496 research outputs found

    RBM19 is essential for preimplantation development in the mouse

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    <p>Abstract</p> <p>Background</p> <p>RNA-binding motif protein 19 (RBM19, NCBI Accession # NP_083038) is a conserved nucleolar protein containing 6 conserved RNA recognition motifs. Its biochemical function is to process rRNA for ribosome biogenesis, and it has been shown to play a role in digestive organ development in zebrafish. Here we analyzed the role of RBM19 during mouse embryonic development by generating mice containing a mutation in the <it>Rbm19 </it>locus via gene-trap insertion.</p> <p>Results</p> <p>Homozygous mutant embryos failed to develop beyond the morula stage, showing defective nucleologenesis, activation of apoptosis, and upregulation of P53 target genes. A unique feature of RBM19 is its localization to the cytoplasm in morula stage-embryos, whereas most other nucleolar proteins are localized to the nucleolar precursor body (NPB). The nucleoli in the <it>Rbm19 </it>mutant embryos remain immature, yet they can carry out rRNA synthesis. The timing of developmental arrest occurs after expression of the inner cell mass markers OCT3/4 and NANOG, but prior to the specification of trophectoderm as reflected by CDX2 expression.</p> <p>Conclusion</p> <p>The data indicate that RBM19 is essential for preimplantation development, highlighting the importance of de novo nucleologenesis during this critical developmental stage.</p

    Carbohydrate-derived amphiphilic macromolecules: a biophysical structural characterization and analysis of binding behaviors to model membranes.

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    The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation of a Quantitative Structural Activity Relationship model (QSAR) to make a priori predictions. Amphiphilic macromolecules (AMs) "stealth lipids" built on aldaric and uronic acids frameworks attached to poly(ethylene glycol) (PEG) polymer tails were developed to form self-assembling micelles. In the present study, a defined set of novel AM structures were investigated in terms of their binding to lipid membrane bilayers using Quartz Crystal Microbalance with Dissipation (QCM-D) experiments coupled with computational coarse-grained molecular dynamics (CG MD) and all-atom MD (AA MD) simulations. The CG MD simulations capture the insertion dynamics of the AM lipophilic backbones into the lipid bilayer with the PEGylated tail directed into bulk water. QCM-D measurements with Voigt viscoelastic model analysis enabled the quantitation of the mass gain and rate of interaction between the AM and the lipid bilayer surface. Thus, this study yielded insights about variations in the functional activity of AM materials with minute compositional or stereochemical differences based on membrane binding, which has translational potential for transplanting these materials in vivo. More broadly, it demonstrates an integrated computational-experimental approach, which can offer a promising strategy for the in silico design and screening of therapeutic candidate materials

    Fluorine Effect in the Gelation Ability of Low Molecular Weight Gelators

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    The three gelators presented in this work (Boc-D-Phe-L-Oxd-OH F0, Boc-D-F1Phe-L-Oxd-OH F1 and Boc-D-F2Phe-L-Oxd-OH F2) share the same scaffold and differ in the number of fluorine atoms linked to the aromatic ring of phenylalanine. They have been applied to the preparation of gels in 0.5% or 1.0% w/v concentration, using three methodologies: solvent switch, pH change and calcium ions addition. The general trend is an increased tendency to form structured materials from F0 to F1 and F2. This property ends up in the formation of stronger materials when fluorine atoms are present. Some samples, generally formed by F1 or F2 in 0.5% w/v concentration, show high transparency but low mechanical properties. Two gels, both containing fluorine atoms, show increased stiffness coupled with high transparency. The biocompatibility of the gelators was assessed exposing them to fibroblast cells and demonstrated that F1 and F2 are not toxic to cells even in high concentration, while F0 is not toxic to cells only in a low concentration. In conclusion, the presence of even only one fluorine atom improves all the gelators properties: the gelation ability of the compound, the rheological properties and the transparency of the final materials and the gelator biocompatibility

    Allergic anaphylactic risk in farming activities: A systematic review

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    Allergic disorders in the agriculture sector are very common among farm workers, causing many injuries and occupational diseases every year. Agricultural employees are exposed to multiple conditions and various allergenic substances, which could be related to onset of anaphylactic reactions. This systematic review highlights the main clinical manifestation, the allergens that are mostly involved and the main activities that are usually involved. This research includes articles published on the major databases (PubMed, Cochrane Library, Scopus), using a combination of keywords. The online search yielded 489 references; after selection, by the authors, 36 articles (nine reviews and 27 original articles) were analyzed. From this analysis, the main clinical problems that were diagnosed in this category were respiratory (ranging from rhinitis to asthma) and dermatological (eczema, dermatitis, hives) in nature, with a wide symptomatology (from a simple local reaction to anaphylaxis). The main activities associated with these allergic conditions are harvesting or cultivation of fruit and cereals, beekeepers and people working in greenhouses. Finally, in addition to the allergens already known, new ones have emerged, including triticale, wine, spider and biological dust. For these reasons, in the agricultural sector, research needs to be amplified, considering new sectors, new technologies and new products, and ensuring a system of prevention to reduce this risk.peer-reviewe

