Use of digital health tools in inflammatory bowel disease. / Uso de herramientas digitales en salud en enfermedad inflamatoria intestinal.

OBJECTIVE: To analyse the characteristics and use of digital health tools (DHT) in inflammatory bowel disease (IBD). METHODS: We performed a qualitative study based on a narrative literature review, a questionnaire and on the opinion of 3 expert gastroenterologists. Several searches were carried out until September 2022 through Medline to identify articles on the use of DHT in IBD by healthcare professionals. A structured questionnaire was designed to be answered by health professionals involved in the care of patients with IBD. The experts generated a set of recommendations. RESULTS: There are multiple DHT for IBD with different characteristics and contents. We received 29 questionnaires. Almost 50% of the participants were 41-50 years old, the majority were women (83%) and 90% were gastroenterologists. A total of 96% reported the use of several DHT, but 20% used them occasionally or infrequently. Web pages were found the most used (62%). DHT are mostly used to get information (80%), followed by clinical practice issues (70%) and educational purposes (62%). G-Educainflamatoria website is the best known and most used HDS (96% and 64%, respectively). The main barriers to the use of DHT in IBD were the lack of time (55%), doubts about the benefit of DHT (50%) and the excess of information (40%). CONCLUSIONS: Healthcare professionals involved in the care of patients with to IBD frequently use DHT, although actions are needed to optimize their use and to guarantee their efficient and safe use.

Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

Deafness in Australian Cattle Dogs associated to QTL on chromosome 20 in genome-wide association study analyses.

Pigment-associated deafness is a common hereditary condition in a range of dog breeds. The aim of this study was to perform a genome-wide association analysis to investigate the genetic architecture of deafness in Australian Cattle Dogs. Genotypes for 104 757 polymorphisms in 216 dogs were available for analyses after quality control. A genomic relationship matrix was used in the mixed model analyses to account for polygenic effects, as we tested each polymorphism for its association with deafness, in a case/control experimental design. Three approaches were used to code the genotypes and test for additive, recessive and dominant SNP effects. The genome-wide association study analyses identified a clear association peak on CFA20, with the most significant SNPs on this chromosome (1.29 × 10-4 ) in the vicinity of MITF. Variants in MITF have been associated with white pigmentation in dogs and with deafness in humans and other species, supporting the premise that canine deafness is associated with variants in or near this gene. A recessive inheritance for the peak in CFA20 is possible given the significant results in the recessive model; however, the estimated heritability was low (4.54 × 10-5 ). Further validation, identification of variants and testing in other dog breeds are needed.

Design of a Pilot SOFC System for the Combined Production of Hydrogen and Electricity under Refueling Station Requirements.

The objective of the current work is to support the design of a pilot hydrogen and electricity producing plant that uses natural gas (or biomethane) as raw material, as a transition option towards a 100% renewable transportation system. The plant, with a solid oxide fuel cell (SOFC) as principal technology, is intended to be the main unit of an electric vehicle station. The refueling station has to work at different operation periods characterized by the hydrogen demand and the electricity needed for supply and self-consumption. The same set of heat exchangers has to satisfy the heating and cooling needs of the different operation periods. In order to optimize the operating variables of the pilot plant and to provide the best heat exchanger network, the applied methodology follows a systematic procedure for multi-objective, i.e. maximum plant efficiency and minimum number of heat exchanger matches, and multi-period optimization. The solving strategy combines process flow modeling in steady state, superstructure-based mathematical programming and the use of an evolutionary-based algorithm for optimization. The results show that the plant can reach a daily weighted efficiency exceeding 60%, up to 80% when considering heat utilization.

Short-term creatine supplementation changes protein metabolism signaling in hindlimb suspension.

The effect of a short-term creatine supplementation on hindlimb suspension (HS)-induced muscle atrophy was investigated. Creatine monohydrate (5 g/kg b.w. per day) or placebo, divided in 2 daily doses, was given by oral gavage for 5 days. Rats were maintained in HS with dietary supplementation concomitantly for 5 days. Body weight, soleus and EDL muscle masses, and cross-sectional areas (CSA) of the muscle fibers were measured. Signaling pathways associated with skeletal muscle mass regulation (FST, MSTN, FAK, IGF-1, MGF, Akt, mTOR, atrogin-1, and MuRF1 expressions, and Akt, S6, GSK3B, and 4EBP1 proteins) were evaluated in the muscles. Soleus muscle exhibited more atrophy than the EDL muscle due to HS. Creatine supplementation attenuated the decrease of wet weight and increased p-4EBP1 protein in the EDL muscle of HS rats. Also, creatine increased mTOR and atrogin-1 expressions in the same muscle and condition. In the absence of HS, creatine supplementation increased FAK and decreased MGF expressions in the EDL muscle. Creatine attenuated the increase in FST expression due to HS in the soleus muscle. MuRF1 expression increased in the soleus muscle due to creatine supplementation in HS animals whereas atrogin-1 expression increased still further in this group compared with untreated HS rats. In conclusion, short-term creatine supplementation changed protein metabolism signaling in soleus and EDL muscles. However, creatine supplementation only slightly attenuated the mass loss of both muscles and did not prevent the CSA reduction and muscle strength decrease induced by HS for 5 days.

Genomic clues of the evolutionary history of Bos indicus cattle.

Together with their sister subspecies Bos taurus, zebu cattle (Bos indicus) have contributed to important socioeconomic changes that have shaped modern civilizations. Zebu cattle were domesticated in the Indus Valley 8000 years before present (YBP). From the domestication site, they expanded to Africa, East Asia, southwestern Asia and Europe between 4000 and 1300 YBP, intercrossing with B. taurus to form clinal variations of zebu ancestry across the landmass of Afro-Eurasia. In the past 150 years, zebu cattle reached the Americas and Oceania, where they have contributed to the prosperity of emerging economies. The zebu genome is characterized by two mitochondrial haplogroups (I1 and I2), one Y chromosome haplogroup (Y3) and three major autosomal ancestral groups (Indian-Pakistani, African and Chinese). Phenotypically, zebu animals are recognized by their hump, large ears and excess skin. They are rustic, resilient to parasites and capable of bearing the hot and humid climates of the tropics. Many resources are available to study the zebu genome, including commercial arrays of SNP, reference assemblies and publicly available genotypes and whole-genome sequences. Nevertheless, many of these resources were initially developed to support research and subsidize industrial applications in B. taurus, and therefore they can produce bias in data analysis. The combination of genomics with precision agriculture holds great promise for the identification of genetic variants affecting economically important traits such as tick resistance and heat tolerance, which were naturally selected for millennia and played a major role in the evolution of B. indicus cattle.

Short-term creatine supplementation changes protein metabolism signaling in hindlimb suspension

The effect of a short-term creatine supplementation on hindlimb suspension (HS)-induced muscle atrophy was investigated. Creatine monohydrate (5 g/kg b.w. per day) or placebo, divided in 2 daily doses, was given by oral gavage for 5 days. Rats were maintained in HS with dietary supplementation concomitantly for 5 days. Body weight, soleus and EDL muscle masses, and cross-sectional areas (CSA) of the muscle fibers were measured. Signaling pathways associated with skeletal muscle mass regulation (FST, MSTN, FAK, IGF-1, MGF, Akt, mTOR, atrogin-1, and MuRF1 expressions, and Akt, S6, GSK3B, and 4EBP1 proteins) were evaluated in the muscles. Soleus muscle exhibited more atrophy than the EDL muscle due to HS. Creatine supplementation attenuated the decrease of wet weight and increased p-4EBP1 protein in the EDL muscle of HS rats. Also, creatine increased mTOR and atrogin-1 expressions in the same muscle and condition. In the absence of HS, creatine supplementation increased FAK and decreased MGF expressions in the EDL muscle. Creatine attenuated the increase in FST expression due to HS in the soleus muscle. MuRF1 expression increased in the soleus muscle due to creatine supplementation in HS animals whereas atrogin-1 expression increased still further in this group compared with untreated HS rats. In conclusion, short-term creatine supplementation changed protein metabolism signaling in soleus and EDL muscles. However, creatine supplementation only slightly attenuated the mass loss of both muscles and did not prevent the CSA reduction and muscle strength decrease induced by HS for 5 days.

