Shifts in the gut microbiota of mice in response to dexamethasone administration.

Glucocorticoids (GCs) are an important anti-inflammatory drug, used widely, regardless of its side effects. GCs can affect intestinal flora directly or indirectly, though few studies have focused on the changes of gut microbiota composition. In this study, ICR mice were randomly divided into three groups, gavage administration with saline, and different doses of dexamethasone (DEX): 0.1 mg/kg and 1 mg/kg. Five days later, the microbial diversity of the colon contents was analyzed. A significant loss in weight was observed in the DEX1.0 group as compared with the control group (P = 0.011). The gut microbiota richness (ACE, P = 0.01; Chao, P = 0.013) and diversity (Shannon, P = 0.035; Simpson, P = 0.032) were decreased in DEX group. The proportions of genus Butyricicoccus, Oscillibacter, Anaerotruncus, Ruminiclostridium, Ruminococcaceae, and Lachnospiraceae were the most abundant and predominant followed by Lactobacillus, Pseudomonas, and Enterorhabdus. Dex administration led to changes in the liver/body ratio and spleen/body ratio. The results obtained from our study indicate that DEX can decrease the level of WBC and change the structure of the gut microbiota composition; moreover, the results of this study provide new insight into alleviating the clinical side effects of GC therapy.

Rapid functional divergence after small-scale gene duplication in grasses.

BACKGROUND: Gene duplication has played an important role in the evolution and domestication of flowering plants. Yet little is known about how plant duplicate genes evolve and are retained over long timescales, particularly those arising from small-scale duplication (SSD) rather than whole-genome duplication (WGD) events. RESULTS: We address this question in the Poaceae (grass) family by analyzing gene expression data from nine tissues of Brachypodium distachyon, Oryza sativa japonica (rice), and Sorghum bicolor (sorghum). Consistent with theoretical predictions, expression profiles of most grass genes are conserved after SSD, suggesting that functional conservation is the primary outcome of SSD in grasses. However, we also uncover support for widespread functional divergence, much of which occurs asymmetrically via the process of neofunctionalization. Moreover, neofunctionalization preferentially targets younger (child) duplicate gene copies, is associated with RNA-mediated duplication, and occurs quickly after duplication. Further analysis reveals that functional divergence of SSD-derived genes is positively correlated with both sequence divergence and tissue specificity in all three grass species, and particularly with anther expression in B. distachyon. CONCLUSIONS: Our results suggest that SSD-derived grass genes often undergo rapid functional divergence that may be driven by natural selection on male-specific phenotypes. These observations are consistent with those in several animal species, suggesting that duplicate genes take similar evolutionary trajectories in plants and animals.

Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion.

The origin of feathers is an important question in Evo-Devo studies, with the eventual evolution of vaned feathers which are aerodynamic, allowing feathered dinosaurs and early birds to fly and venture into new ecological niches. Studying how feathers and scales are developmentally specified provides insight into how a new organ may evolve. We identified feather-associated genes using genomic analyses. The candidate genes were tested by expressing them in chicken and alligator scale forming regions. Ectopic expression of these genes induced intermediate morphotypes between scales and feathers which revealed several major morphogenetic events along this path: Localized growth zone formation, follicle invagination, epithelial branching, feather keratin differentiation, and dermal papilla formation. In addition to molecules known to induce feathers on scales (retinoic acid, ß-catenin), we identified novel scale-feather converters (Sox2, Zic1, Grem1, Spry2, Sox18) which induce one or more regulatory modules guiding these morphogenetic events. Some morphotypes resemble filamentous appendages found in feathered dinosaur fossils, whereas others exhibit characteristics of modern avian feathers. We propose these morpho-regulatory modules were used to diversify archosaur scales and to initiate feather evolution. The regulatory combination and hierarchical integration may have led to the formation of extant feather forms. Our study highlights the importance of integrating discoveries between developmental biology and paleontology.

Crude fiber modulates the fecal microbiome and steroid hormones in pregnant Meishan sows.

