Direct genetic demonstration of Gα13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement

G2A is an orphan G protein-coupled receptor (GPCR), expressed predominantly in T and B cells and homologous to a small group of GPCRs of unknown function expressed in lymphoid tissues. G2A is transcriptionally induced in response to diverse stimuli, and its ectopic expression suppresses transformation of B lymphoid precursors by BCR-ABL. G2A induces morphological transformation of NIH 3T3 fibroblasts. Microinjection of constructs encoding G2A into Swiss 3T3 fibroblasts induces actin reorganization into stress fibers that depends on RhoA, but not CDC42 or RAC. G2A elicits RhoA-dependent transcriptional activation of serum response factor. Direct evaluation of RhoA activity demonstrates elevated levels of RhoA-GTP in G2A-expressing cells. Microinjection of embryonic fibroblasts derived from various Galpha knockout mice establishes a requirement for Galpha 13 but not Galpha 12 or Galpha q/11 in G2A-induced actin rearrangement. In conclusion, G2A represents a family of GPCRs expressed in lymphocytes that may link diverse stimuli to cytoskeletal reorganization and transcriptional activation through a pathway involving Galpha 13 and RhoA

AEGIS: Enhancement of Dust-enshrouded Star Formation in Close Galaxy Pairs and Merging Galaxies up to z ~ 1

Using data from the DEEP2 Galaxy Redshift Survey and HST/ACS imaging in the Extended Groth Strip, we select nearly 100 interacting galaxy systems including kinematic close pairs and morphologically identified merging galaxies. Spitzer MIPS 24 micron fluxes of these systems reflect the current dusty star formation activity, and at a fixed stellar mass (M_{*}) the median infrared luminosity (L_{IR}) among merging galaxies and close pairs of blue galaxies is twice (1.9 +/- 0.4) that of control pairs drawn from isolated blue galaxies. Enhancement declines with galaxy separation, being strongest in close pairs and mergers and weaker in wide pairs compared to the control sample. At z ~ 0.9, 7.1% +/- 4.3% of massive interacting galaxies (M_{*} > 2*10^{10} M_{solar}) are found to be ULIRGs, compared to 2.6% +/- 0.7% in the control sample. The large spread of IR luminosity to stellar mass ratio among interacting galaxies suggests that this enhancement may depend on the merger stage as well as other as yet unidentified factors (e.g., galaxy structure, mass ratio, orbital characteristics, presence of AGN or bar). The contribution of interacting systems to the total IR luminosity density is moderate (<= 36 %).Comment: 12 pages, 2 figures, 1 table, minor changes to match the proof version, accepted for publication in the ApJL AEGIS Special Issu

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P \u3c 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension

Double diffusion, shear instabilities, and heat impacts of a pacific summer water intrusion in the Beaufort Sea

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Fine, E., MacKinnon, J., Alford, M., Middleton, L., Taylor, J., Mickett, J., Cole, S., Couto, N., Boyer, A., & Peacock, T. Double diffusion, shear instabilities, and heat impacts of a pacific summer water intrusion in the Beaufort Sea. Journal of Physical Oceanography, 52(2), (2022): 189–203, https://doi.org/10.1175/jpo-d-21-0074.1.Pacific Summer Water eddies and intrusions transport heat and salt from boundary regions into the western Arctic basin. Here we examine concurrent effects of lateral stirring and vertical mixing using microstructure data collected within a Pacific Summer Water intrusion with a length scale of ∼20 km. This intrusion was characterized by complex thermohaline structure in which warm Pacific Summer Water interleaved in alternating layers of O(1) m thickness with cooler water, due to lateral stirring and intrusive processes. Along interfaces between warm/salty and cold/freshwater masses, the density ratio was favorable to double-diffusive processes. The rate of dissipation of turbulent kinetic energy (ε) was elevated along the interleaving surfaces, with values up to 3 × 10−8 W kg−1 compared to background ε of less than 10−9 W kg−1. Based on the distribution of ε as a function of density ratio Rρ, we conclude that double-diffusive convection is largely responsible for the elevated ε observed over the survey. The lateral processes that created the layered thermohaline structure resulted in vertical thermohaline gradients susceptible to double-diffusive convection, resulting in upward vertical heat fluxes. Bulk vertical heat fluxes above the intrusion are estimated in the range of 0.2–1 W m−2, with the localized flux above the uppermost warm layer elevated to 2–10 W m−2. Lateral fluxes are much larger, estimated between 1000 and 5000 W m−2, and set an overall decay rate for the intrusion of 1–5 years.This work was supported by ONR Grant N00014-16-1-2378 and NSF Grants PLR 14-56705 and PLR-1303791, NSF Graduate Research Fellowship Grant DGE-1650112, as well as by the Postdoctoral Scholar Program at Woods Hole Oceanographic Institution, with funding provided by the Weston Howland Jr. Postdoctoral Scholarship

Effectiveness of community outreach HIV prevention programs in Vietnam: A mixed methods evaluation

