Researchers have discovered a key cellular mechanism that may help the brain control how much we eat, what we weigh, and how much energy we have.
Viral Genomes - Molecular Structure, Diversity, Gene Expression Mechanisms and Host-Virus Interactions | Biochemistry, Genetics and Molecular Biology | InTechOpen
OPEN ACCESS BOOK Viruses are small infectious agents that can replicate only inside the living cells of susceptible organisms. The understanding of the molecular events underlying the infectious process has been of central interest to improve strategies aimed at combating viral diseases of medical, veterinary and agricultural importance. Some of the viruses cause dreadful diseases, while others are also of interest as tools for gene transduction and expression and in non-poluting insect pest management strategies. The contributions in this book provide the reader with a perspective on the wide spectrum of virus-host systems. They are organized in sections based on the major topics covered: viral genomes organization, regulation of replication and gene expression, genome diversity and evolution, virus-host interactions, including clinically relevant features. The chapters also cover a wide range of technical approaches, including high throughput methods to assess genome variation or stability. This book should appeal to all those interested in fundamental and applied aspects of virology.
Slowing or preventing the development of Alzheimer's disease, a fatal brain condition expected to hit one in 85 people globally by 2050, may be as simple as ensuring a brain protein's sugar levels are maintained.
(Medical Xpress) -- During depression, the brain becomes less plastic and adaptable, and thus less able to perform certain tasks, like storing memories. Researchers at Karolinska Institutet have now traced the brain's lower plasticity to reduced functionality in its support cells, and believe that learning more about these cells can pave the way for radical new therapies for depression.
People are relying on sleeping pills more than ever to get a good night's rest, but a new study by Scripps Clinic researchers links the medications to a 4.6 times higher risk of death and a significant increase in cancer cases among regular pill users.
It is estimated that half of all deaths in the United States are linked to behavioral and social factors such as smoking, diet and physical inactivity. Despite these causal links, of the $2 trillion spent annually on health care in the U.S., only 5 percent of that is devoted to addressing behavioral and social risk factors.
Adults with disabilities are at much greater risk of violence than adults without disabilities, according to a new meta-analysis published Online First in The Lancet. Adults with mental illness appear to be particularly vulnerable and are nearly four times as likely to be a victim of violence than adults without a disability, with an estimated one in four having experienced violence in the past year.
In a look at how major stressors during childhood can change a person's biological risk for psychiatric disorders, researchers at Butler Hospital have discovered a genetic alteration at the root of the association. The research, published online in PLoS ONE on January 25, 2012, suggests that childhood adversity may lead to epigenetic changes in the human glucocorticoid receptor gene, an important regulator of the biological stress response that may increase risk for psychiatric disorders.
A group of scientists from across the world have provided new insights into how fructose causes obesity and metabolic syndrome, more commonly known as diabetes. Researchers found that fructose can be metabolized by an enzyme that exists in two forms. One form appears to be responsible for causing how fructose causes fatty liver, obesity, and insulin resistance. The other form may actually protect animals from developing these features in response to sugar.
Heart disease patients who took statins, the drugs prescribed for lowering cholesterol, were significantly less likely to develop depression than counterparts who did not take the drugs, according to a new study led by Dr Mary Whooley, a professor of medicine at the University of California, San Francisco. The researchers write about their findings in an article published online in the Journal of Clinical Psychiatry on 21 February.
A diet lacking in omega-3 fatty acids, nutrients commonly found in fish, may cause your brain to age faster and lose some of its memory and thinking abilities, according to a study published in the February 28, 2012, print issue of Neurology, the medical journal of the American Academy of Neurology. Omega-3 fatty acids include the nutrients called docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).
|Image via Wikipedia|
Air pollution—already tied to asthma and heart attacks—appears also to wreak havoc in the brain. Particles that enter the body through the nose or lungs may lead to cognitive decline or strokes, suggest a trio of papers that came out in the February 13 Archives of Internal Medicine.
Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls.MethodWe recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma Questionnaire (CTQ). Using enzyme-linked immunosorbent assay (ELISA) techniques, we measured peripheral levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α. These immune parameters were compared in schizophrenia with childhood trauma, schizophrenia without childhood trauma and healthy controls.
