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Abstract Major strike-slip faults that develop between strong and weaker regions are thought to focus along narrow shear zones at the rheological boundary. Here we present the InSAR-derived velocity field spanning almost the entire length of one such fault, the 1600 km-long Altyn Tagh Fault (ATF), and analyse the strain distribution. We find that localisation of strain is actually variable, in contrast to other major strike-slip faults that show little variation, with strain concentrated at the fault for some sections and distributed over broad (>100 km) shear zones for others. Slip rate along the ATF is also variable, decreasing along the fault from 11.6 ± 1.6 mm/yr in the west to 7.2 ± 1.4 mm/yr in the central portion, before increasing again to 11.7 ± 0.9 mm/yr over the eastern portion. We show that the variable shear zone width may be linked to geological variability and the influence of heat flow, and the results imply that sub-parallel faults play an important role in the overall deformation field. This demonstrates the significance of accurately characterising strain rates over a broad region when assessing seismic hazard.

Abstract Sphaeropsidins are iso-pimarane diterpenes produced by phytopathogenic fungi that display promising anticancer activities. Sphaeropsidin A, in particular, has been shown to counteract regulatory volume increase, a process used by cancer cells to avoid apoptosis. This study reports the hemi-synthesis of new lipophilic derivatives obtained by modifications of the C15,C16-alkene moiety. Several of these compounds triggered severe ER swelling associated with strong proteasomal inhibition and consequently cell death, a feature that was not observed with respect to mode of action of the natural product. Significantly, an analysis from the National Cancer Institute sixty cell line testing did not reveal any correlations between the most potent derivative and any other compound in the database, except at high concentrations (LC50). This study led to the discovery of a new set of sphaeropsidin derivatives that may be exploited as potential anti-cancer agents, notably due to their maintained activity towards multidrug resistant models.

Summary: Interactions between cells in the tumor microenvironment (TME) shape cancer progression and patient prognosis. To gain insights into how the TME influences cancer outcomes, we derive gene expression signatures indicative of signaling between stromal fibroblasts and cancer cells, and demonstrate their prognostic significance in multiple and independent squamous cell carcinoma cohorts. By leveraging information within the signatures, we discover that the HB-EGF/EGFR/MAPK axis represents a hub of tumor-stroma crosstalk, promoting the expression of CSF2 and LIF and favoring the recruitment of macrophages. Together, these analyses demonstrate the utility of our approach for interrogating the extent and consequences of TME crosstalk.

Abstract CRISPR-Cas9 is a powerful tool for genome editing, but the strict requirement for an NGG protospacer-adjacent motif (PAM) sequence immediately next to the DNA target limits the number of editable genes. Recently developed Cas9 variants have been engineered with relaxed PAM requirements, including SpG-Cas9 (SpG) and the nearly PAM-less SpRY-Cas9 (SpRY). However, the molecular mechanisms of how SpRY recognizes all potential PAM sequences remains unclear. Here, we combine structural and biochemical approaches to determine how SpRY interrogates DNA and recognizes target sites. Divergent PAM sequences can be accommodated through conformational flexibility within the PAM-interacting region, which facilitates tight binding to off-target DNA sequences. Nuclease activation occurs ~1000-fold slower than for Streptococcus pyogenes Cas9, enabling us to directly visualize multiple on-pathway intermediate states. Experiments with SpG position it as an intermediate enzyme between Cas9 and SpRY. Our findings shed light on the molecular mechanisms of PAMless genome editing.

Abstract The iconic European stag beetle (Lucanus cervus) (Coleoptera: Lucanidae) is one of the largest terrestrial beetles in Europe. Due to decreasing population numbers, thought to be a consequence of habitat loss, this beetle has become a near-threatened species across much of Europe, and a reliable monitoring system is required to measure its future population trends. As part of a programme aimed at conserving UK populations, we have investigated the chemical ecology of the beetle, with a view to developing an efficient semiochemical-based monitoring system. Such a scheme will be beneficial not only in the UK but across the European range of the species, where the beetle is of conservation concern. Here, we report on a surprising discovery of a male-produced pheromone, which provokes initial sexual receptivity in females, and which has not been previously identified in the animal kingdom. Furthermore, we assign sex pheromone function to a previously described female-specific compound.

This paper introduces the ‘Australian Park Life Project’ and describes a protocol to standardise the capture and collation of public open greenspace spatial data across Australian cities. This method will progress greenspace research allowing for unique coherent national analyses and comparative research across Australia. We also outline the development of the Park Life public participatory geographic information system (PPGIS) to spatially explore what, and how, public open greenspaces are being used by Australian communities. The combination of community crowdsourced spatial data providing location-specific information on the green public open spaces used, in combination with the national spatial layer of greenspace allows for unique analyses exploring the role of greenspace provision and design on use and represents a transformative strategy in shaping public open space policy and strategy. • A spatial layer of public open greenspace was created for the eight Australian State and Territory capital cities using a standardised data capture and collection method from local government planning schemes and land use data, and listings of managed and demarcated parks and reserves. • The Park Life public participatory geographic information system (PPGIS) was built to capture spatially referenced information on the use of greenspaces - specifically what spaces are used, and how they are used.

Forced copulation is common, presumably because it can increase male reproductive success. Forced extra-pair copulation (FEPC) occurs in birds, even though most species lack a penis and are widely thought to require female cooperation for fertilization. How FEPC persists, despite a presumed lack of siring success and likely non-negligible costs to the male, is unknown. Using the jackdaw (Corvus monedula) as a case study, we use SNPs to quantify the extra-pair paternity rate through FEPC and evaluate explanations for the persistence of FEPC in species without a penis. We then collate evidence for FEPC across penis-lacking birds. Combining genetic and behavioural analyses, our study suggests that the most likely explanations for the maintenance of FEPC in jackdaws are that it provides a selective advantage to males or it is a relic. Our literature review shows that across birds lacking a penis, FEPC is taxonomically widespread, and yet, little is known about its evolution. A broader implementation of the approach used here, combining both genetic and behavioural data, may shed light on why this widespread sexual behaviour persists. Additional work is necessary to understand whether a penis is needed for paternity through forced copulation and to quantify the costs of FEPC.

