Analysis Of Mitochondrial Alterations In Brazilian Patients With Sensorineural Hearing Loss Using Maldi-tof Mass Spectrometry

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Mutations in the mitochondrial DNA (mtDNA) have been associated with aminoglycoside-induced and nonsyndromic deafness in different populations. In the present study, we investigated the contribution of mutations in mitochondrial genes to the etiology of hearing loss in a Brazilian sample. Methods: Using mass spectrometry genotyping technology, combined with direct sequencing, 50 alterations previously described in 14 mitochondrial genes were screened in 152 patients with sensorineural hearing loss and in 104 normal hearing controls. Results: Fifteen known mitochondrial alterations were detected (G709A, A735G, A827G, G988A, A1555G, T4363C, T5628C, T5655C, G5821A, C7462T, G8363A, T10454C, G12236A, T1291C, G15927A). Pathogenic mutations in MT-RNR1 and MT-TK genes were detected in 3 % (5/152) of the patients with hearing loss. Conclusions: This study contributed to show the spectrum of mitochondrial variants in Brazilian patients with hearing loss. Frequency of A1555G was relatively high (2.6 %), indicating that this mutation is an important cause of hearing loss in our population. This work reports for the first time the investigation and the detection of the tRNALys G8363A mutation in Brazilian patients with maternally inherited sensorineural hearing loss.17Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The carboxylic acid transporters Jen1 and Jen2 affect the architecture and fluconazole susceptibility of Candida albicans biofilm in the presence of lactate

Candida albicans has the ability to adapt to different host niches, often glucose-limited but rich in alternative carbon sources. In these glucose-poor microenvironments, this pathogen expresses JEN1 and JEN2 genes, encoding carboxylate transporters, which are important in the early stages of infection. This work investigated how host microenvironments, in particular acidic containing lactic acid, affect C. albicans biofilm formation and antifungal drug resistance. Multiple components of the extracellular matrix were also analysed, including their impact on antifungal drug resistance, and the involvement of both Jen1 and Jen2 in this process. The results show that growth on lactate affects biofilm formation, morphology and susceptibility to fluconazole and that both Jen1 and Jen2 might play a role in these processes. These results support the view that the adaptation of Candida cells to the carbon source present in the host niches affects their pathogenicity.This study was funded by the Portuguese Foundation for Science and Technology (FCT) [grant number PTDC/BIAMIC/5184/2014]. SM, CFR and RA received FCT PhD studentships [grant numbers SFRH/BD/74790/2010, SFRH/ BD/93078/2013, PD/BD/113813/2015, respectively]. The work on CBMA was supported by FCT [grant number UID/ BIA/04050/2013] and COMPETE 2020 [grant number POCI01-0145-FEDER-007569]. The work on CEB was supported by FCT [grant number UID/BIO/04469/2013], COMPETE 2020 [grant number POCI-01-0145-FEDER-006684] and BioTecNorte operation [grant number NORTE-01-0145FEDER-000004] funded by the ERDF under the scope of Norte2020 – Programa Operacional Regional do Norte. AJPB was funded by the UK Medical Research Council [grant number MR/M026663/1]; by the UK Biotechnology and Biological Research Council [grant number BB/K017365/1]; and by the MRC Centre for Medical Mycology and the University of Aberdeen [grant number MR/M026663/1]. The funders had no role in study design, data collection and analysis, the decision to publish, or in the preparation of the manuscript.info:eu-repo/semantics/publishedVersio

The EMBLA survey - metal-poor stars in the Galactic bulge

Cosmological models predict the oldest stars in the Galaxy should be found closest to the centre of the potential well, in the bulge. The Extremely Metal-poor BuLge stars with AAOmega survey (EMBLA) successfully searched for these old, metal-poor stars by making use of the distinctive SkyMapper photometric filters to discover candidate metal-poor stars in the bulge. Their metal-poor nature was then confirmed using the AAOmega spectrograph on the Anglo-Australian Telescope. Here we present an abundance analysis of 10 bulge stars with −2.8 < [Fe/H] < −1.7 from MIKE/Magellan observations, in total determining the abundances of 22 elements. Combining these results with our previous high-resolution data taken as part of the Gaia-ESO Survey, we have started to put together a picture of the chemical and kinematic nature of the most metal-poor stars in the bulge. The currently available kinematic data are consistent with the stars belonging to the bulge, although more accurate measurements are needed to constrain the stars’ orbits. The chemistry of these bulge stars deviates from that found in halo stars of the same metallicity. Two notable differences are the absence of carbon-enhanced metal-poor bulge stars, and the α element abundances exhibit a large intrinsic scatter and include stars which are underabundant in these typically enhanced elements.LMH and MA have been supported by the Australian Research Council (grant FL110100012). ARC acknowledges support from the European Union FP7 programme through ERC grant number 320360. DY is supported through an Australian Research Council Future Fellowship (FT140100554). Research on metal-poor stars with SkyMapper is supported through Australian Research Council Discovery Projects grants DP120101237 and DP150103294 (PI: Da Costa). This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. This paper includes data gathered with the 6.5 metre Magellan Telescopes located at Las Campanas Observatory, Chile.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/mnras/stw100

Constraining parameter space in type-II two-Higgs doublet model in light of a 126 GeV Higgs boson

We explore the implications of a 126 GeV Higgs boson indicated by the recent LHC results for two-Higgs doublet model (2HDM). Identifying the 126 GeV Higgs boson as either the lighter or heavier of CP even neutral Higgs bosons in 2HDM, we examine how the masses of Higgs fields and mixing parameters can be constrained by the theoretical conditions and experimental constraints. The theoretical conditions taken into account are the vacuum stability, perturbativity and unitarity required to be satisfied up to a cut-off scale. We also show how bounds on the masses of Higgs bosons and mixing parameters depend on the cut-off scale. In addition, we investigate whether the allowed regions of parameter space can accommodate particularly the enhanced di-photon signals, ZZ* and WW* decay modes of the Higgs boson, and examine the prediction of the signal strength of Z{\gamma} decay mode for the allowed regions of the parameter space.Comment: To be published in JHEP, 20 pages, 11 figures, Figures and results are updated for the recent LHC result

Virulence in Murine Model Shows the Existence of Two Distinct Populations of Brazilian Vaccinia virus Strains

Brazilian Vaccinia virus had been isolated from sentinel mice, rodents and recently from humans, cows and calves during outbreaks on dairy farms in several rural areas in Brazil, leading to high economic and social impact. Some phylogenetic studies have demonstrated the existence of two different populations of Brazilian Vaccinia virus strains circulating in nature, but little is known about their biological characteristics. Therefore, our goal was to study the virulence pattern of seven Brazilian Vaccinia virus strains. Infected BALB/c mice were monitored for morbidity, mortality and viral replication in organs as trachea, lungs, heart, kidneys, liver, brain and spleen. Based on the virulence potential, the Brazilian Vaccinia virus strains were grouped into two groups. One group contained GP1V, VBH, SAV and BAV which caused disease and death in infected mice and the second one included ARAV, GP2V and PSTV which did not cause any clinical signals or death in infected BALB/c mice. The subdivision of Brazilian Vaccinia virus strains into two groups is in agreement with previous genetic studies. Those data reinforce the existence of different populations circulating in Brazil regarding the genetic and virulence characteristics

Methylated BSA Mimics Amyloid-Related Proteins and Triggers Inflammation

The mechanistic study of inflammatory or autoimmune diseases requires the generation of mouse models that reproduce the alterations in immune responses observed in patients. Methylated bovine serum albumin (mBSA) has been widely used to induce antigen-specific inflammation in targeted organs or in combination with single stranded DNA (ssDNA) to generate anti-nucleic acids antibodies in vivo. However, the mechanism by which this modified protein triggers inflammation is poorly understood. By analyzing the biochemical properties of mBSA, we found that mBSA exhibits features of an intermediate of protein misfolding pathway. mBSA readily interact with a list of dyes that have binding specificity towards amyloid fibrils. Intriguingly, mBSA displayed cytotoxic activity and its binding to ssDNA further enhanced formation of beta-sheet rich amyloid fibrils. Moreover, mBSA is recognized by the serum amyloid P, a protein unanimously associated with amyloid plaques in vivo. In macrophages, we observed that mBSA disrupted the lysosomal compartment, signaled along the NLRP3 inflammasome pathway, and activated caspase 1, which led to the production of IL-1β. In vivo, mBSA triggered rapid and prominent immune cell infiltration that is dependent on IL-1β induction. Taken together, these data demonstrate that by mimicking amyloidogenic proteins mBSA exhibits strong innate immune functions and serves as a potent adjuvant. These findings advance our understanding on the underlying mechanism of how aberrant immune responses lead to autoimmune reactions

Mycotic aneurysm of the femoral artery complicating Staphylococcus aureus bacteremia: a case report

INTRODUCTION: Staphylococcus aureus is the major cause of bacteremia, with the potential for some complications, namely mycotic aneurysms, defined as irreversible dilatation of an artery due to destruction of the vessel wall by infection. CASE PRESENTATION: The authors present the case of a 52 year-old-Caucasian male, admitted with Staphylococcus aureus bacteremia and mycotic aneurysm of the right superficial femoral artery, associated with advanced atherosclerotic process. CONCLUSION: Mycotic aneurysms are rare, and a high index of suspicion is needed, because appropriate treatment will certainly affect the outcome, as they are associated with high morbidity and mortality

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets