Cell-Type Specificity of Mosaic Chromosome 1q Gain Resolved by snRNA-seq in a Case of Epilepsy With Hyaline Protoplasmic Astrocytopathy.

Objectives: Mosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathologic finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown.

Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy.

Introduction: Mosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathological finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown.

In vitro efficacy of plumbagin and thymol against .

Unlabelled: Phytochemical compounds, plumbagin and thymol were evaluated for their efficacy against using MTT cell viability assay. Plumbagin and thymol were found to be effective in preventing the proliferation of infected bovine lymphocytes. The IC values of plumbagin and thymol were 0.

Viral E Protein Neutralizes BET Protein-Mediated Post-Entry Antagonism of SARS-CoV-2.

Inhibitors of Bromodomain and Extra-terminal domain (BET) proteins are possible anti-SARS-CoV-2 prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here, we show that BET proteins should not be inactivated therapeutically as they are critical antiviral factors at the post-entry level. Knockouts of BRD3 or BRD4 in cells overexpressing ACE2 exacerbate SARS-CoV-2 infection; the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during infection, and not before.

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding.

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding.

Dynamics of Mud Blister Worm Infestation and Shell Repair by Oysters.

AbstractMud blister worms bore into oyster shells; and oysters respond to shell penetration by secreting new layers of shell, resulting in mud blisters on inner surfaces of oyster shells. We conducted two experiments in off-bottom oyster farms along Alabama's coast in summer 2017 to explore the dynamics of worm infestation, blister formation, and shell repair. Results support our hypothesis that only a small proportion of worms that bore into oysters cause blisters.

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses.

The structure of a calsequestrin filament reveals mechanisms of familial arrhythmia.

Mutations in the calcium-binding protein calsequestrin cause the highly lethal familial arrhythmia catecholaminergic polymorphic ventricular tachycardia (CPVT). In vivo, calsequestrin multimerizes into filaments, but there is not yet an atomic-resolution structure of a calsequestrin filament. We report a crystal structure of a human cardiac calsequestrin filament with supporting mutational analysis and in vitro filamentation assays.

An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of -Catecholaminergic Polymorphic Ventricular Tachycardia.

Background: Genetic variants in calsequestrin-2 () cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of -CPVT was sought through an international multicenter collaboration.

Methods: Genotype-phenotype segregation in -CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models.

Magnitude, trends and prevention of road traffic accidents in the Republic of South Africa.

Road traffic injuries (RTIs) constitute one of the five major disease burdens in South Africa with high mortality and morbidity. Thus far, the scientific enquiry into this burden has not been accompanied by successful government efforts to meet the challenge. Currently, more than 1.

A review of CBRN topics related to military and civilian patient exposure and decontamination.

Chemical and biological (CB) warfare have long been practiced, and although these types of warfare are not acceptable in modern times, this does not prevent them from occurring. This makes it important for societies to be able to appropriately respond to these events, including the best way to decontaminate victims to keep them and emergency responders safe. Decontamination methods such as chemical, physical, wet, and dry methods are discussed, as well as their downsides.

Biochemical and behavioral responses of zebrafish embryos to magnetic graphene/nickel nanocomposites.

Graphene nanocomposites are emerging carbon-based materials with interesting electrical, mechanical, optical and magnetic properties, relevant for applications in different fields. Despite this increased use, the impact of graphene nanocomposites residues in the environment has not been properly studied. Thus, the goal of this work was to assess the toxicity of two nickel/graphene nanocomposites (G/Ni1 and G/Ni2) differing in size and shape to Danio rerio embryos.

Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies.

Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging essential genes (EGs) that are indispensable for hPSC fitness, defined as cell reproduction in this study. To map essential genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify EGs.

Do Floral Resources Benefit the Herbivorous Sawfly, Cephus cinctus (Hymenoptera: Cephidae), a Major Pest of Wheat in North America?

