Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated. 108 ME/CFS patients and 90 practically healthy persons were enrolled in the study. Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels-by ELISA, HHV-6 variants-by restriction analysis. Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines' levels was detected in patients during active viral infection. Definite relationship was observed between active betaherpesvirus infection and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain. Neuropsychological disturbances were detected in all patients. The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection. The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines' level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS.

Why Is Exercise Good For Mental Health?

We all know that exercise is good for mental health, but why? What factors involved in physical activity, sports and/or exercise are good for our minds? Researchers from the Trimbos Institute in the Netherlands believe that certain psychological factors that are linked to exercise - mainly body image and social interaction - play major roles in boosting mental health.

Benzodiazepines For Insomnia Or Anxiety Raises Dementia Risk Among Elderly

Patients over 65 years of age who take popular insomnia and anxiety drugs, (benzodiazepines), have a 50% higher risk of developing dementia during the following 15 years compared to people of the same age who never took the medication, researchers reported in the BMJ (British Medical Journal).

New way of fighting high cholesterol upends assumptions

Atherosclerosis – the hardening of arteries that is a primary cause of cardiovascular disease and death – has long been presumed to be the fateful consequence of complicated interactions between overabundant cholesterol and resulting inflammation in the heart and blood vessels. However, researchers at the University of California, San Diego School of Medicine, with colleagues at institutions across the country, say the relationship is not exactly what it appears, and that a precursor to cholesterol actually suppresses inflammatory response genes. This precursor molecule could provide a new target for drugs designed to treat atherosclerosis.

Read more at: http://medicalxpress.com/news/2012-09-high-cholesterol-upends-assumptions.html#jCp

Childhood obesity epidemic is clearly tied to easy availability of junk food

There's no real mystery here," said Willett. "In some ways, the obesity epidemic is the inevitable consequence of our capitalistic food supply. Food and beverage companies are competing with each other to get people to buy their products, and they work hard to make those unhealthy products even more seductive to kids

Read more at: http://medicalxpress.com/news/2012-09-childhood-obesity-epidemic-tied-easy.html#jCp

Futurity.org – How stem cells ‘grow up’ to cause inflammation

Scientists have determined how T cells that cause inflammatory ailments, such as Crohn’s disease, multiple sclerosis, and arthritis, develop from stem cells.

The robust electrochemical detection of a Parkinson's disease marker in whole blood sera - Chemical Science (RSC Publishing)

Protein aggregation, leading to amyloid deposition in the brain, is implicated in the pathology of a number of increasingly prevalent neurodegeneration states such as Parkinson's disease (PD), Alzheimer's disease and prion diseases. The body's protective response to the formation of such deposits is to generate specific autoimmune antibodies. Alpha-synuclein, a natively unfolded protein relatively abundant in the brain, is the main constituent of Lewy body amyloid dispositions in PD. Previous assays determining content of alpha-synuclein in bodily fluids have proven to be largely inconclusive. Here we have taken a novel approach in utilising alpha-synuclein modified electrodes to sample the autoantibodies generated as the body responds to changes in its homeostasis. We show that these electroanalytical assays not only robustly distinguish between disease state and control individuals but also map out disease progression with unprecedented sensitivity and clarity. The impedimetric electrode surfaces are highly specific, reusable, exhibit a linear range from 0.5 to 10 nM and a detection limit of 55 ± 3 pM. We believe electroanalyses such as these, possible with less than 10 microlitres of fluid and a total assay time of only a few minutes, to be of value for early diagnosis of PD and possibly other alpha-synucleinopathies, and for monitoring disease progression and effects of possible disease modifying interventions.

Antibiotics could replace surgery for appendicitis, research suggests

Dioxin causes disease and reproductive problems across generations

Michael Skinner and members of his lab say dioxin administered to pregnant rats resulted in a variety of reproductive problems and disease in subsequent generations. The first generation of rats had prostate disease, polycystic ovarian disease and fewer ovarian follicles, the structures that contain eggs. To the surprise of Skinner and his colleagues, the third generation had even more dramatic incidences of ovarian disease and, in males, kidney disease.

Read more at: http://medicalxpress.com/news/2012-09-dioxin-disease-reproductive-problems.html#jCp

A metagenome-wide association study of gut microbiota in type 2 diabetes : Nature : Nature Publishing Group

Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.

Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis.


Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however.

METHODS:

Prospective cohort of 198 persons with clinically definite MS, followed 2002-5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein-Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed-effects linear regression.

RESULTS:

For the 145 persons with relapsing-remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend (p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males.

DISCUSSION:

These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing-remitting MS clinical course.

Novel biomarkers for pre-diabetes identified by metabolomics: Molecular Systems Biology

Type 2 diabetes (T2D) can be prevented in pre-diabetic individuals with impaired glucose tolerance (IGT). Here, we have used a metabolomics approach to identify candidate biomarkers of pre-diabetes. We quantified 140 metabolites for 4297 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) cohort. Our study revealed significant metabolic variation in pre-diabetic individuals that are distinct from known diabetes risk indicators, such as glycosylated hemoglobin levels, fasting glucose and insulin. We identified three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2) and acetylcarnitine) that had significantly altered levels in IGT individuals as compared to those with normal glucose tolerance, with P-values ranging from 2.4 × 10−4 to 2.1 × 10−13. Lower levels of glycine and LPC were found to be predictors not only for IGT but also for T2D, and were independently confirmed in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Using metabolite–protein network analysis, we identified seven T2D-related genes that are associated with these three IGT-specific metabolites by multiple interactions with four enzymes. The expression levels of these enzymes correlate with changes in the metabolite concentrations linked to diabetes. Our results may help developing novel strategies to prevent T2D.

