Ivan R. Nabi, Ben Cardoen, Ismail M. Khater
et al.
Super-resolution microscopy, or nanoscopy, enables the use of fluorescent-based molecular localization tools to study molecular structure at the nanoscale level in the intact cell, bridging the mesoscale gap to classical structural biology methodologies. Analysis of super-resolution data by artificial intelligence (AI), such as machine learning, offers tremendous potential for discovery of new biology, that, by definition, is not known and lacks ground truth. Herein, we describe the application of weakly supervised paradigms to super-resolution microscopy and its potential to enable the accelerated exploration of the nanoscale architecture of subcellular macromolecules and organelles.
A bstractA search is presented for a heavy resonance decaying into either a pair of Z bosons or a Z boson and a W boson (ZZ or WZ), with a Z boson decaying into a pair of neutrinos and the other boson decaying hadronically into two collimated quarks that are reconstructed as a highly energetic large-cone jet. The search is performed using the data collected with the CMS detector at the CERN LHC during 2016 in proton-proton collisions at a center-of-mass energy of 13 TeV, corresponding to a total integrated luminosity of 35.9 fb−1. No excess is observed in data with regard to background expectations. Results are interpreted in scenarios of physics beyond the standard model. Limits at 95% confidence level on production cross sections are set at 0.9 fb (63 fb) for spin-1 W′ bosons, included in the heavy vector triplet model, with mass 4.0 TeV (1.0 TeV), and at 0.5 fb (40 fb) for spin-2 bulk gravitons with mass 4.0 TeV (1.0 TeV). Lower limits are set on the masses of W′ bosons in the context of two versions of the heavy vector triplet model of 3.1TeV and 3.4 TeV, respectively.
Regulating the upstream of the cytokines production could be a promising strategy to the treatment of COVID-19. We suggest to pay more attention to the dysregulated IFN-I production in COVID-19 and to considerate cGAS, ALK and STING as potential therapeutic targets preventing cytokine storm. Approved drugs like suramin and ALK inhibitors are worthy of clinical trials.
Synthesis of biopolymers such as DNA, RNA, and proteins are biophysical processes aided by enzymes. Performance of these enzymes is usually characterized in terms of their average error rate and speed. However, because of thermal fluctuations in these single-molecule processes, both error and speed are inherently stochastic quantities. In this paper, we study fluctuations of error and speed in biopolymer synthesis and show that they are in general correlated. This means that, under equal conditions, polymers that are synthesized faster due to a fluctuation tend to have either better or worse errors than the average. The error-correction mechanism implemented by the enzyme determines which of the two cases holds. For example, discrimination in the forward reaction rates tends to grant smaller errors to polymers with faster synthesis. The opposite occurs for discrimination in monomer rejection rates. Our results provide an experimentally feasible way to identify error-correction mechanisms by measuring the error-speed correlations.
DNA and RNA quadruplexes are extensively studied for the key roles they are suspected to play in the cellular regulation networks at both genomic and transcriptomic levels. The reliable detection of quadruplexes in cells was and remains a challenging task. Here, we describe the various strategies that have been implemented over the past years to visualize functionally relevant DNA and RNA quadruplexes in human cells, from immunodetection studies to the design and use of quadruplex-specific turn-on fluorescent probes.
We report a successful observation of pressure-induced superconductivity in a topological compound Bi2Te3 with Tc of ∼3 K between 3 to 6 GPa. The combined high-pressure structure investigations with synchrotron radiation indicated that the superconductivity occurred at the ambient phase without crystal structure phase transition. The Hall effects measurements indicated the hole-type carrier in the pressure-induced superconducting Bi2Te3 single crystal. Consequently, the first-principles calculations based on the structural data obtained by the Rietveld refinement of X-ray diffraction patterns at high pressure showed that the electronic structure under pressure remained topologically nontrivial. The results suggested that topological superconductivity can be realized in Bi2Te3 due to the proximity effect between superconducting bulk states and Dirac-type surface states. We also discuss the possibility that the bulk state could be a topological superconductor.
