Interferons (IFNs) are one of the hallmarks of host antiviral immunity. IFNs exert their antiviral activities through the induction of IFN-stimulated genes (ISGs) and antiviral proteins; however, the mechanism by which ISGs inhibit adenovirus (Ad) replication is not clearly understood. IFNs repress Ad immediate early gene expression and, consequently, all subsequent aspects of the viral life cycle.
View Article and Find Full Text PDFObjective: Children born preterm are at increased risk for autism spectrum disorder (ASD). However, early diagnosis of ASD is challenging because conventional screening Level 1 tools are less reliable in this population. We sought to determine whether the Autism Detection in Early Childhood (ADEC) and Child Behavior Checklist (CBCL) could accurately identify children at risk for ASD in a NICU Follow-up setting and thus facilitate referral for formal ASD evaluation.
View Article and Find Full Text PDFMolecular virology tools are critical for basic studies of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. Experimental systems that do not rely on viruses capable of spread are needed for potential use in lower-containment settings. In this work, we use a yeast-based reverse genetics system to develop spike-deleted SARS-CoV-2 self-replicating RNAs.
View Article and Find Full Text PDFDuring voluntary contractions, limb muscle motor unit (MU) firing rates accelerate over a small force range and saturate in response to increasing contraction intensity. In comparison, facial muscles are cranially innervated, and some function without crossing joints. Therefore, the MU firing rate behaviour and characteristics of saturation were explored in a facial muscle that moves skin and facia during voluntary contractions.
View Article and Find Full Text PDFBiotherapeutics are an important class of molecules for the treatment of a wide range of diseases. They include low molecular weight peptides, highly engineered protein scaffolds and monoclonal antibodies. During their discovery and development, assessments of the biophysical attributes is critical to understanding the solution behavior of therapeutic proteins and for de-risking liabilities.
View Article and Find Full Text PDFDiimine metal complexes have significant relevance in the development of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) applications. In particular, complexes of the TAP ligand (1,4,5,8-tetraazaphenanthrene) are known to lead to photoinduced oxidation of DNA, while TAP- and triazole-based complexes are also known to undergo photochemical ligand release processes relevant to PACT. The photophysical and photochemical properties of heteroleptic complexes [Ru(TAP)(btz)] (btz = 1,1'-dibenzyl-4,4'-bi-1,2,3-triazolyl, = 1 (), 2 ()) have been explored.
View Article and Find Full Text PDFNew Findings: What is the central question of this study? Is the degree of in human muscle affected by different shortening velocities, or contraction type? What are the main findings and their importance? The PAP response following maximal concentric contractions was independent of velocity. Slow and moderate velocity maximal contractions produced PAP responses like those from maximal isometric contractions when matched for contraction duration. Despite contraction type differences in cross-bridge and Ca kinetics, maximal contractions, regardless of contraction modality, likely generate sufficient Ca to induce maximal PAP.
View Article and Find Full Text PDFMonoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease. Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-19. Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19.
View Article and Find Full Text PDFObjectives: Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case-control study assessed the contribution of genetics and exposure in the development of BeS and CBD.
Methods: Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities.
Objective: An Abdominal aortic aneurysm (AAA), a deadly disease in elderly population, is featured by expansion of aortic diameter, degradation and weakening of vasculature. Its common and significant characteristics are disarray and inflammation in vasculature. We tested the hypothesis that the reversal of abdominal aortic aneurysm by pentagalloyl glucose-loaded nanoparticles (PGG-NPs) therapy that targets degraded elastin suppresses inflammatory and immune markers to ameliorate the pathophysiology of the disease in advance stage aneurysm in a porcine pancreatic elastase (PPE)-induced mouse model of AAA.
View Article and Find Full Text PDFWith effects of aging, voluntary neural drive to the muscle, measured as motor unit (MU) firing rate, is lower in older adults during sustained isometric contractions compared with young adults, but differences remain unknown during limb movements. Therefore, our purpose was to compare MU firing rates during both isometric and shortening contractions between two adult age groups. We analyzed intramuscular electromyography of single-MU recordings in the anconeus muscle of young ( = 8, 19-33 yr) and very old ( = 13, 78-93 yr) male adults during maximal voluntary contractions (MVCs).
View Article and Find Full Text PDFGlobal and related pathogen infections are increasing, and place both wildlife species and humans at risk. Notably, is now considered to be an emerging and zoonotic pathogen. Mouse monoclonal antibodies (mAbs) were generated against bull shark, , and spotted eagle ray, , IgM, and bottlenose dolphin, , IgG.
View Article and Find Full Text PDFThe current study investigated the antioxidant capacity of enzymatically cleaved low acyl gellan gum (LA-GAGR) fragments, named midi-GAGR (MW : 1.2 × 10 Da) and mini-GAGR (MW : 2.5 × 10 Da).
View Article and Find Full Text PDFBackground: It is unclear whether the patient's perception of attending physician empathy and the patient's satisfaction can be affected when attending physicians work alongside residents. We aim to determine the influence residents may have on (1) patient perception of attending physician empathy and (2) patient satisfaction as it relates to their respective attending physicians.
Methods: This is a prospective single-center observational study.
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.
View Article and Find Full Text PDFBackground: Non-White children with developmental disabilities are frequently identified later than White children and therefore miss out on opportunities for early intervention (EI). Recent research indicates that conjoint monitoring and screening is more strongly associated with EI receipt than monitoring or screening alone.
Objective: To determine if there are racial/ethnic inequities in the conjoint receipt of monitoring and screening.
Noncanonical inflammasome activation by cytosolic lipopolysaccharide (LPS) is a critical component of the host response to Gram-negative bacteria. Cytosolic LPS recognition in macrophages is preceded by a Toll-like receptor (TLR) priming signal required to induce transcription of inflammasome components and facilitate the metabolic reprograming that fuels the inflammatory response. Using a genome-scale arrayed siRNA screen to find inflammasome regulators in mouse macrophages, we identified the mitochondrial enzyme nucleoside diphosphate kinase D (NDPK-D) as a regulator of both noncanonical and canonical inflammasomes.
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