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Until recently, our understanding of the genetics of speciation was limited to a narrow group of model species with a specific set of characteristics that made genetic analysis feasible. Rapidly advancing genomic technologies are eliminating many of the distinctions between laboratory and natural systems. In light of these genomic developments, we review the history of speciation genetics, advances that have been gleaned from model and non-model organisms, the current state of the field, and prospects for broadening the diversity of taxa included in future studies. Responses to a survey of speciation scientists across the world reveal the ongoing division between the types of questions that are addressed in model and non-model organisms. To bridge this gap, we suggest integrating genetic studies from model systems that can be reared in the laboratory or greenhouse with genomic studies in related non-models where extensive ecological knowledge exists.

The prevalence of highly marbled cattle breeds, such as Wagyu, has increased in the US due to consumer demand for higher-quality beef. The ability to grade highly marbled carcasses accurately and consistently, particularly with quantifying intramuscular fat content for validation, remains a challenging task for the Wagyu beef industry. New camera grading technologies have been proposed by VIAS VBG 2000 (e+v Technology GmbH & Co. KG, 2021), Meat Image Japan (MIJ), and MasterBeef (MB) for Wagyu-influenced beef carcass assessment based on advanced image analysis. However, the intramuscular fat measurements of these camera technologies and the actual percent intramuscular fat (%IMF) in the longissimus at the 12/13th rib have yet to be investigated. Chilled carcasses (n = 173) from F1 Wagyu cattle were ribbed between the 12th and 13th ribs, and the left carcass sides were imaged with the E+V, MIJ, and MB cameras. Additionally, the marbling score was assigned by a team of 3 US Department of Agriculture (USDA) graders. Samples from the longissimus thoracis were collected, and the %IMF of the muscle was determined in triplicate. Linear regressions and descriptive statistics were done using JMP (Statistical Discovery, NC, USA) software. Camera fat-related measurements were linearly correlated, and R2 was calculated. The E+V camera had the highest %IMF predictability of all cameras (P < 0.0001) using the marbling score (R2 = 0.6450) estimate. The MIJ camera presented prediction accuracy between the other 2 technologies (P < 0.0001) of %IMF with identical R2 for fat percent and fat score estimates (R2 = 0.5952). The MB camera had the lowest predictability (P < 0.0001) of %IMF using the measured marbling score (R2 = 0.3269), marbling area (R2 = 0.3333), and marbling percent (R2 = 0.3269) estimates from the instrument. As technology advances, new technologies will provide alternative means for grading Wagyu-influenced carcasses. Additionally, these findings could aid the implementation of the USDA pilot program for remote carcass grading.

Abstract Behavioral variation abounds in nature. This variation is important for adaptation and speciation, but its molecular basis remains elusive. Here, we use a hybrid zone between two subspecies of songbirds that differ in migration – an ecologically important and taxonomically widespread behavior---to gain insight into this topic. We measure gene expression in five brain regions. Differential expression between migratory states was dominated by circadian genes in all brain regions. The remaining patterns were largely brain-region specific. For example, expression differences between the subspecies that interact with migratory state likely help maintain reproductive isolation in this system and were documented in only three brain regions. Contrary to existing work on regulatory mechanisms underlying species-specific traits, two lines of evidence suggest that trans- (vs. cis) regulatory changes underlie these patterns – no evidence for allele-specific expression in hybrids and minimal associations between genomic differentiation and expression differences. Additional work with hybrids shows expression levels were often distinct (transgressive) from parental forms. Behavioral contrasts and functional enrichment analyses allowed us to connect these patterns to mitonuclear incompatibilities and compensatory responses to stress that could exacerbate selection on hybrids and contribute to speciation.

