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A new method for determining the onset voltage of electrospray thrusters is proposed, which specifically focuses on electrospray thrusters manufactured by laser drilling through flat plates. The novelty of this method is that it accounts for the effect of the thickness of the plate on the electrospray onset voltage requirements, while traditional methods do not. Key results from this study indicate that for certain materials a change in thickness results in a notable change in the onset voltage, which implies that the plate thickness needs to be considered when planning the design of the thruster emitters. This methodology allows for a robust method of observing the influence of key parameters on the onset voltage. These developments can potentially facilitate and improve the design of these thrusters, enabling an accurate understanding of the power requirements before manufacture.

In order to extend the orbital lifetime of spacecraft operating in Very-Low Earth Orbit (VLEO), Atmosphere-Breathing Electric Propulsion (ABEP) can be employed for atmospheric drag compensation. The concept is based on the ingestion of rarefied atmospheric particles to be used as propellant for an electric thruster, thereby removing the need for onboard propellant. The present paper aims to design and analyse a passive ABEP intake optimised for the RF Helicon-based Plasma Thruster (IPT), which is selected as the most promising system due to its electrodeless design, as it removes the issue of thruster corrosion, and reduced susceptibility to atmospheric variations. This is achieved by implementing the analytical model, referred to as the Balancing Model (BM), along with its main performance parameters. The Direct Simulation Monte Carlo (DSMC) solver dsmcFoam+ is thus employed to simulate the transmission probability of cylinders and hexagonal prisms with non-zero entrance velocity, yielding a mean percentage error of 2% when compared to independent DSMC results. In addition, a novel DSMC transmittance investigation of square prisms is performed. Various design configurations are optimised for circular and hexagonal intakes based on the functional requirements of the thruster, leading to a maximum collection efficiency of 45% for a cylindrical intake with a hexagonal honeycomb. The optimal intake is hence simulated via DSMC, showing a good accuracy with the BM with or without intermolecular collisions, yielding a percentage error of 0.22% in the former case and 5.53% in the latter one. The variation of incidence flow angle, accommodation coefficient and thruster transmission probability is finally investigated, and the results are validated by the agreement shown with values retrieved from the literature.

Auger-based transportation systems are a promising method to transport lunar regolith for in situ resource utilisation. An analytical model based on terrestrial auger conveyor industry guidelines is used to predict the behaviour and performance parameters of an auger conveyor system under a range of initial conditions. Key aspects of the model have been validated with published experimental data. The proposed model produces more accurate predictions than previous methods and calculates the inclination angle with the best conveying efficiency. The proposed model output flow predictions have on average $$47\%$$ 47 % less deviation from the experimental data mean than previous model predictions, while the predictions for power requirements without considering energy losses present 42.9% and $$59.2\%$$ 59.2 % less deviation than previous predictions. When the losses are considered, the proposed model predictions are 70% and $$86.4\%$$ 86.4 % more accurate than the previous models, which have been found to underestimate the power requirements of this type of conveyors.

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

Establishing a permanent human presence on the Moon or Mars requires a secure supply of oxygen for life support and refueling. The electrolysis of water has attracted significant attention in this regard as water-ice may exist on both the Moon and Mars. However, to date there has been no study examining how the lower gravitational fields on the Moon and Mars might affect gas-evolving electrolysis when compared to terrestrial conditions. Herein we provide experimental data on the effects of gravitational fields on water electrolysis from 0.166 g (lunar gravity) to 8 g (eight times the Earth’s gravity) and show that electrolytic oxygen production is reduced by around 11% under lunar gravity with our system compared to operation at 1 g. Moreover, our results indicate that electrolytic data collected using less resource-intensive ground-based experiments at elevated gravity (>1 g) may be extrapolated to gravitational levels below 1 g.

