A little bit of lithium does a lot for hydrogen.
Ontology highlight
ABSTRACT:
SUBMITTER: Zurek E
PROVIDER: S-EPMC2764941 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Transcription factors regulate gene activity by binding specific regions of genomic DNA thanks to a subtle interplay of specific and nonspecific interactions that is challenging to quantify. Here, we exploit Reflective Phantom Interface (RPI), a label-free biosensor based on optical reflectivity, to investigate the binding of the N-terminal domain of Gal4, a well-known gene regulator, to double-stranded DNA fragments containing or not its consensus sequence. The analysis of RPI-binding curves provides interaction strength and kinetics and their dependence on temperature and ionic strength. We found that the binding of Gal4 to its cognate site is stronger, as expected, but also markedly slower. We performed a combined analysis of specific and nonspecific binding-equilibrium and kinetics-by means of a simple model based on nested potential wells and found that the free energy gap between specific and nonspecific binding is of the order of one kcal/mol only. We investigated the origin of such a small value by performing all-atom molecular dynamics simulations of Gal4-DNA interactions. We found a strong enthalpy-entropy compensation, by which the binding of Gal4 to its cognate sequence entails a DNA bending and a striking conformational freezing, which could be instrumental in the biological function of Gal4.
| S-EPMC8067546 | biostudies-literature
Project description:Glycosylation is one of the most common forms of protein post-translational modification, but is also the most complex. Dealing with glycoproteins in structure model building, refinement, validation and PDB deposition is more error-prone than dealing with nonglycosylated proteins owing to limitations of the experimental data and available software tools. Also, experimentalists are typically less experienced in dealing with carbohydrate residues than with amino-acid residues. The results of the reannotation and re-refinement by PDB-REDO of 8114 glycoprotein structure models from the Protein Data Bank are analyzed. The positive aspects of 3620 reannotations and subsequent refinement, as well as the remaining challenges to obtaining consistently high-quality carbohydrate models, are discussed.
| S-EPMC6096482 | biostudies-literature
Project description:Most people have a desire to live in a just world, a place where good things happen to good people and bad things happen to bad people. And yet, injustices do occur: good things happen to bad people and bad things happen to good people. Across four experiments, we show that people respond quite differently to correct these two types of injustices. When bad things happen to good people, individuals are eager to compensate a good person's losses, but only do so to a small degree. In contrast, when a good thing happens to a bad person, because the only perceived appropriate act of punishment is to fully strip the bad actor of all his or her illegitimate gains, few people choose to punish in this costly way. However, when they do, they do so to very large degrees. Moreover, we demonstrate that differential psychological mechanisms drive this asymmetry.
| S-EPMC6328196 | biostudies-literature
Project description: Not available
| S-EPMC8344109 | biostudies-literature
Project description:BackgroundIn the absence of sex and recombination, genomes are expected to accumulate deleterious mutations via an irreversible process known as Muller's ratchet, especially in the case of polyploidy. In contrast, no genome-wide mutation accumulation was detected in a transcriptome of facultative apomictic, hexaploid plants of the Ranunculus auricomus complex. We hypothesize that mutations cannot accumulate in flowering plants with facultative sexuality because sexual and asexual development concurrently occurs within the same generation. We assume a strong effect of purging selection on reduced gametophytes in the sexual developmental pathway because previously masked recessive deleterious mutations would be exposed to selection.ResultsWe test this hypothesis by modeling mutation elimination using apomictic hexaploid plants of the R. auricomus complex. To estimate mean recombination rates, the mean number of recombinants per generation was calculated by genotyping three F1 progeny arrays with six microsatellite markers and character incompatibility analyses. We estimated the strength of purging selection in gametophytes by calculating abortion rates of sexual versus apomictic development at the female gametophyte, seed and offspring stage. Accordingly, we applied three selection coefficients by considering effects of purging selection against mutations on (1) male and female gametophytes in the sexual pathway (additive, s = 1.000), (2) female gametophytes only (s = 0.520), and (3) on adult plants only (sporophytes, s = 0.212). We implemented recombination rates into a mathematical model considering the three different selection coefficients, and a genomic mutation rate calculated from genome size of our plants and plant-specific mutation rates. We revealed a mean of 6.05% recombinants per generation. This recombination rate eliminates mutations after 138, 204 or 246 generations, depending on the respective selection coefficients (s = 1.000, 0.520, and 0.212).ConclusionsOur results confirm that the empirically observed frequencies of facultative recombination suffice to prevent accumulation of deleterious mutations via Muller's ratchet even in a polyploid genome. The efficiency of selection is in flowering plants strongly increased by acting on the haplontic (reduced) gametophyte stage.
| S-EPMC6694583 | biostudies-literature
Project description:AimsHighly structured, intensive behavioral lifestyle interventions have been shown to be efficacious in research settings for type 2 diabetes management and weight loss. We sought to evaluate the benefit of participation in more limited counseling and/or education among individuals with newly diagnosed type 2 diabetes in more modest real-world clinical settings.MethodsElectronic Health Records of newly diagnosed type 2 diabetes patients age 35-74 from a large ambulatory group practice were analyzed (n = 1,314). We examined participation in clinic-based lifestyle counseling/education and subsequent weight loss.ResultsOf the total cohort, 599 (45.6%) patients received counseling/education with (26.2%) and without (19.4%) medication, 298(22.7%) patients received a prescription for medication alone, and 417(31.7%) patients were only monitored. On average, those who participated in counseling/education attended 2.5 sessions (approximately 2-3 hours). The average weight loss of patients who received counseling/education alone during the follow-up period (up to three years post-exposure to participation) was 6.3 lbs. (3.3% of body weight), and, if received with medication prescription, 8.1 lbs. (4.0% of body weight) (all at P<0.001). The weight loss associated with medication was only 3.5 lbs. (P<0.001). No significant weight change was observed in the monitoring only group.ConclusionsWhile efforts to improve both the short-term and long-term effectiveness of behavioral lifestyle interventions in real-world settings are ongoing, it is important for clinicians to continue to utilize less intensive, existing resources. Even relatively small "doses" of health education may help in promoting weight loss and may potentially reduce cardiometabolic risk.
| S-EPMC4459994 | biostudies-literature
Project description:While linking records across large administrative datasets ["big data"] has the potential to revolutionize empirical social science research, many administrative data files do not have common identifiers and are thus not designed to be linked to others. To address this problem, researchers have developed probabilistic record linkage algorithms which use statistical patterns in identifying characteristics to perform linking tasks. Naturally, the accuracy of a candidate linking algorithm can be substantially improved when an algorithm has access to "ground-truth" examples-matches which can be validated using institutional knowledge or auxiliary data. Unfortunately, the cost of obtaining these examples is typically high, often requiring a researcher to manually review pairs of records in order to make an informed judgement about whether they are a match. When a pool of ground-truth information is unavailable, researchers can use "active learning" algorithms for linking, which ask the user to provide ground-truth information for select candidate pairs. In this paper, we investigate the value of providing ground-truth examples via active learning for linking performance. We confirm popular intuition that data linking can be dramatically improved with the availability of ground truth examples. But critically, in many real-world applications, only a relatively small number of tactically-selected ground-truth examples are needed to obtain most of the achievable gains. With a modest investment in ground truth, researchers can approximate the performance of a supervised learning algorithm that has access to a large database of ground truth examples using a readily available off-the-shelf tool.
| S-EPMC10072450 | biostudies-literature
Project description:ObjectivesOur objective was to examine the kilocalorie (kcal) content of starters, sides and desserts served in major UK restaurant chains, comparing the kcal content of these dishes in fast-food and full-service restaurants.DesignObservational study.SettingMenu and nutritional information provided online by major UK restaurant chains.MethodDuring October to November 2018, we accessed websites of restaurant chains with 50 or more outlets in the UK. Menu items that constituted starters, sides or desserts were identified and their kcal content was extracted. Accompanying beverages were not included. We used multilevel modelling to examine whether mean kcal content of dishes differed in fast-food versus full-service restaurants.Main outcome measuresThe mean kcal content of dishes and the proportion of dishes exceeding public health recommendations for energy content in a main meal (>600 kcal).ResultsA total of 1009 dishes (212 starters, 318 sides and 479 desserts) from 27 restaurant chains (21 full-service, 6 fast-food) were included. The mean kcal content of eligible dishes was 488.0 (SE=15.6) for starters, 397.5 (SE=14.9) for sides and 430.6 (SE=11.5) for desserts. The percentage of dishes exceeding 600 kcal was 26.4% for starters, 21.7% for sides and 20.5% for desserts. Compared with fast-food chains, desserts offered at full-service restaurants were on average more calorific and were significantly more likely to exceed 600 kcal.ConclusionsThe average energy content of sides, starters and desserts sold in major UK restaurants is high. One in four starters and one in five sides and desserts in UK chain restaurants exceed the recommended energy intake for an entire meal.
| S-EPMC6797243 | biostudies-literature
Project description:Glucose homeostasis is performed by specialized cells types that detect and respond to changes in systemic glucose concentration. Hepatocytes, β-cells and hypothalamic tanycytes are part of the glucosensor cell types, which express several proteins involved in the glucose sensing mechanism such as GLUT2, Glucokinase (GK) and Glucokinase regulatory protein (GKRP). GK catalyzes the phosphorylation of glucose to glucose-6-phosphate (G-6P), and its activity and subcellular localization are regulated by GKRP. In liver, when glucose concentration is low, GKRP binds to GK holding it in the nucleus, while the rise in glucose concentration induces a rapid export of GK from the nucleus to the cytoplasm. In contrast, hypothalamic tanycytes display inverse compartmentalization dynamic in response to glucose: a rise in the glucose concentration drives nuclear compartmentalization of GK. The underlying mechanism responsible for differential GK subcellular localization in tanycytes has not been described yet. However, it has been suggested that relative expression between GK and GKRP might play a role. To study the effects of GKRP expression levels in the subcellular localization of GK, we used insulinoma 832/13 cells and hypothalamic tanycytes to overexpress the tanycytic sequences of Gckr. By immunocytochemistry and Western blot analysis, we observed that overexpression of GKRP, independently of the cellular context, turns GK localization to a liver-like fashion, as GK is mainly localized in the nucleus in response to low glucose. Evaluating the expression levels of GKRP in relation to GK through RT-qPCR, suggest that excess of GKRP might influence the pattern of GK subcellular localization. In this sense, we propose that the low expression of GKRP (in relation to GK) observed in tanycytes is responsible, at least in part, for the compartmentalization pattern observed in this cell type. Since GKRP behaves as a GK inhibitor, the regulation of GKRP expression levels or activity in tanycytes could be used as a therapeutic target to regulate the glucosensing activity of these cells and consequently to regulate feeding behavior.
| S-EPMC6449865 | biostudies-literature
Project description:Catastrophic events can have profound effects on the demography of a population and consequently on genetic diversity. The dynamics of postcatastrophic recovery and the role of sexual versus asexual reproduction in buffering the effects of massive perturbations remain poorly understood, in part because the opportunity to document genetic diversity before and after such events is rare. Six natural (purely sexual) and seven cultivated (mainly clonal due to farming practices) populations of the red alga Agarophyton chilense were surveyed along the Chilean coast before, in the days after and 2 years after the 8.8 magnitude earthquake in 2010. The genetic diversity of sexual populations appeared sensitive to this massive perturbation, notably through the loss of rare alleles immediately after the earthquake. By 2012, the levels of diversity returned to those observed before the catastrophe, probably due to migration. In contrast, enhanced rates of clonality in cultivated populations conferred a surprising ability to buffer the instantaneous loss of diversity. After the earthquake, farmers increased the already high rate of clonality to maintain the few surviving beds, but most of them collapsed rapidly. Contrasting fates between sexual and clonal populations suggest that betting on strict clonality to sustain production is risky, probably because this extreme strategy hampered adaptation to the brutal environmental perturbation induced by the catastrophe.
| S-EPMC7463374 | biostudies-literature