Hypoxia significantly reduces aminolaevulinic acid-induced protoporphyrin IX synthesis in EMT6 cells

We have studied the effects of hypoxia on aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) synthesis in EMT6 monolayer cultures characterized by different cell densities and proliferation rates. Specifically, after ALA incubation under hypoxic or normoxic conditions, we detected spectrofluorometrically the PpIX content of the following populations: (a) low-density exponentially growing cells; (b) high-density fed-plateau cells; and (c) high-density unfed-plateau cells. These populations were selected either for the purpose of comparison with other in vitro studies (low-density exponentially growing cells) or as representatives of tumour regions adjacent to (high-density fed-plateau cells) and further away from (high-density unfed-plateau cells) capillaries. The amount of PpIX per cell produced by each one of these populations was higher after normoxic ALA incubation. The magnitude of the effect of hypoxia on PpIX synthesis was dependent on cell density and proliferation rate. A 42-fold decrease in PpIX fluorescence was observed for the high-density unfed-plateau cells. PpIX production by the low-density exponential cells was affected the least by ALA incubation under hypoxic conditions (1.4-fold decrease), whereas the effect on the high-density fed-plateau population was intermediate (20-fold decrease). © 1999 Cancer Research Campaig

Seawater redox variations during the deposition of the Kimmeridge Clay Formation, United Kingdom (Upper Jurassic): evidence from molybdenum isotopes and trace metal ratios

The Kimmeridge Clay Formation (KCF) and its equivalents worldwide represent one of the most prolonged periods of organic carbon accumulation of the Mesozoic. In this study, we use the molybdenum (Mo) stable isotope system in conjunction with a range of trace metal paleoredox proxies to assess how seawater redox varied both locally and globally during the deposition of the KCF. Facies with lower organic carbon contents (TOC 1–7 wt %) were deposited under mildly reducing (suboxic) conditions, while organic-rich facies (TOC >7 wt %) accumulated under more strongly reducing (anoxic or euxinic) local conditions. Trace metal abundances are closely linked to TOC content, suggesting that the intensity of reducing conditions varied repeatedly during the deposition of the KCF and may have been related to orbitally controlled climate changes. Long-term variations in ?98/95Mo are associated with the formation of organic-rich intervals and are related to third-order fluctuations in relative sea level. Differences in the mean ?98/95Mo composition of the organic-rich intervals suggest that the global distribution of reducing conditions was more extensive during the deposition of the Pectinatites wheatleyensis and lower Pectinatites hudlestoni zones than during the deposition of the upper Pectinatites hudlestoni and Pectinatites pectinatus zones. The global extent of reducing conditions during the Kimmerigidan was greater than today but was less widespread than during the Toarcian (Early Jurassic) oceanic anoxic event. This study also demonstrates that the Mo isotope system in Jurassic seawater responded to changes in redox conditions in a manner consistent with its behavior in present-day sedimentary environment

Return of the Great Spaghetti Monster : Learnings from a Twelve-Year Adventure in Web Software Development

The widespread adoption of the World Wide Web has fundamentally changed the landscape of software development. Only ten years ago, very few developers would write software for the Web, let alone consider using JavaScript or other web technologies for writing any serious software applications. In this paper, we reflect upon a twelve-year adventure in web development that began with the development of the Lively Kernel system at Sun Microsystems Labs in 2006. Back then, we also published some papers that identified important challenges in web-based software development based on established software engineering principles. We will revisit our earlier findings and compare the state of the art in web development today to our earlier learnings, followed by some reflections and suggestions for the road forward.Peer reviewe

Testing Meson Portal Dark Sector Solutions to the MiniBooNE Anomaly at CCM

A solution to the MiniBooNE excess invoking rare three-body decays of the charged pions and kaons to new states in the MeV mass scale was recently proposed as a dark-sector explanation. This class of solution illuminates the fact that, while the charged pions were focused in the target-mode run, their decay products were isotropically suppressed in the beam-dump-mode run in which no excess was observed. This suggests a new physics solution correlated to the mesonic sector. We investigate an extended set of phenomenological models that can explain the MiniBooNE excess as a dark sector solution, utilizing long-lived particles that might be produced in the three-body decays of the charged mesons and the two-body anomalous decays of the neutral mesons. Over a broad set of interactions with the long-lived particles, we show that these scenarios can be compatible with constraints from LSND, KARMEN, and MicroBooNE, and evaluate the sensitivity of the ongoing and future data taken by the Coherent CAPTAIN Mills experiment (CCM) to a potential discovery in this parameter space.Comment: 15 pages, 14 figures. Planned submission for PR

Islands beneath islands: phylogeography of a groundwater amphipod crustacean in the Balearic archipelago