Pre- and post-puberty expression of genes and proteins in the uterus of Bos indicus heifers: the luteal phase effect post-puberty.

Progesterone signaling and uterine function are crucial in terms of pregnancy establishment. To investigate how the uterine tissue and its secretion changes in relation to puberty, we sampled tissue and uterine fluid from six pre- and six post-pubertal Brahman heifers. Post-pubertal heifers were sampled in the luteal phase. Gene expression of the uterine tissue was investigated with RNA-sequencing, whereas the uterine fluid was used for protein profiling with mass spectrometry. A total of 4034 genes were differentially expressed (DE) at a nominal P-value of 0.05, and 26 genes were significantly DE after Bonferroni correction (P < 3.1 × 10-6 ). We also identified 79 proteins (out of 230 proteins) that were DE (P < 1 × 10-5 ) in the uterine fluid. When we compared proteomics and transcriptome results, four DE proteins were identified as being encoded by DE genes: OVGP1, GRP, CAP1 and HBA. Except for CAP1, the other three had lower expression post-puberty. The function of these four genes hypothetically related to preparation of the uterus for a potential pregnancy is discussed in the context of puberty. All DE genes and proteins were also used in pathway and ontology enrichment analyses to investigate overall function. The DE genes were enriched for terms related to ribosomal activity. Transcription factors that were deemed key regulators of DE genes are also reported. Transcription factors ZNF567, ZNF775, RELA, PIAS2, LHX4, SOX2, MEF2C, ZNF354C, HMG20A, TCF7L2, ZNF420, HIC1, GTF3A and two novel genes had the highest regulatory impact factor scores. These data can help to understand how puberty influences uterine function.

Adipose tissue proteomic analyses to study puberty in Brahman heifers.

The adipose tissue has been recognized as an active endocrine organ which can modulate numerous physiological processes such as metabolism, appetite, immunity, and reproduction. The aim of this study was to look for differentially abundant proteins and their biological functions in the abdominal adipose tissue between pre- and postpubertal Brahman heifers. Twelve Brahman heifers were divided into 2 groups and paired on slaughter day. Prepubertal heifers had never ovulated and postpubertal heifers were slaughtered on the luteal phase of their second estrous cycle. After ensuring the occurrence of puberty in postpubertal heifers, abdominal adipose tissue samples were collected. Mass spectrometry proteomic analysis identified 646 proteins and revealed that 171 proteins showed differential abundance in adipose tissue between the pre- and postpuberty groups (adjusted P-value < 0.05). Data are available via ProteomeXchange with identifier PXD009452. Using a list of 51 highly differentially abundant proteins as the target (adjusted P-value < 10-5), we found 14 enriched pathways. The results indicated that gluconeogenesis was enhanced when puberty approached. The metabolism of glucose, lipids, and AA in the adipose tissue mainly participated in oxidation and energy supply for heifers when puberty occurred. Our study also revealed the differentially abundant proteins were enriched for estrogen signaling and PI3K-Akt signaling pathways, which are known integrators of metabolism and reproduction. These results suggest new candidate proteins that may contribute to a better understanding of the signaling mechanisms that relate adipose tissue function to puberty. Protein-protein interaction network analysis identified 4 hub proteins that had the highest degrees of connection: PGK1, ALDH5A1, EEF2, and LDHB. Highly connected proteins are likely to influence the functions of all differentially abundant proteins identified, directly or indirectly.

Morphological defects, sperm DNA integrity, and protamination of bovine spermatozoa.

