Renewal of the catecholamine-secreting chromaffin cell population of the adrenal medulla is necessary for physiological homeostasis throughout life. Definitive evidence for the presence or absence of an adrenomedullary stem cell has been enigmatic. In this work, we demonstrate that a subset of sustentacular cells endowed with a support role, are in fact adrenomedullary stem cells.
View Article and Find Full Text PDFTranscription initiation involves the coordination of multiple events, starting with activators binding specific DNA target sequences, which recruit transcription coactivators to open chromatin and enable binding of general transcription factors and RNA polymerase II to promoters. Two key human transcriptional coactivator complexes, ATAC (ADA-two-A-containing) and SAGA (Spt-Ada-Gcn5 acetyltransferase), containing histone acetyltransferase (HAT) activity, target genomic loci to increase promoter accessibility. To better understand the function of ATAC and SAGA HAT complexes, we used in vitro biochemical and biophysical assays to characterize human ATAC and SAGA HAT module interactions with nucleosomes and how a transcription factor (TF) coordinates these interactions.
View Article and Find Full Text PDFAim: Paediatricians using instant messaging phone apps for informal medical discussions poses ethical and legal risks. We filled a gap in the research, by assessing the use of apps and the possible risks.
Methods: A national, cross-sectional, questionnaire study was conducted in Israel from 11 August to 20 November 2019.
Patients with ureteral stones are often managed with a spontaneous trial of passage. While cost effective, the current literature has not examined the effects of a trial of passage on patients' work productivity. In this study, we aim to characterize work absence and productivity losses in a cohort of patients undergoing a trial of passage for ureteral stones.
View Article and Find Full Text PDFEfficient genome editing by using CRISPR technologies requires simultaneous and efficient delivery of multiple genetically encoded components to mammalian cells. Amongst all editing approaches, prime editing (PE) has the unique potential to perform seamless genome rewriting, in the absence of DNA double-strand breaks (DSBs). The cargo capacity required for efficient PE delivery to mammalian cells stands at odd with the limited packaging capacity of traditional viral delivery vectors.
View Article and Find Full Text PDFBackground: Indwelling catheterization following radical prostatectomy is used to aid healing and urinary drainage. While early removal is well investigated, prolonged catheterization has only been investigated in terms of urinary incontinence. Other complications such as anastomotic strictures are unexplored so far.
View Article and Find Full Text PDFChildren with attention-deficit/hyperactivity disorder show deficits in processing speed, as well as aberrant neural oscillations, including both periodic (oscillatory) and aperiodic (1/f-like) activity, reflecting the pattern of power across frequencies. Both components were suggested as underlying neural mechanisms of cognitive dysfunctions in attention-deficit/hyperactivity disorder. Here, we examined differences in processing speed and resting-state-Electroencephalogram neural oscillations and their associations between 6- and 12-year-old children with (n = 33) and without (n = 33) attention-deficit/hyperactivity disorder.
View Article and Find Full Text PDFTriple-negative breast cancer (TNBC) is characterised by its aggressiveness and resistance to chemotherapy, demanding the development of effective strategies against its unique characteristics. Derived from lapacho tree bark, β-lapachone (β-LP) selectively targets cancer cells with elevated levels of the detoxifying enzyme NQO1. Hydroxytyrosol (HT) is a phenolic compound derived from olive trees with important anticancer properties that include the inhibition of cancer stem cells (CSCs) and metastatic features in TNBC, as well as relevant antioxidant activities by mechanisms such as the induction of NQO1.
View Article and Find Full Text PDFInsect Conserv Divers
March 2023
Entomology is key to understanding terrestrial and freshwater ecosystems at a time of unprecedented anthropogenic environmental change and offers substantial untapped potential to benefit humanity in a variety of ways, from improving agricultural practices to managing vector-borne diseases and inspiring technological advances.We identified high priority challenges for entomology using an inclusive, open, and democratic four-stage prioritisation approach, conducted among the membership and affiliates (hereafter 'members') of the UK-based Royal Entomological Society (RES).A list of 710 challenges was gathered from 189 RES members.
