Overview of Recognition and Prevention of Child Sex Trafficking in the Primary Care Setting: A Primer for Nurse Practitioners

Child sex trafficking (CST) has become a global public health crisis and is a $150 billion criminal enterprise. Nurse practitioners are key in the recognition and prevention of CST in health care settings. Evidence demonstrates that up to 80% of CST victims have had a recent health care encounter. It is the role of the NP in practice to understand risk factors, screen for CST, and educate parents and caregivers on signs of victimization and prevention.     

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Drosophila E-cadherin is required for the maintenance of ring canals anchoring to mechanically withstand tissue growth

Intercellular bridges called “ring canals” (RCs) resulting from incomplete cytokinesis play an essential role in intercellular communication in somatic and germinal tissues. During Drosophila oogenesis, RCs connect the maturing oocyte to nurse cells supporting its growth. Despite numerous genetic screens aimed at identifying genes involved in RC biogenesis and maturation, how RCs anchor to the plasma membrane (PM) throughout development remains unexplained. In this study, we report that the clathrin adaptor protein 1 (AP-1) complex, although dispensable for the biogenesis of RCs, is required for the maintenance of the anchorage of RCs to the PM to withstand the increased membrane tension associated with the exponential tissue growth at the onset of vitellogenesis. Here we unravel the mechanisms by which AP-1 enables the maintenance of RCs’ anchoring to the PM during size expansion. We show that AP-1 regulates the localization of the intercellular adhesion molecule E-cadherin and that loss of AP-1 causes the disappearance of the E-cadherin–containing adhesive clusters surrounding the RCs. E-cadherin itself is shown to be required for the maintenance of the RCs’ anchorage, a function previously unrecognized because of functional compensation by N-cadherin. Scanning block-face EM combined with transmission EM analyses reveals the presence of interdigitated, actin- and Moesin-positive, microvilli-like structures wrapping the RCs. Thus, by modulating E-cadherin trafficking, we show that the sustained E-cadherin–dependent adhesion organizes the microvilli meshwork and ensures the proper attachment of RCs to the PM, thereby counteracting the increasing membrane tension induced by exponential tissue growth.E-cadherin (E-Cad) is a core component of intercellular adhesion complexes in cohesive metazoan tissues. E-Cad assembles into clusters that are stabilized by actin filaments via β- and α-catenin at the level of adherens junctions and form an adhesive belt mechanically linking cells together. A key feature of adherens junctions is their plasticity, which enables tissue remodeling, sustained by a constant endocytosis- and exocytosis-regulated E-Cad turnover (1) that is critical for various morphogenetic processes in epithelia (2–5).Drosophila oogenesis is a rich, multifaceted developmental process during which E-Cad function is not limited to epithelia, because it also regulates intercellular collective migration (6, 7) and the adhesion of stem cells to their niche (8). Cells derived from two different stem cell populations initially assemble into egg chambers composed of a follicular epithelium surrounding a 16-cell germline cyst (GC), itself composed of one oocyte and 15 nurse cells. During the next 64 h, GC cells grow to hundreds of times their initial volume. Oocyte growth is supported by cytoplasmic connections with nurse cells through ring canals (RCs) (Fig. 1 A and B), intercellular bridges that, instead of undergoing abscission, are stabilized on arrested cleavage furrows (9, 10). Recent findings revealed that RCs play a vital role in germline as well as in somatic tissues (10). RCs are composed of a noncontracting subcortical actin ring (11), the inner rim, attached to an electron-dense plasma membrane (PM) (12), the outer rim (Fig. 1A). RCs have been studied mainly in Drosophila female GCs (9) where genetic screens uncovered a variety of actin regulators controlling their establishment at the onset of oogenesis and their growth throughout the entire process (13–17). However, the molecular machinery involved in anchoring the PM to the RC remains unknown. Mutations in several membrane-traffic regulators affect the integrity of nurse cells’ PM, causing multinucleation and giving rise to remnants of detached RCs (18–24); these observations suggest that an unidentified membrane cargo is required for anchoring RCs to the PM.Open in a separate windowFig. 1.Nurse cells’ multinucleation in AP-1 mutant female GCs. (A) Schematic representation of the GC consisting of a single oocyte (Oo, nucleus) connected to 15 nurse cells (blue) via RCs (red) and a surrounding monolayer of about 650 somatic follicle cells (green). (Inset) Schematic representation of a transverse section through the RCs composed of an inner rim [red, containing the Adducin-like Hu-li tai shao (Hts) (13, 15) and the filamin Cheerio (16)] contacting an electron-dense PM (outer rim, black) that itself is connected to the rest of the nurse cell PM (gray). (B) Stereotyped organization of the female GC before and after detachment of nurse cells’ RCs. The oocyte has a gray nucleus; nurse cells have colored nuclei. (C) Stage 8 wild-type and AP-1 mutant [identified by the loss of nuclear localization signal (NLS)::GFP, blue] GCs stained for actin (green) and DAPI (red). Arrows indicate RCs connecting nurse cells in control GCs. Arrowheads indicate RCs floating in the cytoplasm of multinucleated nurse cells in AP-1 mutant GCs (at least one floating ring was observed in 29 of 34 mutant stage 8 or older GCs). (C′) Quantitation of multinucleated AP-1 mutant GCs at stage 7 to stage 9 or older. (D) Maximal projections of 5 µm of anchored and clustered floating RCs in control and AP-1 mutant GCs.Here we describe an RC detachment phenotype in mutants of the clathrin adaptor protein 1 (AP-1), a protein complex regulating polarized membrane protein sorting from the trans-Golgi network and endosomal compartments (25), and provide direct evidence that polarized membrane trafficking to RCs allows an E-Cad–mediated mechanical strengthening of RC anchoring necessary to resist the membrane tension generated by cellular growth.     

