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The recent advances in high‐throughput next‐generation sequencing technologies have heralded the arrival of the Big Data era. As a result, the use of pharmacogenetics in drug discovery and individualized drug therapy has transformed the field of precision medicine. This paradigm shift in drug development programs has effectively reshaped the old drug development practices, which were primarily concerned with the physiological status of patients for drug development. Pharmacogenomics bridges the gap between pharmacodynamics and pharmacokinetics, advancing current diagnostic and treatment strategies and enabling personalized and targeted drug therapy. The primary goals of pharmacogenetic studies are to improve drug efficacy and minimize toxicities, to identify novel drug targets, to estimate drug dosage for personalized medicine, and to incorporate it as a routine diagnostic for disease susceptibility. Although pharmacogenetics has numerous applications in individualized drug therapy and drug development, it is in its infancy in veterinary medicine. The objective of this review is to present an overview of historical landmarks, current developments in various animal species, challenges and future perspectives of genomics in drug development and dosage optimization for individualized medicine in veterinary subjects. [ABSTRACT FROM AUTHOR]

Half a century ago, a seminal article on the hitchhiking effect by Smith and Haigh inaugurated the concept of the selection signature. Selective sweeps are characterised by the rapid spread of an advantageous genetic variant through a population and hence play an important role in shaping evolution and research on genetic diversity. The process by which a beneficial allele arises and becomes fixed in a population, leading to a increase in the frequency of other linked alleles, is known as genetic hitchhiking or genetic draft. Kimura's neutral theory and hitchhiking theory are complementary, with Kimura's neutral evolution as the 'null model' and positive selection as the 'signal'. Both are widely accepted in evolution, especially with genomics enabling precise measurements. Significant advances in genomic technologies, such as next‐generation sequencing, high‐density SNP arrays and powerful bioinformatics tools, have made it possible to systematically investigate selection signatures in a variety of species. Although the history of selection signatures is relatively recent, progress has been made in the last two decades, owing to the increasing availability of large‐scale genomic data and the development of computational methods. In this review, we embark on a journey through the history of research on selective sweeps, ranging from early theoretical work to recent empirical studies that utilise genomic data. [ABSTRACT FROM AUTHOR]

Over the years, indigenous cattle have not only played an essential role in securing primary food sources but have also been utilized for labor by humans, making them invaluable genetic resources. The Zhaotong cattle, a native Chinese breed from the Yunnan province, possess excellent meat quality and resistance to heat and humidity. Here we used whole genome sequencing data of 104 animals to delve into the population structure, genomic diversity and potential positive selection signals in Zhaotong cattle. The findings of this study demonstrate that the genetic composition of Zhaotong cattle was primarily derived from Chinese indicine cattle and East Asian cattle. The nucleotide diversity of Zhaotong cattle was only lower than that of Chinese indicine cattle, which was much higher than that of other taurine cattle. Genome‐wide selection scans detected a series of positive candidate regions containing multiple key genes related to bone development and metabolism (CA10, GABRG3, GLDN and NOTUM), meat quality traits (ALG8, LINGO2, MYO5B, PRKG1 and GABRB1), immune response (ADA2, BMF, LEF1 and PAK6) and heat resistance (EIF2AK4 and LEF1). In summary, this study supplies essential genetic insights into the genome diversity within Zhaotong cattle and provides a foundational framework for comprehending the genetic basis of indigenous cattle breeds. [ABSTRACT FROM AUTHOR]

Determination of factors affecting sex ratio is important while considering application of sex ratio enrichment approach. Present study aimed to design a SYBR Green qPCR‐based method for measurement of primary sex ratio and to evaluate different factors (genetic group, sire, spermiogenic cycle and processing layer) affecting boar sperm sex ratio. The qPCR was based on relative copy number analysis of sex chromosome‐specific single copy gene fragments with an autosomal gene as reference and was evaluated using DNA dilution series from pigs with numerically normal karyotype. The sex ratio was estimated from genomic DNA samples isolated from boar semen collected from different genetic groups at different time points and different processing layers. The X chromosome frequencies of semen samples revealed significant effect of genetic group. However, significant variation was observed neither within same genetic group nor between ejaculates of different spermatogenic cycles. Among the processing techniques studied, swim‐up technique produced a significant X sperm enrichment in comparison to control whereas, Percoll density gradient failed to show any significant difference among layers. The lower layer in swim‐up technique was found to contain higher proportion of X sperms. The designed qPCR is found to be an easy, less time‐consuming method and does not require high end laboratory facilities or the specialized expertise. The lower layer of swim‐up processing has a scope for X sperm enrichment in boar semen with proper validation. [ABSTRACT FROM AUTHOR]

Natural fibers derived from diverse animal species have gained increased attention in recent years due to their favorable environmental effects, long‐term sustainability benefits, and remarkable physical and mechanical properties that make them valuable raw materials used for textile and non‐textile production. Domestication and selective breeding for the economically significant fiber traits play an imperative role in shaping the genomes and, thus, positively impact the overall productivity of the various fiber‐producing species. These selection pressures leave unique footprints on the genome due to alteration in the allelic frequencies at specific loci, characterizing selective sweeps. Recent advances in genomics have enabled the discovery of selection signatures across the genome using a variety of methods. The increased demand for 'green products' manufactured from natural fibers necessitates a detailed investigation of the genomes of the various fiber‐producing plant and animal species to identify the candidate genes associated with important fiber attributes such as fiber diameter/fineness, color, length, and strength, among others. The objective of this review is to present a comprehensive overview of the concept of selection signature and selective sweeps, discuss the main methods used for its detection, and address the selection signature studies conducted so far in the diverse fiber‐producing animal species. [ABSTRACT FROM AUTHOR]

