Hypothalamic stem cells control ageing speed partly through exosomal miRNAs : Nature : Nature Research

Hypothalamic stem cells control ageing speed partly through exosomal miRNAs : Nature : Nature Research: "It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs."



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Seattle-caught Salmon Found to Contain Drugs - Mad In America

 "From My Science Academy: In a recent study, up to 81 drugs and personal care products were detected in the flesh of salmon caught in Puget Sound. Some of the drugs and contaminates found include Paxil, Valium, Zoloft, Prozac, OxyContin and cocaine.

“Intriguingly, the researchers are not concerned about the effect the cocktail of drugs will have on the humans who eat the fish, but they are concerned about how the chemicals are affecting wildlife. Reportedly, Meador’s other recent work has shown that juvenile chinook salmon migrate through contaminated estuaries in Puget Sound and die at twice the rate of fish elsewhere.

That seems like cause for concern.Unfortunately, it not likely the contamination will let up. According to one study, 97,000 pounds of drugs and chemicals could be entering the Puget Sound each year.”"



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Persistent Herpesvirus Infections and Telomere Attrition Over 3 Years in the Whitehall II Cohort | The Journal of Infectious Diseases | Oxford Academic

Telomere
Telomere (Photo credit: Wikipedia)
 The determinants of telomere attrition, a potential marker of cellular aging, are not well understood. Persistent herpesvirus infections including cytomegalovirus (CMV) infection may be particularly important for telomere dynamics via mechanisms such as inflammation, oxidative stress, and their impact on peripheral blood lymphocyte composition. This study examined the association of 4 human herpesviruses (CMV, herpes simplex virus type 1, human herpesvirus type 6, and Epstein-Barr virus) with change in leukocyte telomere length (LTL) over 3 years in 400 healthy individuals (aged 53–76 years) from the Whitehall II cohort. CMV, herpes simplex virus type 1, and human herpesvirus 6 infection were independently associated with greater 3-year LTL attrition, with no association found for Epstein-Barr virus. The magnitudes of these associations were large, for example, the equivalent of almost 12 years of chronological age for those CMV seropositive. Seropositivity to more herpesviruses was additively associated with greater LTL attrition (3 herpesviruses vs none, β = −0.07 and P = .02; 4 infections vs none, β = −0.14 and P < .001). Higher immunoglobulin G antibody levels among those seropositive to CMV were also associated with shorter LTL at follow-up. These associations were robust to adjustment for age, sex, employment grade, body mass index, and smoking status. These results suggest that exposure to infectious agents should be an important consideration in future studies of telomere dynamics."



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Immune system may mount an attack in Parkinson’s disease | National Institutes of Health (NIH)

Immune system may mount an attack in Parkinson’s disease | National Institutes of Health (NIH): "A research team led by David Sulzer, Ph.D., professor of neurology at Columbia University in New York City and Alessandro Sette, Dr.Biol.Sci., professor of infectious diseases at the La Jolla Institute for Allergy and Immunology in California, examined the role of T cells in PD.

Drs. Sulzer and Sette, along with their colleagues, collected blood samples from 67 individuals with Parkinson’s disease and 36 healthy controls. Immune cells were extracted from the samples and mixed with portions of the alpha-synuclein protein, which accumulates in the brains of people with PD and can result in cell death.

They found that T cells from people with PD responded to the presence of alpha-synuclein to a much greater degree than those gathered from the control group.

In particular, two regions of alpha-synuclein evoked reactions from T cells: a section that often contains mutations linked with PD, and a portion undergoing a chemical change that can lead to accumulation of the protein in the brain.  "

Related articles:

Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein.




