scholarly journals The genome of the biting midge Culicoides sonorensis and gene expression analyses of vector competence for Bluetongue virus

2018 ◽  
Author(s):  
Ramiro Morales-Hojas ◽  
Malcolm Hinsley ◽  
Irina M. Armean ◽  
Rhiannon Silk ◽  
Lara E. Harrup ◽  
...  

AbstractBackgroundThe use of the new genomic technologies has led to major advances in control of several arboviruses of medical importance such as Dengue. However, the development of tools and resources available for vectors of non-zoonotic arboviruses remains neglected. Biting midges of the genus Culicoides transmit some of the most important arboviruses of wildlife and livestock worldwide, with a global impact on economic productivity, health and welfare. The absence of a suitable reference genome has hindered genomic analyses to date in this important genus of vectors. In the present study, the genome of Culicoides sonorensis, a vector of bluetongue virus (BTV) in the USA, has been sequenced to provide the first reference genome for these vectors. In this study, we also report the use of the reference genome to perform initial transcriptomic analyses of vector competence for BTV.ResultsOur analyses reveal that the genome is 197.4 Mb, assembled in 7,974 scaffolds. Its annotation using the transcriptomic data generated in this study and in a previous study has identified 15,629 genes. Gene expression analyses of C. sonorensis females infected with BTV performed in this study revealed 165 genes that were differentially expressed between vector competent and refractory females. Two candidate genes, glutathione S-transferase (gst) and the antiviral helicase ski2, previously recognized as involved in vector competence for BTV in C. sonorensis (gst) and repressing dsRNA virus propagation (ski2), were confirmed in this study.ConclusionsThe reference genome of C. sonorensis has enabled preliminary analyses of the gene expression profiles of vector competent and refractory individuals. The genome and transcriptomes generated in this study provide suitable tools for future research on arbovirus transmission. These provide a significant resource for these vector lineage, which diverged from other major Dipteran vector families over 200 million years ago. The genome will be a valuable source of comparative data for other important Dipteran vector families including mosquitoes (Culicidae) and sandflies (Psychodidae), and yield potential targets for transgenic modification in vector control and functional studies.


BMC Genomics ◽  
2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Ramiro Morales-Hojas ◽  
Malcolm Hinsley ◽  
Irina M. Armean ◽  
Rhiannon Silk ◽  
Lara E. Harrup ◽  
...  


2018 ◽  
Vol 50 (8) ◽  
pp. 615-627
Author(s):  
Sun Hyung Kwon ◽  
Li Li ◽  
Christi M. Terry ◽  
Yan-Ting Shiu ◽  
Philip J. Moos ◽  
...  

Arteriovenous hemodialysis graft (AVG) stenosis results in thrombosis and AVG failure, but prevention of stenosis has been unsuccessful due in large part to our limited understanding of the molecular processes involved in neointimal hyperplasia (NH) formation. AVG stenosis develops chiefly as a consequence of highly localized NH formation in the vein-graft anastomosis region. Surprisingly, the vein region just downstream of the vein-graft anastomosis (herein termed proximal vein region) is relatively resistant to NH. We hypothesized that the gene expression profiles of the NH-prone and NH-resistant regions will be different from each other after graft placement, and analysis of their genomic profiles may yield potential therapeutic targets to prevent AVG stenosis. To test this, we evaluated the vein-graft anastomosis (NH-prone) and proximal vein (NH-resistant) regions in a porcine model of AVG stenosis with a porcine microarray. Gene expression changes in these two distinct vein regions, relative to the gene expression in unoperated control veins, were examined at early (5 days) and later (14 days) time points following graft placement. Global genomic changes were much greater in the NH-prone region than in the NH-resistant region at both time points. In the NH-prone region, genes related to regulation of cell proliferation and osteo-/chondrogenic vascular remodeling were most enriched among the significantly upregulated genes, and genes related to smooth muscle phenotype were significantly downregulated. These results provide insights into the spatial and temporal genomic modulation underlying NH formation in AVG and suggest potential therapeutic strategies to prevent and/or limit AVG stenosis.