Digital innovations in mental health offer great potential, but present unique challenges. Using a consensus development panel approach, an expert, international, cross-disciplinary panel met to provide a framework to conceptualise digital mental health innovations, research into mechanisms and effectiveness and approaches for clinical implementation. Key questions and outputs from the group were agreed by consensus, and are presented and discussed in the text and supported by case examples in an accompanying appendix. A number of key themes emerged. (1) Digital approaches may work best across traditional diagnostic systems: we do not have effective ontologies of mental illness and transdiagnostic/symptom-based approaches may be more fruitful. (2) Approaches in clinical implementation of digital tools/interventions need to be creative and require organisational change: not only do clinicians and patients need training and education to be more confident and skilled in using digital technologies to support shared care decision-making, but traditional roles need to be extended, with clinicians working alongside digital navigators and non-clinicians who are delivering protocolised treatments. (3) Designing appropriate studies to measure the effectiveness of implementation is also key: including digital data raises unique ethical issues, and measurement of potential harms is only just beginning. (4) Accessibility and codesign are needed to ensure innovations are long lasting. (5) Standardised guidelines for reporting would ensure effective synthesis of the evidence to inform clinical implementation. COVID-19 and the transition to virtual consultations have shown us the potential for digital innovations to improve access and quality of care in mental health: now is the ideal time to act. ispartof: BMJ Ment Health vol:26 issue:1 pages:e300670- ispartof: location:England status: published

To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear.To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment.Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered.Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible.An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths.In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations.The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships.Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures.Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Background The COVID-19 pandemic required mental health services around the world to adapt quickly to the new restrictions and regulations put in place to reduce the risk of transmission. As face-to-face contact became difficult, virtual methods were implemented to continue to safely provide mental health care. However, it is unclear to what extent service provision transitioned to telemental health worldwide. Objective We aimed to systematically review the global research literature on how mental health service provision adapted during the first year of the pandemic. Methods We searched systematically for quantitative papers focusing on the impact of the COVID-19 pandemic on mental health services published until April 13, 2021, in the PubMed, Embase, medRxiv, and bioXriv electronic bibliographic databases, using the COVID-19 Open Access Project online platform. The screening process and data extraction were independently completed by at least two authors, and any disagreement was resolved by discussion with a senior member of the team. The findings were summarized narratively in the context of each country’s COVID-19 Stringency Index, which reflects the stringency of a government’s response to COVID-19 restrictions at a specific time. Results Of the identified 24,339 records, 101 papers were included after the screening process. Reports on general services (n=72) showed that several countries’ face-to-face services reduced their activities at the start of the pandemic, with reductions in the total number of delivered visits and with some services forced to close. In contrast, telemental health use rapidly increased in many countries across the world at the beginning of the pandemic (n=55), with almost complete virtualization of general and specialistic care services by the end of the first year. Considering the reported COVID-19 Stringency Index values, the increased use of virtual means seems to correspond to periods when the Stringency Index values were at their highest in several countries. However, due to specific care requirements, telemental health could not be used in certain subgroups of patients, such as those on clozapine or depot treatments and those who continued to need face-to-face visits. Conclusions During the pandemic, mental health services had to adapt quickly in the short term, implementing or increasing the use of telemental health services across the globe. Limited access to digital means, poor digital skills, and patients’ preferences and individual needs may have contributed to differences in implementing and accessing telemental health services during the pandemic. In the long term, a blended approach, combining in-person and virtual modalities, that takes into consideration the needs, preferences, and digital skills of patients may better support the future development of mental health services. It will be required to improve confidence with digital device use, training, and experience in all modalities for both clinicians and service users.

