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Soil dry surface layer (DSL) thickness is often considered a key parameter for land surface resistance to gas exchange. Commonly used, simple models for DSL thickness are typically empirical in nature and based on limited observational evidence. Laboratory experiments were performed to test soil condition and boundary effects on DSL formation. DSL thickness was analyzed in soil columns with varying texture, initial water content, and potential evaporation rate. DSLs formed to greater depth in fine-textured compared to coarse-textured soils, when beginning from similar initial water content. Based on experiments, we compared a simple but physically-based mass balance DSL model to an empirical DSL model from the literature. The mass balance model performed better than the empirical relative-wetness-based model, and is similar in structure to the current DSL parameterization in the Community Land Model. Results suggest soil resistance parameterizations can be improved by employing simple, but texture-dependent, physically-based DSL formulations. [ABSTRACT FROM AUTHOR]

Mechanobiology is a rapidly advancing field, with growing evidence that mechanical signaling plays key roles in health and disease. To accelerate mechanobiology-based drug discovery, novel in vitro systems are needed that enable mechanical perturbation of cells in a format amenable to high throughput screening. Here, both a mechanical stretch device and 192-well silicone flexible linear stretch plate were designed and fabricated to meet high throughput technology needs for cell stretch-based applications. To demonstrate the utility of the stretch plate in automation and screening, cell dispensing, liquid handling, high content imaging, and high throughput sequencing platforms were employed. Using this system, an assay was developed as a biological validation and proof-of-concept readout for screening. A mechano-transcriptional stretch response was characterized using focused gene expression profiling measured by RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Gen sequencing. Using articular chondrocytes, a gene expression signature containing stretch responsive genes relevant to cartilage homeostasis and disease was identified. The possibility for integration of other stretch sensitive cell types (e.g., cardiovascular, airway, bladder, gut, and musculoskeletal), in combination with alternative phenotypic readouts (e.g., protein expression, proliferation, or spatial alignment), broadens the scope of high throughput stretch and allows for wider adoption by the research community. This high throughput mechanical stress device fills an unmet need in phenotypic screening technology to support drug discovery in mechanobiology-based disease areas. [ABSTRACT FROM AUTHOR]

The ability Gram-negative pathogens have at adapting and protecting themselves against antibiotics has increasingly become a public health threat. Data-driven models identifying molecular properties that correlate with outer membrane (OM) permeation and growth inhibition while avoiding efflux could guide the discovery of novel classes of antibiotics. Here we evaluate 174 molecular descriptors in 1260 antimicrobial compounds and study their correlations with antibacterial activity in Gram-negative Pseudomonas aeruginosa. The descriptors are derived from traditional approaches quantifying the compounds' intrinsic physicochemical properties, together with, bacterium-specific from ensemble docking of compounds targeting specific MexB binding pockets, and all-atom molecular dynamics simulations in different subregions of the OM model. Using these descriptors and the measured inhibitory concentrations, we design a statistical protocol to identify predictors of OM permeation/inhibition. We find consistent rules across most of our data highlighting the role of the interaction between the compounds and the OM. An implementation of the rules uncovered in our study is shown, and it demonstrates the accuracy of our approach in a set of previously unseen compounds. Our analysis sheds new light on the key properties drug candidates need to effectively permeate/inhibit P. aeruginosa, and opens the gate to similar data-driven studies in other Gram-negative pathogens. Identifying molecular properties of compounds that best correlate with outer membrane permeation and growth inhibition could guide the discovery of new antibiotics. Here, the authors evaluate 174 molecular descriptors in 1260 antimicrobial compounds and study their correlations with antibacterial activity in Gram-negative Pseudomonas aeruginosa to derive a statistical protocol to identify mechanistic predictors of outer membrane permeation. [ABSTRACT FROM AUTHOR]

Feces of animals that forage on nectar and fruit, including many species of bats, often contain DNA that is low in quality and quantity. We developed an approach based on DNA from feces gathered passively to generate microsatellite data for individual lesser long-nosed bats (Leptonycteris yerbabuenae), which are important pollinators for columnar cacti and agave across much of Mexico and in the southwestern U.S. We collected feces from roosts near the U.S-Mexico border and developed a two-step amplification approach to characterize five highly polymorphic microsatellite loci from fecal DNA. Addition of a multiplex PCR step improved amplification success and conserved DNA extracts with a minimal increase in cost. In our initial screening of 433 samples, five focal loci distinguished individuals reliably, with a probability of identity (i.e., the probability of two unrelated individuals having the same microsatellite profile by chance) of 7.5E-09. Repeated analyses revealed a genotyping error rate < 2%. We explore the benefits and limits of our approach for population studies of lesser long-nosed bats and other nectivorous and frugivorous species that provide key ecosystem services and are often of conservation concern. [ABSTRACT FROM AUTHOR]

Background: Junipers (Juniperus spp.) are woody native, invasive plants that have caused encroachment problems in the U.S. western rangelands, decreasing forage productivity and biodiversity. A potential solution to this issue is using goats in targeted grazing programs. However, junipers, which grow in dry and harsh environmental conditions, use chemical defense mechanisms to deter herbivores. Therefore, genetically selecting goats for increased juniper consumption is of great interest for regenerative rangeland management. In this context, the primary objectives of this study were to: 1) estimate variance components and genetic parameters for predicted juniper consumption in divergently selected Angora (ANG) and composite Boer x Spanish (BS) goat populations grazing on Western U.S. rangelands; and 2) to identify genomic regions, candidate genes, and biological pathways associated with juniper consumption in these goat populations. Results: The average juniper consumption was 22.4% (± 18.7%) and 7.01% (± 12.1%) in the BS and ANG populations, respectively. The heritability estimates (realized heritability within parenthesis) for juniper consumption were 0.43 ± 0.02 (0.34 ± 0.06) and 0.19 ± 0.03 (0.13 ± 0.03) in BS and ANG, respectively, indicating that juniper consumption can be increased through genetic selection. The repeatability values of predicted juniper consumption were 0.45 for BS and 0.28 for ANG. A total of 571 significant SNP located within or close to 231 genes in BS, and 116 SNP related to 183 genes in ANG were identified based on the genome-wide association analyses. These genes are primarily associated with biological pathways and gene ontology terms related to olfactory receptors, intestinal absorption, and immunity response. Conclusions: These findings suggest that juniper consumption is a heritable trait of polygenic inheritance influenced by multiple genes of small effects. The genetic parameters calculated indicate that juniper consumption can be genetically improved in both goat populations. [ABSTRACT FROM AUTHOR]

