Direct and quantitative analysis of tRNA acylation using intact tRNA liquid chromatography-mass spectrometry.

Aminoacyl-tRNA synthetases (aaRSs) provide an essential functional link between an mRNA sequence and the protein it encodes. aaRS enzymes catalyze a two-step chemical reaction that acylates specific tRNAs with a cognate α-amino acid. In addition to their role in translation, acylated tRNAs contribute to non-ribosomal natural product biosynthesis and are implicated in multiple human diseases.

Anti-IL-4Ra therapy is superior to other biologic classes in treating allergic bronchopulmonary aspergillosis.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to . Initial studies suggest that asthma biologics can effectively treat ABPA, but it is unclear which biologic class is superior.

Objective: We sought to compare the effectiveness of asthma biologics in the treatment of ABPA.

MRI-Based Structural Failure Comparison between Chinese and American White Women With Prolapse: A Case-Control Study.

Introduction And Hypothesis: Although some evidence suggests that Chinese and white women might have different pelvic floor anatomy such as levator complex and connective tissue support for pelvic organs, it is unknown if these differences affect the mechanisms of pelvic organ prolapse. We sought to determine whether differences exist in MRI-based structural failure patterns between Chinese and American white women with prolapse.

Methods: This is a case-control study in different racial cohorts recruited in China and the USA.

Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.

The development of potent, specific, and pharmacologically viable chemical probes and therapeutics is a central focus of chemical biology and therapeutic development. However, a significant portion of predicted disease-causal proteins have proven resistant to targeting by traditional small molecule and biologic modalities. Many of these so-called "undruggable" targets feature extended, dynamic protein-protein and protein-nucleic acid interfaces that are central to their roles in normal and diseased signaling pathways.

Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors.

Many oncogenic transcription factors (TFs) are considered to be undruggable because of their reliance on large protein-protein and protein-DNA interfaces. TFs such as hypoxia-inducible factors (HIFs) and X-box-binding protein 1 (XBP1) are induced by hypoxia and other stressors in solid tumors and bind to unfolded protein response element (UPRE) and hypoxia-induced response element (HRE) motifs to control oncogenic gene programs. Here, we report a strategy to create synthetic transcriptional repressors (STRs) that mimic the basic leucine zipper domain of XBP1 and recognize UPRE and HRE motifs.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

Background: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely.

Nebulized hypertonic saline and positive expiratory pressure device use in patients with bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry.

Background: Nebulized Hypertonic saline (HS) and positive expiratory pressure device (PEP) are often used in patients with bronchiectasis. We sought to describe the clinical characteristics in patients using HS and PEP, utilizing a large national database registry.

Methods: Data from the US Bronchiectasis and NTM Research Registry were used in this study.

Postpartum Changes in Levator Plate Shape and Genital Hiatus Size After Vaginal Delivery.

Introduction And Hypothesis: Vaginal delivery is a risk factor for pelvic organ prolapse. We sought to quantify changes in level III pelvic support measurements at 7 weeks and 8 months following vaginal delivery.

Methods: This secondary analysis included primiparous women who underwent pelvic MRI and clinical examinations at 7 weeks and 8 months after vaginal delivery.

Child and family characteristics in multisystemic therapy for child abuse and neglect (MST-CAN): Are there associations with treatment outcome?

Evidence-based indication for targeted interventions is a central approach in the field of child welfare and psychotherapy. This study explored the characteristics of children and families referred to Multisystemic Therapy for Child Abuse and Neglect (MST-CAN) in Switzerland and their associations with treatment outcomes. We sought to identify subgroups of children and families referred to MST-CAN and understand their specific needs and alignment with the program.

Development of a family-based treatment for co-occurring intimate partner violence and child maltreatment: the MST-IPV model.

Intimate partner violence (IPV) is a significant global problem that affects the health of children, parents/caregivers and extended family. The effects can be lifelong and span generations. Treatments for IPV are focused largely on individual work with men as the primary aggressor.

Spatial Chemoproteomics for Mapping the Active Proteome.

Functional regulation of cell signaling through dynamic changes in protein activity state as well as spatial organization represent two dynamic, complex, and conserved phenomena in biology. Seemingly separate areas of -omics method development have focused on building tools that can detect and quantify protein activity states, as well as map sub-cellular and intercellular protein organization. Integration of these efforts, through the development of chemical tools and platforms that enable detection and quantification of protein functional states with spatial resolution provide opportunities to better understand heterogeneity in the proteome within cell organelles, multi-cellular tissues, and whole organisms.

Overactive Bladder in Late Pregnancy to 1 Year After First Vaginal Delivery.

Importance: Understanding overactive bladder (OAB) during pregnancy and postpartum may increase our knowledge of pathophysiology.

Objectives: The purpose of this study was to understand the prevalence and severity of OAB during pregnancy through 1 year postpartum as well as the associated factors.

Study Design: This is a secondary analysis of a prospective cohort study evaluating primiparous women with a singleton term vaginal delivery assessed at the third trimester, 8 weeks postpartum, and 1 year postpartum.