The association between sperm morphology characteristics and DNA conformation and integrity is still controversial. In bulls, major morphological sperm abnormalities have been associated with reduced fertility, and morphological assessment is used to provide an indication of potential fertility of the individual. Sperm DNA fragmentation and damage has a negative effect on embryo development and subsequently fertility, with bull spermatozoa generally displaying low levels of DNA damage and tight chromatin. However, sensitive methods for detecting chromatin damage may reveal associations with morphological defects. The objective was to determine whether morphological sperm abnormalities and variables expressing sperm DNA integrity and protamination are correlated in bulls, using the sperm chromatin structure assay (SCSA) and the sperm protamine deficiency assay (SPDA). Electroejaculated samples (n = 1009) from two-year-old tropically adapted bulls were split and fixed and submitted to microscopic sperm morphology assessment, and snap-frozen for sperm nuclear integrity assessments by SPDA and SCSA. For SPDA, the variables were defective (MCB) and deprotaminated (HCB), and for SCSA, the variables were DNA fragmentation index (DFI) and high DNA stainability (HDS). HCB correlated with DFI; τKen2  = 0.317 and HDS; 0.098, and MCB correlated with DFI; 0.183 (p < 0.001). The percentage of morphological normal spermatozoa was correlated negatively to DFI; τKen2  = -0.168, MCB; -0.116 and HCB; -0.137 (p < 0.001). HCB and DFI were both positively correlated to head defects, proximal droplets, and spermatogenic immaturity, but not to distal droplets, vacuoles, or diadems. Sperm DNA integrity and protamination, using the SCSA and SPDA, respectively, in bulls show associations with morphological parameters, particularly with head shape abnormalities and indicators of spermatogenic immaturity, including proximal droplets. The vacuoles and diadem defects were not correlated with sperm nuclear integrity, and hence, these are likely physiological features that may not directly affect sperm chromatin configuration.

Genomic inbreeding depression for climatic adaptation of tropical beef cattle.

Inbreeding has the potential to negatively impact animal performance. Strategies to monitor and mitigate inbreeding depression require that it can be accurately estimated. Here, we used genomewide SNP data to explore 3 alternative measures of genomic inbreeding: the diagonal elements of the genomic relationship matrix (FGRM), the proportion of homozygous SNP (FHOM), and the proportion of the genome covered by runs of homozygosity (FROH). We used 2,111 Brahman (BR) and 2,550 Tropical Composite (TC) cattle with phenotypes recorded for 10 traits of relevance to tropical adaptation. We further explored 3 marker densities ranging from a high-density chip (729,068 SNP), a medium-density chip (71,726 SNP) specifically designed for cattle, and a low-density chip (18,860 SNP) associated with the measures of inbreeding. Measures of FGRM were highly correlated across the 3 SNP densities and negatively correlated with FHOM and FROH in the BR population. In both populations, there was a strong positive correlation for each measure of inbreeding across the 3 SNP panels. We found significant ( < 0.01) inbreeding depression for various traits, particularly when using the highest-density SNP chip in the BR population, where inbreeding was negatively associated with coat color and coat type such that inbred animals presented shorter, slicker, and lighter coats. Based on FGRM using the medium-density chip, we found that a 1% increase in inbreeding in the BR and TC populations was associated with a decrease of 0.514 and 0.579 kg BW, respectively, in yearlings. In the TC population, a 1% increase in FHOM was associated with a decrease in BCS of -0.636% ( < 0.001). The low-density chip, comprising SNP associated with inbreeding, captured genes, and regions with pleiotropic effects ( < 0.001). However, it did not improve our ability to identify inbreeding depression, relative to the use of higher-density panels. We conclude that where heterogeneous populations are present, such as in tropical environments where composite animals abound, measures of inbreeding that do not depend on allele frequencies, such as FHOM and FROH, are preferable for estimating genomic inbreeding. Finally, the sustainable intensification of livestock systems in tropical regions will rely on genetic safeguards to ensure that productivity is improved while also adapting animals to cope with climate change. The results of this study are a step toward achieving that goal.

Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.

We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken.

Multiple-trait genomewide mapping and gene network analysis for scrotal circumference growth curves in Brahman cattle.

