Combining computational modeling and experimental library screening to affinity-mature VEEV-neutralizing antibody F5.

Engineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand-up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of F5, a monoclonal antibody with potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), to recombinant VEEV (IAB) E1E2 antigen.

Flow cytometric measurement of CFTR-mediated chloride transport in human neutrophils.

Immune cells express a variety of ion channels and transporters in the plasma membrane and intracellular organelles, responsible of the transference of charged ions across hydrophobic lipid membrane barriers. The correct regulation of ion transport ensures proper immune cell function, activation, proliferation, and cell death. Cystic fibrosis (CF) is a genetic disease in which the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel gene is defective, consequently, the CFTR protein is dysfunctional, and the chloride efflux in CF cells is markedly impaired.

Too Soon to Breathe Easy: Trends in Asbestosis Morbidity and Mortality in Wisconsin.

Objectives: This study aimed to describe asbestosis morbidity and mortality in two statewide samples. We considered trends, demographic disparities, and excess mortality.

Methods: We assessed trends and demographic differences in asbestosis morbidity using hospital and emergency department (ED) visits.

A scoping review of applied tick control research in North America: funding, implementation, and advancement.

Geographic ranges of ticks and tick-borne pathogens within North America are shifting due to environmental changes and human-driven activities, with species of public health concern presenting a multifaceted risk to human health. Innovative strategies and continued collaboration to control tick populations are needed to combat this growing threat. We conducted a scoping review of the literature to describe the nature of applied tick control research conducted in North America (Canada, Mexico, and the United States) to date, with the goal of describing key concepts and identifying gaps in this research area.

T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota.

How the gut microbiota and immune system maintain intestinal homeostasis in concert with the enteric nervous system (ENS) remains incompletely understood. To address this gap, we assessed small intestinal transit, enteric neuronal density, enteric neurogenesis, intestinal microbiota, immune cell populations and cytokines in wildtype and T-cell deficient germ-free mice colonized with specific pathogen-free (SPF) microbiota, conventionally raised SPF and segmented filamentous bacteria (SFB)-monocolonized mice. SPF microbiota increased small intestinal transit in a T cell-dependent manner.

Early life microbiota colonization programs nociceptor sensitivity by regulating NGF production in mast cells.

Recent evidence suggests that the gut microbiota can influence pain sensitivity, highlighting the potential for microbiota-targeted pain interventions. During early life, both the microbiota and nociceptors are fine-tuned and respond to environmental factors, however, little is known about how they interact with each other. Using germ-free and gnotobiotic models, we demonstrate that microbiota colonization controls nociceptor sensitivity, partly by modulating mast cell production of nerve growth factor (NGF).

Association Between Employment Factors and Prevalence of Cardiovascular Disease in US Law Enforcement Workers: The National Health Interview Survey, 2006-2018.

Background: Law enforcement workers face a higher risk of cardiovascular disease (CVD), however, employment factors impacting CVD remain systematically understudied, particularly in a national US sample. We describe temporal trends in prevalent CVD including coronary heart disease (CHD), angina, myocardial infarction (MI) and other heart disease; and investigate associations of select employment factors with CVD among law enforcement workers using the National Health Interview Survey (NHIS) from 2006 to 2018.

Methods: We analyzed prevalent CVD in law enforcement workers employed in local, state, and federal establishments using the NHIS, a nationally representative sample of US workers.

Kupffer cell reverse migration into the liver sinusoids mitigates neonatal sepsis and meningitis.

In adults, liver-resident macrophages, or Kupffer cells (KCs), reside in the sinusoids and sterilize circulating blood by capturing rapidly flowing microbes. We developed quantitative intravital imaging of 1-day-old mice combined with transcriptomics, genetic manipulation, and in vivo infection assays to interrogate increased susceptibility of newborns to bloodstream infections. Whereas 1-day-old KCs were better at catching in vitro, we uncovered a critical 1-week window postpartum when KCs have limited access to blood and must translocate from liver parenchyma into the sinusoids.

Edinburgh postnatal depression scale score elevation in caregivers of infants with cystic fibrosis.

Introduction: The diagnosis of cystic fibrosis (CF) can impact the mental health of caregivers. This study aimed to explore prevalence of postpartum depression (PPD) symptoms in caregivers of infants with CF or CFTR-related metabolic syndrome (CRMS).

Methods: This prospective, observational study was conducted in a CF clinic at a tertiary hospital over 4 years.

Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.

Background: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner.

Spatial variation of mercury contamination in yellow-legged gulls (Larus michahellis) in the Western Mediterranean.