Characteristics and Presentations of Hospitalized Children Due to 3 Predominate COVID-19 Variants Within a Health Care Network.

Objective of this article is to describe differences in the demographic and clinical characteristics, severity of illness, and outcomes in pediatric patients with different SARS-CoV-2 variants. We conducted a retrospective study of pediatric patients admitted with COVID-19 during the 3 large waves of infection within a health network in New Jersey. We included demographic characteristics, clinical features, and outcomes and compared the data with respect to the different variants.

Elucidating Sequence-Assembly Relationships for Bilingual PNA Biopolymers.

Nucleic acids and proteins possess encoded "languages" that can be used for information storage or to direct function. However, each biopolymer is limited to encoding its respective "language." Using a peptide nucleic acid (PNA) scaffold, nucleobase and amino acid residues can be installed on a singular backbone, enabling a single biopolymer to encode both languages.

BET Inhibitor JQ1 Attenuates Feline Leukemia Virus DNA, Provirus, and Antigen Production in Domestic Cat Cell Lines.

Feline leukemia virus (FeLV) is a cosmopolitan gammaretrovirus that causes lifelong infections and fatal diseases, including leukemias, lymphomas, immunodeficiencies, and anemias, in domestic and wild felids. There is currently no definitive treatment for FeLV, and while existing vaccines reduce the prevalence of progressive infections, they neither provide sterilizing immunity nor prevent regressive infections that result in viral reservoirs with the potential for reactivation, transmission, and the development of associated clinical diseases. Previous studies of murine leukemia virus (MuLV) established that host cell epigenetic reader bromodomain and extra-terminal domain (BET) proteins facilitate MuLV replication by promoting proviral integration.

Nontuberculous mycobacterial (NTM) infections in bronchiectasis patients: A retrospective US registry cohort study.

Rationale: Longitudinal epidemiological and clinical data are needed to improve the management of patients with bronchiectasis developing nontuberculous mycobacterial (NTM) pulmonary disease.

Objectives: To describe the epidemiology, patient management, and treatment outcomes of NTM infections in patients with bronchiectasis enrolled in the United States Bronchiectasis and NTM Research Registry (US BRR).

Methods: This was a retrospective cohort study of patients with bronchiectasis and NTM infections enrolled with follow-up in the US BRR in 2008-2019.

Expanding the substrate scope of pyrrolysyl-transfer RNA synthetase enzymes to include non-α-amino acids in vitro and in vivo.

The absence of orthogonal aminoacyl-transfer RNA (tRNA) synthetases that accept non-L-α-amino acids is a primary bottleneck hindering the in vivo translation of sequence-defined hetero-oligomers and biomaterials. Here we report that pyrrolysyl-tRNA synthetase (PylRS) and certain PylRS variants accept α-hydroxy, α-thio and N-formyl-L-α-amino acids, as well as α-carboxy acid monomers that are precursors to polyketide natural products. These monomers are accommodated and accepted by the translation apparatus in vitro; those with reactive nucleophiles are incorporated into proteins in vivo.

Association Between Genital Hiatus Size 8 Weeks Postpartum and Pelvic Organ Prolapse 1 Year After the First Vaginal Delivery.

Importance: Evidence suggests that genital hiatus (GH) enlargement precedes pelvic organ prolapse development remote from delivery. However, the association of postpartum GH enlargement and prolapse is unknown.

Objective: The aim of this study was to determine the association between enlarged GH at 8 weeks postpartum and prolapse 1 year after first vaginal delivery.

A comparison of MRI-based pelvic floor support measures between young and old women with prolapse.

Introduction And Hypothesis: We sought to 1) test the hypothesis that young women (≤45 years) with pelvic organ prolapse have a higher prevalence of major levator ani muscle (LAM) defects than old women (≥70 years) with prolapse and 2) compare level II/III measurements between young and old women with prolapse and age-matched controls to evaluate age-related mechanistic differences in the disease process.

Methods: A secondary analysis examined four groups of parous women: young prolapse (YPOP, n = 17); old prolapse (OPOP, n = 17); young controls (YC, n = 15); old controls, (OC, n = 13). Prolapse was defined as any compartment at or beyond the hymen with vaginal bulge symptoms.

Biocatalytic control of site-selectivity and chain length-selectivity in radical amino acid halogenases.

Biocatalytic C-H activation has the potential to merge enzymatic and synthetic strategies for bond formation. Fe/αKG-dependent halogenases are particularly distinguished for their ability both to control selective C-H activation as well as to direct group transfer of a bound anion along a reaction axis separate from oxygen rebound, enabling the development of new transformations. In this context, we elucidate the basis for the selectivity of enzymes that perform selective halogenation to yield 4-Cl-lysine (BesD), 5-Cl-lysine (HalB), and 4-Cl-ornithine (HalD), allowing us to probe how site-selectivity and chain length selectivity are achieved.