Abstract Th17 cells that produce Interleukin IL-17 are pathogenic in many human diseases, including inflammatory bowel disease, but are, paradoxically, essential for maintaining the integrity of the intestinal barrier in a non-inflammatory state. However, the intracellular mechanisms that regulate distinct transcriptional profiles and functional diversity of Th17 cells remain unclear. Here we show Raftlin1, a lipid raft protein, specifically upregulates and forms a complex with RORγt in pathogenic Th17 cells. Disruption of the RORγt-Raftlin1 complex results in the reduction of pathogenic Th17 cells in response to Citrobacter rodentium; however, there is no effect on nonpathogenic Th17 cells in response to commensal segmented filamentous bacteria. Mechanistically, we show that Raftlin1 recruits distinct phospholipids to RORγt and promotes the pathogenicity of Th17 cells. Thus, we have identified a mechanism that drives the pathogenic function of Th17 cells, which could provide a platform for advanced therapeutic strategies to dampen Th17-mediated inflammatory diseases.

Abstract Severe, protracted symptoms are associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a placebo-controlled study of casirivimab and imdevimab (CAS + IMD) in persons at high risk of severe coronavirus disease 2019 (COVID-19; n = 3816), evolution of individual symptoms was assessed for resolution patterns across risk factors, and baseline SARS-CoV-2-specific antibody responses against S1 and N domains. CAS + IMD versus placebo provided statistically significant resolution for 17/23 symptoms, with greater response linked to absence of endogenous anti–SARS-CoV-2 immunoglobulin (Ig)G, IgA, or specific neutralizing antibodies at baseline, or high baseline viral load. Resolution of five key symptoms (onset days 3–5)—dyspnea, cough, feeling feverish, fatigue, and loss of appetite—independently correlated with reduced hospitalization and death (hazard ratio range: 0.31–0.56; P

Abstract While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates of protection against COVID-19 in the casirivimab + imdevimab monoclonal antibody (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and in the mRNA-1273 vaccine trial (ClinicalTrials.gov #NCT04470427). In the mAb trial, protective efficacy of 92% (95% confidence interval (CI): 84%, 98%) is associated with a nAb titer of 1000 IU50/ml, with lower efficacy at lower nAb titers. In the vaccine trial, protective efficacies of 93% [95% CI: 91%, 95%] and 97% (95% CI: 95%, 98%) are associated with nAb titers of 100 and 1000 IU50/ml, respectively. These data quantitate a nAb titer correlate of protection for mAbs benchmarked alongside vaccine induced nAb titers and support nAb titer as a surrogate endpoint for authorizing new mAbs.

Satellite-based earth observation sensors are increasingly able to monitor geophysical signals related to natural hazards, and many groups are working on rapid data acquisition, processing, and dissemination to data users with a wide range of expertise and goals. A particular challenge in the meaningful dissemination of Interferometric Synthetic Aperture Radar (InSAR) data to non-expert users is its unique differential data structure and sometimes low signal-to-noise ratio. In this study, we evaluate the online dissemination of ground deformation measurements from InSAR through Twitter, alongside the provision of open-access InSAR data from the Centre for Observation and Modelling of Earthquakes, Volcanoes and Tectonics (COMET) Looking Into Continents from Space with Synthetic Aperture Radar (LiCSAR) processing system. Our aim is to evaluate (1) who interacts with disseminated InSAR data, (2) how the data are used, and (3) to discuss strategies for meaningful communication and dissemination of open InSAR data. We found that the InSAR Twitter community was primarily composed of non-scientists (62 %), although this grouping included earth observation experts in applications such as commercial industries. Twitter activity was primarily associated with natural hazard response, specifically following earthquakes and volcanic activity, where users disseminated InSAR measurements of ground deformation, often using wrapped and unwrapped interferograms. For earthquake events, Sentinel-1 data were acquired, processed, and tweeted within 4.7±2.8 d (the shortest was 1 d). Open-access Sentinel-1 data dominated the InSAR tweets and were applied to volcanic and earthquake events in the most engaged-with (retweeted) content. Open-access InSAR data provided by LiCSAR were widely accessed, including automatically processed and tweeted interferograms and interactive event pages revealing ground deformation following earthquake events. The further work required to integrate dissemination of InSAR data into longer-term disaster risk-reduction strategies is highly specific, to both hazard type and international community of practice, as well as to local political setting and civil protection mandates. Notably, communication of uncertainties and processing methodologies are still lacking. We conclude by outlining the future direction of COMET LiCSAR products to maximize their useability.

Abstract Biobanks containing formalin-fixed, paraffin-embedded (FFPE) tissues from animals and human atomic-bomb survivors exposed to radioactive particulates remain a vital resource for understanding the molecular effects of radiation exposure. These samples are often decades old and prepared using harsh fixation processes which limit sample imaging options. Optical imaging of hematoxylin and eosin (H&E) stained tissues may be the only feasible processing option, however, H&E images provide no information about radioactive microparticles or radioactive history. Synchrotron X-ray fluorescence microscopy (XFM) is a robust, non-destructive, semi-quantitative technique for elemental mapping and identifying candidate chemical element biomarkers in FFPE tissues. Still, XFM has never been used to uncover distribution of formerly radioactive micro-particulates in FFPE canine specimens collected more than 30 years ago. In this work, we demonstrate the first use of low-, medium-, and high-resolution XFM to generate 2D elemental maps of ~ 35-year-old, canine FFPE lung and lymph node specimens stored in the Northwestern University Radiobiology Archive documenting distribution of formerly radioactive micro-particulates. Additionally, we use XFM to identify individual microparticles and detect daughter products of radioactive decay. The results of this proof-of-principle study support the use of XFM to map chemical element composition in historic FFPE specimens and conduct radioactive micro-particulate forensics.

Adolescents with HIV (AWH) face the double burden of dealing with challenges presented by their developmental phase while coping with stigma related to HIV, affecting their mental health. Poor mental health complicates adherence to daily treatment regimens, requiring innovative psychosocial support strategies for use with adolescents. We assessed the effectiveness of a mindfulness and acceptance-based intervention on the mental health of AWH in Uganda. One hundred and twenty-two AWH, mean age 17 ±1.59 (range 15 to 19 years), 57% female, receiving care at a public health facility in Kampala were enrolled in an open-label randomized trial (ClinicalTrials.gov: NCT05010317) with assessments at pre-and post-intervention. The mindfulness and acceptance-based intervention involved weekly 90-minute group sessions for four consecutive weeks facilitated by two experienced trainers. Sessions involved clarifying values, skillfully relating to thoughts, allowing and becoming aware of experiences non-judgmentally, and exploring life through trial and error. The control group received the current standard of care. Three mental health domains (depression, anxiety, and internalized stigma) were compared between the intervention and control groups. A linear mixed effects regression was used to analyze the effect of the intervention across the two time points. Results showed that the intervention was associated with a statistically significant reduction in symptoms of depression (β = -10.72, 95%CI: 6.25, -15.20; p < .0001), anxiety (β = -7.55, 95%CI: 2.66, -12.43; p = .0003) and stigma (β = -1.40, 95%CI: 0.66 to -2.15; p = .0004) over time. Results suggest that mindfulness and acceptance-based interventions have the potential to improve the mental health of AWH.

Abstract In the age of antimicrobial resistance, the urgency by which novel therapeutic approaches need to be introduced into the clinical pipeline has reached critical levels. Antimicrobial blue light (aBL), as an alternative approach, has demonstrated promise as a stand‐alone therapeutic method, albeit with a limited window of antimicrobial activity. Work by others indicates that treatment with antibiotics increases the production of reactive oxygen species (ROS) which may, in part, contribute to the bactericidal effects of antibiotics. These findings suggest that there may be potential for synergistic interactions with aBL, that similarly generates ROS. Therefore, in this study, the mechanism of aBL is investigated, and the potential for aBL to synergistically promote antibiotic activity is similarly evaluated. Furthermore, the translatability of using aBL and chloramphenicol in combination within a mouse model of Acinetobacter baumanii burn infection is assessed. It is concluded that porphyrins and hydroxyl radicals driven by “free iron” are paramount to the effectiveness of aBL; and aBL is effective at promoting multiple antibiotics in different multidrug‐resistant bacteria. Moreover, rROS up‐regulation, and promoted antibiotic uptake are observed during aBL+antibiotic exposure. Lastly, aBL combined with chloramphenicol appears to be both effective and safe for the treatment of A. baumannii burn infection. In conclusion, aBL may be a useful adjunct therapy to antibiotics to potentiate their action.

Abstract In this work, a multi-resonant metasurface that can be tailored to absorb microwaves at one or more frequencies is explored. Surface shapes based on an ‘anchor’ motif, incorporating hexagonal, square and triangular-shaped resonant elements, are shown to be readily tailorable to provide a targeted range of microwave responses. A metasurface consisting of an etched copper layer, spaced above a ground plane by a thin (

Abstract Measuring and monitoring the spatial distribution of liveability is crucial to ensure that implemented urban and transport planning decisions support health and wellbeing. Spatial liveability indicators can be used to ensure these decisions are effective, equitable and tracked across time. The 2018 Australian National Liveability Study datasets comprise a suite of policy-relevant health-related spatial indicators of local neighbourhood liveability and amenity access estimated for residential address points and administrative areas across Australia’s 21 most populous cities. The indicators and measures encompass access to community and health services, social infrastructure, employment, food, housing, public open space, transportation, walkability and overall liveability. This national ’baseline’ liveability indicators dataset for residential address points and areas can be further linked with surveys containing geocoded participant locations, as well as Census data for areas from the Australian Statistical Geography Standard. The datasets will be of interest to planners, policy makers and researchers interested in modelling and mapping the spatial distribution of urban environmental exposures and their relationship with health and other outcomes.

Abstract In the presented study, advanced experimental techniques, including electronic absorption and fluorescence spectroscopies [with Resonance Light Scattering (RLS)], measurements of fluorescence lifetimes in the frequency domain, calculations of dipole moment fluctuations, quantum yields, and radiative and non-radiative transfer constants, were used to characterize a selected analogue from the group of 1,3,4-thiadiazole, namely: 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol (NTBD), intrinsically capable to demonstrate enol → keto excited-states intramolecular proton transfer (ESIPT) effects. The results of spectroscopic analyses conducted in solvent media as well as selected mixtures were complemented by considering biological properties of the derivative in question, particularly in terms of its potential microbiological activity. The compound demonstrated a dual fluorescence effect in non-polar solvents, e.g. chloroform and DMSO/H2O mixtures, while in polar solvents only a single emission maximum was detected. In the studied systems, ESIPT effects were indeed observed, as was the associated phenomenon of dual fluorescence, and, as demonstrated for the DMSO: H2O mixtures, the same could be relatively easily induced by aggregation effects related to aggregation-induced emission (AIE). Subsequently conducted quantum-chemical (TD-)DFT calculations supported further possibility of ESIPT effects. The following article provides a comprehensive description of the spectroscopic and biological properties of the analyzed 1,3,4-thiadiazole derivatives, highlighting its potential applicability as a very good fluorescence probes as well as a compound capable of high microbiological activity.

Abstract IgA plays an important early neutralizing role after SARS-CoV-2 infection. Systemically administered vaccines typically produce an IgM/IgG predominant response. We evaluated the serum anti-spike (anti-S) IgG, anti-nucleocapsid (anti-N) IgG and anti-S IgA response following vaccination against SARS-CoV-2 in a cohort of first-responders. Among the 378 completely vaccinated participants, 98% were positive for anti-S IgG and 96% were positive for anti-S IgA. Nine percent were positive for anti-N IgG suggesting prior exposure to SARS-CoV-2. No statistically significant difference was seen in IgA response based on prior evidence infection (p = 0.18). Ninety-eight of those receiving the Moderna vaccine (98%) were positive for anti-S IgA as compared to 91% of those who received the Pfizer vaccine (p = 0.0009). The high proportion of participants observed to have a positive anti-S IgA response after vaccination suggests that the vaccines elicit a systemic response characterized by elevated levels of both IgG and IgA.

Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediators of this crosstalk. Here, we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates the complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for the immune defense of the intestine. Instead, C1q-expressing macrophages were located in the intestinal submucosal and myenteric plexuses where they were closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of C1qa showed changes in enteric neuronal gene expression, increased neurogenic activity of peristalsis, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.

Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines.

Cancers, such as squamous cell carcinoma, frequently invade as multicellular units. However, these invading units can be organised in a variety of ways, ranging from thin discontinuous strands to thick ‘pushing’ collectives. Here we employ an integrated experimental and computational approach to identify the factors that determine the mode of collective cancer cell invasion. We find that matrix proteolysis is linked to the formation of wide strands but has little effect on the maximum extent of invasion. Cell-cell junctions also favour wide strands, but our analysis also reveals a requirement for cell-cell junctions for efficient invasion in response to uniform directional cues. Unexpectedly, the ability to generate wide invasive strands is coupled to the ability to grow effectively when surrounded by extracellular matrix in three-dimensional assays. Combinatorial perturbation of both matrix proteolysis and cell-cell adhesion demonstrates that the most aggressive cancer behaviour, both in terms of invasion and growth, is achieved at high levels of cell-cell adhesion and high levels of proteolysis. Contrary to expectation, cells with canonical mesenchymal traits – no cell-cell junctions and high proteolysis – exhibit reduced growth and lymph node metastasis. Thus, we conclude that the ability of squamous cell carcinoma cells to invade effectively is also linked to their ability to generate space for proliferation in confined contexts. These data provide an explanation for the apparent advantage of retaining cell-cell junctions in squamous cell carcinomas.

ImportanceThe COVID-19 pandemic represents a unique stressor in Americans' daily lives and access to health services. However, it remains unclear how the pandemic impacted perceived health status and engagement in health-related behaviors.ObjectiveTo assess changes in self-reported health outcomes during the COVID-19 pandemic, and to explore trends in health-related behaviors that may underlie the observed health changes.DesignInterrupted time series stratified by age, gender, race/ethnicity, educational attainment, household income, and employment status.SettingUnited States.ParticipantsAll adult respondents to the 2016-2020 Behavioral Risk Factor Surveillance System (N = 2,146,384).ExposureSurvey completion following the U.S. public health emergency declaration (March-December 2020). January 2019 to February 2020 served as our reference period.Main outcomes and measuresSelf-reported health outcomes included the number of days per month that respondents spent in poor mental health, physical health, or when poor health prevented their usual activities of daily living. Self-reported health behaviors included the number of hours slept per day, number of days in the past month where alcohol was consumed, participation in any exercise, and current smoking status.ResultsThe national rate of days spent in poor physical health decreased overall (-1.00 days, 95% CI: -1.10 to -0.90) and for all analyzed subgroups. The rate of poor mental health days or days when poor health prevented usual activities did not change overall but exhibited substantial heterogeneity by subgroup. We also observed overall increases in mean sleep hours per day (+0.09, 95% CI 0.05 to 0.13), the percentage of adults who report any exercise activity (+3.28%, 95% CI 2.48 to 4.09), increased alcohol consumption days (0.27, 95% CI 0.18 to 0.37), and decreased smoking prevalence (-1.11%, 95% CI -1.39 to -0.83).Conclusions and relevanceThe COVID-19 pandemic had deleterious but heterogeneous effects on mental health, days when poor health prevented usual activities, and alcohol consumption. In contrast, the pandemic's onset was associated with improvements in physical health, mean hours of sleep per day, exercise participation, and smoking status. These findings highlight the need for targeted outreach and interventions to improve mental health in individuals who may be disproportionately affected by the pandemic.

A SARS-CoV-2 DNA vaccine targeting the spike protein and delivered by jet injection, nCOV-S(JET), previously shown to protect wild-type and immunosuppressed Syrian hamsters (Mesocricetus auratus), was evaluated via two needle-free delivery methods in rhesus macaques (Macaca mulatta). The methods included intramuscular delivery of 2 mg per vaccination with the PharmaJet Stratis device and intradermal delivery of 0.4 mg per vaccination with the PharmaJet Tropis device. We hypothesized that the nCOV-S(JET) vaccine would mount detectable neutralizing antibody responses when delivered by needle-free jet injection by either the intradermal or intramuscular route. When delivered intramuscularly, the vaccines elicited neutralizing and variant (Beta, Gamma, and Delta) cross-neutralizing antibodies against SARS-CoV-2 in all six animals after three vaccinations. The neutralizing response to Omicron was lower with only 4 of 6 animals responding. When delivered at a lower dose by the intradermal route, strong neutralizing antibody responses were only detected in two of six animals. This study confirms that a vaccine previously shown to protect in a hamster model can elicit neutralizing and cross-neutralizing antibodies against SARS-CoV-2 in nonhuman primates. We posit that nCOV-S(JET) has the potential for use as booster vaccine in heterologous vaccination strategies against COVID-19.

The calcium-selective ion channel Orai1 has a complex role in bone homeostasis, with defects in both bone production and resorption detected in Orai1 germline knock-out mice. To determine whether Orai1 has a direct, cell-intrinsic role in osteoblast differentiation and function, we bred Orai1 flox/flox (Orai1fl/fl) mice with Runx2-cre mice to eliminate its expression in osteoprogenitor cells. Interestingly, Orai1 was expressed in a mosaic pattern in Orai1fl/fl-Runx2-cre bone. Specifically, antibody labeling for Orai1 in vertebral sections was uniform in wild type animals, but patchy regions in Orai1fl/fl-Runx2-cre bone revealed Orai1 loss while in other areas expression persisted. Nevertheless, by micro-CT, bones from Orai1fl/fl-Runx2-cre mice showed reduced bone mass overall, with impaired bone formation identified by dynamic histomorphometry. Cortical surfaces of Orai1fl/fl-Runx2-cre vertebrae however exhibited patchy defects. In cell culture, Orai1-negative osteoblasts showed profound reductions in store-operated Ca2+ entry, exhibited greatly decreased alkaline phosphatase activity, and had markedly impaired substrate mineralization. We conclude that defective bone formation observed in the absence of Orai1 reflects an intrinsic role for Orai1 in differentiating osteoblasts.

A SARS-CoV-2 DNA vaccine targeting the spike protein and delivered by jet injection, nCOV-S(JET), previously shown to protect wild-type and immunosuppressed Syrian hamsters (Mesocricetus auratus), was evaluated via two needle-free delivery methods in rhesus macaques (Macaca mulatta). The methods included intramuscular delivery of 2 mg per vaccination with the PharmaJet Stratis device and intradermal delivery of 0.4 mg per vaccination with the PharmaJet Tropis device. We hypothesized that the nCOV-S(JET) vaccine would mount detectable neutralizing antibody responses when delivered by needle-free jet injection by either the intradermal or intramuscular route. When delivered intramuscularly, the vaccines elicited neutralizing and variant (Beta, Gamma, and Delta) cross-neutralizing antibodies against SARS-CoV-2 in all six animals after three vaccinations. The neutralizing response to Omicron was lower with only 4 of 6 animals responding. When delivered at a lower dose by the intradermal route, strong neutralizing antibody responses were only detected in two of six animals. This study confirms that a vaccine previously shown to protect in a hamster model can elicit neutralizing and cross-neutralizing antibodies against SARS-CoV-2 in nonhuman primates. We posit that nCOV-S(JET) has the potential for use as booster vaccine in heterologous vaccination strategies against COVID-19.

BackgroundGut-brain cross-talk may play an important role in modulating neurodevelopment. Few studies have examined the association between antimicrobials that influence infant gut microbiota assemblage and attention deficit hyperactivity disorder (ADHD).ObjectiveTo examine the association between maternal prenatal antimicrobial use and ADHD in offspring at 10 years of age.MethodsData are from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal antimicrobial use was extracted from the medical record. ADHD diagnoses were based on parental report at the 10-year study visit. Poisson regression models with robust error variance were used to calculate risk ratios (RR). Cumulative frequency of exposure to antibiotics, and effect modification were also evaluated.ResultsAmong the 555 children included in the analysis, 108 were diagnosed with ADHD. During pregnancy, 54.1% of mothers used antibiotics while 18.7% used antifungals. Overall, there was no evidence of an association between prenatal antibiotic exposure and ADHD (RR [95% CI] = 0.98 [0.75, 1.29]), but there was an increased risk of ADHD among those with mothers using 3+ courses of antibiotics (RR [95%CI] = 1.58 [1.10, 2.29]). Prenatal exposure to antifungals was associated with a 1.6 times higher risk of ADHD (RR [95% CI] = 1.60 [1.19, 2.15]). In examining effect modification by child sex for antifungal use, there was no evidence of an association among females (RR [95% CI] = 0.97 [0.42, 2.23]), but among males, prenatal antifungal use was associated with 1.82 times higher risk of ADHD (RR [95% CI] = 1.82 [1.29, 2.56]).ConclusionsMaternal prenatal antifungal use and frequent prenatal antibiotic use are associated with an increased risk of ADHD in offspring at age 10. These findings highlight the importance of the prenatal environment and the need for careful use of antimicrobials.

The National Institute on Minority Health and Health Disparities (NIMHD) has developed a framework to guide and orient research into health disparities and minority health. The framework depicts different domains of influence (such as biological and behavioral) and different levels of influence (such as individual and interpersonal). Here, influenced by the “One Health” approach, we propose adding two new levels of influence – interspecies and planetary – to this framework to reflect the interconnected nature of human, animal, and environmental health. Extending the framework in this way will help researchers to create new avenues of inquiry and encourage multidisciplinary collaborations. We then use the One Health approach to discuss how the COVID-19 pandemic has exacerbated health disparities, and show how the expanded framework can be applied to research into health disparities related to antimicrobial resistance and obesity.

Abstract In this work, the electromagnetic response of a mathematically interesting shape—a Möbius strip—is presented, along with a ring resonator for comparison. Both resonators consist of a central lossy dielectric layer bounded by perfectly conducting layers. For the case of the Möbius strips, the computational results show that there are a family of half-integer wavelength modes within the dielectric layer. These additional modes result in increased absorption, and a corresponding reduction in the radar cross section. Interestingly, rotational scans show that these modes can be excited over a large angular range. This investigation gives an understanding of the electromagnetic response of these structures, paving the way for future experiments on Möbius strip resonators.