Background Adjuvant therapies have been approved for resected melanoma based on improved recurrence-free survival. We present early findings from a real-world study on adjuvant treatments for melanoma. Methods A comprehensive chart review was conducted for patients receiving adjuvant systemic therapy for resected high-risk stages III and IV melanoma. Statistical analysis was performed to assess recurrence-free survival and subgroup differences. Results A total of 149 patients (median age = 58.0 years, 61.1% men, 49.7% with BRAF V600E/K genotypes) were included, with 94.6% having resected stage III melanoma. Anti-PD-1 immunotherapy was received by 86.5% of patients, while 13.4% received BRAF-targeted therapy. At a median follow-up of 22.4 months, the recurrence rate was 31.5%, with 1-year and 2-year recurrence-free survival rates of 79% and 62%, respectively. Similar recurrence rates were observed between anti-PD-1 immunotherapy and BRAF-targeted therapy. Long-term toxicity affected 27.4% of patients, with endocrinopathies and late-emergent immune-related adverse events being common. Conclusions Real-world adjuvant systemic therapy aligns with clinical trial practice. Recurrence rates remain high despite treatment, and long-term toxicities, including endocrinopathies and chronic inflammatory conditions, are not uncommon. [ABSTRACT FROM AUTHOR]

Agriculture generates ~83% of total US ammonia (NH3) emissions, potentially adversely impacting sensitive ecosystems through wet and dry deposition. Regions with intense livestock production, such as the dairy region of south-central Idaho, generate hotspots of NH3 emissions. Our objective was to measure the spatial and temporal variability of NH3 across this region and estimate its dry deposition. Ambient NH3 was measured using diffusive passive samplers at 8 sites in two transects across the region from 2018–2020. NH3 fluxes were estimated using the Surface Tiled Aerosol and Gaseous Exchange (STAGE) model. Peak NH3 concentrations were 4–5 times greater at a high-density dairy site compared to mixed agriculture/dairy or agricultural sites, and 26 times greater than non-agricultural sites with prominent seasonal trends driven by temperature. Annual estimated dry deposition rates in areas of intensive dairy production can approach 45 kg N ha−1 y−1, compared to <1 kg N ha−1 y−1 in natural landscapes. Our results suggest that the natural sagebrush steppe landscapes interspersed within and surrounding agricultural areas in southern Idaho receive NH3 dry deposition rates within and above the range of nitrogen critical loads for North American deserts. Finally, our results highlight a need for improved understanding of the role of soil processes in NH3 dry deposition to arid and sparsely vegetated natural ecosystems across the western US. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. Methods: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. Results: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. Discussion: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2D), a major cause of worldwide morbidity and mortality, is characterized by dysfunction of insulin-producing pancreatic islet β cells1,2. T2D genome-wide association studies (GWAS) have identified hundreds of signals in non-coding and β cell regulatory genomic regions, but deciphering their biological mechanisms remains challenging3–5. Here, to identify early disease-driving events, we performed traditional and multiplexed pancreatic tissue imaging, sorted-islet cell transcriptomics and islet functional analysis of early-stage T2D and control donors. By integrating diverse modalities, we show that early-stage T2D is characterized by β cell-intrinsic defects that can be proportioned into gene regulatory modules with enrichment in signals of genetic risk. After identifying the β cell hub gene and transcription factor RFX6 within one such module, we demonstrated multiple layers of genetic risk that converge on an RFX6-mediated network to reduce insulin secretion by β cells. RFX6 perturbation in primary human islet cells alters β cell chromatin architecture at regions enriched for T2D GWAS signals, and population-scale genetic analyses causally link genetically predicted reduced RFX6 expression with increased T2D risk. Understanding the molecular mechanisms of complex, systemic diseases necessitates integration of signals from multiple molecules, cells, organs and individuals, and thus we anticipate that this approach will be a useful template to identify and validate key regulatory networks and master hub genes for other diseases or traits using GWAS data.Integration of multiomics data with functional analysis of pancreatic tissues from individuals with early-stage type 2 diabetes indicates that the genetic risk converges on RFX6, which regulates chromatin architecture at multiple risk loci. [ABSTRACT FROM AUTHOR]

The Kaplan–Meier (KM) estimator is widely used in medical research to estimate the survival function from lifetime data. KM estimation is a powerful tool to evaluate clinical trials due to simple computational requirements, its use of a logrank hypothesis test, and the ability to censor patients. However, KM estimation has several constraints and fails to generalize to ordinal variables of clinical interest, such as toxicity and ECOG performance. We devised weighted trajectory analysis (WTA) to combine the advantages of KM estimation with the ability to visualize and compare treatment groups for ordinal variables and fluctuating outcomes. To assess statistical significance, we developed a new hypothesis test analogous to the logrank test. We demonstrated the functionality of WTA through 1000-fold clinical trial simulations of unique stochastic models of chemotherapy toxicity and schizophrenia disease course. With increments in sample size and hazard ratio, we compared the performance of WTA to KM estimation and the generalized estimating equation (GEE). WTA generally required half the sample size to achieve comparable power to KM estimation; advantages over the GEE included its robust nonparametric approach and summary plot. We also applied WTA to real clinical data: the toxicity outcomes of melanoma patients receiving immunotherapy and the disease progression of patients with metastatic breast cancer receiving ramucirumab. The application of WTA demonstrated that using traditional methods such as KM estimation can lead to both type I and II errors by failing to model illness trajectory. This article outlines a novel method for clinical outcome assessment that extends the advantages of Kaplan–Meier estimates to ordinal outcome variables. [ABSTRACT FROM AUTHOR]

In central north Essex and central south Suffolk there are a number of houses dating from the fifteenth to seventeenth centuries with a form of anchor beam where, unlike those in Denmark and a number of north European countries, the protruding end is not reduced to a tenon that goes through a post, but passes through the wall undiminished with a long wedge, called here a needle, through its protruding end. These anchor beams are not attached to a post or stud but are supported by a rail. Most appear to be sixteenth or, more likely, seventeenth century, and in most cases are used either to insert a floor into an open hall of a medieval house, or of a transitional house built with an open hall heated by a chimney, or simply to remove the need for tiebeams blocking access on the first floor of low buildings. Some do act as anchor beams holding up the side walls. Apart from a few outliers, the list descriptions in the Historic England National Heritage List for England (NHLE) suggests these beams are mostly confined to north Essex and south Suffolk. [ABSTRACT FROM AUTHOR]

Little is known about the effects of woody plant encroachment—a recent but pervasive phenomenon—on the hydraulic properties of bedrock substrates. Recent work using stream solute concentrations paired with weathering models suggests that woody plant encroachment accelerates limestone weathering. In this field study, we evaluate this hypothesis by examining bedrock in the Edwards Plateau, an extensive karst landscape in Central Texas. We compared a site that has been heavily encroached by woody plants (mainly Quercus fusiformis and Juniperus ashei), with an adjacent site that has been maintained free of encroachment for the past eight decades. Both sites share the same bedrock, as confirmed by trenching, and originally had very few trees, which enabled us to evaluate how encroachment impacted the evolution of hydraulic properties over a period of no more than 80 years. Using in situ permeability tests in boreholes drilled into the weathered bedrock, we found that the mean saturated hydraulic conductivity of the bedrock was higher—by an order of magnitude—beneath woody plants than in the areas where woody plants have been continuously suppressed. Additionally, woody plant encroachment was associated with greater regolith thickness, greater plant rooting depths, significantly lower rock hardness, and a 24–44% increase in limestone matrix porosity. These findings are strong indicators that woody plant encroachment enhances bedrock weathering, thereby amplifying its permeability—a cycle of mutual reinforcement with the potential for substantial changes within a few decades. Given the importance of shallow bedrock for ecohydrological and biogeochemical processes, the broader impacts of woody plant encroachment on weathering rates and permeability warrant further investigation. [ABSTRACT FROM AUTHOR]

The viability of spin-coating methods for the self-assembly of 150 nm diameter silica nanocolloids into large crystal structures on mica was investigated using different colloidal concentrations, accelerations, and rotational speeds. The samples were imaged by atomic force microscopy (AFM) in intermittent contact mode. Low colloidal concentration led to a size-dependent ordering configuration. The largest nanocolloidal particles formed crystalline close-packed structures that were surrounded by increasingly smaller nanocolloids configured into more polycrystalline or amorphous formations. This phenomenon became increasingly suppressed by increasing colloidal concentration. Two dimensional-fast Fourier transform (2D-FFT) radially averaged profiles of the topography images revealed increasing interparticle spacing with increasing rotational acceleration, from close-packed structuring at low accelerations to increasingly spaced packing at high acceleration (>800 rpm/s). This behaviour is attributed to rapid liquid shedding from the increased acceleration. Analysis with radial distribution functions quantified the extent of ordering and revealed an optimum spin speed that caused the formation of large, highly crystalline structures. This optimum spin speed is governed by the relationship between the rotational speed and the liquid film thickness that affect the uniformity of the film and the magnitude of the capillary forces generated. [ABSTRACT FROM AUTHOR]

Over the past century, prickly pear (PP) cactus (e.g., genus Opuntia; subgenus Platyopuntia) has increased on semi-arid rangelands. Effective detection of cacti abundance and spatial pattern is challenging due to the inherent heterogeneity of rangeland landscapes. In this study, high-resolution multispectral imageries (0.21 m) were used to test object-based (OB) feature extraction, random forest (RF) machine learning, and spectral endmember (n-D) classification methods to map PP and evaluate its spatial pattern. We trained and tested classification methods using field-collected GPS location, plant cover, and spectrometry from 288 2 m radius polygons before a prescribed burn and 480 samples after the burn within a 69.2-ha burn unit. The most accurate classification method was then used to map PP distribution and quantify abundance before and after fire. As a case study, we assessed the spatial pattern of mapped PP cover, considering topoedaphic setting and burn conditions. The results showed that the endmember classification method, spectral angle mapper (SAM), outperformed the RF and OB classifications with higher kappa coefficients (KC) (0.93 vs. 0.82 and 0.23, respectively) and overall accuracies (OA) (0.96 vs. 0.91 and 0.49) from pre-fire imagery. KC and OA metrics of post-fire imagery were lower, but rankings among classification methods were similar. SAM classifications revealed that fire reduced PP abundance by 46.5%, but reductions varied by soil type, with deeper soils having greater decreases (61%). Kolmogorov-Smirnov tests indicated significant changes before and after fire in the frequency distribution of PP cover within deeper soils (D = 0.64, p = 0.02). A two-way ANOVA revealed that the interaction of season (pre- vs. post-fire) and soils significantly (p < 0.00001) influenced the spatial pattern of PP patches. Fire also reduced the size and shape of PP patches depending on the topoedaphic settings. This study provides an innovative and effective approach for integrating field data collection, remote sensing, and endmember classification methods to map prickly pear and assess the effects of prescribed fire on prickly pear spatial patterns. Accurate mapping of PP can aid in the design and implementation of spatially explicit rangeland management strategies, such as fire, that can help reduce and mitigate the ecological and economic impacts of prickly pear expansion. [ABSTRACT FROM AUTHOR]

As more states in the USA require elementary schools to offer computer science (CS) education, teachers are expected to master the knowledge and skills to teach CS by integrating computational thinking (CT) into content areas. This study presented a research-practice partnership approach to support elementary teachers in a local school district with CT integration. Professional development (PD) followed the technological, pedagogical, and content knowledge (TPACK) framework, and three elementary teachers' PD and classroom implementation experiences were examined and reported as a multiple case study. Interviews, observations, and teacher artifacts and reflections were collected and analyzed. The cross-case analysis revealed that the teachers (1) had an improved understanding of how CS/CT connects with content areas and how to make alignments across content standards, (2) demonstrated concrete strategies for designing and implementing CT-integrated instruction with various coding tools, and (3) provided students with engaging and inclusive learning experiences using a range of pedagogies. The paper discussed the implications for CS education at the elementary level. [ABSTRACT FROM AUTHOR]

Topoisomerase inhibitor camptothecin (CPT) induces fork stalling and is highly toxic to proliferating cells. However, how cells respond to CPT-induced fork stalling has not been fully characterized. Here, we report that Cockayne syndrome group B (CSB) protein inhibits PRIMPOL-dependent fork repriming in response to a low dose of CPT. At a high concentration of CPT, CSB is required to promote the restart of DNA replication through MUS81–RAD52–POLD3-dependent break-induced replication (BIR). In the absence of CSB, resumption of DNA synthesis at a high concentration of CPT can occur through POLQ–LIG3-, LIG4-, or PRIMPOL-dependent pathways, which are inhibited, respectively, by RAD51, BRCA1, and BRCA2 proteins. POLQ and LIG3 are core components of alternative end joining (Alt-EJ), whereas LIG4 is a core component of nonhomologous end joining (NHEJ). These results suggest that CSB regulates fork restart pathway choice following high-dosage CPT-induced fork stalling, promoting BIR but inhibiting Alt-EJ, NHEJ, and fork repriming. We find that loss of CSB and BRCA2 is a toxic combination to genomic stability and cell survival at a high concentration of CPT, which is likely due to accumulation of ssDNA gaps, underscoring an important role of CSB in regulating the therapy response in cancers lacking functional BRCA2. [ABSTRACT FROM AUTHOR]

We studied the nanostructures and ultrathin films resulting from the deposition and adsorption of polystyrene nanocolloidal particles and methoxy poly(ethylene glycol) methacrylate surfactants on mica surfaces from mixed suspensions in water. The samples were prepared by droplet evaporation and dip coating and imaged with atomic force microscopy. Topography and phase imaging revealed a significant richness in morphological features of the deposited/adsorbed films. We observed uniform ultrathin films and extended islands of the surfactant oligomers indicating their self-assembly in monolayers and multilayers, while the polystyrene nanocolloids were embedded within the surfactant structures. Droplet evaporation resulted in the migration of particles towards the edges of the droplet leaving an intricate network of imprints within the surfactant film. Dip coating induced the formation of extended nanocolloid clusters with colloidal crystalline structuring. [ABSTRACT FROM AUTHOR]

The concept of 'trust' is frequently used when discussing the working relationship between deaf signers and signed language interpreters, with interpreters often claiming that trust is a prerequisite to a successful interaction. This paper presents original data from an in-depth research project which used collaborative autoethnography to gather the experiences of seven deaf academics who work regularly with British Sign Language (BSL) interpreters, who interpret between BSL and spoken English, to analyse the concept of 'trust' in our working relations with BSL interpreters. We found that 'trust' is not a useful or productive concept for our interpersonal and professional aims. Instead, we outline multiple ways in which deaf academics can assess and evaluate interpreters' values, competencies, and performance without relying on 'trust'. Our findings provide an important, powerful and under-explored perspective on the working relations between deaf academics and interpreters. We suggest these findings can be applied by deaf BSL signers and interpreters in contexts beyond academia, and constitute an important contribution to the literature on interpreting. [ABSTRACT FROM AUTHOR]