2019 ◽  
Author(s):  
Charity Muriuki ◽  
Stephen J. Bush ◽  
Mazdak Salavati ◽  
Mary E.B. McCulloch ◽  
Zofia M. Lisowski ◽  
...  

AbstractGoats (Capra hircus) are an economically important livestock species providing meat and milk across the globe. They are of particular importance in tropical agri-systems contributing to sustainable agriculture, alleviation of poverty, social cohesion and utilisation of marginal grazing. There are excellent genetic and genomic resources available for goats, including a highly contiguous reference genome (ARS1). However, gene expression information is limited in comparison to other ruminants. To support functional annotation of the genome and comparative transcriptomics we created a mini-atlas of gene expression for the domestic goat. RNA-Seq analysis of 22 transcriptionally rich tissues and cell-types detected the majority (90%) of predicted protein-coding transcripts and assigned informative gene names to more than 1000 previously unannotated protein-coding genes in the current reference genome for goat (ARS1). Using network-based cluster analysis we grouped genes according to their expression patterns and assigned those groups of co-expressed genes to specific cell populations or pathways. We describe clusters of genes expressed in the gastro-intestinal tract and provide the expression profiles across tissues of a subset of genes associated with functional traits. Comparative analysis of the goat atlas with the larger sheep gene expression atlas dataset revealed transcriptional differences between the two species in macrophage-associated signatures. The goat transcriptomic resource complements the large gene expression dataset we have generated for sheep and contributes to the available genomic resources for interpretation of the relationship between genotype and phenotype in small ruminants.



2021 ◽  
Author(s):  
Zhongze Cui ◽  
Shuang He ◽  
Feifei Wen ◽  
Xiaoyang Xu ◽  
Yangyang Li ◽  
...  

Abstract Background: Colon adenocarcinoma (COAD) is one of the most common malignancies worldwide. Although a large number of studies have elucidated the aetiology of colorectal cancer, the exact mechanism of colorectal cancer development remains to be determined.To identify key modules and prognostic genes that may be involved in the occurrence and development of COAD, weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed on datasets GSE41657 and GSE74602 from the Gene Expression Omnibus (GEO) database to screen for prognostic differentially expressed genes. Gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database for verification.Results: Through WGCNA and DEGs analysis, 439 genes in key functional modules were obtained, and 26 prognostic related genes were finally obtained through prognostic analysis: (1) We screened 5 genes(RPP40, DUSP18, PPRC1, MFSD11 and PDCD11) that have not been studied in COAD.(2)We obtained the most critical module in the occurrence and development of colon cancer and obtained one prognosis-related gene, NUP85, from the most critical module.The relationship between it and tumor immune microenvironment was verified.(3) A prognostic model comprising four coexpressed differential genes was constructed; TIMP1, PMM2, E2F3 and MORC2 were selected as the key prognosis-related genes.Conclusions: (1)As new biomarkers,prognostic genes RPP40, DUSP18, PPRC1, MFSD11 and PDCD11 may be potential therapeutic targets for COAD, and provide new ideas for future research on the mechanism of COAD. (2)NUP85 may be an immune-related gene which was negatively correlated with CD4+ T cell and M2 macrophagesthat plays an important role in inhibiting the occurrence and development of colorectal adenocarcinoma. (3)A Cox proportional risk model based on gene expression can be used to predict the prognosis and survival time of patients with colon cancer.



2009 ◽  
Vol 31 (1) ◽  
pp. 19-29
Author(s):  
Orsolya Galamb ◽  
Ferenc Sipos ◽  
Sándor Spisák ◽  
Barnabás Galamb ◽  
Tibor Krenács ◽  
...  