RESULTS:Patients with childhood trauma had higher levels of IL-6 and TNF-α than patients without trauma and healthy controls, and TNF-α levels correlated with the extent of the trauma. Patients with no trauma had similar immune profiles to controls.
CONCLUSIONS:Childhood trauma drives changes, possibly epigenetic, that generate a pro-inflammatory phenotype.
The researchers noted that this linker-cell death pathway is morphologically similar to the neuronal death seen in certain neurodegenerative diseases. “Our results may therefore provide molecular inroads to understanding nonapoptotic cell death in metazoan development and disease,” the authors wrote.
(Medical Xpress) -- University of Alabama researcher Dr. Yasmin Neggers, a professor of human nutrition and hospitality management, found a possible lipid metabolism disorder in children with autism. Even though there were no major differences in what these children ate, those with autism had a lower omega-3 to omega-6 fatty acid ratio and lower levels of high density lipoprotein, more commonly known as HDL. For both levels, it’s often believed, the higher the better.
Eukaryotic cells possess two extensive endomembrane systems, each consisting of several sub-compartments connected by vesicular trafficking. One of these systems, the endocytic pathway, serves incoming traffic, the other system, the secretory pathway, is responsible for surface-bound traffic of intracellularly formed vesicles. Compartments derived of either system can be colonized by intracellular pathogens. In this review, we discuss the interactions between the secretory pathway and prominent intracellular bacterial pathogens of the genera Legionella , Brucella, Chlamydia and Salmonella. We emphasize secreted bacterial effector proteins, which directly manipulate host components of this pathway.
Scientists at Durin Technologies, Inc., and the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine (UMDNJ-SOM) have announced a possible breakthrough in the search for a diagnostic biomarker for Parkinson's disease - a blood test that in the future may be able to detect the disease with high accuracy. In an analysis that included more than 150 blood samples, Nagele and his team employed human protein microarrays to identify specific autoantibody biomarkers that may be able to diagnose Parkinson’s disease with a high level of accuracy.
Advancing personalized medicine:
tailoring drugs to fit a patient’s genetic predisposition - Frontlines - RIKEN RESEARCH
Drugs are not equally effective on all patients. A treatment that is dramatically effective on some patients can be ineffective on others. Drugs can also have serious side effects; in the worst case, a drug used to treat a disease can produce a fatal outcome. By examining genetic differences among individuals and administering drugs on the basis of such findings, the impact of side effects can be reduced. Taisei Mushiroda, the Laboratory Head of the Research Group for Pharmacogenomics at the RIKEN Center for Genomic Medicine, is making advances in personalized medicine with research into how drugs can be tailored to a patient’s genetic information through the analysis of single nucleotide polymorphisms (SNPs).
Researchers at National Jewish Health have discovered specific molecular and signaling events by which vitamin D inhibits inflammation. In their experiments, they showed that low levels of Vitamin D, comparable to levels found in millions of people, failed to inhibit the inflammatory cascade, while levels considered adequate did inhibit inflammatory signaling. They reported their results in the March 1, 2012, issue of The Journal of Immunology.
Bisphenol A (BPA) is a controversial chemical widely used in the plastics industry. A new study followed people over a 10-year time period and shows that healthy people with higher urine concentrations of BPA were more likely to later develop heart disease. But researchers "can't be certain that BPA itself is responsible" -- more research needed to determine whether the link is causal.
Gene-gene and gene-environmental interactions of childhood asthma: a multifactor dimension reduction approach.
The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking.
METHODOLOGY/PRINCIPAL FINDINGS:We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 single-nucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83% with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance.
CONCLUSIONS/SIGNIFICANCE:The results of this study suggest that GSTP1, INSIG2 and IL4Ra may influence the lifetime asthma susceptibility through gene-gene interactions in schoolchildren. Home dampness combined with each one of the genes STAT6, IL13 and ADRB2 could raise the asthma risk.
Triterpenoid modulation of IL-17 and Nrf-2 expression ameliorates neuroinflammation and promotes remyelination in autoimmune encephalomyelitis.
Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of pro-inflammatory transcripts with concomitant induction of anti-inflammatory genes including Ptgds and Hsd11b1. Finally, triterpenoids induced oligodendrocyte maturation in vitro and enhanced myelin repair in an LPC-induced non-inflammatory model of demyelination in vivo. These results demonstrate the unique potential of triterpenoid derivatives for the treatment of neuroinflammatory disorders such as MS.
