Antibodies expand the scope of angiotensin receptor pharmacology.

G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue and cellular levels. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays and structural studies, we develop maternally selective heavy-chain-only antibody ('nanobody') antagonists against the angiotensin II type I receptor and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to angiotensin II type I receptor with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich and evolvable pharmacology, attesting to their potential as next-generation GPCR modulators.

COVID-19 Vaccine Information and Infertility Posts on X: Insights on a Misinformation Pandemic.

OBJECTIVE: This study aimed to evaluate misinformation surrounding infertility and the COVID-19 vaccine on X (formerly known as Twitter) by analyzing the prevalence and content of this misinformation across a sample of posts on X. METHODS: This study is a retrospective review of posts on X (formerly known as tweets) from the COVID-19-TweetIDs dataset from July 2021 and November 2021. Included posts were from crucial time points in the COVID-19 vaccine discourse and contained at least one word related to COVID-19 vaccination and fertility. Posts were analyzed and categorized based on factuality, common words, and hashtags. Descriptive statistics on total followers, account verification status, and engagement were obtained. Differences between posts on X classified as factual and misinformation were examined using analysis of variance or χ2 tests. Sentiment analysis determined if post content was generally positive, neutral, or negative. RESULTS: A total of 17,418 relevant posts on X were reviewed: 11,436 from timeframe 1 (July 2021) and 5982 from timeframe 2 (December 2021). Misinformation posts rose from 29.9% in July 2021 to 45.1% in November 2021. In both timeframes, accounts sharing factual information had more followers (p < 0.001), and verified users were more likely to share accurate posts (p ≤ 0.001). Factual and misinformation posts had similar engagement. Sentiment analysis identified that real posts were more positive and misinformation posts were more negative (p < 0.001). CONCLUSIONS AND RELEVANCE: Misinformation about the COVID-19 vaccine and fertility is highly prevalent on X and threatens vaccine uptake in patients desiring future fertility. Accounts sharing factual information were likely to have more followers and be verified; therefore, verifying more physicians sharing accurate information is critical.

Revisiting poly(vinyl chloride) reactivity in the context of chemical recycling.

Poly(vinyl chloride) (PVC) is one of the highest production volume polymers due to its many applications, and it is one of the least recycled due to its chemical structure and frequent formulation with additives. Developing efficient PVC recycling techniques would enable PVC waste to be reused or repurposed in other processes. Within this context, the literature on PVC modification offers considerable insight into versatile reaction pathways, potentially inspiring new approaches for repurposing PVC waste into value-added products. This perspective provides an overview of PVC functionalization through a lens of chemical recycling, discussing various PVC reactivity trends and their applications with a critical assessment and future outlook of their recycling implications.

Barriers to cervical cancer prevention in a safety net clinic: gaps in HPV vaccine provider recommendation and series completion among Ob/Gyn patients.

Objective: The primary objective of this study was to evaluate patients' knowledge regarding HPV vaccination and vaccine uptake in a diverse patient population. The secondary objective was to evaluate factors influencing the decision to vaccinate, potential barriers to vaccination, and to assess whether HPV vaccines were offered to or discussed with eligible patients in a safety net Obstetrics and Gynecology (Ob/Gyn) clinic. Methods: A 28-item survey was developed using Likert scale survey questions to assess patient agreement with statements regarding HPV and the vaccine. The surveys were administered to patients in the Ob/Gyn outpatient clinics from May 2021 through September 2022. Additionally, pharmacy data were reviewed and chart review was performed as a quality improvement initiative to assess the impact of expanded HPV vaccine eligibility to patients with private insurance on vaccine uptake. Descriptive statistics were performed. Results: 304 patients completed surveys from May 2021 through September 2022. The median age of respondents was 32 (range 18-80). 16 (5%) were Non-Hispanic White, 124 (41%) were Hispanic White, 58 (19%) were Non-Hispanic Black, 6 (2%) were Hispanic Black, 29 (9.5%) were Haitian, 44 (14%) were Hispanic Other, 7 (2%) were Non-Hispanic Other, 20 (6.6%) did not respond. 45 (14%) patients were uninsured. Many patients (62%) reported that a physician had never discussed HPV vaccination with them. Seventy nine percent of patients reported they had never received the HPV vaccine, and 69% of patients reported that lack of a medical provider recommendation was a major barrier. Among patients to whom HPV vaccination had been recommended, 57% reported that the vaccine was not available the same day in clinic. Conclusion: Our study demonstrated that many patients never had a provider discuss HPV vaccination with them and never received the HPV vaccine. Additionally, amongst those who did initiate HPV vaccination, completion of the series remains a key barrier. Ensuring that providers discuss HPV vaccination and that patients receive HPV vaccines, along with expanding access to and convenience of HPV vaccination are critical aspects of preventing cervical cancer.

