1,309 research outputs found

    Brain Differently Changes Its Algorithms in Parallel Processing of Visual Information

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    Feedback from the visual cortex (Vl) to the Lateral Geniculate Nucleus (LGN) in macaque monkey increase contrast gain of LGN neurons for black and white (B&W) and for color (C) stimuli. LGN parvocellular cells responses to B&W gratings are enhanced by feedback multiplicatively and in contrast independent manner. However, in magnocellular neurons corticofugal pathways enhance cells responses in a contrast~dependent non-linear manner. For C stimuli cortical feedback enhances parvocellular neurons responses in a very strong contrast-dependent manner. Based on these results [13] we propose a model which includes excitatory and inhibitory effects on cells activity (shunting equations) in retina and LGN while taking into account the anatomy of cortical feedback connections. The main mechanisms related to different algorithms of the data processing in the visual brain are differences in feedback properties from Vl to parvocellular (PC) and to magnocellular (MC) neurons. Descending pathways from Vl change differently receptive field (RF) structure of PC and MC cells. For B&W stimuli, in PC cells feedback changes gain similarly in the RF center and in the RF surround, leaving PC RF structure invariant. However, feedback influence MC cells in two ways: directly and through LGN interneurons, which together changes gain and sizes of their RF center differently than gain and size of the RF surround. For C stimuli PC cells operate like MC cells for B&W. The first mechanism extracts from the stimulus an important features in a independent way from other stimulus parameters, whereas the second channel changes its tuning properties as a function of other stimulus attributes like contrast and/or spatial extension. The model suggests novel idea about the possible functional role of PC and MC pathways

    Fatal case of sorafenib-associated idiosyncratic hepatotoxicity in the adjuvant treatment of a patient with renal cell carcinoma.

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    BACKGROUND: Sorafenib is an orally available kinase inhibitor with activity at Raf, PDGFβ and VEGF receptors that is licensed for the treatment of advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Current evidence-based post-nephrectomy management of individuals with localized RCC consists of surveillance-based follow up. The SORCE trial is designed to investigate whether treatment with adjuvant sorafenib can reduce recurrence rates in this cohort. CASE PRESENTATION: Here we report an idiosyncratic reaction to sorafenib resulting in fatal hepatotoxicity and associated renal failure in a 62 year-old man treated with sorafenib within the SORCE trial. CONCLUSION: This is the first reported case of sorafenib exposure associated fatal toxicity in the adjuvant setting and highlights the unpredictable adverse effects of novel adjuvant therapies.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    A Review of the Evidence Supporting the Taste of Non‐esterified Fatty Acids in Humans

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    Dietary fats contribute to the flavor of foods by multiple mechanisms. A role for their taste has only recently gained credence. Current evidence indicates non‐esterified fatty acids (NEFA) are the effective stimuli for the taste component. CD36 and GPR120 are putative receptors, but may not fully account for the totality of the range of sensations elicited by fatty acids. The sensory quality of long‐chain NEFA is not adequately characterized by commonly accepted taste primary qualities and has been termed oleogustus. There is marked individual variability in sensitivity to the taste of NEFA prompting hypotheses of genetic and environmental determinants. Though an association with BMI has been proposed, the preponderance of evidence is not supportive. The importance of oleogustus has not been fully established, but likely contributes to flavor, which influences food choice as well as lipid metabolism and chronic disease risk. A better understanding of oleogustus may provide insights useful for product formulation

    Mapping the Distribution of Invasive Staphylococcus aureus across Europe

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    Franklin Lowy discusses a new study in PLoS Medicine in which the investigators developed an interactive tool for analyzing the spatial distribution of invasive Staphylococcus aureus

    Impact of shortened crop rotation of oilseed rape on soil and rhizosphere microbial diversity in relation to yield decline

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    Oilseed rape (OSR) grown in monoculture shows a decline in yield relative to virgin OSR of up to 25%, but the mechanisms responsible are unknown. A long term field experiment of OSR grown in a range of rotations with wheat was used to determine whether shifts in fungal and bacterial populations of the rhizosphere and bulk soil were associated with the development of OSR yield decline. The communities of fungi and bacteria in the rhizosphere and bulk soil from the field experiment were profiled using terminal restriction fragment length polymorphism (TRFLP) and sequencing of cloned internal transcribed spacer regions and 16S rRNA genes, respectively. OSR cropping frequency had no effect on rhizosphere bacterial communities. However, the rhizosphere fungal communities from continuously grown OSR were significantly different to those from other rotations. This was due primarily to an increase in abundance of two fungi which showed 100% and 95% DNA identity to the plant pathogens Olpidium brassicae and Pyrenochaeta lycopersici, respectively. Real-time PCR confirmed that there was significantly more of these fungi in the continuously grown OSR than the other rotations. These two fungi were isolated from the field and used to inoculate OSR and Brassica oleracea grown under controlled conditions in a glasshouse to determine their effect on yield. At high doses, Olpidium brassicae reduced top growth and root biomass in seedlings and reduced branching and subsequent pod and seed production. Pyrenochaeta sp. formed lesions on the roots of seedlings, and at high doses delayed flowering and had a negative impact on seed quantity and quality

    Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

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    Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition

    Holographic Wilsonian flows and emergent fermions in extremal charged black holes

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    We study holographic Wilsonian RG in a general class of asymptotically AdS backgrounds with a U(1) gauge field. We consider free charged Dirac fermions in such a background, and integrate them up to an intermediate radial distance, yielding an equivalent low energy dual field theory. The new ingredient, compared to scalars, involves a `generalized' basis of coherent states which labels a particular half of the fermion components as coordinates or momenta, depending on the choice of quantization (standard or alternative). We apply this technology to explicitly compute RG flows of charged fermionic operators and their composites (double trace operators) in field theories dual to (a) pure AdS and (b) extremal charged black hole geometries. The flow diagrams and fixed points are determined explicitly. In the case of the extremal black hole, the RG flows connect two fixed points at the UV AdS boundary to two fixed points at the IR AdS_2 region. The double trace flow is shown, both numerically and analytically, to develop a pole singularity in the AdS_2 region at low frequency and near the Fermi momentum, which can be traced to the appearance of massless fermion modes on the low energy cut-off surface. The low energy field theory action we derive exactly agrees with the semi-holographic action proposed by Faulkner and Polchinski in arXiv:1001.5049 [hep-th]. In terms of field theory, the holographic version of Wilsonian RG leads to a quantum theory with random sources. In the extremal black hole background the random sources become `light' in the AdS_2 region near the Fermi surface and emerge as new dynamical degrees of freedom.Comment: 37 pages (including 8 pages of appendix), 10 figures and 2 table

    Evidence for the role of EPHX2 gene variants in anorexia nervosa.

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    Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition
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