Experiences and lessons learned from a patient-engagement service established by a national research consortium in the U.S. Veterans Health Administration.

Introduction: Meaningful engagement of patients in the research process has increased over the past 20 years. Few accounts are available of engagement infrastructure and processes used by large research organizations. The Pain/Opioid Consortium of Research (Consortium) is a U.

Newborn screening for homocystinurias: Recent recommendations versus current practice.

Purpose: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations.

Methods: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8).

Racial/Ethnic Disparities in Morbidity and Mortality for Preterm Neonates Admitted to a Tertiary Neonatal Intensive Care Unit.

Objective: The objective of this study was to assess whether in-hospital morbidity or mortality differed by race/ethnicity for preterm neonates admitted to the neonatal intensive care unit (NICU).

Study Design: In a retrospective cohort study, preterm infants, < 37 weeks, were admitted to the NICU from 1994 to 2009. Exclusions included structural anomalies and aneuploidy.

The GlpF residue Trp219 is part of an amino-acid cluster crucial for aquaglyceroporin oligomerization and function.

The vestibule loop regions of aquaglyceroporins are involved in accumulation of glycerol inside the channel pore. Even though most loop regions do not show high sequence similarity among aquaglyceroporins, loop E is highly conserved in aquaglyceroporins, but not in members of the homologous aquaporins. Specifically, a tryptophan residue is extremely conserved within this loop.

The Hemoglobin Homolog Cytoglobin in Smooth Muscle Inhibits Apoptosis and Regulates Vascular Remodeling.

Objective: The role of hemoglobin and myoglobin in the cardiovascular system is well established, yet other globins in this context are poorly characterized. Here, we examined the expression and function of cytoglobin (CYGB) during vascular injury.

Approach And Results: We characterized CYGB content in intact vessels and primary vascular smooth muscle (VSM) cells and used 2 different vascular injury models to examine the functional significance of CYGB in vivo.

Toxoplasmosis, Parvovirus, and Cytomegalovirus in Pregnancy.

There are several infections in adults that warrant special consideration in pregnant women given the potential fetal consequences. Among these are toxoplasmosis, parvovirus B19, and cytomegalovirus. These infections have an important impact on the developing fetus, depending on the timing of infection.

Seronegative Maternal Ocular Myasthenia Gravis and Delayed Transient Neonatal Myasthenia Gravis.

Background Myasthenia gravis (MG) is an autoimmune disorder with fluctuating muscle weakness, divided into generalized and localized (ocular) forms. Maternal antibodies to acetylcholine receptors cross the placenta and may cause transient neonatal myasthenia gravis (TNMG). We present a case of seronegative maternal ocular MG and delayed TNMG.

Referral rates in Swiss primary care with a special emphasis on reasons for encounter.

Questions Under Study: Referrals from primary to secondary care reflect a crucial role of primary care physicians (PCPs). Most referral rates are based on the number of consultations, rather than on the number of problems addressed during consultations (reasons for encounter = RFE). The aim of the study was to update data on consultations, RFE and referrals in Swiss primary care and calculate a referral rate based on RFE rather than on the number of consultations.

The Escherichia coli Envelope Stress Sensor CpxA Responds to Changes in Lipid Bilayer Properties.

The Cpx stress response system is induced by various environmental and cellular stimuli. It is also activated in Escherichia coli strains lacking the major phospholipid, phosphatidylethanolamine (PE). However, it is not known whether CpxA directly senses changes in the lipid bilayer or the presence of misfolded proteins due to the lack of PE in their membranes.

Mutational analyses of YqjA, a Tvp38/DedA protein of E. coli.

Membrane proteins of the DedA/Tvp38 protein family are involved in membrane integrity and virulence of pathogenic organisms. However, the structure and exact function of any member of this large protein family are still unclear. In the present study we analyzed the functional and structural properties of a DedA homolog.

Anti-inflammatory immune skewing is atheroprotective: Apoe−/−FcγRIIb−/− mice develop fibrous carotid plaques.

Background: Stroke, caused by carotid plaque rupture, is a major cause of death in the United States. Whereas vulnerable human plaques have higher Fc receptor (FcγR) expression than their stable counterparts, how FcγR expression impacts plaque histology is unknown. We investigated the role of FcγRIIb in carotid plaque development and stability in apolipoprotein (Apo)e−/− and Apoe−/−FcγRIIb−/− double knockout (DKO) animals.

When two turn into one: evolution of membrane transporters from half modules.

The recently increasing number of atomic structures for active transporters has not only revealed strong conservation in the architecture of sequence-unrelated transporter families, but also identified a unifying element called the 'inverted repeat topology,' which is found in nearly all transporter folds to date. Indeed, most membrane transporters consist of two or more domains with similar structure, so-called repeats. It is tempting to speculate that transporters have evolved by duplication of one repeat followed by gene fusion and modification events.

Mercury bioaccumulation in Southern Appalachian birds, assessed through feather concentrations.

Mercury contamination in wildlife has rarely been studied in the Southern Appalachians despite high deposition rates in the region. From 2006 to 2008 we sampled feathers from 458 birds representing 32 species in the Southern Appalachians for total mercury and stable isotope δ (15)N. Mercury concentrations (mean ± SE) averaged 0.

Homologs of the yeast Tvp38 vesicle-associated protein are conserved in chloroplasts and cyanobacteria.

Vesicle transfer processes in eukaryotes depend on specific proteins, which mediate the selective packing of cargo molecules for subsequent release out of the cells after vesicle fusion to the plasma membrane. The protein Tvp38 is conserved in yeasts and higher eukaryotes and potentially involved in vesicle transfer processes at the Golgi membrane. Members of the so-called "SNARE-associated proteins of the Tvp38-family" have also been identified in prokaryotes and those belong to the DedA protein family.