Mercury (Hg) is a global pollutant of major concern in marine and coastal environments. In the Mediterranean Sea, Hg concentrations in biota are higher than in other seas, even when seawater concentrations are similar. Seabirds, as marine top predators, can reflect Hg contamination on a large spatial scale.

Deletion of endocannabinoid synthesizing enzyme DAGLα from cerebellar Purkinje cells decreases social preference and elevates anxiety.

The endocannabinoid (eCB) signaling system is robustly expressed in the cerebellum starting from the embryonic developmental stages to adulthood. There it plays a key role in regulating cerebellar synaptic plasticity and excitability, suggesting that impaired eCB signaling will lead to deficits in cerebellar adjustments of ongoing behaviors and cerebellar learning. Indeed, human mutations in are associated with neurodevelopmental disorders.

Mercury contamination and potential health risk to French seabirds: A multi-species and multi-site study.

Mercury (Hg) is a naturally occurring highly toxic element which circulation in ecosystems has been intensified by human activities. Hg is widely distributed, and marine environments act as its main final sink. Seabirds are relevant bioindicators of marine pollution and chicks are particularly suitable for biomonitoring pollutants as they reflect contamination at short spatiotemporal scales.

A comparison of antibody-antigen complex sequence-to-structure prediction methods and their systematic biases.

The ability to accurately predict antibody-antigen complex structures from their sequences could greatly advance our understanding of the immune system and would aid in the development of novel antibody therapeutics. There have been considerable recent advancements in predicting protein-protein interactions (PPIs) fueled by progress in machine learning (ML). To understand the current state of the field, we compare six representative methods for predicting antibody-antigen complexes from sequence, including two deep learning approaches trained to predict PPIs in general (AlphaFold-Multimer and RoseTTAFold), two composite methods that initially predict antibody and antigen structures separately and dock them (using antibody-mode ClusPro), local refinement in Rosetta (SnugDock) of globally docked poses from ClusPro, and a pipeline combining homology modeling with rigid-body docking informed by ML-based epitope and paratope prediction (AbAdapt).

Automatic vessel attenuation measurement for quality control of contrast-enhanced CT: Validation on the portal vein.

Background: Adequate image enhancement of organs and blood vessels of interest is an important aspect of image quality in contrast-enhanced computed tomography (CT). There is a need for an objective method for evaluation of vessel contrast that can be automatically and systematically applied to large sets of CT exams.

Purpose: The purpose of this work was to develop a method to automatically segment and measure attenuation Hounsfield Unit (HU) in the portal vein (PV) in contrast-enhanced abdomen CT examinations.

Coumarin-Based Aldo-Keto Reductase Family 1C (AKR1C) 2 and 3 Inhibitors.

A series of 7-substituted coumarin derivatives have been characterized as pan-aldo-keto reductase family 1C (AKR1C) inhibitors. The AKR1C family of enzymes are overexpressed in numerous cancers where they are involved in drug resistance development. 7-hydroxy coumarin ethyl esters and their corresponding amides have high potency for AKR1C3 and AKR1C2 inhibition.

Sleep, Emotional, and Behavioral Problems Among Youth Presenting to Treatment Following Sexual Abuse.

Research indicates that sleep problems are fairly common in childhood. However, the relationship between child sexual abuse (CSA) and sleep problems and how sleep issues influence psychological symptoms in children presenting for treatment remain unclear. The purpose of this study was to examine the presence of sleep problems and the association between sleep problems and psychological symptoms in youth presenting to treatment following CSA.

Innate immune responses are increased in children with acute asthma exacerbation.

Background: Little is known about the immune responses during acute asthma exacerbation. In this study, we examined immune responses in children following an acute asthma exacerbation.

Methods: We evaluated pro-inflammatory cytokine levels and gene expression profiles in blood samples from pediatric patients admitted for acute asthma exacerbation.

4D SPECT/CT: A Hybrid Approach to Primary Hyperparathyroidism.

Our rationale was to review the imaging options for patients with primary hyperparathyroidism and to advocate for judicious use of 4-dimensional (4D) SPECT/CT to visualize diseased parathyroid glands in patients with complex medical profiles or in whom other imaging modalities fail. We review the advantages and disadvantages of traditional imaging modalities used in preoperative assessment of patients with primary hyperparathyroidism: ultrasound, SPECT, and 4D CT. We describe a scheme for optimizing and individualizing preoperative imaging of patients with hyperfunctioning parathyroid glands using traditional modalities in tandem with 4D SPECT/CT.