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991.
The computer program exonsampler automates the sampling of thousands of exon sequences from publicly available reference genome sequences and gene annotation databases. It was designed to provide exon sequences for the efficient, next‐generation gene sequencing method called exon capture. The exon sequences can be sampled by a list of gene name abbreviations (e.g. IFNG, TLR1), or by sampling exons from genes spaced evenly across chromosomes. It provides a list of genomic coordinates (a bed file), as well as a set of sequences in fasta format. User‐adjustable parameters for collecting exon sequences include a minimum and maximum acceptable exon length, maximum number of exonic base pairs (bp) to sample per gene, and maximum total bp for the entire collection. It allows for partial sampling of very large exons. It can preferentially sample upstream (5 prime) exons, downstream (3 prime) exons, both external exons, or all internal exons. It is written in the Python programming language using its free libraries. We describe the use of exonsampler to collect exon sequences from the domestic cow (Bos taurus) genome for the design of an exon‐capture microarray to sequence exons from related species, including the zebu cow and wild bison. We collected ~10% of the exome (~3 million bp), including 155 candidate genes, and ~16 000 exons evenly spaced genomewide. We prioritized the collection of 5 prime exons to facilitate discovery and genotyping of SNPs near upstream gene regulatory DNA sequences, which control gene expression and are often under natural selection. 相似文献
992.
Rafael Luiz Pereira Raphael José Ferreira Felizardo Marcos Ant?nio Cenedeze Meire Ioshie Hiyane ênio José Bassi Mariane Tami Amano Clarice Sylvia Taemi Origassa Reinaldo Correia Silva Cristhiane Fávero Aguiar Sylvia Mendes Carneiro Jo?o Bosco Pesquero Ronaldo Carvalho Araújo Alexandre de Castro Keller Renato C. Monteiro Ivan Cruz Moura Alvaro Pacheco-Silva Niels Olsen Saraiva Camara 《Disease models & mechanisms》2014,7(6):701-710
Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end-stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation, whereas the role of its receptor 2 (B2RBK; also known as BDKRB2) in FSGS has not been studied. FSGS was induced in wild-type and B2RBK-knockout mice by a single intravenous injection of Adriamycin (ADM). In order to further modulate the kinin receptors, the animals were also treated with the B2RBK antagonist HOE-140 and the B1RBK antagonist DALBK. Here, we show that the blockage of B2RBK with HOE-140 protects mice from the development of FSGS, including podocyte foot process effacement and the re-establishment of slit-diaphragm-related proteins. However, B2RBK-knockout mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was upregulated after the injection of ADM and this upregulation was exacerbated in B2RBK-knockout animals. Furthermore, treatment with HOE-140 downregulated the B1RBK receptor. The blockage of B1RBK in B2RBK-knockout animals promoted FSGS regression, with a less-inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in an FSGS model and suggest a possible cross-talk between them in the progression of disease.KEY WORDS: Focal and segmental glomerulosclerosis, Bradykinin receptors, Inflammation, Podocyte, Fibrosis 相似文献
993.
Carlos E. Pedraza Christopher Taylor Albertina Pereira Michelle Seng Chui-Se Tham Michal Izrael Michael Webb 《ASN neuro》2014,6(4)
In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin
degradation results in loss of axonal function and eventual axonal degeneration.
Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to
remyelination of denuded axons occurs regularly in early stages of MS but halts as
the pathology transitions into progressive MS. Pharmacological potentiation of
endogenous OPC maturation and remyelination is now recognized as a promising
therapeutic approach for MS. In this study, we analyzed the effects of modulating the
Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective
inhibitors of ROCK, on the transformation of OPCs into mature, myelinating
oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent
and human origin, that ROCK inhibition in OPCs results in a significant generation of
branches and cell processes in early differentiation stages, followed by accelerated
production of myelin protein as an indication of advanced maturation. Furthermore,
inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons
and remyelination in rat cerebellar tissue explants previously demyelinated with
lysolecithin. Our findings indicate that by direct inhibition of this signaling
molecule, the OPC differentiation program is activated resulting in morphological and
functional cell maturation, myelin formation, and regeneration. Altogether, we show
evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the
induction of remyelination in demyelinating pathologies. 相似文献
994.
Adeliane Castro da Costa Abadio de Oliveira Costa-Júnior Fábio Muniz de Oliveira Sarah Veloso Nogueira Joseane Damaceno Rosa Danilo Pires Resende André Kipnis Ana Paula Junqueira-Kipnis 《PloS one》2014,9(11)
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. 相似文献
995.
Galactodendritic Phthalocyanine Targets Carbohydrate-Binding Proteins Enhancing Photodynamic Therapy
Patrícia M. R. Pereira Sandrina Silva José A. S. Cavaleiro Carlos A. F. Ribeiro Jo?o P. C. Tomé Rosa Fernandes 《PloS one》2014,9(4)
Photosensitizers (PSs) are of crucial importance in the effectiveness of photodynamic therapy (PDT) for cancer. Due to their high reactive oxygen species production and strong absorption in the wavelength range between 650 and 850 nm, where tissue light penetration is rather high, phthalocyanines (Pcs) have been studied as PSs of excellence. In this work, we report the evaluation of a phthalocyanine surrounded by a carbohydrate shell of sixteen galactose units distributed in a dendritic manner (PcGal16) as a new and efficient third generation PSs for PDT against two bladder cancer cell lines, HT-1376 and UM-UC-3. Here, we define the role of galacto-dendritic units in promoting the uptake of a Pc through interaction with GLUT1 and galectin-1. The photoactivation of PcGal16 induces cell death by generating oxidative stress. Although PDT with PcGal16 induces an increase on the activity of antioxidant enzymes immediately after PDT, bladder cancer cells are unable to recover from the PDT-induced damage effects for at least 72 h after treatment. PcGal16 co-localization with galectin-1 and GLUT1 and/or generation of oxidative stress after PcGal16 photoactivation induces changes in the levels of these proteins. Knockdown of galectin-1 and GLUT1, via small interfering RNA (siRNA), in bladder cancer cells decreases intracellular uptake and phototoxicity of PcGal16. The results reported herein show PcGal16 as a promising therapeutic agent for the treatment of bladder cancer, which is the fifth most common type of cancer with the highest rate of recurrence of any cancer. 相似文献
996.