Abstract In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.

Abstract The increased diversity and scale of published biological data has to led to a growing appreciation for the applications of machine learning and statistical methodologies to gain new insights. Key to achieving this aim is solving the Relationship Extraction problem which specifies the semantic interaction between two or more biological entities in a published study. Here, we employed two deep neural network natural language processing (NLP) methods, namely: the continuous bag of words (CBOW), and the bi-directional long short-term memory (bi-LSTM). These methods were employed to predict relations between entities that describe protein subcellular localisation in plants. We applied our system to 1700 published Arabidopsis protein subcellular studies from the SUBA manually curated dataset. The system combines pre-processing of full-text articles in a machine-readable format with relevant sentence extraction for downstream NLP analysis. Using the SUBA corpus, the neural network classifier predicted interactions between protein name, subcellular localisation and experimental methodology with an average precision, recall rate, accuracy and F1 scores of 95.1%, 82.8%, 89.3% and 88.4% respectively (n = 30). Comparable scoring metrics were obtained using the CropPAL database as an independent testing dataset that stores protein subcellular localisation in crop species, demonstrating wide applicability of prediction model. We provide a framework for extracting protein functional features from unstructured text in the literature with high accuracy, improving data dissemination and unlocking the potential of big data text analytics for generating new hypotheses.

Satellite geodesy is capable of observing glacier height changes and most recent studies focus on the decadal scale due to limitations of data acquisition and precision. Glaciers at the Mt. Everest (Qomolangma), locating at the central Himalaya, have been studied from the 1970s to 2015. Here we obtained TerraSAR-X/TanDEM-X images observed in two epochs, a group around 2013 and another in 2017. Together with SRTM observed in 2000, we derived geodetic glacier mass balance between 2000 and 2013 and 2013 and 2017. We proposed two InSAR procedures for deriving the second period, which yields with basically identical results of geodetic glacier mass balance. The differencing between DEMs derived by TerraSAR-X/TanDEM-X shows better precision than that between TerraSAR-X/TanDEM-X formed DEM and SRTM, and it can capable of providing geodetic glacier mass balance at a sub-decadal scale. Glaciers at the Mt. Everest (Qomolangma) and its surroundings present obvious speeding up in mass loss rates before and after 2013 for both the Chinese and the Nepalese sides. The previous obtained spatial heterogeneous pattern for glacier downwasting between 2000 and 2013 generally kept the same after 2013. Glaciers with lacustrine terminus present the most rapid lost rates.

Abstract Diseases and damage to the retina lead to losses in retinal neurons and eventual visual impairment. Although the mammalian retina has no inherent regenerative capabilities, fish have robust regeneration from Müller glia (MG). Recently, we have shown that driving expression of Ascl1 in adult mouse MG stimulates neural regeneration. The regeneration observed in the mouse is limited in the variety of neurons that can be derived from MG; Ascl1-expressing MG primarily generate bipolar cells. To better understand the limits of MG-based regeneration in mouse retinas, we used ATAC- and RNA-seq to compare newborn progenitors, immature MG (P8-P12), and mature MG. Our analysis demonstrated developmental differences in gene expression and accessible chromatin between progenitors and MG, primarily in neurogenic genes. Overexpression of Ascl1 is more effective in reprogramming immature MG, than mature MG, consistent with a more progenitor-like epigenetic landscape in the former. We also used ASCL1 ChIPseq to compare the differences in ASCL1 binding in progenitors and reprogrammed MG. We find that bipolar-specific accessible regions are more frequently linked to bHLH motifs and ASCL1 binding. Overall, our analysis indicates a loss of neurogenic gene expression and motif accessibility during glial maturation that may prevent efficient reprogramming.

Large-volume volcanic eruptions can occur despite only limited precursory activity. Here the authors show that modelling the combined effects of buoyant magma, viscoelastic earth behaviour, and sustained magma channels can explain such behaviour of volcanoes and gives an estimate of pressure evolution in magma bodies.

Understanding metal component microstructure during 3D printing remains a challenge. Here, the authors use local thermal parameters and the solidification microstructure to better understand how the printed microstructure varies with the laser scan strategy.

There are multiple hypotheses for the evolution of cognition. The most prominent hypotheses are the Social Intelligence Hypothesis (SIH) and the Ecological Intelligence Hypothesis (EIH), which are often pitted against one another. These hypotheses tend to be tested using broad-scale comparative studies of brain size, where brain size is used as a proxy of cognitive ability, and various social and/or ecological variables are included as predictors. Here, we test how robust conclusions drawn from such analyses may be. First, we investigate variation in brain and body size measurements across >1000 bird species. We demonstrate that there is substantial variation in brain and body size estimates across datasets, indicating that conclusions drawn from comparative brain size models are likely to differ depending on the source of the data. Following this, we subset our data to the Corvides infraorder and interrogate how modelling decisions impact results. We show that model results change substantially depending on variable inclusion, source and classification. Indeed, we could have drawn multiple contradictory conclusions about the principal drivers of brain size evolution. These results reflect concerns from a growing number of researchers that conclusions drawn from comparative brain size studies may not be robust. We suggest that to interrogate hypotheses of cognitive evolution, a fruitful way forward is to focus on testing cognitive performance within and between closely related taxa, with an emphasis on understanding the relationship between informational uncertainty and cognitive evolution.

Summary: Life history theory predicts a trade-off between the quantity and quality of offspring. Short interbirth intervals—the time between successive births—may increase the quantity of offspring but harm offspring quality. In contrast, long interbirth intervals may bolster offspring quality while reducing overall reproductive output. Further research is needed to determine whether this relationship holds among primates, which have intensive parental investment. Using Cox proportional hazards models, we examined the effects of interbirth intervals (short, normal, or long) on infant survivorship using a large demographic dataset (n = 15,852) of captive callitrichine monkeys (marmosets, tamarins, and lion tamarins). In seven of the nine species studied, infants born after short interbirth intervals had significantly higher risks of mortality than infants born after longer interbirth intervals. These results suggest that reproduction in callitrichine primates may be limited by physiologic constraints, such that short birth spacing drives higher infant mortality.

