Search

Abstract Wrist function is a top priority for transradial amputees. However, the combined functional, biomechanical, and cognitive impact of using a powered prosthetic wrist is unclear. Here, we quantify task performance, compensatory movements, and cognitive load while three transradial amputees performed a modified Clothespin Relocation Task using two myoelectric prostheses with and without the wrists. The two myoelectric prostheses include a commercial prosthesis with a built-in powered wrist, and a newly developed inexpensive prosthetic wrist for research purposes, called the “Utah wrist”, that can be adapted to work with various sockets and prostheses. For these three participants, task failure rate decreased significantly from 66% ± 12% without the wrist to 39% ± 9% with the Utah wrist. Compensatory forward leaning movements also decreased significantly, from 24.2° ± 2.5 without the wrist to 12.6° ± 1.0 with the Utah wrist, and from 23.6° ± 7.6 to 15.3° ± 7.2 with the commercial prosthesis with an integrated wrist. Compensatory leftward bending movements also significantly decreased, from 20.8° ± 8.6 to 12.3° ± 5.3, for the commercial with an integrated wrist. Importantly, simultaneous myoelectric control of either prosthetic wrist had no significant impact on cognitive load, as assessed by the NASA Task Load Index survey and a secondary detection response task. This work suggests that functional prosthetic wrists can improve dexterity and reduce compensation without significantly increasing cognitive effort. These results, and the introduction of a new inexpensive prosthetic wrist for research purposes, can aid future research and development and guide the prescription of upper-limb prostheses.

Background: Obesity is a known risk factor for cholecystitis and is associated with technical complications during laparoscopic procedures. The present study seeks to assess the association between obesity class and conversion to open (CTO) during laparoscopic cholecystectomy (LC). Methods: Adult acute cholecystitis patients with obesity undergoing non-elective LC were identified in the 2017–2020 Nationwide Readmissions Database. Patients were stratified by obesity class; class 1 (Body Mass Index [BMI] = 30.0–34.9), class 2 (BMI = 35.0–39.9), and class 3 (BMI ≥ 40.0). Multivariable regression models were developed to assess factors associated with CTO and its association with perioperative complications and resource utilization. Results: Of 89,476 patients undergoing LC, 40.6 % had BMI ≥ 40.0. Before adjustment, class 3 obesity was associated with increased rates of CTO compared to class 1–2 (4.6 vs 3.8 %; p

ABSTRACT The complexity of modern biology poses challenges in fostering interdisciplinary understanding, particularly between practicing scientists and the public. Furthermore, scientists often lack formal training in science communication, despite various motivations to engage the public. The science literacy of the public in the biological sciences can also vary across socio-economic and cultural backgrounds. Leveraging popular culture and informal learning practices to promote active learning offers promising avenues to enhance public understanding of biological systems. Organized sports hold collective recognition across various communities and cultures, serving as a means to bring people together. Notably, the NCAA March Madness event holds widespread national and international popularity, presenting an opportunity to laterally apply this concept to promote science communication within STEM and biology education. An educational social media and web-based contest tool was developed integrating NCAA-inspired brackets with animal biological systems concepts. The tool featured tournament-style matchups based on animal biological systems, interesting animal facts, and a voting system, all housed within a user-friendly interface. To encourage regular user access to the tool, graphic designs were developed for all social media posts to aid in visual recruitment to the voting website. Based on online metrics, the use of social media garnered repeat users across both the public and educators. The latter noted the tool’s simplicity and informative content. Application of this social media and web-based bracket contest tool, which leverages informal settings for active learning for use in biology education, can foster science communication to engage audiences, improve comprehension, and promote interdisciplinary biology education.

Abstract Dramatic improvements in measuring genetic variation across agriculturally relevant populations (genomics) must be matched by improvements in identifying and measuring relevant trait variation in such populations across many environments (phenomics). Identifying the most critical opportunities and challenges in genome to phenome (G2P) research is the focus of this paper. Previously (Genome Biol, 23(1):1–11, 2022), we laid out how Agricultural Genome to Phenome Initiative (AG2PI) will coordinate activities with USA federal government agencies expand public–private partnerships, and engage with external stakeholders to achieve a shared vision of future the AG2PI. Acting on this latter step, AG2PI organized the “Thinking Big: Visualizing the Future of AG2PI” two-day workshop held September 9–10, 2022, in Ames, Iowa, co-hosted with the United State Department of Agriculture’s National Institute of Food and Agriculture (USDA NIFA). During the meeting, attendees were asked to use their experience and curiosity to review the current status of agricultural genome to phenome (AG2P) work and envision the future of the AG2P field. The topic summaries composing this paper are distilled from two 1.5-h small group discussions. Challenges and solutions identified across multiple topics at the workshop were explored. We end our discussion with a vision for the future of agricultural progress, identifying two areas of innovation needed: (1) innovate in genetic improvement methods development and evaluation and (2) innovate in agricultural research processes to solve societal problems. To address these needs, we then provide six specific goals that we recommend be implemented immediately in support of advancing AG2P research.

Intuitive regression control of prostheses relies on training algorithms to correlate biological recordings to motor intent. The quality of the training dataset is critical to run-time regression performance, but accurately labeling intended hand kinematics after hand amputation is challenging. In this study, we quantified the accuracy and precision of labeling hand kinematics using two common training paradigms: 1) mimic training, where participants mimic predetermined motions of a prosthesis, and 2) mirror training, where participants mirror their contralateral intact hand during synchronized bilateral movements. We first explored this question in healthy non-amputee individuals where the ground-truth kinematics could be readily determined using motion capture. Kinematic data showed that mimic training fails to account for biomechanical coupling and temporal changes in hand posture. Additionally, mirror training exhibited significantly higher accuracy and precision in labeling hand kinematics. These findings suggest that the mirror training approach generates a more faithful, albeit more complex, dataset. Accordingly, mirror training resulted in significantly better offline regression performance when using a large amount of training data and a non-linear neural network. Next, we explored these different training paradigms online, with a cohort of unilateral transradial amputees actively controlling a prosthesis in real-time to complete a functional task. Overall, we found that mirror training resulted in significantly faster task completion speeds and similar subjective workload. These results demonstrate that mirror training can potentially provide more dexterous control through the utilization of task-specific, user-selected training data. Consequently, these findings serve as a valuable guide for the next generation of myoelectric and neuroprostheses leveraging machine learning to provide more dexterous and intuitive control.

Following tetraplegia, independence for completing essential daily tasks, such as opening doors and eating, significantly declines. Assistive robotic manipulators (ARMs) could restore independence, but typically input devices for these manipulators require functional use of the hands. We created and validated a hands-free multimodal input system for controlling an ARM in virtual reality using combinations of a gyroscope, eye-tracking, and heterologous surface electromyography (sEMG). These input modalities are mapped to ARM functions based on the user’s preferences and to maximize the utility of their residual volitional capabilities following tetraplegia. The two participants in this study with tetraplegia preferred to use the control mapping with sEMG button functions and disliked winking commands. Non-disabled participants were more varied in their preferences and performance, further suggesting that customizability is an advantageous component of the control system. Replacing buttons from a traditional handheld controller with sEMG did not substantively reduce performance. The system provided adequate control to all participants to complete functional tasks in virtual reality such as opening door handles, turning stove dials, eating, and drinking, all of which enable independence and improved quality of life for these individuals.

The United Arab Emirates hires many teachers from abroad to work in both the private and public school systems. Recruiting foreign teachers can be exceedingly costly, especially when one considers the financial investment associate with air fare, health insurance, housing, transportation, and a competitive salary, along with the substantial processing time involved in issuing work visas, professional and intercultural training. One way organizations may be able to save on additional expenditures is to retain the teachers who have been hired and are already settled in the country. Naturally, a substantial part of the decision for the teacher to remain working and living in the UAE lies with the expatriate teacher. This exploratory, case study employed a qualitative approach in which descriptive data was collected from six in-depth, semi-structured interviews exploring job satisfaction as one, of what may be other, indicators associated with of length-of-stay among expatriate teachers in the UAE. These descriptive data were analyzed using an interpretive analysis, which culminated with three selective codes: (1) Leadership and community are key to expatriate teacher’s job satisfaction; (2) School leaders’ engagement in improving behavior management would improve satisfaction; and (3) Positive work-life balance may influence expatriate teachers’ length of stay in the UAE. Taken collectively, this data may assist decision-makers, school leaders, and policy-makers on how to foster environments that promote retention among expatriate teachers in the UAE.

Abstract Directional selection alters the genome via hard sweeps, soft sweeps, and polygenic selection. However, mapping polygenic selection is difficult because it does not leave clear signatures on the genome like a selective sweep. In populations with temporally stratified genotypes, the Generation Proxy Selection Mapping (GPSM) method identifies variants associated with generation number (or appropriate proxy) and thus variants undergoing directional allele frequency changes. Here, we use GPSM on two large datasets of beef cattle to detect associations between an animal's generation and 11 million imputed SNPs. Using these datasets with high power and dense mapping resolution, GPSM detected a total of 294 unique loci actively under selection in two cattle breeds. We observed that GPSM has a high power to detect selection in the very recent past (

Global amphibian population decline is a major concern. Therefore, conservation centers have become increasingly needed for population sustainability breeding programs. This need makes proper nutrition programs while in human care imperative. The specific nutritional focus of this current research was to analyze vitamin A, vitamin E, and carotenoid (apocarotenoid, β-carotene, β-carotene ester, β-cryptoxanthin, lutein, lutein ester, zeaxanthin, and zeaxanthin ester) concentrations in the liver of 66 free-range marine toads (Rhinella marina) over a two-month period after entering human management. Toads were fed supplemented crickets randomly assigned to one of two diets: Diet 1 consisted of brown house crickets (Acheta domestica) gut loaded with Mazuri® Cricket Diet 5M38 and small amounts of sweet potato and carrots; Diet 2 consisted of an identical diet with the gut loaded crickets additionally dusted with Repashy® Superfoods Vitamin A Plus. Ten toads were euthanized prior to human management on Day 0 to assess baseline liver nutrients. Seven toads consuming each of the two diets (14 toads total) were euthanized on Days 9, 15, 32, and 62. Regardless of diet treatment, there were decreases (p < 0.05) in all the analyzed nutrient concentrations over the 62-day human management period. The results from this study indicate that higher dietary vitamin A, vitamin E, and carotenoid content may be needed and/or the cricket gut loading and dusting techniques used to feed the amphibians food source insects may be inadequate.

The rumen microbiome provides approximately 70% of the required energy for the host by converting low-quality feedstuffs into usable energy for ruminants. The energy produced by the microorganisms is subsequently absorbed through the rumen epithelium and used towards growth and energy maintenance. There is evidence that ruminal epimural microbes directly interact with the rumen epithelium, acting as an intermediary communicator between the rumen liquid fraction and the host. Epimural microbiota have been demonstrated to be distinct from the ruminal liquid microbiome and perform unique roles within the rumen environment. However, methods to sample epimural communities from the rumen wall are limited and typically invasive, requiring animal fistulation or harvesting. To characterize the epimural communities present on the rumen wall, a novel and minimally-invasive surgical method was developed to swab the epithelium of the ventral sac of the rumen. The objective of this study was to validate this sampling method by comparing epimural and liquid fraction bacterial communities. During a 70-day feeding trial, Angus steers (n = 45) were sampled on day 35 using the novel surgery method and tubed on day 70 to sample rumen liquid content. Genomic DNA was used to generate amplicon libraries of the V4 region of the 16S rRNA gene. There were no differences between alpha diversity indices when comparing rumen versus epimural bacterial communities (P > 0.05). The Bray-Curtis dissimilarity was used to ordinate ASV counts, and then tested for differences between rumen and epimural communities using a PERMANOVA with 999 permutations (P < 0.05). Differential abundances of bacterial communities were tested using ANCOM-BC and MaAsLin2, where significance was determined by Q < 0.05 and overlap between both analysis methods. Within the 91 taxa that differed in abundance, 451 ASVs were found to be different between sample types (Q < 0.05). Unique ASVs associated with Prevotella, Succinivibrio, family-level Eubacterium, and family-level Succinivibrio were in greater abundance for the rumen epithelial-associated bacterial communities (Q < 0.05). The results demonstrate that the novel method of sampling from the rumen wall can capture differences between epimural and ruminal fluid bacterial communities, thus facilitating studies investigating the interactions between epimural bacteria with the host.

Abstract The eight species of bears world-wide consume a wide variety of diets. Some are specialists with extensive anatomical and physiological adaptations necessary to exploit specific foods or environments [e.g., polar bears (Ursus maritimus), giant pandas (Ailuropoda melanoleuca), and sloth bears (Melursus ursinus)], while the rest are generalists. Even though ursids evolved from a high-protein carnivore, we hypothesized that all have become low-protein macronutrient omnivores. While this dietary strategy has already been described for polar bears and brown bears (Ursus arctos), a recent study on giant pandas suggested their macronutrient selection was that of the ancestral high-protein carnivore. Consumption of diets with inappropriate macronutrient profiles has been associated with increased energy expenditure, ill health, failed reproduction, and premature death. Consequently, we conducted feeding and preference trials with giant pandas and sloth bears, a termite and ant-feeding specialist. Both giant pandas and sloth bears branched off from the ursid lineage a million or more years before polar bears and brown bears. We found that giant pandas are low-protein, high-carbohydrate omnivores, whereas sloth bears are low-protein, high-fat omnivores. The preference for low protein diets apparently occurred early in the evolution of ursids and may have been critical to their world-wide spread.

Abstract Background Genotypic information produced from single nucleotide polymorphism (SNP) arrays has routinely been used to identify genomic regions associated with complex traits in beef and dairy cattle. Herein, we assembled a dataset consisting of 15,815 Red Angus beef cattle distributed across the continental U.S. and a union set of 836,118 imputed SNPs to conduct genome-wide association analyses (GWAA) for growth traits using univariate linear mixed models (LMM); including birth weight, weaning weight, and yearling weight. Genomic relationship matrix heritability estimates were produced for all growth traits, and genotype-by-environment (GxE) interactions were investigated. Results Moderate to high heritabilities with small standard errors were estimated for birth weight (0.51 ± 0.01), weaning weight (0.25 ± 0.01), and yearling weight (0.42 ± 0.01). GWAA revealed 12 pleiotropic QTL (BTA6, BTA14, BTA20) influencing Red Angus birth weight, weaning weight, and yearling weight which met a nominal significance threshold (P ≤ 1e-05) for polygenic traits using 836K imputed SNPs. Moreover, positional candidate genes associated with Red Angus growth traits in this study (i.e., LCORL, LOC782905, NCAPG, HERC6, FAM184B, SLIT2, MMRN1, KCNIP4, CCSER1, GRID2, ARRDC3, PLAG1, IMPAD1, NSMAF, PENK, LOC112449660, MOS, SH3PXD2B, STC2, CPEB4) were also previously associated with feed efficiency, growth, and carcass traits in beef cattle. Collectively, 14 significant GxE interactions were also detected, but were less consistent among the investigated traits at a nominal significance threshold (P ≤ 1e-05); with one pleiotropic GxE interaction detected on BTA28 (24 Mb) for Red Angus weaning weight and yearling weight. Conclusions Sixteen well-supported QTL regions detected from the GWAA and GxE GWAA for growth traits (birth weight, weaning weight, yearling weight) in U.S. Red Angus cattle were found to be pleiotropic. Twelve of these pleiotropic QTL were also identified in previous studies focusing on feed efficiency and growth traits in multiple beef breeds and/or their composites. In agreement with other beef cattle GxE studies our results implicate the role of vasodilation, metabolism, and the nervous system in the genetic sensitivity to environmental stress.

This study provides novel data on circulating concentrations of whole-blood fatty acids (FAs) in marine toads (Rhinella marina) via dried blood spot (DBS) card technology as a potential amphibian model species. Free-ranging (n = 10) animals were compared to managed populations fed two diet strategies for 60 days (n = 6 per diet). Thirty-six individual FAs were analyzed, with 28 found in significant reportable quantities. Eight FA groupings were represented. Traditional whole-blood vial (WBV) FA percentages were also collected and compared to DBS after managed care for 60 days. Results showed eleven individual FAs and four FA groups were higher in free-ranging toads (n = 10; p ≤ 0.05), while three FAs and three groups were higher in managed care (n = 12; p ≤ 0.05). FA concentrations compared between DBS cards and WBV at day 60 generally agreed, although two individual FAs and one grouping were higher in DBS (p ≤ 0.05). When free-ranging FAs were analyzed by sex, four individual FAs and two groupings were higher in females, while four individual FAs and one grouping were higher in males. Understanding normal FA circulating levels and how husbandry changes them may impact amphibian health. Additionally, DBS cards may provide a convenient sampling tool for fieldwork.

Corticosterone concentrations have been measured in amphibians by collecting blood or urine samples. However, blood sampling is invasive, and urine can be difficult to collect. A novel method of swabbing the skin of an amphibian has been utilized in numerous species but has not been verified in marine toads (Rhinella marina). This pilot study tested dermal swabs as a noninvasive method for collecting and measuring dermal corticosterone secretions. Swabs were used to collect dermal secretion samples from sixty-six free-ranging marine toads collected on Zoo Miami grounds. The subsequent day the toads were shipped to the North Carolina Zoo where dermal samples were collected again. Additional dermal and urine samples were collected on days 9, 15, 32, and 62 under human care to measure corticosterone concentrations. There was no significant correlation (P ≥ 0.05) noted between corticosterone concentrations reported in dermal swabs and those in urine samples at all four of the euthanasia time points or between the corticosterone concentrations reported in either urine or dermal swabs and the weight of the toads. Dermal swab concentrations (ng/mL) were significantly higher (P ≤ 0.05) on the day of capture (0.64 ± 0.03) and the day of arrival (0.67 ± 0.03) than on day 15 (0.47 ± 0.03). The urine corticosterone concentrations decreased while the toads were in human care with a significant decrease (P ≤ 0.05) between days 9 (0.45 ± 0.07) and 32 (0.21 ± 0.06). This study demonstrated that dermal swabs can be used to collect marine toad corticosterone concentration samples.

Abstract Studies of predator feeding ecology commonly focus on energy intake. However, captive predators have been documented to selectively feed to optimize macronutrient intake. As many apex predators experience environmental changes that affect prey availability, limitations on selective feeding can affect energetics and health. We estimated the protein:fat ratio of diets consumed by wild polar bears using a novel isotope-based approach, measured protein:fat ratios selected by zoo polar bears offered dietary choice and examined potential energetic and health consequences of overconsuming protein. Dietary protein levels selected by wild and zoo polar bears were low and similar to selection observed in omnivorous brown bears, which reduced energy intake requirements by 70% compared with lean meat diets. Higher-protein diets fed to zoo polar bears during normal care were concurrent with high rates of mortality from kidney disease and liver cancer. Our results suggest that polar bears have low protein requirements and that limitations on selective consumption of marine mammal blubber consequent to climate change could meaningfully increase their energetic costs. Although bear protein requirements appear lower than those of other carnivores, the energetic and health consequences of protein overconsumption identified in this study have the potential to affect a wide range of taxa.

Abstract Understanding genotype-by-environment interactions (G × E) is crucial to understand environmental adaptation in mammals and improve the sustainability of agricultural production. Here, we present an extensive study investigating the interaction of genome-wide SNP markers with a vast assortment of environmental variables and searching for SNPs controlling phenotypic variance (vQTL) using a large beef cattle dataset. We showed that G × E contribute 10.1%, 3.8%, and 2.8% of the phenotypic variance of birth weight, weaning weight, and yearling weight, respectively. G × E genome-wide association analysis (GWAA) detected a large number of G × E loci affecting growth traits, which the traditional GWAA did not detect, showing that functional loci may have non-additive genetic effects regardless of differences in genotypic means. Further, variance-heterogeneity GWAA detected loci enriched with G × E effects without requiring prior knowledge of the interacting environmental factors. Functional annotation and pathway analysis of G × E genes revealed biological mechanisms by which cattle respond to changes in their environment, such as neurotransmitter activity, hypoxia-induced processes, keratinization, hormone, thermogenic and immune pathways. We unraveled the relevance and complexity of the genetic basis of G × E underlying growth traits, providing new insights into how different environmental conditions interact with specific genes influencing adaptation and productivity in beef cattle and potentially across mammals.

Abstract Background Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression changes in early disease. In this study, we quantified gene expression changes in the synovium of osteoarthritis-affected joints using an equine metacarpophalangeal joint (MCPJ) chip model of early PTOA. Synovial samples were collected arthroscopically from the MCPJ of 11 adult horses before (preOA) and after (OA) surgical induction of osteoarthritis and from sham-operated joints. After sequencing synovial RNA, Salmon was used to quasi-map reads and quantify transcript abundances. Differential expression analysis with the limma-trend method used a fold-change cutoff of log2(1.1). Functional annotation was performed with PANTHER at FDR

The validation of myoelectric prosthetic control strategies for individuals experiencing upper-limb loss is hindered by the time and cost affiliated with traditional custom-fabricated sockets. Consequently, researchers often rely upon virtual reality or robotic arms to validate novel control strategies, which limits end-user involvement. Prosthetists fabricate diagnostic check sockets to assess and refine socket fit, but these clinical techniques are not readily available to researchers and are not intended to assess functionality for control strategies. Here we present a multi-user, low-cost, transradial, functional-test socket for short-term research use that can be custom-fit and donned rapidly, used in conjunction with various electromyography configurations, and adapted for use with various residual limbs and terminal devices. In this study, participants with upper-limb amputation completed functional tasks in physical and virtual environments both with and without the socket, and they reported on their perceived comfort level over time. The functional-test socket was fabricated prior to participants' arrival, iteratively fitted by the researchers within 10 mins, and donned in under 1 min (excluding electrode placement, which will vary for different use cases). It accommodated multiple individuals and terminal devices and had a total cost of materials under $10 USD. Across all participants, the socket did not significantly impede functional task performance or reduce the electromyography signal-to-noise ratio. The socket was rated as comfortable enough for at least 2 h of use, though it was expectedly perceived as less comfortable than a clinically-prescribed daily-use socket. The development of this multi-user, transradial, functional-test socket constitutes an important step toward increased end-user participation in advanced myoelectric prosthetic research. The socket design has been open-sourced and is available for other researchers.

AbstractThe Neosho madtom (Noturus placidusIctalurus punctatus)Danio rerio

Background Southern white rhinoceroses (Ceratotherium simum simum) are an endangered species in decline due to poaching and negative habitat changes. Conservation of the species has become increasingly important and a focus on better human management has become prevalent. One area of management that impacts southern white rhinoceroses is nutritional health monitoring, which is often conducted through blood analysis. Blood analysis conducted during field research can be difficult due to temperature, distance, and limited technological resources, so new methods of fast, and relatively stable blood collection are being pursued. One method that has been used in humans for many years is beginning to make its way into wildlife studies: the use of dried blood spot (DBS) cards. These cards are used as a tool to store single drops of whole blood on specialized filter paper and, once dried, can be used for nutritional biomarker analysis. An area of interest for southern white rhinoceroses and nutrition is monitoring fatty acid percentages for cardiovascular, immune, and reproductive health. The time and temperature limitations for storing blood fractions or liquid whole blood when analyzing fatty acids have been investigated, but few studies have performed storage studies on DBS cards colder than −20 °C or in non-human species. Methods In order to better understand the limitations of DBS cards and the impact of temperature on fatty acid DBS samples in long-term storage, triplicate samples from seven adult southern white rhinoceroses at the North Carolina Zoo were collected and subjected to three storage treatments (immediate, room temperature (23 °C), or frozen (−80 °C) for 1 year). Results Stearidonic (18:4w3) (Δ 0.3%), arachdic (20:0) (Δ 0.1%), eicosatetraenoic (20:4w3) (Δ 0.2%), and erucic acid (22:1w9) (Δ 0.1%) were in higher concentration in frozen than initial. Fatty acids in higher concentrations in the initial samples than frozen were myristic (14:0) (Δ 0.2%), mead (20:3w9) (Δ 0.1%), docosatetraenoic (22:4w6) (Δ 0.2%), nervonic (24:1) (Δ 0.1%), and total highly unsaturated fatty acids (HUFAs) (Δ 0.7%). Stearic (18:0) (Δ 2.2%), stearidonic (18:4w3) (Δ 0.3%), arachdic (20:0) (Δ 0.2%), paullinic (20:1w7) (Δ 0.4%), eicosatetraenoic (20:4w3) (Δ 0.1%), eicosapentaenoic (20:5w3) (Δ 0.1%), docosatetraenoic (22:4w6) (Δ 0.2%), nervonic acid (24:1) (Δ 0.2%), monoenes (Δ 1.9%), and total saturates (Δ 3.6%) had higher concentrations in room temperature than initial. Linoleic (18:2w6) (Δ 4.9%), mead acid (20:3w9) (Δ 0.1%), total polyunsaturated fatty acids (5.3%), and total omega-6 fatty acids (Δ 4.8%) had higher concentrations in initial compared to room temperature. Arachidonic (20:4w6) (Δ 0.4%) and omega-3 docosapentaenoic acid (22:5w3) (Δ 0.1%), had higher concentrations in frozen than in room temperature. Discussion The frozen samples had the fewest statistical differences compared to room temperature samples and essential omega-3 and -6 fatty acids were stable with freezing up to 1 year. While more research is still warranted, current results suggest that DBS samples are best utilized when immediate analysis or −80 °C storage is available.

Abstract Background Single nucleotide polymorphism (SNP) arrays have facilitated discovery of genetic markers associated with complex traits in domestic cattle; thereby enabling modern breeding and selection programs. Genome-wide association analyses (GWAA) for growth traits were conducted on 10,837 geographically diverse U.S. Gelbvieh cattle using a union set of 856,527 imputed SNPs. Birth weight (BW), weaning weight (WW), and yearling weight (YW) were analyzed using GEMMA and EMMAX (via imputed genotypes). Genotype-by-environment (GxE) interactions were also investigated. Results GEMMA and EMMAX produced moderate marker-based heritability estimates that were similar for BW (0.36–0.37, SE = 0.02–0.06), WW (0.27–0.29, SE = 0.01), and YW (0.39–0.41, SE = 0.01–0.02). GWAA using 856K imputed SNPs (GEMMA; EMMAX) revealed common positional candidate genes underlying pleiotropic QTL for Gelbvieh growth traits on BTA6, BTA7, BTA14, and BTA20. The estimated proportion of phenotypic variance explained (PVE) by the lead SNP defining these QTL (EMMAX) was larger and most similar for BW and YW, and smaller for WW. Collectively, GWAAs (GEMMA; EMMAX) produced a highly concordant set of BW, WW, and YW QTL that met a nominal significance level (P ≤ 1e-05), with prioritization of common positional candidate genes; including genes previously associated with stature, feed efficiency, and growth traits (i.e., PLAG1, NCAPG, LCORL, ARRDC3, STC2). Genotype-by-environment QTL were not consistent among traits at the nominal significance threshold (P ≤ 1e-05); although some shared QTL were apparent at less stringent significance thresholds (i.e., P ≤ 2e-05). Conclusions Pleiotropic QTL for growth traits were detected on BTA6, BTA7, BTA14, and BTA20 for U.S. Gelbvieh beef cattle. Seven QTL detected for Gelbvieh growth traits were also recently detected for feed efficiency and growth traits in U.S. Angus, SimAngus, and Hereford cattle. Marker-based heritability estimates and the detection of pleiotropic QTL segregating in multiple breeds support the implementation of multiple-breed genomic selection.