Leveraging floral resources to promote biological control requires carefully screening prospective floral species for their suitability not just for natural enemies, but also for targeted pests. Here we examined the influence of access to various sugar resources on Cephus cinctus Norton (Hymenoptera: Cephidae), a major pest of wheat in the northern Great Plains of North America. We conducted greenhouse studies to examine the effect of access to a honey-sucrose solution, three flowering plant species, and aphid honeydew, on the longevity and potential fecundity of C.

Visualizing and Calculating Tip-Substrate Distance in Nanoscale Scanning Electrochemical Microscopy Using 3-Dimensional Super-Resolution Optical Imaging.

We report a strategy for the optical determination of tip-substrate distance in nanoscale scanning electrochemical microscopy (SECM) using three-dimensional super-resolution fluorescence imaging. A phase mask is placed in the emission path of our dual SECM/optical microscope, generating a double helix point spread function at the image plane, which allows us to measure the height of emitting objects relative to the focus of the microscope. By exciting both a fluorogenic reaction at the nanoscale electrode tip as well as fluorescent nanoparticles at the substrate, we are able to calculate the tip-substrate distance as the tip approaches the surface with precision better than 25 nm.

Reduced graphene oxide-nickel nanoparticles/biopolymer composite films for the sub-millimolar detection of glucose.

Hybrid conjugates of graphene with metallic/semiconducting nanostructures can improve the sensitivity of electrochemical sensors due to their combination of well-balanced electrical/electrocatalytic properties and superior surface-to-volume ratio. In this study, the synthesis and physical characterization of a hybrid conjugate of reduced graphene oxide and nickel nanoparticles (rGO-Ni NPs) is presented. The conjugate was further deposited onto a glassy carbon electrode as a nanocomposite film of chitosan and glucose oxidase.

Objective-Induced Point Spread Function Aberrations and Their Impact on Super-Resolution Microscopy.

This study demonstrates how different microscope objectives can lead to asymmetric imaging aberrations in the point spread function of dipolar emitters, which can adversely affect the quality of fit in super-resolution imaging. Luminescence from gold nanorods was imaged with four different objectives to measure the diffraction-limited emission and characterize deviations from the expected dipolar emission patterns. Each luminescence image was fit to a three-dipole emission model to generate fit residuals that visually relay aberrations in the point spread function caused by the different microscope objectives.

Observation of nanometer-sized electro-active defects in insulating layers by fluorescence microscopy and electrochemistry.

We report a method to study electro-active defects in passivated electrodes. This method couples fluorescence microscopy and electrochemistry to localize and size electro-active defects. The method was validated by comparison with a scanning probe technique, scanning electrochemical microscopy.

The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing-of expertise and/or funding-has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies.

Triplet-state-mediated super-resolution imaging of fluorophore-labeled gold nanorods.

Triplet-state-mediated super-resolution imaging was used to map the positions of fluorescently labeled double-stranded DNA bound to the surface of gold nanorods. In order to isolate individual fluorophores bound to the nanorod surface, imaging conditions were optimized such that the majority of the fluorophores were forced into a triplet dark state, and fluorescence from approximately one molecule at a time was detected. The fluorescence from the emitting single molecule was then fit to a two-dimensional (2D) Gaussian to localize its position relative to the nanorod substrate.

Superlocalization surface-enhanced Raman scattering microscopy: comparing point spread function models in the ensemble and single-molecule limits.

In this report, we compare the effectiveness of various dipole and Gaussian point spread function (PSF) models for fitting diffraction-limited surface-enhanced Raman scattering (SERS) emission images from rhodamine 6G-labeled nanoparticle dimers at both the high-concentration and single-molecule limit. Of all models tested, a 3-axis dipole PSF gives the best approximation to the experimental PSF, although none of the models utilized in the study were without systematic error when fitting the experimental data. In the high-concentration regime, all models localize the SERS emission to a stationary centroid position, with the dipole models providing additional orientation parameters that closely match the geometry of the dimer, indicating that the molecules are coupled to all resonant plasmon modes of the nanostructure.