Neural tube defects (NTDs), including anencephaly and spina bifida, are common major malformations of fetal development resulting from incomplete closure of the neural tube. These conditions lead to either universal death (anencephaly) or severe lifelong complications (spina bifida). Despite hundreds of genetic mouse models of neural tube defect phenotypes, the genetics of human NTDs are poorly understood. Furthermore, pharmaceuticals, such as antiseizure medications, have been found clinically to increase the risk of NTDs when administered during pregnancy. Therefore, a model that recapitulates human neurodevelopment would be of immense benefit to understand the genetics underlying NTDs and identify teratogenic mechanisms. Using our self-organizing single rosette cortical organoid (SOSR-COs) system, we have developed a high-throughput image analysis pipeline for evaluating the SOSR-CO structure for NTD-like phenotypes. Similar to small molecule inhibition of apical constriction, the antiseizure medication valproic acid (VPA), a known cause of NTDs, increases the apical lumen size and apical cell surface area in a dose-responsive manner. GSK3β and HDAC inhibitors caused similar lumen expansion; however, RNA sequencing suggests VPA does not inhibit GSK3β at these concentrations. The knockout of SHROOM3, a well-known NTD-related gene, also caused expansion of the lumen, as well as reduced f-actin polarization. The increased lumen sizes were caused by reduced cell apical constriction, suggesting that impingement of this process is a shared mechanism for VPA treatment and SHROOM3-KO, two well-known causes of NTDs. Our system allows the rapid identification of NTD-like phenotypes for both compounds and genetic variants and should prove useful for understanding specific NTD mechanisms and predicting drug teratogenicity. [ABSTRACT FROM AUTHOR]

Context: Within each hamstring muscle, there are segments with separate nerve innervation. However, a better understanding of activation levels within these regions during resistance exercise could lead to region-specific training for improved performance and injury prevention. Objective: To compare muscle activation levels within regions of the hamstrings during various resistance exercises. Design: Within-subjects repeated measures. Setting: Biomechanics laboratory. Participants: Eighteen young adult females with previous competitive sport participation and resistance training experience. Intervention: One set of 3 repetitions with an 8RM load on the bilateral squat, modified single-leg squat, stiff-legged dead lift, and leg curl (LC). Main Outcome Measures: Normalized surface electromyography of 4 hamstring regions (proximal-medial, proximal-lateral, distal-medial, and distal-lateral). Results: For LC only, electromyography measures for the proximal-lateral location were significantly lower than for the distal-lateral, t18 = 5.6, P <.001, and proximal-medial, t18 = 2.4, P =.01 locations for concentric contractions. Similar results were observed for eccentric contractions. No other exercises revealed regional activation differences. When comparing the pooled proximal (medial and lateral) region across exercises, the LC demonstrated significantly greater activation than the modified single-leg squat, t18 = 5.20, P <.001, stiff-legged dead lift, t18 = 7.311, P <.001, and bilateral squat, F3,54 = 49.8, P <.001. Similar significantly greater levels were also found during the LC for the pooled distal, medial, and lateral regions. In addition, the modified single-leg squat electromyography was significantly greater at all regions in comparison with the stiff-legged dead lift and bilateral squat. Conclusions: The data did not reveal consistent regional differences within the different exercises included in this study. However, the data indicate that the LC produces the highest hamstring activation in all regions across exercises. Inclusion of single-joint knee-flexion exercises would appear to be most beneficial for hamstrings development in a resistance-training program. [ABSTRACT FROM AUTHOR]

Cigarette smoking (CS) is the leading cause of COPD, and identifying the pathways that are driving pathogenesis in the airway due to CS exposure can aid in the discovery of novel therapies for COPD. An additional barrier to the identification of key pathways that are involved in the CS-induced pathogenesis is the difficulty in building relevant and high throughput models that can recapitulate the phenotypic and transcriptomic changes associated with CS exposure. To identify these drivers, we have developed a cigarette smoke extract (CSE)-treated bronchosphere assay in 384-well plate format that exhibits CSE-induced decreases in size and increase in luminal secretion of MUC5AC. Transcriptomic changes in CSE-treated bronchospheres resemble changes that occur in human smokers both with and without COPD compared to healthy groups, indicating that this model can capture human smoking signature. To identify new targets, we ran a small molecule compound deck screening with diversity in target mechanisms of action and identified hit compounds that attenuated CSE induced changes, either decreasing spheroid size or increasing secreted mucus. This work provides insight into the utility of this bronchopshere model to examine human respiratory disease impacted by CSE exposure and the ability to screen for therapeutics to reverse the pathogenic changes caused by CSE. [ABSTRACT FROM AUTHOR]

Asthma is often characterized by tissue-level mechanical phenotypes that include remodeling of the airway and an increase in airway tightening, driven by the underlying smooth muscle. Existing therapies only provide symptom relief and do not improve the baseline narrowing of the airway or halt progression of the disease. To investigate such targeted therapeutics, there is a need for models that can recapitulate the 3D environment present in this tissue, provide phenotypic readouts of contractility, and be easily integrated into existing assay plate designs and laboratory automation used in drug discovery campaigns. To address this, we have developed DEFLCT, a high-throughput plate insert that can be paired with standard labware to easily generate high quantities of microscale tissues in vitro for screening applications. Using this platform, we exposed primary human airway smooth muscle cell-derived microtissues to a panel of six inflammatory cytokines present in the asthmatic niche, identifying TGF-β1 and IL-13 as inducers of a hypercontractile phenotype. RNAseq analysis further demonstrated enrichment of contractile and remodeling-relevant pathways in TGF-β1 and IL-13 treated tissues as well as pathways generally associated with asthma. Screening of 78 kinase inhibitors on TGF-β1 treated tissues suggests that inhibition of protein kinase C and mTOR/Akt signaling can prevent this hypercontractile phenotype from emerging, while direct inhibition of myosin light chain kinase does not. Taken together, these data establish a disease-relevant 3D tissue model for the asthmatic airway, which combines niche specific inflammatory cues and complex mechanical readouts that can be utilized in drug discovery efforts. [ABSTRACT FROM AUTHOR]