Abstract Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. Branched chain ketoacid dehydrogenase (BCKDH) controls the rate limiting step in BCAA degradation, the activity of which is inhibited by BCKDH kinase (BDK)-mediated phosphorylation. Screening efforts to discover BDK inhibitors led to identification of thiophene PF-07208254, which improved cardiometabolic endpoints in mice. Structure-activity relationship studies led to identification of a thiazole series of BDK inhibitors; however, these inhibitors did not improve metabolism in mice upon chronic administration. While the thiophenes demonstrated sustained branched chain ketoacid (BCKA) lowering and reduced BDK protein levels, the thiazoles increased BCKAs and BDK protein levels. Thiazoles increased BDK proximity to BCKDH-E2, whereas thiophenes reduced BDK proximity to BCKDH-E2, which may promote BDK degradation. Thus, we describe two BDK inhibitor series that possess differing attributes regarding BDK degradation or stabilization and provide a mechanistic understanding of the desirable features of an effective BDK inhibitor.

Abstract Hybrid zones can be used to identify traits that maintain reproductive isolation and contribute to speciation. Cognitive traits may serve as post-mating reproductive isolating barriers, reducing the fitness of hybrids if, for example, misexpression occurs in hybrids and disrupts important neurological mechanisms. We tested this hypothesis in a hybrid zone between two subspecies of Swainson’s thrushes (Catharus ustulatus) using two cognitive tests—an associative learning spatial test and neophobia test. We included comparisons across the sexes and seasons (spring migration and winter), testing if hybrid females performed worse than males (as per Haldane’s rule) and if birds (regardless of ancestry or sex) performed better during migration, when they are building navigational maps and encountering new environments. We documented reduced cognitive abilities in hybrids, but this result was limited to males and winter. Hybrid females did not perform worse than males in either season. Although season was a significant predictor of performance, contrary to our prediction, all birds learned faster during the winter. The hypothesis that cognitive traits could serve as post-mating isolating barriers is relatively new; this is one of the first tests in a natural hybrid zone and non-food-caching species. We also provide one of the first comparisons of cognitive abilities between seasons. Future neurostructural and neurophysiological work should be used to examine mechanisms underlying our behavioral observations.

Night-migrating songbirds utilize the Earth's magnetic field to help navigate to and from their breeding sites each year. A region of the avian forebrain called Cluster N has been shown to be activated during night migratory behavior and it has been implicated in processing geomagnetic information. Previous studies with night-migratory European songbirds have shown that neuronal activity at Cluster N is higher at night than during the day. Comparable work in North American migrants has only been performed in one species of swallows, so extension of examination for Cluster N in other migratory birds is needed. In addition, it is unclear if Cluster N activation is lateralized and the full extent of its boundaries in the forebrain have yet to be described. We used sensory-driven gene expression based on ZENK and the Swainson's thrush, a night-migratory North American songbird, to fill these knowledge gaps. We found elevated levels of gene expression in night- vs. day-active thrushes and no evidence for lateralization in this region. We further examined the anatomical extent of neural activation in the forebrain using 3D reconstruction topology. Our findings demonstrate that Swainson's thrushes possess an extensive bilateral night-activated Cluster N region in the forebrain similar to other European avian species, suggesting that Cluster N is highly conserved in nocturnal migrants.

In Supplementary Table 1 of this Article, 23 samples (B10K-DU-029-32, B10K-DU-029-33, B10K-DU-029-36 to B10K-DU-029-44, B10K-DU- 029-46, B10K-DU-029-47, B10K-DU-029-49 to B10K-DU-029-53, B10K-DU- 029-75 to B10K-DU-029-77, B10K-DU-029-80, and B10K-DU-030-03; styled in boldface in the revised table) were assigned to the incorrect institution. Supplementary Table 1 has been amended to reflect the correct source institution for these samples, and associated data (tissue, museum ID/source specimen ID, site, state/province, latitude, longitude, date collected and sex) have been updated accordingly. The original table is provided as Supplementary Information to this Amendment, and the original Article has been corrected online.

Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.

Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. Opportunistic pharmacokinetic data were collected from pediatric patients receiving enteral or parenteral metoclopramide per standard of care and these data were simultaneously fitted using NONMEM. Allometric scaling with body weight was included a priori in the model. Using the final model, the steady-state maximum concentrations (Css,max ) and the area under the metoclopramide plasma concentration-time curve at steady state from 0 to 6 hours (AUCss,0-6h ) were simulated following 0.1 or 0.15 mg/kg orally every 6 hours in virtual patients, and compared with previously reported ranges associated with toxicity or the efficacy for gastroesophageal reflux in infants. A two-compartment model with first-order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01-19.13]). There were 20 infants (≤ 2 years), 9 children (2 years to age ≤ 12 years), and 21 adolescents (> 12 years). Body weight was the only covariate included in the final model. For > 75% of virtual patients, simulated Css,max and AUCss,0-6h estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients < 2 years. Our study suggests that a metoclopramide enteral dose of 0.1 mg/kg every 6 hours, which was previously recommended for pediatric patients, results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux.

