Immobile lipopolysaccharides and outer membrane proteins differentially segregate in growing .

The outer membrane (OM) of gram-negative bacteria is a robust, impermeable barrier that excludes many classes of antibiotics. Contrary to the classical model of an asymmetric lipid bilayer, recent evidence suggests the OM is predominantly an asymmetric proteolipid membrane (APLM). Outer leaflet lipopolysaccharides (LPS) that surround integral β-barrel outer membrane proteins (OMPs) are shared with other OMPs to form a supramolecular network in which the levels of OMPs approach those of LPS.

De novo missense variants in ZBTB47 are associated with developmental delays, hypotonia, seizures, gait abnormalities, and variable movement abnormalities.

The collection of known genetic etiologies of neurodevelopmental disorders continues to increase, including several syndromes associated with defects in zinc finger protein transcription factors (ZNFs) that vary in clinical severity from mild learning disabilities and developmental delay to refractory seizures and severe autism spectrum disorder. Here we describe a new neurodevelopmental disorder associated with variants in ZBTB47 (also known as ZNF651), which encodes zinc finger and BTB domain-containing protein 47. Exome sequencing (ES) was performed for five unrelated patients with neurodevelopmental disorders.

Depressive symptoms anticipate behavioral and emotional factors among older adults: A prospective cross-lagged panel design.

This study examined the temporal relationship among depression, anxiety, insomnia, perceived stress, and physical activity in adults aged 60+ years with a history of major depressive disorder. We conducted a longitudinal study with 12 weeks of follow-up. Assessments consisted of phone or video interviews and included questionnaires evaluating depression, anxiety, insomnia, perceived stress, and physical activity.

Testing for complete spatial randomness on three dimensional bounded convex shapes.

There is currently a gap in theory for point patterns that lie on the surface of objects, with researchers focusing on patterns that lie in a Euclidean space, typically planar and spatial data. Methodology for planar and spatial data thus relies on Euclidean geometry and is therefore inappropriate for analysis of point patterns observed in non-Euclidean spaces. Recently, there has been extensions to the analysis of point patterns on a sphere, however, many other shapes are left unexplored.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Human Lung Microvascular Endothelial Cells Controls Oxidative Stress, Reactive Oxygen-Mediated Cell Signaling and Inflammatory Responses.

Background: Perturbation of endothelial function in people with cystic fibrosis (CF) has been reported, which may be associated with endothelial cell expression of the cystic fibrosis transmembrane conductance regulator (CFTR). Previous reports indicate that CFTR activity upregulates endothelial barrier function, endothelial nitric oxide synthase (eNOS) expression and NO release, while limiting interleukin-8 (IL-8) release, in human umbilical vein endothelial cells (HUVECs) in cell culture. In view of reported microvascular dysfunction in people with CF we investigated the role of CFTR expression and activity in the regulation of oxidative stress, cell signaling and inflammation in human lung microvascular endothelial cells (HLMVECs) in cell culture.

Fusing multimodal microscopy data for improved cell boundary estimation and fluorophore localization of Pseudomonas aeruginosa.

With advances in experimental technologies, the use of biological imaging has grown rapidly and there is need for procedures to combine data arising from different modalities. We propose a procedure to combine yellow fluorescence protein excitation and differential interference contrast microscopy time lapse videos to better estimate the cellular boundary of Pseudomonas aeruginosa (P. aeruginosa) and localization of it's type VI secretion system (T6SS).

Therapeutic Benefit of Blood Transfusion in a Patient With Novel PGK1 Mutation (c.461T>C [p.L154P]).

Phosphoglycerate kinase (PGK) is glycolytic enzyme critical in the creation of adenosine triphosphate. Mutations in the gene for this enzyme, PGK1, are associated with PGK deficiency, which is characterized by neurologic symptoms, nonhereditary spherocytic hemolytic anemia, and myopathy. We present a 20-year-old male with a novel c.

PEITH(Θ): perfecting experiments with information theory in Python with GPU support.

Motivation: Different experiments provide differing levels of information about a biological system. This makes it difficult, a priori, to select one of them beyond mere speculation and/or belief, especially when resources are limited. With the increasing diversity of experimental approaches and general advances in quantitative systems biology, methods that inform us about the information content that a given experiment carries about the question we want to answer, become crucial.

Exploiting species differences to understand the CFTR Cl- channel.

