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Alcohol use disorder (AUD) is a rapidly growing concern in the United States. Current trending escalations of alcohol use are associated with a concurrent rise in alcohol-related end-organ damage, increasing risk for further diseases. Alcohol-related end-organ damage can be driven by autonomic nervous system dysfunction, however studies on alcohol effects on autonomic control of end-organ function are lacking. Alcohol intake has been shown to reduce insulin secretions from the pancreas. Pancreatic insulin release is controlled in part by preganglionic parasympathetic motor neurons residing in the dorsal motor nucleus of the vagus (DMV) that project to the pancreas. How these neurons are affected by alcohol exposure has not been directly examined. Here we investigated the effects of acute ethanol (EtOH) application on DMV pancreatic-projecting neurons with whole-cell patch-clamp electrophysiology. We found that bath application of EtOH (50 mM) for greater than 30 min significantly enhanced the frequency of spontaneous inhibitory post synaptic current (sIPSC) events of DMV pancreatic-projecting neurons suggesting a presynaptic mechanism of EtOH to increase GABAergic transmission. Thirty-minute EtOH application also decreased action potential firing of these neurons. Pretreatment of DMV slices with 20 μM fluoxetine, a selective serotonin reuptake inhibitor, also increased GABAergic transmission and decreased action potential firing of these DMV neurons while occluding any further effects of EtOH application, suggesting a critical role for serotonin in mediating EtOH effects in the DMV. Ultimately, decreased DMV motor output may lead to alterations in pancreatic secretions. Further studies are needed to fully understand EtOH's influence on DMV neurons as well as the consequences of changes in parasympathetic output to the pancreas.

Despite recent attempts to reassess the culture wars of early Enlightenment England as conversations between educated individuals about pivotal and often technical matters, academics of the period continue to feature in narratives of intellectual change as the gatekeepers of a decrepit religious establishment. The famous contention of John Henry Newman that universities are at best locations for the ‘diffusion and extension of knowledge’ but not for its advancement thus lives on, and has only been heightened by the persistent supposition among historians that the eighteenth-century English universities ‘surrendered their cultural leadership’. This thesis, however, presents an altogether new perspective on the relationship of Oxford and Cambridge to the wider intellectual life of the period, with a focus on the neglected polemical and scholarly writings of ‘early career’ scholars. During a period coloured by anti-institutional sentiments, young scholars in the universities worked tirelessly to defend the system of knowledge that underwrote the curricula of their institutions, and, indeed, academic authority at large. They also aspired to operate smoothly within, and ideally govern, a rapidly expanding vernacular ‘public sphere’, aware that their task of defending the Church of England depended upon them successfully doing so. In my account, the shortcoming of the eighteenth-century English universities in terms of the relative dearth of impartial ‘research’ publications was not a result of their being impervious to ‘polite’ society but rather of their obsessive and often very successful attempts to engage with it.

Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21–78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.

Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic condition characterized by altered skeletal development and extra-skeletal bone formation. All cases of FOP are caused by mutations in the type I BMP receptor geneACVR1that result in over-activation of the BMP signaling pathway. Activation of the wild-type ACVR1 kinase requires assembly of a tetrameric type I and II BMP receptor complex followed by phosphorylation of the ACVR1 GS domain by type II BMP receptors. Previous studies showed that the FOP mutant ACVR1-R206H requires type II BMP receptors and presumptive GS domain phosphorylation for over-active signaling. Structural modeling of the FOP-ACVR1 mutant kinase domain supports that FOP mutations alter the conformation of the GS domain, but it is unclear how this leads to overactive signaling. Here we show using a developing zebrafish embryo BMP signaling assay that the FOP mutant receptors ACVR1-R206H and -G328R have reduced requirements for GS domain phosphorylation sites to signal compared to wild-type ACVR1. Further, ligandindependent and ligand-dependent signaling through the FOP ACVR1 receptors have distinct GS domain phosphorylation site requirements. Moreover, ACVR1-G328 showed increased GS domain serine/threonine requirements for ligand-independent signaling compared to ACVR1-R206H, whereas it exhibited reduced serine/threonine requirements for ligand-dependent signaling. Remarkably, while ACVR1-R206H does not require the type I BMP receptor partner, Bmpr1, to signal, a ligand-dependent GS domain mutant of ACVR1-R206H could signal independently of Bmpr1 only when Bmp7 ligand was overexpressed. Of note, unlike human ACVR1-R206H, the zebrafish paralog Acvr1l-R203H does not show increased signaling activity. However, in domain-swapping studies the human kinase domain, but not the human GS domain, was sufficient to confer overactive signaling to the Acvr1l-R203H receptor. Together these results reflect the importance of GS domain activation and kinase domain functions in regulating ACVR1 signaling and identify mechanisms of reduced regulatory constraints conferred by FOP mutations.

The purpose of this research is to conduct a spend analysis on the Marine Corps Logistics Command’s (MARCORLOGCOM) contracting spend data from Fiscal Year (FY) 2007 to FY 2022 to determine if category management (CM) can be implemented to improve the command's contracting procedures. CM is the purchasing strategy that the Department of Defense (DOD) has chosen to implement within its contracting organizations to increase the efficiency and to reduce costs associated with government purchasing. Although the Office of Management and Budget (OMB) directed the implementation of CM in 2014, it has yet to be fully integrated within all DOD contracting strategies. Our research analyzed MARCORLOGCOM's spend to identify trends with regard to product service codes (PSC), contract types, and contractors. Based on the implications of our research, we determined that although it appears MARCORLOGCOM has attempted to implement CM, there are opportunities for the command to expand its use of the strategy. We concluded our research with three recommendations for implementing CM within MARCORLOGCOM which included using multiple award indefinite delivery contracts (IDCs) rather than single award IDCs; expanding the use of IDCs; and increasing coordination, communication and organization among the command contracting units. Marine Corp Logistics Command Outstanding Thesis Captain, United States Air Force Captain, United States Air Force Captain, United States Air Force Approved for public release. Distribution is unlimited.

The objective of this study was to characterize the color stability of pork loin chops using fresh quality traits and instrumental measures of discoloration. Boneless pork loins (N=484) were evaluated for quality traits at 11 or 14 d post-mortem. One chop was cut from each loin near the 10th rib for retail display, overwrapped, and displayed under constant fluorescent lighting for 7 d. Objective color, myoglobin redox forms, and subjective visual discoloration traits were evaluated daily. After retail display, chops were categorized based on final visual discoloration (Day 7) as Very Color Stable (VCS; 0% to 5% discoloration), Color Stable (CS; 5% to 10% discoloration), Neutral (10% to 25% discoloration), Color Labile (CL; 25% to 30% discoloration), or Very Color Labile (VCL; >30% discoloration). Quality and color traits were analyzed using the GLIMMIX (visual discoloration) or MIXED (all other measures) procedure of SAS. Retail display data were analyzed as repeated measures. Chops ultimately classified as CS or VCS were darker, redder, and had lesser surface metmyoglobin (P

