33 research outputs found

    Non-native species in the north Gulf of Aqaba (Red Sea) revealed from environmental DNA

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    The movement of organisms facilitated by anthropogenic activities is a serious threat to marine diversity, especially for endemic species that may be outcompeted from non-indigenous species (NIS). In this study, we have analyzed communities inhabiting the north of the Gulf of Aqaba, Red Sea, employing environmental DNA (eDNA) metabarcoding. That gulf is especially rich in species and population endemism. We have detected NIS representing 36% of the total number of species found from eDNA. Primary producers were more abundant in the NIS than in the native fraction of species, suggesting that functional diversity could be altered if NIS thrive there. We discuss maritime traffic as a factor that may enhance the introduction of non-natives in this region and emphasize the importance of the control of these species that may threaten the rich endemic biota of the Red Sea

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood-Derived Endothelial Progenitor Cell Immaturity

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    <div><p>Endothelial Colony Forming Cells (ECFCs), a distinct population of Endothelial Progenitor Cells (EPCs) progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree of immaturity retained by EPCs is still confused and poorly defined. Consequently, to better characterize CB-ECFC stemness, we quantified their clonogenic potential and demonstrated that they were reprogrammed into induced pluripotent stem cells (iPSCs) more efficiently and rapidly than adult endothelial cells. Moreover, we analyzed the transcriptional profile of a broad gene panel known to be related to stem cells. We showed that, unlike mature endothelial cells, CB-ECFCs expressed genes involved in the maintenance of embryonic stem cell properties such as <i>DNMT3B</i>, <i>GDF3</i> or <i>SOX2</i>. Thus, these results provide further evidence and tools to appreciate EPC-derived cell stemness. Moreover this novel stem cell transcriptional signature of ECFCs could help better characterizing and ranging EPCs according to their immaturity profile.</p></div

    Structure-Based Virtual Ligand Screening on the XRCC4/DNA Ligase IV Interface

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    International audienceDSBs cytotoxicity is largely exploited in anticancer therapy. Thus, NHEJ is an attractive target for strategies aimed at increasing the sensitivity of tumors to clastogenic anticancer treatments. However the high affinity of the XRCC4/Lig4 interaction and the extended protein-protein interface make drug screening on this target particularly challenging. Here, we conducted a pioneering study aimed at interfering with XRCC4/Lig4 assembly. By Molecular Dynamics simulation using the crystal structure of the complex, we first delineated the Lig4 clamp domain as a limited suitable target. Then, we performed in silico screening of ~95,000 filtered molecules on this Lig4 subdomain. Hits were evaluated by Differential Scanning Fluorimetry, Saturation Transfer Difference-NMR spectroscopy and interaction assays with purified recombinant proteins. In this way we identified the first molecule able to prevent Lig4 binding to XRCC4 in vitro. This compound has a unique tripartite interaction with the Lig4 clamp domain that suggests a starting chemotype for rational design of analogous molecules with improved affinity

    Pluripotency of ECFC-derived iPSCs.

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    <p>(A) Immunostaining of iPSC-derived embryoid bodies revealed the expression of ectodermal (ÎČIII tubulin, nestin), endodermal (AFP, HNF-3ÎČ), mesodermal (CD31, SMA) markers. Nuclei were stained with DAPI. Scale bars represent 100ÎŒm. (B) Immunostaining of teratomas induced in SCID mice after injection of 100,000 ECFC-derived iPSC1 containing derivatives of the 3 germ layers differentiation (ÎČIII tubulin, AFP and SMA). Nuclei were stained with DAPI. Scale bars represent 100ÎŒm. (C) Histology of teratomas (hematoxylin/eosin staining) confirming differentiation into all 3 germ layers: mesoderm (1) endoderm (2) and ectoderm (3).</p

    ECFC-derived iPSCs express typical hESC markers.

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    <p>(A) Immunofluorescence analysis of ECFC-derived iPSC1 line. Expression of stem cell markers: OCT3/4, SOX2, NANOG, PA, SSEA4, TRA-1-81. The cells were stained using the 488 and 546-conjugated Donkey Anti-Goat IgG or Goat Anti-Mouse IgG secondary antibody and the nuclei were counterstained with DAPI (blue). Scale bars represent 100 ÎŒm. (B) Quantitative RT-PCR analysis of the expression of endogenous (endo) and exogenous (exo) markers: <i>OCT3/4</i>, <i>SOX2</i>, <i>KLF4</i> and <i>C-MYC</i> in Ctrl ECFCs, transduced ECFCs (ECFC OKSM) and ECFC-derived iPSC1 at passage 4, 7 and 10. Transcript levels were normalized to GAPDH transcript levels and relative to mean hESCs (H9 samples at P45) as a calibrator.</p

    Phenotypic and functional characterization of iPSC-derived endothelial cells.

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    <p>(A) Expression of specific endothelial markers (KDR, CD31 and CD144) by flow cytometry at passage P4. (B) CD31 and vWF immunofluorescent staining at passage 5. Scale bars represent 50ÎŒm. (C) Vascular-like network structures after 24h onto Matrigel<sup>ℱ</sup> at passage P4. (D) Representative diacetylated low-density lipoprotein incorporation at passage P4. Scale bars represent 25ÎŒm. (E) TNF-α upregulated <i>ICAM-1</i> and <i>VCAM-1</i> at passage P5.</p

    Morphology of ECFC-derived iPSCs and reprogramming efficiency of ECFCs and HAECs.

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    <p>(A) Cobblestone morphology of ECFCs before and 7 days after transduction, ECFC morphology changed and colonies were ALP positives. At passage 5 and 30, ECFC-derived iPSC1 showed typical characteristics of hESC colonies. (B-C) ECFC and HAEC reprogramming efficiency and rate. The reprogramming efficiency was estimated based on the number of ALP positive colonies. Error bars represent SEM (***p < 0.005).</p

    Endothelial and Stemness transcriptional signature of CB-ECFCs.

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    <p>(A) Transcript levels of endothelial markers. Quantitative RT-PCR analysis in ECFCs at passage P1 (n = 6) and adult HAECs at passage P3 (n = 4). Transcript levels were normalized to GAPDH transcript levels and relative to mean HAECs. (B) Transcript levels of stemness markers. Quantitative RT-PCR analysis in ECFCs at passage P1 (n = 6) and adult HAECs at passage P3 (n = 4). Transcript levels were normalized to GAPDH transcript levels and relative to mean hESCs (2 H9 samples at P45 and P52 and 1 H1 sample at P54). Error bars represent SEM (*p < 0.05).</p

    Stemness genes expression array.

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    <p>Data are expressed as ΔCt. Transcript levels were normalized to GAPDH transcript level. Genes whose detection threshold is over 35 cycles are considered as not expressed and symbolized by “X”.</p
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