Metodologia para o cálculo do custo de produção de frango de corte - versão 1.

Metodologia: aspectos gerais; Fórmulas e exemplo de cálculo; Tabelas de custo.bitstream/CNPSA/15778/1/publicacao_e5z35p2o.pd

Novel Insights into RAD52’s Structure, Function, and Druggability for Synthetic Lethality and Innovative Anticancer Therapies

Simple Summary Human RAD52 is a non-essential DNA/RNA-binding protein thought to be involved in many DNA repair mechanisms. Initially regarded as having a major role only in error-prone backup DNA repair mechanisms, RAD52 has recently gained attention because its inhibition induces synthetic lethality in cancer cells with an inactivated homologous recombination pathway (for error-free double-strand-break repair). RAD52 is thus a potential target to overcome resistance and unwanted side effects. Unfortunately, researchers still lack detailed structural and mechanistic information on RAD52 and have identified only a limited number of inhibitors, none of which are in the preclinical phase. This review summarizes the current knowledge on RAD52, highlighting the potential of its inhibition. This review also discusses the critical gaps in knowledge and sets out future directions for effective campaigns to discover RAD52 inhibitors. In recent years, the RAD52 protein has been highlighted as a mediator of many DNA repair mechanisms. While RAD52 was initially considered to be a non-essential auxiliary factor, its inhibition has more recently been demonstrated to be synthetically lethal in cancer cells bearing mutations and inactivation of specific intracellular pathways, such as homologous recombination. RAD52 is now recognized as a novel and critical pharmacological target. In this review, we comprehensively describe the available structural and functional information on RAD52. The review highlights the pathways in which RAD52 is involved and the approaches to RAD52 inhibition. We discuss the multifaceted role of this protein, which has a complex, dynamic, and functional 3D superstructural arrangement. This complexity reinforces the need to further investigate and characterize RAD52 to solve a challenging mechanistic puzzle and pave the way for a robust drug discovery campaign

A critical review of digital technology innovations for early warning of water-related disease outbreaks associated with climatic hazards

Water-related climatic disasters pose a significant threat to human health due to the potential of disease outbreaks, which are exacerbated by climate change. Therefore, it is crucial to predict their occurrence with sufficient lead time to allow for contingency plans to reduce risks to the population. Opportunities to address this challenge can be found in the rapid evolution of digital technologies. This study conducted a critical analysis of recent publications investigating advanced technologies and digital innovations for forecasting, alerting, and responding to water-related extreme events, particularly flooding, which is often linked to disaster-related disease outbreaks. The results indicate that certain digital innovations, such as portable and local sensors integrated with web-based platforms are new era for predicting events, developing control strategies and establishing early warning systems. Other technologies, such as augmented reality, virtual reality, and social media, can be more effective for monitoring flood spread, disseminating before/during the event information, and issuing warnings or directing emergency responses. The study also identified that the collection and translation of reliable data into information can be a major challenge for effective early warning systems and the adoption of digital innovations in disaster management. Augmented reality, and digital twin technologies should be further explored as valuable tools for better providing of communicating complex information on disaster development and response strategies to a wider range of audiences, particularly non-experts. This can help to increase community engagement in designing and operating effective early warning systems that can reduce the health impact of climatic disasters

Pinteiros cobertos - estufas para a redução da síndrome ascítica em frangos de corte.

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Belief revision and uncertain reasoning

When a new piece of information contradicts a currently held belief, one has to modify the set of beliefs in order to restore its consistency. In the case where it is necessary to give up a belief, some of them are less likely to be abandoned than others. The concept of epistemic entrenchment is used by some AI approaches to explain this fact based on formal properties of the belief set (e. g. , transitivity). Two experiments were designed to test the hypothesis that contrary to such views, (i) belief is naturally represented by degrees rather than in an all-or-nothing manner, (ii) entrenchment is primarily a matter of content and not only a matter of form, and (iii) consequently prior degree of belief is a powerful factor of change. The two experiments used Elio and Pelletier's (1997) paradigm in which participants were presented with full simple deductive arguments whose conclusion was denied, following which they were asked to decide which premise to revise

Utilização de soja tostada para suínos em crescimento e terminação.

