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101.
Valentina Ferrari Alison Tarke Hannah Fields Luca Ferrari Trevor Conley Franco Ferrari Zeynep Koşaloğlu-Yalçın Alessandro Sette Bjoern Peters Colin L. McCarthy Asad Bashey Dimitrios Tzachanis Edward D. Ball Tiffany N. Tanaka Rafael Bejar Thomas A. Lane Antonella Vitiello 《Cytotherapy》2021,23(4):320-328
Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden. DNA and RNA from tumor (CD34+) and normal (CD3+) cells isolated from the patients’ blood were sequenced to predict patient-specific MDS neopeptides. Neopeptides representing the somatic variants were used to induce and expand autologous T cells ex vivo, and these were systematically tested in killing assays to determine the proportion of neopeptides yielding neoantigen-specific T cells. The authors identified a total of 32 somatic variants (four to eight per patient) and found that 21 (66%) induced a peptide-specific T-cell response and 19 (59%) induced a T-cell response capable of killing autologous tumor cells. Of the 32 somatic variants, 11 (34%) induced a CD4+ response and 11 (34%) induced a CD8+ response that killed the tumor. These results indicate that in vitro induction of neoantigen-specific T cells is feasible for tumors with very low mutational burden and that this approach warrants investigation as a therapeutic option for such patients. 相似文献
102.
103.
Rodrigo Carregaro Rafael Cunha Carlos Gomes Oliveira Lee E. Brown Martim Bottaro 《Journal of electromyography and kinesiology》2013,23(5):1090-1096
PurposePreload of antagonist muscles can be achieved by reciprocal actions (RAs) or by opposing muscle actions. However, evidence concerning neuromuscular and fatigue responses are scarce.ObjectiveTo compare the effects of different knee flexor (KF) preload methods on knee extension (KE) vastus medialis muscle fatigue, based on EMG-spectral index (FI), load range (LR), total work (TW), blood lactate (LAC) and biceps femoris co-activation (BFc) during resistance exercise.MethodsTwenty-four healthy men (23.5 ± 3.6 yrs) performed three antagonist pre-load isokinetic exercises (4 sets, 10 repetitions, 60° s?1, 1 min rest between sets): RA (KF contraction immediately followed by KE); Superset (SS; one KF set immediately followed by one KE set); Multiple Set (MS; four KF sets followed by four KE sets).ResultsTotal work was significantly greater in RA. There was no significant decrease in LR between sets in RA. The BFc did not differ between protocols (p = 0.063). However, RA presented greater biceps femoriscoactivation. The FI was greater during SS compared to RA and MS (p < 0.05). The SS had greater LAC when compared to MS and RA (p = 0.005 and p = 0.007, respectively).ConclusionIt is suggested that the RA protocol is more neuromuscular and metabolic efficient during the performance of knee extension resistance exercise. 相似文献
104.
Gay–Straight Alliances (GSAs) are student-led, school-based clubs that aim to provide a safe environment in the school context for lesbian, gay, bisexual, and transgender (LGBT) students, as well as their straight allies. The present study examines the potential for GSAs to support positive youth development and to reduce associations among LGBT-specific school victimization and negative young adult well-being. The sample includes 245 LGBT young adults, ages 21–25, who retrospectively reported on the presence of a GSA in their high school, their participation in their school's GSA, and their perceptions of whether or not their GSA was effective in improving school safety. Findings revealed that the presence of a GSA, participation in a GSA, and perceived GSA effectiveness in promoting school safety were differentially associated with young adult well-being and, in some cases, buffered the negative association between LGBT-specific school victimization and well-being. Implications for future research and schools are discussed. 相似文献
105.
106.
Rafael Piovezan Stéfany Larissa Rosa Matheus Luca Rocha Thiago Salomão de Azevedo Cláudio José Von Zuben 《Journal of vector ecology》2013,38(2):317-325
Because of the high adaptive capacity of mosquitoes, studies that focus on transitional environments become very important, such as those in rural areas, which are considered as bridges between wild diseases and human populations of urban areas. In this study, a survey of the existing species of mosquitoes was performed in an Atlantic Forest area of the city of Santa Bárbara d'Oeste, São Paulo state, Brazil, using traps for immatures and analyzing the frequency and distribution of these insects over the sampling months. Five mosquito species were found: Aedes albopictus (the most frequent species), Aedes aegypti, Aedes fluviatilis, Culex quinquefasciatus, and Toxorhynchites theobaldi. The 4,524 eggs collected in ovitraps showed the presence of the tribe Aedini. Aedes aegypti and Ae. albopictus were identified after larval hatching in the laboratory, with different spatial distributions: the first of which coincides with the area of greatest diversity calculated using the Simpson index, while the second does not. The association of ecological analysis of spatial diversity with simple methods of data collection enables the identification of possible epidemiological risk situations and is a strategy that may be implemented to monitor ecological processes resulting from the interaction among different species of mosquitoes. 相似文献
107.
Emilia Mellado Rafael De La Camara Buenaventura Buendía Juan L. Rodriguez-Tudela Manuel Cuenca-Estrella 《Revista iberoamericana de micología》2013,30(1):64-68
BackgroundAn allogeneic hematopoietic cell transplantation (allo-HCT) patient presented with chronic pulmonary aspergillosis associated to pulmonary graft versus host disease (GVHD) and was treated for a long time with several antifungal agents that were administered as prophylaxis, combination therapies, and maintenance treatment. The patient suffered from a breakthrough invasive pulmonary aspergillosis due to Aspergillus fumigatus after long-term antifungal therapy.Material and methodsSeveral isolates were analyzed. First isolates were susceptible in vitro to all azole agents. However, after prolonged treatment with itraconazole and voriconazole a multiple azole resistant A. fumigatus isolate was cultured from bronchoalveolar lavage (BAL) when the patient was suffering from an invasive infection, and cavitary lesions were observed.ResultsAnalysis of the resistant mechanisms operating in the last strain led us to report the first isolation in Spain of an azole resistant A. fumigatus strain harboring the L98H mutation in combination with the tandem repeat (TR) alteration in CYP51A gene (TR-L98H). Long-term azole therapy may increase the risk of resistance selecting strains exhibiting reduced susceptibility to these compounds. However, since the isolates were genetically different the suggestion that could be made is that the resistance was not induced during the prolonged azole therapy but the patient might simply have acquired this resistant isolate from the environment, selected by the therapy.ConclusionsThese findings suggest that in all long-term treatments with antifungal agents, especially with azoles, repeated sampling and regular susceptibility testing of strains isolated is necessary as resistant isolates could be selected. 相似文献
108.
David Malinak Rafael Dolezal Vendula Hepnarova Miroslava Hozova Rudolf Andrys Petr Bzonek 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):478-488
Abstract The series of symmetrical and unsymmetrical isoquinolinium-5-carbaldoximes was designed and prepared for cholinesterase reactivation purposes. The novel compounds were evaluated for intrinsic acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) inhibition, when the majority of novel compounds resulted with high inhibition of both enzymes and only weak inhibitors were selected for reactivation experiments on human AChE or BChE inhibited by sarin, VX, or paraoxon. The AChE reactivation for all used organophosphates was found negligible if compared to the reactivation ability of obidoxime. Importantly, two compounds were found to reactivate BChE inhibited by sarin or VX better to obidoxime at human attainable concentration. One compound resulted as better reactivator of NEMP (VX surrogate)-inhibited BChE than obidoxime. The in vitro results were further rationalized by molecular docking studies showing future directions on designing potent BChE reactivators. 相似文献
109.
To understand current patterns of Pinus invasion in an Araucaria forest in southern Brazil, we quantified invasion at the local scale and compared it with habitat characteristics, propagule size, and number of source populations, using generalized linear models. We also compared observed and expected invasive species status based on a previously developed model (Z scores) using Chi square and correlation tests to evaluate the predictability of species status based on their traits. Of the 16 Pinus species currently present in the site, three are invasive (P. elliottii, P. glabra, and P. taeda), three are naturalized (P. clausa, P. oocarpa, and P. pseudostrobus), and ten are present only as the originally planted individuals. While P. taeda spread the farthest, P. glabra had greater overall density, but none of the invasive species has spread more than 250 m in 45 years. Invasive Pinus plants were found where forest tree density was below 805 trees ha?1, and invasive Pinus density decreased log-linearly with an increase in native tree density. Number of individuals introduced and number of source populations were strong predictors of naturalization, thus both propagule size and propagule diversity can potentially be driving invasion success. Z scores based on species traits did not predict which species would invade in Rio Negro. Our findings suggest that Araucaria forests might not resist invasion by Pinus as recently suggested and support the hypothesis that propagule pressure is a fundamental driver of invasions with propagule diversity being a possible component of this mechanism. 相似文献
110.
Paola Locatelli Fernanda Daniela Olea Anna Hnatiuk Diana Sepúlveda Juan Manuel Pérez Sáez Rafael Argüello Alberto Crottogini 《Cytotherapy》2013,15(2):163-170
Background aimsGiven the close similarity between ovine and human cardiomyocytes, sheep models of myocardial infarction and heart failure are increasingly used in studies of stem cell-mediated heart regeneration. In these studies, mesenchymal stromal cells (MSCs) are frequently employed. To enhance the paracrine effects of these MSCs, ex vivo transfection with genes encoding growth factors has been proposed. Although viral vectors exhibit higher transfection efficiency than plasmids, they entail the risks of uncontrolled transgene expression and immune reactions that preclude repeated administration. Our aim was to optimize the efficiency of plasmid-mediated transfection of ovine MSCs, while preserving cell viability.MethodsVarying amounts of diverse cationic lipids were used to obtain the reagent-to-DNA mass ratio showing highest luciferase activity. Transfection efficiency (flow cytometry) was tested on plasmid-green fluorescent protein-transfected MSCs at increasing DNA mass.ResultsLipofectamine LTX 5 μL and Plus reagent 4 μL with 2 μg of DNA yielded 42.3 ± 4.7% transfection efficiency, while preserving cell viability. Using these transfection conditions, we transfected MSCs with a plasmid encoding human vascular endothelial growth factor (VEGF) and found high VEGF protein concentrations in the culture supernatant from day 2 (1968 ± 324 pg/mL per μg DNA) through at least day 12 (888 ± 386 pg/mL per μg DNA) after transfection.ConclusionsPlasmid-mediated transfection of ovine MSCs to over-express paracrine heart-regenerative growth factors is feasible and efficient and overcomes the risks and limitations associated with the use of viral vectors. 相似文献