The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.

High-mobility group box 1 (HMGB1) is a chromatin-binding nuclear molecule that has potent proinflammatory effects once released by damaged cells. In some disease models, carbon monoxide (CO) exhibits anti-inflammatory and protective properties. Here, we investigated whether the protective effect of CO on renal ischemia-reperfusion injury is associated with the inhibition of HMGB1 translocation and release. A renal ischemia-reperfusion injury model was established with a 100% mortality rate in untreated mice. Pretreatment with the CO-releasing molecule-2 (CORM-2) resulted in 100% survival, maximal preservation of renal function, a marked reduction in pathological damage, and blunted upregulation of TLR4, RAGE, TNF-α, IL-1β, IL-6, and MCP1 mRNA. Interestingly, CORM-2 pretreatment almost completely inhibited ischemia-induced HMGB1 nucleocytoplasmic shuttling and release. This inhibition was associated with a decrease in nuclear histone acetyltransferase activity. Indeed, CORM-2 pretreatment inhibited the acetylation and release of HMGB1 during hypoxic culture of primary mouse renal tubular epithelia cells in vitro. Using the same renal ischemia-reperfusion injury model, neutralization of HMGB1 was protective, and administration of exogenous HMGB1 largely reversed the protective effect of CORM-2 on kidney ischemia-reperfusion injury. Thus, CORM-2-delivered CO protects against lethal renal ischemia-reperfusion injury. This protection is correlated with the prevention of HMGB1 nuclear-cytoplasmic translocation and release.

Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes of Arabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs) with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putative cis-regulatory elements (CREs) associated with male meiocyte-expressed genes using in silico tools. The upstream regions (1 kb) of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.

Maintaining vigilance is possibly the first requirement for surveillance tasks where personnel are faced with monotonous yet intensive monitoring tasks. Decrement in vigilance in such situations could result in dangerous consequences such as accidents, loss of life and system failure. In this paper, we investigate the possibility to enhance vigilance or sustained attention using "challenge integration," a strategy that integrates a primary task with challenging stimuli. A primary surveillance task (identifying an intruder in a simulated factory environment) and a challenge stimulus (periods of rain obscuring the surveillance scene) were employed to test the changes in vigilance levels. The effect of integrating challenging events (resulting from artificially simulated rain) into the task were compared to the initial monotonous phase. EEG and eye tracking data is collected and analyzed for n = 12 subjects. Frontal midline theta power and frontal theta to parietal alpha power ratio which are used as measures of engagement and attention allocation show an increase due to challenge integration (p < 0.05 in each case). Relative delta band power of EEG also shows statistically significant suppression on the frontoparietal and occipital cortices due to challenge integration (p < 0.05). Saccade amplitude, saccade velocity and blink rate obtained from eye tracking data exhibit statistically significant changes during the challenge phase of the experiment (p < 0.05 in each case). From the correlation analysis between the statistically significant measures of eye tracking and EEG, we infer that saccade amplitude and saccade velocity decrease with vigilance decrement along with frontal midline theta and frontal theta to parietal alpha ratio. Conversely, blink rate and relative delta power increase with vigilance decrement. However, these measures exhibit a reverse trend when challenge stimulus appears in the task suggesting vigilance enhancement. Moreover, the mean reaction time is lower for the challenge integrated phase (RTmean = 3.65 ± 1.4s) compared to initial monotonous phase without challenge (RTmean = 4.6 ± 2.7s). Our work shows that vigilance level, as assessed by response of these vital signs, is enhanced by challenge integration.

Quantitative real-time polymerase chain reaction (qRT-PCR) is one of the most common methods for gene expression studies. Data normalization based on reference genes is essential for obtaining reliable results for qRT-PCR assays. This study evaluated potential reference genes of Chinese yam (Dioscorea opposita Thunb.), which is an important tuber crop and medicinal plant in East Asia. The expression of ten candidate reference genes across 20 samples from different organs and development stages was assessed. We identified the most stable genes for qRT-PCR studies using combined samples from different organs. Our results also suggest that different suitable reference genes or combinations of reference genes for normalization should be applied according to different organs and developmental stages. To validate the suitability of the reference genes, we evaluated the relative expression of PE2.1 and PE53, which are two genes that may be associated with microtuber formation. Our results provide the foundation for reference gene(s) selection in D. opposita and will contribute toward more accurate gene analysis studies of the genus Dioscorea.

The NLRP3 inflammasome activation is a key signaling event for activation and secretion of pro-inflammatory cytokines such as IL-1β from macrophages. p58(IPK) is a molecular chaperone that regulates protein homeostasis through inhibiting eIF-2α kinases including double-stranded RNA-dependent protein kinase (PKR), which has been recently implicated in inflammasome activation. Herein we investigate the role of p58(IPK) in TLR4 signaling and inflammasome activation in macrophages. Primary bone marrow-derived macrophages (BMDM) was isolated from p58(IPK) knockout (KO) and wildtype (WT) mice and treated with lipopolysaccharide (LPS) and ATP to activate TLR4 signaling and stimulate inflammasome activation. Compared to WT macrophages, p58(IPK) deficient cells demonstrated significantly stronger activation of PKR, NF-κB, and JNK and higher expression of pro-inflammatory genes TNF-α and IL-1β. Coincidently, p58(IPK) deletion intensified NLRP3-inflammasome activation indicated by enhanced caspase 1 cleavage and increased IL-1β maturation and secretion. Pretreatment with specific PKR inhibitor or overexpression of p58(IPK) largely abolished the changes in inflammasome activation and IL-1β secretion in p58(IPK) null macrophages. Furthermore, immunoprecipitation assay confirmed the binding of p58(IPK) with PKR, but not other TLR4 downstream signaling molecules. Collectively, these results suggest a novel and crucial role of p58(IPK) in regulation of inflammasome activation and IL-1β secretion in macrophages.

Homologous recombination, together with selection, laid the foundation for traditional plant breeding. The recombination process that takes place during meiotic cell division is crucial for the creation of novel variations of highly desired traits by breeders. Gaining control over this process is important for molecular breeding to achieve more precise, large-scale and quicker plant improvement. As conventional ubiquitous promoters are neither tissue-specific nor efficient in driving gene expression in meiocytes, promoters with high meiotic activities are potential candidates for manipulating the recombination process. So far, only a few meiotically-active promoters have been reported. Recently developed techniques to profile the transcriptome landscape of isolated meiocytes provided the means to discover promoters from genes that are actively expressed in meiosis.

Identifying active prophages is critical for studying coevolution of phage and bacteria, investigating phage physiology and biochemistry, and engineering designer phages for diverse applications. We present Prophage Hunter, a tool aimed at hunting for active prophages from whole genome assembly of bacteria. Combining sequence similarity-based matching and genetic features-based machine learning classification, we developed a novel scoring system that exhibits higher accuracy than current tools in predicting active prophages on the validation datasets. The option of skipping similarity matching is also available so that there's higher chance for novel phages to be discovered. Prophage Hunter provides a one-stop web service to extract prophage genomes from bacterial genomes, evaluate the activity of the prophages, identify phylogenetically related phages, and annotate the function of phage proteins. Prophage Hunter is freely available at https://pro-hunter.bgi.com/.

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.