Background: Early-stage breast cancer patients treated with chemotherapy risk the development of metabolic disease and weight gain, which can result in increased morbidity and reduced quality of life in survivorship. We aimed to analyze changes within the gastrointestinal microbiome of early-stage breast cancer patients treated with and without chemotherapy to investigate a potential relationship between dysbiosis, a systemic inflammatory response, and resultant anthropomorphic changes. Methods: We undertook an a priori analysis of serially collected stool and plasma samples from 40 patients with early-stage breast cancer who underwent adjuvant endocrine therapy only, adjuvant chemotherapy only, or both. Gut microbiota were assessed by metagenomic comparison of stool samples following deep sequencing. Inflammatory biomarkers were evaluated by proteomic analysis of plasma and measurement of fecal calprotectin. Body composition was investigated by dual-energy X-ray absorptiometry to determine biomass indices. Results: As opposed to treatment with endocrine therapy only, chemotherapy resulted in statistically and clinically significant weight gain and an increase in the android to gynoid ratio of fat distribution. Patients treated with chemotherapy gained an average of 0.15% total mass per month, as opposed to a significantly different loss of 0.19% in those patients who received endocrine-only therapy. Concurrently, a twofold increase in fecal calprotectin occurred after chemotherapy that is indicative of interferon-dependent inflammation and evidence of colonic inflammation. These anthropomorphic and inflammatory changes occurred in concert with a chemotherapy-dependent effect on the gut microbiome as evidenced by a reduction in both the abundance and variety of microbial species. Conclusions: We confirm the association of chemotherapy treatment with weight gain and potential deleterious anthropometric changes and suggest that alterations of bacterial flora may contribute to these phenomena through the induction of systemic inflammation. Consequently, the gut microbiome may be a future target for intervention in preventing chemotherapy-dependent anthropometric changes. [ABSTRACT FROM AUTHOR]

Introduction: T cell activation can lead to osteoporosis and while there are several case reports of fractures occurring after immune checkpoint inhibitor (ICI) use, to date, there are no population level studies looking at fracture risk related to ICI use. Methods: Using Alberta Cancer Registry data, we identified all individuals treated with ICI for cancer between September 29, 2010, and March 31, 2019. Linked records from Alberta's healthcare administrative databases were assessed for the presence of fracture diagnostic codes in the year prior to and up to two years after ICI initiation. Fracture rate was stratified based on the time-period before and after ICI initiation. Fracture rates after ICI were compared to baseline. Results: The study cohort consisted of 1600 ICI users (mean age 65.7 years, 60% male). Most patients were treated with an anti-PD-1 agent (73.9%). ICIs were initiated on average 707.8 days after cancer diagnosis. 76 (4.8%) individuals had a remote history of a major fracture, and 141 (8.8%) had been treated with an osteoporosis medication prior to ICI treatment. The fracture rate in the year prior to ICI initiation was 11.3 per 1000 patient-years. The fracture rate in the year after ICI initiation was significantly higher at 27.3 per 1000 patient-years. The fracture rate dropped to 17.6 per 1000 patient-years in the second year after ICI initiation. The incidence rate ratio of sustaining a major fracture in the year after compared to the year prior to ICI initiation was 2.43 (95% CI 1.34–4.27). Conclusions: Fracture risk may be increased in cancer patients early after initiation of ICI, and this may represent a novel immune-related adverse event. [ABSTRACT FROM AUTHOR]

Simple Summary: About 40% of people diagnosed with cancer are eligible for treatment with checkpoint inhibitors (CPIs). Little research has been conducted to understand whether CPIs affect cognitive function. Most research that has been conducted included patients who received both CPIs and chemotherapy. This pilot study was conducted with patients receiving CPIs as their first line of cancer treatment. This study's purpose was to show the feasibility of recruiting, retaining, and assessing older adult patients with cancer starting first line CPI treatment and provide early evidence of the impact of CPI on cognitive function. Approximately 40% of patients with cancer are eligible for check-point inhibitor (CPI) therapy. Little research has examined the potential cognitive impact of CPIs. First-line CPI therapy offers a unique research opportunity without chemotherapy-related confounders. The purpose of this prospective, observational pilot was to (1) demonstrate the feasibility of prospective recruitment, retention, and neurocognitive assessment for older adults receiving first-line CPI(s) and (2) provide preliminary evidence of changes in cognitive function associated with CPI(s). Patients receiving first-line CPI(s) (CPI Group) were assessed at baseline (n = 20) and 6 months (n = 13) for self-report of cognitive function and neurocognitive test performance. Results were compared to age-matched controls without cognitive impairment assessed annually by the Alzheimer's Disease Research Center (ADRC). Plasma biomarkers were measured at baseline and 6 months for the CPI Group. Estimated differences for CPI Group scores prior to initiating CPIs (baseline) trended to lower performance on the Montreal Cognitive Assessment-Blind (MOCA-Blind) test compared to the ADRC controls (p = 0.066). Controlling for age, the CPI Group's 6-months MOCA-Blind performance was lower than the ADRC control group's 12-months performance (p = 0.011). No significant differences in biomarkers were detected between baseline and 6 months, although significant correlations were noted for biomarker change and cognitive performance at 6 months. IFNγ, IL-1β, IL-2, FGF2, and VEGF were inversely associated with Craft Story Recall performance (p < 0.05), e.g., higher levels correlated with poorer memory performance. Higher IGF-1 and VEGF correlated with better letter-number sequencing and digit-span backwards performance, respectively. Unexpected inverse correlation was noted between IL-1α and Oral Trail-Making Test B completion time. CPI(s) may have a negative impact on some neurocognitive domains and warrant further investigation. A multi-site study design may be crucial to fully powering prospective investigation of the cognitive impact of CPIs. Establishment of a multi-site observational registry from collaborating cancer centers and ADRCs is recommended. [ABSTRACT FROM AUTHOR]

Assessing nutrient critical load exceedances requires complete and accurate atmospheric deposition budgets for reactive nitrogen (N r). The exceedance is the total amount of N r deposited to the ecosystem in excess of the critical load, which is the amount of N r input below which harmful effects do not occur. Total deposition includes all forms of N r (i.e., organic and inorganic) deposited to the ecosystem by wet and dry pathways. Here we present results from the Southern Appalachian Nitrogen Deposition Study (SANDS), in which a combination of measurements and field-scale modeling was used to develop a complete annual N r deposition budget for a deciduous forest at the Coweeta Hydrologic Laboratory. Wet deposition of ammonium, nitrate, nitrite, and bulk organic N were measured directly. The dry deposited N r fraction was estimated using a bidirectional resistance-based model driven with speciated measurements of N r air concentrations (e.g., ammonia, ammonium aerosol, nitric acid, nitrate aerosol, bulk organic N in aerosol, total alkyl nitrates, and total peroxy nitrates), micrometeorology, canopy structure, and biogeochemistry. Total annual deposition was ∼ 6.7 kg N ha -1 yr -1 , which is on the upper end of N r critical load estimates recently developed for similar ecosystems in the nearby Great Smoky Mountains National Park. Of the total (wet + dry) budget, 51.1 % was contributed by reduced forms of N r (NH x = ammonia + ammonium), with oxidized and organic forms contributing ∼ 41.3 % and 7.6 %, respectively. Our results indicate that reductions in NH x deposition would be needed to achieve the lowest estimates (∼ 3.0 kg N ha -1 yr -1) of N r critical loads in southern Appalachian forests. [ABSTRACT FROM AUTHOR]

