.

Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder.

Previous studies suggest elevated inflammation in schizophrenia and bipolar disorder, with increased activity of the Interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF)-alpha, von Willebrand factor (vWf) and osteoprotegerin (OPG). It is unclear how immune activation is involved in the psychopathology. We investigated if elevated inflammation was associated with disease severity (trait) or current symptom level (state), comparing psychotic with general characteristics.

METHODS:

Plasma levels of sTNF receptor 1 (sTNF-R1), IL-1 receptor antagonist (IL-1Ra), IL-6, vWf and OPG were measured with ELISA techniques in 322 patients with schizophrenia spectrum and bipolar disorder. Current symptom level (state) was measured with Global Assessment of Functioning (GAF) and Positive and Negative Syndrome Scale (PANSS). Disease severity (trait) was measured with premorbid adjustment scale (PAS), age at onset, number of psychotic episodes and number and length of hospitalizations.

RESULTS:

After controlling for confounders, IL-1Ra and TNF-R1 were independently associated with GAF, and significantly correlated with PANSS negative and positive, respectively. In addition, Il-1Ra was associated with PAS, and sTNF-R1 with number of hospitalizations and psychotic episodes. VWf was significantly correlated with psychotic episodes, OPG with hospitalizations and IL-6 with history of psychosis. Linear regression analysis showed that GAF remained associated with sTNF-R1 and IL-1Ra with PANSS, after controlling for the other clinical measures.

CONCLUSIONS:

This supports that inflammatory markers, particularly IL-1Ra and sTNF-R1 are associated with both general disease severity and psychotic features. This supports a role of immune activation in the core pathological mechanisms of severe mental disorders.

Disruption of the human gut microbiota following Norovirus infection.

The gut microbiota, the collection of all bacterial members in the intestinal tract, plays a key role in health. Disruption of the indigenous microbiota by a variety of stressors, including antibiotic therapy and intestinal infections, is associated with multiple health problems. We sought to determine if infection with Norovirus disrupts the gut microbiota. Barcoded pyrosequencing of the 16S rRNA-encoding gene was used to characterize the stool microbiota in Norovirus-infected human patients (n = 38). While the microbiota in most infected patients (n = 31) resembled that seen in uninfected healthy controls, a minority of patients (n = 7) possessed a significantly altered microbiota characterized by reduced relative numbers of Bacteriodetes and a corresponding increase in Proteobacteria. In these patients, the increase in Proteobacteria was due to a single operational taxonomic unit (OTU) of Escherichia coli. We cultured E. coli from Norovirus-infected patients and characterized them using PCR-ribotyping and virulence factor analysis. Multiple ribotypes were encountered, but none possessed typical virulence factors commonly carried by enteropathogenic E. coli strains. Microbiota disruption and elevated Proteobacteria were not significantly correlated to patient age, gender, sampling time following illness onset, or overall gut inflammation. These results demonstrate that some patients have a disrupted microbiota following Norovirus infection, and therefore may be at elevated risk for long-term health complications.

PLOS ONE: Mitotic Spindle Defects and Chromosome Mis-Segregation Induced by LDL/Cholesterol—Implications for Niemann-Pick C1, Alzheimer’s Disease, and Atherosclerosis

Elevated low-density lipoprotein (LDL)-cholesterol is a risk factor for both Alzheimer’s disease (AD) and Atherosclerosis (CVD), suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy–in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß) inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1) high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis’ first prediction, 2) Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3) oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4) LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5) cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6) ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol’s aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol consumption reduces the risk of developing atherosclerosis or AD. These results suggest a novel, cell cycle mechanism by which aberrant cholesterol homeostasis promotes neurodegeneration and atherosclerosis by disrupting chromosome segregation and potentially other aspects of microtubule physiology.

Climate and environmental changes affect the occurrence of diseases transmitted between animals and humans

"How are human and animal diseases in general affected by the climate becoming "wilder, wetter and warmer"? Solveig Jore's doctoral research shows that the tick Ixodes ricinus has spread over larger geographical areas in Norway and that climate and environmental changes, access to host animals and demography affect tick distribution in Norway. Furthermore, local climatic conditions can have a decisive influence on the ability of the tick to spread dangerous viruses. The climate can also play a role in the spread of gastrointestinal infections."