Closely related populations often display similar patterns of genomic differentiation, yet it remains an open question which ecological and evolutionary forces generate these patterns. The leading hypothesis is that this similarity in divergence is driven by parallel natural selection. However, several recent studies have suggested that these patterns may instead be a product of the depletion of genetic variation that occurs as result of background selection (i.e., linked negative selection). To date, there have been few direct tests of these competing hypotheses. To determine the relative contributions of background selection and parallel selection to patterns of repeated differentiation, we examined 24 independently derived populations of freshwater stickleback occupying a variety of niches and estimated genomic patterns of differentiation in each relative to their common marine ancestor. Patterns of genetic differentiation were strongly correlated across pairs of freshwater populations adapting to the same ecological niche, supporting a role for parallel natural selection. In contrast to other recent work, our study comparing populations adapting to the same niche produced no evidence signifying that similar patterns of genomic differentiation are generated by background selection. We also found that overall patterns of genetic differentiation were considerably more similar for populations found in closer geographic proximity. In fact, the effect of geography on the repeatability of differentiation was greater than that of parallel selection. Our results suggest that shared selective landscapes and ancestral variation are the key drivers of repeated patterns of differentiation in systems that have recently colonized novel environments.

Abstract The impact of climate change on spring phenology poses risks to migratory birds, as migration timing is controlled predominantly by endogenous mechanisms. Despite recent advances in our understanding of the underlying genetic basis of migration timing, the ways that migration timing phenotypes in wild individuals may map to specific genomic regions requires further investigation. We examined the genetic architecture of migration timing in a long-distance migratory songbird (purple martin, Progne subis subis) by integrating genomic data with an extensive dataset of direct migratory tracks. A moderate to large amount of variance in spring migration arrival timing was explained by genomics (proportion of phenotypic variation explained by genomics = 0.74; polygenic score R 2 = 0.24). On chromosome 1, a region that was differentiated between migration timing phenotypes contained genes that could facilitate nocturnal flights and act as epigenetic modifiers. Overall, these results advance our understanding of the genomic underpinnings of migration timing.

Abstract Obesity is an increasingly alarming public health threat, with nearly 20% of children classified as obese in the United States today. Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure. However, pharmacokinetic studies in children with obesity are challenging to conduct, so there is limited information to guide fentanyl and methadone dosing in these children. To address this clinical knowledge gap, physiologically‐based pharmacokinetic models of fentanyl and methadone were developed in adults and scaled to children with and without obesity to explore the interplay of obesity, age, and pharmacogenomics. These models included key obesity‐induced changes in physiology and pharmacogenomic effects. Model predictions captured observed concentrations in children with obesity well, with an overall average fold error of 0.72 and 1.08 for fentanyl and methadone, respectively. Model simulations support a reduced fentanyl dose (1 vs. 2 μg/kg/h) starting at an earlier age (6 years) in virtual children with obesity, highlighting the importance of considering both age and obesity status when selecting an infusion rate most likely to achieve steady‐state concentrations within the target range. Methadone dosing simulations highlight the importance of considering genotype in addition to obesity status when possible, as cytochrome P450 (CYP)2B6*6/*6 virtual children with obesity required half the dose to match the exposure of wildtype children without obesity. This physiologically‐based pharmacokinetic modeling approach can be applied to explore dosing of other critical drugs in children with obesity.