Background In 2014, Vietnam was the first Southeast Asian country to commit to achieving the World Health Organization’s 90–90-90 global HIV targets (90% know their HIV status, 90% on sustained treatment, and 90% virally suppressed) by 2020. This pledge represented further confirmation of Vietnam’s efforts to respond to the HIV epidemic, one feature of which has been close collaboration with the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). Starting in 2004, PEPFAR supported community outreach programs targeting high-risk populations (people who inject drugs, men who have sex with men, and sex workers). To provide early evidence on program impact, in 2007–2008 we conducted a nationwide evaluation of PEPFAR-supported outreach programs in Vietnam. The evaluation focused on assessing program effect on HIV knowledge, high-risk behaviors, and HIV testing among high-risk populations—results relevant to Vietnam’s push to meet global HIV goals. Methods We used a mixed-methods cross-sectional evaluation design. Data collection encompassed a quantitative survey of 2199 individuals, supplemented by 125 in-depth interviews. Participants were members of high-risk populations who reported recent contact with an outreach worker (intervention group) or no recent contact (comparison group). We assessed differences in HIV knowledge, risky behaviors, and HIV testing between groups, and between high-risk populations. Results Intervention participants knew significantly more about transmission, prevention, and treatment than comparison participants. We found low levels of injection drug-use-related risk behaviors and little evidence of program impact on such behaviors. In contrast, a significantly smaller proportion of intervention than comparison participants reported risky sexual behaviors generally and within each high-risk population. Intervention participants were also more likely to have undergone HIV testing (76.1% vs. 47.0%, p \u3c 0.0001) and to have received pre-test (78.0% vs. 33.7%, p \u3c 0.0001) and post-test counseling (80.9% vs. 60.5%, p \u3c 0.0001). Interviews supported evidence of high impact of outreach among all high-risk populations. Conclusions Outreach programs appear to have reduced risky sexual behaviors and increased use of HIV testing services among high-risk populations in Vietnam. These programs can play a key role in reducing gaps in the HIV care cascade, achieving the global 90–90-90 goals, and creating an AIDS-free generation

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic M&#xfc;llerian mimicry, thought &#x2013; but rarely demonstrated &#x2013; to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between M&#xfc;llerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

Healthcare without borders : a cross-sectional study of immigrant and nonimmigrant children admitted to a large public sector hospital in the Gauteng province of South Africa

BACKGROUND: Human migration is a worldwide phenomenon that receives considerable attention from the media and healthcare authorities alike. A significant proportion of children seen at public sector health facilities in South Africa (SA) are immigrants, and gaps have previously been METHODS AND FINDINGS: A cross-sectional study was conducted over a 4-month period during 2016 to 2017. Information was obtained through a structured questionnaire and health record review. The enrolled study participants included 508 children divided into 2 groups, namely 271 general paediatric patients and 237 neonates. Twenty-five percent of children in the neonatal group and 22.5% in the general paediatric group were immigrants. The parents/caregivers of the immigrant group had a lower educational level (p < 0.0001 neonatal and paediatric), lower income (neonatal p < 0.001; paediatric p = 0.024), difficulty communicating in English (p < 0.001 neonatal and paediatric), and were more likely residing in informal settlements (neonatal p = 0.001; paediatric p = 0.007) compared to the SA group. In the neonatal group, there was no difference in the number of antenatal care (ANC) visits, type of delivery, gestational age, and birth weight. In the general paediatric group, there was no difference in immunisation and vitamin A supplementation coverage, but when comparing growth, the noted in their healthcare provision. The objective of the study was to describe the characteristics and differences between the immigrant and SA children admitted to Kalafong Provincial Tertiary Hospital (KPTH), a large public sector hospital in the urban Gauteng Province of SA.immigrant group had more malnutrition compared to the SA group (p = 0.029 for wasting). There was no difference in the prevalence of maternal human immunodeficiency virus (HIV) infection, with equally good prevention of mother-to-child transmission (PMTCT) coverage. There was also no difference in reported difficulties by immigrants in terms of access to healthcare (neonatal p = 0.379; paediatric p = 0.246), although a large proportion (10%) of the neonates of immigrant mothers were born outside a medical facility. CONCLUSIONS: Although there were health-related differences between immigrant and SA children accessing in-hospital care, these were fewer than expected. Differences were found in parental educational level and socioeconomic factors, but these did not significantly affect ANC attendance, delivery outcomes, immunisation coverage, HIV prevalence, or PMTCT coverage. The immigrant population should be viewed as a high-risk group, with potential problems including suboptimal child growth. Health workers should advocate for all children in the community they are serving and promote tolerance, respect, and equal healthcare access.https://journals.plos.org/plosmedicinepm2022Paediatrics and Child Healt

Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia

Respiratory viral infections are associated with an increased risk of asthma, but how acute Th1 antiviral immune responses lead to chronic inflammatory Th2 disease remains undefined. We define a novel pathway that links transient viral infection to chronic lung disease with dendritic cell (DC) expression of the high-affinity IgE receptor (FcεRIα). In a mouse model of virus-induced chronic lung disease, in which Sendai virus triggered a switch to persistent mucous cell metaplasia and airway hyperreactivity after clearance of replicating virus, we found that FceRIa−/− mice no longer developed mucous cell metaplasia. Viral infection induced IgE-independent, type I IFN receptor–dependent expression of FcεRIα on mouse lung DCs. Cross-linking DC FcεRIα resulted in the production of the T cell chemoattractant CCL28. FceRIa−/− mice had decreased CCL28 and recruitment of IL-13–producing CD4+ T cells to the lung after viral infection. Transfer of wild-type DCs to FceRIa−/− mice restored these events, whereas blockade of CCL28 inhibited mucous cell metaplasia. Therefore, lung DC expression of FcεRIα is part of the antiviral response that recruits CD4+ T cells and drives mucous cell metaplasia, thus linking antiviral responses to allergic/asthmatic Th2 responses