Long-Acting Reversible Contraception Knowledge Among Female Adolescents Presenting to a Pediatric Emergency Department.

OBJECTIVES: The objective of this study was to assess awareness and use of long-acting reversible contraception (LARC) among female adolescents presenting to a pediatric emergency department (PED). STUDY DESIGN: During routine presentation to an urban PED in New Jersey, female adolescents, aged 15-19 years, were asked to voluntarily complete an electronic survey about sexual practices and contraception. The PED is in an urban teaching hospital, treating 35,000 children annually. Patients could schedule a follow-up appointment at the hospital's obstetrics/gynecology clinic. Data were collected over 13 months, and follow-up was monitored to determine if they attended an outpatient appointment, and if so, what the outcome was. RESULTS: Data for 199 participants were analyzed. The median age of participants was 18 years, whereas 79% self-identified as Black, and 17.6% self-identified as Latina. Twenty-one percent of participants used a form of birth control during their first sexual encounter, the largest percentage being condoms (77.8%). Forty percent of participants reported some prior knowledge about contraceptive implants, and 20% had knowledge about intrauterine devices, whereas only 3 (1.5%) intrauterine devices and 2 (1%) arm implants had been previously used. Of the 78 participants that requested a follow-up, 14 (17.9%) completed their appointment. Of those, 2 (14%) were prescribed contraception (Depo-Provera shot and oral contraceptive pills). CONCLUSIONS: Knowledge about LARC remains low in our PED, despite it being the most effective method of contraception. Even when interventions were made to link interested respondents to outpatient women's health services, follow-up attendance was poor, and no patients obtained LARC. There is a significant discrepancy between the consensus standard of contraception care across all relevant medical specialties and current utilization by high-risk populations. Future efforts must focus on how to close this gap, and the ED could be pivotal for improving both reproductive health education and intervention among adolescent patients.

Making bioinformatics training FAIR: the EMBL-EBI training portal.

EMBL-EBI provides a broad range of training in data-driven life sciences. To improve awareness and access to training course listings and to make digital learning materials findable and simple to use, the EMBL-EBI Training website, www.ebi.ac.uk/training, was redesigned and restructured. To provide a framework for the redesign of the website, the FAIR (findable, accessible, interoperable, reusable) principles were applied to both the listings of live training courses and the presentation of on-demand training content. Each of the FAIR principles guided decisions on the choice of technology used to develop the website, including the details provided about training and the way in which training was presented. Since its release the openly accessible website has been accessed by an average of 58,492 users a month. There have also been over 12,000 unique users creating accounts since the functionality was added in March 2022, allowing these users to track their learning and record completion of training. Development of the website was completed using the Agile Scrum project management methodology and a focus on user experience. This framework continues to be used now that the website is live for the maintenance and improvement of the website, as feedback continues to be collected and further ways to make training FAIR are identified. Here, we describe the process of making EMBL-EBI's training FAIR through the development of a new website and our experience of implementing Agile Scrum.

My Best Alaskan Life: Addressing Adolescent Mental and Reproductive Health in Alaska.

INTRODUCTION: Since 2020, a multisector research team has coordinated a youth-driven, community-based participatory research project to adapt a reproductive life plan for application in a statewide initiative called My Best Alaskan Life (MBAL). The RLP is adapted for Alaskan youth and is intended to support teens in decision-making processes reflecting cultural priorities, personal goals, and sexual and reproductive health. Background. With 46% of youth in Alaska reporting not having used a condom during their last sexual intercourse and 15% not having used contraception, unintended pregnancy and transmission of STIs will continue. Furthermore, Alaskan youth also cite high rates of hopelessness and suicidality, and research shows that poor mental health among adolescents is correlated with developing and maintaining high-risk sexual behaviors. An intervention focusing on supporting mental wellness and developing personal goals in the context of sexual health decision-making may encourage adolescents to adopt safer sexual health behaviors. METHODS: The MBAL research team completed a statewide pilot assessing the design and implementation of the tool, gathering feedback from over 700 survey responses (youth, ages 14-20); conducted 10 in-depth interviews (adult partners at community organizations and clinics); and hosted two youth-led design review sessions. FINDINGS: Questionnaire respondents were overwhelmingly positive about the tool (91% "liked or loved" the tool) and its potential applicability in their community (86% cited "very applicable"). Project next steps include incorporating design recommendations, a statewide randomized control trial and ultimately, open source access for all interested parties.

