Deciphering factors modulating DNA repair in chromatin is of great interest because nucleosomal positioning influences mutation rates. H3K56 acetylation (Ac) is implicated in chromatin landscape ...regulation, impacting genomic stability, yet the effect of H3K56Ac on DNA base excision repair (BER) remains unclear. We determined whether H3K56Ac plays a role in regulating AP site incision by AP endonuclease 1 (APE1), an early step in BER. Our
studies of acetylated, well-positioned nucleosome core particles (H3K56Ac-601-NCPs) demonstrate APE1 strand incision is enhanced compared with that of unacetylated WT-601-NCPs. The high-mobility group box 1 protein enhances APE1 activity in WT-601-NCPs, but this effect is not observed in H3K56Ac-601-NCPs. Therefore, our results suggest APE1 activity on NCPs can be modulated by H3K56Ac.
We introduce a novel magnetic angular rate gravity (MARG) sensor fusion algorithm for inertial measurement. The new algorithm improves the popular gradient descent (ʻMadgwick’) algorithm increasing ...accuracy and robustness while preserving computational efficiency. Analytic and experimental results demonstrate faster convergence for multiple variations of the algorithm through changing magnetic inclination. Furthermore, decoupling of magnetic field variance from roll and pitch estimation is proven for enhanced robustness. The algorithm is validated in a human-machine interface (HMI) case study. The case study involves hardware implementation for wearable robot teleoperation in both Virtual Reality (VR) and in real-time on a 14 degree-of-freedom (DoF) humanoid robot. The experiment fuses inertial (movement) and mechanomyography (MMG) muscle sensing to control robot arm movement and grasp simultaneously, demonstrating algorithm efficacy and capacity to interface with other physiological sensors. To our knowledge, this is the first such formulation and the first fusion of inertial measurement and MMG in HMI. We believe the new algorithm holds the potential to impact a very wide range of inertial measurement applications where full orientation necessary. Physiological sensor synthesis and hardware interface further provides a foundation for robotic teleoperation systems with necessary robustness for use in the field.
•BER is the DNA repair pathway responsible for repairing single strand breaks, base lesions and abasic sites in mammalian cells.•BER intermediates are channeled during the pathway so that release of ...toxic repair intermediates is minimized.•Handoff of repair intermediates from the pol β gap-filling to DNA ligation steps during BER pathway is important for genome stability.•Structural differences that pol β shows after incorrect or oxidized nucleotide insertion could affect accuracy of BER.
DNA lesions arise from many endogenous and environmental agents, and such lesions can promote deleterious events leading to genomic instability and cell death. Base excision repair (BER) is the main DNA repair pathway responsible for repairing single strand breaks, base lesions and abasic sites in mammalian cells. During BER, DNA substrates and repair intermediates are channeled from one step to the next in a sequential fashion so that release of toxic repair intermediates is minimized. This includes handoff of the product of gap-filling DNA synthesis to the DNA ligation step. The conformational differences in DNA polymerase β (pol β) associated with incorrect or oxidized nucleotide (8-oxodGMP) insertion could impact channeling of the repair intermediate to the final step of BER, i.e., DNA ligation by DNA ligase I or the DNA Ligase III/XRCC1 complex. Thus, modified DNA ligase substrates produced by faulty pol β gap-filling could impair coordination between pol β and DNA ligase. Ligation failure is associated with 5′-AMP addition to the repair intermediate and accumulation of strand breaks that could be more toxic than the initial DNA lesions. Here, we provide an overview of the consequences of ligation failure in the last step of BER. We also discuss DNA-end processing mechanisms that could play roles in reversal of impaired BER.
PARP1-dependent poly-ADP-ribosylation (PARylation) participates in the repair of many forms of DNA damage. Here, we used atomic force microscopy (AFM) and single molecule fluorescence microscopy to ...examine the interactions of PARP1 with common DNA repair intermediates. AFM volume analysis indicates that PARP1 binds to DNA at nicks, abasic (AP) sites, and ends as a monomer. Single molecule DNA tightrope assays were used to follow the real-time dynamic behavior of PARP1 in the absence and presence of AP endonuclease (APE1) on AP DNA damage arrays. These experiments revealed that PARP1 conducted damage search mostly through 3D diffusion. Co-localization of APE1 with PARP1 on DNA was found capable of inducing 1D diffusion of otherwise nonmotile PARP1, while excess APE1 also facilitated the dissociation of DNA-bound PARP1. Moreover, auto-PARylation of PARP1 allowed the protein to switch its damage search strategy by causing a 3-fold increase in linear diffusion. Finally, we demonstrated that PARP inhibitor olaparib did not significantly alter the rate of PARP1 dissociation from DNA, but instead resulted in more motility of DNA-bound PARP1 molecules.
