First Ever 'Atlas' Of T Cells In Human Body - Findings Could Lead To New Vaccine Strategies

"We found that T cells are highly compartmentalized - that is, each tissue we examined had its own complement of T cells," said study leader Donna L. Farber, PhD, professor of surgical sciences at CUMC and a principal investigator with the new Columbia Center for Translational Immunology (CCTI), directed by Megan Sykes, MD. "The results were remarkably similar in all donors, even though these people were very different in terms of age, background, and lifestyle." MNT

Infectome: A platform to trace infectious triggers of autoimmunity.

The "exposome" is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases. Environmental triggers are largely subdivided into infectious and non-infectious agents. In this review, we introduce the concept of the "infectome", which is the part of the exposome referring to the collection of an individual's exposures to infectious agents. The infectome directly relates to geoepidemiological, serological and molecular evidence of the co-occurrence of several infectious agents associated with autoimmune diseases that may provide hints for the triggering factors responsible for the pathogenesis of autoimmunity. We discuss the implications that the investigation of the infectome may have for the understanding of microbial/host interactions in autoimmune diseases with long, pre-clinical phases. It may also contribute to the concept of the human body as a superorganism where the microbiome is part of the whole organism, as can be seen with mitochondria which existed as microbes prior to becoming organelles in eukaryotic cells of multicellular organisms over time. A similar argument can now be made in regards to normal intestinal flora, living in symbiosis within the host. We also provide practical examples as to how we can characterise and measure the totality of a disease-specific infectome, based on the experimental approaches employed from the "immunome" and "microbiome" projects.
Enhanced by Zemanta

infectome.org - Host genes involved in viral entry

RNAI
RNAI (Photo credit: Wikipedia)
Infectome.org presents results from RNAi screens done by several groups in Europe in collaboration with the Lucas Pelkmans Lab, with the aim to identify host genes that play a role in the early infection of a large variety of mammalian viruses.
Enhanced by Zemanta

Consuming Avocado With A Burger May Neutralize Interleukin-6

English: Pit of an avocado Deutsch: Kern einer...
English: Pit of an avocado Deutsch: Kern einer Avocado der Sorte "Hass". (Photo credit: Wikipedia)
Consuming half of a fresh Hass avocado with a burger may counteract the protein Interleukin-6 (IL-6), a measure of inflammation, compared to eating a burger without the vegetable.
Enhanced by Zemanta

Incorporating Information of microRNAs into Pathway Analysis in a Genome-Wide Association Study of Bipolar Disorder.

MicroRNAs (miRNAs) are known to be important post-transcriptional regulators that are involved in the etiology of complex psychiatric traits. The present study aimed to incorporate miRNAs information into pathway analysis using a genome-wide association dataset to identify relevant biological pathways for bipolar disorder (BPD). We selected psychiatric- and neurological-associated miRNAs (N = 157) from PhenomiR database. The miRNA target genes (miTG) predictions were obtained from microRNA.org. Canonical pathways (N = 4,051) were downloaded from the Molecule Signature Database. We employed a novel weighting scheme for miTGs in pathway analysis using methods of gene set enrichment analysis and sum-statistic. Under four statistical scenarios, 38 significantly enriched pathways (P-value < 0.01 after multiple testing correction) were identified for the risk of developing BPD, including pathways of ion channels associated (e.g., gated channel activity, ion transmembrane transporter activity, and ion channel activity) and nervous related biological processes (e.g., nervous system development, cytoskeleton, and neuroactive ligand receptor interaction). Among them, 19 were identified only when the weighting scheme was applied. Many miRNA-targeted genes were functionally related to ion channels, collagen, and axonal growth and guidance that have been suggested to be associated with BPD previously. Some of these genes are linked to the regulation of miRNA machinery in the literature. Our findings provide support for the potential involvement of miRNAs in the psychopathology of BPD. Further investigations to elucidate the functions and mechanisms of identified candidate pathways are needed.

Immune system changes may drive aggressiveness of recurrent tumors

Nearly half of the 700,000 cancer patients who undergo surgical removal of a primary tumor each year suffer a recurrence of their disease at some point, and many of those patients will eventually die from their disease. The traditional view of recurrent tumors is that they are resistant to therapy because they've acquired additional genetic mutations that make them more aggressive and impervious to drugs. Now, however, researchers at the Perelman School of Medicine at the University of Pennsylvania show in an animal model that the enhanced aggressiveness of recurrent tumors may be due to changes in the body's immune response. The findings are published this week in the Proceedings of the National Academy of Sciences.

Read more at: http://medicalxpress.com/news/2012-12-immune-aggressiveness-recurrent-tumors.html#jCp

Elevated levels of C-reactive protein appear associated with psychological distress, depression

Elevated levels of C-reactive protein, a marker of inflammatory disease, appear to be associated with increased risk of psychological distress and depression in the general population of adults in Denmark, according to a report published Online First by Archives of General Psychiatry, a JAMA Network publication.

Read more at: http://medicalxpress.com/news/2012-12-elevated-c-reactive-protein-psychological-distress.html#jCp

Fat influences decisions taken by brain cells for production and survival

Swedish scientists from the Karolinska Institute have identified two molecules, cholic acid and 24, 25-epoxycholesteriol,  that play an important role in the survival and production of nerve cells in the brain, including nerve cells that produce dopamine. The discovery, which is published in the journal Nature Chemical Biology, may be significant in the long term for the treatment of several diseases, such as Parkinson's disease.

Study turns toxoplasmosis parasite invasion theory on its head

Current thinking on how theToxoplasma gondii parasite invades its host is incorrect, according to a study published today inNature Methods describing a new technique to knock out genes. The findings could have implications for other parasites from the same family, including malaria, and suggest that drugs that are currently being developed to block this invasion pathway may be unsuccessful.

