JMSE, Vol. 4, Pages 46: Application of a Spectral Wave Model to Assess Breakwater Configurations at a Small Craft Harbour on Lake Ontario

A surface wave model using three nested grids is applied to the eastern end of Lake Ontario to investigate wave propagation from an open lake environment to a small craft harbour protected by a breakwater. The Simulating WAves Nearshore (SWAN) spectral wave model, coupled with the Delft3D hydrodynamic model, is applied to simulate a series of storms in November, 2013. The model results are compared to observations from two pressure sensors, and used to quantify wave properties around existing and future breakwaters to evaluate the bulk changes to the harbour configuration. Overall, the results indicate that the rubblemound breakwater reduces wave heights in the existing harbour by 63% compared to no breakwater, and that the addition of a surface breakwater extension could reduce wave heights by an additional 54%. Wave height attenuation was found to be highly dependent on the incident wave direction relative to breakwater orientation. The spectral wave model is useful for simulating wave transformation for broad directional spectra in wind-sea conditions over large scales to semi-protected areas such as small craft harbours.

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Molecules, Vol. 21, Pages 1028: Glutamine Synthetase Drugability beyond Its Active Site: Exploring Oligomerization Interfaces and Pockets

Background: Glutamine synthetase (GS) is a crucial enzyme to the nitrogen cycle with great commercial and pharmaceutical value. Current inhibitors target the active site, affecting GS activity indiscriminately in all organisms. As the active site is located at the interface between two monomers, the protein-protein interface (PPI) of GSs gains a new role, by providing new targets for enzyme inhibition. Exploring GSs PPI could allow for the development of inhibitors selective for specific organisms. Here we map the PPI of three GSs—human (hsGS), maize (zmGS) and Mycobacterium tuberculosis (mtGS)—and unravel new drugable pockets. Methods: The PPI binding free energy coming from key residues on three GSs from different organisms were mapped by computational alanine scan mutagenesis, applying a multiple dielectric constant MM-PBSA methodology. The most relevant residues for binding are referred as hot-spots. Drugable pockets on GS were detected with the Fpocket software. Results and Conclusions: A total of 23, 19 and 30 hot-spots were identified on hsGS, zmGS and mtGS PPI. Even possessing differences in the hot-spots, hsGS and zmGS PPI are overall very similar. On the other hand, mtGS PPI differs greatly from hsGS and zmGS PPI. A novel drugable pocket was detected on the mtGS PPI. It seems particularly promising for the development of selective anti-tuberculosis drugs given its location on a PPI region that is highly populated with hot-spots and is completely different from the hsGS and zmGS PPIs. Drugs targeting this pockets should be inactive on eukaryotic GS II enzymes.

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Forests, Vol. 7, Pages 174: Major Changes in Growth Rate and Growth Variability of Beech (Fagus sylvatica L.) Related to Soil Alteration and Climate Change in Belgium

Global change—particularly climate change, forest management, and atmospheric deposition—has significantly altered forest growing conditions in Europe. The influences of these changes on beech growth (Fagus sylvatica L.) were investigated for the past 80 years in Belgium, using non-linear mixed effects models on ring-width chronologies of 149 mature and dominant beech trees (87–186 years old). The effects of the developmental stage (i.e., increasing tree size) were filtered out in order to focus on time-dependent growth changes. Beech radial growth was divided into a low-frequency signal (=growth rate), mainly influenced by forest management and atmospheric deposition, and into a high-frequency variability (≈mean sensitivity), mainly influenced by climate change. Between 1930 and 2008, major long-term and time-dependent changes were highlighted. The beech growth rate has decreased by about 38% since the 1950–1960s, and growth variability has increased by about 45% since the 1970–1980s. Our results indicate that (1) before the 1980s, beech growth rate was not predominantly impacted by climate change but rather by soil alteration (i.e., soil compaction and/or nitrogen deposition); and (2) since the 1980s, climate change induced more frequent and intense yearly growth reductions that amplified the growth rate decrease. The highlighted changes were similar in the two ecoregions of Belgium, although more pronounced in the lowlands than in the uplands.

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Crystals, Vol. 6, Pages 90: Simulation of Polymer Crystallization under Isothermal and Temperature Gradient Conditions Using Particle Level Set Method

Morphological models for polymer crystallization under isothermal and temperature gradient conditions with a particle level set method are proposed. In these models, the particle level set method is used to improve the accuracy in studying crystal interaction. The predicted development of crystallinity during crystallization under quiescent isothermal condition by our model is reanalyzed with the Avrami model, and good agreement between the predicted and theoretical values is observed. In the temperature gradient, the computer simulation results with our model are consistent with the experiment results in the literature.

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Religions, Vol. 7, Pages 98: Contemplative Science and Secular Ethics

This article argues that the emerging project of contemplative science will be best served if it is informed by two perspectives. First, attention should be paid not only to non-analytical and/or mindfulness-based practices, but to a fuller range of contemplative practices, including analytical styles of meditation. Second, the issue of ethics must be addressed as a framework within which to understand contemplative practice: both theoretically in order to understand better the practices themselves and the traditions they come from, and practically in order to understand the ways in which contemplative practices are deployed in contemporary societies. The Tibetan Buddhist Lojong (blo sbyong) tradition and secularized practices derived from it, which are now an area of study in contemplative science, are examined as a kind of case study in order to make these two points and illustrate their importance and relevance for the future of this emerging field.

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Entropy, Vol. 18, Pages 284: A Five Species Cyclically Dominant Evolutionary Game with Fixed Direction: A New Way to Produce Self-Organized Spatial Patterns

Cyclically dominant systems are hot issues in academia, and they play an important role in explaining biodiversity in Nature. In this paper, we construct a five-strategy cyclically dominant system. Each individual in our system changes its strategy along a fixed direction. The dominant strategy can promote a change in the dominated strategy, and the dominated strategy can block a change in the dominant strategy. We use mean-field theory and cellular automaton simulation to discuss the evolving characters of the system. In the cellular automaton simulation, we find the emergence of spiral waves on spatial patterns without a migration rate, which suggests a new way to produce self-organized spatial patterns.

http://ift.tt/2b6e8qU

New euprimate postcrania from the early Eocene of Gujarat, India, and the strepsirrhine–haplorhine divergence

Publication date: October 2016
Source:Journal of Human Evolution, Volume 99
Author(s): Rachel H. Dunn, Kenneth D. Rose, Rajendra S. Rana, Kishor Kumar, Ashok Sahni, Thierry Smith
The oldest primates of modern aspect (euprimates) appear abruptly on the Holarctic continents during a brief episode of global warming known as the Paleocene-Eocene Thermal Maximum, at the beginning of the Eocene (∼56 Ma). When they first appear in the fossil record, they are already divided into two distinct clades, Adapoidea (basal members of Strepsirrhini, which includes extant lemurs, lorises, and bushbabies) and Omomyidae (basal Haplorhini, which comprises living tarsiers, monkeys, and apes). Both groups have recently been discovered in the early Eocene Cambay Shale Formation of Vastan lignite mine, Gujarat, India, where they are known mainly from teeth and jaws. The Vastan fossils are dated at ∼54.5 Myr based on associated dinoflagellates and isotope stratigraphy. Here, we describe new, exquisitely preserved limb bones of these Indian primates that reveal more primitive postcranial characteristics than have been previously documented for either clade, and differences between them are so minor that in many cases we cannot be certain to which group they belong. Nevertheless, the small distinctions observed in some elements foreshadow postcranial traits that distinguish the groups by the middle Eocene, suggesting that the Vastan primates—though slightly younger than the oldest known euprimates—may represent the most primitive known remnants of the divergence between the two great primate clades.



