135 research outputs found

    Mass mortality and extraterrestrial impacts

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    The discovery of iridium enrichment at the Cretaceous/Tertiary boundary resulted in formulation of hypothesis of a cometary or asteroid impact as the cause of the biological extinctions at this boundary. Subsequent discoveries of geochemical anomalies at major stratigraphic boundaries like the Precambrian/Cambrian, Permian/Triassic, Middle/Late Jurassic, resulted in the application of similar extraterrestrial impact theories to explain biological changes at these boundaries. Until recently the major physical evidence, as is the location of the impact crater site, to test the impact induced biological extinction was lacking. The diameter of such a crater would be in the range of 60 to 100 km. The recent discovery of the first impact crater in the ocean provide the first opportunity to test the above theory. The crater, named Montagnais and located on the outer shelf off Nova Scotia, Canada, has a minimum diameter of 42 km, with some evidence to a diameter of more than 60 km. At the Montagnais impact site, micropaleontological analysis of the uppermost 80 m of the fall-back breccia represented by a mixture of pre-impact sediments and basement rocks which fills the crater and of the basal 50 m of post-impact marine sediments which overly the impact deposits, revealed presence of diversified foraminiferal and nannoplankton assemblages. The sediments which are intercalated within the uppermost part of the fall-back breccia, had to be deposited before the meteorite impact. The post-impact deposits were laid down almost immediately after the impact as also supported by the micropaleontological data. In conclusion, micropaleontological studies of sediments from the first submarine impact crater site identified in the ocean did not reveal any mass extinction or significant biological changes at the impact site or in the proximal deep ocean basin

    A symmetry group of a Thue-Morse quasicrystal

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    We present a method of coding general self-similar structures. In particular, we construct a symmetry group of a one-dimensional Thue-Morse quasicrystal, i.e., of a nonperiodic ground state of a certain translation-invariant, exponentially decaying interaction.Comment: 6 pages, Late

    The Dababiya corehole, Upper Nile Valley, Egypt : preliminary results

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    Author Posting. © Austrian Geological Society, 2012. This article is posted here by permission of Austrian Geological Society for personal use, not for redistribution. The definitive version was published in Austrian Journal of Earth Sciences 105, no. 1 (2012): 161-168.The Dababiya corehole was drilled in the Dababiya Quarry (Upper Nile Valley, Egypt), adjacent to the GSSP for the Paleocene/ Eocene boundary, to a total depth of 140 m and bottomed in the lower Maastrichtian Globotruncana aegyptiaca Zone of the Dakhla Shale Formation. Preliminary integrated studies on calcareous plankton (foraminifera, nannoplankton), benthic foraminifera, dinoflagellates, ammonites, geochemistry, clay mineralogy and geophysical logging indicate that: 1) The K/P boundary lies between 80.4 and 80.2 m, the Danian/Selandian boundary between ~ 41 and 43 m, the Selandian/Thanetian boundary at ~ 30 m (within the mid-part of the Tarawan Chalk) and the Paleocene/Eocene boundary at 11.75 m (base [planktonic foraminifera] Zone E1 and [calcareous nannoplankton] Zone NP9b); 2) the Dababiya Quarry Member (=Paleocene/Eocene Thermal Maximum interval) extends from 11.75 to 9.5 m, which is ~1 m less than in the adjacent GSSP outcrop.; 3) the Late Cretaceous (Maastrichtian) depositional environment was nearshore, tropical-sub tropical and nutrient rich; the latest Maastrichtian somewhat more restricted (coastal); and the early Danian cooler, low(er) salinity with increasing warmth and depth of water (i.e., more open water); 4) the Paleocene is further characterized by outer shelf (~ 200 m), warm water environments as supported by foraminifera P/B ratios > 85% (~79-28 m), whereas benthic foraminifera dominate (>70%) from ~27-12 m (Tarawan Chalk and Hanadi Member) due, perhaps, in part to increased dissolution (as observed in nearby outcrop samples over this interval); 5) during the PETM, enhanced hydrodynamic conditions are inferred to have occurred on the sea-floor with increased river discharge (in agreement with sedimentologic evidence), itself a likely cause for very high enhanced biological productivity on the epicontinental shelf of Egypt; 6) correlation of in situ measured geophysical logs of Natural Gamma Ray (GR), Single-Point Resistance (PR), Self-Potential (SP), magnetic susceptibility (MS), and Resistivity, and Short Normal (SN) and Long Normal (LN) showed correspondence to the lithologic units. The Dababiya Quarry Member, in particular, is characterized by very high Gamma Ray and Resistivity Short Normal values.The Dababiya corehole was made possible by the financial support of the National Geographic Society

    Molecular Blocking of CD23 Supports Its Role in the Pathogenesis of Arthritis

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    BACKGROUND: CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis. CONCLUSION: CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23

    Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial

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    BACKGROUND: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1β (IL-1β) blockade using canakinumab improves clinical outcome. METHODS: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2^{2} hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. FINDINGS: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. INTERPRETATION: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. FUNDING: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication

    Folding of Matrix Metalloproteinase-2 Prevents Endogenous Generation of MHC Class-I Restricted Epitope

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    BACKGROUND: We previously demonstrated that the matrix metalloproteinase-2 (MMP-2) contained an antigenic peptide recognized by a CD8 T cell clone in the HLA-A*0201 context. The presentation of this peptide on class I molecules by human melanoma cells required a cross-presentation mechanism. Surprisingly, the classical endogenous processing pathway did not process this MMP-2 epitope. METHODOLOGY/PRINCIPAL FINDINGS: By PCR directed mutagenesis we showed that disruption of a single disulfide bond induced MMP-2 epitope presentation. By Pulse-Chase experiment, we demonstrated that disulfide bonds stabilized MMP-2 and impeded its degradation. Finally, using drugs, we documented that mutated MMP-2 epitope presentation used the proteasome and retrotranslocation complex. CONCLUSIONS/SIGNIFICANCE: These data appear crucial to us since they established the existence of a new inhibitory mechanism for the generation of a T cell epitope. In spite of MMP-2 classified as a self-antigen, the fact that cross-presentation is the only way to present this MMP-2 epitope underlines the importance to target this type of antigen in immunotherapy protocols

    Testing for the Dual-Route Cascade Reading Model in the Brain: An fMRI Effective Connectivity Account of an Efficient Reading Style

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    Neuropsychological data about the forms of acquired reading impairment provide a strong basis for the theoretical framework of the dual-route cascade (DRC) model which is predictive of reading performance. However, lesions are often extensive and heterogeneous, thus making it difficult to establish precise functional anatomical correlates. Here, we provide a connective neural account in the aim of accommodating the main principles of the DRC framework and to make predictions on reading skill. We located prominent reading areas using fMRI and applied structural equation modeling to pinpoint distinct neural pathways. Functionality of regions together with neural network dissociations between words and pseudowords corroborate the existing neuroanatomical view on the DRC and provide a novel outlook on the sub-regions involved. In a similar vein, congruent (or incongruent) reliance of pathways, that is reliance on the word (or pseudoword) pathway during word reading and on the pseudoword (or word) pathway during pseudoword reading predicted good (or poor) reading performance as assessed by out-of-magnet reading tests. Finally, inter-individual analysis unraveled an efficient reading style mirroring pathway reliance as a function of the fingerprint of the stimulus to be read, suggesting an optimal pattern of cerebral information trafficking which leads to high reading performance
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