The Functional Impact of VX-770 on the Cystic Fibrosis Transmembrane Conductance Regulator Is Enduring and Increases the Constitutive Activity of This Channel in Primary Airway Epithelia Generated from Healthy Donors.

VX-770 is a small-molecule CFTR potentiator that is highly efficacious in individuals with cystic fibrosis caused by mutations in CFTR that result in a defect in channel gating. While studies have reported on the mechanism of action of VX-770, there is still more to learn about the impact that it has on CFTR function in various contexts. The aim of the present study was to examine the longevity and stability of the effect of VX-770 on CFTR function in cultured airway epithelia and to measure the consequences of this interaction.

Human intestinal stromal cells promote homeostasis in normal mucosa but inflammation in Crohn's disease in a retinoic acid-deficient manner.

Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here, we show that human intestinal vimentinCD90smooth muscle actin SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn's disease SCs (Crohn's SCs), however, synthesized markedly less RA than SCs from healthy intestine (normal SCs).

On the benefits of desulfated seawater flooding in mature hydrocarbon fields.

Removal of sulfate from the injection seawater (desulfation) in hydrocarbon reservoirs is a Modified Salinity Water (MSW) flooding method that mitigates microbial reservoir souring, improves oil recovery, and enables produced-water re-injection (PWRI). Aside from the Improved Oil Recovery (IOR) effect, desulfation results in a cleaner production of oil through enabling PWRI and reducing the environmental impacts associated with reservoir souring and nitrate treatment. However, whether desulfation is still beneficial for mature fields, after years of the injection of untreated seawater, is a valid common concern.

Chemical solutions for restoring scaling-induced injectivity impairment in offshore produced water re-injection.

Produced water re-injection (PWRI) is a promising and sustainable strategy to manage substantial quantities of produced water for subsurface energy production systems. This approach offers an alternative to the environmentally harmful practice of marine disposal. Nonetheless, produced water re-injection may lead to considerable reductions in the injectivity.

Mesna Improves Outcomes of Sulfur Mustard Inhalation Toxicity in an Acute Rat Model.

Inhalation of high levels of sulfur mustard (SM), a potent vesicating and alkylating agent used in chemical warfare, results in acutely lethal pulmonary damage. Sodium 2-mercaptoethane sulfonate (mesna) is an organosulfur compound that is currently Food and Drug Administration (FDA)-approved for decreasing the toxicity of mustard-derived chemotherapeutic alkylating agents like ifosfamide and cyclophosphamide. The nucleophilic thiol of mesna is a suitable reactant for the neutralization of the electrophilic group of toxic mustard intermediates.

Hypocretin/orexin influences chronic sleep disruption injury in the hippocampus.

Unlabelled: Chronic sleep disruption is a risk factor for Alzheimer's disease (AD), yet mechanisms by which sleep disturbances might promote or exacerbate AD are not understood. Short-term sleep loss acutely increases hippocampal amyloid β (Aβ) in wild type (WT) mice and long-term sleep loss increases amyloid plaque in AD transgenic mouse models. Both effects can be influenced by the wake-promoting neuropeptide, hypocretin (HCRT), but whether HCRT influences amyloid accumulation independent of sleep and wake timing modulation remains unclear.

Identification and determination of phenyl methyl carbamate released from adducted hemoglobin for methyl isocyanate exposure verification.

Methyl isocyanate (MIC), an intermediate in the synthesis of carbamate pesticides, is a toxic industrial chemical that causes irritation and damage to the eyes, respiratory tract, and skin. Due to the high reactivity of MIC, it binds to proteins to form protein adducts. While these adducts can be used as biomarkers to verify exposure to MIC, methods to detect MIC adducts are cumbersome, typically involving enzymatic (pronase) or strong acid (Edman degradation) hydrolysis of hemoglobin.

Acute vaping in a golden Syrian hamster causes inflammatory response transcriptomic changes.

E-cigarette vaping is a major aspect of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of subacute and chronic e-cigarette vaping exposure have shown many proinflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting respiratory viruses, including SARS-CoV-2, without genetic alteration of the animal or virus.

Electrokinetic behavior of artificial and natural calcites: A review of experimental measurements and surface complexation models.

The surface charge of calcite in aqueous environments is essential to many industrial and environmental applications. Electrokinetic measurements are usually used to assess the calcite charging behavior and characterize its electrical double layer (EDL). Numerous surface complexation models (SCMs) have been proposed to interpret the effect of different surface interactions on the zeta potential.

Analysis of sodium 2-mercaptoethane sulfonate in rat plasma using high performance liquid chromatography tandem-mass spectrometry.

Sodium 2-mercaptoethane sulfonate (MESNA) is a thiol-containing compound that has proven to be effective in inactivating acrolein, the toxic metabolite of some anti-cancer drugs (e.g., cyclophosphamide and ifosphamide).

geneBasis: an iterative approach for unsupervised selection of targeted gene panels from scRNA-seq.

scRNA-seq datasets are increasingly used to identify gene panels that can be probed using alternative technologies, such as spatial transcriptomics, where choosing the best subset of genes is vital. Existing methods are limited by a reliance on pre-existing cell type labels or by difficulties in identifying markers of rare cells. We introduce an iterative approach, geneBasis, for selecting an optimal gene panel, where each newly added gene captures the maximum distance between the true manifold and the manifold constructed using the currently selected gene panel.

Measurements of spontaneous CFTR-mediated ion transport without acute channel activation in airway epithelial cultures after modulator exposure.