Contents: Developing alternate therapies for bovine endometritis is important in the context of drug residues in the milk and emergence of antimicrobial resistant bacteria. In this regard, we studied the immunomodulatory effect of curcumin 30 µM, on lipopolysaccharide‐ (LPS) and/or flagellin (100 ng/ml each)‐induced prostaglandin E2 (PGE2) and proinflammatory cytokines (PIC) using primary bubaline endometrial stromal cells. After 24 hr treatment, the supernatant was assayed for PGE2 while cells were used for relative quantification of cytokines like IL‐1β, IL‐6, IL‐8 and TNF α transcripts using a control group as calibrator. LPS was found to possess potent stimulatory effect on PGE2 production, whereas the flagellin was not as potent as LPS in stimulating the PGE2 production either per se or in combination with LPS. LPS markedly up‐regulated the transcripts of IL‐8 and IL‐6 as compared to IL‐1β and TNF α in the bubaline endometrial stromal cells. Except for IL‐8, flagellin did not up‐regulate other PICs. There was no additive effect between LPS and flagellin on the up‐regulation of inflammatory cytokines. Curcumin inhibited the LPS‐induced up‐regulation of PIC with strong down‐regulation of IL‐8. The inhibitory effects of curcumin on the inflammatory mediators suggest a potential in the treatment of bovine endometritis. [ABSTRACT FROM AUTHOR]

Contents: Transition proteins (TNPs) are essential in chromatin condensation during spermiogenesis, and hence, they are the candidate genes for identifying sperm motility markers. Coding and in silico predicted promoter regions of these genes were investigated in crossbred and purebred cattle, and also, their mRNA quantification was done to explore its use as a diagnostic tool of infertility. PCR‐SSCP analysis revealed two band patterns in fragment III of TNP1 and fragment II of TNP2 gene. Sequence analysis revealed a deletion of "G" nucleotide in 3′UTR region of TNP1 and C>T SNP in intronic region of TNP2 gene. Least square analysis of variance did not reveal any significant influence of nucleotide deletion on any sperm motility parameters in both crossbred and purebred cattle. However, C>T SNP had a significant effect on initial progressive motility (p < 0.05) in purebred cattle and post‐thaw motility in overall cattle population. RT‐qPCR analysis did not reveal any significant variation in TNP1 and TNP2 gene expression among poorly motile and good quality spermatozoa of Vrindavani bulls. [ABSTRACT FROM AUTHOR]

Contents: Progesterone (P4) plays a key role in the establishment and maintenance of pregnancy in most mammals. Unravelling the expression of progesterone‐regulated genes can expand the understanding of the embryonic mortality. Accordingly, we studied the relative mRNA expression of the P4‐regulated genes in the buffalo. Uteri were collected from the abattoir and categorized into nonpregnant late luteal phase, stage I (28–38th days of gestation) and stage II (48–56th days of gestation) of pregnancy (n = 6/group). After extraction of total RNA from the endometrial tissues, we carried out qRT‐PCR for determining the relative mRNA expression of the P4‐regulated genes using nonpregnant late luteal phase as calibrator group. The expression of LGALS3BP (essential for maternal recognition of pregnancy) gene was found to be significantly upregulated (p < 0.05), while MUC1 (important for embryo attachment) gene was downregulated in stage I and II of pregnancy. We observed no significant change in the expression of LGALS1, LGALS9 and CTSL genes. The SLC5A11 and SLC2A1 genes (involved in the transport of glucose to endometrium) in early pregnancy were upregulated in the pregnancy stage I (p < 0.05) relative to nonpregnant late luteal phase. The CST3 gene was significantly upregulated in pregnancy stage II (p < 0.01). These results provide molecular insights into the specific pathways involved in foeto‐maternal communication during early pregnancy in buffaloes. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? Does the inhibition of the protein kinase casein kinase 2 (CK2) alter the uterine contractility? What is the main finding and its importance? Inhibition of CK2 impaired the spontaneous and oxytocin‐induced contractility in late pregnant mouse uterus. This finding suggests that CK2 is a novel pathway mediating oxytocin‐induced contractility in the uterus and thus opens up the possibility for this class of drugs to be developed as a new class of tocolytics. Abstract: The protein kinase casein kinase 2 (CK2) is a ubiquitously expressed serine or threonine kinase known to phosphorylate a number of substrates. The aim of this study was to assess the effect of CK2 inhibition on spontaneous and oxytocin‐induced uterine contractions in 19 day pregnant mice. The CK2 inhibitor CX‐4945 elicited a concentration‐dependent relaxation in late pregnant mouse uterus. CX‐4945 and another selective CK2 inhibitor, apigenin, also inhibited the oxytocin‐induced contractile response in late pregnant uterine tissue. Apigenin also blunted the prostaglandin F2α response, but CX‐4945 did not. Casein kinase 2 was located in the lipid raft fractions of the cell membrane, and disruption of lipid rafts was found to reverse its effect. The results of the present study suggest that CK2, located in lipid rafts of the cell membrane, is an active regulator of spontaneous and oxytocin‐induced uterine contractions in the late pregnant mouse. [ABSTRACT FROM AUTHOR]