Directed conservation of the world's reef sharks and rays.

Many shark populations are in decline around the world, with severe ecological and economic consequences. Fisheries management and marine protected areas (MPAs) have both been heralded as solutions. However, the effectiveness of MPAs alone is questionable, particularly for globally threatened sharks and rays ('elasmobranchs'), with little known about how fisheries management and MPAs interact to conserve these species. Here we use a dedicated global survey of coral reef elasmobranchs to assess 66 fully protected areas embedded within a range of fisheries management regimes across 36 countries. We show that conservation benefits were primarily for reef-associated sharks, which were twice as abundant in fully protected areas compared with areas open to fishing. Conservation benefits were greatest in large protected areas that incorporate distinct reefs. However, the same benefits were not evident for rays or wide-ranging sharks that are both economically and ecologically important while also threatened with extinction. We show that conservation benefits from fully protected areas are close to doubled when embedded within areas of effective fisheries management, highlighting the importance of a mixed management approach of both effective fisheries management and well-designed fully protected areas to conserve tropical elasmobranch assemblages globally.

Extracellular matrix stiffness controls cardiac fibroblast proliferation via the nuclear factor-Y (NF-Y) transcription factor.

The proliferative expansion of cardiac fibroblasts (CF) contributes towards cardiac fibrosis, which results in myocardial stiffening, cardiac dysfunction, and heart failure. CF sense and respond to increased stiffness of their local extracellular matrix, modulating their phenotype towards increased collagen synthesis and higher proliferation, leading potentially to a vicious circle of positive feedback. Here we describe a novel mechanism that mediates increased CF proliferation in response to a pathologically stiff Exteracellular matrix (ECM). The mechanism we describe is independent of the well-characterised mechano-sensitive transcript factors, YAP-TEAD and MKL1-SRF, which our data indicate are only responsible for part of the genes induced by stiffened ECM. Instead, our data identify Nuclear Factor-Y (NF-Y) as a novel mechanosensitive transcription factor, which mediates enhanced CF proliferation in response to a stiff ECM. We show that levels of NF-YA protein, the major regulatory subunit of NF-Y, and NF-Y transcriptional activity, are increased by a stiff ECM. Indeed, NF-Y activity drives the expression of multiple cell-cycle genes. Furthermore, NF-YA protein levels are dependent on FAK signalling suggesting a mechanistic link to ECM composition. Consistent with its role as a mechano-sensor, inhibition of NF-Y using siRNA or dominant negative mutant blocks CF proliferation on plastic in vitro, which models a stiff ECM, whereas ectopic expression of NF-YA increases the proliferation of cells interacting under conditions that model a physiologically soft ECM. In summary, our data demonstrate that NF-Y is a biomechanically sensitive transcription factor that promotes CF proliferation in a model of pathologically stiffened ECM.

Adverse Childhood Experiences, Substance Use, and Self-Reported Substance Use Problems Among Sexual and Gender Diverse Individuals: Moderation by History of Mental Illness.

Recent research has highlighted the alarmingly high rates at which sexual and gender diverse (SGD) individuals experience Adverse Childhood Experiences (ACE). ACE, in turn, are strongly related to mental illness-an important correlate of substance use. The present study explores whether mental illness moderates the relationship between ACE and substance use outcomes among SGD adults. As part of a larger community-based participatory research study, we assessed ACE, self-reported mental illness, and past-year substance use and misuse among a large and diverse sample of SGD community members in South Central Texas (n = 1,282). Multivariate logistic regression models were used to assess relationships between ACE, mental illness, substance use, and substance misuse (DAST > 3). Interaction terms between ACE and history of mental illness were created to assess moderation effects. Cumulative ACE scores were associated with a significantly higher odds of self-reported past year substance use (AOR = 1.43, 95% CI = 1.34-1.54) and substance misuse (AOR = 1.21, 95% CI = 1.11-1.32). History of mental illness was associated with an increased odds of self-reported substance misuse (AOR = 2.07, 95% CI = 1.20-3.55), but not past year substance use. There was a significant interaction of ACE and history of mental illness on the odds of past year substance use (AOR = 0.78, 95% CI = 0.69-0.89), but not for substance misuse. These results provide support for theoretical models linking ACE, mental illness, and substance use among SGD adults. Longitudinal research designs are needed to address temporality of outcomes and test mediation models of trauma, mental illness, and substance use. Future directions for prevention and intervention are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00560-y.

