Prioritization of vigor QTL-associated genes for future genome-directed Vitis breeding

Vigor control in grapevine may become especially important under climate change. A better understanding of gene-phenotype relationships is required in order to exploit plant genomics for breeding purposes. This research aims to use quantitative trait loci (QTLs) for vigor identified in the progeny from a cross of Ramsey (Vitis champinii) × Riparia Gloire (V. riparia). Genes located 700 kb up and downstream from each QTL position were interrogated for functional enrichment through ShinyGO online tool, based on the gene ontology annotation of Vitis vinifera PN40024. Key biological processes like phloem and xylem development, cell cycle, response to hormones, amino acid transport, tissue development, sugar metabolism, nitrogen transport, and stress/immune responses, showed functional enrichment. Integral response to light and auxin might be required for fine molecular tuning of vegetative growth in Vitis. Fifty out of 1318 candidate genes were prioritized, reducing their amount to a manageable number of candidates for further directed breeding strategies. Highlights Plant vigor control may become especially important under climate change. Genes from various vigor-related QTLs were interrogated for functional enrichment. The analysis reduced candidate gene number based on marker proximity and functional enrichment, constituting a suitable shortcut for target-directed genome-guided breeding strategies. Three TFs are strong candidates for targeted breeding: TIF - HY5, TIF - SUS1, TIF - VOZ1 potentially enhance growth by relating light response to hormone activation, and then to photosynthesis and morphogenesis.

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Advances in Cereal Crop Genomics for Resilience under Climate Change

Life ◽

10.3390/life11060502 ◽

2021 ◽

Vol 11 (6) ◽

pp. 502

Author(s):

Tinashe Zenda ◽

Songtao Liu ◽

Anyi Dong ◽

Huijun Duan

Keyword(s):

Climate Change ◽

Genome Sequencing ◽

Gene Editing ◽

Agronomic Traits ◽

Cereal Crops ◽

Agricultural System ◽

Plant Genomics ◽

Crop Species ◽

Underutilized Species ◽

Recent Developments

Adapting to climate change, providing sufficient human food and nutritional needs, and securing sufficient energy supplies will call for a radical transformation from the current conventional adaptation approaches to more broad-based and transformative alternatives. This entails diversifying the agricultural system and boosting productivity of major cereal crops through development of climate-resilient cultivars that can sustainably maintain higher yields under climate change conditions, expanding our focus to crop wild relatives, and better exploitation of underutilized crop species. This is facilitated by the recent developments in plant genomics, such as advances in genome sequencing, assembly, and annotation, as well as gene editing technologies, which have increased the availability of high-quality reference genomes for various model and non-model plant species. This has necessitated genomics-assisted breeding of crops, including underutilized species, consequently broadening genetic variation of the available germplasm; improving the discovery of novel alleles controlling important agronomic traits; and enhancing creation of new crop cultivars with improved tolerance to biotic and abiotic stresses and superior nutritive quality. Here, therefore, we summarize these recent developments in plant genomics and their application, with particular reference to cereal crops (including underutilized species). Particularly, we discuss genome sequencing approaches, quantitative trait loci (QTL) mapping and genome-wide association (GWAS) studies, directed mutagenesis, plant non-coding RNAs, precise gene editing technologies such as CRISPR-Cas9, and complementation of crop genotyping by crop phenotyping. We then conclude by providing an outlook that, as we step into the future, high-throughput phenotyping, pan-genomics, transposable elements analysis, and machine learning hold much promise for crop improvements related to climate resilience and nutritional superiority.

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Emerging Roles of Protein Deamidation in Innate Immune Signaling

Journal of Virology ◽

10.1128/jvi.01980-15 ◽

2016 ◽

Vol 90 (9) ◽

pp. 4262-4268 ◽

Cited By ~ 20

Author(s):

Jun Zhao ◽

Junhua Li ◽

Simin Xu ◽

Pinghui Feng

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Microbial Pathogens ◽

Biological Processes ◽

Innate Immune Responses ◽

Immune Signaling ◽

Host Immune Responses ◽

Innate Immune Signaling ◽

Enzyme Deficient ◽

Signaling Components

Protein deamidation has been considered a nonenzymatic process associated with protein functional decay or “aging.” Recent studies implicate protein deamidation in regulating signal transduction in fundamental biological processes, such as innate immune responses. Work investigating gammaherpesviruses and bacterial pathogens indicates that microbial pathogens deploy deamidases or enzyme-deficient homologues (pseudoenzymes) to induce deamidation of key signaling components and evade host immune responses. Here, we review studies on protein deamidation in innate immune signaling and present several imminent questions concerning the roles of protein deamidation in infection and immunity.