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Challenges and successes for the grantees and the Technical Advisory Group of WHO’s influenza vaccine technology transfer initiative

Publication date: Available online 6 August 2016
Source:Vaccine
Author(s): Gary Grohmann, Donald P. Francis, Jaspal Sokhey, James Robertson
One of the aims of the WHO Global Action Plan for Influenza Vaccines (GAP) was to transfer influenza vaccine production technology to interested manufacturers and governments in developing countries, to enable greater influenza vaccine manufacturing capacity against any pandemic threat or pandemic. For this objective, the GAP was supported by an independent Technical Advisory Group (TAG) to assist WHO to select vaccine manufacturing proposals for funding and to provide programmatic support for successful grantees. While there were many challenges, for both the TAG and grantees, there were also notable successes with an additional capacity of 338–600 million pandemic vaccine doses being made possible by the programme between 2007 and 2015, and a potential capacity of more than 600 million by 2016/17 with up to one billion doses expected by 2018/19. Seasonal vaccine production was also developed in 4 countries with another 4–5 countries expected to be producing seasonal vaccine by 2018/19. The relatively small WHO investments – in time and funding – made in these companies to develop their own influenza vaccine production facilities have had quite dramatic results.



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Layered Alginate Constructs: A Platform for Co-culture of Heterogeneous Cell Populations

Engineering and analysis of load bearing tissues with heterogeneous cell populations are still a challenge. Here, we describe a method for creating bi-layered alginate hydrogel discs as a platform for co-culture of diverse cell populations within one construct.

http://ift.tt/2bcDdw7

Correlative Light- and Electron Microscopy Using Quantum Dot Nanoparticles

A method is described whereby quantum dot (QD) nanoparticles can be used for correlative immunocytochemical studies of epoxy embedded human pathology tissue. We employ commercial antibody fragment conjugated QDs that are visualized by widefield fluorescence light microscopy and transmission electron microscopy.

http://ift.tt/2b5T2rf

Fabrication of a Dipole-assisted Solid Phase Extraction Microchip for Trace Metal Analysis in Water Samples

The fabrication protocol of a dipole-assisted solid phase extraction microchip for the trace metal analysis is presented.

http://ift.tt/2aJbXY6

Amplification-Free Detection of Circulating microRNA Biomarkers from Body Fluids Based on Fluorogenic Oligonucleotide-Templated Reaction between Engineered Peptide Nucleic Acid Probes: Application to Prostate Cancer Diagnosis

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b01594

http://ift.tt/2b16EVz

Membrane Stabilization and Detoxification of Acetaminophen-Mediated Oxidative Onslaughts in the Kidneys of Wistar Rats by Standardized Fraction of Zea mays L. (Poaceae), Stigma maydis

This study evaluated membrane stabilization and detoxification potential of ethyl acetate fraction of Zea mays L., Stigma maydis in acetaminophen-induced oxidative onslaughts in the kidneys of Wistar rats. Nephrotoxic rats were orally pre- and posttreated with the fraction and vitamin C for 14 days. Kidney function, antioxidative and histological analyses were thereafter evaluated. The acetaminophen-mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium, and tissue levels of oxidized glutathione, protein-oxidized products, lipid peroxidized products, and fragmented DNA were dose-dependently assuaged in the fraction-treated animals. The fraction also markedly improved creatinine clearance rate, glutathione, and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the fraction. The observed effects compared favorably with that of vitamin C and are informative of the fraction's ability to prevent progression of renal pathological conditions and preserve kidney functions as evidently supported by the histological analysis. Although the effects were prominently exhibited in the fraction-pretreated groups, the overall data from the present findings suggest that the fraction could prevent or extenuate acetaminophen-mediated oxidative renal damage via fortification of antioxidant defense mechanisms.