MNT: Neurons Die In Alzheimer's Because Of Faulty Cell Cycle Control Before Plaques And Tangles Appear

The two infamous proteins, amyloid-beta (Aβ) and tau, that characterize advanced Alzheimer's disease (AD), start healthy neurons on the road to cell death long before the appearance of the deadly plaques and tangles by working together to reactivate the supposedly blocked cell cycle in brain cells, according to research presented on Dec. 17 at the American Society for Cell Biology's Annual Meeting in San Francisco. 
Enhanced by Zemanta

An Inflammatory Protein Plays An Unexpected Role In Lung Infections: MNT

The immune system responds to infections in the lungs by recruiting neutrophils, a group of immune cells that are responsible for recognizing and eliminating pathogens, to the site of infection. In addition to killing infectious pathogens, neutrophils also drive inflammation, which can lead to poor lung function and sometimes fatal complications. 

In this issue of the Journal of Clinical Investigation, researchers led by Julia Klesney-Tait at the University of Iowa examined how the loss of the inflammatory protein TREM1 affected the survival of mice infected with pneumonia

Neuroscientists find excessive protein synthesis linked to autistic-like behaviors

Autistic-like behaviors can be partially remedied by normalizing excessive levels of protein synthesis in the brain, a team of researchers has found in a study of laboratory mice. The findings, which appear in the latest issue of Nature, provide a pathway to the creation of pharmaceuticals aimed at treating autism spectrum disorders (ASD) that are associated with diminished social interaction skills, impaired communication ability, and repetitive behaviors.The researchers focused on the EIF4E gene, whose mutation is associated with autism. The mutation causing autism was proposed to increase levels of the eIF4E, the protein product of EIF4E, and lead to exaggerated protein synthesis. Excessive eIF4E signaling and exaggerated protein synthesis also may play a role in a range of neurological disorders, including fragile X syndrome (FXS).

Read more at: http://medicalxpress.com/news/2012-12-neuroscientists-excessive-protein-synthesis-linked.html#jCp

Enhanced by Zemanta

Scientists find mechanism that triggers immune responses to DNA

(Medical Xpress)—Free-floating pieces of DNA in a cell's watery interior can mean bad things: invading viruses, bacteria, or parasites, ruptured cellular membranes, or disease. Genetic material is meant to be contained in a cell's nucleus or key organelles, and when it's loose, it's a sign for the immune system that something is wrong. Now, Howard Hughes Medical Institute scientists have discovered the molecular pathway responsible for detecting loose bits of DNA outside a cell's nucleus in the cytosol and setting off the resulting immune reaction.

Read more at: http://medicalxpress.com/news/2012-12-scientists-mechanism-triggers-immune-responses.html#jCp

Tamibarotene: a candidate retinoid drug for Alzheimer's disease.

Tamibarotene (Am80), a synthetic retinoid approved in Japan for treatment of acute promyelocytic leukemia (APL), is a retinoic acid receptor (RAR) agonist with high specificity for RARα and RARβ over RARγ. Temporarily and spatially specific expression of RARs suggests their pivotal roles in the adult brain. Am80 is considered to be a promising candidate drug for treatment of Alzheimer's disease (AD) because of its transcriptional controls of multiple target genes involved in etiology and pathology of AD. In APP23 AD model mice, administration of Am80 decreased the deposition of insoluble amyloid-β(42). In senescence-accelerated mice (SAMP8), Am80 ameliorated the decrease of cortical acetylcholine, as well as reducing anxiety in behavioral tests and improving the sleep deficit. Am80 also effected a significant improvement of memory in the rat scopolamine-induced memory deficit model. Like other retinoids, Am80 also has an immunomodulatory effect and reduces secretion of proinflammatory cytokines and chemokines by astrocytes and microglia surrounding amyloid-β plaques. In a rat experimental autoimmune encephalomyelitis model, Am80 reduced inflammatory cytokines and showed significant efficacy. Retinoids also promote differentiation of neural stem cells, and Am80 improved the recovery of spinal cord-injured rats. Am80 may also improve vascular factors involved in onset and/or progression of AD. Am80 has been in clinical use for treatment of APL in Japan since 2005, and has been reported to have fewer side effects than other retinoids. We have recently started a clinical study to evaluate the efficacy and safety of Am80 for the treatment of Alzheimer's disease.

Cholesterol boosts the memory of the immune system

The memory of the human immune system is critical for the development of vaccines. Only if the body recognizes a pathogen with which it has already come into contact in the case of a second infection, the immune system can combat it more effectively than it did the first time. The Freiburg immunobiologist Prof. Dr. Wolfgang Schamel from the Institute of Biology III of the University of Freiburg and his colleagues have succeeded in demonstrating how the memory of the immune system functions. Their findings have now been published in the journals Immunity and Journal of Biological Chemistry (JBC).

The complex exogenous RNA spectra in human plasma: ... [PLoS One. 2012] - PubMed - NCBI

Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers. Surveying human plasma for microRNA biomarkers using next generation sequencing technology, we observed that a significant fraction of the circulating RNA appear to originate from exogenous species. With careful analysis of sequence error statistics and other controls, we demonstrated that there is a wide range of RNA from many different organisms, including bacteria and fungi as well as from other species. These RNAs may be associated with protein, lipid or other molecules protecting them from RNase activity in plasma. Some of these RNAs are detected in intracellular complexes and may be able to influence cellular activities under in vitro conditions. These findings raise the possibility that plasma RNAs of exogenous origin may serve as signaling molecules mediating for example the human-microbiome interaction and may affect and/or indicate the state of human health.

Effects of two commonly found strains of influenza a virus on developing dopaminergic neurons, in relation to the pathophysiology of schizophrenia.

Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.

Pocket test measures fifty things in a drop of blood

#biomarkers

Blood groups act as protection against infection

(Medical Xpress)—Humans may have acquired enzymes that make blood groups from bacteria to hinder the spread of viruses in the population, suggests a study led by scientists at the University of Bath."

