Influenza A virus nucleoprotein induces apoptosis in human airway epithelial cells: implications of a novel interaction between nucleoprotein and host protein Clusterin.

Apoptosis induction is an antiviral host response, however, influenza A virus (IAV) infection promotes host cell death. The nucleoprotein (NP) of IAV is known to contribute to viral pathogenesis, but its role in virus-induced host cell death was hitherto unknown. We observed that NP contributes to IAV infection induced cell death and heterologous expression of NP alone can induce apoptosis in human airway epithelial cells. The apoptotic effect of IAV NP was significant when compared with other known proapoptotic proteins of IAV. The cell death induced by IAV NP was executed through the intrinsic apoptosis pathway. We screened host cellular factors for those that may be targeted by NP for inducing apoptosis and identified human antiapoptotic protein Clusterin (CLU) as a novel interacting partner. The interaction between IAV NP and CLU was highly conserved and mediated through β-chain of the CLU protein. Also CLU was found to interact specifically with IAV NP and not with any other known apoptosis modulatory protein of IAV. CLU prevents induction of the intrinsic apoptosis pathway by binding to Bax and inhibiting its movement into the mitochondria. We found that the expression of IAV NP reduced the association between CLU and Bax in mammalian cells. Further, we observed that CLU overexpression attenuated NP-induced cell death and had a negative effect on IAV replication. Collectively, these findings indicate a new function for IAV NP in inducing host cell death and suggest a role for the host antiapoptotic protein CLU in this process.


Lyme Disease Antibodies Attached To Nanotubes, Paving Way For Diagnostic Device

 "Early diagnosis is critical in treating Lyme disease. However, nearly one quarter of Lyme disease patients are initially misdiagnosed because currently available serological tests have poor sensitivity and specificity during the early stages of infection. Misdiagnosed patients may go untreated and thus progress to late-stage Lyme disease, where they face longer and more invasive treatments, as well as persistent symptoms. "


The risk of autism is not increased by 'too many vaccines too soon'

 "Although scientific evidence suggests that vaccines do not cause autism, approximately one-third of parents continue to express concern that they do; nearly 1 in 10 parents refuse or delay vaccinations because they believe it is safer than following the Centers for Disease Control and Prevention's (CDC) schedule. A primary concern is the number of vaccines administered, both on a single day and cumulatively over the first 2 years of life. In a new study scheduled for publication in The Journal of Pediatrics, researchers concluded that there is no association between receiving "too many vaccines too soon" and autism."


BBC News - Synchrotron yields 'safer' vaccine: foot and mouth virus

British scientists have developed a new method to create an entirely synthetic vaccine which doesn't rely on using live infectious virus, meaning it is much safer.

Innate immune system can kill HIV when a viral gene is deactivated

 "A family of human proteins called APOBEC3 effectively restrict the growth of HIV and other viruses, but this action is fully counteracted by the viral infectivity factor gene (vif) in HIV. In the study, researchers intravenously infected humanized mice with HIV. They found that the most commonly transmitted strains of HIV are completely neutralized by APOBEC3 proteins when vif is removed from the virus.
"Without the vif gene, HIV can be completely destroyed by the body's own immune system," said J. Victor Garcia, PhD, professor of medicine at the UNC School of Medicine and senior author on the study. "These results suggest a new target for developing drugs fully capable of killing the virus.""


Combinations of estrogen-mimicking chemicals found to strongly distort hormone action

 "For years, scientists have been concerned about chemicals in the environment that mimic the estrogens found in the body. In study after study, researchers have found links between these "xenoestrogens" and such problems as decreased sperm viability, ovarian dysfunction, neurodevelopmental deficits and obesity. But experimental limitations have prevented them from exploring one of the most serious questions posed by exposure to xenoestrogens: what happens when—as in the real world—an individual is exposed to multiple estrogen-mimicking chemicals at the same time?"

'via Blog this'

Experimental drug may work against hepatitis C

(HealthDay)—An experimental therapy for hepatitis C—a "silent killer" linked to liver cancer and cirrhosis—has shown promise in tamping down virus levels in early trials."


Unraveling the Secrets of the Epigenome: webinar

A section of DNA; the sequence of the plate-li...
A section of DNA; the sequence of the plate-like units (nucleotides) in the center carries information. (Photo credit: Wikipedia)
"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.
"


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Retinoic acid-elicited RARα/RXRα signaling attenuates Aβ production by directly inhibiting γ-secretase-mediated cleavage of amyloid precursor protein.

Retinoic acid (RA)-elicited signaling has been shown to play critical roles in development, organogenesis, and the immune response. RA regulates expression of Alzheimer's disease (AD)-related genes, and attenuates amyloid pathology in a transgenic mouse model. In this study, we investigated whether RA can suppress the production of amyloid- (A) through direct inhibition of γ-secretase activity. We report that RA treatment of cells results in significant inhibition of -secretase-mediated processing of the amyloid precursor protein C-terminal fragment APP-C99, as compared to DMSO-treated controls. RA-elicited signaling was found to significantly increase accumulation of APP-C99, and decrease production of secreted Aβ40. In addition, RA-induced inhibition of -secretase activity was found to be mediated through significant activation of extracellular signal-regulated kinases (ERK1/2). Treatment of cells with the specific ERK inhibitor PD98059 completely abolished RA-mediated inhibition of γ-secretase. Consistent with these findings, RA was observed to inhibit secretase-mediated proteolysis of full-length APP. Finally, we have established that RA inhibits γ-secretase through nuclear retinoic acid receptor-alpha (RARα) and retinoid X receptor-alpha (RXRα). Our findings provide a new mechanistic explanation for the neuroprotective role of RA in AD pathology, and add to the previous data showing the importance of RA signaling as a target for AD therapy.

Nature Genetics - iCOGS: genetic susceptibility to three hormone-related cancers: breast, ovarian and prostate cancer

 "Nature Genetics is pleased to present the iCOGS Focus comprising a collection of 13 papers from COGS, representing a significant advance in our understanding of genetic susceptibility to three hormone-related cancers: breast, ovarian and prostate cancer. We hope that you will find this Focus issue, as well as the accompanying Focus online, a useful guide to this milestone in genetic epidemiology."


