Perspectives on single-nucleus RNA sequencing in different cell types and tissues

Single-cell RNA sequencing has become a powerful and essential tool for delineating cellular diversity in normal tissues and alterations in disease states. For certain cell types and conditions, there are difficulties in isolating intact cells for transcriptome profiling due to their fragility, large size, tight interconnections, and other factors. Single-nucleus RNA sequencing (snRNA-seq) is an alternative or complementary approach for cells that are difficult to isolate. In this review, we will provide an overview of the experimental and analysis steps of snRNA-seq to understand the methods and characteristics of general and tissue-specific snRNA-seq data. Knowing the advantages and limitations of snRNA-seq will increase its use and improve the biological interpretation of the data generated using this technique

Increased Glutathione Synthesis Following Nrf2 Activation by Vanadyl Sulfate in Human Chang Liver Cells

Jeju ground water, containing vanadium compounds, was shown to increase glutathione (GSH) levels as determined by a colorimetric assay and confocal microscopy. To investigate whether the effects of Jeju ground water on GSH were specifically mediated by vanadium compounds, human Chang liver cells were incubated for 10 passages in media containing deionized distilled water (DDW), Jeju ground water (S1 and S3), and vanadyl sulfate (VOSO4). Vanadyl sulfate scavenged superoxide anion, hydroxyl radical and intracellular reactive oxygen species. Vanadyl sulfate effectively increased cellular GSH level and up-regulated mRNA and protein expression of a catalytic subunit of glutamate cysteine ligase (GCLC), which is involved in GSH synthesis. The induction of GCLC expression by vanadyl sulfate was found to be mediated by transcription factor erythroid transcription factor NF-E2 (Nrf2), which critically regulates GCLC by binding to the antioxidant response elements (AREs). Vanadyl sulfate treatment increased the nuclear translocation of Nrf2 and the accumulation of phosphorylated Nrf2. Extracellular regulated kinase (ERK) contributed to ARE-driven GCLC expression via Nrf2 activation. Vanadyl sulfate induced the expression of the active phospho form of ERK. Taken together, these results suggest that the increase in GSH level by Jeju ground water is, at least in part, due to the effects of vanadyl sulfate via the Nrf2-mediated induction of GCLC

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Endoplasmic reticulum transmembrane protein SCOTIN in the regulation of HCV infection and ER stress

1

Nanoscale Intracortical Iron Injection Induces Chronic Epilepsy in Rodent

We studied the electrophysiological, hemodynamic, and cytomorphological consequences of microhemorrhagic brain injury induced by a nanoscale iron injection. Of particular interest were the etiology, development, and treatment of epilepsy associated with this injury. We developed an animal model of chronic epilepsy using nanoscale injection into the adult mouse cortex. Although injection of nanoamounts of iron did not cause clear cell death or damage in the cortex, it elicited varying degrees of spontaneous epileptiform events that could be recorded under anesthesia 3 months postinjection. The influence of these chronic epileptiform events on neurovascular coupling was probed by directly stimulating the cortex ipsilateral to the epileptic focus and by measuring cerebral blood volume simultaneously in both hemispheres using intrinsic signal optical imaging. The ipsilateral hemodynamic response was dramatically lower in animals that exhibited longer, more frequent epileptiform events, but it was unchanged in animals displaying infrequent, short events. In contrast, the contralateral hemodynamic response was augmented in all iron-injected animals compared with the control group. These abnormal hemodynamic responses in chronically epileptic animals were correlated with the degree of reduction in the number of GABAergic interneurons. Therefore, nanoscale iron injection, which mimics some aspects of microhemorrhagic brain injury, generated chronic, yet varying, degrees of spontaneous epileptiform events. Moreover, the severity of the epileptiform events corresponded to the degree of reduction in GABAergic interneurons in the iron-injected hemisphere and the level of autoregulatory dysfunction of cerebral blood flow. © 2013 Wiley Periodicals, Inc.1341sciescopu

Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients

The inactivation of parkin by mutation or post-translational modification contributes to dopaminergic neuronal death in Parkinson’s disease (PD). The substrates of parkin, FBP1 and AIMP2, are accumulated in the postmortem brains of PD patients, and it was recently suggested that these parkin substrates transcriptionally activate deubiquitinase USP29. Herein, we newly identified 160 kDa myb-binding protein (MYBBP1A) as a novel substrate of USP29. Knockdown of parkin increased the level of AIMP2, leading to ultimately USP29 and MYBBP1A accumulation in SH-SY5Y cells. Notably, MYBBP1A was downregulated in the ventral midbrain (VM) of Aimp2 knockdown mice, whereas the upregulation of MYBBP1A was observed in the VM of inducible AIMP2 transgenic mice, as well as in the substantia nigra of sporadic PD patients. These results suggest that AIMP2 upregulates USP29 and MYBBP1A in the absence of parkin activity, contributing to PD pathogenesis

Facile Synthesis of AuPd Nanochain Networks on Carbon Supports and Their Application as Electrocatalysts for Oxygen Reduction Reaction