BACKGROUND The COVID-19 pandemic required mental health services around the world to adapt quickly to the new restrictions and regulations put in place to reduce the risk of transmission. As face-to-face contacts became difficult, virtual methods were implemented to continue to safely provide mental health care. However, it is unclear to what extent service provision transitioned to tele-mental health worldwide. OBJECTIVE We aimed to systematically review the global research literature on how mental health service provision adapted during the first year of the pandemic. METHODS We searched systematically for quantitative papers focussing on the impact of the COVID-19 pandemic on mental health services published until the 13th of April 2021, accessing PubMed, EMBASE, medRxiv and bioXriv electronic bibliographic databases using the COVID-19 Open Access Project online platform. After the screening process and the data extraction, findings were summarised narratively in the context of each country’s COVID-19 stringency index, which reflects the stringency of a government’s response to COVID-19 restrictions at a specific time. RESULTS Of the identified 24339 records, 101 papers were included after the screening process. Reports on general services (n=72) showed that in several countries’ face-to-face services reduced their activities at the start of the pandemic, with a reduction in the total number of delivered visits and some services forced to close. In contrast, the use of tele-mental health rapidly increased in many countries across the world at the beginning of the pandemic (n=55), with almost complete virtualisation of general and specialistic care services by the end of the first year. In light of the reported COVID-19 stringency indexes, the increased use of virtual means seems to correspond to periods when stringency indexes were at their highest in several countries. However, due to specific care requirements, the use of tele-mental health could not be applied to certain subgroups of patients, such as those on clozapine or depot treatments and those who continued to need face-to-face visits. CONCLUSIONS During the pandemic mental health services have had to adapt quickly in the short-term, implementing or increasing the use of tele-mental health services across the globe. In the long-term, a blended approach, combining in-person and virtual modalities, that takes into consideration the needs, preferences, and competences of patients, may better support the future development of mental health services. This will require confidence, training, and experience in all modalities for both clinicians and service-users.

There is increased industry focus on optimised welfare, productivity and antibiotic usage in cattle youngstock, however, little is known about UK farmers' attitudes and practices in rearing calves. In this cross-sectional study, 479 farmers were surveyed online about their cattle youngstock rearing approach and outcomes. Represented were 174 dairy farmers, 255 beef suckler farmers and 50 calf rearers. Farmers showed awareness of good youngstock rearing practices such as colostrum management and housing facilities. Morbidity and mortality from diarrhoea (82%, 48%) and bovine respiratory disease (BRD) (68%, 48%) were high on farms surveyed but farmers did not frequently consult their veterinary surgeon regarding these diseases. Farmers surveyed were not always aware of the efficacy of preventative methods such as vaccination, and frequently used antibiotic treatments (27% for diarrhoea and 40% for BRD) but not diagnostics when animals had disease. Veterinary surgeons could use these insights to better understand farmers' motivations and priorities, to make communication more efficient and align goals.

Background Mannheimia haemolytica is commonly associated with respiratory disease in cattle worldwide as a cause of fibrinous pneumonia, bronchopneumonia and pleuritis. M. haemolytica is further subdivided into 12 serovars, however not all are considered to be pathogenic in cattle. The study aim was to determine the most common serovars of M. haemolytica associated with respiratory disease in cattle in Great Britain, which is currently unknown and could be useful information for clinicians when considering preventative strategies. Results One hundred four M. haemolytica isolates isolated from bovine clinical pathology and post-mortem samples from pneumonia cases between 2016 and 2018 were tested using a multiplex PCR assay to identify M. haemolytica serovars A1, A2 and A6. 46 isolates (44.2%) typed as M. haemolytica serovar A1, 31 (29.8%) as M. haemolytica serovar A2 and 18 isolates (17.3%) as M. haemolytica serovar A6. Nine isolates (8.7%) were not A1, A2 or A6 so were considered to belong to other serovars or were not typable. Conclusion This study highlights the importance of M. haemolytica serovars other than A1 which may be responsible for respiratory disease in cattle and could help guide the veterinarian when making choices on preventative vaccination programmes.

BACKGROUND Bovine respiratory disease (BRD) is common in cattle youngstock on UK dairy farms. The current diagnostic methods lack sensitivity and specificity. Thoracic ultrasound (TUS) is a relatively new BRD diagnostic tool with increased accuracy. METHOD Data were collected from TUS examinations of 347 calves on Scottish dairy farms and compared to farmer BRD treatment rates. A calf health scoring tool was used to collect information on youngstock health and management on these farms. RESULTS Of 347 ultrasonographic examinations, 53 (15.3%) were classified as abnormal and 294 (84.7%) as normal. Of the 53 calves classified as abnormal, only 13 (24.5%) were treated by the farmer; however, of the 294 classified as normal, 22 (7.5%) were treated. CONCLUSION The results indicated farmers were misdiagnosing BRD in youngstock. Use of TUS on UK farms may improve diagnostic rates and accuracy, reduce the unnecessary use of antimicrobials and demonstrate the value of preventive healthcare programmes.

