Th17 Lymphocytes in Respiratory Syncytial Virus Infection

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution licenseStudies of the role of IL-17 in arthritis carried out in our laboratory are generously supported by a research grant from Pfizer

Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection

Explosive Nucleosynthesis: What we learned and what we still do not understand

This review touches on historical aspects, going back to the early days of nuclear astrophysics, initiated by B$^2$FH and Cameron, discusses (i) the required nuclear input from reaction rates and decay properties up to the nuclear equation of state, continues (ii) with the tools to perform nucleosynthesis calculations and (iii) early parametrized nucleosynthesis studies, before (iv) reliable stellar models became available for the late stages of stellar evolution. It passes then through (v) explosive environments from core-collapse supernovae to explosive events in binary systems (including type Ia supernovae and compact binary mergers), and finally (vi) discusses the role of all these nucleosynthesis production sites in the evolution of galaxies. The focus is put on the comparison of early ideas and present, very recent, understanding.Comment: 11 pages, to appear in Springer Proceedings in Physics (Proc. of Intl. Conf. "Nuclei in the Cosmos XV", LNGS Assergi, Italy, June 2018

Characterization and Generation of Male Courtship Song in Cotesia congregata (Hymenoptera: Braconidae)

Background Male parasitic wasps attract females with a courtship song produced by rapid wing fanning. Songs have been described for several parasitic wasp species; however, beyond association with wing fanning, the mechanism of sound generation has not been examined. We characterized the male courtship song of Cotesia congregata (Hymenoptera: Braconidae) and investigated the biomechanics of sound production. Methods and Principal Findings Courtship songs were recorded using high-speed videography (2,000 fps) and audio recordings. The song consists of a long duration amplitude-modulated “buzz” followed by a series of pulsatile higher amplitude “boings,” each decaying into a terminal buzz followed by a short inter-boing pause while wings are stationary. Boings have higher amplitude and lower frequency than buzz components. The lower frequency of the boing sound is due to greater wing displacement. The power spectrum is a harmonic series dominated by wing repetition rate ~220 Hz, but the sound waveform indicates a higher frequency resonance ~5 kHz. Sound is not generated by the wings contacting each other, the substrate, or the abdomen. The abdomen is elevated during the first several wing cycles of the boing, but its position is unrelated to sound amplitude. Unlike most sounds generated by volume velocity, the boing is generated at the termination of the wing down stroke when displacement is maximal and wing velocity is zero. Calculation indicates a low Reynolds number of ~1000. Conclusions and Significance Acoustic pressure is proportional to velocity for typical sound sources. Our finding that the boing sound was generated at maximal wing displacement coincident with cessation of wing motion indicates that it is caused by acceleration of the wing tips, consistent with a dipole source. The low Reynolds number requires a high wing flap rate for flight and predisposes wings of small insects for sound production

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

betabeta-delayed fission of isomers in 188Bi^188Bi

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Insights from computational modeling in inflammation and acute rejection in limb transplantation

Acute skin rejection in vascularized composite allotransplantation (VCA) is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection. © 2014 Wolfram et al

Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection

BACKGROUND: Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought. METHODOLOGY: Healthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1β and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFNγ, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay. CONCLUSIONS: Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni

Evolution of Female Preference for Younger Males

Previous theoretical work has suggested that females should prefer to mate with older males, as older males should have higher fitness than the average fitness of the cohort into which they were born. However, studies in humans and model organisms have shown that as males age, they accumulate deleterious mutations in their germ-line at an ever-increasing rate, thereby reducing the quality of genes passed on to the next generation. Thus, older males may produce relatively poor-quality offspring. To better understand how male age influences female mate preference and offspring quality, we used a genetic algorithm model to study the effect of age-related increases in male genetic load on female mate preference. When we incorporate age-related increases in mutation load in males into our model, we find that females evolve a preference for younger males. Females in this model could determine a male's age, but not his inherited genotype nor his mutation load. Nevertheless, females evolved age-preferences that led them to mate with males that had low mutation loads, but showed no preference for males with respect to their somatic quality. These results suggest that germ-line quality, rather than somatic quality, should be the focus of female preference in good genes models

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges