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The hypothalamus in the mammalian brain is responsible for regulating functions associated with survival and reproduction representing a complex set of highly interconnected, yet anatomically and functionally distinct, sub-regions. It remains unclear what factors drive the spatial organization of sub-regions within the hypothalamus. One potential factor may be structural connectivity of the network that promotes efficient function with well-connected sub-regions placed closer together geometrically, i.e., the strongest axonal signal transferred through the shortest geometrical distance. To empirically test for such efficiency, we use hypothalamic data derived from the Allen Mouse Brain Connectivity Atlas, which provides a structural connectivity map of mouse brain regions derived from a series of viral tracing experiments. Using both cost function minimization and comparison with a weighted, sphere-packing ensemble, we demonstrate that the sum of the distances between hypothalamic sub-regions are not close to the minimum possible distance, consistent with prior whole brain studies. However, if such distances are weighted by the inverse of the magnitude of the connectivity, their sum is among the lowest possible values. Specifically, the hypothalamus appears within the top 94th percentile of neural efficiencies of randomly packed configurations and within one standard deviation of the median efficiency when packings are optimized for maximal neural efficiency. Our results, therefore, indicate that a combination of geometrical and topological constraints help govern the structure of the hypothalamus.

Abstract Nonnative species are a key agent of global change. However, nonnative invertebrates remain understudied at the community scales where they are most likely to drive local extirpations. We use the North American NEON pitfall trapping network to document the number of nonnative species from 51 invertebrate communities, testing four classes of drivers. We sequenced samples using the eDNA from the sample's storage ethanol. We used AICc informed regression to evaluate how native species richness, productivity, habitat, temperature, and human population density and vehicular traffic account for continent‐wide variation in the number of nonnative species in a local community. The percentage of nonnatives varied 3‐fold among habitat types and over 10‐fold (0%–14%) overall. We found evidence for two types of constraints on nonnative diversity. Consistent with Capacity rules (i.e., how the number of niches and individuals reflect the number of species an ecosystem can support) nonnatives increased with existing native species richness and ecosystem productivity. Consistent with Establishment Rules (i.e., how the dispersal rate of nonnative propagules and the number of open sites limits nonnative species richness) nonnatives increased with automobile traffic—a measure of human‐generated propagule pressure—and were twice as common in pastures than native grasslands. After accounting for drivers associated with a community's ability to support native species (native species richness and productivity), nonnatives are more common in communities that are regularly seasonally disturbed (pastures and, potentially deciduous forests) and those experiencing more vehicular traffic. These baseline values across the US North America will allow NEON's monitoring mission to document how anthropogenic change—from disturbance to propagule transport, from temperature to trends in local extinction—further shape biotic homogenization.

IntroductionGiven the role of microbiomes in promoting host health and homeostasis, understanding the factors shaping skin microbial communities in wild vertebrates has become increasingly important in conservation. This goal is even more pressing for amphibians, for which the skin has multiple critical functions, and pathogens currently decimating populations are linked to significant changes in skin microbiomes. However, because microbiomes are also shaped by environmental and ecological influences, as well as by host phylogeny, it is important to quantify these contributions to microbiome structure in the presence of infection.MethodsTo understand the joint influence of these diverse factors shaping microbiomes, we used 16S rRNA sequencing to characterize the skin microbial communities of six salamander species (families Plethodontidae and Salamandridae) found in Oklahoma and contrasted the effects of infection status, phylogeny, host ecology, and host environment (i.e., climate) on skin microbiomes.ResultsDifferences at the level of host family were the main factor influencing microbiome diversity; however, we did not detect a substantial phylogenetic signal. Instead, host ecology and environment were more important in driving microbiome differences among species and genera. Salamanders that tested positive for the skin fungal parasite Batrachochytrium dendrobatidis (Bd) also had slightly less diverse microbiomes than Bd-free animals, but no such differences were associated with the systemic pathogen ranavirus (RV).DiscussionTogether, these results indicate a nuanced relationship between the number and type of microbes present on salamander skin and the factors influencing them. By developing a baseline assessment of the microbiome diversity and richness present on the skin of these focal species, this work also provides a foundation for monitoring and evaluating changes in skin microbiomes as populations continue to experience stressors and diseases.

Abstract Background Mosquitoes are the deadliest organisms in the world, killing an estimated 750,000 people per year due to the pathogens they can transmit. Mosquitoes also pose a major threat to other vertebrate animals. Culex territans is a mosquito species found in temperate zones worldwide that feeds almost exclusively on amphibians and can transmit parasites; however, little is known about its ability to transmit other pathogens, including fungi. Batrachochytrium dendrobatidis (Bd) is a topical pathogenic fungus that spreads through contact. With amphibian populations around the world experiencing mass die-offs and extinctions due to this pathogen, it is critical to study all potential modes of transmission. Because Cx. territans mosquitoes are in contact with their hosts for long periods of time while blood-feeding, we hypothesize that they can transmit and pick up Bd. Methods In this study, we first assessed Cx. territans ability to transfer the fungus from an infected surface to a clean one under laboratory conditions. We also conducted a surveillance study of Bd infections in frogs and mosquitoes in the field (Mountain Lake Biological station, VA, USA). In parallel, we determined Cx. territans host preference via blood meal analysis of field caught mosquitoes. Results We found that this mosquito species can carry the fungus to an uninfected surface, implying that they may have the ability to transmit Bd to their amphibian hosts. We also found that Cx. territans feed primarily on green frogs (Rana clamitans) and bullfrogs (Rana catesbeiana) and that the prevalence of Bd within the frog population at our field site varied between years. Conclusions This study provides critical insights into understanding the role of amphibian-biting mosquitoes in transmitting pathogens, which can be applied to disease ecology of susceptible amphibian populations worldwide. Graphical Abstract

Methods to detect infections are often limited to specific viruses or do not yield information on the immune response. Here, the authors analyse temporal changes in high-dimensional antibody profiles and chart more than 650 infection events across the human virome providing a high-resolution view of host-virus dynamics.

Anurans (frogs and toads) are an ecologically diverse group of vertebrate organisms that display a myriad of reproductive modes and life history traits. To persist in such an expansive array of habitats, these organisms have evolved specialized skin that is used for respiration while also protecting against moisture loss, pathogens, and environmental contaminants. Anuran skin is also colonized by communities of symbiotic microorganisms, and these skin microbiota serve critical roles in numerous processes associated with anuran host health and persistence such as pathogen resistance and immunity. However, gaps remain in our understanding of the environmental and evolutionary processes that shape frog skin microbial communities. Here, we combined existing anuran disease data with 16S rRNA skin microbial inventories to elucidate the roles that geographic location, host evolutionary history, host ecology, and pathogen presence play in the microbial community assemblage of five co-distributed frog host species in Oklahoma. These focal species possess distinct ecological preferences: aquatic, semi-aquatic, and arboreal, and our results indicate that host ecology is the primary driver of frog skin microbial community structure. Additionally, compositional differences were observed among select host species based on geographic location, but this was not consistent among all five frog species. We did not find evidence of phylogenetic signal among our samples and results from the Classification and Regression Tree Analysis revealed that the presence of the amphibian pathogen Batrachochytrium dendrobatidis and the severity of infection were not drivers of skin microbiome differences among our focal host species. Results from this comparative study contribute to our growing understanding of the environmental and host-associated drivers of skin microbial community assemblage and represents one of the first studies on landscape-level variation in skin microbial communities among North American frogs.

Abstract The urban environment influences human health, safety and wellbeing. Cities in Africa are growing faster than other regions but have limited data to guide urban planning and policies. Our aim was to use smart sensing and analytics to characterise the spatial patterns and temporal dynamics of features of the urban environment relevant for health, liveability, safety and sustainability. We collected a novel dataset of 2.1 million time-lapsed day and night images at 145 representative locations throughout the Metropolis of Accra, Ghana. We manually labelled a subset of 1,250 images for 20 contextually relevant objects and used transfer learning with data augmentation to retrain a convolutional neural network to detect them in the remaining images. We identified 23.5 million instances of these objects including 9.66 million instances of persons (41% of all objects), followed by cars (4.19 million, 18%), umbrellas (3.00 million, 13%), and informally operated minibuses known as tro tros (2.94 million, 13%). People, large vehicles and market-related objects were most common in the commercial core and densely populated informal neighbourhoods, while refuse and animals were most observed in the peripheries. The daily variability of objects was smallest in densely populated settlements and largest in the commercial centre. Our novel data and methodology shows that smart sensing and analytics can inform planning and policy decisions for making cities more liveable, equitable, sustainable and healthy.

Background: Noise pollution from transportation is one of the leading contributors to the environmental disease burden in Europe. We provide a novel assessment of spatial variations of these health impacts within a country, using England as an example. Methods: We estimated the burden of annoyance (highly annoyed), sleep disturbance (highly sleep disturbed), ischemic heart disease (IHD), stroke, and diabetes attributable to long-term transportation noise exposures in England for the adult population in 2018 down to local authority level (average adult population: 136,000). To derive estimates, we combined literature-informed exposure-response relationships, with population data on noise exposures, disease, and mortalities. Long-term average noise exposures from road, rail and aircraft were sourced from strategic noise mapping, with a lower exposure threshold of 50 dB (decibels) Lden and Lnight. Results: 40 %, 4.5 % and 4.8 % of adults in England were exposed to road, rail, and aircraft noise exceeding 50 dB Lden. We estimated close to a hundred thousand (∼97,000) disability adjusted life years (DALY) lost due to road-traffic, ∼13,000 from railway, and ∼ 17,000 from aircraft noise. This excludes some noise-outcome pairs as there were too few studies available to provide robust exposure–response estimates. Annoyance and sleep disturbance accounted for the majority of the DALYs, followed by strokes, IHD, and diabetes. London, the South East, and North West regions had the greatest number of road-traffic DALYs lost, while 63 % of all aircraft noise DALYs were found in London. The strategic noise mapping did not include all roads, which may still have significant traffic flows. In sensitivity analyses using modelled noise from all roads in London, the DALYs were 1.1x to 2.2x higher. Conclusion: Transportation noise exposures contribute to a significant and unequal environmental disease burden in England. Omitting minor roads from the noise exposure modelling leads to underestimation of the disease burden.

