Ritchiemelvin2714

Hydrogen embrittlement is shown to proceed through a previously unidentified mechanism. Upon ingress to the microstructure, hydrogen promotes the formation of low-energy dislocation nanostructures. These are characterized by cell patterns whose misorientation increases with strain, which concomitantly attracts further hydrogen up to a critical amount inducing failure. The appearance of the failure zone resembles the "fish eye" associated to inclusions as stress concentrators, a commonly accepted cause for failure. It is shown that the actual crack initiation is the dislocation nanostructure and its associated strain partitioning.Endolysosomes are dynamic, intracellular compartments, regulating their surface-to-volume ratios to counteract membrane swelling or shrinkage caused by osmotic challenges upon tubulation and vesiculation events. While osmosensitivity has been extensively described on the plasma membrane, the mechanisms underlying endolysosomal surface-to-volume ratio changes and identities of involved ion channels remain elusive. Endolysosomes mediate endocytosis, exocytosis, cargo transport, and sorting of material for recycling or degradation. We demonstrate the endolysosomal cation channel TRPML2 to be hypotonicity/mechanosensitive, a feature crucial to its involvement in fast-recycling processes of immune cells. We demonstrate that the phosphoinositide binding pocket is required for TRPML2 hypotonicity-sensitivity, as substitution of L314 completely abrogates hypotonicity-sensitivity. Last, the hypotonicity-insensitive TRPML2 mutant L314R slows down the fast recycling pathway, corroborating the functional importance of hypotonicity-sensitive TRPML2. Our results highlight TRPML2 as an accelerator of endolysosomal trafficking by virtue of its hypotonicity-sensitivity, with implications in immune cell surveillance and viral trafficking.Rationally regulating the reactivity of molecules or functional groups is common in organic chemistry, both in laboratory and industry synthesis. This concept can be applied to inorganic nanomaterials, particularly two-dimensional black phosphorus (BP) nanosheets. The high reactivity of few-layer (even monolayer) BP is expected to be "shut down" when not required and to be resumed upon application. Here, we demonstrate a protective chemistry-based methodology for regulating BP reactivity. #link# The protective step initiates from binding Al3+ with lone pair electrons from P to decrease the electron density on the BP surface, and ends with an oxygen/water-resistant layer through the self-assembly of hydrophobic 1,2-benzenedithiol (BDT) on BP/Al3+ This protective step yields a stabilized BP with low reactivity. Deprotection of the obtained BP/Al3+/BDT is achieved by chelator treatment, which removes Al3+ and BDT from the BP surface. The deprotective process recovers the electron density of BP and thus restores the reactivity of BP.Chaotic itinerancy is a frequently observed phenomenon in high-dimensional nonlinear dynamical systems and is characterized by itinerant transitions among multiple quasi-attractors. Several studies have pointed out that high-dimensional activity in animal brains can be observed to exhibit chaotic itinerancy, which is considered to play a critical role in the spontaneous behavior generation of animals. Thus, how to design desired chaotic itinerancy is a topic of great interest, particularly for neurorobotics researchers who wish to understand and implement autonomous behavioral controls. However, it is generally difficult to gain control over high-dimensional nonlinear dynamical systems. In this study, we propose a method for implementing chaotic itinerancy reproducibly in a high-dimensional chaotic neural network. We demonstrate that our method enables us to easily design both the trajectories of quasi-attractors and the transition rules among them simply by adjusting the limited number of system parameters and by using the intrinsic high-dimensional chaos.Genetic variation around the LRRK2 gene affects risk of both familial and sporadic Parkinson's disease (PD). However, the biological functions of LRRK2 remain incompletely understood. Here, we report that LRRK2 is recruited to lysosomes after exposure of cells to the lysosome membrane-rupturing agent LLOME. Using an unbiased proteomic screen, we identified the motor adaptor protein JIP4 as an LRRK2 partner at the lysosomal membrane. LRRK2 can recruit JIP4 to lysosomes in a kinase-dependent manner via the phosphorylation of RAB35 and RAB10. Using selleckchem -resolution live-cell imaging microscopy and FIB-SEM, we demonstrate that JIP4 promotes the formation of LAMP1-negative tubules that release membranous content from lysosomes. link2 Thus, we describe a new process orchestrated by LRRK2, which we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2), by which lysosomal tubulation is used to release vesicles from lysosomes. Given the central role of the lysosome in PD, LYTL is likely to be disease relevant.Electron microscopy can visualize the structure of complex materials with atomic and subatomic resolution, but investigations of reaction dynamics and light-matter interaction call for time resolution as well, ideally on a level below the oscillation period of light. Here, we report the use of the optical cycles of a continuous-wave laser to bunch the electron beam inside a transmission electron microscope into electron pulses that are shorter than half a cycle of light. The pulses arrive at the target at almost the full average brightness of the electron source and in synchrony to the optical cycles, providing attosecond time resolution of spectroscopic features. The necessary modifications are simple and can turn