Formation of the Legionella-containing vacuole: phosphoinositide conversion,GTPase modulation and ER dynamics

The environmental bacterium Legionella pneumophila replicates in free-living amoeba as well as in alveolar macrophages upon inhalation of bacteria-laden aerosols. Resistance of the opportunistic pathogen to macrophages is a prerequisite to cause a severe pneumonia called Legionnaires’ disease. L. pneumophila grows intracellularly in a unique, ER-associated compartment, the Legionella-containing vacuole (LCV). The bacterial Icm/Dot type IV secretion system represents an essential virulence factor, which translocates approximately 300 “effector proteins” into protozoan or mammalian host cells. Some of these effectors contribute to the formation of the LCV by targeting conserved host factors implicated in membrane dynamics, such as phosphoinositide lipids and small GTPases. Here we review recent findings on the role of phosphoinositides, small and large GTPases as well as ER dynamics for pathogen vacuole formation and intracellular replication of L. pneumophila.     

Localization of EFA6 (exchange factor for ARF6) isoform D in steroidogenic testicular Leydig cells of adult mice

EFA6 (exchange factor for ARF6) activates Arf6 (ADP ribosylation factor 6) by exchanging ADP to ATP and the resulting activated form of Arf6 is involved in the membrane trafficking and actin remodeling of cells. Our previous study has shown the selective expression/localization of EFA6D in steroidogenic adrenocortical cells in situ of adult mice. In view of the previous finding, the present study was undertaken to examine its localization in mouse Leydig cells representing another steroidogenic cell species in order to further support the possible involvement of the EFA6/Arf6 cascade via membrane trafficking in the regulation of steroidogenesis and/or secretion. A distinct band for EFA6D with the same size as that of the brain was detected in the testis of adult mice. In immuno-light microscopy, immunoreactivity for EFA6D was seen throughout the cytoplasm in most Leydig cells without any distinct accumulation along the plasmalemma. Lack of immunoreactivity for EFA6D was seen in the seminiferous tubular epithelium. In immuno-electron microscopy, the immune-labeling was seen in sporadic/focal patterns on plasma membranes and some vesicles and vacuoles subjacent to the plasma membranes. More constant and rather predominant is the labeling on numerous mitochondria. No immuno-labeling was seen in lipid droplets. The present study suggests that EFA6D is somehow involved in regulation of the synthesis and/or secretion of testosterone through the membrane-traffic by activation of Arf6. In addition, EFA6D is suggested to play in mitochondria some yet unidentified roles rather independent of Arf6-activation, which remains to be elucidated.