New insights into how genes turn on and off

Researchers at UC Davis and the University of British Columbia have shed new light on methylation, a critical process that helps control how genes are expressed. Working with placentas, the team discovered that 37 percent of the placental genome has regions of lower methylation, called partially methylated domains (PMDs), in which gene expression is turned off. This differs from most human tissues, in which 70 percent of the genome is highly methylated"


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All-trans retinoic acid rescues memory deficits and neuropathological changes in mouse model of streptozotocin-induced dementia of Alzheimer's type.

Recent studies have revealed that aberrant vitamin A signaling may lead to memory deficits in rodents. Present study investigates the potential of all-trans-retinoic acid (ATRA) an agonist at retinoid acid family of receptors, in cognitive dysfunctions associated with experimental dementia. Streptozotocin (STZ) [3 mg/kg, intracerebroventricularly (i.c.v)] was administered on alternate days (day 1 and day 3) to induce dementia in Swiss albino mice. STZ mice were administered ATRA (10 mg/kg; 20 mg/kg, p.o.) for a total of 19 days following second i.c.v injection of STZ [day 4 to day 22]. Morris water maze (MWM) test was performed on days 19, 20, 21, 22 and 23 to assess learning and memory of the animals. Following MWM test, the animals were sacrificed for biochemical and histopathological studies. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice showed marked accentuation of AChE activity, TBARS and MPO levels along with fall in GSH level. Further the stained micrographs of STZ-treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. ATRA treatment significantly attenuated STZ-induced memory deficits, biochemical and histopathological alterations. The findings demonstrate that the memory restorative ability of ATRA may be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory potential.

FindZebra - The search engine for difficult medical cases

 "There are close to 7,000 rare diseases recognized by rare disease organizations. We index over 31,000 documents covering rare and genetic diseases from 10 reputable sources. Given the number of rare diseases and rate of publication, we think FindZebra is a good companion for medical professionals."


Einstein Study Reveals New Approach for Stopping Herpes Infections | Albert Einstein College of Medicine

Dr. Herold and her colleagues had previously shown that infection by the herpes viruses depends on calcium released within the cells. In this study, they found that calcium release occurs because the viruses activate a critical cell-signaling molecule called Akt1 at the cell membrane.
As part of their investigation of Akt’s role in herpes infections, the researchers took laboratory cultures of those human cell types and mixed them for 15 minutes with four different drugs known to inhibit Akt. The cells were then exposed for one hour to herpes simplex virus 2. All four drugs significantly inhibited herpes virus infection in each of the cell types. By contrast, cells not pretreated with the Akt inhibitors were readily infected on exposure to the virus.

Obesity may be linked to microorganisms living in the gut, study says

The study, which will also appear in JCEM's April 2013 issue, analyzed the breath content of 792 people. Based on the breath tests, four patterns emerged. The subjects either had normal breath content, higher concentrations of methane, higher levels of hydrogen, or higher levels of both gases. Those who tested positive for high concentrations of both gases had significantly higher body mass indexes and higher percentages of body fat.
The presence of methane is associated with a microorganism called Methanobrevibacter smithii. This organism is responsible for the majority of methane production in the human host."

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Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits.

Following antibiotic treatment for Lyme disease, some patients report persistent or relapsing symptoms of pain, fatigue, and/or cognitive deficits. Factors other than active infection, including immune abnormalities, have been suggested, but few clues regarding mechanism have emerged. Furthermore, the effect of antibiotic treatment on immune response in affected individuals remains unknown. In this study, a longitudinal analysis of specific immune markers of interest was carried out in patients with a history of Lyme disease and persistent objective memory impairment, prior to and following treatment with either ceftriaxone or placebo. IFNα activity was measured by detection of serum-induced changes in specific target genes, using a functional cell-based assay and quantitative real-time PCR. Level and pattern of antibody reactivity to brain antigens and to Borrelia burgdorferi proteins were analyzed by ELISA and immunoblotting. Sera from the patient cohort induced significantly higher expression of IFIT1 and IFI44 target genes than those from healthy controls, indicating increased IFNα activity. Antibody reactivity to specific brain and borrelial proteins was significantly elevated in affected patients. IFNα activity and antibody profile did not change significantly in response to ceftriaxone. The heightened antibody response implies enhanced immune stimulation, possibly due to prolonged exposure to the organism prior to the initial diagnosis and antibiotic treatment of Lyme disease. The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.

Other stomach microbiota modulate resistance to H. pylori-driven ulcers

 "Mice with different naturally occurring stomach bacteria have distinct susceptibilities to disease caused by Helicobacter pylori, the well-known cause of ulcers in humans, according to a study published online ahead of print in the journal Infection and Immunity. This is the first study to document (in mice) that the presence of certain bacteria in the stomach microbiota can prevent pathology from H. pylori."


PLOS ONE: Cerebrospinal Fluid PKR Level Predicts Cognitive Decline in Alzheimer’s Disease

The cerebrospinal fluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer’s disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of Aβ peptide (Aβ 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE] = 0.03). A lower MMSE at baseline was associated with lower levels of CSF Aβ 1–42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline.

PKR (EIF2AK2) is activated by viral DNA

Hunger-spiking neurons could help control autoimmune diseases

 "Neurons that control hunger in the central nervous system also regulate immune cell functions, implicating eating behavior as a defense against infections and autoimmune disease development, Yale School of Medicine researchers have found in a new study published in the Proceedings of the National Academy of Sciences (PNAS)."

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Could that cold sore and other infections increase your risk of memory problems?

"The virus that causes cold sores, along with other viral or bacterial infections, may be associated with cognitive problems, according to a new study published in the March 26, 2013, print issue of Neurology."For the study, researchers tested thinking and memory in 1,625 people with an average age of 69 from northern Manhattan in New York. Participants gave blood samples that were tested for five common low grade infections: three viruses (herpes simplex type 1 (oral) and type 2 (genital), and cytomegalovirus), chlamydia pneumoniae (a common respiratory infection) and Helicobacter pylori (a bacteria found in the stomach).

