Effects of poly (ADP-ribose) polymerase inhibitor treatment on the repair process of ischemic acute kidney injury.

Excessive activation of poly (ADP-ribose) polymerase (PARP) contributes to ischemic acute kidney injury (AKI). PARP inhibition has been shown to be beneficial in renal ischemia-reperfusion injury (IRI) in the early phase, but its role in the repair process remains unclear. The effects of JPI-289, a novel PARP inhibitor, during the healing phase after renal IRI were investigated. IRI was performed on 9-week-old male C57BL/6 mice. Saline or JPI-289 100 mg/kg was intraperitoneally administered once at 24 h or additionally at 48 h after IRI. Hypoxic HK-2 cells were treated with JPI-289. Renal function and fibrosis extent were comparable between groups. JPI-289 treatment caused more prominent tubular atrophy and proinflammatory intrarenal leukocyte phenotypes and cytokines/chemokines changes at 12 weeks after unilateral IRI. JPI-289 treatment enhanced gene expressions associated with collagen formation, toll-like receptors, and the immune system in proximal tubules and endothelial cells after IRI. JPI-289 treatment at 3 or 6 h after hypoxia facilitated proliferation of hypoxic HK-2 cells, whereas further treatment after 24 h suppressed proliferation. Delayed inhibition of PARP after renal IRI did not facilitate the repair process during the early healing phase but rather may aggravate renal tubular atrophy during the late healing phase in ischemic AKI.

Enhanced Symbiotic Characteristics in Bacterial Genomes with the Disruption of rRNA Operon.

Ribosomal RNA is an indispensable molecule in living organisms that plays an essential role in protein synthesis. Especially in bacteria, 16S, 23S, and 5S rRNAs are usually co-transcribed as operons. Despite the positive effects of rRNA co-transcription on growth and reproduction rate, a recent study revealed that bacteria with unlinked rRNA operons are more widespread than expected. However, it is still unclear why the rRNA operon is broken. Here, we explored rRNA operon linkage status in 15,898 bacterial genomes and investigated whether they have common features or lifestyles; 574 genomes were found to have unlinked rRNA operons and tended to be phylogenetically conserved. Most of them were symbionts and showed enhanced symbiotic genomic features such as reduced genome size and high adenine-thymine (AT) content. In an eggNOG-mapper analysis, they were also found to have significantly fewer genes than rRNA operon-linked bacteria in the "transcription" and "energy production and conversion in metabolism" categories. These genomes also tend to decrease RNases related to the synthesis of ribosomes and tRNA processing. Based on these results, the disruption of the rRNA operon seems to be one of the tendencies associated with the characteristics of bacteria requiring a low dynamic range.

Complete Genome of Lactobacillus iners KY Using Flongle Provides Insight Into the Genetic Background of Optimal Adaption to Vaginal Econiche.

Despite the importance of Lactobacillus iners and its unique characteristics for the study of vaginal adaption, its genome and genomic researches for identifying molecular backgrounds of these specific phenotypes are still limited. In this study, the first complete genome of L. iners was constructed using a cost-effective long-read sequencing platform, Flongle from Oxford Nanopore, and comparative genome analysis was conducted using a total of 1,046 strain genomes from 10 vaginal Lactobacillus species. Single-molecule sequencing using Flongle effectively resolved the limitation of the 2nd generation sequencing technologies in dealing with genomic regions of high GC contents, and comparative genome analysis identified three potential core genes (INY, ZnuA, and hsdR) of L. iners which was related to its specific adaption to the vaginal environment. In addition, we performed comparative prophage analysis for 1,046 strain genomes to further identify the species specificity. The number of prophages in L. iners genomes was significantly smaller than other vaginal Lactobacillus species, and one of the specific genes (hsdR) was suggested as the means for defense against bacteriophage. The first complete genome of L. iners and the three specific genes identified in this study will provide useful resources to further expand our knowledge of L. iners and its specific adaption to the vaginal econiche.

Origin and spread of Thoroughbred racehorses inferred from complete mitochondrial genome sequences: Phylogenomic and Bayesian coalescent perspectives.