Background: As most colorectal cancers (CRC) develop from villous adenomas, studying alterations in gene expression profiles across the colorectal adenoma–dysplasia–carcinoma sequence may yield potential biomarkers of disease progression.Methods: Total RNA was extracted, amplified, and biotinylated from colonic biopsies of 15 patients with CRC, 15 with villous adenoma and 8 normal controls. Gene expression profiles were evaluated using HGU133Plus2.0 microarrays and disease progression associated data were validated with RT-PCR. The potential biomarkers were also tested at the protein level using tissue microarray samples of 103 independent and 16 overlapping patients.Results: 17 genes were validated to show sequentially altered expression at mRNA level through the normal–adenoma–dysplasia–carcinoma progression. Prostaglandin-D2 receptor (PTGDR) and amnionless homolog (AMN) genes revealed gradually decreasing expression while the rest of 15 genes including osteonectin, osteopontin, collagen IV–alpha 1, biglycan, matrix GLAprotein, and von Willebrand factor demonstrated progressively increasing expression. Similar trends of expression were confirmed at protein level for PTGDR, AMN, osteopontin and osteonectin.Conclusion: Downregulated AMN and PTGDR and upregulated osteopontin and osteonectin were found as potential biomarkers of colorectal carcinogenesis and disease progression to be utilized for prospective biopsy screening both at mRNA and protein levels. Gene alterations identified here may also add to our understanding of CRC progression.



2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kathleen C. Light ◽  
Andrea T. White ◽  
Scott Tadler ◽  
Eli Iacob ◽  
Alan R. Light

In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information. This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels. The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed.



Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 226
Author(s):  
Bethany L. McGregor ◽  
C. Roxanne Connelly ◽  
Joan L. Kenney

Oropouche virus (OROV), a vector-borne Orthobunyavirus circulating in South and Central America, causes a febrile illness with high rates of morbidity but with no documented fatalities. Oropouche virus is transmitted by numerous vectors, including multiple genera of mosquitoes and Culicoides biting midges in South America. This study investigated the vector competence of three North American vectors, Culex tarsalis, Culex quinquefasciatus, and Culicoides sonorensis, for OROV. Cohorts of each species were fed an infectious blood meal containing 6.5 log10 PFU/mL OROV and incubated for 10 or 14 days. Culex tarsalis demonstrated infection (3.13%) but not dissemination or transmission potential at 10 days post infection (DPI). At 10 and 14 DPI, Cx. quinquefasciatus demonstrated 9.71% and 19.3% infection, 2.91% and 1.23% dissemination, and 0.97% and 0.82% transmission potential, respectively. Culicoides sonorensis demonstrated 86.63% infection, 83.14% dissemination, and 19.77% transmission potential at 14 DPI. Based on these data, Cx. tarsalis is unlikely to be a competent vector for OROV. Culex quinquefasciatus demonstrated infection, dissemination, and transmission potential, although at relatively low rates. Culicoides sonorensis demonstrated high infection and dissemination but may have a salivary gland barrier to the virus. These data have implications for the spread of OROV in the event of a North American introduction.



2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunling Zhu ◽  
Yuting Jiang ◽  
Qianghui Zhang ◽  
Jian Gao ◽  
Chaojie Li ◽  
...  