Abstract Timing is essential for survival and reproduction of organisms across the tree of life. The core circadian clock gene Clk is involved in the regulation of annual timing events and shows highly conserved sequence homology across vertebrates except for one variable region of poly-glutamine repeats. Clk genotype varies in some species with latitude, seasonal timing and migration. However, findings are inconsistent, difficult to disentangle from environmental responses, and biased towards high latitudes. Here we combine field data with a common-garden experiment to study associations of Clk polymorphism with latitude, migration and annual-cycle timing within the stonechat species complex across its trans-equatorial distribution range. Our dataset includes 950 records from 717 individuals from nine populations with diverse migratory strategies. Gene diversity was lowest in resident African and Canary Island populations and increased with latitude, independently of migration distance. Repeat length and annual-cycle timing was linked in a population-specific way. Specifically, equatorial African stonechats showed delayed timing with longer repeat length for all annual-cycle stages. Our data suggest that at low latitudes with nearly constant photoperiod, Clk genotype might orchestrate a range of consistent, individual chronotypes. In contrast, the influence of Clk on annual-cycle timing at higher latitudes might be mediated by its interactions with genes involved in (circadian) photoperiodic pathways.

ABSTRACT Microbial communities which persist in food processing facilities may have a detrimental impact on food safety and spoilage. In meat processing, Listeria monocytogenes is an organism of concern due to its ability to cause significant human illnesses and persist in refrigerated environments. The microbial ecology of Listeria spp. in small meat processing facilities has not been well characterized. Therefore, we collected samples from a newly constructed meat processing facility as an opportunity to investigate several research objectives: (i) to determine whether a stable, consistent microbiome develops in a small meat processing facility during the first 18 months of operation, (ii) to evaluate the environmental factors that drive microbial community formation, and (iii) to elucidate the relationship between microbial communities and the presence of Listeria species. We evaluated microbiomes using 16S rRNA gene sequencing and Listeria presence using quantitative PCR. We demonstrated that microbial communities differentiate by the functional room type, which is representative of several environmental differences such as temperature, sources of microbes, and activity. Temperature was an especially important factor; in rooms with low temperatures, communities were dominated by psychotrophs, especially Pseudomonas, while warmer rooms supported greater diversity. A stable core community formed in facility drains, indicating that mechanisms which cause persistence are present in the communities. The overall presence of Listeria in the facility was low but could be tied to specific organisms within a room, and the species of Listeria could be stratified by room function. IMPORTANCE This study provides critical knowledge to improve meat safety and quality from small meat processing facilities. Principally, it demonstrates the importance of facility design and room condition to the development of important microbial communities; temperature, sanitation regimen, and physical barriers all influence the ability of microorganisms to join the stable core community. It also demonstrates a relationship between the microbial community and Listeria presence in the facility, showing the importance of managing facility sanitation plans for not only pathogens, but also the general facility microbiome.

The AMP-activated protein kinase (AMPK) is a cellular sensor of energetics and when activated in skeletal muscle during contraction can impart changes in skeletal muscle metabolism. Therapeutics that selectively activate AMPK have been developed to lower glucose levels through increased glucose disposal rates as an approach to abrogate the hyperglycemic state of diabetes; however, the metabolic fate of glucose following AMPK activation remains unclear. We have used a combination of in vivo evaluation of glucose homeostasis and ex vivo skeletal muscle incubation to systematically evaluate metabolism following pharmacological activation of AMPK with PF-739, comparing this with AMPK activation through sustained intermittent electrical stimulation of contraction. These methods to activate AMPK result in increased glucose uptake but divergent metabolism of glucose: pharmacological activation results in increased glycogen accumulation while contraction-induced glucose uptake results in increased lactate formation and glucose oxidation. These results provide additional evidence to support a role for AMPK in control of skeletal muscle metabolism and additional insight into the potential for AMPK stimulation with small molecule direct activators.

Adaptation to new environments often occurs in the face of gene flow. Under these conditions, gene flow and recombination can impede adaptation by breaking down linkage disequilibrium between locally adapted alleles. Theory predicts that this decay can be halted or slowed if adaptive alleles are tightly linked in regions of low recombination, potentially favouring divergence and adaptive evolution in these regions over others. Here, we compiled a global genomic data set of over 1,300 individual threespine stickleback from 52 populations and compared the tendency for adaptive alleles to occur in regions of low recombination between populations that diverged with or without gene flow. In support of theory, we found that putatively adaptive alleles (FST and dXY outliers) tend to occur more often in regions of low recombination in populations where divergent selection and gene flow have jointly occurred. This result remained significant when we employed different genomic window sizes, controlled for the effects of mutation rate and gene density, controlled for overall genetic differentiation, varied the genetic map used to estimate recombination and used a continuous (rather than discrete) measure of geographic distance as proxy for gene flow/shared ancestry. We argue that our study provides the first statistical evidence that the interaction of gene flow and selection biases divergence toward regions of low recombination.