View Article and Find Full Text PDFCRISPR-based DNA editing technologies enable rapid and accessible genome engineering of eukaryotic cells. However, the delivery of genetically encoded CRISPR components remains challenging and sustained Cas9 expression correlates with higher off-target activities, which can be reduced via Cas9-protein delivery. Here we demonstrate that baculovirus, alongside its DNA cargo, can be used to package and deliver proteins to human cells.
View Article and Find Full Text PDFAttention deficit and hyperactivity disorder (ADHD) affects many life aspects of children and adults. Accurate identification, diagnosis and treatment of ADHD can facilitate better care. However, ADHD diagnosis and treatment methods are subject of controversy.
View Article and Find Full Text PDFAdenovirus-derived nanoparticles (ADDomer) comprise 60 copies of adenovirus penton base protein (PBP). ADDomer is thermostable, rendering the storage, transport, and deployment of ADDomer-based therapeutics independent of a cold chain. To expand the scope of ADDomers for new applications, we engineered ADDobodies, representing PBP crown domain, genetically separated from PBP multimerization domain.
View Article and Find Full Text PDFSnakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom-polyclonal antibodies isolated from the plasma of hyperimmunised animals-which is associated with numerous deficiencies.
View Article and Find Full Text PDFBackground: Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens.
Methods: Here, we developed an integrated approach combining synthetic, computational and structural methods with antibody selection and immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Results: Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs).
Nat Struct Mol Biol
November 2023
To understand how the nucleosome remodeling and deacetylase (NuRD) complex regulates enhancers and enhancer-promoter interactions, we have developed an approach to segment and extract key biophysical parameters from live-cell three-dimensional single-molecule trajectories. Unexpectedly, this has revealed that NuRD binds to chromatin for minutes, decompacts chromatin structure and increases enhancer dynamics. We also uncovered a rare fast-diffusing state of enhancers and found that NuRD restricts the time spent in this state.
View Article and Find Full Text PDFIntroduction: Rural patients lack access to urological services, and high local prices may dissuade underinsured patients from surgery. We sought to describe commercially insured prices for 3 urological procedures at rural vs metropolitan and for-profit vs nonprofit hospitals.
Methods: A cross-sectional analysis of commercially insured prices from the Turquoise Health Transparency data set was performed for ureteroscopy with laser lithotripsy, transurethral resection of bladder tumor, and transurethral resection of prostate.
Introduction: Mild intellectual disability or borderline intellectual functioning (MID/BIF) are common in people with severe mental health problems (SMHP). Despite this, there is a lack of treatments adapted for this group of clients.
Methods: This qualitative study describes the development of a new intervention, guided by the principles of action research, for people with SMHP and MID/BIF and mental health professionals to help them talk about all aspects of the process of recovery.
Non-invasive brain stimulation has been suggested as a potential treatment for improving symptomology and cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD), the most common childhood neurodevelopmental disorder. Here, we examined whether a novel form of stimulation, high-frequency transcranial random noise stimulation (tRNS), applied with cognitive training (CT), may impact symptoms and neural oscillations in children with ADHD. We conducted a randomized, double-blind, sham-controlled trial in 23 unmedicated children with ADHD, who received either tRNS over the right inferior frontal gyrus (rIFG) and left dorsolateral prefrontal cortex (lDLPFC) or sham stimulation for 2 weeks, combined with CT.
View Article and Find Full Text PDFObjective: The reflux pathophysiology of the saphenofemoral junction (SFJ) of the insufficient great saphenous vein (GSV) has already been investigated and stratified. These results are still lacking for the small saphenous vein (SSV). The aim of the study was to analyze the pathophysiology of the saphenopopliteal junction (SPJ) in case of refluxing SSV.
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