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Characterization of ADAMTS9 proteoglycanase activity: Comparison with ADAMTS1, ADAMTS4, and ADAMTS5
TUG protein acts through a disordered region to organize the early secretory pathway
Abstract The Endoplasmic Reticulum (ER)-Golgi Intermediate Compartment (ERGIC) is a network of tubules and vesicles known for producing COPI vesicles and receiving COPII vesicles from the ER. Much about its identity, stability, and regulation remains unknown. Here, we show that TUG (UBXN9, Aspscr1) protein, a central regulator of GLUT4 trafficking, localizes to the ERGIC, and that its deletion enhances anterograde flux of a model soluble cargo protein. TUG deletion redistributes ERGIC markers to the cis-Golgi and alters Golgi morphology. TUG forms biomolecular condensates in vitro and contains a central disordered region that mediates its recruitment to ERGIC membranes. A distinct N-terminal region mediates its oligomerization in cells. TUG deletion disrupts ERGIC-dependent processes, including autophagy and collagen secretion, and alters the targeting of the CFTR chloride channel. We conclude that TUG organizes and stabilizes ERGIC membranes to support their roles in diverse secretory and degradative membrane trafficking pathways.
DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication
Abstract The replication stress response is an essential pathway that deals with the obstacles that halt the progression of DNA replication forks even during an unperturbed S phase. Basal activation of the ATR and CHK1 kinases prevents the premature firing of origins of replication during S phase, avoiding the activation of an excessive number of replication forks and the appearance of genomic instability. However, the mechanisms that regulate ATR activation in the unperturbed S phase have not been fully determined. Here we present evidence that the AAA ATPase VCP/p97 regulates the presence of the DNA polymerase α/Primase complex (POLA/PRIM) on chromatin, thus limiting its activity and hampering the subsequent activation of ATR by TOPBP1. As a consequence, inhibiting VCP/p97 activates ATR and CHK1 and leads to a cell cycle arrest in G2/M. We propose that the priming activity of POLA/PRIM in the lagging strand is one of the determinants of the basal activation of ATR during an unperturbed S phase and VCP/p97 limits this activation through the extraction of POLA/PRIM from chromatin.
Uncovering memorization effect in the presence of spurious correlations
Neutrophil to albumin ratio predicts cardiovascular and all cause mortality in CVD patients with abnormal glucose metabolism
Machine learning analysis of kinematic movement features during functional tasks to discriminate chronic neck pain patients from asymptomatic controls
Large tolerance for incidence angle in Terahertz parametric detection
A 22 month prospective assessment of neutralizing and IgG antibody levels against SARS-CoV-2 variants following homologous and heterologous BNT162b2 boosting
A graph-based computational approach for modeling physicochemical properties in drug design
Integrated artificial intelligence in healthcare and the patient’s experience of care
Determination of bisphenol A in different types of soft drink samples by MSPE-GC/MS technique and contribution to risk assessment
Clinical characteristics and comparative analysis of PD-1/PD-L1 inhibitor-induced pituitary dysfunction versus other pituitary disorders
The effects of frailty, mental health, and cardiac function on quality of life in patients undergoing transcatheter aortic valve replacement
HIPK4 accelerates cutaneous squamous cell carcinoma progression by phosphorylating TAp63 and inhibiting EFEMP1 expression
Nitrogen and phosphorus differentially control marine biomass production and stoichiometry
A molecularly defined brain circuit module for regulating panic-like defensive state
Layered polymer-perovskite composite membranes for ultraflexible fatigue-tolerant optoelectronics
Abstract Flexible integration of perovskite materials has driven diverse applications, from wearable detectors, portable energy systems to foldable displays. However, due to the intrinsic brittleness of perovskite, mechanical strain inevitably causes the degradation and variation of electronic performance of the devices. Here, we establish a periodic multilayered polymer-perovskite membrane that showcases plastic-like mechanical behaviors of small Young’s modulus (5.41 GPa) and bending tolerance (radius of 0.5 mm), yet retains the perovskite’s carrier transport capacity (μτ product of 1.04 × 10−4 cm2 V−1). The mechanistic study shows that the formation of bicontinuous perovskite-polyimide structure in the membrane accounts for the carrier transport and load transfer functions, respectively, thus unifies paradoxical mechanical and electronic properties. Using a lateral device configuration, X-ray detector based on the membrane delivers a high X-ray sensitivity of 8380.80 μC Gyair −1 cm−2, and withstands 30,000 repeated bending cycles under a bending radius of 1.5 mm without notable performance degradation.