The Tyrosine Kinase BceF and the Phosphotyrosine Phosphatase BceD of Burkholderia contaminans Are Required for Efficient Invasion and Epithelial Disruption of a Cystic Fibrosis Lung Epithelial Cell Line

Bacterial tyrosine kinases and their cognate protein tyrosine phosphatases are best known for regulating the biosynthesis of polysaccharides. Moreover, their roles in the stress response, DNA metabolism, cell division, and virulence have also been documented. The aim of this study was to investigate the pathogenicity and potential mechanisms of virulence dependent on the tyrosine kinase BceF and phosphotyrosine phosphatase BceD of the cystic fibrosis opportunistic pathogen Burkholderia contaminans IST408. The insertion mutants bceD::Tp and bceF::Tp showed similar attenuation of adhesion and invasion of the cystic fibrosis lung epithelial cell line CFBE41o- compared to the parental strain B. contaminans IST408. In the absence of bceD or bceF genes, B. contaminans also showed a reduction in the ability to translocate across polarized epithelial cell monolayers, demonstrated by a higher transepithelial electrical resistance, reduced flux of fluorescein isothiocyanate-labeled bovine serum albumin, and higher levels of tight junction proteins ZO-1, occludin, and claudin-1 present in monolayers exposed to these bacterial mutants. Furthermore, bceD::Tp and bceF::Tp mutants induced lower levels of interleukin-6 (IL-6) and IL-8 release than the parental strain. In conclusion, although the mechanisms of pathogenicity dependent on BceD and BceF are not understood, these proteins contribute to the virulence of Burkholderia by enhancement of cell attachment and invasion, disruption of epithelial integrity, and modulation of the proinflammatory response

Malaria Vaccine Development: Are Bacterial Flagellin Fusion Proteins the Bridge between Mouse and Humans?

In the past 25 years, the development of an effective malaria vaccine has become one of the biggest riddles in the biomedical sciences. Experimental data using animal infection models demonstrated that it is possible to induce protective immunity against different stages of malaria parasites. Nonetheless, the vast body of knowledge has generated disappointments when submitted to clinical conditions and presently a single antigen formulation has progressed to the point where it may be translated into a human vaccine. In parallel, new means to increase the protective effects of antigens in general have been pursued and depicted, such as the use of bacterial flagellins as carriers/adjuvants. Flagellins activate pathways in the innate immune system of both mice and humans. The recent report of the first Phase I clinical trial of a vaccine containing a Salmonella flagellin as carrier/adjuvant may fuel the use of these proteins in vaccine formulations. Herein, we review the studies on the use of recombinant flagellins as vaccine adjuvants with malarial antigens in the light of the current state of the art of malaria vaccine development. The available information indicates that bacterial flagellins should be seriously considered for malaria vaccine formulations to the development of effective human vaccines

Localized holes and delocalized electrons in photoexcited inorganic perovskites: Watching each atomic actor by picosecond X-ray absorption spectroscopy

We report on an element-selective study of the fate of charge carriers in photoexcited inorganic CsPbBr3 and CsPb(ClBr)3 perovskite nanocrystals (NCs) in toluene solutions using time-resolved X-ray absorption spectroscopy with 80 ps time resolution. Probing the Br K-edge, the Pb L3-edge and the Cs L2-edge, we find that holes in the valence band are localized at Br atoms, forming small polarons, while electrons appear as delocalized in the conduction band. No signature of either electronic or structural changes are observed at the Cs L2-edge. The results at the Br and Pb edges suggest the existence of a weakly localized exciton, while the absence of signatures at the Cs edge indicates that the Cs+ cation plays no role in the charge transport, at least beyond 80 ps. These results can explain the rather modest charge carrier mobilities in these materials.Comment: 19 pages, 3 figure

Canonical Correlation Analysis and Partial Least Squares for identifying brain-behaviour associations: a tutorial and a comparative study

Canonical Correlation Analysis (CCA) and Partial Least Squares (PLS) are powerful multivariate methods for capturing associations across two modalities of data (e.g., brain and behaviour). However, when the sample size is similar or smaller than the number of variables in the data, CCA and PLS models may overfit, i.e., find spurious associations that generalise poorly to new data. Dimensionality reduction and regularized extensions of CCA and PLS have been proposed to address this problem, yet most studies using these approaches have some limitations. This work gives a theoretical and practical introduction into the most common CCA/PLS models and their regularized variants. We examine the limitations of standard CCA and PLS when the sample size is similar or smaller than the number of variables. We discuss how dimensionality reduction and regularization techniques address this problem and explain their main advantages and disadvantages. We highlight crucial aspects of the CCA/PLS analysis framework, including optimising the hyperparameters of the model and testing the identified associations for statistical significance. We apply the described CCA/PLS models to simulated data and real data from the Human Connectome Project and the Alzheimer's Disease Neuroimaging Initiative (both of n>500). We use both low and high dimensionality versions of each data (i.e., ratios between sample size and variables in the range of ∼1-10 and ∼0.1-0.01) to demonstrate the impact of data dimensionality on the models. Finally, we summarize the key lessons of the tutorial

Uso de perfis cromatográficos de voláteis de cafés arábicas torrados para a diferenciação das amostras segundo o sabor, o aroma e a qualidade global da bebida

In this work, the volatile chromatographic profiles of roasted Arabica coffees, previously analyzed for their sensorial attributes, were explored by principal component analysis. The volatile extraction technique used was the solid phase microextraction. The correlation optimized warping algorithm was used to align the gas chromatographic profiles. Fifty four compounds were found to be related to the sensorial attributes investigated. The volatiles pyrrole, 1-methyl-pyrrole, cyclopentanone, dihydro-2-methyl-3-furanone, furfural, 2-ethyl-5-methyl-pyrazine, 2-etenyl-n-methyl-pyrazine, 5-methyl-2-propionyl-furan compounds were important for the differentiation of coffee beverage according to the flavour, cleanliness and overall quality. Two figures of merit, sensitivity and specificity (or selectivity), were used to interpret the sensory attributes studied

The use of chromatographic profiles from roasted arabica coffees to differentiate samples according to cleanliness, flavour and overall quality of the beverage

In this work, the volatile chromatographic profiles of roasted Arabica coffees, previously analyzed for their sensorial attributes, were explored by principal component analysis. The volatile extraction technique used was the solid phase microextraction. The correlation optimized warping algorithm was used to align the gas chromatographic profiles. Fifty four compounds were found to be related to the sensorial attributes investigated. The volatiles pyrrole, 1-methyl-pyrrole, cyclopentanone, dihydro-2-methyl-3-furanone, furfural, 2-ethyl-5-methyl-pyrazine, 2-etenyl-n-methyl-pyrazine, 5-methyl-2-propionyl-furan compounds were important for the differentiation of coffee beverage according to the flavour, cleanliness and overall quality. Two figures of merit, sensitivity and specificity (or selectivity), were used to interpret the sensory attributes studied.1897190

Identification Of Anln As Etv6 Partner Gene In Recurrent T(7;12)(p15;p13): A Possible Role Of Deregulated Anln Expression In Leukemogenesis

The ETV6 gene encodes an ETS family transcription factor that is involved in a myriad of chromosomal rearrangements found in hematological malignancies and other neoplasms. A recurrent ETV6 translocation, previously described in patients with acute myeloid leukemia (AML) (Genes Chromosomes Cancer 51:328-337,2012, Leuk Res 35:e212-214, 2011), whose partner has not been identified is t(7; 12)(p15; p13). We herein report that the t(7; 12)(p15; p13) fuses ETV6 to ANLN, a gene not previously implicated in the pathogenesis of hematological malignancies, and we demonstrate that this translocation leads to high expression of the fusion transcript in the myeloid and lymphoid lineages.1

Secondary metabolites from the sponges Aplysina fistularis and Dysidea sp. and the antituberculosis activity of 11-ketofistularin-3

The present investigation reports the isolation of aeroplysinin-2, 2-(3,5-dibromo-4-methoxyphenyl)-N,N,N-trimethyletanamonium, 7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-trien-3-carboxylic acid and its methyl ester, 11-oxoaerothionin, aerothionin, 11-keto-12-hydroxyaerothionin, 11-ketofistularin-3 and fistularin-3 from Aplysina fistularis, as well as of furodysinin lactone and 9α,11α-epoxicholest-7-en-3β,5α,6α,10-tetrol-6-acetate from Dysidea sp. Although the extracts of both sponges displayed antituberculosis activity, only 11-ketofistularin-3 isolated from A. fistularis displayed antimycobacterial activity against Mycobacterium tuberculosis H34Rv, with MIC at 16 μg/mL and SI of 40, a result that reinforce that fistularin-3 derivatives are interesting leads for the development of antituberculosis drugs.American Society of Pharmacognosy FoundationFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)BIOTA/FAPESP - BIOprospecTAUSP - PIBIC/CNPqFAPES

Emergence of winner-takes-all connectivity paths in random nanowire networks

Nanowire networks are promising memristive architectures for neuromorphic applications due to their connectivity and neurosynaptic-like behaviours. Here, we demonstrate a self-similar scaling of the conductance of networks and the junctions that comprise them. We show this behavior is an emergent property of any junction-dominated network. A particular class of junctions naturally leads to the emergence of conductance plateaus and a “winner-takes-all” conducting path that spans the entire network, and which we show corresponds to the lowest-energy connectivity path. The memory stored in the conductance state is distributed across the network but encoded in specific connectivity pathways, similar to that found in biological systems. These results are expected to have important implications for development of neuromorphic devices based on reservoir computing

Broad Geographic Distribution of Roundscale Spearfish (Tetrapturus georgii) (Teleostei, Istiophoridae) in the Atlantic Revealed by DNA Analysis: Implications for White Marlin and Roundscale Spearfish Management

The recent validation of the roundscale spearfish (Tetrapturus georgii) within the western North Atlantic has introduced new complexities in the management of the overfished white marlin (Kajikia albida) in this region due to historical and contemporary misidentification between the two morphologically similar species. Compounding the management challenge for white marlin, which is currently assessed as a single Atlantic-wide stock, is an unclear picture of the extent of the roundscale spearfish\u27s overall Atlantic distribution. By using genetic tools (mitochondrial DNA ND4L-ND4 locus sequences) for species identification, we confirm that the roundscale spearfish has a much broader distribution than previously known, including the central North Atlantic and much of the western South Atlantic to at least 28°52′S. This much wider Atlantic distribution of the roundscale spearfish sympatric with its morphologically similar congeners, the white marlin and longbill spearfish (Tetrapturus pfluegeri), raises further management complexities: it increases the geographic scale for species misidentification in catch records that form the basis for stock assessments and uncertainty in currently accepted white marlin biological parameters. Additional vigilance in obtaining accurate species identification by improved fishery onboard observer training and incorporation of genetic tools is recommended for informing management of white marlin, longbill spearfish and roundscale spearfish throughout the Atlantic