Did evolution give us inflammatory disease?

 "The findings suggest that in the past these variants rose in frequency in the human population to help protect us against viruses, bacteria and other pathogens. But now in our modern world, the environment and exposure to pathogens has changed, and the genetic variants that were originally meant to protect us, now make an autoimmune reaction more likely. These results are consistent with the hygiene hypothesis in which our cleaner environment is thought to contribute to the increasing prevalence of inflammatory diseases."

Shielding Babies From Certain Foods And Dust Mites May Prevent Asthma

 "Arshad and his colleagues analyzed 120 patients with a family history of allergy who were found to be at high risk of allergy at birth 23 years ago. Their aim was to explore whether mothers who breastfeed and their kids who followed an exact diet, in combination with the use of vinyl mattress covers and pesticides to eliminate dust mites, had a decreased risk of developing asthma.
The diet included, soy, fish and nuts, eggs and dairy products"
The paper is here:-


Multifaceted allergen avoidance during infancy reduces asthma during childhood with the effect persisting until age 18 years

Promising Phase II Data For New Alzheimer's Disease Drug Presented

A novel drug (ORM-12741) developed by Orion Corporation could improve cognitive and behavioral symptoms in patients with Alzheimer's disease. According to a Phase IIa study, presented yesterday at American Academy of Neurology's Annual Meeting in San Diego, ORM-12741 (a potent and selective alpha-2c adrenoceptor  antagonist  ) showed significant positive effects on episodic memory in patients with moderate Alzheimer's disease.

Atherosclerosis: Specific microRNAs promote inflammation

 "Atherosclerosis, an inflammatory reaction, is at the root of the most common forms of cardiovascular disease. Researchers at Ludwig-Maximilians-Universitaet in Munich have now identified a microRNA that plays a prominent role in the process, and offers a promising target for new therapies."

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Researchers define how a gene mutated in Parkinson's disease may normally function to ensure neuronal health

Cell biologists studying Parkinson's disease are training their sights on mitochondria, the energy source of the cell, whose activity in neurons appears to go awry in this devastating neurodegenerative illness. A neuron needs its mitochondria to be healthy and mobile, particularly during their continual cycles of fission and fusion in which damaged bits are removed and healthy mitochondria are renewed.

Read more at: http://medicalxpress.com/news/2013-03-gene-mutated-parkinson-disease-function.html#jCp

Naproxen Shows Anti-Viral Activity Against Flu

MNT: The over-the-counter anti-inflammatory drug naproxen may also exhibit antiviral activity against influenza A virus, according to a team of French scientists. The finding, the result of a structure-based investigation, is published online ahead of print in the journal Antimicrobial Agents and Chemotherapy. 

The landscape of host transcriptional response programs commonly perturbed by bacterial pathogens: towards host-oriented broad-spectrum drug targets.

The emergence of drug-resistant pathogen strains and new infectious agents pose major challenges to public health. A promising approach to combat these problems is to target the host's genes or proteins, especially to discover targets that are effective against multiple pathogens, i.e., host-oriented broad-spectrum (HOBS) drug targets. An important first step in the discovery of such drug targets is the identification of host responses that are commonly perturbed by multiple pathogens.

RESULTS:

In this paper, we present a methodology to identify common host responses elicited by multiple pathogens. First, we identified host responses perturbed by each pathogen using a gene set enrichment analysis of publicly available genome-wide transcriptional datasets. Then, we used biclustering to identify groups of host pathways and biological processes that were perturbed only by a subset of the analyzed pathogens. Finally, we tested the enrichment of each bicluster in human genes that are known drug targets, on the basis of which we elicited putative HOBS targets for specific groups of bacterial pathogens. We identified 84 up-regulated and three down-regulated statistically significant biclusters. Each bicluster contained a group of pathogens that commonly dysregulated a group of biological processes. We validated our approach by checking whether these biclusters correspond to known hallmarks of bacterial infection. Indeed, these biclusters contained biological process such as inflammation, activation of dendritic cells, pro- and anti- apoptotic responses and other innate immune responses. Next, we identified biclusters containing pathogens that infected the same tissue. After a literature-based analysis of the drug targets contained in these biclusters, we suggested new uses of the drugs Anakinra, Etanercept, and Infliximab for gastrointestinal pathogens Yersinia enterocolitica, Helicobacter pylori kx2 strain, and enterohemorrhagic Escherichia coli and the drug Simvastatin for hematopoietic pathogen Ehrlichia chaffeensis.

CONCLUSIONS:

Using a combination of automated analysis of host-response gene expression data and manual study of the literature, we have been able to suggest host-oriented treatments for specific bacterial infections. The analyses and suggestions made in this study may be utilized to generate concrete hypothesis on which gene sets to probe further in the quest for HOBS drug targets for bacterial infections. All our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/murali/supplements/2013-kidane-plos-one.

Antipurinergic Therapy Corrects the Autism-Like Features in the Poly(IC) Mouse Model.

Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act to connect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry of the cell and its environment. Mitochondrial ATP and other metabolites are mitokines-signaling molecules made in mitochondria-that undergo regulated release from cells to communicate cellular health and danger to neighboring cells via purinergic signaling. The role of purinergic signaling has not yet been explored in autism spectrum disorders.

OBJECTIVES AND METHODS:

We used the maternal immune activation (MIA) mouse model of gestational poly(IC) exposure and treatment with the non-selective purinergic antagonist suramin to test the role of purinergic signaling in C57BL/6J mice.

RESULTS:

We found that antipurinergic therapy (APT) corrected 16 multisystem abnormalities that defined the ASD-like phenotype in this model. These included correction of the core social deficits and sensorimotor coordination abnormalities, prevention of cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.

CONCLUSIONS:

Hyperpurinergia is a fundamental and treatable feature of the multisystem abnormalities in the poly(IC) mouse model of autism spectrum disorders. Antipurinergic therapy provides a new tool for refining current concepts of pathogenesis in autism and related spectrum disorders, and represents a fresh path forward for new drug development.

