A novel spalt gene expressed in branchial arches affects the ability of cranial neural crest cells to populate sensory ganglia

Cranial neural crest cells differentiate into diverse derivatives including neurons and glia of the cranial ganglia, and cartilage and bone of the facial skeleton. Here, we explore the function of a novel transcription factor of the spalt family that might be involved in early cell-lineage decisions of the avian neural crest. The chicken spalt4 gene (csal4) is expressed in the neural tube, migrating neural crest, branchial arches and, transiently, in the cranial ectoderm. Later, it is expressed in the mesectodermal, but not neuronal or glial, derivatives of midbrain and hindbrain neural crest. After over-expression by electroporation into the cranial neural tube and neural crest, we observed a marked redistribution of electroporated neural crest cells in the vicinity of the trigeminal ganglion. In control-electroporated embryos, numerous, labeled neural crest cells ([similar]80% of the population) entered the ganglion, many of which differentiated into neurons. By contrast, few ([similar]30% of the population) spalt-electroporated neural crest cells entered the trigeminal ganglion. Instead, they localized in the mesenchyme around the ganglionic periphery or continued further ventrally to the branchial arches. Interestingly, little or no expression of differentiation markers for neurons or other cell types was observed in spalt-electroporated neural crest cells

Spalt4 mediates invagination and otic placode gene expression in cranial ectoderm

Vertebrate placodes are regions of thickened head ectoderm that contribute to paired sensory organs and cranial ganglia. We demonstrate that the transcription factor Spalt4 (also known as Sall4) is broadly expressed in chick preplacodal epiblast and later resolves to otic, lens and olfactory placodes. Ectopic expression of Spalt4 by electroporation is sufficient to induce invagination of non-placodal head ectoderm and prevent neurogenic placodes from contributing to cranial ganglia. Conversely, loss of Spalt4 function in the otic placode results in abnormal otic vesicle development. Intriguingly, Spalt4 appears to initiate a placode program appropriate for the axial level but is not involved in later development of specific placode fates. Fgfs can regulate Spalt4, since implantation of Fgf2 beads into the area opaca induces its expression. The results suggest that Spalt4 is involved in early stages of placode development, initiating cranial ectodermal invagination and region-specific gene regulatory networks

Are Rural and Urban Newly Licensed Nurses Different? A Longitudinal Study of a Nurse Residency Programme

Aim This study aimed to compare rural and urban nurse residency programme participants’ personal and job characteristics and perceptions of decision-making, job satisfaction, job stress, nursing performance and organisational commitment over time. Background Nurse residency programmes are an evolving strategy to foster transition to practice for new nurses. However, there are limited data available for programme outcomes particularly for rural nurses. Method A longitudinal design sampled 382 urban and 86 rural newly licensed hospital nurses during a 12-month nurse residency programme. Data were collected at the start of the programme, at 6 months and the end of the programme. Results At the end of the programme, rural nurses had significantly higher job satisfaction and lower job stress compared with urban nurses. Across all time-periods rural nurses had significantly lower levels of stress caused by the physical work environment and at the end of the programme had less stress related to staffing compared with urban nurses. Perceptions of their organisational commitment and competency to make decisions and perform role elements were similar. Conclusions Differences in these outcomes may be result from unique characteristics of rural vs. urban nursing practice that need further exploration. Implications for nursing management Providing a nurse residency programme in rural and urban hospitals can be a useful recruitment and retention strategy

Identification and dissection of a key enhancer mediating cranial neural crest specific expression of transcription factor, Ets-1

Neural crest cells form diverse derivatives that vary according to their level of origin along the body axis, with only cranial neural crest cells contributing to facial skeleton. Interestingly, the transcription factor Ets-1 is uniquely expressed in cranial but not trunk neural crest, where it functions as a direct input into neural crest specifier genes, Sox10 and FoxD3. We have isolated and interrogated a cis-regulatory element, conserved between birds and mammals, that drives reporter expression in a manner that recapitulates that of endogenous Ets-1 expression in the neural crest. Within a minimal Ets-1 enhancer region, mutation of putative binding sites for SoxE, homeobox, Ets, TFAP2 or Fox proteins results in loss or reduction of neural crest enhancer activity. Morpholino-mediated loss-of-function experiments show that Sox9, Pax7, Msx1/2, Ets-1, TFAP2A and FoxD3, all are required for enhancer activity. In contrast, mutation of a putative cMyc/E-box sequence augments reporter expression, consistent with this being a repressor binding site. Taken together, these results uncover new inputs into Ets-1, revealing critical links in the cranial neural crest gene regulatory network

A Comparison of Quality of Care in Critical Access Hospitals and Other Rural Hospitals

