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Limb immobilization causes rapid declines in muscle strength and mass. Given the role of the nervous system in immobilization‐induced weakness, targeted interventions may be able to preserve muscle strength, but not mass, and vice versa. The purpose of this study was to assess the effects of two distinct interventions during 1 week of knee joint immobilization on muscle strength (isometric and concentric isokinetic peak torque), mass (bioimpedance spectroscopy and ultrasonography), and neuromuscular function (transcranial magnetic stimulation and interpolated twitch technique). Thirty‐nine healthy, college‐aged adults (21 males, 18 females) were randomized into one of four groups: immobilization only (n = 9), immobilization + action observation/mental imagery (AOMI) (n = 10), immobilization + neuromuscular electrical stimulation (NMES) (n = 12), or control group (n = 8). The AOMI group performed daily video observation and mental imagery of knee extensions. The NMES group performed twice daily stimulation of the quadriceps femoris. Based on observed effect sizes, it appears that AOMI shows promise as a means of preserving voluntary strength, which may be modulated by neural adaptations. Strength increased from PRE to POST in the AOMI group, with +7.2% (Cohen's d = 1.018) increase in concentric isokinetic peak torque at 30°/s. However, NMES did not preserve muscle mass. Though preliminary, our findings highlight the specific nature of clinical interventions and suggest that muscle strength can be independently targeted during rehabilitation. This study was prospectively registered: ClinicalTrials.gov NCT05072652. What is the central question of this study?Action observation and mental imagery (AOMI) may be a possible and potentially promising rehabilitation strategy via facilitation of neural adaptations, whereas neuromuscular electrical stimulation (NMES) may augment muscle strength and mass via peripheral mechanisms. We compared the ability of these interventions to distinctly preserve strength versus mass during one week of knee joint immobilization.What is the main finding and its importance?Effect sizes suggested that AOMI preserved voluntary strength, and may be used therapeutically to target neural adaptations during immobilization. [ABSTRACT FROM AUTHOR]

Does police militarization influence government use of repression? While comparative work examines police militarization, violence, human rights abuses, and torture, it does not integrate militarized police within existing theories of repression. Connecting police militarization and repression, this article argues that police militarization increases the police's perception of threat as well as their coercive capacity, thereby increasing their willingness to repress. As such, we hypothesize police militarization increases repression. To evaluate the theory, we conduct an international analysis using existing datasets covering 102 countries from 1994 to 2010. Employing several statistical models, the data supports the conclusion that police militarization increases the likelihood of government repression, specifically through extrajudicial killing and torture. Aside from highlighting a consequence of police militarization policy, the findings point to police militarization as an important omitted variable in cross-national models of repression and human rights. [ABSTRACT FROM AUTHOR]

Background: Muscle-invasive bladder cancer (MIBC) is a potentially fatal disease, especially in the setting of locally advanced or node-positive disease. Adverse outcomes have also primarily been associated with low-income status, as has been reported in other cancers. While the adoption of neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) and pelvic lymph node dissection (PLND) has improved outcomes, these standard-of-care treatments may be underutilized in lower-income patients. We sought to investigate the economic disparities in NAC and PLND receipt and survival outcomes in MIBC. Methods: Utilizing the National Cancer Database, a retrospective cohort analysis of cT2-4N0-3M0 BCa patients with urothelial histology who underwent RC was conducted. The impact of income level on overall survival (OS) and the likelihood of receiving NAC and PLND was evaluated. Results: A total of 25,823 patients were included. This study found that lower-income patients were less likely to receive NAC and adequate PLND (≥15 LNs). Moreover, lower-income patients exhibited worse OS (Median OS 55.9 months vs. 68.2 months, p < 0.001). Our findings also demonstrated that higher income, treatment at academic facilities, and recent years of diagnosis were associated with an increased likelihood of receiving standard-of-care modalities and improved survival. Conclusions: Even after controlling for clinicodemographic variables, income independently influenced the receipt of standard MIBC treatments and survival. Our findings identify an opportunity to improve the quality of care for lower-income MIBC patients through concerted efforts to regionalize multi-modal urologic oncology care. [ABSTRACT FROM AUTHOR]

Recent observations suggest that El Niño–Southern Oscillation (ENSO) impacts basal melting of West Antarctic ice shelves, yet sparse ocean observations limit our understanding of the associated processes. Here we investigate how ENSO events modulate subsurface West Antarctic shelf temperatures using high‐resolution global ocean‐sea ice model simulations. During El Niño, the subsurface shelf warming between 150 m and the shelf bottom can be up to 0.5°C in front of ice shelves. This warming arises from a weaker Amundsen Sea Low (ASL) and weaker coastal easterlies that reduce on‐shelf Ekman transport of cold surface waters, enabling enhanced transport of warm Circumpolar Deep Water (CDW) onto the shelf. A largely opposite response occurs during La Niña, with a stronger ASL and stronger Ekman transport that results in less cross‐shelf CDW transport and cooling in the subsurface. These findings have implications for interpreting basal melting on interannual to decadal time‐scales in West Antarctica. Plain Language Summary: El Niño‐Southern Oscillation (ENSO) is the Earth's dominant year‐to‐year climate variation. The impacts of its two phases, El Niño and La Niña, extend from the tropics to Antarctica through atmospheric waves. Past studies have suggested that West Antarctic ice shelves melt more during El Niño because of warmer ocean waters at the ice shelf bases. However, oceanic changes during El Niño lead to warming on the shelf near the ice which is difficult to isolate. That is because ENSO is only one of many drivers that impact shelf water temperatures. In this work, we simulate isolated ENSO events using an ocean circulation model. We show that during El Niño, the on‐shelf flow of cold surface waters in West Antarctica, driven by coastal easterly winds, is reduced because the winds weaken. To balance out this mass deficit at the surface, more warm CDW flows onto the continental shelf below. During La Niña, we see a largely opposite response. Stronger coastal easterlies increase the on‐shelf flow of cold surface waters and less CDW is flowing onto the shelf. Our results show the link between ENSO and mass loss of the West Antarctic ice shelves and ice sheet. Key Points: Ocean‐sea ice model simulations of El Niño and La Niña events illustrate how they modulate West Antarctic shelf temperaturesEl Niño weakens coastal easterlies, reduces on‐shelf Ekman flow of cold waters, increasing cross‐shelf flow of warm Circumpolar Deep Water (CDW)The La Niña shelf circulation response is largely opposite and reduces cross‐shelf transport of warm CDW [ABSTRACT FROM AUTHOR]

Rock textures observed via thin section are skewed from their true 3D nature. This is due to various cut effects—artifacts introduced due to the lower dimensional nature of the thin section relative to the rock. These cut effects can be corrected, and several methods have been developed to invert crystal shape and crystal size, but with each process performed separately and sequentially. With the ongoing adoption of electron backscatter diffraction (EBSD) by petrologists, an additional data stream has now become available: the 3D orientation of 2D grain sections. For EBSD analysis, no stereological corrections are typically applied for interpreting the data. This study tests whether this orientational information is skewed due to a fabric cut effect. We test this by numerically generating synthetic crystal datasets representative of several crystal shapes and population sizes. We find that EBSD orientational data has a fabric cut effect since crystals oriented with long axes perpendicular to the thin section are more likely to be sampled compared to those with long axes oriented parallel to it. This effect must be accounted for to interpret the true 3D fabric accurately. Towards this end, we develop two new tools for working with EBSD-derived fabric: (1) a simple first-order test for determining if a measured fabric exceeds that of the fabric cut effect, and (2) a method of inverting cut fabrics that provides robust error estimations. We demonstrate the applicability and accuracy of these methods using a range of synthetic examples and a natural sample. With these newly developed tools, there is clear potential for a new textural toolkit framework, to further our ability to correct for the various cut effects while also providing accurate uncertainty estimates. [ABSTRACT FROM AUTHOR]

