230 research outputs found

    Twist/Writhe Partitioning in a Coarse-Grained DNA Minicircle Model

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    Here we present a systematic study of supercoil formation in DNA minicircles under varying linking number by using molecular dynamics simulations of a two-bead coarse-grained model. Our model is designed with the purpose of simulating long chains without sacrificing the characteristic structural properties of the DNA molecule, such as its helicity, backbone directionality and the presence of major and minor grooves. The model parameters are extracted directly from full-atomistic simulations of DNA oligomers via Boltzmann inversion, therefore our results can be interpreted as an extrapolation of those simulations to presently inaccessible chain lengths and simulation times. Using this model, we measure the twist/writhe partitioning in DNA minicircles, in particular its dependence on the chain length and excess linking number. We observe an asymmetric supercoiling transition consistent with experiments. Our results suggest that the fraction of the linking number absorbed as twist and writhe is nontrivially dependent on chain length and excess linking number. Beyond the supercoiling transition, chains of the order of one persistence length carry equal amounts of twist and writhe. For longer chains, an increasing fraction of the linking number is absorbed by the writhe.Comment: 21 pages, 7 figures, 1 tabl

    Diet and Anxiety: A Scoping Review.

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    Anxiety disorders are the most common group of mental disorders. There is mounting evidence demonstrating the importance of nutrition in the development and progression of mental disorders such as depression; however, less is known about the role of nutrition in anxiety disorders. This scoping review sought to systematically map the existing literature on anxiety disorders and nutrition in order to identify associations between dietary factors and anxiety symptoms or disorder prevalence as well as identify gaps and opportunities for further research. The review followed established methodological approaches for scoping reviews. Due to the large volume of results, an online program (Abstrackr) with artificial intelligence features was used. Studies reporting an association between a dietary constituent and anxiety symptoms or disorders were counted and presented in figures. A total of 55,914 unique results were identified. After a full-text review, 1541 articles met criteria for inclusion. Analysis revealed an association between less anxiety and more fruits and vegetables, omega-3 fatty acids, "healthy" dietary patterns, caloric restriction, breakfast consumption, ketogenic diet, broad-spectrum micronutrient supplementation, zinc, magnesium and selenium, probiotics, and a range of phytochemicals. Analysis revealed an association between higher levels of anxiety and high-fat diet, inadequate tryptophan and dietary protein, high intake of sugar and refined carbohydrates, and "unhealthy" dietary patterns. Results are limited by a large percentage of animal and observational studies. Only 10% of intervention studies involved participants with anxiety disorders, limiting the applicability of the findings. High quality intervention studies involving participants with anxiety disorders are warranted

    Does Race Play a Role in Complications and Outcomes of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms?

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    BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known vascular complications. The role race and ethnicity play in these complications is less defined. We aimed to further evaluate the role of race in patients without a history of previous thrombotic or hemorrhagic events. METHODS: In this retrospective study, 300 adult patients with MPN were included; 270 (90.0%) were White and 30 (10.0%) were non-White. The non-White group primarily consisted of African American or Black (26 patients), followed by others. Median age at diagnosis was 58 years for White patients and 61.5 years for non-White patients. The interaction between outcomes and vascular events with race was evaluated using multivariate logistical regression models. RESULTS: The incidence of thrombotic events was inversely correlated with age at diagnosis, with younger patients demonstrating a higher rate of thrombotic events over time (p < .001). The incidence of thrombotic or hemorrhagic events did not differ between White and non-White patients. A statistically significant difference in median survival was observed between White and non-White patients: 29 years (95% confidence interval [CI]: 21.8-not reached) versus 13 years (95% CI: 5.7-22.7), respectively (p = .016). CONCLUSION: This study did not find a significant difference in the rate of thrombotic or hemorrhagic events between White and non-White patients with MPN but suggested that non-White patients had significantly shorter median survival than White patients. Such observations may inform future studies to further characterize racial disparities in outcomes

    Topical Application of an Irreversible Small Molecule Inhibitor of Lysyl Oxidases Ameliorates Skin Scarring and Fibrosis

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    Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases
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