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Almost every animal lineage is characterized by unique sex-specific traits, implying that such traits are gained and lost frequently in evolution. However, the genetic mechanisms responsible for these changes are not understood. In Drosophila, the activity of the sex determination pathway is restricted to sexually dimorphic tissues, suggesting that spatial regulation of this pathway may contribute to the evolution of sex-specific traits. We examine the regulation and function of doublesex (dsx), the main transcriptional effector of the sex determination pathway, in the development and evolution of Drosophila sex combs. Sex combs are a recent evolutionary innovation and show dramatic diversity in the relatively few Drosophila species that have them. We show that dsx expression in the presumptive sex comb region is activated by the HOX gene Sex combs reduced (Scr), and that the male isoform of dsx up-regulates Scr so that both genes become expressed at high levels in this region in males but not in females. Precise spatial regulation of dsx is essential for defining sex comb position and morphology. Comparative analysis of Scr and dsx expression reveals a tight correlation between sex comb morphology and the expression patterns of both genes. In species that primitively lack sex combs, no dsx expression is observed in the homologous region, suggesting that the origin and diversification of this structure were linked to the gain of a new dsx expression domain. Two other, distantly related fly lineages that independently evolved novel male-specific structures show evolutionary gains of dsx expression in the corresponding tissues, where dsx may also be controlled by Scr. These findings suggest that changes in the spatial regulation of sex-determining genes are a key mechanism that enables the evolution of new sex-specific traits, contributing to some of the most dramatic examples of phenotypic diversification in nature.

Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics. Using genetic deletion in preclinical mouse models, here we show that PD-L1 from disparate cellular sources, including tumour cells, myeloid or other immune cells can similarly modulate the degree of cytotoxic T-cell function and activity in the tumour microenvironment. PD-L1 expression in both the host and tumour compartment contribute to immune suppression in a non-redundant fashion, suggesting that both sources could be predictive of sensitivity to therapeutic agents targeting the PD-L1/PD-1 axis. PD-L1, the ligand for T-cell inhibitory receptor PD-1, can be expressed by various cell types in the tumour microenvironment. Here, the authors show that, in mouse models, the expression of PD-L1 from both cancerous and normal host immune cells is important for suppressing anti-tumour immune responses.

Using data from the National LGBT Alumni Survey, we examined generational perceptions of campus climate for LGBTQ undergraduate students who graduated from 1944 through 2013 (N = 3,121) with Renn and Arnold's (2003) reconceptualized ecological model as a framework. Results demonstrate differences in LGBTQ student campus climate perceptions across generations and highlight academic experiences, cocurricular experiences, and institutional variables as important influences on climate for LGBTQ undergraduates.

Background Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. Results We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. Conclusions Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors.

Background Drosophila melanogaster undergoes a complete metamorphosis, during which time the larval male and female forms transition into sexually dimorphic, reproductive adult forms. To understand this complex morphogenetic process at a molecular-genetic level, whole genome microarray analyses were performed. Results The temporal gene expression patterns during metamorphosis were determined for all predicted genes, in both somatic and germline tissues of males and females separately. Temporal changes in transcript abundance for genes of known functions were found to correlate with known developmental processes that occur during metamorphosis. We find that large numbers of genes are sex-differentially expressed in both male and female germline tissues, and relatively few are sex-differentially expressed in somatic tissues. The majority of genes with somatic, sex-differential expression were found to be expressed in a stage-specific manner, suggesting that they mediate discrete developmental events. The Sex-lethal paralog, CG3056 , displays somatic, male-biased expression at several time points in metamorphosis. Gene expression downstream of the somatic, sex determination genes transformer and doublesex (dsx) was examined in two-day old pupae, which allowed for the identification of genes regulated as a consequence of the sex determination hierarchy. These include the homeotic gene abdominal A , which is more highly expressed in females as compared to males, as a consequence of dsx . For most genes regulated downstream of dsx during pupal development, the mode of regulation is distinct from that observed for the well-studied direct targets of DSX, Yolk protein 1 and 2 . Conclusion The data and analyses presented here provide a comprehensive assessment of gene expression during metamorphosis in each sex, in both somatic and germline tissues. Many of the genes that underlie critical developmental processes during metamorphosis, including sex-specific processes, have been identified. These results provide a framework for further functional studies on the regulation of sex-specific development.

This article examines how three congregations influence the incorporation of Mexican, Colombian and Guatemalan immigrants in the South, where churches are central to social and civic life. By shaping various dimensions of assimilation, churches are intervening institutions that promote integration for some and hinder it for others. I argue that distinctions within rather than between Protestant and Catholic congregations drive how churches affect Latinos’ divergent pathways. The dynamics of a liberal Protestant congregation are more conducive to integration than those of more conservative counterparts. Similarly, the dynamics of a Catholic church with a grass-roots organization promote integration, while the hierarchical organization of other Catholic congregations delays incorporation.