Abstract Background During the last decade, the use of common-variant array-based single nucleotide polymorphism (SNP) genotyping in the beef and dairy industries has produced an astounding amount of medium-to-low density genomic data. Although low-density assays work well in the context of genomic prediction, they are less useful for detecting and mapping causal variants and the effects of rare variants are not captured. The objective of this project was to maximize the accuracies of genotype imputation from medium- and low-density assays to the marker set obtained by combining two high-density research assays (~ 850,000 SNPs), the Illumina BovineHD and the GGP-F250 assays, which contains a large proportion of rare and potentially functional variants and for which the assay design is described here. This 850 K SNP set is useful for both imputation to sequence-level genotypes and direct downstream analysis. Results We found that a large multi-breed composite imputation reference panel that includes 36,131 samples with either BovineHD and/or GGP-F250 genotypes significantly increased imputation accuracy compared with a within-breed reference panel, particularly at variants with low minor allele frequencies. Individual animal imputation accuracies were maximized when more genetically similar animals were represented in the composite reference panel, particularly with complete 850 K genotypes. The addition of rare variants from the GGP-F250 assay to our composite reference panel significantly increased the imputation accuracy of rare variants that are exclusively present on the BovineHD assay. In addition, we show that an assay marker density of 50 K SNPs balances cost and accuracy for imputation to 850 K. Conclusions Using high-density genotypes on all available individuals in a multi-breed reference panel maximized imputation accuracy for tested cattle populations. Admixed animals or those from breeds with a limited representation in the composite reference panel were still imputed at high accuracy, which is expected to further increase as the reference panel expands. We anticipate that the addition of rare variants from the GGP-F250 assay will increase the accuracy of imputation to sequence level.

Objective: To determine the symptomatic and disease-modifying capabilities of sEH and COX inhibitors during joint inflammation.Methods: Using a blinded, randomized, crossover experimental design, 6 adult healthy horses were injected with lipopolysaccharide (LPS; 3 μg) from E. coli in a radiocarpal joint and concurrently received the non-selective cyclooxygenase (COX) inhibitor phenylbutazone (2 mg/kg), the sEH inhibitor t-TUCB (1 mg/kg) or both (2 mg/kg phenylbutazone and 0.1, 0.3, and 1 mg/kg t-TUCB) intravenously. There were at least 30 days washout between treatments. Joint pain (assessed via inertial sensors and peak vertical forces), synovial fluid concentrations of prostanoids (PGE2, TxB2), cytokines (IL-1β, IL-6, TNF-α) and biomarkers of collagen synthesis (CPII) and degradation (C2C) were measured at pre-determined intervals over a 48-h period. The anti-apoptotic effect of COX and sEH inhibitors was determined via ELISA technique in primary equine chondrocytes incubated with TNF-α (10 ng/ml) for 24 h. Apoptosis was also determined in chondrocytes incubated with sEH-generated metabolites.Results: Combined COX and sEH inhibition produced significantly better control of joint pain, prostanoid responses, and collagen synthesis-degradation balance compared to each compound separately. When administered separately, pain control was superior with COX vs. sEH inhibition. Cytokine responses were not different during COX and/or sEH inhibition. In cultured chondrocytes, sEH inhibition alone or combined with COX inhibition, but not COX inhibition alone had significant anti-apoptotic effects. However, sEH-generated metabolites caused concentration-dependent apoptosis.Conclusions: Combined COX and sEH inhibition optimize pain control, attenuate loss of articular cartilage matrix during joint inflammation and cytokine-induced chondrocyte apoptosis.

Selection on complex traits can rapidly drive evolution, especially in stressful environments. This polygenic selection does not leave intense sweep signatures on the genome, rather many loci experience small allele frequency shifts, resulting in large cumulative phenotypic changes. Directional selection and local adaptation are changing populations; but, identifying loci underlying polygenic or environmental selection has been difficult. We use genomic data on tens of thousands of cattle from three populations, distributed over time and landscapes, in linear mixed models with novel dependent variables to map signatures of selection on complex traits and local adaptation. We identify 207 genomic loci associated with an animal's birth date, representing ongoing selection for monogenic and polygenic traits. Additionally, hundreds of additional loci are associated with continuous and discrete environments, providing evidence for historical local adaptation. These candidate loci highlight the nervous system's possible role in local adaptation. While advanced technologies have increased the rate of directional selection in cattle, it has likely been at the expense of historically generated local adaptation, which is especially problematic in changing climates. When applied to large, diverse cattle datasets, these selection mapping methods provide an insight into how selection on complex traits continually shapes the genome. Further, understanding the genomic loci implicated in adaptation may help us breed more adapted and efficient cattle, and begin to understand the basis for mammalian adaptation, especially in changing climates. These selection mapping approaches help clarify selective forces and loci in evolutionary, model, and agricultural contexts.

