Fabertermansen7962

Fission yeast Erh1 exists in a complex with RNA-binding protein Mmi1. Deletion of erh1 upregulates the phosphate homeostasis gene pho1, which is normally repressed by transcription in cis of a 5' flanking prt lncRNA. Here we present evidence that de-repression of pho1 by erh1∆ is achieved through precocious 3'-processing/termination of prt lncRNA synthesis, to wit (i) erh1∆ does not affect the activity of the prt or pho1 promoters per se; (ii) de-repression by erh1∆ depends on CPF (cleavage and polyadenylation factor) subunits Ctf1, Dis2, Ssu72, Swd22, and Ppn1 and on termination factor Rhn1; (iii) de-repression requires synthesis by the Asp1 IPP kinase of inositol 1-pyrophosphates (1-IPPs); (iv) de-repression is effaced by mutating Thr4 of the RNA polymerase II CTD to alanine; and (v) erh1∆ exerts an additive effect on pho1 de-repression in combination with mutating CTD Ser7 to alanine and with deletion of the IPP pyrophosphatase Aps1. These findings point to Erh1 as an antagonist of lncRNA termination in the prt-pho1 axis. By contrast, in mmi1∆ cells there is a reduction in pho1 mRNA and increase in the formation of a prt-pho1 read-through transcript, consistent with Mmi1 being an agonist of prt termination. We envision that Erh1 acts as a brake on Mmi1's ability to promote CPF-dependent termination during prt lncRNA synthesis. Consistent with this idea, erh1∆ de-repression of pho1 was eliminated by mutating the Mmi1-binding sites in the prt lncRNA.Background Diabetes affects 30.3 million people in the USA. Among these people, a major risk factor for microvascular complications is having a glycated haemoglobin (HbA1c) value of ≥75 mmol/mol; therefore, it would be helpful to identify patients who will obtain future HbA1c values of less then 75 mmol/mol. Objectives To develop and validate two prediction rules among patients with diabetes having a baseline HbA1c value of ≥75 mmol/mol (1) HbA1c measurement ever less then 75 mmol/mol and (2) final HbA1c measurement of less then 75 mmol/mol. Methods Retrospective cohort study using a registry extracting data from the Department of Veterans Affairs's (VA's) electronic health records system. Baseline was 1 Jul 2013-30 June 2014; patients were followed up until 31 July 2016. Results Our population consisted of 145 659 patients. Across models, predictors were age, sex, minority status, baseline HbA1c value, time, HbA1c≥75 mmol/mol, receiving insulin treatment and consecutive number of HbA1c values of 75 mmol/mol. The overall likelihood of a patient ever having an HbA1c less then 75 mmol/mol was 73.65%; with the rule, predicted probabilities were 38.94%, 50.75% and 78.88%. The overall likelihood of patients having a final HbA1c measurement of less then 75 mmol/mol was 55.35%; the rule provided predicted probabilities of 29.93%, 50.17% and 68.58%. Conclusions Within each rule, there were similar observed and predicted tertile probabilities; maintaining HbA1c values of less then 75 mmol/mol resulted in probability shifts in the majority of patients. We recommend psychosocial screening for 15% of patients for whom there is less than one-third chance of maintaining HbA1c less then 75 mmol/mol. We plan to conduct additional research to see whether this approach helps.Objectives To develop, calibrate, test and validate a logistic regression model for accurate risk prediction of sudden cardiac death (SCD) and non-fatal sudden cardiac arrest (SCA) in adults with congenital heart disease (ACHD), based on baseline lesion-specific risk stratification and individual's characteristics, to guide primary prevention strategies. Methods We combined data from a single-centre cohort of 3311 consecutive ACHD patients (50% male) at 25-year follow-up with 71 events (53 SCD and 18 non-fatal SCA) and a multicentre case-control group with 207 cases (110 SCD and 97 non-fatal SCA) and 2287 consecutive controls (50% males). Cumulative incidences of events up to 20 years for specific lesions were determined in the prospective cohort. Risk model and its 5-year risk predictions were derived by logistic regression modelling, using separate development (18 centres 144 cases and 1501 controls) and validation (two centres 63 cases and 786 controls) datasets. Results According to the combined SCD/SCA cumulative 20 years incidence, a lesion-specific stratification into four clusters-very-low (12%)-was built. Multivariable predictors were lesion-specific cluster, young age, male sex, unexplained syncope, ischaemic heart disease, non-life threatening ventricular arrhythmias, QRS duration and ventricular systolic dysfunction or hypertrophy. The model very accurately discriminated (C-index 0.91; 95% CI 0.88 to 0.94) and calibrated (p=0.3 for observed vs expected proportions) in the validation dataset. Compared with current guidelines approach, sensitivity increases 29% with less than 1% change in specificity. Conclusions Predicting the risk of SCD/SCA in ACHD can be significantly improved using a baseline lesion-specific stratification and simple clinical variables.Taro (Colocasia esculenta) is a food staple widely cultivated in the humid tropics of Asia, Africa, Pacific and the Caribbean. https://www.selleckchem.com/products/4-phenylbutyric-acid-4-pba-.html One of the greatest threats to taro production is Taro Leaf Blight caused by the oomycete pathogen Phytophthora colocasiae Here we describe a de novo taro genome assembly and use it to analyze sequence data from a Taro Leaf Blight resistant mapping population. The genome was assembled from linked-read sequences (10x Genomics; ∼60x coverage) and gap-filled and scaffolded with contigs assembled from Oxford Nanopore Technology long-reads and linkage map results. The haploid assembly was 2.45 Gb total, with a maximum contig length of 38 Mb and scaffold N50 of 317,420 bp. A comparison of family-level (Araceae) genome features reveals the repeat content of taro to be 82%, >3.5x greater than in great duckweed (Spirodela polyrhiza), 23%. Both genomes recovered a similar percent of Benchmarking Universal Single-copy Orthologs, 80% and 84%, based on a 3,236 gene database for monocot plants. A greater number of nucleotide-binding leucine-rich repeat disease resistance genes were present in genomes of taro than the duckweed, ∼391 versus ∼70 (∼182 and ∼46 complete). The mapping population data revealed 16 major linkage groups with 520 markers, and 10 quantitative trait loci (QTLs) significantly associated with Taro Leaf Blight disease resistance. The genome sequence of taro enhances our understanding of resistance to TLB, and provides markers that may accelerate breeding programs. This genome project may provide a template for developing genomic resources in other understudied plant species.