During the evolution of the human genome, a number of retroviral integrations have occurred creating a group of human endogenous retroviruses (HERVs). As of now several studies have pointed to the association of HERVs with certain autoimmune diseases such as RA, SLE, multiple sclerosis (MS) and SS as well as various neoplasms. In this study, we investigated the prevalence of HERV-K113 in patients with RA, SLE and in healthy subjects in the Polish population.
METHODS:Genomic DNA samples from 155 RA patients, 139 SLE patients and 261 newborns (as controls) were tested for the presence of the HERV-K113 allele using PCR. Each individual's DNA was genotyped for null, homozygous or heterozygous insertion of HERV-K113.
RESULTS:Our data revealed statistically significant differences in the insertion frequencies of HERV-K113 between the groups of RA and SLE patients vs healthy controls (provirus DNA was found in 14.19, 15.11 and 8.05% of individuals, respectively). No homozygous individuals for the K113 allele were found in each of the groups. There was no evidence for HERV-K113 association with clinical features in either group.
CONCLUSION:Our study-the first such performed for the Polish population-provides a consistent observation with previous reports on the genetic association of HERV-K113 integrations in autoimmune disorders. Here, we found that the prevalence of insertionally polymorphic HERV-K113 was significantly increased in Polish patients with SLE and RA.
The purpose of this study was to delineate the spectrum of neurological diseases attributed to Epstein-Barr virus (EBV) activity. The approach was a retrospective study on patients with EBV activity proven by a positive EBV antibody-specific index (AI) and/or cerebrospinal fluid (CSF) PCR. One hundred six children and adults (AI positive = 77, AI + PCR positive = 3, PCR positive = 26) were identified, most with reactivated infections. Twenty-eight showed typical EBV-related diseases (encephalitis, neuritis, meningitis), 19 further infections (HSV encephalitis, neuroborreliosis, HIV infection, bacterial meningitis), nine immune-mediated disorders (multiple sclerosis, optic neuritis), and 50 further diseases not typical for EBV. The highest AI values occurred in patients with encephalitis. No relationship between disease category or AI values and viral loads was found. Additional reanalysis of 1,500 consecutive CSF EBV PCR studies revealed the highest positive rates among patients with further infections (n = 18/227, 7.9%) but lower rates among patients with typical EBV-related disorders (5/395; 1.3%), immune-mediated disorders (n = 2/174; 1.1%) and other conditions (n = 4/704; 0.6%). Intrathecal EBV activity is not restricted to typical EBV-related disorders, unexpectedly frequent in further CNS infections and also present in non-inflammatory conditions. Prospective studies should assess the pathogenic role of EBV in these different diseases.
Two mechanisms of innate immunity, i.e. resistance to viral infection and the production of cytokines by leukocytes, were compared in blood isolated from four groups of donors: healthy young (19-35 years old), healthy elderly (over 60), elderly Alzheimer's disease (AD) patients, and elderly patients with alimentary tract cancer (CA). Peripheral blood leukocytes (PBLs) were isolated by gradient centrifugation in Gradisol G. The degree of resistance was calculated from the kinetics of vesicular stomatitis virus (VSV) replication in the PBLs. Cytokine (TNFα, IFNα, IFNγ, IL-12, and IL-10) levels were determined by ELISA. The antiviral resistance of the PBLs varied, but a difference was observed only between the young and elderly groups and not between the healthy elderly controls and those with AD or cancer. Differences observed in all the groups concerned the ability and intensity of cytokine production. The most impressive results were obtained for spontaneous TNF and IFNα release. While TNF was released spontaneously by the PBLs of the elderly CA patients and the young healthy group, it was usually undetected in the AD and only sometimes in the healthy elderly group. Leukocytes isolated from the elderly groups responded to VSV infection with more intense IFNα and IFNγ production than the younger group.
UC Davis scientists have uncovered a key suspect in the destructive inflammation that underlies heart disease and diabetes. The new research shows elevated levels of a receptor present on leucocytes of the innate immune response in people at risk for these chronic diseases. The receptors are the body's first line of defense against infectious invaders, and they trigger a rush of cytokines, the body's aggressive immune soldiers, into the bloodstream.