A new antibiotic traps lipopolysaccharide in its intermembrane transporter.

Gram-negative bacteria are extraordinarily difficult to kill because their cytoplasmic membrane is surrounded by an outer membrane that blocks the entry of most antibiotics. The impenetrable nature of the outer membrane is due to the presence of a large, amphipathic glycolipid called lipopolysaccharide (LPS) in its outer leaflet1. Assembly of the outer membrane requires transport of LPS across a protein bridge that spans from the cytoplasmic membrane to the cell surface. Maintaining outer membrane integrity is essential for bacterial cell viability, and its disruption can increase susceptibility to other antibiotics2-6. Thus, inhibitors of the seven lipopolysaccharide transport (Lpt) proteins that form this transenvelope transporter have long been sought. A new class of antibiotics that targets the LPS transport machine in Acinetobacter was recently identified. Here, using structural, biochemical and genetic approaches, we show that these antibiotics trap a substrate-bound conformation of the LPS transporter that stalls this machine. The inhibitors accomplish this by recognizing a composite binding site made up of both the Lpt transporter and its LPS substrate. Collectively, our findings identify an unusual mechanism of lipid transport inhibition, reveal a druggable conformation of the Lpt transporter and provide the foundation for extending this class of antibiotics to other Gram-negative pathogens.

Social concerns about anxious arousal explain the association between neural responses to anxious arousal pictures and social anxiety.

Cognitive theories propose that social anxiety disorder involves heightened attention to anxious arousal symptoms due to worries that they may evoke rejection from others. Supporting this, studies have shown that social anxiety is related to greater attention to representations of anxious arousal and to anxiety sensitivity social concerns, which refers to sensitivity to feelings of anxious arousal during social situations. However, this has not yet been tested using neural indices of attention to images depicting anxious arousal. To examine these associations, the current study examined early and sustained attentional bias to anxious arousal images using the P2 and the late positive potential (LPP), respectively. Electroencephalogram data were collected while a non-clinical sample of undergraduate students (N = 106) viewed images of people exhibiting anxious arousal in addition to blocks of negative and neutral images from the IAPS. The neural response to anxious arousal images was isolated using residual scores (e.g., using linear regression to predict the P2 elicited by anxious arousal images from the P2 elicited by neutral images (P2neutral→AA) or negative images (P2negative→AA), then saving the unstandardized residuals). There was an indirect effect of the P2neutral→AA and P2negative→AA waveforms that was explained by anxiety sensitivity social concerns. Additionally, there was an indirect effect of both LPP waveforms on social anxiety symptoms during the early time window of the LPP (400-700 ms). At the later time window of the LPP (700-1000 ms), there was an indirect effect of the LPPneutral→AA residual waveform, but not the LPPnegative→AA, on social anxiety symptoms.

Chemogenetic activation of CRF neurons as a model of chronic stress produces sex-specific physiological and behavioral effects.

Trauma and chronic stress exposure are the strongest predictors of lifetime neuropsychiatric disease presentation. These disorders often have significant sex biases, with females having higher incidences of affective disorders such as major depression, anxiety, and PTSD. Understanding the mechanisms by which stress exposure heightens disease vulnerability is essential for developing novel interventions. Current rodent stress models consist of a battery of sensory, homeostatic, and psychological stressors that are ultimately integrated by corticotropin-releasing factor (CRF) neurons to trigger corticosteroid release. These stress paradigms, however, often differ between research groups in the type, timing, and duration of stressors utilized. These inconsistencies, along with the variability of individual animals' perception and response to each stressor, present challenges for reproducibility and translational relevance. Here, we hypothesized that a more direct approach using chemogenetic activation of CRF neurons would recapitulate the effects of traditional stress paradigms and provide a high-throughput method for examining stress-relevant phenotypes. Using a transgenic approach to express the Gq-coupled Designer Receptor Exclusively Activated by Designer Drugs (DREADD) receptor hM3Dq in CRF-neurons, we found that the DREADD ligand clozapine-N-oxide (CNO) produced an acute and robust activation of the hypothalamic-pituitary-adrenal (HPA) axis, as predicted. Interestingly, chronic treatment with this method of direct CRF activation uncovered a novel sex-specific dissociation of glucocorticoid levels with stress-related outcomes. Despite hM3Dq-expressing females producing greater corticosterone levels in response to CNO than males, hM3Dq-expressing males showed significant typical physiological stress sensitivity with reductions in body and thymus weights. hM3Dq-expressing females while resistant to the physiological effects of chronic CRF activation, showed significant increases in baseline and fear-conditioned freezing behaviors. These data establish a novel mouse model for interrogating stress-relevant phenotypes and highlight sex-specific stress circuitry distinct for physiological and limbic control that may underlie disease risk.

