Adipose Tissue Remodeling during Cancer Cachexia

Cancer-induced cachexia (CC), characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling, and muscle wasting, is a malignant metabolic syndrome with an undefined etiology. There is a consensus that multiple factors contribute to cancer-induced AT remodeling, and longitudinal studies show that patients lose AT before they start losing muscle mass. In CC, AT remodeling occurs predominantly through adipocyte atrophy, impairment of fatty acid turnover, inflammation, rearrangement of extracellular matrix (ECM), and browning of AT. More recently, some studies have shown that AT is affected early in the course of cachexia. Additionally, studies using experimental models have consistently indicated that the alterations in adipocyte metabolism begin quite early, followed by the downregulation of adipogenic and thermogenic genes. These sets of changes, in addition to metabolites derived from this process, maybe the initial (sterile) trigger of the sequence of events that result in the remodeling and dysfunction of AT in cachexia. Therefore, the present chapter aims to describe state of the art related to the subject of interest by analyzing the primary studies that have addressed the possible interface between inflammation and morphofunctional alterations of AT, in addition to the possible repercussions of this process during the development of CC

Extracting Reward Functions from Diffusion Models

Diffusion models have achieved remarkable results in image generation, and have similarly been used to learn high-performing policies in sequential decision-making tasks. Decision-making diffusion models can be trained on lower-quality data, and then be steered with a reward function to generate near-optimal trajectories. We consider the problem of extracting a reward function by comparing a decision-making diffusion model that models low-reward behavior and one that models high-reward behavior; a setting related to inverse reinforcement learning. We first define the notion of a relative reward function of two diffusion models and show conditions under which it exists and is unique. We then devise a practical learning algorithm for extracting it by aligning the gradients of a reward function -- parametrized by a neural network -- to the difference in outputs of both diffusion models. Our method finds correct reward functions in navigation environments, and we demonstrate that steering the base model with the learned reward functions results in significantly increased performance in standard locomotion benchmarks. Finally, we demonstrate that our approach generalizes beyond sequential decision-making by learning a reward-like function from two large-scale image generation diffusion models. The extracted reward function successfully assigns lower rewards to harmful images

Adipose Tissue Inflammation and Metabolic Disorders

Adipose tissue not only possesses an important role in the storage of excess nutrients but also acts as a critical immune and endocrine organ. Researchers and clinicians now consider adipose tissue to be an active endocrine organ that secretes various humoral factors called “adipokines,” which imparts important systemic metabolic effects, from food intake to glucose tolerance. Along with its production of specialized adipokines, adipose tissue also secretes proinflammatory cytokines that likely contributes to the low-level systemic inflammation that has become a hallmark of various metabolic syndrome-associated chronic pathologies, such as obesity and cancer cachexia. These systemic effects may be mediated by communication networks arising from the multitude of resident adipose cells, including adipocytes, endothelial cells, neuronal cells, stem cells and other precursors, and a wide variety of immune cell populations that recent studies have demonstrated play a crucial role in the development of adipose inflammation and systemic metabolic abnormalities. In this chapter, we detail various molecular pathways linking excess adipose lipid storage to chronic inflammation and review the current knowledge as to what triggers obesity- and cachexia-associated inflammation in adipose tissue. Finally, we describe how the cross talk between adipose tissue inflammation and the non-adipocyte resident cells present in tissue is involved in this metabolic disruption

LLC tumor cells-derivated factors reduces adipogenesis in co-culture system

Cancer cachexia (CC) is a multifactorial syndrome with an unknown etiology. The primary symptom is the progressive reduction of the body weight. Recently, down-regulation of adipogenic and lipogenic genes were demonstrated to be early affected during cachexia progression in adipose tissue (AT), resulting in AT remodeling. Thus, this study aimed to evaluate in a co-culture system the influence of the Lewis Lung Carcinoma (LLC) tumor cells (c/c-LLC) in an established pre-adipocyte cell line 3T3-L1 adipogenic capacity. c/c-LLC in the presence of 3T3-L1 caused a reduction in lipids accumulation, suggesting that secretory tumor cells products may affect adipogenesis. Interestingly, a very early (day 2) down-regulation of proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha), followed by late genes (day 4 and 8), adiponectin, perilipin, and fatty acid-binding protein 4 (FABP4). Caspase-3 expression was increased on the last day of cell differentiation; it occurred in the expression of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). Overall, our results suggest that LLC secretory products impair adipocyte differentiation in a co-culture system and increased apoptosis. In summary, our study has shown the inhibition of the adipogenic process in the 3T3-L1 co-culture system with LLC cells

Potencial de geração de créditos de carbono via compostagem de resíduos orgânicos de grandes geradores: uma alternativa à disposição final em aterros sanitários

