Impact of Bacillus licheniformis from yaks following antibiotic therapy in mouse model.

Gut microorganism (GM) is an integral component of the host microbiome and health system. Abuse of antibiotics disrupts the equilibrium of the microbiome, affecting environmental pathogens and host-associated bacteria alike. However, relatively little research on Bacillus licheniformis alleviates the adverse effects of antibiotics. To test the effect of B. licheniformis as a probiotic supplement against the effects of antibiotics, cefalexin was applied, and the recovery from cefalexin-induced jejunal community disorder and intestinal barrier damage was investigated by pathology, real-time PCR (RT-PCR), and high-throughput sequencing (HTS). The result showed that A group (antibiotic treatment) significantly reduced body weight and decreased the length of jejunal intestinal villi and the villi to crypt (V/C) value, which also caused structural damage to the jejunal mucosa. Meanwhile, antibiotic treatment suppressed the mRNA expression of tight junction proteins ZO-1, claudin, occludin, and Ki67 and elevated MUC2 expression more than the other Groups (P < 0.05 and P < 0.01). However, T group (B. licheniformis supplements after antibiotic treatment) restored the expression of the above genes, and there was no statistically significant difference compared to the control group (P > 0.05). Moreover, the antibiotic treatment increased the relative abundance of 4 bacterial phyla affiliated with 16 bacterial genera in the jejunum community, including the dominant Firmicutes, Proteobacteria, and Cyanobacteria in the jejunum. B. licheniformis supplements after antibiotic treatment reduced the relative abundance of Bacteroidetes and Proteobacteria and increased the relative abundance of Firmicutes, Epsilonbacteraeota, Lactobacillus, and Candidatus Stoquefichus. This study uses mimic real-world exposure scenarios by considering the concentration and duration of exposure relevant to environmental antibiotic contamination levels. We described the post-antibiotic treatment with B. licheniformis could restore intestinal microbiome disorders and repair the intestinal barrier. KEY POINTS: • B. licheniformis post-antibiotics restore gut balance, repair barrier, and aid health • Antibiotics harm the gut barrier, alter structure, and raise disease risk • Long-term antibiotics affect the gut and increase disease susceptibility.

Seaweed polysaccharides treatment alleviates injury of inflammatory responses and gut barrier in LPS-induced mice.

Gastrointestinal (GI) disease is a common digestive tract disease effects health of millions of human globally each year, thus the role of intestinal microflora had been emphasized. Seaweed polysaccharides featured a wide range of pharmacological activities, such as antioxidant activity and pharmacological action, but whether they can alleviate the dysbiosis of gut microbial ecology caused by lipopolysaccharide (LPS) exposure has not been well conducted. In this study, we investigated the effects of different concentration of seaweed polysaccharides on LPS-induced intestinal disorder by using hematoxylin and eosin (H&E) staining and 16S rRNA high-throughput sequencing. Histopathological results indicated that the intestinal structure in the LPS-induced group was damaged. Furthermore, LPS exposure not only reduced the intestinal microbial diversity in mice but also induced considerable transformation in its composition, along with significant increase in pathogenic bacteria (Helicobacter, Citrobacter and Mucispirillum) and decrease in beneficial bacteria (Firmicutes, Lactobacillus, Akkermansia and Parabacteroides). Nonetheless, seaweed polysaccharides administration could recover the gut microbial dysbiosis and the loss of gut microbial diversity induced by LPS exposure. In summary, seaweed polysaccharides were effective against LPS-induced intestinal damage in mice via the modulation of intestinal microecology.

Nuclear receptor REVERBα is a state-dependent regulator of liver energy metabolism.

The nuclear receptor REVERBα is a core component of the circadian clock and proposed to be a dominant regulator of hepatic lipid metabolism. Using antibody-independent ChIP-sequencing of REVERBα in mouse liver, we reveal a high-confidence cistrome and define direct target genes. REVERBα-binding sites are highly enriched for consensus RORE or RevDR2 motifs and overlap with corepressor complex binding. We find no evidence for transcription factor tethering and DNA-binding domain-independent action. Moreover, hepatocyte-specific deletion of Reverbα drives only modest physiological and transcriptional dysregulation, with derepressed target gene enrichment limited to circadian processes. Thus, contrary to previous reports, hepatic REVERBα does not repress lipogenesis under basal conditions. REVERBα control of a more extensive transcriptional program is only revealed under conditions of metabolic perturbation (including mistimed feeding, which is a feature of the global Reverbα-/- mouse). Repressive action of REVERBα in the liver therefore serves to buffer against metabolic challenge, rather than drive basal rhythmicity in metabolic activity.

