Modulation of CD4 T cell function via CD6-targeting

In recent years molecules involved on the immune synapse became successful targets for therapeutic immune modulation. CD6 has been extensively studied, yet, results regarding CD6 biology have been controversial, in spite of the ubiquitous presence of this molecule on virtually all CD4 T cells. We investigated the outcome of murine and human antibodies targeting CD6 domain 1. We found that CD6-targeting had a major impact on the functional specialization of CD4 cells, both human and murine. Differentiation of CD4 T cells towards a Foxp3+ Treg fate was prevented with increasing doses of anti-CD6, while Th1 polarization was favoured. No impact was observed on Th2 or Th17 specialization. These in vitro results provided an explanation for the dose-dependent outcome of in vivo anti-CD6 administration where the anti-inflammatory action is lost at the highest doses. Our data show that therapeutic targeting of the immune synapse may lead to paradoxical dose-dependent effects due to modification of T cell fate.Funded by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT) / Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) throught Fundos do Orçamento do Estado, pela Fundação para a Ciência e a Tecnologia (FCT) ( PTDC/DTP-FTO/3080/2014 ); and by the project SRecognite Infect - ERA/0003/2015 using national funds through FCT . Funders did not have a role in study design, data collection, analysis, and interpretation, or in the writing of the manuscript

Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202

Selectivity of Pesticides used in Integrated Apple Production to the Lacewing, Chrysoperla externa

This research aimed to assess the toxicity of the pesticides abamectin 18 CE (0.02 g a.i. L-1), carbaryl 480 SC (1.73 g a.i. L-1), sulfur 800 GrDA (4.8 g a.i. L-1), fenitrothion 500 CE (0.75 g a.i. L-1), methidathion 400 CE (0.4 g a.i. L-1), and trichlorfon 500 SC (1.5 g a.i. L-1) as applied in integrated apple production in Brazil on the survival, oviposition capacity, and egg viability of the lacewing, Chrysoperla externa (Hagen) (Neuroptera: Chrysopidae) from Bento Gonçalves and Vacaria, Rio Grande do Sul State, Brazil. An attempt was made to study morphological changes caused by some of these chemicals, by means of ultrastructural analysis, using a scanning electronic microscope. Carbaryl, fenitrothion, and methidathion caused 100% adult mortality for both populations, avoiding evaluation of pesticides' effects on predator reproductive parameters. Abamectin and sulfur also affected the survival of these individuals with mortality rates of 10% and 6.7%, respectively, for adults from Bento Gonçalves, and were harmless to those from Vacaria at the end of evaluation. Trichlorfon was also harmless to adults from both populations. No compound reduced oviposition capacity. C. externa from Vacaria presented higher reproductive potential than those from Bento Gonçalves. In relation to egg viability, sulfur was the most damaging compound to both populations of C. externa. Ultrastructural analyses showed morphological changes in the micropyle and the chorion of eggs laid by C. externa treated with either abamectin or sulfur. The treatment may have influenced the fertilization of C. externa eggs and embryonic development. Sulfur was responsible for malformations in the end region of the abdomen and genitals of treated females. When applied to adults, abamectin, sulfur, and trichlorfon were harmless, while carbaryl, fenitrothion, and methidathion were harmful, according to the IOBC classification

Regular Strength and Sprint Training Counteracts Bone Aging: A 10-Year Follow-Up in Male Masters Athletes

Cross-sectional and interventional studies suggest that high-intensity strength and impact-type training provide a powerful osteogenic stimulus even in old age. However, longitudinal evidence on the ability of high-intensity training to attenuate age-related bone deterioration is currently lacking. This follow-up study assessed the role of continued strength and sprint training on bone aging in 40- to 85-year-old male sprinters (n = 69) with a long-term training background. Peripheral quantitative computed tomography (pQCT)-derived bone structural, strength, and densitometric parameters of the distal tibia and tibia midshaft were assessed at baseline and 10 years later. The groups of well-trained (actively competing, sprint training including strength training ≥2 times/week; n = 36) and less-trained (<2 times/week, no strength training, switched to endurance training; n = 33) athletes were formed according to self-reports at follow-up. Longitudinal changes in bone traits in the two groups were examined using linear mixed models. Over the 10-year period, group-by-time interactions were found for distal tibia total bone mineral content (BMC), trabecular volumetric bone mineral density (vBMD), and compressive strength index, and for mid-tibia cortical cross-sectional area, medullary area, total BMC, and BMC at the anterior and posterior sites (polar mass distribution analysis) (p < 0.05). These interactions reflected maintained (distal tibia) or improved (mid-tibia) bone properties in the well-trained and decreased bone properties in the less-trained athletes over the 10-year period. Depending on the bone variable, the difference in change in favor of the well-trained group ranged from 2% to 5%. The greatest differences were found in distal tibia trabecular vBMD and mid-tibia posterior BMC, which remained significant (p < 0.05) after adjustment for multiple testing. In conclusion, our longitudinal findings indicate that continued strength and sprint training is associated with maintained or even improved tibial properties in middle-aged and older male sprint athletes, suggesting that regular, intensive exercise counteracts bone aging. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

The effects of exercise training in a weight loss lifestyle intervention on asthma control, quality of life and psychosocial symptoms in adult obese asthmatics: protocol of a randomized controlled trial

Abstract\ud \ud Background\ud Asthma and obesity are public health problems with increasing prevalence worldwide. Clinical and epidemiologic studies have demonstrated that obese asthmatics have worse clinical control and health related quality of life (HRQL) despite an optimized medical treatment. Bariatric surgery is successful to weight-loss and improves asthma control; however, the benefits of nonsurgical interventions remain unknown.\ud \ud \ud Methods/Design\ud This is a randomized controlled trial with 2-arms parallel. Fifty-five moderate or severe asthmatics with grade II obesity (BMI ≥ 35 kg/m2) under optimized medication will be randomly assigned into either weight-loss program + sham (WL + S group) or weight-loss program + exercise (WL + E group). The weight loss program will be the same for both groups including nutrition and psychological therapies (every 15 days, total of 6 sessions, 60 min each). Exercise program will include aerobic and resistance muscle training while sham treatment will include a breathing and stretching program (both programs twice a week, 3 months, 60 min each session). The primary outcome variable will be asthma clinical control. Secondary outcomes include HRQL, levels of depression and anxiety, lung function, daily life physical activity, body composition, maximal aerobic capacity, strength muscle and sleep disorders. Potential mechanism (changes in lung mechanical and airway/systemic inflammation) will also be examined to explain the benefits in both groups.\ud \ud \ud Discussion\ud This study will bring a significant contribution to the literature evaluating the effects of exercise conditioning in a weight loss intervention in obese asthmatics as well as will evaluate possible involved mechanisms.\ud \ud \ud Trial registration\ud \ud \ud NCT02188940The study was supported by the São Paulo Research Foundation (FAPESP;\ud Grants 2012/16700-9 and 2012/16134-3) and Conselho Nacional de Pesquisa (CNPq Grants 485065/2012-6)