scholarly journals Gut transcriptome reveals differential gene expression and enriched pathways linked to immune activation in response to weaning in pigs.

2021 ◽  
Author(s):  
Melanie Le Bon ◽  
Sabine Tötemeyer ◽  
Richard D Emes ◽  
Kenneth H Mellits
Keyword(s):  
Rna Sequencing ◽  
Immune Activation ◽  
Disease Risk ◽  
Critical Role ◽  
Cell Signalling ◽  
Antibiotic Use ◽  
Interferon Response ◽  
Critical Periods ◽  
Pig Production ◽  
Microbial Invasion

Weaning represents one of the most critical periods in pig production associated with increase in disease risk, reduction in performance and economic loss. Physiological changes faced by piglets during the weaning period have been well characterised, however little is currently known about the underlying molecular pathways involved in these processes. As pig meat remains one of the most consumed sources of protein worldwide, understanding how these changes are mediated is critical to improve pig production and consequently sustainable food production globally. In this study, we evaluated the effect of weaning on transcriptomic changes in the colon of healthy piglets over time using an RNA-sequencing approach. The findings revealed a complex and coordinated response to weaning with the majority of genes found to be rapidly differentially expressed within one day post weaning. Multiple genes and pathways affected by weaning in the colon were associated with immune regulation, cell signalling and bacterial defence. NOD-like receptors, Toll-like receptor and JAK-STAT signalling pathways were amongst the pathways significantly enriched. Immune activation was evidenced by the enrichment of pathways involved in interferon response, cytokines interactions, oxidoreductase activities and response to microbial invasion. Biosynthesis of amino acids, in particular arginine, was also amongst the most enriched KEGG pathways in weaned pigs, reinforcing the critical role of arginine in gut homeostasis under stress conditions. Overall, transcriptomic and physiological results suggest that pigs going through the weaning transition undergo a transient period of inflammatory state with a temporary breakdown of barrier functions in the gut. These findings could provide valuable tools to monitor host response post weaning, and may be of particular relevance for the investigation and development of intervention strategies aimed to reduce antibiotic use and improve pig health and performance. Keywords: Pig, Weaning, RNA-sequencing, Transcriptomic, Gut, Immune response.

scholarly journals Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lianwei Ma ◽  
Hui Zhang ◽  
Yue Zhang ◽  
Hailong Li ◽  
Minghui An ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Expression Profiles ◽  
Critical Role ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Target Mrnas ◽  
Immunodeficiency Virus ◽  
Mirna Sequencing ◽  
Hiv 1

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

Services and surveillance during the pandemic lockdown: Residents’ committees in Wuhan and Beijing

2021 ◽  
pp. 0920203X2110128
Author(s):  
Zhenjie Yang ◽  
Guilan Zhu ◽  
Linda Chelan Li ◽  
Yilong Sheng
Keyword(s):  
Local Community ◽  
Critical Role ◽  
Control Measures ◽  
Critical Periods ◽  
Prevention Policy ◽  
Grass Roots ◽  
National Capital ◽  
Prevention And Control Measures ◽  
And Control ◽  
Residents Committee

The COVID-19 pandemic caused a lockdown of Wuhan, and strict control was imposed in many major Chinese cities, including the national capital of Beijing. Residents’ committee workers at the grass-roots level have played a critical role in the enforcement of the government’s pandemic prevention and control measures, through their day-to-day service and surveillance as local community managers. This article examines their work in Wuhan and Beijing neighbourhoods during the most critical periods of the outbreak, from late January to June 2020, and the challenges the workers faced as executors of the government’s community-based prevention policy. The two cities have developed different community strategies because of very different epidemiological situations and city functions.

Cell-type specific calcium signalling in a Drosophila epithelium

1997 ◽  
Vol 110 (15) ◽  
pp. 1683-1692 ◽  
Author(s):  
P. Rosay ◽  
S.A. Davies ◽  
Y. Yu ◽  
A. Sozen ◽  
K. Kaiser ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Critical Role ◽  
Cell Signalling ◽  
Calcium Signalling ◽  
Malpighian Tubule ◽  
Fluid Secretion ◽  
Cell Types ◽  
Cytosolic Calcium ◽  
Atpase Inhibitor ◽  
Principal Cells

Calcium is a ubiquitous second messenger that plays a critical role in both excitable and non-excitable cells. Calcium mobilisation in identified cell types within an intact renal epithelium, the Drosophila melanogaster Malpighian tubule, was studied by GAL4-directed expression of an aequorin transgene. CAP2b, a cardioactive neuropeptide that stimulates fluid secretion by a mechanism involving nitric oxide, causes a rapid, dose-dependent rise in cytosolic calcium in only a single, genetically-defined, set of 77 principal cells in the main (secretory) segment of the tubule. In the absence of external calcium, the CAP2b-induced calcium response is abolished. In Ca2+-free medium, the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, elevates [Ca2+]i only in the smaller stellate cells, suggesting that principal cells do not contain a thapsigargin-sensitive intracellular pool. Assays for epithelial function confirm that calcium entry is essential for CAP2b to induce a physiological response in the whole organ. Furthermore, the data suggest a role for calcium signalling in the modulation of the nitric oxide signalling pathway in this epithelium. The GAL4-targeting system allows general application to studies of cell-signalling and pharmacology that does not rely on invasive or cytotoxic techniques.

