240 research outputs found

    Biology of the redspotted tonguesole Cynoglossus Zanzibarensis (Pleuronectiformes: Cynoglossidae) on the Agulhas bank, South Africa

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    The biology of the redspotted tonguesole Cynoglossus zanzibarensis, a common African cynoglossid inhabiting the Agulhas Bank, South Africa, is described. Growth studies based on sectioned sagittal otoliths revealed that C. zanzibarensis is relatively fast-growing and long-lived, attaining ages >8 years. Growth in length was rapid in immature fish, fish attaining 56% of their maximum size within their first year. By sexual maturity, fish had attained 28% of their maximum age and 68% of their maximum length. Total length-at-age was best described by the Von Bertalanffy growth model with combined-sex growth described as Lt = 354.78(1–e-0.43 (t+1.17)) mm TL. Sexually dimorphic growth patterns were evident, females attaining larger lengths, but at a slower growth rate than males. Despite the similar mean size of adult fish, the trawl-sampled adult population was dominated by females, with a sex ratio of 1 male:2.4 females. Female C. zanzibarensis mature in their second year of life (275 mm TL), after which they spawn small, pelagic eggs throughout the year. Approximations of the rates of total, natural and fishing mortality were estimated to be 0.62, 0.48 and 0.14 year-1 respectively

    Fragmentation and disk formation in high-mass star formation: The ALMA view of G351.77-0.54 at 0.06" resolution

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    Aims: We resolve the small-scale structure around the high-mass hot core region G351.77-0.54 to investigate its disk and fragmentation properties. Methods: Using ALMA at 690GHz with baselines exceeding 1.5km, we study the dense gas, dust and outflow emission at an unprecedented spatial resolution of 0.06" ([email protected]). Results: Within the inner few 1000AU, G351.77 fragments into at least four cores (brightness temperatures between 58 and 197K). The central structure around the main submm source #1 with a diameter of ~0.5" does not show additional fragmentation. While the CO(6-5) line wing emission shows an outflow lobe in the north-western direction emanating from source #1, the dense gas tracer CH3CN shows a velocity gradient perpendicular to the outflow that is indicative of rotational motions. Absorption profile measurements against the submm source #2 indicate infall rates on the order of 10^{-4} to 10^{-3}M_sun/yr which can be considered as an upper limit of the mean accretion rates. The position-velocity diagrams are consistent with a central rotating disk-like structure embedded in an infalling envelope, but they may also be influenced by the outflow. Using the CH_3CN(37_k-36_k) k-ladder with excitation temperatures up to 1300K, we derive a gas temperature map of source #1 exhibiting temperatures often in excess of 1000K. Brightness temperatures of the submm continuum never exceed 200K. This discrepancy between gas temperatures and submm dust brightness temperatures (in the optically thick limit) indicates that the dust may trace the disk mid-plane whereas the gas could be tracing a hotter gaseous disk surface layer. In addition, we conduct a pixel-by-pixel Toomre gravitational stability analysis of the central rotating structure. The derived high Q values throughout the structure confirm that this central region appears stable against gravitational instability

    Imatinib Mesylate Induces Necroptotic Cell Death and Impairs Autophagic Flux in Human Cardiac Progenitor Cells

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    The receptor tyrosine kinase inhibitor imatinib improves patient cancer survival but is linked to cardiotoxicity. This study investigated imatinib’s effects on cell viability, apoptosis, autophagy, and necroptosis in human cardiac progenitor cells in vitro. Imatinib reduced cell viability (75.9 ± 2.7% vs. 100.0 ± 0.0%) at concentrations comparable to peak plasma levels (10 µM). Imatinib reduced cells’ TMRM fluorescence (74.6 ± 6.5% vs. 100.0 ± 0.0%), consistent with mitochondrial depolarisation. Imatinib increased lysosome and autophagosome content as indicated by LAMP2 expression (2.4 ± 0.3-fold) and acridine orange fluorescence (46.0 ± 5.4% vs. 9.0 ± 3.0), respectively. Although imatinib increased expression of autophagy-associated proteins and also impaired autophagic flux, shown by proximity ligation assay staining for LAMP2 and LC3II (autophagosome marker): 48 h of imatinib treatment reduced visible puncta to 2.7 ± 0.7/cell from 11.3 ± 2.1 puncta/cell in the control. Cell viability was partially recovered by autophagosome inhibition by wortmannin, with the viability increasing 91.8 ± 8.2% after imatinib-wortmannin co-treatment (84 ± 1.5% after imatinib). Imatinib-induced necroptosis was associated with an 8.5 ± 2.5-fold increase in mixed lineage kinase domain-like pseudokinase activation. Imatinib-induced toxicity was rescued by RIP1 inhibition: 88.6 ± 3.0% vs. 100.0 ± 0.0% in the control. Imatinib applied to human cardiac progenitor cells depolarises mitochondria and induces cell death through necroptosis, recoverable by RIP1 inhibition, with a partial role for autophagy