The beneficial effects of dietary fiber on the reproductive performance and welfare of sows have been discussed broadly, but few researches examined the causal changes and the association of gut microbiota and the steroid hormones, the main regulators of reproductive function. To shed light on this, thirty-six Meishan sows were allocated into 2.5% crude fiber (CF) group and 7.5% CF group respectively for an entire farrowing interval. On the 90th day of gestation, the saliva and fresh stool of sows were individually collected in the morning (06:00-07:00) for steroid hormones, short-chain fatty acids (SCFAs) and microbiome analysis. In addition, the parameter of pregnant behavioral and farrowing performance was recorded and evaluated. We observed that, as compared with the 2.5% CF treatment, 7.5% CF significantly increased the litter size (p = 0.01), reduced the stereotypic behaviors including sham chewing, rolling tongue and licking ground (p = 0.02, 0.04, 0.01) at later gestation stage, but increased lying time (p = 0.00). In coincide with this, 7.5% CF diet increased the salivary progesterone (p = 0.00), fecal estradiol and progesterone (p = 0.01, 0.02) level, fecal water and SCFAs content (p = 0.02, 0.03), decreased the salivary and fecal cortisol (p = 0.01, 0.00) level. Further, 7.5% CF diet increased the fecal microbiota richness (ACE, p = 0.04; Chao, p = 0.07) and diversity (Shannon, p = 0.01; Simpson, p = 0.04), the proportion of genus Ruminococcus, Butyrivibrio, Lactobacillus and Fibrobacter (p = 0.02, 0.05, 0.04, 0.00), whereas reduced the proportion of genus Clostridium, Streptococcus, Bacteroides and Escherichia-Shigella (p = 0.00, 0.00, 0.04, 0.04). These results indicate that, fibrous diet can regulate the steroid hormones secretion and modulate the gut with more cellulose-degrading and probiotic bacterium, but less opportunistic pathogens, and this may contribute to the improvement of reproductive performance and welfare in sows.

Natural Selection Drives Rapid Functional Evolution of Young Drosophila Duplicate Genes.

Gene duplication is thought to play a major role in phenotypic evolution. Yet the forces involved in the functional divergence of young duplicate genes remain unclear. Here, we use population-genetic inference to elucidate the role of natural selection in the functional evolution of young duplicate genes in Drosophila melanogaster. We find that negative selection acts on young duplicates with ancestral functions, and positive selection on those with novel functions, suggesting that natural selection may determine whether and how young duplicate genes are retained. Moreover, evidence of natural selection is strongest in protein-coding regions and 3' UTRs of young duplicates, indicating that selection may primarily target encoded proteins and regulatory sequences specific to 3' UTRs. Further analysis reveals that natural selection acts immediately after duplication and weakens over time, possibly explaining the observed bias toward the acquisition of new functions by young, rather than old, duplicate gene copies. Last, we find an enrichment of testis-related functions in young duplicates that underwent recent positive selection, but not in young duplicates that did not undergo recent positive selection, or in old duplicates that either did or did not undergo recent positive selection. Thus, our findings reveal that natural selection is a key player in the functional evolution of young duplicate genes, acts rapidly and in a region-specific manner, and may underlie the origin of novel testis-specific phenotypes in Drosophila.

AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress.

Drug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins.

miR-16 promotes the apoptosis of human cancer cells by targeting FEAT.