Road traffic has become the leading source of air pollution in fast-growing sub-Saharan African cities. Yet, there is a dearth of robust city-wide data for understanding space-time variations and inequalities in combustion related emissions and exposures. We combined nitrogen dioxide (NO _2 ) and nitric oxide (NO) measurement data from 134 locations in the Greater Accra Metropolitan Area (GAMA), with geographical, meteorological, and population factors in spatio-temporal mixed effects models to predict NO _2 and NO concentrations at fine spatial (50 m) and temporal (weekly) resolution over the entire GAMA. Model performance was evaluated with 10-fold cross-validation (CV), and predictions were summarized as annual and seasonal (dusty [Harmattan] and rainy [non-Harmattan]) mean concentrations. The predictions were used to examine population distributions of, and socioeconomic inequalities in, exposure at the census enumeration area (EA) level. The models explained 88% and 79% of the spatiotemporal variability in NO _2 and NO concentrations, respectively. The mean predicted annual, non-Harmattan and Harmattan NO _2 levels were 37 (range: 1–189), 28 (range: 1–170) and 50 (range: 1–195) µ g m ^−3 , respectively. Unlike NO _2 , NO concentrations were highest in the non-Harmattan season (41 [range: 31–521] µ g m ^−3 ). Road traffic was the dominant factor for both pollutants, but NO _2 had higher spatial heterogeneity than NO. For both pollutants, the levels were substantially higher in the city core, where the entire population (100%) was exposed to annual NO _2 levels exceeding the World Health Organization (WHO) guideline of 10 µ g m ^−3 . Significant disparities in NO _2 concentrations existed across socioeconomic gradients, with residents in the poorest communities exposed to levels about 15 µ g m ^−3 higher compared with the wealthiest ( p < 0.001). The results showed the important role of road traffic emissions in air pollution concentrations in the GAMA, which has major implications for the health of the city’s poorest residents. These data could support climate and health impact assessments as well as policy evaluations in the city.

Abstract We describe the development and validation of a qPCR assay to detect Poecilia reticulata, a highly invasive species of freshwater fish invasive to the Caribbean islands, through environmental DNA (eDNA) sampling. Originating from Trinidad, this species is invasive and detrimental to countless native tropical fish communities. A qPCR assay, consisting of a set of primers and a fluorescent probe, amplifying a 214 base pair target region of the mitochondrial Cytochrome B gene was designed for P. reticulata from existing DNA sequence data. The assay was assessed for target specificity, with no evidence of amplification in closely related or sympatrically distributed non‐target species. In vitro tests indicate that the assay consistently detects P. reticulata down to concentrations of 2.0 × 10−5 ng/μl. The developed assay provides a new, practical tool for monitoring freshwater habitats throughout the Caribbean, allowing for early and rapid detection of invasive fish species of conservation concern.

Vascular smooth muscle cells (VSMCs) are the key moderators of cerebrovascular dynamics in response to the brain’s oxygen and nutrient demands. Crucially, VSMCs may provide a sensitive biomarker for neurodegenerative pathologies where vasculature is compromised. An increasing body of research suggests that VSMCs have remarkable plasticity and their pathophysiology may play a key role in the complex process of neurodegeneration. Furthermore, extrinsic risk factors, including environmental conditions and traumatic events can impact vascular function through changes in VSMC morphology. VSMC dysfunction can be characterised at the molecular level both preclinically, and clinically ex vivo. However the identification of VSMC dysfunction in living individuals is important to understand changes in vascular function at the onset and progression of neurological disorders such as dementia, Alzheimer’s disease, and Parkinson’s disease. A promising technique to identify changes in the state of cerebral smooth muscle is cerebrovascular reactivity (CVR) which reflects the intrinsic dynamic response of blood vessels in the brain to vasoactive stimuli in order to modulate regional cerebral blood flow (CBF). In this work, we review the role of VSMCs in the most common neurodegenerative disorders and identify physiological systems that may contribute to VSMC dysfunction. The evidence collected here identifies VSMC dysfunction as a strong candidate for novel therapeutics to combat the development and progression of neurodegeneration, and highlights the need for more research on the role of VSMCs and cerebrovascular dynamics in healthy and diseased states.

Quantifying the burden of disease from exposure to poor indoor air pollution can support policy development. In England, there is current regulatory and public attention on the health implications of residential exposure to formaldehyde, damp and mould. However, there is scarce information on these health impacts at the population scale. As such, we assessed the burden of key respiratory diseases from residential formaldehyde, damp and/or mould for the English population aged 0–14 and 15–49. We obtained data on the percentage of dwellings affected by damp and/or mould from the English Housing Survey and estimated the distribution of residential formaldehyde concentrations (annual average (μg/m3)) by pooling data from monitoring studies conducted in England. Exposures were combined with epidemiological relationships and national health data to estimate Population Attributable Fractions (PAFs), disease incidence, and Disability Adjusted Life Years (DALYs) lost associated with residential formaldehyde or damp and/or mould exposure in England. We made estimates for the year 2019 but also looked back several years in time. Exposure to formaldehyde was associated with approximately 4000 new cases of childhood asthma (~800 DALYs lost) in 2019, though the estimates were sensitive to the placement of the lower exposure threshold. Exposure to damp and/or mould was associated with approximately 5000 new cases of asthma (~2200 DALYs) and approximately 8500 lower respiratory infections (~600 DALYs) among children and adults in 2019, though the PAFs were unequally distributed across dwellings based on income and ethnicity. Alternative data sources suggest that the percentage of dwellings affected by damp and/or mould may even be higher, resulting in a possible 3–8-fold greater number of cases and DALYs. Our assessment emphasizes a potential respiratory health burden in England associated with residential formaldehyde as well as damp and/or mould, further highlighting the public health importance of good indoor air quality and good quality housing.

Summary: The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later time points. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

Abstract Urban noise pollution is an emerging public health concern in growing cities in sub-Saharan Africa (SSA), but the sound environment in SSA cities is understudied. We leveraged a large-scale measurement campaign to characterize the spatial and temporal patterns of measured sound levels and sound sources in Accra, Ghana. We measured sound levels and recorded audio clips at 146 representative locations, involving 7-days (136 locations) and 1-year measurements between 2019 and 2020. We calculated metrics of noise levels and intermittency and analyzed audio recordings using a pre-trained neural network to identify sources. Commercial, business, and industrial areas and areas near major roads had the highest median daily sound levels (LAeq24hr: 69 dBA and 72 dBA) and the lowest percentage of intermittent sound; the vice-versa was found for peri urban areas. Road-transport sounds dominated the overall sound environment but mixtures of other sound sources, including animals, human speech, and outdoor music, dominated in various locations and at different times. Environmental noise levels in Accra exceeded both international and national health-based guidelines. Detailed information on the acoustical environmental quality (including sound levels and types) in Accra may guide environmental policy formulation and evaluation to improve the health of urban residents.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated global public health systems and economies, with over 52 million people infected, millions of jobs and businesses lost, and more than 1 million deaths recorded to date. Contact with surfaces contaminated with droplets generated by infected persons through exhaling, talking, coughing and sneezing is a major driver of SARS-CoV-2 transmission, with the virus being able to survive on surfaces for extended periods of time. To interrupt these chains of transmission, there is an urgent need for devices that can be deployed to inactivate the virus on both recently and existing contaminated surfaces. Here, we describe the inactivation of SARS-CoV-2 in both wet and dry format using radiation generated by a commercially available Signify ultraviolet (UV)-C light source at 254 nm. We show that for contaminated surfaces, only seconds of exposure is required for complete inactivation, allowing for easy implementation in decontamination workflows.

After successful laboratory rearing of both males and females from a single clutch of eggs, the genus Nanophyllium Redtenbacher, 1906 (described only from males) and the frondosum species group within Phyllium (Pulchriphyllium) Griffini, 1898 (described only from females) are found to be the opposite sexes of the same genus. This rearing observation finally elucidates the relationship of these two small body sized leaf insect groups which, for more than a century, have never been linked before. This paper synonymizes the frondosum species group with Nanophyllium Redtenbacher, 1906 in order to create a singular and clearly defined taxonomic group. Five species are transferred from the Phyllium (Pulchriphyllium) frondosum species group and create the following new combinations: Nanophyllium asekiense (Größer, 2002), comb. nov.; Nanophyllium chitoniscoides (Größer, 1992), comb. nov.; Nanophyllium frondosum (Redtenbacher, 1906), comb. nov.; Nanophyllium keyicum (Karny, 1914), comb. nov.; Nanophyllium suzukii (Größer, 2008), comb. nov. The only taxon from this species group not transferred from the frondosum species group to Nanophyllium is Phyllium (Pulchriphyllium) groesseri Zompro, 1998. Based on protibial exterior lobes, this species belongs in the schultzei species group as described in Hennemann et al. 2009 and is therefore excluded from further discussion here. The rearing of Nanophyllium also yielded the male Nanophyllium asekiense (Größer, 2002), comb. nov. thus, enabling comparison of this male to the other previously known Nanophyllium species. Two new species of nano-leaf insects are described within, Nanophyllium miyashitai sp. nov., from Morobe Province, Papua New Guinea, and Nanophyllium daphne sp. nov., from Biak Island, Papua Province, Indonesia. With such distinct sexual dimorphism in Nanophyllium between sexes, which have only now been matched up via captive rearing, illustrated within are numerous specimens which might represent the unknown opposite sexes of the many currently known species of Nanophyllium. Due to pronounced sexual dimorphism in Nanophyllium, only future captive rearing or molecular analysis will match up the many unknown sexes. To conclude, with the description of two new Nanophyllium species, dichotomous keys to species for known males and females are presented.

We investigated how lithospheric heat fluxes varied temporally and spatially on the Saturnian moon Tethys, focusing on the region of Ithaca Chasma that overprints Telemus Impact Basin. Our results, derived from flexure associated with Ithaca, indicate elastic thicknesses of 4.1 ± 0.3 km to 6.4 ± 0.4 km and heat fluxes ranging from 12 to 39 mW m ^−2 assuming a nonporous pure H _2 O ice lithosphere. Our results for Ithaca’s south limb are similar to previous estimates within the north limb, indicating consistent heat fluxes across a large spatial extent in this area. However, our estimates are lower than those for the older Telemus Basin (>60 mW m ^−2 ), revealing evidence that Tethys experienced a substantial temporal variation in heat fluxes in this region. Heat fluxes reflected by Ithaca are similar to previous estimates for Tethys’s two youngest impact basins, Melanthius and Odysseus, suggesting that Ithaca may also be relatively young. If Tethys’s lithosphere is porous, then our heat flux estimates for Ithaca Chasma drop to 12–38 mW m ^−2 , 11–35 mW m ^−2 , and 10–33 mW m ^−2 for 5%, 15%, and 25% porosities, respectively. If Tethys’s lithosphere includes ∼10% NH _3 -hydrates, then the estimates are 5–16 mW m ^−2 , 5–15 mW m ^−2 , 4–14 mW m ^−2 , and 4–13 mW m ^−2 for 0%, 5%, 15%, and 25% porosities, respectively. Although we find that some ground-based reflectance spectra hint at 2.2 μ m bands that may result from NH _3 -bearing species, the detected features are weak and may not result from surface constituents. Consequently, our heat flux estimates that assume a pure H _2 O ice lithosphere are likely more accurate.

Summary: RBFOX2, which has a well-established role in alternative splicing, is linked to heart diseases. However, it is unclear whether RBFOX2 has other roles in RNA processing that can influence gene expression in muscle cells, contributing to heart disease. Here, we employ both 3ʹ-end and nanopore cDNA sequencing to reveal a previously unrecognized role for RBFOX2 in maintaining alternative polyadenylation (APA) signatures in myoblasts. RBFOX2-mediated APA modulates mRNA levels and/or isoform expression of a collection of genes, including contractile and mitochondrial genes. Depletion of RBFOX2 adversely affects mitochondrial health in myoblasts, correlating with disrupted APA of mitochondrial gene Slc25a4. Mechanistically, RBFOX2 regulation of Slc25a4 APA is mediated through consensus RBFOX2 binding motifs near the distal polyadenylation site, enforcing the use of the proximal polyadenylation site. In sum, our results unveil a role for RBFOX2 in fine-tuning expression of mitochondrial and contractile genes via APA in myoblasts relevant to heart diseases.

Background Body-mass index (BMI) and blood pressure (BP) levels are rising in sub-Saharan African cities, particularly among women. However, there is very limited information on how much they vary within cities, which could inform targeted and equitable health policies. Our study aimed to analyse spatial variations in BMI and BP for adult women at the small area level in the city of Accra, Ghana. Methods and findings We combined a representative survey of adult women’s health in Accra, Ghana (2008 to 2009) with a 10% random sample of the national census (2010). We applied a hierarchical model with a spatial term to estimate the associations of BMI and systolic blood pressure (SBP) and diastolic blood pressure (DBP) with demographic, socioeconomic, behavioural, and environmental factors. We then used the model to estimate BMI and BP for all women in the census in Accra and calculated mean BMI, SBP, and DBP for each enumeration area (EA). BMI and/or BP were positively associated with age, ethnicity (Ga), being currently married, and religion (Muslim) as their 95% credible intervals (95% CrIs) did not include zero, while BP was also negatively associated with literacy and physical activity. BMI and BP had opposite associations with socioeconomic status (SES) and alcohol consumption. In 2010, 26% of women aged 18 and older had obesity (BMI ≥ 30 kg/m2), and 21% had uncontrolled hypertension (SBP ≥ 140 and/or DBP ≥ 90 mm Hg). The differences in mean BMI and BP between EAs at the 10th and 90th percentiles were 2.7 kg/m2 (BMI) and in BP 7.9 mm Hg (SBP) and 4.8 mm Hg (DBP). BMI was generally higher in the more affluent eastern parts of Accra, and BP was higher in the western part of the city. A limitation of our study was that the 2010 census dataset used for predicting small area variations is potentially outdated; the results should be updated when the next census data are available, to the contemporary population, and changes over time should be evaluated. Conclusions We observed that variation of BMI and BP across neighbourhoods within Accra was almost as large as variation across countries among women globally. Localised measures are needed to address this unequal public health challenge in Accra. Sierra N. Clark and colleagues analyze spatial variations of blood pressure and body mass index, and associated factors in Ghanaian women. Author summary Why was this study done? The social, physical, and food environment influence the spatial distribution of noncommunicable diseases and their risk factors such as blood pressure (BP) and body-mass index (BMI) within and across neighbourhoods in cities. In sub-Saharan Africa (SSA), where cities are growing rapidly and BMI and BP have risen, there is limited information on within-city variation in cardiometabolic risk factors. This information could inform targeted and equitable public health programmes. What did the researchers do and find? We combined data from an epidemiological study that had randomly sampled women in Accra and geospatial data on roads and community biomass fuel use to understand how individual and household factors as well as residence predict BMI and BP. Data were analysed in a Bayesian spatial model and then used together with the data from the census to predict BP and BMI levels for all women in Accra. Local area variation in BMI and BP is large within Accra, similar to patterns seen in other cities and regions around the world. Average BMI was higher among women with higher socioeconomic status (SES), as measured by ownership of assets and household infrastructure. What do these findings mean? The spatial variations in BMI and BP across neighbourhoods in Accra were almost as high as variation seen between countries. Localised public health actions can help address these disparities and reduce the resulting overall public health burden.

OBJECTIVES/GOALS: The primary goals of this study are 1) expand our understanding of the neural circuitry influenced by the neuropeptide Neuromedin U (NMU) via its receptor Neuromedin U Receptor 2 (NMUR2), and 2) provide alternative top-down mechanisms for how NMU regulates high fat food intake and cocaine taking. METHODS/STUDY POPULATION: Immunohistochemistry (IHC) for NMUR2 and cell markers was performed on rat brain tissue containing the medial prefrontal cortex (mPFC). To identify the source of the presynaptic NMUR2, anterograde tracing from the paraventricular nucleus or dorsal raphe nucleus to the mPFC utilizing an AAV2- dsRed-synaptobrevin fusion protein were performed (n=3) and will be followed by IHC. Using in vivo calcium imaging technology (InScopix nVista), neuronal activity (calcium transients) was recorded from the mPFC of two awake, freely behaving rats. Each animal underwent a single session of 30 minutes baseline activity, intraperitoneal NMU administration, and 30 minutes of post-treatment activity. Activity was then processed and recorded as distinct events using the InScopix data acquisition software. RESULTS/ANTICIPATED RESULTS: Medial prefrontal cortex staining for NMUR2 revealed a characteristic “beads on a string” motif, consistent with presynaptic receptor expression. Furthermore, we expect the anterograde tracing experiment will show colocalization of the dsRed-synaptobrevin fusion protein with NMUR2 on synaptic inputs into the medial prefrontal cortex. Following quantification of pre- and post- treatment events using the InScopix data acquisition software, total events during the pre- and post-treatment time periods were calculated. In these studies, both animals demonstrated a clear increase in calcium transient activity between pre- and post- treatment evaluations, suggesting that NMU administration increases the neuronal activity of neurons in the prefrontal cortex. DISCUSSION/SIGNIFICANCE: This research provides a new site of action for the known therapeutic effects of NMU. We demonstrate the presence of presynaptic NMUR2 in the mPFC and show that systemic administration of NMU increases mPFC neuronal activity. This illustrates NMU may act as a top-down mediator for substance use disorders and binge eating behaviors.

Abstract While the ongoing COVID‐19 pandemic affirms an urgent global need for effective vaccines as second and third infection waves are spreading worldwide and generating new mutant virus strains, it has also revealed the importance of mitigating the transmission of SARS‐CoV‐2 through the introduction of restrictive social practices. Here, it is demonstrated that an architecturally‐ and chemically‐diverse family of nanostructured anionic polymers yield a rapid and continuous disinfecting alternative to inactivate coronaviruses and prevent their transmission from contact with contaminated surfaces. Operating on a dramatic pH‐drop mechanism along the polymer/pathogen interface, polymers of this archetype inactivate the SARS‐CoV‐2 virus, as well as a human coronavirus surrogate (HCoV‐229E), to the minimum detection limit within minutes. Application of these anionic polymers to frequently touched surfaces in medical, educational, and public‐transportation facilities, or personal protection equipment, can provide rapid and repetitive protection without detrimental health or environmental complications.

High spatial resolution information on urban air pollution levels is unavailable in many areas globally, partially due to the high input data needs of existing estimation approaches. We introduced a computer vision method to estimate annual means for air pollution levels from street-level images. We used annual mean estimates of NO2 and PM2.5 concentrations from locally calibrated models as labels from London, New York, and Vancouver to allow for compilation of a sufficiently large dataset (~250 k images for each city). Our experimental setup is designed to quantify intra- and intercity transferability of image-based model estimates. Performances were high and comparable to traditional land-use regression (LUR) and dispersion models when training and testing images from the same city (R2 values between 0.51 and 0.95 when validated on data from ground monitoring stations). Similar to LUR models, transferability of models between cities in different geographies is more difficult. Specifically, transferability between the three cities (London, New York, and Vancouver), which have similar pollution source profiles, was moderately successful (R2 values between zero and 0.67). Comparatively, performances when transferring models trained on cities with very different source profiles, such as Accra in Ghana and Hong Kong, were lower (R2 between zero and 0.21). This suggests a need for local calibration, using additional measurement data from cities that share similar source profiles.

The gastrointestinal tract (GIT) of vertebrates contains a series of organs beginning with the mouth and ending with the anus or cloacal opening. Each organ represents a unique environment for resident microorganisms. Due to their simple digestive anatomy, snakes are good models for studying microbiome variation along the GIT. Cloacal sampling captures the majority of the microbial diversity found in the GIT of snakes—yet little is known about the oral microbiota of snakes. Most research on the snake mouth and gut microbiota are limited to studies of a single species or captive-bred individuals. It therefore remains unclear how a host’s life history, diet, or evolutionary history correlate with differences in the microbial composition within the mouths and guts of wild snakes. We sampled the mouth and gut microbial communities from three species of Asian venomous snakes and utilized 16S rRNA microbial inventories to test if host phylogenetic and ecological differences correlate with distinct microbial compositions within the two body sites. These species occupy three disparate habitat types: marine, semi-arboreal, and arboreal, our results suggest that the diversity of snake mouth and gut microbial communities correlate with differences in both host ecology and phylogeny.

Introduction Air and noise pollution are emerging environmental health hazards in African cities, with potentially complex spatial and temporal patterns. Limited local data are a barrier to the formulation and evaluation of policies to reduce air and noise pollution.Methods and analysis We designed a year-long measurement campaign to characterise air and noise pollution and their sources at high-resolution within the Greater Accra Metropolitan Area (GAMA), Ghana. Our design uses a combination of fixed (year-long, n=10) and rotating (week-long, n =~130) sites, selected to represent a range of land uses and source influences (eg, background, road traffic, commercial, industrial and residential areas, and various neighbourhood socioeconomic classes). We will collect data on fine particulate matter (PM2.5), nitrogen oxides (NOx), weather variables, sound (noise level and audio) along with street-level time-lapse images. We deploy low-cost, low-power, lightweight monitoring devices that are robust, socially unobtrusive, and able to function in Sub-Saharan African (SSA) climate. We will use state-of-the-art methods, including spatial statistics, deep/machine learning, and processed-based emissions modelling, to capture highly resolved temporal and spatial variations in pollution levels across the GAMA and to identify their potential sources. This protocol can serve as a prototype for other SSA cities.Ethics and dissemination This environmental study was deemed exempt from full ethics review at Imperial College London and the University of Massachusetts Amherst; it was approved by the University of Ghana Ethics Committee (ECH 149/18-19). This protocol is designed to be implementable in SSA cities to map environmental pollution to inform urban planning decisions to reduce health harming exposures to air and noise pollution. It will be disseminated through local stakeholder engagement (public and private sectors), peer-reviewed publications, contribution to policy documents, media, and conference presentations.

Sub-Saharan Africa (SSA) is rapidly urbanizing, and ambient air pollution has emerged as a major environmental health concern in growing cities. Yet, effective air quality management is hindered by limited data. We deployed robust, low-cost and low-power devices in a large-scale measurement campaign and characterized within-city variations in fine particulate matter (PM _2.5 ) and black carbon (BC) pollution in Accra, Ghana. Between April 2019 and June 2020, we measured weekly gravimetric (filter-based) and minute-by-minute PM _2.5 concentrations at 146 unique locations, comprising of 10 fixed (∼1 year) and 136 rotating (7 day) sites covering a range of land-use and source influences. Filters were weighed for mass, and light absorbance (10 ^−5 m ^−1 ) of the filters was used as proxy for BC concentration. Year-long data at four fixed sites that were monitored in a previous study (2006–2007) were compared to assess changes in PM _2.5 concentrations. The mean annual PM _2.5 across the fixed sites ranged from 26 μ g m ^−3 at a peri-urban site to 43 μ g m ^−3 at a commercial, business, and industrial (CBI) site. CBI areas had the highest PM _2.5 levels (mean: 37 μ g m ^−3 ), followed by high-density residential neighborhoods (mean: 36 μ g m ^−3 ), while peri-urban areas recorded the lowest (mean: 26 μ g m ^−3 ). Both PM _2.5 and BC levels were highest during the dry dusty Harmattan period (mean PM _2.5 : 89 μ g m ^−3 ) compared to non-Harmattan season (mean PM _2.5 : 23 μ g m ^−3 ). PM _2.5 at all sites peaked at dawn and dusk, coinciding with morning and evening heavy traffic. We found about a 50% reduction (71 vs 37 μ g m ^−3 ) in mean annual PM _2.5 concentrations when compared to measurements in 2006–2007 in Accra. Ambient PM _2.5 concentrations in Accra may have plateaued at levels lower than those seen in large Asian megacities. However, levels are still 2- to 4-fold higher than the WHO guideline. Effective and equitable policies are needed to reduce pollution levels and protect public health.

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.

This paper presents a framework for the evaluation of system complexity and utility and the identification of bottlenecks in the deployment of field-based, high-throughput phenotyping (FB-HTP) systems. Although the capabilities of technology used for high-throughput phenotyping has improved and costs decreased, there have been few, if any, successful attempts at developing turnkey field-based phenotyping systems. To identify areas for future improvement in developing turnkey FB-HTP solutions, a framework for evaluating their complexity and utility was developed and applied to total of 10 case studies to highlight potential barriers in their development and adoption. The framework performs system factorization and rates the complexity and utility of subsystem factors, as well as each FB-HTP system as a whole, and provides data related to the trends and relationships within the complexity and utility factors. This work suggests that additional research and development are needed focused around the following areas: (i) data handling and management, specifically data transfer from the field to the data processing pipeline, (ii) improved human-machine interaction to facilitate usability across multiple users, and (iii) design standardization of the factors common across all FB-HTP systems to limit the competing drivers of system complexity and utility. This framework can be used to evaluate both previously developed and future proposed systems to approximate the overall system complexity and identify areas for improvement prior to implementation.

Knowledge of processes leading to crop damage is central to devising rational approaches to disease management. Multiple experiments established that infection of hop cones by Podosphaera macularis was most severe if inoculation occurred within 15 to 21 days after bloom. This period of infection was associated with the most pronounced reductions in alpha acids, cone color, and accelerated maturation of cones. Susceptibility of cones to powdery mildew decreased progressively after the transition from bloom to cone development, although complete immunity to the disease failed to develop. Maturation of cone tissues was associated with multiple significant affects on the pathogen manifested as reduced germination of conidia, diminished frequency of penetration of bracts, lengthening of the latent period, and decreased sporulation. Cones challenged with P. macularis in juvenile developmental stages also led to greater frequency of colonization by a complex of saprophytic, secondary fungi. Since no developmental stage of cones was immune to powdery mildew, the incidence of powdery mildew continued to increase over time and exceeded 86% by late summer. In field experiments with a moderately susceptible cultivar, the incidence of cones with powdery mildew was statistically similar when fungicide applications were made season-long or targeted only to the juvenile stages of cone development. These studies establish that partial ontogenic resistance develops in hop cones and may influence multiple phases of the infection process and pathogen reproduction. The results further reinforce the concept that the efficacy of a fungicide program may depend largely on timing of a small number of sprays during a relatively brief period of cone development. However in practice, targeting fungicide and other management tactics to periods of enhanced juvenile susceptibility may be complicated by a high degree of asynchrony in cone development and other factors that are situation-dependent.

The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naive to SARS-CoV-2; however, almost all have previously encountered other coronaviruses (CoVs), and the role of this immunity in shaping the vaccine response remains uncharacterized. Here, we use longitudinal samples and highly multiplexed serology to identify mRNA-1273 vaccine-induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS-CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later time points. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.

BackgroundAnkylosing spondylitis (AS) is a chronic, progressive, inflammatory disease of the spine and SI joints. Diagnostic criteria and treatments have continued to evolve, necessitating a historical compendium of AS and its management. This paper aims to review the historical context underlying the discovery of AS, as well as the major diagnostic and therapeutic discoveries in the last two centuries.MethodsA scoping review of the literature pertaining to AS was performed via the Pubmed, Scopus, and Web of Science databases. Future directions of AS treatments were assessed by querying the clinicaltrials.gov website.ResultsThe history of AS can be traced as far back as ancient Egypt (as evidenced by the discovery of its presence in ancient Egyptian mummies) to the late 20th century, when the inherited nature of AS was linked to a genetic factor, HLA-B27. Each discovery made throughout the years led to further investigations into the pathophysiology, diagnosis, and treatment of AS. The criteria to differentiate AS from rheumatoid arthritis were first reported in 1893. Since then, diagnostic criteria for AS have undergone a series of changes before the present-day diagnostic criteria for AS were ultimately determined in 2009 by the Assessment of Spondyloarthritis International Society.ConclusionAs the pathophysiology of AS is better understood, healthcare providers are able to diagnose and treat the condition more effectively. In particular, earlier diagnosis and multiple treatment options have facilitated efficient and more effective treatment.

We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.