Glucose‐6‐phosphate dehydrogenase (G6PD) is the rate‐limiting enzyme of the pentose phosphate pathway. Many scientists think that the roles and regulation of G6PD in physiology and pathophysiology ...have been well established as the enzyme was first identified 80 years ago. And that G6PD has been extensively studied especially with respect to G6PD deficiency and its association with hemolysis, and with respect to the role G6PD plays in lipid metabolism. But there has been a growing understanding of the central importance of G6PD to cellular physiology as it is a major source of NADPH that is required by many essential cellular systems including the antioxidant pathways, nitric oxide synthase, NADPH oxidase, cytochrome p450 system, and others. Indeed G6PD is essential for cell survival. It has also become evident that G6PD is highly regulated by many signals that affect transcription, post‐translation, intracellular location, and interactions with other protein. Pathophysiologic roles for G6PD have also been identified in such disease processes as diabetes, aldosterone‐induced endothelial dysfunction, cancer, and others. It is now clear that G6PD is under complex regulatory control and of central importance to many cellular processes. In this review the biochemistry, regulatory signals, physiologic roles, and pathophysiologic roles for G6PD that have been elucidated over the past 20 years are discussed. 2012 IUBMB IUBMB Life, 2012
Decline of the North American avifauna Rosenberg, Kenneth V; Dokter, Adriaan M; Blancher, Peter J ...
Science,
10/2019, Letnik:
366, Številka:
6461
Journal Article
Recenzirano
Odprti dostop
Species extinctions have defined the global biodiversity crisis, but extinction begins with loss in abundance of individuals that can result in compositional and functional changes of ecosystems. ...Using multiple and independent monitoring networks, we report population losses across much of the North American avifauna over 48 years, including once-common species and from most biomes. Integration of range-wide population trajectories and size estimates indicates a net loss approaching 3 billion birds, or 29% of 1970 abundance. A continent-wide weather radar network also reveals a similarly steep decline in biomass passage of migrating birds over a recent 10-year period. This loss of bird abundance signals an urgent need to address threats to avert future avifaunal collapse and associated loss of ecosystem integrity, function, and services.
•“Predict and act” decision making is ineffective in the face of deep uncertainty.•Decision making under deep uncertainty (DMDU) methods support robust and adaptable decisions.•However, DMDU methods ...do not fully reflect the context in which decisions are made.•This influences the availability of feasible options and limits capacity for change.•Decision contexts signpost the selection of full or “hybrid” DMDU approaches.
Deep uncertainties like environmental and socio-economic changes create challenges to decision making. Decision Making under Deep Uncertainty (DMDU) methods are recognised approaches to navigate deep uncertainties and support robust and adaptable decisions. However, their ability to fully reflect the context in which these decisions are made has been criticised. This paper presents a synthesis across cases and methods to provide a holistic understanding of the application of DMDU methods to support long-term decision making. We carried out a structured literature review and analysed 37 infrastructure DMDU case studies. The analysis shows that DMDU methods are effective at developing plans to address a range of deep uncertainties and in some cases, reflecting the institutional context of the decision. However, they largely overlook the organisational and individual contexts in which decision making happens. We argue that the use of existing DMDU methods in practice should start with a better understanding of the institutional, organisational and individual contexts. We then suggest modifications to the applications of DMDU methods, i.e. internalising the context at different stages of the decision-making process and developing a decision typology to signpost decision makers to the best approach for a specific context.
Vibration energy harvesting research has largely focused on linear electromechanical devices excited at resonance. Considering that most realistic vibration environments are more accurately described ...as either stochastic, multi-frequency, time varying, or some combination thereof, narrowband linear systems are fated to be highly inefficient under these conditions. Nonlinear systems, on the other hand, are capable of responding over a broad frequency range; suggesting an intrinsic suitability for efficient performance in realistic vibration environments. Since a number of nonlinear dynamical responses emerge from dissipative systems undergoing a homoclinic saddle-point bifurcation, we validate this concept with a bistable inertial oscillator comprised of permanent magnets and a piezoelectric cantilever beam. The system is analytically modeled, numerically simulated, and experimentally realized to demonstrate enhanced capabilities and new challenges. In addition, a bifurcation parameter within the design is examined as either a fixed or an adaptable tuning mechanism for enhanced sensitivity to ambient excitation.