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Influenza infection triggers disease in a genetic model of experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we used an autoimmune-prone T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus to test the hypothesis that upper-respiratory viral infection can cause glial activation, promote immune cell trafficking to the CNS, and trigger disease. Specifically, we inoculated 2D2 mice with influenza A virus (Puerto Rico/8/34; PR8) and then monitored them for symptoms of inflammatory demyelination. Clinical and histological experimental autoimmune encephalomyelitis was observed in ∼29% of infected 2D2 mice. To further understand how peripheral infection could contribute to disease onset, we inoculated wild-type C57BL/6 mice and measured transcriptomic alterations occurring in the cerebellum and spinal cord and monitored immune cell surveillance of the CNS by flow cytometry. Infection caused temporal alterations in the transcriptome of both the cerebellum and spinal cord that was consistent with glial activation and increased T-cell, monocyte, and neutrophil trafficking to the brain at day 8 post infection. Finally, Cxcl5 expression was up-regulated in the brains of influenza-infected mice and was elevated in cerebrospinal fluid of MS patients during relapse compared with specimens acquired during remission. Collectively, these data identify a mechanism by which peripheral infection may exacerbate MS as well as other neurological diseases."



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Polymicrobial Infections In Brain Tissue From Alzheimer's Disease Patients.

Several studies have advanced the idea that the etiology of Alzheimer's disease (AD) could be microbial in origin. In the present study, we tested the possibility that polymicrobial infections exist in tissue from the entorhinal cortex/hippocampus region of patients with AD using immunohistochemistry (confocal laser scanning microscopy) and highly sensitive (nested) PCR. We found no evidence for expression of early (ICP0) or late (ICP5) proteins of herpes simplex virus type 1 (HSV-1) in brain sections. A polyclonal antibody against Borrelia detected structures that appeared not related to spirochetes, but rather to fungi. These structures were not found with a monoclonal antibody. Also, Borrelia DNA was undetectable by nested PCR in the ten patients analyzed. By contrast, two independent Chlamydophila antibodies revealed several structures that resembled fungal cells and hyphae, and prokaryotic cells, but most probably were unrelated to Chlamydophila spp. Finally, several structures that could belong to fungi or prokaryotes were detected using peptidoglycan and Clostridium antibodies, and PCR analysis revealed the presence of several bacteria in frozen brain tissue from AD patients. Thus, our results show that polymicrobial infections consisting of fungi and bacteria can be revealed in brain tissue from AD patients."



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Study on the Association among Mycotoxins and other Variables in Children with Autism.

 Environmental factors and genetic susceptibility are implicated in the increased risk of autism spectrum disorder (ASD). Mycotoxins are agricultural contaminants of fungal origin that represent real risk factors for human health and especially for children. Thus, the main hypothesis of this work is that the deterioration of the clinical manifestation of autism in children may result from the exposure to mycotoxins through the consumption of contaminated food. Within a cross-sectional study, a group of autistic children (n = 172) and a group of controls (n = 61) (siblings and non-parental) were recruited in North and South Italy. All children had blood and urine samples taken, for testing some mycotoxins by a LC-MS/MS validated method. Blood samples were also tested for assessing specific IgG against food and fungal antigens and cytokines. The analyses outputs highlighted statistically significant differences comparing mycotoxins levels between (i) children groups both in urine (deoxynivalenol and de-epoxydeoxynivalenol, p = 0.0141 and p = 0.0259, respectively) and serum (aflatoxin M1, ochratoxin A and fumonisin B1, p = 0.0072, p = 0.0141 and p = 0.0061, respectively); (ii) a group of selected fungal IgGs, and IgGs against wheat and gluten and (iii) cytokines. These results suggest the need for a deeper examination of the role that mycotoxins may have on the etiology of ASD."



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Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies

 BACKGROUND Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. 

METHODS We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.

 RESULTS From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference −0.37 kg/m2; 95% confidence interval [CI] −1.10 to 0.36; I2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.

 INTERPRETATION Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749"



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The association between total phthalate concentration and non-communicable diseases and chronic inflammation in South Australian urban dwelling men - ScienceDirect

