A joint analysis using exome and transcriptome data identifiescandidate polymorphisms and genes involved with umbilical hernia in pigs

Abstract Background Umbilical Hernia (UH) is characterized by the passage of part of the intestine through the umbilical canal forming the herniary sac. There are several potential causes that can lead to the umbilical hernia such as bacterial infections, management conditions and genetic factors. Since the genetic components involved with UH are poorly understood, this study aimed to identify polymorphisms and genes associated with the manifestation of umbilical hernia in pigs using exome and transcriptome sequencing in a case and control design. Results In the exome sequencing, 119 variants located in 58 genes were identified differing between normal and UH-affected pigs, and in the umbilical ring transcriptome, 46 variants were identified, located in 27 genes. Comparing the two methodologies, we obtained 34 concordant variants between the exome and transcriptome analyses, which were located in 17 genes, distributed in 64 biological processes (BP). Among the BP involved with UH it is possible to highlight cell adhesion, cell junction regulation, embryonic morphogenesis, ion transport, muscle contraction, within others. Conclusions We have generated the first exome sequencing related to normal and umbilical hernia-affected pigs, which allowed us to identify several variants possibly involved with this disorder. Many of those variants present in the DNA were confirmed with the RNA-Seq results. The combination of both exome and transcriptome sequencing approaches allowed us to better understand the complex molecular mechanisms underlying UH in pigs and possibly in other mammals, including humans. Some variants found in genes and other regulatory regions are highlighted as strong candidates to the development of UH in pigs and should be further investigated.

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Didelphis albiventris: an overview of an unprecedented transcriptome sequencing of the white-eared opossum

10.21203/rs.2.12871/v1 ◽

2019 ◽

Author(s):

Íria Gabriela Dias dos Santos ◽

Tiago Antônio de Oliveira Mendes ◽

Gerluza Aparecida Borges Silva ◽

Amanda Maria Sena Reis ◽

Cláudia Barros Monteiro Vitorello ◽

...

Keyword(s):

Limb Development ◽

Transcriptome Sequencing ◽

Molecular Mechanisms ◽

De Novo ◽

Mammalian Species ◽

Rna Seq ◽

Go Annotation ◽

Development And Differentiation ◽

Marsupial Species ◽

Didelphis Albiventris

Abstract Background The white-eared opossum (Didelphis albiventris) is widely distributed throughout Brazil and South America. They have been used as animal models to study different aspects in science, from the restoration of degraded green areas to medical aspects of the Chagas disease, leishmaniasis and resistance against snake venom. As a marsupial, D. albiventris can also aid the comprehension of the molecular mechanisms that govern the different stages of organogenesis, as their joeys are born after only 13 days, depending on placentation, and the final stages of organogenesis occurs when the neonates are inside the pouch, depending on lactation. As the genome of this opossum species, and/or its transcriptome, had not been completely sequenced yet, the use of D. albiventris as an animal model is limited. In this work, we have sequenced the D. albiventris transcriptome, by RNA-seq, to obtain the first catalogue of differentially expressed genes (DE) and gene ontology (GO) annotation during the neonatal stages of the marsupial development. Results The D. albiventris transcriptome was obtained from whole neonates harvested at birth (P0), at five days old (P5) and ten days old (P10). The de novo assembly of these transcripts allowed us to obtain 85,338 transcripts. Only ~30% of these transcripts could be mapped against M. domestica genome, the closest phylogenetic relative with available nucleotide sequences. Among the expressed transcripts, 2,077 were found to be DE between P0 and P5, 13,780 between P0 and P10, and 1,453 between P5 and P10. Enriched GO terms were mainly related to immune system, blood tissue development and differentiation, vision, hearing, digestion, CNS and limb development. Conclusions The unveiling of opossum transcriptomes provides an out-group to better understand the distinct characteristics associated with the evolution of mammalian species. Nevertheless, this is the first transcriptome sequencing and available catalogue of genes of a marsupial species at different neonatal stages, allowing the study of mechanisms involved in the organogenesis.

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Unperturbed Expression Bias of Imprinted Genes in Schizophrenia

10.1101/329748 ◽

2018 ◽

Cited By ~ 1

Author(s):

Attila Gulyás-Kovács ◽

Ifat Keydar ◽

Eva Xia ◽

Menachem Fromer ◽

Gabriel Hoffman ◽

...

Keyword(s):

Joint Analysis ◽

Imprinted Genes ◽

Rna Seq ◽

Specific Expression ◽

Human Genes ◽

Expression Bias ◽

Dorsolateral Prefrontal ◽

Allele Specific ◽

And Control ◽

Allelic Bias

AbstractHow gene expression correlates with schizophrenia across individuals is beginning to be examined through analyses of RNA-seq from post-mortem brains of individuals with disease and control brains. Here we focus on variation in allele-specific expression, following up on the Common Mind Consortium (CMC) RNA-seq experiments of nearly 600 human dorsolateral prefrontal cortex (DLPFC) samples. Analyzing the extent of allelic expression bias—a hallmark of imprinting—we find that the number of imprinted human genes is consistent with lower estimates (≈0.5% of all genes) and thus contradicts much higher estimates. Moreover, the handful of putatively imprinted genes are all in close genomic proximity to known imprinted genes. Joint analysis of the imprinted genes across hundreds of individuals allowed us to establish how allelic bias depends on various factors. We find that age and genetic ancestry have gene-specific, differential effect on allelic bias. In contrast, allelic bias appears to be independent of schizophrenia.

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The Protective Effects of Green Tea Catechins in the Management of Neurodegenerative Diseases: A Review

Current Drug Discovery Technologies ◽

10.2174/1570163815666180219115453 ◽

2019 ◽

Vol 16 (1) ◽

pp. 57-65 ◽

Cited By ~ 3

Author(s):

Tahereh Farkhondeh ◽

Hanieh Shaterzadeh Yazdi ◽

Saeed Samarghandian

Keyword(s):

Neurodegenerative Diseases ◽

Signaling Pathways ◽

Green Tea ◽

Molecular Mechanisms ◽

Main Role ◽

Related Factor ◽

Protective Effects ◽

Tea Catechins ◽

Green Tea Catechins ◽

And Control

Background: The therapeutic strategies to manage neurodegenerative diseases remain limited and it is necessary to discover new agents for their prevention and control. Oxidative stress and inflammation play a main role in the pathogenesis of neurodegenerative diseases. The aim of this study is to review the effects of green tea catechins against the Neurodegenerative Diseases. Methods: In this study, we extensively reviewed all articles on the terms of Green tea, catechins, CNS disorders, and different diseases in PubMed, Science Direct, Scopus, and Google Scholar databases between the years 1990 and 2017. Results: The present study found that catechins, the major flavonoids in green tea, are powerful antioxidants and radical scavengers which possess the potential roles in the management of neurodegenerative diseases. Catechins modulate the cellular and molecular mechanisms through the inflammation-related NF-&#954;B and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Conclusion: The findings of the present review shows catechins could be effective against neurodegenerative diseases due to their antioxidation and anti-inflammation effects and the involved biochemical pathways including Nrf2 and NF-kB signaling pathways.<P>

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PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

Nature Communications ◽

10.1038/s41467-021-23925-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Aubrey N. Michi ◽

Bryan G. Yipp ◽

Antoine Dufour ◽

Fernando Lopes ◽

David Proud

Keyword(s):

Host Defense ◽

Barrier Function ◽

Bacterial Infections ◽

Molecular Mechanisms ◽

Cellular Damage ◽

Epithelial Barrier ◽

Airway Epithelial ◽

Barrier Dysfunction ◽

Epithelial Barrier Function ◽

Epithelial Damage

AbstractHuman rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

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Comparative Transcriptome Analysis Reveals Sex-Based Differences during the Development of the Adult Parasitic Wasp Cotesia vestalis (Hymenoptera: Braconidae)

Genes ◽

10.3390/genes12060896 ◽

2021 ◽

Vol 12 (6) ◽

pp. 896

Author(s):

Yuenan Zhou ◽

Pei Yang ◽

Shuang Xie ◽

Min Shi ◽

Jianhua Huang ◽

...