Osman Kahraman, Yiwei Li, Christoph A. Haselwandter
Motivated by single-molecule experiments on synaptic membrane protein domains, we use a stochastic lattice model to study protein reaction and diffusion processes in crowded membranes. We find that the stochastic reaction-diffusion dynamics of synaptic proteins provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the single-molecule trajectories observed for synaptic proteins, and spatially inhomogeneous protein lifetimes at the cell membrane. Our results suggest that central aspects of the single-molecule and collective dynamics observed for membrane protein domains can be understood in terms of stochastic reaction-diffusion processes at the cell membrane.
Induced effects by direct exposure to ionizing radiation (IR) are a central issue in many fields like radiation protection, clinic diagnosis and oncological therapies. Direct irradiation at certain doses induce cell death, but similar effects can also occur in cells no directly exposed to IR, a mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce the death of cells loaded with MNPs in a focused oncological therapy known as magnetic hyperthermia. Indirect mechanisms are also able to induce the death of unloaded MNPs cells. Using in vitro cell models, we found that colocalization of the MNPs at the lysosomes and the non-increase of the temperature induces bystander effect under non-IR. Our results provide a landscape in which bystander effects are a more general mechanism, up to now only observed and clinically used in the field of radiotherapy.
Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (non-flow correlations). Using data for Au + Au collisions at sqrt{s_{NN}} = 130 GeV from the STAR TPC, it is found that four-particle correlation analyses can reliably separate flow and non-flow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of two. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.
Alok Kumar Maity, Arnab Bandyopadhyay, Pinaki Chaudhury
et al.
We present a stochastic formalism for signal transduction processes in bacterial two-component system. Using elementary mass action kinetics, the proposed model takes care of signal transduction in terms of phosphotransfer mechanism between the cognate partners of a two-component system, viz, the sensor kinase and the response regulator. Based on the difference in functionality of the sensor kinase, the noisy phosphotransfer mechanism has been studied for monofunctional and bifunctional two component system using the formalism of linear noise approximation. Steady state analysis of both models quantifies different physically realizable quantities, e.g., variance, coefficient of variation, mutual information. The resultant data reveals that both systems reliably transfer information of extra-cellular environment under low external stimulus and at high kinase and phosphatase regime. We extend our analysis further by studying the role of two-component system in downstream gene regulation.
Recent experimental results on the effect of miRNA on the decay of its target mRNA have been analyzed against a previously hypothesized single molecule degradation pathway. According to that hypothesis, the silencing complex (miRISC) first interacts with its target mRNA and then recruits the protein complexes associated with NOT1 and PAN3 to trigger deadenylation (and subsequent degradation) of the target mRNA. Our analysis of the experimental decay patterns allowed us to refine the structure of the degradation pathways at the single molecule level. Surprisingly, we found that if the previously hypothesized network was correct, only about 7% of the target mRNA would be regulated by the miRNA mechanism, which is inconsistent with the available knowledge. Based on systematic data analysis, we propose the alternative hypothesis that NOT1 interacts with miRISC before binding to the target mRNA. Moreover, we show that when miRISC binds alone to the target mRNA, the mRNA is degraded more slowly, probably through a deadenylation-independent pathway. The new biochemical pathway we propose both fits the data and paves the way for new experimental work to identify new interactions.
Calcium is an ubiquitous second messenger that triggers a plethora of key physiological responses. The events are initiated in micro- or nano-sized compartments and determined by the complex interactions with calcium-binding proteins and mechanisms of calcium clearance. Local calcium increases in the vicinity of single channels represent an essentially non-linear reaction-diffusion problem that have been analysed previously using various linearized approximations. I revisited the problem of stationary patterns that can be generated by the point calcium source in the presence of buffer and obtained new explicit solutions. Main results of the analysis of the calcium buffering are supplemented with pertinent derivations and discussion of respective mathematical problems in Appendices. I show that for small calcium influx the calcium gradients around established around channel lumen have quasi-exponential form. For bigger fluxes, when the buffer is saturated, the model predicts periodic patterns. The transition between the two regimes depend on the capacity of buffer and its mobility. Theoretical predictions were examined using a model one-dimensional system. For sufficiently big fluxes the oscillatory calcium patterns were observed. Theoretical and experimental results are discussed in terms of their possible physiological implications.