The fate of acetic acid during glucose co-metabolism by the spoilage yeast Zygosaccharomyces bailii

Zygosaccharomyces bailii is one of the most widely represented spoilage yeast species, being able to metabolise acetic acid in the presence of glucose. To clarify whether simultaneous utilisation of the two substrates affects growth efficiency, we examined growth in single- and mixed-substrate cultures with glucose and acetic acid. Our findings indicate that the biomass yield in the first phase of growth is the result of the weighted sum of the respective biomass yields on single-substrate medium, supporting the conclusion that biomass yield on each substrate is not affected by the presence of the other at pH 3.0 and 5.0, at least for the substrate concentrations examined. In vivo(13)C-NMR spectroscopy studies showed that the gluconeogenic pathway is not operational and that [2-(13)C]acetate is metabolised via the Krebs cycle leading to the production of glutamate labelled on C(2), C(3) and C(4). The incorporation of [U-(14)C]acetate in the cellular constituents resulted mainly in the labelling of the protein and lipid pools 51.5% and 31.5%, respectively. Overall, our data establish that glucose is metabolised primarily through the glycolytic pathway, and acetic acid is used as an additional source of acetyl-CoA both for lipid synthesis and the Krebs cycle. This study provides useful clues for the design of new strategies aimed at overcoming yeast spoilage in acidic, sugar-containing food environments. Moreover, the elucidation of the molecular basis underlying the resistance phenotype of Z. bailii to acetic acid will have a potential impact on the improvement of the performance of S. cerevisiae industrial strains often exposed to acetic acid stress conditions, such as in wine and bioethanol production.This work was supported by Fundacao para a Ciencia e Tecnologia (FCT), Portugal Grant PTDC/AGR-ALI/102608/2008 and by project FCOMP-01-0124-FEDER- 007047 and by FEDER through POFC - COMPETE and national funds from FCT - project PEst-C/BIA/UI4050/2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The physiological responses of cacao to the environment and the implications for climate change resilience. A review

Cacao (Theobroma cacao L.) is a tropical perennial crop which is of great economic importance to the confectionary industry and to the economies of many countries of the humid tropics where it is grown. Some recent studies have suggested climate change could severely impact cacao production in West Africa. It is essential to incorporate our understanding of the physiology and genetic variation within cacao germplasm when discussing the implications of climate change on cacao productivity and developing strategies for climate resilience in cacao production. Here we review the current research on the physiological responses of cacao to various climate factors. Our main findings are 1) water limitation causes significant yield reduction in cacao but genotypic variation in sensitivity is evident, 2) in the field cacao experiences higher temperatures than is often reported in the literature, 3) the complexity of the cacao/ shade tree interaction can lead to contradictory results, 4) elevated CO2 may alleviate some negative effects of climate change 5) implementation of mitigation strategies can help reduce environmental stress, 6) significant gaps in the research need addressing to accelerate the development of climate resilience. Harnessing the significant genetic variation apparent within cacao germplasm is essential to develop modern varieties capable of high yields in non-optimal conditions. Mitigation strategies will also be essential but to use shading to best effect shade tree selection is crucial to avoid resource competition. Cacao is often described as being sensitive to climate change but genetic variation, adaptive responses, appropriate mitigation strategies and interactive climate effects should all be considered when predicting the future of cacao production. Incorporating these physiological responses to various environmental conditions and developing a deeper understanding of the processes underlying these responses will help to accelerate the development of a more resource use efficient tree ensuring sustainable production into the future

Obesity and male breast cancer: Provocative parallels?

While rare compared to female breast cancer the incidence of male breast cancer (MBC) has increased in the last few decades. Without comprehensive epidemiological studies, the explanation for the increased incidence of MBC can only be speculated. Nevertheless, one of the most worrying global public health issues is the exponential rise in the number of overweight and obese people, especially in the developed world. Although obesity is not considered an established risk factor for MBC, studies have shown increased incidence among obese individuals. With this observation in mind, this article highlights the correlation between the increased incidence of MBC and the current trends in obesity as a growing problem in the 21st century, including how this may impact treatment. With MBC becoming more prominent we put forward the notion that, not only is obesity a risk factor for MBC, but that increasing obesity trends are a contributing factor to its increased incidence