The offspring of women who were given micronutrient supplements (minerals needed in small quantities, such as iron, iodine and vitamin A) before they became pregnant had gene modifications (methylation) at birth as well as when they were tested at 9 months.
New research suggests women who have migraine or have had them in the past are at an increased risk for developing depression compared to women who have never had migraine. The study was released today and will be presented at the American Academy of Neurology's 64th Annual Meeting in New Orleans April 21 to April 28, 2012.
Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play a major role in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (PolyI:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia.
A novel bacterium (Streptococcus tigurinus), thought to be a common inhabitant of the oral cavity, has the potential to cause serious disease if it enters the bloodstream, according to a study in the International Journal of Systematic and Evolutionary Microbiology. Its identification will allow scientists to work out how it causes disease and evaluate the risk that it poses.
OBJECTIVES:Beneficial microbes and probiotics are promising agents for the prevention and treatment of enteric and diarrheal diseases in children. However, little is known about their in vivo mechanisms of action. We used a neonatal mouse model of rotavirus diarrhea to gain insight into how probiotics ameliorate acute gastroenteritis.
MATERIALS AND METHODS:Rotavirus-infected mice were treated with one of two strains of human-derived Lactobacillus reuteri. We assessed intestinal microbiome composition with 16S metagenomic sequencing, enterocyte migration and proliferation with 5-bromo-2'-deoxyuridine, and antibody and cytokine concentrations with multiplex analyses of intestinal explant cultures.
RESULTS:Probiotics reduced diarrhea duration, improved intestinal histopathology, and enhanced intestinal microbiome richness and phylogenetic diversity. The magnitude of reduction of diarrhea by probiotics was strain-specific and influenced by nutritional status. L. reuteri DSM 17938 reduced diarrhea duration by zero, one, and two days in underweight, normal weight, and overweight pups, respectively. The magnitude of reduction of diarrhea duration correlated with increased enterocyte proliferation and migration. Strain ATCC PTA 6475 reduced diarrhea duration by one day in all mice without increasing enterocyte proliferation. Both probiotic strains decreased concentrations of proinflammatory cytokines, including MIP-1α and IL-1β, in all animals, and increased rotavirus-specific antibodies in all but underweight animals. Body weight also influenced the host response to rotavirus, in terms of diarrhea duration, enterocyte turnover, and antibody production.
CONCLUSIONS:These data suggest that probiotic enhancement of enterocyte proliferation, villus repopulation, and virus-specific antibodies may contribute to diarrhea resolution, and that nutritional status influences the host response to both beneficial microbes and pathogens.
Researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have found new evidence to explain how cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol from "good" high density lipoproteins (HDLs) to "bad" low density lipoproteins (LDLs). These findings point the way to the design of safer, more effective next generation CETP inhibitors that could help prevent the development of heart disease.
The levels of the environmental pollutant perfluorooctanoic acid (PFOA) that mothers had in their blood during pregnancy increased the risk of obesity in their daughters at 20 years of age. The findings come from a recent study of Danish women in which the Norwegian Institute of Public Health participated.
Stress has numerous detrimental effects on the human body. Many of these effects are acutely felt by the sufferer, but many more go 'unseen', one of which is shortening of telomere length.
neuGRID, the European Online Diagnosis Tool for Alzheimer’s, Goes Global with outGRID and the ITU - FierceBiotech
neuGRID, a cloud-computing infrastructure funded by the European Commission that stores and analyses a vast database of 3D brain scans, is now expanding globally to help find treatments for Alzheimer’s. This ground-breaking initiative will help develop a global online system to centralise and boost Alzheimer’s research initiatives.
The flu and herpes viruses are bad enough already. But Harvard Medical School scientists believe that they may cause lasting brain cell damage, making sufferers vulnerable to neurodegenerative diseases like Alzheimer's and Parkinson's.
Everything you know about dieting is wrong, say US scientists who have devised a new formula for calculating calories and weight loss that they hope will revolutionize the way people tackle obesity.
According to a team from the National Institute on Ageing in Baltimore, America, fasting for one or two days a week may protect against Alzheimer’s, Parkinson’s and other degenerative brain conditions.
