The Michaelis constant KM describes the affinity of an enzyme for a specific substrate and is a central parameter in studies of enzyme kinetics and cellular physiology. As measurements of KM are ...often difficult and time-consuming, experimental estimates exist for only a minority of enzyme-substrate combinations even in model organisms. Here, we build and train an organism-independent model that successfully predicts KM values for natural enzyme-substrate combinations using machine and deep learning methods. Predictions are based on a task-specific molecular fingerprint of the substrate, generated using a graph neural network, and on a deep numerical representation of the enzyme's amino acid sequence. We provide genome-scale KM predictions for 47 model organisms, which can be used to approximately relate metabolite concentrations to cellular physiology and to aid in the parameterization of kinetic models of cellular metabolism.
Objective To examine the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for Irritable Bowel Syndrome (IBS) and draw out the implications of the results for both theoretical models of IBS ...and treatment options. The UK prevalence rate is approximately twice as high in women as in men (23% vs 11%) and thus the issues were examined first among women. Methods IBS patients were randomly assigned to a Mindfulness group (who received a course of MBCT treatment) or to a Waitlist group as control condition. Treatment consisted of weekly sessions delivered by clinical psychologists and each lasting two hours, with daily practice of up to one hour. Patients completed a set of standardised self-report measures whose assessments included IBS symptom severity, IBS quality of life, maladaptive illness cognitions (catastrophizing, visceral anxiety sensitivity) Results Compared to the Waitlist group, the Mindfulness group experienced significantly reduced IBS symptoms and improved quality of life. At the post-treatment stage the overall severity of IBS was reduced relative to baseline by 13%, and at the six-week follow-up stage the reduction had increased to 28%. Further analyses identified significant mediators of this reduction. Conclusion MBCT adapted for IBS delivered significant and sustained amelioration of the condition. Identification of mediating factors suggested underlying processes and particular directions in which to refine treatment further.
The kinetics of the esterification of free fatty acids (FFA) in sunflower oil with methanol in the presence of sulphuric acid at concentrations of 5 and 10
wt% relative to free acids as catalyst and ...methanol/oleic acid mole ratios from 10:1 to 80:1 was studied. The experimental results were found to fit a first-order kinetic law for the forward reaction and a second-order one for the reverse reaction.
The influence of temperature on the kinetic constants was determined by fitting the results to the Arrhenius equation. The energy of activation for the forward reaction decreased with increasing catalyst concentration from 50
745 to 44
559
J/mol.
Based on the experimental results, a methanol/oleic acid mole ratio of 60:1, a catalyst (sulphuric acid) concentration of 5
wt% and a temperature of 60
°C provided a final acid value for the oil lower than 1
mg
KOH/g oil within 120
min. This is a widely endorsed limit for efficient separation of glycerin and biodiesel during production of the latter.
Putrescine and cadaverine are among the most common biogenic amines (BA) in foods, but it is advisable that their accumulation be avoided. Present knowledge about their toxicity is, however, limited; ...further research is needed if qualitative and quantitative risk assessments for foods are to be conducted. The present work describes a real-time analysis of the cytotoxicity of putrescine and cadaverine on intestinal cell cultures. Both BA were cytotoxic at concentrations found in BA-rich foods, although the cytotoxicity threshold for cadaverine was twice that of putrescine. Their mode of cytotoxic action was similar, with both BA causing cell necrosis; they did not induce apoptosis. The present results may help in establishing legal limits for both putrescine and cadaverine in food.
Phenotypic Plasticity and Species Coexistence Turcotte, Martin M.; Levine, Jonathan M.
Trends in ecology & evolution (Amsterdam),
October 2016, 2016-10-00, 20161001, Letnik:
31, Številka:
10
Journal Article
Recenzirano
Ecologists are increasingly interested in predicting how intraspecific variation and changing trait values impact species interactions and community composition. For many traits, much of this ...variation is caused by phenotypic plasticity, and thus the impact of plasticity on species coexistence deserves robust quantification. Partly due to a lack of sound theoretical expectations, empirical studies make contradictory claims regarding plasticity effects on coexistence. Our critical review of this literature, framed in modern coexistence theory, reveals that plasticity affects species interactions in ways that could impact stabilizing niche differences and competitive asymmetries. However, almost no study integrates these measures to quantify the net effect of plasticity on species coexistence. To address this challenge, we outline novel empirical approaches grounded in modern theory.
Phenotypic plasticity due to competing species can promote or hinder coexistence.
Coexistence theory can guide experiments designed to test the effects of plasticity.
Manipulations of plasticity can robustly test how it modulates competitive outcomes.
Strongly interacting quantum many-body systems arise in many areas of physics, but their complexity generally precludes exact solutions to their dynamics. We explored a strongly interacting two-level ...system formed by the clock states in 87 Sr as a laboratory for the study of quantum many-body effects. Our collective spin measurements reveal signatures of the development of many-body correlations during the dynamical evolution. We derived a many-body Hamiltonian that describes the experimental observation of atomic spin coherence decay, density-dependent frequency shifts, severely distorted lineshapes, and correlated spin noise. These investigations open the door to further explorations of quantum many-body effects and entanglement through use of highly coherent and precisely controlled optical lattice clocks.
DNA methylation is the most well studied of the epigenetic regulators in relation to environmental exposures. To date, numerous studies have detailed the manner by which DNA methylation is influenced ...by the environment, resulting in altered global and gene-specific DNA methylation. These studies have focused on prenatal, early-life, and adult exposure scenarios. The present review summarizes currently available literature that demonstrates a relationship between DNA methylation and environmental exposures. It includes studies on aflatoxin B
1
, air pollution, arsenic, bisphenol A, cadmium, chromium, lead, mercury, polycyclic aromatic hydrocarbons, persistent organic pollutants, tobacco smoke, and nutritional factors. It also addresses gaps in the literature and future directions for research. These gaps include studies of mixtures, sexual dimorphisms with respect to environmentally associated methylation changes, tissue specificity, and temporal stability of the methylation marks.
Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of ...measurement reproducibility within and between laboratories.
We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR) performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques.
Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63-0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant (P = 0.06). Gel-based and PCR-based techniques were not different in accuracy.
Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories.
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