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Health Care Providers’ Knowledge and Practice Gap towards Joint Zoonotic Disease Surveillance System: Challenges and Opportunities, Gomma District, Southwest Ethiopia

Background. Health care providers play a crucial role for realization of joint zoonotic diseases surveillance by human and animal health sectors, yet there is limited evidence. Hence, this study aimed to determine knowledge and practice gap of health care providers towards the approach for Rabies and Anthrax in Southwest Ethiopia. Methods. A cross-sectional survey was conducted from December 16, 2014, to January 14, 2015. Eligible health care providers were considered for the study. Data were entered in to Epi-data version 3.1 and analyzed using SPSS version 20. Results. A total of 323 (92.02%) health care providers participated in the study. Three hundred sixteen (97.8%) of participants reported that both human and animal health sectors can work together for zoonotic diseases while 96.9% of them replied that both sectors can jointly conduct surveillance. One hundred seventeen (36.2%) of them reported that their respective sectors had conducted joint surveillance for zoonotic diseases. Their involvement was, however, limited to joint outbreak response. Conclusion. There is good opportunity in health care providers' knowledge even though the practice was unacceptably low and did not address all surveillance components. Therefore, formal joint surveillance structure should be in place for optimal implementation of surveillance.

http://ift.tt/2awIe0Y

Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation

Publication date: October 2016
Source:Free Radical Biology and Medicine, Volume 99
Author(s): Zhilei Liu, Yadong Hu, Yiyi Gong, Wenhao Zhang, Chongdong Liu, Qingtao Wang, Haiteng Deng
Isoform 1 of uracil-DNA glycosylase (UNG1) is the major protein for initiating base-excision repair in mitochondria and is in close proximity to the respiratory chain that generates reactive oxygen species (ROS). Effects of ROS on the stability of UNG1 have not been well characterized. In the present study, we found that overexpression of UNG1 enhanced cells' resistance to oxidative stress and protected mitochondrial DNA (mtDNA) from oxidation. Proteomics analysis showed that UNG1 bound to eight proteins in the mitochondria, including PAPSS2, CD70 antigen, and AGR2 under normal growth conditions, whereas UNG1 mainly bound to Peroxiredoxin 3 (PRDX3) via a disulfide linkage under oxidative stress. We further demonstrated that the UNG1-PRDX3 interaction protected UNG1 from ROS-mediated degradation and prevented mtDNA oxidation. Moreover, our results show that ROS-mediated UNG1 degradation was Lon protease 1 (LonP1)-dependent and mitochondrial UNG1 degradation was aggravated by knockdown of PRDX3 expression. Taken together, these results reveal a novel function of UNG1 in the recruitment of PRDX3 to mtDNA under oxidative stress, enabling protection of UNG1 and UNG1-bound DNA from ROS damage and enhancing cell resistance to oxidative stress.

Graphical abstract

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4-Hydroxyhexenal and 4-hydroxynonenal are mediators of the anti-cachectic effect of n-3 and n-6 polyunsaturated fatty acids on human lung cancer cells

Publication date: October 2016
Source:Free Radical Biology and Medicine, Volume 99
Author(s): G. Muzio, M. Ricci, N. Traverso, F. Monacelli, M. Oraldi, M. Maggiora, R.A. Canuto
Cachexia, the most severe paraneoplastic syndrome, occurs in about 80% of patients with advanced cancer; it cannot be reverted by conventional, enteral, or parenteral nutrition. For this reason, nutritional interventions must be based on the use of substances possessing, alongside nutritional and energetic properties, the ability to modulate production of the pro-inflammatory factors responsible for the metabolic changes characterising cancer cachexia. In light of their nutritional and anti-inflammatory properties, polyunsaturated fatty acids (PUFAs), and in particular n-3, have been investigated for treating cachexia; however, the results have been contradictory.Since both n-3 and n-6 PUFAs can affect cell functions in several ways, this research investigated the possibility that the effects of both n-3 and n-6 PUFAs could be mediated by their major aldehydic products of lipid peroxidation, 4-hydroxyhexenal (HHE) and 4-hydroxynonenal (HNE), and by their anti-inflammatory properties. An "in vitro" cancer cachexia model, consisting of human lung cancer cells (A427) and murine myoblasts (C2C12), was used.The results showed that: 1) both n-3 and n-6 PUFAs reduced the growth of lung cancer cells without causing cell death, increased lipid peroxidation and Peroxisome Proliferator-Activated Receptor (PPAR)α, and decreased TNFα; 2) culture medium conditioned by A427 cells grown in the absence of PUFAs blocked myosin production and the differentiation of C2C12 muscle cells; conversely, muscle cells grown in culture medium conditioned by the same cells in the presence of PUFAs showed myosin expression and formed myotubes; 3) adding HHE or HNE directly to C2C12 cells maintained in culture medium conditioned by A427 cells in the absence of PUFAs stimulated myosin production and myotube formation; 4) putative consensus sequences for (PPARs) have been found in genes encoding fast isoforms of myosin heavy chain, by a bioinformatics approach.The overall results show, first, the ability of both n-3 and n-6 PUFAs and their lipid peroxidation products to prevent the blocking of myosin expression and myotube formation caused in C2C12 cells by medium conditioned by human lung tumour cells. The C2C12 cell differentiation can be due to direct effect of lipid peroxidation products, as evidenced by treating C2C12 cells with HHE and HNE, and to the decrease of pro-inflammatory TNFα in A427 cell culture medium. The presence of consensus sequences for PPARs in genes encoding the fast isoforms of myosin heavy chain suggests that the effects of PUFAs, HHE, and HNE are PPAR-mediated.