Fertility traits are economically important in cattle breeding programs. Scrotal circumference (SC) measures are repeatable, easily obtained, highly heritable, and positively correlated with female fertility traits and sperm quality traits in males. A useful approach to summarize SC measures over time is using nonlinear models, which summarize specific measures of SC in a few parameters with biological interpretation. This approach facilitates the selection of bulls with larger SC and maturity index (K), that is, early maturing animals. Because SC is a sex-limited trait, identifying the underlying genomics of growth curve parameters will allow selection across both males and females. We reported the first multitrait genomewide association study (GWAS) of estimated growth curve parameters for SC data in Brahman cattle. Five widely used nonlinear models were tested to fit a total of 3,612 SC records, measured at 6, 12, 18, and 24 mo of age. The von Bertalanffy model, individually fitted for each animal, best fit this SC data. Parameter estimates SC at maturity (A) and K as well as SC at all ages were jointly analyzed in a GWAS to identify 1-Mb regions most strongly associated with each trait. Heritabilities were 0.25 for K and 0.32 for A and ranged from 0.51 to 0.72 for SC at 6 (SC6), 12 (SC12), 18 (SC18), and 24 mo of age (SC24). An overlapping window on chromosome 14 explaining around 0.8% of genetic variance for K, SC12, SC18, and SC24 was observed. The major positional candidate genes within 1 Mb upstream and downstream of this overlapping window were , , , and . Windows of 1 Mb explaining more than 0.4% of each trait on chromosomes 1, 3, 6, 7, 14, 17, 18, 24, 25, and 26 were identified. Pathways and net-work analyses were indicated through transcription factors playing a role on fertility traits: , , , , , , and . Further validation studies on larger populations or other breeds are required to validate these findings and to improve our understanding of the biology and complex genetic architecture of traits associated with scrotal growth and male fertility in cattle.

Global differential gene expression in the pituitary gland and the ovaries of pre- and postpubertal Brahman heifers.

To understand genes, pathways, and networks related to puberty, we characterized the transcriptome of two tissues: the pituitary gland and ovaries. Samples were harvested from pre- and postpubertal Brahman heifers (same age group). Brahman heifers () are older at puberty compared with , a productivity issue. With RNA sequencing, we identified differentially expressed (DEx) genes and important transcription factors (TF) and predicted coexpression networks. The number of DEx genes detected in the pituitary gland was 284 ( < 0.05), and was the most DEx gene (fold change = 4.12, = 0.01). The gene promotes bone mineralization through transforming growth factor-ß (TGFß) signaling. Further studies of the link between bone mineralization and puberty could target . In ovaries, 3,871 genes were DEx ( < 0.05). Four highly DEx genes were noteworthy for their function: (a γ-aminobutyric acid [GABA] transporter), (), and () and its receptor . These genes had higher ovarian expression in postpubertal heifers. The GABA and its receptors and transporters were expressed in the ovaries of many mammals, suggesting a role for this pathway beyond the brain. The pathway has been known to influence the timing of puberty in rats, via modulation of GnRH. The effects of at the hypothalamus, pituitary gland, and ovaries have been documented. and its receptors are known factors in the release of GnRH, similar to and GABA, although their roles in ovarian tissue are less clear. Pathways previously related to puberty such as TGFß signaling ( = 6.71 × 10), Wnt signaling ( = 4.1 × 10), and peroxisome proliferator-activated receptor (PPAR) signaling ( = 4.84 × 10) were enriched in our data set. Seven genes were identified as key TF in both tissues: , , , , , , and a novel gene. An ovarian subnetwork created with TF and significant ovarian DEx genes revealed five zinc fingers as regulators: , , , , and . Recent work of hypothalamic gene expression also pointed to zinc fingers as TF for bovine puberty. Although some zinc fingers may be ubiquitously expressed, the identification of DEx genes in common across tissues points to key regulators of puberty. The hypothalamus and pituitary gland had eight DEx genes in common. The hypothalamus and ovaries had 89 DEx genes in common. The pituitary gland and ovaries had 48 DEx genes in common. Our study confirmed the complexity of puberty and suggested further investigation on genes that code zinc fingers.

SNP detection using RNA-sequences of candidate genes associated with puberty in cattle.