Mechanism that leads to sporadic Parkinson's disease identified

Exposure to toxins associated with Parkinson's can increase the abundance of a longer transcript form of alpha-synuclein, which is more toxic.

Obesity promotes prostate cancer by altering gene regulation

Prostate cancer is one of the most common cancers in men and early treatment is usually very successful. However, like other cancers, obesity increases the risk of aggressive prostate disease. New research, published in BioMed Central's open access journalBMC Medicine, finds that the fat surrounding the prostate of overweight or obese men with prostate cancer provides a favorable environment to promote cancer growth.

EHP – Prenatal Methylmercury, Postnatal Lead Exposure, and Evidence of Attention Deficit Hyperactivity Disorder among Inuit Children in Arctic Québec


Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) has been associated with impaired performance on attention tasks in previous studies, but the extent to which these cognitive deficits translate into behavioral problems in the classroom and attention deficit hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has been associated with ADHD and disruptive behaviors in several studies.
Objectives: This study examined the relation of developmental exposure to MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed from their traditional diet.
Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants was measured at birth and at school age. An assessment of child behavior (N = 279; mean age = 11.3 years) was obtained from the child’s classroom teacher on the Teacher Report Form (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD).
Results: Cord blood mercury concentrations were associated with higher TRF symptom scores for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations were associated with higher TRF symptom scores for externalizing problems and with symptoms of ADHD (hyperactive-impulsive type) based on the DBD.
Conclusions: To our knowledge, this study is the first to identify an association between prenatal MeHg and ADHD symptomatology in childhood and the first to replicate previously reported associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb primarily from dietary sources.


Chronic exposure to dim light may raise depression risk

Two years ago, Randy Nelson, Ph.D., chair of neuroscience at Ohio State University, doctoral student Tracy Bedrosian, and colleagues reported that dim-light exposure at night was capable of triggering depressive-like behaviors in animals. The dim-light exposure, they explained, was comparable to having a television on in a darkened room.

Read more at: http://medicalxpress.com/news/2012-09-chronic-exposure-dim-depression.html#jCp

Viral perturbations of host networks reflect disease etiology.

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia.

Toxoplasma on the Brain: Understanding Host-Pathogen Interactions in Chronic CNS Infection

Toxoplasma gondii is a prevalent obligate intracellular parasite which chronically infects more than a third of the world's population. Key to parasite prevalence is its ability to form chronic and nonimmunogenic bradyzoite cysts, which typically form in the brain and muscle cells of infected mammals, including humans. While acute clinical infection typically involves neurological and/or ocular damage, chronic infection has been more recently linked to behavioral changes. Establishment and maintenance of chronic infection involves a balance between the host immunity and parasite evasion of the immune response. Here, we outline the known cellular interplay between Toxoplasma gondii and cells of the central nervous system and review the reported effects of Toxoplasma gondii on behavior and neurological disease. Finally, we review new technologies which will allow us to more fully understand host-pathogen interactions.

The T.Gondii host/pathogen interactome 

New Clue To Slower Progression Of AIDS: MNT

The average time from HIV infection to full-blown AIDS in the absence of treatment is about 10 years, and while some people succumb much sooner, others, known as the "slow progressors", can remain healthy for another 20 years or more. Now scientists at the University of California, Los Angeles (UCLA), believe they may have uncovered a new clue as to why.

Sugary Drinks Linked To Genetic Risk Of Obesity

People who regularly consume sugary drinks are genetically more susceptible to becoming obese or overweight, researchers from the Harvard School of Public Health reported in NEJM (New England Journal of Medicine), September 21, 2012 issue.

................Or to put it another way; Sugary drinks only make certain people obese - those with a genetic disposition .    At the end of the day it's the sugar that makes them obese -not the genes ..........?

Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson's disease, including greater susceptibility of females.

Toll-like receptors 1-9 are elevated in livers with fructose-induced hepatic steatosis.

Studies in animals and human subjects indicate that gut-derived bacterial endotoxins may play a critical role in the development of non-alcoholic fatty liver disease (NAFLD). In the present study, we investigated if the liver is also sensitised by other microbial components during the onset of fructose-induced steatosis in a mouse model. C57BL/6 mice were either fed with 30 % fructose solution or tap water (control) with or without antibiotics for 8 weeks. Expression of toll-like receptors (TLR)1-9, TNF-α, inducible NO synthase (iNOS), myeloid differentiation factor 88 (MyD88) and number of F4/80 positive cells in the liver were assessed. Occludin protein, DNA of microbiota in the small and large intestine and retinol binding protein 4 (RBP4) in plasma were analysed using Western blot, DNA fingerprinting and ELISA, respectively. F4/80 positive cells were determined by immunohistochemistry. The accumulation of TAG found in the livers of fructose-fed mice was associated with a significant induction of TLR 1-4 and 6-8. Plasma RBP4 concentration and hepatic mRNA expression levels of TNF-α, iNOS, MyD88 and number of F4/80 positive cells of fructose-fed animals were significantly higher than those of controls; however, these effects of fructose were attenuated in antibiotic-treated mice. Whereas protein concentration of occludin was lower in the duodenum of fructose-treated mice, no systematic alterations of microbiota were found in this part of the intestine. Taken together, these data support the hypothesis that (1) an increased intestinal translocation of microbial components and (2) an increased number of F4/80 positive cells and induction of several TLR and dependent pathways (e.g. MyD88 and iNOS) may be involved in the onset of fructose-induced NAFLD.