<p>Abstract</p> <p>Background</p> <p>Metacrangonyctidae (Amphipoda, Crustacea) is an enigmatic continental subterranean water family of marine origin (thalassoid). One of the species in the genus, <it>Metacrangonyx longipes</it>, is endemic to the Balearic islands of Mallorca and Menorca (W Mediterranean). It has been suggested that the origin and distribution of thalassoid crustaceans could be explained by one of two alternative hypotheses: (1) active colonization of inland freshwater aquifers by a marine ancestor, followed by an adaptative shift; or (2) passive colonization by stranding of ancestral marine populations in coastal aquifers during marine regressions. A comparison of phylogenies, phylogeographic patterns and age estimations of clades should discriminate in favour of one of these two proposals.</p> <p>Results</p> <p>Phylogenetic relationships within <it>M. longipes </it>based on three mitochondrial DNA (mtDNA) and one nuclear marker revealed five genetically divergent and geographically structured clades. Analyses of cytochrome oxidase subunit 1 (<it>cox1</it>) mtDNA data showed the occurrence of a high geographic population subdivision in both islands, with current gene flow occurring exclusively between sites located in close proximity. Molecular-clock estimations dated the origin of <it>M. longipes </it>previous to about 6 Ma, whereas major cladogenetic events within the species took place between 4.2 and 2.0 Ma.</p> <p>Conclusions</p> <p><it>M. longipes </it>displayed a surprisingly old and highly fragmented population structure, with major episodes of cladogenesis within the species roughly correlating with some of the major marine transgression-regression episodes that affected the region during the last 6 Ma. Eustatic changes (vicariant events) -not active range expansion of marine littoral ancestors colonizing desalinated habitats-explain the phylogeographic pattern observed in <it>M. longipes</it>.</p

The E Sibling Project - exploratory randomised controlled trial of an online multi-component psychoeducational intervention for siblings of individuals with first episode psychosis

Background:Siblings of individuals with first episode psychosis are natural partners to promote service users’recovery and are themselves vulnerable to mental ill health due to the negative impact of psychosis withinthe family. This study aims to develop and undertake a preliminary evaluation of the efficacy of an onlinemulti-component psychoeducational intervention for siblings of individuals with first episode psychosis. Theimpetus for the intervention arose from siblings' expressed needs for peer support and information on psychosis,coping and management strategies for common symptoms and ways to promote recovery. Methods/Design:The project design draws on the Medical Research Council framework for the design andevaluation of complex interventions. Mixed methods comprising collection of qualitative focus group data,systematic review and expert advisory group consultation are used to develop the theoretical basis for and designof the intervention. This protocol focuses on the modelling and piloting phase which uses a randomised controlledtrial with factorial design to test the efficacy of the intervention. Outcome data on participants’mental wellbeing,knowledge, perceived self-efficacy and experiences of caregiving will be assessed at baseline, at end of theintervention (10 weeks later) and at 10 week follow-up. In addition, a post-intervention semi-structured interviewwith 20% of the participants will explore their experiences and acceptability of the intervention. Discussion:This multi-component online psychoeducational intervention aims to enhance siblings' knowledgeabout psychosis and their coping capacity, thus potentially improving their own mental wellbeing and promotingtheir contribution to service users’recovery. The factorial design randomised controlled trial with a supplementaryprocess evaluation using semi-structured interviews and usage-monitoring will collect preliminary evidence ofefficacy, feasibility and acceptability, as well as feedback about the barriers and strategies to using such aninnovative resource. The RCT will provide data for estimating the likely effect size of the intervention on outcomesfor siblings and inform the development of a definitive future trial

Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling

The Notch pathway controls proliferation during development and in adulthood, and is frequently affected in many disorders. However, the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging. Here, we address the complexity of Notch signaling with respect to proliferation, using the developing Drosophila CNS as model. We find that a Notch/Su(H)/E(spl)-HLH cascade specifically controls daughter, but not progenitor proliferation. Additionally, we find that different E(spl)-HLH genes are required in different neuroblast lineages. The Notch/Su(H)/E(spl)-HLH cascade alters daughter proliferation by regulating four key cell cycle factors: Cyclin E, String/Cdc25, E2f and Dacapo (mammalian p21CIP1/p27KIP1/p57Kip2). ChIP and DamID analysis of Su(H) and E(spl)-HLH indicates direct transcriptional regulation of the cell cycle genes, and of the Notch pathway itself. These results point to a multi-level signaling model and may help shed light on the dichotomous proliferative role of Notch signaling in many other systems

Selenium isotope evidence for progressive oxidation of the Neoproterozoic biosphere

Neoproterozoic (1,000–542 Myr ago) Earth experienced profound environmental change, including ‘snowball’ glaciations, oxygenation and the appearance of animals. However, an integrated understanding of these events remains elusive, partly because proxies that track subtle oceanic or atmospheric redox trends are lacking. Here we utilize selenium (Se) isotopes as a tracer of Earth redox conditions. We find temporal trends towards lower δ82/76Se values in shales before and after all Neoproterozoic glaciations, which we interpret as incomplete reduction of Se oxyanions. Trends suggest that deep-ocean Se oxyanion concentrations increased because of progressive atmospheric and deep-ocean oxidation. Immediately after the Marinoan glaciation, higher δ82/76Se values superpose the general decline. This may indicate less oxic conditions with lower availability of oxyanions or increased bioproductivity along continental margins that captured heavy seawater δ82/76Se into buried organics. Overall, increased ocean oxidation and atmospheric O2 extended over at least 100 million years, setting the stage for early animal evolution

Crafting organization

The recent shift in attention away from organization studies as science has allowed for consideration of new ways of thinking about both organization and organizing and has led to several recent attempts to \u27bring down\u27 organizational theorizing. In this paper, we extend calls for organization to be represented as a creative process by considering organization as craft. Organizational craft, we argue, is attractive, accessible, malleable, reproducible, and marketable. It is also a tangible way of considering organization studies with irreverence. We draw on the hierarchy of distinctions among fine art, decorative art, and craft to suggest that understanding the organization of craft assists in complicating our understanding of marginality. We illustrate our argument by drawing on the case of a contemporary Australian craftworks and marketplace known initially as the Meat Market Craft Centre (\u27MMCC\u27) and then, until its recent closure, as Metro! &Dagger; Stella Minahan was a board member and then the Chief Executive Officer of the Metro! Craft Centre.<br /