911 research outputs found

    Reactive block copolymers for patterned surface immobilization with sub-30 nm spacing

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    Phase-segregating block copolymers are powerful platforms for nanofabrication, particularly when employed as lithographic mask precursors. Surface-reactive polymeric films with distinct sub-30 nm domains are also proposed as covalent docking platforms for scalable, high-resolution molecular patterned immobilization. Here, the well-known self-assembling polystyrene-block-polyisoprene system is the starting point to produce a small library of derivatives with distinct reactive pendant groups (halide, azide, pentafluorophenylalkyl) by nitroxide-mediated radical polymerization. We find that controlling film thickness is crucial to obtain a perpendicular lamellar morphology and that the presence of the functional groups has a limited impact on self-assembly, yet may influence characteristic domain dimensions. Differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), and atomic force microscopy (AFM) are utilized in concert to assess the phase behavior of the polymers and the surface features of the nanostructures. As a proof-of-concept for the surface reactivity, click chemistry-driven immobilization of a model water-soluble polymer is evidenced by X-ray photoelectron spectroscopy (XPS) and preservation of the underlying morphology is investigated by AFM

    Exergaming in a Multiplayer and Inter-Team Competition Mode with Play Lü: Effects on Adolescents’ Moderate-to-Vigorous Physical Activity and Situational Interest

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    Objective: The goal of this study was to evaluate the impact of a Play Lü inter-team competition exergame on adolescents’ moderate-to-vigorous physical activity (MVPA) and situational interest (SI). Materials and Methods: A total of 110 students (Mage = 13.7 ± 1.1, 12-16 years, 53.7 % girls, MBMI = 19.9 ± 3.2) from a secondary school located in Switzerland participated to the study. They played three separate 20-min games in a counterbalance allocated order: (1) Play Lü multiplayer and inter-team competition exergame; (2) Play Lü single-player competition exergame; and (3) Tic-Tac-Toe multiplayer and inter-team competition game. The participants’ MVPA was measured during each 20-min game using ActiGraph GT3X+ accelerometers and SI was measured immediately after each game. Results: Regarding Play Lü, the results showed higher MVPA and SI scores in the multiplayer and inter-team competition mode than in the single-player competition mode. Moreover, Play Lü elicited greater effects compared to the Tic-Tac-Toe game within a multiplayer and inter-team competition mode. Conclusion: The Play Lü inter-team competition exergame might be considered as a relevant strategy to improve adolescents’ motivation and physical activity, which can be applied in a physical education context

    Hepatocellular Carcinoma in Cirrhotic Versus Non-Cirrhotic Patients: A Retrospective Study of 483 Patients

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    Background and Aim: Although cirrhosis is a classical risk factor for the development of hepatocellular carcinoma (HCC), its absence does not exclude this risk. We aimed to assess the clinical characteristics and outcomes of cirrhotic HCC (C-HCC) and non-cirrhotic HCC (NC-HCC) patients. Methods: Patients consecutively included in a prospective HCC cohort (University Hospital Bern) were analysed. They were categorised into two groups, based on the basis of histology or combined radiological and laboratory characteristics. Results: 20.4% of patients were NC-HCC. This group was characterized by a higher median age and a higher female prevalence compared to the C-HCC group. Non-alcoholic fatty liver disease (NAFLD) (25.7%) and HBV infection (14.9%) were the main risk factors in this group, whereas alcohol abuse (26%) and HCV (21.6%) in C-HCC, P<0.001. 19.4% of them were diagnosed during a screening programme. Resection was performed in 54.5% of NC HCC patients despite the advanced stage (BCLC stage B and C). No statistically significant difference in survival rate was observed between C and NC-HCC patients (24 months vs. 33.9 months, P=0.162). In multivariate analysis, in the NC-HCC group each unit increase in BMI was associated with mortality while liver transplantation and resection were positively associated with survival. In the C-HCC group, the BCLC stage C was negatively associated with survival while all the therapeutic lines were negative factors for mortality. Conclusion: NC-HCC patients were diagnosed more often outside a screening programme. The patients were older, with a higher female prevalence and despite an advanced stage, were often amenable to surgery

