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Abstract: Cells have several sensory systems that detect energy and metabolic status and adjust flux through metabolic pathways accordingly. Many of these sensors and signaling pathways are conserved from yeast to mammals. In this review, we bring together information about five different nutrient-sensing pathways (AMP kinase, mTOR, PAS kinase, hexosamine biosynthesis and Sir2), highlighting their similarities, differences and roles in disease. [Copyright &y& Elsevier]

Examines the contribution of the structural maintenance of chromosome proteins on yeast. Recovery of adenosine triphosphotase activity by molar mixing of purified proteins; Promotion of change in circular DNA trapped as knots by topoisomerase; Capture of DNA duplexes within a heterodimer.

Part I. Describes the use of rapid chemical quench techniques to follow the production of adenosine phosphate (ADP) by yeast topoisomerase II. Materials and methods used; What are type II deoxyribonucleic acid (DNA) topoisomerases; Discussion on the results.

Focuses on DNA topoisomerase II from Saccharomyces cerevisiae. Function as homodimeric enzymes in transiently cleaving double-stranded DNA; Frequency or reassociation by monomers of topoisomerase II dimers; Description of formation of a dimer by two monomers; Necessity for tight association between topoisomerase monomers.

Studies by single-turnover kinetics the mechanism by which T7 DNA polymerase (exo) bypasses N-2-acetylaminofluorene (AAF) and N-2-aminofluorene (AF) adducts. Multiple nucleotide incorporation studies; Single nucleotide incorporation studies; Discrimination between correct and incorrect nucleotides incorporated by the polymerase.

Regulation of cellular functions can be accomplished by many mechanisms, including transcriptional regulation, alternative splicing, translational regulation, phosphorylation and other posttranslational covalent modifications, degradation, localization, protein-protein interactions, and small-molecule allosteric effectors. Largely because of advances in the techniques of molecular biology in the past few decades, our knowledge of regulation by most of these mechanisms has expanded enormously. Regulation by small-molecule, allosteric interactions is an exception. Many of the best-known allosteric regulators were discovered decades ago, when we knew little about all of these other forms of regulation. Allostery is the most direct, rapid, and efficient regulatory mechanism to sense changes in the concentration of small molecules and alter cellular responses to maintain homeostasis. In this perspective, we present the argument that allosteric regulation is underappreciated in the systems biology world and that many allosteric effectors remain to be discovered. [ABSTRACT FROM AUTHOR]

The structural integrity of mitotic chromosomes is essential for proper chromatid segregation. In this issue of Cell, show that vertebrates contain two distinct condensin complexes, both of which are required for normal mitotic chromosome morphology. [Copyright &y& Elsevier]

Discusses why ligand-induced allosteric changes in proteins are important in their cellular functions and regulation. Uses an enzyme with one immunotagged subunit defective in ATP binding and one wild-type subunit to show that ATP binding to one promoter can induce a concerted conformational change in the entire enzyme. Investigation of the ATP usage and DNA transport by type II DNA topoisomerases; More.

The article provides information on a study which hypothesized that communally embracing and exploring the uncertainty caused by the Covid-19 pandemic would support students in developing coping skills and preparing for the often uncertain nature of clinical medicine. Topics discussed include details of a four-week remote course titled "Covid-19 Exploration in Real Time," and implication of the success of the course on medical education initiatives capitalising on public health events.

Part II. Presents results that are consistent with topoisomerase II hydrolyzing its two bound adenosine triphosphate (ATP) sequentially. Materials and methods used; Why the proposed mechanism for ATP is complex; Results and discussion on the study.

Phenomenon: Because of its importance in residency selection, the United States Medical Licensing Examination Step 1 occupies a critical position in medical education, stimulating national debate about appropriate score use, equitable selection criteria, and the goals of undergraduate medical education. Yet, student perspectives on these issues and their implications for engagement with health systems science-related curricular content are relatively underexplored. Approach: We conducted an online survey of medical students at 19 American allopathic medical schools from March-July, 2019. Survey items were designed to elicit student opinions on the Step 1 examination and the impact of the examination on their engagement with new, non-test curricular content related to health systems science. Findings: A total of 2856 students participated in the survey, representing 23.5% of those invited. While 87% of students agreed that doing well on the Step 1 exam was their top priority, 56% disagreed that studying for Step 1 had a positive impact on engagement in the medical school curriculum. Eighty-two percent of students disagreed that Step 1 scores should be the top item residency programs use to offer interviews. When asked whether Step 1 results should be reported pass/fail with no numeric score, 55% of students agreed, while 33% disagreed. The majority of medical students agreed that health systems science topics were important but disagreed that studying for Step 1 helped learn this content. Students reported being more motivated to study a topic if it was on the exam, part of a course grade, prioritized by residency program directors, or if it would make them a better physician in the future. Insights: These results confirm the primacy of the United States Medical Licensing Examination Step 1 exam in preclinical medical education and demonstrate the need to balance the objectives of medical licensure and residency selection with the goals of the broader medical profession. The survey responses suggest several potential solutions to increase student engagement in health systems science curricula which may be especially important after Step 1 examination results are reported as pass/fail. [ABSTRACT FROM AUTHOR]

The article presents an abstract of the article "What's in a Transition? An Integrative Perspective on Transitions in Medical Education" which was presented at the 2016 annual spring meeting of the Association of American Medical Colleges Region Group on Educational Affairs.

The article provides an example of how a student-led initiative united administration towards action to develop professionalism standards catalysing curricular, cultural and administrative change. Topics discussed include major categories of the professionalism themes based on the survey results, lessons learned from the initiative, and significance of this student-led process to the University of Utah School of Medicine (UUSOM).

Small molecule allostery modifies protein function but is not easily discovered. We introduce mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS), a method for identifying physiologically relevant, low-affinity metabolite-protein interactions using unmodified proteins and complex mixtures of unmodified metabolites. In a pilot experiment using five proteins, we identified 16 known and 13 novel interactions. The known interactions included substrates, products, intermedi-ates, and allosteric regulators of their protein partners. MIDAS does not depend upon enzymatic measurements, but most of the new interactions affect the enzymatic activity of the protein partner. We found that the fatty acid palanitate interacts with both glucokinase and glycogen phosphorylase. Further character-ization revealed that palinitate inhibited both enzymes, possibly providing a mechanism fur sparing carbohydrate catabolism when fatty acids are abundant. [ABSTRACT FROM AUTHOR]

Smc2⁄4 forms the core of the Saccharomyces cerevisiae condensin, which promotes metaphase chromosome compaction. To understand how condensin manipulates DNA, we used two in vitro assays to study the role of SMC (structural maintenance of chromosome) proteins and ATP in reconfiguring the path of DNA. The first assay evaluated the topology of knots formed in the presence of topoisomerase II. Unexpectedly, both wild-type Smc2⁄4 and an ATPase mutant promoted (+) chiral knotting of nicked plasmids, revealing that ATP hydrolysis and the non-SMC condensins are not required to compact DNA chirally. The second assay measured Smc2⁄4-dependent changes in linking number (Lk). Smc2⁄4 did not induce (+) supercoiling, but instead induced broadening of topoisomer distributions in a cooperative manner without altering Lko. To explain chiral knotting in substrates devoid of chiral supercoiling, we propose that Smc2⁄4 directs chiral DNA compaction by constraining the duplex to retrace its own path. In this highly cooperative process, both (+) and (-) loops are sequestered (about one per kb), leaving net writhe and twist unchanged while broadening Lk. We have developed a quantitative theory to account for these results. Additionally, we have shown at higher molar stoichiometries that Smc2/4 prevents relaxation by topoisomerase 1 and nick closure by DNA ligase, indicating that Smc2⁄4 can saturate DNA. By electron microscopy of Smc2⁄4-DNA complexes, we observed primarily two protein-laden bound species: long flexible filaments and uniform rings or ‘doughnuts.’ Close packing of Smc2⁄4 on DNA explains the substrate protection we observed. Our results support the hypothesis that SMC proteins bind multiple DNA duplexes. [ABSTRACT FROM AUTHOR]

Develops a novel selection system for chromosome translocations in Saccharomyces cerevisiae. Effects of chromosome translocations on cell proliferation; Involvement of MLL genes in translocations among leukemia patients; Genetic consequences of chromosome translocations.