The clock gene Bmal1 inhibits macrophage motility, phagocytosis, and impairs defense against pneumonia.

The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice show both reduced weight loss and lower bacterial burden in circulating blood. In vivo studies of macrophage phagocytosis reveal increased bacterial ingestion following Bmal1 deletion, which was also seen in vitro. BMAL1-/- macrophages exhibited marked differences in actin cytoskeletal organization, a phosphoproteome enriched for cytoskeletal changes, with reduced phosphocofilin and increased active RhoA. Further analysis of the BMAL1-/- macrophages identified altered cell morphology and increased motility. Mechanistically, BMAL1 regulated a network of cell movement genes, 148 of which were within 100 kb of high-confidence BMAL1 binding sites. Links to RhoA function were identified, with 29 genes impacting RhoA expression or activation. RhoA inhibition restored the phagocytic phenotype to that seen in control macrophages. In summary, we identify a surprising gain of antibacterial function due to loss of BMAL1 in macrophages, associated with a RhoA-dependent cytoskeletal change, an increase in cell motility, and gain of phagocytic function.

Hedyotis diffusa alleviate aflatoxin B1-induced liver injury in ducks by mediating Nrf2 signaling pathway.

Aflatoxin B1 (AFB1), the most harmful aflatoxins, is a frequent contamination in feed and food items, raising global concerns in animal production and human public health. Also, AFB1 induces oxidative stress, cytotoxicity, mutations, and DNA lesions through its metabolic transformation into aflatoxin B1-8,9-epoxide (AFBO) by cytochrome P450 (CYP450). Hedyotis diffusa (HD) is a traditional Chinese herbal medicine known for its multiple pharmacological activities, including antioxidant, anti-inflammatory, and immunomodulatory. Yet, the influence of HD on AFB1-induced liver injury in ducks is still unknown. Here, we investigated whether HD positively affects AFB1-induced liver injury in ducks. Results revealed that I) AFB1 caused significant changes in serum biochemical indices and decreased growth performance of ducks (such as ALT, AST, ALP, TP, ALB, final body weight, and body weight gain), whereas HD supplementation at 200 mg/kg mitigated these alterations. II) HD alleviated hepatic histopathological changes and liver index induced by AFB1 in ducks. III) HD significantly attenuated AFB1-induced oxidative stress, as measured by increased antioxidant enzyme activities such as SOD, GPx, and T-AOC and decreased MDA levels. Furthermore, HD reduced the level of AFB1-DNA adduct in duck liver. IV) HD significantly promoted the transcriptional expression of NF-E2-related nuclear factor 2 (Nrf2) and associated genes, including heme oxygenase 1 (HO-1), NAD(P)H dehydrogenase quinone 1 (NQO1), glutamate-cysteine ligase catalytic (GCLC). In conclusion, these results demonstrated that HD could activate the Nrf2 pathway in ducks to reduce the hepatotoxicity driven by AFB1. This finding also provides theoretical and data support for a deeper understanding of the toxic mechanisms of AFB1 and its prevention.

Baicalin inhibits apoptosis and enhances chondrocyte proliferation in thiram-induced tibial dyschondroplasia in chickens by regulating Bcl-2/Caspase-9 and Sox-9/Collagen-II expressions.