Genome-wide Association Study of Periodontal Pathogen Colonization.

Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom "checkerboard" DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: "high red" and "high orange" bacterial complexes, and "high" Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10(-8)). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10(-6)) of association. All associations reported for "red" and "orange" complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease.

Prenatal activation of Toll-like receptors-3 by administration of the viral mimetic poly(I:C) changes synaptic proteins, N-methyl-D-aspartate receptors and neurogenesis markers in offspring.


There is mounting evidence for a neurodevelopmental basis for disorders such as autism and schizophrenia, in which prenatal or early postnatal events may influence brain development and predispose the young to develop these and related disorders. We have now investigated the effect of a prenatal immune challenge on brain development in the offspring. Pregnant rats were treated with the double-stranded RNA polyinosinic:polycytidylic acid (poly(I:C); 10mg/kg) which mimics immune activation occurring after activation of Toll-like receptors-3 (TLR3) by viral infection. Injections were made in late gestation (embryonic days E14, E16 and E18), after which parturition proceeded naturally and the young were allowed to develop up to the time of weaning at postnatal day 21 (P21). The brains of these animals were then removed to assess the expression of 13 different neurodevelopmental molecules by immunoblotting.

RESULTS:

Measurement of cytokine levels in the maternal blood 5 hours after an injection of poly(I:C) showed significantly increased levels of monocyte chemoattractant protein-1 (MCP-1), confirming immune activation. In the P21 offspring, significant changes were detected in the expression of GluN1 subunits of NMDA receptors, with no difference in GluN2A or GluN2B subunits or the postsynaptic density protein PSD-95 and no change in the levels of the related small GTPases RhoA or RhoB, or the NMDA receptor modulator EphA4. Among presynaptic molecules, a significant increase in Vesicle Associated Membrane Protein-1 (VAMP-1; synaptobrevin) was seen, with no change in synaptophysin or synaptotagmin. Proliferating Cell Nuclear Antigen (PCNA), as well as the neurogenesis marker doublecortin were unchanged, although Sox-2 levels were increased, suggesting possible changes in the rate of new cell differentiation.

CONCLUSIONS:

The results reveal the induction by prenatal poly(I:C) of selective molecular changes in the brains of P21 offspring, affecting primarily molecules associated with neuronal development and synaptic transmission. These changes may contribute to the behavioural abnormalities that have been reported in adult animals after exposure to poly(I:C) and which resemble symptoms seen in schizophrenia and related disorders.

Alzheimer's disease: preventative measures can delay onset

"We cannot prevent Alzheimer's, but we can delay the onset of the disease until an advanced age with the right measures," says Peter Dal-Bianco, Alzheimer's expert from the MedUni Vienna's University Department of Neurology as part of World Alzheimer's Day on 21st September. The right preventative measures make it possible to delay the onset of the condition. These include, for example, plenty of exercise, not smoking or the increased intake of fruit and vegetables.

Read more at: http://medicalxpress.com/news/2012-09-alzheimer-disease-onset.html#jCp

Too Much Tuna Can Cause Mercury Poisoning In Children

MNT: Children should be consuming considerably less canned tuna, otherwise their risk of serious mercury poisoning could become a public health issue in years to come, the Mercury Policy Project explained in a report issued yesterday.

The authors added that albacore tuna should never be given to children.

Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature.

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease.


Anti-interferon-gamma autoantibodies cause adult-onset immunodeficiency disease similar to patients with advanced HIV infection | The Virology Hub

Work by Browne, S. K. et al (2012) showed that anti–interferon (IFN)-gamma autoantibodies found in a group of Asian adults with disseminated nontuberculous mycobacterial infection, alone or with another opportunistic infection, had an adult-onset immunodeficiency disease similar in nature to that seen in patients with advanced HIV infection. The cause of the anti-interferon-gamma autoantibodies appeared unrelated to a singular genetic predisposition and the authors speculate that an environmental factor or opportunistic infection could be the trigger.

Cause of diabetes may be linked to iron transport

Scientists have been trying to explain the causes of diabetes for many years. Researchers at the University of Copenhagen and Novo Nordisk A/S have now shown that the increased activity of one particular iron-transport protein destroys insulin-producing beta cells. In addition, the new research shows that mice without this iron transporter are protected against developing diabetes.

