How bacteria behind serious childhood disease evolve to evade vaccines
Genetics has provided surprising insights into why vaccines used in both the UK and US to combat serious childhood infections can eventually fail. The study, recently published in Nature Genetics, which investigates how bacteria change their disguise to evade the vaccines, has implications for how future vaccines can be made more effective.
A glass of milk a day could benefit your brain
Pouring at least one glass of milk each day could not only boost your intake of much-needed key nutrients, but it could also positively impact your brain and mental performance, according to a recent study in the International Dairy Journal. Researchers found that adults with higher intakes of milk and milk products scored significantly higher on memory and other brain function tests than those who drank little to no milk. Milk drinkers were five times less likely to "fail" the test, compared to non milk drinkers.
A Large-Scale Twin Study Aims to Elucidate Common Disease | Genome Technology | Sequencing | GenomeWeb
A large-scale epigenetic study of common diseases in twins, particularly those discordant for a disease, may provide new targets for therapy.
"Identical twins and epigenetics are the ideal partners because we know there's both genetic effects and environmental effects," says Timothy Spector of King's College London. "In non-twin populations, you'd have to do studies that were perhaps 10 to 20 times as large to find the same results."
"Identical twins and epigenetics are the ideal partners because we know there's both genetic effects and environmental effects," says Timothy Spector of King's College London. "In non-twin populations, you'd have to do studies that were perhaps 10 to 20 times as large to find the same results."
Genetic regulation of metabolomic biomarkers: Paths to cardiovascular diseases and type 2 diabetes
In a study to the genetic variance of human metabolism, researchers have identified thirty one regions of the genome that were associated with levels of circulating metabolites, i.e., small molecules that take part in various chemical reactions of human body. Many of the studied metabolites are biomarkers for cardiovascular disease or related disorders, thus the loci uncovered may provide valuable insight into the biological processes leading to common diseases.
Body clock receptor linked to diabetes in new genetic study
A study recently published in Nature Genetics has found new evidence for a link between the body clock hormone melatonin and type 2 diabetes. The study found that people who carry rare genetic mutations in the receptor for melatonin have a much higher risk of type 2 diabetes.
Immuno-microbiota cross and talk: The new paradigm of metabolic diseases.
Over the last decades the rising occurrence of metabolic diseases throughout the world points to the failure of preventive and therapeutic strategies and of the corresponding molecular and physiological concepts. Therefore, a new paradigm needs to be elucidated. Very recently the intimate cross talk of the intestinal microbiota with the host immune system has opened new avenues. The large diversity of the intestinal microbes' genome, i.e. the metagenome, and the extreme plasticity of the immune system provide a unique balance which, when finely tuned, maintains a steady homeostasis. The discovery that a new microbiota repertoire is one of the causes responsible for the onset of metabolic disease suggests that the relationship with the immune system is impaired. Therefore, we here review the recent arguments that support the view that an alteration in the microbiota to host immune system balance leads to an increased translocation of bacterial antigens towards metabolically active tissues, and could result in a chronic inflammatory state and consequently impaired metabolic functions such as insulin resistance, hepatic fat deposition, insulin unresponsiveness, and excessive adipose tissue development. This imbalance could be at the onset of metabolic diseas, and therefore the early treatment of the microbiota dysbiosis or immunomodulatory strategies should prevent and slow down the epidemic of metabolic diseases and hence the corresponding lethal cardiovascular consequences.
Microbiota in autoimmunity and tolerance.
The composition of a host's intestinal microbiota directs the type of mucosal and systemic immune responses by affecting the proportion and number of functionally distinct T cell subsets. In particular, the microbiota composition affects the differentiation of intestinal Th17 cells and Foxp3(+) regulatory T cells, both of which play critical roles in maintaining mucosal barrier functions and in controlling immunological homeostasis. In this review, we discuss the recent advances in our understanding of how the intestinal microbiota affects T cell differentiation and host susceptibility to autoimmune disease.
Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active Multiple Sclerosis.
Multiple Sclerosis (MS) is considered to be an autoimmune disease with unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS.Human Endogenous Retroviruses (HERVs) constitute 5-8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. The HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS.The authors studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in PBMCs from healthy controls and from MS patients with non-active or active disease. There was a significant increase in HERV-H/F Gag expression in CD4+ (P<0.001***) and CD8+ T lymphocytes (P<0.001***), and in monocytes (P=0.0356*) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute Q-PCR evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We have found a 4 fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS as compared with healthy controls (P<0.001***). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expressions will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.