Milene Mesquita Paola Resende Andressa Marttorelli Viviane Machado Carolina Q. Sacramento Natalia Fintelman-Rodrigues Juliana L. Abrantes Rita Tavares Marcelo Schirmer Marilda M. Siqueira Thiago Moreno L. Souza 《PloS one》2014,9(4)
The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT. 相似文献
997.
998.
Aline Lima Leite Janete Gualiume Vaz Madureira Lobo Heloísa Aparecida Barbosa da Silva Pereira Mileni Silva Fernandes Tatiani Martini Fernanda Zucki Dóris Hissako Sumida Alfredo Rigalli Marília Afonso Rabelo Buzalaf 《PloS one》2014,9(9)
Administration of high doses of fluoride (F) can alter glucose homeostasis and lead to insulin resistance (IR). This study determined the profile of protein expression in the gastrocnemius muscle of rats with streptozotocin-induced diabetes that were chronically exposed to F. Male Wistar rats (60 days old) were randomly distributed into two groups of 18 animals. In one group, diabetes was induced through the administration of streptozotocin. Each group (D-diabetic and ND-non-diabetic) was further divided into 3 subgroups each of which was exposed to a different F concentration via drinking water (0 ppm, 10 ppm or 50 ppm F, as NaF). After 22 days of treatment, the gastrocnemius muscle was collected and submitted to proteomic analysis (2D-PAGE followed by LC-MS/MS). Protein functions were classified by the GO biological process (ClueGO v2.0.7+Clupedia v1.0.8) and protein-protein interaction networks were constructed (PSICQUIC, Cytoscape). Quantitative intensity analysis of the proteomic data revealed differential expression of 75 spots for ND0 vs. D0, 76 for ND10 vs.D10, 58 spots for ND50 vs. D50, 52 spots for D0 vs. D10 and 38 spots for D0 vs. D50. The GO annotations with the most significant terms in the comparisons of ND0 vs. D0, ND10 vs. D10, ND50 vs. D50, D0 vs. D10 and D0 vs. D50, were muscle contraction, carbohydrate catabolic processes, generation of precursor metabolites and energy, NAD metabolic processes and gluconeogenesis, respectively. Analysis of subnetworks revealed that, in all comparisons, proteins with fold changes interacted with GLUT4. GLUT4 interacting proteins, such as MDH and the stress proteins HSPB8 and GRP78, exhibited decreased expression when D animals were exposed to F. The presence of the two stress proteins indicates an increase in IR, which might worsen diabetes. Future studies should evaluate whether diabetic animals treated with F have increased IR, as well as which molecular mechanisms are involved. 相似文献
999.
Alessandra Pereira Lopes Tania Fagundes Macedo Evandro Silva Freire Coutinho Ivan Figueira Paula Rui Ventura 《PloS one》2014,9(10)
Natural disasters can have devastating consequences. Each year, about 225 million people are victims of natural disasters worldwide, and up to 13,5 million of these people can develop post-traumatic stress disorder (PTSD) in the first or second year following the disaster. Cognitive-behavior therapy (CBT) is the first-choice treatment for this disorder. In order to evaluate the efficacy of psychotherapeutic treatment based on cognitive-behavior therapy for people who developed post traumatic stress disorder after natural disasters we conducted a systematic search of published studies. We used the terms reported below in the electronic databases ISI Web of Science, PsycINFO, PubMed, PILOTS and Scopus with no restrictions of language or publication date. Articles that described randomized controlled, non-randomized controlled and non controlled studies on the efficacy of cognitive-behavior therapy for individuals diagnosed with post-traumatic stress disorder after exposure to a natural disaster were eligible for inclusion. The studies were required to use a standardized measure of effectiveness before and after the intervention and have a group of patients who had used cognitive-behavior therapy as the only intervention. Our search identified 820 studies, and 11 were selected for this review. These 11 studies involved 742 subjects, 10 related to earthquakes and 1 to a hurricane. The cognitive-behavior therapy techniques used were various: 7 studies used exposure therapy, 2 studies used problem solving, and the only 2 studies with adolescents used techniques including reconstructions and reprocessing of the traumatic experience. As limitations, the search involved only five electronic databases, no experts in the field were consulted, and the heterogeneity of the findings made it impossible to perform a meta-analysis. The results suggest the efficacy of cognitive-behavior therapy, particularly exposure techniques, for the treatment of post-traumatic stress disorder after earthquakes. However, further studies with stronger methodologies, i.e. randomized-control trials and non-randomized controlled trials, are needed. 相似文献
1000.
Edward C. Jones-López Soyeon Kim Geisa Fregona Patricia Marques-Rodrigues David Jamil Hadad Lucilia Pereira Dutra Molina Solange Vinhas Nancy Reilly Stephanie Moine Soumitesh Chakravorty Mary Gaeddert Rodrigo Ribeiro-Rodrigues Padmini Salgame Moises Palaci David Alland Jerrold J. Ellner Reynaldo Dietze 《PloS one》2014,9(7)