Adaptation to different types of stress converge on mitochondrial metabolism

Yeast cell factories encounter physical and chemical stresses when used for industrial production of fuels and chemicals. These stresses reduce productivity and increase bioprocess costs. Understanding the mechanisms of the stress response is essential for improving cellular robustness in platform strains. We investigated the three most commonly encountered industrial stresses for yeast (ethanol, salt, and temperature) to identify the mechanisms of general and stress-specific responses under chemostat conditions in which specific growth rate-dependent changes are eliminated. By applying systems-level analysis, we found that most stress responses converge on mitochondrial processes. Our analysis revealed that stress-specific factors differ between applied stresses; however, they are underpinned by an increased ATP demand. We found that when ATP demand increases to high levels, respiration cannot provide sufficient ATP, leading to onset of respirofermentative metabolism. Although stress-specific factors increase ATP demand for cellular growth under stressful conditions, increased ATP demand for cellular maintenance underpins a general stress response and is responsible for the onset of overflow metabolism

Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects

Serial hemodynamic and plasma catecholamine responses were compared among 10 healthy men (27 ± 3 years) ( ± 1 standard deviation) during symptom-limited handgrip (33% maximal voluntary contraction for 4.4 ± 1.8 minutes), cold pressor testing (6 minutes) and symptom-limited supine bicycle exercise (22 ± 5 minutes). Plasma catecholamine concentrations were measured by radioenzymatic assays; ejection fraction and changes in cardiac volumes were assessed by equilibrium radionuclide angiography. During maximal supine exercise, plasma norepinephrine and epinephrine concentrations increased three to six times more than during either symptom-limited handgrip or cold pressor testing. Additionally, increases in heart rate, systolic blood pressure, rate-pressure product, stroke volume, ejection fraction and cardiac output were significantly greater during bicycle exercise than during the other two tests. A decrease in ejection fraction of 0.05 units or more was common in young normal subjects during the first 2 minutes of cold pressor testing (6 of 10 subjects) or at symptom-limited handgrip (3 of 10), but never occurred during maximal supine bicycle exercise.The magnitude of hemodynamic changes with maximal supine bicycle exercise was greater, more consistent and associated with much higher sympathetic nervous system activation, making this a potentially more useful diagnostic stress than either handgrip exercise or cold pressor testing

Apparatus and method for three-dimensional contouring

A device and method for contouring three-dimensionally curved surfaces includes an elongated contouring assembly that is supported at two locations by height adjustment mechanisms that raise and lower the two locations of the contouring assembly independently of each other. The contouring assembly creates a three-dimensionally curved surface as it passes over an area to be contoured. The control of at least one location of the contouring assembly is based on a comparison of the measured position of one portion of the contouring assembly with a profile of the surface to be leveled that is stored in a computer memory. Control of the height of the other location is preferably based on the height above a physical reference measured with a proximity sensor. A pivot or tilting controller may control the tilting of the contouring assembly to follow the slope of the profile stored in computer memory.https://digitalcommons.mtu.edu/patents/1031/thumbnail.jp

Apparatus and method for three-dimensional contouring

A device and method for contouring three-dimensionally curved surfaces includes an elongated contouring assembly that is supported at opposite ends by height adjustment mechanisms. The height adjustment mechanisms raise and lower the ends of the contouring assembly independently of each other, thereby allowing the contouring assembly to create a three-dimensionally curved surface as it passes over an area to be contoured. The control of at least one end of the contouring assembly is based on a comparison of its measured position with a profile of the surface to be leveled that is stored in a computer memory. A pivot or tilting controller may control the tilting of the contouring assembly to follow the slope of the profile stored in computer memory.https://digitalcommons.mtu.edu/patents/1114/thumbnail.jp

Apparatus and method for three-dimensional contouring

A contouring device and method for contouring three- dimensionally curved surfaces includes an elongated contouring assembly that is supported at opposite ends by a pair of fluid cylinders. The fluid cylinders are controlled to raise and lower the ends of the contouring assembly independently of each other, thereby allowing the contouring assembly to create a three-dimensionally curved surface as it passes over an area to be contoured. The control of one of the fluid cylinders is based on a comparison of the measured position of a first end of the contouring assembly with a profile of the surface to be leveled that is stored in a computer memory. The measurement of the position of the first end of the contouring assembly is achieved by a tracking device which tracks the position of a target positioned on the first end of the contouring assembly and which determines the three dimensional position of the target. A proximity sensor measures the position of the second end of the contouring assembly from a surface and outputs a control signal that adjusts the height of the second end of the contouring assembly to follow the surface. Alternatively, a second target positioned on the second contouring assembly end is tracked by a second tracking device to determine the three-dimensional position of the second end. The contouring assembly preferably has a plow, rotating auger, and a vibratory screed positioned adjacent and parallel to one another in an orientation transverse to the direction of motion of the contouring assembly. The plow, rotating auger, and vibratory screed are all pivotable about an axis parallel to their longitudinal direction. A pivot or tilting controller controls the tilting of the plow, rotating auger, and vibratory screed to follow the slope of the profile stored in computer memory.https://digitalcommons.mtu.edu/patents/1062/thumbnail.jp

