The Devil\u27s Love Song

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Enzyme Kinetics of the Mitochondrial Deoxyribonucleoside Salvage Pathway Are Not Sufficient to Support Rapid mtDNA Replication

Using a computational model, we simulated mitochondrial deoxynucleotide metabolism and mitochondrial DNA replication. Our results indicate that the output from the mitochondrial salvage enzymes alone is inadequate to support a mitochondrial DNA replication duration of as long as 10 hours. We find that an external source of deoxyribonucleoside diphosphates or triphosphates (dNTPs), in addition to those supplied by mitochondrial salvage, is essential for the replication of mitochondrial DNA to complete in the experimentally observed duration of approximately 1 to 2 hours. For meeting a relatively fast replication target of 2 hours, almost two-thirds of the dNTP requirements had to be externally supplied as either deoxyribonucleoside di- or triphosphates, at about equal rates for all four dNTPs. Added monophosphates did not suffice. However, for a replication target of 10 hours, mitochondrial salvage was able to provide for most, but not all, of the total substrate requirements. Still, additional dGTPs and dATPs had to be supplied. Our analysis of the enzyme kinetics also revealed that the majority of enzymes of this pathway prefer substrates that are not precursors (canonical deoxyribonucleosides and deoxyribonucleotides) for mitochondrial DNA replication, such as phosphorylated ribonucleotides, instead of the corresponding deoxyribonucleotides. The kinetic constants for reactions between mitochondrial salvage enzymes and deoxyribonucleotide substrates are physiologically unreasonable for achieving efficient catalysis with the expected in situ concentrations of deoxyribonucleotides

Evaporation of a packet of quantized vorticity

A recent experiment has confirmed the existence of quantized turbulence in superfluid He3-B and suggested that turbulence is inhomogenous and spreads away from the region around the vibrating wire where it is created. To interpret the experiment we study numerically the diffusion of a packet of quantized vortex lines which is initially confined inside a small region of space. We find that reconnections fragment the packet into a gas of small vortex loops which fly away. We determine the time scale of the process and find that it is in order of magnitude agreement with the experiment.Comment: figure 1a,b,c and d, figure2, figure

Developing and Assessing Respect for Human Dignity in College Students

Academic institutions are now expected to engage in developing and assessing learning outcomes; however, responsibility outcomes, such as respect for human dignity (RFHD), can be particularly challenging. As part of our Biopsychology course and Sensation and Perception course over the past decade, we applied the scientist-educator model of learning and drew from the literature on prejudice reduction to develop our RFHD interventions, which involved face-to-face interactions with others who had sensory deficits or brain/spinal cord injuries. We iteratively created two pre-post measures to assess development of different aspects of RFHD: a Behavioral Tendencies Questionnaire and a 4-Factor RFHD Model Questionnaire. Recently, we modified the intervention and the assessments for adoption in our Class, Race, and Ethnicity in Society course. This paper reports findings from these three courses and a control course in engineering (n = 153). Findings support our two sets of hypotheses, regarding 1) the efficacy of the assessments to capture different likelihoods for interacting with others targeted by the interventions and changes over time in these factors, and 2) positive effects of the face-to-face intervention activities. This study demonstrates RFHD can be developed and assessed in a college course and provides new assessments for RFHD that are easily modified for a variety of types of others (e.g., individuals who are homeless versus blind or of a particular race). Click here to read the corresponding ISSOTL blog post

Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors

BACKGROUND: The presence of somatic mitochondrial DNA (mtDNA) mutations in cancer cells has been interpreted in controversial ways, ranging from random neutral accumulation of mutations, to positive selection for high pathogenicity, or conversely to purifying selection against high pathogenicity variants as occurs at the population level. METHODS: Here we evaluated the predicted pathogenicity of somatic mtDNA mutations described in cancer and compare these to the distribution of variations observed in the global human population and all possible protein variations that could occur in human mtDNA. We focus on oncocytic tumors, which are clearly associated with mitochondrial dysfunction. The protein variant pathogenicity was predicted using two computational methods, MutPred and SNPs&GO. RESULTS: The pathogenicity score of the somatic mtDNA variants were significantly higher in oncocytic tumors compared to non-oncocytic tumors. Variations in subunits of Complex I of the electron transfer chain were significantly more common in tumors with the oncocytic phenotype, while variations in Complex V subunits were significantly more common in non-oncocytic tumors. CONCLUSIONS: Our results show that the somatic mtDNA mutations reported over all tumors are indistinguishable from a random selection from the set of all possible amino acid variations, and have therefore escaped the effects of purifying selection that act strongly at the population level. We show that the pathogenicity of somatic mtDNA mutations is a determining factor for the oncocytic phenotype. The opposite associations of the Complex I and Complex V variants with the oncocytic and non-oncocytic tumors implies that low mitochondrial membrane potential may play an important role in determining the oncocytic phenotype