The Thoroughbred horse breed was developed primarily for racing, and has a significant contribution to the qualitative improvement of many other horse breeds. Despite the importance of Thoroughbred racehorses in historical, cultural, and economical viewpoints, there was no temporal and spatial dynamics of them using the mitogenome sequences. To explore this topic, the complete mitochondrial genome sequences of 14 Thoroughbreds and two Przewalski's horses were determined. These sequences were analyzed together along with 151 previously published horse mitochondrial genomes from a range of breeds across the globe using a Bayesian coalescent approach as well as Bayesian inference and maximum likelihood methods. The racing horses were revealed to have multiple maternal origins and to be closely related to horses from one Asian, two Middle Eastern, and five European breeds. Thoroughbred horse breed was not directly related to the Przewalski's horse which has been regarded as the closest taxon to the all domestic horses and the only true wild horse species left in the world. Our phylogenomic analyses also supported that there was no apparent correlation between geographic origin or breed and the evolution of global horses. The most recent common ancestor of the Thoroughbreds lived approximately 8,100-111,500 years ago, which was significantly younger than the most recent common ancestor of modern horses (0.7286 My). Bayesian skyline plot revealed that the population expansion of modern horses, including Thoroughbreds, occurred approximately 5,500-11,000 years ago, which coincide with the start of domestication. This is the first phylogenomic study on the Thoroughbred racehorse in association with its spatio-temporal dynamics. The database and genetic history information of Thoroughbred mitogenomes obtained from the present study provide useful information for future horse improvement projects, as well as for the study of horse genomics, conservation, and in association with its geographical distribution.

Selective pressure on the protein-coding genes of the pufferfish is correlated with phenotypic traits.

The pufferfish accumulates neurotoxic tetrodotoxin in its body and inflates by filling its stomach with water. These traits are unique to this species, and may be a result of adaptation post-divergence of Tetraodontidae. However, evolution of the protein-coding genes in the pufferfish has not yet been well elucidated. Detection of positive selection on these genes can help us understand the mechanisms associated with functional evolution. We downloaded well-annotated gene information of two pufferfish species, Takifugu rubripes and Tetraodon nigroviridis, from the public ENSEMBL database. In order to detect selective pressure on protein-coding sequences, we performed dN/dS estimation using codeml within the PAML software package. We selected one to one orthologous genes among seven fish species (Gasterosteus aculeatus, Oryzias latipes, Poecilia formosa, Takifugu rubripes, Tetraodon nigroviridis, and Xiphophorus maculatus). Results of dN/dS analysis on orthologous genes indicate that pufferfish showed high non-synonymous substitution rate for positively selected genes, and the evolutionary rate was faster during the diversification of two pufferfishes after divergence. Additionally, a candidate mechanism for regulation of neuro-toxicity of tetrodotoxin was identified from functional annotation of positively selected genes. These results support positive selection on protein-coding genes of the pufferfish with the acquisition of specific phenotypic traits.

Effects of road transportation on metabolic and immunological responses in Holstein heifers.

This study examined the effects of road transportation on metabolic and immunological responses in dairy heifers. Twenty Holstein heifers in early pregnancy were divided into non-transported (NT; n = 7) and transported (T; n = 13) groups. Blood was collected before transportation (BT), immediately after transportation for 100 km (T1) and 200 km (T2), and 24 h after transportation (AT). The T heifers had higher (P < 0.05) blood cortisol and non-esterified fatty acid concentrations after T1 and T2 than did NT heifers. By contrast, the T heifers had lower (P < 0.05) serum triglyceride concentrations after T1 and T2 than had the NT heifers. The serum cortisol and triglyceride concentrations returned (P > 0.05) to the BT concentrations at 24 h AT in the T heifers. The granulocyte-to-lymphocyte ratio and the percentage of monocytes were higher (P < 0.05) after T2 in the T heifers than in the NT heifers, suggesting that transportation stress increased the numbers of innate immune cells. T heifers had higher (P < 0.01) plasma haptoglobin concentrations than NT heifers 24 h AT. In conclusion, transportation increased cortisol secretion and was correlated with increased metabolic responses and up-regulation of peripheral innate immune cells in dairy heifers.

Gut microbiota Modulated by Probiotics and Garcinia cambogia Extract Correlate with Weight Gain and Adipocyte Sizes in High Fat-Fed Mice.