Background The efficient acquisition of two critical but spatially separated resources –food and oxygen– governs the daily movements and diving patterns of air-breathing aquatic animals. Unlike pinnipeds, turtles and seabirds, fully marine (‘true’) sea snakes spend their entire lifecycle at sea and have evolved specialised movement behaviours. However, fine-scale data on the diving behaviour of free-ranging sea snakes remain scarce, limiting our understanding of their ecology and vulnerability to anthropogenic threats. Methods We used acoustic telemetry to track five individuals of two benthic-foraging sea snake species ( Hydrophis stokesii , H. major ) in Exmouth Gulf, Western Australia, and Baie des Citrons, New Caledonia. Each snake was continuously tracked using a directional hydrophone for up to 18 h, generating high-resolution, three-dimensional dive paths. After filtering, we analysed 106 dives from 46 h of tracking. Results Sea snakes primarily conducted U- and S-shaped dives and spent on average 97.2% of their time submerged. Most U-shaped dives were characterised by limited vertical and horizontal movement. S-shaped dives were more complex, with variable time on the seafloor and occasionally interrupted gradual ascents. Dive duration was positively correlated with post-dive surface interval, while depth and duration of the gradual ascent phase were influenced by environmental depth. We also identified distinctive, repetitive undulations (‘wiggles’) in the depth profiles of several dives completed by all three tracked H. stokesii . Conclusions These high-resolution data provide the first insights into the fine-scale diving patterns of benthic-foraging sea snakes. Like surface-foraging species, they appear to regulate air intake based on environmental depth and may be neutrally buoyant in the gradual ascent phase of S-shaped dives. We hypothesise that this phase facilitates efficient horizontal travel, despite potential increases in predation risk. The ‘wiggles’ observed in H. stokesii may have a functional role in buoyancy control, energy conservation, or foraging. Our study contributes to a deeper understanding of sea snake diving strategies, with implications for their ecology, physiology, and conservation.

This study examines the relationship between undergraduate experience and alumnx factors on perceptions of campus climate for lesbian, gay, bisexual, trans*, and queer (LGBTQ) graduates of four-year higher education institutions in the U.S. Data originate from The National LGBT Alumni Survey, with 2,725 participants representing all 50 U. S. states and all Carnegie institution classifications. Findings from the step-wise regression explained 45% of the variance in perceptions of campus climate for LGBTQ alumnx. The strongest relationship with alumnx campus climate perceptions included campus climate for LGBTQ undergraduate students, graduation year, LGBTQ student services availability, and both membership and leadership within alumnx associations and LGBTQ alumnx groups.

Immigration raids exemplify the reach of immigration law enforcement into the lives of Latino community members, yet little research characterizes the health effects of these raids. We examined the health implications of an immigration raid that resulted in multiple arrests and deportations and occurred midway through a community survey of a Latino population. We used linear regression following principal axis factoring to examine the influence of raid timing on immigration enforcement stress and self-rated health. We controlled for age, sex, relationship status, years in the county in which the raid occurred, children in the home, and nativity. 325 participants completed the survey before the raid and 151 after. Completing the survey after the raid was associated with higher levels of immigration enforcement stress and lower self-rated health scores. Findings indicate the negative impact of immigration raids on Latino communities. Immigration discussions should include holistic assessments of health.

INTRODUCTION:Health Technology Assessment (HTA) reports may have a major impact on the health care provided in a country. Hence, one would assume that these reports have a high methodological quality and thus represent a potentially important source of information, for instance, for identifying primary studies for inclusion in the evidence syntheses (for example, systematic reviews, Cochrane reviews, HTA reports). The aim of the present analysis is to evaluate the methodological quality of HTA reports used as a literature source for HTA reports produced by the German Institute for Quality and Efficiency in Health Care (IQWiG).METHODS:Eligible IQWiG reports were assessments of drug or non-drug interventions considering HTA reports as the literature source for primary studies and published up to October 2016. An HTA report included in the IQWIG report was considered in the analysis if it was a complete report published in English or German and indexed in the Health Technology Assessment Database (Wiley) or MEDLINE. Only the most current HTA report in an IQWiG report was considered; if more than one current HTA report was available, the one for inclusion in the analysis was randomly selected. The methodological quality of the HTA reports identified was evaluated with the AMSTAR (\"Assessment of Multiple Systematic Reviews\") tool (1), which comprises 11 items on methodological quality (meaning a maximum achievable score of 11).RESULTS:A total of fifty eligible IQWiG reports using fourty-one eligible HTA reports as literature sources were identified. The mean AMSTAR score of these HTA reports was 5.3 (95 percent Confidence Interval, CI: 4.3, 6.2). None of the HTA reports achieved a score of 11, nineteen (46 percent) had a score between 6 and 10, and twenty-two had a score below 6.CONCLUSIONS:HTA reports included in IQWiG reports only have an average methodological quality.