Antiviral CD8(+) T cells cause an experimental autoimmune encephalomyelitis-like disease in naive mice.
Major histocompatibility complex class I-restricted CD8(+) cytotoxic T lymphocytes are involved in the pathogenesis of multiple sclerosis (MS) and both autoimmune, experimental autoimmune encephalomyelitis, and viral, Theiler's murine encephalomyelitis virus (TMEV) infection, animal models of MS. Following TMEV infection, certain T cell hybridomas, generated from cloned TMEV-induced CD8(+) T cells, were able to produce clinical signs of disease (flaccid hind limb paralysis) upon adoptive transfer into naive mice. Dual T cell receptors (TCR) are present on the surface of these cells as both Vβ3 and Vβ6 were detected by polymerase chain reaction (PCR) screening and flow cytometry and multiple Vα mRNAs were detected by PCR screening. This is the first demonstration of antiviral CD8(+) T cells having more than one TCR initiating an autoimmune disease in the natural host of the virus. We hypothesize that this is a potential mechanism for virus-induced autoimmune disease initiated by CD8(+) T cells.
Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress
Chronic fatigue syndrome (CFS) is a complex illness, which is often
misdiagnosed as a psychiatric illness. In two previous reports, using
(1) H MRSI, we found significantly higher levels of ventricular
cerebrospinal fluid (CSF) lactate in patients with CFS relative to those
with generalized anxiety disorder and healthy volunteers (HV), but not
relative to those with major depressive disorder (MDD). In this third
independent cross-sectional neuroimaging study, we investigated a
pathophysiological model which postulated that elevations of CSF lactate
in patients with CFS might be caused by increased oxidative stress,
cerebral hypoperfusion and/or secondary mitochondrial dysfunction.
Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the
following modalities: (i) (1) H MRSI to measure CSF lactate; (ii)
single-voxel (1) H MRS to measure levels of cortical glutathione (GSH)
as a marker of antioxidant capacity; (iii) arterial spin labeling (ASL)
MRI to measure regional cerebral blood flow (rCBF); and (iv) (31) P MRSI
to measure brain high-energy phosphates as objective indices of
mitochondrial dysfunction. We found elevated ventricular lactate and
decreased GSH in patients with CFS and MDD relative to HVs. GSH did not
differ significantly between the two patient groups. In addition, we
found lower rCBF in the left anterior cingulate cortex and the right
lingual gyrus in patients with CFS relative to HVs, but rCBF did not
differ between those with CFS and MDD. We found no differences between
the three groups in terms of any high-energy phosphate metabolites. In
exploratory correlation analyses, we found that levels of ventricular
lactate and cortical GSH were inversely correlated, and significantly
associated with several key indices of physical health and disability.
Collectively, the results of this third independent study support a
pathophysiological model of CFS in which increased oxidative stress may
play a key role in CFS etiopathophysiology. Copyright © 2012 John Wiley
& Sons, Ltd.
PLoS Pathogens: The Circadian Clock Protein Timeless Regulates Phagocytosis of Bacteria in Drosophila
Survival of bacterial infection is the result of complex host-pathogen
interactions. An often-overlooked aspect of these interactions is the
circadian state of the host. Previously, we demonstrated that Drosophila mutants lacking the circadian regulatory proteins Timeless (Tim) and Period (Per) are sensitive to infection by S. pneumoniae.
Sensitivity to infection can be mediated either by changes in
resistance (control of microbial load) or tolerance (endurance of the
pathogenic effects of infection). Here we show that Tim regulates
resistance against both S. pneumoniae and S. marcescens. We set out to characterize and identify the underlying mechanism of resistance that is circadian-regulated. Using S. pneumoniae, we found that resistance oscillates daily in adult wild-type flies and that these oscillations are absent in Tim mutants. Drosophila
have at least three main resistance mechanisms to kill high levels of
bacteria in their hemolymph: melanization, antimicrobial peptides, and
phagocytosis. We found that melanization is not circadian-regulated. We
further found that basal levels of AMP gene expression exhibit
time-of-day oscillations but that these are Tim-independent; moreover,
infection-induced AMP gene expression is not circadian-regulated. We
then show that phagocytosis is circadian-regulated. Wild-type flies
exhibit up-regulated phagocytic activity at night; Tim mutants
have normal phagocytic activity during the day but lack this night-time
peak. Tim appears to regulate an upstream event in phagocytosis, such as
bacterial recognition or activation of phagocytic hemocytes.