Quantitation of CFTR function in vitro is commonly performed by acutely stimulating then inhibiting ion transport through CFTR and measuring the resulting changes in transepithelial voltage (V) and current (I). While this technique is suitable for measuring the maximum functional capacity of CFTR, it may not provide an accurate estimate of in vivo CFTR activity. To test if CFTR-mediated ion transport could be measured in the absence of acute CFTR stimulation, primary airway epithelia were analyzed in an Ussing chamber with treatment of amiloride followed by CFTR(inh)-172 without acute activation of CFTR.

Heightened turnover and failed maturation of monocyte-derived macrophages in murine chronic granulomatous disease.

Loss of NADPH oxidase activity leads to altered phagocyte responses and exaggerated inflammation in chronic granulomatous disease (CGD). We sought to assess the effects of Nox2 absence on monocyte-derived macrophages (MoMacs) in gp91phox-/y mice during zymosan-induced peritonitis. MoMacs from CGD and wild-type (WT) peritonea were characterized over time after zymosan injection.

Importance of thermodynamics dependent kinetic parameters in nitrate-based souring mitigation studies.

Souring is the unwanted formation of hydrogen sulfide (HS) by sulfate-reducing microorganisms (SRM) in sewer systems and seawater flooded oil reservoirs. Nitrate treatment (NT) is one of the major methods to alleviate souring: The mechanism of souring remediation by NT is stimulation of nitrate reducing microorganisms (NRM) that depending on the nitrate reduction pathway can outcompete SRM for common electron donors, or oxidize sulfide to sulfate. However, some nitrate reduction pathways may challenge the efficacy of NT.

Altered cellular localisation and expression, together with unconventional protein trafficking, of prion protein, PrP, in type 1 diabetes.

Aims/hypothesis: Normal cellular prion protein (PrP) is a conserved mammalian glycoprotein found on the outer plasma membrane leaflet through a glycophosphatidylinositol anchor. Although PrP is expressed by a wide range of tissues throughout the body, the complete repertoire of its functions has not been fully determined. The misfolded pathogenic isoform PrP (the scrapie form of PrP) is a causative agent of neurodegenerative prion diseases.

A novel relationship for the maximum specific growth rate of a microbial guild.

One of the major parameters that characterizes the kinetics of microbial processes is the maximum specific growth rate. The maximum specific growth rate for a single microorganism (${\mu _{max}}$) is fairly constant. However, a certain microbial process is typically catalyzed by a group of microorganisms (guild) that have various ${\mu _{max}}$ values.

Monogenic Diabetes and Integrated Stress Response Genes Display Altered Gene Expression in Type 1 Diabetes.

Type 1 diabetes (T1D) has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with and at risk for T1D would exhibit dysregulated expression of genes associated with monogenic forms of diabetes caused by nonredundant single-gene mutations. Using a "monogenetic transcriptomic strategy," we measured the expression of these genes in human T1D, autoantibody-positive (autoantibody+), and control pancreas tissues with real-time quantitative PCR in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines.

The Impact of Spatially Correlated Heterogeneity and Adsorption on Modified Salinity Water in Carbonates.

Modified salinity water (MSW) core flooding tests conducted in carbonates often exhibit a delay in the additional oil recovery. It has been suggested that the ionic adsorption process controls this delay. In this study, we examine the adverse effect of the adsorption process on the performance of MSW flooding in various models categorized as layered and heterogeneous reservoirs and a North Sea field sector model.

Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.

Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases.

Researcher Knowledge, Attitudes, and Communication Practices for Genomic Data Sharing.

This study examines knowledge, attitudes, and communication practices toward genomic data sharing among principal investigators and research coordinators engaged in cancer and non-cancer studies. We conducted 25 individual semi-structured interviews and conducted a qualitative thematic analysis. Most interviewees had basic knowledge of data sharing requirements, but lacked specific details of recent changes to NIH policy.

Physics-informed neural networks for solving nonlinear diffusivity and Biot's equations.

This paper presents the potential of applying physics-informed neural networks for solving nonlinear multiphysics problems, which are essential to many fields such as biomedical engineering, earthquake prediction, and underground energy harvesting. Specifically, we investigate how to extend the methodology of physics-informed neural networks to solve both the forward and inverse problems in relation to the nonlinear diffusivity and Biot's equations. We explore the accuracy of the physics-informed neural networks with different training example sizes and choices of hyperparameters.

Alleviation of methyl isocyanate-induced airway obstruction and mortality by tissue plasminogen activator.

Methyl isocyanate (MIC, "Bhopal agent") is a highly reactive, toxic industrial chemical. Inhalation of high levels (500-1000 ppm) of MIC vapor is almost uniformly fatal. No therapeutic interventions other than supportive care have been described that can delay the onset of illness or death due to MIC.

ATM is a key driver of NF-κB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging.

NF-κB is a transcription factor activated in response to inflammatory, genotoxic and oxidative stress and important for driving senescence and aging. Ataxia-telangiectasia mutated (ATM) kinase, a core component of DNA damage response signaling, activates NF-κB in response to genotoxic and oxidative stress via post-translational modifications. Here we demonstrate that ATM is activated in senescent cells in culture and murine tissues from -deficient mouse models of accelerated aging, as well as naturally aged mice.

Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues.

Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g.

A sulfur and nitrogen cycle informed model to simulate nitrate treatment of reservoir souring.

Nitrate treatment has been widely used in various seawater injection projects to treat biologic sulfate reduction or reservoir souring. To design a promising nitrate treatment plan, it is essential to have a comprehensive understanding of reactions that represent the microbial communities of the reservoir and mechanisms through which the souring process is inhibited. We employ a new approach of evaluating different reaction pathways to design reaction models that reflect governing microbial processes in a set of batch and flow experiments.