Scanning Electron Microscopy Studies of Staphylococcal Adherence to Heart Valve Endothelial Cells in Organ Culture: An In Vitro Model of Acute Endocarditis

Organ cultures of human heart valves were used as a model to study the initial pathobiology of acute infective bacterial endocarditis. We used Staphylococcus aureus isolated from a case of infective endocarditis to infect the in vitro culture of the heart valves. Using scanning electron microscopy, we assessed the initial damage, attachment to and invasion of the endothelial cell layer by staphylococci. Our results indicate there is initial damage to the endothelium prior to observation of staphylococci attaching to the endothelial cell. By 12 h post infection, there is significant attachment and damage. At 24 h after infection, destruction of the heart valve endothelium is complete. The attachment and destruction arc progressive events and can be correlated quantitatively with bacterial numbers from the culture medium and those attached to the valves. This is correlated with increasing adherence ratios of the attaching staphylococci

Integrated Administrative Data for Early Childhood Iowa: A Governance Model to inform Policy and Program Collaboration

In response to demands on public systems to do more, do better, and cost less, the value of integrated administrative data systems (IDS) for social policy is increasing (Fantuzzo & Culhane, 2016). This is particularly relevant in programming for young children where services are historically fragmented, disconnected from systems serving school-aged children, and siloed among health, human services, and education agencies. Guided by the vision that Iowa’s early childhood system will be effectively and efficiently coordinated to support healthy families, we are developing an early childhood IDS to address this disconnection and facilitate relevant and actionable social policy research. Iowa’s IDS is a state-university partnership that acknowledges the need for agencies to retain control of their data while enabling it to be integrated across systems for social policy research. The innovative governance model deliberately incorporates procedures for stakeholder engagement at critical tension points between executive leaders, program managers, researchers, and practitioners. Standing committees (Governance Board, Data Stewardship, and Core team) authorize and implement the work of the IDS, while ad-hoc committees are solicited for specific projects to advise and translate research into practice. This paper will articulate the Iowa IDS governance model that was informed by means tested principles articulated by the Actionable Intelligence for Social Policy Network. It will include our collaborative development process; articulated mission and principles that guided discussions about legal authorization, governance, and use cases; and the establishment of governance committees to implement our vision for ethical and efficient use of administrative data for social policy

Signaling from the plasma-membrane localized plant immune receptor RPM1 requires self-association of the full-length protein

Pathogen recognition first occurs at the plasma membrane, where receptor-like kinases perceive pathogen-derived molecules and initiate immune responses. To abrogate this immune response, pathogens evolved effector proteins that act as virulence factors, often following delivery to the host cell. Plants evolved intracellular receptors, known as NOD-like receptors (NLRs), to detect effectors, thereby ensuring activation of effector-triggered immunity. However, despite their importance in immunity, the molecular mechanisms underlying effector recognition and subsequent immune activation by membrane-localized NLRs remain to be fully elucidated. Our analyses reveal the importance of and need for self-association and the coordinated interplay of specific domains and conserved residues for NLR activity. This could provide strategies for crop improvement, contributing to effective, environmentally friendly, and sustainable solutions for future agriculture

LIN28A expression reduces sickling of cultured human erythrocytes

Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with sickle cell disease (SCD) and the beta-thalassemias. It was recently reported that increased expression of LIN28 proteins or decreased expression of its target let-7 miRNAs enhances HbF levels in cultured primary human erythroblasts from adult healthy donors. Here LIN28A effects were studied further using erythrocytes cultured from peripheral blood progenitor cells of pediatric subjects with SCD. Transgenic expression of LIN28A was accomplished by lentiviral transduction in CD34(+) sickle cells cultivated ex vivo in serum-free medium. LIN28A over-expression (LIN28A-OE) increased HbF, reduced beta (sickle)-globin, and strongly suppressed all members of the let-7 family of miRNAs. LIN28A-OE did not affect erythroblast differentiation or prevent enucleation, but it significantly reduced or ameliorated the sickling morphologies of the enucleated erythrocytes

TIR-only protein RBA1 recognizes a pathogen effector to regulate cell death in Arabidopsis

Multicellular organisms must have complex immune systems to detect and defeat pathogens. Plants rely on nucleotide binding site leucine rich repeat (NLR) intracellular receptors to detect pathogens. For hundreds of years, plant breeders have selected for disease-resistance traits derived from NLR genes. Despite the molecular cloning of the first NLRs more than 20 y ago, we still do not understand how these sensors function at a mechanistic level. Here, we identified a truncated NLR protein that activates cell death in response to a specific pathogen effector. Understanding how truncated NLRs function will provide a better mechanistic understanding of the plant immune system and an expanded toolkit with which to engineer disease resistance rationally in crops

Labrador retrievers under primary veterinary care in the UK: demography, mortality and disorders

