Applying Community-based System Dynamics to promote child health equity: the case of healthy and fit kids in Milwaukee, WI.

Background: Child health equity is influenced by complex systemic factors, including structural racism, socioeconomic disparities, and access to resources. Traditional public health interventions often target individual behaviors, but there is a growing need for systems approaches that address these root causes. This study examines coalition members' perspectives on promoting child health equity in Milwaukee as a result of participating in an intervention that includes Community-based System Dynamics (CBSD).

C-terminal processing of GlyGly-CTERM containing proteins by rhombosortase in Vibrio cholerae.

Vibrio cholerae and a subset of other Gram-negative bacteria, including Acinetobacter baumannii, express proteins with a C-terminal tripartite domain called GlyGly-CTERM, which consists of a motif rich in glycines and serines, followed by a hydrophobic region and positively charged residues. Here we show that VesB, a V. cholerae serine protease, requires the GlyGly-CTERM domain, the intramembrane rhomboid-like protease rhombosortase, and the type II secretion system (T2SS) for localization at the cell surface.

Homeodomain Proteins Directly Regulate ATM Kinase Activity.

Ataxia-telangiectasia mutated (ATM) is a serine/threonine kinase that coordinates the response to DNA double-strand breaks and oxidative stress. NKX3.1, a prostate-specific transcription factor, was recently shown to directly stimulate ATM kinase activity through its highly conserved homeodomain.

MRI Is a DNA Damage Response Adaptor during Classical Non-homologous End Joining.

The modulator of retrovirus infection (MRI or CYREN) is a 30-kDa protein with a conserved N-terminal Ku-binding motif (KBM) and a C-terminal XLF-like motif (XLM). We show that MRI is intrinsically disordered and interacts with many DNA damage response (DDR) proteins, including the kinases ataxia telangiectasia mutated (ATM) and DNA-PKcs and the classical non-homologous end joining (cNHEJ) factors Ku70, Ku80, XRCC4, XLF, PAXX, and XRCC4. MRI forms large multimeric complexes that depend on its N and C termini and localizes to DNA double-strand breaks (DSBs), where it promotes the retention of DDR factors.

Enhancing Community Education Through Innovative Teaching Strategies in a Baccalaureate Nursing Program.

Background: Nurse educators are relentlessly in search of innovative measures that enhance student learning and offer opportunities that prepare them for clinical practice. Collaborative opportunities between schools of nursing and community settings are beneficial for students and the community.

Method: One strategy was developed by a southeastern baccalaureate nursing program through the assistance of the National Institutes of Health mini-grants program, related to their Safe Sleep campaign.

Targeting the Type II Secretion System: Development, Optimization, and Validation of a High-Throughput Screen for the Identification of Small Molecule Inhibitors.

Nosocomial pathogens that develop multidrug resistance present an increasing problem for healthcare facilities. Due to its rapid rise in antibiotic resistance, is one of the most concerning gram-negative species. typically infects immune compromised individuals resulting in a variety of outcomes, including pneumonia and bacteremia.

Factors Associated With First-Time NCLEX-RN Success: A Descriptive Research Study.

Background: The purpose of this study was to identify variables associated with scores achieved on the Health Education Systems, Inc. (HESI) exit examination and successful first-time NCLEX-RN pass rates.

Method: A retrospective descriptive study examined the administrative data of 211 baccalaureate nursing students.

Acinetobacter baumannii Is Dependent on the Type II Secretion System and Its Substrate LipA for Lipid Utilization and In Vivo Fitness.

Unlabelled: Gram-negative bacteria express a number of sophisticated secretion systems to transport virulence factors across the cell envelope, including the type II secretion (T2S) system. Genes for the T2S components GspC through GspN and PilD are conserved among isolates of Acinetobacter baumannii, an increasingly common nosocomial pathogen that is developing multidrug resistance at an alarming rate. In contrast to most species, however, the T2S genes are dispersed throughout the genome rather than linked into one or two operons.

Outer Membrane Vesicle-Mediated Export of Processed PrtV Protease from Vibrio cholerae.

Background: Outer membrane vesicles (OMVs) are known to release from almost all Gram-negative bacteria during normal growth. OMVs carry different biologically active toxins and enzymes into the surrounding environment. We suggest that OMVs may therefore be able to transport bacterial proteases into the target host cells.

Teaching Nursing Leadership: Comparison of Simulation versus Traditional Inpatient Clinical.

Nurse educators claim accountability to ensure their students are prepared to assume leadership responsibilities upon graduation. Although front-line nurse leaders and nurse executives feel new graduates are not adequately prepared to take on basic leadership roles, professional nursing organizations such as the American Nurses Association (ANA) and the Association of Colleges of Nursing (AACN) deem leadership skills are core competencies of new graduate nurses. This study includes comparison of a leadership-focused multi-patient simulation and the traditional leadership clinical experiences in a baccalaureate nursing leadership course.

Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN.

The Type II secretion system delivers matrix proteins for biofilm formation by Vibrio cholerae.

Gram-negative bacteria have evolved several highly dedicated pathways for extracellular protein secretion, including the type II secretion (T2S) system. Since substrates secreted via the T2S system include both virulence factors and degradative enzymes, this secretion system is considered a major survival mechanism for pathogenic and environmental species. Previous analyses revealed that the T2S system mediates the export of ≥ 20 proteins in Vibrio cholerae, a human pathogen that is indigenous to the marine environment.

Fluorescence microscopy and proteomics to investigate subcellular localization, assembly, and function of the type II secretion system.