Abstract Background Zika virus (ZIKV) is transmitted to humans primarily by Aedes aegypti. Previous studies on Ae. aegypti from Jiegao (JG) and Mengding (MD) in Yunnan province, China have shown that these mosquitoes are able to transmit ZIKV to their offspring through vertical transmission, indicating that these two Ae. aegypti strains pose a potential risk for ZIKV transmission. However, the vector competence of these two Ae. aegypti strains to ZIKV has not been evaluated and the molecular mechanisms influencing vector competence are still unclear. Methods Aedes aegypti mosquitoes from JG and MD were orally infected with ZIKV, and the infection rate (IR), dissemination rate (DR), transmission rate (TR) and transmission efficiency (TE) of these two mosquito strains were explored to evaluate their vector competence to ZIKV. On 2, 4 and 6 days post-infection (dpi), the small RNA profiles between ZIKV-infected and non-infected Ae. aegypti midgut and salivary gland tissues were compared to gain insights into the molecular interactions between ZIKV and Ae. aegypti. Results There were no significant differences in the IR, DR, TR and TE between the two Ae. aegypti strains (P > 0.05). However, ZIKV RNA appeared 2 days earlier in saliva of the JG strain, which indicated a higher competence of the JG strain to transmit ZIKV. Significant differences in the microRNA (miRNA) expression profiles between ZIKV-infected and non-infected Ae. aegypti were found in the 2-dpi libraries of both the midgut and salivary gland tissues from the two strains. In addition, 27 and 74 miRNAs (|log2 fold change| > 2) were selected from the miRNA expression profiles of ZIKV-infected and non-infected midgut and salivary gland tissues from the JG and MD strains, respectively. Conclusions Our results provide novel insights into the ZIKV–mosquito interactions and build a foundation for future research on how miRNAs regulate the vector competence of mosquitoes to this arbovirus. Graphical abstract



Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 73-110 ◽  
Author(s):  
Francis J. Giles ◽  
Armand Keating ◽  
Anthony H. Goldstone ◽  
Irit Avivi ◽  
Cheryl L. Willman ◽  
...  

Abstract In this chapter, Drs. Keating and Willman review recent advances in our understanding of the pathophysiology of acute myeloid leukemia (AML) and allied conditions, including the advanced myelodysplastic syndromes (MDS), while Drs. Goldstone, Avivi, Giles, and Kantarjian focus on therapeutic data with an emphasis on current patient care and future research studies. In Section I, Dr. Armand Keating reviews the role of the hematopoietic microenvironment in the initiation and progression of leukemia. He also discusses recent data on the stromal, or nonhematopoietic, marrow mesenchymal cell population and its possible role in AML. In Section II, Drs. Anthony Goldstone and Irit Avivi review the current role of stem cell transplantation as therapy for AML and MDS. They focus on data generated on recent Medical Research Council studies and promising investigation approaches. In Section III, Dr. Cheryl Willman reviews the current role of molecular genetics and gene expression analysis as tools to assist in AML disease classification systems, modeling of gene expression profiles associated with response or resistance to various interventions, and identifying novel therapeutic targets. In Section IV, Drs. Hagop Kantarjian and Francis Giles review some promising agents and strategies under investigation in the therapy of AML and MDS with an emphasis on novel delivery systems for cytotoxic therapy and on targeted biologic agents.



2016 ◽  
Vol 19 (4) ◽  
pp. 849-857 ◽  
Author(s):  
M. Garncarz ◽  
M. Hulanicka ◽  
H. Maciejewski ◽  
M. Parzeniecka-Jaworska ◽  
M. Jank

Abstract Studies identifying specific pathologically expressed genes have been performed on diseased myocardial tissue samples, however less invasive studies on gene expression of peripheral blood mononucleated cells give promising results. This study assessed transcriptomic data that may be used to evaluate Dachshunds with chronic mitral valve disease. Dachshunds with different stages of heart disease were compared to a control, healthy group. Microarray data analysis revealed clusters of patients with similar expression profiles. The clusters were compared to the clinical classification scheme. Unsupervised classification of the studied groups showed three clusters. Clinical and laboratory parameters of patients from the cluster 1 were in accordance with those found in patients without heart disease. Data obtained from patients from the cluster 3 were typical of advanced heart failure patients. Comparison of the cluster 1 and 3 groups revealed 1133 differentially expressed probes, 7 significantly regulated process pathways and 2 significantly regulated Ariadne Metabolic Pathways. This study may serve as a guideline for directing future research on gene expression in chronic mitral valve disease.



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