New diagnostic technology points to possible new antibody blood tests for conditions from Alzheimer's to autoimmune diseases

"Researchers at The Scripps Research Institute (TSRI) in Jupiter, FL, have developed cutting-edge technology that can successfully screen human blood for disease markers. This tool may hold the key to better diagnosing and understanding today's most pressing and puzzling health conditions, including autoimmune diseases."

This concerns the use of thousands of randomly synthesised peptoid antigens: Blood borne antibodies bind to some of these providing a profile that is of diagnostic use.  

Chemical compounds that halt virus replication identified

"In this study, researchers identified a new chemical class of compounds that effectively blocked genetically diverse viruses from replicating by limiting RNA production by the virus in cell culture. These indoline alkaloid-type compounds inhibited a number of viruses from replicating, including Ebola."

Paper in Chemistry and Biology:-

Identification of a broad-spectrum inhibitor of virus RNA synthesis: validation of a prototype virus-based approach

Quirky Lyme disease bacteria: Unlike most organisms, they don't need iron, but crave manganese

 "Scientists have confirmed that the pathogen that causes Lyme Disease -- unlike any other known organism -- can exist without iron, a metal that all other life needs to make proteins and enzymes. Instead of iron, the bacteria substitute manganese to make an essential enzyme, thus eluding immune system defenses that protect the body by starving pathogens of iron."Borrelia burgdorferi requires unusually high levels of manganese, according to scientists at Johns Hopkins University (JHU), Woods Hole Oceanographic Institution (WHOI), and the University of Texas


180,000 deaths worldwide may be associated with sugary soft drinks | American Heart Association

 "Sugar-sweetened beverages are consumed throughout the world, and contribute to excess body weight, which increases the risk of developing diabetes, cardiovascular diseases and some cancers. Using data collected as part of the 2010 Global Burden of Diseases Study, the researchers linked intake of sugar- sweetened beverages to 133,000 diabetes deaths, 44,000 deaths from cardiovascular diseases and 6,000 cancer deaths. Seventy-eight percent of these deaths due to over-consuming sugary drinks were in low and middle-income countries, rather than high-income countries."


Researchers identify new substance in olive oil that reduces risk of Alzheimer's disease

chemical structure of oleocanthal
chemical structure of oleocanthal (Photo credit: Wikipedia)
"Amal Kaddoumi and colleagues note that Alzheimer's disease affects about 30 million people worldwide, but the prevalence is lower in Mediterranean countries. Scientists once attributed it to the high concentration of healthful monounsaturated fats in olive oil - consumed in large amounts in the Mediterranean diet. Newer research suggested that the actual protective agent might be a substance called oleocanthal, which has effects that protect nerve cells from the kind of damage that occurs in AD. "


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Excellent Results For MS Drug "Plegridy"

MNT "Biogen Idec has just announced its final first year results of the Phase 3 trial of its relapsing-remitting multiple sclerosis drug Plegridy (peginterferon beta-1a). The drug met all primary and secondary endpoints of the trial results indicating that it is very effective at reducing multiple sclerosis (MS) disease activity. "

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Major Discovery For Alzheimer's Disease

MNT  "scientists were able to identify centaurin alpha 1 ( ADAP1 or CENTA1) and measure its negative effects on neurons. Utilizing an RNA silencing technique, they turned down the cellular production of CentA1, and showed that affected neurons, exposed to Amyloid beta and exhibiting Alzheimer's related symptoms, returned to normal morphology and synaptic function, even with the continued presence of Amyloid beta. They further found that increased CentA1 activates a series of proteins, and these proteins form a signaling pathway from CentA1 to neuronal dysfunction. Thus, inhibiting other proteins in the pathway also "cured" affected neurons. "
J. Neurosci paper
Centaurin-α1-Ras-Elk-1 Signaling at Mitochondria Mediates β-Amyloid-Induced Synaptic Dysfunction

Alzheimer's therapeutics: continued clinical failures question the validity of the amyloid hypothesis-but what lies beyond?

Healthy brain (bottom) versus brain of a donor...
Healthy brain (bottom) versus brain of a donor with Alzheimer's disease. Notable is the "shrink" that has occurred in Alzheimer's disease; the brain was decreased in size. (Photo credit: Wikipedia)
The worldwide incidence of Alzheimer's disease (AD) is increasing with estimates that 115 million individuals will have AD by 2050, creating an unsustainable healthcare challenge due to a lack of effective treatment options highlighted by multiple clinical failures of agents designed to reduce the brain amyloid burden considered synonymous with the disease. The amyloid hypothesis that has been the overarching focus of AD research efforts for more than two decades has been questioned in terms of its causality but has not been unequivocally disproven despite multiple clinical failures, This is due to issues related to the quality of compounds advanced to late stage clinical trials and the lack of validated biomarkers that allow the recruitment of AD patients into trials before they are at a sufficiently advanced stage in the disease where therapeutic intervention is deemed futile. Pursuit of a linear, reductionistic amyloidocentric approach to AD research, which some have compared to a religious faith, has resulted in other, equally plausible but as yet unvalidated AD hypotheses being underfunded leading to a disastrous roadblock in the search for urgently needed AD therapeutics. Genetic evidence supporting amyloid causality in AD is reviewed in the context of the clinical failures, and progress in tau-based and alternative approaches to AD, where an evolving modus operandi in biomedical research fosters excessive optimism and a preoccupation with unproven, and often ephemeral, biomarker/genome-based approaches that override transparency, objectivity and data-driven decision making, resulting in low probability environments where data are subordinate to self propagating hypotheses.
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Genetic susceptibility loci, environmental exposures, and Parkinson's disease: A case-control study of gene-environment interactions.

BACKGROUND:
Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility.

METHODS:

Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script.

RESULTS:

Five pairwise interactions had uncorrected P-values < 0.05. These included pairings of pesticides × SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction.

CONCLUSIONS:

This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.

Maternal diabetes impairs methylation of imprinted gene in oocytes

 "For the first time, researchers have shown that poorly controlled maternal diabetes has an adverse effect on methylation of the maternal imprinting gene Peg3, contributing to impaired development in offspring."


