1,591 research outputs found

    Photoreceptors generate neuronal diversity in their target field through a Hedgehog morphogen gradient in Drosophila

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    Defining the origin of neuronal diversity is a major challenge in developmental neurobiology. The Drosophila visual system is an excellent paradigm to study how cellular diversity is generated. Photoreceptors from the eye disc grow their axons into the optic lobe and secrete Hedgehog (Hh) to induce the lamina, such that for every unit eye there is a corresponding lamina unit made up of post-mitotic precursors stacked into columns. Each differentiated column contains five lamina neuron types (L1-L5), making it the simplest neuropil in the optic lobe, yet how this diversity is generated was unknown. Here, we found that Hh pathway activity is graded along the distal-proximal axis of lamina columns and further determined that this gradient in pathway activity arises from a gradient of Hh ligand. We manipulated Hh pathway activity cell-autonomously in lamina precursors and non-cell autonomously by inactivating the Hh ligand, and by knocking it down in photoreceptors. These manipulations showed that different thresholds of activity specify unique cell identities, with more proximal cell types specified in response to progressively lower Hh levels. Thus, our data establish that Hh acts as a morphogen to pattern the lamina. Although, this is the first such report during Drosophila nervous system development, our work uncovers a remarkable similarity with the vertebrate neural tube, which is patterned by Sonic Hedgehog. Altogether, we show that differentiating neurons can regulate the neuronal diversity of their distant target fields through morphogen gradients

    Critical thinking in community nursing: Is this the 7th C?

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    Compassion in practice and the drive to deliver the 6Cs—care, compassion, competence, communication, courage, and commitment—has been embraced within community nursing practice since its launch in 2012 (Commissioning Board Chief Nursing Officer and Department of Health (DH) Chief Nursing Adviser, 2012). Following the shortcomings in care discovered at the Mid-Staffordshire NHS Foundation Trust and the findings of inquiries (e.g. Francis, 2013; Keogh, 2013), nursing as a profession has been under pressure to demonstrate to the public that nurses do care. This need comes under increasing scrutiny when working in the homes of patients, who rightly require demonstration of accountability of care. Effective therapeutic relationships with patients in the community are built on trust, and patients should feel confident that clinical care is appropriate and evidence based (Griffith, 2015). A strong focus upon the core themes of the 6Cs is both integral to and apparent in daily practice within the community setting. The terminology of the 6Cs is a frequent feature of discussions, supervision, teaching, and record keeping. However, is it possible that in this drive to improve the public image of nursing through the focus of care and compassion, the concept of critical thinking is considered secondary? Should critical thinking in community nursing practice be awarded a ‘C’ in its own right

    The flux and provenance of dust delivered to the SW Pacific during the last glacial maximum

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    The funding for the TAN1106 voyage was from the Coasts and Oceans Physical Resources program awarded to the National Institute of Water and Atmospheric Research, New Zealand. This work was funded by NERC studentship NE/L002531/1 to R.S. and NERC grant NE/J021075/1 to G.L.F. R.G. and A.B. were supported by NERC grant NE/M004619/1 awarded to A.B.Atmospheric dust is a primary source of iron (Fe) to the open ocean, and its flux is particularly important in the high nutrient, low chlorophyll (HNLC) Southern Ocean where Fe currently limits productivity. Alleviation of this Fe limitation in the Subantarctic Zone of the Atlantic by increased dust-borne Fe supply during glacial periods has been shown to increase primary productivity. However, previous work has found no such increase in productivity in the Pacific sector. In order to constrain the relative importance of Southern Ocean Fe fertilization on glacial-interglacial carbon cycles, records of dust fluxes outside of the Atlantic sector of the Southern Ocean at the Last Glacial Maximum (LGM) are required. Here we use grain size and U-series analyses to reconstruct lithogenic and CaCO3 fluxes, and Nd, Sr and Pb isotopes to ascertain the provenance of terrigenous material delivered to four deep-water cores in the SW Pacific Ocean over the last ~30kyr. We find evidence for an increase in the relative proportion of fine-grained (0.5-12 ?m) terrigenous sediment and higher detrital fluxes during the LGM compared to the Holocene. The provenance of the LGM dust varied spatially, with an older, more "continental" signature (low εNd, high 87Sr/86Sr) sourced from Australia in the northern cores, and a younger, more volcanogenic source in the southern cores (high εNd, low 87Sr/86Sr), likely sourced locally from New Zealand. Given this increase in lithogenic flux to the HNLC subantarctic Pacific Southern Ocean during the LGM, factors besides Fe-supply must have regulated the biological productivity here.Publisher PDFPeer reviewe

    Differentiation signals from glia are fine-tuned to set neuronal numbers during development