'via Blog this'

China researchers link obesity to bacteria

Chinese researchers have identified a bacteria (ENTEROBACTER )which may cause obesity, according to a new paper suggesting diets that alter the presence of microbes in humans could combat the condition.

Read more at: http://medicalxpress.com/news/2012-12-china-link-obesity-bacteria.html#jCp

High-throughput sequencing shows potentially hundreds of gene mutations related to autism


Genomic technology has revolutionized gene discovery and disease understanding in autism, according to an article published in the December 20 issue of the journal Neuron.

Read more at: http://medicalxpress.com/news/2012-12-high-throughput-sequencing-potentially-hundreds-gene.html#jCp

Full text in Neuron

The Autism Sequencing Consortium: Large-Scale, High-Throughput Sequencing in Autism Spectrum Disorders

Auto-immune disease: The viral route is confirmed

Why would our immune system turn against our own cells? This is the question that the combined Inserm/CNRS/ Pierre and Marie Curie University/Association Institut de Myologie have strived to answer in their "Therapies for diseases of striated muscle", concentrating in particular on the auto-immune disease known as myasthenia gravis. Through the project known as FIGHT-MG (Fight Myasthenia Gravis), financed by the European Commission and coordinated by Inserm, Sonia Berrih-Aknin and Rozen Le Panse have contributed proof of the concept that a molecule imitating a virus may trigger an inappropriate immune response, causing muscular function to deteriorate. These results have been published in Annals of Neurology, accessible on line.

Read more at: http://medicalxpress.com/news/2012-12-auto-immune-disease-viral-route.html#jCp
Enhanced by Zemanta

Molecular Psychiatry - Abstract of article: Potential metabolite markers of schizophrenia

Schizophrenia is a severe mental disorder that affects 0.5–1% of the population worldwide. Current diagnostic methods are based on psychiatric interviews, which are subjective in nature. The lack of disease biomarkers to support objective laboratory tests has been a long-standing bottleneck in the clinical diagnosis and evaluation of schizophrenia. Here we report a global metabolic profiling study involving 112 schizophrenic patients and 110 healthy subjects, who were divided into a training set and a test set, designed to identify metabolite markers. A panel of serum markers consisting of glycerate, eicosenoic acid, β-hydroxybutyrate, pyruvate and cystine was identified as an effective diagnostic tool, achieving an area under the receiver operating characteristic curve (AUC) of 0.945 in the training samples (62 patients and 62 controls) and 0.895 in the test samples (50 patients and 48 controls). Furthermore, a composite panel by the addition of urine β-hydroxybutyrate to the serum panel achieved a more satisfactory accuracy, which reached an AUC of 1 in both the training set and the test set. Multiple fatty acids and ketone bodies were found significantly (P<0.01) elevated in both the serum and urine of patients, suggesting an upregulated fatty acid catabolism, presumably resulting from an insufficiency of glucose supply in the brains of schizophrenia patients.

Molecular Psychiatry - Abstract of article: The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)

Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.

Why are the neurodegenerative disease-related pathways overrepresented in primary HIV-infected peripheral blood mononuclear cells: a genome-wide perspective.

We demonstrate for the first time that the genome-wide profiling of HIV-infected peripheral blood mononuclear cells (PBMCs) from HIV-patients free of neurologic disease show overrepresentation of neurodegenerative pathways (Alzheimer's, Parkinson's, ALS, Huntington's and Prion Disease, etc.) in genome-wide microarray analysis, which suggests that this genome-wide representation of neurodegenerative diseases-related pathways in PBMCs could possibly be a subcellular manifestation of neurologic interference by HIV. Further, the cell-tagging analysis attested this belief showing the large majority of genes tagged with cells of monocyte and macrophage lineage, which are implicated in neuronal dysfunction in both viral and non-viral neurodegenerative diseases. Together, these findings suggest that the genomic interference of HIV with neurodegenerative pathways is not by chance, but may be an early sign of HIV-mediated sub-genomic and sub-cellular manifestation of neurologic disease. Moreover, these findings signify the utility of PBMC and genome-wide mapping of the host gene expression as a powerful tool in predicting possible early events in neurologic deterioration in HIV patients.

Cells Transport Materials Along Crowded Intercellular 'Highways' And Failure Of The System Can Lead To Neurodegenerative Diseases And Cancer

The interior of an animal cell is like a small city, with factories - called organelles - dedicated to manufacturing, energy production, waste processing, and other life functions. A network of intercellular "highways," called microtubules, enables bio-molecular complexes, products, and other cargo to move speedily about the cell to keep this vital machinery humming. A new paper published online in the journalProceedings of the National Academy of Sciences sheds new light on how cells manage to keep traffic flowing smoothly along this busy transportation network that is vital to the survival of cells and whose failure can lead to a variety of diseases, including Alzheimer's and cancer

There is a wonderful video of The Inner life of the cell from Harvard Biovisions where traffic is well illustrated.

A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1-2% in people >60 and 3-4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10(-16)) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the 'regulation of leucocyte/lymphocyte activity' and also 'cytokine-mediated signalling' as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated.

Fierce competition between Toxoplasma and Chlamydia for host cell structures in dually infected cells.

The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to colonize their host cell and salvage nutrients from organelles. In order to gain fundamental knowledge on the pathogenicity of these microorganisms, we have established a cell culture model whereby single fibroblasts are co-infected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in co-infected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our co-infection studies by examining the respective abilities of Chlamydia and Toxoplasma to co-opt the host cytoskeleton and recruit organelles. We demonstrate that the two pathogen-containing vacuoles migrate independently to the host perinuclear region and rearrange the host microtubular network around each vacuole. However, Toxoplasma out-competes Chlamydia to the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected with Chlamydia, the centrosomes become associated with the chlamydial inclusion while the Toxoplasma parasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by both Chlamydia and Toxoplasma depends on the capability of each pathogen to successfully adhere to a finely tuned developmental program that aims to remodel the host cell for the pathogen's benefit. In particular, this investigation emphasizes the essentiality of host organelle interception by intravacuolar pathogens to facilitate access to nutrients.