Understanding the Experiences of Latinx LGBTQ Texans at the Beginning of the COVID-19 Pandemic.

Marginalized communities have been disproportionately affected by COVID-19, including both racial/ethnic minority and sexual minority populations. To date, there has been little research examining the impact of the COVID-19 pandemic at the intersections of marginalized identities. Furthermore, available national data on COVID-19 outcomes may obscure our understanding of region-specific outcomes, particularly in the U.S. South. Using an intersectional approach, we explore differences in worries over COVID-19, preventative behaviors, and COVID-19 outcomes in the early months of the pandemic in a diverse sample of LGBTQ people (N = 1076) living in Texas. Our findings indicated that LGBTQ Latinx people in Texas reported more COVID-19 related worries and adverse outcomes than non-Latinx LGBTQ people. These findings are in line with previous research that found that the increased risk to Latinx and LGBTQ populations in public health crises is often overlooked and can be attributed to many factors such as socioeconomic status, occupational propensity, disparities in physical health, and barriers to healthcare access. Furthermore, our findings suggest the necessity of utilizing an intersectional approach when examining the disproportionate burden marginalized communities face in public health crises.

Widespread diversity deficits of coral reef sharks and rays.

A global survey of coral reefs reveals that overfishing is driving resident shark species toward extinction, causing diversity deficits in reef elasmobranch (shark and ray) assemblages. Our species-level analysis revealed global declines of 60 to 73% for five common resident reef shark species and that individual shark species were not detected at 34 to 47% of surveyed reefs. As reefs become more shark-depleted, rays begin to dominate assemblages. Shark-dominated assemblages persist in wealthy nations with strong governance and in highly protected areas, whereas poverty, weak governance, and a lack of shark management are associated with depauperate assemblages mainly composed of rays. Without action to address these diversity deficits, loss of ecological function and ecosystem services will increasingly affect human communities.

Vertical space use and thermal range of the great hammerhead (Sphyrna mokarran), (Rüppell, 1837) in the western North Atlantic.

The great hammerhead (Sphyrna mokarran) is a highly mobile, large-bodied shark primarily found in coastal-pelagic and semi-oceanic waters across a circumtropical range. It is a target or by-catch species in multiple fisheries, and as a result, rapid population declines have occurred in many regions. These declines have contributed to the species being assessed as globally critically endangered on the IUCN Red List. Although conservation and management measures have yielded promising results in some regions, such as the United States, high levels of at-vessel and post-release mortality remain a major concern to the species population recovery. This examined the vertical space use and thermal range of pop-off archival satellite-tagged S. mokarran in the western North Atlantic Ocean, expanding the understanding of the ecological niche of this species and providing insight into by-catch mitigation strategies for fisheries managers. The results showed that S. mokarran predominantly used shallow depths (75% of records <30 m) and had a narrow temperature range (89% of records between 23 and 28°C). Individual differences in depth use were apparent, and a strong diel cycle was observed, with sharks occupying significantly deeper depths during the daytime. Furthermore, two individuals were confirmed pregnant with one migrating from the Bahamas to South Carolina, U.S.A., providing further evidence of regional connectivity and parturition off the U.S. East Coast. The findings suggest that S. mokarran may be vulnerable to incidental capture in the western North Atlantic commercial longline fisheries due to substantial vertical overlap between the species and the gear. The results can be incorporated into conservation and management efforts to develop and/or refine mitigation measures focused on reducing the by-catch and associated mortality of this species, which can ultimately aide S. mokarran population recovery in areas with poor conservation status.

Combined role for YAP-TEAD and YAP-RUNX2 signalling in substrate-stiffness regulation of cardiac fibroblast proliferation.

Cardiac fibrosis is associated with increased stiffness of the myocardial extracellular matrix (ECM) in part mediated by increased cardiac fibroblast proliferation However, our understanding of the mechanisms regulating cardiac fibroblast proliferation are incomplete. Here we characterise a novel mechanism involving a combined activation of Yes-associated protein (YAP) targets RUNX Family Transcription Factor 2 (RUNX2) and TEA Domain Transcription Factor (TEAD). We demonstrate that cardiac fibroblast proliferation is enhanced by interaction with a stiff ECM compared to a soft ECM. This is associated with activation of the transcriptional co-factor, YAP. We demonstrate that this stiffness induced activation of YAP enhances the transcriptional activity of both TEAD and RUNX2 transcription factors. Inhibition of either TEAD or RUNX2, using gene silencing, expression of dominant-negative mutants or pharmacological inhibition, reduces cardiac fibroblast proliferation. Using mutants of YAP, defective in TEAD or RUNX2 activation ability, we demonstrate a dual role of YAP-mediated activation of TEAD and RUNX2 for substrate stiffness induced cardiac fibroblast proliferation. Our data highlights a previously unrecognised role of YAP mediated RUNX2 activation for cardiac fibroblast proliferation in response to increased ECM stiffness.