Genetic variation is a fundamental component of biodiversity, and studying population structure, gene flow and demographic history can help guide conservation strategies for many species. Like other aerial insectivores, the purple martin Progne subis is in decline, and yet their genetic background remains largely unknown. To address this knowledge gap, we assessed population structure in the nominate eastern subspecies (P. s. subis) with relation to natal dispersal and examined historical genetic patterns in all three subspecies (P. s. subis, P. s. arboricola, P. s. hesperia) across their North American breeding range by estimating effective population sizes over time. We used next‐generation sequencing strategies for genomic analyses, integrating whole‐genome resequencing data with continent‐wide band encounter records to examine natal dispersal. We documented population structure across P. s. subis, with the highest differentiation between the northern (Alberta) and more southern colonies and following patterns of isolation‐by‐distance. Consistent with spatial patterns of genetic differentiation, we also found greater longitudinal than latitudinal natal dispersal distances, signifying potential latitudinal constraints on gene flow. Earlier contractions in effective population sizes in the western P. s. arboricola and P. s. hesperia compared to the eastern P. s. subis subspecies suggest these subspecies originated from two different glacial refugia. Together, these findings support latitudinal distinction in P. s. subis, and elucidate the origin of subspecies differentiation, highlighting the importance of conserving populations across the range to maximize genetic diversity and adaptive potential in the purple martin.

Ruminants are a critical human food source and have been implicated as a potentially important source of global methane emissions. Because of their unique digestive physiology, ruminants rely upon a symbiotic relationship with the complex and rich community of microorganism in the foregut to allow digestion of complex carbohydrates. This study used 16S rRNA gene sequencing to investigate the composition of microbial communities from three rumen micro-environments of cattle fed identical diets: (1) free fluid, (2) the fibrous pack, and (3) the mucosa. Community composition analysis revealed that while a phylogenetic core including the most abundant and most common ruminal taxa (members of Bacteroidetes and Firmicutes) existed across micro-environments, the abundances of these taxa differed significantly between fluid- and mucosa-associated communities, and specific lineages were discriminant of individual micro-environments. Members of Firmicutes, specifically Clostridiales, Lachnospiraceae, Mogibacteriaceae, Christenellaceae, and Erysipelotrichaceae were significantly more abundant in fluid communities, while members of Bacteroidetes, namely Muribaculaceae and Prevotellaceae were more abundant in mucosa-associated communities. Additionally, Methanobacteriaceae, a family of methanogenic Archaea, was more abundant in fluid-associated communities. A set of four more diverse lineages were discriminant of pack-associated communities that included Succinivibrionaceae, RFP12 (Verruco-5), Fibrobacteraceae, and Spirochaetaceae. Our findings indicate that different ecological niches within each micro-environment have resulted in significant differences in the diversity and community structure of microbial communities from rumen fluid, pack, and mucosa without the influence of diet that will help contextualize the influence of other environmental factors.

Abstract Background Weight is critical for the medical management of infants; however, scales can be unavailable or inaccessible in some practice settings. We recently developed and validated a robust infant weight estimation method based on chest circumference (CC) and head circumference (HC). This study was designed to determine the human factors (HF) experience with, and predictive performance of, an infant weight estimation device that implements this method. Methods Prospective, multi-center, observational, masked study of 486 preterm and term infants (0–90 days) assessed by 15 raters. Raters measured the infant using calibrated scales/measures and masked versions of the device. Raters also evaluated critical tasks associated with device use. Mean error (ME) and mean percentage error (MPE) were used to assess predictive performance. Result Among 486 infants enrolled (36.8 ± 4.0 weeks gestational age, 31.5 ± 28.6 days postnatal age), predicted weight correlated highly with actual weight (r = 0.97, ME: − 69 ± 257 g, MPE: − 1.3 ± 6.9%). Predicted weight was within 10 and 15% of actual weight in 86 and 99%, of infants. HF errors were low, 0.1–0.8% depending on task. In all cases raters were confident or very confident in their measurements. Conclusion The device was statistically equivalent to the method on which it was based and approximated weight with acceptable variance from the true weight. HF data suggest the device is easy to use. This device can be used to estimate weight in infants when calibrated scales are impractical or unavailable.