BACKGROUND: Although human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers. One such gene, FEAT (faint expression in normal tissues, aberrant overexpression in tumors), is uniformly overexpressed in a variety of human cancers and plays an important role in tumorigenesis by suppressing apoptosis. However, the precise molecular mechanism through which FEAT is upregulated during tumorigenesis remains largely unknown. METHODS: In this study, we used bioinformatic analyses to search for miRNAs that potentially target FEAT. We examined the expression of FEAT protein level by western blotting and miR-16 level by qRT-PCR assay. Cancer cell lines (A549, MCF-7 and Huh-7) with miR-16 upregulation and FEAT silencing were established and the effects on apoptosis of cancer cells in vitro were assessed. Luciferase reporter assay was also performed to investigate the interaction between miR-16 and FEAT. RESULTS: We identified a specific target site for miR-16 in the 3'-untranslated region (3'-UTR) of FEAT. Consistent with the bioinformatic analyses, we identified an inverse correlation between the miR-16 and FEAT protein levels in lung cancer, breast cancer, and hepatocellular cancer tissues. We then experimentally validated miR-16 as a direct regulator of FEAT using cell transfection and luciferase assays. Finally, we demonstrated that the repression of FEAT by miR-16 promoted the apoptosis of cancer cells. CONCLUSIONS: Our findings provide the first clues regarding the role of miR-16 as a tumor suppressor in cancer cells through the inhibition of FEAT translation.

Effect of Day Length on Growth and Gonadal Development in Meishan Male Pigs.

Day length is a critical environmental factor for regulating animal growth and development. This study aimed to investigate the effects of different day lengths on the developmental changes of growth parameters, testicular sizes, testosterone secretion in Meishan male pigs, and steroidogenesis proteins and melatonin receptors. Fourteen Meishan male pigs (10 weeks (wks) of age) with the same parity, paired in litter and body weight (BW), were evenly allocated into a short-day-length group (SDL, 10 light/14 dark) and long-day-length group (LDL, 14 light/10 dark). After 12 wks of the experiment, the LDL-treated boars had more lying time and less exploring time. The LDL treatment led to significant increases in body height, chest circumference, testicular length, testicular weight, crude protein digestibility, and fecal testosterone at the 10th and 12th wks of the experiment, and cortisol at the 10th wk, compared to the SDL treatment, with no differences in the final BW, testicular width, and epididymis weight. Furthermore, the LDL treatment significantly increased the protein levels of melatonin receptor 1b (MT2), aromatase (CYP19), and steroidogenic factor 1 (SF1) in the testis, with no differences in the protein levels of melatonin receptor 1a (MT1), steroidogenic acute regulatory (StAR), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), and cholesterol side-chain cleavage enzyme (P450scc). The present study suggests that day length has an effect on the growth and gonadal development in male pigs maybe via MT2 and influences steroid synthesis and secretion in the testis. Therefore, proper day length should be considered in male pig breeding.

The identification of novel targets of miR-16 and characterization of their biological functions in cancer cells.

BACKGROUND: In eukaryotes, miR-16 is an important microRNA (miRNA) that is involved in numerous biological processes. However, it is not fully understood how miR-16 executes its physiological functions. In the present study, we aimed to identify novel miR-16 targets and study their biological functions. METHODS: Candidate target genes of miR-16 were screened by microarray analysis of mRNA levels in several cancer cell lines with enhanced miR-16. Three bioinformatics algorithms, including TargetScan, PicTar, and miRanda, were used in combination to calculate the miR-16 targets. The expression levels of miR-16 and target mRNA were examined by relative quantification RT-PCR, and the expression levels of target protein were detected by Western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. The effect of miR-16 and target gene on cell viability was evaluated using MTT assays. The effects of miR-16 and target gene on apoptosis and cell cycle distribution were evaluated by flow cytometry analysis. RESULTS: By overexpressing miR-16 in several cancer cell lines and measuring global mRNA levels using microarray analysis, we identified 27 genes that may be regulated by miR-16. After the bioinformatics filtering process, 18 genes were selected as candidate miR-16 targets. Furthermore, we experimentally validated three of these candidates, MAP7 (microtubule-associated protein 7), PRDM4 (PR domain containing 4) and CDS2 (CDP-diacylglycerol synthase 2), as direct targets of miR-16. Finally, we demonstrated that miR-16 targeting MAP7 played a critical role in regulating proliferation but not apoptosis and cell cycle progression in cancer cells. CONCLUSION: In summary, the present study identifies several novel miR-16 targets and illustrates a novel function of miR-16 targeting MAP7 in modulating proliferation in cancer cells.

