CRISPR-Cas guide RNA indel analysis using CRISPResso2 with Nanopore sequencing data.

Objective: Insertion and deletion (indel) analysis of CRISPR-Cas guide RNAs (gRNAs) is crucial in gene editing to assess gRNA efficiency and indel frequency. This study evaluates the utility of CRISPResso2 with Oxford Nanopore sequencing data (nCRISPResso2) for gRNA indel screening, compared to two common Sanger sequencing-based methods, TIDE and ICE. To achieve this, sheep and horse fibroblasts were transfected with Cas9 and a gRNA targeting the myostatin (MSTN) gene.

Injectable shear-thinning hydrogels promote oligodendrocyte progenitor cell survival and remyelination in the central nervous system.

Cell therapy for the treatment of demyelinating diseases such as multiple sclerosis is hampered by poor survival of donor oligodendrocyte cell preparations, resulting in limited therapeutic outcomes. Excessive cell death leads to the release of intracellular alloantigens, which likely exacerbate local inflammation and may predispose the graft to eventual rejection. Here, we engineered innovative cell-instructive shear-thinning hydrogels (STHs) with tunable viscoelasticity and bioactivity for minimally invasive delivery of primary human oligodendrocyte progenitor cells (hOPCs) to the brain of a mouse, a model of congenital hypomyelinating disease.

Discovery of RXFP2 genetic association in resistant hypertensive men and RXFP2 antagonists for the treatment of resistant hypertension.

Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women.

Dysregulated Cholinergic Signaling Inhibits Oligodendrocyte Maturation Following Demyelination.

Dysregulation of oligodendrocyte progenitor cell (OPC) recruitment and oligodendrocyte differentiation contribute to failure of remyelination in human demyelinating diseases such as multiple sclerosis (MS). Deletion of muscarinic receptor enhances OPC differentiation and remyelination. However, the role of ligand-dependent signaling versus constitutive receptor activation is unknown.

Hepatosplenic Alpha-Beta T-Cell Lymphoma: A Challenging Diagnostic Entity.

Hepatosplenic T-cell lymphoma (HSTCL) is rare and clinically very aggressive T-cell lymphoma. The majority of cases harbor γδ T-cell receptors (TCRs); however, in some even rarer cases, tumor cells harbor αβ TCR. Recent studies suggest that αβ cases may have distinct morphological characteristics and demonstrate an even more aggressive course.

Virus surrogates throughout a full-scale advanced water reuse system.

Water reuse as an alternative water supply is increasing throughout the world due to water stress and scarcity; however, there are no standard practices for monitoring virus pathogens in such systems. This study aimed to identify suitable surrogates for virus fate, transport, and removal throughout a water reuse scheme. Various microbial targets (11 viruses, two phage, and three bacteria) were monitored using molecular and culture methods across all treatment stages in a wastewater reclamation facility and advanced water treatment facility.

Alkaline earth metal-assisted dinitrogen activation at nickel.

Rare examples of trinuclear [Ni-N-M-N-Ni] core (M = Ca, Mg) with linear bridged dinitrogen ligands are reported in this work. The reduction of [PrNN]Ni(μ-Br)Li(thf) (1) (PrNN = 2,4-bis-(2,6-diisopropylphenylimido)pentyl) with elemental Mg or Ca in THF under an atmosphere of dinitrogen yields the complex {PrNNNi(μ-N)}M (thf) (M = Mg, complex 2 and M = Ca, complex 3). The bridging end-on (μ-N)M(thf) moiety connects the two [PrNNNi] nickelate fragments.

Clinical, microbiological and genomic characterization of Gram-negative bacteria with dual carbapenemases as identified by rapid molecular testing.

Objective: Dual carbapenemase-producing organisms (DCPOs) are an emerging threat that expands the spectrum of antimicrobial resistance. There is limited literature on the clinical and genetic epidemiology of DCPOs.

Methods: DCPO isolates were identified by Xpert Carba-R PCR testing of routine diagnostic cultures performed from 2018 to 2021 at a New York City health system.