Reports of APOE4-associated neurovascular dysfunction during aging and in neurodegenerative disorders has led to ongoing research to identify underlying mechanisms. In this study, we focused on whether the APOE genotype of brain endothelial cells modulates their own phenotype. We utilized a modified primary mouse brain endothelial cell isolation protocol that enabled us to perform experiments without subculture. Through initial characterization we found, that compared to APOE3, APOE4 brain endothelial cells produce less apolipoprotein E (apoE) and have altered metabolic and inflammatory gene expression profiles. Further analysis revealed APOE4 brain endothelial cultures have higher preference for oxidative phosphorylation over glycolysis and, accordingly, higher markers of mitochondrial activity. Mitochondrial activity generates reactive oxygen species, and, with APOE4, there were higher mitochondrial superoxide levels, lower levels of antioxidants related to heme and glutathione and higher markers/outcomes of oxidative damage to proteins and lipids. In parallel, or resulting from reactive oxygen species, there was greater inflammation in APOE4 brain endothelial cells including higher chemokine levels and immune cell adhesion under basal conditions and after low-dose lipopolysaccharide (LPS) treatment. In addition, paracellular permeability was higher in APOE4 brain endothelial cells in basal conditions and after high-dose LPS treatment. Finally, we found that a nuclear receptor Rev-Erb agonist, SR9009, improved functional metabolic markers, lowered inflammation and modulated paracellular permeability at baseline and following LPS treatment in APOE4 brain endothelial cells. Together, our data suggest that autocrine signaling of apoE in brain endothelial cells represents a novel cellular mechanism for how APOE regulates neurovascular function.

The Caribbean is a genetically diverse region with heterogeneous admixture compositions influenced by local island ecologies, migrations, colonial conflicts, and demographic histories. The Commonwealth of Dominica is a mountainous island in the Lesser Antilles historically known to harbor communities with unique patterns of migration, mixture, and isolation. This community-based population genetic study adds biological evidence to inform post-colonial narrative histories in a Dominican horticultural village. High density single nucleotide polymorphism data paired with a previously compiled genealogy provide the first genome-wide insights on genetic ancestry and population structure in Dominica. We assessed family-based clustering, inferred global ancestry, and dated recent admixture by implementing the fastSTRUCTURE clustering algorithm, modeling graph-based migration with TreeMix, assessing patterns of linkage disequilibrium decay with ALDER, and visualizing data from Dominica with Human Genome Diversity Panel references. These analyses distinguish family-based genetic structure from variation in African, European, and indigenous Amerindian admixture proportions, and analyses of linkage disequilibrium decay estimate admixture dates 5-6 generations (~160 years) ago. African ancestry accounts for the largest mixture components, followed by European and then indigenous components; however, our global ancestry inferences are consistent with previous mitochondrial, Y chromosome, and ancestry marker data from Dominica that show uniquely higher proportions of indigenous ancestry and lower proportions of African ancestry relative to known admixture in other French- and English-speaking Caribbean islands. Our genetic results support local narratives about the community's history and founding, which indicate that newly emancipated people settled in the steep, dense vegetation along Dominica's eastern coast in the mid-19th century. Strong genetic signals of post-colonial admixture and family-based structure highlight the localized impacts of colonial forces and island ecologies in this region, and more data from other groups are needed to more broadly inform on Dominica's complex history and present diversity.

Fatty acids, especially omega-3 and omega-6 fatty acids, are important for reproductive and cardiovascular health in animals. While monitoring fatty acids is traditionally conducted using frozen blood fractions such as serum and plasma, advancements in analytical technology have developed a method of collecting microsamples of dried whole blood on Ahlstrom 226 grade filter paper that can provide information on long-term fatty acid status of animals. Blood samples were collected from five male pigs in both the traditional frozen method and on dried blood spot cards (DBS). The DBS samples were collected with untreated syringes and tubes, and approximately 320 μL of blood was placed on each card with approximately 80 μL per spot (4 spots). Statistical analysis was performed to compare the two sample groups to each other using the Mann–Whitney U-test and determine if DBS samples were similar to traditional whole blood samples. Of the 30 fatty acids and fatty acid groups with measurable concentrations, only four individual fatty acids, behenic acid, omega-3 docosapentaenoic acid, nervonic acid, and adrenic acid, had statistical differences. Most of these differences were minor and could be due to analytical errors or contamination. Comparisons between sample types found similar concentrations of key omega fatty acids and PUFAs and support the use of DBS collection as a less invasive method of blood collection and fatty acid analysis.

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1-4. Despite the clinical evidence1,5-7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8-10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.

The United Arab Emirates hires many teachers from abroad to work in both the private and public school systems. Recruiting foreign teachers can be exceedingly costly, especially when one considers the financial investment associate with air fare, health insurance, housing, transportation, and a competitive salary, along with the substantial processing time involved in issuing work visas, professional and intercultural training. One way organizations may be able to save on additional expenditures is to retain the teachers who have been hired and are already settled in the country. Naturally, a substantial part of the decision for the teacher to remain working and living in the UAE lies with the expatriate teacher. This exploratory, case study employed a qualitative approach in which descriptive data was collected from six in-depth, semi-structured interviews exploring job satisfaction as one, of what may be other, indicators associated with of length-of-stay among expatriate teachers in the UAE. These descriptive data were analyzed using an interpretive analysis, which culminated with three selective codes: (1) Leadership and community are key to expatriate teacher's job satisfaction; (2) School leaders' engagement in improving behavior management would improve satisfaction; and (3) Positive work-life balance may influence expatriate teachers' length of stay in the UAE. Taken collectively, this data may assist decision-makers, school leaders, and policy-makers on how to foster environments that promote retention among expatriate teachers in the UAE.

