Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S versus R rats

<p>Abstract</p> <p>Background</p> <p>To test whether epithelial sodium channel (ENaC) genes' variants contribute to salt sensitive hypertension in Dahl rats, we screened ENaC α, β, and γ genes entire coding regions, intron-exon junctions, and the 3' and 5' flanking regions in Dahl S, R and Wistar rats using both Denaturing High Performance Liquid Chromatography (DHPLC) and sequencing.</p> <p>Results</p> <p>Our analysis revealed no sequence variability in the three genes encoding ENaC in Dahl S <it>versus </it>R rats. One homozygous sequence variation predicted to result in a D75E substitution was identified in Dahl and Wistar rat ENaC α compared to Brown Norway. Six and two previously reported polymorphic sites in Brown Norway sequences were lost in Dahl and Wistar rats, respectively. In the 5' flanking regions, we found a deletion of 5GCTs in Dahl and Wistar rat ENaC α gene, five new polymorphic sites in ENaC β and γ genes, one homozygous sequence variation in Dahl and Wistar rat ENaC γ gene, as well as one Dahl rat specific homozygous insertion of -1118CCCCCA in ENaC γ gene. This insertion created additional binding sites for Sp1 and Oct-1. Five and three Brown Norway polymorphic sites were lost in Dahl and Wistar rats, respectively. No sequence variability in ENaC 3' flanking regions was identified in Dahl compared to Brown Norway rats.</p> <p>Conclusion</p> <p>The first comprehensive sequence analysis of ENaC genes did not reveal any differences between Dahl S and R rats that were isogenic in the regions screened. Mutations in ENaC genes intronic sequence or in ENaC-regulatory genes might possibly account for increased ENaC activity in Dahl S <it>versus </it>R rats.</p

ATTR amyloidosis during the COVID-19 pandemic: insights from a global medical roundtable

BACKGROUND: The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing the ongoing coronavirus disease 2019 (COVID-19) pandemic has raised serious concern for patients with chronic disease. A correlation has been identified between the severity of COVID-19 and a patient's preexisting comorbidities. Although COVID-19 primarily involves the respiratory system, dysfunction in multiple organ systems is common, particularly in the cardiovascular, gastrointestinal, immune, renal, and nervous systems. Patients with amyloid transthyretin (ATTR) amyloidosis represent a population particularly vulnerable to COVID-19 morbidity due to the multisystem nature of ATTR amyloidosis. MAIN BODY: ATTR amyloidosis is a clinically heterogeneous progressive disease, resulting from the accumulation of amyloid fibrils in various organs and tissues. Amyloid deposition causes multisystem clinical manifestations, including cardiomyopathy and polyneuropathy, along with gastrointestinal symptoms and renal dysfunction. Given the potential for exacerbation of organ dysfunction, physicians note possible unique challenges in the management of patients with ATTR amyloidosis who develop multiorgan complications from COVID-19. While the interplay between COVID-19 and ATTR amyloidosis is still being evaluated, physicians should consider that the heightened susceptibility of patients with ATTR amyloidosis to multiorgan complications might increase their risk for poor outcomes with COVID-19. CONCLUSION: Patients with ATTR amyloidosis are suspected to have a higher risk of morbidity and mortality due to age and underlying ATTR amyloidosis-related organ dysfunction. While further research is needed to characterize this risk and management implications, ATTR amyloidosis patients might require specialized management if they develop COVID-19. The risks of delaying diagnosis or interrupting treatment for patients with ATTR amyloidosis should be balanced with the risk of exposure in the health care setting. Both physicians and patients must adapt to a new construct for care during and possibly after the pandemic to ensure optimal health for patients with ATTR amyloidosis, minimizing treatment interruptions

Genomic-based-breeding tools for tropical maize improvement

Maize has traditionally been the main staple diet in the Southern Asia and Sub-Saharan Africa and widely grown by millions of resource poor small scale farmers. Approximately, 35.4 million hectares are sown to tropical maize, constituting around 59% of the developing worlds. Tropical maize encounters tremendous challenges besides poor agro-climatic situations with average yields recorded <3 tones/hectare that is far less than the average of developed countries. On the contrary to poor yields, the demand for maize as food, feed, and fuel is continuously increasing in these regions. Heterosis breeding introduced in early 90 s improved maize yields significantly, but genetic gains is still a mirage, particularly for crop growing under marginal environments. Application of molecular markers has accelerated the pace of maize breeding to some extent. The availability of array of sequencing and genotyping technologies offers unrivalled service to improve precision in maize-breeding programs through modern approaches such as genomic selection, genome-wide association studies, bulk segregant analysis-based sequencing approaches, etc. Superior alleles underlying complex traits can easily be identified and introgressed efficiently using these sequence-based approaches. Integration of genomic tools and techniques with advanced genetic resources such as nested association mapping and backcross nested association mapping could certainly address the genetic issues in maize improvement programs in developing countries. Huge diversity in tropical maize and its inherent capacity for doubled haploid technology offers advantage to apply the next generation genomic tools for accelerating production in marginal environments of tropical and subtropical world. Precision in phenotyping is the key for success of any molecular-breeding approach. This article reviews genomic technologies and their application to improve agronomic traits in tropical maize breeding has been reviewed in detail

Comparison of cervicovaginal proinflammatory cytokine with fetal fibronectin and cervical length in predicting preterm labor in Egyptian women

Spontaneous preterm birth remains a significant problem allover the world despite increase research to decrease its prevalence. Strategies have been limited by inability to identify patients at risk for preterm birth, as the majority of patients don`t have historical risk factors. The development of an assay to detect cervicovaginal fetal fibronectin (fFN), proinflammatory cytokines along with transvaginal cervical length determination has greatly increased our ability to identify those patients with high risk. We performed quantitative analysis of fFN, IL-1&beta;, IL-6 and IL-8 in cervicovaginal secretions by ELISA to predict preterm delivered patients with intact membrane and cervical dilatation of &le; 3cm. Our results revealed marked significant increase in both cervicovaginal fetal fibronectin and IL-6 levels, and non significant increase for both cervicovaginal IL-1&beta; and IL-8inspontaneous preterm delivered patients compared with non preterm delivered patients. Furthermore, significant correlations were found between cervical lengths and both fFN and IL-6, while no significant correlations existed with other measured inflammatory cytokines. Ourresults concluded that fetal fibronectin and IL-6 may add a prognosticvalue to that provided by sonographic cervical length in patients withpreterm uterine contractions and intact membranes.Keywords: Preterm delivery (PTD), fetal fibronectin (fFN),Interleukine1&beta; (IL-1&beta;), Interleukine-6 (IL-6) and Interleukine-8 (IL-8)

Location of the variants identified in the 5' flanking region of Dahl S, R, and Wistar rats ENaC α gene on the Brown Norway rat genomic sequence 15

<p><b>Copyright information:</b></p><p>Taken from "Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S R rats"</p><p>http://www.biomedcentral.com/1471-2156/8/35</p><p>BMC Genetics 2007;8():35-35.</p><p>Published online 25 Jun 2007</p><p>PMCID:PMC1933436.</p><p></p> Position of the variants identified in the current study is highlighted in bold. Boxes represent the putative transcription factor-binding sequences; the putative binding sequences found during the present sequence analysis are labeled in bold; the factor names are written above the boxes. The first three bases for the major kidney and brain transcription start sites are italicized and bold. The translation initiation codon (+1) is underlined. TFSEARCHscores for the newly assigned putative binding sequences are 93.1, 89.7, and 89.7 for GATA 1, 2, 3 respectively; 89.0 and 88.5 for GATA 1, 2 respectively and 85.8 for YY1; 88.5 for GATA 2, and 87.7 for Sp1

Location of the variants identified in the 5' flanking region of Dahl S, R, and Wistar rats ENaC γ gene on the Brown Norway rat genomic sequence 15

<p><b>Copyright information:</b></p><p>Taken from "Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S R rats"</p><p>http://www.biomedcentral.com/1471-2156/8/35</p><p>BMC Genetics 2007;8():35-35.</p><p>Published online 25 Jun 2007</p><p>PMCID:PMC1933436.</p><p></p> Position of the variants identified in the current study is highlighted in bold. Boxes represent the putative transcription factor-binding sequences; the putative binding sequences found during the present sequence analysis are labeled in bold; the factor names are written above the boxes. The first three bases for the major kidney and brain transcription start sites are italicized and bold. The translation initiation codon (+1) is underlined. TFSEARCHscores for the newly assigned putative binding sequences are 89.2, 87.4, and 89.0 for C/EBP a & b and CRE, respectively; 85.8 for Oct-1; 89.3 for C/EBP, 87.9 and 85.5 for CRE and C/EBPb respectively; 87.7 for Sp1, 91.0 and 87.4 for c-Myc and C/EBPb respectively; and 85.9 for USF

Location of the variants identified in the 5' flanking region of Dahl S, R, and Wistar rats ENaC β gene on the Brown Norway rat genomic sequence 15

<p><b>Copyright information:</b></p><p>Taken from "Sequence analysis of coding and 3' and 5' flanking regions of the epithelial sodium channel α, β, and γ genes in Dahl S R rats"</p><p>http://www.biomedcentral.com/1471-2156/8/35</p><p>BMC Genetics 2007;8():35-35.</p><p>Published online 25 Jun 2007</p><p>PMCID:PMC1933436.</p><p></p> Position of the variants identified in the current study is highlighted in bold. Boxes represent the putative transcription factor-binding sequences; the putative binding sequences found during the present sequence analysis are labeled in bold; the factor names are written above the boxes. The first three bases for the major kidney and brain transcription start sites are italicized and bold. TFSEARCHscore for the newly assigned putative binding sequence for STATX is 92.3