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N-Acetyl Galactosamine Targeting: Paving the Way for Clinical Application of Nucleotide Medicines in Cardiovascular Diseases

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316290 ◽

2021 ◽

Author(s):

Erik A.L. Biessen ◽

Theo J.C. Van Berkel

Keyword(s):

Immune Responses ◽

Targeted Delivery ◽

Antisense Oligonucleotides ◽

Sugar Metabolism ◽

Innate Immune ◽

Future Research ◽

Clinical Use ◽

Innate Immune Responses ◽

Chemically Modified ◽

Intrinsic Capacity

While the promise of oligonucleotide therapeutics, such as (chemically modified) ASO (antisense oligonucleotides) and short interfering RNAs, is undisputed from their introduction onwards, their unfavorable pharmacokinetics and intrinsic capacity to mobilize innate immune responses, were limiting widespread clinical use. However, these major setbacks have been tackled by breakthroughs in chemistry, stability and delivery. When aiming an intervention hepatic targets, such as lipid and sugar metabolism, coagulation, not to mention cancer and virus infection, introduction of N-acetylgalactosamine aided targeting technology has advanced the field profoundly and by now a dozen of N-acetylgalactosamine therapeutics for these indications have been approved for clinical use or have progressed to clinical trial stage 2 to 3 testing. This technology, in combination with major advances in oligonucleotide stability allows safe and durable intervention in targets that were previously deemed undruggable, such as Lp(a) and PCSK9, at high efficacy and specificity, often with as little as 2 doses per year. Their successful use even the most visionary would not have predicted 2 decades ago. Here, we will review the evolution of N-acetylgalactosamine technology. We shall outline their fundamental design principles and merits, and their application for the delivery of oligonucleotide therapeutics to the liver. Finally, we will discuss the perspectives of N-acetylgalactosamine technology and propose directions for future research in receptor targeted delivery of these gene medicines.

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SiteOut: an online tool to design binding site-free DNA sequences

10.1101/029645 ◽

2015 ◽

Cited By ~ 1

Author(s):

Javier Estrada ◽

Teresa Ruiz-Herrero ◽

Clarissa Scholes ◽

Zeba Wunderlich ◽

Angela DePace

Keyword(s):

Binding Site ◽

Dna Sequences ◽

Binding Sites ◽

Regulatory Proteins ◽

Biological Processes ◽

Major Goal ◽

Specific Sequence ◽

Online Tool ◽

Protein Binding Sites ◽

Regulatory Dna

DNA-binding proteins control many fundamental biological processes such as transcription, recombination and replication. A major goal is to decipher the role that DNA sequence plays in orchestrating the binding and activity of such regulatory proteins. To address this goal, it is useful to rationally design DNA sequences with desired numbers, affinities and arrangements of protein binding sites. However, removing binding sites from DNA is computationally non-trivial since one risks creating new sites in the process of deleting or moving others. Here we present an online binding site removal tool, SiteOut, that enables users to design arbitrary DNA sequences that entirely lack binding sites for factors of interest. SiteOut can also be used to delete sites from a specific sequence, or to introduce site-free spacers between functional sequences without creating new sites at the junctions. In combination with commercial DNA synthesis services, SiteOut provides a powerful and flexible platform for synthetic projects that interrogate regulatory DNA. Here we describe the algorithm and illustrate the ways in which SiteOut can be used; it is publicly available at https://depace.med.harvard.edu/siteout/

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Integrating miRNA and mRNA Profiling to Assess the Potential miRNA–mRNA Modules Linked With Testicular Immune Homeostasis in Sheep

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.647153 ◽

2021 ◽

Vol 8 ◽

Author(s):

Taotao Li ◽

Xia Wang ◽

Ruirui Luo ◽

Xuejiao An ◽

Yong Zhang ◽

...

Keyword(s):

Immune Responses ◽

Germ Cells ◽

Expression Profiles ◽

Immune Privilege ◽

Functional Enrichment ◽

Immunofluorescent Staining ◽

Luciferase Reporter ◽

Immune Homeostasis ◽

Schematic Model ◽

Mrna Levels

Beyond its well-known role in spermatogenesis and androgen production, mammalian testes are increasingly recognized as an immune-privileged organ for protecting autoantigenic germ cells, especially meiotic and postmeiotic germ cells, from systemic immune responses. Despite its importance, the molecular mechanisms underlying this regulation in mammals, including sheep, are far from known. In this study, we searched for the genes associated with testicular immune privilege and assessed their possible modulating mechanisms by analyzing systematic profiling of mRNAs and miRNAs on testicular tissues derived from prepubertal and postpubertal Tibetan sheep acquired by RNA sequencing. We identified 1,118 differentially expressed (DE) mRNAs associated with immunity (245 increased mRNAs and 873 decreased mRNAs) and 715 DE miRNAs (561 increased miRNAs and 154 decreased miRNAs) in postpubertal testes compared with prepuberty. qPCR validations for 20 DE mRNAs and 16 miRNAs showed that the RNA-seq results are reliable. By using Western blot, the postpubertal testes exhibited decreased protein abundance of CD19 and TGFBR2 (two proteins encoded by DE mRNAs) when compared with prepuberty, consistent with mRNA levels. The subsequent immunofluorescent staining showed that the positive signals for the CD19 protein were observed mainly in Sertoli cells and the basement membrane of pre- and postpubertal testes, as well as the prepubertal testicular vascular endothelium. The TGFBR2 protein was found mostly in interstitial cells and germ cells of pre- and postpubertal testes. Functional enrichment analysis indicated that DE mRNAs were mainly enriched in biological processes or pathways strongly associated with the blood–testis barrier (BTB) function. Many decreased mRNAs with low expression abundance were significantly enriched in pathways related to immune response. Also, multiple key miRNA-target negative correlation regulatory networks were subsequently established. Furthermore, we verified the target associations between either oar-miR-29b or oar-miR-1185-3p and ITGB1 by dual-luciferase reporter assay. Finally, a putative schematic model of the miRNA-mRNA-pathway network mediated by immune homeostasis-related genes was proposed to show their potential regulatory roles in sheep testicular privilege. Taken together, we conclude that many immune-related genes identified in this study are negatively regulated by potential miRNAs to participate in the homeostatic regulation of testicular immune privilege of sheep by sustaining BTB function and inhibiting immune responses under normal physiological conditions. This work offers the first global view of the expression profiles of miRNAs/mRNAs involved in sheep testicular immune privilege and how the genes potentially contribute to immune-homeostatic maintenance.

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The RhoA-ROCK pathway in the regulation of T and B cell responses

F1000Research ◽

10.12688/f1000research.7522.1 ◽

2016 ◽

Vol 5 ◽

pp. 2295 ◽

Cited By ~ 14

Author(s):

Edd Ricker ◽

Luvana Chowdhury ◽

Woelsung Yi ◽

Alessandra B. Pernis

Keyword(s):

Immune Responses ◽

Biological Processes ◽

Dynamic Interactions ◽

Cell Responses ◽

Important Mediator ◽

Downstream Effectors ◽

Wide Range ◽

Response To Stress ◽

The Impact ◽

Rho Kinases

Effective immune responses require the precise regulation of dynamic interactions between hematopoietic and non-hematopoietic cells. The Rho subfamily of GTPases, which includes RhoA, is rapidly activated downstream of a diverse array of biochemical and biomechanical signals, and is emerging as an important mediator of this cross-talk. Key downstream effectors of RhoA are the Rho kinases, or ROCKs. The ROCKs are two serine-threonine kinases that can act as global coordinators of a tissue’s response to stress and injury because of their ability to regulate a wide range of biological processes. Although the RhoA-ROCK pathway has been extensively investigated in the non-hematopoietic compartment, its role in the immune system is just now becoming appreciated. In this commentary, we provide a brief overview of recent findings that highlight the contribution of this pathway to lymphocyte development and activation, and the impact that dysregulation in the activation of RhoA and/or the ROCKs may exert on a growing list of autoimmune and lymphoproliferative disorders.

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Integrated lncRNA and mRNA Transcriptome Analyses in the Ovary of Cynoglossus semilaevis Reveal Genes and Pathways Potentially Involved in Reproduction

Frontiers in Genetics ◽

10.3389/fgene.2021.671729 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yani Dong ◽

Likang Lyu ◽

Daiqiang Zhang ◽

Jing Li ◽

Haishen Wen ◽

...

Keyword(s):

Signaling Pathways ◽

Target Genes ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Cynoglossus Semilaevis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Biological Processes ◽

Tongue Sole ◽

Oocyte Meiosis

Long non-coding RNAs (lncRNAs) have been reported to be involved in multiple biological processes. However, the roles of lncRNAs in the reproduction of half-smooth tongue sole (Cynoglossus semilaevis) are unclear, especially in the molecular regulatory mechanism driving ovarian development and ovulation. Thus, to explore the mRNA and lncRNA mechanisms regulating reproduction, we collected tongue sole ovaries in three stages for RNA sequencing. In stage IV vs. V, we identified 312 differentially expressed (DE) mRNAs and 58 DE lncRNAs. In stage V vs. VI, we identified 1,059 DE mRNAs and 187 DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DE mRNAs were enriched in ECM-receptor interaction, oocyte meiosis and steroid hormone biosynthesis pathways. Furthermore, we carried out gene set enrichment analysis (GSEA) to identify potential reproduction related-pathways additionally, such as fatty metabolism and retinol metabolism. Based on enrichment analysis, DE mRNAs with a potential role in reproduction were selected and classified into six categories, including signal transduction, cell growth and death, immune response, metabolism, transport and catabolism, and cell junction. The interactions of DE lncRNAs and mRNAs were predicted according to antisense, cis-, and trans-regulatory mechanisms. We constructed a competing endogenous RNA (ceRNA) network. Several lncRNAs were predicted to regulate genes related to reproduction including cyp17a1, cyp19a1, mmp14, pgr, and hsd17b1. The functional enrichment analysis of these target genes of lncRNAs revealed that they were involved in several signaling pathways, such as the TGF-beta, Wnt signaling, and MAPK signaling pathways and reproduction related-pathways such as the progesterone-mediated oocyte maturation, oocyte meiosis, and GnRH signaling pathway. RT-qPCR analysis showed that two lncRNAs (XR_522278.2 and XR_522171.2) were mainly expressed in the ovary. Dual-fluorescence in situ hybridization experiments showed that both XR_522278.2 and XR_522171.2 colocalized with their target genes cyp17a1 and cyp19a1, respectively, in the follicular cell layer. The results further demonstrated that lncRNAs might be involved in the biological processes by modulating gene expression. Taken together, this study provides lncRNA profiles in the ovary of tongue sole and further insight into the role of lncRNA involvement in regulating reproduction in tongue sole.

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Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis

PeerJ ◽

10.7717/peerj.11321 ◽

2021 ◽

Vol 9 ◽

pp. e11321

Author(s):

Di Zhang ◽

Pengguang Yan ◽

Taotao Han ◽

Xiaoyun Cheng ◽

Jingnan Li

Keyword(s):

Ulcerative Colitis ◽

Mitochondrial Dysfunction ◽

Single Gene ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Cell Junction ◽

Biological Processes ◽

Hub Genes ◽

Key Genes

Background Ulcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC. Methods Microarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the “limma” R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the “clusterProfiler” R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene. Results Six functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3. Conclusions Using WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.

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Is the climate change mitigation effect of enhanced silicate weathering governed by biological processes?

Global Change Biology ◽

10.1111/gcb.15993 ◽

2021 ◽

Author(s):

Sara Vicca ◽

Daniel Goll ◽

Mathilde Hagens ◽

Jens Hartmann ◽

Ivan A. Janssens ◽

...

Keyword(s):

Climate Change ◽

Climate Change Mitigation ◽

Silicate Weathering ◽

Biological Processes ◽

Change Mitigation

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QA4SM – An online tool for satellite soil moisture data validation

10.5194/egusphere-egu21-7398 ◽

2021 ◽

Author(s):

Samuel Scherrer ◽

Wolfgang Preimesberger ◽

Monika Tercjak ◽

Zoltan Bakcsa ◽

Alexander Boresch ◽

...

Keyword(s):

Climate Change ◽

Soil Moisture ◽

Land Surface ◽

Global Climate ◽

European Space Agency ◽

Land Surface Model ◽

Surface Model ◽

Space Applications ◽

Online Tool ◽

Soil Moisture Data

To validate satellite soil moisture products and compare their quality with other products, standardized, fully traceable validation methods are required. The QA4SM (Quality Assurance for Soil Moisture; ) free online validation tool provides an easy-to-use implementation of community best practices and requirements set by the Global Climate Observing System and the Committee on Earth Observation Satellites. It sets the basis for a community wide standard for validation studies.QA4SM can be used to preprocess, intercompare, store, and visualise validation results. It uses state-of-the-art open-access soil moisture data records such as the European Space Agency&#8217;s Climate Change Initiative (ESA CCI) and the Copernicus Climate Change Services (C3S) soil moisture datasets, as well as single-sensor products, e.g. H-SAF Metop-A/B ASCAT surface soil moisture, SMOS-IC, and SMAP L3 soil moisture. Non-satellite data include in-situ data from the International Soil Moisture Network (ISMN: ), as well as land surface model or reanalysis products, e.g. ERA5 soil moisture.Users can interactively choose temporal or spatial subsets of the data and apply filters on quality flags. Additionally, validation of anomalies and application of different scaling methods are possible. The tool provides traditional validation metrics for dataset pairs (e.g. correlation, RMSD) as well as triple collocation metrics for dataset triples. All results can be visualised on the webpage, downloaded as figures, or downloaded in NetCDF format for further use. Archiving and publishing features allow users to easily store and share validation results. Published validation results can be cited in reports and publications via DOIs.The new version of the service provides support for high-resolution soil moisture products (from Sentinel-1), additional datasets, and improved usability.We present an overview and examples of the online tool, new features, and give an outlook on future developments.Acknowledgements: This work was supported by the QA4SM & QA4SM-HR projects, funded by the Austrian Space Applications Programme (FFG).

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