Co-operation between different targeting pathways during integration of a membrane protein.

Membrane protein assembly is a fundamental process in all cells. The membrane-bound Rieske iron-sulfur protein is an essential component of the cytochrome bc(1) and cytochrome b(6)f complexes, and it is exported across the energy-coupling membranes of bacteria and plants in a folded conformation by the twin arginine protein transport pathway (Tat) transport pathway. Although the Rieske protein in most organisms is a monotopic membrane protein, in actinobacteria, it is a polytopic protein with three transmembrane domains.

Orai3 is an estrogen receptor α-regulated Ca²⁺ channel that promotes tumorigenesis.

Store-operated Ca(2+) entry (SOCE) encoded by Orai1 proteins is a ubiquitous Ca(2+)-selective conductance involved in cellular proliferation and migration. We recently described up-regulation of Orai3 channels that selectively mediate SOCE in estrogen receptor α-expressing (ERα(+)) breast cancer cells. However, the connection between ERα and Orai3 and the role of Orai3 in tumorigenesis remain unknown.

Molecular dissection of TatC defines critical regions essential for protein transport and a TatB-TatC contact site.

The twin arginine transport (Tat) system transports folded proteins across the prokaryotic cytoplasmic membrane and the plant thylakoid membrane. TatC is the largest and most conserved component of the Tat machinery. It forms a multisubunit complex with TatB and binds the signal peptides of Tat substrates.

Ultrasound biomicroscopy for longitudinal studies of carotid plaque development in mice: validation with histological endpoints.

Atherosclerosis is responsible for the death of thousands of Americans each year. The carotid constriction model of plaque development has recently been presented as a model for unstable plaque formation in mice. In this study we 1) validate ultrasound biomicroscopy (UBM) for the determination of carotid plaque size, percent stenosis, and plaque development in live animals, 2) determine the sensitivity of UBM in detecting changes in blood flow induced by carotid constriction and 3) test whether plaque formation can be predicted from blood flow parameters measured by UBM.

Signal integration by the Cpx-envelope stress system.

The Cpx-envelope stress system coordinates the expression and assembly of surface structures important for the virulence of Gram-negative pathogenic bacteria. It is comprised of the membrane-anchored sensor kinase CpxA, the cytosolic response regulator CpxR and the accessory protein CpxP. Characteristic of the group of two-component systems, the Cpx system responds to a broad range of stimuli including pH, salt, metals, lipids and misfolded proteins that cause perturbation in the envelope.

Iron-sulfur cluster engineering provides insight into the evolution of substrate specificity among sulfonucleotide reductases.

Assimilatory sulfate reduction supplies prototrophic organisms with reduced sulfur that is required for the biosynthesis of all sulfur-containing metabolites, including cysteine and methionine. The reduction of sulfate requires its activation via an ATP-dependent activation to form adenosine-5'-phosphosulfate (APS). Depending on the species, APS can be reduced directly to sulfite by APS reductase (APR) or undergo a second phosphorylation to yield 3'-phosphoadenosine-5'-phosphosulfate (PAPS), the substrate for PAPS reductase (PAPR).

Transforming growth factor-β1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein.

Serum response factor (SRF) plays a central role in regulating expression of smooth muscle-specific genes partly by associating with the potent tissue-specific cofactor myocardin. Previous studies have shown that transforming growth factor-β1-induced transcript 1 (TGFB1I1, also known as Hic-5) is a TGF-β-responsive gene and is involved in the cellular response to vascular injury, but the regulation of TGFB1I1 expression remains elusive. In this report, we demonstrated that TGFB1I1 is a novel marker for the smooth muscle contractile phenotype and is regulated by SRF/myocardin.

Ligation of macrophage Fcγ receptors recapitulates the gene expression pattern of vulnerable human carotid plaques.

Stroke is a leading cause of death in the United States. As ∼60% of strokes result from carotid plaque rupture, elucidating the mechanisms that underlie vulnerability is critical for therapeutic intervention. We tested the hypothesis that stable and vulnerable human plaques differentially express genes associated with matrix degradation.

Different regulatory regions are located on the sensor domain of CpxA to fine-tune signal transduction.

In Gram-negative bacteria, the Cpx signal transduction pathway (CpxAR) has an overall regulatory function, but the mechanism of its activation is still poorly understood. Here we investigated the impact of the periplasmic sensor domain of CpxA on signalling by mutational analysis in vitro. Substitutions (R33C and L38P) in the N-terminal region significantly increased CpxA autophosphorylation, whereas a substitution in a predicted beta sheet (E92K), which impaired the inhibitory effect of the auxiliary CpxP protein, had no significant effect on catalytic activity.

Structural basis for two-component system inhibition and pilus sensing by the auxiliary CpxP protein.

Bacteria are equipped with two-component systems to cope with environmental changes, and auxiliary proteins provide response to additional stimuli. The Cpx two-component system is the global modulator of cell envelope stress in gram-negative bacteria that integrates very different signals and consists of the kinase CpxA, the regulator CpxR, and the dual function auxiliary protein CpxP. CpxP both inhibits activation of CpxA and is indispensable for the quality control system of P pili that are crucial for uropathogenic Escherichia coli during kidney colonization.

Misfolded maltose binding protein MalE219 induces the CpxRA envelope stress response by stimulating phosphoryl transfer from CpxA to CpxR.

In Escherichia coli, the CpxRA sensor regulator system is induced by a variety of signals, including pH, osmolarity, metals and misfolded envelope proteins. Here, we analyzed the effect of the folding defective maltose binding protein MalE219 on the reconstituted Cpx signalling pathway in detail. Surprisingly, autokinase and phosphatase activities of the reconstituted CpxA-6His protein remained unaffected, whereas phosphotransfer to CpxR became activated by MalE219.