Characterization of the promoter and upstream activation sequences of sporulation-specific genes SPR1 (SSG1) and SPR2 in saccharomyces cerevisiae

Sporulation is a developmental process in which temporally distinct sets of genes regulate the processes of meiosis and ascospore formation. Sporulation-specific genes are classified into early, middle, and late genes based on their peak time of expression during sporulation. Regulation of two late genes, SPR1 and SPR2, was studied. The function of SPR2 is unknown. Its regulatory region contains two Mid Sporulation Elements (MSE) repeated in tandem that are sufficient to confer sporulation-specific regulation to a CYCl-lacZ reporter. These sequences have UAS (upstream activation sequence) properties, as each 14 base pair element is sufficient to confer sporulation-specific regulation independent of orientation. A greater than 5-fold higher induction is observed with the tandem MSEs compared to the individual elements. Mutations within a GC rich region indicate that these sequences are necessary for MSE function. The SPR1 gene encodes a 1,3-β-glucanase that is believed to be involved in spore wall maturation. The 5’ regulatory region of SPR1 was studied by constructing a series of translational and transcriptional fusions. Studies using the translational fusions suggest that sequences from -268 to +1 are sufficient to confer sporulation-specific regulation, and that SPR1 is controlled by a TATA-less promoter that lies between -151 to +1. In addition, homology searches revealed two sequences with weak matches to known activation sequences: (a) sequences from -293 to -279 have 10/15 matches to the UAS of SPS4; (b) sequences from -252 to -236 have 12/17 matches to the MSE of SPR2. Internal deletion and transcriptional fusion studies, taken together, indicate that both the UAS-like and MSE-like sequences are necessary but not sufficient for temporal regulation of SPR1. This evidence suggests that SPR1 is regulated by a composite promoter with essential elements lying downstream of -268 and other weaker positive elements which are dispersed from -268 to -762. Studies with mutants of ime2, ume6 and ndt80 suggest that all three proteins are positive regulators of the SPR1 and SPR2 genes. Distinct banding patterns observed during mobility shift assays with extracts from vegetative and sporulating cells, suggest that different protein complexes bind the regulatory sequences during vegetative growth and sporulation. Recombinant Ndt80p shows DNA protein interactions with both SPR1 and SPR2 probes. This evidence suggests that Ndt80p regulates SPR2 via the MSE, while it regulates SPR1 via other sequences

The Role Of Media Relations In Corporate Public Relations Practice : A Study On 15 Public Listed Companies In The Klang Valley [HD59.6. S531 2007 f rb].

Tesis ini mengemukakan hasil kajian kualitatif tentang sama ada perhubungan media memainkan peranan yang strategik dalam amalan perhubungan awam korporat di Malaysia. This thesis presents findings from a qualitative investigation of whether media relations plays a strategic role in corporate public relations practice in Malaysia. The primary objective was to discover how media relations was viewed and utilised in Malaysian organisations

A common variant near TGFBR3 is associated with primary open angle glaucoma

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution.We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

<p>Abstract</p> <p>Background</p> <p>The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite <it>P. vivax </it>remain little characterized.</p> <p>Results</p> <p>We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of <it>P. vivax </it>in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for ~40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of <it>P. vivax</it>. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the <it>pvmdr-1 </it>locus, putatively associated with drug resistance.</p> <p>Conclusion</p> <p>These findings support the feasibility of genome-wide association studies in carefully selected populations of <it>P. vivax</it>, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.</p> <p>See commentary: <url>http://www.biomedcentral.com/1741-7007/8/90</url></p

Downloaded from

Abstract Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array ), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, OR G-allele = 1.13, P meta = 1.60 × 10 −8 ). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial

Background: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. Methods: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5–12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0–94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96–1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of −0·040 (95% central range −0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. Interpretation: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. Funding: National Institute for Health Research Health Technology Assessment Programme