Defects in a protein that functions as a dietary fat sensor may be a cause of obesity and liver disease, according to a study published in the journal Nature, led by researchers at Imperial College London. The findings highlight a promising target for new drugs to treat obesity and metabolic disorders.The protein GPR120 is found on the surface of cells in the gut, liver and fat tissue and allows cells to detect and respond to unsaturated fatty acids from the diet, especially the omega-3 fatty acids which are believed to have a beneficial impact on health
Alzheimer's disease drugs now being tested in clinical trials may have potentially adverse side effects, according to new Northwestern Medicine research. A study with mice suggests the drugs could act like a bad electrician, causing neurons to be miswired and interfering with their ability to send messages to the brain. Working with BACE1, Vassar discovered the animals' olfactory system – used for the sense of smell -- was incorrectly wired. The axons of the olfactory neurons were not wired properly to the olfactory bulb of the brain. The findings show the key role of BACE1 in axonal guidance.
(Medical Xpress) -- A University of Alberta researcher and Canada Excellence Research Chair in Virology has made the discovery of a vaccine that will potentially help combat hepatitis C. Michael Houghton, who led the team that discovered the hepatitis C virus in 1989, announced his findings at the Canada Excellence Research Chairs Summit in Vancouver this afternoon. Currently, there are no vaccines against the disease available.
Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV and the host immune system is one of the main determinants of the infection outcome. Chemokines play relevant roles in antiviral response and immunopathology, but the modulation of chemokine function by HSV is not well understood. We have addressed the modulation of chemokine function mediated by HSV. By using surface plasmon resonance and crosslinking assays we show that secreted glycoprotein G (SgG) from both HSV-1 and HSV-2 binds chemokines with high affinity. Chemokine binding activity was also observed in the supernatant of HSV-2 infected cells and in the plasma membrane of cells infected with HSV-1 wild type but not with a gG deficient HSV-1 mutant. Cell-binding and competition experiments indicate that the interaction takes place through the glycosaminoglycan-binding domain of the chemokine. The functional relevance of the interaction was determined both in vitro, by performing transwell assays, time-lapse microscopy, and signal transduction experiments; and in vivo, using the air pouch model of inflammation. Interestingly, and in contrast to what has been observed for previously described viral chemokine binding proteins, HSV SgGs do not inhibit chemokine function. On the contrary, HSV SgGs enhance chemotaxis both in vitro and in vivo through increasing directionality, potency and receptor signaling. This is the first report, to our knowledge, of a viral chemokine binding protein from a human pathogen that increases chemokine function and points towards a previously undescribed strategy of immune modulation mediated by viruses.
|Image via Wikipedia|
Recent genome-wide studies have reported novel associations between common polymorphisms and susceptibility to many major infectious diseases in humans. In parallel, an increasing number of rare mutations underlying susceptibility to specific phenotypes of infectious disease have been described. Together, these developments have highlighted a key role for host genetic variation in determining the susceptibility to infectious disease. They have also provided insights into the genetic architecture of infectious disease susceptibility and identified immune molecules and pathways that are directly relevant to the human host defence.
"Our results demonstrate, for the first time for many of these pathogens (Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and -2, human herpesvirus-6, and varicella zoster virus ), that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance."
See also: Human genetic susceptibility to infectious disease from Nature Reviews
See also: Human genetic susceptibility to infectious disease from Nature Reviews
As people seek healthier dietary regimens they often turn to things labeled "organic." Lurking in the background, however, is an ingredient that may be a hidden source of arsenic -- an element known to be both toxic and potentially carcinogenic.
At 24 months, 28 infants (30 percent) met criteria for ASDs while 64 infants (70 percent) did not. The two groups differed in white matter fiber tract development -- pathways that connect brain regions -- as measured by fractional anisotropy (FA). FA measures white matter organization and development, based on the movement of water molecules through brain tissue.
According to the study, high-intensity, short-term exposure to the particles initially blocked iron absorption, whereas longer-term exposure caused intestinal cell structures to change, allowing for a compensating uptick in iron absorption.