'via Blog this'

Luminous Bacteria Control Clock Genes In Host's Body

MNY: Another new study takes a further step toward revealing the pervasive influence microbial communities that inhabit plants and animals have on their biology. Scientists in the US have discovered that the luminous bacterium Vibrio fischeri regulates the daily rhythm of its host, the Hawaiian bobtail squid, by interacting with its clock genes. "

Influenza A viruses grow in human pancreatic cells and cause pancreatitis and diabetes in an animal model.

Influenza A viruses commonly cause pancreatitis in naturally and experimentally infected animals. In this study, we report the results of in vivo investigations carried out to establish whether influenza virus infection could cause metabolic disorders linked to pancreatic infection. In addition, in vitro tests in human pancreatic islets and in human pancreatic cell lines were performed to evaluate viral growth and cell damage. Infection of an avian model with two low-pathogenicity avian influenza isolates caused pancreatic damage resulting in hyperlipasemia in over 50% of subjects, which evolved into hyperglycemia and subsequently diabetes. Histopathology of the pancreas showed signs of an acute infection resulting in severe fibrosis and disruption of the structure of the organ. Influenza virus nucleoprotein was detected by immunohistochemistry (IHC) in the acinar tissue. Human seasonal H1N1 and H3N2 viruses and avian H7N1 and H7N3 influenza virus isolates were able to infect a selection of human pancreatic cell lines. Human viruses were also shown to be able to infect human pancreatic islets. In situ hybridization assays indicated that viral nucleoprotein could be detected in beta cells. The cytokine activation profile indicated a significant increase of MIG/CXCL9, IP-10/CXCL10, RANTES/CCL5, MIP1b/CCL4, Groa/CXCL1, interleukin 8 (IL-8)/CXCL8, tumor necrosis factor alpha (TNF-α), and IL-6. Our findings indicate that influenza virus infection may play a role as a causative agent of pancreatitis and diabetes in humans and other mammals.

Detection of mycotoxins in patients with chronic fatigue syndrome.

Over the past 20 years, exposure to mycotoxin producing mold has been recognized as a significant health risk. Scientific literature has demonstrated mycotoxins as possible causes of human disease in water-damaged buildings (WDB). This study was conducted to determine if selected mycotoxins could be identified in human urine from patients suffering from chronic fatigue syndrome (CFS). Patients (n = 112) with a prior diagnosis of CFS were evaluated for mold exposure and the presence of mycotoxins in their urine. Urine was tested for aflatoxins (AT), ochratoxin A (OTA) and macrocyclic trichothecenes (MT) using Enzyme Linked Immunosorbent Assays (ELISA). Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin (one in the equivocal range). Almost 30% of the cases had more than one mycotoxin present. OTA was the most prevalent mycotoxin detected (83%) with MT as the next most common (44%). Exposure histories indicated current and/or past exposure to WDB in over 90% of cases. Environmental testing was performed in the WDB from a subset of these patients. This testing revealed the presence of potentially mycotoxin producing mold species and mycotoxins in the environment of the WDB. Prior testing in a healthy control population with no history of exposure to a WDB or moldy environment (n = 55) by the same laboratory, utilizing the same methods, revealed no positive cases at the limits of detection

The power of cocoa polyphenols against neurodegenerative diseases

Epidemiological studies have indicated that dietary habits and antioxidants from diet can influence the incidence of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In recent years, a number of papers have reported on neuroprotective effects of polyphenols in cell and animal models. However, the majority of these studies have focused only on the anti-oxidant properties of these compounds and less on the mechanisms of action at cellular and molecular levels. A new study from the Sbarro Health Research Organization (SHRO, Center for Biotechnology, Temple University, Philadelphia PA USA) and the University of L'Aquila (Italy) shows that cocoa polyphenols triggers neuroprotection by activating BDNF survival pathway, both on Aß plaque treated cells and on Aß oligomers treated cells, resulting in the counteraction of neurite dystrophy."

