bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting the mTOR Pathway in Leukemia
Authors: Dinner Shira , Platanias Leonidas C. 
Published: March 2016

ABSTRACTOptimal function of multiple intracellular signaling pathways is essential for normal regulation of cellular transcription, translation, growth, proliferation, and survival. Dysregulation or aberrant activation of such cascades can lead to inappropriate cell survival and abnormal cell proliferation in leukemia. Successful treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors targeting the BCR‐ABL fusion gene is a prime example of effectively inhibiting intracellular signaling cascades. However, even in these patients resistance can develop via emergence of mutations or feedback activation of other pathways that cause refractory disease. Constitutive activation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway has been observed in different types of leukemia, including CML, acute myeloid leukemia, and acute lymphoblastic leukemia. Abnormal mTOR activity may contribute to chemotherapy resistance, while it may also be effectively targeted via molecular means and/or development of specific pharmacological inhibitors. This review discusses the role of PI3K/Akt/mTOR dysre‐gulation in leukemia and summarizes the emergence of preliminary data for the development of novel therapeutic approaches. J. Cell. Biochem. 117: 1745–1752, 2016. © 2016 Wiley Periodicals, Inc.
The Tyrosine Kinome Dictates Breast Cancer Heterogeneity and Therapeutic Responsiveness
Authors: Ha Jacqueline R. , Siegel Peter M. , Ursini‐Siegel Josie 
Published: March 2016

ABSTRACTPhospho‐tyrosine signaling networks control numerous biological processes including cellular differentiation, cell growth and survival, motility, and invasion. Aberrant regulation of the tyrosine kinome is a hallmark of malignancy and influences all stages of breast cancer progression, from initiation to the development of metastatic disease. The success of specific tyrosine kinase inhibitors strongly validates the clinical relevance of tyrosine phosphorylation networks in breast cancer pathology. However, a significant degree of redundancy exists within the tyrosine kinome. Numerous receptor and cytoplasmic tyrosine kinases converge on a core set of signaling regulators, including adaptor proteins and tyrosine phosphatases, to amplify pro‐tumorigenic signal transduction pathways. Mutational activation, amplification, or overexpression of one or more components of the tyrosine kinome represents key contributing events responsible for the tumor heterogeneity that is observed in breast cancers. It is this molecular heterogeneity that has become the most significant barrier to durable clinical responses due to the development of therapeutic resistance. This review focuses on recent literature that supports a prominent role for specific components of the tyrosine kinome in the emergence of unique breast cancer subtypes and in shaping breast cancer plasticity, sensitivity to targeted therapies, and the eventual emergence of acquired resistance. J. Cell. Biochem. 117: 1971–1990, 2016. © 2016 Wiley Periodicals, Inc.
Saturation Numbers in Tripartite Graphs
Authors: Sullivan Eric , Wenger Paul S. 
Published: March 2016

AbstractGiven graphs H and F, a subgraph is an F‐saturated subgraph of H if , but for all . The saturation number of F in H, denoted , is the minimum number of edges in an F‐saturated subgraph of H. In this article, we study saturation numbers of tripartite graphs in tripartite graphs. For and n1, n2, and n3 sufficiently large, we determine and exactly and within an additive constant. We also include general constructions of ‐saturated subgraphs of with few edges for .
Linear Clique‐Width for Hereditary Classes of Cographs
Authors: Brignall Robert , Korpelainen Nicholas , Vatter Vincent 
Published: March 2016

AbstractThe class of cographs is known to have unbounded linear clique‐width. We prove that a hereditary class of cographs has bounded linear clique‐width if and only if it does not contain all quasi‐threshold graphs or their complements. The proof borrows ideas from the enumeration of permutation classes.
Occlusal pattern of cheek teeth in extant Spermophilus: A new approach to the identification of species
Authors: Popova Lilia 
Published: March 2016