Purpose: The United States has about 2100 rural hospitals. Approximately 1300 are Critical Access Hospitals (CAHs) with 25 beds or less. CAHs receive cost-based reimbursement through the federal Flex program with the goal to improve quality and access to health care. Reports on quality of care (QOC) and factors that influence quality in CAHs are mixed. This study compared QOC and factors that influence QOC in CAHs and other rural hospitals. Sample: 385 staff nurses in 6 CAHs and 9 other rural hospitals in North Carolina and Virginia. Method: Descriptive cross-sectional design using nurse surveys aggregated to the hospital level, data from provider of services file, and the United States Department of Agriculture, Economic Research files. Variables on community, hospital, and nursing unit characteristics, the nurse work environment, nurse rated QOC and community perception of hospital quality were compared using t-test or chi-square. Findings: There were no differences in the majority of factors influencing QOC. A culture of safety, the nurse work environment, and QOC were rated high in all hospitals. Compared to other rural hospitals CAHs tend to be located in communities with better economic status and their nurses had more years of nursing experience. More nurses in CAHs felt their community recognized their hospital as a good place for minor health issues and would recommend the hospital to family and friends. Conclusions: The high ratings of QOC were accompanied with the presence of safety cultures and work environments rated as highly as in Magnet hospitals. The lower poverty levels in communities with CAHs suggest possible community financial benefits from CAHs. More studies are warranted to explore these relationships. Further reporting to public quality indicator databases by all CAHs should be encouraged and QOC measures relevant for small rural hospitals should be developed

Stage-dependent plasticity of the anterior neural folds to form neural crest

The anterior neural fold (ANF) is the only region of the neural tube that does not produce neural crest cells. Instead, ANF cells contribute to the olfactory and lens placodes, as well as to the forebrain and epidermis. Here, we test the ability of the ANF to form neural crest by performing heterotopic transplantation experiments in the chick embryo. We find that, at the neurula stage (HH stage 7), the chick ANF retains the ability to form migrating neural crest cells when transplanted caudally to rostral hindbrain levels. This ability is gradually lost, such that by HH9, this tissue appears to no longer have the potential to form neural crest. In contrast to the ANF, hindbrain dorsal neural folds transplanted rostrally fail to contribute to the olfactory placode but instead continue to generate neural crest cells. The transcription factor GANF is expressed in the ANF and its morpholino-mediated knock-down expands the neural crest domain rostrally and results in the production of migratory cells emerging from the ANF; however, these cells fail to express the HNK1 neural crest marker, suggesting only partial conversion. Our results show that environmental factors can imbue the chick anterior neural folds to assume a neural crest cell fate via a mechanism that partially involves loss of GANF

The role of incubator support in new firms accumulation of resources and capabilities

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Routledge (Taylor & Francis group) in Innovation: Organization and Management on 21/11/2019.Available online: https://www.tandfonline.com/doi/full/10.1080/14479338.2019.1684204acceptedVersio

Lunatic fringe causes expansion and increased neurogenesis of trunk neural tube and neural crest populations

Both neurons and glia of the PNS are derived from the neural crest. In this study, we have examined the potential function of lunatic fringe in neural tube and trunk neural crest development by gain-of-function analysis during early stages of nervous system formation. Normally lunatic fringe is expressed in three broad bands within the neural tube, and is most prominent in the dorsal neural tube containing neural crest precursors. Using retrovirally-mediated gene transfer, we find that excess lunatic fringe in the neural tube increases the numbers of neural crest cells in the migratory stream via an apparent increase in cell proliferation. In addition, lunatic fringe augments the numbers of neurons and upregulates Delta-1 expression. The results indicate that, by modulating Notch/Delta signaling, lunatic fringe not only increases cell division of neural crest precursors, but also increases the numbers of neurons in the trunk neural crest

Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism

The aim of the present study was to analyze possible relationships between pulmonary vessel obstruction and clinically relevant parameters and scores in patients with pulmonary embolism (PE). Overall, 246 patients (48.8% women and 51.2% men) with a mean age of 64.0 17.1 years were involved in the retrospective study. The following clinical scores were calculated in the patients: Wells score, Geneva score, and pulmonary embolism severity index (PESI) score. Levels of D-dimer (g/mL), lactate, pH, troponin, and N-terminal natriuretic peptide (BNP, pg/mL) were acquired. Thrombotic obstruction of the pulmonary arteries was quantified according to Mastora score. The data collected were evaluated by means of descriptive statistics. Spearman’s correlation coeffcient was used to analyze associations between the investigated parameters. P values < 0.05 were taken to indicate statistical significance. Mastora score correlated weakly with lactate level and tended to correlate with D-dimer and BNP levels. No other clinical or serological parameters correlated significantly with clot burden. Thrombotic obstruction of pulmonary vessels did not correlate with clinical severity of PE

Pax2 and Pea3 synergize to activate a novel regulatory enhancer for spalt4 in the developing ear

The transcription factor spalt4 is a key early-response gene in otic placode induction. Here, we characterize the cis-regulatory regions of spalt4 responsible for activation of its expression in the developing otic placode and report the isolation of a novel core enhancer. Identification and mutational analysis of putative transcription factor binding sites reveal that Pea3, a downstream effector of FGF signaling, and Pax2 directly activate spalt4 during ear development. Morpholino-mediated knock-down of each factor reduces or eliminates reporter expression. In contrast, combined over-expression of Pea3 and Pax2 drives ectopic reporter expression, suggesting that they function synergistically. These studies expand the gene regulatory network underlying early otic development by identifying direct inputs that mediate spalt4 expression