    Lethal Nipah Virus Infection Induces Rapid Overexpression of CXCL10

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    Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis

    Use of artificial nutrition near the end of life: Results from a French national population-based study of hospitalized cancer patients

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    International audienceBackgroundThe use of artificial nutrition, defined as a medical treatment that allows a non‐oral mechanical feeding, for cancer patients with limited life expectancy is deemed nonbeneficial. High‐quality evidence about the use of artificial nutrition near the end of life is lacking. This study aimed (a) to quantify the use of artificial nutrition near the end‐of‐life, and (b) to identify the factors associated with the use of artificial nutrition.MethodsThis was a retrospective cohort study of decedents based on data from the French national hospital database. The study population included adult cancer patients who died in hospitals in France between 2013 and 2016 and defined to be in a palliative condition. Use of artificial nutrition during the last 7 days before death was the primary endpoint.ResultsA total of 398 822 patients were included. The median duration of the last hospital stay was 10 (interquartile range, 4‐21) days. The artificial nutrition was used for 11 723 (2.9%) during the last 7 days before death. Being a man, younger, having digestive cancers, metastasis, comorbidities, malnutrition, absence of dementia, and palliative care use were the main factors associated to the use of artificial nutrition.ConclusionThis study indicates that the use of artificial nutrition near the end of life is in keeping with current clinical guidelines. The identification of factors associated with the use of artificial nutrition, such as cancer localization, presence of comorbidities or specific symptoms, may help to better manage its use

    BMC Biology BMC Biology The toxoplasma-host cell junction is anchored to the cell cortex to sustain parasite invasive force

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    International audienceBackgroundThe public health threats imposed by toxoplasmosis worldwide and by malaria in sub-Saharan countries are directly associated with the capacity of their closely related causative agents Toxoplasma and Plasmodium, respectively to colonize and expand inside host cells. Therefore, deciphering how these two Apicomplexan protozoan parasites access their hosting cells has been highlighted as a high priority research with the relevant perspective of designing anti-invasive molecules to prevent diseases. Central to the mechanistic base of invasion for both genera is mechanical force, which is thought to be applied by the parasite at the interface between the two cells following assembly of a unique cell junction but this model lacks direct evidence and has been challenged by recent genetic and cell biology studies. In this work, using parasites expressing the fluorescent core component of this junction, we analyse characteristic features of the kinematics of penetration of more than 1000 invasion events.ResultsThe majority of invasion events occur with a typical forward rotational progression of the parasite through a static junction into a vacuole formed from the invaginating host cell plasma membrane, in which the parasite subsequently replicates. However, if parasites encounter resistance and if the junction is not strongly anchored to the host cell cortex, as when parasites do not secrete the toxofilin protein and therefore are unable to locally remodel the cortical actin cytoskeleton, the junction is capped backwards and travels retrogradely with the host cell membrane along the parasite surface as it is enclosed within a functional vacuole. Kinetic measurements of the invasive trajectories strongly support a similar parasite driven force in both static and capped junctions, both of which lead to successful invasion. However about 20% of toxofilin mutants fail to enter and eventually disengage from the host cell membrane while the secreted RON2 molecules are capped at the posterior pole before being cleaved and released in the medium. By contrast in cells characterized by low cortex tension and high cortical actin dynamics, junction capping and entry failure are drastically reduced.ConclusionThis kinematic analysis of pre-invasive and invasive T. gondii tachyzoite behaviors newly highlights that to invade cells, parasites need to engage their motor with the junction molecular complex where force is efficiently applied only upon proper anchorage to the host cell membrane and cortex

    Characterization of human herpesvirus 6A/B U94 as ATPase, helicase, exonuclease and DNA-binding proteins

