PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration

A fundamental property of neural crest (NC) migration is contact inhibition of locomotion (CIL), a process by which cells change their direction of migration upon cell contact. CIL has been proven to be essential for NC migration in amphibians and zebrafish by controlling cell polarity in a cell contact-dependent manner. Cell contact during CIL requires the participation of the cell adhesion molecule N-cadherin, which starts to be expressed by NC cells as a consequence of the switch between E- and N-cadherins during epithelial-to-mesenchymal transition (EMT). However, the mechanism that controls the upregulation of N-cadherin remains unknown. Here, we show that platelet-derived growth factor receptor alpha (PDGFRα) and its ligand platelet-derived growth factor A (PDGF-A) are co-expressed in migrating cranial NC. Inhibition of PDGF-A/PDGFRα blocks NC migration by inhibiting N-cadherin and, consequently, impairing CIL. Moreover, we identify phosphatidylinositol-3-kinase (PI3K)/AKT as a downstream effector of the PDGFRα cellular response during CIL. Our results lead us to propose PDGF-A/ PDGFRα signalling as a tissue-autonomous regulator of CIL by controlling N-cadherin upregulation during EMT. Finally, we show that once NC cells have undergone EMT, the same PDGF-A/PDGFRα works as an NC chemoattractant, guiding their directional migration

Cryoelectron-microscopy structure of the enteropathogenic Escherichia coli type III secretion system EspA filament.

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) utilize a macromolecular type III secretion system (T3SS) to inject effector proteins into eukaryotic cells. This apparatus spans the inner and outer bacterial membranes and includes a helical needle protruding into the extracellular space. Thus far observed only in EPEC and EHEC and not found in other pathogenic Gram-negative bacteria that have a T3SS is an additional helical filament made by the EspA protein that forms a long extension to the needle, mediating both attachment to eukaryotic cells and transport of effector proteins through the intestinal mucus layer. Here, we present the structure of the EspA filament from EPEC at 3.4 Å resolution. The structure reveals that the EspA filament is a right-handed 1-start helical assembly with a conserved lumen architecture with respect to the needle to ensure the seamless transport of unfolded cargos en route to the target cell. This functional conservation is despite the fact that there is little apparent overall conservation at the level of sequence or structure with the needle. We also unveil the molecular details of the immunodominant EspA epitope that can now be exploited for the rational design of epitope display systems

Flagellin outer domain dimerization modulates motility in pathogenic and soil bacteria from viscous environments.

Flagellar filaments function as the propellers of the bacterial flagellum and their supercoiling is key to motility. The outer domains on the surface of the filament are non-critical for motility in many bacteria and their structures and functions are not conserved. Here, we show the atomic cryo-electron microscopy structures for flagellar filaments from enterohemorrhagic Escherichia coli O157:H7, enteropathogenic E. coli O127:H6, Achromobacter, and Sinorhizobium meliloti, where the outer domains dimerize or tetramerize to form either a sheath or a screw-like surface. These dimers are formed by 180° rotations of half of the outer domains. The outer domain sheath (ODS) plays a role in bacterial motility by stabilizing an intermediate waveform and prolonging the tumbling of E. coli cells. Bacteria with these ODS and screw-like flagellar filaments are commonly found in soil and human intestinal environments of relatively high viscosity suggesting a role for the dimerization in these environments

Quality of Care for HIV Infection Provided by Ryan White Program-Supported versus Non-Ryan White Program-Supported Facilities

BACKGROUND: The Ryan White HIV/AIDS Care Act (now the Treatment Modernization Act; Ryan White Program, or RWP) is a source of federal public funding for HIV care in the United States. The Health Services and Resources Administration requires that facilities or providers who receive RWP funds ensure that HIV health services are accessible and delivered according to established HIV-related treatment guidelines. We used data from population-based samples of persons in care for HIV infection in three states to compare the quality of HIV care in facilities supported by the RWP, with facilities not supported by the RWP. METHODOLOGY/PRINCIPAL FINDINGS: Within each area (King County in Washington State; southern Louisiana; and Michigan), a probability sample of patients receiving care for HIV infection in 1998 was drawn. Based on medical records abstraction, information was collected on prescription of antiretroviral therapy according to treatment recommendations, prescription of prophylactic therapy, and provision of recommended vaccinations and screening tests. We calculated population-level estimates of the extent to which HIV care was provided according to then-current treatment guidelines in RWP-supported and non-RWP-supported facilities. For all treatment outcomes analyzed, the compliance with care guidelines was at least as good for patients who received care at RWP-supported (vs non-RWP supported) facilities. For some outcomes in some states, delivery of recommended care was significantly more common for patients receiving care in RWP-supported facilities: for example, in Louisiana, patients receiving care in RWP-supported facilities were more likely to receive indicated prophylaxis for Pneumocystis jirovecii pneumonia and Mycobacterium avium complex, and in all three states, women receiving care in RWP-supported facilities were more likely to have received an annual Pap smear. CONCLUSIONS/SIGNIFICANCE: The quality of HIV care provided in 1998 to patients in RWP-supported facilities was of equivalent or better quality than in non-RWP supported facilities; however, there were significant opportunities for improvement in all facility types. Data from population-based clinical outcomes surveillance data can be used as part of a broader strategy to evaluate the quality of publicly-supported HIV care

Patient safety culture in Norwegian home health nursing: a cross-sectional study of healthcare provider’s perceptions of the teamwork and safety climates