The COVID-19 pandemic and its aftermath have increased pre-existing inequalities and risk factors for mental disorders in general, but perinatal mental disorders are of particular concern. They are already underdiagnosed and undertreated, and this has been magnified by the pandemic. Access to services (both psychiatric and obstetric) has been reduced, and in-person contact has been restricted because of the increased risks. Rates of perinatal anxiety and depressive symptoms have increased. In the face of these challenges, clear guidance in perinatal mental health is needed for patients and clinicians. However, a systematic search of the available resources showed only a small amount of guidance from a few countries, with a focus on the acute phase of the pandemic rather than the challenges of new variants and variable rates of infection. Telepsychiatry offers advantages during times of restricted social contact and also as an additional route for accessing a wide range of digital technologies. While there is a strong evidence base for general telepsychiatry, the particular issues in perinatal mental health need further examination. Clinicians will need expertise and training to navigate a hybrid model, flexibly combining in person and remote assessments according to risk, clinical need and individual patient preferences. There are also wider issues of care planning in the context of varying infection rates, restrictions and vaccination access in different countries. Clinicians will need to focus on prevention, treatment, risk assessment and symptom monitoring, but there will also need to be an urgent and coordinated focus on guidance and planning across all organisations involved in perinatal mental health care.

Significance Many of the world’s marine fish spend the first days to weeks feeding and developing at the ocean surface. However, very little is known about the ocean processes that govern larval fish survivorship and hence adult fish populations that supply essential nutrients and protein to human societies. We demonstrate that surface slicks, meandering lines of convergence on the ocean surface, are important larval fish nurseries that disproportionately accumulate nonnutritious, toxin-laden prey-size plastics. Plastic pieces were found in numerous larval fish taxa at a time when nutrition is critical for survival. Surface slicks are a ubiquitous coastal ocean feature, suggesting that plastic accumulation in these larval fish nurseries could have far reaching ecological and socioeconomic impacts., Life for many of the world’s marine fish begins at the ocean surface. Ocean conditions dictate food availability and govern survivorship, yet little is known about the habitat preferences of larval fish during this highly vulnerable life-history stage. Here we show that surface slicks, a ubiquitous coastal ocean convergence feature, are important nurseries for larval fish from many ocean habitats at ecosystem scales. Slicks had higher densities of marine phytoplankton (1.7-fold), zooplankton (larval fish prey; 3.7-fold), and larval fish (8.1-fold) than nearby ambient waters across our study region in Hawai‘i. Slicks contained larger, more well-developed individuals with competent swimming abilities compared to ambient waters, suggesting a physiological benefit to increased prey resources. Slicks also disproportionately accumulated prey-size plastics, resulting in a 60-fold higher ratio of plastics to larval fish prey than nearby waters. Dissections of hundreds of larval fish found that 8.6% of individuals in slicks had ingested plastics, a 2.3-fold higher occurrence than larval fish from ambient waters. Plastics were found in 7 of 8 families dissected, including swordfish (Xiphiidae), a commercially targeted species, and flying fish (Exocoetidae), a principal prey item for tuna and seabirds. Scaling up across an ∼1,000 km2 coastal ecosystem in Hawai‘i revealed slicks occupied only 8.3% of ocean surface habitat but contained 42.3% of all neustonic larval fish and 91.8% of all floating plastics. The ingestion of plastics by larval fish could reduce survivorship, compounding threats to fisheries productivity posed by overfishing, climate change, and habitat loss.