Development of sourness in beef round muscle cuts, such as knuckles, has been a long-standing issue in the beef industry with little characterization. Therefore, the objective of this study was to investigate and characterize the sour odor associated with beef knuckles using sensory, analytical (gas chromatography-mass spectrometry [GC-MS]), and microbiological approaches. Knuckles (n = 10) with no sour odor (control), a slight sour odor, or severe sour odor were collected during fabrication from a commercial beef processing plant. In addition, the synovial fluid from the femur joint, and the femur surface associated with the collected knuckles, were sponge-sampled. Knuckles were separated into 2 halves, with one half subjected to an odor panel, GC-MS, and microbial analyses on the day of collection (day 0). The remaining half was analyzed for odor and microbial populations following 35 d of vacuum-packaged storage at 0°C ± 2°C (day 35). Odor panelists identified differences (P < 0.05) between control and sour knuckles (slight sour odor and severe sour odor) for all attributes tested (off-odor, oxidation, putrid, and sour notes) regardless of storage day. GC-MS analysis found no statistical difference (P > 0.05) in volatiles between control and severe-sour-odor samples. Microbial analysis (aerobic plate counts and lactic acid bacteria counts) of muscle tissue on day 0 and day 35 of storage revealed no (P > 0.05) differences between the 3 treatment groups. Similarly, no (P > 0.05) differences between the treatment groups were obtained following analysis of synovial fluid and femur surface sponge samples for psychrotrophic anaerobic sporeformer counts. The findings of the study indicated that the souring condition in knuckles exists at identifiable intensities with no volatile acid or microbial population differences; therefore, further investigation is needed to determine the etiology.

Seasonal migration is a taxonomically widespread behaviour that integrates across many traits. The European blackcap exhibits enormous variation in migration and is renowned for research on its evolution and genetic basis. We assembled a reference genome for blackcaps and obtained whole genome resequencing data from individuals across its breeding range. Analyses of population structure and demography suggested divergence began ~30,000 ya, with evidence for one admixture event between migrant and resident continent birds ~5000 ya. The propensity to migrate, orientation and distance of migration all map to a small number of genomic regions that do not overlap with results from other species, suggesting that there are multiple ways to generate variation in migration. Strongly associated single nucleotide polymorphisms (SNPs) were located in regulatory regions of candidate genes that may serve as major regulators of the migratory syndrome. Evidence for selection on shared variation was documented, providing a mechanism by which rapid changes may evolve.

Ractopamine hydrochloride (RAC) is a beta-agonist approved by the U.S. Food and Drug Administration (FDA) as a medicated feed ingredient for cattle during the final days of finishing to improve feed efficiency and growth. Maximum residue limits and U.S. FDA residue tolerances for target tissues have defined management practices around RAC usage in the U.S. However, many countries have adopted zero tolerance policies and testing of off-target tissues, presenting a major challenge for international export. Therefore, the objective this study was to determine the necessary withdrawal time among cattle group-fed RAC to achieve residue concentrations below tolerance levels in muscle and off-target tissues. Specifically, both total and parent RAC residues were quantified in muscle, adipose tissue, rendered tallow, and large intestines from animals group-fed RAC and subjected to withdrawal 2, 4, or 7 days before harvest. Ractopamine (parent and total) residues were below the assay limit of detection (< 0.12 ng/g) in all muscle and adipose tissue samples from animals in control groups (no RAC). However, RAC residues were detectable, but below the limit of quantitation, in 40% of tallow and 17% of large intestine samples from control animals. As expected, mean RAC residue concentrations in muscle, adipose tissue, and large intestine samples decreased (P < 0.05) as the RAC withdrawal duration (days) was extended. Irrespective of RAC withdrawal duration, mean parent RAC residue concentrations in muscle, adipose tissue, and large intestine ranged from 0.33 to 0.76 ng/g, 0.16 to 0.26 ng/g, 3.97 to 7.44 ng/g, respectively and all tallow samples were > 0.14 ng/g (detectable but below the limit of quantitation). Results of this study provide a baseline for the development of management protocol recommendations associated with withdrawal following group-feeding of RAC to beef cattle in countries that allow RAC use and intend to export to global markets which may be subject to zero tolerance policies and off-target tissue testing.

Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models. PF-06409577 is able to inhibit de novo lipid and cholesterol synthesis pathways, and causes a reduction in hepatic lipids and mRNA expression of markers of hepatic fibrosis. These effects require AMPK activity in the hepatocytes. Treatment of hyperlipidemic rats or cynomolgus monkeys with PF-06409577 for 6 weeks resulted in a reduction in circulating cholesterol. Together these data suggest that activation of AMPK β1 complexes with PF-06409577 is capable of impacting multiple facets of liver disease and represents a promising strategy for the treatment of NAFLD and NASH in humans. Keywords: AMPK, NAFLD, Lipogenesis, ACC, Hyperlipidemia

Background: Anthropometric data prove valuable for screening and monitoring various medical conditions. In young infants, however, only weight, length and head circumference are represented in publicly accessible databases. Aim: To characterise length and circumferential measures in pre-term and full-term infants up to 90 days post-natal. Subjects and methods: In eight US medical centres, trained raters recorded humeral, ulnar, femoral, tibial and fibular lengths along with mid-upper arm, mid-thigh, chest, abdominal and neck circumference. Data were pooled by post-menstrual age into 1-week intervals and population curves created using the lambda, mu and sigma (LMS) method. Goodness-of-fit was assessed by examining de-trended quantile-quantile plots, Q statistics and fitted centiles overlaid on empirical centiles. Results: In total, 2097 infants were enrolled in this study with a mean ± SD gestational age and post-natal age of 37.1 ± 3.3 weeks and 27.3 ± 25.3 days, respectively. A re-scale option was used to describe all curves. The resultant models reliably characterised anthropometric measures from 33–52 weeks PMA, with less certainty at the extremes (27–55 weeks). Conclusion: The population curves generated under this investigation expand existing reference data on a comprehensive set of anthropometric traits in infants through the first 90 days post-natal.

The objective of this study was to evaluate the roles that cooking rate and relative humidity has on the sensory development of beef strip steaks. Thirty USDA Choice beef strip loins were collected from a commercial packing facility. Each strip loin was cut into steaks and randomly assigned to 1 of 6 cooking methods utilizing 2 oven temperatures (80°C and 204°C) and 3 levels of relative humidity [zero (ZH), mid (MH), and high (HH)]. Cooked steaks were used to evaluate internal and external color, Warner-Bratzler and slice shear force, total collagen content, protein denaturation, and trained sensory ratings. Relative humidity greatly reduced cooking rate, especially at 80°C. Steaks cooked at 80°C-ZH had the greatest (P < 0.01) cook loss of all treatments, and cook loss was not affected (P > 0.05). Steaks cooked at 80°C-ZH appeared the most (P < 0.01) well-done and had the darkest (P > 0.01) surface color. Total collagen was greatest (P < 0.01) in steaks cooked with ZH, regardless of oven temperature. Myosin denaturation was not affected (P > 0.05) by treatment. Increased (P = 0.02) sarcoplasmic protein denaturation was observed with ZH and MH, while increased (P = 0.02) actin denaturation was observed only with ZH. Oven temperature did not influence (P > 0.05) protein denaturation. Trained panelists rated steaks the most tender (P < 0.01) when cooked at 80°C and with ZH and MH. Humidity did not affect (P > 0.05) juiciness at 204°C; however, MH and HH produced a juicier (P < 0.01) steak when cooked at 80°C. Humidity hindered (P < 0.01) the development of beefy/brothy and brown/grilled flavors but increased (P = 0.01) metallic/bloody intensity. Lower oven temperatures and moderate levels of humidity could be utilized to maximize tenderness, while minimally affecting flavor development.