Antibacterial Efficacy of a Chitosan-Based Hydrogel Modified With Epsilon-Poly-l-Lysine Against Pseudomonas aeruginosa in a Murine-Infected Burn Wound Model.

Introduction: Because antibiotic resistance is increasing worldwide and the leading cause of death in burn patients is an infection, an urgent need exists for nonantibiotic approaches to eliminate multidrug-resistant bacteria from burns to prevent their systemic dissemination and sepsis. We previously demonstrated the significant antibiofilm activity of a chitosan (CS) hydrogel containing the antimicrobial peptide epsilon-poly-l-lysine (EPL) against multidrug-resistant Pseudomonas aeruginosa using ex vivo porcine skin. In this study, we evaluated the in vivo antibacterial efficacy of a CS/EPL hydrogel against P.

[Body composition models based on anthropometry, systematic literature review].

The body composition determination is carried out through measurement methods that require the use of specialized equipment that is difficult to acquire and manipulate. Therefore, different authors have developed mathematical models for its calculation. The target of this review was to analyze the work carried out on mathematical models of body composition variables from different anthropometric measurements, answering the following questions: what is the corporal variable that the model predicts?, what are the input variables for model development?, how is the patients typification in each model?, what data analysis method has been used?, and how has been the model evaluated? The search was limited to journals found in repositories in the areas of Medicine, Nursing, Biochemistry, Biology, Health, Pharmacology, Immunology, Engineering, and Mathematics.

Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants.

Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.

A study of gene expression in the living human brain.

A goal of medical research is to determine the molecular basis of human brain health and illness. One way to achieve this goal is through observational studies of gene expression in human brain tissue. Due to the unavailability of brain tissue from living people, most such studies are performed using tissue from postmortem brain donors.

Automatic Method for Vickers Hardness Estimation by Image Processing.

Hardness is one of the most important mechanical properties of materials, since it is used to estimate their quality and to determine their suitability for a particular application. One method of determining quality is the Vickers hardness test, in which the resistance to plastic deformation at the surface of the material is measured after applying force with an indenter. The hardness is measured from the sample image, which is a tedious, time-consuming, and prone to human error procedure.

Chronic demyelination of rabbit lesions is attributable to failed oligodendrocyte progenitor cell repopulation.

The failure of remyelination in the human CNS contributes to axonal injury and disease progression in multiple sclerosis (MS). In contrast to regions of chronic demyelination in the human brain, remyelination in murine models is preceded by abundant oligodendrocyte progenitor cell (OPC) repopulation, such that OPC density within regions of demyelination far exceeds that of normal white matter (NWM). As such, we hypothesized that efficient OPC repopulation was a prerequisite of successful remyelination, and that increased lesion volume may contribute to the failure of OPC repopulation in human brain.

A Narrative Review of the Pathophysiology and Treatment of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic autosomal dominant disorder of the heart muscle that is characterized by left ventricular hypertrophy and sudden cardiac death. It is the most common inherited cardiac disease. HCM is defined by sarcomeric mutations that result in fibrosis of the heart, affecting contraction.

The Covid-19 impacts on the European Union aquaculture sector.

There have been a number of indications of strong negative impacts of Covid-19 and the preventive measures associated with the pandemic for all food sectors. However, there is increasing evidence that the picture is quite nuanced where the Covid related measures are creating challenges for some and opportunities for others. In this paper we investigate the impacts of Covid-19 on the aquaculture sector in the European Union using two approaches; a survey where industry representatives and experts assess the impacts on key economic indicators allowing for positive as well as negative impacts, and recently published aquaculture production data for Denmark and Spain.

CRISPRi screening reveals regulators of tau pathology shared between exosomal and vesicle-free tau.

The aggregation of the microtubule-associated protein tau is a defining feature of Alzheimer's disease and other tauopathies. Tau pathology is believed to be driven by free tau aggregates and tau carried within exosome-like extracellular vesicles, both of which propagate trans-synaptically and induce tau pathology in recipient neurons by a corrupting process of seeding. Here, we performed a genome-wide CRISPRi screen in tau biosensor cells and identified cellular regulators shared by both mechanisms of tau seeding.

SARS-CoV-2 genetic material is removed during municipal wastewater treatment and is undetectable after advanced treatment.

