Challenges and pitfalls of antipsychotic prescribing in people with learning disability

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The role of social networks in the transitional experiences of international African doctoral students at one university in South Africa

International doctoral students’ sojourn encompasses three transitional processes: to the new country, to the university and to a new academic identity as a researcher in a specific discipline. This article examines the role of social networks in facilitating these transitions for international doctoral students at one South African university. It is based on qualitative interviews conducted with 23 international PhD students representing eight different disciplines and various countries in Africa. The findings suggest that students are involved in a number of social networks, which all, apart from the academic network, exclude local students. This close-knit co-national network, while providing international PhD students with a well documented survival mechanism, may hinder their international experiences and limit the acquisition of the inter-cultural skills necessary for global citizenship in the twenty-first century. The findings also indicated that family networks back home played a role in instilling worries and doubts among students related to xenophobic attacks against foreignerhttp://www.tandfonline.com/loi/cher202020-06-18hj2019Education Management and Policy Studie

Deformability of Tumor Cells versus Blood Cells

The potential for circulating tumor cells (CTCs) to elucidate the process of cancer metastasis and inform clinical decision-making has made their isolation of great importance. However, CTCs are rare in the blood, and universal properties with which to identify them remain elusive. As technological advancements have made single-cell deformability measurements increasingly routine, the assessment of physical distinctions between tumor cells and blood cells may provide insight into the feasibility of deformability-based methods for identifying CTCs in patient blood. To this end, we present an initial study assessing deformability differences between tumor cells and blood cells, indicated by the length of time required for them to pass through a microfluidic constriction. Here, we demonstrate that deformability changes in tumor cells that have undergone phenotypic shifts are small compared to differences between tumor cell lines and blood cells. Additionally, in a syngeneic mouse tumor model, cells that are able to exit a tumor and enter circulation are not required to be more deformable than the cells that were first injected into the mouse. However, a limited study of metastatic prostate cancer patients provides evidence that some CTCs may be more mechanically similar to blood cells than to typical tumor cell lines.Janssen Pharmaceutical Ltd.National Cancer Institute (U.S.). Physical Sciences Oncology Center (U54CA143874)MIT-Harvard Center of Cancer Nanotechnology Excellence (Grant 26697290-47281-A)Stand Up To CancerNational Institutes of Health (U.S.). P41 Biotechnology Resource CenterNational Cancer Institute (U.S.) (Koch Institute Support Grant P30-CA14051

Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells

Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and found that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, suggesting that glutamine's ability to replenish tricarboxylic acid cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis.National Institutes of Health (U.S.) (Grant U54CA143874

Aplicación de Altas Presiones Hidrostáticas en jamón serrano: efecto sobre la intención de compra y las expectativas del consumidor.

La aplicación de nuevas tecnologías en productos tradicionales puede modificar su percepción entre los consumidores así como su valor de mercado. Por ello, es interesante evaluar no sólo la aceptación sino también el precio que estaría dispuesto a pagar el consumidor por un producto innovado. El objetivo de este trabajo es evaluar la respuesta del consumidor español ante la aplicación de altas presiones hidrostáticas en un producto tradicional como el jamón serrano. Para ello se realizó un estudio de consumidores (n=229) organizado en dos etapas. En la primera se evaluaron dos productos (jamón serrano tratado y no tratado con altas presiones hidrostáticas) en tres condiciones: cata a ciegas, expectativas y cata informada. En la segunda etapa, se determinó el precio que estaría dispuesto a pagar el consumidor por ambos productos (jamón serrano con y sin tratamiento por altas presiones) mediante subastas experimentales. No se observaron diferencias estadísticamente significativas en la aceptación ni en el precio que estaría dispuesto a pagar el consumidor por el jamón tratado frente al no tratado. Se puede concluir que el consumidor español acepta el tratamiento de altas presiones hidrostáticas en el jamón serrano, aunque no está dispuesto a pagar más por dicha innovación

The effect of mutated mitochondrial ribosomal proteins S16 and S22 on the assembly of the small and large ribosomal subunits in human mitochondria