Avian tibial dyschondroplasia (TD) is a skeletal disease affecting fast growing chickens, resulting in non-mineralized avascular cartilage. This metabolic disorder is characterized by lameness and reduced growth performance causing economic losses. The aim of this study was to investigate the protective effects of baicalin against TD caused by thiram exposure. A total of two hundred and forty (n = 240) one day-old broiler chickens were uniformly and randomly allocated into three different groups (n = 80) viz. control, TD, and baicalin groups. All chickens received standard feed, however, to induce TD, the TD and baicalin groups received thiram (tetramethylthiuram disulfide) at a rate of 50 mg/kg feed from days 4-7. The thiram induction in TD and baicalin groups resulted in lameness, high mortality, and enlarged growth-plate, poor production performance, reduction in ALP, GSH-Px, SOD, and T-AOC levels, and increased AST and ALT, and MDA levels. Furthermore, histopathological results showed less vascularization, and mRNA and protein expression levels of Sox-9, Col-II, and Bcl-2 showed significant downward trend, while caspase-9 displayed significant up-regulation in TD-affected chickens. After the TD induction, the baicalin group was orally administered with baicalin at a rate of 200 mg/kg from days 8-18. Baicalin administration increased the vascularization, and chondrocytes with intact nuclei, alleviated lameness, decreased GP size, increased productive capacity, and restored the liver antioxidant enzymes and serum biochemical levels. Furthermore, baicalin significantly up-regulated the gene and protein expressions of Sox-9, Col-II, and Bcl-2, and significantly down-regulated the expression of caspase-9 (p < 0.05). Therefore, the obtained results suggest that baicalin could be a possible choice in thiram toxicity alleviation by regulating apoptosis and chondrocyte proliferation in thiram-induced tibial dyschondroplasia.

Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional HDAC6 pathway.

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR, also known as NR3C1) to regulate immunity, energy metabolism and tissue repair. Upon ligand binding, activated GR mediates cellular effects by regulating gene expression, but some GR effects can occur rapidly without new transcription. Here, we show that GCs rapidly inhibit cell migration, in response to both GR agonist and antagonist ligand binding. The inhibitory effect on migration is prevented by GR knockdown with siRNA, confirming GR specificity, but not by actinomycin D treatment, suggesting a non-transcriptional mechanism. We identified a rapid onset increase in microtubule polymerisation following GC treatment, identifying cytoskeletal stabilisation as the likely mechanism of action. HDAC6 overexpression, but not knockdown of αTAT1, rescued the GC effect, implicating HDAC6 as the GR effector. Consistent with this hypothesis, ligand-dependent cytoplasmic interaction between GR and HDAC6 was demonstrated by quantitative imaging. Taken together, we propose that activated GR inhibits HDAC6 function, and thereby increases the stability of the microtubule network to reduce cell motility. We therefore report a novel, non-transcriptional mechanism whereby GCs impair cell motility through inhibition of HDAC6 and rapid reorganization of the cell architecture.This article has an associated First Person interview with the first author of the paper.

Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management.

The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian-rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening/night-time. Patients with psoriasis have changes in circadian oscillations of blood pressure and heart rate, supporting wider circadian disruption. In addition, shift work, a circadian misalignment challenge, is associated with psoriasis. These features may be due to underlying circadian control of key effector elements known to be relevant in psoriasis such as cell cycle, proliferation, apoptosis and inflammation. Indeed, peripheral clock pathology may lead to hyperproliferation of keratinocytes in the basal layers, insufficient apoptosis of differentiating keratinocytes in psoriatic epidermis, dysregulation of skin-resident and migratory immune cells and modulation of angiogenesis through circadian oscillation of vascular endothelial growth factor A (VEGF-A) in epidermal keratinocytes. Chronotherapeutic effects of topical steroids and topical vitamin D analogues have been reported, suggesting that knowledge of circadian phase may improve the efficacy, and therapeutic index of treatments for psoriasis. In this viewpoint essay, we review the current literature on circadian disruption in psoriasis. We explore the hypothesis that psoriasis is circadian-driven. We also suggest that investigation of the circadian components specific to psoriasis and that the in vitro investigation of circadian regulation of psoriasis will contribute to the development of a novel chronotherapeutic treatment strategy for personalised psoriasis management. We also propose that circadian oscillations of VEGF-A offer an opportunity to enhance the efficacy and tolerability of a novel anti-VEGF-A therapeutic approach, through the timed delivery of anti-VEGF-A drugs.

Sodium butyrate ameliorates thiram-induced tibial dyschondroplasia and gut microbial dysbiosis in broiler chickens.

