4,548 research outputs found

    An eighth-century inscribed cross-slab in Dull, Perthshire

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    The discovery of a cross-inscribed slab with an inscription is described. Because of its importance it was decided to invite specialist comment on this piece of sculpture and to publish it in advance of the full report on the excavations. The form of the monument, its inscription and archaeological context are considered. The text appears to consist of a Gaelic personal name. The script is a form of geometrical lettering which can be dated to the opening quarter of the eighth century. The form of the cross has Columban associations which sit well with place-name and other evidence which points to Dull having been a monastery founded from Iona by c. AD 700

    Upregulation of the Coagulation Factor VII Gene during Glucose Deprivation Is Mediated by Activating Transcription Factor 4

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    Background: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Methodology/Principal Findings: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/− SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/−15% to 188+/−27% and 100+/−8.8% to 176.3+/−17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Conclusions/Significance: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress

    Effect of natural products on the production and activity of Clostridium difficile toxins in vitro

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    Clostridium difficile infection is a toxin-mediated disease of the colon. C. difficile virulence is primarily attributed to the production of toxin A and toxin B; thus this study was aimed to investigate the effect of a range of natural products on the production and activity of C. difficile toxins in vitro. Twenty-two natural products were investigated against four C. difficile strains. The activity of products against toxins was determined using Vero and HT-29 cells cytotoxicity and neutral red uptake assays. The indirect effect of products on toxin-mediated cytotoxicity was determined using the same cell lines. The effect of seven products on toxin production by C. difficile was determined using ELISA. Zingerone (0.3 mg/ml) protected both cell lines from C. difficile cytopathic effects, confirmed by the neutral red uptake assay (P \u3c 0.05). Three Leptospermum honeys (4% w/v), fresh onion bulb extract (12.5% v/v) and trans-cinnamaldehyde (0.005% v/v) all reduced toxin production and activity significantly (P ≤ 0.023). Garlic clove powder (4.7 mg/ml) only reduced toxin activity (P ≤ 0.047). Overall, several natural products had activity against C. difficile toxins in vitro encouraging further investigation against C. difficile toxins in vivo

    Night-time lighting alters the composition of marine epifaunal communities

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    Marine benthic communities face multiple anthropogenic pressures that compromise the future of some of the most biodiverse and functionally important ecosystems in the world. Yet one of the pressures these ecosystems face, night-time lighting, remains unstudied. Light is an important cue in guiding the settlement of invertebrate larvae, and altering natural regimes of nocturnal illumination could modify patterns of recruitment among sessile epifauna. We present the first evidence of night-time lighting changing the composition of temperate epifaunal marine invertebrate communities. Illuminating settlement surfaces with white light-emitting diode lighting at night, to levels experienced by these communities locally, both inhibited and encouraged the colonization of 39% of the taxa analysed, including three sessile and two mobile species. Our results indicate that ecological light pollution from coastal development, shipping and offshore infrastructure could be changing the composition of marine epifaunal communities.European Research Council under the European Union's Seventh Framework programme (FP7/2007-2013

    Difference in Structure and Electronic Properties of Oxygen Vacancies in α-Quartz and α-Cristobalite Phases of SiO2

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    α-cristobalite (α-C) is a polymorph of silica, mainly found in space exploration and geochemistry research. Due to similar densities, α-C is often used as a proxy for amorphous SiO2, particularly in computer simulations of SiO2 surfaces and interfaces. However, little is known about the properties of α-C and its basic oxygen defects. Using density functional theory (DFT) simulations we provide a comprehensive report on the properties of perfect structure and oxygen vacancies in α-C. The calculated properties of α-C are compared with those of the better-characterized α-quartz (α-Q). Our results demonstrated that the positively charged O vacancy in α-C is most stable in the dimer configuration, in contrast to α-Q, which favors the puckered configuration. A back-projected configuration was also predicted in both polymorphs. We calculated the optical transition energies and isotropic hyperfine constants for O vacancies in both α-Q and α-C, and compared our findings with the results of previous studies and experiments. This work, thus, offers one of the first in-depth investigations of the properties of oxygen vacancies in α-C

    Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening

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    Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process
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