This paper introduces a comprehensive method to measure the implementation of residential apartment design policies in Australia. It describes a protocol for extracting and measuring potentially health-enhancing policy-specific design requirements derived from three current residential apartment design policies in Sydney, Melbourne and Perth. These requirements focus on ten key design elements: (1) solar access, (2) natural ventilation, (3) private open space, (4) communal open space, (5) circulation spaces, (6) acoustic privacy, (7) outlook and (8) visual privacy, (9) bicycle and car parking and (10) apartment mix. This paper also describes the computation of scores to quantify the levels of on-ground implementation of the design requirements and compliance with the policies. The method will allow researchers to objectively quantify, benchmark and assess the uptake of apartment policy in apartment design and construction to inform future policy development.• Measurements were developed to systematically assess apartment buildings for their implementation of specific design requirements stipulated by State Government design policies.• Policy implementation was defined as the degree to which the apartment buildings adhered to the requirements outlined by the apartment design policies. A scoring system was developed to quantify policy implementation at both the apartment and building levels.• This method can be replicated to allow researchers to objectively quantify, benchmark and assess the uptake of apartment policy in apartment design and construction to inform future policy development.

High viral transmission in the COVID-19 pandemic has enabled SARS-CoV-2 to acquire new mutations that may impact genome sequencing methods. The ARTIC.v3 primer pool that amplifies short amplicons in a multiplex-PCR reaction is one of the most widely used methods for sequencing the SARS-CoV-2 genome. We observed that some genomic intervals are poorly captured with ARTIC primers. To improve the genomic coverage and variant detection across these intervals, we designed long amplicon primers and evaluated the performance of a short (ARTIC) plus long amplicon (MRL) sequencing approach. Sequencing assays were optimized on VR-1986D-ATCC RNA followed by sequencing of nasopharyngeal swab specimens from fifteen COVID-19 positive patients. ARTIC data covered 94.47% of the virus genome fraction in the positive control and patient samples. Variant analysis in the ARTIC data detected 217 mutations, including 209 single nucleotide variants (SNVs) and eight insertions & deletions. On the other hand, long-amplicon data detected 156 mutations, of which 80% were concordant with ARTIC data. Combined analysis of ARTIC + MRL data improved the genomic coverage to 97.03% and identified 214 high confidence mutations. The combined final set of 214 mutations included 203 SNVs, 8 deletions and 3 insertions. Analysis showed 26 SARS-CoV-2 lineage defining mutations including 4 known variants of concern K417N, E484K, N501Y, P618H in spike gene. Hybrid analysis identified 7 nonsynonymous and 5 synonymous mutations across the genome that were either ambiguous or not called in ARTIC data. For example, G172V mutation in the ORF3a protein and A2A mutation in Membrane protein were missed by the ARTIC assay. Thus, we show that while the short amplicon (ARTIC) assay provides good genomic coverage with high throughput, complementation of poorly captured intervals with long amplicon data can significantly improve SARS-CoV-2 genomic coverage and variant detection.

Abstract While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D‐bioassembly platform is introduced to primarily study fusion of cartilage–cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D‐bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type‐II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D‐model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high‐throughput 3D‐bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis.

Individuals are expected to manage their social relationships to maximize fitness returns. For example, reports of some mammals and birds offering unsolicited affiliation to distressed social partners (commonly termed ‘consolation’) are argued to illustrate convergent evolution of prosocial traits across divergent taxa. However, most studies cannot discriminate between consolation and alternative explanations such as self-soothing. Crucially, no study that controls for key confounds has examined consolation in the wild, where individuals face more complex and dangerous environments than in captivity. Controlling for common confounds, we find that male jackdaws (Corvus monedula) respond to their mate's stress-states, but not with consolation. Instead, they tended to decrease affiliation and partner visit rate in both experimental and natural contexts. This is striking because jackdaws have long-term monogamous relationships with highly interdependent fitness outcomes, which is precisely where theory predicts consolation should occur. Our findings challenge common conceptions about where consolation should evolve, and chime with concerns that current theory may be influenced by anthropomorphic expectations of how social relationships should be managed. To further our understanding of the evolution of such traits, we highlight the need for our current predictive frameworks to incorporate the behavioural trade-offs inherent to life in the wild.

In high-income countries, one’s relative socio-economic position and economic inequality may affect health and well-being, arguably via psychosocial stress. We tested this in a small-scale subsistence society, the Tsimane, by associating relative household wealth (n = 871) and community-level wealth inequality (n = 40, Gini = 0.15–0.53) with a range of psychological variables, stressors, and health outcomes (depressive symptoms [n = 670], social conflicts [n = 401], non-social problems [n = 398], social support [n = 399], cortisol [n = 811], body mass index [n = 9,926], blood pressure [n = 3,195], self-rated health [n = 2523], morbidities [n = 1542]) controlling for community-average wealth, age, sex, household size, community size, and distance to markets. Wealthier people largely had better outcomes while inequality associated with more respiratory disease, a leading cause of mortality. Greater inequality and lower wealth were associated with higher blood pressure. Psychosocial factors did not mediate wealth-health associations. Thus, relative socio-economic position and inequality may affect health across diverse societies, though this is likely exacerbated in high-income countries.

Abstract Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.

