218 research outputs found

    Short-time dynamics in the 1D long-range Potts model

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    We present numerical investigations of the short-time dynamics at criticality in the 1D Potts model with power-law decaying interactions of the form 1/r^{1+sigma}. The scaling properties of the magnetization, autocorrelation function and time correlations of the magnetization are studied. The dynamical critical exponents theta' and z are derived in the cases q=2 and q=3 for several values of the parameter σ\sigma belonging to the nontrivial critical regime.Comment: 8 pages, 8 figures, minor changes - several typos fixed, one reference change

    MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

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    Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

    From amino acid sequence to bioactivity: the biomedical potential of antitumor peptides

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    Chemoprevention is the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. In this field, the use of antitumor peptides is of interest as, (i) these molecules are small in size, (ii) they show good cell diffusion and permeability, (iii) they affect one or more specific molecular pathways involved in carcinogenesis, and (iv) they are not usually genotoxic. We have checked the Web of Science Database (23/11/2015) in order to collect papers reporting on bioactive peptide (1691 registers), which was further filtered searching terms such as antiproliferative, antitumoral, or apoptosis among others. Works reporting the amino acid sequence of an antiproliferative peptide were kept (60 registers), and this was complemented with the peptides included in CancerPPD, an extensive resource for antiproliferative peptides and proteins. Peptides were grouped according to one of the following mechanism of action: inhibition of cell migration, inhibition of tumor angiogenesis, antioxidative mechanisms, inhibition of gene transcription/cell proliferation, induction of apoptosis, disorganization of tubulin structure, cytotoxicity, or unknown mechanisms. The main mechanisms of action of those antiproliferative peptides with known amino acid sequences are presented and finally, their potential clinical usefulness and future challenges on their application is discussed.Grant sponsor: Spanish Programa Estatal de Investigacion, Desarrollo e Inovacion Orientada a los Retos de la Sociedad; Grant number: AGL2013-44039-R; Grant sponsor: Plan galego de investigacion, innovacion e crecemento 2011-2015; Grant number: EM2014/046; Grant sponsor: University of Vigo; Grant number: 14VI05; Grant sponsor: Spanish Ministerio de Economia y Competividad (Ramon y Cajal postdoctoral contract); Grant number: RYC-2012-10052 (to Borja Sanchez)

    Effect of feed pressure and long-term separation performance of Pebax-ionic liquid membranes for the recovery of difluoromethane (R32) from refrigerant mixture R410A

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    The R410A refrigerant blend (GWP = 2088), a near azeotropic and equimass mixture of difluoromethane (R32, GWP = 675) and pentafluoroethane (R125, GWP = 3500), has been included in the HFC phase down road map established worldwide. In this context, the recovery of value-added R32 from R410A using membrane technology would be a breakthrough in the refrigeration and air conditioning sector, given that conventional distillation cannot be applied to this separation. For the first time, this work has taken advantage of the combination of ionic liquids and polymeric membranes for the separation of the constituents of the R410A mixture. Results show a remarkable improvement in terms of R32 permeability and R32/R125 selectivity in the composite membranes containing 40 wt % [C2mim][SCN] (αR32/R125 up to 14.5) and [C2mim][BF4] (αR32/R125 up to 11.0) with respect to the neat polymer membranes (αR32/R125 up to 6.9). Besides, the long-term stability was successfully tested for 25 days under high pressure conditions (7 and 12 bar), which makes these composite membranes excellent candidates for the development of membrane-based R32 separation and recovery processes.This research is supported by Project KET4F-Gas – SOE2/P1/P0823, which is co-financed by the European Regional Development Fund within the framework of Interreg Sudoe Programme, and Project PID2019-105827RB-I00, Ministerio de Ciencia e Innovación (Spain). The authors acknowledge the collaboration of Dr. Rosario Benavente (Institute of Polymer Science and Technology-CSIC) to perform the DSC experiments. Dr. Fernando Pardo, acknowledges the post-doctoral fellowship (FJCI-2017-32884, ‘Juan de la Cierva Formación’) from the Spanish Ministry of Science, Innovation and Universities

    Arctigenin Efficiently Enhanced Sedentary Mice Treadmill Endurance

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    Physical inactivity is considered as one of the potential risk factors for the development of type 2 diabetes and other metabolic diseases, while endurance exercise training could enhance fat oxidation that is associated with insulin sensitivity improvement in obesity. AMP-activated protein kinase (AMPK) as an energy sensor plays pivotal roles in the regulation of energy homeostasis, and its activation could improve glucose uptake, promote mitochondrial biogenesis and increase glycolysis. Recent research has even suggested that AMPK activation contributed to endurance enhancement without exercise. Here we report that the natural product arctigenin from the traditional herb Arctium lappa L. (Compositae) strongly increased AMPK phosphorylation and subsequently up-regulated its downstream pathway in both H9C2 and C2C12 cells. It was discovered that arctigenin phosphorylated AMPK via calmodulin-dependent protein kinase kinase (CaMKK) and serine/threonine kinase 11(LKB1)-dependent pathways. Mice treadmill based in vivo assay further indicated that administration of arctigenin improved efficiently mice endurance as reflected by the increased fatigue time and distance, and potently enhanced mitochondrial biogenesis and fatty acid oxidation (FAO) related genes expression in muscle tissues. Our results thus suggested that arctigenin might be used as a potential lead compound for the discovery of the agents with mimic exercise training effects to treat metabolic diseases

    A photometric stereo-based 3D imaging system using computer vision and deep learning for tracking plant growth