The aim of this study was to establish whether SARS-CoV-2 genetic material is detectable after municipal wastewater treatment and to verify its expected removal from purified water that is reclaimed for potable reuse. Viral loads of SARS-CoV-2 (N1 and N2 genes) were monitored in raw influent wastewater (sewage) entering a water reclamation facility and in subsequent advanced treatment. Despite the large viral RNA load in raw sewage during peak COVID-19 outbreaks, substantial amounts of SARS-CoV-2 genetic material were removed during the conventional wastewater treatment process.

On the Electronic Structure of 2H-MoS: Correlating DFT Calculations and In-Situ Mechanical Bending on TEM.

We present a systematic density functional theory study to determine the electronic structure of bending 2H-MoS layers up to 75° using information from in-situ nanoindentation TEM observations. The results from HOMO/LUMO and density of states plots indicate a metallic transition from the typical semiconducting phase, near Fermi energy level () as a function of bending, which can mainly occur due to bending curvatures inducing a stretching and contracting of sulfur-sulfur chemical bonds located mostly over basal (001)-plane; furthermore, molybdenum ions play a major role in such transitions due to reallocation of their metallic -character orbitals and the creation of "", possibly having an overlap between Mo and Mo orbitals. This research on the metallic transition of 2H-MoS allows us to understand the high catalytic activity for MoS nanostructures as extensively reported in the literature.

A concerning trend in geriatric pharmacy that merits evidence-based intervention.

The effects of polypharmacy on geriatric populations are an emerging concern that merits more exploration. The primary goal of this review was to evaluate the current body of knowledge on polypharmacy and explore the preventive and corrective measures to avoid negative outcomes. Even if a medication has an appropriate indication, polypharmacy in the geriatric population is associated with an increased risk of drug-drug or drug-condition interactions.

Effects of a Short-Term Heat Acclimation Protocol in Elite Amateur Boxers.

Stone, BL, Ashley, JD, Skinner, RM, Polanco, JP, Walters, MT, Schilling, BK, and Kellawan, JM. Effects of a short-term heat acclimation protocol in elite amateur boxers. J Strength Cond Res 36(7): 1966-1971, 2022-Boxing requires proficient technical and tactical skills coupled with high levels of physiological capacity.

Everybody nose: molecular and clinical characteristics of nasal colonization during active methicillin-resistant Staphylococcus aureus bloodstream infection.

Background: Healthcare-associated infections pose a potentially fatal threat to patients worldwide and Staphylococcus aureus is one of the most common causes of healthcare-associated infections. S. aureus is a common commensal pathogen and a frequent cause of bacteremia, with studies demonstrating that nasal and blood isolates from single patients match more than 80% of the time.

Oscillatory calcium release and sustained store-operated oscillatory calcium signaling prevents differentiation of human oligodendrocyte progenitor cells.

Endogenous remyelination in demyelinating diseases such as multiple sclerosis is contingent upon the successful differentiation of oligodendrocyte progenitor cells (OPCs). Signaling via the Gα-coupled muscarinic receptor (MR) inhibits human OPC differentiation and impairs endogenous remyelination in experimental models. We hypothesized that calcium release following Gα-coupled receptor (GR) activation directly regulates human OPC (hOPC) cell fate.

Vortex clustering, polarisation and circulation intermittency in classical and quantum turbulence.

The understanding of turbulent flows is one of the biggest current challenges in physics, as no first-principles theory exists to explain their observed spatio-temporal intermittency. Turbulent flows may be regarded as an intricate collection of mutually-interacting vortices. This picture becomes accurate in quantum turbulence, which is built on tangles of discrete vortex filaments.

Effect of Steel Fibre Reinforcement on Flexural Fatigue Behaviour of Notched Structural Concrete.

One of the biggest challenges in facilitating the installation of concrete is the development of fibre-reinforced concrete. Although nowadays fibre reinforced concrete is relatively common, it is still necessary to deepen in the study on its behaviour, especially regarding its fatigue behaviour. This paper proposes a new methodology to analyse the bending fatigue behaviour of notched test specimens.