Immune response linked to key Sirtuin enzyme

The enzyme Sirtuin-6 (SIRT6) promotes the secretion of a signaling molecule called tumor necrosis factor-alpha (TNF), which is important for triggering immune responses in mammalian cells.

Promising new antibiotic targets potentially deadly gut infections

Researchers at the University of Virginia School of Medicine have developed a promising new antibiotic to treat potentially deadly gastrointestinal infections without harming the beneficial probiotic bacteria that help prevent relapse.The investigational drug, Amixicile, can take down even hyper-virulent strains of drug-resistant Clostridium difficile – commonly called "C. diff" – which kills 14,000 Americans each year. It also shows efficacy against Cryptosporidium (protozoans that cause diarrhea) and Helicobacter pylori in mouse models of infection and potentially against many other human pathogens, including Campylobacter jejuni. 

Humans Have Antibodies against a Plant Virus: Evidence from Tobacco Mosaic Virus.

Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies (IgG, IgG1, IgG3, IgG4, IgA, and IgM) in all subjects enrolled in the study (20 healthy smokers, 20 smokeless-tobacco users, and 20 non-smokers). Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L (an outer mitochondrial membrane 40 homolog - like translocase) contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson's disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson's disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored.

'Backbone' of mental illness stigma common in 16 countries studied

Even in countries with cultures more accepting of mental illness, the "backbone" of stigma was detected, encompassing issues involving caring for children, marriage, self-harm and holding roles of authority or civic responsibility. The stigma was even stronger toward people with schizophrenia.

New findings on the brain's immune cells during Alzheimer's disease progression

 "The plaque deposits in the brain of Alzheimer's patients are surrounded by the brain's own immune cells, the microglia. This was already recognized by Alois Alzheimer more than one hundred years ago. But until today it still remains unclear what role microglia play in Alzheimer's disease. Do they help to break down the plaque deposit? A study by researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité -- Universitätsmedizin Berlin has now shed light on these mysterious microglia during the progression of Alzheimer's disease."

Some types of papilloma virus might prevent cervical cancer

Certain types of papilloma virus might actually prevent cervical cancer, according to a new study by researchers from The University of Manchester.

Blocking a key protein boosts immune system's ability to clear chronic infection / UCLA Newsroom

Paradoxically, a temporary break in interferon (IFN-1) signaling improved the immune system's ability to control infection. Our next step will be to figure out why and how to harness it for therapies to treat humans.

A correlation study between multiple sclerosis and type 1 diabetes incidences and geochemical data in Europe.

Complex multifactorial disorders usually arise in individuals genetically at risk in the presence of permissive environmental factors. For many of these diseases, predisposing gene variants are partly known while the identification of the environmental component is much more difficult. This study aims to investigate whether there are correlations between the incidence of two complex traits, multiple sclerosis and type 1 diabetes, and some chemical elements and compounds present in soils and stream sediments in Europe. Data were obtained from the published literature and analyzed by calculating the mean values of each element and of disease incidence for each Country, respectively, 17 for multiple sclerosis and 21 for type 1 diabetes. Correlation matrices and regression analyses were used in order to compare incidence data and geochemical data. R correlation index and significance were evaluated. The analyses performed in this study have revealed significant positive correlations between barium and sodium oxide on one hand and multiple sclerosis and diabetes incidences on the other hand that may suggest interactions to be evaluated between silicon-rich lithologies and/or marine environments. The negative correlations shown by cobalt, chromium and nickel (typical of silicon-poor environment), which in this case can be interpreted as protective effects against the two diseases onset, make the split between favorable and protective environments even more obvious. In conclusion, if other studies will confirm the involvement of the above elements and compounds in the etiology of these pathologies, then it will be possible to plan strategies to reduce the spread of these serious pandemics.

Gene-environment interaction in Alzheimer's disease.

The aim was to examine the gene environment (GxE) interaction with reference to APO E genotypes, serum lipids and organochlorine pesticides (OCPs) as one of the factors in the etiology of Alzheimer's disease (AD).

METHODS:

A case control study was used to examine, APOE HhaI polymorphism by polymerase chain reaction (PCR)/PCRrestriction fragment length polymorphism method, serum lipids by autoanalyser and OCPs by gas chromatography (GC).

RESULTS:

APOE ∈4 allele frequency was significantly high (p=0.000, OR=5.73, CI=2.68-12.50) in AD as compared to controls. The serum cholesterol, β- hexachlorocyclohexane and dieldrin are risk factors for AD independent of the APOE ∈4 risk allele, recording an odds ratio of 1.16, 11.38 and 10.45 respectively.

CONCLUSION:

GxE interactions exist with APOE ∈4 allele status that need to be considered for the study design and analysis of such data in future studies of AD.

Study reveals function of thousands of autoantibodies in blood

"Using human protein microarrays, the researchers examined the immune-response profiling of 166 individuals, including subject groups of Alzheimer's, Parkinson's, multiple sclerosis and breast cancer patients. Among the study's startling findings:
Most people have more than 1,000 discrete autoantibodies present in their blood and an individual's unique autoantibody profile remains relatively consistent over time.
Women have significantly more autoantibodies than men which may account for the higher incidence of autoimmune diseases among women.
Increasing age is accompanied by a corresponding increase in the number of detectable autoantibodies.
Alzheimer's, Parkinson's, multiple sclerosis and breast cancer patients all had measurably lower numbers of autoantibodies than age- and gender-matched controls."

JAMA NetworkGenomes of Microbes Inhabiting the Body Offer Clues to Human Health and Disease

When the Human Genome Project revealed that human chromosomes encode a paltry 21 500 genes, far fewer than anticipated, scientists began to think outside the genome to find additional factors that could be involved in the complexities of human health and disease.

They didn't have to look far. The human microbiome, the constellation of microbes living in and on the body, harbors millions of additional genes that contribute to the well-being of their host.

Although much is known about how pathogens contribute to disease, the roles played by the more abundant beneficial and benign members of the microbiome are less well understood. Often this is because it is very difficult or impossible to culture these organisms outside of the human host. Through research in metagenomics, in which genomic analyses of entire microbial communities are carried out, and investigations into host-microbe interactions, researchers are studying the microbial contributions to health and disease and using what they are learning to develop new diagnostic and therapeutic strategies.

The relationship between prenatal stress and obesity is confirmed in rats

"The growing prevalence of obesity cannot be solely attributed to genetic factors or poor nutrition, but also to lifestyle and adverse environmental factors," as explained to SINC by Javier Campión, lead researcher of this new study. "The said environmental factors could have a bearing on epigenetic mechanisms, which are responsible for the control of genes beyond the genetic code itself".

Omega-3 fatty acids more effective at inhibiting growth of triple-negative breast cancer

 "Researchers from Fox Chase Cancer Center have found that omega-3 fatty acids and their metabolite products slow or stop the proliferation, or growth in the number of cells, of triple-negative breast cancer cells more effectively than cells from luminal types of the disease. The omega-3s worked against all types of cancerous cells, but the effect was observed to be stronger in triple-negative cell lines, reducing proliferation by as much as 90 percent. The findings will be presented at the AACR Annual Meeting 2013 on Tuesday, April 9."

Plastic chemical may expose foetuses to cancer

 "France said Tuesday it would call for Europe-wide controls on a paper product containing bisphenol A after a watchdog agency said the widely-used chemical may expose unborn children to breast cancer later in life."

Google searches about mental illness follow seasonal patterns

 "A new study published in the May issue of the American Journal of Preventive Medicine finds that Google searches for information across all major mental illnesses and problems followed seasonal patterns, suggesting mental illness may be more strongly linked with seasonal patterns than previously thought."

UCLA researchers find potential link between auto pollution, some childhood cancers / UCLA Newsroom

 "The researchers found that heightened exposure to traffic-related air pollution was associated with increases in three rare types of childhood cancer: acute lymphoblastic leukemia (white blood cell cancer), germ-cell tumors (cancers of the testicles, ovaries and other organs) and retinoblastoma (eye cancer), particularly bilateral retinoblastoma, in which both eyes are affected.