The anion channel cystic fibrosis transmembrane conductance regulator (CFTR) is a unique ATP-binding cassette (ABC) transporter. CFTR plays a pivotal role in transepithelial ion transport as its dysfunction in the genetic disease cystic fibrosis (CF) dramatically demonstrates. Phylogenetic analysis suggests that CFTR first appeared in aquatic vertebrates fulfilling important roles in osmosensing and organ development.

Impact of the F508del mutation on ovine CFTR, a Cl- channel with enhanced conductance and ATP-dependent gating.

Key Points: Malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), a gated pathway for chloride movement, causes the common life-shortening genetic disease cystic fibrosis (CF). Towards the development of a sheep model of CF, we have investigated the function of sheep CFTR. We found that sheep CFTR was noticeably more active than human CFTR, while the most common CF mutation, F508del, had reduced impact on sheep CFTR function.

Functional outcomes following ankle arthrodesis in males with haemophilia: analyses using the CDC's Universal Data Collection surveillance project.

In persons with haemophilia (PWH), repeated ankle haemarthroses lead to pain, loss of joint range of motion (ROM), and limitations in activity and participation in society. PWH are offered ankle arthrodesis (AA) to eliminate pain. In our experience, PWH are hesitant to proceed to AA due to concerns regarding gait anomalies, functional decline and complete loss of ROM.

Loop diuretics are open-channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics.

Background And Purpose: Loop diuretics are widely used to inhibit the Na(+), K(+), 2Cl(-) co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade.

Experimental Approach: Using the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR.

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC.

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e.

Effect of Annexin A5 on CFTR: regulated traffic or scaffolding?

Previous studies have implicated annexins in regulating ion channels and in particular annexin A5 (AnxA5) in the traffic of the cystic fibrosis transmembrane conductance regulator (CFTR). In the present study, we further investigated the role of AnxA5 in regulating CFTR function and intracellular trafficking in both Xenopus oocytes and mammalian cells. Although we could confirm the previously reported CFTR/AnnxA5 interaction, we found that in oocytes AnxA5 inhibits CFTR-mediated whole-cell membrane conductance presumably by a mechanism independent of PDZ-binding domain at the C-terminus of CFTR but protein kinase C (PKC)-dependent and results from either endocytosis activation and/or exocytosis block.

Deletion of Phe508 in the first nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator increases its affinity for the heat shock cognate 70 chaperone.

The primary cause of cystic fibrosis (CF), the most frequent fatal genetic disease in Caucasians, is deletion of phenylalanine at position 508 (F508del), located in the first nucleotide-binding domain (NBD1) of the CF transmembrane conductance regulator (CFTR) protein. F508del-CFTR is recognized by the endoplasmic reticulum quality control (ERQC), which targets it for proteasomal degradation, preventing this misfolded but partially functional Cl(-) channel from reaching the cell membrane. We recently proposed that the ERQC proceeds along several checkpoints, the first of which, utilizing the chaperone heat shock cognate 70 (Hsc70), is the major one directing F508del-CFTR for proteolysis.

Mutual respect in healthcare: assessing cultural competence for the University of Utah Interdisciplinary Health Sciences.

Introduction: The University initiated an Interdisciplinary Health Sciences Students (IHSS) education program, Cultural Competency & Mutual Respect (CCMR), for medicine (MED), pharmacy (PHARM), nursing (NSG), physical (PT) and occupational therapy (OT). This study assessed CCMR pre/post learning outcomes through the Inventory for Assessing the Process of Cultural Competence-Revised((c)) (IAPCC-R).

Methods: Subjects included: 100 MED, 140 NSG, 36 PT, 11 OT and 53 PHARM IHSS.

Burn rehabilitation and research: proceedings of a consensus summit.

Burn rehabilitation is an essential component of successful patient care. In May 2008, a group of burn rehabilitation clinicians met to discuss the status and future needs of burn rehabilitation. Fifteen topic areas pertinent to clinical burn rehabilitation were addressed.

Direct ex vivo evaluation of long-lived protective antiviral memory B cell responses against hepatitis B virus.

Background: The frequency of protective antiviral memory B cells after hepatitis B virus (HBV) vaccination is unknown.

Methods: A novel 2-step immunomagnetic protocol to assess the ex vivo frequency of protective HBV surface antigen (HBsAg)-specific memory B cells was used.

Results: HBsAg-specific memory B cells were detected in vaccinated individuals, although at very low frequency (median, 0.