Fertility traits, such as heifer pregnancy, are economically important in cattle production systems, and are therefore, used in genetic selection programs. The aim of this study was to identify single nucleotide polymorphisms (SNPs) using RNA-sequencing (RNA-Seq) data from ovary, uterus, endometrium, pituitary gland, hypothalamus, liver, longissimus dorsi muscle, and adipose tissue in 62 candidate genes associated with heifer puberty in cattle. RNA-Seq reads were assembled to the bovine reference genome (UMD 3.1.1) and analyzed in five cattle breeds; Brangus, Brahman, Nellore, Angus, and Holstein. Two approaches used the Brangus data for SNP discovery 1) pooling all samples, and 2) within each individual sample. These approaches revealed 1157 SNPs. These were compared with those identified in the pooled samples of the other breeds. Overall, 172 SNPs within 13 genes (CPNE5, FAM19A4, FOXN4, KLF1, LOC777593, MGC157266, NEBL, NRXN3, PEPT-1, PPP3CA, SCG5, TSG101, and TSHR) were concordant in the five breeds. Using Ensembl's Variant Effector Predictor, we determined that 12% of SNPs were in exons (71% synonymous, 29% nonsynonymous), 1% were in untranslated regions (UTRs), 86% were in introns, and 1% were in intergenic regions. Since these SNPs were discovered in RNA, the variants were predicted to be within exons or UTRs. Overall, 160 novel transcripts in 42 candidate genes and five novel genes overlapping five candidate genes were observed. In conclusion, 1157 SNPs were identified in 62 candidate genes associated with puberty in Brangus cattle, of which, 172 were concordant in the five cattle breeds. Novel transcripts and genes were also identified.

Genomic analyses of tropical beef cattle fertility based on genotyping pools of Brahman cows with unknown pedigree.

We introduce an innovative approach to lowering the overall cost of obtaining genomic EBV (GEBV) and encourage their use in commercial extensive herds of Brahman beef cattle. In our approach, the DNA genotyping of cow herds from 2 independent properties was performed using a high-density bovine SNP chip on DNA from pooled blood samples, grouped according to the result of a pregnancy test following their first and second joining opportunities. For the DNA pooling strategy, 15 to 28 blood samples from the same phenotype and contemporary group were allocated to pools. Across the 2 properties, a total of 183 pools were created representing 4,164 cows. In addition, blood samples from 309 bulls from the same properties were also taken. After genotyping and quality control, 74,584 remaining SNP were used for analyses. Pools and individual DNA samples were related by means of a "hybrid" genomic relationship matrix. The pooled genotyping analysis of 2 large and independent commercial populations of tropical beef cattle was able to recover significant and plausible associations between SNP and pregnancy test outcome. We discuss 24 SNP with significant association ( < 1.0 × 10) and mapped within 40 kb of an annotated gene. We have established a method to estimate the GEBV in young herd bulls for a trait that is currently unable to be predicted at all. In summary, our novel approach allowed us to conduct genomic analyses of fertility in 2 large commercial Brahman herds managed under extensive pastoral conditions.

Transcriptome analyses identify five transcription factors differentially expressed in the hypothalamus of post- versus prepubertal Brahman heifers.

Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: , , , , and . These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric ( < 0.05). Two of these 5 TF, and , were zinc fingers, belonging to a gene family previously reported to have a central regulatory role in mammalian puberty. The gene belongs to the family of homologues of Drosophila sine oculis () genes implicated in transcriptional regulation of gonadotrope gene expression. Tumor-related genes such as and are known to affect basic cellular processes that are relevant in both cancer and developmental processes. Mutations in were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy.

Effect of maternal nutrition and days of gestation on pituitary gland and gonadal gene expression in cattle.

