Blockade of equilibrative nucleoside transporter 1/2 protects against Pseudomonas aeruginosa-induced acute lung injury and NLRP3 inflammasome activation.

Pseudomonas aeruginosa infections are increasingly multidrug resistant and cause healthcare-associated pneumonia, a major risk factor for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Adenosine is a signaling nucleoside with potential opposing effects; adenosine can either protect against acute lung injury via adenosine receptors or cause lung injury via adenosine receptors or equilibrative nucleoside transporter (ENT)-dependent intracellular adenosine uptake. We hypothesized that blockade of intracellular adenosine uptake by inhibition of ENT1/2 would increase adenosine receptor signaling and protect against P.

Assessment for oil spill chemicals: Current knowledge, data gaps, and uncertainties addressing human physical health risk.

Limited models are available to estimate human physical health risks (e.g., probability of outcomes such as lung disease, cancer, skin disease) from exposure to chemicals resulting from oil spills that may occur offshore and later impact coastline spills.

An Automatic Approach to Reestablish Final Dental Occlusion for 1-Piece Maxillary Orthognathic Surgery.

Accurately establishing a desired final dental occlusion of the upper and lower teeth is a critical step in orthognathic surgical planning. Traditionally, the final occlusion is established by hand-articulating the stone dental models. However, this process is inappropriate to digitally plan the orthognathic surgery using computer-aided surgical simulation.

Impact of Maternal Obesity on Perinatal Outcomes in Preterm Prelabor Rupture of Membranes ≥34 Weeks.

Objective: This study aimed to compare pregnancy outcomes in obese and nonobese women with preterm prelabor rupture of membranes (PPROM) ≥34 weeks.

Study Design: The present study is a secondary analysis of a multicenter retrospective cohort of singletons with PPROM from 2011 to 2017. Women with a delivery body mass index (BMI) ≥30 kg/m (obese) were compared with women with a BMI < 30 kg/m (nonobese).

Peripheral Delivery of Neural Precursor Cells Ameliorates Parkinson's Disease-Associated Pathology.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of motor control due to a wide loss of dopaminergic neurons along the nigro-striatal pathway. Some of the mechanisms that contribute to this cell death are inflammation, oxidative stress, and misfolded alpha-synuclein-induced toxicity. Current treatments are effective at managing the early motor symptoms of the disease, but they become ineffective over time and lead to adverse effects.

Influence of the phosphoenolpyruvate:carbohydrate phosphotransferase system on toxin gene expression and virulence in Bacillus anthracis.

AtxA, the master virulence gene regulator of Bacillus anthracis, is a PRD-Containing Virulence Regulator (PCVR) as indicated by the crystal structure, post-translational modifications and activity of the protein. PCVRs are transcriptional regulators, named for PTS Regulatory Domains (PRDs) subject to phosphorylation by the phosphoenolpyruvate phosphotransferase system (PEP-PTS) and for their impact on virulence gene expression. Here we present data from experiments employing physiological, genetic and biochemical approaches that support a model in which the PTS proteins HPr and Enzyme I (EI) are required for transcription of the atxA gene, rather than phosphorylation of AtxA.

Seeking mTORC1 Inhibitors Through Molecular Dynamics Simulation of Arginine Analogs Inhibiting CASTOR1.

Background: Hyperactivity of the mechanistic target of rapamycin complex 1 (mTORC1) is implicated in a variety of diseases such as cancer and diabetes. Treatment may benefit from effective mTORC1 inhibition, which can be achieved by preventing arginine from disrupting the cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1)-GTPase-activating proteins toward RAGS subcomplex 2 (GATOR2) complex through binding with CASTOR1. An attractive idea is to determine analogues of arginine that are as competent as arginine in binding with CASTOR1, but without disrupting the CASTOR1-GATOR2 interaction.

Importance of phosphorylation/dephosphorylation cycles on lipid-dependent modulation of membrane protein topology by posttranslational phosphorylation.

Posttranslational modifications of proteins, such as phosphorylation and dephosphorylation, play critical roles in cellular functions through diverse cell signaling pathways. Protein kinases and phosphatases have been described early on as key regulatory elements of the phosphorylated state of proteins. Tight spatial and temporal regulation of protein kinase and phosphatase activities has to be achieved in the cell to ensure accurate signal transduction.

Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility.

The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury associated with a disruption in mitochondrial metabolic agility, inflammation, and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes. Marked systemic elevation in C5a activity was demonstrated in patients with diabetes; conventional renoprotective agents did not therapeutically target this elevation.

Proteomic Analysis of Infants Undergoing Cardiopulmonary Bypass Using Contemporary Ontological Tools.

Background: Cardiopulmonary bypass (CPB) is essential for the repair of many congenital cardiac defects in infants but is associated with significant derangements in hemostasis and systemic inflammation. As a result, hemorrhagic complications and thrombosis are major challenges in the management of children requiring CPB or extracorporeal membrane oxygenation. Conventional clinical laboratory tests capture individual hemostatic derangements (low platelets, elevated fibrinogen) but fail to describe the complex, overlapping interactions among the various components of coagulation, including cellular interactions, contact activation, fibrinolysis, and inflammation.

Natural Products as Modulators of the Proteostasis Machinery: Implications in Neurodegenerative Diseases.

Proteins play crucial and diverse roles within the cell. To exert their biological function they must fold to acquire an appropriate three-dimensional conformation. Once their function is fulfilled, they need to be properly degraded to hamper any possible damage.

Placental growth factor predicts time to delivery in women with signs or symptoms of early preterm preeclampsia: a prospective multicenter study.

Background: There is a robust association between altered angiogenic factor concentrations, which includes placental growth factor and clinically recognized preeclampsia. Alterations in concentrations of angiogenic factors precede the clinical onset of preeclampsia by several weeks. The temporal relationship between the measured angiogenic factors and the time to delivery in women with suspected preeclampsia at <35 weeks gestation, however, remains to be clarified.

Gene-based association analysis of survival traits via functional regression-based mixed effect cox models for related samples.

The importance to integrate survival analysis into genetics and genomics is widely recognized, but only a small number of statisticians have produced relevant work toward this study direction. For unrelated population data, functional regression (FR) models have been developed to test for association between a quantitative/dichotomous/survival trait and genetic variants in a gene region. In major gene association analysis, these models have higher power than sequence kernel association tests.

Xanthogranulomatous Sialadenitis, an Uncommon Reactive Change is Often Associated with Warthin's Tumor.

Xanthogranulomatous sialadenitis (XGS) is rare in salivary glands and only reported in the literature as single cases. Here we report a cohort of four cases with XGS and summarize the clinicopathologic features of these cases. All four patients had persistent mass lesions concerning for neoplasm.

Integration of cortical population signals for visual perception.

Visual stimuli evoke heterogeneous responses across nearby neural populations. These signals must be locally integrated to contribute to perception, but the principles underlying this process are unknown. Here, we exploit the systematic organization of orientation preference in macaque primary visual cortex (V1) and perform causal manipulations to examine the limits of signal integration.

Pediatric Surgeon Perceptions of Participation in External Patient Safety Programs: impact on Patient Safety.

Introduction: Surgeons play a crucial role in preventing harm and contributing to the safety culture of their institutions. External safety data programs are designed to review adverse events and provide performance benchmarks to ameliorate future adverse events. The extent to which pediatric surgeons are aware of these programs, utilize data from these programs, and believe that they improve patient safety, is unknown.