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Phytotoxicity and allelopathic potential of extracts from rhizomes and leaves of Arundo donax, an invasive grass in neotropical savannas

The perennial rhizomatous grass Arundo donax L. (Poaceae), the giant reed, is an exotic invasive species in several countries of Europe that is rapidly spreading in the savannas of Central Brazil, locally known as Cerrado. Allelopathy could facilitate the successful invasion of this species by hampering or suppressing the regeneration of the native vegetation. However, information on the phytotoxicity of A. donax extracts is limited.  We investigated the allelopathic potential of A. donax leaf and rhizome extracts, screened them for phytochemicals by thin-layer chromatography (TLC) and nuclear magnetic resonance (1H-NMR), and tested the extracts for antioxidant activity, antimicrobial activity, and cytotoxicity against Artemia salina. Aqueous and methanolic extracts were initially tested in germination and seedling growth bioassays using Lactuca sativa L. (Asteraceae). The aqueous extracts were then tested on five Cerrado tree species and on Megathyrsus maximus, an invasive, alien grass in the Cerrado. Extracts negatively affected germination and seedling growth of the target species. Leaf extracts were more inhibitory. Extracts did not show antioxidant and cytotoxic activity and had very low antimicrobial activity. Flavonoids, and other phenolics were detected mostly in leaves. Terpenes, which were also present in the leaves, were the main secondary metabolites in rhizomes. Alkaloids were detected by TLC in leaf methanolic extracts. However, 1H-NMR revealed the presence of indole alkaloids in methanolic extracts from rhizomes and leaves. We confirmed the allelopathic potential of this species and caution against weed control methods relying on cutting the plant back to soil level for favouring release of allelochemicals

Isolation and Characterization of Monomeric Human RAD51: A Novel Tool for Investigating Homologous Recombination in Cancer

RAD51 is a key player in the homologous recombination pathway. Upon DNA damage, RAD51 is transported into the nucleus by BRCA2, where it can repair DNA double-strand breaks. Due to the structural complexity and dynamics, researchers have not yet clarified the mechanistic details of every step of RAD51 recruitment and DNA repair. RAD51 possesses an intrinsic tendency to form oligomeric structures, which make it challenging to conduct biochemical and biophysical investigations. Here, for the first time, we report on the isolation and characterization of a human monomeric RAD51 recombinant form, obtained through a double mutation, which preserves the protein’s integrity and functionality. We investigated different buffers to identify the most suitable condition needed to definitively stabilize the monomer. The monomer of human RAD51 provides the community with a unique biological tool for investigating RAD51-mediated homologous recombination, and paves the way for more reliable structural, mechanistic, and drug discovery studies

Author Correction: Combining CRISPRi and metabolomics for functional annotation of compound libraries

No abstract available

Combining CRISPRi and metabolomics for functional annotation of compound libraries

Molecular profiling of small molecules offers invaluable insights into the function of compounds and allows for hypothesis generation about small-molecule direct targets and secondary effects. However, current profiling methods are limited in either the number of measurable parameters or throughput. Here we developed a multiplexed, unbiased framework that, by linking genetic to drug-induced changes in nearly a thousand metabolites, allows for high-throughput functional annotation of compound libraries in Escherichia coli. First, we generated a reference map of metabolic changes from CRISPR interference (CRISPRi) with 352 genes in all major essential biological processes. Next, on the basis of the comparison of genetic changes with 1,342 drug-induced metabolic changes, we made de novo predictions of compound functionality and revealed antibacterials with unconventional modes of action (MoAs). We show that our framework, combining dynamic gene silencing with metabolomics, can be adapted as a general strategy for comprehensive high-throughput analysis of compound functionality from bacteria to human cell lines