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Abstract With the upsurge of crossbreeding in India, the admixture levels are highly unpredictable in the composite breeds. Hence, in the present study, 72 Vrindavani animals were assessed for the level of admixture from their known ancestors that are Holstein–Friesian, Jersey, Brown Swiss, and Hariana, through three different software, namely, STRUCTURE, ADMIXTURE, and frappe. The genotype data for ancestral breeds were obtained from a public repository, i.e., DRYAD. The Frieswal crossbred cattle along with ancestral breeds like Holstein–Friesian and Sahiwal were also investigated for the level of admixture with the help of the above-mentioned software. The Frieswal population was found to comprise an average of 62.49, 61.12, and 61.21% of Holstein–Friesian and 37.50, 38.88, and 38.80% of Sahiwal estimated through STRUCTURE, ADMIXTURE, and frappe, respectively. The Vrindavani population was found to consist of on average 39.5, 42.4, and 42.3% of Holstein–Friesian; 22.9, 22.3, and 21.7% of Jersey; 10.7, 10.6, and 11.9% of Brown Swiss; and 26.9, 24.7, and 24.1% of Hariana blood estimated through STRUCTURE, ADMIXTURE, and frappe, respectively. A greater degree of variation was noted in the results from STRUCTURE vs. frappe, STRUCTURE vs. ADMIXTURE than in ADMIXTURE vs. frappe. From this study, we conclude that the admixture analysis based on a single software should be validated through the use of many different approaches for better prediction of admixture levels.

The present study was undertaken to evaluate the effect of kaempferol in isoprenaline (ISP)-induced myocardial injury in rats. ISP was administered subcutaneously for two subsequent days to induce myocardial injury. Assessment of myocardial injury was done by estimation of hemodynamic functions, myocardial infarcted area, cardiac injury markers, lipid profile, oxidative stress, pro-inflammatory cytokines and histopathology of heart and liver. Rats pretreated with kaempferol showed reduction in the myocardial infarcted area and heart rate. However, no improvement was observed in change in body weight, mean arterial, systolic and diastolic blood pressure. Kaempferol showed significant decrease in serum LDH, CK-MB, troponin-I and lipid profile. However, highest dose of kaempferol did not reduce the serum triglyceride level. Further, antioxidant enzymes, SOD and catalase, were also higher. However, reduced glutathione, serum SGOT and creatinine did not show any improvement. Kaempferol showed reduction in MDA level. Kaempferol at highest dose showed reduction in pro-MMP-2 expression and MMP-9 level. mRNA expression level of TNF-α was not different in kaempferol-pretreated myocardial injured rats with ISP-alone group. Pretreatment with kaempferol at highest dose showed mild mononuclear infiltration and degenerative changes in heart tissue section of myocardial injured rats. Rats pretreated with kaempferol at higher concentration showed normal cordlike arrangement of hepatocytes with moderate swelling of hepatocytes (vacuolar degeneration) around the central vein. Study suggests that kaempferol attenuated lipid profile, infarcted area and oxidative stress in ISP-induced myocardial injury in rats.

The incidence of infections caused by Candida species, specifically by drug-resistant isolates, is a major health concern as they can disseminate to and colonize most vital organs, enhancing morbidity and mortality. Several molecular mechanisms have been reported to be involved in drug resistance. These are mostly drug- and isolate-specific. Here, we characterized three different genetically modified strains of C. albicans that were multi-drug-resistant (MDR) and deciphered a uniform mechanism responsible for resistance. DNA polymerase epsilon (Polε) is a leading strand-specific polymerase consisting of four subunits, namely, Pol2, Dpb2, Dpb3, and Dpb4. The deletion of one or both of the Dpb3 and Dpb4 subunits in C. albicans rendered multi-drug resistance. A detailed characterization of these strains revealed that acquired mutagenesis, drug efflux pumps, and other known mechanisms did not play a significant role because the complemented strain showed drug sensitivity. More importantly, the function of heat shock protein 90 (Hsp90) in these knockout strains is critical for reducing susceptibility to several antifungal drugs. Cell wall deformity and composition in these strains can add to such a phenotype. The inhibition of Hsp90 function by geldanamycin and tricostatin A sensitized the MDR strains to antifungals. Considering our earlier research and this report, we suggest that replication stress induces Hsp90 expression and activity in order to orchestrate a cellular stress response circuit and thus develop fungal drug resistance. Thus, Hsp90 is an important drug target for use in combinatorial therapy.

