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Abstract Most genetic variants associated with fertility in mammals fall in non-coding regions of the genome and it is unclear how these variants affect fertility. Here we use genome-wide association summary statistics for Heifer puberty (pubertal or not at 600 days) from 27,707 Bos indicus, Bos taurus and crossbred cattle; multi-trait GWAS signals from 2119 indicine cattle for four fertility traits, including days to calving, age at first calving, pregnancy status, and foetus age in weeks (assessed by rectal palpation of the foetus); and expression quantitative trait locus for whole blood from 489 indicine cattle, to identify 87 putatively functional genes affecting cattle fertility. Our analysis reveals a significant overlap between the set of cattle and previously reported human fertility-related genes, impling the existence of a shared pool of genes that regulate fertility in mammals. These findings are crucial for developing approaches to improve fertility in cattle and potentially other mammals.

Alcohol use disorders (AUDs) are common mental health issues worldwide and can lead to other chronic diseases. Stress is a major factor in the development and continuation of AUDs, and adolescent alcohol exposure can lead to enhanced stress-responsivity and increased risk for AUD development in adulthood. The exact mechanisms behind the interaction between adolescence, stress, and alcohol are not fully understood and require further research. In this regard, the nucleus of the tractus solitarius (NTS) provides dense norepinephrine projections to the extended amygdala, providing a key pathway for stress-related alcohol behaviors. While NTS norepinephrine neurons are known to be alcohol sensitive, whether adolescent alcohol disrupts NTS-norepinephrine neuron development and if this is related to altered stress-sensitivity and alcohol preference in adulthood has not previously been examined. Here, we exposed male and female C57Bl/6J mice to the commonly used adolescent intermittent ethanol (AIE) vapor model during postnatal day 28-42 and examined AIE effects on: 1) tyrosine hydroxylase (TH) mRNA expression in the NTS across various ages (postnatal day 21-90), 2) behavioral responses to acute stress in the light/dark box test in adulthood, 3) NTS TH neuron responses to acute stress and ethanol challenges in adulthood, and 4) ethanol conditioned place preference behavior in adulthood. Overall the findings indicate that AIE alters NTS TH mRNA expression and increases anxiety-like behaviors following acute stress exposure in a sex-dependent manner. These mRNA expression and behavioral changes occur in the absence of AIE-induced changes in NTS TH neuron sensitivity to either acute stress or acute alcohol exposure or changes to ethanol conditioned place preference.

Abstract 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

The many possible treatments and continuously changing consumer trends present a challenge when selecting antimicrobial interventions during pork processing. Thirty-five potential antimicrobials were screened at commercial working concentrations by individually adding them to miniaturized (69 cm3) disks of pork loin ends, followed by inoculation with Salmonella Typhimurium ATCC 19585. Two organic acids and nine essential oils significantly inhibited Salmonella counts on pork (p < 0.05). However, six compounds that represent different levels of significance (p < 0.05–p < 0.0001) were selected as independent variables to build a Response Surface Methodology model based on a Doehlert matrix (Doehlert Matrix—RSM): lactic acid 1.25%, formic acid 0.25%, cumin 0.25%, clove 0.25%, peppermint 0.5%, and spearmint 0.5%. The goal of the Doehlert Matrix—RSM was to study single and paired effects of these antimicrobials on the change in Salmonella over 24 h. The Doehlert Matrix—RSM model predicted that lactic acid, formic acid, cumin, peppermint, and spearmint significantly reduced Salmonella when added alone, while no significant interactions between these antimicrobials were found. A laboratory-scale validation was carried out on pork loin end slices, which confirmed the results predicted by the model. While this screening did not identify novel synergistic combinations, our approach to screening a variety of chemical compounds by implementing a miniaturized pork loin disk model allowed us to identify the most promising antimicrobial candidates to then formally design experiments to study potential interactions with other antimicrobials.

Abstract 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.

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.

Abstract 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.

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.

Abstract 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.

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.

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.

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 BRAFV600E intestines, and the oncogenic capacity of BRAFV600E 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.

