Specific and Nonhomologous Isofunctional Enzymes of the Genetic Information Processing Pathways as Potential Therapeutical Targets for Tritryps

Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryps) are unicellular protozoa that cause leishmaniasis, sleeping sickness and Chagas' disease, respectively. Most drugs against them were discovered through the screening of large numbers of compounds against whole parasites. Nonhomologous isofunctional enzymes (NISEs) may present good opportunities for the identification of new putative drug targets because, though sharing the same enzymatic activity, they possess different three-dimensional structures thus allowing the development of molecules against one or other isoform. From public data of the Tritryps' genomes, we reconstructed the Genetic Information Processing Pathways (GIPPs). We then used AnEnPi to look for the presence of these enzymes between Homo sapiens and Tritryps, as well as specific enzymes of the parasites. We identified three candidates (ECs 3.1.11.2 and 6.1.1.-) in these pathways that may be further studied as new therapeutic targets for drug development against these parasites

Effects of periodontal therapy on white blood cell count and levels of transforming growth factor beta in serum of subjects with severe periodontitis

This study aimed to investigate the effects of nonsurgical periodontal therapy on white blood cell (WBC) count and levels of transforming growth factor beta (TGF—β) in serum from subjects with severe periodontitis. Serum from 28 subjects with periodontitis (mean age: 34.36±6.24; 32% men) and 27 healthy controls (mean age: 33.18±6.42; 33% men) were collected prior to therapy. Blood samples were obtained from 23 subjects who completed therapy (9—12 months). A well—controlled periodontal treatment protocol was established in three stages: mechanical periodontal therapy (scaling and root planning), reinstrumentation of dental sites, and supportive periodontal therapy. Periodontal and systemic parameters such as the total number of WBCs and TGF—β levels, accessed by enzyme—linked immunosorbent assay (ELISA), were included. After therapy, all clinical periodontal parameters decreased (

In silico Strategies to Support Fragment-to-Lead Optimization in Drug Discovery.

Fragment-based drug (or lead) discovery (FBDD or FBLD) has developed in the last two decades to become a successful key technology in the pharmaceutical industry for early stage drug discovery and development. The FBDD strategy consists of screening low molecular weight compounds against macromolecular targets (usually proteins) of clinical relevance. These small molecular fragments can bind at one or more sites on the target and act as starting points for the development of lead compounds. In developing the fragments attractive features that can translate into compounds with favorable physical, pharmacokinetics and toxicity (ADMET-absorption, distribution, metabolism, excretion, and toxicity) properties can be integrated. Structure-enabled fragment screening campaigns use a combination of screening by a range of biophysical techniques, such as differential scanning fluorimetry, surface plasmon resonance, and thermophoresis, followed by structural characterization of fragment binding using NMR or X-ray crystallography. Structural characterization is also used in subsequent analysis for growing fragments of selected screening hits. The latest iteration of the FBDD workflow employs a high-throughput methodology of massively parallel screening by X-ray crystallography of individually soaked fragments. In this review we will outline the FBDD strategies and explore a variety of in silico approaches to support the follow-up fragment-to-lead optimization of either: growing, linking, and merging. These fragment expansion strategies include hot spot analysis, druggability prediction, SAR (structure-activity relationships) by catalog methods, application of machine learning/deep learning models for virtual screening and several de novo design methods for proposing synthesizable new compounds. Finally, we will highlight recent case studies in fragment-based drug discovery where in silico methods have successfully contributed to the development of lead compounds

‘People lie’: overcoming obstacles to incorporate social science research to biodiversity conservation

Mesmo com o reconhecimento da importância da interdisciplinaridade na conservação da biodiversidade, ainda há resistência em incorporar a pesquisa em ciências sociais (PCS) ao pensamento e à prática conservacionista. As razões para tal resistência podem ser resumidas em três afirmações gerais ainda comumente atribuídas à PCS: 'tem pouca utilidade' e 'menos rigor metodológico' quando comparada à pesquisa em ciências naturais e, sobretudo, é pouco confiável porque 'as pessoas mentem'. Neste ensaio, desenvolvido a partir da experiência dos participantes de uma comunidade de prática, formada por profissionais de diversas áreas e setores relacionados à conservação, e das discussões geradas nesse espaço de aprendizado coletivo, abordamos as limitações e os equívocos por trás das afirmações acima. A PCS não é menos útil na conservação e nem tem menos rigor metodológico do que a pesquisa em ciências naturais, e quando as pessoas mentem para o pesquisador o problema não está na pesquisa em si, mas na relação entre sujeito e pesquisador. Argumentamos que à medida que os conservacionistas se familiarizam com a PCS e que os princípios de equidade e justiça são incorporados aos valores e objetivos da conservação, a importância e necessidade da PCS na conservação tornam-se óbvias, e a falta de confiança entre pesquisador e sujeitos deixa de ser uma preocupação significativa. Capacitar, integrar e apoiar são nossas recomendações básicas para pesquisadores, educadores, gestores e tomadores de decisão nas áreas de conservação, ensino, publicação e financiamento, para que a PCS cumpra plenamente seu papel na conservação.Despite the acknowledged importance of interdisciplinarity in biodiversity conservation, there is still resistance to incorporate social science research (SSR) to both conservationist thinking and practice. The reasons for such a resistance can be summarized in three general statements still commonly attributed to SSR, namely: it is of 'little use' and it has 'less methodological rigor' than research in the natural sciences and, above all, it is unreliable because 'people lie'. The current essay was developed based on the experience of participants of a community of practice (formed by professionals from different fields and sectors  associated with conservation), as well as on discussions held in this space of collective learning. It addresses the limitations and misconceptions behind the aforementioned statements. SSR is not less useful in conservation and not less methodologically rigorous than research conducted in the natural sciences. When researchers are lied to, the problem does not lie on the research itself, but on the subject-researcher relationship. We herein argue that as conservationists become more familiar with SSR, and as principles like equity and justice are incorporated to conservation values and goals, both the importance and need of SSR in conservation become obvious, making the lack of trust between researcher and subjects no longer a significant concern. Increasing capacity, integrating and supporting are our basic recommendations for researchers, educators, managers and decision-makers in the conservation, teaching, publishing and funding fields, so that SSR can fully fulfill its role in conservation

A inclusão de pessoas com o transtorno do espectro autista no ensino superior

O Transtorno do espectro autista (TEA) é caracterizado como um transtorno do neurodesenvolvimento que afeta a comunicação, a socialização, além da detenção de padrões de comportamento e interesses restritos e/ou específicos. Durante toda a fase estudantil do autista, a grande maioria se depara com adversidades que prejudicam a adesão e continuidade do estudo. No ambiente universitário essa realidade não é diferente, são encontrados vários desafios para alunos com TEA se adaptarem a nova realidade e, devido a isso, é muito importante um conjunto de ações e serviços destinadas a eles, a fim de que tenha inclusão desses alunos no ensino superior. Diante disso o objetivo dessa pesquisa é contribuir para a melhoria da experiência acadêmica de estudantes com transtorno do espectro autista no Centro Universitário de Anápolis – UniEVANGÉLICA. Esse estudo é quantitativo analítico – seccional. O local de realização será o Centro Universitário de Anápolis – UniEVANGÉLICA. A população será estudantes maiores de 18 anos nos cursos com as áreas do conhecimento de humanas, biológicas, exatas e saúde. A coleta da pesquisa de campo contará com a utilização do questionário de triagem do TEA em adultos: RAADS-14, acrescido de perguntas sobre inclusão e adaptação do ambiente universitário conforme as necessidades especiais de alunos autistas. Diante disso espera-se proporcionar maior adesão no ensino superior aos alunos portadores de TEA no centro universitário e ainda proporcionar medidas educacionais de inclusão

The Barretos Cancer Hospital Animal Facility: implementation and results of a dedicated platform for preclinical oncology models

The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.This study was funded by the Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer) and by Pio XII Foundation, Barretos Cancer Hospital internal funds, Grant Number: 13/2021

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

COVID-19 outcomes in people living with HIV: Peering through the waves

Objective: To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. Methods: This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. Results: Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). Conclusions: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group

Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates

Unidad de excelencia María de Maeztu CEX2019-000940-MAim: To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period: Tree-inventory plots established between 1934 and 2019. Major taxa studied: Trees with a diameter at breast height (DBH) ≥ 9.55 cm. Location: Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods: We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results: Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions: The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types