Abstract Viral diseases of crustaceans are increasingly recognised as challenges to shellfish farms and fisheries. Here we describe the first naturally-occurring virus reported in any clawed lobster species. Hypertrophied nuclei with emarginated chromatin, characteristic histopathological lesions of DNA virus infection, were observed within the hepatopancreatic epithelial cells of juvenile European lobsters (Homarus gammarus). Transmission electron microscopy revealed infection with a bacilliform virus containing a rod shaped nucleocapsid enveloped in an elliptical membrane. Assembly of PCR-free shotgun metagenomic sequencing produced a circular genome of 107,063 bp containing 97 open reading frames, the majority of which share sequence similarity with a virus infecting the black tiger shrimp: Penaeus monodon nudivirus (PmNV). Multiple phylogenetic analyses confirm the new virus to be a novel member of the Nudiviridae: Homarus gammarus nudivirus (HgNV). Evidence of occlusion body formation, characteristic of PmNV and its closest relatives, was not observed, questioning the horizontal transmission strategy of HgNV outside of the host. We discuss the potential impacts of HgNV on juvenile lobster growth and mortality and present HgNV-specific primers to serve as a diagnostic tool for monitoring the virus in wild and farmed lobster stocks.

With the advances of ESA’s Sentinel-1 InSAR (Interferometric Synthetic Aperture Radar) mission, there are freely available remote sensing ground deformation observations all over the globe that allow continuous monitoring of natural hazards and structural instabilities. The Digital Environment initiative in the UK aims to include these remote sensing data in the effort at forecasting and mitigating hazards across the UK. In this paper, we present a case study of the Hollin Hill landslide in North Yorkshire where a variety of ground-based geophysical measurements are available for comparison with InSAR data. To include Sentinel-1 data in the UK’s Digital Environment, it is important to understand the advantages and limitations of these observations and interpret them appropriately. The Hollin Hill landslide observatory (HHLO) is used by the British Geological Survey to understand landslide processes, and to trial new technologies and methodologies for slope stability characterisation and monitoring. In July 2019, six corner reflectors were installed to improve the coherence of the InSAR measurements. We use Sentinel-1 InSAR data acquired between October 2015 and January 2019 to study the behaviour of this landslide, and find that the line-of-sight component of the down-slope movement is 2.7 mm/year in the descending track, and 7.5–7.7 mm/year in the ascending track. The InSAR measurements also highlight the seasonal behaviour of this landslide. Using InSAR data after the installation of the six corner reflectors, we are able to track the most recent movement on the landslide that occurred in January 2021. This result is in agreement with other ground-based measurements such as tracking of pegs, and soil moisture data derived from electrical resistivity tomography.

Summary: Photovoltaic devices based on perovskite materials have a great potential to become an exceptional source of energy while preserving the environment. However, to enter the global market, they require further development to achieve the necessary performance requirements. The environmental performance of a pre-industrial process of production of a large-area carbon stack perovskite module is analyzed in this work through life cycle assessment (LCA). From the pre-industrial process an ideal process is simulated to establish a benchmark for pre-industrial and laboratory-scale processes. Perovskite is shown to be the most harmful layer of the carbon stack module because of the energy consumed in the preparation and annealing of the precursor solution, and not because of its Pb content. This work stresses the necessity of decreasing energy consumption during module preparation as the most effective way to reduce environmental impacts of perovskite solar cells. : Materials Science; Energy Materials; Materials Design Subject Areas: Materials Science, Energy Materials, Materials Design

Ribosomal profiling is an emerging experimental technology to measure protein synthesis by sequencing short mRNA fragments undergoing translation in ribosomes. Applied on the genome wide scale, this is a powerful tool to profile global protein synthesis within cell populations of interest. Such information can be utilized for biomarker discovery and detection of treatment-responsive genes. However, analysis of ribosomal profiling data requires careful preprocessing to reduce the impact of artifacts and dedicated statistical methods for visualizing and modeling the high-dimensional discrete read count data. Here we present Ribosomal Profiling Reports (RP-REP), a new open-source cloud-enabled software that allows users to execute start-to-end gene-level ribosomal profiling and RNA-Seq analysis on a pre-configured Amazon Virtual Machine Image (AMI) hosted on AWS or on the user’s own Ubuntu Linux server. The software works with FASTQ files stored locally, on AWS S3, or at the Sequence Read Archive (SRA). RP-REP automatically executes a series of customizable steps including filtering of contaminant RNA, enrichment of true ribosomal footprints, reference alignment and gene translation quantification, gene body coverage, CRAM compression, reference alignment QC, data normalization, multivariate data visualization, identification of differentially translated genes, and generation of heatmaps, co-translated gene clusters, enriched pathways, and other custom visualizations. RP-REP provides functionality to contrast RNA-SEQ and ribosomal profiling results, and calculates translational efficiency per gene. The software outputs a PDF report and publication-ready table and figure files. As a use case, we provide RP-REP results for a dengue virus study that tested cytosol and endoplasmic reticulum cellular fractions of human Huh7 cells pre-infection and at 6 h, 12 h, 24 h, and 40 h post-infection. Case study results, Ubuntu installation scripts, and the most recent RP-REP source code are accessible at GitHub. The cloud-ready AMI is available at AWS (AMI ID: RPREP RSEQREP (Ribosome Profiling and RNA-Seq Reports) v2.1 (ami-00b92f52d763145d3)).

Airborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne transmission of SARS-CoV-2 have not been investigated. A comparative evaluation of COVID-19 in African green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to SARS-CoV-2 was performed to determine critical disease parameters associated with disease progression, and establish correlations between primate and human COVID-19. Respiratory abnormalities and viral shedding were noted for all animals, indicating successful infection. Cynomolgus macaques developed fever, and thrombocytopenia was measured for African green monkeys and rhesus macaques. Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys. The data indicate that, in addition to African green monkeys, macaques can be successfully infected by airborne SARS-CoV-2, providing viable macaque natural transmission models for medical countermeasure evaluation.