Cyclic-AMP Increases Nuclear Actin Monomer Which Promotes Proteasomal Degradation of RelA/p65 Leading to Anti-Inflammatory Effects.

The second messenger, cAMP has potent immunosuppressive and anti-inflammatory actions. These have been attributed, in part, to the ability of cAMP-induced signals to interfere with the function of the proinflammatory transcription factor Nuclear Factor-kappa B (NF-κB). However, the mechanisms underlying the modulation of NF-κB activity by cAMP remain unclear. Here we demonstrate an important role for cAMP-mediated increase in nuclear actin monomer levels in inhibiting NF-κB activity. Elevated cAMP or forced expression of a nuclear localised polymerisation defective actin mutant (NLS-ActinR62D) inhibited basal and TNFα induced mRNA levels of NF-κB-dependent genes and NF-κB-dependent reporter gene activity. Elevated cAMP or NLS-ActinR62D did not affect NF-κB nuclear translocation but did reduce total cellular and nuclear RelA/p65 levels. Preventing the cAMP-induced increase in nuclear actin monomer, either by expressing a nuclear localised active mutant of the actin polymerising protein mDIA, silencing components of the nuclear actin import complex IPO9 and CFL1 or overexpressing the nuclear export complex XPO6, rescued RelA/p65 levels and NF-κB reporter gene activity in forskolin-stimulated cells. Elevated cAMP or NLS-ActinR62D reduced the half-life of RelA/p65, which was reversed by the proteasome inhibitor MG132. Accordingly, forskolin stimulated association of RelA/p65 with ubiquitin affinity beads, indicating increased ubiquitination of RelA/p65 or associated proteins. Taken together, our data demonstrate a novel mechanism underlying the anti-inflammatory effects of cAMP and highlight the important role played by nuclear actin in the regulation of inflammation.

The Relationship Between Adverse Childhood Experiences and Utilization of Different HIV Testing Strategies Among Young Men Who Have Sex with Men in Texas.

Adverse childhood experiences (ACEs) are a well-documented HIV-risk factor, but less is known about the relationship between ACEs and different HIV testing strategies. This study used data from an LGBTQ + community health assessment, that was part of a multi-staged community-based participatory research project in San Antonio, Texas. Overall, 464 young men who have sex with men (YMSM; < 36-years-old) completed an online, cross-sectional survey that included questions about ACEs and HIV testing behavior. An association between increased ACEs exposure and the odds of clinic-based testing and HIVST HIV significantly decreased relative to never testing for HIV. Additionally, greater ACEs exposure was significantly associated with increased odds of reporting community-based testing (AOR = 1.09, 95% CI = 1.00, 1.20) and significantly reduced odds of HIV self-testing (AOR = 0.72, 95% CI = 0.63, 0.82) compared to clinic-based testing. Cumulative ACEs exposure is important in understanding HIV testing behaviors in YMSM and should be considered when developing HIV testing programs.

Development and psychometric properties of the sexual and gender minority adverse childhood experiences (SGM-ACEs): Effect on sexual and gender minority adult mental health.