Post-translational modifications (PTM) in myoglobin (Mb) can influence fresh meat color stability. Dietary supplementation of vitamin E improves beef color stability by delaying lipid oxidation–induced Mb oxidation and influences proteome profile of postmortem beef skeletal muscles. Nonetheless, the influence of vitamin E on Mb PTM in postmortem beef skeletal muscles has yet to be investigated. Therefore, the objective of the current study was to examine the effect of dietary vitamin E on Mb PTM in postmortem beef longissimus lumborum muscle. Beef longissimus lumborum muscle samples (24 h postmortem) were obtained from the carcasses of 9 vitamin E–supplemented (VITE; 1,000 IU vitamin E diet/heifer·d−1for 89 d) and 9 control (CONT; no supplemental vitamin E) heifers. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to separate Mb from other sarcoplasmic proteins of beef longissimus lumborum muscle. Tandem mass spectrometry identified multiple PTM (phosphorylation, acetylation, 4-hydroxynonenalalkylation, methylation, dimethylation, trimethylation, and carboxymethylation) in the protein bands (17 kDa) representing Mb. The amino acids susceptible to phosphorylation were threonine (T) and tyrosine (Y), whereas lysine (K) residues were prone to other PTM. The same sites of phosphorylation (T34, T67, Y103), carboxymethylation (K77, K78), and 4-hydroxynonenal alkylation (K77, K78, K79) were identified in Mb from CONT and VITE samples, indicating that these PTM were not influenced by the vitamin E supplementation in cattle. Nonetheless, differential occurrence of acetylation, methylation, dimethylation, and trimethylation were identified in Mb from CONT and VITE samples. Overall, a greater number of amino acids were modified in CONT than VITE, suggesting that the supplementation of vitamin E decreased thenumbers of post-translationally modified residues in Mb. Additionally, PTM at K87, K96, K98, and K102 were unique to CONT, whereas PTM at K118 were unique to VITE. These findings suggested that dietary supplementation of vitamin E in beef cattle might protect amino acid residues in Mb—especially those located spatially close to proximal histidine—from undergoing PTM, thereby improving Mb redox stability.

Feeding growing-finishing pigs supplemental fat is a common practice in the swine industry and can result in improved feed efficiency and reduced feed intake; however, dietary lipids also play a key role in determining pork quality. Objectives of the study were to evaluate the effects of feeding graded levels of high oleic soybean oil (HOSO) on loin and belly quality. A total of 288 pig raised in two separate blocks (144 pigs each) were assigned to one of four diets containing either 25% dried distiller's grains with solubles (DDGS), 2% high oleic soybean oil (HOSO2), 4% high oleic soybean oil (HOSO4), or 6% high oleic soybean oil (HOSO6). Following the conclusion of the feeding trial, 144 pigs were slaughtered at the University of Illinois Meat Science Laboratory. Following fabrication, loins were collected for the evaluation of fresh quality measurements and color stability. Belly quality and fatty acid composition were evaluated using skin-on natural fall bellies. There were no differences (P ≥ 0.11) in pH, visual color, lightness (L*), drip loss, or WBSF among dietary treatments. However, visual marbling was increased (P ≤ 0.01) in loin chops from pigs fed HOSO4 and HOSO6 treatments compared with chops from pigs fed the DDGS dietary treatment. Additionally, loin chops were more red (a*) (P ≤ 0.01) from pigs fed HOSO diets when compared with pigs fed DDGS. Extractable lipid was decreased (P ≤ 0.01) in fresh loin chops from pigs fed DDGS and HOSO2 diets compared with pigs fed HOSO6. There were no differences (P ≥ 0.75) in trained sensory tenderness, juiciness, or flavor for loin chops from pigs fed different dietary treatments. Pork fatty acid composition was altered by dietary HOSO inclusion, with pigs fed DDGS having (P ≤ 0.01) the greatest concentration of C16:0 and was decreased with increasing levels of HOSO inclusion. Inversely, the percentage of C18:1n-9 was least (P ≤ 0.01) in pigs fed DDGS and increased with increasing levels of HOSO inclusion. Pigs fed DDGS produced wider (P ≤ 0.03) and thinner (P ≤ 0.04) bellies with reduced flop distance compared with pigs fed HOSO diets. Overall, HOSO diets did not negatively affect fresh loin quality or sensory traits of loin chops. Furthermore, feeding HOSO to swine resulted in bellies containing greater percentages of oleic acid and reduced percentages of palmitic and linoleic acid.Feeding pigs supplemental fat to increase caloric density is a common practice in the swine industry. However, dietary fats are also a key determinant of pork fat composition and may influence product quality. High oleic soybean oil (HOSO), a relatively new feed ingredient, differs from conventional soybean oil in that it contains an increased proportion of oleic acid, a monounsaturated fatty acid. However, HOSO has not been extensively researched in pig diets. Therefore, our goal was to investigate the use of dietary HOSO on fresh belly and loin quality. A total of 144 pigs, fed one of four diets that differed in fat source, were slaughtered at the University of Illinois Meat Science Laboratory. One diet contained 25% dried distiller’s grains with solubles (DDGS), while the other three had graded levels of high oleic soybean oil (2%, 4%, or 6%). Pigs were fed diets for the last 14 weeks leading up to slaughter. Pigs fed HOSO produced thicker, firmer bellies and fat tissue containing a decreased proportion of polyunsaturated fatty acids compared with DDGS-fed pigs. Feeding HOSO had little impact on fresh loin quality and palatability compared with feeding an industry-reference diet containing DDGS.

Background Cytoplasmic and nuclear maturation of oocytes, as well as interaction with the surrounding cumulus cells, are important features relevant to the acquisition of developmental competence. Methods Here, we utilized Brilliant cresyl blue (BCB) to distinguish cattle oocytes with low activity of the enzyme Glucose-6-Phosphate Dehydrogenase, and thus separated fully grown (BCB positive) oocytes from those in the growing phase (BCB negative). We then analyzed the developmental potential of these oocytes, mitochondrial DNA (mtDNA) copy number in single oocytes, and investigated the transcriptome of single oocytes and their surrounding cumulus cells of BCB positive versus BCB negative oocytes. Results The BCB positive oocytes were twice as likely to produce a blastocyst in vitro compared to BCB- oocytes (P P = 0.004). There was no differential transcript abundance of genes expressed in oocytes, however, 172 genes were identified in cumulus cells with differential transcript abundance (FDR n = 75) and their surrounding cumulus cells (n = 108) compose a unique profile of the cumulus-oocyte complex. Conclusions If oocytes transition from BCB negative to BCB positive, there is a greater likelihood of producing a blastocyst, and a reduction of mtDNA copies, but there is no systematic variation of transcript abundance. Cumulus cells present changes in transcript abundance, which reflects in a dynamic co-expression between the oocyte and cumulus cells.

Background Genomic prediction describes the use of SNP genotypes to predict complex phenotypes and has been widely applied in humans and agriculture species. Genotyping-by-sequencing, a method which uses low-coverage sequence data paired with genotype imputation, is becoming increasingly popular for SNP genotyping. The development of Oxford Nanopore Technologies’ (ONT) MinION sequencer has now made genotyping-by-sequencing portable and rapid. Here we evaluate the speed and accuracy of genomic predictions using low-coverage ONT sequence data in a population of cattle using four imputation approaches. We also investigate the effect of SNP reference panel size on their performance. Results SNP array genotypes and ONT sequence data for 64 beef heifers were used to calculate genomic estimated breeding values (GEBVs) from 641k SNP for four traits. Accuracy of the GEBVs was much higher when flanking SNP from sequence data was used to help impute the 641k panel used for genomic predictions. Using the imputation package QUILT, correlations between ONT and low-density SNP array genomic breeding values were greater than 0.91 and up to 0.97 for sequencing coverages as low as 0.1x using a panel of 48 million SNP that flanked the 641k in the prediction equation. Imputation time was significantly reduced by decreasing the number of flanking sequence SNP used in imputation for all methods. Genomic breeding values calculated using QUILT also had higher correlations to high density SNP arrays than genomic breeding values from imputed-low density arrays for coverages as low as 0.5x. Conclusions Here we demonstrated accurate genomic prediction is possible with ONT sequence data from sequencing coverages as low as 0.1x, and imputation time can be as short as 10 minutes per sample.