Mutations in mitochondrial small subunit ribosomal proteins MRPS16 or MRPS22 cause severe, fatal respiratory chain dysfunction due to impaired translation of mitochondrial mRNAs. The loss of either MRPS16 or MRPS22 was accompanied by the loss of most of another small subunit protein MRPS11. However, MRPS2 was reduced only about 2-fold in patient fibroblasts. This observation suggests that the small ribosomal subunit is only partially able to assemble in these patients. Two large subunit ribosomal proteins, MRPL13 and MRPL15, were present in substantial amounts suggesting that the large ribosomal subunit is still present despite a nonfunctional small subunit

Evidence that histidine protonation of receptor-bound anthrax protective antigen is a trigger for pore formation

The protective antigen (PA) component of the anthrax toxin forms pores within the low pH environment of host endosomes, through mechanisms that are poorly understood. It has been proposed that pore formation is dependent on histidine protonation. In previous work, we biosynthetically incorporated 2-fluorohistidine (2-FHis), an isosteric analog of histidine with a significantly reduced pKa (~1), into PA, and showed that the pH-dependent conversion from the soluble prepore to a pore was unchanged. However, we also observed that 2-FHisPA was non-functional in the ability to mediate cytotoxicity of CHO-K1 cells by LFN-DTA, and was defective in translocation through planar lipid bilayers. Here, we show that the defect in cytotoxicity is due to both a defect in translocation and, when bound to the host cellular receptor, an inability to undergo low pH-induced pore formation. Combining X-ray crystallography with hydrogen-deuterium (H-D) exchange mass spectrometry, our studies lead to a model in which hydrogen bonds to the histidine ring are strengthened by receptor binding. The combination of both fluorination and receptor binding is sufficient to block low pH-induced pore formation

Propofol Inhibits Glioma Stem Cell Growth and Migration and Their Interaction with Microglia via BDNF-AS and Extracellular Vesicles

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. GBM contains a small subpopulation of glioma stem cells (GSCs) that are implicated in treatment resistance, tumor infiltration, and recurrence, and are thereby considered important therapeutic targets. Recent clinical studies have suggested that the choice of general anesthetic (GA), particularly propofol, during tumor resection, affects subsequent tumor response to treatments and patient prognosis. In this study, we investigated the molecular mechanisms underlying propofol\u27s anti-tumor effects on GSCs and their interaction with microglia cells. Propofol exerted a dose-dependent inhibitory effect on the self-renewal, expression of mesenchymal markers, and migration of GSCs and sensitized them to both temozolomide (TMZ) and radiation. At higher concentrations, propofol induced a large degree of cell death, as demonstrated using microfluid chip technology. Propofol increased the expression of the lncRNA BDNF-AS, which acts as a tumor suppressor in GBM, and silencing of this lncRNA partially abrogated propofol\u27s effects. Propofol also inhibited the pro-tumorigenic GSC-microglia crosstalk via extracellular vesicles (EVs) and delivery of BDNF-AS. In conclusion, propofol exerted anti-tumor effects on GSCs, sensitized these cells to radiation and TMZ, and inhibited their pro-tumorigenic interactions with microglia via transfer of BDNF-AS by EVs

Using quantitative descriptive analysis and temporal dominance of sensations analysis as complementary methods for profiling commercial blackcurrant squashes

Quantitative descriptive analysis (QDA) is used to describe the nature and the intensity of sensory properties from a single evaluation of a product, whereas temporal dominance of sensation (TDS) is primarily used to identify dominant sensory properties over time. Previous studies with TDS have focused on model systems, but this is the first study to use a sequential approach, i.e. QDA then TDS in measuring sensory properties of a commercial product category, using the same set of trained assessors (n = 11). The main objectives of this study were to: (1) investigate the benefits of using a sequential approach of QDA and TDS and (2) to explore the impact of the sample composition on taste and flavour perceptions in blackcurrant squashes. The present study has proposed an alternative way of determining the choice of attributes for TDS measurement based on data obtained from previous QDA studies, where available. Both methods indicated that the flavour profile was primarily influenced by the level of dilution and complexity of sample composition combined with blackcurrant juice content. In addition, artificial sweeteners were found to modify the quality of sweetness and could also contribute to bitter notes. Using QDA and TDS in tandem was shown to be more beneficial than each just on its own enabling a more complete sensory profile of the products