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    Human herpesvirus-6A (HHV-6A) and HHV-6B integrate their genomes into the telomeres of human chromosomes, however, the mechanisms leading to integration remain unknown. HHV-6A/B encode a protein that has been proposed to be involved in integration termed U94, an ortholog of adeno-associated virus type 2 (AAV-2) Rep68 integrase. In this report, we addressed whether purified recombinant maltose-binding protein (MBP)-U94 fusion proteins of HHV-6A/B possess biological functions compatible with viral integration. We could demonstrate that MBP-U94 efficiently binds both dsDNA and ssDNA containing telomeric repeats using gel shift assay and surface plasmon resonance. MBP-U94 is also able to hydrolyze adenosine triphosphate (ATP) to ADP, providing the energy for further catalytic activities. In addition, U94 displays a 3′ to 5′ exonuclease activity on dsDNA with a preference for 3′-recessed ends. Once the DNA strand reaches 8–10 nt in length, the enzyme dissociates it from the complementary strand. Lastly, MBP-U94 compromises the integrity of a synthetic telomeric D-loop through exonuclease attack at the 3′ end of the invading strand. The preferential DNA binding of MBP-U94 to telomeric sequences, its ability to hydrolyze ATP and its exonuclease/helicase activities suggest that U94 possesses all functions required for HHV-6A/B chromosomal integratio

    Graphite based heat exchangers for fouling control in dairy industry

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    Fouling of heat exchangers is a major problem in the dairy industry. Deposits indeed produce a thermally insulating layer over the surface of the heat exchanger that decreases the heat transfer toward fluids and increases the pressure drop. Additionally , fouling can seriously affect the quality of food products by favoring the development of harmful bacteria, and thus increase the costs and environmental impacts because thorough cleaning procedures have to be used. In this context, fouling control solut ions are thus required. The present work thus aimed at testin g graphite -based materials to heat exchangers for the dairy industry. The fouling behavior was analyzed for four commercial graphite plates, submitted to pasteurization conditions in a pilot pasteurizer

    Mining rare Earth elements: Identifying the plant species most threatened by ore extraction in an insular hotspot

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    Conservation efforts in global biodiversity hotspots often face a common predicament: an urgent need for conservation action hampered by a significant lack of knowledge about that biodiversity. In recent decades, the computerisation of primary biodiversity data worldwide has provided the scientific community with raw material to increase our understanding of the shared natural heritage. These datasets, however, suffer from a lot of geographical and taxonomic inaccuracies. Automated tools developed to enhance their reliability have shown that detailed expert examination remains the best way to achieve robust and exhaustive datasets. In New Caledonia, one of the most important biodiversity hotspots worldwide, the plant diversity inventory is still underway, and most taxa awaiting formal description are narrow endemics, hence by definition hard to discern in the datasets. In the meantime, anthropogenic pressures, such as nickel-ore mining, are threatening the unique ultramafic ecosystems at an increasing rate. The conservation challenge is therefore a race against time, as the rarest species must be identified and protected before they vanish. In this study, based on all available datasets and resources, we applied a workflow capable of highlighting the lesser known taxa. The main challenges addressed were to aggregate all data available worldwide, and tackle the geographical and taxonomic biases, avoiding the data loss resulting from automated filtering. Every doubtful specimen went through a careful taxonomic analysis by a local and international taxonomist panel. Geolocation of the whole dataset was achieved through dataset cross-checking, local botanists’ field knowledge, and historical material examination. Field studies were also conducted to clarify the most unresolved taxa. With the help of this method and by analysing over 85,000 data, we were able to double the number of known narrow endemic taxa, elucidate 68 putative new species, and update our knowledge of the rarest species’ distributions so as to promote conservation measures

    Experimental Infection of Squirrel Monkeys with Nipah Virus

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    We infected squirrel monkeys (Saimiri sciureus) with Nipah virus to determine the monkeys’ suitability for use as primate models in preclinical testing of preventive and therapeutic treatments. Infection of squirrel monkeys through intravenous injection was followed by high death rates associated with acute neurologic and respiratory illness and viral RNA and antigen production
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