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    © The Author(s) 2019. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Tracking and predicting the growth performance of plants in different environments is critical for predicting the impact of global climate change. Automated approaches for image capture and analysis have allowed for substantial increases in the throughput of quantitative growth trait measurements compared with manual assessments. Recent work has focused on adopting computer vision and machine learning approaches to improve the accuracy of automated plant phenotyping. Here we present PS-Plant, a low-cost and portable 3D plant phenotyping platform based on an imaging technique novel to plant phenotyping called photometric stereo (PS). Results: We calibrated PS-Plant to track the model plant Arabidopsis thaliana throughout the day-night (diel) cycle and investigated growth architecture under a variety of conditions to illustrate the dramatic effect of the environment on plant phenotype. We developed bespoke computer vision algorithms and assessed available deep neural network architectures to automate the segmentation of rosettes and individual leaves, and extract basic and more advanced traits from PS-derived data, including the tracking of 3D plant growth and diel leaf hyponastic movement. Furthermore, we have produced the first PS training data set, which includes 221 manually annotated Arabidopsis rosettes that were used for training and data analysis (1,768 images in total). A full protocol is provided, including all software components and an additional test data set. Conclusions: PS-Plant is a powerful new phenotyping tool for plant research that provides robust data at high temporal and spatial resolutions. The system is well-suited for small- and large-scale research and will help to accelerate bridging of the phenotype-to-genotype gap

    The T1405N Carbamoyl Phosphate Synthetase Polymorphism Does Not Affect Plasma Arginine Concentrations in Preterm Infants

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    A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1) has been associated with changes in plasma concentrations of L-arginine in term and near term infants but not in adults. In preterm infants homozygosity for the CPS1 Thr1405 variant (CC genotype) was associated with an increased risk of having necrotizing enterocolitis (NEC). Plasma L-arginine concentrations are decreased in preterm infants with NEC.To examine the putative association between the CPS1 T1405N polymorphism and plasma arginine concentrations in preterm infants.Prospective multicenter cohort study. Plasma and DNA samples were collected from 128 preterm infants (<30 weeks) between 6 and 12 hours after birth. Plasma amino acid and CPS1 T1405N polymorphism analysis were performed.Distribution of genotypes did not differ between the preterm (CC:CA:AA = 55.5%:33.6%:10.9%, n = 128) and term infants (CC:CA:AA = 54.2%:35.4%:10.4%, n = 96). There was no association between the CPS1 genotype and plasma L-arginine or L-citrulline concentration, or the ornithine to citrulline ratio, which varies inversely with CPS1 activity. Also the levels of asymmetric dimethylarginine, and symmetric dimethylarginine were not significantly different among the three genotypes.The present study in preterm infants did not confirm the earlier reported association between CPS1 genotype and L-arginine levels in term infants

    Mild Mitochondrial Uncoupling and Calorie Restriction Increase Fasting eNOS, Akt and Mitochondrial Biogenesis

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    Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis

    Photoredox Catalysts Based on Earth-abundant Metal Complexes

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    We would like to thank the Engineering and Physical Sciences Research Council and CRITICAT Centre for Doctoral Training for financial support [Ph.D. studentship to B.H.; Grant code: EP/L016419/1]. C.L thanks the Prof. & Mrs Purdie Bequests Scholarship and AstraZeneca for his PhD Studentship.Over the last decade, visible light photoredox catalysis has exploded into the consciousness of the synthetic chemist. The principal photocatalysts used are based on rare and toxic ruthenium(II) and iridium(III) complexes. This critical review focusses on Earth-abundant metal complexes as potential replacement photocatalysts and summarizes the use of photoactive Cu(I), Zn(II), Ni(0), V(V), Zr(IV), W(0), W(VI), Mo(0), Cr(III) , Co(III) and Fe(II) complexes in photoredox reactions. The optoelectronic properties of these complexes and relevant structurally related analogs, not yet used for photoredox catalysis, are disccussed in combination with the reaction scope reported for each photocatalyst. Prospects for the future of photocatalyst design are considered.PostprintPeer reviewe

    Cellular Phenotype-Dependent and -Independent Effects of Vitamin C on the Renewal and Gene Expression of Mouse Embryonic Fibroblasts

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    Vitamin C has been shown to delay the cellular senescence and was considered a candidate for chemoprevention and cancer therapy. To understand the reported contrasting roles of vitamin C: growth-promoting in the primary cells and growth-inhibiting in cancer cells, primary mouse embryonic fibroblasts (MEF) and their isogenic spontaneously immortalized fibroblasts with unlimited cell division potential were used as the model pair. We used microarray gene expression profiling to show that the immortalized MEF possess human cancer gene expression fingerprints including a pattern of up-regulation of inflammatory response-related genes. Using the MEF model, we found that a physiological treatment level of vitamin C (10−5 M), but not other unrelated antioxidants, enhanced cell growth. The growth-promoting effect was associated with a pattern of enhanced expression of cell cycle- and cell division-related genes in both primary and immortalized cells. In the immortalized MEF, physiological treatment levels of vitamin C also enhanced the expression of immortalization-associated genes including a down-regulation of genes in the extracellular matrix functional category. In contrast, confocal immunofluorescence imaging of the primary MEF suggested an increase in collagen IV protein upon vitamin C treatment. Similar to the cancer cells, the growth-inhibitory effect of the redox-active form of vitamin C was preferentially observed in immortalized MEF. All effects of vitamin C required its intracellular presence since the transporter-deficient SVCT2−/− MEF did not respond to vitamin C. SVCT2−/− MEF divided and became immortalized readily indicating little dependence on vitamin C for the cell division. Immortalized SVCT2−/− MEF required higher concentration of vitamin C for the growth inhibition compared to the immortalized wildtype MEF suggesting an intracellular vitamin C toxicity. The relevance of our observation in aging and human cancer prevention was discussed
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