Microrollers flow uphill as granular media Wilson-Whitford, Samuel R; Gao, Jinghui; Roffin, Maria Chiara ...
Nature communications,
09/2023, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
Pour sand into a container and only the grains near the top surface move. The collective motion associated with the translational and rotational energy of the grains in a thin flowing layer ...is quickly dissipated as friction through multibody interactions. Alternatively, consider what will happen to a bed of particles if one applies a torque to each individual particle. In this paper, we demonstrate an experimental system where torque is applied at the constituent level through a rotating magnetic field in a dense bed of microrollers. The net result is the grains roll uphill, forming a heap with a negative angle of repose. Two different regimes have been identified related to the degree of mobility or fluidisation of the particles in the bulk. Velocimetry of the near surface flowing layer reveals the collective motion of these responsive particles scales in a similar way to flowing bulk granular flows. A simple granular model that includes cohesion accurately predicts the apparent negative coefficient of friction. In contrast to the response of active or responsive particles that mimic thermodynamic principles, this system results in macroscopic collective behavior that has the kinematics of a purely dissipative granular system.
Summary
The symbiotic cyanobacterium UCYN‐A is one of the most globally abundant marine dinitrogen (N2)‐fixers, but cultures have not been available and its biology and ecology are poorly understood. ...We used cultivation‐independent approaches to investigate how UCYN‐A single‐cell N2 fixation rates (NFRs) and nifH gene expression vary as a function of depth and photoperiod. Twelve‐hour day/night incubations showed that UCYN‐A only fixed N2 during the day. Experiments conducted using in situ arrays showed a light‐dependence of NFRs by the UCYN‐A symbiosis, with the highest rates in surface waters (5–45 m) and lower rates at depth (≥ 75 m). Analysis of NFRs versus in situ light intensity yielded a light saturation parameter (Ik) for UCYN‐A of 44 μmol quanta m−2 s−1. This is low compared with other marine diazotrophs, suggesting an ecological advantage for the UCYN‐A symbiosis under low‐light conditions. In contrast to cell‐specific NFRs, nifH gene‐specific expression levels did not vary with depth, indicating that light regulates N2 fixation by UCYN‐A through processes other than transcription, likely including host–symbiont interactions. These results offer new insights into the physiology of the UCYN‐A symbiosis in the subtropical North Pacific Ocean and provide clues to the environmental drivers of its global distributions.
Summary
The symptoms and sequelae of sickle cell anaemia (SCA) are caused by the polymerization of deoxygenated sickle haemoglobin, and people with SCA may be uniquely susceptible to adverse outcomes ...from hypoxia and haemoglobin desaturation. We examined by oximetry adults (aged 18–45 years) with SCA presenting symptoms indicative of polysomnography, at a single institution, irrespective of treatment, for nocturnal hypoxaemia. Clinical labs and blood for in vitro assessments were taken upon enrolment and after 8–12 weeks of oxygen therapy or observation. Of 21 screened participants, nine (43%) had sufficient nocturnal hypoxaemia to warrant oxygen therapy (≥5 min at SpO2 ≤ 88%). Time spent at SpO2 ≤ 88% associated with age (p = 0.0092), annual hospitalizations (p = 0.0018) and anaemia (p = 0.0139), as well as plasma levels of TNFα (p = 0.0019) and IL‐4 (p = 0.0147). Longitudinal analysis showed that WBC significantly decreased during the follow‐up period in hypoxic individuals but not in non‐hypoxic individuals (p = 0.0361 and p = 0.6969 respectively). Plasma levels of CCL2 and IL‐1ra tended to increase, while levels of red blood cell reactive oxygen species tended to decrease with oxygen therapy. Overall, nocturnal hypoxaemia was common in this pilot study population and associated with plausible clinical comorbidities; oxygen therapy may decrease inflammation and oxidative damage in hypoxic individuals.
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