 Objective
To investigate associations between urinary total phthalate concentration, chronic low-grade inflammation and non-communicable diseases in a cohort of South Australian men.
Methods
1504 men aged 39–84 years who provided a urinary sample at the follow-up visit of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study, a randomly-selected group of urban-dwelling, community-based men from Adelaide, Australia (n = 2038; study participation rate: 78.1%). Total phthalate concentration was quantified in fasting morning urine samples. Chronic diseases were assessed through self-report questionnaire or directly measured using standardised clinical and laboratory procedures. Inflammatory biomarkers were assayed by ELISA or spectroscopy. Multivariable linear and logistic regression models were applied to determine associations of log-transformed urinary phthalate concentration with inflammation and chronic disease.
Results
Total phthalates were detected in 99.6% of urinary samples; geometric mean (95% CI) was 114.1 (109.5–118.9) µg/g creatinine. Higher total phthalate levels were associated with higher levels of hs-CRP, IL-6 (all p < 0.05) and TNF-α but not MPO. Urinary total phthalate concentrations were positively associated with cardiovascular disease, type-2-diabetes and hypertension. Comparing extreme quartiles of total phthalate, prevalence ratios were 1.78 (95% CI 1.17 – 2.71, p-trend = 0.001) for cardiovascular disease and 1.84 (95%CI 1.34 – 2.51, p-trend = 0.001) for type-2-diabetes and 1.14 (95%CI 1.01 – 1.29, p-trend = 0.013) for hypertension. Total phthalates and asthma and depression were not significantly associated.
Conclusion
A positive association between total phthalates and cardiovascular disease, type-2-diabetes, hypertension and increased levels of chronic low-grade inflammatory biomarkers was observed in urban-dwelling Australian men."



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Characterization of Adipogenic Activity of House Dust Extracts and Semi-Volatile Indoor Contaminants in 3T3-L1 Cells - Environmental Science & Technology (ACS Publications)

  "Obesity and metabolic disorders are of great societal concern and generate significant human health care costs. Recently, attention has focused on the potential for environmental contaminants to act as metabolic disruptors. This study sought to evaluate the adipogenic activity of indoor house dust extracts and a suite of semivolatile organic chemicals (SVOCs) that are often ubiquitously detected in indoor environments. 3T3-L1 cells were exposed to extracts of indoor dust or individual SVOCs and assessed for triglyceride accumulation and preadipocyte proliferation. Ten of 11 house dust extracts exhibited significant triglyceride accumulation and/or proliferation at environmentally relevant levels (<20 μg of dust/well), and significant adipogenic activity was also exhibited by 28 of the SVOCs. Notably, pyraclostrobin, dibutyl phthalate, tert-butyl-phenyl diphenyl phosphate, and the isopropylated triaryl phosphates (ITPs) exhibited near maximal or supra-maximal triglyceride accumulation relative to the rosiglitazone-induced maximum. The adipogenic activity in house dust occurred at concentrations below EPA estimated child exposure levels, and raises concerns for human health impacts, particularly in children. Our results delineate a novel potential health threat and identify putative causative SVOCs that are likely contributing to this activity."



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Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

 "Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease."



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Hidden herpes virus may play key role in MS, other brain disorders -- ScienceDaily

 "The ubiquitous human herpesvirus 6 (HHV-6) may play a critical role in impeding the brain's ability to repair itself in diseases like multiple sclerosis. The findings, which appear in the journal Scientific Reports, may help explain the differences in severity in symptoms that many people with the disease experience.

"While latent HHV-6 -- which can be found in cells throughout the brain -- has been associated with demyelinating disorders like multiple sclerosis it has not been clear what role, if any, it plays in these diseases," said Margot Mayer-Proschel, Ph.D., an associate professor at the University of Rochester Medical Center Department of Biomedical Genetics and co-author of the study. "These findings show that, while in the process of hiding from the immune system, the virus produces a protein that has the potential to impair the normal ability of cells in the brain to repair damaged myelin.""



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Sugar intake during pregnancy is associated with allergy and allergic asthma in children

 "High maternal sugar intake during pregnancy may increase the risk of allergy and allergic asthma in the offspring, according to an early study led by Queen Mary University of London (QMUL) involving almost 9,000 mother-child pairs."



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Rat Brain-Connectome

 ChemNetDB is an open access constantly evolving neurochemical connectivity database obtained from the rat brain. By utilizing advanced neuroinformatics methods, we have integrated over 50 years of neuroanatomical and neurochemical research on rat brain into a consistent, brain-wide, multi-scale neurochemical cerebral connectome. This connectome differs from the previously suggested neuronal networks of rat brain in two major aspects:

it integrates information on transmitter systems and receptors on the network topology;
it is unbiased and hypothesis-free as the connectome was obtained by consistent and systematic procedures without a priori assumptions."