Context Beef cattle breeds in Australia can broadly be broken up into two subspecies, namely, Bos indicus and Bos taurus. Due to the time since divergence between the subspecies, it is likely that mutations affecting quantitative traits have developed independently in each. Aims We hypothesise that this will affect the prediction accuracy of genomic selection of admixed and composite populations that include both ancestral subspecies. Our study investigates methods to quantify population stratification in a multibreed population of tropically adapted heifers, with the aim of improving prediction accuracy of genomic selection for reproductive maturity score. Methods We used genotypes and reproductive maturity phenotypes from 3695 tropically adapted heifers from three purebred populations, namely, Brahman, Santa Gertrudis and Droughtmaster. Two of these breeds, Santa Gertrudis and Droughtmaster, are stabilised composites of varying B. indicus × B. taurus ancestry, and the third breed, Brahman, has predominately B. indicus ancestry. Genotypes were imputed to three marker-panel densities and population stratification was accounted for in genomic relationship matrices by using breed-specific allele frequencies when calculating the genomic relationships among animals. Prediction accuracy and bias were determined using a five-fold cross validation of randomly selected multibreed cohorts. Key Results Our results showed that the use of breed-adjusted genomic relationship matrices did not improve either prediction accuracy or bias for a lowly heritable trait such as reproductive maturity score. However, using breed-adjusted genomic relationship matrices allowed the capture of a higher proportion of additive genetic effects when estimating variance components. Conclusions These findings suggest that, despite seeing no improvement in prediction accuracy, it may still be beneficial to use breed-adjusted genomic relationship matrices in multibreed populations to improve the estimation of variance components. Implications As such, genomic evaluations using breed-adjusted genomic relationship matrices may be beneficial in multibreed populations.

The Quiet Classroom Game (Radley in School Psychological Review 45: 93–108, 2016) is a class-wide behavior intervention involving an interdependent group contingency based on classroom noise level. It has been shown to be effective at increasing academically engaged behavior, decreasing disruptive behavior, and decreasing classroom noise level in three first-grade classrooms. The current study was undertaken to replicate and extend research on the QCG. Using an ABAB design, we investigated the impact of the QCG on on-task behavior, off-task behavior, and classroom noise level across three seventh-grade classrooms. We also investigated a procedure for systematically fading the teacher feedback component of the QCG in a maintenance phase. Results were not supportive of a functional relation between the QCG and on-task behavior and off-task behavior for any of the three classrooms. However, there was a functional relation between the QCG and classroom noise level for two of three classrooms. Implications for researchers and practitioners, limitations, and future directions are discussed.

Pork hot carcass weights (HCW) have been increasing 0.6 kg per year, and if they continue to increase at this rate, they are projected to reach an average weight of 118 kg by the year 2050. This projection in weight is a concern for pork packers and processors given the challenges in product quality from heavier carcasses of broiler chickens. However, previous work demonstrated that pork chops from heavier carcasses were more tender than those from lighter carcasses. Therefore, the objective was to determine the effects of pork hot carcass weights, ranging from 90 to 145 kg with an average of 119 kg, on slice shear force and sensory traits of Longissimus dorsi chops when cooked to 63 or 71 °C, and to assess if differences in chilling rate can explain differences in sensory traits. Carcasses were categorized retrospectively into fast, medium, or slow chilling-rates based on their chilling rate during the first 17 h postmortem. Loin chops cut from 95 boneless loins were cooked to either 63 or 71 °C and evaluated for slice shear force and trained sensory panel traits (tenderness, juiciness, and flavor) using two different research laboratories. Slopes of regression lines and coefficients of determination between HCW and sensory traits were calculated using the REG procedure in SAS and considered different from 0 at P ≤ 0.05. As hot carcass weight increased, chops became more tender as evidenced by a decrease in SSF (63 °C β = -0.0412, P = 0.01; 71 °C β = -0.1005, P0.001). Furthermore, HCW explained 25% (R2 = 0.2536) of the variation in chilling rate during the first 5 h of chilling and 32% (R2 = 0.3205) of the variation in chilling rate from 5 to 13 h postmortem. Slow- and medium-rate chilling carcasses were approximately 12 kg heavier (P0.05) than fast chilling carcasses. Slice shear force of chops cooked to 63 and 71 °C was reduced in slow and medium chilling compared with fast chilling carcasses. Carcass temperature at 5 h postmortem explained the greatest portion of variation (R2 = 0.071) in slice shear force of chops cooked to 63 °C. These results suggest that carcasses tend to chill slower as weight increases, which resulted in slight improvements in sensory traits of boneless pork chops regardless of final degree of doneness cooking temperature.Pork carcass weights have increased year over year for at least the past 25 yr. The poultry industry has experienced similar increases in carcass weights in the recent past. The increases in broiler carcass weights have resulted in detrimental impacts on quality. Contrary to the poultry industry, increases in pork carcass weights have resulted in a general improvement in pork quality, including tenderness. The underlying cause of these improvements has not been explained. In the present study, chilling rate was associated with carcass weights, particularly during the first 5 h postmortem. In fact, carcass temperature measured in the Longissimus dorsi muscle at 5 h postmortem was the most predictive of instrumental tenderness values when boneless pork chops were cooked according to UDSA guidelines for whole-muscle pork products. The metabolic conversion of muscle to meat is most active during this initial chilling period. Therefore, chilling rate, which is associated with carcass weight, may be influencing the conversion of muscle to meat and provide some explanation as to why heavy carcasses result in more tender pork chops.

Tagging studies are often used to measure survival and growth in wild populations. However, issues such as low returns of tagged animals, tag loss, and handling mortality can affect the precision and accuracy of demographic estimates if not accounted for. We conducted a mark-recapture study to measure the survival and growth of juvenile and adult wavy turban snails Megastraea undosa. Our study highlights several methodological advances, including a method for estimating a single growth function by analyzing the joint changes in length and weight of tagged animals; a simple method for estimating rates of tag loss when some animals are double tagged; and a way to estimate handling mortality by comparing encounter histories of animals immediately after tagging and after several weeks in the field. Tag loss was moderate (≈15% over a 100 d period) and handling mortality was substantial during the fall (≈55%), but negligible during the spring. If we did not account for tag loss and handling mortality, our estimate of survival would have been severely underestimated (≈46% lower over a 100 d period). After accounting for such effects, our study revealed that survival probably increased sharply with body size, but survival did not differ among seasons. These snails are slow-growing, mature after approximately 6 yr, and can routinely grow to >10 yr old. There is an emerging fishery for this species, and because our results suggest that the oldest snails have a very high reproductive value, measures that protect these large individuals are likely to be beneficial for the resilience of these populations.

The northern Australia beef cattle industry operates in harsh environmental conditions which consistently suppress female fertility. To better understand the environmental effect on cattle raised extensively in northern Australia, new environmental descriptors were defined for 54 commercial herds located across the region. Three fertility traits, based on the presence of a corpus luteum at 600 d of age, indicating puberty, (CL Presence, n = 25,176), heifer pregnancy (n = 20,989) and first lactation pregnancy (n = 10,072) were recorded. Temperature, humidity, and rainfall were obtained from publicly available data based on herd location. Being pubertal at 600 d (i.e. CL Presence) increased the likelihood of success at heifer pregnancy and first lactation pregnancy (P < 0.05), underscoring the importance of early puberty in reproductive success. A temperature humidity index (THI) of 65–70 had a significant (P < 0.05) negative effect on first lactation pregnancy rate, heifer pregnancy and puberty at 600 d of age. Area under the curve of daily THI was significant (P < 0.05) and reduced the likelihood of pregnancy at first lactation and puberty at 600 days. Deviation from long-term average rainfall was not significant (P < 0.05) for any trait. Average daily weight gain had a significant and positive relationship (P < 0.05) for heifer and first lactation pregnancy. The results indicate that chronic or cumulative heat load is more determinantal to reproductive performance than acute heat stress. The reason for the lack of a clear relationship between acute heat stress and reproductive performance is unclear but may be partially explained by peak THI and peak nutrition coinciding at the same time. Sufficient evidence was found to justify the use of average daily weight gain and chronic heat load as descriptors to define an environmental gradient.

