In utero and early-life nitrate in drinking water impacts lung function of weanling rats.

Consumption of nitrate in drinking water has previously been associated with a range of adverse health effects, including methemoglobinemia and potentially cancer. In animal models, it has been shown to impact respiratory structure and function, however, there is a paucity of data of the effects of in utero exposure on the respiratory health of offspring. In this study, pregnant rats were given drinking water containing nitrate at 50 or 100 mg/L (or control).

Profiling epithelial viral receptor expression in amniotic membrane and nasal epithelial cells at birth.

Introduction: Children with wheeze and asthma present with airway epithelial vulnerabilities, such as impaired responses to viral infection. It is postulated that the in utero environment may contribute to the development of airway epithelial vulnerabilities. The aims of the study were to establish whether the receptors for rhinovirus (RV), respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are expressed in the amniotic membrane and whether the pattern of expression is similar to newborn nasal epithelium.

Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model.

Aim: Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model.

Materials And Methods: In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures.

An infant mouse model of influenza-driven nontypeable colonization and acute otitis media suitable for preclinical testing of novel therapies.

Nontypeable (NTHi) is a major otitis media (OM) pathogen, with colonization a prerequisite for disease development. Most acute OM is in children <5 years old, with recurrent and chronic OM impacting hearing and learning. Therapies to prevent NTHi colonization and/or disease are needed, especially for young children.

Fe protein docking transduces conformational changes to MoFe nitrogenase active site in a nucleotide-dependent manner.

The reduction of dinitrogen to ammonia catalyzed by nitrogenase involves a complex series of events, including ATP hydrolysis, electron transfer, and activation of metal clusters for N reduction. Early evidence shows that an essential part of the mechanism involves transducing information between the nitrogenase component proteins through conformational dynamics. Here, millisecond time-resolved hydrogen-deuterium exchange mass spectrometry was used to unravel peptide-level protein motion on the time scale of catalysis of Mo-dependent nitrogenase from Azotobacter vinelandii.

Application of platform process development approaches to the manufacturing of Mabcalin™ bispecifics.

Bispecific biotherapeutics offer potent and highly specific treatment options in oncology and immuno-oncology. However, many bispecific formats are prone to high levels of aggregation and instability, leading to prolonged development timelines, inefficient manufacturing, and high costs. The novel class of Mabcalin™ molecules consist of Anticalin® proteins fused to an IgG and are currently being evaluated in pre-clinical and clinical studies.

Comparative polar and lipid plasma metabolomics differentiate KSHV infection and disease states.

Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there.

Element distribution in electrochemically treated mine wastewater for efficient resource recovery and water treatment: A pilot study.

The feasibility of recovering major and critical elements from acid mine drainage using a pilot-scale electrochemical reactor (ECR) was investigated by assessing elements concentration and species distribution in the liquid and solid phase (sludge) in multistage tests. These were carried out at different electrical currents (18-22 amps) and thus, pH (8-12). The results showed that major metals Al, Cu and Fe were removed from the liquid phase at pH 5.

Genome of Paspalum vaginatum and the role of trehalose mediated autophagy in increasing maize biomass.

A number of crop wild relatives can tolerate extreme stress to a degree outside the range observed in their domesticated relatives. However, it is unclear whether or how the molecular mechanisms employed by these species can be translated to domesticated crops. Paspalum (Paspalum vaginatum) is a self-incompatible and multiply stress-tolerant wild relative of maize and sorghum.

Structural Dynamics and Activity of B19V VP1u during the pHs of Cell Entry and Endosomal Trafficking.

Parvovirus B19 (B19V) is a human pathogen that is the causative agent of fifth disease in children. It is also known to cause hydrops in fetuses, anemia in AIDS patients, and transient aplastic crisis in patients with sickle cell disease. The unique N-terminus of Viral Protein 1 (VP1u) of parvoviruses, including B19V, exhibits phospholipase A (PLA) activity, which is required for endosomal escape.

Exacerbation of chronic cigarette-smoke induced lung disease by rhinovirus in mice.

A significant proportion of chronic obstructive pulmonary disease exacerbations are strongly associated with rhinovirus infection (HRV). In this study, we combined long-term cigarette smoke exposure with HRV infection in a mouse model. Our aim was to better understand the effects of HRV infection on such exacerbations, using a realistic method for generating a COPD-like phenotype.