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Objective: The authors sought to determine the efficacy of targeted naltrexone in sexual and gender minority men (SGM) who binge drink and have mild to moderate alcohol use disorder.Methods: In a double-blind placebo-controlled trial, a total of 120 SGM who binge drink and have mild to moderate alcohol use disorder were randomized in a 1:1 ratio to receive targeted oral naltrexone (50 mg) or placebo with weekly counseling for 12 weeks. The study's primary endpoints were binge-drinking intensity, defined as 1) number of drinks in the past 30 days; 2) any binge drinking in the past week; 3) number of binge-drinking days in the past week; and 4) number of drinking days in the past week. The study also measured changes in alcohol use with two alcohol biomarker measures: ethyl glucuronide in urine samples and phosphatidylethanol (PEth) in dried blood spot samples.Results: Ninety-three percent completed the trial, with 85% of weekly follow-up visits completed. In intention-to-treat analyses, naltrexone was associated with a significantly reduced reported number of binge-drinking days (incidence rate ratio [IRR]=0.74, 95% CI=0.56, 0.98; number needed to treat [NNT]=2), weeks with any binge drinking (IRR=0.83, 95% CI=0.72, 0.96; NNT=7.4), number of drinks per month (IRR=0.69, 95% CI=0.52, 0.91; NNT=5.7 for 10 drinks), and alcohol craving scores (coefficient=-9.25, 95% CI=-17.20, -1.31). In as-treated analyses among those who took their medication on average at least 2.5 days per week (the median frequency in the study), naltrexone reduced any binge drinking (IRR=0.84, 95% CI=0.71, 0.99), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.96), and PEth concentrations (coefficient=-55.47, 95% CI=-110.75, -0.20). At 6 months posttreatment, naltrexone had sustained effects in number of drinks per month (IRR=0.69, 95% CI=0.50, 0.97), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.95), and any binge drinking in the past week (IRR=0.79, 95% CI=0.63, 0.99).Conclusions: Targeted naltrexone significantly reduced drinking outcomes among SGM with mild to moderate alcohol use disorder during treatment, with sustained effects at 6 months posttreatment. Naltrexone may be an important pharmacotherapy to address binge drinking in populations with mild to moderate alcohol use disorder. [ABSTRACT FROM AUTHOR]

Plant‐parasitic cyst nematodes use a stylet to deliver effector proteins produced in oesophageal gland cells into root cells to cause disease in plants. These effectors are deployed to modulate plant defence responses and developmental programmes for the formation of a specialized feeding site called a syncytium. The Hg2D01 effector gene, coding for a novel 185‐amino‐acid secreted protein, was previously shown to be up‐regulated in the dorsal gland of parasitic juveniles of the soybean cyst nematode Heterodera glycines, but its function has remained unknown. Genome analyses revealed that Hg2D01 belongs to a highly diversified effector gene family in the genomes of H. glycines and the sugar beet cyst nematode Heterodera schachtii. For functional studies using the model Arabidopsis thaliana–H. schachtii pathosystem, we cloned the orthologous Hs2D01 sequence from H. schachtii. We demonstrate that Hs2D01 is a cytoplasmic effector that interacts with the intracellular kinase domain of HAESA (HAE), a cell surface‐associated leucine‐rich repeat (LRR) receptor‐like kinase (RLK) involved in signalling the activation of cell wall‐remodelling enzymes important for cell separation during abscission and lateral root emergence. Furthermore, we show that AtHAE is expressed in the syncytium and, therefore, could serve as a viable host target for Hs2D01. Infective juveniles effectively penetrated the roots of HAE and HAESA‐LIKE2 (HSL2) double mutant plants; however, fewer nematodes developed on the roots, consistent with a role for this receptor family in nematode infection. Taken together, our results suggest that the Hs2D01–AtHAE interaction may play an important role in sugar beet cyst nematode parasitism. [ABSTRACT FROM AUTHOR]

Different functions are used to account for turbulence strength in the atmospheric boundary layer for different stability regimes. These functions are one of the sources for differences among different atmospheric models' predictions and associated biases. Also, turbulence strength is underrepresented in some of the resistance formulations. To address these issues with dry deposition, firstly we take advantage of three‐dimensional (3‐D) turbulence information in estimating resistances by proposing and validating a 3‐D turbulence velocity scale that is relevant for different stability regimes of boundary layer. Secondly, we hypothesize and validate that friction velocity measured by 3‐D sonic anemometer can be effectively replaced by the new turbulence velocity scale multiplied by the von Karman constant. Finally, we (a) present a set of resistance formulations for ozone (O3) based on the 3‐D turbulence velocity scale; (b) intercompare estimations of such resistances with those obtained using existing formulations; and, (c) evaluate simulated O3 fluxes using a single‐point dry deposition model against long‐term observations of O3 fluxes at the Harvard Forest (MA) site. Results indicate that the new resistance formulations work very well in simulating surface latent heat and O3 fluxes when compared to respective existing formulations and measurements at a decadal time scale. Findings from this research may help to improve the capability of dry deposition schemes for better estimation of dry deposition fluxes and create opportunities for the development of a community dry deposition model for use in regional/global air quality models. Plain Language Summary: Chaotic air motions control the amount of pollutant transfer to the surface during dry conditions, which can impact ecosystems, and is a helpful process that can reduce human exposure to air pollutants. Existing pollutant transfer equations use adjustment methods to account for chaotic air motions for different dry conditions. These methods can be sources of errors in estimating pollutant transfer. To avoid using such methods, we propose and evaluate a new velocity parameter derived from using chaotic air energy, which is estimated using other air parameters. Then, we validate the new velocity parameter using sophisticated instrument measurements for chaotic motions. Further, we assume and prove that a constant fraction of that new velocity parameter can be used to avoid adjustment methods and accurately represent strength of chaotic air motions. Finally, we use that new velocity parameter in developing new equations that estimate ozone transfer via various routes to the surface. We used a computer based tool to validate new equations using decadal measurements of ozone fluidities at the Harvard Forest site. Results indicate that our new equations work very well in estimating pollutant transfer. This research has the potential to help manifest a community science package for use in mathematical models. Key Points: Turbulence velocity scale is introduced to represent 3‐D turbulence strength in the estimation of dry depositionProven measured friction velocity can be replaced by von Karman constant and turbulence velocity scale product to avoid stability functionsNew formulations based on turbulence velocity scale simulated realistic surface latent heat and ozone deposition fluxes at decadal time scales [ABSTRACT FROM AUTHOR]

The importance of human cell-based in vitro tools to drug development that are robust, accurate, and predictive cannot be understated. There has been significant effort in recent years to develop such platforms, with increased interest in 3D models that can recapitulate key aspects of biology that 2D models might not be able to deliver. We describe the development of a 3D human cell-based in vitro assay for the investigation of nephrotoxicity, using RPTEC-TERT1 cells. These RPTEC-TERT1 proximal tubule organoids 'tubuloids' demonstrate marked differences in physiologically relevant morphology compared to 2D monolayer cells, increased sensitivity to nephrotoxins observable via secreted protein, and with a higher degree of similarity to native human kidney tissue. Finally, tubuloids incubated with nephrotoxins demonstrate altered Na+/K+-ATPase signal intensity, a potential avenue for a high-throughput, translatable nephrotoxicity assay. [ABSTRACT FROM AUTHOR]