For providing advanced desalination the combination of the improvement of water recovery ratio in the reverse osmosis (RO) process and the No-Chlorine/No-Sodium Bisulfite (SBS) Dosing process was studied. In order to prevent membrane fouling even in high recovery water operations, an advanced two-stage design was implemented to (1) control the permeate flux through the RO membrane module, (2) optimize the system to reduce contaminant build-up and (3) eliminate the use of chlorine and SBS, which can accelerate membrane fouling. The system was evaluated by monitoring the biofouling and the microorganisms proliferation on the membrane surface based on membrane biofilm formation rate (mBFR). The pilot plant was operated in the condition of a water recovery rate of 55%. As a result, the system was operated for longer than four months without membrane cleaning (clean in place; CIP) and the possibility of operation for seven months without CIP was confirmed by the extrapolation of the pressure values. In addition, the mBFR is a reliable tool for water quality assessment, based on a comparison between the fouling tendency estimated from the mBFR and the actual membrane surface condition from autopsy study and the effectiveness No-Chlorine/No-SBS Dosing process was verified from mBFR of pretreated seawater.

ObjectiveTo determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers.Summary of background and dataTailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown.MethodsIn 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity").ResultsNeither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls.ConclusionsThis pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.

BackgroundMajor advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10-12 years. These tools depend upon the Bos taurus reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies.ResultsWe present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250× more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use.ConclusionsWe demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species.

Checkpoint blockade immunotherapy targeting the PD-1/PD-L1 inhibitory axis has produced remarkable results in the treatment of several types of cancer. Whereas cytotoxic T cells are known to provide important antitumor effects during checkpoint blockade, certain cancers with low MHC expression are responsive to therapy, suggesting that other immune cell types may also play a role. Here, we employed several mouse models of cancer to investigate the effect of PD-1/PD-L1 blockade on NK cells, a population of cytotoxic innate lymphocytes that also mediate antitumor immunity. We discovered that PD-1 and PD-L1 blockade elicited a strong NK cell response that was indispensable for the full therapeutic effect of immunotherapy. PD-1 was expressed on NK cells within transplantable, spontaneous, and genetically induced mouse tumor models, and PD-L1 expression in cancer cells resulted in reduced NK cell responses and generation of more aggressive tumors in vivo. PD-1 expression was more abundant on NK cells with an activated and more responsive phenotype and did not mark NK cells with an exhausted phenotype. These results demonstrate the importance of the PD-1/PD-L1 axis in inhibiting NK cell responses in vivo and reveal that NK cells, in addition to T cells, mediate the effect of PD-1/PD-L1 blockade immunotherapy.

Wrist function is a top priority for transradial amputees. However, the combined functional, biomechanical, and cognitive impact of using a powered prosthetic wrist is unclear. Here, we quantify task performance, compensatory movements, and cognitive load while three transradial amputees performed a modified Clothespin Relocation Task using two myoelectric prostheses with and without the wrists. The two myoelectric prostheses include a commercial prosthesis with a built-in powered wrist, and a newly developed inexpensive prosthetic wrist for research purposes, called the "Utah wrist", that can be adapted to work with various sockets and prostheses. For these three participants, task failure rate decreased significantly from 66% ± 12% without the wrist to 39% ± 9% with the Utah wrist. Compensatory forward leaning movements also decreased significantly, from 24.2° ± 2.5 without the wrist to 12.6° ± 1.0 with the Utah wrist, and from 23.6° ± 7.6 to 15.3° ± 7.2 with the commercial prosthesis with an integrated wrist. Compensatory leftward bending movements also significantly decreased, from 20.8° ± 8.6 to 12.3° ± 5.3, for the commercial with an integrated wrist. Importantly, simultaneous myoelectric control of either prosthetic wrist had no significant impact on cognitive load, as assessed by the NASA Task Load Index survey and a secondary detection response task. This work suggests that functional prosthetic wrists can improve dexterity and reduce compensation without significantly increasing cognitive effort. These results, and the introduction of a new inexpensive prosthetic wrist for research purposes, can aid future research and development and guide the prescription of upper-limb prostheses. [ABSTRACT FROM AUTHOR]

We evaluated student perceptions of an inquiry-based, karaoke video exercise in six university classes ranging from first year to graduate level. Students created a 3-4 minute karaoke video on a topic relevant to class. Student responses to the project based on questionnaires and triangulation interviews were strongly positive. Students did not demonstrate a preference for the different parts of the exercise (e.g., writing lyrics, research, singing, etc.). Musical experience (low, average, high) had a significant effect on the number of positive responses from students; however, students' majors had no impact on their responses. Triangulation interviews from students in all classes were strongly positive, and a simple trend analysis indicated that many students found the exercise: (a) was new, (b) was creative, (c) facilitated deeper learning, and (d) was enjoyable. Studies that evaluate inquiry-based classroom exercises over multiple classes and university levels are uncommon, and this is one of the first to show strong positive student responses to an inquiry-based, music-based exercise over courses ranging from first-year to graduate seminars.