Previous Influenza Infection Exacerbates Allergen Specific Response and Impairs Airway Barrier Integrity in Pre-Sensitized Mice.

In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed.

The Best of Both Worlds: Eliminating Creatine Kinase-Muscle/Brain (CK-MB) Testing in the Emergency Department Leads to Lower Costs Without Missed Clinical Diagnoses.

The 2014 American Heart Association/American College of Cardiology (AHA/ACC) clinical guidelines recommend cardiac troponin as a superior biomarker to creatine kinase (CK) and creatine kinase-muscle/brain (CK-MB) for the detection of acute coronary syndrome (ACS), namely myocardial infarction and unstable angina. In April 2018, our Emergency Department (ED) transitioned from using standard troponin to using high-sensitivity troponin T, and adopted a clinical guideline consistent with the AHA/ACC. The guideline recommended high-sensitivity troponin T without CK/CK-MB testing in the majority of clinical situations, limiting CK/CK-MB testing to two specific clinical cases: 1) estimated glomerular filtration rate (eGFR) value <15 mL/min, or 2) recent acute coronary syndrome (ACS) event.

Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling.

Background: Climate change models predict that atmospheric carbon dioxide [] levels will be between 700 and 900 ppm within the next 80 y. Despite this, the direct physiological effects of exposure to slightly elevated atmospheric (as compared with experienced today), especially when exposures extend from preconception to adulthood, have not been thoroughly studied.

Objectives: In this study we aimed to assess the respiratory structure and function effects of long-term exposure to from preconception to adulthood using a mouse model.

Staged electrochemical treatment guided by modelling allows for targeted recovery of metals and rare earth elements from acid mine drainage.

Acid mine drainage (AMD) is a challenge for current and legacy mining operations worldwide given its potential to severely harm ecosystems and communities if inadequately managed. Treatment costs for AMD are amongst the highest in the industrial wastewater treatment sector, with limited sustainable options available to date. This work demonstrates a novel chemical-free approach to tackle AMD, whereby staged electrochemical neutralisation is employed to treat AMD and concomitantly recover metals as precipitates.

Novel phenolic antimicrobials enhanced activity of iminodiacetate prodrugs against biofilm and planktonic bacteria.

Prodrugs are pharmacologically attenuated derivatives of drugs that undergo bioconversion into the active compound once reaching the targeted site, thereby maximizing their efficiency. This strategy has been implemented in pharmaceuticals to overcome obstacles related to absorption, distribution, and metabolism, as well as with intracellular dyes to ensure concentration within cells. In this study, we provide the first examples of a prodrug strategy that can be applied to simple phenolic antimicrobials to increase their potency against mature biofilms.

The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis.

Introduction: Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their detection has a deleterious effect on structural lung disease.

The Role of Mass Spectrometry in Structural Studies of Flavin-Based Electron Bifurcating Enzymes.

For decades, biologists and biochemists have taken advantage of atomic resolution structural models of proteins from X-ray crystallography, nuclear magnetic resonance spectroscopy, and more recently cryo-electron microscopy. However, not all proteins relent to structural analyses using these approaches, and as the depth of knowledge increases, additional data elucidating a mechanistic understanding of protein function is desired. Flavin-based electron bifurcating enzymes, which are responsible for producing high energy compounds through the simultaneous endergonic and exergonic reduction of two intercellular electron carriers (i.

Hydrogen Deuterium Exchange Mass Spectrometry of Oxygen Sensitive Proteins.

The protocol detailed here describes a way to perform hydrogen deuterium exchange coupled to mass spectrometry (HDX-MS) on oxygen sensitive proteins. HDX-MS is a powerful tool for studying the protein structure-function relationship. Applying this technique to anaerobic proteins provides insight into the mechanism of proteins that perform oxygen sensitive chemistry.

Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner.

Epidemiological studies demonstrate an association between intrauterine growth restriction (IUGR) and asthma; however the underlying mechanism is unknown. We investigated the impact of maternal hypoxia-induced IUGR on airway responsiveness in male and female mice during juvenility and adulthood. Pregnant BALB/c mice were housed under hypoxic conditions for gestational days 11-17.

Airway surface liquid pH is not acidic in children with cystic fibrosis.

Modulation of airway surface liquid (ASL) pH has been proposed as a therapy for cystic fibrosis (CF). However, evidence that ASL pH is reduced in CF is limited and conflicting. The technical challenges associated with measuring ASL pH in vivo have precluded accurate measurements in humans.