A novel perspective on PRDM9-directed meiotic recombination:How interallelic interactions between meiotic regulator PRDM9 and X-chromosomal hybrid sterility locus HstX2 regulate hybrid fertility phenotypes

Meiotic recombination between homologsis initiated in accessible chromatin loops along the genomes of many mammalian species. To induce recombination, chro-matin is first made locally accessible for the meiotic recombination machinery through interprotein collaborations between the central Zinc finger protein PRDM9 with HELLS and Zcwpw1 as well asthe proteins of the COMPASS-Complex. Re-combination itself is induced by a number of recombinases, including Rec8, DMC1 and SPO11, which introduce double-strandedbreaks (DSBs) at a subset of PRDM9-directed positions, mediate homology search, guide the broken ends towards each and eventually accomplish the physical exchange of homologous parental alleles through DSB-repair. The Results of such meiotic recombination events are either rare reciprocal cross-overs (CO) or, more frequently, non-reciprocal non-crossovers (NCO). While all these processes appear to be standardized at first sight, the di-verse outcomes of meiotic recombination, observable as haploid gametes with unique genomes, but also as a wide spectrum of fertility phenotypes. Especially in F1 hybrid males from crosses between female PWD (Laboratory strain ofMus mus-culus musculus)and male B6 mice (Laboratory strain ofMus musculus domesticus), F1 hybrid sterility (HS) results from allelic incompatibilities between heterozygous intersubspecific PRDM9 variants. Cytologically, the HS phenotype is characterized by asymmetric recombination landscapes with perturbated homology search, DSB repair and early meiotic breakdown. However, HS does not occur universally as other hybrid offspring, including the reciprocal cross of HS, remains fertile. This model led to the discovery of the X-linked hybrid sterility locus HstX2, which struc-turally differs betweenPWD and B6 miceand leads to sterility when the HstX2PWDis active in the PWDXB6genome. This work investigates which mechanistic role variants of PRDM9 and HstX2 play in functional meiosis of intra-(B6XDBA) and intersubspecific (B6XCAST) hybrids atthe initiation stages of meiotic recombination. The presented analyses reveal that HstX2 impacts spermatogenic processes at an earlier timepoint in intrasubspecific hybrids than in intersubspecific hybrids. Fur-thermore, a very active hybrid recombinationhotspot is characterized, in intersub-specific B6XCAST hybrids, undermining the role of novel PRDM9-directed hotspots for hybrid fertility. ChIP-sequencingtogether with insilicopredictions con-firm that, while this hotspot is unknown to both parental genomes, it allows func-tional homologous meiotic recombination in intersubspecific hybrids

Weightism: Can Personality Characteristics Predict Prejudice in College Students?

Bias toward individuals who are obese is one of the last bastions of permissible prejudice. The people who are obese report discrimination in a variety of settings; they experience it with families, employers, teachers, and health-care professionals. Research regarding obesity bias indicates that attribution of personal responsibility is correlated with negative attitudes toward individuals who are obese. Attribution of causality and resulting bias has been linked to specific personality characteristics, specifically the Big Five traits Agreeableness and Openness to Experience. The purpose of this study was to examine the relationship between personality characteristics and obesity bias. Students at a large mid-Atlantic University completed three measures; one personality measure, the NEO---PI---R and two measures of obesity bias, the Anti-fat Attitudes Questionnaire and a Weight Implicit Association Test. It was predicted that low Agreeableness and Openness to Experience was would predict anti-fat bias. Regression analyses did not indicate relationships between these variables, as expected. However, the obesity bias measures demonstrated bias was present within this sample. These findings are inconsistent with previous research regarding prejudice which used the NEO---PI---R. Limitations of this study, recommendations for future research, and clinical implications are discussed, including reducing myths regarding obesity, and advocacy for individuals who are obese

In-work support : what is the role of in-work support in a successful transition to sustained employment? (TM Case Study Summary Theme Report)

This report focuses on the role that in-work support plays in helping employment programme beneficiaries move into sustained employment. It draws on finding from the Talent Match (TM) National Evaluation. TM is a Big Lottery Fund strategic programme investing £108 million in 21 Local Enterprise Partnership (LEP) areas, which have experienced particularly high levels of youth unemployment. The focus of the programme is on developing holistic approaches to combating worklessness amongst long-term NEETs (i.e. young people who are not in education, employment or training). A key aspect of the programme is to bring young people closer to, and into employment. Part One of this report outlines what in-work support is and why it is important. Part Two presents findings from analysis of programme monitoring data on the provision of in-work support and insights from qualitative research in four TM partnerships and case studies of provision of in-work support. Part Three sets out the learning on in-work support emerging from this research

Imaging spectroscopy to assess the composition of ice surface materials and their impact on glacier mass balance