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    Neural circuit formation and function require that diverse neurons are specified in appropriate numbers. Known strategies for controlling neuronal numbers involve regulating either cell proliferation or survival. We used the Drosophila visual system to probe how neuronal numbers are set. Photoreceptors from the eye-disc induce their target field, the lamina, such that for every unit eye there is a corresponding lamina unit (column). Although each column initially contains ~6 post-mitotic lamina precursors, only 5 differentiate into neurons, called L1-L5; the 'extra' precursor, which is invariantly positioned above the L5 neuron in each column, undergoes apoptosis. Here, we showed that a glial population called the outer chiasm giant glia (xgO), which resides below the lamina, secretes multiple ligands to induce L5 differentiation in response to EGF from photoreceptors. By forcing neuronal differentiation in the lamina, we uncovered that though fated to die, the 'extra' precursor is specified as an L5. Therefore, two precursors are specified as L5s but only one differentiates during normal development. We found that the row of precursors nearest to xgO differentiate into L5s and, in turn, antagonise differentiation signalling to prevent the 'extra' precursors from differentiating, resulting in their death. Thus, an intricate interplay of glial signals and feedback from differentiating neurons defines an invariant and stereotyped pattern of neuronal differentiation and programmed cell death to ensure that lamina columns each contain exactly one L5 neuro

    The Gregory-Laflamme instability for the D2-D0 bound state

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    The D2-D0 bound state exhibits a Gregory-Laflamme instability when it is sufficiently non-extremal. If there are no D0-branes, the requisite non-extremality is finite. When most of the extremal mass comes from D0-branes, the requisite non-extremality is very small. The location of the threshhold for the instability is determined using a local thermodynamic analysis which is then checked against a numerical analysis of the linearized equations of motion. The thermodynamic analysis reveals an instability of non-commutative field theory at finite temperature, which may occur only at very long wavelengths as the decoupling limit is approached.Comment: 19 pages, Latex2e. v2: two refs added. v3: clearer exposition in section

    Fitness, fatness and active school commuting among Liverpool schoolchildren

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    This study investigated differences in health outcomes between active and passive school commuters, and examined associations between parent perceptions of the neighborhood environment and active school commuting (ASC). One hundred-ninety-four children (107 girls), aged 9–10 years from ten primary schools in Liverpool, England, participated in this cross-sectional study. Measures of stature, body mass, waist circumference and cardiorespiratory fitness (CRF) were taken. School commute mode (active/passive) was self-reported and parents completed the neighborhood environment walkability scale for youth. Fifty-three percent of children commuted to school actively. Schoolchildren who lived in more deprived neighborhoods perceived by parents as being highly connected, unaesthetic and having mixed land-use were more likely to commute to school actively (p < 0.05). These children were at greatest risk of being obese and aerobically unfit(p < 0.01). Our results suggest that deprivation may explain the counterintuitive relationship between obesity, CRF and ASC in Liverpool schoolchildren. These findings encourage researchers and policy makers to be equally mindful of the social determinants of health when advocating behavioral and environmental health interventions. Further research exploring contextual factors to ASC, and examining the concurrent effect of ASC and diet on weight status by deprivation is needed

    What Is the Best Way to Identify Malignant Transformation Within Pancreatic IPMN: A Systematic Review and Meta-Analyses

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    OBJECTIVES: Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the usefulness of tumor markers in serum and cyst fluid to predict malignancy in IPMN. METHODS: Databases were searched from November 2006 to March 2014. Pooled sensitivity and specificity of diagnostic techniques/imaging features of suspected malignancy in IPMN using a hierarchical summary receiver operator characteristic (HSROC) approach were performed. RESULTS: A total of 467 eligible studies were identified, of which 51 studies met the inclusion criteria and 37 of these were incorporated into meta-analyses. The pooled sensitivity and specificity for risk features predictive of malignancy on computed tomography/magnetic resonance imaging were 0.809 and 0.762 respectively, and on positron emission tomography were 0.968 and 0.911. Mural nodule, cyst size, and main pancreatic duct dilation found on imaging had pooled sensitivity for prediction of malignancy of 0.690, 0.682, and 0.614, respectively, and specificity of 0.798, 0.574, and 0.687. Raised serum carbohydrate antigen 19-9 (CA19-9) levels yielded sensitivity of 0.380 and specificity of 0903. Combining parameters yielded a sensitivity of 0.743 and specificity of 0.906. CONCLUSIONS: PET holds the most promise in identifying malignant transformation within an IPMN. Combining parameters increases sensitivity and specificity; the presence of mural nodule on imaging was the most sensitive whereas raised serum CA19-9 (>37 KU/l) was the most specific feature predictive of malignancy in IPMNs
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