Genetic evidence that new therapies targeting Synuclein in Parkinson's disease may cause harm

 "NorthShore University HealthSystem (NorthShore) and Mayo Clinic researchers have partnered on a study that shows genetic and clinical evidence that therapies targeting the expression of alpha-synuclein -- a gene whose function is involved in the development and progression of Parkinson's disease -- may accelerate disease progression and increase the risk of physical incapacitation and dementia. If replicated, the findings will have profound implications for therapies under development for Parkinson's disease."


Older grandfathers pass on autism risk through generations

Reports of autism cases per 1,000 children gre...
Reports of autism cases per 1,000 children grew dramatically in the US from 1996 to 2007. It is unknown how much, if any, growth came from changes in autism's prevalence. (Photo credit: Wikipedia)
The study found that the risk of autism in the grandchild increased the older the age of the grandfather at the time his son or daughter was born. Men who had a daughter when they were 50 or older were 1.79 times more likely to have a grandchild with autism. Men who had a son when they were 50 or older were 1.67 times more likely to have a grandchild with autism, compared to men who had children when they were 20-24.
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Fetal exposure to antiepileptic drug valproate impairs cognitive development

 "(Medical Xpress)—The effects of antiepileptic drugs during pregnancy have long been a concern of clinicians and women of childbearing age whose seizures can only be controlled by medications. In 1999, a study called the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) began following the children of women who were taking a single antiepileptic agent during pregnancy. The drugs included carbamazepine, lamotrigine, phenytoin or valproate."

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A New Target for Lupus Treatment: Scripps

A team at The Scripps Research Institute (TSRI) has made a discovery that may lead to better treatments for lupus, a debilitating autoimmune disease that affects tens of millions of people all over the world.
Therapies for lupus do exist, but they do not directly target its underlying causes, primarily because the origins of the condition are not entirely known. The condition appears to arise from both genetic and environmental factors and involves complex autoimmune processes. A key feature of the disease is the activity of antibodies – also known as "autoantibodies" – that attack the patient's own cellular proteins, including DNA and RNA. "In this new study, TSRI researchers determined that the absence of a certain type of immune cell – or a key signaling molecule within the cell ( SLC15A4 )– could protect against lupus. In a mouse model of the disease, patients without the cell or signaling molecule showed little impairment of their normal immune functions.


Omega-3 Fatty Acids Enhance Phagocytosis of Alzheimer's Disease-Related Amyloid-β42 by Human Microglia and Decrease Inflammatory Markers.

The use of supplements with omega-3 (ω3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is widespread due to proposed beneficial effects on the nervous and cardiovascular systems. Many effects of ω3 FAs are believed to be caused by down-regulation and resolution of inflammation. Alzheimer's disease (AD) is associated with inflammation mediated by microglia and astrocytes, and ω3 FAs have been proposed as potential treatments for AD. The focus of the present study is on the effects of DHA and EPA on microglial phagocytosis of the AD pathogen amyloid-β (Aβ), on secreted and cellular markers of immune activity, and on production of brain-derived neurotrophic factor (BDNF). Human CHME3 microglial cells were exposed to DHA or EPA, with or without the presence of Aβ42. Phagocytosis of Aβ42 was analyzed by flow cytometry in conjunction with immunocytochemistry using antibodies to cellular proteins. Secreted proteins were analyzed by ELISA. Both DHA and EPA were found to stimulate microglial phagocytosis of Aβ42. Phagocytosis of Aβ42 was performed by microglia with a predominance of M2 markers. EPA increased the levels of BDNF in the culture medium. The levels of TNF-α were decreased by DHA. Both DHA and EPA decreased the pro-inflammatory M1 markers CD40 and CD86, and DHA had a stimulatory effect on the anti-inflammatory M2 marker CD206. DHA and EPA can be beneficial in AD by enhancing removal of Aβ42, increasing neurotrophin production, decreasing pro-inflammatory cytokine production, and by inducing a shift in phenotype away from pro-inflammatory M1 activation.

Futurity.org – Does low-fat milk make kids heavier?

Preschoolers who drink low-fat milk are more likely to be overweight or obese than kids given 2 percent or whole milk, new research suggests.

Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings.

It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants.

OBJECTIVES:

To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants.

DESIGN:

We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population.

SETTING:

Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register.

PARTICIPANTS:

In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden.

MAIN OUTCOME MEASURES:

Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status.

RESULTS:

Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In the case of depression, this more than compensated for the lower fecundity of affected individuals.

CONCLUSIONS:

Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.

The ISME Journal - An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice

Lipopolysaccharide endotoxin is the only known bacterial product which, when subcutaneously infused into mice in its purified form, can induce obesity and insulin resistance via an inflammation-mediated pathway. Here we show that one endotoxin-producing bacterium isolated from a morbidly obese human’s gut induced obesity and insulin resistance in germfree mice. The endotoxin-producing Enterobacter decreased in relative abundance from 35% of the volunteer’s gut bacteria to non-detectable, during which time the volunteer lost 51.4kg of 174.8kg initial weight and recovered from hyperglycemia and hypertension after 23 weeks on a diet of whole grains, traditional Chinese medicinal foods and prebiotics. A decreased abundance of endotoxin biosynthetic genes in the gut of the volunteer was correlated with a decreased circulating endotoxin load and alleviated inflammation. Mono-association of germfree C57BL/6J mice with strain Enterobacter cloacae B29 isolated from the volunteer’s gut induced fully developed obesity and insulin resistance on a high-fat diet but not on normal chow diet, whereas the germfree control mice on a high-fat diet did not exhibit the same disease phenotypes. The Enterobacter-induced obese mice showed increased serum endotoxin load and aggravated inflammatory conditions. The obesity-inducing capacity of this human-derived endotoxin producer in gnotobiotic mice suggests that it may causatively contribute to the development of obesity in its human host.

Global rise in type 1 diabetes may be linked to reduced exposure to pathogens in early life

 "Countries with lower mortality from infectious disease exhibit higher rates of type 1 diabetes, according to a new study by Dr. A. Abela and Professor S. Fava of the University of Malta. The findings, collating data from three major international studies and presented at the Society for Endocrinology annual conference in Harrogate UK, suggest that the as yet unexplained global rise in type 1 diabetes may be linked to reduced exposure to pathogens in early life."

