Viruses transfer the antiviral second messenger cGAMP between cells

 "Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development."



Prostate 'organoid' hints at how early BPA exposure may increase cancer risk


Metagenome-wide association study on oral microbiome uncovered markers for rheumatoid arthritis

"Metagenome-wide association studies (MGWAS) have proved to be a powerful approach to study gut microbiome for type 2 diabetes, colorectal cancer, etc. This is the first study on dental and saliva microbiomes. The researchers found that, Haemophilus sp. is depleted in rheumatoid arthritis (RA) patients at all three gut and oral sites and negatively correlates with RA auto-antibodies, while Lactobacillus salivarius is over-represented in RA patients at all three sites, especially in the very active cases.
Functional convergence was also observed—the RA gut and oral microbiomes show abnormalities in the redox environment, iron, sulfur, zinc and arginine transport and metabolism, and possible molecular mimicry to RA-related human antigens."



Scientists show a link between intestinal bacteria and depression

In this study, researchers subjected mice to early life stress with a procedure of maternal separation, meaning that from day three to 21, newborn mice were separated for three hours each day from their mothers and then put back with them.
First, Bercik and his team confirmed that conventional mice with complex microbiota, which had been maternally separated, displayed anxiety and depression-like behaviour, with abnormal levels of the stress hormone corticosterone. These mice also showed gut dysfunction based on the release of a major neurotransmitter, acetylcholine.
Then, they repeated the same experiment in germ-free conditions and found that in the absence of bacteria mice which were maternally separated still have altered stress hormone levels and gut dysfunction, but they behaved similar to the , not showing any signs of anxiety or depression.

Comprehensive serological profiling of human populations using a synthetic human virome

Introduction The collection of viruses found to infect humans can have profound effects on human health. In addition to directly causing acute or chronic illness, viral infection can alter host immunity in more subtle ways, leaving an indelible footprint on the immune system. This interplay between virome and host immunity has been implicated in the pathogenesis of complex diseases such as type 1 diabetes, inflammatory bowel disease, and asthma. Despite the growing appreciation for the importance of interactions between the virome and host, a comprehensive method to systematically characterize these interactions has yet to be developed.
Rationale Current serological methods to detect viral infections are predominantly limited to testing one pathogen at a time and are therefore used primarily to address specific clinical hypotheses. A method that could simultaneously detect responses to all human viruses would allow hypothesis-free analysis to detect associations between past viral infections and particular diseases or population structures. Humoral responses to infection typically arise within 10 to 14 days of initial exposure and can persist over years or decades, thus providing a rich source of the history of pathogen encounters. In this work, we present VirScan, a high-throughput method that allows comprehensive analysis of antiviral antibodies in human sera. VirScan uses DNA microarray synthesis and bacteriophage display to create a uniform, synthetic representation of peptide epitopes comprising the human virome. Immunoprecipitation and high-throughput DNA sequencing reveal the peptides recognized by antibodies in the sample. The analysis requires less than 1 μl of blood. Results We screened sera from 569 human donors across four continents, assaying a total of over 108 antibody-peptide interactions for reactivity to 206 human viral species and >1000 strains. We found that VirScan’s performance in detecting known infections and distinguishing between exposures to related viruses is comparable to that of classical serum antibody tests for single viruses. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Our approach maps antibody targets at 56–amino acid resolution, and our results nearly double the number of previously established viral B cell epitopes. Although rates of specific virus exposure varied depending on age, HIV status, and geographic location of the donor, we observed strong similarities in antibody responses across individuals. In particular, we found multiple instances of single peptides that were recurrently recognized by antibodies in the vast majority of donors. We performed tiling mutagenesis and found that these antibody responses targeted substantially conserved “public epitopes” for each virus, suggesting that antibodies with highly similar specificities, and possibly structures, are elicited across individuals.
Conclusion VirScan is a method that enables human virome-wide exploration, at the epitope level, of immune responses in large numbers of individuals. We have demonstrated its effectiveness for determining viral exposure and characterizing viral B cell epitopes in high throughput and at high resolution. Our preliminary studies have revealed intriguing general properties of the human immune system, both at the individual and the population scale. VirScan may prove to be an important tool for uncovering the effect of host-virome interactions on human health and disease and could easily be expanded to include new viruses as they are discovered, as well as other human pathogens, such as bacteria, fungi, and protozoa.

Helicobacter pylori infection as a protective factor against multiple sclerosis risk in females.

In recent years, a relationship between Helicobacter pylori and many disease conditions has been reported, however, studies in its relationship with multiple sclerosis (MS) have had contradictory results.

OBJECTIVE:

To determine the association between the H. pylori infection and MS.