Results of recent studies on gut microbiota have suggested that obesogenic bacteria exacerbate obesity and metabolic dysfunction in the host when fed a high fat diet (HFD). In order to explore obesity-associated bacterial candidates and their response to diet, the composition of faecal bacterial communities was investigated by analyzing 16S rRNA gene sequences in mice. Dietary intervention with probiotics and Garcinia cambogia extract attenuated weight gain and adipocyte size in HFD-fed mice. To identify obesity-causative microbiota, two statistical analyses were performed. Forty-eight bacterial species were found to overlap between the two analyses, indicating the commonly identified species as diet-driven and obesity-associated, which would make them strong candidates for host-microbiome interaction on obesity. Finally, correlation based network analysis between diet, microbe, and host revealed that Clostridium aminophilum, a hyper-ammonia-producing bacterium, was highly correlated with obesity phenotypes and other associated bacteria, and shown to be suppressed by the combination of probiotics and Garcinia cambogia extract. Results of the present study suggest that probiotics and Garcinia cambogia extract alleviate weight gain and adiposity, in part via differentially modulating the composition of gut microbiota in HFD fed mice.

Status of dosage compensation of X chromosome in bovine genome.

Dosage compensation system with X chromosome upregulation and inactivation have evolved to overcome the genetic imbalance between sex chromosomes in both male and female of mammals. Although recent development of chromosome-wide technologies has allowed us to test X upregulation, discrete data processing and analysis methods draw disparate conclusions. A series of expression studies revealed status of dosage compensation in some species belonging to monotremes, marsupials, rodents and primates. However, X upregulation in the Artiodactyla order including cattle have not been studied yet. In this study, we surveyed the genome-wide transcriptional upregulation in X chromosome in cattle RNA-seq data using different gene filtration methods. Overall examination of RNA-seq data revealed that X chromosome in the pituitary gland expressed more genes than in other peripheral tissues, which was consistent with the previous results observed in human and mouse. When analyzed with globally expressed genes, a median X:A expression ratio was 0.94. The ratio of 1-to-1 ortholog genes between chicken and mammals, however, showed considerable reduction to 0.68. These results indicate that status of dosage compensation for cattle is not deviated from those found in rodents and primate, and this is consistent with the evolutionary history of cattle.

Differential Evolution between Monotocous and Polytocous Species.

One of the most important traits for both animal science and livestock production is the number of offspring for a species. This study was performed to identify differentially evolved genes and their distinct functions that influence the number of offspring at birth by comparative analysis of eight monotocous mammals and seven polytocous mammals in a number of scopes: specific amino acid substitution with site-wise adaptive evolution, gene expansion and specific orthologous group. The mutually exclusive amino acid substitution among the 16 mammalian species identified five candidate genes. These genes were both directly and indirectly related to ovulation. Furthermore, in monotocous mammals, the EPH gene family was found to have undergone expansion. Previously, the EPHA4 gene was found to positively affect litter size in pigs and supports the possibility of the EPH gene playing a role in determining the number of offspring per birth. The identified genes in this study offer a basis from which the differences between monotocous and polytocous species can be studied. Furthermore, these genes may harbor some clues to the underlying mechanism, which determines litter size and may prove useful for livestock breeding strategies.

Peeling back the evolutionary layers of molecular mechanisms responsive to exercise-stress in the skeletal muscle of the racing horse.

The modern horse (Equus caballus) is the product of over 50 million yrs of evolution. The athletic abilities of the horse have been enhanced during the past 6000 yrs under domestication. Therefore, the horse serves as a valuable model to understand the physiology and molecular mechanisms of adaptive responses to exercise. The structure and function of skeletal muscle show remarkable plasticity to the physical and metabolic challenges following exercise. Here, we reveal an evolutionary layer of responsiveness to exercise-stress in the skeletal muscle of the racing horse. We analysed differentially expressed genes and their co-expression networks in a large-scale RNA-sequence dataset comparing expression before and after exercise. By estimating genome-wide dN/dS ratios using six mammalian genomes, and FST and iHS using re-sequencing data derived from 20 horses, we were able to peel back the evolutionary layers of adaptations to exercise-stress in the horse. We found that the oldest and thickest layer (dN/dS) consists of system-wide tissue and organ adaptations. We further find that, during the period of horse domestication, the older layer (FST) is mainly responsible for adaptations to inflammation and energy metabolism, and the most recent layer (iHS) for neurological system process, cell adhesion, and proteolysis.

Analyses of pig genomes provide insight into porcine demography and evolution.

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.