Neurons are highly complex polarized cells, displaying an extraordinary degree of spatial compartmentalization. At presynaptic and postsynaptic sites, far from the cell body, local protein synthesis is utilized to continually modify the synaptic proteome, enabling rapid changes in protein production to support synaptic function. Synapses undergo diverse forms of plasticity, resulting in long-term, persistent changes in synapse strength, which are paramount for learning, memory, and cognition. It is now well-established that local translation of numerous synaptic proteins is essential for many forms of synaptic plasticity, and much work has gone into deciphering the strategies that neurons use to regulate activity-dependent protein synthesis. Recent studies have pointed to a coordination of the local mRNA translation required for synaptic plasticity and the trafficking of membranous organelles in neurons. This includes the co-trafficking of RNAs to their site of action using endosome/lysosome “transports,” the regulation of activity-dependent translation at synapses, and the role of mitochondria in fueling synaptic translation. Here, we review our current understanding of these mechanisms that impact local translation during synaptic plasticity, providing an overview of these novel and nuanced regulatory processes involving membranous organelles in neurons.

Mitochondria are critical metabolic and signaling hubs and dysregulated mitochondrial homeostasis is implicated in many diseases. Degradation of damaged mitochondria by selective GABARAP/LC3-dependent macro-autophagy (mitophagy) is critical for maintaining mitochondrial homeostasis. To identify alternate forms of mitochondrial quality control that functionally compensate if mitophagy is inactive, we selected for autophagy-dependent cancer cells that survived loss of LC3-dependent autophagosome formation caused by inactivation of ATG7 or RB1CC1/FIP200. We discovered rare surviving autophagy-deficient clones that adapted to maintain mitochondrial homeostasis after gene inactivation and identified two co-opted mechanisms including enhanced mitochondrial dynamics and enhanced mitochondrial derived vesicles (MDVs). To further understand the mechanism behind MDV formation, we utilized a novel technique to quantify MDVs via flow cytometry and confirmed an SNX9-mediated mechanism necessary for flux of MDVs to lysosomes. We show that the autophagy-dependent cells acquire novel dependencies on these processes, indicating that these alternate forms of mitochondrial homeostasis compensate for loss of autophagy to maintain mitochondrial health.

The basolateral amygdala (BLA) plays a vital role in associating sensory stimuli with salient valence information. Excitatory principal neurons (PNs) undergo plastic changes to encode this association; however, local BLA inhibitory interneurons (INs) gate PN plasticity via feedforward inhibition (FFI). Despite literature implicating parvalbumin expressing (PV+) INs in FFI in cortex and hippocampus, prior anatomical experiments in BLA implicate somatostatin expressing (Sst+) INs. The lateral entorhinal cortex (LEC) projects to BLA where it drives FFI. In the present study, we explored the role of interneurons in this circuit. Using mice, we combined patch clamp electrophysiology, chemogenetics, unsupervised cluster analysis, and predictive modeling and found that a previously unreported subpopulation of fast-spiking Sst+ INs mediate LEC→BLA FFI.

GABAergic synaptic inhibition controls neuronal firing, excitability, and synaptic plasticity to regulate neuronal circuits. Following an acute excitotoxic insult, inhibitory synapses are eliminated, reducing synaptic inhibition, elevating circuit excitability, and contributing to the pathophysiology of brain injuries. However, mechanisms that drive inhibitory synapse disassembly and elimination are undefined. We find that inhibitory synapses are disassembled in a sequential manner following excitotoxicity: GABA

Lines of smooth ocean surface water known as “slicks” appear in coastal waters worldwide and can be caused by a number of natural mechanisms. Off the western coast of the island of Hawai‘i, USA, internal waves, submarine groundwater discharge, tidal fronts, and headland fronts were all observed to cause the formation of slicks. Neuston net sampling showed slicks to contain enhanced densities of phytoplankton, zooplankton, larval invertebrates, larval fish, and plastic fragments when compared to ambient water. In particular, internal wave slicks were observed to be both the most frequently occurring type of slick and the overall strongest accumulator of neustonic organisms and plastics when compared to the other types of slicks. Satellite imagery illustrated that slicks are visible along most of the West Hawai‘i coastline more than 75% of the time. Furthermore, acoustic backscatter observations showed that the accumulation associated with slicks frequently extended from the surface to depths of 5 m. These findings highlight the important roles internal wave slicks can have in coastal ecosystems.