A variety of endogenous and exogenous insults are capable of impeding replication fork progression, leading to replication stress. Several SNF2 fork remodelers have been shown to play critical roles in resolving this replication stress, utilizing different pathways dependent upon the nature of the DNA lesion, location on the DNA, and the stage of the cell cycle, to complete DNA replication in a manner preserving genetic integrity. Under certain conditions, however, the attempted repair may lead to additional genetic instability. Cockayne syndrome group B (CSB) protein, a SNF2 chromatin remodeler best known for its role in transcription-coupled nucleotide excision repair, has recently been shown to catalyze fork reversal, a pathway that can provide stability of stalled forks and allow resumption of DNA synthesis without chromosome breakage. Prolonged stalling of replication forks may collapse to give rise to DNA double-strand breaks, which are preferentially repaired by homology-directed recombination. CSB plays a role in repairing collapsed forks by promoting break-induced replication in S phase and early mitosis. In this review, we discuss roles of CSB in regulating the sources of replication stress, replication stress response, as well as the implications of CSB for cancer therapy. [ABSTRACT FROM AUTHOR]

Objective: Depression, and its treatment, is a concern among college students. Research indicates decision aids (DA) improve patients' treatment knowledge, decision making, and decisional conflict; however, it is unknown whether they are helpful for disseminating depression treatment information to college students. This study evaluated a DA for depression and its impact on college students' knowledge and treatment decision making. Methods: College students (N = 144) completed questionnaires pre-, post-, and at 1-month follow-up after reviewing an evidence-based DA for depression. Results: Participants rated the DA as highly acceptable and useful, and their knowledge increased at post-treatment and follow-up. However, treatment option presentation order influenced decision making. Conclusions: This DA is a useful and acceptable decision-making tool, and increased knowledge of depression and its treatment among college students. This study proposes a novel tool for educating college students about depression treatment, furthering our understanding of factors influencing treatment preferences. [ABSTRACT FROM AUTHOR]

Background: Heavy alcohol use, including binge drinking, is associated with high morbidity and mortality among men who have sex with men (MSM). Self‐reported alcohol measures may lead to inaccurate estimates due to recall and social desirability biases. Objective alcohol biomarkers like phosphatidylethanol (PEth) can be used to corroborate self‐report and could help to inform treatment approaches and research strategies for alcohol using MSM. Methods: From 2015 to 2020, alcohol using MSM ≥18 years were enrolled in a randomized controlled trial evaluating the efficacy of naltrexone in reducing binge drinking. Using this trial's baseline data, we applied multivariable logistic regression to identify the correlates of high PEth levels (i.e., ≥87 ng/ml) and concordance between PEth levels and self‐reported heavy drinking. Results: Of 118 MSM, 64% had PEth levels ≥87 ng/ml and 72% had PEth levels that were concordant with self‐reported heavy alcohol use. Factors significantly associated in separate models with elevated PEth levels were income ≥$60,000 (adjusted odds ratio [aOR] = 4.09; 95% CI = 1.13 to 14.82), being employed (aOR = 4.04; 95% CI = 1.45 to 11.32), episodic cannabis use (aOR = 4.63; 95% CI = 1.27 to 16.92), and any alcohol/substance use prior to or during anal intercourse (aOR = 2.52; 95% CI = 1.08 to 5.90). Living with HIV was associated with significantly lower odds of elevated PEth levels (aOR = 0.23; 95% CI = 0.09 to 0.61). Factors associated with significantly higher concordance between PEth levels and self‐reported heavy alcohol use included at least weekly use of poppers (aOR = 6.41; 95% CI = 1.27 to 32.28) and polysubstance use (aOR = 2.53; 95% CI = 1.02 to 6.27). Living with HIV was associated with lower odds of concordance (aOR = 0.36; 95% CI = 0.14 to 0.97). Conclusions: PEth may enhance the detection of heavy drinking among MSM, including the identification of subpopulations that may benefit from targeted alcohol reduction interventions. However, PEth values for MSM living with HIV showed modest concordance with self‐reported alcohol use and may need to be supplemented with additional biomarkers or evaluated against a different cutoff. [ABSTRACT FROM AUTHOR]

Postgraduate students often find work and thesis preparation demands compelling which in turn affect their thesis completion. The authors conducted a descriptive survey with a sample of 161 graduate thesis candidates (representing a 57% data collection return rate) using the census of the target population. Three scales were used to measure academic stress, academic burnout, and thesis completion, respectively; the questionnaires were administered via Google Forms. The data were analysed using Pearson's correlation coefficient and multiple linear regression. We found that lack of or inadequate sponsorship from beneficent organisations, several administrative bureaucracies, and inaccessibility to research databases, among others, place academic stress on graduate candidates, which connects with burnout, affecting thesis completion. The study also found that academic stress and burnout are essential determinants and predictors of thesis completion. The authors thus recommend that postgraduate schools design and implement thesis preparation schemes that consider this study's findings, especially those that recognise the elements of academic stress and its related burnout concerns for thesis candidates. [ABSTRACT FROM AUTHOR]

The microbial population in the gastrointestinal tract of ruminant animals aids in the utilization of forages with high levels of secondary plant compounds. Two divergent bloodlines of meat goats have been selected by screening fecal samples with near-infrared reflectance spectroscopy to assess the goat's consumption of high or low levels of Juniperus sp. leaves containing several monoterpenes, including camphor. The mechanism by which these goats can consume greater concentrations of Juniperus spp. leaves than their counterparts is unclear, and therefore, this study was designed to determine if differences existed between the ruminal microbial populations of the low and high juniper-consuming bloodlines (LJC vs. HJC) by analyzing their ruminal microbiota and fermentation end products. In the present study, concentrations (0.00, 0.5, 0.99, 1.97, or 5.91 mM) of camphor were added to mixed ruminal microorganism fermentation. Five LJC and five HJC goats were fed a juniper-free diet (n = 10), and five LJC and five HJC goats (n = 10) were fed a diet that contained 30% fresh Juniperus ashei leaves for 21 d prior to ruminal fluid collection. In vitro fermentations used LJC and HJC, ruminal fluid inoculum added (33% v/v) to anoxic media in sealed Balch tubes. Camphor increased (P < 0.05) total short-chain fatty acid (SCFA) concentrations for all but one experimental group. Between the main dietary and bloodline goat effects, the diet was significant for all SCFA results except butyrate. In contrast, bloodline was only significant for acetate and butyrate molar proportions. Rumen fluid from juniper-free-fed goats exhibited greater concentrations of Ruminococcaceae , whereas juniper-fed goats contained more Coriobacteriaceae. Results demonstrated that mixed ruminal microorganisms fermentations from HJC goats did not produce greater concentrations of SCFAs or have the ability to degrade camphor at a higher rate than did that from LJC goats. Results suggest that camphor tolerance from J. ashei , was related to hepatic catabolic mechanisms instead of ruminal microbial degradation; however, further in vivo work is warranted. [ABSTRACT FROM AUTHOR]