This study investigated effects of maternal overnutrition on gonadal development and pituitary-gonadal gene expression in cattle fetuses at mid- and late-gestation. Twenty-seven multiparous dry cows were fed either high (ad libitum, H) or moderate (M) intake of the same diet. Twelve cows from H (n=6) and M (n=6) intake carrying females fetuses were euthanized at 199 and 268d of gestation (DG; n=3 for H or M on each DG). Fifteen cows from H (n=6) and M intake (n=9) carrying male fetuses were euthanized at 139, 199, and 241 DG (n=2 for H and n=3 for M on each DG). Fetal gonads and pituitary gland were sampled for gene expression and histological analyses. Sex-specific responses to maternal intake were observed. Primordial and total follicle numbers were lower in fetal ovaries from H than in M intake cows. These results were the reverse for preantral and antral follicles. Volumetric proportion and diameter of seminiferous cord were lower in fetal testis of H than M intake cows. The expression level of FSHB was greater in pituitary gland of the female fetus from H compared with M intake cows, irrespective of DG, whereas LHB gene expression did not differ. In males, FSHB and LHB gene expression levels were similar between maternal intake groups. Fetal ovarian expression of P450 aromatase, StAR, BMPR2, TGFBR1, GDF9, FSHR, Bax, and CASP3 genes were higher in H than in M intake cows, irrespective of DG. Fetal testicular expression of StAR, HSD17B3, IGF1, IGF2, and IGF1R genes was higher in M than in H intake cows. The differences in gene expression for steroidogenesis, folliculogenesis, and apoptosis may explain the distinct pattern of follicular growth between offspring of M and H intake cows. By contrast, the lower volumetric proportion, diameter, and length of seminiferous cord may relate to decreased gene expression in fetal testis from H intake cows. In conclusion, maternal H intake seems to affect fetal ovarian follicular growth and number of follicles, which may affect the size of ovarian reserve in their offspring. In male fetus, maternal H intake seems to disturb testicular development and may have implications on sperm production. The underlying mechanism of differential gene expression and the effect on offspring reproductive potential should be the focus of further research, especially considering larger sample size, reducing the chance for type I errors.

Post-exercise hot water immersion induces heat acclimation and improves endurance exercise performance in the heat.

We examined whether daily hot water immersion (HWI) after exercise in temperate conditions induces heat acclimation and improves endurance performance in temperate and hot conditions. Seventeen non-heat-acclimatized males performed a 6-day intervention involving a daily treadmill run for 40 min at 65% V̇O2max in temperate conditions (18 °C) followed immediately by either HWI (N = 10; 40 °C) or thermoneutral (CON, N = 7; 34 °C) immersion for 40 min. Before and after the 6-day intervention, participants performed a treadmill run for 40 min at 65% V̇O2max followed by a 5-km treadmill time trial (TT) in temperate (18 °C, 40% humidity) and hot (33 °C, 40% humidity) conditions. HWI induced heat acclimation demonstrated by lower resting rectal temperature (Tre , mean, -0.27 °C, P < 0.01), and final Tre during submaximal exercise in 18 °C (-0.28 °C, P < 0.01) and 33 °C (-0.36 °C, P < 0.01). Skin temperature, Tre at sweating onset and RPE were lower during submaximal exercise in 18 °C and 33 °C after 6 days in HWI (P < 0.05). Physiological strain and thermal sensation were also lower during submaximal exercise in 33 °C after 6 days in HWI (P < 0.05). HWI improved TT performance in 33 °C (4.9%, P < 0.01) but not in 18 °C. Thermoregulatory measures and performance did not change in CON. Hot water immersion after exercise on 6 days presents a simple, practical, and effective heat acclimation strategy to improve endurance performance in the heat.

Accuracy of genomic selection for age at puberty in a multi-breed population of tropically adapted beef cattle.

Genomic selection is becoming a standard tool in livestock breeding programs, particularly for traits that are hard to measure. Accuracy of genomic selection can be improved by increasing the quantity and quality of data and potentially by improving analytical methods. Adding genotypes and phenotypes from additional breeds or crosses often improves the accuracy of genomic predictions but requires specific methodology. A model was developed to incorporate breed composition estimated from genotypes into genomic selection models. This method was applied to age at puberty data in female beef cattle (as estimated from age at first observation of a corpus luteum) from a mix of Brahman and Tropical Composite beef cattle. In this dataset, the new model incorporating breed composition did not increase the accuracy of genomic selection. However, the breeding values exhibited slightly less bias (as assessed by deviation of regression of phenotype on genomic breeding values from the expected value of 1). Adding additional Brahman animals to the Tropical Composite analysis increased the accuracy of genomic predictions and did not affect the accuracy of the Brahman predictions.