Keyword(s):

Alternative Splicing ◽

Adult Development ◽

Sexual Development ◽

Molecular Mechanisms ◽

Parasitic Wasp ◽

Differentially Expressed Gene ◽

Regulation Mechanism ◽

Rna Seq ◽

Male And Female ◽

Cotesia Vestalis

The endoparasitic wasp Cotesia vestalis is an important biological agent for controlling the population of Plutella xylostella, a major pest of cruciferous crops worldwide. Though the genome of C. vestalis has recently been reported, molecular mechanisms associated with sexual development have not been comprehensively studied. Here, we combined PacBio Iso-Seq and Illumina RNA-Seq to perform genome-wide profiling of pharate adult and adult development of male and female C. vestalis. Taking advantage of Iso-Seq full-length reads, we identified 14,466 novel transcripts as well as 8770 lncRNAs, with many lncRNAs showing a sex- and stage-specific expression pattern. The differentially expressed gene (DEG) analyses showed 2125 stage-specific and 326 sex-specific expressed genes. We also found that 4819 genes showed 11,856 alternative splicing events through combining the Iso-Seq and RNA-Seq data. The results of comparative analyses showed that most genes were alternatively spliced across developmental stages, and alternative splicing (AS) events were more prevalent in females than in males. Furthermore, we identified six sex-determining genes in this parasitic wasp and verified their sex-specific alternative splicing profiles. Specifically, the characterization of feminizer and doublesex splicing between male and female implies a conserved regulation mechanism of sexual development in parasitic wasps.

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Analysis of saponins detoxification genes in Ilyonectria mors-panacis G3B inducing root rot of Panax notoginseng by RNA-Seq

Archives of Microbiology ◽

10.1007/s00203-021-02502-4 ◽

2021 ◽

Author(s):

Guohong Zeng ◽

Jin Li ◽

Yuxiu Ma ◽

Qian Pu ◽

Tian Xiao ◽

...

Keyword(s):

Root Rot ◽

Molecular Mechanisms ◽

Management Strategies ◽

Panax Notoginseng ◽

Glycoside Hydrolases ◽

Rna Seq ◽

Host Interaction ◽

Excellent Starting Point ◽

Starting Point ◽

Genes Encoding

AbstractSaponins are kinds of antifungal compounds produced by Panax notoginseng to resist invasion by pathogens. Ilyonectria mors-panacis G3B was the dominant pathogen inducing root rot of P. notoginseng, and the abilities to detoxify saponins were the key to infect P. notoginseng successfully. To research the molecular mechanisms of detoxifying saponins in I. mors-panacis G3B, we used high-throughput RNA-Seq to identify 557 and 1519 differential expression genes (DEGs) in I. mors-panacis G3B with saponins treatments for 4H (Hours) and 12H (Hours) compared with no saponins treatments, respectively. Among these DEGs, we found 93 genes which were simultaneously highly expressed in I. mors-panacis G3B with saponins treatments for 4H and 12H, they mainly belong to genes encoding transporters, glycoside hydrolases, oxidation–reduction enzymes, transcription factors and so on. In addition, there were 21 putative PHI (Pathogen–Host Interaction) genes out of those 93 up-regulated genes. In this report, we analyzed virulence-associated genes in I. mors-panacis G3B which may be related to detoxifying saponins to infect P. notoginseng successfully. They provided an excellent starting point for in-depth study on pathogenicity of I. mors-panacis G3B and developed appropriate root rot disease management strategies in the future.

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Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽

10.1186/s40168-021-01027-8 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Orit Malka ◽

Dorin Kalson ◽

Karin Yaniv ◽

Reut Shafir ◽

Manikandan Rajendran ◽

...

Keyword(s):

Quorum Sensing ◽

Gut Microbiome ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Molecular Mechanisms ◽

Human Microbiome ◽

Cell Communication ◽

Probiotic Yeast ◽

Gut Pathogen ◽

Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

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Non-Coding RNA Signatures of B-Cell Acute Lymphoblastic Leukemia

International Journal of Molecular Sciences ◽

10.3390/ijms22052683 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2683

Author(s):

Princess D. Rodriguez ◽

Hana Paculova ◽

Sophie Kogut ◽

Jessica Heath ◽

Hilde Schjerven ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

B Cell ◽

Molecular Mechanisms ◽

Lymphoblastic Leukemia ◽

Transcriptome Profiling ◽

Rna Seq ◽

Protein Coding ◽

Non Coding Rna ◽

Technological Developments ◽

Cell Acute Lymphoblastic Leukemia

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell acute lymphoblastic leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

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Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications

BioMed Research International ◽

10.1155/2018/8584136 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Lingyu Yang ◽

Dehai Xian ◽

Xia Xiong ◽

Rui Lai ◽

Jing Song ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathways ◽

Molecular Mechanisms ◽

Metabolic Diseases ◽

Low Cost ◽

Natural Agents ◽

Molecular Damage ◽

And Control

Proanthocyanidins (PCs) are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerousin vitroandin vivostudies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, anti-inflammation, immunomodulation, DNA repair, and antitumor activity. Accumulation of prooxidants such as reactive oxygen species (ROS) exceeding cellular antioxidant capacity results in oxidative stress (OS), which can damage macromolecules (DNA, lipids, and proteins), organelles (membranes and mitochondria), and whole tissues. OS is implicated in the pathogenesis and exacerbation of many cardiovascular, neurodegenerative, dermatological, and metabolic diseases, both through direct molecular damage and secondary activation of stress-associated signaling pathways. PCs are promising natural agents to safely prevent acute damage and control chronic diseases at relatively low cost. In this review, we summarize the molecules and signaling pathways involved in OS and the corresponding therapeutic mechanisms of PCs.

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Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

Reproductive Sciences ◽

10.1177/1933719119828042 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1485-1492

Author(s):

Xiaochun Yi ◽

Jie Zhang ◽

Huixiang Liu ◽

Tianxia Yi ◽

Yuhua Ou ◽

...

Keyword(s):

Immune System ◽

Differentially Expressed ◽

Rna Seq ◽

Poor Treatment ◽

Polymerase Chain ◽

Poor Treatment Outcome ◽

Immune Related Genes ◽

And Control ◽

Upregulated Genes ◽

Tgf Β1

The adverse clinical result and poor treatment outcome in recurrent spontaneous abortion (RSA) make it necessary to understand the pathogenic mechanism. The mating combination CBA/J × DBA/2 has been widely used as an abortion-prone model compared to DBA/2-mated CBA/J mice. Here, we used RNA-seq to get a comprehensive catalogue of genes differentially expressed between survival placenta in abortion-prone model and control. Five hundred twenty-four differentially expressed genes were obtained followed by clustering analysis, Gene Ontology analysis, and pathway analysis. We paid more attention to immune-related genes namely “immune response” and “immune system process” including 33 downregulated genes and 28 upregulated genes. Twenty-one genes contribute to suppressing immune system and 7 are against it. Six genes were validated by reverse transcription-polymerase chain reaction, namely Ccr1l1, Tlr4, Tgf-β1, Tyro3, Gzmb, and Il-1β. Furthermore, Tlr4, Tgf-β1, and Il-1β were analyzed by Western blot. Such immune profile gives us a better understanding of the complicated immune processing in RSA and immunosuppression can rescue pregnancy loss.

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