New study links antibiotic resistance to common household disinfectant triclosan

 "Scientists from the University of Birmingham and Norwich Research Park have discovered a link between a major mechanism of antibiotic resistance and resistance to the disinfectant triclosan which is commonly found in domestic products."



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Study finds link between upper GI infections and protein (synuclein) implicated in Parkinson’s disease

 "Acute and chronic infections in a person's upper gastrointestinal tract appear to be linked to Parkinson's disease, say scientists at Georgetown University Medical Center and their collaborators at the National Institutes of Health and other institutions.

Their study, published in the Journal of Innate Immunity, finds that alpha-Synuclein (αS), the protein implicated in Parkinson's disease and other forms of neurodegenerative diseases, is released when an infection occurs in the upper GI tract (the esophagus, stomach, and duodenum) inducing an immune response as part of the body's innate immune system. The researchers say that these findings suggest that frequent or chronic upper GI infections could overwhelm the body's capacity to clear αS, leading to disease."



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Banned chemicals pass through umbilical cord from mother to baby, research finds

 "Trace amounts of flame retardants, banned in the U.S. for more than a decade, are still being passed through umbilical cord blood from mothers to their babies, according to new Indiana University research. The chemicals are linked to health concerns including hormone disruption and low birth weight.
PBDEs, or polybrominated diphenyl ethers, were commonly used flame retardants in building materials, electronics and textiles until they were banned in 2004. The chemicals leach into the environment, where they persist and are found today in virtually every population worldwide."



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What's on your skin? Archaea, that's what: Study on human skin microbiome finds archaea abundance associated with age -- ScienceDaily

 "It turns out your skin is crawling with single-celled microorganisms -- and they're not just bacteria. A study by the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) and the Medical University of Graz has found that the skin microbiome also contains archaea, a type of extreme-loving microbe, and that the amount of it varies with age."



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Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival | eLife

 Myelin, made by oligodendrocytes, is essential for rapid information transfer in the central nervous system. Oligodendrocyte precursors (OPs) receive glutamatergic synaptic input from axons but how this affects their development is unclear. Murine OPs in white matter express AMPA receptor (AMPAR) subunits GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, which respectively reduced or abolished AMPAR-mediated input to OPs. In both double- and triple-knockouts OP proliferation and number were unchanged but ~25% fewer oligodendrocytes survived in the subcortical white matter during development. In triple knockouts, this shortfall persisted into adulthood. The oligodendrocyte deficit resulted in ~20% fewer myelin sheaths but the average length, number and thickness of myelin internodes made by individual oligodendrocytes appeared normal. Thus, AMPAR-mediated signalling from active axons stimulates myelin production in developing white matter by enhancing oligodendrocyte survival, without influencing myelin synthesis per se.



The effect of smallpox and BCG vaccination on the risk of HIV-1 infection in Guinea-Bissau and Denmark | Open Forum Infectious Diseases | Oxford Academic

Background:
The live smallpox and BCG vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, HIV-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and tested this hypothesis both in Guinea-Bissau and in Denmark.

Methods:
We conducted two studies, a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1,751 individuals, and a case-base study with a background population of 46,239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission is almost exclusively sexually transmitted, in Denmark we excluded intravenous drug users. Data was analysed using logistic regression.

Results:
BCG and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval (CI) 0.36-1.07) in Guinea-Bissau and 0.70 (95%CI 0.43-1.15) in Denmark. Combining results from both settings in a meta-analysis gave an aOR of 0.66 (95%CI 0.46-0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR of 0.27 (95%CI 0.10-0.75); women: 0.18 (95%CI 0.05-0.64), men: 0.52 (95%CI 0.12-2.33), sex-differential effect, p-value = 0.29).


Conclusions:
The studies from Guinea-Bissau and Denmark, two very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine."


Related:- Cowpox Helped Against Smallpox; Will the Goat Lentivirus (Caprine Arthritis Encephalitis Virus) Help Against HIV-1?

Vaccinia and other viruses with available vaccines show marked homology with the HIV-1 envelope glycoprotein: the prospect of using existing vaccines to stem the AIDS pandemic.