46 research outputs found

    Arterial Mesenteric Thrombosis as a Complication of SARS-CoV-2 Infection

    Get PDF
    A 52-year-old patient with SARS-CoV-2 was diagnosed with interstitial pneumonia and treated with darunavir/ritonavir, hydroxychloroquine, azithromycin and low molecular weight heparin (LMWH). After LMWH cessation, he developed superior mesenteric arterial thrombosis. An abdominal CT scan showed arterial thrombosis of vessels efferent of the superior mesenteric artery with bowel distension. COVID-19 may predispose to venous and arterial thromboembolism. Anticoagulation prophylaxis should be considered in hospitalized patients with COVID-19, and potential thromboembolism investigated in each symptomatic patient affected by SARS-CoV-2

    Hes3 regulates cell number in cultures from glioblastoma multiforme with stem cell characteristics

    Get PDF
    Tumors exhibit complex organization and contain a variety of cell populations. The realization that the regenerative properties of a tumor may be largely confined to a cell subpopulation (cancer stem cell) is driving a new era of anti-cancer research. Cancer stem cells from Glioblastoma Multiforme tumors express markers that are also expressed in non-cancerous neural stem cells, including nestin and Sox2. We previously showed that the transcription factor Hes3 is a marker of neural stem cells, and that its expression is inhibited by JAK activity. Here we show that Hes3 is also expressed in cultures from glioblastoma multiforme which express neural stem cell markers, can differentiate into neurons and glia, and can recapitulate the tumor of origin when transplanted into immunocompromised mice. Similar to observations in neural stem cells, JAK inhibits Hes3 expression. Hes3 RNA interference reduces the number of cultured glioblastoma cells suggesting a novel therapeutic strategy

    Anlisis Technology Acceptance Model Pada Industri Perbankan

    Full text link
    The first aim of this study was to determine the influence perception of the perceived benefits (PU) and perceived ease of use (PEU) of the attitude (ATU) in receiving information technology (ATI). This research is an explanatory research. Respondents are bank employees as much as 118 peoples. To test the effect of each variable used structural equation modeling analysis techniques (SEM). The results showed a variable perception ease of use (PEU) positive and significant impact on the attitude of using IT (ATU). Variable perception perceived benefits (PU) is positive but not significant effect on attitudes using IT (ATU). Variable perception easy to use (PEU) positive and significant impact on the perceived benefits perception variables (PU). Variable attitude of using IT (ATU) positive and significant impact on the acceptance of IT (ATI). There are research findings that do not support the results of previous studies, namely, perception perceived benefits (PU) but not significant positive effect on the attitude of using IT (ATU). This shows the attitude of the management agreed that the use of information technology is an important banking and its presence is felt very beneficial to the organization and operational staff, but not the key element in determining the attitude to use IT. The management should be able to realize the quality of skilled workers and professional service. The banking industry can standardize that can be used as a reference for the development of IT. IT use also should be able to grow the level of trust and a culture conducive to the customer as a party that directly or indirectly affect the use of IT

    Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts

    Get PDF
    Background: Mesenchymal stem/stromal cells (MSCs) represent an attractive tool for cell-based cancer therapy mainly because of their ability to migrate to tumors and to release bioactive molecules. However, the impact of MSCs on tumor growth has not been fully established. We previously demonstrated that murine MSCs show a strong tropism towards glioblastoma (GBM) brain xenografts and that these cells are able to uptake and release the chemotherapeutic drug paclitaxel (PTX), maintaining their tropism towards the tumor. Here, we address the therapy-relevant issue of using MSCs from human donors (hMSCs) for local or systemic administration in orthotopic GBM models, including xenografts of patient-derived glioma stem cells (GSCs). Methods: U87MG or GSC1 cells expressing the green fluorescent protein (GFP) were grafted onto the striatum of immunosuppressed rats. Adipose hMSCs (Ad-hMSCs), fluorescently labeled with the mCherry protein, were inoculated adjacent to or into the tumor. In rats bearing U87MG xenografts, systemic injections of Ad-hMSCs or bone marrow (BM)-hMSCs were done via the femoral vein or carotid artery. In each experiment, either PTX-loaded or unloaded hMSCs were used. To characterize the effects of hMSCs on tumor growth, we analyzed survival, tumor volume, tumor cell proliferation, and microvascular density. Results: Overall, the AD-hMSCs showed remarkable tropism towards the tumor. Intracerebral injection of Ad-hMSCs significantly improved the survival of rats with U87MG xenografts. This effect was associated with a reduction in tumor growth, tumor cell proliferation, and microvascular density. In GSC1 xenografts, intratumoral injection of Ad-hMSCs depleted the tumor cell population and induced migration of resident microglial cells. Overall, PTX loading did not significantly enhance the antitumor potential of hMSCs. Systemically injected Ad- and BM-hMSCs homed to tumor xenografts. The efficiency of hMSC homing ranged between 0.02 and 0.5% of the injected cells, depending both on the route of cell injection and on the source from which the hMSCs were derived. Importantly, systemically injected PTX-loaded hMSCs that homed to the xenograft induced cytotoxic damage to the surrounding tumor cells. Conclusions: hMSCs have a therapeutic potential in GBM brain xenografts which is also expressed against the GSC population. In this context, PTX loading of hMSCs seems to play a minor role

    Glioblastoma endothelium drives bevacizumab-induced infiltrative growth via modulation of PLXDC1

    Get PDF
    Bevacizumab, a VEGF-targeting monoclonal antibody, may trigger an infiltrative growth pattern in glioblastoma. We investigated this pattern using both a human specimen and rat models. In the human specimen, a substantial fraction of infiltrating tumor cells were located along perivascular spaces in close relationship with endothelial cells. Brain xenografts of U87MG cells treated with bevacizumab were smaller than controls (p = 0.0055; Student t-test), however, bands of tumor cells spread through the brain farther than controls (p < 0.001; Student t-test). Infiltrating tumor Cells exhibited tropism for vascular structures and propensity to form tubules and niches with endothelial cells. Molecularly, bevacizumab triggered an epithelial to mesenchymal transition with over-expression of the receptor Plexin Domain Containing 1 (PLXDC1). These results were validated using brain xenografts of patient-derived glioma stem-like cells. Enforced expression of PLXDC1 in U87MG cells promoted brain infiltration along perivascular spaces. Importantly, PLXDC1 inhibition prevented perivascular infiltration and significantly increased the survival of bevacizumab-treated rats. Our study indicates that bevacizumab-induced brain infiltration is driven by vascular endothelium and depends on PLXDC1 activation of tumor cells

    High prevalence and genetic diversity of Treponema paraluisleporidarum isolates in European lagomorphs

    Get PDF
    The bacterium Treponema paraluisleporidarum causes syphilis in lagomorphs. In a set of 1,095 samples from four species—European brown hare, mountain hare, Corsican hare, and European rabbit—we tested for infection and genotyped the strains that infect wild lagomorphs. Samples originate from Sweden, the Netherlands, the United Kingdom, Germany, the Czech Republic, and Italy. The phylogenetic analyses of two informative gene targets (tp0488 and tp0548) showed high genetic diversity among the lagomorph-infecting treponemes. More specifically, we found a high number of nucleotide variants and various short repeat units in the tp0548 locus that have not been described for human syphilis and primate yaws causing Treponema pallidum. While the functional aspect of these short repeat units remains subject to ongoing investigations, it likely enables the pathogen to better survive in its lagomorph host. Our data did not support any geographic clustering, which is equally reflected in the host population genetics as shown by mitochondrial genome data corresponding to the sampled lagomorph populations. This is unexpected and in contrast with what has been shown for nonhuman primate infection with T. pallidum. In the future, the combination of multi-locus sequence typing and whole genome data from modern and ancient samples from a wide geographic range and multiple lagomorph species will contribute to a better understanding of the epidemiology and evolutionary path of lagomorph-infecting treponemes. In conclusion, our current study demonstrates widespread infection and a high genetic variation of the syphilis-causing pathogen in a higher number of positively PCR-tested European lagomorphs (n = 302/1,095)