Celiac 'epidemics' link to infections early in life

Celiac disease affects about 1% of the population but occasional ‘epidemics’ have been noticed along with a seasonal variation in number of cases diagnosed. New research published in BioMed Central’s open access journal BMC Pediatrics indicates that repeated infections early in life increases the risk for celiac disease

Transcriptomine: Nuclear receptor Transcription targets

Transcriptomine is a tool for mining tissue-specific nuclear receptor transcriptomes based on annotated published genome wide transcriptional profiling experiments in the field of nuclear receptor signaling.

BMC Evolutionary Biology | Abstract | Evidence for selection at HIV host susceptibility genes in a West Central African human population


HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes) that carries strains of SIV ancestral to HIV-1.

Results

SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of P. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at CUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A CUL5 allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at TRIM5, which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in TRIM5 had the highest frequency in Biaka compared to other African populations, as did a protective allele for APOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for APOBEC3H, CXCR6 and HLA-C were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at TSG101, an inhibitor of HIV-1 viral budding.

Conclusions

We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes CCR5 and CCL3L1. Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.

Host cholesterol secretion likely to influence gut microbiota

For more than half a century, researchers have known that the bacteria that colonize the gastrointestinal tract of mammals influence their host's cholesterol metabolism. Now, Jens Walter and colleagues of the University of Nebraska show that changes in cholesterol metabolism induced by diet can alter the gut flora. The research was published online ahead of print in the journal Applied and Environmental Microbiology."


Silent stroke can cause Parkinson's disease

Whilst conditions such as a severe stroke have been linked to Parkinson's disease, for many sufferers the tremors and other symptoms of Parkinson's disease can appear to come out of the blue. Researchers at the university's Faculty of Life Sciences have now discovered that a small stroke, also known as a silent stroke, can cause Parkinson's disease. Their findings have been published in the journal "Brain Behaviour and Immunity".

Read more at: http://medicalxpress.com/news/2012-12-silent-parkinson-disease.html#jCp

Association of Parkinson's disease with infections and occupational exposure to possible vectors.

The ultimate causes of idiopathic Parkinson's disease (PD) are not fully known, but environmental and occupational causes are suspected. Postencephalitic parkinsonism has been linked to influenza, and other viral infections have also been suspected to relate to PD. We estimated the relationship between PD and both infections and possible vectors of infection (i.e., animal and human) in a population-based, case-control study in British Columbia, Canada. We recruited 403 cases detected by their use of antiparkinsonian medications and 405 controls from the registrants of the provincial universal health insurance plan. Severe influenza was associated with PD (odds ratio [OR]: 2.01; 95% confidence interval [CI]: 1.16-3.48), although this effect was attenuated when reports were restricted to those occurring 10 or more years before diagnosis. Childhood illnesses were inversely associated with PD, particularly red measles (OR: 0.65; 95% CI: 0.48-0.90). Several animal exposures were associated with PD, with statistically significant effects for cats (OR: 2.06; 95% CI: 1.09-3.92) and cattle (OR: 2.23; 95% CI: 1.22-4.09). Influenza infection may be associated with PD. The inverse relationships with childhood infections may suggest an increased risk with subclinical or asymptomatic childhood infections. Occupational exposure to animals may increase risk through transmission of infections or may indicate exposure to another agent of interest (e.g., bacterial endotoxin).

Interactome3D from the University of Barcelona

Interactome3D is a web service for the structural annotation of protein-protein interaction networks. Submit your interactions and the server will find all the available structural data for both the single interactors and the interactions themselves. Additionally you can also visualize and download structural information for interactions involving a set of proteins or interactomes for one of the precalculated organisms.

Increasing autism prevalence in metropolitan New Jersey

High baseline autism spectrum disorder prevalence estimates in New Jersey led to a follow-up surveillance. The objectives were to determine autism spectrum disorder prevalence in the year 2006 in New Jersey and to identify changes in the prevalence of autism spectrum disorder or in the characteristics of the children with autism spectrum disorder, between 2002 and 2006. The cohorts included 30,570 children, born in 1998 and 28,936 children, born in 1994, residing in Essex, Hudson, Union, and Ocean counties, New Jersey. Point prevalence estimates by sex, ethnicity, autism spectrum disorder subtype, and previous autism spectrum disorder diagnosis were determined. For 2006, a total of 533 children with autism spectrum disorder were identified, consistent with prevalence of 17.4 per 1000 (95% confidence interval = 15.9–18.9), indicating a significant increase in the autism spectrum disorder prevalence (p < 0.001), between 2002 (10.6 per 1000) and 2006. The rise in autism spectrum disorder was broad, affecting major demographic groups and subtypes. Boys with autism spectrum disorder outnumbered girls by nearly 5:1. Autism spectrum disorder prevalence was higher among White children than children of other ethnicities. Additional studies are needed to specify the influence of better awareness of autism spectrum disorder prevalence estimates and to identify possible autism spectrum disorder risk factors. More resources are necessary to address the needs of individuals affected by autism spectrum disorder.

Genetic manipulation of urate alters neurodegeneration in mouse model of Parkinson's disease

A study by Massachusetts General Hospital researchers adds further support to the possibility that increasing levels of the antioxidant urate may protect against Parkinson's disease. In their report published in PNAS Early Edition, the investigators report that mice with a genetic mutation increasing urate levels were protected against the kind of neurodegeneration that underlies Parkinson's disease, while the damage was worse in animals with abnormally low urate.