Graphical abstract

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Quercetin reduces manic-like behavior and brain oxidative stress induced by paradoxical sleep deprivation in mice

Publication date: October 2016
Source:Free Radical Biology and Medicine, Volume 99
Author(s): Luiz K.S. Kanazawa, Débora D. Vecchia, Etiéli M. Wendler, Palloma de A.S. Hocayen, Francislaine A. dos Reis Lívero, Maria Carolina Stipp, Inara M.R. Barcaro, Alexandra Acco, Roberto Andreatini
Quercetin is a known antioxidant and protein kinase C (PKC) inhibitor. Previous studies have shown that mania involves oxidative stress and an increase in PKC activity. We hypothesized that quercetin affects manic symptoms. In the present study, manic-like behavior (hyperlocomotion) and oxidative stress were induced by 24h paradoxical sleep deprivation (PSD) in male Swiss mice. Both 10 and 40mg/kg quercetin prevented PSD-induced hyperlocomotion. Quercetin reversed the PSD-induced decrease in glutathione (GSH) levels in the prefrontal cortex (PFC) and striatum. Quercetin also reversed the PSD-induced increase in lipid peroxidation (LPO) in the PFC, hippocampus, and striatum. Pearson's correlation analysis revealed a negative correlation between locomotor activity and GSH in the PFC in sleep-deprived mice and a positive correlation between locomotor activity and LPO in the PFC and striatum in sleep-deprived mice. These results suggest that quercetin exerts an antimanic-like effect at doses that do not impair spontaneous locomotor activity, and the antioxidant action of quercetin might contribute to its antimanic-like effects.



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Data of intracellular insulin protein reduced by autophagy in INS-1E cells

Publication date: September 2016
Source:Data in Brief, Volume 8
Author(s): Han Sung Kim, Yeong-Min Yoo
Autophagy appears to be involved in maintaining normal intracellular insulin content by accelerating the insulin degradation rate in β-cells (Marsh et al., 2007) [1]. 2-deoxy-d-glucose (2-DG) is metabolized by hexokinase, and acts as an inhibitor of glycolysis. 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways (Aghaee et al., 2012) [2], and appears to be an ideal tool for studying autophagy. Rapamycin induced upregulation of autophagy in both cultured isolated islets and pancreatic β-cells (Tanemura et al., 2012) [3]. Here, we examined that 2-DG or rapamycin-induced autophagy may decrease the production of intracellular insulin in INS-1E insulinoma cells. Data showed that autophagy was increased by 2-DG or rapamycin by Western blotting and Immunofluorescence staining analyses. Also, intracellular insulin decreased by 2-DG or rapamycin. Furthermore, the autophagy inhibitors, bafilomycin A1 and/or 3-methyladenine, in the presence or absence of 2-DG or rapamycin increased intracellular insulin in INS-1E insulinoma cells.