Hepatitis C virus (HCV) entry is a multiple-step process involving a number of host factors and hence represents a promising target for new antiviral drug development. In search of novel inhibitors of HCV infection, we found that a human apolipoprotein E (apoE) peptide, hEP, containing both a receptor binding fragment and a lipid binding fragment of apoE, specifically blocked the entry of cell culture grown HCV (HCVcc) at sub-micromolar concentrations. hEP caused little cytotoxicity in vitro and remained active even if left 24 hours in cell culture. Interestingly, hEP inhibited neither HIV-HCV pseudotypes (HCVpp) nor HIV and Dengue virus (DENV) infection. Further characterization mapped the anti-HCV activity to a 32-residue region that harbors the receptor binding domain of apoE, but this fragment must contain a cysteine residue at the N-terminus to mediate dimer formation. The anti-HCV activity of the peptide appears to be dependent on both its length and sequence and correlates with its ability to bind lipids. Finally, we demonstrated that the apoE-derived peptides directly blocked the binding of both HCVcc and patient serum-derived virus to hepatoma cells as well as primary human hepatocytes. CONCLUSION: apoE peptides potently inhibit HCV infection and suggest a direct role of apoE in mediating HCV entry. Our findings also highlight the potential of developing apoE mimetic peptides as novel HCV entry inhibitors by targeting HCV-host interactions. (HEPATOLOGY 2012.).
The team identified miR-132, a "master" gene regulatory microRNA molecule, and discovered altered levels of miR-132 localized in the frontal region of the brain cortex in individuals with schizophrenia.
The Relationship Between Toxoplasma Gondii Infection and Mood Disorders in the Third National Health and Nutrition Survey.
Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite that causes persistent infection in humans. A substantial literature suggests that schizophrenia is associated with increased seroprevalence of T. gondii, but a possible link of the parasite with mood disorders has not been as thoroughly investigated.
METHODS:We examined the association of Toxoplasma-specific immunoglobulin G results with mood disorder outcomes in 7440 respondents from the third National Health and Nutrition Survey, which is a nationally representative sample of the United States noninstitutionalized civilian population. Regression models were adjusted for numerous potential confounders, including tobacco smoking and C-reactive protein levels.
RESULTS:No statistically significant associations were found between T. gondii seroprevalence and a history of major depression (n = 574; adjusted odds ratio [OR]: .8; 95% confidence interval [CI]: .5-1.2), severe major depression (n = 515; adjusted OR: .8; 95% CI: .6-1.2), dysthymia (n = 548; adjusted OR: 1.1; 95% CI: .7-1.8), or dysthymia with comorbid major depression (n = 242, adjusted OR: 1.2; 95% CI: .6-2.4), all p values were > .05, including analysis stratified by gender. However, there was a significant relationship between T. gondii seroprevalence and bipolar disorder type I for respondents in which both manic and major depression symptoms were reported (n = 41; adjusted OR: 2.4; 95% CI: 1.2-4.8; p < .05).
CONCLUSIONS:In a population-based sample, T. gondii seroprevalence is not elevated in unipolar mood disorders but is higher in a subset of respondents with a history of bipolar disorder type 1.
DNA origami, a technique for making structures from DNA, may be more than just a cool design concept. It can also be used to build devices that can seek out and destroy living cells.
The nanorobots, as the researchers call them, use a similar system to cells in the immune system to engage with receptors on the outside of cells. With a video from the Wyss Institute
The nanorobots, as the researchers call them, use a similar system to cells in the immune system to engage with receptors on the outside of cells. With a video from the Wyss Institute
Proper understanding of the effects of human migration on genetic risk of disease is paramount for addressing these risks in today's diverse populations. The following visualizations display genetic data across 51 worldwide populations provided by the Human Genome Diversity Project. This work was completed in the Butte Lab at Stanford University.
Mice genetically engineered to be susceptible to autism-like behaviors that were exposed to a common flame retardant were less fertile and their offspring were smaller, less sociable and demonstrated marked deficits in learning and long-term memory when compared with the offspring of normal unexposed mice, a study by researchers at UC Davis has found. The researchers said the study is the first to link genetics and epigenetics with exposure to a flame retardant chemical.
It's been said that timing is everything, and that may be particularly true when it comes to the ability to fight off disease. New research published by Cell Press in the February issue of the journal Immunity shows that the success of host immune defense depends in part on an organism's "body clock." The study may lead to therapeutic strategies designed to optimize the immune response and to protect patients at the time when they are most vulnerable.