The influence of interactions with pet dogs on psychological distress.

Many people, including nearly half of American households, own a pet dog. Previous work has found that therapy dog interactions reduce distress, but little work to date has empirically established the mood-enhancing effects of interaction with one's own pet dog. In this study, dog owners (N = 73; 86.3% female, 13.7% male; age 25-77 years) underwent a stress-inducing task followed by random assignment to either (a) interacting with their dog (n = 24), (b) an expectancy control (n = 25; "stress-reducing" coloring books), or (c) a waiting control (n = 24). We compared the effects of each condition on affect and state anxiety. Participants assigned to the dog interaction showed greater increases in positive affect, as well as greater reductions in anxiety compared to both expectancy and waiting controls (ds > 0.72, ps < .018). No significant reductions in negative affect were detected. Second, we found that self-reported experiences with animals, attitudes toward animals, or bondedness with their dog did not differentially predict the condition's impact on the owner's mood. Finally, we coded participants' degree of engagement (e.g., time spent playing) with the dog and found that higher engagement predicted reduced negative affect. Overall, interacting with one's own pet dog reduced owners' distress. Such interactions, which occur commonly in daily life, may have the potential to alleviate distress at a large scale. Precisely how this works and for whom it is especially well suited remain intriguing open questions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Probabilistic reaction norm reveals family-related variation in the association between size, condition, and sexual maturation onset in Atlantic salmon (Salmo salar).

This study investigated the relationship between the size, condition, year class, family, and sexual maturity of Atlantic salmon (Salmo salar) using data collected in an aquaculture selective breeding programme. Males that were sexually mature at 2 years of age (maiden spawn) have, on average, greater fork length and condition factor (K) at 1 year of age than their immature counterparts. For every 10-mm increase in fork length or 0.1 increase in K at 1 year of age, the odds of sexual maturity at 2 years of age increased by 1.48 or 1.22 times, respectively. Females that were sexually mature at 3 years of age (maiden spawn) have, on average, greater fork length and K at 2 years of age than their immature counterparts. For every 10-mm increase in fork length or 0.1 increase in K at 2 years of age, the odds of sexual maturity at 3 years of age increased by 1.06 or 1.44 times, respectively. The family explained 34.93% of the variation in sexual maturity among 2-year-old males that was not attributable to the average effects of fork length and K at 1 year of age and year class. The proportion of variation in sexual maturity among 3-year-old females explained by the family could not be investigated. These findings suggest that the onset of sexual maturation in Atlantic salmon is conditional on performance (with respect to energy availability) surpassing a threshold, the magnitude of which can vary between families and is determined by a genetic component. This could support the application of genetic selection to promote or inhibit the onset of sexual maturation in farmed stocks.

Barriers to Family Building Among Physicians and Medical Students.

Importance: Physicians and medical students who desire to build families face significant barriers due to the structure and culture of medicine. Objective: To understand the barriers and facilitators to family building for all people in medicine-not only individuals who can become pregnant-through an open-ended, qualitative analysis of survey responses. Design, Setting, and Participants: This qualitative study used a survey conducted in April and May 2021 with a broad sample of physicians and medical students. Participants were recruited through social media, targeting physician and medical student communities. Physicians (residents, fellows, and physicians in independent practice) and medical students of all gender identities and sexual orientations were included. Informed by a postpositivist approach, coding reliability thematic analysis was performed on 3 open-ended survey questions on family-building experiences (what they would do differently, what advice they have for others, and anything else they wished to share). Main Outcomes and Measures: Identified themes were mapped to the social-ecological model, a model used in public health to examine how a spectrum of factors is associated with health outcomes. Results: A total of 2025 people (1860 [92%] women; 299 [15%] Asian, 151 [8%] Black, and 1303 [64%] White; 1730 [85%] heterosexual; and 1200 [59%] physicians who had completed training) responded to at least 1 of 3 open-ended questions. Themes mapped to social-ecological model levels included: (1) cultural, eg, medical training being at odds with family building; (2) organizational, eg, lack of institutional support for the range of family-building routes; (3) interpersonal, eg, impact of social support on family building; and (4) individual, eg, socioeconomic status and other individual factors that facilitate or inhibit family building. Recommendations to improve family-building experiences include implementing family-building curricula at medical schools, providing adequate parental leave for all physicians and medical students who become parents, and providing insurance coverage for all family-building routes. Conclusions and Relevance: In this qualitative study of physicians and medical students, self-reported barriers to family building were identified at each level of the social-ecological model. Addressing these barriers is critical to creating a more equitable family-building environment for physicians and medical students.