Modification of Inclusions by Rare Earth Elements in a High-Strength Oil Casing Steel for Improved Sulfur Resistance.

Steel casing pipes used in the construction of deep oil wells usually require both high strength and corrosion-resistant behavior. Due to the exploration of deep H2S-bearing oil reservoirs, sulfide stress cracking (SSC) is becoming an increasingly serious concern for casing steel. The nonmetallic inclusions in the steel are among the key reasons for its service failure. The rare earth element Ce can be used to modify the inclusions in casing steel and improve its SSC resistance. Here, taking C110 grade casing steel (the highest class currently in service) as the investigated object, the modification behavior of Ce inclusions in the steel and the effect of the addition of Ce in varying amounts (0.01, 0.024, and 0.042 wt.%) on the modified products were studied through high-temperature tube furnace experiments and thermodynamic calculations. The results showed that Ce had an obvious modification effect on the CaO·Al2O3 inclusions in casing steel, and the diffusion of dissolved Ce in the steel was the limiting step of the modification reaction. With the extension of reaction time, the sequence describing the modification of inclusions in the steel was determined as follows: CaO·Al2O3 → CeAlO3 → Ce2O3/Ce2O2S. The final stable product after modification depended on the amount of Ce added. With 0.01 wt.% Ce, the stable phase in molten steel was Ce2O3; on the other hand, upon adding ≥0.024 wt.% Ce, the stable phase became Ce2O2S. In addition, the thermodynamic stability of Ce2O3 decreased, and it was transformed into CeAlO3, Ce2O2S, Ce2S3, and CeS during solidification. On the basis of our results and the considerations for smooth casting, the addition of a proper amount of a rare earth element is suggested for industrial trials, following the achievement of a significant and surprising improvement in the qualified rate of SSC resistance for the final steel products. The relevant mechanism is also analyzed.

Comparison of the Microbiome-Metabolome Response to Copper Sulfate and Copper Glycinate in Growing Pigs.

This study aims to compare the fecal microbiome-metabolome response to copper sulfate (CuSO4) and copper glycinate (Cu-Gly) in pigs. Twelve Meishan gilts were allocated into the CuSO4 group and the Cu-Gly group (fed on a basal diet supplemented with 60 mg/kg copper from CuSO4 or Cu-Gly) paired in litter and body weight. After a two-week feeding trial, the Cu-Gly group had a higher copper digestibility, blood hemoglobin, and platelet volume and higher levels of plasma iron and insulin-like growth factor-1 than the CuSO4 group. The Cu-Gly treatment increased the abundance of the Lachnospiraceae family and the genera Lachnospiraceae XPB1014, Corprococcus_3, Anaerorhabdus_furcosa_group, Lachnospiraceae_FCS020_group, and Lachnospiraceae_NK4B4_group and decreased the abundance of the Synergistetes phylum and Peptostreptococcaceae family compared to the CuSO4 treatment. Moreover, the Cu-Gly group had a lower concentration of 20-Oxo-leukotriene E4 and higher concentrations of butyric acid, pentanoic acid, isopentanoic acid, coumarin, and Nb-p-Coumaroyl-tryptamine than the CuSO4 group. The abundance of Synergistetes was positively correlated with the fecal copper content and negatively correlated with the fecal butyric acid content. The abundance of the Lachnospiraceae_XPB1014_group genus was positively correlated with the plasma iron level and fecal contents of coumarin and butyric acid. In conclusion, Cu-Gly and CuSO4 could differentially affect fecal microbiota and metabolites, which partially contributes to the intestinal health of pigs in different manners.

Fecal microbial composition associated with testosterone in the development of Meishan male pigs.

Introduction: The gut microbiota closely relates to host health, whereas the relationship between gut microbiota and testosterone during the development of Meishan male pigs remains unclear. This study investigated the fecal microbiota composition and testosterone level during development in Meishan male pigs. Methods: Fresh fecal samples of 20 healthy Meishan male pigs were individually collected at 10 and 22 weeks (wk) of age for testosterone content detection and bacteria pyrosequencing analysis. Anaerobic culture experiment of fecal bacteria in vitro was performed for bacteria pyrosequencing analysis. Results: The fecal testosterone content increased significantly from 10 weeks (wk) to 22 wk of age (P < 0.05). Meanwhile, the boars at 22 wk had a lower abundance of phylum Bacteroidetes and Proteobacteria, and genus Alloprevotella, Prevotella_1, Prevotellaceae_NK3B31_group, and Streptococcus in the fecal microbiota composition (P < 0.05). but higher proportions of the phylum Actinobacteria, Firmicutes, Kiritimatiellaeota, and Tenericutes, and genus Clostridium_sensu_stricto_1, Muribaculaceae and Terrisporobacter than that at 10 wk (P < 0.05), and the Firmicutes to Bacteroidetes ratio was higher at 22 wk than 10 wk (P < 0.05). Moreover, the fecal testosterone level significantly correlated with the relative abundance of the phylum Actinobacteria, Firmicutes, and Tencuteseri, and genus Alloprevotella, Clostridium_sensu_stricto_1, Muribaculaceae, Prevotella_1 and Streptococcus. Furthermore, the in vitro experiments indicated that the abundance of the phylum Proteobacteria and genus Escherichia-Shigella reduced with the increase of supplemental testosterone level. In contrast, the proportion of Firmicutes phylum increased with additional testosterone levels. Discussion: Testosterone could modulate the microflora structure. Meanwhile, the bacteria could degrade the testosterone in a dose testosterone-dependent manner. These results provide us with new insights into the relationship between the gut microbiome and testosterone and the contributions of the gut microbiome in physiological regulation in response to gonad development.

Melatonin mediates via melatonin receptor 1 in a temperature-dependent manner regulating ATP metabolism and antioxidative enzyme activity of boar spermatozoa in vitro.

Researches indicated that melatonin (MLT) could ameliorate oxidative damage and increase sperm motility for conservation sperms, whereas the underlying mechanism remains unknown. And elucidating this, present study was designed to investigate the energy metabolism of sperm throughout preservation at 17 °C and activating with 37 °C. Herein, semen of ten Landrace boars (16∼18 months of age) were diluted and treated with gradient concentrations of MLT (0 nM, 1 nM, 10 nM, 1 µM, 1 mM and 5 mM), and kept away from light in the incubator of 17 °C for 5 days (preservation), and the sperm motility was evaluated after 37 °C incubation for 10 min (activating). The results showed that 1.0 µM MLT treated-sperms had higher motility than other treatments from the 2nd onward. On the 3rd day 17 °C storage, 1.0 µM MLT significantly decreased the ATP content and the mRNA abundance of mitochondrial DNA encoding genes, including NADH dehydrogenase subunits (NDs) 1-4 and 4L, cytochrome b (CYTB), cytochrome c oxidases (COXs) 1 and 3, ATP synthase 6, but increased the hexokinase activity (HK) and the malondialdehyde (MDA) content compared to that of the control. Whereas after 10 min 37 °C incubation, 1.0 µM MLT increased the ATP content, and the mRNA expressions of ND2 and 4L, CYTB, COX1, ATP6, and the activities of mitochondrial respiratory chain complex I and superoxide dismutase (SOD), but depressed the pyruvate kinase (PK) activity in contrast to that at 17 °C. Furthermore, 1.0 µM MLT treated sperms had a higher MLT receptor 1 (MT1) protein level at 17 °C storage than that after 10 min 37 °C incubation, no changes of the MT2 expression were observed at different temperature. This study suggests that MLT might mediate via MT1 in a temperature-dependent manner regulating sperm ATP generation and antioxidative enzyme activity in vitro.

Acute mesenteric ischemia secondary to oral contraceptive-induced portomesenteric and splenic vein thrombosis: A case report.

BACKGROUND: Mesenteric ischemia represents an uncommon complication of splanchnic vein thrombosis, and it is less infrequently seen in young women using oral contraceptives. Diagnosis is often delayed in the emergency room; thus, surgical intervention may be inevitable and the absence of thrombus regression or collateral circulation may lead to further postoperative ischemia and a fatal outcome. CASE SUMMARY: We report a 28-year-old female patient on oral contraceptives who presented with acute abdominal pain. Her physical examination findings were not consistent with her symptoms of severe pain and abdominal distention. These findings and her abnormal blood tests raised suspicion of acute mesenteric ischemia (AMI) induced by splanchnic vein thrombosis. Contrast-enhanced abdominal computed tomography revealed ischemia of the small intestine with portomesenteric and splenic vein thrombosis (PMSVT). We treated the case promptly by anticoagulation after diagnosis. We then performed delayed segmental bowel resection after thrombus regression and established collateral circulation guided by collaboration with a multidisciplinary team. The patient had an uneventful postoperative course and was discharged 14 d after surgery and took rivaroxaban orally for 6 mo. In subsequent follow-up to date, the patient has not complained of any other discomfort. CONCLUSION: AMI induced by PMSVT should be considered in young women who are taking oral contraceptives and have acute abdominal pain. Prompt anticoagulation followed by surgery is an effective treatment strategy.

Study on a new "One-stop-shop" scan protocol combining brain CT perfusion and head-and-neck CT angiography by using 256-detector CT for stroke patients.

PURPOSE: We sought to evaluate the performance of a new "one-stop-shop" scan protocol combining brain computed tomography perfusion (CTP) and head-and-neck CT angiography (CTA) imaging for acute stroke patients using a 256-detector CT scanner. METHOD: From March to August 2020, 60 patients (30 men and 30 women) aged 22-88 years with suspected acute stroke were enrolled and randomly divided into 2 groups to undergo brain CTP and head-and-neck CTA with a 256-detector CT system. Group A used traditional scan protocol with a separate brain CTP and head-and-neck CT examination that included non-contrast-enhanced and contrast-enhanced acquisitions; group B used the new "one-stop-shop" scan protocol with head-and-neck CTA data inserted into brain CTP scans at the peak time (PT) of the arterial phase. The insertion point of the head-and-neck CTA data was determined by a test bolus. The examination time, contrast dose, radiation dose, and image quality were compared between the groups. RESULTS: The total contrast dose was reduced by 40% in group B compared to group A (60 mL vs. 100 mL). The imaging time was 52.5 ± 2.6 s in group B and 74.9 ± 3.3 s in group A, showing a reduction of approximately 43% in group B. There was no significant difference in image quality both quantitatively and qualitatively between the groups (all P > 0.05). Group B had a slight reduction in dose length product (1139.0 ± 45.3 vs. 1211.6 ± 31.9 mGy·cm, P < 0.001). CONCLUSIONS: The proposed "one-stop-shop" scan protocol combining brain CTP and head-and-neck CTA on a 256-detector CT system can reduce imaging time and contrast dose, without affecting image quality or perfusion results, compared to the traditional protocol of separating the examinations.

Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system.

The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

Population-Specific Genetic and Expression Differentiation in Europeans.

Much of the enormous phenotypic variation observed across human populations is thought to have arisen from events experienced as our ancestors peopled different regions of the world. However, little is known about the genes involved in these population-specific adaptations. Here, we explore this problem by simultaneously examining population-specific genetic and expression differentiation in four human populations. In particular, we derive a branch-based estimator of population-specific differentiation in four populations, and apply this statistic to single-nucleotide polymorphism and RNA-seq data from Italian, British, Finish, and Yoruban populations. As expected, genome-wide estimates of genetic and expression differentiation each independently recapitulate the known relationships among these four human populations, highlighting the utility of our statistic for identifying putative targets of population-specific adaptations. Moreover, genes with large copy number variations display elevated levels of population-specific genetic and expression differentiation, consistent with the hypothesis that gene duplication and deletion events are key reservoirs of adaptive variation. Further, many top-scoring genes are well-known targets of adaptation in Europeans, including those involved in lactase persistence and vitamin D absorption, and a handful of novel candidates represent promising avenues for future research. Together, these analyses reveal that our statistic can aid in uncovering genes involved in population-specific genetic and expression differentiation, and that such genes often play important roles in a diversity of adaptive and disease-related phenotypes in humans.

