Immune homeostasis requires a balance of inflammatory and suppressive activities. To design cells potentially useful for local immune suppression, we engineered conventional CD4 T cells with synthetic Notch (synNotch) receptors driving antigen-triggered production of anti-inflammatory payloads. Screening a diverse library of suppression programs, we observed the strongest suppression of cytotoxic T cell attack by the production of both anti-inflammatory factors (interleukin-10, transforming growth factor-β1, programmed death ligand 1) and sinks for proinflammatory cytokines (interleukin-2 receptor subunit CD25).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Mitochondrial biogenesis relies on both the nuclear and mitochondrial genomes, and imbalance in their expression can lead to inborn errors of metabolism, inflammation, and aging. Here, we investigate N6AMT1, a nucleo-cytosolic methyltransferase that exhibits genetic codependency with mitochondria. We determine transcriptional and translational profiles of and report that it is required for the cytosolic translation of TRMT10C (MRPP1) and PRORP (MRPP3), two subunits of the mitochondrial RNAse P enzyme.
View Article and Find Full Text PDFIn the world of elite soccer, or football as we call it in the UK, a player who cannot play for any length of time costs the team money and team performance. The time to return to play (RTP) is crucial in any player's career, and the use of ultrasound-guided ultrasound injections has become important in the management of injury. In this article, I will explain the importance of good practice when performing these procedures and the use of steroids, sodium hyaluronic acid, platelet-rich plasma (PRP), and other therapies in achieving the goal of decreasing the time of RTP for the footballer.
View Article and Find Full Text PDFObjective: To quantify differences in levator veli palatini (LVP) muscle dimensions based on age, sex, and race and determine the typical range of asymmetry between the left and right sides of the LVP under age 2.
Design: Retrospective cohort study.
Setting: Children's tertiary care hospital.
In this paper, we investigate the Gaussian graphical model inference problem in a novel setting that we call measurements, referring to irregularly measured or observed data. For graphs, this results in different node pairs having vastly different sample sizes which frequently arises in data integration, genomics, neuroscience, and sensor networks. Existing works characterize the graph selection performance using the minimum pairwise sample size, which provides little insights for erosely measured data, and no existing inference method is applicable.
View Article and Find Full Text PDFAir pollution from residential wood heating (RWH) presents challenges at the intersection of climate and public health. With a revised National Ambient Air Quality Standard (NAAQS, at 9 μg/m) for particulate matter (PM) in the United States (U.S.
View Article and Find Full Text PDFProtein Eng Des Sel
January 2024
Antibodies play a crucial role in monitoring post-translational modifications, like phosphorylation, which regulates protein activity and location; however, commercial polyclonal and monoclonal antibodies have limitations in renewability and engineering compared to recombinant affinity reagents. A scaffold based on the Forkhead-associated domain (FHA) has potential as a selective affinity reagent for this post-translational modification. Engineered FHA domains, termed phosphothreonine-binding domains (pTBDs), with limited cross-reactivity were isolated from an M13 bacteriophage display library by affinity selection with phosphopeptides corresponding to human mTOR, Chk2, 53BP1, and Akt1 proteins.
View Article and Find Full Text PDFPurpose: The purpose of the present study is to (a) provide quantitative data on the growth of levator veli palatini (LVP), velopharyngeal (VP), and craniofacial dimensions in children under 12 months while controlling for corrected age and sex and (b) compare variability within age and sex groups.
Method: Magnetic resonance imaging scans of 75 infants between 0 and 12 months were measured and divided into four age groups. These data were obtained as part of a larger retrospective study.
Objectives: We previously derived the updated Pediatric Sepsis Biomarker Risk for Acute Kidney Injury (PERSEVERE-II AKI) prediction model, which had robust diagnostic test characteristics for severe AKI on day 3 (D3 severe AKI) of septic shock. We now sought to validate this model in an independent cohort of children to the one in which the model was developed.
Design: A secondary analysis of a multicenter, prospective, observational study carried out from January 2019 to December 2022.
Objective: There are inconsistent reports of factors relating to injury, illness and tactical performance in law enforcement recruits. Our objectives were to: (1) report physical and psychological risk factors and protective factors for injury and illness and (2) report physical and psychological risk factors and protective factors for tactical performance success.
Design: Systematic epidemiological review.
Purpose: To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA -mutated non-small cell lung cancer (NSCLC).
Patients And Methods: This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) -mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469).
Objective: To evaluate rebiopsy rates and clinicopathologic outcomes in patients after a negative MRI-guided biopsy to better inform the management of these patients.
Methods: Patients were included with a clinical suspicion of prostate cancer (PCa) referred for fusion biopsy for a PI-RADS v2.1 lesion ≥ 3 on multiparametric MRI and a negative MRI fusion biopsy.
Background And Objectives: Alarms at hospitals are frequent and can lead to alarm fatigue posing patient safety risks. We aimed to describe alarm burden over a 1-year period and explored variations in alarm rates stratified by unit type, alarm source, and cause.
Methods: A retrospective study of inpatient alarm and patient census data at 1 children's hospital from January 1, 2019, to December 31, 2019, including 8 inpatient units: 6 medical/surgical unit (MSU), 1 PICU, and 1 NICU.
Background And Objectives: Few data exist to guide optimal communication practices for surgical oncologists. VitalTalk, an evidence-based communication skills training model for clinicians, offers the five-step ADAPT tool for discussing prognosis. This study aimed to characterize surgeon communication of pancreatic cancer prognosis using VitalTalk's ADAPT framework.
View Article and Find Full Text PDFAtmospheric CO and temperature are rising concurrently, and may have profound impacts on the transcriptional, physiological and behavioural responses of aquatic organisms. Further, spring snowmelt may cause transient increases of pCO in many freshwater systems. We examined the behavioural, physiological and transcriptomic responses of an ancient fish, the lake sturgeon (Acipenser fulvescens) to projected levels of warming and pCO during its most vulnerable period of life, the first year.
View Article and Find Full Text PDFRNA helicases-central enzymes in RNA metabolism-often feature intrinsically disordered regions (IDRs) that enable phase separation and complex molecular interactions. In the bacterial pathogen Pseudomonas aeruginosa, the non-redundant RhlE1 and RhlE2 RNA helicases share a conserved REC catalytic core but differ in C-terminal IDRs. Here, we show how the IDR diversity defines RhlE RNA helicase specificity of function.
View Article and Find Full Text PDFBacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus.
View Article and Find Full Text PDFAccurate quantification of methane emissions from landfills is crucial for improving greenhouse gas inventories and mitigating climate change impacts. Existing methodologies, such as theoretical gas production models and labour-intensive measurement approaches, present limitations including large uncertainties and high operational costs. This study adds to a growing body of research and applications which aim to bridge this gap.
View Article and Find Full Text PDFObjectives: Compare the feeding management practices in infants with cleft palate with and without Pierre Robin sequence (PRS) and determine if specific feeding difficulties or interventions predict delayed palate repair.
Design: Retrospective cross-sectional study.
Setting: Seventeen cleft palate teams contributed data.
Comp Biochem Physiol A Mol Integr Physiol
June 2024
The excretory mechanisms of stenohaline marine osmoconforming crabs are often compared to those of the more extensively characterized euryhaline osmoregulating crabs. These comparisons may have limitations, given that unlike euryhaline brachyurans the gills of stenohaline marine osmoconformers possess ion-leaky paracellular pathways and lack the capacity to undergo ultrastructural changes that can promote ion-transport processes in dilute media. Furthermore, the antennal glands of stenohaline marine osmoconformers are poorly characterized making it difficult to determine what role urinary processes play in excretion.
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