Thiram is a dithiocarbamate pesticide widely used in agriculture as a fungicide for storing grains to prevent fungal diseases. However, its residues have threatened the safety of human beings and the stability of the ecosystem by causing different disease conditions, e.g., tibial dyschondroplasia (TD), which results in a substantial economic loss for the poultry industry. So, the research on TD has a great concern for the industry and the overall GDP of a country. In current study, we investigated whether different concentrations (300, 500, and 700 mg/kg) of sodium butyrate alleviated TD induced under acute thiram exposure by regulating osteogenic gene expression, promoting chondrocyte differentiation, and altering the gut microbial community. According to the findings, sodium butyrate restored clinical symptoms in broilers, improved growth performance, bone density, angiogenesis, and chondrocyte morphology and arrangement. It could activate the signal transduction of the Wnt/ß-catenin pathway, regulate the expression of GSK-3ß and ß-catenin, and further promote the production of osteogenic transcription factors Runx2 and OPN for restoration of lameness. In addition, the 16S rRNA sequencing revealed a significantly different community composition among the groups. The TD group increased the abundance of the harmful bacteria Proteobacteria, Subdoligranulum, and Erysipelatoclostridium. The sodium butyrate enriched many beneficial bacteria, such as Bacteroidetes, Verrucomicrobia, Faecalibacterium, Barnesiella, Rikenella, and Butyricicoccus, etc., especially at the concentration of 500 mg/kg. The mentioned concentration significantly limited the intestinal disorders under thiram exposure, and restored bone metabolism.

Characterization of fungal microbial diversity in healthy and diarrheal Tibetan piglets.

BACKGROUND: Diarrhea is an important ailment limiting the production of the Tibetan pig industry. Dynamic balance of the intestinal microbiota is important for the physiology of the animal. The objective of this work was to study fungal diversity in the feces of early weaning Tibetan piglets in different health conditions. RESULTS: In the present study, we performed high-throughput sequencing to characterize the fungal microbial diversity in healthy, diarrheal and treated Tibetan piglets at the Tibet Autonomous Region of the People's Republic of China. The four alpha diversity indices (Chao1, ACE, Shannon and Simpson) revealed no significant differences in the richness across the different groups (P > 0.05). In all samples, the predominant fungal phyla were Ascomycota, Basidiomycota and Rozellomycota. Moreover, the healthy piglets showed a higher abundance of Ascomycota than the treated ones with a decreased level of Basidiomycota. One phylum (Rozellomycota) showed higher abundance in the diarrheal piglets than in the treated. At genus level, compared with that to the healthy group, the proportion of Derxomyces and Lecanicillium decreased, whereas that of Cortinarius and Kazachstania increased in the diarrheal group. The relative abundances of Derxomyces, Phyllozyma and Hydnum were higher in treated piglets than in the diarrheal ones. CONCLUSIONS: A decreased relative abundance of beneficial fungi (e.g. Derxomyces and Lecanicillium) may cause diarrhea in the early-weaned Tibetan piglets. Addition of probiotics into the feed may prevent diarrhea at this stage. This study presented the fungal diversity in healthy, diarrheal and treated early-weaned Tibetan piglets.

Albendazole and mebendazole in the treatment of ancylostomiasis in school children between the ages of 6-15 in Swat, Pakistan.

A cross-sectional study was conducted from March to September, 2018 on the efficacies of albendazole and mebendazole against ancylostomiasis in school children of district Swat, Pakistan. Faecal samples were collected from primary school children and preserved in 10% formalin. The samples were then sent to the Laboratory of Parasitology, in the University of Malakand for microscopic analysis. On the basis of drug availability, the Ancylostoma dueodenale infected students were divided into two groups. Group A was treated with Albendazole 400-450mg while group B was orally treated with Mebendazole 350-400mg. Eggs per gram were calculated before and after the treatment. From the total sample of 296, 192 (64.8%) children were found infected with Ancylostoma duodenale. Of the total number of infected children, this study found 87.8% (n=137/156)of them with light intensity of infection, 10.8%(n=17/156) with moderate and 1.2% (n=2/156) with heavy intensity of infection. Albendazole showed a high rate 75% of efficacy than mebendazole 71% (p<0.05). The present study concluded that albendazole and mebendazole are drugs of choice for the treatment of Ancylostomiasis.

Probiotic potential and safety assessment of Lactobacillus isolated from yaks.

Current problem of antibiotic resistance and the high incidence of bacterial diseases has brought huge losses to the yak breeding industry in Tibet. Therefore, the purpose of this study was to isolate Lactobacillus with safety and beneficial probiotic potential for the prophylaxis of intestinal diseases in yaks. After 16S rDNA sequence, four strains i.e. Lactobacillus sakei (named L4), Enterococcus hirae (named E5), Pediococcus acidilactici (named P7), Weissella confusa (named W8) were isolated from feces of yaks. The results of tolerance to acid, bile salt, enzyme and temperature showed that P7 was highly tolerant to acid, bile salt and digestive enzyme, while E5 was more resistant to temperature. The antibacterial assay showed L4 had a strong inhibitory effect against Staphylococcus aureus (BNCC186335), and E5, P7, W8 had effective antibacterial ability against Escherichia coli (C83902). In addition, L4, E5, P7 and W8 mainly produced organic acids and bacteriocin production to inhibit common intestinal pathogens. The results of antibiotic susceptibility assay indicated that L4, E5, P7 and W8 were highly sensitive to most clinically used antibiotics and didn't contain the VanA and VanB genes on the basis of PCR amplification, and L4, E5, P7 and W8 didn't exhibit hemolytic activity. The animal toxicity experiment results showed that no obvious pathological change was found in intestinal tissue sections, and L4, E5 and W8 strains also promoted the growth performance of mice, consequently, the L4, E5, P7 and W8 had no toxic effect on mice. In conclusion, lactobacillus isolated from feces of yaks not only have potential probiotics and strong antibacterial ability in vitro, but also are safe. Therefore, they have the potential to reduce the occurrence of bacterial diseases as new feed additives.

Comparative analysis of microbial community structure in the ponds with different aquaculture model and fish by high-throughput sequencing.

The pond has a complex microbial ecosystem, including microorganisms in water and sediment, which plays an important role in the health of fish and water quality. The microbial community structure in the ponds can be easily affected by many factors. However, not much is known about the role of different aquaculture model and fish on the microbial community structure in ponds. The purpose of the study was to investigate the microbial diversity and composition of the ponds with different aquaculture model and fish by high-throughput sequencing. A total of 3835072 valid sequences were achieved from 60 samples. Additionally, 2064 and 1917 core OTUs were observed in water and sediment samples, respectively. Our results suggested that sediment samples have a higher abundance and diversity of microbial community than water samples. In all the samples, the four most dominant phyla were Proteobacteria, Cyanobacteria, Actinomycetes and Bacteroides. At the genus level, hgcI_clade and CL500-29_marine_group were the dominant bacteria shared by the water samples and sediment samples. In addition, more bacteria related to eutrophication were found in the group of BF, BC and HSB, which suggested that these ponds may have been eutrophicated. In conclusion, the present study revealed the differences in the structure and diversity of microbial communities in ponds with different aquaculture model and fish. Furthermore, changes in typical bacteria of the ponds contribute to detect water quality and prevent water eutrophication.

Comparative analysis of microbial community structure between healthy and Aeromonas veronii-infected Yangtze finless porpoise.

BACKGROUND: The gut microbiota is a complex ecosystem, which is essential for the metabolism, health and immunity of host. Many diseases have been shown to be closely related to the alteration of intestinal flora. Aeromonas veronii as a conditioned pathogen can cause disease in Yangtze finless porpoise through intestinal infections. However, it is not clear whether the disease caused by Aeromonas veronii is related to changes of intestinal flora. In the current study, the diversity and composition of gut microbiota in the healthy and Aeromonas veronii-infected Yangtze finless porpoise were evaluated by high-throughput sequencing to further investigate the potential association between intestinal flora alteration and pathogen invasion. RESULTS: A total of 127,3276 high-quality sequences were achieved and 2465 operational taxonomic units (OTUs) were in common among all samples. The results of alpha diversity showed that there was no obvious difference in richness and diversity between healthy and Aeromonas veronii-infected Yangtze finless porpoise. Firmicutes, Bacteroidetes and Proteobacteria were the most dominant phyla in all samples. In addition, the healthy Yangtze finless porpoise exhibited higher abundance of Firmicutes and Fusobacteria than Aeromonas veronii-infected Yangtze finless porpoise, while, the level of Proteobacteria was decreased. At the genus level, Paeniclostridium and Paraclostridium were the predominant bacteria genera in the CK (healthy Yangtze finless porpoise) group. In the DIS (Aeromonas veronii-infected Yangtze finless porpoise) group, Lactobacillus and unidentified_Enterobacteriaceae were the dominant bacteria genera and the proportion of Paeniclostridium, Paraclostridium, Terrisporobacter, Cetobacterium, Candidatus Arthromitus, Terrabacter and Dechloromonas were reduced. CONCLUSIONS: In conclusion, our results showed that Aeromonas veronii infection can alter the gut microbiota of the Yangtze finless porpoise by affecting the number of harmful bacteria and beneficial bacteria.