Relations between heart failure, ejection fraction, arrhythmia suppression and mortality: Analysis of the Cardiac Arrhythmia Suppression Trial

Objectives.We studied the relations between heart failure, ejection fraction, arrhythmia suppression and mortality.Background.Both left ventricular ejection fraction and functional class of heart failure are strongly associated with mortality after acute myocardial infarction. Both are also related to the presence of ventricular arrhythmias and have been identified as factors related to the ability to suppress ventricular arrhythmias. Little has been reported about the relations between these two factors and arrhythmia suppression or mortality.Methods.Baseline data from the Cardiac Arrhythmia Suppression Trial were used to define several categories of heart failure and to relate both the resulting categories and ejection fraction to arrhythmia suppression and mortality using logistic and survival regression analytic methodologies.Results.Regardless of the prospective baseline definition of heart failure used, the data consistently showed that heart failure was a more powerful predictor of subsequent congestive heart failure events and arrhythmia suppression and was equally powerful in predicting death. However, each variable provided incremental information when included in the prediction model. Heart failure and ejection fraction appeared to be independent predictors of death. Interactions were observed: A low ejection fraction was more predictive of failure of arrhythmia suppression in patients with than without evidence of heart failure before or at baseline; a low ejection fraction was more predictive of subsequent congestive heart failure events in patients without than with evidence of heart failure before or at baseline.Conclusions.Although heart failure as a prognostic feature appears to be somewhat superior to ejection fraction, both are powerful predictors of arrhythmia suppression and cardiac events in patients with ventricular arrhythmia after myocardial infarction. Each provides incremental prediction

Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain

Background: A Saccharomyces cerevisiae strain carrying deletions in all three pyruvate decarboxylase (PDC) genes (also called Pdc negative yeast) represents a non-ethanol producing platform strain for the production of pyruvate derived biochemicals. However, it cannot grow on glucose as the sole carbon source, and requires supplementation of C2 compounds to the medium in order to meet the requirement for cytosolic acetyl-CoA for biosynthesis of fatty acids and ergosterol. Results: In this study, a Pdc negative strain was adaptively evolved for improved growth in glucose medium via serial transfer, resulting in three independently evolved strains, which were able to grow in minimal medium containing glucose as the sole carbon source at the maximum specific rates of 0.138, 0.148, 0.141 h(-1), respectively. Several genetic changes were identified in the evolved Pdc negative strains by genomic DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase, and RPD3 encoding a histone deacetylase. Reverse engineering of the non-evolved Pdc negative strain through introduction of the MTH1(81D) allele restored its growth on glucose at a maximum specific rate of 0.053 h(-1) in minimal medium with 2% glucose, and the CIT1 deletion in the reverse engineered strain further increased the maximum specific growth rate to 0.069 h(-1). Conclusions: In this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing expression of several hexose transporter genes. The non-synonymous mutations in HXT2 and CIT1 may function in the presence of mutated MTH1 alleles and could be related to an altered central carbon metabolism in order to ensure production of cytosolic acetyl-CoA in the Pdc negative strain

Stories of Hell and Healing: Internet Users’ Construction of Benzodiazepine Distress and Withdrawal

Abstract Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recovery on Internet support sites and YouTube. Our analysis indicated that users employ rich metaphors to portray the psychologically disturbing and protracted nature of their suffering. We identified seven major themes: hell and isolation, anxiety and depression, alienation, physical distress, anger and remorse, waves and windows, and healing and renewal. By posting success stories, ex-users make known that “healing” can be a long, unpredictable process, but distress does lessen, and recovery can happen

STALK users guide

STALK is a system that models molecular docking between two proteins. A problem is posed as an optimization problem where the objective is to minimize the free energy of the molecular system by maximizing the intermolecular interaction energy between the molecules. The possible number of conformations between the two molecules can be very large. A parallel genetic algorithm (GA) is used to explore the conformation space and identify the low-energy molecular configurations. The CAVE, a virtual reality environment, can be used to visualize and interact with the systems while it is executing

Sand River Headwaters Green Infrastructure Project, City of Aiken, South Carolina: A Collaborative Team Approach to Implementing Green Infrastructure Practices

2010 S.C. water Resources Conference - Science and Policy Challenges for a Sustainable Futur