84 research outputs found
Cervico-vaginal immunoglobulin g levels increase post-ovulation independently of neutrophils
The prevalence of sexually transmitted infections (STIs) is often higher in females than in males. Although the reproductive cycle profoundly modulates local immunity in the female reproductive tract (FRT) system, significant gaps in our knowledge of the immunobiology of the FRT still exist. An intriguing and frequently observed characteristic of the FRT is the predominant presence of immunoglobulin (Ig) G in cervico-vaginal secretions. We show here that in the mouse, IgG accumulation was enhanced approximately 5-fold post-ovulation, and was accompanied by an influx of neutrophils into the FRT. To determine whether these two events were causally related, we performed short-term neutrophil depletion experiments at individual stages throughout the estrous cycle. Our results demonstrate that neutrophils were not necessary for cycle-dependent tissue remodeling and cycle progression and that cycle-dependent IgG accumulation occurred independent of neutrophils. We thus conclude that neutrophil influx and IgG accumulation are independent events that occur in the FRT during the reproductive cycle
The TERT variant rs2736100 is associated with colorectal cancer risk
BACKGROUND: Polymorphic variation at the 5p15.33 (TERT-CLPTM1L) locus is associated with the risk of many cancers but a relationship with colorectal cancer (CRC) risk has yet to be defined. METHODS: We used data from six genome-wide association studies (GWAS) of CRC, linkage disequilibrium mapping and imputation, to examine the relationship between 73 single-nucleotide polymorphisms at 5p15.33 and CRC risk in detail. RESULTS: rs2736100, which localises to intron 2 of TERT, provided the strongest evidence of an association with CRC (P=2.28 Γ 10β»β΄). The association was also shown in an independent series of 10β047 CRC cases and 6918 controls (P=0.02). A meta-analysis of all seven studies (totalling 16β039 cases, 16β430 controls) provided increased evidence of association (P=2.49 Γ 10β»β΅; per allele odds ratio=1.07). The association of rs2736100 on CRC risk was shown to be independent of 15 low-penetrance variants previously identified. CONCLUSION: The rs2736100 association demonstrates an influence of variation at 5p15.33 on CRC risk and further evidence that the 5p15.33 (TERT-CLPTM1L) locus has pleiotropic effects (reflecting generic or lineage-specific effects) on cancer risk
Stable Isotope Tracking of Endangered Sea Turtles: Validation with Satellite Telemetry and Ξ΄15N Analysis of Amino Acids
Effective conservation strategies for highly migratory species must incorporate information about long-distance movements and locations of high-use foraging areas. However, the inherent challenges of directly monitoring these factors call for creative research approaches and innovative application of existing tools. Highly migratory marine species, such as marine turtles, regularly travel hundreds or thousands of kilometers between breeding and feeding areas, but identification of migratory routes and habitat use patterns remains elusive. Here we use satellite telemetry in combination with compound-specific isotope analysis of amino acids to confirm that insights from bulk tissue stable isotope analysis can reveal divergent migratory strategies and within-population segregation of foraging groups of critically endangered leatherback sea turtles (Dermochelys coriacea) across the Pacific Ocean. Among the 78 turtles studied, we found a distinct dichotomy in Ξ΄15N values of bulk skin, with distinct βlow Ξ΄15Nβ and βhigh Ξ΄15Nβ groups. Ξ΄15N analysis of amino acids confirmed that this disparity resulted from isotopic differences at the base of the food chain and not from differences in trophic position between the two groups. Satellite tracking of 13 individuals indicated that their bulk skin Ξ΄15N value was linked to the particular foraging region of each turtle. These findings confirm that prevailing marine isoscapes of foraging areas can be reflected in the isotopic compositions of marine turtle body tissues sampled at nesting beaches. We use a Bayesian mixture model to show that between 82 and 100% of the 78 skin-sampled turtles could be assigned with confidence to either the eastern Pacific or western Pacific, with 33 to 66% of all turtles foraging in the eastern Pacific. Our forensic approach validates the use of stable isotopes to depict leatherback turtle movements over broad spatial ranges and is timely for establishing wise conservation efforts in light of this speciesβ imminent risk of extinction in the Pacific
Network Topologies and Dynamics Leading to Endotoxin Tolerance and Priming in Innate Immune Cells
The innate immune system, acting as the first line of host defense, senses
and adapts to foreign challenges through complex intracellular and
intercellular signaling networks. Endotoxin tolerance and priming elicited by
macrophages are classic examples of the complex adaptation of innate immune
cells. Upon repetitive exposures to different doses of bacterial endotoxin
(lipopolysaccharide) or other stimulants, macrophages show either suppressed or
augmented inflammatory responses compared to a single exposure to the
stimulant. Endotoxin tolerance and priming are critically involved in both
immune homeostasis and the pathogenesis of diverse inflammatory diseases.
However, the underlying molecular mechanisms are not well understood. By means
of a computational search through the parameter space of a coarse-grained
three-node network with a two-stage Metropolis sampling approach, we enumerated
all the network topologies that can generate priming or tolerance. We
discovered three major mechanisms for priming (pathway synergy, suppressor
deactivation, activator induction) and one for tolerance (inhibitor
persistence). These results not only explain existing experimental
observations, but also reveal intriguing test scenarios for future experimental
studies to clarify mechanisms of endotoxin priming and tolerance.Comment: 15 pages, 8 figures, submitte
Genome-wide association studies of cancer: current insights and future perspectives.
Genome-wide association studies (GWAS) provide an agnostic approach for investigating the genetic basis of complex diseases. In oncology, GWAS of nearly all common malignancies have been performed, and over 450 genetic variants associated with increased risks have been identified. As well as revealing novel pathways important in carcinogenesis, these studies have shown that common genetic variation contributes substantially to the heritable risk of many common cancers. The clinical application of GWAS is starting to provide opportunities for drug discovery and repositioning as well as for cancer prevention. However, deciphering the functional and biological basis of associations is challenging and is in part a barrier to fully unlocking the potential of GWAS
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