METHODS:

550 patients with MS were included in the study and were matched by gender and year of birth to 299 controls. Patients were assessed for clinical and demographic parameters. An enzyme immunoassay was used to detect the presence of specific IgG antibodies against H. pylori in the serum sample of both groups.

RESULTS:

H. pylori seropositivity was found to be lower in the patients with MS than in controls (16% vs 21%) with the decrease pertaining to females (14% vs 22%, p=0.027) but not males (19% vs 20%, p=1.0). When adjusted for age at onset, year of birth and disease duration, H. pylori seropositive females presented with a lower disability score than seronegative females (p=0.049), while among males the reverse was true (p=0.025). There was no significant association between H. pylori seropositivity and relapse rate.

CONCLUSIONS:

Our results could reflect a protective role of H. pylori in the disease development. However, it may be that H. pylori infection is a surrogate marker for the 'hygiene hypothesis', a theory which postulates that early life infections are essential to prime the immune system and thus prevent allergic and autoimmune conditions later in life. The fact that the association between H. pylori seropositivity and MS risk was seen almost exclusively in females requires further investigation.

Atlas of Cancer Signalling Networks -- Institut Curie

Iron-containing inflammatory cells seen in Alzheimer's brains -- ScienceDaily

Examining post-mortem tissue from the brains of people with Alzheimer's disease, Stanford University School of Medicine investigators identified what appear to be iron-containing microglia -- specialized scavenger cells that sometimes become inflammatory -- in a particular part of the hippocampus, a key brain structure whose integrity is critical to memory formation.
The bulk of microglia found in association with iron in the study were in an activated, inflammatory state. Alzheimer's is increasingly understood to involve brain inflammation, and groups led by Stanford researchers such as neurologists Katrin Andreasson, MD, and Tony Wyss-Coray, PhD, and neurobiologist Ben Barres, MD, PhD, have previously fingered microglia as potential suspects in the early inflammatory pathology of the disease. This study adds the new finding that inflamed, iron-associated microglia are present in the hippocampus in Alzheimer's and are observable by 7T MRI, which could advance the scientific community's understanding of the disease.

Study finds autism, ADHD run high in children of chemically intolerant mothers


Cerebrospinal Fluid from Alzheimer’s Disease Patients Contains Fungal Proteins and DNA - IOS Press

The identification of biomarkers for Alzheimer’s disease is important for patient management and to assess the effectiveness of clinical intervention. Cerebrospinal fluid (CSF) biomarkers constitute a powerful tool for diagnosis and monitoring disease progression. We have analyzed the presence of fungal proteins and DNA in CSF from AD patients. Our findings reveal that fungal proteins can be detected in CSF with different anti-fungal antibodies using a slot-blot assay. Additionally, amplification of fungal DNA by PCR followed by sequencing distinguished several fungal species. The possibility that these fungal macromolecules could represent AD biomarkers is discussed.

Occupational exposures and Parkinson's disease mortality in a prospective Dutch cohort. - PubMed - NCBI

We investigated the association between six occupational exposures (ie, pesticides, solvents, metals, diesel motor emissions (DME), extremely low frequency magnetic fields (ELF-MF) and electric shocks) and Parkinson's disease (PD) mortality in a large population-based prospective cohort study.

METHODS:

The Netherlands Cohort Study on diet and cancer enrolled 58,279 men and 62,573 women aged 55-69 years in 1986. Participants were followed up for cause-specific mortality over 17.3 years, until December 2003, resulting in 402 male and 207 female PD deaths. Following a case-cohort design, a subcohort of 5,000 participants was randomly sampled from the complete cohort. Information on occupational history and potential confounders was collected at baseline. Job-exposure matrices were applied to assign occupational exposures. Associations with PD mortality were evaluated using Cox regression.

RESULTS:

Among men, elevated HRs were observed for exposure to pesticides (eg, ever high exposed, HR 1.27, 95% CI 0.86 to 1.88) and ever high exposed to ELF-MF (HR 1.54, 95% CI 1.00 to 2.36). No association with exposure duration or trend in cumulative exposure was observed for any of the occupational exposures. Results among women were unstable due to small numbers of high-exposed women.

CONCLUSIONS:

Associations with PD mortality were observed for occupational exposure to pesticides and ELF-MF. However, the weight given to these findings is limited by the absence of a monotonic trend with either duration or cumulative exposure. No associations were found between PD mortality and occupational exposure to solvents, metals, DME or electric shocks.

Colonic bacterial composition in Parkinson's disease. - PubMed - NCBI

INTRODUCTION:

We showed that Parkinson's disease (PD) patients have alpha-synuclein (α-Syn) aggregation in their colon with evidence of colonic inflammation. If PD patients have altered colonic microbiota, dysbiosis might be the mechanism of neuroinflammation that leads to α-Syn misfolding and PD pathology.