ScienceDirect.com - Trends in Immunology - Drug targets in the cytokine universe for autoimmune disease

In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the ‘cytokine milieu’ that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders.

Autoimmune disease—retraining white blood cells

Symptoms of an autoimmune disease disappeared after a team of scientists retrained the white blood cells. This method is extremely promising for treating diseases such as type I diabetes and multiple sclerosis.

Read more at: http://medicalxpress.com/news/2012-12-autoimmune-diseaseretraining-white-blood-cells.html#jCp

Neurons die in Alzheimer's because of faulty cell cycle control before plaques and tangles appear

The two infamous proteins, amyloid-beta (Aβ) and tau, that characterize advanced Alzheimer's disease (AD), start healthy neurons on the road to cell death long before the appearance of the deadly plaques and tangles by working together to reactivate the supposedly blocked cell cycle in brain cells, according to research presented on Dec. 17 at the American Society for Cell Biology's Annual Meeting in San Francisco.

Read more at: http://medicalxpress.com/news/2012-12-neurons-die-alzheimer-faulty-cell.html#jCp

Physicians should not prescribe ADD drugs to healthy people

Physicians in Canada should consider refusing to prescribe cognitive enhancement medications—also used to treat attention deficit disorder (ADD)—to healthy patients, states an analysis article in CMAJ (Canadian Medical Association Journal). Lack of evidence for benefits and possibility of harm, limited health care resources and professional integrity of physicians are reasons why this use is not acceptable.

Read more at: http://medicalxpress.com/news/2012-12-physicians-drugs-healthy-people.html#jCp

Link Between Fragile X Protein And Nearly 100 Genes Involved In Autism

MNT: Doctors have known for many years that patients with fragile X syndrome, the most common form of inherited intellectual disability, are often also diagnosed with autism. But little has been known about how the two diagnoses are related.
Now a collaborative research effort at Duke University Medical Center and Rockefeller University has pinpointed the precise genetic footprint that links the two. The findings, published online in the journalNature, point the way toward new genetic testing that could more precisely diagnose and categorize the spectrum of autism-related disorders. 


Dieting Can Lead To Food Withdrawal And Depression

Eating fatty and sugary foods can cause chemical changes in the brain, making a person on a diet feel like they are having drug withdrawals.The chemicals changed by diet are associated with depression. A change of diet then causes withdrawal symptoms and a greater sensitivity to stressful situations, launching a vicious cycle of poor eating." MNT

PLOS ONE: Effects of Two Commonly Found Strains of Influenza A Virus on Developing Dopaminergic Neurons, in Relation to the Pathophysiology of Schizophrenia

Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.

Oligodendrocyte killing by quinolinic acid in vitro. (2001)

Quinolinic acid, which is produced by macrophages and microglia, can kill neurons in vivo and in vitro. To test whether quinolinic acid is toxic to oligodendrocytes, glial cells cultured from the brains of 2-day-old rats were incubated with quinolinic acid at concentrations known to kill neurons. The cells were then fixed and immunostained with MAbO4 to mark immature and mature oligodendrocytes and anti-myelin basic protein (MBP) to mark mature oligodendrocytes. The data indicated up to 54% reductions in the numbers of O4-positive cells in cultures after incubation with quinolinic acid. Apoptosis of O4-positive cells began during the first 6 h, and some of the apoptotic cells became fragmented. Further apoptosis, and clumping of dead MBP-positive oligodendrocytes, occurred during longer incubation with quinolinic acid. Thus, quinolinic acid arising from macrophages and microglia during autoimmune disease may take part in a mechanism of oligodendrocyte injury and killing.
Enhanced by Zemanta

Futurity.org – Inflammation chemical, quinolinic acid, linked to suicide

Scientists report the first proof that a chemical in the brain called glutamate is linked to suicidal behavior—findings that offer new hope for prevention.They found that suicide attempters had more than twice as much quinolinic acid in their spinal fluid as the healthy people, which indicated increased glutamate signaling between nerve cells. Those who reported the strongest desire to kill themselves also had the highest levels of the acid.

Genes Are Not The Only Drivers Of Colon Cancer

Using lab-bred mice with poor immune systems to grow human colorectal cancers , they found biological factors and cell behavior, not just genes, drove growth and contributed to treatment failure and relapse.  MNT
Enhanced by Zemanta

New study brings long-sought vaccines for Toxoplasmosis closer to reality

One major cause of illness from food-borne diseases is the parasite Toxoplasma gondii (T. gondii). New insights into how the immune system combats T. gondii are provided in a study published by Cell Press December 13th in the journal Immunity. The findings could lead to the development of long-sought vaccines to protect against T. gondii and related parasites.

Read more at: http://medicalxpress.com/news/2012-12-long-sought-vaccines-deadly-parasite-closer.html#jCp

Futurity.org – Drug design takes aim at multi-gene diseases

Scientists have created a way to make designer drugs that hit multiple protein targets at once—an advance for treating “complex” diseases with numerous genetic and non-genetic factors.
Enhanced by Zemanta

Infections During Pregnancy and After Birth, and the Risk of Autism Spectrum Disorders: A Register-based Study Utilizing a Danish Historic Birth Cohort

Mounting evidence suggests that immune dysfunction may play a crucial role in the pathophysiology of autism spectrum disorders (ASD). In addition, several studies have reported that congenital and postnatal infections may contribute to the neurobiological basis of ASD. This study aimed to investigate the relationship between infections during pregnancy and after birth, and ASD.

METHODS:

A case-control study design was adopted. Both cases and controls were retrieved from a historic birth cohort (HBC) maintained at Statens Serum Institute in Copenhagen/Denmark and were followed up retrospectively during pregnancy and after birth over four pre-defined periods. Study subjects were followed-up utilizing Danish nation-wide health registers for outpatient and hospital admissions due to infections. Associations between infections and ASD were analyzed using Mantel-Haenszel estimate of the odds ratio (OR) and logistic regression models.