The neurobiological mechanisms that regulate the development and maintenance of alcohol use disorder (AUD) are complex and involve a wide variety of within and between systems neuroadaptations. While classic reward, preoccupation, and withdrawal neurocircuits have been heavily studied in terms of AUD, viable treatment targets from this established literature have not proven clinically effective as of yet. Therefore, examination of additional neurocircuitries not classically studied in the context of AUD may provide novel therapeutic targets. Recent studies demonstrate that various neuropeptides systems are important modulators of alcohol reward, seeking, and intake behaviors. This includes neurocircuitry within the dorsal vagal complex (DVC), which is involved in the control of the autonomic nervous system, control of intake of natural rewards like food, and acts as a relay of interoceptive sensory information via interactions of numerous gut-brain peptides and neurotransmitter systems with DVC projections to central and peripheral targets. DVC neuron subtypes produce a variety of neuropeptides and transmitters and project to target brain regions critical for reward such as the mesolimbic dopamine system as well as other limbic areas important for the negative reinforcing and aversive properties of alcohol withdrawal such as the extended amygdala. This suggests the DVC may play a role in the modulation of various aspects of AUD. This review summarizes the current literature on neurotransmitters and neuropeptides systems in the DVC (e.g., norepinephrine, glucagon-like peptide 1, neurotensin, cholecystokinin, thyrotropin-releasing hormone), and their potential relevance to alcohol-related behaviors in humans and rodent models for AUD research. A better understanding of the role of the DVC in modulating alcohol related behaviors may lead to the elucidation of novel therapeutic targets for drug development in AUD.

Feeding growing-finishing pigs supplemental fat is a common practice in the swine industry and can result in improved feed efficiency and reduced feed intake; however, dietary lipids also play a key role in determining pork composition. The objectives of the current study were to evaluate the effects of feeding graded levels of high oleic soybean oil (HOSO) on growth performance and carcass characteristics. A total of 288 pigs raised in two separate blocks (144 pigs each) were assigned to one of four diets containing either 25% dried distiller's grains with solubles (DDGS), 2% high oleic soybean oil (HOSO2), 4% high oleic soybean oil (HOSO4), or 6% high oleic soybean oil (HOSO6). Pigs were housed 4 per pen and fed for 98 d using a 3-phase feeding system. Pigs were individually weighed and feed intake was recorded throughout the trial to calculate average daily feed intake (ADFI) and gain to feed ratio (G:F). A total of 144 pigs were transported to the University of Illinois Meat Science Laboratory and fabricated into primal and subprimal cuts to calculate carcass cutting yields. Differences in growth performance were observed, with pigs fed the DDGS treatment exhibiting greater (P ≤ 0.01) overall ADFI consuming 0.21, 0.18, and 0.28 kg/d more than HOSO2, HOSO4, and HOSO6 diets, respectively. Pigs fed the HOSO6 diet had greater (P ≤ 0.03) overall G:F than pigs fed DDGS and HOSO2 diets but did not differ (P = 0.12) from pigs fed HOSO4. Furthermore, differences in carcass traits were observed. Hot carcass weight was increased (P ≤ 0.03) in pigs fed the HOSO6 diet compared with pigs fed the DDGS and HOSO2 diets, while pigs fed HOSO4 did not differ (P0.05) from either extreme. Additionally, pigs fed HOSO4 and HOSO6 produced fatter (P ≤ 0.01) carcasses with reduced (P ≤ 0.01) standardized fat-free lean. Minimal differences were observed in primal weights expressed as a percentage of chilled side including bone-in Boston butt, trimmed loin, and trimmed ham with primal weights decreasing with increasing inclusion of dietary HOSO. Overall, pigs fed HOSO2 had reduced ADFI with similar backfat thickness and standardized fat-free lean compared with pigs fed the DDGS treatment. However, pigs fed HOSO 4% and 6% not only had improvements in ADFI and G:F but also had increased backfat thickness, which resulted in reductions in standardized fat-free lean and primal weights expressed as a percentage of chilled side weight.Feeding pigs supplemental fat to increase caloric density is a common practice in the swine industry and can result in improved feed efficiency. However, high oleic soybean oil (HOSO), a relatively new feed ingredient, has not been extensively researched in pig diets. HOSO differs from conventional soybean oil in that it contains an increased proportion of oleic acid, a monounsaturated fatty acid. Therefore, our goal was to investigate the use of HOSO in the diets of pigs in the weeks leading up to marketing. A total of 288 pigs were fed one of four diets that differed in their source of fat. One diet contained 25% dried distiller’s grains with solubles (DDGS), while the other three had graded levels of HOSO (2%, 4%, or 6%). Pigs were fed diets for the last 14 wk leading up to slaughter. Pigs fed the highest level of HOSO grew more efficiently and were heavier than those fed the diet containing DDGS. However, pigs fed 6% HOSO were also fatter and yielded a reduced percentage of boneless meat cuts than those fed DDGS.

Infertility is a challenging phenomenon in cattle that reduces the sustainability of beef production worldwide. Here, we tested the hypothesis that gene expression profiles of protein-coding genes expressed in peripheral white blood cells (PWBCs), and circulating micro RNAs in plasma, are associated with female fertility, measured by pregnancy outcome. We drew blood samples from 17 heifers on the day of artificial insemination and analyzed transcript abundance for 10,496 genes in PWBCs and 290 circulating micro RNAs. The females were later classified as pregnant to artificial insemination, pregnant to natural breeding or not pregnant. We identified 1860 genes producing significant differential coexpression (eFDR

Extensively grazed cattle are often mustered only once a year. Therefore, birthdates are typically unknown or inaccurate. Birthdates would be useful for deriving important traits (growth rate; calving interval), breed registrations, and making management decisions. Epigenetic clocks use methylation of DNA to predict an individual’s age. An epigenetic clock for cattle could provide a solution to the challenges of industry birthdate recording. Here we derived the first epigenetic clock for tropically adapted cattle using portable sequencing devices from tail hair, a tissue which is widely used in industry for genotyping. Cattle (n= 66) with ages ranging from 0.35 to 15.7 years were sequenced using Oxford Nanopore Technologies MinION and methylation was called at CpG sites across the genome. Sites were then filtered and used to calculate a covariance relationship matrix based on methylation state. Best linear unbiased prediction was used with 10-fold cross validation to predict age. A second methylation relationship matrix was also calculated that contained sites associated with genes used in the dog and human epigenetic clocks. The correlation between predicted age and actual age was 0.71 for all sites and 0.60 for dog and human gene epigenetic clock sites. The mean absolute deviation was 1.4 years for animals aged less than 3 years of age, and 1.5 years for animals aged 3–10 years. This is the first reported epigenetic clock using industry relevant samples in cattle.

Background: Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer's disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. Methods: The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3-6 months old) and aged (9-14 months old) mice. All data were initially analyzed by multifactorial ANOVA with variables of genotype, age, treatment, and sex considered as dependent variables.Results: We found that daily RCAN1 levels in the hippocampi of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and -overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 knockout and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and -overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. Conclusions: Collectively, this study's findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and aging.