Encroaching plant species in West Texas continues to significantly reduce livestock production capacity and cause an imbalance between plant and livestock ecology. Juniperus ashei and Juniperus pinchotii are encroaching species rarely used by browsing animals, mainly due to phytochemical defenses. Juniperus spp. contain large concentrations of monoterpenes in their essential oil profiles to deter herbivory. Since 2003, two divergent bloodlines of meat goats have been selected to consume low or high (LJC or HJC) amounts of juniper foliage, through screening fecal samples with near-infrared reflectance spectroscopy. However, it remains unclear whether HJC goats expressed a physiological ability to consume a greater amount of juniper or if they were colonized by a ruminal microbial population that could detoxify juniper phytochemicals. Therefore, this study aimed to investigate the impact of 0.00 and 1.97 mM of camphor on the mixed ruminal microorganism fermentation after 0, 1, 2, 4, 12, and 24 h of incubation. Five LJC and five HJC goats were fed a juniper-free diet (n = 10) and five LJC and five HJC goats (n = 10), were fed a diet containing 30% fresh J. ashei leaves for 21 days prior to ruminal fluid collection. In vitro fermentations used LJC and HJC, ruminal fluid inoculum was added (33% v/v) to anoxic media in sealed Balch tubes. Total short-chain fatty acid (SCFA) production and acetate to propionate ratio were increased (P < 0.05), but there was no effect on pH (6.56 ± 0.09). Goats that received the juniper-free diet had higher (P < 0.05) SCFA production than juniper-containing diets. There was no consistent difference in LJC and HJC microbial fermentation end products caused by the addition of 1.97 mM of camphor, and goats receiving a juniper-free diet consistently generated more SCFAs in the presence of 1.97 mM of camphor. Furthermore, bloodline differences in juniper consumption were likely related to physiological adaption capacities within the animal and not a ruminal microbial detoxification advantage. [ABSTRACT FROM AUTHOR]

Assessing nutrient critical load exceedances requires complete and accurate atmospheric deposition budgets for reactive nitrogen (Nr). The exceedance is the total amount of Nr deposited to the ecosystem in excess of the critical load, which is the amount of Nr input below which harmful effects do not occur. Total deposition includes all forms of Nr (i.e., organic and inorganic) deposited to the ecosystem by wet and dry pathways. Here we present results from the Southern Appalachian Nitrogen Deposition Study (SANDS), in which a combination of measurements and fieldscale modeling were used to develop a complete annual Nr deposition budget for a deciduous forest at the Coweeta Hydrologic Laboratory. Wet deposition of ammonium, nitrate, nitrite, and bulk organic N were measured directly. The dry deposited Nr fraction was estimated using a bidirectional resistance-based model driven with speciated measurements of Nr air concentrations (e.g., ammonia, ammonium aerosol, nitric acid, nitrate aerosol, bulk organic N in aerosol, total alkyl nitrates, and total peroxy nitrates), micrometeorology, canopy structure, and biogeochemistry. Total annual deposition was  6.6 kg N ha-1 yr-1, which is on the upper end of Nr critical load estimates recently developed for similar ecosystems in nearby Great Smoky Mountains National Park. Of the total (wet + dry) budget, 50.7% was contributed by reduced forms of Nr (NHx = ammonia + ammonium), with oxidized and organic forms contributing  41.6% and 7.7%, respectively. Our results indicate that reductions in NHx deposition would be needed to achieve the lowest estimates ( 3.0 kg N ha-1 yr-1) of Nr critical loads in southern Appalachian forests. [ABSTRACT FROM AUTHOR]

Introduction: For patients with locally advanced cutaneous squamous cell carcinoma (LA-cSCC), radiotherapy alone (RT) is often the only treatment option with modest tumor response. We report the outcomes of using combination of programmed cell death protein-1 (PD-1) inhibitor and RT in the treatment of inoperable LA-cSCC. The study presents the efficacy and safety data for the patients with LA-cSCC treated with this combination. Methods: During the period 2018-2020, a total of 7 patients with biopsy proven inoperable LA-cSCC were treated with combination of PD-1 inhibitor cemiplimab and concurrent RT (Cem-RT). The patients were followed up for safety and efficacy of the Cem-RT regimen and the primary endpoints were objective tumor response and toxicity. Results: The median age of patients was 68 years (range, 64-94). All patients had ECOG performance score 0-1. Six patients initially received cemiplimab and concurrent RT was added to PD-1 inhibitor when there was an inadequate therapeutic response. One patient received concurrent Cem-RT. RT with PD-1 antibody was well tolerated. Six patients developed grade ≤2 dermatitis and 1 patient (patient no. 3) developed acute grade 3 skin reaction. During the post-RT follow up, 3 patients discontinued cemiplimab due to significant toxicities. At the time of reporting, 5 patients remain in complete remission. One patient developed lung metastasis and is currently receiving best supportive care. Conclusions: The Cem-RT combination was safe and well tolerated with significant tumor response suggesting Cem-RT may be a viable therapeutic option for LA-cSCC. Our hypothesis generating data support the rationale for future prospective studies. [ABSTRACT FROM AUTHOR]

The Llanos de Mojos of the Bolivian Amazon is a domesticated landscape with a long history of management by pre-Columbian communities. This paper uses a landscape approach to interpret the settlement patterns of pre-Columbian raised-field farmers in west central Mojos. The pre-Columbian landscape was reconstructed by mapping the distribution of three types of landscape features: forest islands, raised agricultural fields, and water systems (rivers, streams and wetlands). Previous research has identified four types of patterned clustering or 'constellations' of these landscape features in west central Mojos. These constellations and the immediate area of the landscape that surrounds them afforded Mojos farmers a specific set of tasks or activities to take part in as part of harnessing resources from the landscape. The mapping of landscape features and their associated tasks onto the landscape provides insight into the organization of the communities that constructed and managed them. It was found that the landscape of west central Mojos is organized into two distinct regional patterns. In the northern part of the region, evidence of large farming communities is dispersed along the banks of the permanent rivers with networks of landscape features extending off into remote areas of the savanna. In the southern part of the region, evidence for large farming communities is clustered closer together in remote areas of the savanna with networks of landscape features extending back towards the permanent rivers. The two regions are melded together by a transitional zone that implies a type of interaction between the regions rather than a distinct separation. [ABSTRACT FROM AUTHOR]

Woody plant encroachment – the conversion of open grasslands and savannas to woodlands – represents one of the gravest threats to grassland biomes worldwide. This is especially true for the Great Plains of the US. We contend that the widespread adoption of pyric herbivory (the synergistic application of fire and grazing) and mixed‐species grazing (cattle [Bos taurus] and goats [Capra spp]) would not only make grasslands and savannas more resilient to woody plant encroachment but would also enhance the profitability and resiliency of livestock production systems. These management strategies control woody plants, increase biodiversity, improve grassland ecosystem function, and favor livestock production. Although this management paradigm holds tremendous potential by mimicking original grassland disturbance regimes, it has not been widely adopted because of cultural constraints. Saving the remaining natural grasslands in the Great Plains and elsewhere will require a widespread shift in cultural norms – facilitated by targeted government incentives and a coordinated program of regional research, extension, and education that involves farmers and ranchers as key stakeholders. [ABSTRACT FROM AUTHOR]