RESULTS:

In total, 414 ASD cases and 820 controls were followed-up during pregnancy and a mean 16.3 years after birth. Crude, but not adjusted estimates showed that ASD cases had an increased risk of hospital admission due to infection at the end of the first year of life (OR = 1.48 [range: 1.07-2.05], P = 0.02) and at the end of the follow-up period (OR = 1.30 [range: 1.02-1.64], P = 0.03).

CONCLUSION:

The present findings indicate that infections have a potential role in the pathophysiology of ASD; however, further studies are necessary to determine if infections etiologically contribute to ASD or if they act as an epiphenomenon due to distorted immunity in children with ASD.

Split-second control of specific dopamine neurones can switch depression-related behavior on and off (NIH)

A specific pattern of neuronal firing in a brain reward circuit instantly rendered mice vulnerable to depression-like behavior induced by acute severe stress, a study supported by the National Institutes of Health has found. When researchers used a high-tech method to mimic the pattern, previously resilient mice instantly succumbed to a depression-like syndrome of social withdrawal and reduced pleasure-seeking &mdash: they avoided other animals and lost their sweet tooth. When the firing pattern was inhibited in vulnerable mice, they instantly became resilient.

Futurity.org – Can grilled steak make you fat?

The chemicals that make a grilled steak taste so good ( glycated proteins) could add inches to your waistline and may be linked to cardiovascular and other diseases.

Treat obesity as physiology, not physics : Nature News & Comment

“It is better to know nothing,” wrote French physiologist Claude Bernard in An Introduction to the Study of Experimental Medicine (1865), “than to keep in mind fixed ideas based on theories whose confirmation we constantly seek.” 
Is the obesity epidemic caused at least in part by the research community's failure to understand the nature of the disease, and by the food industry's exploitation of that failure ?.

Immune-Mediated Regression of Established B16F10 Melanoma by Intratumoral Injection of Attenuated Toxoplasma gondii Protects against Rechallenge.

Immune recognition of tumors can limit cancer development, but antitumor immune responses are often blocked by tumor-mediated immunosuppression. Because microbes or microbial constituents are powerful adjuvants to stimulate immune responses, we evaluated whether intratumoral administration of a highly immunogenic but attenuated parasite could induce rejection of an established poorly immunogenic tumor. We treated intradermal B16F10 murine melanoma by intratumoral injection of an attenuated strain of Toxoplasma gondii (cps) that cannot replicate in vivo and therefore is not infective. The cps treatment stimulated a strong CD8(+) T cell-mediated antitumor immune response in vivo that regressed established primary melanoma. The cps monotherapy rapidly modified the tumor microenvironment, halting tumor growth, and subsequently, as tumor-reactive T cells expanded, the tumors disappeared and rarely returned. The treatment required live cps that could invade cells and also required CD8(+) T cells and NK cells, but did not require CD4(+) T cells. Furthermore, we demonstrate that IL-12, IFN-γ, and the CXCR3-stimulating cytokines are required for full treatment efficacy. The treatment developed systemic antitumor immune activity as well as antitumor immune memory and therefore might have an impact against human metastatic disease. The approach is not specific for either B16F10 or melanoma. Direct intratumoral injection of cps has efficacy against an inducible genetic melanoma model and transplantable lung and ovarian tumors, demonstrating potential for broad clinical use. The combination of efficacy, systemic antitumor immune response, and complete attenuation with no observed host toxicity demonstrates the potential value of this novel cancer therapy.
Enhanced by Zemanta

The Relationship between Tourette's Syndrome and Infections.

Increasing evidence shows that infections and an activated immune status might be involved in the pathogene-sis of tic disorders. Studies discuss the influence of neurotrophic bacteria and viruses on different psychiatric disorders. In addition, signs of inflammation and immunological abnormalities have been described especially in schizophrenia and Tourette's syndrome (tic disorder). Neuroimaging studies revealed increased microglial activation in psychiatric diseases; indicating an inflammatory state of the CNS.However, it still remains unclear what the underlying mechanism is of how infectious agents could contribute to tic symp-toms. One hypothesis is that not only one particular infectious agent causes directly to the disease; instead different (chronic) infections influence the immune balance and are therefore involved in the pathology. In tic disorders, infections with group A streptococci, Borrelia burgdorferi or Mycoplasma pneumoniae seem to be associated with symptoms of the disease. Studies have shown that immunologic treatment improves and prevents the re-occurrence of clinical symptoms in Tourette's syndrome. Also post-infectious events by cross-reactive antibodies(against M-protein) and an altered dopamine rgic(noradrenergic) neurotransmission as well as inflammatory/immunological dysregulations were considered as possible mechanisms to cause symptoms. Another contributing factor to the pathogenesis of these diseases could be an activation of the tryptophan catabolism through infectious agents. Tryptophan functions as a precursor for neurotransmitters like se-rotonin and becomes degraded to products that can modulate the neurotransmitter balance.A deeper insight into the precise mechanism of how infectious agents influence immune parameter, tryptophan metabo-lism and the resulting neurotransmitter availability could help finding new therapeutic strategies.
Enhanced by Zemanta

Gene expression analysis reveals schizophrenia-associated dysregulation of immune pathways in peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMCs) represent an accessible tissue source for gene expression profiling in schizophrenia that could provide insight into the molecular basis of the disorder. This study used the Illumina HT_12 microarray platform and quantitative real time PCR (QPCR) to perform mRNA expression profiling on 114 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric controls from the Australian Schizophrenia Research Bank (ASRB). Differential expression analysis revealed altered expression of 164 genes (59 up-regulated and 105 down-regulated) in the PBMCs from patients with schizophrenia compared to controls. Bioinformatic analysis indicated significant enrichment of differentially expressed genes known to be involved or associated with immune function and regulating the immune response. The differential expression of 6 genes, EIF2C2 (Ago 2), MEF2D, EVL, PI3, S100A12 and DEFA4 was confirmed by QPCR. Genome-wide expression analysis of PBMCs from individuals with schizophrenia was characterized by the alteration of genes with immune system function, supporting the hypothesis that the disorder has a significant immunological component in its etiology.