The repertoire and abundance of proteins displayed on the surface of neuronal dendrites are tuned by regulated fusion of recycling endosomes (REs) with the dendritic plasma membrane. While this process is critical for neuronal function and plasticity, how synaptic activity drives RE fusion remains unexplored. We demonstrate a multistep fusion mechanism that requires Ca2+ from distinct sources. NMDA receptor Ca2+ initiates RE fusion with the plasma membrane, while L-type voltage-gated Ca2+ channels (L-VGCCs) regulate whether fused REs collapse into the membrane or reform without transferring their cargo to the cell surface. Accordingly, NMDA receptor activation triggered AMPA-type glutamate receptor trafficking to the dendritic surface in an L-VGCC-dependent manner. Conversely, potentiating L-VGCCs enhanced AMPA receptor surface expression only when NMDA receptors were also active. Thus L-VGCCs play a role in tuning activity-triggered surface expression of key synaptic proteins by gating the mode of RE fusion.

Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded byCDH10within the ASD risk locus 5p14.1, maintains both excitatory and inhibitory synaptic scaffold structure in cultured cortical neurons from rats of both sexes. Cadherin-10 localizes to both excitatory and inhibitory synapses in neocortex, where it is organized into nanoscale puncta that influence the size of their associated PSDs. Knockdown of cadherin-10 reduces excitatory but increases inhibitory synapse size and strength, altering the E/I ratio in cortical neurons. Furthermore, cadherin-10 exhibits differential participation in complexes with PSD-95 and gephyrin, which may underlie its role in maintaining the E/I ratio. Our data provide a new mechanism whereby a protein encoded by a common ASD risk factor controls E/I ratios by regulating excitatory and inhibitory synapses in opposing directions.SIGNIFICANCE STATEMENTThe correct balance between excitatory/inhibitory (E/I) is crucial for normal brain function and is altered in psychiatric disorders such as autism. However, the molecular mechanisms that underlie this balance remain elusive. To address this, we studied cadherin-10, an adhesion protein that is genetically linked to autism and understudied at the cellular level. Using a combination of advanced microscopy techniques and electrophysiology, we show that cadherin-10 forms nanoscale puncta at excitatory and inhibitory synapses, maintains excitatory and inhibitory synaptic structure, and is essential for maintaining the correct balance between excitation and inhibition in neuronal dendrites. These findings reveal a new mechanism by which E/I balance is controlled in neurons and may bear relevance to synaptic dysfunction in autism.

Brain ischemia causes oxygen and glucose deprivation (OGD) in neurons, triggering a cascade of events leading to synaptic accumulation of glutamate. Excessive activation of glutamate receptors causes excitotoxicity and delayed cell death in vulnerable neurons. Following global cerebral ischemia, hippocampal CA1 pyramidal neurons are more vulnerable to injury than theircortical counterparts, but the mechanisms that underlie this difference are unclear. Signaling via Rho-family small GTPases, their upstream guanine nucleotide exchange factors, and GTPase-activating proteins (GAPs) is differentially dysregulated in response to OGD/ischemia in hippocampal and cortical neurons. Increased Rac1 activity caused by OGD/ischemia contributesto neuronal death in hippocampal neurons via diverse effects on NADPH oxidase activity and dendritic spine morphology. The Rac1 guanine nucleotide exchange factor Tiam1 mediates an OGD-induced increase in Rac1 activity in hippocampalneurons; however, the identity of an antagonistic GAP remains elusive. Here we show that the Rac1 GAP breakpoint cluster region (BCR) associates with NMDA receptors (NMDARs) along with Tiam1 and that this protein complex is more abundant in hippocampal compared with cortical neurons. Although total BCR is similar in the two neuronal types, BCR is more active in hippocampal compared with cortical neurons. OGD causes an NMDAR- and Ca2-permeable AMPARdependent deactivation of BCR in hippocampal but not corticalneurons. BCR knockdown occludes OGD-induced Rac1 activation in hippocampal neurons. Furthermore, disrupting the Tiam1–NMDAR interaction with a fragment of Tiam1 blocks OGD-induced Tiam1 activation but has no effect on the deactivation of BCR. This work identifies BCR as a critical player in Rac1 regulation during OGD in hippocampal neurons.

