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71.
72.
Milton Maciel Jr. Fábia da Silva Pereira Cruz Marli Tenório Cordeiro Márcia Archer da Motta Klécia Marília Soares de Melo Cassemiro Rita de Cássia Carvalho Maia Regina Célia Bressan Queiroz de Figueiredo Ricardo Galler Marcos da Silva Freire Joseph Thomas August Ernesto T. A. Marques Rafael Dhalia 《PLoS neglected tropical diseases》2015,9(4)
Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies. 相似文献
73.
Julio Cesar Madureira de-Freitas-Junior Sandra Carvalho Ana M. Dias Patrícia Oliveira Joana Cabral Raquel Seruca Carla Oliveira José Andrés Morgado-Díaz Celso A. Reis Salomé S. Pinho 《PloS one》2013,8(11)
Changes in glycosylation are considered a hallmark of cancer, and one of the key targets of glycosylation modifications is E-cadherin. We and others have previously demonstrated that E-cadherin has a role in the regulation of bisecting GlcNAc N-glycans expression, remaining to be determined the E-cadherin-dependent signaling pathway involved in this N-glycans expression regulation. In this study, we analysed the impact of E-cadherin expression in the activation profile of receptor tyrosine kinases such as insulin receptor (IR) and IGF-I receptor (IGF-IR). We demonstrated that exogenous E-cadherin expression inhibits IR, IGF-IR and ERK 1/2 phosphorylation. Stimulation with insulin and IGF-I in MDA-MD-435 cancer cells overexpressing E-cadherin induces a decrease of bisecting GlcNAc N-glycans that was accompanied with alterations on E-cadherin cellular localization. Concomitantly, IR/IGF-IR signaling activation induced a mesenchymal-like phenotype of cancer cells together with an increased tumor cell invasion capability. Altogether, these results demonstrate an interplay between E-cadherin and IR/IGF-IR signaling as major networking players in the regulation of bisecting N-glycans expression, with important effects in the modulation of epithelial characteristics and tumor cell invasion. Here we provide new insights into the role that Insulin/IGF-I signaling play during cancer progression through glycosylation modifications. 相似文献
74.
Erpan Ahat Sarah Bui Jianchao Zhang Felipe da Veiga Leprevost Lisa Sharkey Whitney Reid Alexey I. Nesvizhskii Henry L. Paulson Yanzhuang Wang 《The Journal of biological chemistry》2022,298(8)
Recent studies demonstrated that the Golgi reassembly stacking proteins (GRASPs), especially GRASP55, regulate Golgi-independent unconventional secretion of certain cytosolic and transmembrane cargoes; however, the underlying mechanism remains unknown. Here, we surveyed several neurodegenerative disease–related proteins, including mutant huntingtin (Htt-Q74), superoxide dismutase 1 (SOD1), tau, and TAR DNA–binding protein 43 (TDP-43), for unconventional secretion; our results show that Htt-Q74 is most robustly secreted in a GRASP55-dependent manner. Using Htt-Q74 as a model system, we demonstrate that unconventional secretion of Htt is GRASP55 and autophagy dependent and is enhanced under stress conditions such as starvation and endoplasmic reticulum stress. Mechanistically, we show that GRASP55 facilitates Htt secretion by tethering autophagosomes to lysosomes to promote autophagosome maturation and subsequent lysosome secretion and by stabilizing p23/TMED10, a channel for translocation of cytoplasmic proteins into the lumen of the endoplasmic reticulum–Golgi intermediate compartment. Moreover, we found that GRASP55 levels are upregulated by various stresses to facilitate unconventional secretion, whereas inhibition of Htt-Q74 secretion by GRASP55 KO enhances Htt aggregation and toxicity. Finally, comprehensive secretomic analysis identified novel cytosolic cargoes secreted by the same unconventional pathway, including transgelin (TAGLN), multifunctional protein ADE2 (PAICS), and peroxiredoxin-1 (PRDX1). In conclusion, this study defines the pathway of GRASP55-mediated unconventional protein secretion and provides important insights into the progression of Huntington’s disease. 相似文献
75.
Freshwater finfish species richness and level of endemism in East, and South and South‐East Asia that included 17 nations were studied using available databases, and included nation‐wise distribution, habitat types, and conservation status. The number of endemic finfish species in the region was 559, belonging to 47 families. Families Cyprinidae and Balitoridae accounted for 43.5% and 16.2% of the total number of endemic species in the region, respectively, followed by Sisoridae (25), Gobiidae (20), Melanotaeniidae (19), and Bagridae (16), and the other 41 families had at least one endemic species. Nation‐wise the most number of endemic freshwater finfish species occur in India (191), followed by China (88), Indonesia (84), and Myanmar (60). In India, the endemic species accounted for 26.4% of the native freshwater fish fauna, followed by South Korea (16.9%), the Philippines, (16.3%) and Myanmar (15.7%). Statistically significant relationships discerned between the number of indigenous and endemic species richness to land area (Xla in 103 km2) of the nations in the region were, Yin = 218.961 Ln(Xla) – 843.1 (R2 = 0.735; P < 0.001) and Ye = 28.445 Ln Xla?134.47 (R2 = 0.534; P < 0.01), respectively, and between indigenous and endemic species richness was Ye = 0.079Xn? 1.558 (R2 = 0.235; P < 0.05). The overall conservation status of endemic finfish in Asia was satisfactory in that only 92 species were in some state of vulnerability, of which 37 species (6.6%) are endangered or critically endangered. However, the bulk of these species (83.7%) were cave‐ and or lake‐dwelling fish. However, nation‐wise, the endemic freshwater finfish fauna of the Philippines and Sri Lanka, based on the imperilment index, were found to be in a highly vulnerable state. Among river basins, the Mekong Basin had the highest number of endemic species (31.3%). The discrepancies between databases are highlighted and the need to consolidate information among databases is discussed. It is suggested that the Mekong Basin be considered as a biodiversity hotspot, and appropriate management strategies be introduced in this regard. 相似文献
76.
77.
A population of Channa gachua in a small irrigation canal that supplies rice fields was studied by monthly sampling over 2 years. The population density was positively correlated with the rainfall and varied from 0.34 to 0.95 individuals m−2 . The growth parameters of the von Bertalanffy growth equation determined on monthly size–frequency data were Lx = 179 mm total length and K =0.50. Overall male to female ratio was 0.82 and there were more females than males in the middle size classes. Spawning occurred throughout the year, but all evidence indicated enhanced breeding during major rainy periods of May to July and October to December. The length at first spawning was 102 mm, which is reached in about 20 months. Fecundity, which varied between 389 and 2130, was positively correlated with gonad weight, body weight and total length. Longevity and natural mortality were estimated as 6 years and l.27 yr−1 , respectively. However, 99% of the population appeared to live for only 3 years. The mean biomass, average annual production and turnover ratio of the population were 7.35 g m−2 , 12.06 g m−2 and 1.64, respectively. 相似文献
78.
Paulo Bentes de Carvalho-Neto Marcelo dos Santos Marcos Brasilino de Carvalho Ana Maria da Cunha Mercante Viviane Priscila Pina dos Santos Patrícia Severino Eloiza Helena Tajara Iuri Drumond Louro Adriana Madeira álvares da Silva-Conforti 《PloS one》2013,8(7)
FAS/FASL altered expression may cause tumor protecting immunomodulation, with a direct impact on patient prognosis. FAS expression was studied in 60 squamous cell carcinomas of the oral cavity. FAS expression did not show a significant association with tumor histopathological characteristics, but was significantly associated with lymph node positivity. FAS expression was significantly associated with disease specific death and negative FAS expression was an independent risk factor, increasing risk 4 times when compared to positive expression. When FAS and FASL expression results were combined, we were able to define high, intermediate and low risk profiles. Disease-free and disease-specific survival were significantly correlated with FAS/FASL expression profiles. The high risk category was an independent marker for earlier disease relapse and disease-specific death, with approximately 4- and 6-fold increased risk, respectively, when compared to the low risk profile. Risk profiles based on FAS/FASL expression showed that high risk was significantly associated with increased disease relapse and death, as well as shorter disease-free or disease-specific survival. This categorization, added to patient clinical data, may facilitate the choice of therapy, minimizing treatment failure and increasing disease control. 相似文献
79.
Effect of genetic modifications by selection for immunological tolerance on fungus infection in mice
da Silva AC Bezerra LM Aguiar TS Tavares D Araujo LM Pinto CE Ribeiro OG 《Microbes and infection / Institut Pasteur》2001,3(3):215-222
Two strains of mice genetically selected for extreme phenotypes of immunological tolerance to ovalbumin, susceptible (TS) and resistant (TR), were experimentally infected with Sporothrix schenckii. The objective was to observe whether the genetic modifications produced by the selection might be associated with interstrain differences in adaptive immune and innate responses to infection. Therefore, we evaluated the LD(50), CFU, phagocytic index, fungicidal activity, pro-inflammatory cytokines, specific antibody titres, and the delayed-type hypersensitivity reactivity. TR mice were tenfold more susceptible to infection than TS mice, as shown by LD(50) (5 x 10(6) conidia i.v.). In TS mice, the resistance was a consequence of the tissue fungal load reduction, consistent specific T-cell-mediated immunity, and tumour necrosis factor (TNF)-alpha activity at onset of infection. In TR mice, these responses were not precociously detected. Therefore, the absence of CD4(+) T-cell response in the first week of infection might explain the non-clearance of pathogen in TR mice. However, TR mice did show an increase in TNF level and delayed-type hypersensitivity response after the first week post-infection; there was also expansion and increase in granulomatous foci and CFU in the spleen. The expansion of granulomatous foci and the increase in TNF-alpha and tissue fungal load to damaging levels induced severe tissue destruction, general failure of the organs, cachexy and death in TR mice. The results show that genetic selection for extreme phenotypes of immunological tolerance also modified the responses to S. schenckii infection. 相似文献
80.
Tatiana P. da Silva Carmem B. W. Giacoia-Gripp Carolina A. Schmaltz Flavia M. Sant` Anna Valeria Rolla Mariza G. Morgado 《PloS one》2013,8(6)