Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic changes in the abundance of glucose can undergo growth arrest. We show that this failure is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. The imbalance arises largely from the fundamental design of glycolysis, making this state of glycolysis a generic risk. Cells with unbalanced glycolysis coexisted with vital cells. Spontaneous, nongenetic metabolic variability among individual cells determines which state is reached and, consequently, which cells survive. Transient ATP (adenosine 5'-triphosphate) hydrolysis through futile cycling reduces the probability of reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.

The collection of fog water is a simple and sustainable technology to obtain fresh water for afforestation, gardening, and as a drinking water source for human and animal consumption. In regions where fresh water is sparse and fog frequently occurs, it is feasible to set up a passive mesh system for fog water collection. The mesh is directly exposed to the atmosphere, and the foggy air is pushed through the mesh by the wind. Fog droplets are deposited on the mesh, combine to form larger droplets, and run down passing into a storage tank. Fog water collection rates vary dramatically from site to site but yearly averages from 3 to 10 l m -2 of mesh per day are typical of operational projects. The scope of this article is to review fog collection projects worldwide, to analyze factors of success, and to evaluate the prospects of this technology.

When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation—known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells.

Natural selection has shaped the strategies for survival and growth of microorganisms. The success of microorganisms depends not only on slow evolutionary tuning but also on the ability to adapt to unpredictable changes in their environment. In principle, adaptive strategies range from purely deterministic mechanisms to those that exploit the randomness intrinsic to many cellular and molecular processes. Depending on the environment and selective pressures, particular strategies can lie somewhere along this continuum. In recent years, non-genetic cell-to-cell differences have received a lot of attention, not least because of their potential impact on the ability of microbial populations to survive in dynamic environments. Using several examples, we describe the origins of spontaneous and induced mechanisms of phenotypic adaptation. We identify some of the commonalities of these examples and consider the potential role of chance and constraints in microbial phenotypic adaptation.

BackgroundReducing the burden of disease relies on availability of evidence-based clinical practice guidelines (CPGs). There is limited data on availability, quality and content of guidelines within the Southern African Development Community (SADC). This evaluation aims to address this gap in knowledge and provide recommendations for regional guideline development.MethodsWe prioritised five diseases: HIV in adults, malaria in children and adults, pre-eclampsia, diarrhoea in children and hypertension in primary care. A comprehensive electronic search to locate guidelines was conducted between June and October 2010 and augmented with email contact with SADC Ministries of Health. Independent reviewers used the AGREE II tool to score six quality domains reporting the guideline development process. Alignment of the evidence-base of the guidelines was evaluated by comparing their content with key recommendations from accepted reference guidelines, identified with a content expert, and percentage scores were calculated.FindingsWe identified 30 guidelines from 13 countries, publication dates ranging from 2003-2010. Overall the 'scope and purpose' and 'clarity and presentation' domains of the AGREE II instrument scored highest, median 58%(range 19-92) and 83%(range 17-100) respectively. 'Stakeholder involvement' followed with median 39%(range 6-75). 'Applicability', 'rigour of development' and 'editorial independence' scored poorly, all below 25%. Alignment with evidence was variable across member states, the lowest scores occurring in older guidelines or where the guideline being evaluated was part of broader primary healthcare CPG rather than a disease-specific guideline.ConclusionThis review identified quality gaps and variable alignment with best evidence in available guidelines within SADC for five priority diseases. Future guideline development processes within SADC should better adhere to global reporting norms requiring broader consultation of stakeholders and transparency of process. A regional guideline support committee could harness local capacity to support context appropriate guideline development.