A mother's nutrition—before pregnancy—may alter the function of her children's genes

Everyone knows that what mom eats when pregnant makes a huge difference in the health of her child. Now, new research in mice suggests that what she ate before pregnancy might be important too. According to a new research report published online in The FASEB Journal, what a group of female mice ate—before pregnancy—chemically altered their DNA and these changes were passed to her offspring. These DNA alterations, called "epigenetic" changes, drastically affected the pups' metabolism of many essential fatty acids. These results could have a profound impact on future research for diabetes, obesity, cancer, and immune disorders.

Read more at: http://medicalxpress.com/news/2012-09-mother-nutritionbefore-pregnancymay-function-children.html#jCp

PLOS Genetics: De Novo CNV Formation in Mouse Embryonic Stem Cells Occurs in the Absence of Xrcc4-Dependent Nonhomologous End Joining

Spontaneous copy number variant (CNV) mutations are an important factor in genomic structural variation, genomic disorders, and cancer. A major class of CNVs, termed nonrecurrent CNVs, is thought to arise by nonhomologous DNA repair mechanisms due to the presence of short microhomologies, blunt ends, or short insertions at junctions of normal and de novopathogenic CNVs, features recapitulated in experimental systems in which CNVs are induced by exogenous replication stress. To test whether the canonical nonhomologous end joining (NHEJ) pathway of double-strand break (DSB) repair is involved in the formation of this class of CNVs, chromosome integrity was monitored in NHEJ–deficient Xrcc4−/− mouse embryonic stem (ES) cells following treatment with low doses of aphidicolin, a DNA replicative polymerase inhibitor. Mouse ES cells exhibited replication stress-induced CNV formation in the same manner as human fibroblasts, including the existence of syntenic hotspot regions, such as in the Auts2 and Wwoxloci. The frequency and location of spontaneous and aphidicolin-induced CNV formation were not altered by loss of Xrcc4, as would be expected if canonical NHEJ were the predominant pathway of CNV formation. Moreover, de novo CNV junctions displayed a typical pattern of microhomology and blunt end use that did not change in the absence of Xrcc4. A number of complex CNVs were detected in both wild-type and Xrcc4−/− cells, including an example of a catastrophic, chromothripsis event. These results establish that nonrecurrent CNVs can be, and frequently are, formed by mechanisms other than Xrcc4-dependent NHEJ.

Human blood metabolite timetable indicates internal body time: PNAS

A convenient way to estimate internal body time (BT) is essential for chronotherapy and time-restricted feeding, both of which use body-time information to maximize potency and minimize toxicity during drug administration and feeding, respectively. Previously, we proposed a molecular timetable based on circadian-oscillating substances in multiple mouse organs or blood to estimate internal body time from samples taken at only a few time points. Here we applied this molecular-timetable concept to estimate and evaluate internal body time in humans. We constructed a 1.5-d reference timetable of oscillating metabolites in human blood samples with 2-h sampling frequency while simultaneously controlling for the confounding effects of activity level, light, temperature, sleep, and food intake. By using this metabolite timetable as a reference, we accurately determined internal body time within 3 h from just two anti-phase blood samples. Our minimally invasive, molecular-timetable method with human blood enables highly optimized and personalized medicine.

MS Relapses Reduced In Trials Of New Pill: MNT

Two studies of a new pill for multiple sclerosis (dimethyl fumarate ) suggest it may reduce relapses and disability progression in people with the more common, relapsing-remitting form of the neurological condition, which accounts for around 85% of cases.

Diseases of aging map to a few 'hotspots' on the human genome

The two major hotspots related to the MHC locus (autoimmune diseases such as arthritis, celiac disease, Type I diabetes, asthma, psoriasis, and lupus) and the INK4/ARF (or CDKN2a) tumor suppressor locus (aging: atherosclerosis, heart attacks, stroke, Type II diabetes, glaucoma and various cancers)

A Neuron-Specific Role for Autophagy in Antiviral Defense against Herpes Simplex Virus.

Type I interferons (IFNs) are considered to be the universal mechanism by which viral infections are controlled. However, many IFN-stimulated genes (ISGs) rely on antiviral pathways that are toxic to host cells, which may be detrimental in nonrenewable cell types, such as neurons. We show that dorsal root ganglionic (DRG) neurons produced little type I IFNs in response to infection with a neurotropic virus, herpes simplex type 1 (HSV-1). Further, type I IFN treatment failed to completely block HSV-1 replication or to induce IFN-primed cell death in neurons. We found that DRG neurons required autophagy to limit HSV-1 replication both in vivo and in vitro. In contrast, mucosal epithelial cells and other mitotic cells responded robustly to type I IFNs and did not require autophagy to control viral replication. These findings reveal a fundamental difference in the innate antiviral strategies employed by neurons and mitotic cells to control HSV-1 infection.

Allen Brain Atlas - The human brain whole genome transcriptome


An "all genes, all structures" gene expression survey in multiple adult control brains.
  • > 62,000 gene probes per profile
  • ~ 500 samples per hemisphere across cerebrum, cerebellum and brainstem
  • Data mapped with histology into unified 3-D anatomic framework based on MRI

Resveratrol inhibits epstein barr virus lytic cycle in burkitt's lymphoma cells by affecting multiple molecular targets.