Background Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer’s disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. Methods The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3–6 months old) and aged (9–14 months old) mice of both sexes. Results We found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN. Conclusions Collectively, this study’s findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging.

This paper proposes an estimator of factor strength and establishes its consistency and asymptotic distribution. The proposed estimator is based on the number of statistically significant factor loadings, taking account of the multiple testing problem. We focus on the case where the factors are observed which is of primary interest in many applications in macroeconomics and finance. We also consider using cross section averages as a proxy in the case of unobserved common factors. We face a fundamental factor identification issue when there are more than one unobserved common factors. We investigate the small sample properties of the proposed estimator by means of Monte Carlo experiments under a variety of scenarios. In general, we find that the estimator, and the associated inference, perform well. The test is conservative under the null hypothesis, but, nevertheless, has excellent power properties, especially when the factor strength is sufficiently high. Application of the proposed estimation strategy to factor models of asset returns shows that out of 146 factors recently considered in the finance literature, only the market factor is truly strong, while all other factors are at best semi-strong, with their strength varying considerably over time. Similarly, we only find evidence of semi-strong factors in an updated version of the Stock and Watson (2012) macroeconomic dataset.

Fat deposition is important to carcass value and some palatability characteristics. Carcasses with higher USDA quality grades produce more value for producers and processors in the US system and are more likely to have greater eating satisfaction. Using genomics to identify genes impacting marbling deposition provides insight into muscle biochemistry that may lead to ways to better predict fat deposition, especially marbling and thus quality grade. Hereford steers (16) were managed the same from birth through harvest after 270 days on feed. Samples were obtained for tenderness and transcriptome profiling. As expected, steaks from Choice carcasses had a lower shear force value than steaks from Select carcasses, however, steaks from Standard carcasses were not different from steaks from Choice carcasses. A significant number of differentially expressed (DE) genes was observed in the longissimus lumborum between Choice and Standard carcass RNA pools (1257 genes, p &lt, 0.05), but not many DE genes were observed between Choice and Select RNA pools. Exploratory analysis of global muscle tissue transcriptome from Standard and Choice carcasses provided insight into muscle biochemistry, specifically the upregulation of extracellular matrix development and focal adhesion pathways and the downregulation of RNA processing and metabolism in Choice versus Standard. Additional research is needed to explore the function and timing of gene expression changes.

Heifers that have an earlier age at puberty often have greater lifetime productivity. Age at puberty is moderately heritable so selection should effectively reduce the number of days to puberty, and improve heifer productivity and profitability as a result. However, recording age at puberty is intensive, requiring repeat ovarian scanning to determine age at first corpus luteum (AGECL). Genomic selection has been proposed as a strategy to select for earlier age at puberty; however, large reference populations of cows with AGECL records and genotypes would be required to generate accurate GEBV for this trait. Reproductive maturity score (RMS) is a proxy trait for age at puberty for implementation in northern Australia beef herds, where large scale recording of AGECL is not feasible. RMS assigns a score of 0 to 5 from a single ovarian scan to describe ovarian maturity at ~600 d. Here we use multivariate genomic prediction to evaluate the value of a large RMS data set to improve accuracy of GEBV for age at puberty (AGECL). There were 882 Brahman and 990 Tropical Composite heifers with AGECL phenotypes, and an independent set of 974 Brahman, 1,798 Santa Gertrudis, and 910 Droughtmaster heifers with RMS phenotypes. All animals had 728,785 real or imputed SNP genotypes. The correlation of AGECL and RMS (h2 = 0.23) was estimated as -0.83 using the genomic information. This result also demonstrates that using genomic information it is possible to estimate genetic correlations between traits collected on different animals in different herds, with minimal or unknown pedigree linkage between them. Inclusion of heifers with RMS in the multi-trait model improved the accuracy of genomic evaluations for AGECL. Accuracy of RMS GEBV generally did not improve by adding heifers with AGECL phenotypes into the reference population. These results suggest that RMS and AGECL may be used together in a multi-trait prediction model to increase the accuracy of prediction for age at puberty in tropically adapted beef cattle.

The prevalence of psychiatry disorders such as anxiety and depression has steadily increased in recent years in the United States. This increased risk for anxiety and depression is associated with excess weight gain, which is often due to over-consumption of western diets that are typically high in fat, as well as with binge eating disorders, which often overlap with overweight and obesity outcomes. This finding suggests that diet, particularly diets high in fat, may have important consequences on the neurocircuitry regulating emotional processing as well as metabolic functions. Depression and anxiety disorders are also often comorbid with alcohol and substance use disorders. It is well-characterized that many of the neurocircuits that become dysregulated by overconsumption of high fat foods are also involved in drug and alcohol use disorders, suggesting overlapping central dysfunction may be involved. Emerging preclinical data suggest that high fat diets may be an important contributor to increased susceptibility of binge drug and ethanol intake in animal models, suggesting diet could be an important aspect in the etiology of substance use disorders. Neuroinflammation in pivotal brain regions modulating metabolic function, food intake, and binge-like behaviors, such as the hypothalamus, mesolimbic dopamine circuits, and amygdala, may be a critical link between diet, ethanol, metabolic dysfunction, and neuropsychiatric conditions. This brief review will provide an overview of behavioral and physiological changes elicited by both diets high in fat and ethanol consumption, as well as some of their potential effects on neurocircuitry regulating emotional processing and metabolic function.

AKT is implicated in neurological disorders. AKT has three isoforms, AKT1/AKT2/AKT3, with brain cell type-specific expression that may differentially influence behavior. Therefore, we examined single Akt isoform, conditional brain-specific Akt1, and double Akt1/3 mutant mice in behaviors relevant to neuropsychiatric disorders. Because sex is a determinant of these disorders but poorly understood, sex was an experimental variable in our design. Our studies revealed AKT isoform- and sex-specific effects on anxiety, spatial and contextual memory, and fear extinction. In Akt1 mutant males, viral-mediated AKT1 restoration in the prefrontal cortex rescued extinction phenotypes. We identified a novel role for AKT2 and overlapping roles for AKT1 and AKT3 in long-term memory. Finally, we found that sex-specific behavior effects were not mediated by AKT expression or activation differences between sexes. These results highlight sex as a biological variable and isoform- or cell type-specific AKT signaling as potential targets for improving treatment of neuropsychiatric disorders.

The Drosophila melanogaster male embryonic gonad is an advantageous model to study various aspects of developmental biology including, but not limited to, germ cell development, piRNA biology, and niche formation. Here, we present a dissection technique to live-image the gonad ex vivo during a period when in vivo live-imaging is highly ineffective. This protocol outlines how to transfer embryos to an imaging dish, choose appropriately-staged male embryos, and dissect the gonad from its surrounding tissue while still maintaining its structural integrity. Following dissection, gonads can be imaged using a confocal microscope to visualize dynamic cellular processes. The dissection procedure requires precise timing and dexterity, but we provide insight on how to prevent common mistakes and how to overcome these challenges. To our knowledge this is the first dissection protocol for the Drosophila embryonic gonad, and will permit live-imaging during an otherwise inaccessible window of time. This technique can be combined with pharmacological or cell-type specific transgenic manipulations to study any dynamic processes occurring within or between the cells in their natural gonadal environment.

Studies have demonstrated successful return to sport rates following Achilles tendon rupture and repair. The purpose of this study is to understand the subjective intrinsic and extrinsic motivational factors influencing an athlete's return to pre-injury level of sport following Achilles tendon repair. Qualitative, semi-structured interviews of 23 athletes who had undergone Achilles tendon repair were conducted and analyzed to derive codes, categories, and themes. Three major themes affecting return to sport were elucidated from the interviews: personal motivation, shift in focus, and confidence in healthcare team. These findings can direct healthcare teams on how to better guide patients post-operatively.

A neuroprotective peptide protects mice against ischemic stroke injury by disrupting Kv2.1 potassium channel clusters in neurons., Kv2.1 channels mediate cell death–enabling loss of cytosolic potassium in neurons following plasma membrane insertion at somatodendritic clusters. Overexpression of the carboxyl terminus (CT) of the cognate channel Kv2.2 is neuroprotective by disrupting Kv2.1 surface clusters. Here, we define a seven–amino acid declustering domain within Kv2.2 CT (DP-2) and demonstrate its neuroprotective efficacy in a murine ischemia-reperfusion model. TAT-DP-2, a membrane-permeable derivative, induces Kv2.1 surface cluster dispersal, prevents post-injurious pro-apoptotic potassium current enhancement, and is neuroprotective in vitro by disrupting the association of Kv2.1 with VAPA. TAT-DP-2 also induces Kv2.1 cluster dispersal in vivo in mice, reducing infarct size and improving long-term neurological function following stroke. We suggest that TAT-DP-2 induces Kv2.1 declustering by disrupting Kv2.1-VAPA association and scaffolding sites required for the membrane insertion of Kv2.1 channels following injury. We present the first evidence of targeted disruption of Kv2.1-VAPA association as a neuroprotective strategy following brain ischemia.

Background In tropically-adapted beef heifers, application of genomic prediction for age at puberty has been limited due to low prediction accuracies. Our aim was to investigate novel methods of pre-selecting whole-genome sequence (WGS) variants and alternative analysis methodologies; including genomic best linear unbiased prediction (GBLUP) with multiple genomic relationship matrices (MGRM) and Bayesian (BayesR) analyses, to determine if prediction accuracy for age at puberty can be improved. Methods Genotypes and phenotypes were obtained from two research herds. In total, 868 Brahman and 960 Tropical Composite heifers were recorded in the first population and 3695 Brahman, Santa Gertrudis and Droughtmaster heifers were recorded in the second population. Genotypes were imputed to 23 million whole-genome sequence variants. Eight strategies were used to pre-select variants from genome-wide association study (GWAS) results using conditional or joint (COJO) analyses. Pre-selected variants were included in three models, GBLUP with a single genomic relationship matrix (SGRM), GBLUP MGRM and BayesR. Five-way cross-validation was used to test the effect of marker panel density (6 K, 50 K and 800 K), analysis model, and inclusion of pre-selected WGS variants on prediction accuracy. Results In all tested scenarios, prediction accuracies for age at puberty were highest in BayesR analyses. The addition of pre-selected WGS variants had little effect on the accuracy of prediction when BayesR was used. The inclusion of WGS variants that were pre-selected using a meta-analysis with COJO analyses by chromosome, fitted in a MGRM model, had the highest prediction accuracies in the GBLUP analyses, regardless of marker density. When the low-density (6 K) panel was used, the prediction accuracy of GBLUP was equal (0.42) to that with the high-density panel when only six additional sequence variants (identified using meta-analysis COJO by chromosome) were included. Conclusions While BayesR consistently outperforms other methods in terms of prediction accuracies, reasonable improvements in accuracy can be achieved when using GBLUP and low-density panels with the inclusion of a relatively small number of highly relevant WGS variants.

Infertility is a disease that affects humans and cattle in similar ways. The resemblance includes complex genetic architecture, multiple etiology, low heritability of fertility related traits in females, and the frequency in the female population. Here, we used cattle as a biomedical model to test the hypothesis that gene expression profiles of protein-coding genes expressed in peripheral white blood cells (PWBCs), and circulating micro RNAs in plasma, are associated with female fertility, measured by pregnancy outcome. We drew blood samples from 17 female calves on the day of artificial insemination and analyzed transcript abundance for 10496 genes in PWBCs and 290 circulating micro RNAs. The females were later classified as pregnant to artificial insemination, pregnant to natural breeding or not pregnant. We identified 1860 genes producing significant differential coexpression (eFDR

The objective was to test inherent cooking rate differences on tenderness values of boneless pork chops when exogenous factors known to influence cooking rate were controlled. Temperature and elapsed time were monitored during cooking for all chops. Cooking rate was calculated as the change in °C per minute of cooking time. Warner-Bratzler shear force (WBSF) was measured on chops cooked to either 63 °C or 71 °C. Slopes of regression lines and coefficients of determination between cooking rate and tenderness values for both degrees of doneness (DoD) were calculated. Shear force values decreased as cooking rate increased regardless of DoD (p ≤ 0.05), however changes in tenderness due to increased cooking rate were limited (β1 = −0.201 for 63 °C; β1 = −0.217 for 71 °C). Cooking rate only explained 3.2% and 5.4% of variability in WBSF of chops cooked to 63 °C and 71 °C, respectively. Cooking loss explained the most variability in WBSF regardless of DoD (partial R2 = 0.09–0.12). When all factors were considered, a stepwise regression model explained 20% of WBSF variability of chops cooked to 63 °C and was moderately predictive of WBSF (model R2 = 0.34) for chops cooked to 71 °C. Overall, cooking rate had minimal effect on pork chop tenderness.

During development, the embryo transitions from a metabolism favoring glycolysis to a metabolism favoring mitochondrial respiration. How metabolic shifts regulate developmental processes, or how developmental processes regulate metabolic shifts, remains unclear. To test the requirement of mitochondrial function in developing endoderm-derived tissues, we genetically inactivated the mitochondrial transcription factor, Tfam, using the Shh-Cre driver. Tfam mutants did not survive postnatally, exhibiting defects in lung development. In the developing intestine, TFAM-loss was tolerated until late fetal development, during which the process of villus elongation was compromised. While progenitor cell populations appeared unperturbed, markers of enterocyte maturation were diminished and villi were blunted. Loss of TFAM was also tested in the adult intestinal epithelium, where enterocyte maturation was similarly dependent upon the mitochondrial transcription factor. While progenitor cells in the transit amplifying zone of the adult intestine remained proliferative, intestinal stem cell renewal was dependent upon TFAM, as indicated by molecular profiling and intestinal organoid formation assays. Taken together, these studies point to critical roles for the mitochondrial regulator TFAM for multiple aspects of intestinal development and maturation, and highlight the importance of mitochondrial regulators in tissue development and homeostasis.

Beef cow stayability is a complex, economically important trait often used as an indicator of a cow's potential lifetime productivity. Stayability is defined as capability of a cow to maintain a perfect record up to 6 yr of age. This age is commonly cited as a financial break-even point, where initial costs of cow development and maintenance are recovered by her cumulative net income from yearly calf receipts. Later-maturing Bos indicus-Bos taurus crossbred cows may experience reproductive difficulty early in life but have a high potential for a long reproductive life span. It was the objective of this study to identify genetic variants associated with measures of beef cow stayability. A population of B. indicus-B. taurus crossbred cows (n = 305) from central Texas was used. Phenotypes for various measures of stayability to 6 yr of age were produced by artificially imposing five different culling criteria on data from the population. Cows were scored either as a 1 (indicating a perfect record through 6 yr) or a 0 (indicating failure at or before 6 yr), under each criterion. Genome-wide association studies (GWAS) were conducted for each criterion using univariate procedures and prefitting the fixed effect of cow contemporary group. SNP associations for two criteria surpassed the false discovery threshold of 0.15, when a cow was scored as 0 upon her first failure to wean a calf, regardless of reason, through 6 yr (criterion 2), and when a cow was scored as 0 upon her first failure to give birth to a calf, through 6 yr (criterion 3). Associated SNP were found on bovine chromosomes (BTA) 1, 2, 5, 9, 18, and 21 for criterion 2 and on BTA 1, 5, 11, 15, and 24 for criterion 3. A critical region on BTA 5: 43-50 Mb was identified for each criterion. Due to the similarities to prior work, the tendency for B. indicus cattle to experience reproductive difficulties early in life, and due to the large proportion of cows that left the herd at an early age under these criteria, these results suggest that the associations are likely driven by an early life trait such as age at puberty or rate of heifer development.