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, ...general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Nearly 100 years ago, Otto Warburg undertook a study of tumor metabolism, and discovered increased lactate caused by increased glycolysis in cancer cells. His experiments were conducted in the ...presence of excess oxygen, but today tumor tissue is known to be a hypoxic environment. However, an increase of glycolysis and lactate production is still a valid observation. Numerous abnormalities and mutations of metabolic enzymes have been found in many cancers. For example, pyruvate kinase M2 has been associated with many cancers and is a major contributor to directing glycolysis into fermentation, forming lactate. Increases in several enzymes, including glucose 6-phosphate dehydrogenase, pyruvate kinase M2, Rad6, or deficiency of other enzymes such as succinate dehydrogenase, all may contribute directly or indirectly to increases in lactate associated with the Warburg effect. In addition, the increased lactate and acid-base changes are modified further by monocarboxylate transporters and carbonic anhydrase, which contribute to alkalinizing tumor cells while acidifying the tumor extracellular environment. This acidification leads to cancer spread. Fully understanding the mechanisms underlying the Warburg effect should provide new approaches to cancer treatment.
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, ...general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics. These programs consist of integrated genetic circuits that ...individually implement operations ranging from digital logic to dynamic circuits, and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is that the circuits are based on biochemical interactions occurring in the confined volume of the cell, so the size of programs has been limited to a few circuits. Here we apply part mining and directed evolution to build a set of transcriptional AND gates in Escherichia coli. Each AND gate integrates two promoter inputs and controls one promoter output. This allows the gates to be layered by having the output promoter of an upstream circuit serve as the input promoter for a downstream circuit. Each gate consists of a transcription factor that requires a second chaperone protein to activate the output promoter. Multiple activator-chaperone pairs are identified from type III secretion pathways in different strains of bacteria. Directed evolution is applied to increase the dynamic range and orthogonality of the circuits. These gates are connected in different permutations to form programs, the largest of which is a 4-input AND gate that consists of 3 circuits that integrate 4 inducible systems, thus requiring 11 regulatory proteins. Measuring the performance of individual gates is sufficient to capture the behaviour of the complete program. Errors in the output due to delays (faults), a common problem for layered circuits, are not observed. This work demonstrates the successful layering of orthogonal logic gates, a design strategy that could enable the construction of large, integrated circuits in single cells.
People in romantic relationships often benefit from improved mental and physical health and well-being. Today, these relationships can be recreated using virtual agents. For instance, some people ...anthropomorphize and fall in love with a virtual partner in a romantic video game. Although previous psychological research has examined anthropomorphized agents, it has neglected virtual romantic relationships. This study aims to examine the desire to play underlying playing romantic video games (RVGs). In Study 1, 43 Japanese participants completed a survey about their desire to play RVGs and their current romantic relationship status. The research revealed that a human-like voice and the use of touch were perceived as important factors in anthropomorphized relationships. In Study 2, an independent sample of 281 Japanese participants replicated the results of Study 1 regarding the importance of voice and touch in RVGs. Moreover, we found that a desire to develop social skills and alleviate negative emotions independently desire to play RVG use. As an important first step, these findings reveal several factors which might contribute to developing a romantic relationship with a virtual agent.
The COVID-19 pandemic has highlighted that new diagnostic technologies are essential for controlling disease transmission. Here, we develop SHINE (Streamlined Highlighting of Infections to Navigate ...Epidemics), a sensitive and specific diagnostic tool that can detect SARS-CoV-2 RNA from unextracted samples. We identify the optimal conditions to allow RPA-based amplification and Cas13-based detection to occur in a single step, simplifying assay preparation and reducing run-time. We improve HUDSON to rapidly inactivate viruses in nasopharyngeal swabs and saliva in 10 min. SHINE's results can be visualized with an in-tube fluorescent readout - reducing contamination risk as amplification reaction tubes remain sealed - and interpreted by a companion smartphone application. We validate SHINE on 50 nasopharyngeal patient samples, demonstrating 90% sensitivity and 100% specificity compared to RT-qPCR with a sample-to-answer time of 50 min. SHINE has the potential to be used outside of hospitals and clinical laboratories, greatly enhancing diagnostic capabilities.
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