Background: The threefold aim of this study was to (1) describe attitudes to patient safety among healthcare providers in home health nursing (HHN), (2) investigate differences in attitudes due to age, education level, years of healthcare work experience, and years at current workplace, and (3) compare attitudes of these HHN healthcare providers with available benchmark data from other healthcare settings. Methods: One hundred sixty HHN healthcare providers in Mid-Norway answered a survey covering the teamwork climate and safety climate in the Safety Attitudes Questionnaire (SAQ). Data were analyzed by descriptive statistics, t test, and ANOVA. Results: The overall mean score was 79.1 for teamwork climate and 72.3 for safety climate. The proportion of positive responses (i.e., scale scores ≥ 75) was 73% on teamwork climate and 53% on safety climate. For teamwork and safety climates, employees with the longest employment at the current workplace had significantly higher mean scores than those with shorter employment. No significant differences were found in mean scores for age, education level, and length of experience in healthcare. Compared to benchmark data from other studies, the mean HHN scores for both safety and teamwork climates were higher than in the vast majority of other Healthcare settings and significant differences were found for both dimensions. Conclusion: HHN has higher scores for both safety climate and teamwork climate compared to the vast majority of other healthcare settings, but there is room for improvement in the patient safety culture within the Norwegian HHN. Further research on patient safety culture in HHN is needed.publishedVersio

High performing hospitals: a qualitative systematic review of associated factors and practical strategies for improvement.

BACKGROUND: High performing hospitals attain excellence across multiple measures of performance and multiple departments. Studying high performing hospitals can be valuable if factors associated with high performance can be identified and applied. Factors leading to high performance are complex and an exclusive quantitative approach may fail to identify richly descriptive or relevant contextual factors. The objective of this study was to undertake a systematic review of qualitative literature to identify methods used to identify high performing hospitals, the factors associated with high performers, and practical strategies for improvement. METHODS: Methods used to collect and summarise the evidence contributing to this review followed the 'enhancing transparency in reporting the synthesis of qualitative research' protocol. Peer reviewed studies were identified through Medline, Embase and Cinahl (Jan 2000-Feb 2014) using specified key words, subject terms, and medical subject headings. Eligible studies required the use of a quantitative method to identify high performing hospitals, and qualitative methods or tools to identify factors associated with high performing hospitals or hospital departments. Title, abstract, and full text screening was undertaken by four reviewers, and inter-rater reliability statistics were calculated for each review phase. Risk of bias was assessed. Following data extraction, thematic syntheses identified contextual factors important for explaining success. Practical strategies for achieving high performance were then mapped against the identified themes. RESULTS: A total of 19 studies from a possible 11,428 were included in the review. A range of process, output, outcome and other indicators were used to identify high performing hospitals. Seven themes representing factors associated with high performance (and 25 sub-themes) emerged from the thematic syntheses: positive organisational culture, senior management support, effective performance monitoring, building and maintaining a proficient workforce, effective leaders across the organisation, expertise-driven practice, and interdisciplinary teamwork. Fifty six practical strategies for achieving high performance were catalogued. CONCLUSIONS: This review provides insights into methods used to identify high performing hospitals, and yields ideas about the factors important for success. It highlights the need to advance approaches for understanding what constitutes high performance and how to harness factors associated with high performance

New early-maturing germplasm lines for utilization in chickpea improvement

Early-maturity helps chickpea to avoid terminal heat and drought and increases its adaptation especially in the sub-tropics. Breeding for early-maturing, high-yielding and broad-based cultivars requires diverse sources of early-maturity. Twenty-eight early-maturing chickpea germplasm lines representing wide geographical diversity were identified using core collection approach and evaluated with four control cultivars in five environments for 7 qualitative and 16 quantitative traits at ICRISAT Centre, Patancheru, India. Significant genotypic variance was observed for days to flowering and maturity in all the environments indicating scope for selection. Genotypes × environment interactions were significant for days to flowering and maturity and eight other agronomic traits. ICC 16641, ICC 16644, ICC 11040, ICC 11180, and ICC 12424 were very early-maturing, similar to or earlier than control cultivars Harigantars and ICCV 2. The early-maturing accessions produced on average 22.8% more seed yield than the mean of four control cultivars in the test environments. ICC 14648, ICC 16641 and ICC 16644 had higher 100-seed weight than control cultivars, Annigeri and ICCV 2. Cluster analysis delineated three clusters, which differed significantly for all the traits. First cluster comprised three controls, ICCV 96029, Harigantars, ICCV 2 and two germplasm lines, ICC 16644 and ICC 16641, second cluster comprised 13 germplasm lines and control cultivar Annigeri, and third cluster comprised 13 germplasm lines. Maturity was main basis of delineation of the first cluster from others. Plot yield and its associated traits were the main basis for delineation of the second cluster

Distinct Functional Constraints Partition Sequence Conservation in a cis-Regulatory Element

Different functional constraints contribute to different evolutionary rates across genomes. To understand why some sequences evolve faster than others in a single cis-regulatory locus, we investigated function and evolutionary dynamics of the promoter of the Caenorhabditis elegans unc-47 gene. We found that this promoter consists of two distinct domains. The proximal promoter is conserved and is largely sufficient to direct appropriate spatial expression. The distal promoter displays little if any conservation between several closely related nematodes. Despite this divergence, sequences from all species confer robustness of expression, arguing that this function does not require substantial sequence conservation. We showed that even unrelated sequences have the ability to promote robust expression. A prominent feature shared by all of these robustness-promoting sequences is an AT-enriched nucleotide composition consistent with nucleosome depletion. Because general sequence composition can be maintained despite sequence turnover, our results explain how different functional constraints can lead to vastly disparate rates of sequence divergence within a promoter