Proteomic analysis of cytosolic proteins associated with petite mutations in Candida glabrata

The incidence of superficial or deep-seated infections due to Candida glabrata has increased markedly, probably because of the low intrinsic susceptibility of this microorganism to azole antifungals and its relatively high propensity to acquire azole resistance. To determine changes in the C. glabrata proteome associated with petite mutations, cytosolic extracts from an azole-resistant petite mutant of C. glabrata induced by exposure to ethidium bromide, and from its azole-susceptible parent isolate were compared by two-dimensional polyacrylamide gel electrophoresis. Proteins of interest were identified by peptide mass fingerprinting or sequence tagging using a matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometer. Tryptic peptides from a total of 160 Coomassie-positive spots were analyzed for each strain. Sixty-five different proteins were identified in the cytosolic extracts of the parent strain and 58 in the petite mutant. Among the proteins identified, 10 were higher in the mutant strain, whereas 23 were lower compared to the parent strain. The results revealed a significant decrease in the enzymes associated with the metabolic rate of mutant cells such as aconitase, transaldolase, and pyruvate kinase, and changes in the levels of specific heat shock proteins. Moreover, transketolase, aconitase and catalase activity measurements decreased significantly in the ethidium bromide-induced petite mutant. These data may be useful for designing experiments to obtain a better understanding of the nuclear response to impairment of mitochondrial function associated with this mutation in C. glabrata

Expression analysis of transcription factors from the interaction between cacao and Moniliophthora perniciosa (Tricholomataceae)

Cacao (Theobroma cacao) is one of the most important tropical crops; however, production is threatened by numerous pathogens, including the hemibiotrophic fungus Moniliophthora perniciosa, which causes witches' broom disease. To understand the mechanisms that lead to the development of this disease in cacao, we focused our attention on cacao transcription factors (TFs), which act as master regulators of cellular processes and are important for the fine-tuning of plant defense responses. We developed a macroarray with 88 TF cDNA from previously obtained cacao-M. perniciosa interaction libraries. Seventy-two TFs were found differentially expressed between the susceptible (Catongo) and resistant (TSH1188) genotypes and/or during the disease time course - from 24 h to 30 days after infection. Most of the differentially expressed TFs belonged to the bZIP, MYB and WRKY families and presented opposite expression patterns in susceptible and resistant cacao-M. perniciosa interactions (i.e., up-regulated in Catongo and down-regulated in TSH1188). The results of the macroarray were confirmed for bZIP and WRKY TFs by real-time PCR. These differentially expressed TFs are good candidates for subsequent functional analysis as well as for plant engineering. Some of these TFs could also be localized on the cacao reference map related to witches' broom resistance, facilitating the breeding and selection of resistant cacao trees. (Résumé d'auteur

A prediction algorithm for drug response in patients with mesial temporal lobe epilepsy based on clinical and genetic information

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide121FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2013/07559-

Fundamental Superstrings as Holograms

The worldsheet of a macroscopic fundamental superstring in the Green-Schwarz light-cone gauge is viewed as a possible boundary hologram of the near horizon region of a small black string. For toroidally compactified strings, the hologram has global symmetries of AdS_3 \times S^{d-1} \times T^{8-d}, (d =3,..,8), only some of which extend to local conformal symmetries. We construct the bulk string theory in detail for the particular case of d=3. The symmetries of the hologram are correctly reproduced from this exact worldsheet description in the bulk. Moreover, the central charge of the boundary Virasoro algebra obtained from the bulk agrees with the Wald entropy of the associated small black holes. This construction provides an exact CFT description of the near horizon region of small black holes both in Type-II and heterotic string theory arising from multiply wound fundamental superstrings.Comment: 46 pages, JHEP style. v2: Comments, references adde

Glucose modifies the effect of endovascular thrombectomy in patients with acute stroke: a pooled-data meta-analysis

Background and Purpose: Hyperglycemia is a negative prognostic factor following acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy in patients with large vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of endovascular thrombectomy in acute stroke. Methods: Seven randomized trials compared endovascular thrombectomy with standard care between 2010 and 2017 (HERMES Collaboration). 1764 patients with large vessel stroke were allocated to endovascular thrombectomy (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome [modified Rankin Scale (mRS) range: 0-6; lower scores indicating less disability] at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results: Median (IQR) serum glucose on admission was 120 (104-140) mg/dl [6.6mmol/l (5.7-7.7) mmol/l]. Endovascular thrombectomy (EVT) was better than standard care in the overall pooled-data analysis [common odds ratio (acOR), 2.00 (95% CI 1.69–2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or > 90mg/dl (5.0mmol/l) [(p=0.019 for interaction, acOR 3.81 (95% CI 1.73–8.41) for patients < 90 mg/dl vs 1.83 (95% CI 1.53–2.19) for patients > 90 mg/dl], and glucose < or > 100mg/dl (5.5mmol/l) [(p=0.004 for interaction, acOR 3.17 (95% CI 2.04–4.93) vs acOR 1.72 (95% CI 1.42–2.08)], but not between subgroups above these levels of glucose. Conclusions: Endovascular thrombectomy improved stroke outcomes compared to standard treatment regardless of glucose levels but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100mg/dl (5.0-5.5mmol/l). Whether tight control of glucose improves the efficacy of endovascular thrombectomy following large vessel stroke warrants appropriate testing