http://ift.tt/2aEj7fq

Pulse Wave Variation during the Menstrual Cycle in Women with Menstrual Pain

Objective. This study is performed to obtain objective diagnostic indicators associated with menstrual pain using pulse wave analysis. Methods. Using a pulse diagnostic device, we measured the pulse waves of 541 women aged between 19 and 30 years, placed in either an experimental group with menstrual pain () or a control group with little or no menstrual pain (). Measurements were taken during both the menstrual and nonmenstrual periods, and comparative analysis was performed. Results. During the nonmenstrual period, the experimental group showed a significantly higher value in the left radial artery for the radial augmentation index (RAI) () but significantly lower values for pulse wave energy () and time to first peak from baseline () () in the right radial artery. During the menstrual period, the experimental group showed significantly lower values in the left radial artery for cardiac diastole and pulse wave area during diastole and significantly higher values for pulse wave area during systole, ratio of systolic phase to the full heartbeat, and systolic-diastolic ratio. Conclusion. We obtained indicators of menstrual pain in women during the menstrual period, including prolonged systolic and shortened diastolic phases, increases in pulse wave energy and area of representative pulse wave, and increased blood vessel resistance.

http://ift.tt/2aD6j5L

Examining Anxiety Sensitivity as an Explanatory Construct Underlying HIV-Related Stigma: Relations to Anxious Arousal, Social Anxiety, and HIV Symptoms Among Persons Living with HIV

Publication date: Available online 6 August 2016
Source:Journal of Anxiety Disorders
Author(s): Charles P. Brandt, Daniel J. Paulus, Charles Jardin, Luke Heggeness, Chad Lemaire, Michael J. Zvolensky




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Chemomics-Integrated Proteomics Analysis of Jie-Geng-Tang to Ameliorate Lipopolysaccharide-Induced Acute Lung Injury in Mice

Jie-Geng-Tang (JGT), a classic and famous traditional Chinese medicine (TCM) prescription composed of Platycodon grandiflorum (Jacq.) A. DC. (PG) and Glycyrrhiza uralensis Fisch. (GU), is well known for "clearing heat and relieving toxicity" and its ability to "diffuse the lung and relieve sore throat." However, the mechanism underlying its action remains unclear. In this study, potential anti-inflammatory ingredients were screened and submitted to PharmMapper and the KEGG bioinformatics website to predict the target proteins and related pathways, respectively. Differentially expressed candidate proteins from acute lung injury (ALI) mice treated with JGT were identified by isobaric tags for relative and absolute quantitation (iTRAQ) and LC Triple-TOF. Eleven potential anti-inflammatory ingredients were found, including the derivatives of glycyrrhizic acid, licorice-saponin, liquiritin, and platycodigenin. A total of sixty-seven differentially expressed proteins were confirmed after JGT treatment with four therapeutic functions, including immunoregulation, anti-inflammation, ribosome, and muscle contraction. PG and GU comediate PI3K/Akt signal pathway inhibition of NF-κB, VCAM1, and ICAM1 release which primarily act on PI3K, PDK1, AKT, and GSK3β. GU markedly inhibits the ERK/MAPK signaling pathways and primarily acts on LCK, RAS, and MEK. A network was constructed using bioactive ingredients, targets, and pathways to determine the mechanism underlying JGT treatment of ALI.

http://ift.tt/2bbOWv1

Cloning, Expression, and Characterization of a Novel Thermophilic Monofunctional Catalase from Geobacillus sp. CHB1