    Eating well, living well and weight management: A co-produced semi-qualitative study of barriers and facilitators experienced by adults with intellectual disabilities

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    Adults with intellectual disabilities in England experience health inequalities. They are more likely than their non-disabled peers to be obese and at risk of serious medical conditions such as heart disease, stroke and type 2 diabetes. This semi-qualitative study engaged adults with intellectual disabilities in a co-production process to explore their perceived barriers and facilitators to eating well, living well and weight management. Nineteen participants with intellectual disabilities took part in four focus groups and one wider group discussion. They were supported by eight of their carers or support workers. Several barriers were identified including personal income restrictions, carers’ and support workers’ unmet training needs, a lack of accessible information, inaccessible services and societal barriers such as the widespread advertising of less healthy foodstuffs. A key theme of frustration with barriers emerged from analysis of participants’ responses. Practical solutions suggested by participants included provision of clear and accessible healthy lifestyle information, reasonable adjustments to services, training, ‘buddying’ support systems or schemes and collaborative working to improve policy and practice

    Quantum Memories. A Review based on the European Integrated Project "Qubit Applications (QAP)"

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    We perform a review of various approaches to the implementation of quantum memories, with an emphasis on activities within the quantum memory sub-project of the EU Integrated Project "Qubit Applications". We begin with a brief overview over different applications for quantum memories and different types of quantum memories. We discuss the most important criteria for assessing quantum memory performance and the most important physical requirements. Then we review the different approaches represented in "Qubit Applications" in some detail. They include solid-state atomic ensembles, NV centers, quantum dots, single atoms, atomic gases and optical phonons in diamond. We compare the different approaches using the discussed criteria.Comment: 22 pages, 12 figure

    Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging

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    Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH2I2 and CH2BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH2I2, the structural evolution of the neutral molecule was simultaneously characterized along the C-I and I-C-I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom

    IL4Rα signaling abrogates hypoxic neutrophil survival and limits acute lung injury responses <i>in vivo</i>

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    Rationale: Acute respiratory distress syndrome is defined by the presence of systemic hypoxia and consequent on disordered neutrophilic inflammation. Local mechanisms limiting the duration and magnitude of this neutrophilic response remain poorly understood.  Objectives: To test the hypothesis that during acute lung inflammation tissue production of proresolution type 2 cytokines (IL-4 and IL-13) dampens the proinflammatory effects of hypoxia through suppression of HIF-1a (hypoxia-inducible factor-1a)mediated neutrophil adaptation, resulting in resolution of lung injury.  Methods: Neutrophil activation of IL4Ra (IL-4 receptor a) signaling pathways was explored ex vivo in human acute respiratory distress syndrome patient samples, in vitro after the culture of human peripheral blood neutrophils with recombinant IL-4 under conditions of hypoxia, and in vivo through the study of IL4Ra-deficient neutrophils in competitive chimera models and wild-type mice treated with IL-4.  Measurements and Main Results: IL-4 was elevated in human BAL from patients with acute respiratory distress syndrome, and its receptor was identified on patient blood neutrophils. Treatment of human neutrophils with IL-4 suppressed HIF-1a-dependent hypoxic survival and limited proinflammatory transcriptional responses. Increased neutrophil apoptosis in hypoxia, also observed with IL-13, required active STAT signaling, and was dependent on expression of the oxygen-sensing prolyl hydroxylase PHD2. In vivo, IL-4Ra-deficient neutrophils had a survival advantage within a hypoxic inflamed niche; in contrast, inflamed lung treatment with IL-4 accelerated resolution through increased neutrophil apoptosis.  Conclusions: We describe an important interaction whereby IL4Ra-dependent type 2 cytokine signaling can directly inhibit hypoxic neutrophil survival in tissues and promote resolution of neutrophil-mediated acute lung injury

    Virologic Failure of Protease Inhibitor-Based Second-Line Antiretroviral Therapy without Resistance in a Large HIV Treatment Program in South Africa

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    Background: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal Findings HIV-infected patients ≥\geq15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance: Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure
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