    High Field Studies of the Hidden Order Transition in URu2_2Si2_2

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    We studied in detail the low temperature/high magnetic field phases of URu2_{2}Si2_{2} single crystals with specific heat, magnetocaloric effect, and magnetoresistance in magnetic fields up to 45 T. Data obtained down to 0.5 K, and extrapolated to T = 0, show a suppression of the hidden order phase at Ho_{o}(0) = 35.9 ±\pm 0.35 T and the appearance of a new phase for magnetic fields in excess of H1_{1}(0) = 36.1 ±\pm 0.35 T observed \textit{only} at temperatures lower than 6 K. In turn, complete suppression of this high field state is attained at a critical magnetic field H2_{2}(0) = 39.7 ±\pm 0.35 T. No phase transitions are observed above 40 T. We discuss our results in the context of itinerant vs. localized \textit{f}-electron behavior and consider the implications for the hidden order phase.Comment: 4 pages, 3 figures Submitted May 10, 2002. Revised Sep 17, 200

    Biosensors in occupational safety and health management: A narrative review

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    A sensor is a device used to gather information registered by some biological, physical or chemical change, and then convert the information into a measurable signal. The first biosensor prototype was conceived more than a century ago, in 1906, but a properly defined biosensor was only developed later in 1956. Some of them have reached the commercial stage and are routinely used in environmental and agricultural applications, and especially, in clinical laboratory and industrial analysis, mostly because it is an economical, simple and efficient instrument for the in situ detection of the bioavailability of a broad range of environmental pollutants. We propose a narrative review, that found 32 papers and aims to discuss the possible uses of biosensors, focusing on their use in the area of occupational safety and health (OSH)

    Direct detection of spin polarization in photoinduced charge transfer through a chiral bridge

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    It is well assessed that the charge transport through a chiral potential barrier can result in spin-polarized charges. The possibility of driving this process through visible photons holds tremendous potential for several aspects of quantum information science, e.g., the optical control and readout of qubits. In this context, the direct observation of this phenomenon via spin-sensitive spectroscopies is of utmost importance to establish future guidelines to control photo-driven spin selectivity in chiral structures. Here, we provide direct proof that time-resolved electron paramagnetic resonance (EPR) can be used to detect long-lived spin polarization generated by photoinduced charge transfer through a chiral bridge. We propose a system comprising CdSe quantum dots (QDs), as a donor, and C60, as an acceptor, covalently linked through a saturated oligopeptide helical bridge (χ) with a rigid structure of ∼10 Å. Time-resolved EPR spectroscopy shows that the charge transfer in our system results in a C60 radical anion, whose spin polarization maximum is observed at longer times with respect to that of the photogenerated C60 triplet state. Notably, the theoretical modelling of the EPR spectra reveals that the observed features may be compatible with chirality-induced spin selectivity, but the electronic features of the QD do not allow the unambiguous identification of the CISS effect. Nevertheless, we identify which parameters need optimization for unambiguous detection and quantification of the phenomenon. This work lays the basis for the optical generation and direct manipulation of spin polarization induced by chirality

    Differential Diagnosis and Clinical Management of a Case of COVID-19 in a Patient With Stage III Lung Cancer Treated With Radio-chemotherapy and Durvalumab

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    none14nononeGuerini A.E.; Borghetti P.; Filippi A.R.; Bonu M.L.; Tomasini D.; Greco D.; Imbrescia J.; Volpi G.; Triggiani L.; Borghesi A.; Maroldi R.; Pasinetti N.; Buglione M.; Magrini S.M.Guerini, A. E.; Borghetti, P.; Filippi, A. R.; Bonu, M. L.; Tomasini, D.; Greco, D.; Imbrescia, J.; Volpi, G.; Triggiani, L.; Borghesi, A.; Maroldi, R.; Pasinetti, N.; Buglione, M.; Magrini, S. M

    Prospects and Bottlenecks of Reciprocal Partnerships Between the Private and Humanitarian Sectors in Cash Transfer Programming for Humanitarian Response

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    As an alternative to commodity-based programming (in-kind aid), Cash Transfer Programming is attracting both humanitarian organizations' and institutional donors' attention. Unlike in-kind aid, Cash Transfer Programming transfers purchasing power directly to beneficiaries in the form of currency or vouchers for them to obtain goods and/or services directly from the local market. In distributing currency to beneficiaries, the private sector, especially financial service providers, plays a prominent role, due to the humanitarian sector's limited relevant resources. The present work unveils challenges for the private and humanitarian sectors, which hinder implementing Cash Transfer Programming. Based on primary and secondary qualitative data, the paper presents the main characteristics and the mechanisms of Cash Transfer Programming to explore how the private sector is involved with Cash Transfer Programming. Then, this study presents bottlenecks of reciprocal relationships between financial service providers and humanitarian organizations in Cash Transfer Programming
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