Abstract Background Labrador retrievers are reportedly predisposed to many disorders but accurate prevalence information relating to the general population are lacking. This study aimed to describe demography, mortality and commonly recorded diseases in Labrador retrievers under UK veterinary care. Methods The VetCompass™ programme collects electronic patient record data on dogs attending UK primary-care veterinary practices. Demographic analysis covered all33,320 Labrador retrievers in the VetCompass™ database under veterinary care during 2013 while disorder and mortality data were extracted from a random sample of 2074 (6.2%) of these dogs. Results Of the Labrador retrievers with information available, 15,427 (46.4%) were female and 15,252 (53.6%) were male. Females were more likely to be neutered than males (59.7% versus 54.8%, P <  0.001). The overall mean adult bodyweight was 33.0 kg (SD 6.1). Adult males were heavier (35.2 kg, SD 5.9 kg) than adult females (30.4 kg, SD 5.2 kg) (P <  0.001). The median longevity of Labrador retrievers overall was 12.0 years (IQR 9.9–13.8, range 0.0–16.0). The most common recorded colours were black (44.6%), yellow (27.8%) and liver/chocolate (reported from hereon as chocolate) (23.8%). The median longevity of non-chocolate coloured dogs (n = 139, 12.1 years, IQR 10.2–13.9, range 0.0–16.0) was longer than for chocolate coloured animals (n = 34, 10.7 years, IQR 9.0–12.4, range 3.8–15.5) (P = 0.028). Of a random sample of 2074 (6.2%) Labrador retrievers under care in 2013 that had full disorder data extracted, 1277 (61.6%) had at least one disorder recorded. The total number of dogs who died at any date during the study was 176. The most prevalent disorders recorded were otitis externa (n = 215, prevalence 10.4%, 95% CI: 9.1–11.8), overweight/obesity (183, 8.8%, 95% CI: 7.6–10.1) and degenerative joint disease (115, 5.5%, 95% CI: 4.6–6.6). Overweight/obesity was not statistically significantly associated with neutering in females (8.3% of entire versus 12.5% of neutered, P = 0.065) but was associated with neutering in males (4.1% of entire versus 11.4% of neutered, P < 0.001). The prevalence of otitis externa in black dogs was 12.8%, in yellow dogs it was 17.0% but, in chocolate dogs, it rose to 23.4% (P < 0.001). Similarly, the prevalence of pyo-traumatic dermatitis in black dogs was 1.1%, in yellow dogs it was 1.6% but in chocolate dogs it rose to 4.0% (P = 0.011). Conclusions The current study assists prioritisation of health issues within Labrador retrievers. The most common disorders were overweight/obesity, otitis externa and degenerative joint disease. Males were significantly heavier females. These results can alert prospective owners to potential health issues and inform breed-specific wellness checks

Trans-endocytosis of CD80 and CD86:a molecular basis for the cell-extrinsic function of CTLA-4

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system

Identifying Key Factors Associated with Aggression on Acute Inpatient Psychiatric Wards

Aggressive behaviour is a critical issue for modern acute psychiatric services, not just because of the adverse impact it has on patients and staff, but also because it puts a financial strain on service providers. The aim of this study was to assess the relationship of patient violence to other variables: patient characteristics, features of the service and physical environment, patient routines, staff factors, the use of containment methods, and other patient behaviours. A multivariate cross sectional design was utilised. Data were collected for a six month period on 136 acute psychiatric wards in 26 NHS Trusts in England. Multilevel modelling was conducted to ascertain those factors most strongly associated with verbal aggression, aggression toward objects, and physical aggression against others. High levels of aggression were associated with a high proportion of patients formally detained under mental health legislation, high patient turnover, alcohol use by patients, ward doors being locked, and higher staffing numbers (especially qualified nurses). The findings suggest that the imposition of restrictions on patients exacerbates the problem of violence, and that alcohol management strategies may be a productive intervention. Insufficient evidence is available to draw conclusions about the nature of the link between staffing numbers and violence

The Gaseous Electronics Conference radio‐frequency reference cell: A defined parallel‐plate radio‐frequency system for experimental and theoretical studies of plasma‐processing discharges

A ‘‘reference cell’’ for generating radio‐frequency (rf) glow discharges in gases at a frequency of 13.56 MHz is described. The reference cell provides an experimental platform for comparing plasma measurements carried out in a common reactor geometry by different experimental groups, thereby enhancing the transfer of knowledge and insight gained in rf discharge studies. The results of performing ostensibly identical measurements on six of these cells in five different laboratories are analyzed and discussed. Measurements were made of plasma voltage and current characteristics for discharges in pure argon at specified values of applied voltages, gas pressures, and gas flow rates. Data are presented on relevant electrical quantities derived from Fourier analysis of the voltage and current wave forms. Amplitudes, phase shifts, self‐bias voltages, and power dissipation were measured. Each of the cells was characterized in terms of its measured internal reactive components. Comparing results from different cells provides an indication of the degree of precision needed to define the electrical configuration and operating parameters in order to achieve identical performance at various laboratories. The results show, for example, that the external circuit, including the reactive components of the rf power source, can significantly influence the discharge. Results obtained in reference cells with identical rf power sources demonstrate that considerable progress has been made in developing a phenomenological understanding of the conditions needed to obtain reproducible discharge conditions in independent reference cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70394/2/RSINAK-65-1-140-1.pd