Glacier surfaces are not only composed of ice or snow but are heterogeneous mixtures of different materials. The occurrence and dynamics of light-absorbing impurities affect ice surface characteristics and strongly influence glacier melt processes. However, our understanding of the spatial distribution of impurities and their impact on ice surface characteristics and the glacier's energy budget is still limited. We use imaging spectroscopy in combination with in-situ experiments to assess the composition of ice surface materials and their respective impact on surface albedo and glacier melt rates. Spectroscopy data were acquired in August 2013 using the Airborne Prism EXperiment (APEX) imaging spectrometer and were used to map the abundances of six predominant surface materials on Glacier de la Plaine Morte, Swiss Alps. A pixel-based classification revealed that about 10% of the ice surface is covered with snow, water or debris. The remaining 90% of the surface can be divided into three types of glacier ice, namely ~ 7% dirty ice, ~ 43% pure ice and ~ 39% bright ice. Spatially distributed spectral albedo derived from APEX reflectance data in combination with in-situ multi-angular spectroscopic measurements was used to analyse albedo patterns present on the glacier surface. About 85% of all pixels exhibit a low albedo between 0.1 and 0.4 (mean albedo 0.29 ± 0.12), indicating that Glacier de la Plaine Morte is covered with a significant amount of light-absorbing impurities, resulting in a strong ice-albedo feedback during the ablation season. Using a pixel-based albedo map instead of a constant albedo for ice (0.34) as input for a mass balance model revealed that the glacier-wide total ablation remained similar (10% difference). However, the large local variations in mass balance can only be reproduced using the pixel-based albedo derived from APEX, emphasizing the need to quantify spatial albedo differences as an important input for glacier mass balance models

Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival.

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p < 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure

Effects of atmospheric, topographic, and BRDF correction on imaging spectroscopy-derived data products

Surface reflectance is an important data product in imaging spectroscopy for obtaining surface information. The complex retrieval of surface reflectance, however, critically relies on accurate knowledge of atmospheric absorption and scattering, and the compensation of these effects. Furthermore, illumination and observation geometry in combination with surface reflectance anisotropy determine dynamics in retrieved surface reflectance not related to surface absorption properties. To the best of authors’ knowledge, no comprehensive assessment of the impact of atmospheric, topographic, and anisotropy effects on derived surface information is available so far.This study systematically evaluates the impact of these effects on reflectance, albedo, and vegetation products. Using three well-established processing schemes (ATCOR F., ATCOR R., and BREFCOR), high-resolution APEX imaging spectroscopy data, covering a large gradient of illumination and observation angles, are brought to several processing states, varyingly affected by mentioned effects. Pixel-wise differences of surface reflectance, albedo, and spectral indices of neighboring flight lines are quantitatively analyzed in their respective overlapping area. We found that compensation of atmospheric effects reveals actual anisotropy-related dynamics in surface reflectance and derived albedo, related to an increase in pixel-wise relative reflectance and albedo differences of more than 40%. Subsequent anisotropy compensation allows us to successfully reduce apparent relative reflectance and albedo differences by up to 20%. In contrast, spectral indices are less affected by atmospheric and anisotropy effects, showing relative differences of 3% to 10% in overlapping regions of flight lines.We recommend to base decisions on the use of appropriate processing schemes on individual use cases considering envisioned data products

Ecosystem service change caused by climatological and non‐climatological drivers: A Swiss case study

Understanding the drivers of ecosystem change and their effects on ecosystem services are essential for management decisions and verification of progress towards national and international sustainability policies (e.g. Aichi Biodiversity Targets, Sustainable Development Goals). We aim to disentangle spatially the effect of climatological and non‐climatological drivers on ecosystem service supply and trends. Therefore, we explored time series of three ecosystem services in Switzerland between 2004 and 2014: carbon dioxide regulation, soil erosion prevention, and air quality regulation. We applied additive models to describe the spatial variation attributed to climatological (i.e. temperature, precipitation and relative sunshine duration) and non‐climatological drivers (i.e. random effects representing other spatially structured processes) that may affect ecosystem service change. Obtained results indicated strong influences of climatological drivers on ecosystem service trends in Switzerland. We identified equal contributions of all three climatological drivers on trends of carbon dioxide regulation and soil erosion prevention, while air quality regulation was more strongly influenced by temperature. Additionally, our results showed that climatological and non‐climatological drivers affected ecosystem services both negatively and positively, depending on the regions (in particular lower and higher altitudinal areas), drivers, and services assessed. Our findings highlight stronger effects of climatological compared to non‐climatological drivers on ecosystem service change in Switzerland. Furthermore, drivers of ecosystem change display a spatial heterogeneity in their influence on ecosystem service trends. We propose an approach building on an additive model to disentangle the effect of climatological and non‐climatological drivers on ecosystem service trends. Such analyses should be extended in the future to ecosystem service flow and demand to complete ecosystem service assessments and to demonstrate and communicate more clearly the benefits of ecosystem services for human well‐being

A poke in the eye: Inhibiting HIV-1 protease through its flap-recognition pocket

A novel mechanism of inhibiting HIV-1 protease (HIVp) is presented. Using computational solvent mapping to identify complementary interactions and the Multiple Protein Structure method to incorporate protein flexibility, we generated a receptor-based pharmacophore model of the flexible flap region of the semiopen, apo state of HIVp. Complementary interactions were consistently observed at the base of the flap, only within a cleft with a specific structural role. In the closed, bound state of HIVp, each flap tip docks against the opposite monomer, occupying this cleft. This flap-recognition site is filled by the protein and cannot be identified using traditional approaches based on bound, closed structures. Virtual screening and dynamics simulations show how small molecules can be identified to complement this cleft. Subsequent experimental testing confirms inhibitory activity of this new class of inhibitor. This may be the first new inhibitor class for HIVp since dimerization inhibitors were introduced 17 years ago. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 643–652, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected] Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58588/1/20993_ftp.pd