We conducted a randomized controlled trial to examine choral singing's effect on cognitive decline in aging. Older Singaporeans who were at high risk of future dementia were recruited: 47 were assigned to choral singing intervention (CSI) and 46 were assigned to health education program (HEP). Participants attended weekly one-hour choral singing or weekly one-hour health education for two years. Change in cognitive function was measured by a composite cognitive test score (CCTS) derived from raw scores of neuropsychological tests; biomarkers included brain magnetic resonance imaging, oxidative damage and immunosenescence. The average age of the participants were 70 years and 73/93 (78.5%) were female. The change of CCTS from baseline to 24 months was 0.05 among participants in the CSI group and -0.1 among participants in the HEP group. The between-group difference (0.15, p=0.042) became smaller (0.12, p=0.09) after adjusting for baseline CCTS. No between-group differences on biomarkers were observed. Our data support the role of choral singing in improving cognitive health in aging. The beneficial effect is at least comparable than that of health education in preventing cognitive decline in a community of elderly people. Biological mechanisms underlying the observed efficacy should be further studied.

Protein regulator of cytokinesis 1 (PRC1) has been reported to play important role in the pathogenesis of various cancers. However, its role in colon cancer has not been studied. Here, we aimed to investigate the biological functions and potential mechanism of PRC1 in colon cancer.

Increasing evidences indicate that high-risk HPV variants are heterogeneous in carcinogenicity and ethnic dispersion. In this work, we identified genetic signatures for convenient determination of lineage/sublineage of HPV16, 18, 52 and 58 variants. Using publicly available genomes, we found that E2 of HPV16, L2 of HPV18, L1 and LCR of HPV52, and L2, LCR and E1 of HPV58 contain the proper genetic signature for lineage/sublineage classification. Sets of hierarchical signature nucleotide positions were further confirmed for high accuracy (>95%) by classifying HPV genomes obtained from Chinese females, which included 117 HPV16 variants, 48 HPV18 variants, 117 HPV52 variants and 89 HPV58 variants. The circulation of HPV variants posing higher cancer risk in Eastern China, such as HPV16 A4 and HPV58 A3, calls for continuous surveillance in this region. The marker genes and signature nucleotide positions may facilitate cost-effective diagnostic detections of HPV variants in clinical settings.

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein in mammals. When released into the extracellular space, it acts as a damage-associated molecular pattern. This study investigates whether increased HMGB1 levels are found in the intestinal mucosa of ulcerative colitis (UC) patients, and whether an anti-HMGB1 neutralizing-antibody (HnAb) can inhibit the intestinal inflammation elicited by dextran sulfate sodium (DSS) in mice. Because toll-like receptor 4 (TLR4) is implicated in HMGB1-mediated immune cell activation, DSS colitis was also elicited in TLR4-deficient mice in the presence and absence of HnAb. The expression of HMGB1 in UC patients was examined. HnAb was administered via intraperitoneal injection to TLR4 deficient mice and their wild-type littermates, both being induced to colitis with DSS. Finally, the protective effect of HnAb and TLR4 deficiency were evaluated. In UC patients, HMGB1 was up-regulated in the inflamed colon. When administered during DSS application, HnAb alleviated the severity of colitis with a lower disease activity index, limited histological damages, and reduced production of proinflammatory cytokines. This antibody also limited colonic barrier loss, decreased colonic lamina propria macrophages and partially reversed the DSS treatment-associated dysbiosis. The protective effect of this antibody was enhanced in TLR4-deficient mice in some aspects, indicating that both additional HMGB1-mediated as well as TLR4-mediated inflammatory signaling pathways were involved in the induction of colitis by DSS. HnAb ameliorated colitis via macrophages inhibition and colonic barrier protection. It may therefore be a novel treatment option in colitis.

A method with high sensitivity, good accuracy and fast response is of ever increasing importance for the simultaneous detection of AA, DA and UA. In this paper, a simple and sensitive electrochemical sensor, which based on the polyvinylpyrrolidone (PVP)-graphene composite film modified glassy carbon electrode (PVP-GR/GCE), was presented for detecting ascorbic acid (AA), dopamine (DA) and uric acid (UA) simultaneously. The PVP-GR/GCE has excellent electrocatalytic activity for the oxidation of AA, DA and UA. The second-order derivative linear sweep voltammetry was used for the electrochemical measurements. The peak potential differences of DA-AA, DA-UA, and UA-AA (measured on the PVP-GR/GCE) were 212, 130 and 342 mV respectively. Besides, the over potential of AA, DA and UA reduced obviously, so did the peak current increase. Under the optimum conditions, the linear ranges of AA, DA and UA were 4.0 μM-1.0 mM, 0.02-100 μM, and 0.04-100 μM, respectively. The detection limits were 0.8 μM, 0.002 μM and 0.02 μM for AA, DA, and UA. The electrochemical sensor presented the advantages of high sensitivity and selectivity, excellent reproducibility and long-term stability. Furthermore, the sensor was successfully applied to the analysis of real samples.

With the development and progression of genetic technology, preimplantation genetic testing (PGT) has made it possible to block the inheritance of autosomal dominant polycystic kidney disease (ADPKD) as early as possible. However, we need to know the patients' fertility intentions and their acceptance of PGT.

Chinese yam (Dioscorea opposita) is an important tuberous crop used for both food and medicine. Despite a long history of cultivation, the understanding of D. opposita genetics and molecular biology remains scant, which has limited its genetic improvement. This work presents a de novo transcriptome sequencing analysis of microtuber formation in D. opposita. We assembled cDNA libraries from different stages during the process of microtuber formation, designated as initial explants (EXP), axillary bud proliferation after three weeks (BUD), and microtuber visible after four weeks (MTV). More differentially expressed genes (DEGs) and pathways were identified between BUD vs. EXP than in MTV vs. BUD, indicating that proliferation of the axillary bud is the key stage of microtuber induction. Gene classification and pathway enrichment analysis showed that microtuber formation is tightly coordinated with primary metabolism, such as amino acid biosynthesis, ribosomal component biosynthesis, and starch and sucrose metabolism. The formation of the microtuber is regulated by a variety of plant hormones, including ABA. Combined with analysis of physiological data, we suggest that ABA positively regulates tuberization in D. opposita. This study will serve as an empirical foundation for future molecular studies and for the propagation of D. opposita germplasm in field crops.

Echinococcus tapeworms cause a severe helminthic zoonosis called echinococcosis. The genus comprises various species and genotypes, of which E. granulosus (sensu stricto) represents a significant global public health and socioeconomic burden. Mitochondrial (mt) genomes have provided useful genetic markers to explore the nature and extent of genetic diversity within Echinococcus and have underpinned phylogenetic and population structure analyses of this genus. Our recent work indicated a sequence gap (> 1 kb) in the mt genomes of E. granulosus genotype G1, which could not be determined by PCR-based Sanger sequencing. The aim of the present study was to define the complete mt genome, irrespective of structural complexities, using a long-read sequencing method.

Introduction This study investigated the effect of combining hypoglossal-facial nerve "side"-to-side neurorrhaphy and electrical myostimulation in a rat model of facial palsy. Methods Rats with facial nerve crush injury were subjected to control condition, monotherapy of either neurorrhaphy or electrical myostimulation, or bitherapy of the two treatments. After 1, 3, and 6 months, rats were performed the facial symmetry evaluation, electrophysiological examination and the retrograde labeling of motor neurons. Results As early as 3 months after injury, face symmetry significantly improved in rats of the bitherapy group. At 3 or 6 months after injury, either the parameters of electrophysiological examination or the number of labeled motor neurons were significantly increased in the bitherapy group than in any other group. Discussion The combination of neurorrhaphy and electrical myostimulation effectively promoted the functional recovery after facial nerve crush injury.

COVID-19 (coronavirus disease 2019) has caused a major epidemic worldwide; however, much is yet to be known about the epidemiology and evolution of the virus partly due to the scarcity of full-length SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) genomes reported. One reason is that the challenges underneath sequencing SARS-CoV-2 directly from clinical samples have not been completely tackled, i.e., sequencing samples with low viral load often results in insufficient viral reads for analyses.