Evaluation of the CNS and cardiovascular effects of prolonged exposure to bromotrifluromethane (CBrF3)

The proposed use of bromotrifluoromethane (CBrF3) as a fire extinguishant in aircraft, spacecraft and submarines has stimulated increasing interest and research in the toxicological properties of this compound. In a spacecraft, because of its unique recirculating life support system, the introduction of CBrF3 by leakage or intentional discharge, will result in continuous exposure of crewman to low concentrations of this compound for periods of up to 7 days, or possibly even longer. The effects of low concentrations of CBrF3, under continuous exposure conditions, on the CNS and cardiovascular systems of animals to enable an assessment of these risks were investigated

Nutritional Quality of Available Forages for Small Stock during a Drought in an Arid Pastoral Landscape in South Africa

This study aimed to assess the nutritional quality of the available forage species during a drought in an arid pastoral system in South Africa. Forage biomass was collected during the wet and dry seasons whilst following livestock herds consisting of boer goats, swakara sheep and mixed breed sheep, in both the summer and winter rainfall regions of the pastoral system. Mineral nutrient content in the plant species revealed that the forages utilized by the livestock generally contained adequate concentrations of Mg, Ca, Na, and K to meet the dietary requirements of the small stock in both the winter and summer rainfall areas. Zinc concentrations in more than half of the forages sampled in the summer rainfall area, during both wet and dry seasons, however, were below the required concentrations for small stock. When considering all plant species utilised, the diets were generally adequate in all mineral nutrients. However, none of the forage species contained sufficiently high concentrations of protein to meet the minimum requirements for small stock. These findings therefore show that pastoralists have to deal with chronic low levels of protein during droughts, and their inability to purchase supplementary feed, or to cultivate fodder crops, or temporary emigrate out of the system puts their livelihoods at high risk to climate change

Pre-pregnancy predictors of hypertension in pregnancy among Aboriginal and Torres Strait Islander women in north Queensland, Australia; a prospective cohort study

BACKGROUND Compared to other Australian women, Indigenous women are frequently at greater risk for hypertensive disorders of pregnancy. We examined pre-pregnancy factors that may predict hypertension in pregnancy in a cohort of Aboriginal and Torres Strait Islander women in north Queensland. METHODS Data on a cohort of 1009 Indigenous women of childbearing age (15–44 years) who participated in a 1998–2000 health screening program in north Queensland were combined with 1998–2008 Queensland hospitalisations data using probabilistic data linkage. Data on the women in the cohort who were hospitalised for birth (n = 220) were further combined with Queensland perinatal data which identified those diagnosed with hypertension in pregnancy. RESULTS Of 220 women who gave birth, 22 had hypertension in the pregnancy after their health check. The mean age of women with and without hypertension was similar (23.7 years and 23.9 years respectively) however Aboriginal women were more affected compared to Torres Strait Islanders. Pre-pregnancy adiposity and elevated blood pressure at the health screening program were predictors of a pregnancy affected by hypertension. After adjusting for age and ethnicity, each 1 cm increase in waist circumference showed a 4% increased risk for hypertension in pregnancy (PR 1.04; 95% CI; 1.02-1.06); each 1 point increase in BMI showed a 9% adjusted increase in risk (1.09; 1.04-1.14). For each 1 mmHg increase in baseline systolic blood pressure there was an age and ethnicity adjusted 6% increase in risk and each 1 mmHg increase in diastolic blood pressure showed a 7% increase in risk (1.06; 1.03-1.09 and 1.07; 1.03-1.11 respectively). Among those free of diabetes at baseline, the presence of the metabolic syndrome (International Diabetes Federation criteria) predicted over a three-fold increase in age-ethnicity-adjusted risk (3.5; 1.50-8.17). CONCLUSIONS Pre-pregnancy adiposity and features of the metabolic syndrome among these young Aboriginal and Torres Strait Islander women track strongly to increased risk of hypertension in pregnancy with associated risks to the health of babies.Sandra K Campbell, John Lynch, Adrian Esterman and Robyn McDermot