Puerarin enhance vascular proliferation and halt apoptosis in thiram-induced avian tibial dyschondroplasia by regulating HIF-1α, TIMP-3 and BCL-2 expressions.

Tetramethyl thiuram disulfide (thiram) is a dithiocarbamate pesticide used for crop protection and storage. But, it's widespread utilization is associated with deleterious growth plate cartilage disorder in broilers termed as avian tibial dyschondroplasia (TD). TD results in non-mineralized and less vascularized proximal tibial growth plate cartilage causing lameness and poor growth performance. This study investigated the therapeutic potential of puerarin against thiram toxicity in TD affected chickens. One-day-old broiler chickens (n = 240) were alienated into three equal groups i.e. control, TD and puerarin (n = 80) and were offered standard feed. Additionally, TD and puerarin groups were offered thiram at 50 mg/kg of feed from 4 to 7 days for TD induction followed by puerarin therapy at 120 mg/kg to puerarin group only from 8 to 18 days for TD treatment. Thiram feeding to TD and puerarin group chickens caused lameness, mortality, and increased the aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) levels and growth plate (GP) size and upregulated HIF-1α expression. Besides, the production parameters, alkaline phosphatase (ALP), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels and the expressions of TIMP-3 and BCL-2 were decreased (p < 0.05). Puerarin alleviated lameness, enhanced angiogenesis and growth performance and serum and antioxidant enzymes, decreased apoptosis and recuperated GP width by significantly downregulating HIF-1α and upregulating the TIMP-3 and BCL-2 mRNA and protein expressions in puerarin group chickens (p < 0.05). In conclusion, the toxic effects associated with thiram can be mitigated using puerarin.

Effect of syringin (eleutheroside B) on the physiological and hematological parameters in STZ induced Type II diabetic Wistar rats.

To investigate the physiological indices such as body weight, food and fluid drinking concern to antidiabetic properties of syringin and its useful outcome on hematological parameters in streptozotocin stimulated diabetic rats. Six normal and 18 diabetic rats totally 24 rats have been used for the present investigation. Streptozotocin was injected in male Wistar rats to induce diabetes through intraperitoneal route. After the confirmation of diabetes, the test animals were treated with distilled water through oral route or syringin 5 mg/kg body weight/ rat /day for 10 days. The diabetic treated groups compared with the controls were evaluated based on their hematological parameters such as red blood cells, white blood cells and its functional indices. The blood glucose levels significantly decreased in syringin injected rats. The intake of water and feed in diabetic rats were significantly decreased, whereas after syringin administration the weight loss was minimized. Congruently, the level of red blood cells, white blood cells and their functional key characters were also considerably enhanced. It can be conjectured that syringin has antihyperglycemic properties. In addition, it can positively amend some hematological parameters.

Influence of dietary supplementation with Bacillus velezensis on intestinal microbial diversity of mice.

Yaks are an aboriginal breed of the Qinghai-Tibet plateau (3000 m), which are highly adaptable to cold and hypoxic environments. It is noticed that hypoxia and hypothermia can induce changes in intestinal microbial structure in animals. Increasing evidences suggested that probiotics supplementation can improve the balance of gut microbiota of animals. However, so far, very few studies have emphasized on the probiotics isolated from yaks in the Qinghai-Tibet Plateau. Therefore, a potential probiotic strain Bacillus velezensis was isolated from yaks. In the present study, a total of 18 Kunming mice (15-18 g) were equally distributed into two groups; control and probiotic treated groups (1 × 109 CFU/day). During the experimental period, all the mice from both groups were given standard normal diet ad libitum. At the end of the experiment, mice were euthanized and the intestines (duodenum, jejunum, ileum, and cecum) were removed for high-throughput sequencing. The results demonstrated that Bacillus velezensis supplementation showed beneficial effects on the gut microbiota of mice. Specifically, Bacillus velezensis supplementation increased the population of Lactobacillus and Ruminococcus in the duodenum, and Candidatus Arthromitus in the jejunum. Additionally, Acinetobacter in the duodenum and Helicobacter in the cecum were decreased after feeding Bacillus velezensis. Altogether, these findings suggested that Bacillus velezensis isolated from Tibetan yaks can improve gut microbiota of mice.

Probiotic potential of Lactobacillus on the intestinal microflora against Escherichia coli induced mice model through high-throughput sequencing.

The aim of this study was to evaluate the antibacterial potential of Lactobacillus screened from Tibetan yaks on clinical symptoms and intestinal microflora in enteroinvasive Escherichia coli (EIEC) induced mice model. In vitro study, Lactobacillus reuteri (LR1) exhibited stronger resistance to acid and bile and inhibited the growth of EIEC than Lactobacillus mucosae (LM1). The mice were randomly divided into four groups i.e. the LR1 group (LR1 1 × 109 CFU/day), LM1 group (LM1 1 × 109 CFU/day), blank control group and control group. Mice in control, LR1, and LM1 groups were challenged with EIEC on day 23. The body weight in the control and LM1 groups were significantly decreased after the infection with EIEC (P < 0.05), whereas the body weight of mice in the LR1 group did not change significantly (P > 0.05). The lowest diarrhea rate was recorded in the LR1 group after infection with EIEC. The results showed that the number of pathogens in the control group was higher than that in the experimental groups. The sequence analysis and OTU classification showed that the duodenum, ileum, and cecum of mice in the LR1 group had the highest number of OTUs compared with other groups. Whereas, the diversity analysis showed that in duodenum, ileum and cecum of mice in the LR1 group had the highest abundance and diversity. The composition of intestinal microbes indicated the presence of high proportions of Firmicutes, Proteobacteria and Bacteroidetes. Heat map analysis indicated high abundance of Bdello vibrio in the duodenum of mice in the LR1 group, while many pathogens were found in the different part of intestines in the control group, such as Streptococcus, Clostridium and Pseudomonas. In conclusion, pre-supplementation of LR1 alleviate the clinical symptoms caused by E. coli, and promote a healthy gut flora.

PP2A-3 interacts with ACR4 and regulates formative cell division in the Arabidopsis root.

In plants, the generation of new cell types and tissues depends on coordinated and oriented formative cell divisions. The plasma membrane-localized receptor kinase ARABIDOPSIS CRINKLY 4 (ACR4) is part of a mechanism controlling formative cell divisions in the Arabidopsis root. Despite its important role in plant development, very little is known about the molecular mechanism with which ACR4 is affiliated and its network of interactions. Here, we used various complementary proteomic approaches to identify ACR4-interacting protein candidates that are likely regulators of formative cell divisions and that could pave the way to unraveling the molecular basis behind ACR4-mediated signaling. We identified PROTEIN PHOSPHATASE 2A-3 (PP2A-3), a catalytic subunit of PP2A holoenzymes, as a previously unidentified regulator of formative cell divisions and as one of the first described substrates of ACR4. Our in vitro data argue for the existence of a tight posttranslational regulation in the associated biochemical network through reciprocal regulation between ACR4 and PP2A-3 at the phosphorylation level.

Efficient inference for sparse latent variable models of transcriptional regulation.

MOTIVATION: Regulation of gene expression in prokaryotes involves complex co-regulatory mechanisms involving large numbers of transcriptional regulatory proteins and their target genes. Uncovering these genome-scale interactions constitutes a major bottleneck in systems biology. Sparse latent factor models, assuming activity of transcription factors (TFs) as unobserved, provide a biologically interpretable modelling framework, integrating gene expression and genome-wide binding data, but at the same time pose a hard computational inference problem. Existing probabilistic inference methods for such models rely on subjective filtering and suffer from scalability issues, thus are not well-suited for realistic genome-scale applications. RESULTS: We present a fast Bayesian sparse factor model, which takes input gene expression and binding sites data, either from ChIP-seq experiments or motif predictions, and outputs active TF-gene links as well as latent TF activities. Our method employs an efficient variational Bayes scheme for model inference enabling its application to large datasets which was not feasible with existing MCMC-based inference methods for such models. We validate our method on synthetic data against a similar model in the literature, employing MCMC for inference, and obtain comparable results with a small fraction of the computational time. We also apply our method to large-scale data from Mycobacterium tuberculosis involving ChIP-seq data on 113 TFs and matched gene expression data for 3863 putative target genes. We evaluate our predictions using an independent transcriptomics experiment involving over-expression of TFs. AVAILABILITY AND IMPLEMENTATION: An easy-to-use Jupyter notebook demo of our method with data is available at https://github.com/zhenwendai/SITAR. CONTACT: mudassar.iqbal@manchester.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.