59 research outputs found

    Effect of clay type on dispersion and barrier properties of hydrophobically modified poly(vinyl alcohol)-bentonite nanocomposites

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    The oxygen and water vapor permeability at high relative humidity was studied for composite films formed by incorporation of three different bentonites (MMT) into an ethylene-modified, water-soluble poly(vinyl alcohol), EPVOH. The oxygen permeability decreased linearly with an increased addition of hydrophilic MMTs. X-ray diffraction and Fourier transform infrared spectroscopy suggested a homogeneous distribution in the thickness direction with disordered and probably exfoliated structures for hydrophilic MMTs. In contrast, organophilic modified clay showed an intercalated structure with the clay preferentially located at the lower film surface, a combination which was however efficient in reducing the water vapor- and oxygen permeabilities at low addition levels. Composite films of EPVOH and Na+-exchanged MMT resulted in high resistance to dissolution in water, which was ascribed to strong interactions between the components resulting from matching polarities. Annealing the films at 120°C resulted in enhanced resistance to water dissolution and a further reduction in oxygen permeabilit

    Loss of signalling via Gα13 in germinal center B-cell-derived lymphoma

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    Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined1,2. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells3,4. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma

    The Process of Deciding About Prophylactic Surgery for Breast and Ovarian Cancer: Patient Questions, Uncertainties, and Communication

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    Many, women who have, or are at risk for, BRCA, 1/2 mutations or breast cancer decline prophylactic surgery, but questions remain as to how they make and experience these decisions. Our methods consisted of interviewing 32 women for 2 hr each; 19 were tested, 20 were symptomatic. Our results showed that these surgical options forced women to confront questions, involving stresses and uncertainties, regarding: implications of test results, prognoses with and without surgery, and effects of surgery (e.g., on self‐image). Given these dilemmas, many women turned to doctors who then ranged in what and how they communicated about these issues, and how strongly they offered input. Some patients felt disappointed at provider non‐directiveness, while others found providers too directive. Patients turned to family members and friends, who also ranged in how and what they communicated, and whether they agreed with the patient and/or each other. Many women turned to patient communities, but then had to decide how involved to be, and what information to provide or accept. These data suggest that providers and others may need to be more aware of the series of questions, involving stresses and uncertainties, that these women face, and the complex roles providers themselves may play. These data highlight needs for physicians to be able to address these issues flexibly, gauging patient preferences for information and paternalism (vs. autonomy). These data suggest areas for future research: for example, on how providers decide whether, what and how to communicate about these issues, and how these choices shape treatment decisions

    TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts

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    Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient DNA replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate—a covalent TOP1-DNA adduct known as a TOP1 cleavage complex (TOP1cc)—is stabilised. TOP1ccs are highly cytotoxic and a failure to resolve them underlies the pathology of neurological disorders but is also exploited in cancer therapy where TOP1ccs are the target of widely used frontline anti-cancer drugs. A critical enzyme for TOP1cc resolution is the tyrosyl-DNA phosphodiesterase (TDP1), which hydrolyses the bond that links a tyrosine in the active site of TOP1 to a 3’ phosphate group on a single-stranded (ss)DNA break. However, TDP1 can only process small peptide fragments from ssDNA ends, raising the question of how the ~90 kDa TOP1 protein is processed upstream of TDP1. Here we find that TEX264 fulfils this role by forming a complex with the p97 ATPase and the SPRTN metalloprotease. We show that TEX264 recognises both unmodified and SUMO1-modifed TOP1 and initiates TOP1cc repair by recruiting p97 and SPRTN. TEX264 localises to the nuclear periphery, associates with DNA replication forks, and counteracts TOP1ccs during DNA replication. Altogether, our study elucidates the existence of a specialised repair complex required for upstream proteolysis of TOP1ccs and their subsequent resolution

    Managing Phenol Contents in Crop Plants by Phytochemical Farming and Breeding—Visions and Constraints

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    Two main fields of interest form the background of actual demand for optimized levels of phenolic compounds in crop plants. These are human health and plant resistance to pathogens and to biotic and abiotic stress factors. A survey of agricultural technologies influencing the biosynthesis and accumulation of phenolic compounds in crop plants is presented, including observations on the effects of light, temperature, mineral nutrition, water management, grafting, elevated atmospheric CO2, growth and differentiation of the plant and application of elicitors, stimulating agents and plant activators. The underlying mechanisms are discussed with respect to carbohydrate availability, trade-offs to competing demands as well as to regulatory elements. Outlines are given for genetic engineering and plant breeding. Constraints and possible physiological feedbacks are considered for successful and sustainable application of agricultural techniques with respect to management of plant phenol profiles and concentrations

    A Comparison of Vocational Agricultural Facilities in Utah High Schools and Those in Selected States of the Western Region as Perceived by Vocational Agriculture Teachers

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    This study was limited to vocational agricultural teachers in Utah and ten agricultural teachers randomly selected from each of the following states: Arizona, Colorado, Idaho, Montana, Nevada, New Mexico and Wyoming. Questionnaires were completed and returned by a total of 54 Utah vocational agricultural teachers and 50 teachers from the other states. The questionnaires were designed to collect data concerning class size, requirements of the physical facilities and the budget allowed for teaching agricultural mechanics. The study revealed a larger number of non-vocational agriculture students are enrolled in the agricultural programs in Utah than in the other states. The data indicated there are more total students enrolled in Utah vocational agricultural programs than in the other states per teacher. The facilities available in Utah were generally smaller and less equipped for teaching basic agricultural mechanics as compared to other states. Many of the teachers in both groups perceived their facilities inadequate and all recommended improvements. The study also indicated that Utah teachers were receiving a lower budget based on student hours than we re the teachers from other states. Many teachers surveyed did not know the amount of their capita l or operating budgets for their vocational agricultural programs
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