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Single Mutations In VCP Gene Implicated In A Number Of Neurodegenerative Diseases

MNT  "New research, published in Neuron, gives insight into how single mutations in the VCP gene cause a range of neurological conditions including a form of dementia called Inclusion Body Myopathy, Paget's Disease of the Bone and Frontotemporal Dementia (IBMPFD), and the motor neuron disease Amyotrophic Lateral Sclerosis (ALS). "

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PLOS Biology: Neuronal Expression of Glucosylceramide Synthase in Central Nervous System Regulates Body Weight and Energy Homeostasis

"Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide glucosyltransferase). As a major mechanism of central nervous system (CNS) metabolic control, we demonstrate that GCS-derived gangliosides interacting with leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. Furthermore, ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in response to alterations in peripheral energy signals. Consequently, mice with inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg delivery to the arcuate nucleus (Arc) significantly ameliorated obesity, specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis."

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NIMH · Developing Male Brain Exposed to Less Stress-Protective Protein

"Why are rates of schizophrenia and autism higher in males? New evidence implicates an enzyme expressed in the placenta that helps protect the developing fetal brain from adverse effects of maternal stress early in pregnancy. Video: NIMH grantee Tracy Bale, Ph.D., of the University of Pennsylvania, discussed her line of research into how maternal stress might differentially affect the developing male brain during an interview at the 2011 Society for Neuroscience meeting."

Howerton CL, Morgan CP, Fischer DB, Bale TL. O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development. PNAS, March 5, 2013

JAMA Network | JAMA | Crossing the Omic ChasmA Time for Omic Ancillary SystemsOmic Ancillary Systems

Despite the information gains from genome-wide association studies and next-generation sequencing (NGS), there remains a chasm between this scientific knowledge and daily clinical practice. Leveraging recent advances in genomics to improve patient care will require electronic health record (EHR) systems that incorporate genomic clinical decision support (CDS). The eMerge (Electronic Medical Records and Genomics)consortium is bridging this chasm by developing interoperable systems that can integrate large-scale genomic data with clinical workflows. According to a recent Institute of Medicine report,3 the current document-centric approach to omic (eg, genomic, epigenomic, proteomic, metabolomic) data will not scale, making storage of raw omic data in current-generation EHRs not feasible. Although commercial EHRs may eventually evolve to handle omic data efficiently, dedicated omic ancillary systems will be essential in the interim.

Chemicals pollutants threaten health in the Arctic

This image shows the Arctic as observed by the...
This image shows the Arctic as observed by the Advanced Microwave Scanning Radiometer for EOS (AMSR-E) aboard NASA’s Aqua satellite on September 16, 2007. The image shows a record sea ice minimum in the Arctic. (Photo credit: Wikipedia)
"People living in Arctic areas can be more sensitive to pollutants due to their genetics, says researcher Arja Rautio at the Centre for Arctic Medicine in theUniversity of Oulu, Finland. This is unfortunate since the northernmost areas of Europe are receiving more harmful chemicals. Scientists believe climate change may be a culprit as air and water mass movements push some of these undesirable chemicals towards the Arctic. "In real life, people are exposed to lots of chemicals," says Rautio, who leads studies into the human health effects from contaminants and the influence of climate change in a EU-funded project called ArcRisk, "and I think the people of the north are exposed to higher levels than for example the general population in Europe.""

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Drug shows potential to delay onset or progression of Alzheimer's disease

A research team led by Robert Nagele, PhD, of the New Jersey Institute for Successful Aging (NJISA) at the University of Medicine and Dentistry of New Jersey (UMDNJ)-School of Osteopathic Medicine, has demonstrated that the anti-atherosclerosis drug darapladib can significantly reduce leaks in the blood brain barrier. This finding potentially opens the door to new therapies to prevent the onset or the progression of Alzheimer's disease.

Subgingival microbiome in smokers and non-smokers in periodontitis: an exploratory study using traditional targeted techniques and a next-generation sequencing.

To compare the results of two targeted techniques to an open-ended technique in periodontitis patients, differentiated on the basis of smoking habit.

MATERIALS & METHODS:

Thirty periodontitis patients (15 smokers and 15 non-smokers) provided subgingival plaque samples for 16S rRNA gene amplicon sequencing, culturing and quantitative polymerase chain reaction (qPCR).

RESULTS:

No differences were found in the composition of the subgingival microbiome between smokers and non-smokers with culture and qPCR. With pyrosequencing, operational taxonomic units (OTUs) classified to genera Fusobacterium, Prevotella and Selenomonas were more abundant in smokers, while OTUs belonging to the genera Peptococcus and Capnocytophaga were more abundant in non-smokers. Principal coordinate analysis identified two clusters; one was composed mainly of smokers (80%) and revealed significantly lower taxonomic diversity, higher attachment loss and higher proportion of the genera Fusobacterium, Paludibacter and Desulfobubus.

CONCLUSION:

In periodontitis, there is a difference in the composition of the subgingival microbiome between smokers and non-smokers, as revealed by pyrosequencing. This difference was not identified by the targeted techniques. Low taxonomic diversity was associated with higher disease severity, especially in smokers. This supports the hypothesis of the ecological microbial-host interaction in the severity of periodontal disease.

The mysterious GRIN3A and the cause of schizophrenia

"When the GluN3A subunit is incorporated, it prevents the NMDA receptor from being activated by glutamate, almost as if the receptor had been blocked by phencyclidine."