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life

Quantitative and qualitative analysis on the legislative production relating to healthcare in passage in the National Congress in the years 2007 and 2008

CONTEXT AND OBJECTIVES:The Federal Constitution of 1988 allowed the National Congress to contribute towards formulation of new public policies. The objective of this study was to analyze the legislative production that dealt with health issues that was in passage in the National Congress between January 2007 and December 2008.DESIGN AND SETTING:Descriptive-exploratory cross-sectional study with quantitative and qualitative approaches, conducted in a federal university.METHODS:The analysis material for the study comprised 144 draft bills that were classified and subsequently randomly evaluated by 155 professionals working within the healthcare system.RESULTS:The analysis showed that the Workers' Party (PT) and Brazilian Democratic Movement Party (PMDB) were the parties that presented the largest proportions of the draft bills (12.5% and 11.1%); 25.4% of the draft bills were presented by congress members with academic qualifications within healthcare and only 1.4% of the draft bills became transformed into legal regulations. In questionnaire responses, 51.5% of the evaluators did not consider the draft bills to be viable, 40.6% did not consider them to be relevant and 52.5% said that if the draft bills were not approved it would not be harmful to Brazilian society.CONCLUSION:In analyzing the data from this study, it was noted that the legislative production relating to healthcare was low and the transformation rate from draft bill to legal regulation was negligible. The results from the evaluation showed that the quality of legislative production was impaired.CONTEXTO E OBJETIVOS:A Constituição Federal de 1988 possibilitou ao Congresso Nacional contribuir na formulação de novas políticas públicas. O objetivo do estudo foi analisar a produção legislativa que trata de questões de saúde, em tramitação no Congresso Nacional, entre janeiro de 2007 a dezembro de 2008.TIPO DE ESTUDO E LOCAL:Estudo descritivo-exploratório com corte transversal e abordagem quantitativa e qualitativa, conduzido em uma universidade federal.MÉTODOS:O material de análise do estudo foi constituído por 144 projetos de lei (PLs), classificados e posteriormente avaliados, aleatoriamente, por 155 profissionais do sistema de saúde.RESULTADOS:A análise mostrou que o Partido dos Trabalhadores (PT) e o Partido do Movimento Democrático Brasileiro (PMDB) foram os partidos que mais apresentaram PLs (12,5% e 11,1%), 25,4% dos PLs foram apresentados por parlamentares com formação na área da saúde e apenas 1,4% dos PLs foram transformados em norma jurídica. Em relação aos questionários, 51,5% dos avaliadores não consideraram os PLs viáveis, 40,6% não consideraram os PLs relevantes e 52,5% disseram que a eventual não aprovação do projeto de lei não seria prejudicial para a sociedade brasileira.CONCLUSÃO:Ao analisar os dados deste estudo, percebeu-se que a produção legislativa no âmbito da saúde foi baixa, a transformação dos projetos de lei em norma jurídica foi mínima, e os resultados da avaliação mostraram que a qualidade da produção legislativa está comprometida.Universidade Federal de Minas Gerais Health Economics Research Group Center for Health Economics and ResearcherUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of MedicineUNIFESP, EPM, Department of MedicineSciEL

Modern computing: Vision and challenges

Over the past six decades, the computing systems field has experienced significant transformations, profoundly impacting society with transformational developments, such as the Internet and the commodification of computing. Underpinned by technological advancements, computer systems, far from being static, have been continuously evolving and adapting to cover multifaceted societal niches. This has led to new paradigms such as cloud, fog, edge computing, and the Internet of Things (IoT), which offer fresh economic and creative opportunities. Nevertheless, this rapid change poses complex research challenges, especially in maximizing potential and enhancing functionality. As such, to maintain an economical level of performance that meets ever-tighter requirements, one must understand the drivers of new model emergence and expansion, and how contemporary challenges differ from past ones. To that end, this article investigates and assesses the factors influencing the evolution of computing systems, covering established systems and architectures as well as newer developments, such as serverless computing, quantum computing, and on-device AI on edge devices. Trends emerge when one traces technological trajectory, which includes the rapid obsolescence of frameworks due to business and technical constraints, a move towards specialized systems and models, and varying approaches to centralized and decentralized control. This comprehensive review of modern computing systems looks ahead to the future of research in the field, highlighting key challenges and emerging trends, and underscoring their importance in cost-effectively driving technological progress