Interestingly, inhibition of phagocytosis in wild type flies results in
survival kinetics similar to Tim mutants after infection with S. pneumoniae.
Taken together, these results suggest that loss of circadian
oscillation of a specific immune function (phagocytosis) can have
significant effects on long-term survival of infection.
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination.
Commensal gut flora-in the absence of pathogenic agents-is essential in
triggering immune processes, leading to a relapsing-remitting
autoimmune disease driven by myelin-specific CD4(+) T cells.
MicrobeWorld - Viruses con bacteria into working for them
These viruses are carrying genetic material taken from their previous
bacterial hosts that tricks the new host into using its own machinery to
activate the genes:
IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways in inflammatory and neuroprogressive pathology
Depression is characterized by IgM-related autoimmune responses directed
against a) neoepitopes that are normally not detected by the immune
system but that due to damage by oxidative and nitrosative stress have become immunogenic; and
b) anchorage epitopes, i.e. palmitic and myristic acids, and
S-farnesyl-L-cysteine. These autoimmune responses play a role in the
inflammatory and oxidative and nitrosative stress pathophysiology of depression and may mediate
the cellular dysfunctions that contribute to neuroprogression, e.g.
aberrations in signal transduction, cellular differentiation and
apoptosis.
Measles IgG antibody index correlates with t2 lesion load on MRI in patients with early multiple sclerosis.
B cells and humoral immune responses play an important role in the
pathogenesis and diagnosis of multiple sclerosis (MS). A characteristic
finding in patients with MS is a polyspecific intrathecal B cell
response against neurotropic viruses, specifically against measles
virus, rubella virus, and varicella zoster virus, also known as an MRZ
reaction (MRZR). Here, we correlated from the routine clinical
diagnostics individual IgG antibody indices (AIs) of MRZR with magnetic
resonance imaging (MRI) findings in patients with first MS diagnosis.
Multiple sclerosis
Multiple sclerosis
How viruses evolve, and in some cases, become deadly
Researchers at Michigan State University (MSU) have demonstrated how a new virus evolves, shedding light on how easy it can be for diseases to gain dangerous mutations. The findings appear in the current issue of the journal Science.
Scientists map one of life's molecular mysteries: Visualisation of the molecular gateway across and into cellular membranes
All living organisms are made up of cells, behind these intricate life forms lie complex cellular processes that allow our bodies to function. Researchers working on protein secretion -- a fundamental process in biology -- have revealed how protein channels in the membrane are activated by special signals contained in proteins destined for secretion. The results help explain the underlying mechanism responsible for the release of proteins such as hormones and antibodies into the blood stream.
De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia
In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case copy number variations were enriched for members of the NMDAR complex (P=0.0015) but not ARC (P=0.14).
Our data indicate that defects in NMDAR postsynaptic signalling and,
possibly, neuronal activity-regulated cytoskeleton-associated protein (ARC) complexes, which are known to be important in synaptic
plasticity and cognition, play a significant role in the pathogenesis of
schizophrenia.
Mutation drives viral sensors to initiate autoimmune disease
A new study uses a mouse model of a human autoimmune disease to
reveal how abnormal regulation of the intracellular sensors that detect
invading viruses can lead to autoimmune pathology. The research,
published online on January 26th in the journal Immunity by Cell
Press, provides key insight into mechanisms that underlie the
development of autoimmune disease and may lead to more effective
strategies for therapeutic intervention.
Elevated risk factors linked to major cardiovascular disease events across a lifetime, January 25, 2012 News Release - National Institutes of Health (NIH)
This National Institutes of Health-supported study used health data from 257,384 people and was the first to look simultaneously at multiple risk factors for cardiovascular disese across age, sex, race, and birth generation.The risk equates to a summation of effects, many of which are avoidable.
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