The Outer Continental Shelf of the Gulf of Mexico (GOM) is populated with numerous oil and natural gas (ONG) platforms which produce NOx (NOx = NO + NO2), a major component of air pollution. The Bureau of Ocean Energy Management (BOEM) is mandated to ensure that the air quality of coastal states is not degraded by these emissions. As part of a NASA‐BOEM collaboration, we conducted a satellite data‐based analysis of nitrogen dioxide (NO2) patterns and trends in the GOM. Data from the OMI and TROPOMI sensors were used to obtain 18+ year records of tropospheric column (TrC) NO2 in three GOM regions: (a) Houston urban area, (b) near shore area off the Louisiana coast, and a (c) deepwater area off the Louisiana coast. The 2004–2022 time series show a decreasing trend for the urban (−0.027 DU/decade) and near shore (−0.0022 DU/decade) areas, and an increasing trend (0.0019 DU/decade) for the deepwater area. MERRA‐2 wind and TROPOMI NO2 data were used to reveal several NO2 hotspots (up to 25% above background values) under calm wind conditions near individual platforms. The NO2 signals from these deepwater platforms and the high density of shallow water platforms closer to shore were confirmed by TrC NO2 anomalies of up to 10%, taking into account the monthly TrC NO2 climatology over the GOM. The results presented in this study establish a baseline for future estimates of emissions from the ONG hotspots and provide a methodology for analyzing NO2 measurements from the new geostationary TEMPO instrument. Plain Language Summary: Oil and natural gas operations emit nitrogen oxides (NOx), which are major air pollutants and precursors to ground‐level ozone. The Bureau of Ocean Energy Management (BOEM) agency is responsible for managing planned oil and natural gas (ONG) activity on the outer continental shelf, and is mandated to ensure related emissions do not degrade air quality of coastal states. In collaboration with BOEM, we used satellite data from the OMI and TROPOMI sensors to construct an 18+ year record of tropospheric nitrogen dioxide (NO2), a proxy for NOx, in the Gulf Coast region. These time series focused on three areas: (a) Houston urban, (b) off the Louisiana coast, and (c) deepwater Gulf off Louisiana. These regions experienced changes in tropospheric column NO2 of −13.7%, −5.8%, and +5.4% per decade, respectively. We also identified NO2 hotspots from ONG platforms using TROPOMI NO2 averages under calm wind conditions. The ONG deepwater platforms enhance NO2 background amounts by 7%–13% on average, and up to 25% for the Mars and Olympus platforms combined. The results presented here will facilitate our work on emissions estimates from these sources and on applications to the recently launched TEMPO instrument. Key Points: Satellite NO2 records and trends of urban, coastal and deep water areas from 2005 to 2022, are presentedClassifying NO2 over the Gulf of Mexico (GOM) under various wind conditions highlights typical patterns in average NO2 valuesGOM NO2 hotspots from deepwater platforms were identified by TROPOMI under calm wind conditions, the largest of which is over Mars/Olympus [ABSTRACT FROM AUTHOR]

Background: Widespread transmission of COVID-19 continues to threaten public health, particularly of rural, American Indian communities. Although COVID-19 risk factors for severe disease and clinical characteristics are well described in the general population, there has been little shared on hospitalized American Indian populations. Methods: In this observational study, we performed chart extractions on all persons hospitalized with COVID-19 from April 1 through July 31, 2020 among an exclusively American Indian population living on or near Tribal lands in eastern Arizona. We provide descriptive statistics for the cohort stratified by presentation, comparing those who self-presented or were referred by an outreach program. Exploratory analyses were performed to identify risk factors for morbidity and mortality. Results: During the observation period, 2262 persons were diagnosed with COVID-19 and 490 (22%) were hospitalized. Hospitalized persons had a median age of 54 years; 92% had at least one comorbidity, 72% had greater than one comorbidity, and 60% had a BMI of > 30. Most persons required supplemental oxygen (83%), but the majority (62%) only required nasal cannula and only 11% were intubated. The case fatality rates were 1.7% for the population, 7.1% among hospitalizations, and 9.3% among hospitalized patients 50 years and older. All rates that are significantly lower than those reported nationally during the same period. Conclusions: We observed a cohort of American Indian patients hospitalized secondary to COVID-19 with greater number of comorbidities compared to the general population but with lower mortality rates. We posit that the primary driver of mortality reduction for this population and the hospitalized cohort was a community-based referral program that led to disproportionately lower fatality rates among the oldest persons. [ABSTRACT FROM AUTHOR]

Recent research has shown more favorable training adaptations for inactive adults when cardiorespiratory fitness (CRF) exercise is prescribed with the use of ventilatory thresholds compared to percentages of heart rate reserve (HRR). However, there is limited research on changes in health-related outcomes with the use of these CRF methods in combination with muscular fitness exercises. The objective of this study was to compare the effectiveness of two training programs for improving CRF, muscular fitness, and cardiometabolic risk factors. Inactive men and women (n=109, aged 49.3±15.5 years) were randomized to a non-exercise control group or one of two exercise training groups. The exercise training groups consisted of 13 weeks of structured exercise with progression using either CRF exercise prescribed with the use of ventilatory thresholds and functional training for muscular fitness (THRESH group) or HRR and traditional muscular fitness training (STND group). After the 13-week protocol, there were significant differences in body weight, body composition, systolic blood pressure, high-density lipoprotein cholesterol (HDL-c), VO2max, 5-repetition maximum (RM) bench press, and 5-RM leg press for both treatment groups compared to the control group after controlling for baseline values. However, the THRESH group had significantly more desirable outcomes for VO2max, 5-RM bench press, 5-RM leg press, body composition, and HDL-c when compared to both the STND and control group. Additionally, the proportion of individuals estimated as likely to respond above 3.5 mL½kg-1½min-1 in VO2max (i.e., the minimal clinically important difference) was 76.4%, 20.8%, and 0.13% for the THRESH, STND, and control groups, respectively. While both exercise programs elicited favorable health-related adaptations after 13 weeks, these results suggest that a personalized program with exercise prescribed based on ventilatory threshold and with the use of functional muscular fitness training may yield greater training adaptations. [ABSTRACT FROM AUTHOR]

Summary: The biosynthesis of specialized metabolites is strictly regulated by environmental inputs such as the day–night cycle, but the underlying mechanisms remain elusive. In Petunia hybrida cv. Mitchell flowers, the biosynthesis and emission of volatile compounds display a diurnal pattern with a peak in the evening to attract nocturnal pollinators.Using petunia flowers as a model system, we found that chromatin level regulation, especially histone acetylation, plays an essential role in mediating the day–night oscillation of the biosynthetic gene network of specialized metabolites.By performing time‐course chromatin immunoprecipitation assays for histone modifications, we uncovered that a specific group of genes involved in the regulation, biosynthesis, and emission of floral volatile compounds, which displays the greatest magnitude in day–night oscillating gene expression, is associated with highly dynamic histone acetylation marks H3K9ac and H3K27ac. Specifically, the strongest oscillating genes featured a drastic removal of histone acetylation marks at night, potentially to shut down the biosynthesis of floral volatile compounds during the morning when they are not needed. Inhibiting daytime histone acetylation led to a compromised evening induction of these genes.Overall, our study suggested an active role of chromatin modification in the diurnal oscillation of specialized metabolic network. [ABSTRACT FROM AUTHOR]

Hop production utilizes exclusively female plants, whereas male plants only serve to generate novel variation within breeding programs through crossing. Currently, hop lacks a rapid and accurate diagnostic marker to determine whether plants are male or female. Without a diagnostic marker, breeding programs may take 1–2 years to determine the sex of new seedlings. Previous research on sex-linked markers was restricted to specific populations or breeding programs and therefore had limited transferability or suffered from low scalability. A large collection of 765 hop genotypes with known sex phenotypes, genotyping-by-sequencing, and genome-wide association mapping revealed a highly significant marker on the sex chromosome (LOD score = 208.7) that predicted sex within our population with 96.2% accuracy. In this study, we developed a PCR allele competitive extension (PACE) assay for the diagnostic SNP and tested three quick DNA extraction methodologies for rapid, high-throughput genotyping. Additionally, the marker was validated in a separate population of 94 individuals from 15 families from the USDA-ARS hop breeding program in Prosser, WA with 96% accuracy. This diagnostic marker is located in a gene predicted to encode the basic helix-loop-helix transcription factor protein, a family of proteins that have been previously implicated in male sterility in a variety of plant species, which may indicate a role in determining hop sex. The marker is diagnostic, accurate, affordable, and highly scalable and has the potential to improve efficiency in hop breeding. [ABSTRACT FROM AUTHOR]

Adenine nucleotide translocator (ANT) is a mitochondrial protein involved in the exchange of ADP and ATP across the mitochondrial inner membrane. It plays a crucial role in cellular energy metabolism by facilitating the transport of ATP synthesized within the mitochondria to the cytoplasm. The isoform ANT1 predominately expresses in cardiac and skeletal muscles. Mutations or dysregulation in ANT1 have been implicated in various mitochondrial disorders and neuromuscular diseases. We aimed to examine whether ANT1 deletion may affect mitochondrial redox state in our established ANT1-deficient mice. Hearts and quadriceps resected from age-matched wild type (WT) and ANT1-deficient mice were snap-frozen in liquid nitrogen. The Chance redox scanner was utilized to perform 3D optical redox imaging. Each sample underwent scanning across 3–5 sections. Global averaging analysis showed no significant differences in the redox indices (NADH, flavin adenine dinucleotide containing-flavoproteins Fp, and the redox ratio Fp/(NADH+Fp) between WT and ANT1-deficient groups. However, quadriceps had higher Fp than hearts in both groups (p = 0. 0 0 0 4 and 0.01, respectively). Furthermore, the quadriceps were also more oxidized (a higher redox ratio) than hearts in WT group (p = 0. 0 0 4). NADH levels were similar in all cases. Our data suggest that under non-stressful physical condition, the ANT1-deficient muscle cells were in the same mitochondrial state as WT ones and that the significant difference in the mitochondrial redox state between quadriceps and hearts found in WT might be diminished in ANT1-deficient ones. Redox imaging of muscles under physical stress can be conducted in future. [ABSTRACT FROM AUTHOR]

The heterohexameric ATPases associated with diverse cellular activities (AAA)-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses the energy from ATP hydrolysis to mechanically thread substrate proteins through its central pore, thereby unfolding them. In related AAA-ATPase motors, substrates are recruited through binding to the motor's N-terminal domains or N terminally bound cofactors. Here, we use structural and biochemical techniques to characterize the function of the N1 domain in Pex6 from budding yeast, Saccharomyces cerevisiae. We found that although Pex1/ΔN1-Pex6 is an active ATPase in vitro, it does not support Pex1/Pex6 function at the peroxisome in vivo. An X-ray crystal structure of the isolated Pex6 N1 domain shows that the Pex6 N1 domain shares the same fold as the N-terminal domains of PEX1, CDC48, and NSF, despite poor sequence conservation. Integrating this structure with a cryo-EM reconstruction of Pex1/Pex6, AlphaFold2 predictions, and biochemical assays shows that Pex6 N1 mediates binding to both the peroxisomal membrane tether Pex15 and an extended loop from the D2 ATPase domain of Pex1 that influences Pex1/Pex6 heterohexamer stability. Given the direct interactions with both Pex15 and the D2 ATPase domains, the Pex6 N1 domain is poised to coordinate binding of cofactors and substrates with Pex1/Pex6 ATPase activity. [ABSTRACT FROM AUTHOR]

Ecosystem function is a foundational part of ecosystem health, but it is often neglected in the practice of ecosystem monitoring. We conducted a review of freshwater ecosystem management literature, analysing 60 documents across multiple organisations to understand the prevalence of function in conceptualisations and measures of ecosystem health. Only 28% (n = 13) of analysed documents included definitions of waterway health that included function, and only 30% (n = 18) integrated function into their conceptualisations of waterway health. More generally, we observed noticeable deviation in analysed documents from management best practices advocated for by contemporary ecosystem science – including unclear rationales, vague language, and imprecise metrics for assessing waterway health. We discuss these findings in broader ecosystem management contexts. Our findings support previous observations of a strong structural bias in current ecosystem health monitoring and suggest the need for closer examinations into the processes and rationales by which such an important factor could be absent from monitoring programs. [ABSTRACT FROM AUTHOR]

Access points to Heliophysics information are often poorly inter-linked to one another, making it challenging for researchers to integrate information, mature their understanding, and incorporate more complex ideas and relationships into their analyses. The authors reason this behavior to be a direct conseaquence of the lack of infrastructure for knowledge and data discovery in Heliophysics. Building an online library resource for Heliophysics addresses this gap in resources, and can also address other troublesome gaps related to community-building, such as access to help from other scientists, example analysis tutorials, and collaboration opportunities. This paper envisions a resource that better connects existing Heliophysics information and knowledge sources, the LIbrary for KnowledgE and Discovery (LIKED), which will be an online resource that interlinks information across databases (e.g., observational and publication), researcher interactions (e.g., conferences and discussion boards), and educational materials. The result is a rich and searchable environment to provide users a more productive experience for research and collaboration. In this paper, we provide the conceptual model for LIKED. We expand to detail how LIKED will serve to connect the various knowledge and research components available internationally together in an uniformly searchable manner. Finally, this work outlines various contributions the community can make towards this goal. [ABSTRACT FROM AUTHOR]

The ability to distinguish between the abdominal conditions of adult female mosquitoes has important utility for the surveillance and control of mosquito-borne diseases. However, doing so requires entomological training and time-consuming manual effort. Here, we design computer vision techniques to determine stages in the gonotrophic cycle of female mosquitoes from images. Our dataset was collected from 139 adult female mosquitoes across three medically important species—Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus—and all four gonotrophic stages of the cycle (unfed, fully fed, semi-gravid, and gravid). From these mosquitoes and stages, a total of 1959 images were captured on a plain background via multiple smartphones. Subsequently, we trained four distinct AI model architectures (ResNet50, MobileNetV2, EfficientNet-B0, and ConvNeXtTiny), validated them using unseen data, and compared their overall classification accuracies. Additionally, we analyzed t-SNE plots to visualize the formation of decision boundaries in a lower-dimensional space. Notably, ResNet50 and EfficientNet-B0 demonstrated outstanding performance with an overall accuracy of 97.44% and 93.59%, respectively. EfficientNet-B0 demonstrated the best overall performance considering computational efficiency, model size, training speed, and t-SNE decision boundaries. We also assessed the explainability of this EfficientNet-B0 model, by implementing Grad-CAMs—a technique that highlights pixels in an image that were prioritized for classification. We observed that the highest weight was for those pixels representing the mosquito abdomen, demonstrating that our AI model has indeed learned correctly. Our work has significant practical impact. First, image datasets for gonotrophic stages of mosquitoes are not yet available. Second, our algorithms can be integrated with existing citizen science platforms that enable the public to record and upload biological observations. With such integration, our algorithms will enable the public to contribute to mosquito surveillance and gonotrophic stage identification. Finally, we are aware of work today that uses computer vision techniques for automated mosquito species identification, and our algorithms in this paper can augment these efforts by enabling the automated detection of gonotrophic stages of mosquitoes as well. [ABSTRACT FROM AUTHOR]

Environmental stimuli trigger rapid transcriptional reprogramming of gene networks. These responses occur in the context of the local chromatin landscape, but the contribution of organ-specific dynamic chromatin modifications in responses to external signals remains largely unexplored. We treated tomato seedlings with a supply of nitrate and measured the genome-wide changes of four histone marks, the permissive marks H3K27ac, H3K4me3, and H3K36me3 and repressive mark H3K27me3, in shoots and roots separately, as well as H3K9me2 in shoots. Dynamic and organ-specific histone acetylation and methylation were observed at functionally relevant gene loci. Integration of transcriptomic and epigenomic datasets generated from the same organ revealed largely syngenetic relations between changes in transcript levels and histone modifications, with the exception of H3K27me3 in shoots, where an increased level of this repressive mark is observed at genes activated by nitrate. Application of a machine learning approach revealed organ-specific rules regarding the importance of individual histone marks, as H3K36me3 is the most successful mark in predicting gene regulation events in shoots, while H3K4me3 is the strongest individual predictor in roots. Our integrated study substantiates a view that during plant environmental responses, the relationships between histone code dynamics and gene regulation are highly dependent on organ-specific contexts. Analysis of ChIP-Seq of multiple histone modifications across shoots and roots in two nutrient supply conditions, coupled with machine learning, reveals new organ-specific patterns of epigenetic regulation in response to nitrate in tomatoes. [ABSTRACT FROM AUTHOR]

Starry stonewort (Nitellopsis obtusa) (Desvaux in Loiseleur) J. Groves is an invasive macro alga that can take over entire water columns and outcompete native species. Previous research has quantified seasonal life history and phenology but there is no research quantifying carbohydrate allocation. The current study utilized samples harvested from Lake Koronis, Minnesota, USA from 2020 and 2021 to quantify starch allocation patterns in N. obtusa. Starch was quantified using the amylase/amyloglucosidase method. Starch data were compared to light transmittance (%), pH and water temperature (°C) via mixed procedures models in SAS. Seasonal average low and high points of starch storage were observed to be June (3.3%) and April (9.9%) for thalli biomass then June (41.7%) and November (54.6%) for bulbils. In regard to allocation patterns, above ground thalli reallocates carbohydrate stores to the below ground rhizoids in May. Carbohydrates are then transported to bulbils from July through September as rhizoid starch decreases and the bulbil starch increases. Ultimately, the carbohydrates are converted to starch and stored in bulbils (21.0–73.7%). In its invaded range, bulbils are important for energy store, vegetative reproduction and spread, as well as temporal distribution. These bulbils spread easily, spread rapidly, can store a lot of energy (73% starch), and are a major concern for the invasion of N. obtusa. Water temperature and light availability were shown to negatively influence starch content of thalli. These findings suggest that in the invaded range, N. obtusa is capable of accumulating large amounts of starch later into the growing season. The energy reserves may give N. obtusa a competitive advantage over native species by allowing a longer growing season resulting in the production of more vegetative propagules and greater longevity in the environments it invades. [ABSTRACT FROM AUTHOR]

A central challenge in population genetics is the detection of genomic footprints of selection. As machine learning tools including convolutional neural networks (CNNs) have become more sophisticated and applied more broadly, these provide a logical next step for increasing our power to learn and detect such patterns; indeed, CNNs trained on simulated genome sequences have recently been shown to be highly effective at this task. Unlike previous approaches, which rely upon human-crafted summary statistics, these methods are able to be applied directly to raw genomic data, allowing them to potentially learn new signatures that, if well-understood, could improve the current theory surrounding selective sweeps. Towards this end, we examine a representative CNN from the literature, paring it down to the minimal complexity needed to maintain comparable performance; this low-complexity CNN allows us to directly interpret the learned evolutionary signatures. We then validate these patterns in more complex models using metrics that evaluate feature importance. Our findings reveal that preprocessing steps, which determine how the population genetic data is presented to the model, play a central role in the learned prediction method. This results in models that mimic previously-defined summary statistics; in one case, the summary statistic itself achieves similarly high accuracy. For evolutionary processes that are less well understood than selective sweeps, we hope this provides an initial framework for using CNNs in ways that go beyond simply achieving high classification performance. Instead, we propose that CNNs might be useful as tools for learning novel patterns that can translate to easy-to-implement summary statistics available to a wider community of researchers. Author summary: The ever-increasing power and complexity of machine learning tools presents the scientific community with both unique opportunities and unique challenges. On the one hand, these data-driven approaches have led to state-of-the-art advances on a variety of research problems spanning many fields. On the other, these apparent performance improvements come at the cost of interpretability: it is difficult to know how a model makes its predictions. This is compounded by the computational sophistication of machine learning models which can lend an air of objectivity, often masking ways in which bias may be baked into the modeling decisions or the data itself. We present here a case study, examining these issues in the context of a central problem in population genetics: detecting patterns of selection from genome data. Through this application, we show how human decision-making can encourage the model to see what we want it to see in various ways. By understanding how these models work, and how they respond to the particular way in which data is presented, we have a chance of creating new frameworks that are capable of discovering novel patterns. [ABSTRACT FROM AUTHOR]

The periplasmic chaperone SilF has been identified as part of an Ag(I) detoxification system in Gram-negative bacteria. Sil proteins also bind Cu(I) but with reported weaker affinity, therefore leading to the designation of a specific detoxification system for Ag(I). Using isothermal titration calorimetry, we show that binding of both ions is not only tighter than previously thought but of very similar affinities. We investigated the structural origins of ion binding using molecular dynamics and QM/MM simulations underpinned by structural and biophysical experiments. The results of this analysis showed that the binding site adapts to accommodate either ion, with key interactions with the solvent in the case of Cu(I). The implications of this are that Gram-negative bacteria do not appear to have evolved a specific Ag(I) efflux system but take advantage of the existing Cu(I) detoxification system. Therefore, there are consequences for how we define a particular metal resistance mechanism and understand its evolution in the environment. [ABSTRACT FROM AUTHOR]

Development of biocomposite scaffolds has gained tremendous attention due to their potential for tissue regeneration. However, most scaffolds often contain animal-derived collagen that may elicit an immunological response, necessitating the development of new biomaterials. Herein, we developed a new collagen-like peptide,(Pro-Ala-His)10 (PAH)10, and explored its ability to be utilized as a functional biomaterial by incorporating it with a newly synthesized peptide-based self-assembled gel. The gel was prepared by conjugating a pectin derivative, galataric acid, with a pro-angiogenic peptide (LHYQDLLQLQY) and further functionalized with a cortistatin-derived peptide, (Phe-Trp-Lys-Thr)4 (FWKT)4, and the bio-ionic liquid choline acetate. The self-assembly of (PAH)10 and its interactions with the galactarate-peptide conjugates were examined using replica exchange molecular dynamics (REMD) simulations. Results revealed the formation of a multi-layered scaffold, with enhanced stability at higher temperatures. We then synthesized the scaffold and examined its physicochemical properties and its ability to integrate with aortic smooth muscle cells. The scaffold was further utilized as a bioink for bioprinting to form three-dimensional cell-scaffold matrices. Furthermore, the formation of actin filaments and elongated cell morphology was observed. These results indicate that the (PAH)10 hybrid scaffold provides a suitable environment for cell adhesion, proliferation and growth, making it a potentially valuable biomaterial for tissue engineering. [ABSTRACT FROM AUTHOR]

The deliberate removal of photovoltaic modules from a string can occur for various reasons encompassing maintenance, measurements, theft, or failure, reducing that string length relative to others when replacement modules are not available and there are not any viable alternative makes and models that could be inserted. This phenomenon, delineated in our prior experimentally validated research, manifests two significant effects: (1) a shift in the ideal maximum power point and (2) the induction of potentially substantial reverse currents in the shortened strings at open-circuit voltage, VOC. However, the scalability and asymptotic limits of these observed behaviors concerning array size remained undetermined. In this study, we elucidate the operational dynamics of such arrays by manipulating two mismatch-contributing variables in simulated arrays of up to 900 strings: the number of removed modules per string (indicative of the level of mismatch, ranging up to 5) and the quantity of shortened strings (1 to 60). Simulation outcomes underscore that mismatch severity impacts array operation more than the proportion of shortened strings. This research delves into the practical ramifications of operating with shortened strings, including implications for low-irradiance operation and the manifestation of deleterious reverse currents (>35 A in specific cases), emphasizing the need for careful array configuration for optimal performance and safety in these implementations. [ABSTRACT FROM AUTHOR]

Prime editing in vivo is systematically improved with an eye to clinical translation. [ABSTRACT FROM AUTHOR]

Local studies show upslope shifts in the distribution of tropical birds in response to warming temperatures. Unanswered is whether these upward shifts occur regionally across many species. We considered a nearly 2000‐km length of the Northern Andes, where deforestation, temperature, and extreme weather events have increased during the past decades. Range‐restricted bird species are particularly vulnerable to such events and occur in exceptionally high numbers in this region. Using abundant crowd‐sourced data from the Cornell Lab of Ornithology database, eBird, and the Global Biodiversity Information Facility, we documented distributions of nearly 200 such species. We examined whether species shifted their elevational ranges over time by comparing observed versus expected occurrences below a low elevational threshold and above a high elevational threshold for 2 periods: before and after 2005. We predicted fewer observations at lower elevations (those below the threshold) and more at upper elevations (those above the threshold) after 2005. We also tested for deforestation effects at lower elevations within each species' distribution ranges. We compared relative forest loss with the differences between observed and expected occurrences across the elevational range. Species' retreats from lower elevations were ubiquitous and involved a 23–40% decline in prevalence at the lowest elevations. Increases at higher elevations were not consistent. The retreats occurred across a broad spectrum of species, from predominantly lowland to predominantly highland. Because deforestation showed no relationship with species retreats, we contend that a warming climate is the most parsimonious explanation for such shifts. [ABSTRACT FROM AUTHOR]

Background: Colostral immunoglobulin G (IgG) concentration is critical to the attainment of adequate transfer of passive immunity in cattle, however, studies comparing available tools for measurement of colostral IgG concentration in beef cattle are limited. Objectives: To report the agreement between 3 commercially available tests for evaluating IgG concentration in beef colostrum. Animals: Two hundred six beef‐breed cows hospitalized for calving management or dystocia. Methods: Retrospective study to assess IgG of whole colostrum measured stall‐side via turbidimetric immunoassay (TI) and brix refractometry (BRIX), compared to fat separated (FS) analysis via single radial‐immunodiffusion (RID; reference standard), TI‐FS and BRIX‐FS. Test performance was assessed using Passing Bablock regression, Bland‐Altman analysis, and area under the curve to determine optimal thresholds. Results: Correlation between RID and TI‐FS, BRIX‐FS, or BRIX was similar (Spearman's ρ = 0.717, 0.715, 0.716, respectively) but correlation for TI was poor (ρ = 0.586). Regression analysis identified a substantial constant (−214.75 [CI: −272.03 to −178.07]) and proportional (13.24 [CI: 11.81‐15.37]) bias between the RID and TI‐FS which was similar for TI. TI‐FS concentrations of 28.47, 38.75, and 50.62 g/L, BRIX‐FS of ≤21.9%, ≤24.0%, and ≤27.4%, and BRIX of ≤21.3%, ≤23.8%, and ≤26.4% indicated IgG concentrations <50, <100, and <150 g/L, respectively; appropriate cutoffs for TI could not be generated. Conclusions and Clinical Importance: Both TI and TI‐FS demonstrated a large constant and proportional bias compared to RID; BRIX and BRIX‐FS were well correlated with RID and remain a reliable method for estimation of colostral IgG concentration in beef cattle. [ABSTRACT FROM AUTHOR]

Background: Attainment of adequate transfer of passive immunity (TPI) is critical to health of calves; however, studies comparing available tools for measurement of TPI in individual beef animals are limited. Objectives: To report agreement between 4 tests evaluating individual TPI status in beef calves. Animals: One hundred ninety‐six beef calves born to cows and heifers presenting for calving management or dystocia. Methods: Retrospective study to assess serum immunoglobulin (IgG) concentrations via turbidimetric immunoassay (TI), gamma‐glutamyl transferase (GGT), serum total protein (TP), and single radial immunodiffusion (RID; reference standard). Test agreement was evaluated using Passing‐Bablok regression, Bland‐Altman analysis, Cohen's kappa, and receiver operating characteristic (ROC) curves with and without covariate adjustment to determine optimal thresholds. Results: Correlation between RID and test results varied: TI, ρ = 0.757; TP, ρ = 0.715; GGT: ρ = 0.413. For the TI compared to RID, regression analysis identified a constant (intercept = −0.51 [CI: −2.63, 3.05]) and proportional (slope = 1.87 [CI: 1.69, 2.08]) bias. Based on ROC, TI concentrations of ≤9.89 and ≤13.76 g/L, and TP concentrations of ≤5.5 and ≤6.0 g/dL, indicated IgG concentrations <18.0 and <25.0 g/L, respectively. Conclusions and Clinical Importance: Within this cohort of calves, TI demonstrated the best correlation with RID; however, significant bias was identified which led to frequent underestimation of IgG concentration. Serum total protein demonstrated less correlation with RID but had less misclassification than TI. Both TI and TP demonstrated less correlation for calves that received colostrum replacement prompting clinical awareness of colostrum type when evaluating individual TPI in beef calves. [ABSTRACT FROM AUTHOR]

Connectivity is critical for stream fish persistence, and fish passage structures are a useful conservation tool to reconnect fragmented systems. The design of fish passage structures is a tradeoff between the area available for construction, slope, and costs associated with the structure. The Longrie–Fecteau fish passage structure was designed to be modular, adjustable to barrier-specific needs, and to have a low slope (2%) to pass small-bodied fishes. We evaluated fish passage through this structure in Fountain Creek, Colorado, USA, via a PIT tag mark–recapture study. We documented four native Great Plains fish species successfully ascending the passage structure, with most passage occurring at night. We estimated a 3% probability of a released fish entering the structure, then 89% and 99% passage to the midpoint and exit of the 123 m structure, respectively. Low entrance efficiency was due to low recapture probability of small-bodied study organisms in a relatively large system, and the low percentage of space of the entryway on this barrier (<3% of the length of the barrier). Fish that entered the structure ascended quickly, with median time for successful ascent of 19 min, and minimum time of 6 min. The Longrie–Fecteau fish passage structure is a conservation tool that may broaden the adoption of fish passage structures for small-bodied fishes due to its modularity and low slope. [ABSTRACT FROM AUTHOR]

Parametric modeling of downwelling longwave irradiance under all‐sky conditions (LW↓) typically involves "correcting" a clear‐ (or non‐overcast) sky model estimate using solar‐irradiance‐based proxies of cloud cover in lieu of actual cloud cover given uncertainties and measurement challenges of the latter. While such approaches are deemed sound, their application in time and space is inherently limited. We report on a correction model free of solar irradiance‐derived cloud proxies that is applicable at the true daily (24 hr) and global scales. The new "cloud‐free" correction model demonstrates superior performance in a range of environments relative to existing cloud‐free modeling approaches and to corrections based on solar‐derived cloudiness proxies. Literature‐based performance benchmarking indicates a performance that is often comparable to—and in some cases superior to—performances yielded by conventional parametric modeling approaches employing locally or regionally calibrated parameters, as well as to performances of satellite‐based algorithms. Plain Language Summary: Downwelling longwave irradiance (LW↓) is a major component of Earth's surface energy budget and is often modeled indirectly using routinely measured surface meteorological variables. In overcast (or "all‐sky") conditions, LW↓ is typically estimated by correcting an estimate valid for non‐overcast (or "clear‐sky") conditions using information about cloud cover or cloudiness proxies derived from solar irradiance variables. Cloud cover information is often unavailable and uncertain, and proxies based on solar irradiance variables inherently limit the correction to the daytime. Here, we present a correction model that circumvents the dependence on cloud variables or their proxies and document its performance when applied under a variety of conditions. Key Points: A model free of cloud variables or their solar‐based proxies is proposed to correct clear‐sky longwave irradiances under all‐sky conditionsModel performance is weakly sensitive to the underlying clear‐sky model when jointly parameterizedThe model yields daily errors of 3.9%–4.5% over ocean and 5.5%–7% over land, depending on the error metric and underlying clear‐sky model [ABSTRACT FROM AUTHOR]

Alcohol is one of the most commonly used substances and frequently abused, yet little is known about the neural underpinnings driving variability in inhibitory control performance after ingesting alcohol. This study was a single-blind, placebo-controlled, randomized design with participants (N = 48 healthy, social drinkers) completing three study visits. At each visit participants received one of three alcohol doses; namely, a placebo dose [equivalent Blood Alcohol Concentration (BAC) = 0.00%], a low dose of alcohol (target BAC = 0.04%), or a moderate dose of alcohol (target BAC = 0.08%). To measure inhibitory control, participants completed a Go/No-go task paradigm twice during each study visit, once immediately before dosing and once after, while their brain activity was measured with time-domain functional near-infrared spectroscopy (TD-fNIRS). BAC and subjective effects of alcohol were also assessed. We report decreased behavioral performance for the moderate dose of alcohol, but not the low or placebo doses. We observed right lateralized inhibitory prefrontal activity during go-no-go blocks, consistent with prior literature. Using standard and novel metrics of lateralization, we were able to significantly differentiate between all doses. Lastly, we demonstrate that these metrics are not only related to behavioral performance during inhibitory control, but also provide complementary information to the legal gold standard of intoxication (i.e. BAC). [ABSTRACT FROM AUTHOR]

Virus host shifts, where a virus transmits to and infects a novel host species, are a major source of emerging infectious disease. Genetic similarity between eukaryotic host species has been shown to be an important determinant of the outcome of virus host shifts, but it is unclear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Here, we measure the susceptibility of 64 strains of Staphylococcaceae bacteria (48 strains of Staphylococcus aureus and 16 non-S. aureus species spanning 2 genera) to the bacteriophage ISP, which is currently under investigation for use in phage therapy. Using three methods–plaque assays, optical density (OD) assays, and quantitative (q)PCR–we find that the host phylogeny explains a large proportion of the variation in susceptibility to ISP across the host panel. These patterns were consistent in models of only S. aureus strains and models with a single representative from each Staphylococcaceae species, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using OD and qPCR and variable correlations between plaque assays and either OD or qPCR, suggesting that plaque assays alone may be inadequate to assess host range. Furthermore, we demonstrate that the phylogenetic relationships between bacterial hosts can generally be used to predict the susceptibility of bacterial strains to phage infection when the susceptibility of closely related hosts is known, although this approach produced large prediction errors in multiple strains where phylogeny was uninformative. Together, our results demonstrate the ability of bacterial host evolutionary relatedness to explain differences in susceptibility to phage infection, with implications for the development of ISP both as a phage therapy treatment and as an experimental system for the study of virus host shifts. Author summary: Virus host shifts, where a virus jumps into a new host from another species, are a major source of emerging infectious diseases. Virus host shifts have been shown to be more likely between animals and plant species that are closely related. However, there is much to learn about how relatedness predicts susceptibility in bacterial hosts. Here, we used a panel of 64 Staphylococcus bacteria and a virus that infects them to investigate how the relationship between host species influences their susceptibility to infection. We find high variation in susceptibility to infection across the host panel and that most of that variation can be explained by the relationship between hosts. This effect is seen consistently using three methods for assessing susceptibility and can be seen both within and between species. Additionally, we find that the relationship between hosts allows us to predict the susceptibility of an unknown host with some accuracy, although there are instances where susceptibility cannot be predicted. Overall, this suggests that closely related hosts will show similar susceptibility to infection and that the relationship between bacterial hosts can be used to predict the susceptibility of an unknown host with limited success. [ABSTRACT FROM AUTHOR]

Objectives Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients. Methods In a prospective observational study, 475 patients with RA were treated with certolizumab (n  = 192) or adalimumab (n  = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs. Results Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P  = 0.04 and P  = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive. Conclusion In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Comorbidity indices can help identify patients at risk for postoperative complications. Purpose of this study was to compare different comorbidity indices to predict discharge destination and complications after shoulder arthroplasty. Methods: Retrospective review of institutional shoulder arthroplasty database of primary anatomic (TSA) and reverse (RSA) shoulder arthroplasties. Patient demographic information was collected in order to calculate Modified Frailty Index (mFI-5), Charlson Comorbidity Index (CCI), age adjusted CCI (age-CCI), and American Society of Anesthesiologists physical status classification system (ASA). Statistical analysis performed to analyze length of stay (LOS), discharge destination, and 90-day complications. Results: There were 1365 patients included with 672 TSA and 693 RSA patients. RSA patients were older and had higher CCI, age adjusted CCI, ASA, and mFI-5 (p < 0.001). RSA patients had longer lengths of stay (LOS), more likely to have an adverse discharge (p < 0.001), and higher reoperation rate (p = 0.003). Age-CCI was most predictive of adverse discharge (AUC 0.721, 95% CI 0.704–0.768). Discussion: Patients undergoing RSA had more medical comorbidities, experienced greater LOS, higher reoperation rate, and were more likely to have an adverse discharge. Age-CCI had the best ability to predict which patients were likely to require higher-level discharge planning. [ABSTRACT FROM AUTHOR]

Accurate predictions of drug uptake transporter involvement in renal excretion of xenobiotics require determination of in vitro transport kinetic parameters under initial-rate conditions. The purpose of the present study was to determine how changing the incubation time from initial rate to steady state influences ligand interactions with the renal organic anion transporter 1 (OAT1), and the impact of the different experimental conditions on pharmacokinetic predictions. Transport studies were performed with Chinese hamster ovary cells expressing OAT1 (CHO-OAT1) and the Simcyp Simulator was used for physiological-based pharmacokinetic predictions. Maximal transport rate and intrinsic uptake clearance (CLint) for PAH decreased with increasing incubation time. The CLint values ranged 11-fold with incubation times spanning from 15 s (CLint,15s, initial rate) to 45 min (CLint,45min, steady state). The Michaelis constant (Km) was also influenced by the incubation time with an apparent increase in the Km value at longer incubation times. Inhibition potency of five drugs against PAH transport was tested using incubation times of either 15 s or 10 min. There was no effect of time on inhibition potency for omeprazole or furosemide, whereas indomethacin was less potent, and probenecid (~2-fold) and telmisartan (~7-fold) more potent with the longer incubation time. Notably, the inhibitory effect of telmisartan was reversible, albeit slowly. A pharmacokinetic model was developed for PAH using the CLint,15s value. The simulated plasma concentration-time profile, renal clearance, and cumulative urinary excretion-time profile of PAH agreed well with reported clinical data, and the PK parameters were sensitive to the time-associated CLint value used in the model. [ABSTRACT FROM AUTHOR]

Rivers and lakes are intrinsically connected waterbodies yet they are rarely used to hydrologically constrain one another with remote sensing. Here we begin to bridge the gap between river and lake hydrology with the introduction of the LakeFlow algorithm. LakeFlow uses river‐lake mass conservation and observations from the Surface Water and Ocean Topography (SWOT) satellite to provide river discharge estimates of lake and reservoir inflows and outflows. We test LakeFlow performance at three lakes using a synthetic SWOT data set assuming the maximum measurement errors defined by the mission science requirements, and we include modeled lateral inflow and lake evaporation data to further constrain the mass balance. We find that LakeFlow produces promising discharge estimates (median Nash‐Sutcliffe efficiency = 0.88, relative bias = 14%). LakeFlow can inform water resources management by providing global lake inflow and outflow estimates, highlighting a path for recognizing rivers and lakes as an interconnected system. Plain Language Summary: Effective water resource management depends on our ability to monitor and understand lake and reservoir inflows and outflows. Satellite remote sensing of lakes and rivers has become increasingly important for water management but little work has been done to estimate streamflow at river‐lake interfaces. Here we present the LakeFlow algorithm that leverages satellite observations of lakes and rivers to estimate streamflow at lake inflows and outflows. We test LakeFlow using synthetic data at three U.S. lakes in Georgia, Arizona and Kansas, and find that it yields promising estimates of streamflow at river‐lake boundaries. LakeFlow provides valuable insights into river‐lake streamflow dynamics, which can inform water management decisions and is a step forward in the integration of river and lake studies. Key Points: LakeFlow is a new algorithm that uses Surface Water and Ocean Topography (SWOT) satellite data to estimate river inflow and outflow at lakes via mass conservationApplying LakeFlow to three sample lake systems shows promising performance for estimating lake inflows and outflows (median Nash‐Sutcliffe Efficiency = 0.88)Including modeled estimates of non SWOT‐observed evaporation and tributary inflows can further improve LakeFlow discharge estimates [ABSTRACT FROM AUTHOR]

Interactions between coinfecting pathogens have the potential to alter the course of infection and can act as a source of phenotypic variation in susceptibility between hosts. This phenotypic variation may influence the evolution of host-pathogen interactions within host species and interfere with patterns in the outcomes of infection across host species. Here, we examine experimental coinfections of two Cripaviruses–Cricket Paralysis Virus (CrPV), and Drosophila C Virus (DCV)–across a panel of 25 Drosophila melanogaster inbred lines and 47 Drosophilidae host species. We find that interactions between these viruses alter viral loads across D. melanogaster genotypes, with a ~3 fold increase in the viral load of DCV and a ~2.5 fold decrease in CrPV in coinfection compared to single infection, but we find little evidence of a host genetic basis for these effects. Across host species, we find no evidence of systematic changes in susceptibility during coinfection, with no interaction between DCV and CrPV detected in the majority of host species. These results suggest that phenotypic variation in coinfection interactions within host species can occur independently of natural host genetic variation in susceptibility, and that patterns of susceptibility across host species to single infections can be robust to the added complexity of coinfection. Author summary: The susceptibility of a host to infection can be influenced by the presence of co-occurring (i.e., coinfecting) pathogens, which can interact by suppressing and activating host immunity, and competing for host resources. The influence of coinfections on host susceptibility could have ramifications for the evolution of hosts and pathogens, and this may be seen within a single host species as a change in the contribution of host genetics to susceptibility during coinfections, and across host species as a change in the ability of evolutionary relationships to explain similarities in susceptibility. Here, we test these possibilities by measuring susceptibility to two different Cripaviruses during single infections and coinfections across different insect host genotypes and host species. We find that these two viruses interact during coinfections within the fruit fly Drosophila melanogaster, altering host susceptibility, but that variation in this interaction didn't show any evidence of being influenced by host genetics. Similarly, we find little evidence of the explanatory power of evolutionary relationships across host species changing between single infections and coinfections. These results suggest that variation in interactions between pathogens can occur without the influence of host genetics, and that it is possible for patterns in susceptibility across host species measured during single infection to be maintained during coinfection. [ABSTRACT FROM AUTHOR]

Muscular dystrophies (MDs) comprise a diverse group of inherited disorders characterized by progressive muscle loss and weakness. Given the genetic etiology underlying MDs, researchers have explored the potential of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing as a therapeutic intervention, resulting in significant advances. Here, we review recent progress on the use of CRISPR/Cas9 genome editing as a potential therapy for MDs. Significant strides have been made in this realm, made possible through innovative techniques such as precision genetic editing by modified forms of CRISPR/Cas9. These approaches have shown varying degrees of success in animal models of MD, including Duchenne MD, congenital muscular dystrophy type 1A, and myotonic dystrophy type 1. Even so, there are several challenges facing the development of CRISPR/Cas9-based MD therapies, including the targeting of satellite cells, improved editing efficiency in skeletal and cardiac muscle tissue, delivery vehicle enhancements, and the host immunogenic response. Although more work is needed to advance CRISPR/Cas9 genome editing past the preclinical stages, its therapeutic potential for MD is extremely promising and justifies concentrated efforts to move into clinical trials. [ABSTRACT FROM AUTHOR]

Extratropical cyclones develop in regions of enhanced baroclinicity and progress along climatological storm tracks. Numerous studies have noted an influence of terrestrial snow cover on atmospheric baroclinicity. However, these studies have less typically examined the role that continental snow cover extent and changes anticipated with anthropogenic climate change have on cyclones' intensities, trajectories, and precipitation characteristics. Here, we examined how projected future poleward shifts in North American snow extent influence extratropical cyclones. We imposed 10th, 50th, and 90th percentile values of snow retreat between the late 20th and 21st centuries as projected by 14 Coupled Model Intercomparison Project Phase Five (CMIP5) models to alter snow extent underlying 15 historical cold-season cyclones that tracked over the North American Great Plains and were faithfully reproduced in control model cases, providing a comprehensive set of model runs to evaluate hypotheses. Simulations by the Advanced Research version of the Weather Research and Forecast Model (WRF-ARW) were initialized at four days prior to cyclogenesis. Cyclone trajectories moved on average poleward (μ = 27 +/− σ = 17 km) in response to reduced snow extent while the maximum sea-level pressure deepened (μ = −0.48 +/− σ = 0.8 hPa) with greater snow removed. A significant linear correlation was observed between the area of snow removed and mean trajectory deviation (r2 = 0.23), especially in mid-winter (r2 = 0.59), as well as a similar relationship for maximum change in sea-level pressure (r2 = 0.17). Across all simulations, 82% of the perturbed simulation cyclones decreased in average central sea-level pressure (SLP) compared to the corresponding control simulation. Near-surface wind speed increased, as did precipitation, in 86% of cases with a preferred phase change from the solid to liquid state due to warming, although the trends did not correlate with the snow retreat magnitude. Our results, consistent with prior studies noting some role for the enhanced baroclinity of the snow line in modulating storm track and intensity, provide a benchmark to evaluate future snow cover retreat impacts on mid-latitude weather systems. [ABSTRACT FROM AUTHOR]

Leukocyte telomere length (LTL) gets shorter with each cell division and is also sensitive to reactive oxygen species damage and inflammatory processes. Studies in adults with non-alcoholic fatty liver disease (NAFLD) have found that increased fibrosis but not ALT levels are associated with shorter LTL. Few pediatric studies have been conducted; as such, we sought to evaluate potential associations between LTL and liver disease and liver disease progression in pediatric patients. Using data from the Treatment of NAFLD in Children (TONIC) randomized controlled trial, we assessed the potential predictive relationship between LTL and liver disease progression based on two successive liver biopsies over 96 weeks. We assessed the potential relationship between LTL and child age, sex, and race/ethnicity and features of liver disease including components of histology. We subsequently evaluated predictors for improvement in non-alcoholic steatohepatitis (NASH) at 96 weeks including LTL. We also assessed predictors of lobular inflammation improvement at 96 weeks using multivariable models. Mean LTL at baseline was 1.33 ± 0.23 T/S. Increasing lobular and portal inflammation were associated with longer LTL. In multivariable models, greater lobular inflammation at baseline was associated with longer LTL (Coeff 0.03, 95% CI 0.006–0.13; p = 0.03). Longer LTL at baseline was associated with worsening lobular inflammation at 96 weeks (Coeff 2.41, 95% CI 0.78–4.04; p < 0.01). There was no association between liver fibrosis and LTL. The association between LTL and pediatric NASH does not parallel adults with no association between fibrosis stage and NASH. Conversely, longer LTL was associated with more lobular inflammation at baseline and increased lobular inflammation over the 96-week period. Longer LTL in children may indicate greater risk for future complications from NASH. [ABSTRACT FROM AUTHOR]

The major immediate early enhancer and promoter (MIEP) of human cytomegalovirus (HCMV) drives the transcription of the immediate early one (IE1) and IE2 genes, whose encoded proteins stimulate productive, lytic replication. The MIEP is activated by the virally encoded and tegument-delivered pp71 protein at the start of de novo lytic infections of fully differentiated cells. Conversely, the MIEP is silenced at the start of de novo latent infections within incompletely differentiated myeloid cells in part because tegument-delivered pp71 is sequestered in the cytoplasm in these cells, but also by viral factors that repress transcription from this locus, including the UL138 protein. During both modes of infection, MIEP activity can be increased by the histone deacetylase inhibitor valproic acid (VPA); however, UL138 inhibits the VPA-responsiveness of the MIEP. Here, we show that two families of cellular transcription factors, NF- kB and cAMP response element- binding protein (CREB), together control the VPA-mediated activation and UL138- mediated repression of the HCMV MIEP. IMPORTANCE Artificial regulation of the HCMV MIEP, either activation or repression, is an attractive potential means to target the latent reservoirs of virus for which there is currently no available intervention. The MIEP could be repressed to prevent latency reactivation or induced to drive the virus into the lytic stage that is visible to the immune system and inhibited by multiple small-molecule antiviral drugs. Understanding how the MIEP is regulated is a critical part of designing and implementing either strategy. Our revelation here that NF- kB and CREB control the responsiveness of the MIEP to the viral UL138 protein and the FDA-approved drug VPA could help in the formulation and execution of promoter regulatory strategies against latent HCMV. [ABSTRACT FROM AUTHOR]

This article outlines the design and implementation of an internet-of-things (IoT) platform for the monitoring of soil carbon dioxide (CO2) concentrations. As atmospheric CO2 continues to rise, accurate accounting of major carbon sources, such as soil, is essential to inform land management and government policy. Thus, a batch of IoT-connected CO2 sensor probes were developed for soil measurement. These sensors were designed to capture spatial distribution of CO2 concentrations across a site and communicate to a central gateway using LoRa. CO2 concentration and other environmental parameters, including temperature, humidity and volatile organic compound concentration, were logged locally and communicated to the user through a mobile (GSM) connection to a hosted website. Following three field deployments in summer and autumn, we observed clear depth and diurnal variation of soil CO2 concentration within woodland systems. We determined that the unit had the capacity to log data continuously for a maximum of 14 days. These low-cost systems have great potential for better accounting of soil CO2 sources over temporal and spatial gradients and possibly flux estimations. Future testing will focus on divergent landscapes and soil conditions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research was to develop, implement, and test the efficacy of a theory-driven, evidence-informed peer leadership program for elementary school students (Grade 6 and 7; age 11–12 years) and the Grade 3/4 students with whom they were partnered. The primary outcome was teacher ratings of their Grade 6/7 students' transformational leadership behaviors. Secondary outcomes included: Grade 6/7 students' leadership self-efficacy, as well as Grade 3/4 motivation, perceived competence, general self-concept, fundamental movement skills, school-day physical activity, and program adherence, and program evaluation. Methods: We conducted a two-arm cluster randomized controlled trial. In 2019, 6 schools comprising 7 teachers, 132 leaders, and 227 grade 3 and 4 students were randomly allocated to the intervention or waitlist control conditions. Intervention teachers took part in a half-day workshop (January 2019), delivered 7 x 40 minute lessons to Grade 6/7 peer leaders (February and March 2019), and these peer leaders subsequently ran a ten-week physical literacy development program for Grade 3/4 students (2x30 minutes sessions per week). Waitlist-control students followed their usual routines. Assessments were conducted at baseline (January 2019) and immediately post-intervention (June 2019). Results: The intervention had no significant effect on teacher ratings of their students' transformational leadership (b = 0.201, p =.272) after controlling for baseline and gender. There was no significant condition effect for Grade 6/7 student rated transformation leadership (b = 0.077, p =.569) or leadership self-efficacy (b = 3.747, p =.186) while controlling for baseline and gender. There were null findings for all outcomes related to Grade 3 and 4 students. Discussion: Adaptions to the delivery mechanism were not effective in increasing leadership skills of older students or components of physical literacy in younger Grade 3/4 students. However, teacher self-reported adherence to the intervention delivery was high. Trial registration: This trial was registered on December 19th, 2018 with Clinicaltrials.gov (NCT03783767), https://clinicaltrials.gov/ct2/show/NCT03783767. [ABSTRACT FROM AUTHOR]

Background: 7-Methylxanthine, a derivative of caffeine noted for its lack of toxicity and ability to treat and even prevent myopia progression, is a high-value biochemical with limited natural availability. Attempts to produce 7-methylxanthine through purely chemical methods of synthesis are faced with complicated chemical processes and/or the requirement of a variety of hazardous chemicals, resulting in low yields and racemic mixtures of products. In recent years, we have developed engineered microbial cells to produce several methylxanthines, including 3-methylxanthine, theobromine, and paraxanthine. The purpose of this study is to establish a more efficient biosynthetic process for the production of 7-methylxanthine from caffeine. Results: Here, we describe the use of a mixed-culture system composed of Escherichia coli strains engineered as caffeine and theobromine "specialist" cells. Optimal reaction conditions for the maximal conversion of caffeine to 7-methylxanthine were determined to be equal concentrations of caffeine and theobromine specialist cells at an optical density (600 nm) of 50 reacted with 2.5 mM caffeine for 5 h. When scaled-up to 560 mL, the simple biocatalytic reaction produced 183.81 mg 7-methylxanthine from 238.38 mg caffeine under ambient conditions, an 85.6% molar conversion. Following HPLC purification and solvent evaporation, 153.3 mg of dried 7-methylxanthine powder was collected, resulting in an 83.4% product recovery. Conclusion: We present the first report of a biocatalytic process designed specifically for the production and purification of the high-value biochemical 7-methylxanthine from caffeine using a mixed culture of E. coli strains. This process constitutes the most efficient method for the production of 7-methylxanthine from caffeine to date. [ABSTRACT FROM AUTHOR]

Even as novel technologies emerge and medicines advance, pathogen-transmitting mosquitoes pose a deadly and accelerating public health threat. Detecting and mitigating the spread of Anopheles stephensi in Africa is now critical to the fight against malaria, as this invasive mosquito poses urgent and unprecedented risks to the continent. Unlike typical African vectors of malaria, An. stephensi breeds in both natural and artificial water reservoirs, and flourishes in urban environments. With An. stephensi beginning to take hold in heavily populated settings, citizen science surveillance supported by novel artificial intelligence (AI) technologies may offer impactful opportunities to guide public health decisions and community-based interventions. Coalitions like the Global Mosquito Alert Consortium (GMAC) and our freely available digital products can be incorporated into enhanced surveillance of An. stephensi and other vector-borne public health threats. By connecting local citizen science networks with global databases that are findable, accessible, interoperable, and reusable (FAIR), we are leveraging a powerful suite of tools and infrastructure for the early detection of, and rapid response to, (re)emerging vectors and diseases. [ABSTRACT FROM AUTHOR]

Extreme weather events are predicted to occur with increasing frequency as a result of global climate change. These extremes take multiple forms. This note reports an abnormal weather event in which winds, apparently Force 10 on the Beaufort Scale (90-100 km/hour), killed hundreds of birds at a farmhouse in the Karoo, South Africa. The wind was so strong that it removed birds from their roosts in trees and flung them against the walls of the farmhouse with such force that it killed them. There are no published accounts of comparable events in southern Africa. [ABSTRACT FROM AUTHOR]

Background: To characterize the safety, immunogenicity, and outcomes of patients with high-grade serous ovarian cancer (HGSOC) in second or greater remission treated with a polyvalent antigen-KLH plus OPT-821 vaccine construct and bevacizumab. Methods: Patients with recurrent HGSOC were treated with the vaccine plus bevacizumab at our institution from 01/05/2011 to 03/20/2012. Follow-up continued until 03/2021. Blood/urine samples were collected. "Responders" had an immunogenic response to ≥ 3 antigens; "non-responders" to ≤ 2 antigens. Results: Twenty-one patients were treated on study. One developed a dose-limiting toxicity (grade 4 fever). Two (10%) experienced bevacizumab-related grade 3 hypertension. Thirteen (68%) and 16 (84%) of 19 responded to ≥ 3 and ≥ 2 antigens, respectively (Globo-H, GM2, TF cluster Tn, MUC-1). Four of 21 patients were alive > 5 years post-treatment. Responders and non-responders had a median PFS of 4.9 months (95% CI: 2.8–8.1) and 5.0 months (95% CI: 0.7-cannot estimate), respectively; median OS was 30.7 months (95% CI: 16.9–52.0) and 34.2 months (95% CI: 12.8-cannot estimate), respectively. On two-timepoint analysis (baseline, week 17), increased IL-8 exhibited improved PFS (HR as 10-unit increase, 0.43; p = 0.04); increased PDGF exhibited worse OS (HR as 10-unit increase, 1.01; p = 0.02). Conclusions: This is the longest follow-up of vaccine administration with bevacizumab in patients with ovarian cancer. The vaccine was well tolerated with bevacizumab. Response was not associated with improved survival. On two-timepoint analysis, increased IL-8 was associated with significant improvement in PFS; increased PDGF with significantly worse OS. For all timepoint measurements, cytokine levels were not significantly associated with survival. Trial registration: NCT01223235. [ABSTRACT FROM AUTHOR]

OBJECTIVE: An institution's tobramycin pharmacokinetics (PK) database was reviewed to evaluate the efficacy and safety of empiric tobramycin dosing and monitoring strategies used in pediatric patients with cystic fibrosis (CF). The relationship between patient age and tobramycin dosing needed to achieve the area under the curve (AUC) goal was investigated. METHODS: Retrospective chart review was performed for patients who received tobramycin during a CF exacerbation from 2009 to 2019 who received PK monitoring by pediatric pharmacists. Tobramycin dosing needed to achieve an AUC of 100 mg·hr/L was calculated for each patient. Serum creatinine and concomitant nephrotoxin use were collected as surrogate nephrotoxicity endpoints to evaluate safety. RESULTS: Goal AUC (100 ± 15 mg·hr/L) was achieved based on initial or repeat PK calculations in 43.5% (95% CI, 37.7-49.3) of 85 unique patients across 326 encounters. Patients with calculated recommended doses of 9.5 to 11.9 mg/kg every 24 hours empirically achieved goal AUC in 77% (78/101) of encounters. The odds of achieving goal AUC were 56% higher for children aged 10 vs 5 years (OR = 1.56; 95% CI, 1.04-2.34; p = 0.033) and 32% higher for children aged 15 vs 10 years (OR = 1.32; 95% CI, 1.07-1.61; p = 0.008). Overall rates of acute kidney injury and concomitant nephrotoxin use were 10.8% (95% CI, 6.2-15.5) and 80.7% (95% CI, 74.3-87.1), respectively. CONCLUSIONS: Desired AUC was achieved by 43.5% of pediatric patients with CF using tobramycin 10 mg/kg every 24 hours. Older patient age was associated with higher initial AUC attainment and fewer dose modifications. Younger children may require higher weight-based dosing to meet AUC goals. [ABSTRACT FROM AUTHOR]

There is considerable variation in the surgical techniques for transsphenoidal excision of pituitary tumors. Recently, an extracapsular method has been developed that involves using the tumor pseudocapsule as a dissection plane to increase the extent of resection. This review assessed the outcomes of this new approach as compared with standard transsphenoidal surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE/PubMed, the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch), and LILACS databases for relevant literature and checked reference lists of relevant articles. Randomized controlled trials and prospective and retrospective cohort studies comparing extracapsular and intracapsular resection of pituitary tumors were included in the review. Five cohort studies with 1,588 participants were included. Extracapsular resection was associated with a higher likelihood of complete excision (relative risk [RR] 1.31, 95% confidence interval [CI] 1.01–1.70, p = 0.04) and endocrinologic remission (RR 1.26, 95% CI 1.03–1.54, p = 0.02). Because there was a significant risk of bias and substantial heterogeneity, the estimates of effect may not be robust. In patients with pituitary adenomas undergoing transsphenoidal excision, extracapsular resection may be associated with higher rates of complete excision and endocrinologic remission, but the evidence is not strong. Hence, randomized controlled trials to determine the magnitude of benefit and identify an improvement in progression-free or overall survival are warranted. [ABSTRACT FROM AUTHOR]

Short peptide sequences and bolaamphiphiles derived from natural proteins are gaining importance due to their ability to form unique nanoscale architectures for a variety of biological applications. In this work, we have designed six short peptides (triplet or monomeric forms) and two peptide bolaamphiphiles that either incorporate the bioactive collagen motif (Gly-X–Y) or sequences where Gly, Pro, or hydroxyproline (Hyp) are replaced by Ala or His. For the bolaamphiphiles, a malate moiety was used as the aliphatic linker for connecting His with Hyp to create collagen mimics. Stability of the assemblies was assessed through molecular dynamics simulations and results indicated that (Pro-Ala-His)3 and (Ala-His-Hyp)3 formed the most stable structures, while the amphiphiles and the monomers showed some disintegration over the course of the 200 ns simulation, though most regained structural integrity and formed fibrillar structures, and micelles by the end of the simulation, likely due to the formation of more thermodynamically stable conformations. Multiple replica simulations (REMD) were also conducted where the sequences were simulated at different temperatures. Our results showed excellent convergence in most cases compared to constant temperature molecular dynamics simulation. Furthermore, molecular docking and MD simulations of the sequences bound to collagen triple helix structure revealed that several of the sequences had a high binding affinity and formed stable complexes, particularly (Pro-Ala-His)3 and (Ala-His-Hyp)3. Thus, we have designed new hybrid-peptide-based sequences which may be developed for potential applications as biomaterials for tissue engineering or drug delivery. [ABSTRACT FROM AUTHOR]