Increasing densities of Pacific crown-of-thorns starfish (Acanthaster cf. solaris) at Lizard Island, northern Great Barrier Reef, resolved using a novel survey method.

Recurrent population irruptions of Pacific crown-of-thorns starfish (CoTS, Acanthaster cf. solaris) are among the foremost causes of coral mortality on Australia's Great Barrier Reef (GBR). Early intervention during the initiation of new population irruptions represents the best opportunity to effectively manage this threat. However, current survey methods are not sufficiently sensitive to detect changes in CoTS densities during the early onset of population irruptions. Using scooter-assisted large area diver-based (SALAD) surveys, this study revealed increasing densities of CoTS at Lizard Island from 2019 to 2022. Inferred densities of adult CoTS (which account for distinct sets of observed feeding scars where starfish were not detected) increased from 4.90 ha-1 (± 0.85 SE) in 2019 to 17.71 ha-1 (± 2.3 SE) in 2022. A wide range of size classes were recorded suggesting that recruitment over several years is contributing to increasing densities. Importantly, the sustained density increases reported here denote that renewed CoTS population irruptions may soon become fully established at Lizard Island and more broadly in the northern GBR, especially without early intervention through effective population management.

"You rise up and then you start pulling people up with you": Patient experiences with a peer-delivered behavioral activation intervention to support methadone treatment.

BACKGROUND: Although medications for opioid use disorder (MOUD) are efficacious treatments for opioid use disorder, retention remains low. Peer recovery specialists (PRSs), individuals with lived substance use and recovery experience, may be particularly well-suited to support patients receiving MOUD. While PRSs are rarely trained in evidence-based behavioral interventions other than motivational interviewing, preliminary evidence suggests that peers can deliver brief behavioral interventions, such as behavioral activation, with efficacy and fidelity. This qualitative study sought to explore patient perspectives on receiving an adapted PRS-delivered behavioral activation intervention (Peer Activate) to support patients receiving methadone treatment. METHODS: The sample (N = 26) included patients recently starting or demonstrating challenges with adherence at a community-based methadone treatment program who received the Peer Activate intervention in a pilot trial. Participants were invited to participate in in-depth, semi-structured interviews at study completion or discontinuation, assessing perceived acceptability and feasibility of Peer Activate, and stigma-related barriers. Interview transcripts were coded using codebook/template thematic analysis. RESULTS: Analysis revealed the importance of two areas to promote intervention acceptability: 1) connection with intervention content and skill building, and 2) valued PRS-specific qualities. Intervention flexibility was found to promote feasibility of the intervention in the context of chaotic and challenging life circumstances. Additionally, participants described stigma towards substance use and methadone treatment as potential barriers to engaging in methadone treatment. CONCLUSION: Results support the acceptability and feasibility to patients of this PRS-delivered behavioral activation intervention in the context of outpatient MOUD treatment among a low-income, majority racially minoritized patient population. Future intervention adaptation and implementation should focus on incorporating content related to relationships and interpersonal skills; balancing behavioral intervention content with system navigation support; maintaining flexibility; and further investigation of the impact of individual PRS attributes, including shared lived experiences, on intervention acceptability and shifts in stigma.

Induction of larval settlement in crown-of-thorns starfish is not mediated by conspecific cues.

Population irruptions of crown-of-thorns starfish (COTS; Acanthaster spp.) remain a major cause of coral reef degradation throughout the Pacific and Indian Oceans and are inherently modulated by larval settlement and recruitment success. Gregarious larval settlement, as exhibited by many other ecologically important marine invertebrates, can catalyse population growth and replenishment. However, whether conspecific cues induce or influence the settlement of COTS larvae remains a critical information gap. This experimental study examined the induction of COTS settlement in response to a range of conspecific cues associated with early- and late-stage herbivorous juveniles, corallivorous juveniles and adults. Competent COTS larvae were generally not induced to settle by the presence of conspecifics or cues associated with conspecifics, while the settlement success of COTS in the presence of coralline algae was not inhibited or enhanced by adding conspecific conditioned seawater. Rather than being reinforced by gregarious settlement, the recruitment of COTS populations appears dependent on associative settlement cues (i.e., coralline algae and/or associated microbial communities) signalling suitable benthic habitat.

Antibodies Expand the Scope of Angiotensin Receptor Pharmacology.

G protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue, and cellular level. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays, and structural studies, we develop maternally selective heavy chain-only antibody ("nanobody") antagonists against the angiotensin II type I receptor (AT1R) and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to AT1R with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich and evolvable pharmacology, attesting to their potential as next-generation GPCR modulators.

Regulatory response to a hybrid ancestral nitrogenase in Azotobacter vinelandii.

Biological nitrogen fixation, the microbial reduction of atmospheric nitrogen to bioavailable ammonia, represents both a major limitation on biological productivity and a highly desirable engineering target for synthetic biology. However, the engineering of nitrogen fixation requires an integrated understanding of how the gene regulatory dynamics of host diazotrophs respond across sequence-function space of its central catalytic metalloenzyme, nitrogenase. Here, we interrogate this relationship by analyzing the transcriptome of Azotobacter vinelandii engineered with a phylogenetically inferred ancestral nitrogenase protein variant. The engineered strain exhibits reduced cellular nitrogenase activity but recovers wild-type growth rates following an extended lag period. We find that expression of genes within the immediate nitrogen fixation network is resilient to the introduced nitrogenase sequence-level perturbations. Rather the sustained physiological compatibility with the ancestral nitrogenase variant is accompanied by reduced expression of genes that support trace metal and electron resource allocation to nitrogenase. Our results spotlight gene expression changes in cellular processes adjacent to nitrogen fixation as productive engineering considerations to improve compatibility between remodeled nitrogenase proteins and engineered host diazotrophs. IMPORTANCE Azotobacter vinelandii is a key model bacterium for the study of biological nitrogen fixation, an important metabolic process catalyzed by nitrogenase enzymes. Here, we demonstrate that compatibilities between engineered A. vinelandii strains and nitrogenase variants can be modulated at the regulatory level. The engineered strain studied here responds by adjusting the expression of proteins involved in cellular processes adjacent to nitrogen fixation, rather than that of nitrogenase proteins themselves. These insights can inform future strategies to transfer nitrogenase variants to non-native hosts.

Impacts of ocean warming on echinoderms: A meta-analysis.

Rising ocean temperatures are threatening marine species and populations worldwide, and ectothermic taxa are particularly vulnerable. Echinoderms are an ecologically important phylum of marine ectotherms and shifts in their population dynamics can have profound impacts on the marine environment. The effects of warming on echinoderms are highly variable across controlled laboratory-based studies. Accordingly, synthesis of these studies will facilitate the better understanding of broad patterns in responses of echinoderms to ocean warming. Herein, a meta-analysis incorporating the results of 85 studies (710 individual responses) is presented, exploring the effects of warming on various performance predictors. The mean responses of echinoderms to all magnitudes of warming were compared across multiple biological responses, ontogenetic life stages, taxonomic classes, and regions, facilitated by multivariate linear mixed effects models. Further models were conducted, which only incorporated responses to warming greater than the projected end-of-century mean annual temperatures at the collection sites. This meta-analysis provides evidence that ocean warming will generally accelerate metabolic rate (+32%) and reduce survival (-35%) in echinoderms, and echinoderms from subtropical (-9%) and tropical (-8%) regions will be the most vulnerable. The relatively high vulnerability of echinoderm larvae to warming (-20%) indicates that this life stage may be a significant developmental bottleneck in the near-future, likely reducing successful recruitment into populations. Furthermore, asteroids appear to be the class of echinoderms that are most negatively affected by elevated temperature (-30%). When considering only responses to magnitudes of warming representative of end-of-century climate change projections, the negative impacts on asteroids, tropical species and juveniles were exacerbated (-51%, -34% and -40% respectively). The results of these analyses enable better predictions of how keystone and invasive echinoderm species may perform in a warmer ocean, and the possible consequences for populations, communities and ecosystems.