3,638 research outputs found

    Genomic Expression Program Involving the Haalp-Regulation in Saccharomyces cerevisiae response to acetic acid

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    The alterations occurring in yeast genomic expression during early response to acetic acid and the involvement of the transcription factor Haa1p in this transcriptional reprogramming are described in this study. Haa1p was found to regulate, directly or indirectly, the transcription of approximately 80% of the acetic acid-activated genes, suggesting that Haa1p is the main player in the control of yeast response to this weak acid. The genes identified in this work as being activated in response to acetic acid in a Haa1p-dependent manner include protein kinases, multidrug resistance transporters, proteins involved in lipid metabolism, in nucleic acid processing, and proteins of unknown function. Among these genes, the expression of SAP30 and HRK1 provided the strongest protective effect toward acetic acid. SAP30 encode a subunit of a histone deacetylase complex and HRK1 encode a protein kinase belonging to a family of protein kinases dedicated to the regulation of plasma membrane transporters activity. The deletion of the HRK1 gene was found to lead to the increase of the accumulation of labeled acetic acid into acid-stressed yeast cells, suggesting that the role of both HAA1 and HRK1 in providing protection against acetic acid is, at least partially, related with their involvement in the reduction of intracellular acetate concentration

    The Major Facilitator Superfamily Transporter ZIFL2 Modulates Cesium and Potassium Homeostasis in Arabidopsis

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    Potassium (K(+)) is an essential mineral nutrient for plant growth and development, with numerous membrane transporters and channels having been implicated in the maintenance and regulation of its homeostasis. The cation cesium (Cs(+)) is toxic for plants but shares similar chemical properties to the K(+) ion and hence competes with its transport. Here, we report that K(+) and Cs(+) homeostasis in Arabidopsis thaliana also requires the action of ZIFL2 (Zinc-Induced Facilitator-Like 2), a member of the Major Facilitator Superfamily (MFS) of membrane transporters. We show that the Arabidopsis ZIFL2 is a functional transporter able to mediate K(+) and Cs(+) influx when heterologously expressed in yeast. Promoter-reporter, reverse transcription-PCR and fluorescent protein fusion experiments indicate that the predominant ZIFL2.1 isoform is targeted to the plasma membrane of endodermal and pericyle root cells. ZIFL2 loss of function and overexpression exacerbate and alleviate plant sensitivity, respectively, upon Cs(+) and excess K(+) supply, also influencing Cs(+) whole-plant partitioning. We propose that the activity of this Arabidopsis MFS carrier promotes cellular K(+) efflux in the root, thereby restricting Cs(+)/K(+) xylem loading and subsequent root to shoot translocation under conditions of Cs(+) or high K(+) external supply.FCT fellowships: (SFRH/BPD/44640/2008, SFRH/BPD/81221/2011)

    Avaliação e ações prioritárias para conservação do Bioma Caatinga.

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    Este documento sintetiza as informações geradas nas duas últimas décadas por várias Instituições de Pesquisa, Desenvolvimento e Ensino do Brasil, no que se refere a elaboração de um diagnóstico do quadro natural e agrossocioeconômico deste tão importante ecossistema.bitstream/item/136247/1/ID-8676.pdfDocumento para discussão em Grupo de Trabalho-GT fatores abióticos, apresentado no Seminário Biodiversidade da Caatinga, 2000, Petrolina,PE

    Contact Manifolds, Contact Instantons, and Twistor Geometry

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    Recently, Kallen and Zabzine computed the partition function of a twisted supersymmetric Yang-Mills theory on the five-dimensional sphere using localisation techniques. Key to their construction is a five-dimensional generalisation of the instanton equation to which they refer as the contact instanton equation. Subject of this article is the twistor construction of this equation when formulated on K-contact manifolds and the discussion of its integrability properties. We also present certain extensions to higher dimensions and supersymmetric generalisations.Comment: v3: 28 pages, clarifications and references added, version to appear in JHE

    Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patient

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    BACKGROUND: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. METHODS: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. RESULTS: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample

    Kalirin: a novel genetic risk factor for ischemic stroke

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    Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases

    The modified patient enablement instrument: a Portuguese cross-cultural adaptation, validity and reliability study

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    "Article number: 16087"Enabling patients with asthma to obtain the knowledge, confidence and skills they need in order to assume a major role in the management of their disease is cost effective. It should be an integral part of any plan for long-term control of asthma. The modified Patient Enablement Instrument (mPEI) is an easily administered questionnaire that was adapted in the United Kingdom to measure patient enablement in asthma, but its applicability in Portugal is not known. Validity and reliability of questionnaires should be tested before use in settings different from those of the original version. The purpose of this study was to test the applicability of the mPEI to Portuguese asthma patients after translation and cross-cultural adaptation, and to verify the structural validity, internal consistency and reproducibility of the instrument. The mPEI was translated to Portuguese and back translated to English. Its content validity was assessed by a debriefing interview with 10 asthma patients. The translated instrument was then administered to a random sample of 142 patients with persistent asthma. Structural validity and internal consistency were assessed. For reproducibility analysis, 86 patients completed the instrument again 7 days later. Item-scale correlations and exploratory factor analysis were used to assess structural validity. Cronbach's alpha was used to test internal consistency, and the intra-class correlation coefficient was used for the analysis of reproducibility. All items of the Portuguese version of the mPEI were found to be equivalent to the original English version. There were strong item-scale correlations that confirmed construct validity, with a one component structure and good internal consistency (Cronbach's alpha >0.8) as well as high test-retest reliability (ICC=0.85). The mPEI showed sound psychometric properties for the evaluation of enablement in patients with asthma making it a reliable instrument for use in research and clinical practice in Portugal. Further studies are needed to confirm its responsiveness.Financial support for this work was provided by FEDER funds through the Operational Programme Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038, and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

    The N-terminal half of the peroxisomal cycling receptor Pex5p is a natively unfolded domain

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    Targeting of most newly synthesised peroxisomal matrix proteins to the organelle requires Pex5p, the so-called PTS1 receptor. According to current models of peroxisomal biogenesis, Pex5p interacts with these proteins in the cytosol, transports them to the peroxisomal membrane and catalyses their translocation across the membrane. Presently, our knowledge on the structural details behind the interaction of Pex5p with the cargo proteins is reasonably complete. In contrast, information regarding the structure of the Pex5p N-terminal half (a region containing its peroxisomal targeting domain) is still limited. We have recently observed that the Stokes radius of this Pex5p domain is anomalously large, suggesting that this portion of the protein is either a structured elongated domain or that it adopts a low compactness conformation. Here, we address this issue using a combination of biophysical and biochemical approaches. Our results indicate that the N-terminal half of Pex5p is best described as a natively unfolded premolten globule-like domain. The implications of these findings on the mechanism of protein import into the peroxisome are discussed
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