Resveratrol (RV), a polyphenolic natural product present in many plants and fruits, exibits anti-inflammatory, cardio-protective and antiproliferative properties. Moreover, RV affects a wide variety of viruses including members of the Herpesviridae family, retroviruses, influenza A virus and polyomavirus by altering cellular pathways that affect viral replication itself. Epstein Barr Virus (EBV), the causative agent of infectious mononucleosis, is associated with different proliferative diseases in which it establishes a latent and/or a lytic infection. In this study, we examined the antiviral activity of RV against the EBV replicative cycle and investigated the molecular targets possibly involved. In a cellular context that allows in vitro EBV activation and lytic cycle progression through mechanisms closely resembling those that in vivo initiate and enable productive infection, we found that RV inhibited EBV lytic genes expression and the production of viral particles in a dose-dependent manner. We demonstrated that RV inhibited protein synthesis, decreased reactive oxygen species (ROS) levels, and suppressed the EBV-induced activation of the redox sensitive transcription factors NF-kB and AP1. Further insights into the signaling pathways and molecular targets modulated by RV may provide the basis for exploiting the antiviral activity of this natural product on EBV replication.

Prevention of Virus-Induced Type 1 Diabetes with Antibiotic Therapy.

Microbes were hypothesized to play a key role in the progression of type 1
diabetes (T1D). We used the LEW1.WR1 rat model of Kilham rat virus (KRV)-induced
T1D to test the hypothesis that the intestinal microbiota is involved in the
mechanism leading to islet destruction. Treating LEW1.WR1 rats with KRV and a
combination of trimethoprim and sulfamethoxazole (Sulfatrim) beginning on the day
of infection protected the rats from insulitis and T1D. Pyrosequencing of
bacterial 16S rRNA and quantitative RT-PCR indicated that KRV infection resulted
in a transient increase in the abundance of Bifidobacterium spp. and Clostridium
spp. in fecal samples from day 5- but not day 12-infected versus uninfected
animals. Similar alterations in the gut microbiome were observed in the jejunum
of infected animals on day 5. Treatment with Sulfatrim restored the level of
intestinal Bifidobacterium spp. and Clostridium spp. We also observed that virus
infection induced the expression of KRV transcripts and the rapid upregulation of
innate immune responses in Peyer's patches and pancreatic lymph nodes. However,
antibiotic therapy reduced the virus-induced inflammation as reflected by the
presence of lower amounts of proinflammatory molecules in both the Peyer's
patches and pancreatic lymph nodes. Finally, Sulfatrim treatment reduced the
number of B cells in Peyer's patches and downmodulated adaptive immune responses
to KRV, but did not interfere with antiviral Ab responses or viral clearance from
the spleen, pancreatic lymph nodes, and serum. The data suggest that gut
microbiota may be involved in promoting virus-induced T1D in the LEW1.WR1 rat
model.

Identical twins with Leucine rich repeat kinase type 2 mutations discordant for Parkinson's disease.

So what conditions the effects of LRKK2 ?????

Compartmentalized control of skin immunity by resident commensals.

Intestinal commensal bacteria induce protective and regulatory responses that maintain host-microbial mutualism. However, the contribution of tissue-resident commensals to immunity and inflammation at other barrier sites has not been addressed. We found that in mice, the skin microbiota have an autonomous role in controlling the local inflammatory milieu and tuning resident T lymphocyte function. Protective immunity to a cutaneous pathogen was found to be critically dependent on the skin microbiota but not the gut microbiota. Furthermore, skin commensals tuned the function of local T cells in a manner dependent on signaling downstream of the interleukin-1 receptor. These findings underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization, and provide insight into mechanisms of immune system regulation by resident commensal niches in health and disease.

New study finds chronic fatigue syndrome not linked to XMRV and pMLV viruses

The causes of chronic fatigue syndrome (CFS) have long eluded scientists. In 2009, a paper in the journal Science linked the syndrome—sometimes called myalgic encephalomyelitis (ME)—to infection with a mouse retrovirus called XMRV (xenotropic murine leukemia virus (MLV)-related virus). Given that affected patients often have symptoms consistent with a chronic infection, this viral connection seemed plausible, and the findings were celebrated as a major achievement for a complex disease that afflicts nearly 1 million in the U.S. Another study in early 2010 published in Proceedings of the National Academy of Sciences detected murine retrovirus-like sequences (designated pMLV: polytropic MLV) in CFS/ME patients, which provided further support for a viral theory.

Read more at: http://medicalxpress.com/news/2012-09-chronic-fatigue-syndrome-linked-xmrv.html#jCp

Oral bacteria may signal pancreatic cancer risk

A new study finds significant associations between antibodies for multiple oral bacteria and the risk of pancreatic cancer, adding support for the emerging idea that the ostensibly distant medical conditions are related.