Systemic candidiasis inflicts ~1.2 million deaths annually worldwide. Despite its severity, an approved antifungal vaccine remains an unmet human need. In a quest to design a live-whole cell vaccine, we characterized and demonstrated the vaccine potential of two dual DNA polymerase-defective strains of Candida albicans . While the deletion of POL32 in a hyper-virulent rad30 ΔΔ strain attenuated the virulence, the deletion of RAD30 in an avirulent pol32 ΔΔ did not revert to a hypervirulence phenotype. Both the dual polymerase-defective strains replicate transiently in the host and trigger immune responses to prevent reinfections in mice by employing a concerted involvement of innate, adaptive, and trained immunity. The cellular and molecular depletion in immunized mice suggested the role of B- and T-cells, neutrophils, and macrophages in antifungal immunity. Altogether, our results confirmed that Pol32 is a true virulence factor and intravenous vaccination with these attenuated strains could prevent systemic candidiasis in the preclinical models without evident safety concerns; thus, these candidate strains have enormous translational potential to fully develop as antifungal vaccines.

With more and more Single Nucleotide Polymorphisms (SNPs) being identified throughout the genome, some of those SNPs will be found to be located within candidate genes, allowing the researchers to use the candidate gene approach on a genomewide scale. SNPs have some drawbacks but when compared to other markers they are more efficient and SNP consortium is growing to meet the requirements of genome-wide scans. Genomic selection should be able to at least double the rate of genetic gain in the dairy industry but the incorporation of genomic information into the breeding programs must be carefully considered. One needs to have around 2000 genotypes means a large reference population (population with both phenotype and genotype recorded) to achieve meaningful increases in accuracy. The available information, selection objectives, production circumstances and benefit/cost analysis must be evaluated in order to decide whether or not the population is suitable for GS implementation, and which would be the most convenient way, if any, for its implementation. Animal breeders will need to lead the way on the integration of genomic and phenotypic data into a new era of genome-enabled animal improvement and management. Keywords: Breeding practice, Domestic Animals, DNA, Genome

The main objective of the current research was to locate, annotate, and highlight specific areas of the bovine genome that are undergoing intense positive selection. Here, we are analyzing selection signatures in crossbred (Bos taurus X Bos indicus), taurine (Bos taurus), and indicine (Bos indicus) cattle breeds. Indicine cattle breeds found throughout India are known for their higher heat tolerance and disease resilience. More breeds and more methods can provide a better understanding of the selection signature. So, we have worked on nine distinct cattle breeds utilizing seven different summary statistics, which is a fairly extensive approach. In this study, we carried out a thorough genome-wide investigation of selection signatures using bovine 50K SNP data. We have included the genotyped data of two taurine, two crossbreds, and five indicine cattle breeds, for a total of 320 animals. During the 1950s, these indicine (cebuine) cattle breeds were exported with the aim of enhancing the resilience of taurine breeds in Western countries. For this study, we employed seven summary statistics, including intra-population, i.e., Tajima’s D, CLR, iHS, and ROH and inter-population statistics, i.e., FST, XP-EHH, and Rsb. The NCBI database, PANTHER 17.0, and CattleQTL database were used for annotation after finding the important areas under selection. Some genes, including EPHA6, CTNNA2, NPFFR2, HS6ST3, NPR3, KCNIP4, LIPK, SDCBP, CYP7A1, NSMAF, UBXN2B, UGDH, UBE2K, and DAB1, were shown to be shared by three or more different approaches. Therefore, it gives evidence of the most intense selection in these areas. These genes are mostly linked to milk production and adaptability traits. This study also reveals selection regions that contain genes which are crucial to numerous biological functions, including those associated with milk production, coat color, glucose metabolism, oxidative stress response, immunity and circadian rhythms.

Background Endoplasmic reticulum (ER) stress plays an important role in the development of chronic kidney disease (CKD). Sigma-1 receptors (σ1Rs) are novel chaperone proteins that regulate ER stress. However, effect of σ1R activation on renal ER stress is yet unexplored. So, in the present study we investigated the effects of PRE-084, a σ1R agonist on renal injury and ER stress in the rat model of CKD. Methods CKD group rats were fed adenine for 28 days and CKD treatment group rats were additionally administered PRE-084 intraperitoneally at 1, 3 and 10 mg/kg body weight dose from Day 22–28. ER stress markers were evaluated using molecular biology techniques such as immunohistochemistry and Western blot. Results Marked kidney injury was observed in CKD rats as revealed by biochemical and histological findings. Expression of ER stress proteins such as phosphorylated protein kinase R-like ER kinase (p-PERK), cleaved activating transcription factor-6 (ATF-6f), phosphorylated inositol requiring enzyme1α (p-IRE1α) and caspase-12 were higher in CKD rats. Nevertheless, CKD rats treated with PRE-084 particularly at 10 mg/kg dose showed considerably lesser kidney injury along with higher expression of σ1R and marked reduction of all the ER stress proteins studied. Conclusion Results reveal that PRE-084 likely ameliorated the adenine-induced kidney injury by lowering ER stress through increased σ1R expression.