Investigation of secretion systems is often critical to understanding the virulence mechanisms of bacterial pathogens. With estimates as high as 30-40% of proteins secreted or localized to the cell envelope, information about the subcellular localization and organization of secretion complexes and identification and functional characterization of their substrates are key steps toward understanding these intricate systems. Here we describe a protocol using fluorescent live-cell imaging of fusion proteins that can provide a powerful tool to potentially examine the localization, assembly, and role of each component in the secretion complex.

Structural and functional studies on the interaction of GspC and GspD in the type II secretion system.

Type II secretion systems (T2SSs) are critical for secretion of many proteins from Gram-negative bacteria. In the T2SS, the outer membrane secretin GspD forms a multimeric pore for translocation of secreted proteins. GspD and the inner membrane protein GspC interact with each other via periplasmic domains.

Long helical filaments are not seen encircling cells in electron cryotomograms of rod-shaped bacteria.

How rod-shaped bacteria form and maintain their shape is an important question in bacterial cell biology. Results from fluorescent light microscopy have led many to believe that the actin homolog MreB and a number of other proteins form long helical filaments along the inner membrane of the cell. Here we show using electron cryotomography of six different rod-shaped bacterial species, at macromolecular resolution, that no long (> 80 nm) helical filaments exist near or along either surface of the inner membrane.

Type II Secretion in Escherichia coli.

The type II secretion system (T2SS) is used by Escherichia coli and other gram-negative bacteria to translocate many proteins, including toxins and proteases, across the outer membrane of the cell and into the extracellular space. Depending on the bacterial species, between 12 and 15 genes have been identified that make up a T2SS operon. T2SSs are widespread among gram-negative bacteria, and most E.

The three-dimensional structure of the cytoplasmic domains of EpsF from the type 2 secretion system of Vibrio cholerae.

The type 2 secretion system (T2SS), a multi-protein machinery that spans both the inner and the outer membranes of Gram-negative bacteria, is used for the secretion of several critically important proteins across the outer membrane. Here we report the crystal structure of the N-terminal cytoplasmic domain of EpsF, an inner membrane spanning T2SS protein from Vibrio cholerae. This domain consists of a bundle of six anti-parallel helices and adopts a fold that has not been described before.

Biochemical characterization of riboflavin carrier protein (RCP) in prostate cancer.

Riboflavin carrier protein (RCP) is a growth- and development-specific protein. Here, we characterized the expression of this protein in prostate cancer by polyclonal and monoclonal antibodies against chicken RCP. RCP was localized to both androgen-dependent and independent prostate cancer cell lines.

Docking and assembly of the type II secretion complex of Vibrio cholerae.

Secretion of cholera toxin and other virulence factors from Vibrio cholerae is mediated by the type II secretion (T2S) apparatus, a multiprotein complex composed of both inner and outer membrane proteins. To better understand the mechanism by which the T2S complex coordinates translocation of its substrates, we are examining the protein-protein interactions of its components, encoded by the extracellular protein secretion (eps) genes. In this study, we took a cell biological approach, observing the dynamics of fluorescently tagged EpsC and EpsM proteins in vivo.

Synthesis of a 35-member stereoisomer library of bistramide A: evaluation of effects on actin state, cell cycle and tumor cell growth.

Synthesis and preliminary biological evaluation of a 35-member library of bistramide A stereoisomers are reported. All eight stereoisomers of the C1-C13 tetrahydropyran fragment of the molecule were prepared utilizing crotylsilane reagents 9 and 10 in our [4+2]-annulation methodology. In addition, the four isomers of the C14-C18 gamma-amino acid unit were accessed via a Lewis acid mediated crotylation reaction with use of both enantiomers of organosilane 11.

Mapping critical interactive sites within the periplasmic domain of the Vibrio cholerae type II secretion protein EpsM.

The type II secretion (T2S) system is present in many gram-negative species, both pathogenic and nonpathogenic, where it supports the delivery of a variety of toxins, proteases, and lipases into the extracellular environment. In Vibrio cholerae, the T2S apparatus is composed of 12 Eps proteins that assemble into a multiprotein complex that spans the entire cell envelope. Two of these proteins, EpsM and EpsL, are key components of the secretion machinery present in the inner membrane.

Natural products active in aberrant c-Kit signaling.

Development of modulators of constitutively active, kinase domain mutants of c-Kit has proved to be very difficult. Therefore, a high-throughput differential cytotoxicity assay was developed to screen for compounds that preferentially kill cells expressing constitutively active c-Kit. The cells used in the assay, murine IC2 mast cells, express either the D814Y activating mutation (functionally equivalent to human D816Y) or wild type protein.

Synergistic stimulation of EpsE ATP hydrolysis by EpsL and acidic phospholipids.

EpsE is a cytoplasmic component of the type II secretion system in Vibrio cholerae. Through ATP hydrolysis and an interaction with the cytoplasmic membrane protein EpsL, EpsE supports secretion of cholera toxin across the outer membrane. In this study, we have determined the effect of the cytoplasmic domain of EpsL (cyto-EpsL) and purified phospholipids on the ATPase activity of EpsE.

Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease.

Several lines of evidence implicate the beta-galactoside-binding lectin galectin-3 in development and pathological processes in renal collecting ducts: galectin-3 is expressed in the ureteric bud/collecting duct lineage during nephrogenesis, modulates collecting duct growth/differentiation in vitro, and is expressed in human autosomal recessive polycystic kidney disease in cyst epithelia, almost all of which arise from collecting ducts. Moreover, exogenous galectin-3 restricts growth of cysts generated by Madin-Darby canine kidney collecting duct-derived cells in three-dimensional culture in collagen. Using the cpk mouse model of recessively inherited polycystic kidney disease, we observed widespread galectin-3 mRNA and protein in cyst epithelia.