Read more at: http://medicalxpress.com/news/2012-09-oral-bacteria-pancreatic-cancer.html#jCp

Association Between Urinary Bisphenol A Concentration and Obesity Prevalence in Children and AdolescentsUrinary Bisphenol A Levels and Childhood Obesity


Bisphenol A (BPA), a manufactured chemical, is found in canned food, polycarbonate-bottled liquids, and other consumer products. In adults, elevated urinary BPA concentrations are associated with obesity and incident coronary artery disease. BPA exposure is plausibly linked to childhood obesity, but evidence is lacking to date.
Objective  To examine associations between urinary BPA concentration and body mass outcomes in children.
Design, Setting, and Participants  Cross-sectional analysis of a nationally representative subsample of 2838 participants aged 6 through 19 years randomly selected for measurement of urinary BPA concentration in the 2003-2008 National Health and Nutrition Examination Surveys.
Main Outcome Measures  Body mass index (BMI), converted to sex- and age-standardized zscores and used to classify participants as overweight (BMI ≥85th percentile for age/sex) or obese (BMI ≥95th percentile).
Results  Median urinary BPA concentration was 2.8 ng/mL (interquartile range, 1.5-5.6). Of the participants, 1047 (34.1% [SE, 1.5%]) were overweight and 590 (17.8% [SE, 1.3%]) were obese. Controlling for race/ethnicity, age, caregiver education, poverty to income ratio, sex, serum cotinine level, caloric intake, television watching, and urinary creatinine level, children in the lowest urinary BPA quartile had a lower estimated prevalence of obesity (10.3% [95% CI, 7.5%-13.1%]) than those in quartiles 2 (20.1% [95% CI, 14.5%-25.6%]), 3 (19.0% [95% CI, 13.7%-24.2%]), and 4 (22.3% [95% CI, 16.6%-27.9%]). Similar patterns of association were found in multivariable analyses examining the association between quartiled urinary BPA concentration and BMI z score and in analyses that examined the logarithm of urinary BPA concentration and the prevalence of obesity. Obesity was not associated with exposure to other environmental phenols commonly used in other consumer products, such as sunscreens and soaps. In stratified analysis, significant associations between urinary BPA concentrations and obesity were found among whites (P < .001) but not among blacks or Hispanics.
Conclusions  Urinary BPA concentration was significantly associated with obesity in this cross-sectional study of children and adolescents. Explanations of the association cannot rule out the possibility that obese children ingest food with higher BPA content or have greater adipose stores of BPA.

Prenatal damage from dioxin shown to involve microRNAs

ScienceDaily (Sep. 17, 2012) — Research carried out at the University of South Carolina has identified novel mechanisms through which dioxin, a well-known environmental contaminant, can alter physiological functions, according to a study published online in the journal PLOS ONE.

Most extensive pictures ever of an organism's DNA mutation processes

Biologists and informaticists at Indiana University have produced one of the most extensive pictures ever of mutation processes in the DNA sequence of an organism, elucidating important new evolutionary information about the molecular nature of mutations and how fast those heritable changes occur.

Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study.


This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer's disease (AD).

METHODS:

In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus.

RESULTS:

Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I and II.

CONCLUSIONS:

Unexpectedly, the extent of innate immune gene upregulation in AD was modest relative to the robust response apparent in the aged brain, consistent with the emerging idea of a critical involvement of inflammation in the earliest stages, perhaps even in the preclinical stage, of AD. Ultimately, our data suggest that an important strategy to maintain cognitive health and resilience involves reducing chronic innate immune activation that should be initiated in late midlife.

The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol.

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). Epidemiological studies revealed that consumption of docosahexaenoic acid (DHA: 22 : 6 (ω3)), a major brain polyunsaturated fatty acid, is protective for AD and that elevated cholesterol levels are an AD risk factor. We presently investigated the extent to which the pathological effects of apoE4 in vivo can be prevented by consuming fish oil (DHA) or can be modified by cholesterol. Accordingly, apoE3- and apoE4-targeted replacement mice were subjected, following weaning, to a fish oil diet enriched in DHA and to a cholesterol-containing diet under regular and enriched environments. Cholesterol metabolism in the hippocampus and the corresponding phospholipid and fatty acid levels were affected by fish oil (DHA) and cholesterol diets and by environmental stimulation. Importantly, cholesterol metabolism and the fatty acid levels were not affected by apoE4. The phospholipid levels were, however, affected by apoE4. This effect was most pronounced in the cholesterol-fed mice and was abolished by the fish oil (DHA) diet. ApoE4 elevated hippocampal intraneuronal amyloid-β levels under regular conditions and lowered them following environmental stimulation, relative to those of the apoE3 mice. ApoE4 also elevated the levels of the presynaptic transporters Vglut and Vgat, and decreased behavioral performance in an object recognition test. Importantly, all of these apoE4 phenotypes were abolished by the fish oil (DHA) diet, whereas the cholesterol diet modified them. These findings suggest that a fish oil (DHA) diet could be used to attenuate the effects of apoE4 in AD.

Toxic protein build-up in blood shines light on Huntington's disease

A new light-based technique for measuring levels of the toxic protein that causes Huntington's disease (HD) has been used to demonstrate that the protein builds up gradually in blood cells. Published today in the Journal of Clinical Investigation, the findings shed light on how the protein causes damage in the brain, and could be useful for monitoring the progression of HD, or testing new drugs aimed at suppressing production of the harmful protein.