This study seeks a comprehensive exploration of genome-wide selective processes impacting morphometric traits across diverse cattle breeds, utilizing an array of statistical methods. Morphometric traits, encompassing both qualitative and quantitative variables, play a pivotal role in characterizing and selecting livestock breeds based on their external appearance, size, and physical attributes. While qualitative traits, such as color, horn structure, and coat type, contribute to adaptive features and breed identification, quantitative traits like body weight and conformation measurements bear a closer correlation with production characteristics. This study employs advanced genotyping technologies, including the Illumina BovineSNP50 Bead Chip and next-generation sequencing methods like Reduced Representation sequencing, to identify genomic signatures associated with these traits. We applied four intra-population methods to find evidence of selection, such as Tajima’s D, CLR, iHS, and ROH. We found a total of 40 genes under the selection signature, that were associated with morphometric traits in five cattle breeds (Kankrej, Tharparkar, Nelore, Sahiwal, and Gir). Crucial genes such as ADIPDQ, DPP6, INSIG1, SLC35D2 in Kankrej, LPL, ATP6V1B2, CDC14B in Tharparkar, HPSE2, PLAG1 in Nelore, PCSK1, PRKD1 in Sahiwal, and GNAQ, HPCAL1 in Gir were identified in our study. This approach provides valuable insights into the genetic basis of variations in body weight and conformation traits, facilitating informed selection processes and offering a deeper understanding of the evolutionary and domestication processes in diverse cattle breeds.

Nanobiotechnology is an emerging field that is potentially changing the way we treat diseases through drug delivery and tissue engineering. Methods of targeting nanoparticles to specific sites of the body while avoiding capture by vital organs are major hurdles that need to be answered. Whether actual or perceived, the potential health hazards associated with the production, distribution and use of nanomaterial must be balanced by the overall benefit that nanobiotech-nology has to offer biomedical science such as therapeutic and diagnostic applications. It would be difficult to deny the potential benefits of nanobiotechnology and stop development of research related to it since it has already begun to penetrate many different fields of research. However, nanobiotechnology can be developed using guidelines to insure that the technology does not become too potentially harmful. As Richard Feynmann has rightly predicted that \"There is plenty of room at the bottom\" to modify and enhance existing technologies by manipulating material properties at the nanoscale, therefore with sufficient time and research nanobiotechnology based early detection, diagnosis and treatment of various diseases may become a reality. Nanobiotechnology may bring immense paradigm shift that we would wonder that how did we live without it?

Betulinic acid (BA) exhibits many biological effects including anti-inflammatory and anti-oxidant activities. Free radicals and pro-inflammatory mediators play an important role in the pathology of inflammatory bowel disease (IBD) and associated pain. We, therefore, examined the anti-oxidant, anti-inflammatory, and anti-nociceptive potential of BA in colitis. Colitis was induced with 3% (w/v) dextran sulfate sodium (DSS) in drinking water in mice for 1to7 days. BA (3, 10 and 30 mg/kg) was given orally for 0 to 7 days. BA was also tested for its efficacy in acetic acid and mustard oil-induced visceral nociception in mice at same doses. BA significantly prevented diarrhea; bleeding and colonic pathological changes induced by DSS. Further, BA reduced the colon nitrite, malondialdehyde, myeloperoxidase, and lipid hydroperoxide levels and restored the superoxide dismutase, catalase and reduced glutathione levels to normalize the redox balance in DSS-exposed mice. Inflammatory mediators like matrix metalloproteinase-9 and prostaglandin E2 levels were also significantly attenuated by BA in colitis mice. Additionally, BA reduced acetic acid and mustard oil-induced visceral pain in mice. In conclusion, the results of the present study suggest that BA possesses good anti-nociceptive activity and the anti-IBD effects of BA are due to its anti-oxidant and anti-inflammatory potential.