The pollution-exposure estimates were highly correlated across pregnancy trimesters and the first year of life, meaning that even in areas of high exposure, no particular period stood out as a higher-exposure time. This, the scientists said, made it difficult to determine if one period of exposure was more dangerous than any other."

USF Health News » USF study finds plant proteins control chronic disease in Toxoplasma infections

A new discovery about the malaria-related parasite Toxoplasma gondii — which can threaten babies, AIDS patients, the elderly and others with weakened immune function — may help solve the mystery of how this single-celled parasite establishes life-long infections in people.

The study, led by a University of South Florida research team, places the blame squarely on a family of proteins, known as AP2 factors, which evolved from the regulators of flowering in plants.

Immune System Development and Vitamin D levels Influenced By Birth Month

MNT: Newborn babies' immune systems and vitamin D levels vary, depending on which month of the year they were born. The study gives a possible biological platform as to why a person's risk of developing muliple sclerosis is impacted by the month they were born in. Additionally, it identifies the need for more research into the possible advantages of vitamin D supplementation during pregnancy.

First Mutations Leading To Leukemia Identified

MNT "The first mutations leading to leukemia in the mother's womb have been identified, according to researchers who sequenced the entire genomes of identical twins with the disease."

Unraveling the Secrets of the Epigenome:Webinar

 "While the human genome continues to intrigue researchers with the complexities embedded in the entirety of its DNA sequence, what’s on DNA and how it's packaged are increasingly important for understanding disease, including cancer. This second webinar in The Scientist's Decoding DNA series will cover the Secrets of the Epigenome, discussing what is currently known about DNA methylation, histone modifications, and chromatin remodeling and how this knowledge can translate to useful therapies. Following brief presentations by our panel of experts, there will be a live Q&A session during which attendees can ask questions and discuss issues related to the burgeoning field of epigenetics.
"

Minocycline, an antibiotic, improves behavior for children with fragile X syndrome

 "Minocycline, an older, broad-spectrum antibiotic in the tetracycline family, provides meaningful improvements as a therapeutic for children with fragile X syndrome, a study by researchers at the UC Davis MIND Institute has found. The finding is important, the researchers said, because minocycline is a targeted treatment for the condition that is readily available by prescription."

'via Blog this'

Fetal exposure to excessive stress hormones in the womb linked to adult mood disorders

"Exposure of the developing fetus to excessive levels of stress hormones in the womb can cause mood disorders in later life and now, for the first time, researchers have found a mechanism that may underpin this process, according to research presented April 7 at the British Neuroscience Association Festival of Neuroscience (BNA2013) in London."

Higher mercury levels in humans associated with increased risk for diabetes

 "A new study found that higher levels of mercury exposure in young adults increased their risks for type 2 diabetes later in life by 65 percent. The study, led by Indiana University School of Public Health-Bloomington epidemiologist Ka He, is the first to establish the link between mercury and diabetes in humans."

Fecal Microbiota Composition Differs Between Children With β-Cell Autoimmunity and Those Without

The role of the intestinal microbiota as a regulator of autoimmune diabetes in animal models is well-established, but data on human type 1 diabetes are tentative and based on studies including only a few study subjects. To exclude secondary effects of diabetes and HLA risk genotype on gut microbiota, we compared the intestinal microbiota composition in children with at least two diabetes-associated autoantibodies (n = 18) with autoantibody-negative children matched for age, sex, early feeding history, and HLA risk genotype using pyrosequencing. Principal component analysis indicated that a low abundance of lactate-producing and butyrate-producing species was associated with β-cell autoimmunity. In addition, a dearth of the two most dominant Bifidobacterium species,Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and an increased abundance of the Bacteroides genus were observed in the children with β-cell autoimmunity. We did not find increased fecal calprotectin or IgA as marker of inflammation in children with β-cell autoimmunity. Functional studies related to the observed alterations in the gut microbiome are warranted because the low abundance of bifidobacteria and butyrate-producing species could adversely affect the intestinal epithelial barrier function and inflammation, whereas the apparent importance of the Bacteroides genus in development of type 1 diabetes is insufficiently understood.