How Glucocorticoid Hormones Shut Off Key Immune System Genes

MNT: Researchers at Emory University School of Medicine have obtained a detailed molecular picture that shows how glucocorticoid hormones shut off key immune system genes.

Does the brain become unglued in autism?

A new study published in Biological Psychiatry suggests that autism is associated with reductions in the level of cellular adhesion molecules in the blood, where they play a role in immune function.

Read more at: http://medicalxpress.com/news/2012-12-brain-unglued-autism.html#jCp

Are Mycobacterium avium subsp. paratuberculosis and Epstein-Barr virus triggers of multiple sclerosis in Sardinia?

Sardinia acts as an ideal setting for multiple sclerosis (MS) studies because its prevalence of MS is one of the highest worldwide. Several pathogens have been investigated amongst 119 Sardinian MS patients and 117 healthy controls to determine whether they might have a role in triggering MS in genetically predisposed individuals. Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein Barr virus DNA were detected in 27.5% and 17.3%, respectively, of the MS patients. Moreover an extremely high humoral immune response against MAP recombinant protein MAP FprB (homologous to human myelin P0) was observed, whereas no significant results were found against Mycobacterium tuberculosis FprA and Helicobacter pylori HP986 protein.

Altered natural killer cells' response to herpes virus infection in multiple sclerosis involves KIR2DL2 expression.

The role of herpes viruses as potential triggers of multiple sclerosis (MS) is still debated. Peripheral blood mononuclear cells from MS patients and controls were treated with CpG sequences (potential methylation targets) and infected in vitro with HSV-1. Samples were analyzed for viral yield, TLR9 pathways, cytokine secretion, NK cell activation and killer immunoglobulin-like receptor (KIR) expression. CpG treatment promoted an unexpected sensitivity to herpes virus infection in a subset of MS patients: TLR9 pathways did not show defects while NK cells presented decreased degranulation and cytotoxicity and up-regulated the inhibitory KIR2DL2 receptor. CpG treatment of purified NK cells affected directly KIR2DL2 modulation and cell activation. These data suggest potential implications for viral pathogenesis of MS.

Impact of chronic Helicobacter pylori infection on Alzheimer's disease

Recent case-control studies reported an association between H. pylori infection and Alzheimer's disease (AD). Our aim was to compare cognitive impairment, neuroinflammation, and cerebrovascular lesion load in a group of AD patients according to their H. pylori status. For the 53 AD patients included, we assessed: clinical data (vascular comorbidities and cognitive assessment), biological data (especially fibrinogen, homocysteine levels, apolipoprotein E4 genotype; cerebrospinal fluid [CSF] total tau protein [Tau], phospho-tau(181) protein [pTau(181)]), and amyloid beta peptide levels, serum/CSF-cytokines (interleukin [IL]-1β, IL-6, IL-8, tumor necrosis factor [TNF]-α) and pepsinogen I/pepsinogen II (PgI/PgII) ratio, and cerebrovascular lesion load (magnetic resonance imaging [MRI] fluid-attenuated inversion recovery [FLAIR] with the Fazekas and Schmidt scale). H. pylori infection was diagnosed by enzyme-linked immunosorbent assay (ELISA) and immunoblot test. H. pylori infection was associated with a decreased Mini Mental State Examination (MMS) (p = 0.024), and higher CSF pTau(181) (p = 0.014) and tau (p = 0.021) levels. A decreased PgI/II ratio (i.e., an increased gastric atrophy) was associated with the infection (p = 0.005). Homocysteine levels were positively correlated to Fazekas score (r = 0.34; p = 0.032) and to H. pylori immunoglobulin (Ig)G levels (r = 0.44; p = 0.001). Higher CSF cytokine levels (IL-8, p = 0.003; TNF-α, p = 0.019) were associated with the infection, but systemic inflammation results were controversial. Finally, in multivariate analysis, a lower MMSE score (odds ratio [OR], 0.83 [0.72-0.97]; p = 0.017), plasma IL-1β level (OR, 0.31 [0.11-0.87]; p = 0.025), an increased gastric atrophy, i.e., a lower PgI/PgII ratio (OR, 0.63 [0.43-0.93]; p = 0.020) were still associated with the infection. AD patients infected by H. pylori tended to be more cognitively impaired. Studies are needed to attest to the impact of H. pylori infection on AD course, especially on cerebrovascular lesions and neuroinflammation.

Pleiotropic protective effects of phytochemicals in Alzheimer's disease.

Alzheimer's disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

Experiment finds Achilles' heel of ulcer bug, H. pylori

Dec. 10, 2012 — Experiments at the U.S. Department of Energy's (DOE) SLAC National Accelerator Laboratory have revealed a potential new way to attack common stomach bacteria that cause ulcers and significantly increase the odds of developing stomach cancer.

Brain displays an intrinsic mechanism for fighting infection

Dec. 10, 2012 — White blood cells have long reigned as the heroes of the immune system. When an infection strikes, the cells, produced in bone marrow, race through the blood to fight off the pathogen. But new research is emerging that individual organs can also play a role in immune system defense, essentially being their own hero. In a study examining a rare and deadly brain infection,due to Herpes simplex,  scientists at The Rockefeller University have found that the brain cells of healthy people likely produce their own immune system molecules, mediated via toll; receptor TLR3, demonstrating an "intrinsic immunity" that is crucial for stopping an infection.

Iron supplements reduce ADHD in low birth weight infants

In a study published today in Pediatrics, scientists at Umeå University in Sweden conclude that giving iron supplements to low birth weight infants reduces the risk of behavior problems like ADHD later in life.