The objectives were to determine effects of salt inclusion on production yields, commercial slicing yields, sensory characteristics, and lipid oxidation of bacon. A total of 144 bellies that ranged in weight from 5.8 to 6.6 kg were selected from 2 different suppliers. Fresh bellies were weighed to determine an initial weight (green weight). Then, bellies were randomly assigned to salt levels of 1.2, 1.5, or 1.8% in the final product and manufactured into bacon. Bacon was stored frozen, in aerobic packages, for approximately 0 d, 30 d, 60 d, or 90 d and analyzed for lipid oxidation. Sensory analysis was conducted approximately 14 d after slicing and again 90 d later. Cook yield was increased ( ≤ 0.05) in 1.2% bacon compared with 1.5 and 1.8% bacon, but slicing yield was 1% unit greater ( ≤ 0.05) in 1.8% bacon compared with 1.2% bacon. Increasing salt content from 1.5 to 1.8% increased the number of bacon slices generated from a slab of bacon by 12 slices and by nearly 16 slices when compared with the 1.2% treatment. Sensory saltiness increased ( ≤ 0.05) as intended salt level increased. Lipid oxidation and oxidized odor and flavor intensity was not different among salt treatment levels within any storage period. Reducing salt from 1.8 to 1.2% in bacon can adversely affect slicing yield, but was not detrimental to cook yield and did not reduce the rate of lipid oxidation of bacon.

AKT is a kinase regulating numerous cellular processes in the brain, and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes. We also find isoform-specific roles for AKT in multiple paradigms of hippocampal synaptic plasticity in area CA1. AKT1, but not AKT2 or AKT3, is required for L-LTP through regulating activity-induced protein synthesis. Interestingly, AKT activity inhibits mGluR-LTD, with overlapping functions for AKT1 and AKT3. In summary, our studies identify distinct expression patterns and roles in synaptic plasticity for AKT isoforms in the hippocampus.

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.

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., Author(s): Bailey N. Chapman [sup.1], Daniel D. Drevon [sup.1], Andrea D. Jasper [sup.2] Author Affiliations: (1) grid.253856.f, 0000 0001 2113 4110, Department of Psychology , Central Michigan University, , Mount [...]

This study intended to investigate the effects of varying factorson the use of verbal and implicit classification systems whenlearning novel categories in an interactive video gameenvironment by measuring the effects of feature type (easy vsdifficult to describe verbally). Verbal and implicitclassification were operationalized by measuring rule-basedand family resemblance strategy use respectively. Thisexperiment found that participants presented with stimuli thatwere easy to describe verbally were more likely to use rule-based classification, while participants presented with stimulithat were difficult to describe verbally showed no preferencefor one form of classification. The results of this study open upa novel field of research within category learning, furtherexploring the effects of feature verbalizablity.

The presence of a rotating disk adjacent to a stationary disk forms a rotor–stator cavity known as a wheel-space. It is necessary for gas turbine wheel-spaces to be purged with sealing flow bled from the compressor to counteract the harmful effects of ingress. This paper presents a combined experimental, theoretical, and computational study of rotationally induced ingress in rotor–stator systems. Measurements were made in a wheel-space with an axial clearance rim seal under axisymmetric conditions in the absence of a mainstream annulus through-flow. Ingress was quantified using a gas concentration technique and the flow structure in the cavity was explored with static and total pressure measurements to determine the swirl ratio. A low-order theoretical model was developed based on the boundary layer momentum-integral equations. The theory gave excellent results when predicting the effects of ingress and purge flows on the radial pressure and swirl gradients. Unsteady Reynolds-Averaged Navier–Stokes computations were conducted to provide greater fluid dynamic insight into the wheel-space flow structure and ingress through the rim seal. The computational results demonstrated some of the closest agreement with experimental measurements of ingress available in the literature, showing that rotationally induced ingress is dominated by unsteady large-scale structures in the rim seal gap instead of the previously ascribed disk-pumping effect. The study serves as an important validation case for investigations of ingress in rotor–stator systems in more complex environments. [ABSTRACT FROM AUTHOR]

The capability of nanostructured ferritic alloys (NFAs) to manage high levels of transmutation product helium will help resolve one of the grand challenges to transforming the promise of C-free fusion energy into a reality. NFAs are dispersion strengthened by an ultrahigh density of Y-Ti-O nano-oxides (NOs), which result in both high strength and temperature limits, as well as unique irradiation tolerance. Here, aberration-corrected high-resolution transmission electron microscopy was used to characterize the NOs in four NFA conditions, including following severe deformation and extreme neutron radiation exposure. Fast Fourier Transform analysis of focal series images revealed the NO crystal structure, including the smallest at < 2 nm in diameter, to be Y2Ti2O7 pyrochlore in all cases, consistent with both exit wave analysis and scanning transmission Z-contrast imaging of the atomic columns in a larger feature. The faceted NOs exhibit a quasi-epitaxial orientation relationship with the ferrite matrix: [110]YTO||[100]Fe and [001]YTO||[010]Fe, forming a 5 × 7 near coincidence site interface. The NOs also exhibit size-dependent strains in both the oxide and matrix ferrite phases.