the neck and so cannot be relied on to direct surgical management of the neck in patients with head and neck cancer.The flagella of Chlamydomonas reinhardtii possess fibrous ultrastructures of a nanometer-scale thickness known as mastigonemes. These structures have been widely hypothesized to enhance flagellar thrust; however, detailed hydrodynamic analysis supporting this claim is lacking. In this study, we present a comprehensive investigation into the hydrodynamic effects of mastigonemes using a genetically modified mutant lacking the fibrous structures. Through high-speed observations of freely swimming cells, we found the average and maximum swimming speeds to be unaffected by the presence of mastigonemes. In addition to swimming speeds, no significant difference was found for flagellar gait kinematics. After our observations of swimming kinematics, we present direct measurements of the hydrodynamic forces generated by flagella with and without mastigonemes. These measurements were conducted using optical tweezers, which enabled high temporal and spatial resolution of hydrodynamic forces. Through our measurements, we found no significant difference in propulsive flows due to the presence of mastigonemes. Direct comparison between measurements and fluid mechanical modeling revealed that swimming hydrodynamics were accurately captured without including mastigonemes on the modeled swimmer's flagella. Therefore, mastigonemes do not appear to increase the flagella's effective area while swimming, as previously thought. Our results refute the longstanding claim that mastigonemes enhance flagellar thrust in C. reinhardtii, and so, their function still remains enigmatic.Intrinsically disordered proteins are proteins whose native functional states represent ensembles of highly diverse conformations. Such ensembles are a challenge for quantitative structure comparisons because their conformational diversity precludes optimal superimposition of the atomic coordinates necessary for deriving common similarity measures such as the root mean-square deviation of these coordinates. Here, we introduce superimposition-free metrics that are based on computing matrices of the Cα-Cα distance distributions within ensembles and comparing these matrices between ensembles. Differences between two matrices yield information on the similarity between specific regions of the polypeptide, whereas the global structural similarity is captured by the root mean-square difference between the medians of the Cα-Cα distance distributions of two ensembles. Together, our metrics enable rigorous investigations of structure-function relationships in conformational ensembles of intrinsically disordered proteins derived using experimental restraints or by molecular simulations and for proteins containing both structured and disordered regions.The TSC complex is the cognate GTPase-activating protein (GAP) for the small GTPase Rheb and a crucial regulator of the mechanistic target of rapamycin complex 1 (mTORC1). Mutations in the TSC1 and TSC2 subunits of the complex cause tuberous sclerosis complex (TSC). We present the crystal structure of the catalytic asparagine-thumb GAP domain of TSC2. A model of the TSC2-Rheb complex and molecular dynamics simulations suggest that TSC2 Asn1643 and Rheb Tyr35 are key active site residues, while Rheb Arg15 and Asp65, previously proposed as catalytic residues, contribute to the TSC2-Rheb interface and indirectly aid catalysis. The TSC2 GAP domain is further stabilized by interactions with other TSC2 domains. We characterize TSC2 variants that partially affect TSC2 functionality and are associated with atypical symptoms in patients, suggesting that mutations in TSC1 and TSC2 might predispose to neurological and vascular disorders without fulfilling the clinical criteria for TSC.Intake of fructose-containing sugars is strongly associated with metabolic syndrome. Compared with other sugars, dietary fructose is uniquely metabolized by fructokinase. However, the tissue-specific role of fructokinase in sugar-induced metabolic syndrome, and the specific roles of glucose and fructose in driving it, is not fully understood. Here, we show that in mice receiving excess fructose-glucose solutions, whole-body deletion of fructokinase, and thus full blockade of fructose metabolism, is sufficient to prevent metabolic syndrome. This protection is not only due to reduced fructose metabolism, but also due to decreased sugar intake. https://www.selleckchem.com/products/Calcitriol-(Rocaltrol).html Furthermore, by using tissue-specific fructokinase-deficient mice, we determined that while sugar intake is controlled by intestinal fructokinase activity, metabolic syndrome is driven by fructose metabolism in the liver. Our findings show a two-pronged role for fructose metabolism in sugar-induced metabolic syndrome, one arm via the intestine that mediates sugar intake and a second arm in the liver that drives metabolic dysfunction.We identified alternative scoring strategies for the Female Athlete Triad Coalition cumulative risk assessment (CRA) tool to be utilized when particular risk factors (bone mineral density (BMD), oligomenorrhea/amenorrhea) cannot be determined, objectively defined dietary restriction, and explored proxy measures of energy deficiency. This cross-sectional investigation of exercising women (n=166) utilized an existing database derived from multiple studies designed to assess health, exercise, and menstrual function. Data from the screening/baseline period of each study included anthropometrics, DXA, disordered eating questionnaires, descriptive data, and proxy measures of energy deficiency (total triiodothyronine (TT3) and ratio of measured-to-predicted resting metabolic rate (mRMR/pRMR)). Substituting delayed menarche for BMD was the best-fit replacement resulting in 15 (9%) participants being categorized in different clearance categories. When menstrual status cannot be assessed, such as during hormonal contraceptive use, low energy availability (EA) determined using self-report and disordered eating questionnaires was the best substitution resulting in 34 (20%) participants being categorized in different clearance categories. Based on original clearance categorizations, the "Provisional" group had lower TT3 (78.3±2.2ng/dL; 92.7±2.7ng/dL) and Harris-Benedict mRMR/pRMR (0.85±0.01; 0.90±0.01) than the "Full" group. Until an updated risk assessment tool is developed, delayed menarche can substitute for low BMD and low EA for oligomenorrhea/amenorrhea. Novelty • This investigation addresses previous limitations of the Triad CRA tool. • Disordered eating questionnaires can be used to objectively identify dietary restriction for the low EA risk factor. • When a risk factor cannot be assessed, delayed menarche can substitute for low BMD and low EA for oligomenorrhea/amenorrhea.