The present work reports the facile synthesis and characterization of carbon-supported porous Pd shell coated Au nanochain networks (AuPdNNs/C). By using Co nanoframes as sacrificial templates, AuPdNNs/C series have been prepared by a two-step galvanic replacement reaction (GRR) technique. In the first step, the Au metal precursor, HAuCl4, reacts spontaneously with the formed Co nanoframes through the GRR, resulting in Au nanochain networks (AuNNs). The second GRR is performed with various concentrations of Pd precursor (0.1, 1, and 10mM PdCl2), resulting in AuPdNNs/C. The synthesized AuPdNNs/C series are investigated as electrocatalysts for oxygen reduction reaction (ORR) in alkaline solution. The physical properties of the AuPdNNs/C catalysts are characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), UV-vis absorption spectroscopy, and cyclic voltammetry (CV). Rotating disk electrode (RDE) voltammetric studies show that the Au0.8Pd0.2NNs/C (prepared using 1mM PdCl2) has the highest ORR activity among all the AuPdNNs/C series, which is comparable to commercial Pt catalyst (E-TEK). The ORR activity of AuPdNNs/C is presumably due to the enhanced Pd surface area and high porosity of Pd nanoshells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of Ca-doping in layered perovskite PrBaCo2O5+delta on the phase transition and cathodic performance of a solid oxide fuel cell

Layered perovskite oxides with the formula LnBaCo(2)O(5+delta) (Ln = Pr, Nd, Sm and Gd) have received attention as promising cathode materials for solid oxide fuel cells (SOFCs) because of their high oxygen diffusion and surface exchange coefficients. Recently, many researchers have reported that substituting barium with strontium or calcium can increase the structural stability, electrical conductivity, and catalytic activity of LnBaCo(2)O(5+delta). In this study, we investigated the effect of Ca doping on the structural, electrical, and electrochemical properties of PrBa1-xCaxCo2O5+delta (x = 0, 0.1, 0.2, 0.3 and 0.4). Increasing the amount of Ca dopant changed the structure of PrBa1-xCaxCo2O5+delta from a layered perovskite to a simple perovskite. At x = 0.3, co-existence of the simple and the layered perovskite structure is observed. Electrical conductivity and electro-chemical performance were improved with increasing amount of Ca in the layered perovskite structure and declined with increasing amount of the simple perovskite phase.clos

Degradation of ciprofloxacin and inactivation of ciprofloxacin resistant E. faecium during UV -LED (275 nm)/chlorine process

Ciprofloxacin and ciprofloxacin-resistant bacteria are emerging concerns that threaten public health due to the heavy use of antibiotics and the development of bacterial resistance in water environments. In this study, we examined an energy-efficient treatment driven by a UV-LED/chlorine reaction with UV-LED chip emitting UV275 nm to remove ciprofloxacin and ciprofloxacin-resistant bacteria in water. Ciprofloxacin degradation during the UV-LED/chlorine reaction followed pseudo-first-order kinetics, and the excessive chlorine dosage has a negative effect on ciprofloxacin removal. Alkaline pH showed the best efficiency for ciprofloxacin removal, and the reactive chlorine species (RCS) played a major role at alkaline pH values. The cleavages of piperazine, cyclopropyl, and quinolone moieties are considered as the principal degradation reactions in the UV-LED/chlorine reaction. Seven byproducts (m/z = 362.9262, 306.1246, 289.0995, 288.1504, 263.0825, 147.0657, and 1183.9977), two chlorinated compounds (chloroform and chlorate) and two anions (formate and nitrate ions) were observed as the identified byproducts. Toxicity of tentatively identified byproducts were estimated by using quantitative structure activity relationship (QSAR). The complete detoxification of was achieved when applying UV-LED/chlorine process into hospital wastewater containing CIP. The UV-LED/chlorine process showed the best disinfection ability of E. faecium compared to UV-LED photolysis, chlorination, and UV-LED/H2O2 reactions. A significantly lower EE/O value (6.63 × 10−2 kWh/m3/order) during the UV-LED/chlorine reaction was also observed. Our results indicate that the UV-LED/chlorine process can effectively degrade ciprofloxacin and inactivate ciprofloxacin-resistant bacteria.N

Flexible, Transparent, and Noncytotoxic Graphene Electric Field Stimulator for Effective Cerebral Blood Volume Enhancement

Enhancing cerebral blood volume (CBV) of a targeted area without causing side effects is a primary strategy for treating cerebral hypoperfusion. Here, we report a new nonpharmaceutical and nonvascular surgical method to increase CBV. A flexible, transparent, and skin-like biocompatible graphene electrical field stimulator was placed directly onto the cortical brain, and a noncontact electric field was applied at a specific local blood vessel. Effective CBV increases in the blood vessels of mouse brains were directly observed from <i>in vivo</i> optical recordings of intrinsic signal imaging. The CBV was significantly increased in arteries of the stimulated area, but neither tissue damage nor unnecessary neuronal activation was observed. No transient hypoxia was observed. This technique provides a new method to treat cerebral blood circulation deficiencies at local vessels and can be applied to brain regeneration and rehabilitation