Hospital‐acquired pressure injuries create a tremendous cost to health care organizations and negatively affect quality and patient safety. Surgical patients are at an increased risk for skin injury, particularly a pressure injury, because of a lack of sensation and immobility during a procedure. An interprofessional team at our facility identified factors that place surgical patients at risk for skin injury. We developed a risk assessment protocol in March 2021 using the Six Sigma DMAIC (define, measure, analyze, improve, and control) method. After data review and analysis, we identified age of 65 years or older, existence of a skin condition, and procedural duration greater than four hours as significant predictors for postoperative skin injury. Our findings reinforce the benefit of using an appropriate risk assessment protocol that alerts the perioperative team members to at‐risk patients. [ABSTRACT FROM AUTHOR]

Weight is the foremost marker of health outcomes in infants; however, the majority of community workers and health care providers in remote, resource-constrained settings have limited access to functional scales. This study develops and validates a simple weight estimation strategy for infants that addresses the limitations of current approaches. Circumferential and segmental anthropometric measures were evaluated for their relationship to infant weight and length. Data derived from 2097 US infants (n = 1681 for model development, n = 416 for validation). Statistical and practical considerations informed final measurement selection. Head circumference and chest circumference demonstrated the best correlations with weight ( r = 0.89) and length ( r = 0.94 and 0.93), and were among the most reproducible as reflected by intraclass correlation coefficients (>0.98). The head circumference and chest circumference combination offered better goodness-of-fit and smaller limits of agreement than did either measure alone. The final model predicted weight within 10% and 15% of actual for 84% and 94% of infants, respectively, with no bias for postnatal age ( P = .76), gestational age ( P = .10), and sex ( P = .25). The model requires simple summation to generate a weight estimate and can be embodied as a low-cost, paper-based device.

Background Zones of contact between closely related taxa with divergent migratory routes, termed migratory divides, have been suggested as areas where hybrid offspring may have intermediate and inferior migratory routes, resulting in low fitness of hybrids and thereby promoting speciation. In the Rocky Mountains of Canada there is a narrow hybrid zone between Audubon’s and myrtle warblers that is likely maintained by selection against hybrids. Band recoveries and isotopic studies indicate that this hybrid zone broadly corresponds to the location of a possible migratory divide, with Audubon’s warblers migrating south-southwest and myrtle warblers migrating southeast. We tested a key prediction of the migratory divide hypothesis: that genetic background would be predictive of migratory orientation among warblers in the center of the hybrid zone. Methods We recorded fall migratory orientation of wild-caught migrating warblers in the center of the hybrid zone as measured by video-based monitoring of migratory restlessness in circular orientation chambers. We then tested whether there was a relationship between migratory orientation and genetic background, as measured using a set of species-specific diagnostic genetic markers. Results We did not detect a significant association between orientation and genetic background. There was large variation among individuals in orientation direction. Mean orientation was towards the NE, surprising for birds on fall migration, but aligned with the mountain valley in which the study took place. Conclusions Only one other study has directly analyzed migratory orientation among naturally-produced hybrids in a migratory divide. While the other study showed an association between genetic background and orientation, we did not observe such an association in yellow-rumped warblers. We discuss possible reasons, including the possibility of a lack of a strong migratory divide in this hybrid zone and/or methodological limitations that may have prevented accurate measurements of long-distance migratory orientation.

Most often, homeless students are members of minority groups who have attended several schools during their school career, are from single-parent households, and have histories of irregular school attendance. These students also frequently suffer from physical and mental challenges that are rooted in poverty, lack access to medical care, and have family members affected by mental health and alcohol and other drugs (AOD) issues. O'Keeffe Middle School in Madison, Wisconsin, is the prime recipient of homeless middle school students for a school district with 25,000 students and 11 middle schools. Although responding to homeless students in a caring and educationally responsible manner can be a challenge, following a comprehensive intake process--as well as providing ongoing student contact and support once the student is enrolled--allows the school to assimilate more than 60 homeless students each school year. In this article, the author describes how O'Keeffe Middle School welcomes homeless students, addresses the challenges presented by them, and provides ongoing support to these students.