Catalases are widely used in many scientific areas. A catalase gene (Kat) from Geobacillus sp. CHB1 encoding a monofunctional catalase was cloned and recombinant expressed in Escherichia coli (E. coli), which was the first time to clone and express this type of catalase of genus Geobacillus strains as far as we know. This Kat gene was 1,467 bp in length and encoded a catalase with 488 amino acid residuals, which is only 81% similar to the previously studied Bacillus sp. catalase in terms of amino acid sequence. Recombinant catalase was highly soluble in E. coli and made up 30% of the total E. coli protein. Fermentation broth of the recombinant E. coli showed a high catalase activity level up to 35,831 U/mL which was only lower than recombinant Bacillus sp. WSHDZ-01 among the reported catalase production strains. The purified recombinant catalase had a specific activity of 40,526 U/mg and of 51.1 mM. The optimal reaction temperature of this recombinant enzyme was 60°C to 70°C, and it exhibited high activity over a wide range of reaction temperatures, ranging from 10°C to 90°C. The enzyme retained 94.7% of its residual activity after incubation at 60°C for 1 hour. High yield and excellent thermophilic properties are valuable features for this catalase in industrial applications.

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High Mobility Group Box1 Protein Is Involved in Endoplasmic Reticulum Stress Induced by Clostridium difficile Toxin A

High Mobility Group Box (HMGB1), a damage-associated inflammatory factor, plays an important role in the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, the role of the HMGB1 in TcdA-induced ER stress was identified. Clostridium difficile toxin A is one of the major virulence factors of C. difficile infection (CDI) and has been proved to induce apoptotic cell death through ER stress. Our results showed that HMGB1 might play an important role in the TcdA-induced ER stress and unfolded protein response. HMGB1 activated molecular markers and induced the C/EBP homologous protein upregulation (CHOP). This study may provide the essential information for better understanding of the molecular mechanisms involved in CDI.

http://ift.tt/2armGHn

Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells

Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver diseases. Activation and proliferation of hepatic stellate cells (HSCs) represent a key aspect of fibrogenesis and are associated with progressive reduction of HSC apoptosis. Bcl-x, an antiapoptotic member of Bcl-2 gene family, plays a role in apoptosis regulation in mammalian cells. Through alternative splicing, the Bcl-x gene yields two major protein isoforms with opposing functions, antiapoptotic Bcl- and proapoptotic Bcl-. This study aimed to investigate the role of Bcl-x and its alternate splicing in HSC apoptosis. The results indicated that the expression of Bcl- was dramatically higher than Bcl-2 in activated human HSCs. The relative expression of Bcl- over Bcl- increased gradually when HSCs were activated in cell culture, which was consistent with the increase in apoptosis resistance of activated HSCs. Redirection of Bcl-x splicing by an antisense oligonucleotide from the antiapoptotic isoform to the proapoptotic isoform induced death of HSCs without other apoptosis stimuli. We conclude that Bcl-x plays a role in regulation of HSC apoptosis and modulation of Bcl-x alternative splicing may become a novel molecular therapy for liver fibrosis.

http://ift.tt/2armvvV

No fixed item limit in visuospatial working memory

Publication date: Available online 6 August 2016
Source:Cortex
Author(s): Sebastian Schneegans, Paul M. Bays
Investigations of working memory capacity in the visual domain have converged on the concept of a limited supply of a representational medium, flexibly distributed between objects. Current debate centers on whether this medium is continuous, or quantized into 2 or 3 memory "slots". The latter model makes the strong prediction that, if an item in memory is probed, behavioral parameters will plateau when the number of items is the same or more than the number of slots. Here we examine short-term memory for object location using a two-dimensional pointing task. We show that recall variability for items in memory increases monotonically from 1 to 8 items. Using a novel method to isolate only those trials on which a participant correctly identifies the target, we show that response latency also increases monotonically from 1 to 8 items. We argue that both these findings are incompatible with a quantized model.Keywords: working memory; resource; spatial; variability; Bayesian.