Read more at: http://medicalxpress.com/news/2012-09-toxic-protein-build-up-blood-huntington.html#jCp

Neglected Babies Develop Less Myelin | The Scientist

Isolating mouse pups from their mothers early in development can reduce the insulation surrounding neurons of the brain, which leads to problems with memory and socialization, a study in Science reported last week (September 14). The study provides a molecular explanation for the cognitive deficits observed in children raised in orphanages where they are rarely touched

PLOS Computational Biology: An Online Bioinformatics Curriculum

This reviews the many online bioinformatics courses available.

Elevated serum level of type-2 cytokines and low IL-17 in first episode psychosis and schizophrenia in relapse.

Schizophrenia is chronic and debilitating mental disorder. In broad spectrum of possible causes or contributing factors, immune system and cytokines were investigated in the onset and development of schizophrenia. The aim of our study was to analyze the serum concentrations of type-1 cytokines: TNF-α, IFN-γ, type-2 cytokines: IL-4, IL-10, type-17 cytokine: IL-17 and regulatory cytokines: TGF-β, IL-27, IL-6, in drug-naive patients with First Episode Psychosis - FEP (n = 88) and Schizophrenia in relapse - SC in relapse patients (n = 45), comparing to healthy controls (n = 36). Also, we attempted to determine potential correlation between cytokine levels and/or cytokine ratios with clinical parameters, such as severity of illness, positive, negative and general psychopathology. Our results showed decreased levels of IL-17 (p = 0.018), demonstrating that type-17 response is blunted in psychotic episode. Increased levels of IL-4 (p = 0.033) showed that type-2 response is overweight in psychotic episode. Also, levels of IL-4 in serum of SC in relapse patients were higher than controls (p < 0.0005) and patient with FEP (p = 0.003). This alteration was accompanied with increase in production of TGF-β in psychotic patients (p = 0.009) and also in FEP (p < 0.0005) and SC in relapse (p < 0.0005). Analysis showed that TGF-β can be a valuable marker for psychosis. The presence of enhanced anti-inflammatory/immunosuppressive activity in schizophrenia may be an attempt to counteract or limit ongoing pro-inflammatory processes and downregulating chronic inflammation. Finally we have documented decreased levels of IL-17 and IL-17/TGF-β ratio in these types of psychotic patients, suggesting the new aspects of schizophrenia pathophysiology.

Modulation of experimental herpes encephalitis-associated neurotoxicity through sulforaphane treatment. Schachtele SJ, Hu S, L

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection.

Towards a Predictive Model of Alzheimer's Disease Progression Using Capillary Electrophoresis-Mass Spectrometry Metabolomics.

Alzheimer´s disease (AD) is the most prevalent form of dementia with an estimated worldwide prevalence of over 30 million people, its incidence is expected to increase dramatically with an increasing elderly population. Up to date, cerebrospinal fluid (CSF) has been the preferred sample to investigate central nervous system (CNS) disorders since its composition is directly related to metabolite production in brain. In this work, a non-targeted metabolomic approach based on capillary electrophoresis-mass spectrometry (CE-MS) is developed to examine metabolic differences in CSF samples from subjects with different cognitive status related to AD progression. To do this, CSF samples from 85 subjects were obtained from patients with (i) subjective cognitive impairment (SCI, i.e. control group), (ii) mild cognitive impairment (MCI) which remained stable after a follow-up period of 2 years, (iii) MCI which progressed to AD within two-year time after the initial MCI diagnostic and, (iv) diagnosed AD. A prediction model for AD progression using multivariate statistical analysis based on CE-MS metabolomics of CSF samples was obtained using 73 CSF samples. Using our model, we were able to correctly classify 97-100% of the samples in the diagnostic groups. The prediction power was confirmed in a blind small test set of 12 CSF samples, reaching a 83% of diagnostic accuracy. The obtained predictive values were higher than those reported with classical CSF AD biomarkers (A42 and tau), but need to be confirmed in larger samples cohorts. Choline, dimethylarginine, arginine, valine, proline, serine, histidine, creatine, carnitine and suberylglycine were identified as possible disease progression biomarkers. Our results suggest that CE-MS metabolomics of CSF samples can be a useful tool to predict AD progression.

Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease.


Chronic inflammation in periodontal disease has been suggested as a potential risk factor in Alzheimer's disease (AD). The purpose of this study was to examine serum antibody levels to bacteria of periodontal disease in participants who eventually converted to AD compared with the antibody levels in control subjects.

METHODS:

Serum samples from 158 participants in the Biologically Resilient Adults in Neurological Studies research program at the University of Kentucky were analyzed for immunoglobulin G antibody levels to seven oral bacteria associated with periodontitis, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Treponema denticola, Fusobacterium nucleatum, Tannerella forsythia, and Prevotella intermedia. All 158 participants were cognitively intact at baseline venous blood draw. In all, 81 of the participants developed either mild cognitive impairment (MCI) or AD or both, and 77 controls remained cognitively intact in the years of follow-up. Antibody levels were compared between controls and subjects with AD at baseline draw and after conversion and controls and subjects with MCI at baseline draw and after conversion using the Wilcoxon rank-sum test. AD and MCI participants were not directly compared. Linear regression models were used to adjust for potential confounding.

RESULTS:

Antibody levels to F nucleatum and P intermedia were significantly increased (α = 0.05) at baseline serum draw in the patients with AD compared with controls. These results remained significant when controlling for baseline age, Mini-Mental State Examination score, and apolipoprotein epsilon 4 status.