BACKGROUND: Research has consistently shown a relationship between adverse childhood experiences (ACEs) and poor mental health outcomes, and recent research shows that sexual and gender minority (SGM) individuals are at increased risk for ACEs. Moreover, SGM individuals may experience unique ACEs. Increased risk for exposure to traditional and SGM-specific ACEs are related to heterosexism. OBJECTIVE: The purpose of this paper is two-fold. First, establish the need for an SGM specific ACEs framework that accounts for exposure to heterosexism. Second, assess the psychometric properties of the SGM-ACEs scale. PARTICIPANTS AND SETTING: Data were collected using a multifaceted sampling strategy. In total, 1725 self-identified SGM Texans completed an online survey about ACEs, SGM-ACEs, mental health diagnoses, and demographic characteristics. RESULTS: The most commonly reported SGM-ACEs were seeing or hearing of other SGM being physical harmed (71.2%), being bullied in school for being SGM (67.9%), and hearing religious leaders say homophobic, biphobic, or transphobic things (60.8%). The EFA showed that 7-items loaded onto a single factor and the CFA indicated a good model fit, with items showing a significant factor loading higher than 0.60. SGM-ACE showed adequate to good psychometric properties and predicted depression (AOR = 1.49, CI = 1.20, 1.86), anxiety (AOR = 1.61, CI = 1.25, 2.00), and PTSD (AOR = 1.97, CI = 1.47, 2.66), when controlling for ACEs and demographic factors. CONCLUSIONS: The 7-item SGM-ACEs measure is a psychometrically sound and unidimensional measure that can be quickly used to assess common adverse childhood experiences related to heterosexism.

Epigenetic Regulation of F2RL3 Associates With Myocardial Infarction and Platelet Function.

BACKGROUND: DNA hypomethylation at the F2RL3 (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. F2RL3 encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease. METHODS: We conducted multiple independent experiments to assess whether DNA hypomethylation at F2RL3 in response to smoking is associated with risk of myocardial infarction via changes to platelet reactivity. Using cohort data (N=3205), we explored the relationship between smoking, DNA hypomethylation at F2RL3, and myocardial infarction. We compared platelet reactivity in individuals with low versus high DNA methylation at F2RL3 (N=41). We used an in vitro model to explore the biological response of F2RL3 to cigarette smoke extract. Finally, a series of reporter constructs were used to investigate how differential methylation could impact F2RL3 gene expression. RESULTS: Observationally, DNA methylation at F2RL3 mediated an estimated 34% of the smoking effect on increased risk of myocardial infarction. An association between methylation group (low/high) and platelet reactivity was observed in response to PAR4 (protease-activated receptor 4) stimulation. In cells, cigarette smoke extract exposure was associated with a 4.9% to 9.3% reduction in DNA methylation at F2RL3 and a corresponding 1.7-(95% CI, 1.2-2.4, P=0.04) fold increase in F2RL3 mRNA. Results from reporter assays suggest the exon 2 region of F2RL3 may help control gene expression. CONCLUSIONS: Smoking-induced epigenetic DNA hypomethylation at F2RL3 appears to increase PAR4 expression with potential downstream consequences for platelet reactivity. Combined evidence here not only identifies F2RL3 DNA methylation as a possible contributory pathway from smoking to cardiovascular disease risk but from any feature potentially influencing F2RL3 regulation in a similar manner.

Protective factors in preventing delinquency: Caregiver support, caregiver monitoring, and school engagement.

Youth who are potential victims of maltreatment are more likely to commit delinquent acts, which may lead to incarceration. Applying a resiliency framework may shift the focus to positive adaptation. For instance, protective mechanisms promote social, academic, and conduct competencies for at-risk youth. This analysis estimated the protective effects of caregiver perceived support, and caregiver monitoring, and school engagement. It used delinquency as a measure of conduct competence. A latent variable structural equation model was developed using a sample of 1054 youth aged 11-17 who were involved with Child Protective Services. Participants were drawn from the second National Survey for Child and Adolescent Well-Being. Results indicated that perceived support and school engagement reduced minor offenses, and the latter additionally reduced crimes against persons and property. Perceived caregiver monitoring, in contrast, increased minor offenses and crimes against persons. Generally, delinquent acts were associated with lower levels of the protective mechanisms, which, in turn, led to future delinquent acts. Results highlight the important role schools play as a resource for at-risk youth. Additionally, caregiver monitoring may better serve as a protective mechanism when youth voluntarily offer information. Strengths and limitations are discussed.

Moray eels are more common on coral reefs subject to higher human pressure in the greater Caribbean.

Proximity and size of the nearest market ('market gravity') have been shown to have strong negative effects on coral reef fish communities that can be mitigated by the establishment of closed areas. However, moray eels are functionally unique predators that are generally not subject to targeted fishing and should therefore not directly be affected by these factors. We used baited remote underwater video systems to investigate associations between morays and anthropogenic, habitat, and ecological factors in the Caribbean region. Market gravity had a positive effect on morays, while the opposite pattern was observed in a predator group subject to exploitation (sharks). Environmental DNA analyses corroborated the positive effect of market gravity on morays. We hypothesize that the observed pattern could be the indirect result of the depletion of moray competitors and predators near humans.