The Microbiome-Metabolome Response in the Colon of Piglets Under the Status of Weaning Stress.

Weaning is stressful for piglets involving nutritional, physiological, and psychological challenges, leading to an increase in the secretion of cortisol, changes in gut microbiome and metabolites, whereas the underlying relationships remain unclear. To elucidate this, 14 Meishan female piglets were divided into the weaning group and the suckling group at the age of 21 days paired by litter and body weight. After 48 h of experiment, weaned piglets had lower body weight, but higher salivary cortisol level than that of their suckling litter mates (P < 0.05). The composition of the colonic bacterial community and metabolites were different between the two groups, and the first predominant genus of the suckling and weaned piglets colonic microbiome were Bacteroides and Prevotellaceae-NK3B31 group respectively. The suckling piglets had higher proportions of phylum Bacteroidetes and Lentisphaerae, and genus Bacteroides and Lactobacillus in the colonic microbial community, but lower abundance of genus Prevotellaceae-NK3B31 group than that of the weaned piglets (P < 0.05). Accordingly, there were 15 colonic metabolites differed between the two groups, in which 2 metabolites (phenylacetic acid and phenol) negatively related to the abundant of Lactobacillus genus (P < 0.05), while 9 metabolites (acetic acid, arabitol, benzoic acid, caprylic acid, cholesterol, dihydrocholesterol, galactinol, glucose phenol, phenylacetic acid, and oxamic acid, glycerol, propionic acid) positively associated with the proportion of Prevotellaceae-NK3B31 group genus (P < 0.05). Furthermore, the salivary cortisol level negatively associated with the abundance of phylum Lentisphaerae, but positively associated with the phylum Bacteroidetes and the genus Prevotellaceae-NK3B31 group (P < 0.05) respectively. These results provide us with new insights into the cause of the gut microbiome and stress, and the contributions of gut microbiome in metabolic and physiological regulation in response to weaning stress.

HDMCP uncouples yeast mitochondrial respiration and alleviates steatosis in L02 and hepG2 cells by decreasing ATP and H2O2 levels: a novel mechanism for NAFLD.

BACKGROUND/AIMS: To explore the uncoupling activity of hepatocelluar downregulated mitochondrial carrier protein (HDMCP) in a yeast expression system and its function in non-alcoholic fatty liver disease (NAFLD). METHODS: Molecular cloning and RT-PCR were used for yeast protein expression and uncoupling activity was assessed. Western blot analysis was used to determine HDMCP level in rat NAFLD and steatotic L02 and hepG2 cell models where their presence was confirmed by pathologic (Nile red and H-E staining) and biochemical changes. RNA interference was used to knock down HDMCP level and mitochondrial ATP and hydroperoxide levels were measured for potential mechanism exploration. RESULTS: We found a significant GDP insensitive uncoupling activity of HDMCP in yeast mitochondria and its increased expression in animal and cell models. HDMCP was significantly increased with culture time and steatosis was aggravated when HDMCP level was knocked down. Furthermore, we found that HDMCP might function through promoting ATP depletion and decreasing H(2)O(2) production. CONCLUSION: This study adds supportive data to the hypothesis that HDMCP might be a long postulated liver-specific uncoupling protein and broadens our understanding of the pathogenesis of NAFLD. More importantly, HDMCP might become a novel drug target for its ability in alleviating hepatic steatosis.