The influence of rotation on the structure and propagation of internal tides around O'ahu, Hawai'i is investigated using in situ observations and a tidally forced, primitive equation model with realistic bathymetry and stratification. Particular attention is given to the diurnal internal tide, which largely has been de-emphasized in previous studies of the region because of the dominance of the semidiurnal internal tide but has been determined by recent studies to be a significant contributor to baroclinic variability. Though both diurnal and semidiurnal internal tides are generated primarily over Ka'ena Ridge to the northwest of the island, the diurnal internal tide propagates clockwise around the island as an imperfectly trapped wave, while the semidiurnal internal tide propagates away from the ridge, unaffected by rotation. The diurnal and semidiurnal internal tides fall into the superinertial frequency range; however, the diurnal frequency apparently is sufficiently close to inertial (∼ 1.4f) for rotation to affect internal tide propagation. The in situ observations support the model finding that diurnal trapping provides the primary source of baroclinic variability along the eastern coast of the island, a stretch of coastline otherwise sheltered from the internal tide energy generated over the Hawaiian Ridge. The findings in Hawai'i suggest that coastal trapping of superinertial internal tides may be a significant source of variability and mixing in other nearshore systems around the world.

The Hawaiian mesopelagic boundary community is a slope-associated assemblage of micronekton that undergoes diel migrations along the slopes of the islands, residing at greater depths during the day and moving upslope to forage in shallower water at night. The timing of these migrations may be influenced by environmental factors such as moon phase or ambient light. To investigate the movements of this community, we examined echo intensity data from acoustic Doppler current profilers (ADCPs) deployed at shallow and deep sites on the southern slope of Oahu, Hawaii. Diel changes in echo intensity (and therefore in estimated backscatter) were observed and determined to be caused, at least in part, by the horizontal migration of the mesopelagic boundary community. Generalized additive modeling (GAM) was used to assess the impact of environmental factors on the migration timing. Sunset time and lunar illumination were found to be significant factors. Movement speeds of the mesopelagic boundary community were estimated at 1.25–1.99 km h-1 (35–55 cm s-1). The location at which the migrations were observed is the future site of a seawater air conditioning system, which will cause artificial upwelling at our shallow observation site and may cause animal entrainment at the seawater intake near our deep water observation site. This study is the first to observe the diel migration of the mesopelagic boundary community on southern Oahu in both deep and shallow parts of the habitat, and it is also the first to examine migration trends over long time scales, which allows a better assessment of the effects of seasons and lunar illumination on micronekton migrations. Understanding the driving mechanisms of mesopelagic boundary community behavior will increase our ability to assess and manage coastal ecosystems in the face of increasing anthropogenic impacts.

Summary: Inhibitory synapses mediate the majority of synaptic inhibition in the brain, thereby controlling neuronal excitability, firing, and plasticity. Although essential for neuronal function, the central question of how these synapses are organized at the subsynaptic level remains unanswered. Here, we use three-dimensional (3D) super-resolution microscopy to image key components of the inhibitory postsynaptic domain and presynaptic terminal, revealing that inhibitory synapses are organized into nanoscale subsynaptic domains (SSDs) of the gephyrin scaffold, GABAARs and the active-zone protein Rab3-interacting molecule (RIM). Gephyrin SSDs cluster GABAAR SSDs, demonstrating nanoscale architectural interdependence between scaffold and receptor. GABAAR SSDs strongly associate with active-zone RIM SSDs, indicating an important role for GABAAR nanoscale organization near sites of GABA release. Finally, we find that in response to elevated activity, synapse growth is mediated by an increase in the number of postsynaptic SSDs, suggesting a modular mechanism for increasing inhibitory synaptic strength. : Crosby et al. reveal that inhibitory synapses are composed of nanoscale subsynaptic domains of GABAA receptors, the inhibitory scaffold gephyrin and the active-zone protein RIM. During plasticity, additional subsynaptic domains are recruited to the synapse, suggesting a mechanism for activity-dependent synaptic growth. Keywords: GABAA receptor, gephyrin, RIM, VGAT, super-resolution nanoscopy, inhibitory synapse, homeostatic plasticity, structured illumination microscopy