METHODS:

Sixty-six sigmoid mucosal biopsies and 65 fecal samples were collected from 38 PD patients and 34 healthy controls. Mucosal-associated and feces microbiota compositions were characterized using high-throughput ribosomal RNA gene amplicon sequencing. Data were correlated with clinical measures of PD, and a predictive assessment of microbial community functional potential was used to identify microbial functions.

RESULTS:

The mucosal and fecal microbial community of PD patients was significantly different than control subjects, with the fecal samples showing more marked differences than the sigmoid mucosa. At the taxonomic level of genus, putative, "anti-inflammatory" butyrate-producing bacteria from the genera Blautia, Coprococcus, and Roseburia were significantly more abundant in feces of controls than PD patients. Bacteria from the genus Faecalibacterium were significantly more abundant in the mucosa of controls than PD. Putative, "proinflammatory" Proteobacteria of the genus Ralstonia were significantly more abundant in mucosa of PD than controls. Predictive metagenomics indicated that a large number of genes involved in metabolism were significantly lower in the PD fecal microbiome, whereas genes involved in lipopolysaccharide biosynthesis and type III bacterial secretion systems were significantly higher in PD patients.

CONCLUSION:

This report provides evidence that proinflammatory dysbiosis is present in PD patients and could trigger inflammation-induced misfolding of α-Syn and development of PD pathology. © 2015 International Parkinson and Movement Disorder Society.



Maternal Mild Thyroid Hormone Insufficiency in Early Pregnancy and Attention-Deficit/Hyperactivity Disorder Symptoms in Children. - PubMed - NCBI

Maternal thyroid hormone insufficiency during pregnancy can affect children's cognitive development. Nevertheless, the behavioral outcomes of children exposed prenatally to mild thyroid hormone insufficiency are understudied.

OBJECTIVE:

To examine whether exposure to maternal mild thyroid hormone insufficiency in early pregnancy was related to symptoms of attention-deficit/hyperactivity disorder (ADHD) in children at 8 years of age.

DESIGN, SETTING, AND PARTICIPANTS:

The study was embedded within the Generation R, a population-based birth cohort in the Netherlands. Children in the Generation R Study are followed up from birth (April 1, 2002, through January 31, 2006) until young adulthood. Of the 4997 eligible mother-child pairs with data on maternal thyroid levels (excluding twins), 3873 pairs of children and caregivers (77.5%) visited the Generation R research center for in-depth assessments and were included in the main analyses. Data collection in Generation R started December 1, 2001 (enrollment of pregnant women), and is ongoing. For this study, we used the data that were collected until January 1, 2014. Data analyses started on January 31 and finished June 30, 2014.

MAIN OUTCOMES AND MEASURES:

Maternal hypothyroxinemia, characterized by low levels of free thyroxine coexisting with reference thyrotropin levels, and children's symptoms of ADHD. Maternal thyroid hormone levels (thyrotropin, free thyroxine, thyroid peroxidase antibodies) were measured at a mean (SD) of 13.6 (1.9) weeks of gestation. Children's ADHD symptoms were assessed at 8 years of age using the Conners' Parent Rating Scale-Revised Short Form; higher scores indicate more ADHD symptoms (possible range, 0-36).

RESULTS:

Maternal hypothyroxinemia (n = 127) in early pregnancy was associated with higher scores for ADHD symptoms in children at 8 years of age after adjustments for child and maternal factors (ie, sex, ethnicity, maternal age, maternal educational level, and income) (increase in ADHD scores, 7% [95% CI, 0.3%-15%]). The results remained essentially unchanged when women with elevated levels of thyroid peroxidase antibodies were excluded from the analyses (increase in ADHD scores, 8% [95% CI, 1%-16%]). Additional adjustment for children's IQ or comorbid autistic symptoms attenuated the association (increase in ADHD scores adjusted for autistic symptoms, 7% [95% CI, 1%-15%]; increase in ADHD scores adjusted for IQ, 6% [95% CI, 1%-14%]).

CONCLUSIONS AND RELEVANCE:

Children exposed to maternal hypothyroxinemia in early pregnancy had more ADHD symptoms, independent of confounders. This finding suggests that intrauterine exposure to insufficient thyroid hormone levels influences neurodevelopment in offspring.

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host’s ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat."



'via Blog this'

Latent virus and life expectancy: Virus shortens telomeres - Medical News Today

The telomeres are repetitive DNA sequences at each end of our chromosomes. Studies show that in every cell division, the telomere is shortened. As a result, the telomere limits the cell to a fixed number of divisions and a limited life span. An essential part of human cells they affect how our cells age - as people with longer telomeres live longer lives. Surprisingly, people who are infected with a latent virus, that is, an asymptomatic virus, have shorter telomeres. This is an important observation and a great mystery. Is the virus causing the telomere shortening, and how? And if this is the case, what does it mean in terms of the relationship between the latent viruses and longevity?
Now, an article "The Latent Cytomegalovirus Decreases Telomere Length By Microcompetition" by Hanan Polansky and Adrian Javaherian, published in Open Medicine by De Gruyter Open, provides some answers to these questions. As it turns out, a certain gene, called telomere repeat binding factor 2 (Terf2), belongs to a complex of six telomere-associated proteins, termed shelterin. The protein produced by this gene protects the chromosome ends of the DNA from damage, and controls telomere maintenance by the telomerase enzyme. When does a cell produce the Terf2 protein? After receiving a signal that tells a transcription factor called GABP to bind the Terf2 gene. One can think of GABP as a finger that pushes the "ON" button on the Terf2 gene. Now consider a case where a latent virus called CMV infects the cell. As it turns out, the CMV virus also uses the GABP transcription factor to press the "ON" button on its own genes. When the CMV virus steals the GABP "fingers" from the Terf2 gene, there are no fingers left to press the "ON" button on the Terf2 gene, and the Terf2 gene fails to produce the Terf2 protein. What is the result of a shortage of Terf2 proteins? Short telomeres. In his book "Microcompetition with Foreign DNA and the Origin of Chronic Disease", Dr. Polansky used the term Microcompetition to describe this event.

Can autism be measured in a sniff?

Imagine the way you might smell a rose. You'd take a nice big sniff to breathe in the sweet but subtle floral scent. Upon walking into a public restroom, you'd likely do just the opposite—abruptly limiting the flow of air through your nose. Now, researchers reporting in the Cell Press journal Current Biology on July 2 have found that people with autism spectrum disorder (ASD) don't make this natural adjustment like other people do. Autistic children go right on sniffing in the same way, no matter how pleasant or awful the scent.

Here's the paper:-

Mechanistic Link between Olfaction and Autism Spectrum Disorder

Stealth Adapted Viruses – Possible Drivers of Major Neuropsychiatric Illnesses Including Alzheimer’s Disease

Mainstream neurologists and psychiatrists have largely refrained from serious
consideration of a virus cause of common brain diseases. This is mainly because
of the general lack of any accompanying immune system stimulated inflammatory reaction within the brain. This article exposes a weakness in this argument by describing the process of “stealth adaptation” of viruses. Deletion or mutation of relatively few virus components can result in derivative viruses, which are no longer effectively recognized by the cellular immune system. Consequently, there is no triggering of the inflammatory response. Furthermore, the brain is uniquely susceptible to symptomatic illness caused by stealth adapted viruses.
An understanding of stealth adaptation greatly expands the potential scope of
viral illnesses. It also underscores the value of using virus cultures as a diagnostic tool and of taking appropriate measures to avoid transmission of infection. More
importantly, therapeutic measures are available for suppressing both stealth
adapted and conventional virus infections through enhancement of the alternative
cellular energy (ACE) pathway. Such measures are available for clinical evaluation in treating many of the major illnesses affecting the brain, including Alzheimer’s
disease.

Immune response to a flu protein yields new insights into narcolepsy

An international team of researchers has found some of the first solid
evidence that narcolepsy may be a so-called "hit-and-run" autoimmune
disease.

The authors propose a hit-and-run autoimmune mechanism for how both
swine flu and the vaccine Pandemrix might cause narcolepsy. They suggest that in
genetically predisposed people, high levels of the H1N1 protein
stimulate the production of large amounts of antibodies to both the
virus (or vaccine) and the hypocretin receptor. These antibodies may persist in the
blood for months. Either the large numbers of antibodies or inflammation
from an unrelated infection could alter the blood-brain barrier,
allowing the antibodies to enter the brain. There, the antibodies may
latch onto hypocretin receptors, possibly directing the immune system to
destroy or suppress brain cells critical to regulating sleep-wake
cycles.

Omega-3 supplements, antioxidants may help with preclinical Alzheimer's disease: Clinical trials of omega-3, antioxidant supplementation should be undertaken for people with Alzheimer's disease with mild clinical impairment -- ScienceDaily

Here's more evidence that fish oil supplementation and antioxidants might be beneficial for at least some people facing Alzheimer's disease: A new report published in the July 2015 issue of The FASEB Journal describes the findings of a very small study in which people with mild clinical impairment, such as those in the very early stages of the disease, saw clearance of the hallmark amyloid-beta protein and reduced inflammation in neurological tissues. Although the findings involved just 12 patients over the course of 4 to 17 months, the findings suggest further clinical study of this relatively inexpensive and plentiful supplement should be conducted.