How often were you traumatized? Reconceptualizing adverse childhood experiences for sexual and gender minorities.

INTRODUCTION: The manifold consequences of adverse childhood experiences (ACEs) are well-documented. Recent research has demonstrated that sexual and gender minorities (SGMs) typically encounter ACEs more often than cisgender heterosexual individuals. Given the higher exposure rate, the measurement of frequency of exposure to traumatic events may be relevant for SGMs. METHODS: We changed the response options of the ACEs index from dichotomous to a five-point Likert scale that described frequency of exposure. As part of a larger community-based participatory research study, the Likert ACEs measure was distributed to a large and diverse sample of SGM participants in San Antonio. RESULTS: A cross-validation design demonstrated that the Likert ACEs scores outperformed the traditional ACEs index in predicting self-reported anxiety and post-traumatic stress disorder. Half of the SGMs in this sample experienced 3 or more ACEs, compared to only 10% of Americans in a nationally representative sample. LIMITATIONS: These analyses were based on retrospective self-report data instead of structured clinical interviews. Since only the Likert ACEs was administered, we had to assume that any response other than "never" on Likert ACEs corresponded to "yes" on the ACEs Index. CONCLUSIONS: Future research may assess the utility of the Likert ACEs approach with other minoritized or intersectional populations. For clinical practitioners, these results suggest that a better way to measure ACEs for SGMs is to ask them how often they were exposed, rather than asking whether they were exposed.

Author Correction: Global status and conservation potential of reef sharks.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Global status and conservation potential of reef sharks.

Decades of overexploitation have devastated shark populations, leaving considerable doubt as to their ecological status1,2. Yet much of what is known about sharks has been inferred from catch records in industrial fisheries, whereas far less information is available about sharks that live in coastal habitats3. Here we address this knowledge gap using data from more than 15,000 standardized baited remote underwater video stations that were deployed on 371 reefs in 58 nations to estimate the conservation status of reef sharks globally. Our results reveal the profound impact that fishing has had on reef shark populations: we observed no sharks on almost 20% of the surveyed reefs. Reef sharks were almost completely absent from reefs in several nations, and shark depletion was strongly related to socio-economic conditions such as the size and proximity of the nearest market, poor governance and the density of the human population. However, opportunities for the conservation of reef sharks remain: shark sanctuaries, closed areas, catch limits and an absence of gillnets and longlines were associated with a substantially higher relative abundance of reef sharks. These results reveal several policy pathways for the restoration and management of reef shark populations, from direct top-down management of fishing to indirect improvement of governance conditions. Reef shark populations will only have a high chance of recovery by engaging key socio-economic aspects of tropical fisheries.

Nuclear actin regulates cell proliferation and migration via inhibition of SRF and TEAD.

Actin dynamics regulate cell behaviour in response to physiological signals. Here we demonstrate a novel role for nuclear actin in inhibiting cell proliferation and migration. We demonstrate that physiological signals that elevate cAMP, which is anti-mitogenic in vascular smooth muscle cells, increases nuclear actin monomer levels. Expression of a nuclear-targeted polymerisation-defective actin mutant (NLS-ActinR62D) inhibited proliferation and migration. Preventing nuclear actin monomer accumulation by enhancing its nuclear export or polymerisation reversed the anti-mitogenic and anti-migratory effects of cAMP. Transcriptomic analysis identified repression of proliferation and migration associated genes regulated by serum response factor (SRF) and TEA Domain (TEAD) transcription factors. Accordingly, NLS-ActinR62D inhibited SRF and TEAD activity and target gene expression, and these effects were reversed by constitutively-active mutants of the TEAD and SRF co-factors YAP, TAZ and MKL1. In summary, intranuclear actin inhibits proliferation and migration by inhibiting YAP-TEAD and MKL-SRF activity. This mechanism explains the anti-mitogenic and anti-migratory properties of physiological signals that elevate cAMP. SUMMARY: McNeill et al show that increased levels of intranuclear actin monomer inhibit cell proliferation and migration by inhibiting MKL1-SRF and YAP/TAZ-TEAD-dependent gene expression. This mechanism mediates the anti-mitogenic and anti-migratory effects of physiological signals that elevate cyclic-AMP.