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Cristina Peligero Jordi Argilaguet Roberto Güerri-Fernandez Berta Torres Carmen Ligero Pilar Colomer Montserrat Plana Hernando Knobel Felipe García Andreas Meyerhans 《PLoS pathogens》2015,11(12)
Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject’s plasma viremia. 相似文献
104.
G. Kharmanda 《Computer methods in biomechanics and biomedical engineering》2016,19(14):1557-1566
A new strategy of multi-objective structural optimization is integrated into Austin-Moore prosthesis in order to improve its performance. The new resulting model is so-called Improved Austin-Moore. The topology optimization is considered as a conceptual design stage to sketch several kinds of hollow stems according to the daily loading cases. The shape optimization presents the detailed design stage considering several objectives. Here, A new multiplicative formulation is proposed as a performance scale in order to define the best compromise between several requirements. Numerical applications on 2D and 3D problems are carried out to show the advantages of the proposed model. 相似文献
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Roberto López-Píriz Eva Solá-Linares Mercedes Rodriguez-Portugal Beatriz Malpica Idoia Díaz-Güemes Silvia Enciso Leticia Esteban-Tejeda Belén Cabal Juan José Granizo José Serafín Moya Ramón Torrecillas 《PloS one》2015,10(10)
ObjectivesThe aim of the present study is to evaluate, in a ligature-induced peri-implantitis model, the efficacy of three antimicrobial glassy coatings in the prevention of biofilm formation, intrasulcular bacterial growth and the resulting peri-implant bone loss.MethodsMandibular premolars were bilaterally extracted from five beagle dogs. Four dental implants were inserted on each hemiarch. Eight weeks after, one control zirconia abutment and three with different bactericidal coatings (G1n-Ag, ZnO35, G3) were connected. After a plaque control period, bacterial accumulation was allowed and biofilm formation on abutments was observed by Scanning Electron Microscopy (SEM). Peri-implantitis was induced by cotton ligatures. Microbial samples and peri-implant crestal bone levels of all implant sites were obtained before, during and after the breakdown period.ResultsDuring experimental induce peri-implantitis: colony forming units counts from intrasulcular microbial samples at implants with G1n-Ag coated abutment remained close to the basal inoculum; G3 and ZnO35 coatings showed similar low counts; and anaerobic bacterias counts at control abutments exhibited a logarithmic increase by more than 2. Bone loss during passive breakdown period was no statistically significant. Additional bone loss occurred during ligature-induce breakdown: 0.71 (SD 0.48) at G3 coating, 0.57 (SD 0.36) at ZnO35 coating, 0.74 (SD 0.47) at G1n-Ag coating, and 1.29 (SD 0.45) at control abutments; and statistically significant differences (p<0.001) were found. The lowest bone loss at the end of the experiment was exhibited by implants dressing G3 coated abutments (mean 2.1; SD 0.42).SignificanceAntimicrobial glassy coatings could be a useful tool to ward off, diminish or delay peri-implantitis progression. 相似文献
107.
Harriet M. Jackson Kristen D. Onos Keating W. Pepper Leah C. Graham Ellen C. Akeson Candice Byers Laura G. Reinholdt Wayne N. Frankel Gareth R. Howell 《PloS one》2015,10(5)
Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs) and neuronal dysfunction. Early onset AD (EOAD) is commonly caused by mutations in amyloid precursor protein (APP) or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2). In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but significant levels of seizure susceptibility. To investigate the effect of genetic background on these phenotypes, we generated APPswe and PSEN1de9 transgenic mice on the seizure prone inbred strain background, DBA/2J. Previous studies show that the DBA/2J genetic background modifies plaque deposition in the presence of mutant APP but the impact of PSEN1de9 has not been tested. Our study shows that DBA/2J.APPswePSEN1de9 mice are significantly more prone to premature lethality, likely to due to lethal seizures, compared to B6.APPswePSEN1de9 mice—70% of DBA/2J.APPswePSEN1de9 mice die between 2-3 months of age. Of the DBA/2J.APPswePSEN1de9 mice that survived to 6 months of age, plaque deposition was greatly reduced compared to age-matched B6.APPswePSEN1de9 mice. The reduction in plaque deposition appears to be independent of microglia numbers, reactive astrocytosis and complement C5 activity. 相似文献
108.
Valeria L. Martin-Albarracin Guillermo C. Amico Daniel Simberloff Martin A. Nu?ez 《PloS one》2015,10(11)
Introduction and naturalization of non-native species is one of the most important threats to global biodiversity. Birds have been widely introduced worldwide, but their impacts on populations, communities, and ecosystems have not received as much attention as those of other groups. This work is a global synthesis of the impact of nonnative birds on native ecosystems to determine (1) what groups, impacts, and locations have been best studied; (2) which taxonomic groups and which impacts have greatest effects on ecosystems, (3) how important are bird impacts at the community and ecosystem levels, and (4) what are the known benefits of nonnative birds to natural ecosystems. We conducted an extensive literature search that yielded 148 articles covering 39 species belonging to 18 families -18% of all known naturalized species. Studies were classified according to where they were conducted: Africa, Asia, Australasia, Europe, North America, South America, Islands of the Indian, of the Pacific, and of the Atlantic Ocean. Seven types of impact on native ecosystems were evaluated: competition, disease transmission, chemical, physical, or structural impact on ecosystem, grazing/ herbivory/ browsing, hybridization, predation, and interaction with other non-native species. Hybridization and disease transmission were the most important impacts, affecting the population and community levels. Ecosystem-level impacts, such as structural and chemical impacts were detected. Seven species were found to have positive impacts aside from negative ones. We provide suggestions for future studies focused on mechanisms of impact, regions, and understudied taxonomic groups. 相似文献
109.
Elsa Youngsteadt R. Holden Appler Margarita M. López-Uribe David R. Tarpy Steven D. Frank 《PloS one》2015,10(11)
Given the role of infectious disease in global pollinator decline, there is a need to understand factors that shape pathogen susceptibility and transmission in bees. Here we ask how urbanization affects the immune response and pathogen load of feral and managed colonies of honey bees (Apis mellifera Linnaeus), the predominant economically important pollinator worldwide. Using quantitative real-time PCR, we measured expression of 4 immune genes and relative abundance of 10 honey bee pathogens. We also measured worker survival in a laboratory bioassay. We found that pathogen pressure on honey bees increased with urbanization and management, and the probability of worker survival declined 3-fold along our urbanization gradient. The effect of management on pathogens appears to be mediated by immunity, with feral bees expressing immune genes at nearly twice the levels of managed bees following an immune challenge. The effect of urbanization, however, was not linked with immunity; instead, urbanization may favor viability and transmission of some disease agents. Feral colonies, with lower disease burdens and stronger immune responses, may illuminate ways to improve honey bee management. The previously unexamined effects of urbanization on honey-bee disease are concerning, suggesting that urban areas may favor problematic diseases of pollinators. 相似文献
110.
Heat-shock protein 70 accumulation was induced by both increasesand decreases in temperature. An upward temperature shift ofabout 15C or a downward shift of about 10C was needed forthe response. In each case the accumulation was significantwithin 2 h and complete within about 6 h. Heat-shocked tissuecontained two new HSP70 isotypes not seen in the control tissueor in the cold-shocked tissue. Key words: Heat-shock protein, heat stress, cold stress, mung bean 相似文献