Read more at: http://medicalxpress.com/news/2012-12-iron-supplements-adhd-birth-weight.html#jCp

Study finds association between oxygen deprivation before birth and ADHD

Children who had in-utero exposure to ischemic-hypoxic conditions, situations during which the brain is deprived of oxygen, were significantly more likely to develop attention deficit hyperactivity disorder later in life as compared to unexposed children, according to a Kaiser Permanente study published in the journal Pediatrics. The findings suggest that events in pregnancy may contribute to the occurrence of ADHD over and above well-known familial and genetic influences of the disorder."

'via Blog this'

Intestinal microbiota promote enteric virus replication and systemic pathogenesis.

Intestinal bacteria aid host health and limit bacterial pathogen colonization. However, the influence of bacteria on enteric viruses is largely unknown. We depleted the intestinal microbiota of mice with antibiotics before inoculation with poliovirus, an enteric virus. Antibiotic-treated mice were less susceptible to poliovirus disease and supported minimal viral replication in the intestine. Exposure to bacteria or their N-acetylglucosamine-containing surface polysaccharides, including lipopolysaccharide and peptidoglycan, enhanced poliovirus infectivity. We found that poliovirus binds lipopolysaccharide, and exposure of poliovirus to bacteria enhanced host cell association and infection. The pathogenesis of reovirus, an unrelated enteric virus, also was more severe in the presence of intestinal microbes. These results suggest that antibiotic-mediated microbiota depletion diminishes enteric virus infection and that enteric viruses exploit intestinal microbes for replication and transmission.

PLOS Pathogens: GABAergic Signaling Is Linked to a Hypermigratory Phenotype in Dendritic Cells Infected by Toxoplasma gondii

During acute infection in human and animal hosts, the obligate intracellular protozoan Toxoplasma gondii infects a variety of cell types, including leukocytes. Poised to respond to invading pathogens, dendritic cells (DC) may also be exploited by T. gondiifor spread in the infected host. Here, we report that human and mouse myeloid DC possess functional γ-aminobutyric acid (GABA) receptors and the machinery for GABA biosynthesis and secretion. Shortly after T. gondii infection (genotypes I, II and III), DC responded with enhanced GABA secretion in vitro. We demonstrate that GABA activates GABAAreceptor-mediated currents in T. gondii-infected DC, which exhibit a hypermigratory phenotype. Inhibition of GABA synthesis, transportation or GABAA receptor blockade in T. gondii-infected DC resulted in impaired transmigration capacity, motility and chemotactic response to CCL19 in vitro. Moreover, exogenous GABA or supernatant from infected DC restored the migration of infected DCin vitro. In a mouse model of toxoplasmosis, adoptive transfer of infected DC pre-treated with GABAergic inhibitors reduced parasite dissemination and parasite loads in target organs, e.g. the central nervous system. Altogether, we provide evidence that GABAergic signaling modulates the migratory properties of DC and that T. gondii likely makes use of this pathway for dissemination. The findings unveil that GABA, the principal inhibitory neurotransmitter in the brain, has activation functions in the immune system that may be hijacked by intracellular pathogens.
See also the T.Gondii host/pathogen interactome

Epigenetic Mechanisms in Psychiatry :Reviws in Neuropsychopharmacology

This issue of Neuropsychopharmacology Reviews is focused on epi- (Greek for ‘over’ or ‘above’) genetics, which, in its broadest definition, concerns the regulation of chromatin structure and function (including but not limited to gene expression) in dividing and non-dividing cells. Many epigenetic markings such as DNA methylation, post-translational histone modifications, and histone variants, in concert, define three-dimensional genome architectures inside the nucleus and are thought to serve as a ‘molecular bridge’ by which myriads of external (environmental) and internal factors mold and shape the nascent genetic material throughout the brain and peripheral tissues over the entire lifespan of an organism.

Emerging risk factors for postpartum depression: serotonin transporter genotype and omega-3 Fatty Acid status.

Depression is a leading cause of disability and hospitalization. Women are at the highest risk of depression during their childbearing years, and the birth of a child may precipitate a depressive episode in vulnerable women. Postpartum depression (PPD) is associated with diminished maternal somatic health as well as health and developmental problems in their offspring. This review focuses on 2 PPD risk factors of emerging interest: serotonin transporter (5-HTT) genotype and omega-3 polyunsaturated fatty acid (n-3 PUFA) status. Method: The MEDLINE, PubMed, and Web of Science databases were searched using the key words postpartum depression, nutrition, omega-3 fatty acids, and serotonin transporter gene. Studies were also located by reviewing the reference lists of selected articles. Results: Seventy-five articles were identified as relevant to this review. Three carefully conducted studies reported associations between the 5-HTT genotype and PPD. As well, there is accumulating evidence that n-3 PUFA intake is associated with risk of PPD. Preliminary evidence suggests that there could be an interaction between these 2 emerging risk factors. However, further studies are required to confirm such an interaction and to elucidate the underlying mechanisms. Conclusions: Evidence to date supports a research agenda clarifying the associations between n-3 PUFAs, the 5-HTT genotype, and PPD. This is of particular interest owing to the high prevalence of poor n-3 PUFA intake among women of childbearing age and the consequent potential for alternative preventive measures and treatments for PPD.

New antidepressant acts very rapidly and is long lasting

A first-of-its-kind antidepressant drug discovered by a Northwestern University professor and now tested on adults who have failed other antidepressant therapies has been shown to alleviate symptoms within hours, have good safety and produce positive effects that last for about seven days from a single dose.GLYX-13 works by modulating the NMDA (N-methyl-D-aspartate) receptor in the brain, as do current NMDA receptor antagonists such as ketamine, but GLYX-13 does not have their serious and limiting side effects, such as hallucinations and schizophrenia-like effects.4