A Formalized Extension of the Substitution Lemma in Coq

The substitution lemma is a renowned theorem within the realm of lambda-calculus theory and concerns the interactional behaviour of the metasubstitution operation. In this work, we augment the lambda-calculus's grammar with an uninterpreted explicit substitution operator, which allows the use of our framework for different calculi with explicit substitutions. Our primary contribution lies in verifying that, despite these modifications, the substitution lemma continues to remain valid. This confirmation was achieved using the Coq proof assistant. Our formalization methodology employs a nominal approach, which provides a direct implementation of the alpha-equivalence concept. The strategy involved in variable renaming within the proofs presents a challenge, specially on ensuring an exploration of the implications of our extension to the grammar of the lambda-calculus.Comment: In Proceedings FROM 2023, arXiv:2309.1295

Cholesterol affects African swine fever virus infection

African swine fever virus (ASFV) enters cells by receptor mediated endocytosis and requires a fusion event between the viral envelope and the limiting membrane of the endosome at low pH. In order to investigate the role of cholesterol in the early stages of ASFV infection, we have studied the effect of the removal of cell and viral membrane cholesterol by cholesterol oxidase treatment of cells and virions, as well as the effect of some inhibitors of cholesterol synthesis on the infectious pathway. In addition, we have investigated viral infection in cholesterol-depleted Vero cells. Both cholesterol-depleted and cholesterol oxidase-treated Vero cells were unaltered in their ability to bind or internalize the virus, but were blocked in ASFV fusion and subsequent virus replication. Our results indicate that ASFV infection is affected by cholesterol in the target membrane.http://www.sciencedirect.com/science/article/B6T1X-3V3N06F-2/1/e52e3430df628f470dc4b0b8400b4b2

Expressão da progranulina durante os primeiros estágios de desenvolvimento hepático em ratos Fischer 344

Transplants are the only effective therapy for the treatment of advanced liver diseases such as cirrhosis. Given the limited number of organ donors, regenerative medicine has sought for sources of cells and tissues for replacement therapy. Embryonic stem cells are a promising source of material for transplantation because of their exclusive property of being expanded indefinitely in culture, thus, they are a source of replacement tissue. Moreover, they are capable of differentiating into practically all cell types, and may be utilized in replacement therapy in various diseases. The liver bud has bipotent stem cells that have not yet differentiated into hepatocytes or biliary duct cells; however, they have great potential of proliferation and differentiation. Thus, the challenge is to identify methods that promote their differentiation in specific and functional strains. This study aimed to evaluate the role of the progranulin growth factor PGRN during the liver development of rats F344, since this growth factor could be utilized in protocols of differentiation of stem cells of the liver bud in functional hepatocytes. The results showed that PGRN is present during different periods of hepatogenesis in F344 rats, and that this growth factor should be involved in the process of differentiation of hepatoblasts into hepatocytes after activation by HNF4α , however, PGRN seems not to exert a cellular proliferation function during the hepatogenesis. Thus, PGRN can be used in future protocols of liver cell differentiation directed toward cellular therapy in Regenerative Medicine.Os transplantes são a única terapia eficaz para o tratamento de doenças hepáticas avançadas, como a cirrose. Dado o número limitado de doadores de órgãos, a medicina regenerativa tem procurado fontes de células para a terapia de substituição. As células embrionárias são uma fonte promissora de material para o transplante devido à sua propriedade exclusiva de ser expandida indefinidamente em cultura, assim, elas são uma fonte de tecido de substituição. Além disso, são capazes de se diferenciar em praticamente todos os tipos celulares, e podem ser utilizadas na terapia de substituição em várias doenças. O broto hepático tem células-tronco (CT) bipotenciais que ainda não se diferenciam em hepatócitos ou células do ducto biliar, contudo, elas têm um grande potencial de proliferação e de diferenciação. Desse modo, o desafio é identificar métodos que promovam sua diferenciação em linhagens específicas e funcionais. Este estudo teve como objetivo avaliar o papel do fator de crescimento progranulina (PGRN) durante o desenvolvimento hepático em ratos F344, uma vez que a PGRN poderia ser utilizada em protocolos de diferenciação de CT do broto hepático em hepatócitos funcionais. Os resultados mostraram que PGRN está presente durante diferentes períodos da hepatogênese em ratos F344, e que a mesma deve estar envolvida no processo de diferenciação de hepatoblastos em hepatócitos após ativação por HNF4α, no entanto, a PGRN parece não desempenhar uma função de proliferação celular durante a hepatogênese. Assim, a PGRN pode ser usada em futuros protocolos de diferenciação de células hepáticas voltadas para a terapia celular na medicina regenerativa

MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease

AbstractIntroductionMononuclear phagocytes play a critical role during Alzheimer's disease (AD) pathogenesis due to their contribution to innate immune responses and amyloid beta (Aβ) clearance mechanisms.MethodsBlood-derived monocytes (BDMs) and monocyte-derived macrophages (MDMs) were isolated from blood of AD, mild cognitive impairment (MCI) patients, and age-matched healthy controls for molecular and phenotypic comparisons.ResultsThe chemokine/chemokine receptor CCL2/CCR2 axis was impaired in BDMs from AD and MCI patients, causing a deficit in cell migration. Changes were also observed in MDM-mediated phagocytosis of Aβ fibrils, correlating with alterations in the expression and processing of the triggering receptor expressed on myeloid cells 2 (TREM2). Finally, immune-related microRNAs (miRNAs), including miR-155, -154, -200b, -27b, and -128, were found to be differentially expressed in these cells.DiscussionThis work provides evidence that chemotaxis and phagocytosis, two crucial innate immune functions, are impaired in AD and MCI patients. Correlations with miRNA levels suggest an epigenetic contribution to systemic immune dysfunction in AD

Fusion activity and inactivation of influenza virus: Kinetics of low pH-induced fusion with cultured cells

The kinetics of fusion of influenza virus (A/PR/8/34) with human promyelocytic leukaemia (HL-60), human T lymphocytic leukaemia (CEM) and murine lymphoma (S49) cells were investigated. Fusion was demonstrated by electron microscopy, and monitored by fluorescence dequenching of octadecylrhodamine incorporated in the virus membrane. Rapid fusion was induced upon mild acidification of the medium. At pH 5, all virus particles were capable of fusing with the cells. The initial rate and the extent of fusion were maximal between pH 4.9 and 5.2 and declined sharply below and above this range. The rate constants of adhesion of influenza virus to cells or erythrocyte ghosts were large, indicating a diffusion-controlled process. The rate constants of fusion of the virus with cells were smaller than those found previously for fusion with various liposomes. Although preincubation of the virus at acidic pH in the absence of target membranes almost completely inactivated the virus in its ability to fuse with erythrocyte ghosts, it reduced the extent of fusion with cultured cells by only 20 to 40%. Kinetic analysis of fusion revealed a mode of inactivation of the virus bound to erythrocyte ghosts or suspension cells, below pH 5.4, different from that of the virus preincubated at low pH without target membranes

Histochemical Evaluation of Human Prostatic Tissues with Cratylia mollis Seed Lectin

Lectins, proteins which selectively recognize carbohydrates, have been used in histochemistry for the evaluation of changes in glycosylation in processes of cellular differentiation and/or dedifferentiation. Cratylia mollis seed lectins (Cramoll 1,4 and Cramoll 3), conjugated to horseradish peroxidase, were used as histochemical probes in human prostate tissues: normal (NP), hyperplasia (BPH), and prostate carcinoma (PCa). The staining pattern of Con-A and Cramoll 1,4 in BPH was more intense than in NP. These lectins also showed staining differences between BPH and PCa; the latter showing decreased staining intensity with an increased degree of malignancy. PNA and Cramoll 3 stained epithelial cells similarly in all diagnoses although they did present intense staining of PCa glands lumen. Corpora amylacea were not differentially recognized by any of the lectins. Cramoll 1,4 and Cramoll 3 seed lectins present themselves as candidates for histochemical probes for prostate pathologies when compared to commercial lectins such as Con-A and PNA

Hierarchical effects of historical and environmental factors on lizard assemblages in the upper Madeira River, Brazilian Amazonia

Investigating the role of historical and ecological factors structuring assemblages is relevant to understand mechanisms and processes affecting biodiversity across heterogeneous habitats. Considering that community assembly often involves scale-dependent processes, different spatial scales may reveal distinct factors structuring assemblages. In this study we use arboreal and leaf-litter lizard abundance data from 83 plots to investigate assemblage spatial structure at two distinct scales in southwestern Brazilian Amazonia. At a regional scale, we test the general hypothesis that the Madeira River acts as a barrier to dispersal of some lizard species, which results in distinct assemblages between river banks. At a local scale, we test the hypothesis that assemblages are not evenly distributed across heterogeneous habitats but respond to a continuum of inadequate-to-optimal portions of environmental predictors. Our results show that regional lizard assemblages are structured by the upper Madeira River acting as a regional barrier to 29.62% of the species sampled. This finding suggests species have been historically isolated at one of the river banks, or that distinct geomorphological features influence species occurrence at each river bank. At a local scale, different sets of environmental predictors affected assemblage composition between river banks or even along a river bank. These findings indicate that environmental filtering is a major cause of lizard assemblage spatial structure in the upper Madeira River, but predictor variables cannot be generalized over the extensive (nearly 500 km) study area. Based on a single study system we demonstrate that lizard assemblages along the forests near the banks of the upper Madeira River are not randomly structured but respond to multiple factors acting at different and hierarchical spatial scales. © 2020 Marques Peixoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Identification of New Genes Related to Virulence of Xanthomonas axonopodis Pv. Citri during Citrus Host Interactions

A mutant library of the bacterium Xanthomonas citri subsp. citri strain 306 pathotype A (Xac), the causative agent of most aggressive Asiatic type A citrus canker, was screened regarding altered canker symptoms after inoculations into Citrus sinensis and Citrus limonia host leaves. Twenty-six mutants have shown phenotypic virulence changes and have respectively knocked out gene identified by sequencing. In vivo growth curves were obtained for nine mutants to quantify how the mutations could affect pathogen's adaptability to growth inside and attack host plant infected tissue. Among identified genes in mutated strains, we could find those that until now had not been reported as being involved in Xac adaptation and/or virulence, such as predicted to encode for xylose repressor-like protein (XAC Delta xylR), Fe-S oxidoredutase (XAC Delta aslB), helicase IV (XAC Delta helD), ubiquinol cytochrome c oxidoreductase iron-sulfur subunit (XAC Delta petA), chromosome partitioning protein (XAC Delta parB) and cell division protein FtsB (XAC Delta ftsB), in addition to genes predicted to encode for hypothetical proteins. The new genes found in this study as being relevant to adaptation and virulence, improve the understanding of Xac fitness during citrus plant attack and canker symptoms development.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior-CAPESCNPqFundo de Defesa da Citricultura (FUNDECITRUS)CAPESFUNDECITRUSFAPESPSao Paulo State Univ UNESP, Fac Agr Sci & Vet, Dept Technol, Jaboticabal, SP, BrazilCitriculture Res Ctr Sylvio Moreira IAC Campinas, Campinas, SP, BrazilUniv Fed Ouro Preto, Inst Exact & Biol Sci, Dept Biol Sci, Ouro Preto, MG, BrazilUniv Fed Ouro Preto, Res Ctr Biol Sci NUPEB, Inst Exact & Biol Sci, Dept Biol Sci, Ouro Preto, MG, BrazilSao Paulo State Univ UNESP, Fac Agr Sci & Vet, Plant Hlth Dept, Jaboticabal, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilFAPESP: 04/02006-7Web of Scienc

Valores de referência para carboxiemoglobina

INTRODUCTION: The reference values (RV) of biological indicators are used in the interpretation of the results of such indicators in individuals occupationally exposed to chemical agents. The Brazilian Group for the Establishment of Reference Values has worked on these definitions for the purpose of establishing RVs for several bioindicators in various regions of the country. In the present study, the RV for carboxyhemoglobin (COHb) was determined for the South of Minas Gerais. MATERIAL AND METHOD: The COHb was analyzed by the Beutler and West (1984) spectrophotometric method, optimized in our laboratory. In all the samples, analyses of some biochemical and hematological parameters were made to evaluate the health condition of a population of 200 volunteer non-smokers occupationally not exposed to CO. Each individual answered a questionnaire to obtain data pertinent to the interpretation of the results. The reference values were expressed as mean values ± standard deviation, with a 95% confidence interval, and an upper reference value. The statistical distribution of the results was made so as to enable comparisons between the results of groups of workers, rather than individual evaluations, to be made. RESULTS AND CONCLUSION: The mean value ± standard deviation was 1.0% ± 0.75; the 95% confidence interval was 0,9 - 1.1% and the upper reference value was 2.5%. By the t Student test (p < 0.05), no difference was detected between the values related to sex, age or ingestion of alcoholic beverages. The reference values obtained were close to those reported for others countries.INTRODUÇÃO: Os valores de referência de indicadores biológicos são utilizados como parâmetros para interpretação de resultados de valores obtidos em indivíduos expostos ocupacionalmente aos agentes químicos. O Grupo Brasileiro para Estabelecimento dos Valores de Referência tem se dedicado a estas determinações objetivando estabelecer valores de referência para os diferentes bioindicadores em diversas regiões do País. Determinaram-se os valores de referência para a carboxiemoglobina (COHb) no Sul de Minas Gerais. MATERIAL E MÉTODO: A COHb foi analisada pelo método espectrofométrico, otimizado no laboratório de análises toxicológicas. Em todas as amostras também foram realizadas análises de alguns parâmetros bioquímicos e hematológicos para atestar o estado de saúde da população, constituída de 200 voluntários não-fumantes e não-expostos, por motivo profissional, ao monóxido de carbono. Cada indivíduo respondeu um questionário para levantamento de dados relevantes à interpretação dos resultados. Os valores de referência foram expressos em termos da média ± desvio-padrão, intervalo de confiança 95% e valor de referência superior. A distribuição estatística dos resultados obtidos foi realizada para possibilitar sua comparação com grupos de trabalhadores, preferentemente à avaliação individual. RESULTADOS E CONCLUSÕES: O valor médio ± desvio-padrão para a carboxiemoglobina foi de 1,0 % ± 0,75; o intervalo de confiança 95%, entre 0,9 e 1,1 % e o valor de referência superior, de 2,5%. Através do teste t de Student (p < 0,05) não foi detectada diferença nos valores de acordo com o sexo, idade ou uso de bebidas alcoólicas. Os valores de referência encontrados foram similares aos reportados em outros países

Effectiveness of different cellulose-based filtration materials against inhalation of SARS-CoV-2-like particles

The respiratory protection equipment (RPE) used by health professionals consists of an essential device to prevent infectious diseases, especially those caused by biological agents such as the coronavirus (SARS-CoV-2). The current epidemiological panorama is worrying, and the context of creation and production of the mask has emerged as an alternative to RPE to face the public health crisis worldwide. The aim of this work is to present a low-cost alternative as an FFP2-like filter for a reusable respirator face mask. This study presents the comparison of different cellulose-based filtering materials performed by retention testing, time saturation testing, aerosol penetration testing, nanoparticle (~140 nm) filtration testing, bacterial filtration efficiency (BFE), analysis of material morphology and usability. The reusable respirator face mask used in this study is an open-source innovation, using 3D printing. Cotton disc proved to be the best filter material for the reusable mask, with satisfactory results and a performance similar to that shown by the N95-type mask. The cotton disc ensured effectiveness over 6 h of use, and after that, the reusable respirator face mask (here, Delfi-TRON®) needed to be sanitized and replenished with a new cotton disc. Upon preliminary analyses of filtration efficiency, the selected filter was shown to be a low-cost biodegradable and biocompatible alternative.info:eu-repo/semantics/publishedVersio