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An Antioxidant May Prevent Neuron Loss In Schizophrenia And Depression

MNT "Gamma-aminobutyric acid (GABA) deficits have been implicated in schizophrenia and depression. In schizophrenia, deficits have been particularly well-described for a subtype of GABA neuron, the parvalbumin fast-spiking interneurons. The activity of these neurons is critical for proper cognitive and emotional functioning. Parvalbumin neurons are particularly vulnerable to oxidative stress, a factor that may emerge commonly in development, particularly in the context of psychiatric disorders like schizophrenia or bipolar disorder, where compromised mitochondrial function plays a role. parvalbumin neurons may be protected from this effect by N-acetylcysteine, also known as Mucomyst, a medication commonly prescribed to protect the liver against the toxic effects of acetaminophen (Tylenol) overdose, reports a new study in the current issue of Biological Psychiatry. "

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Some bacteria may protect against disease caused by H.Pylori stomach infection

: "Half of the world's human population is infected with the stomach bacteria called Helicobacter pylori, yet it causes disease in only about 10 percent of those infected. Other bacteria living in the stomach may be a key factor in whether or not H. pylori causes disease, according to a new study led by scientists at the University of California, Santa Cruz."


Prenatal exposure to pesticide DDT linked to adult high blood pressure

"Infant girls exposed to high levels of the pesticide DDT while still inside the womb are three times more likely to develop hypertension when they become adults, according to a new study led by the University of California, Davis."


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Prenatal exposure to mercury and fish consumption during pregnancy and attention-deficit/hyperactivity disorder-related behavior in children.

To investigate the association of prenatal mercury exposure and fish intake with attention-deficit/hyperactivity disorder (ADHD)-related behavior.

METHODS:

For a population-based prospective birth cohort recruited in New Bedford, Massachusetts (1993-1998), we analyzed data for children examined at age 8 years with peripartum maternal hair mercury measures (n = 421) or maternal report of fish consumption during pregnancy (n = 515). Inattentive and impulsive/hyperactive behaviors were assessed using a teacher rating scale and neuropsychological testing.

RESULTS:

The median maternal hair mercury level was 0.45 μg/g (range, 0.03-5.14 μg/g), and 52% of mothers consumed more than 2 fish servings weekly. In multivariable regression models, mercury exposure was associated with inattention and impulsivity/hyperactivity; some outcomes had an apparent threshold with associations at 1 μg/g or greater of mercury. For example, at 1 μg/g or greater, the adjusted risk ratios for mild/markedly atypical inattentive and impulsive/hyperactive behaviors were 1.4 (95% CI, 1.0-1.8) and 1.7 (95% CI, 1.2-2.4), respectively, for an interquartile range (0.5 μg/g) mercury increase; there was no confounding by fish consumption. For neuropsychological assessments, mercury and behavior associations were detected primarily for boys. There was a protective association for fish consumption (>2 servings per week) with ADHD-related behaviors, particularly impulsive/hyperactive behaviors (relative risk = 0.4; 95% CI, 0.2-0.6).

CONCLUSIONS:

Low-level prenatal mercury exposure is associated with a greater risk of ADHD-related behaviors, and fish consumption during pregnancy is protective of these behaviors. These findings underscore the difficulties of balancing the benefits of fish intake with the detriments of low-level mercury exposure in developing dietary recommendations in pregnancy.

Blood-based protein biomarkers for diagnosis of Alzheimer disease.


A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β(2) microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve.

CONCLUSIONS:

This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.

Epigenetics mechanism may help explain effects of mom's nutrition on her children's health

Pioneering studies by U. S. Department of Agriculture-funded research molecular geneticist Robert A. Waterland are helping explain how the foods that soon-to-be-moms eat in the days and weeks around the time of conception -- or what's known as periconceptional nutrition-may affect the way genes function in her children, and her children's health.

Folic acid lowers risk of autism, study finds

 "Women who take a vitamin B9 supplement (folic acid) during the beginning weeks of their pregnancy can cut the risk of having a child with autism in half. But the supplement has no effect if it is started more than 8 weeks into the pregnancy."


Maternal obesity and vitamin D sufficiency are associated with cord blood vitamin D insufficiency.

An inverse relationship between total serum 25-hydroxyvitamin D (25-OH D) and increased adiposity has been established in children, adolescents, and adults. However, the relationship between neonatal adiposity and vitamin D status has not been reported. Both maternal obesity and vitamin D deficiency in pregnancy are common and are associated with adverse pregnancy outcomes.

OBJECTIVE:

The aim of the study was to determine the relationship between vitamin D levels in mothers and newborns, as influenced by maternal obesity, and evaluate these associations with neonatal adiposity.

DESIGN, SETTING, AND PATIENTS:

Sixty-one maternal-neonatal pairs participated in this cross-sectional study at an academic medical center. Mothers had a prepregnancy body mass index that was normal or obese.

OUTCOME MEASURES:

Maternal and cord blood sera were assayed for 25-OH D, and neonatal body composition was measured by air displacement plethysmography.

RESULTS:

Mothers had similar and sufficient levels of 25-OH D when measured at 36-38 wk gestation, irrespective of body mass index category (normal weight, 46.05, vs. obese, 49.84 ng/ml; P = not significant). However, cord blood 25-OH D was higher in neonates of normal-weight mothers compared to neonates of obese mothers (27.45 vs. 20.81 ng/ml; P = 0.02). The variance in cord blood 25-OH D was explained by four factors: maternal 25-OH D level, the presence of maternal obesity, maternal age, and neonatal adiposity (r(2) = 0.66).

CONCLUSION:

Obese women transfer less 25-OH D to offspring than normal-weight women, despite similar serum levels. Cord blood 25-OH D levels directly correlate to neonatal percentage body fat. These novel findings underscore the evolving relationships between maternal obesity, vitamin D nutritional status, and adiposity in the neonatal period that may influence subsequent childhood and adulthood vitamin D-dependent processes.

Cell - The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza

 "Influenza A viruses are a major cause of mortality. Given the potential for future lethal pandemics, effective drugs are needed for the treatment of severe influenza such as that caused by H5N1 viruses. Using mediator lipidomics and bioactive lipid screen, we report that the omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protectin D1 (PD1) markedly attenuated influenza virus replication via RNA export machinery. Production of PD1 was suppressed during severe influenza and PD1 levels inversely correlated with the pathogenicity of H5N1 viruses. Suppression of PD1 was genetically mapped to 12/15-lipoxygenase activity. Importantly, PD1 treatment improved the survival and pathology of severe influenza in mice, even under conditions where known antiviral drugs fail to protect from death. These results identify the endogenous lipid mediator PD1 as an innate suppressor of influenza virus replication that protects against lethal influenza virus infection."

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Can hormone help treat multiple sclerosis long-term?

"A new study suggests that treatment with adrenocorticotropic hormone (ACTH) may be helpful for people whose multiple sclerosis (MS) is not well-controlled through their regular treatment. The study was released today and will be presented at the American Academy of Neurology's 65th Annual Meeting in San Diego, March 16 to 23, 2013."

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Scientists identify buphenyl as a possible drug for Alzheimer's disease

Studies in mice with Alzheimer's disease (AD) have shown that sodium phenylbutyrate, known as Buphenyl, successfully increases factors for neuronal growth and protects learning and memory, according to neurological researchers at the Rush University Medical Center."


Brigham And Women's Hospital - Press Releases

Effect of Intestinal Microbial Ecology on the Developing Brain

The mammalian gastrointestinal tract harbors a highly diverse microbial population that plays a major role in nutrition, metabolism, protection against pathogens, and development of the immune system. It is estimated that at least 1000 different bacterial species cohabit the human intestinal tract. Most recently, the Human Microbiome Project, using new genomic technologies, has started a catalog of specific microbiome composition and its correlation with health and specific diseases. Herein we provide a brief review of the intestinal microbiome, with a focus on new studies showing that there is an important link between the microbes that inhabit the intestinal tract and the developing brain. With future research, an understanding of this link may help us to treat various neurobehavioral problems such as autism, schizophrenia, and anxiety.

Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells.

Activation of Toll-like receptors (TLRs) by pathogens triggers cytokine production and T cell activation, immune defense mechanisms that are linked to immunopathology. Here we show that IFN-γ production by CD4(+) T(H)1 cells during mucosal responses to the protozoan parasite Toxoplasma gondii resulted in dysbiosis and the elimination of Paneth cells. Paneth cell death led to loss of antimicrobial peptides and occurred in conjunction with uncontrolled expansion of the Enterobacteriaceae family of Gram-negative bacteria. The expanded intestinal bacteria were required for the parasite-induced intestinal pathology. The investigation of cell type-specific factors regulating T(H)1 polarization during T. gondii infection identified the T cell-intrinsic TLR pathway as a major regulator of IFN-γ production in CD4(+) T cells responsible for Paneth cell death, dysbiosis and intestinal immunopathology.

Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity

Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.

Some brain cells are better virus fighters

"Viruses often spread through the brain in patchwork patterns, infecting some cells but missing others. New research at Washington University School of Medicine in St. Louis helps explain why. The scientists showed that natural immune defenses that resist viral infection are turned on in some brain cells but switched off in others."

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Researchers find industrial chemicals in food samples

 "Researchers at The University of Texas Health Science Center at Houston (UTHealth) have discovered phthalates, industrial chemicals, in common foods purchased in the United States. Phthalates can be found in a variety of products and food packaging material, child-care articles and medical devices."

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Soaking up the Competition – Circular RNAs as Molecular Sponges for miRNAs | EpiBeat

 "Numerous families of non-coding RNAs have been identified in mammalian cells, including lncRNA, miRNA, siRNA, and piRNA.  Another type of RNA called circular RNA (circRNA) has remained a mysterious class, as the exact function of these molecules has not been described. Usually, circRNAs result from spicing events and have been identified in plants, animals, and archaea.   Recently, Memczak et al. published a paper in Nature reporting evidence that circRNAs tend to show specific expression profiles that are associated with different tissues and developmental phases and function as post-transcriptional regulators."


The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude --

Month of birth has previously been described as a risk factor for multiple sclerosis (MS). This has been hypothesised to be related to maternal vitamin D levels during pregnancy, although conclusive evidence to support this is lacking. To date, no large studies of latitudinal variation in the month of birth effect have been performed to advance this hypothesis.
Methods Previously published data on month of birth from 151 978 MS patients were compared to expected birth rates. A linear regression model was used to assess the relationship between latitude and observed:expected birth ratio of MS patients for each month.
Results Analysis of all reported data demonstrated a significant excess of MS risk in those born in April (observed:expected 1.05, p=0.05) and reduction in risk in those born in October (0.95, p=0.04) and November (0.92 p=0.01). A conservative analysis of 78 488 patients revealed an excess MS risk in those born in April (1.07, p=0.002) and May (1.11, p=0.0006), and a reduced risk in those born in October (ratio 0.94, p=0.004) and November (0.88, p=0.0002). A significant relationship between latitude and observed:expected ratio was demonstrated in December, and borderline significant relationships in May and August.
Conclusions Month of birth has a significant effect on subsequent MS risk. This is likely to be due to ultraviolet light exposure and maternal vitamin D levels, as demonstrated by the relationship between risk and latitude.

Excess dietary salt identified as autoimmune trigger

"For the past few decades, health officials have been reporting increases in the incidence of autoimmune diseases such as multiple sclerosis (MS). Now researchers at Yale School of Medicine, Harvard Medical School and the Broad Institute have identified a prime suspect in the mystery—dietary salt."

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Brain injury may be autoimmune phenomenon, like multiple sclerosis, research finds

 "Most scientists are starting to agree that repeat, sub-concussive hits to the head are dangerous and linked to neurological disorders later in life. A new collaborative study, though, attempted to find out why – and discovered that damage to the blood-brain barrier and the resulting autoimmune response might be the culprit."

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Gene identified that causes obesity in mice: Deleting gene eliminates obesity, could work for humans

The research team created a strain of mice without the Plin2 gene which produces a protein that regulates fat storage and metabolism. They immediately found that the mice were resistant to obesity.

Alzheimer's risk gene discovered using imaging method that screens brain's connections / UCLA Newsroom

"Hundreds of computers, calculating for months, sifted through more than 4,000 brain connections and the entire genetic code, comparing connection patterns in people with different genetic variations. In people whose genetic code differed in one specific gene called SPON1, weaker connections were found between brain centers controlling reasoning and emotion. The rogue gene also affects how senile plaques build up in the brain — one of the hallmarks of Alzheimer's disease."

SPON1 is an extracellular ligand for APP

Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage.