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The cell reaction to fluid shear involves CD18 integrins, nitric oxide, cGMP and Rho GTPases, is attenuated in the presence of inflammatory mediators and modified by glucocorticoids. The mechanism is abolished in disease models (genetic hypertension and hypercholesterolemia) leading to an increased number of activated leukocytes in the circulation with enhanced microvascular resistance and cell entrapment. In addition to their role in binding to biochemical agonists/antagonists, membrane receptors appear to play a second role to monitor local fluid shear stress levels. The fluid shear stress control of many circulating cell types such as lymphocytes, stem cells, tumor cells remains to be elucidated.Thrombosis is one of the main causes of failure in device implantation. Computational thrombosis simulation is a convenient approach to evaluate the risk of thrombosis for a device. However, thrombosis is a complicated process involving multiple species and reactions. Application of a macroscopic, single-scale computational model for device-induced thrombosis is a cost-effective approach. The current study has refined an existing thrombosis model, which simulated thrombosis by tracing four species in blood non-activated platelets, activated platelets, surface adherent platelets, and ADP. Platelets are activated mechanically by shear stress, and chemically by ADP. Platelet adhesion occurs on surfaces with low wall shear stress with platelet aggregation inhibited in regions of high shear stress. The study improves the existing thrombosis model by 1) Modifying the chemical platelet activation function so that ADP activates platelets; 2) Modifying the function describing thrombus deposition and growth to distinguish between thrombus deposition on wall surfaces and thrombus growth on existing thrombus surfaces; 3) Modifying the thrombus breakdown function to allow for thrombus breakdown by shear stress; 4) Modeling blood flow as non-Newtonian. The results show that the inclusion of ADP and the use of a non-Newtonian model improve agreement with experimental data.Previous studies investigating white matter organization in attention deficit hyperactivity disorder (ADHD) have adopted diffusion tensor imaging (DTI). However, attempts to derive pathophysiological models from this research have had limited success, possibly reflecting limitations of the DTI method. This study investigated the organization of white matter tracts in ADHD using fixel based analysis (FBA), a fiber specific analysis framework that is well placed to provide novel insights into the pathophysiology of ADHD. High angular diffusion weighted imaging and clinical data were collected in a large paediatric cohort (N = 144; 76 with ADHD; age range 9-11 years). White matter tractography and FBA were performed across 14 white matter tracts. Permutation based inference testing (using FBA derived measures of fiber density and morphology) assessed differences in white matter tract profiles between children with and without ADHD. Analysis further examined the association between white matter properties and ADHD symptom severity. Relative to controls, children with ADHD showed reduced white matter connectivity along association and projection pathways considered critical to behavioral control and motor function. Increased ADHD symptom severity was associated with reduced white matter organization in fronto-pontine fibers projecting to and from the supplementary motor area. Providing novel insight into the neurobiological foundations of ADHD, this is the first research to uncover fiber specific white matter alterations across a comprehensive set of white matter tracts in ADHD using FBA. Findings inform pathophysiological models of ADHD and hold great promise for the consistent identification and systematic replication of brain differences in this disorder.The brain of deaf people is definitely not just deaf, and we have to reconsider what we know about the impact of hearing loss on brain development in light of comorbid vestibular impairments.Organizing matter at the atomic scale is a central goal of nanotechnology. Bottom-up approaches, in which molecular building blocks are programmed to assemble via supramolecular interactions, are a proven and versatile route to new and useful nanomaterials. Although a wide variety of molecules have been used as building blocks, proteins have several intrinsic features that present unique opportunities for designing nanomaterials with sophisticated functions. There has been tremendous recent progress in designing proteins to fold and assemble to highly ordered structures. Here we review the leading approaches to the design of closed polyhedral protein assemblies, highlight the importance of considering the assembly process itself, and discuss various applications and future directions for the field. We emphasize throughout the exciting opportunities presented by recent advances as well as challenges that remain.YY1-associated factor 2 (YAF2) was frequently reported to modulate target gene transcription through both epigenetic and non-epigenetic means. However, other mechanisms were also utilized by YAF2 to carry out its biological functions. Here, we demonstrated that YAF2 from human tumor and non-tumor cells were mainly expressed as Serine 167 phosphorylated form. Further studies showed that the phosphorylated YAF2 up-regulated while its knockdown by specific siRNAs reduced fibronectin type III and ankyrin repeat domains 1 (FANK1) protein level. Mechanistic exploration disclosed that phosphorylated YAF2 inhibit proteasomal degradation of polyubiquitinated FANK1, leading to its increased stability. We then validated their interaction, and displayed that the FN3 domain of FANK1 binds to amino-terminal of YAF2. Functional studies showed that phosphorylated YAF2 inhibits tumor cell apoptosis in a FANK1-dependent manner. Taken together, our current findings demonstrated that phosphorylated YAF2 exhibits anti-apoptotic activity through targeting FANK1 expression in human tumor cells.Under natural conditions, plants are exposed to solar ultraviolet (UV) radiation, which damages chromosomal DNA. Although plant responses to UV-induced DNA damage have recently been elucidated in detail, revealing a set of DNA repair mechanisms and translesion synthesis (TLS), limited information is currently available on UV-induced mutations in plants. We previously reported the development of a supF-based system for the detection of a broad spectrum of mutations in the chromosomal DNA of Arabidopsis. In the present study, we used this system to investigate UV-induced mutations in plants. The irradiation of supF-transgenic plants with UV-C (500 and 1000 J/m2) significantly increased mutation frequencies (26- and 45-fold, respectively). GC to AT transitions (43-67% of base substitutions) dominated in the mutation spectrum and were distributed throughout single, tandem, and multiple base substitutions. selleck kinase inhibitor Most of these mutations became undetectable with the subsequent illumination of UV-irradiated plants with white light for photoreactivation (PR).