CONCLUSIONS:

This study provides initial data that demonstrate elevated antibodies to periodontal disease bacteria in subjects years before cognitive impairment and suggests that periodontal disease could potentially contribute to the risk of AD onset/progression. Additional cohort studies profiling oral clinical presentation with systemic response and AD and prospective studies to evaluate any cause-and-effect association are warranted

PLOS ONE: Borna Disease Virus Infection Perturbs Energy Metabolites and Amino Acids in Cultured Human Oligodendroglia Cells

Borna disease virus is a neurotropic, non-cytolytic virus that has been widely employed in neuroscientific research. Previous studies have revealed that metabolic perturbations are associated with Borna disease viral infection. However, the pathophysiological mechanism underlying its mode of action remains unclear.

METHODOLOGY:

Human oligodendroglia cells infected with the human strain Borna disease virus Hu-H1 and non-infected matched control cells were cultured in vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based metabonomic approach was used to differentiate the metabonomic profiles of 28 independent intracellular samples from Borna disease virus-infected cells (n = 14) and matched control cells (n = 14). Partial least squares discriminant analysis was performed to demonstrate that the whole metabonomic patterns enabled discrimination between the two groups, and further statistical testing was applied to determine which individual metabolites displayed significant differences between the two groups.

FINDINGS:

Metabonomic profiling revealed perturbations in 23 metabolites, 19 of which were deemed individually significant: nine energy metabolites (α-glucose, acetate, choline, creatine, formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate) and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine, isoleucine, phenylalanine, threonine, tyrosine, valine). Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between the two groups.

CONCLUSION:

Borna disease viral infection perturbs the metabonomic profiles of several metabolites in human oligodendroglia cells cultured in vitro. The findings suggest that Borna disease virus manipulates the host cell's metabolic network to support viral replication and proliferation.


Persistent infection with neurotropic herpes viruses and cognitive impairment.

Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens.

RESULTS:

PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (β = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status.

CONCLUSIONS:

Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.

Diabetes drug could help fight Alzheimer's disease, study reveals

 A drug designed for diabetes sufferers could have the potential to treat neurodegenerative diseases like Alzheimer's, a study by scientists at the University of Ulster has revealed.

Study finds that natural killer T-cells in fat tissue guard against obesity

Invariant natural killer T-cells (iNKT) are a unique subset of immune cells that are known to influence inflammatory responses. Now, a scientific team led by researchers at Beth Israel Deaconess Medical Center (BIDMC) has found that iNKT cells play a protective role in guarding against obesity and the metabolic syndrome, a major consequence of obesity.

Read more at: http://medicalxpress.com/news/2012-09-natural-killer-t-cells-fat-tissue.html#jCp

Increased dietary fructose linked to elevated uric acid levels and lower liver energy stores

Obese patients with type 2 diabetes who consume higher amounts of fructose display reduced levels of liver adenosine triphosphate (ATP)—a compound involved in the energy transfer between cells. The findings, published in the September issue of Hepatology, a journal of the American Association for the Study of Liver Diseases, indicate that elevated uric acid levels (hyperuricemia) are associated with more severe hepatic ATP depletion in response to fructose intake.

Read more at: http://medicalxpress.com/news/2012-09-dietary-fructose-linked-elevated-uric.html#jCp

Methylphenidate Modifies the Motion of the Circadian Clock

People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light–dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light–dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.

Mycoplasma pneumonia seroposivity in Iranian... [J Pak Med Assoc. 2012] - PubMed - NCBI


Environmental factors, such as different infections, have proposed to be involved in the pathogenesis of multiple sclerosis (MS). This study aimed to the evaluate mycoplasma pneumonia seropositivity, as a common cause of community-acquired pneumonia in patients with relapsing-remitting multiple sclerosis (RRMS).

METHODOLOGY:

Using ELISA method, IgM and IgG antibodies to Mycoplasma pneumoniae were determined in 130 patients with relapsing-remittingmultiple sclerosis (85 Remitted and 45 Relapsed) and 50 sex- and age-matched controls. The groups were compared using Kruskal-Wallis test at the significant level of p < 0.05.

RESULTS:

The median [interquartile range] titer of IgG in remitted multiple sclerosis group was 65.3 [51.1-75.2] RU/ml versus 64 [52.6-71.4] RU/ml in relapsed group and 57.5 [29.2-74.3] RU/ml in control group (p = 0.442). There was not any significant difference between the groups base on median titer of IgM too (p = 0.446). The median [interquartile range] titer of Mycoplasma pneumoniae (MPn) IgG in women was 69.2 [56.4-77.4] RU/ml in remitted patients versus 63.85 [52.45-71.25] RU/ml in relapsed patients and 55.2 [29.17-72.75] RU/ml in controls (p = 0.022). Post hoc analysis demonstrated significant difference between remitted patients and controls (p = 0.002). There was not any significant difference between men in the groups (p = 0.7).

CONCLUSIONS:

Mycoplasma seroposivity in relapsing-remitting multiple sclerosis was not significantly different in various phases of activity of disease compare to controls; but in women, seroposivity of Mycoplasma antibodies were more than controls.