almost any electron microscope into an attosecond instrument that may be useful for visualizing the inner workings of light-matter interaction on the basis of the atoms and the cycles of light.Data-driven discovery of cancer driver genes, including tumor suppressor genes (TSGs) and oncogenes (OGs), is imperative for cancer prevention, diagnosis, and treatment. Although epigenetic alterations are important for tumor initiation and progression, most known driver genes were identified based on genetic alterations alone. Here, we developed an algorithm, DORGE (Discovery of Oncogenes and tumor suppressoR genes using Genetic and Epigenetic features), to identify TSGs and OGs by integrating comprehensive genetic and epigenetic data. DORGE identified histone modifications as strong predictors for TSGs, and it found missense mutations, super enhancers, and methylation differences as strong predictors for OGs. We extensively validated DORGE-predicted cancer driver genes using independent functional genomics data. We also found that DORGE-predicted dual-functional genes (both TSGs and OGs) are enriched at hubs in protein-protein interaction and drug-gene networks. Overall, our study has deepened the understanding of epigenetic mechanisms in tumorigenesis and revealed previously undetected cancer driver genes.In the plasma membrane and in synthetic membranes, resident lipids may laterally unmix to form domains of distinct biophysical properties. Whether lipids also drive the lateral organization of intracellular membranes is largely unknown. Here, we describe genetically encoded fluorescent reporters visualizing local variations in bilayer thickness. Using them, we demonstrate that long-chained ceramides promote the formation of discrete domains of increased bilayer thickness in the yeast ER, particularly in the future plane of cleavage and at ER-trans-Golgi contact sites. Thickening of the ER membrane in the cleavage plane contributed to the formation of lateral diffusion barriers, which restricted the passage of short, but not long, protein transmembrane domains between the mother and bud ER compartments. Together, our data establish that the ER membrane is laterally organized and that ceramides drive this process, and provide insights into the physical nature and biophysical mechanisms of the lateral diffusion barriers that compartmentalize the ER.Eukaryotic cells have evolved organelles that allow the compartmentalization and regulation of metabolic processes. Knowledge of molecular mechanisms that allow temporal and spatial organization of enzymes within organelles is therefore crucial for understanding eukaryotic metabolism. link3 Here, we show that the yeast malate dehydrogenase 2 (Mdh2) is dually localized to the cytosol and to peroxisomes and is targeted to peroxisomes via association with Mdh3 and a Pex5-dependent piggybacking mechanism. This dual localization of Mdh2 contributes to our understanding of the glyoxylate cycle and provides a new perspective on compartmentalization of cellular metabolism, which is critical for the perception of metabolic disorders and aging.The Chronic Renal Insufficiency Cohort (CRIC) Study is an ongoing, multicenter, longitudinal study of nearly 5500 adults with CKD in the United States. Over the past 10 years, the CRIC Study has made significant contributions to the understanding of factors associated with CKD progression. This review summarizes findings from longitudinal studies evaluating risk factors associated with CKD progression in the CRIC Study, grouped into the following six thematic categories (1) sociodemographic and economic (sex, race/ethnicity, and nephrology care); (2) behavioral (healthy lifestyle, diet, and sleep); (3) genetic (apoL1, genome-wide association study, and renin-angiotensin-aldosterone system pathway genes); (4) cardiovascular (atrial fibrillation, hypertension, and vascular stiffness); (5) metabolic (fibroblast growth factor 23 and urinary oxalate); and (6) novel factors (AKI and biomarkers of kidney injury). Additionally, we highlight areas where future research is needed, and opportunities for interdisciplinary collaboration.Circular RNA (circRNA) is an endogenous RNA molecule with a stable closed-loop structure. The circular RNA HIPK3 (circHIPK3) is highly expressed in hepatocellular carcinoma and facilitates tumor growth. However, its role in cervical cancer (CC) and its regulatory mechanisms are not well-studied. This study aimed for investigating the function of circHIPK3 on proliferation and metastasis of CC cells. In this study, quantitative real-time PCR assay was adopted to delve into the circHIPK3 expression in CC cell lines. Cell counting kit-8 and colony formation assays were used to evaluate the influence of overexpression and knockdown of circHIPK3 on CC cell proliferation. Dual-luciferase reporter assay was employed to probe into the binding of miR-485-3p to circHIPK3 and miR-485-3p to the 3' untranslated region (UTR) of fibroblast growth factor 2 (FGF2), respectively. FGF2 protein expression was detected by western blot analysis. This study confirmed that circHIPK3 was highly expressed in CC tissues. Overexpressed circHIPK3 could remarkably expedite the proliferation, migration and invasion of SiHa cells, and knocking down circHIPK3 could significantly impede the proliferation, migration and invasion of HeLa cells. MiR-485-3p can directly bind to circHIPK3 and the 3'UTR of FGF2. Overexpression of circHIPK3 triggered the upregulation of FGF2 expression while knockdown of circHIPK3 reduced FGF2 expression in CC cells, and the transfection of miR-485-3p mimics reversed the upregulation of FGF2 expression and enhanced malignant phenotypes in CC cells with overexpressed circHIPK3.