Qualitatively and quantitatively, we have demonstrated that airborne polychlorinated biphenyl (PCB) concentrations in the air surrounding New Bedford Harbor (NBH) are caused by its water PCB emissions. We measured airborne PCBs at 18 homes and businesses near NBH in 2015, with values ranging from 0.4 to 38 ng m–3, with a very strong Aroclor 1242/1016 signal that is most pronounced closest to the harbor and reproducible over three sampling rounds. Using U.S. Environmental Protection Agency (U.S. EPA) water PCB data from 2015 and local meteorology, we predicted gas-phase fluxes of PCBs from 160 to 1200 μg m–2 day–1. Fluxes were used as emissions for AERMOD, a widely applied U.S. EPA atmospheric dispersion model, to predict airborne PCB concentrations. The AERMOD predictions were within a factor of 2 of the field measurements. PCB emission from NBH (110 kg year–1, average 2015) is the largest reported source of airborne PCBs from natural waters in North America, and the source of high ambient air PCB concentrations in locations close to NBH. It is likely that NBH has been an important source of airborne PCBs since it was contaminated with Aroclors more than 60 years ago.

From the time oocytes leave quiescence, there are constant microenvironmental influences contributing to development, thus acquiring developmental competence is not a simple, linear phenomenon. During folliculogenesis, oocytes experience many morphological and cytological changes that contribute toward the acquisition of developmental competence, a process defined by an oocyte's ability to progress through folliculogenesis, be fertilized, undergo cleavage, and develop into an embryo. Many factors, such as ovarian follicle size, cow age, and the morphology of the cumulus–oocyte complex, have been extensively investigated to understand this process. In parallel to aiding in the understanding of oocyte biology, these features have been used to characterize an oocyte's ability to achieve competence. In addition, oocytes undergo intense gene transcription and protein translation to accumulate the maternal stores. When the oocyte is fully grown, most genes are transcriptionally inactive, and the chromatin is densely compacted. More recently, RNA profiling has been used to further define the transcriptional parameters that are associated with oocyte development. Here, focusing on cattle, we provide an overview of the experimental models commonly used to understand the underlying biology related to oocyte developmental competence. We compiled public data and showed that cattle oocytes can express over 15 000 protein-coding genes, suggesting a complex transcriptome landscape. Surprisingly, less than 2% of the expressed genes have been linked to developmental competence. The identification of the gene products that contribute to oocyte development, and understanding their biological function, are a vital component of our quest toward defining oocyte developmental competence at the molecular level.Summary SentenceDevelopmental competence acquired by an oocyte throughout folliculogenesis is dependent upon fine-tuned gene regulation and transcript accumulation.

This study consisted of two experiments intended to investigate the effects of varying factors on the use of verbal and implicit classification systems when learning novel categories in an interactive video game environment. Experiment 1 measured the effects of feature type (easy vs difficult to describe verbally), and Experiment 2 measured the effect of direct vs indirect feedback. Verbal and implicit classification were operationalized by measuring rule-based and family resemblance strategy use respectively. Experiment 1 found that participants presented with stimuli that were easy to describe verbally were more likely to use rule-based classification, while participants presented with stimuli that were difficult to describe verbally showed no preference for one form of classification. Experiment 2 found that participants favoured rule-based classification regardless of whether they received direct or indirect feedback. The results of this study open up a novel field of research within category learning, further exploring the effects of feature verbalizablity.

Background Artificial insemination is a preferred breeding method for beef heifers as it advances the genetic background, produces a predictive and profitable calving season, and extends the heifer’s reproductive life span. As reproductive efficiency in heifers is key for the success of beef cattle production systems, following artificial insemination, heifers are exposed to a bull for the remainder of the breeding season. Altogether, up to 95% of heifers might become pregnant in their first breeding season. Heifers that do not become pregnant at the end of the breeding season represent an irreparable economical loss. Additionally, heifers conceiving late in the breeding season to natural service, although acceptable, poses serious losses to producers. To minimize losses due to reproductive failure, different phenotypic parameters can be assessed and utilized as selection tools. Here, we tested the hypothesis that in a group of pre-selected heifers, records of weaning weight, age at weaning, age at artificial insemination, and age of dam differ among heifers of varied reproductive outcomes during the first breeding season. Results None of the parameters tested presented predictive ability to discriminate the heifers based on the response variable (‘pregnant to artificial insemination’, ‘pregnant to natural service’, ‘not pregnant’). Heifers categorized with body condition score = 6 and reproductive tract score ≥ 4 had the greatest proportion of pregnancy to artificial insemination (49% and 44%, respectively). Furthermore, it was notable that heifers presenting body condition score = 6 and reproductive tract score = 5 presented the greatest pregnancy rate at end of the breeding season (89%). Heifers younger than 368 d at the start of the breeding season did not become pregnant to artificial insemination. Those young heifers had 12.5% chance to become pregnant in their first breeding season, compared to 87.5% if the heifers were older than 368 days. Conclusion Our results suggest that beef heifers with body condition score = 6 and reproductive tract score ≥ 4 are more likely to become pregnant to artificial insemination. Careful assessment should be undertaken when developing replacement heifers that will not reach 12 months of age by the beginning of the breeding season. Electronic supplementary material The online version of this article (10.1186/s40104-019-0329-6) contains supplementary material, which is available to authorized users.

A new tract scoring system for age at puberty (RTSCORE) has been proposed for application in Northern Australian beef herds. RTSCORE is an indirect measure of age at first corpus luteum (AGECL), which is an accurate, intensively collected phenotype but has limited feasibility for large scale commercial application. When measurements are taken in unrelated herds it is possible to use multivariate genomic prediction to compare RTSCORE to other puberty related traits, such as AGECL. Here we use this methodology to evaluate the ability of RTSCORE to accurately predict genomic estimated breeding values (GEBV) for age at puberty. We also evaluate the effect of including AGECL phenotypes on GEBV accuracy for RTSCORE. Multi-trait best linear unbiased prediction with a multi-breed, across-population genomic relationship matrix derived from 728,000 imputed SNP markers was used to compare AGECL in a population of 894 Brahman and 1088 Tropical Composite heifers and RTSCORE in a population of 979 Brahman, 1803 Santa Gertrudis, and 914 Droughtmaster heifers. GEBV accuracy from within-herd predictions of puberty were compared to GEBV accuracies from a combined reference population containing both measures of puberty. The inclusion of heifers with RTSCORE and corresponding genotypes improved the accuracy of genomic evaluations for AGECL compared to within-herd predictions. Although across-herd prediction of puberty using RTSCORE for training resulted in accuracies that were low, this was expected given a correlation between RTSCORE and AGECL of -0.66. These results suggest that RTSCORE is an appropriate measure of puberty and can be used to accurately predict age at puberty. Including both populations in the reference herd for prediction of RTSCORE resulted in either no change or slight improvement in accuracy. As RTSCORE is not an exact measure of puberty, AGECL should be included with RTSCORE when predicting genomic breeding values for puberty in a commercial setting.