    Périgord black truffle genome uncovers evolutionary origins and mechanisms of symbiosis

    Get PDF
    LetterInternational audienceThe Périgord black truffle (Tuber melanosporumTuber\ melanosporum Vittad.) and the Piedmont white truffle dominate today's truffle market. The hypogeous fruiting body of T. melanosporumT.\ melanosporum is a gastronomic delicacy produced by an ectomycorrhizal symbiont endemic to calcareous soils in southern Europe. The worldwide demand for this truffle has fuelled intense efforts at cultivation. Identification of processes that condition and trigger fruit body and symbiosis formation, ultimately leading to efficient crop production, will be facilitated by a thorough analysis of truffle genomic traits. In the ectomycorrhizal Laccaria bicolorLaccaria\ bicolor, the expansion of gene families may have acted as a 'symbiosis toolbox'. This feature may however reflect evolution of this particular taxon and not a general trait shared by all ectomycorrhizal species. To get a better understanding of the biology and evolution of the ectomycorrhizal symbiosis, we report here the sequence of the haploid genome of T. melanosporumT.\ melanosporum, which at \sim125 megabases is the largest and most complex fungal genome sequenced so far. This expansion results from a proliferation of transposable elements accounting for \sim58% of the genome. In contrast, this genome only contains \sim7,500 protein-coding genes with very rare multigene families. It lacks large sets of carbohydrate cleaving enzymes, but a few of them involved in degradation of plant cell walls are induced in symbiotic tissues. The latter feature and the upregulation of genes encoding for lipases and multicopper oxidases suggest that T. melanosporumT.\ melanosporum degrades its host cell walls during colonization. Symbiosis induces an increased expression of carbohydrate and amino acid transporters in both L. bicolorL.\ bicolor and T. melanosporumT.\ melanosporum, but the comparison of genomic traits in the two ectomycorrhizal fungi showed that genetic predispositions for symbiosis -'the symbiosis toolbox'- evolved along different ways in ascomycetes and basidiomycete

    The Timing of Differentiation of Adult Hippocampal Neurons Is Crucial for Spatial Memory

    Get PDF
    Adult neurogenesis in the dentate gyrus plays a critical role in hippocampus-dependent spatial learning. It remains unknown, however, how new neurons become functionally integrated into spatial circuits and contribute to hippocampus-mediated forms of learning and memory. To investigate these issues, we used a mouse model in which the differentiation of adult-generated dentate gyrus neurons can be anticipated by conditionally expressing the pro-differentiative gene PC3 (Tis21/BTG2) in nestin-positive progenitor cells. In contrast to previous studies that affected the number of newly generated neurons, this strategy selectively changes their timing of differentiation. New, adult-generated dentate gyrus progenitors, in which the PC3 transgene was expressed, showed accelerated differentiation and significantly reduced dendritic arborization and spine density. Functionally, this genetic manipulation specifically affected different hippocampus-dependent learning and memory tasks, including contextual fear conditioning, and selectively reduced synaptic plasticity in the dentate gyrus. Morphological and functional analyses of hippocampal neurons at different stages of differentiation, following transgene activation within defined time-windows, revealed that the new, adult-generated neurons up to 3–4 weeks of age are required not only to acquire new spatial information but also to use previously consolidated memories. Thus, the correct unwinding of these key memory functions, which can be an expression of the ability of adult-generated neurons to link subsequent events in memory circuits, is critically dependent on the correct timing of the initial stages of neuron maturation and connection to existing circuits
    corecore