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Here, we systematically address this problem using magnetic tweezers. Remarkably, we find that the persistence length of DNA remains constant independent of the amount of bound YOYO-1, which contrasts previous assumptions. We furthermore determine important structural parameters such as the binding site size, the elongation, as well as the untwisting angle per bound YOYO-1 molecule. We expect that our assay, in which all the parameters are determined within a single experiment, will be beneficial for a large range of other DNA binding drugs. Single-molecule fluorescence microscopy has become an extremely versatile tool to explore the statistical—mechanical properties of DNA duplexes and their influence on transport 1 , stretching in liquid flow 2 and in confined geometries 3 , entropic recoiling 4 , self-diffusion in 2D 5 and electrophoresis of DNA 6. It exhibits a high association constant and a strong fluorescence enhancement upon binding to double-stranded DNA dsDNA , thus providing high signal-to-noise ratios 7.
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Physiological and Epigenetic Features of Yoyo Dieting and Weight Control

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Physiological and Epigenetic Features of Yoyo Dieting and Weight Control

Obesity and being overweight have become a worldwide epidemic affecting more than 1. Efforts to curb this global health burden by developing effective long-term non-surgical weight loss interventions continue to fail due to weight regain after weight loss. Weight cycling, often referred to as Yoyo dieting, is driven by physiological counter-regulatory mechanisms that aim at preserving energy, i. Models based on genetically determined set points explained some of the weight control mechanisms, but exact molecular underpinnings remained elusive. Today, gene—environment interactions begin to emerge as likely drivers for the obesogenic memory effect associated with weight cycling. Here, epigenetic mechanisms, including histone modifications and DNA methylation, appear as likely factors that underpin long-lasting deleterious adaptations or an imprinted obesogenic memory to prevent weight loss maintenance.
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