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951.
Ana Claudia Silva Braga Bruno Moreira Carneiro Mariana Nogueira Batista Mônica Mayumi Akinaga Paula Rahal 《Cell stress & chaperones》2017,22(1):113-122
Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in the folding of cellular and viral proteins and also interacts with HCV proteins. In the present study, we knocked down the expression of the Hsp90 gene and inhibited viral replication using siRNA molecules. Reducing the expression of Hsp90 successfully decreased HCV replication. All siRNA molecules specific to the viral genome showed the efficient inhibition of viral replication, particularly siRNA targeted to the 5′UTR region. The combination of siRNAs targeting the viral genome and Hsp90 mRNA also successfully reduced HCV replication and reduced the occurrence of viral resistance. Moreover, these results suggest that an approach based on the combination of cellular and viral siRNAs can be used as an effective alternative for hepatitis C viral suppression. 相似文献
952.
953.
Augusto Schneider Joseph M. Dhahbi Hani Atamna Josef P. Clark Ricki J. Colman Rozalyn M. Anderson 《Aging cell》2017,16(5):1200-1203
Caloric restriction (CR) is one of the most robust interventions shown to delay aging in diverse species, including rhesus monkeys (Macaca mulatta). Identification of factors involved in CR brings a promise of translatability to human health and aging. Here, we show that CR induced a profound change in abundance of circulating microRNAs (miRNAs) linked to growth and insulin signaling pathway, suggesting that miRNAs are involved in CR's mechanisms of action in primates. Deep sequencing of plasma RNA extracts enriched for short species revealed a total of 243 unique species of miRNAs including 47 novel species. Approximately 70% of the plasma miRNAs detected were conserved between rhesus monkeys and humans. CR induced or repressed 24 known and 10 novel miRNA species. Regression analysis revealed correlations between bodyweight, adiposity, and insulin sensitivity for 10 of the CR‐regulated known miRNAs. Sequence alignment and target identification for these 10 miRNAs identify a role in signaling downstream of the insulin receptor. The highly abundant miR‐125a‐5p correlated positively with adiposity and negatively with insulin sensitivity and was negatively regulated by CR. Putative target pathways of CR‐associated miRNAs were highly enriched for growth and insulin signaling that have previously been implicated in delayed aging. Clustering analysis further pointed to CR‐induced miRNA regulation of ribosomal, mitochondrial, and spliceosomal pathways. These data are consistent with a model where CR recruits miRNA‐based homeostatic mechanisms to coordinate a program of delayed aging. 相似文献
954.
Litterfall is an essential component of tropical forest productivity, transferring nutrients from the vegetation back to soils. Here, we summarize the data from 105 estimates of fine litterfall production from 45 sites in the Atlantic Forest domain, including two types of forests, evergreen and seasonal, and two successional stages, secondary and old growth. The overall litterfall average was 8.0 ± 2.5 Mg/ha. Litterfall was significantly in higher seasonal forests than in evergreen forests and in old growth versus secondary forests. Leaves were the major component of litterfall, contributing 68 percent to the total. The second most important component was branches, contributing 22 percent, followed by reproductive organs (flowers and fruits), at 6 percent. Accurate measurements of tropical forest productivity are crucial for estimating their role in sequestering atmospheric carbon, and we suggest some ways to standardize litterfall sampling to obtain better estimates. 相似文献
955.
Joyneel Misra Srinivas Govinda Surampudi Manasij Venkatesh Chirag Limbachia Joseph Jaja Luiz Pessoa 《PLoS computational biology》2021,17(9)
Insights from functional Magnetic Resonance Imaging (fMRI), as well as recordings of large numbers of neurons, reveal that many cognitive, emotional, and motor functions depend on the multivariate interactions of brain signals. To decode brain dynamics, we propose an architecture based on recurrent neural networks to uncover distributed spatiotemporal signatures. We demonstrate the potential of the approach using human fMRI data during movie-watching data and a continuous experimental paradigm. The model was able to learn spatiotemporal patterns that supported 15-way movie-clip classification (∼90%) at the level of brain regions, and binary classification of experimental conditions (∼60%) at the level of voxels. The model was also able to learn individual differences in measures of fluid intelligence and verbal IQ at levels comparable to that of existing techniques. We propose a dimensionality reduction approach that uncovers low-dimensional trajectories and captures essential informational (i.e., classification related) properties of brain dynamics. Finally, saliency maps and lesion analysis were employed to characterize brain-region/voxel importance, and uncovered how dynamic but consistent changes in fMRI activation influenced decoding performance. When applied at the level of voxels, our framework implements a dynamic version of multivariate pattern analysis. Our approach provides a framework for visualizing, analyzing, and discovering dynamic spatially distributed brain representations during naturalistic conditions. 相似文献
956.
957.
Laura Azeredo Miranda Mota Jo?o Roberto Neto Ver?nica Gomes Monteiro Caroliny Samary Silva Lobato Marco Antonio de Oliveira Maura da Cunha Heloisa D’ávila Sérgio Henrique Seabra Patrícia Torres Bozza Renato Augusto DaMatta 《Memórias do Instituto Oswaldo Cruz》2014,109(6):767-774
Lipid bodies [lipid droplets (LBs)] are lipid-rich organelles involved in lipid
metabolism, signalling and inflammation. Recent findings suggest a role for LBs in
host response to infection; however, the potential functions of this organelle
in Toxoplasma gondii infection and how it alters macrophage
microbicidal capacity during infection are not well understood. Here, we investigated
the role of host LBs in T. gondii infection in mouse peritoneal
macrophages in vitro. Macrophages cultured with mouse serum (MS) had higher numbers
of LBs than those cultured in foetal bovine serum and can function as a model to
study the role of LBs during intracellular pathogen infection. LBs were found in
association with the parasitophorous vacuole, suggesting that T. gondii
may benefit from this lipid source. Moreover, increased numbers of
macrophage LBs correlated with high prostaglandin E2 (PGE2) production and decreased
nitric oxide (NO) synthesis. Accordingly, LB-enriched macrophages cultured with MS
were less efficient at controlling T. gondii growth. Treatment of
macrophages cultured with MS with indomethacin, an inhibitor of PGE2 production,
increased the microbicidal capacity against T. gondii. Collectively,
these results suggest that culture with MS caused a decrease in microbicidal activity
of macrophages against T. gondii by increasing PGE2 while lowering
NO production. 相似文献
958.
Fernanda Aparecida Nieri-Bastos Marcos Gomes Lopes Paulo Henrique Duarte Can?ado Giselle Ayres Razera Rossa Jo?o Luiz Horácio Faccini Solange Maria Gennari Marcelo Bahia Labruna 《Memórias do Instituto Oswaldo Cruz》2014,109(2):259-261
Adult ticks of the species Amblyomma parvum were collected from the
vegetation in the Pantanal biome (state of Mato Grosso do Sul) and from horses in the
Cerrado biome (state of Piauí) in Brazil. The ticks were
individually tested for rickettsial infection via polymerase chain reaction (PCR)
targeting three rickettsial genes, gltA, ompA and
ompB. Overall, 63.5% (40/63) and 66.7% (2/3) of A.
parvum ticks from Pantanal and Cerrado, respectively, contained
rickettsial DNA, which were all confirmed by DNA sequencing to be 100% identical to
the corresponding fragments of the gltA, ompA and
ompB genes of Candidatus Rickettsia andeanae.
This report is the first to describe Ca. R. andeanae in Brazil. 相似文献
959.
Sergio Luiz Montego Ferreira Junior Elis Regina Dalla Costa Paula Gon?alves dos Santos Harrison Magdinier Gomes Marcia Susana Nunes Silva Leonardo Souza Esteves Martha Maria Oliveira Raquel de Abreu Maschmann Afranio Lineu Kritski Philip Noel Suffys Maria Lucia Rosa Rossetti 《Memórias do Instituto Oswaldo Cruz》2014,109(3):307-314
Drug-resistant tuberculosis (TB) threatens global TB control and is a major public
health concern in several countries. We therefore developed a multiplex assay
(LINE-TB/MDR) that is able to identify the most frequent mutations related to
rifampicin (RMP) and isoniazid (INH) resistance. The assay is based on multiplex
polymerase chain reaction, membrane hybridisation and colorimetric detection
targeting of rpoB and katG genes, as well as the
inhA promoter, which are all known to carry specific mutations
associated with multidrug-resistant TB (MDR-TB). The assay was validated on a
reference panel of 108 M. tuberculosis isolates that were characterised by the
proportion method and by DNA sequencing of the targets. When comparing the
performance of LINE-TB/MDR with DNA sequencing, the sensitivity, specificity and
agreement were 100%, 100% and 100%, respectively, for RMP and 77.6%, 90.6% and 88.9%,
respectively, for INH. Using drug sensibility testing as a reference standard, the
performance of LINE-TB/MDR regarding sensitivity, specificity and agreement was 100%,
100% and 100% (95%), respectively, for RMP and 77%, 100% and 88.7% (82.2-95.1),
respectively, for INH. LINE-TB/MDR was compared with GenoType MTBDRplus for 65
isolates, resulting in an agreement of 93.6% (86.7-97.5) for RIF and 87.4%
(84.3-96.2) for INH. LINE-TB/MDR warrants further clinical validation and may be an
affordable alternative for MDR-TB diagnosis. 相似文献
960.
Aline Garcia Kozlowski Megmar Aparecida dos Santos Carneiro Márcia Alves Dias de Matos Sheila Araújo Teles Jo?o Alves Araújo Filho Koko Otsuki Ana Carolina Paulo Vicente Regina Maria Bringel Martins 《Memórias do Instituto Oswaldo Cruz》2014,109(1):118-121
Human T-cell lymphotropic virus (HTLV) may impact the clinical course of tuberculosis
(TB). Both infections are highly endemic in Brazil. The aim of this study was to
assess the prevalence of HTLV-1/2 in TB patients in Central-West Brazil and to
perform a genetic characterisation of the respective isolates. Of the 402 patients,
six (1.49%) were positive for anti-HTLV and five (1.24%; 95% confidence interval:
0.46-3.05) were infected with HTLV-1/2. Genetic characterisation demonstrated that
the four HTLV-1 isolates belonged to the Transcontinental subgroup A of the
Cosmopolitan subtype a and that the HTLV-2 isolate belonged to subtype a (HTLV-2a/c).
The prevalence of HTLV infection observed in this study is higher than that observed
in local blood donors and the HTLV-1 and 2 subtypes identified are consistent with
those circulating in Brazil. 相似文献