This study aims to measure the potential for reducing Greenhouse Gases by surveying the amount of methane avoided by a company that collects and processes organic waste from large generators through composting. The applied methodology was the avoidance of methane emissions through composting, from the Clean Development Mechanism, considering as a baseline the emissions of the Santa Rosa sanitary landfill, located in the city of Seropédica, state of Rio de Janeiro, Brazil. With data on the amount of organic waste composted by the company, the emissions of carbon dioxide equivalent (CO2eq) were calculated, considering the standard emission factors established in the methodological instrument. The data show that the emission of 22,062 tons of CO2eq was avoided, which corresponds to a reduction of 83.5% of CH4 emissions, if the waste composted by the company were deposited in the Santa Rosa sanitary landfill. In terms of carbon credit, according to the calculation, this value would correspond to approximately 17 thousand euros annually (considering current values). Thus, the applicability of this study contributes as a scientific basis to assist decision-making and effectiveness of other composting projects, enabling greater reductions in emissions of Greenhouse Gases in the long term and adequacy to the future perspectives of carbon market development. At the same time, it contributes to the construction of alternative scenarios for mitigation and reduction of Greenhouse Gases emissions in Brazil and promotes sustainable waste management, as determined by the National Solid Waste Policy.O presente estudo tem o objetivo de mensurar o potencial de redução de Gases do Efeito Estufa por meio do levantamento da geração de metano evitada por uma empresa de coleta e do tratamento dos resíduos orgânicos de grandes geradores através da compostagem. A metodologia utilizada foi a avoidance of methane emissions through composting, do Mecanismo de Desenvolvimento Limpo, considerando como linha de base as emissões do aterro sanitário Central de Tratamento de Resíduos Santa Rosa, localizado em Seropédica, Rio de Janeiro. Com os dados de quantidade de resíduos orgânicos compostados pela empresa, foram calculadas as emissões de CO2eq em função dos fatores de emissão padrão estabelecidos na ferramenta metodológica. Os dados mostram que se evitou que 22.062 toneladas de CO2 equivalentes fossem lançadas na atmosfera, o que corresponde a uma redução de 83,5% das emissões de CH4 que ocorreriam caso os resíduos compostados pela empresa fossem destinados à Central de Tratamento de Resíduos Santa Rosa. Contabilizando, em termos de crédito de carbono, esse valor corresponderia, atualmente, a aproximadamente 17 mil euros anualmente. Dessa forma, a aplicabilidade deste trabalho contribui como base científica para auxiliar a tomada de decisão e efetividade de demais projetos de compostagem, possibilitando ainda mais reduções de emissões de Gases do Efeito Estufa em longo prazo, bem como adequação às perspectivas futuras de desenvolvimento do mercado de carbono. Ao mesmo tempo, esperamos contribuir para a construção de cenários alternativos para mitigação e redução das emissões de Gases do Efeito Estufa no Brasil e promover a gestão de resíduos sustentável, como determinado pela Política Nacional de Resíduos Sólidos

Algae in acid mine drainage and relationships with pollutants in a degraded mining ecosystem

Acid mine drainage represents an extreme environment with high concentrations of potentially toxic elements and low pH values. These aquatic habitats are characterised by harsh conditions for biota, being dominated by acidophilic organisms. The study site, São Domingos mine, located in one of the largest metallogenetic provinces in the world, the Iberian Pyrite Belt, was closed without preventive measures. To identify the algae species and understand the relationships with abiotic parameters of the ecosystem, water and biological material were collected and analysed. Digital terrain models were obtained with an unmanned aerial vehicle for geomorphological and hydrologic characterisation of the mine degraded landscape. The results show two types of algal colours that seem to represent different degrees of photosynthetic activity. Optical and scanning electron microscopy revealed 14 taxa at the genus level, divided into eight classes. The genus Mougeotia is the most abundant multicellular algae. With respect to unicellular algae, diatoms are ubiquitous and abundant. Abiotic analyses expose typical features of acid mine drainage and support an inverse relationship between chemical contamination and biological diversity. Factorial correspondence analysis indicates three groups of attributes and samples by their relationship with specific toxic elements. This analysis also suggests a close association between Spirogyra and Pb, together composing a structurally simple ecosystem. The highest contamination in the river system is related to the hydrologic patterns obtained from photogrammetric products, such as the digital surface model and flow map accumulation, indicating the input of leachates from the section having the finest sulfide-rich wastes. Information about the algae community and their association with flow patterns of toxic elements is a relevant tool from a biomonitoring perspective.info:eu-repo/semantics/publishedVersio

Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming

BACKGROUND: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood. METHODS and RESULTS: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT. CONCLUSIONS: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT

O INSTITUTO JURÍDICO DA PROVA NO DIREITO PROCESSUAL BRASILEIRO E SUA (RE)CONSTRUÇÃO HISTÓRICA

O presente estudo científico busca analisar o sistema histórico de apreciação da prova, destacando os percursos da legislação processual no Brasil. Neste quadro, serão analisados sistemas da Prova Legal, da Livre Convicção e da Persuasão Racional, cada qual em seu período de aplicação e a sucessão das fases, com repercussões nas decisões judiciais, para finalmente fazer uma análise crítica, sobretudo das atuais previsões do CPC/2015 quanto à apreciação da prova, em atenção inafastável aos princípios institutivos do processo. Adota-se, como marco teórico, processo constitucional no Estado Democrático de Direito, com pesquisa bibliográfica e o método jurídico-dedutivo.

O INSTITUTO JURÍDICO DA PROVA NO DIREITO PROCESSUAL BRASILEIRO E SUA (RE)CONSTRUÇÃO HISTÓRICA

O presente estudo científico busca analisar o sistema histórico de apreciação da prova, destacando os percursos da legislação processual no Brasil. Neste quadro, serão analisados sistemas da Prova Legal, da Livre Convicção e da Persuasão Racional, cada qual em seu período de aplicação e a sucessão das fases, com repercussões nas decisões judiciais, para finalmente fazer uma análise crítica, sobretudo das atuais previsões do CPC/2015 quanto à apreciação da prova, em atenção inafastável aos princípios institutivos do processo. Adota-se, como marco teórico, processo constitucional no Estado Democrático de Direito, com pesquisa bibliográfica e o método jurídico-dedutivo.