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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A number of researchers have shown that brokers (e.g., navigators and street-level bureaucrats) bridge access to healthcare services and information for immigrant patients through rich personal ...relationships and a mission of ethical care. An open question remains concerning how the increasing rationalization of healthcare over the past few decades influences brokerage for undocumented immigrant patients. Drawing from fieldwork and interviews conducted in California, as the Affordable Care Act (ACA) was implemented, I develop the concept of the “double-embedded-liaison.” While other studies treat brokers as acting either as gatekeepers or patient representatives, this study explains how brokers simultaneously operate on multiple planes when new roles are added. I argue that with more formalization and scrutiny at health centers, the impact of brokerage is destabilized and, subsequently, diminished. Two consequences of the double-embedded-liaison brokerage form are: (1) some brokers become disillusioned and exit –resulting in the loss of valuable resources at the health centers, and (2) immigrants move away from the health centers that historically served them. In looking at brokers’ simultaneous performance as gatekeepers and representatives, this research extends brokerage typologies and street-level bureaucracy arguments that largely treat brokerage in a mono-planar rather than in a bi-planar mode. Furthermore, in examining the risks and opportunities brokerage brings to addressing health disparities, the study provides insights into the effects of replacing the ACA or repealing it all together in the Post-Obama era.
•Brokerage is key to healthcare access for immigrants.•The rationalization of healthcare is accelerating and altering brokerage.•Brokerage in healthcare is moving from a mono-planar to a bi-planar structure.•Bi-planar brokerage leads to betrayal and diminished trust for immigrant patients.•Diminished trust leads to reduced access to healthcare for vulnerable populations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Brokerage is a prominent mechanism that explains access for Latino immigrants to many American institutions. However, few studies examine the dual nature of brokerage in answering questions on access ...to health care for undocumented Latino immigrants. The growing importance of Federally Qualified Health Centers (FQHCs) and ethnic navigators connecting immigrants to health care under the 2010 Affordable Care Act calls attention to the duality of brokers and its role in access. The study draws from 44 in-depth interviews with providers, clinic directors, navigators, and immigrant patients and two years of fieldwork in FQHCs in California's San Francisco Bay Area (2011-2013). Results show that brokers enable access through coaching and myth-busting but they also hinder it through scrutiny and bureaucratic filtering. The widespread dependence on brokerage, I argue, leads to ersatz brokerage, such as when providers navigate the health-care system for the undocumented without the appropriate linguistic resources or coordination. Furthermore, the study shows that the duality in brokerage generates misinformation, churning, and alienation. Understanding the relational processes that both include and exclude vulnerable populations from needed services enhances theories of immigrant integration and can help design more efficient policies and address inequalities related to documentation status.
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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.
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.
In 2006, millions of immigrants engaged in boycotts and marches for immigrant rights. Many of these protests occurred in new destinations, places with little prior history of collective mobilisation ...by non-citizens. We focus on the U.S. South, a region noteworthy for the recent, unprecedented growth in its non-citizen population and its unexpected role in the 2006 protests. Drawing from a unique dataset of immigration-related news stories from ten newspapers across the South from 2005 to 2007, we examine variation in public immigration discourse during this 'unsettled' period of heightened political mobilisation and marked public anxiety around immigration. We supplement this analysis with a close examination of immigration news coverage in English and Spanish-language newspapers in South Carolina. Regional analysis reveals minimal shifts in public immigration discourse during this time period; however, the South Carolina case study reveals subtle yet noteworthy variation in the cultural categories used to label immigrants, the moral characterisations of immigrants, and the salience of the immigrant-native boundary. The English-language press increasingly portrayed immigrants from Mexico as cultural threats. After the marches, the Spanish-language press emphasised immigrants' work ethic. These findings have implications for our understanding of social dynamics in new destinations and the cultural dimensions of political mobilisation.
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doublesex (
dsx) encodes sex-specific transcription factors (DSX
F in females and DSX
M in males) that act at the bottom of the
Drosophila somatic sex determination hierarchy.
dsx, which is conserved ...among diverse taxa, is responsible for directing all aspects of
Drosophila somatic sexual differentiation outside the nervous system. The role of
dsx in the nervous system remains
minimally understood. Here, the mechanisms by which DSX acts to establish dimorphism in the central nervous system were examined. This study shows that the number of DSX-expressing cells in the central nervous system is sexually dimorphic during both pupal and adult stages. Additionally, the number of DSX-expressing cells depends on both the amount of DSX and the isoform present. One cluster of DSX-expressing neurons in the ventral nerve cord undergoes female-specific cell death that is DSX
F-dependent. Another DSX-expressing cluster in the posterior brain undergoes more cell divisions in males than in females. Additionally, early in development, DSX
M is present in a portion of the neural circuitry in which the male-specific product of
fruitless (
fru) is produced, in a region that has been shown to be critical for sex-specific behaviors. This study demonstrates that DSX
M and FRU
M expression patterns are established independent of each other in the regions of the central nervous system examined. In addition to the known role of
dsx in establishing sexual dimorphism outside the central nervous system, the results demonstrate that DSX establishes sex-specific differences in neural circuitry by regulating the number of neurons using distinct mechanisms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Embedded and External Brokers López-Sanders, Laura
The American behavioral scientist (Beverly Hills),
02/2014, Volume:
58, Issue:
2
Journal Article
Peer reviewed
Immigration scholars have made great strides in documenting the role of labor agents in connecting immigrant workers with jobs, though less attention has centered on whether such brokerage ...exacerbates existing workplace inequalities. Based on participant observation and in-depth interviews over 15 months in seven workplaces, I examine power dynamics and relations between brokers and immigrant workers. My analyses show that temporary agencies and embedded brokers play a complementary role in incorporating undocumented immigrants into jobs. Yet important power imbalances develop within these relationships, with implications for the inequalities that the most vulnerable workers experience.
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Undisturbed lysimeters are widely used to study water and solute transport, where both natural and unnatural preferential flow can greatly influence leaching rates. The objective of this study was to ...use chemical and isotopic tracers to quantify the effect of initial soil water content and lysimeter design on preferential flows. Ten undisturbed lysimeters (900 cm2) were collected from an agricultural field, with the gap between the soil and lysimeter casing sealed with petroleum jelly for five lysimeters. Lysimeters were subjected to two rainfall simulations (3.3 cm h−1) under contrasting initial soil water contents, and leachate near the soil‐casing interface was collected separately from leachate through the bulk soil. Three‐component hydrograph separation revealed that event water comprised 21–59% of total leachate irrespective of initial soil water content and lysimeter design. Sealing the edges of the lysimeters with petroleum jelly greatly reduced but did not eliminate edge flow during rainfall simulations. Although water and solute transport were similar in both sealed and unsealed lysimeters under dry antecedent conditions due to the formation of shrinkage cracks on the soil surface, edge flow was substantially greater for the unsealed lysimeters under wet antecedent conditions. Unsealed edges under wet antecedent conditions facilitated the preferential transport of both event and pre‐event water, resulting in greater solute leaching. Using multiple tracers to contrast lysimeter designs under different initial soil water contents not only allowed for rigorous testing of a commonly used edge‐flow suppression technique but also provided new insights into preferential flow processes and patterns.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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.
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.
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