The ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates.
View Article and Find Full Text PDFEukaryotic chromosome segregation requires kinetochores, multi-megadalton protein machines that assemble on the centromeres of chromosomes and mediate attachments to dynamic spindle microtubules. Kinetochores are built from numerous complexes, and understanding how they are arranged is key to understanding how kinetochores perform their multiple functions. However, an integrated understanding of kinetochore architecture has not yet been established.
View Article and Find Full Text PDFMany teleosts possess a unique set of respiratory characteristics allowing enhanced oxygen unloading to the tissues during stress. This system comprises three major components: highly pH sensitive haemoglobins (large Bohr and Root effects), rapid red blood cell (RBC) intracellular pH (pHi) protection, and a heterogeneous distribution of membrane-bound plasma-accessible carbonic anhydrase (paCA; absence in the gills). The first two components have received considerable research effort; however, the evolutionary loss of branchial paCA has received little attention.
View Article and Find Full Text PDFObjective: To reveal barriers and opportunities to implement evidence for the management of pediatric kidney stone disease, we determined surgeon and institutional factors associated with preferences for the type of surgical intervention for kidney and ureteral stones.
Methods: We conducted a cross-sectional study of urologists participating in the Pediatric KIDney Stone Care Improvement Network (PKIDS) trial. Questionnaires ascertained strengths of urologists' preferences for types of surgery as well as characteristics of participating urologists and institutions.
IEEE Trans Instrum Meas
December 2023
In this article, we present a four-channel direct digital synthesis (DDS) design that operates with a common clock ranging from 500 MHz to 24 GHz and generates output frequencies up to 1.75 GHz. A key feature of this board is its custom field-programmable gate array (FPGA)-based synchronization method, which ensures alignment accuracy of 170 ps between the channels, enabling precise frequency and phase relationship settings.
View Article and Find Full Text PDFHigh-coverage sequencing allows the study of variants occurring at low frequencies within samples, but is susceptible to false-positives caused by sequencing error. Ion Torrent has a very low single nucleotide variant (SNV) error rate and has been employed for the majority of human papillomavirus (HPV) whole genome sequences. However, benchmarking of intrahost SNVs (iSNVs) has been challenging, partly due to limitations imposed by the HPV life cycle.
View Article and Find Full Text PDFBackground: People who use opioids (PWUO) are at increased risk for HIV. Pre-exposure prophylaxis (PrEP) is effective but underutilized as HIV prevention among PWUO. This study examined predictors of willingness to take daily oral PrEP and long-acting injectable (LAI) PrEP among PWUO across eight Southern urban cities with high HIV incidence.
View Article and Find Full Text PDFIntroduction: Breast tumors often display an astonishing degree of spatial and temporal heterogeneity, which are associated with cancer progression, drug resistance, and relapse. Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous subtype for which targeted therapies are scarce. Consequently, patients with TNBC have a poorer overall prognosis compared to other breast cancer patients.
View Article and Find Full Text PDFPurpose: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy.
Methods: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.
Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states.
View Article and Find Full Text PDFBackground: Opioid use prior to total joint arthroplasty may be associated with poorer postoperative outcomes. However, few studies have reported the impact on postoperative recovery of mobility. We hypothesized that chronic opioid users would demonstrate impaired objective and subjective mobility recovery compared to nonusers.
View Article and Find Full Text PDFObjectives: Male rectal and anal cancer patients demonstrate high rates of sexual dysfunction. This pilot randomized controlled trial tested a psychoeducational intervention designed to improve psychosexual adjustment.
Methods: Rectal or anal cancer patients were randomized to a Sexual Health Intervention for Men (intervention) or to a referral and information control (control).
Identification of Alzheimer's disease (AD) onset risk can facilitate interventions before irreversible disease progression. We demonstrate that electronic health records from the University of California, San Francisco, followed by knowledge networks (for example, SPOKE) allow for (1) prediction of AD onset and (2) prioritization of biological hypotheses, and (3) contextualization of sex dimorphism. We trained random forest models and predicted AD onset on a cohort of 749 individuals with AD and 250,545 controls with a mean area under the receiver operating characteristic of 0.
View Article and Find Full Text PDFIn this edition of Mythbusters, we examine the premise that prevalence of vesicoureteral reflux (VUR) in children varies by race. Specifically, we consider whether there is evidence supporting the contention that VUR is more common in White children and less common in Black children. Statements regarding the lower prevalence of VUR in Black children are ubiquitous in both research papers and reviews.
View Article and Find Full Text PDFHuman cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy.
View Article and Find Full Text PDFExposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. As these outcomes are related to alterations in developmental processes, growing evidence suggests that deficits in executive functions-inhibitory control in particular-may, in part, explain this relationship. However, literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how low resource settings might exacerbate the link between inhibitory control and health outcomes.
View Article and Find Full Text PDFThe following cases demonstrate a proof of concept for the safe and effective use of the glucagon-like-peptide-1 receptor agonist (GLP-1 RA) semaglutide for weight loss in obese, non-diabetic, end stage kidney disease (ESKD) patients on haemodialysis (HD), who are unable to undergo renal transplantation due to obesity. Obesity is a common barrier to wait-listing for renal transplantation with effective, broadly applicable weight loss strategies lacking. GLP-1 RAs have been shown to be effective adjuncts to achieve weight loss in non-diabetic obese people.
View Article and Find Full Text PDFSoil biocrusts are characterized by the spatial self-organization of resident microbial populations at small scales. The cyanobacterium Microcoleus vaginatus, a prominent primary producer and pioneer biocrust former, relies on a mutualistic carbon (C) for nitrogen (N) exchange with its heterotrophic cyanosphere microbiome, a mutualism that may be optimized through the ability of the cyanobacterium to aggregate into bundles of trichomes. Testing both environmental populations and representative isolates, we show that the proximity of mutualistic diazotroph populations results in M.
View Article and Find Full Text PDFBackground: Chronic kidney disease affects more than 10% of the world's population and is a non-communicable disease of global concern and priority. There is a significant implementation gap between best practice guideline recommendations and current kidney disease management. Previous research has shown the need to partner with primary care to improve education, collaboration, and kidney disease awareness.
View Article and Find Full Text PDFThis educational article highlights the critical role of pediatric urology nursing research in improving the care of children with urological conditions. It discusses the multifaceted nature of pediatric urology nursing, addresses challenges such as limited nurse scientists and resource constraints, and highlights the need to overcome barriers to increase research involvement. The authors emphasize the importance of prioritizing research areas, the promotion of collaboration, and the provision of adequate funding and academic time for pediatric nurses to contribute to evidence-based practice, to improve patient outcomes.
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