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Expression Profile of p53 and p21 in Large Bowel Mucosa as Biomarkers of Inflammatory-Related Carcinogenesis in Ulcerative Colitis

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease that slightly increases the risk of colorectal cancer in patients with long-standing extended disease. Overexpression of p53 and p21 in colonic epithelia is usually detected in UC patients when no dysplasia is histologically seen and it is used by pathologists as a discriminator between regenerative changes and intraepithelial neoplasia, as well as a tissue biomarker useful to predict the risk of evolution toward malignancy. We present a one-year prospective observational study including a cohort of 45 patients with UC; p53 and p21 were evaluated in epithelial cells. p53 was positive in 74 samples revealed in 5% to 90% of epithelial cells, while 63 biopsies had strong positivity for p21 in 5% to 50% of epithelial cells. Architectural distortion was significantly correlated with p53 overexpression in epithelial cells. Thus, we consider that architectural distortion is a good substitute for p53 and p21 expression. We recommend use of p53 as the most valuable tissue biomarker in surveillance of UC patients, identifying the patients with higher risk for dysplasia. Association of p21 is also recommended for a better quantification of risk and for diminishing the false-negative results.

http://ift.tt/2aEfmcK

Comprehensive Evaluation of Personal, Clinical, and Radiation Dosimetric Parameters for Acute Skin Reaction during Whole Breast Radiotherapy

Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The (volume receiving 100% of prescribed radiation dose, , both axilla and inferior fold) and age ( for axilla and 0.026 for inferior fold) were significant parameters in multivariate analyses. The calculated axilla dose () and breast separation () were also risk factors for axilla and inferior fold, respectively. Young age and large are significant factors for acute skin reaction that can be simply and cost-effectively measured.

http://ift.tt/2aCKrHI

Positive-Unlabeled Learning for Pupylation Sites Prediction

Pupylation plays a key role in regulating various protein functions as a crucial posttranslational modification of prokaryotes. In order to understand the molecular mechanism of pupylation, it is important to identify pupylation substrates and sites accurately. Several computational methods have been developed to identify pupylation sites because the traditional experimental methods are time-consuming and labor-sensitive. With the existing computational methods, the experimentally annotated pupylation sites are used as the positive training set and the remaining nonannotated lysine residues as the negative training set to build classifiers to predict new pupylation sites from the unknown proteins. However, the remaining nonannotated lysine residues may contain pupylation sites which have not been experimentally validated yet. Unlike previous methods, in this study, the experimentally annotated pupylation sites were used as the positive training set whereas the remaining nonannotated lysine residues were used as the unlabeled training set. A novel method named PUL-PUP was proposed to predict pupylation sites by using positive-unlabeled learning technique. Our experimental results indicated that PUL-PUP outperforms the other methods significantly for the prediction of pupylation sites. As an application, PUL-PUP was also used to predict the most likely pupylation sites in nonannotated lysine sites.

http://ift.tt/2aDPtal

Influence of Botulinumtoxin A on the Expression of Adult MyHC Isoforms in the Masticatory Muscles in Dystrophin-Deficient Mice (Mdx-Mice)

The most widespread animal model to investigate Duchenne muscular dystrophy is the mdx-mouse. In contrast to humans, phases of muscle degeneration are replaced by regeneration processes; hence there is only a restricted time slot for research. The aim of the study was to investigate if an intramuscular injection of BTX-A is able to break down muscle regeneration and has direct implications on the gene expression of myosin heavy chains in the corresponding treated and untreated muscles. Therefore, paralysis of the right masseter muscle was induced in adult healthy and dystrophic mice by a specific intramuscular injection of BTX-A. After 21 days the mRNA expression and protein content of MyHC isoforms of the right and left masseter, temporal, and the tongue muscle were determined using quantitative RT-PCR and Western blot technique. MyHC-IIa and MyHC-I-mRNA expression significantly increased in the paralyzed masseter muscle of control-mice, whereas MyHC-IIb and MyHC-IIx/d-mRNA were decreased. In dystrophic muscles no effect of BTX-A could be detected at the level of MyHC. This study suggests that BTX-A injection is a suitable method to simulate DMD-pathogenesis in healthy mice but further investigations are necessary to fully analyse the BTX-A effect and to generate sustained muscular atrophy in mdx-mice.

http://ift.tt/2aRC65Z