Heifers that have an earlier age at puberty often have greater lifetime productivity. Age at puberty is moderately heritable so selection should effectively reduce the number of days to puberty, and improve heifer productivity and profitability as a result. However, recording age at puberty is intensive, requiring repeat ovarian scanning to determine age at first corpus luteum (AGECL). Genomic selection has been proposed as a strategy to select for earlier age at puberty; however, large reference populations of cows with AGECL records and genotypes would be required to generate accurate GEBV for this trait. Reproductive maturity score (RMS) is a proxy trait for age at puberty for implementation in northern Australia beef herds, where large scale recording of AGECL is not feasible. RMS assigns a score of 0 to 5 from a single ovarian scan to describe ovarian maturity at ~600 d. Here we use multivariate genomic prediction to evaluate the value of a large RMS data set to improve accuracy of GEBV for age at puberty (AGECL). There were 882 Brahman and 990 Tropical Composite heifers with AGECL phenotypes, and an independent set of 974 Brahman, 1,798 Santa Gertrudis, and 910 Droughtmaster heifers with RMS phenotypes. All animals had 728,785 real or imputed SNP genotypes. The correlation of AGECL and RMS (h(2) = 0.23) was estimated as −0.83 using the genomic information. This result also demonstrates that using genomic information it is possible to estimate genetic correlations between traits collected on different animals in different herds, with minimal or unknown pedigree linkage between them. Inclusion of heifers with RMS in the multi-trait model improved the accuracy of genomic evaluations for AGECL. Accuracy of RMS GEBV generally did not improve by adding heifers with AGECL phenotypes into the reference population. These results suggest that RMS and AGECL may be used together in a multi-trait prediction model to increase the accuracy of prediction for age at puberty in tropically adapted beef cattle.

Background The widespread popularity of e-cigarettes, particularly JUUL, has led to an alarming increase in teen nicotine use, reversing a 40-year trend. One key question is how sensitive teens’ demand for JUUL is to changes in price. Methods We estimate the price elasticity of demand using results from an experimental auction where teen nicotine users and nonusers bid on a JUUL kit. Results We find that a 10 % increase in price leads to as much as a 24 % reduction in JUUL demand among teens using nicotine, and as much as a 45 % reduction among teens not currently using nicotine. The teens in our study were more price sensitive than older adults who took part in a similar earlier study. Conclusions From a public health standpoint, these are promising results. High e-cigarette taxes may dissuade relatively few older adult cigarette smokers from switching to e-cigarettes, but at the same time be highly effective at preventing teens from becoming e-cigarette users in the first place.

Meta-analyses techniques using 11 independent datasets were used to determine correlations between pork loin quality evaluated at 1-d postmortem and quality evaluated at 12- to 28-d postmortem. Datasets encompassed approximately 3,957 loins. The effects of aging on ventral loin surface quality were determined using a paired-T test. Ventral loin surfaces become 8% lighter (P < 0.0001), 44.5% redder (P < 0.0001), and 46% more yellow (P < 0.0001) during the aging period. Therefore, it is apparent that loin quality changes during postmortem aging. Because of this, it becomes necessary to determine the correlation between early and aged pork quality parameters. Pearson correlation coefficients within original datasets were calculated, and then sample-weighted mean correlations [Formula: see text] and variances [Var(r)] were calculated across datasets. Early postmortem ventral instrumental lightness (L*) was moderately correlated with aged ventral L* [Formula: see text] = 0.50), aged ventral visual color [Formula: see text] = −0.38), aged chop face (freshly cut) L* [Formula: see text] = 0.44), and aged chop face visual color [Formula: see text] = −0.38). Early postmortem ventral instrumental redness (a*) was moderately correlated with aged ventral a* [Formula: see text] = 0.49) and aged chop face a* [Formula: see text] = 0.46). Early postmortem ventral visual color was moderately correlated with aged ventral L* [Formula: see text] = −0.51), aged ventral color ([Formula: see text] = 0.50), aged chop face L* [Formula: see text] = −0.43), and aged chop face visual color [Formula: see text] = 0.43). However, no instrumental or visual color parameters were moderately or strongly correlated with instrumental tenderness or sensory panel ratings of tenderness and juiciness (| [Formula: see text] | ≤ 0.36). Early postmortem ventral visual marbling was moderately correlated with aged ventral marbling [Formula: see text] = 0.63) and aged chop face visual marbling [Formula: see text] = 0.56). Visual marbling was not (| [Formula: see text] | ≤ 0.12) correlated with instrumental tenderness or sensory panel ratings of tenderness and juiciness. Stepwise regression, using a holo-analysis approach, was used to determine the predictive ability of early postmortem ventral color, marbling, firmness, and pH on sensory panels ratings of tenderness (R(2) = 0.13), juiciness (R(2) = 0.09), and flavor (R(2) = 0.28). Early postmortem color and marbling are important pork quality traits in consumers purchasing decisions, but are poorly related to traits associated with eating experience. Still, they may be predicative of traits associated with purchasing intent.

Summary Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors ( Smad4 or Cdx2 ), stem cell activity is restored in BRAF V600E intestines, and the oncogenic capacity of BRAF V600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.

Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a component of the metastatic signatures of melanoma, breast cancer, glioblastoma, lung cancer and head and neck squamous cell carcinoma (HNSCC). Here we tested the efficacy of NEDD9's domains in stimulating matrix metalloproteinase (MMP) secretion and invadopodia formation in cells stably expressing various NEDD9 mutants. Replacement of the 13 YxxP motif substrate domain (SD) tyrosines and the C-terminal Y629 with phenylalanines (F14NEDD9) eliminated tyrosine phosphorylation, MMP9 secretion and loss of invadopodia formation. Mutation of the N-terminal SH3 domain Y12 to glutamic acid (Y12ENEDD9) or phenylalanine (Y12FNEDD9) reduced MMP9 secretion and inhibited invadopodia formation. SH3 domain deletion (∆SH3NEDD9) resulted in the loss of MMP9 secretion and a lack of invadopodia formation. The SH3-SD domain (SSNEDD9) construct exhibited tyrosine phosphorylation and stimulated MMP9 secretion, as did ∆CTNEDD9 which lacked the C-terminus (∆C-terminal; ∆CT). E13NEDD9 expression blocked MMP9 secretion and invadopodia formation. MICAL1 (molecule interacting with Cas-L1) silencing with a short hairpin RNA reduced MMP9 secretion, vimentin and E-cadherin levels while increasing N-cadherin and Rab6 levels, consistent with reduced invasive behavior. These findings indicate that NEDD9 SD phosphorylation and SH3 domain interactions are necessary for increasing MMP9 secretion and invadopodia formation.

Urban and rural locations may have different levels of poverty or social exclusion but also different combinations of problems or forms of exclusion. Understanding these differences is important both for the allocation of resources but also for the development of appropriate policies or interventions. Overall, this chapter argues that the similarities between urban and rural areas are greater than the differences. There are substantial levels of poverty in urban and rural locations although most measures show higher levels in more urban locations. There are notable differences between measures, however, with low income measures inflating estimates of poverty in more rural locations compared with other measures, notably those based on deprivation. Contrary to expectations in much of the literature, we do not find strong differences in the forms of exclusion in different areas: some aspects are worse in urban locations (notably neighbourhood problems and subjective well-being), while others are worse in rural places (notably transport and access to services). The experience of poverty is equally shaming in urban and rural locations. The main message for policy is the need to focus on core national policies to tackle poverty and exclusion in rural and urban locations alike.