ABSTRACTDiscrete characters of the occlusal surface (additional cusps) have been studied to elaborate a new approach to the identification of the Ground Squirrel species Spermophilus odessanus, S. suslicus, S. pygmaeus, S. citellus, and S. xanthoprymnus. Data on the presence/absence of the additional cusps have been represented as star plots and, in addition, have been studied using discriminant function analysis. The species‐specific sets of the characters (patterns of bunodonty) have been revealed and are of high diagnostic value. The Citellus‐set is defined by the presence of mesostyles and the rareness of the metastylids, paraconules and metaconules, hypostyles and protostyles. The Pygmaeus‐set is characterized by the presence of additional cusps in the lower cheek teeth. The Odessanus‐oriented set is found in the Spermophilus pygmaeus, S. odessanus, and S. suslicus. The relatively high frequency of additional cusps of the metaloph and the paraloph is characteristic for this set. The Plesiomorphic‐set (characters shared by all the studied species and for this reason regarded herein as ancestral) is found in S. xanthoprymnus. The patterns of bunodonty serve as diagnostic criteria only as a whole: the shape of a star plot (relations among the character frequencies), rather than certain character values, is indicative. An optimal level of identification of species is possible based on the combination of the discrete characters mentioned and on the size parameters of the third upper molar. The occlusal sets are intended to remain stable during the time of species existence and seem to correspond to trends in specialization. The functional meaning of the sets can be explained by the dependence between the presence/absence of the discrete characters and the shape of the crown and its main lophs. Each pattern is likely to correspond to a trophic niche, and this niche corresponds to the species. J. Morphol. 277:814–825, 2016. © 2016 Wiley Periodicals, Inc.
Inclusion of Global Navigation Satellite System radio occultation data into Center for Weather Forecast and Climate Studies Local Ensemble Transform Kalman Filter (LETKF) using the Radio Occultation Processing Package as an observation operator
Authors: Sapucci Luiz F. , Diniz Fábio L. R. , Bastarz Carlos F. , Avanço Lucas A. 
Published: March 2016

ABSTRACTThe Local Ensemble Transform Kalman Filter (LETKF) is a system for data assimilation in the testing phase at the Center for Weather Forecast and Climate Studies of the Brazilian Institute for Space Research (CPTEC/INPE). This system introduces significant advantages over the traditional variational methodology in the inclusion of new observation systems because determining the observation operator does not involve inverse problems. The refractivity profile from the Global Navigation Satellite System (GNSS) radio occultation (RO) technique is an example of an additional source of unconventional observation with promising results over regions with low data coverage. To assimilate RO profiles using the LETKF system at CPTEC/INPE, the Radio Occultation Processing Package (ROPP) from Radio Occultation Meteorology Satellite Applications Facilities/European Organization for the Exploration of Meteorological Satellites (ROM SAF/EUMETSAT) was used as an observation operator. The goal of this work was to investigate the impact on the Atmospheric General Circulation Model of the CPTEC using ROPP as an operator of the assimilation of RO data into the LETKF system. The results showed that positive impacts were obtained in several evaluated variables, including humidity, particularly over South America, where the model used by the CPTEC produces better results.
How to take into account exposure to drugs over time in pharmacoepidemiology studies of pregnant women?
Authors: Hurault‐Delarue Caroline , Chouquet Cécile , Savy Nicolas , Lacroix Isabelle , Beau Anna‐Belle , Montastruc Jean‐Louis , Damase‐Michel Christine 
Published: March 2016

AbstractPurposeThe aim of this study was to develop a new pharmacoepidemiological method to take into account intensity and evolution of drug exposure, applied to pregnant women.MethodsPregnant women were classified according to their drug exposure, in three steps:

Conversion of prescription data into exposure variables (using ATC‐DDD)
Construction of individual trajectories of exposure
Clustering of individual trajectories of exposure (using the R package Kml)
We applied this method to psychotropic drugs prescribed during pregnancy. The present study involved women, included in the EFEMERIS database, who gave birth in Haute‐Garonne (France) between 2004 and 2010 (N = 54 918).ResultsExposure to psychotropic drugs of 3708 pregnant women was studied (6.7%). The pregnant women could be classified into four groups with homogeneous trajectories of exposure: low constant exposure during pregnancy (Cluster A: 70.8% of women); decreasing exposure during the first trimester of pregnancy and low constant exposure thereafter (Cluster B: 19.6%); moderate constant exposure (Cluster C: 8.2%); and high albeit decreasing exposure (Cluster D: 1.4%).ConclusionsThe proposed new method enabled us to describe more precisely women's exposure to drugs during pregnancy, and to distinguish different profiles of exposure. This method could be used to investigate specific outcomes related to duration and intensity of drug exposure during pregnancy, and also to study adverse drug reactions throughout life. Copyright © 2016 John Wiley & Sons, Ltd.
Activin A regulates microRNAs and gene expression in LNCaP cells
Authors: Ottley Edward Christopher , Nicholson Helen Diana , Gold Elspeth Joan 
Published: March 2016

BACKGROUNDProstate cancer (PCa) is an increasing health issue worldwide. For patients with advanced castration‐resistant PCa (CRPC) treatment options are limited and overall survival is relatively short. Paired with this, non‐invasive diagnostic options are yet to be established. Activins are members of the TGF‐β superfamily and have been linked to prostate physiology. For instance, activin A is an inhibitor of growth in the prostate. A novel class of non‐coding RNA, microRNAs (miRNAs) have been intrinsically linked to a range of cellular processes and carcinogenesis. No studies have investigated the impact of activin A on miRNA expression in PCa cell lines. Hence, the objective of this study was to determine the effect of activin A on miRNA expression and downstream target genes in PCa.METHODSActivin‐sensitive (LNCaP) and insensitive (PC3) prostate cells were treated with 50 ng/ml of activin A for 72 hr. To examine miRNA expression following treatment, SYBR RT‐qPCR miRNA arrays were used in conjunction with TaqMan RT‐qPCR. MiRPath‐TarBase analysis was conducted using the miRNAs that were significantly altered following activin A treatment of LNCaP cells to highlight enriched target genes within biological pathways. Highlighted target genes were assessed using pathway‐focused TGF‐β and cell cycle SYBR RT‐qPCR arrays.RESULTSActivin A treatment altered nine miRNAs in LNCaP cells: miR‐222‐3p, miR‐15b‐5p, miR‐93‐5p, miR‐18a‐5p, and let‐7i‐5p were significantly decreased, while miR‐30a/30d‐5p, let‐7c, and miR‐196b‐5p were significantly increased versus media control. In PC3 cells five miRNAs were altered: miR‐130a‐3p, miR‐7‐5p, and miR‐140‐3p were significantly decreased while miR‐191‐5p and miR‐26a‐5p were significantly increased versus media control. MiRPath‐TarBase analysis highlighted that the miRNAs significantly altered in LNCaP cells targeted genes contained in activin A‐related KEGG pathways. Furthermore, when LNCaP cells were treated with activin A the expression of the targeted genes was the inverse of the expression of activin A‐mediated miRNAs.CONCLUSIONSThis study demonstrated the ability of activin A to modulate miRNA expression in PCa cell lines and suggests a correlative relationship between miRNA expression and downstream target genes in LNCaP cells. This study provides impetus for further studies into activin A and miRNAs in PCa. Prostate 76:951–963, 2016. © 2016 Wiley Periodicals, Inc.
Exploring Temporal Patterns of Stress in Adolescent Girls with Headache
Authors: Björling Elin A. , Singh Narayan 
Published: March 2016

AbstractAs part of a larger study on perceived stress and headaches in 2009, momentary perceived stress, head pain levels and stress‐related symptom data were collected. This paper explores a temporal analysis of the patterns of stress, as well as an analysis of momentary and retrospective stress‐related symptoms compared by level of headache activity. Adolescent girls (N = 31) ages 14–18 were randomly cued by electronic diaries 7 times per day over a 21‐day period responding to momentary questions about level of head pain, perceived stress and stress‐related symptoms. Multivariate general linear modelling was used to determine significant differences among headache groups in relation to temporal patterns of stress. Significant headache group differences were found on retrospective and momentary stress‐related symptom measures. A total of 2841 diary responses captured stress levels, head pain and related symptoms. The chronic headache (CH) group reported the highest levels of hourly and daily stress, followed by the moderate headache (MH) and low headache (LH) groups. Patterns of stress for the three headache groups were statistically distinct, illustrating increased stress in girls with more frequent head pain. This evidence suggests that because of increased stress, girls with recurrent head pain are likely a vulnerable population who may benefit from stress‐reducing interventions. Copyright © 2016 John Wiley & Sons, Ltd.
Harmonization of Mangiferin on methylmercury engendered mitochondrial dysfunction
Authors: Das Shubhankar , Paul Ajanta , Mumbrekar Kamalesh D. , Rao Satish B. S. 
Published: March 2016

ABSTRACTMangiferin (MGN), a C‐glucosylxanthone abundantly found in mango plants, was studied for its potential to ameliorate methylmercury (MeHg) induced mitochondrial damage in HepG2 (human hepatocarcinoma) cell line. Cell viability experiments performed using 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐ diphenyltetrazolium bromide (MTT) showed protective property of MGN in annulling MeHg‐induced cytotoxicity. Conditioning the cells with optimal dose of MGN (50 µM) lowered MeHg‐induced oxidative stress, calcium influx/efflux, depletion of mitochondrial trans‐membrane potential and prevented mitochondrial fission as observed by decrease in Mitotracker red fluorescence, expression of pDRP1 (serine 616), and DRP1 levels. MGN pre‐treated cells demonstrated elevation in the activities of glutathione (GSH), Glutathione‐S‐transferase (GST), Glutathione peroxidase (GPx), Glutathione reductase (GR), reduced levels of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) and mitochondrial electron transport chain (ETC) enzyme complexes. In addition, the anti‐apoptotic effect of MGN was clearly indicated by the reduction in MeHg‐induced apoptotic cells analyzed by flowcytometric analysis after Annexin V‐FITC/propidium iodide staining. In conclusion, the present work demonstrates the ability of a dietary polyphenol, MGN to ameliorate MeHg‐mediated mitochondrial dysfunction in human hepatic cells in vitro. This hepatoprotective potential may be attributed predominantly to the free radical scavenging/antioxidant property of MGN, by facilitating the balancing of cellular Ca2+ ions, maintenance of redox homeostasis and intracellular antioxidant activities, ultimately preserving the mitochondrial function and cell viability after MeHg intoxication. As MeHg intoxication occurs over a period of time, continuous consumption of such dietary compounds may prove to be very useful in promoting human health. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 630–644, 2017.
mRNAtrans‐splicing in gene therapy for genetic diseases
Authors: Berger Adeline , Maire Séverine , Gaillard Marie‐Claude , Sahel José‐Alain , Hantraye Philippe , Bemelmans Alexis‐Pierre 
Published: March 2016

Spliceosome‐mediated RNA trans‐splicing, or SMaRT, is a promising strategy to design innovative gene therapy solutions for currently intractable genetic diseases. SMaRT relies on the correction of mutations at the post‐transcriptional level by modifying the mRNA sequence. To achieve this, an exogenous RNA is introduced into the target cell, usually by means of gene transfer, to induce a splice event in trans between the exogenous RNA and the target endogenous pre‐mRNA. This produces a chimeric mRNA composed partly of exons of the latter, and partly of exons of the former, encoding a sequence free of mutations. The principal challenge of SMaRT technology is to achieve a reaction as complete as possible, i.e., resulting in 100% repairing of the endogenous mRNA target. The proof of concept of SMaRT feasibility has already been established in several models of genetic diseases caused by recessive mutations. In such cases, in fact, the repair of only a portion of the mutant mRNA pool may be sufficient to obtain a significant therapeutic effect. However in the case of dominant mutations, the target cell must be freed from the majority of mutant mRNA copies, requiring a highly efficient trans‐splicing reaction. This likely explains why only a few examples of SMaRT approaches targeting dominant mutations are reported in the literature. In this review, we explain in details the mechanism of trans‐splicing, review the different strategies that are under evaluation to lead to efficient trans‐splicing, and discuss the advantages and limitations of SMaRT. WIREs RNA 2016, 7:487–498. doi: 10.1002/wrna.1347This article is categorized under:

RNA Processing > Splicing Mechanisms
RNA Processing > RNA Editing and Modification
The reciprocal regulation between splicing and 3′‐end processing
Authors: Kaida Daisuke 
Published: March 2016

Most eukaryotic precursor mRNAs are subjected to RNA processing events, including 5′‐end capping, splicing and 3′‐end processing. These processing events were historically studied independently; however, since the early 1990s tremendous efforts by many research groups have revealed that these processing factors interact with each other to control each other's functions. U1 snRNP and its components negatively regulate polyadenylation of precursor mRNAs. Importantly, this function is necessary for protecting the integrity of the transcriptome and for regulating gene length and the direction of transcription. In addition, physical and functional interactions occur between splicing factors and 3′‐end processing factors across the last exon. These interactions activate or inhibit splicing and 3′‐end processing depending on the context. Therefore, splicing and 3′‐end processing are reciprocally regulated in many ways through the complex protein–protein interaction network. Although interesting questions remain, future studies will illuminate the molecular mechanisms underlying the reciprocal regulation. WIREs RNA 2016, 7:499–511. doi: 10.1002/wrna.1348This article is categorized under:

RNA Processing > Splicing Regulation/Alternative Splicing
RNA Processing > 3′ End Processing
Anhydrobiosis in yeast: cell wall mannoproteins are important for yeast Saccharomyces cerevisiae resistance to dehydration
Authors: Borovikova Diana , Teparić Renata , Mrša Vladimir , Rapoport Alexander 
Published: March 2016

AbstractThe state of anhydrobiosis is linked with the reversible delay of metabolism as a result of strong dehydration of cells, and is widely distributed in nature. A number of factors responsible for the maintenance of organisms' viability in these conditions have been revealed. This study was directed to understanding how changes in cell wall structure may influence the resistance of yeasts to dehydration–rehydration. Mutants lacking various cell wall mannoproteins were tested to address this issue. It was revealed that mutants lacking proteins belonging to two structurally and functionally unrelated groups (proteins non‐covalently attached to the cell wall, and Pir proteins) possessed significantly lower cell resistance to dehydration–rehydration than the mother wild‐type strain. At the same time, the absence of the GPI‐anchored cell wall protein Ccw12 unexpectedly resulted in an increase of cell resistance to this treatment; this phenomenon is explained by the compensatory synthesis of chitin. The results clearly indicate that the cell wall structure/composition relates to parameters strongly influencing yeast viability during the processes of dehydration–rehydration, and that damage to cell wall proteins during yeast desiccation can be an important factor leading to cell death. Copyright © 2016 John Wiley & Sons, Ltd.
Outlining the influence of non‐conventional yeasts in wine ageing over lees
Authors: Belda Ignacio , Navascués Eva , Marquina Domingo , Santos Antonio , Calderón Fernando , Benito Santiago 
Published: March 2016

AbstractDuring the last decade, the use of innovative yeast cultures of both Saccharomyces cerevisiae and non‐Saccharomyces yeasts as alternative tools to manage the winemaking process have turned the oenology industry. Although the contribution of different yeast species to wine quality during fermentation is increasingly understood, information about their role in wine ageing over lees is really scarce. This work aims to analyse the incidence of three non‐Saccharomyces yeast species of oenological interest (Torulaspora delbrueckii, Lachancea thermotolerans and Metschnikowia pulcherrima) and of a commercial mannoprotein‐overproducer S. cerevisiae strain compared with a conventional industrial yeast strain during wine ageing over lees. To evaluate their incidence in mouthfeel properties of wine after 4 months of ageing, the mannoprotein content of wines was evaluated, together with other wine analytic parameters, such as colour and aroma, biogenic amines and amino acids profile. Some differences among the studied parameters were observed during the study, especially regarding the mannoprotein concentration of wines. Our results suggest that the use of T. delbrueckii lees in wine ageing is a useful tool for the improvement of overall wine quality by notably increasing mannoproteins, reaching values higher than obtained using a S. cerevisiae overproducer strain. Copyright © 2016 John Wiley & Sons, Ltd.
Linkages of Firmicutes and Bacteroidetes populations to methanogenic process performance
Authors: Chen Si , Cheng Huicai , Wyckoff Kristen N , He Qiang 
Published: March 2016

Abstract
To identify potential linkages between specific bacterial populations and process performance in anaerobic digestion, the dynamics of bacterial community structure was monitored with high-throughput sequencing in triplicate anaerobic digesters treating animal waste. Firmicutes and Bacteroidetes were found as the two most abundant populations, however, with contrasting population dynamics in response to organic overloading. Firmicutes dominated the bacterial community during stable process performance at low organic loading rate, representing over 50 % of the bacterial abundance. In contrast, the onset of organic overloading raised the relative abundance of Bacteroidetes from 20 ± 2.6 to 44 ± 3.1 %. In addition to the significant negative correlation between the relative abundance of Firmicutes and Bacteroidetes, populations of Firmicutes and Bacteroidetes were found to be linked to process parameters including organic loading rate, volatile fatty acids concentration, and methane production. Therefore, the population abundance ratio of Firmicutes to Bacteroidetes (F/B ratio) was suggested as a potential indicator for process performance. The interactions between Firmicutes and Bacteroidetes populations could be exploited to develop strategies for the prevention of performance perturbation in anaerobic digestion processes.