Evidence for a mitogenic effect of Wnt-1 in the developing mammalian central nervous system

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1453-1471 ◽  
Author(s):  
M.E. Dickinson ◽  
R. Krumlauf ◽  
A.P. McMahon
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Critical Role ◽  
Cell Signalling ◽  
Mitogenic Effect ◽  
Mammalian Central Nervous System ◽  
Number Of Cells

The analysis of mutant alleles at the Wnt-1 locus has demonstrated that Wnt-1-mediated cell signalling plays a critical role in development of distinct regions of the embryonic central nervous system (CNS). To determine how these signals participate in the formation of the CNS, we have ectopically expressed this factor in the spinal cord under the control of the Hoxb-4 Region A enhancer. Ectopic Wnt-1 expression causes a dramatic increase in the number of cells undergoing mitosis in the ventricular region and a concomitant ventricular expansion. Although this leads to consistent changes in the relative proportions of dorsal and ventral regions, Wnt-1 does not appear to act as a primary patterning signal. Rather, our experiments indicate that Wnt-1 can act as a mitogen in the developing CNS.

scholarly journals Quality assessment of systematic reviews and meta-analyses that examine preventive antibiotic uses and management practices designed to prevent disease in livestock

2019 ◽  
Vol 20 (2) ◽  
pp. 305-318
Author(s):  
Rachael Vriezen ◽  
Jan M. Sargeant ◽  
Ellen Vriezen ◽  
Charlotte B. Winder ◽  
Annette M. O'Connor
Keyword(s):  
Quality Assessment ◽  
Systematic Reviews ◽  
Management Practices ◽  
Disease Risk ◽  
Data Extraction ◽  
A Priori ◽  
Antibiotic Use ◽  
Study Selection ◽  
Meta Analyses

AbstractTo implement effective stewardship in food animal production, it is essential that producers and veterinarians are aware of preventive interventions to reduce illness in livestock. Systematic reviews and meta-analyses (SR/MA) provide transparent, replicable, and quality-assessed overviews. At present, it is unknown how many SR/MA evaluate preventive antibiotic use or management practices aimed at reducing disease risk in animal agriculture. Further, the quality of existing reviews is unknown. Our aim was to identify reviews investigating these topics and to provide an assessment of their quality. Thirty-eight relevant reviews were identified. Quality assessment was based on the AMSTAR 2 framework for the critical appraisal of systematic reviews. The quality of most of the reviews captured was classified as critically low (84.2%, n = 32/38), and only a small percentage of the evaluated reviews did not contain critical weaknesses (7.9%, n = 3/38). Particularly, a small number of reviews reported the development of an a priori protocol (15.8%, n = 6/38), and few reviews stated that key review steps were conducted in duplicate (study selection/screening: 26.3%, n = 10/38; data extraction: 15.8%, n = 6/38). The development of high-quality reviews summarizing evidence on approaches to antibiotic reduction is essential, and thus greater adherence to quality conduct guidelines for synthesis research is crucial.

scholarly journals Critical Role for Alpha/Beta and Gamma Interferons in Persistence of Lymphocytic Choriomeningitis Virus by Clonal Exhaustion of Cytotoxic T Cells

2001 ◽  
Vol 75 (18) ◽  
pp. 8407-8423 ◽  
Author(s):  
Rong Ou ◽  
Shenghua Zhou ◽  
Lei Huang ◽  
Demetrius Moskophidis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Critical Role ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Interferon Response ◽  
Type I ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Alpha Beta

ABSTRACT Under conditions of high antigenic load during infection with invasive lymphocytic choriomeningitis virus (LCMV) strains, virus can persist by selective clonal exhaustion of antigen-specific CD8+ T cells. In this work we studied the down-regulation of the virus-specific CD8+-T-cell response during a persistent infection of adult mice, with particular emphasis on the contribution of the interferon response in promoting host defense. Studies were conducted by infecting mice deficient in receptors for type I (alpha/beta interferon [IFN-α/β]), type II (IFN-γ), and both type I and II IFNs with LCMV isolates that vary in their capacity to induce T-cell exhaustion. The main conclusions of this study are as follows. (i) IFNs play a critical role in LCMV infection by reducing viral loads in the initial stages of infection and thus modifying both the extent of CD8+-T-cell exhaustion and the course of infection. The importance of IFNs in this context varies with the biological properties of the LCMV strain. (ii) An inverse correlation exists between antigen persistence and responsiveness of virus-specific CD8+ T cells. This results in distinct programs of activation or tolerance (functional unresponsiveness and/or physical elimination of antigen-specific cells) during acute and chronic virus infections, respectively. (iii) A successful immune response associated with definitive viral clearance requires an appropriate balance between cellular and humoral components of the immune system. We discuss the role of IFNs in influencing virus-specific T cells that determine the outcome of persistent infections.

scholarly journals Female behaviour plays a critical role in controlling murine pregnancy block

2009 ◽  
Vol 276 (1662) ◽  
pp. 1723-1729 ◽  
Author(s):  
Stuart D Becker ◽  
Jane L Hurst
Keyword(s):  
Critical Period ◽  
Critical Role ◽  
Reproductive Investment ◽  
Dominant Male ◽  
Critical Periods ◽  
Nest Sites ◽  
Bruce Effect ◽  
Male Scent ◽  
Female Behaviour ◽  
Mated Female

Exposure of recently mated female rodents to unfamiliar male scents during daily prolactin surges results in pregnancy failure (the ‘Bruce effect’). Control of nasal contact with male scents during these narrow windows of sensitivity could allow females to maintain or terminate pregnancy, but female behavioural changes specifically during this critical period have not been investigated. We examined the approach or avoidance of familiar stud strain and unfamiliar male scents by recently mated female mice. Females that maintained pregnancy avoided both unfamiliar and familiar male scent during critical periods of susceptibility for the Bruce effect. By contrast, females that did not maintain pregnancy showed a sharp rise in the time spent with unfamiliar male scent during this critical period. Manipulation of the social status of unfamiliar and stud strain scent donors did not affect the likelihood of pregnancy block, although females spent more time with dominant male scents across all time periods. The ability to control the Bruce effect through behaviour during brief sensitivity just before dusk, when females are likely to be in nest sites, provides a mechanism by which females may adjust their reproductive investment according to nest site social stability and likelihood of offspring survival.

Survey of the immunogenomic landscape of solid tumors through clinical DNA and RNA sequencing.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 153-153
Author(s):  
Denise Lau ◽  
Alan Chang ◽  
Jason Perera ◽  
Ariane Lozac'hmeur ◽  
Alexandria Bobe ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Solid Tumors ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Immune Activation ◽  
Clinical Care ◽  
Relative Proportion ◽  
Tumor Infiltration ◽  
Sequencing Data ◽  
Dna And Rna

153 Background: In the past decade, immunotherapy has emerged as an important new modality in cancer treatment. However, studies have shown that only a fraction of patients will experience any clinical benefit when treated with immune checkpoint blockade drugs. Given the cost and potent adverse events associated with immunotherapy, the need for effective biomarkers is clear. We sought to understand the role of key immunotherapy biomarkers, like tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 immunohistochemistry (IHC), in the context of the greater immunogenomic landscape of solid tumors in patients. Methods: We analyzed data from a cohort of 500 patients across 10 cancer types who received the Tempus xT 595 gene targeted DNA sequencing assay and whole transcriptome sequencing assay as part of their clinical care. We determined the TMB, MSI status, and neoantigen load for each sample using the DNA sequencing data. We used the RNA expression data to evaluate immune activation and tumor infiltration by determining the expression of inflammatory gene signatures and estimating the relative proportion of key immune cell types. Results: Integrative analysis of the DNA and RNA sequencing data showed that the immunogenicity of the tumor, as measured by TMB or neoantigen load, correlates with levels of immune activation and tumor infiltration. Inflammatory immune cells, like CD8 T cells and M1 polarized macrophages, were significantly higher in TMB-high samples; while non-inflammatory immune cells, like monocytes, were significantly lower in TMB-high samples. Additionally, samples could be clustered into immunologically active “hot” tumors or immunologically silent “cold” tumors based on gene expression. The immunologically “hot” population was enriched for samples that were TMB-high, MSI-high or PD-L1 IHC positive. Conclusions: Paired next generation DNA and RNA sequencing assays allows for the identification of patients that have immunologically active tumors that lack traditional immunotherapy biomarkers. These patients represent an interesting new population who may potentially benefit from immunotherapy.

scholarly journals NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

2009 ◽  
Vol 5 (7) ◽  
pp. e1000500 ◽  
Author(s):  
Amit K. Pandey ◽  
Yibin Yang ◽  
Zhaozhao Jiang ◽  
Sarah M. Fortune ◽  
Francois Coulombe ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I Interferon ◽  
Critical Role ◽  
Interferon Response ◽  
Type I

scholarly journals Variations in Adipokine GenesAdipoQ,Lep, andLepRAre Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jennifer Emily Enns ◽  
Carla G. Taylor ◽  
Peter Zahradka
Keyword(s):  
Metabolic Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Disease Risk ◽  
Critical Role ◽  
Nucleotide Polymorphisms ◽  
Nutrient Interactions ◽  
The Metabolic Syndrome ◽  
Susceptible Populations

Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations.

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