bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Silico Analysis To Explore Novel Inhibitors For Human Proto-oncogene Tyrosine Protein Kinase Src
Authors: Mahanandi Nagapriya , Pradhan Dibyabhaba , Umamaheswari Amineni 
Published: October 2010

AbstractThe first oncogene and the first non receptor tyrosine kinase, Src, plays a key role in cell morphology, motility, proliferation and survival. Over expression of Src kinase activity disrupts the RAS pathway in signaling pathway, where it loses its ability to hydrolyse GTP and thus, leads to cancer. A wide range of evidences indicated that Src-signaling was important in the oncogenesis of prostate cancer and other tumours. Src-signaling is involved in androgen-induced proliferation of prostate cancer in cancer tissue of patients having castration-refractory prostate cancer. Once prostate cancer becomes castration-resistant, bone metastases become significant problem for which treatment options are limited. As Src is involved in multiple signaling pathways, central to prostate cancer development, progression, and metastasis, in addition to normal and pathologic osteoclast activities, Src inhibition becomes a valid therapeutic strategy for investigation. Existing Src kinase inhibitors are less efficient towards prostate cancer and bone metastasis. Hence an in silico work was carried out to identify novel potent inhibitors. Three published inhibitors of human Src kinase those are currently under clinical trial such as AZDO530, bosutinib and dasatinib were subjected to high-throughput screening from more than million entries of Ligand.Info Meta-Database, based on the assumption that small molecules with similar structure have similar pharmacological properties. The ligand dataset of 1152 generated through this approach were prepared using LigPrep to generate possible conformations of each ligand molecule, and at the same time duplicate conformers, conformations with reactive functional group and ADME violaters were rejected. The human Src kinase co-crystal structure with AZDO530 was analyzed to find the inhibitor binding site. The crystal structure was optimized and energy was minimized applying OPLS force field in Maestro v9.0. Glide 5.5 docking was performed to predict the binding orientation of prepared ligand molecule into a grid of 20 x 20 x 20 Å created around the centroid of optimized human Src kinase. Ten lead molecules with good binding affinity with human Src were identified. In silico pharmacokinetics study for these ten lead molecules had shown no ADME violation. Analysis of Lead ‘1’ - human Src docking complex had revealed a XP Gscore of -11.56 kcal/mol with highly stabilized hydrogen bond network with Ala390, Asn391, Lys295, W543 and W640 and good Van der Waals interactions. The docking complex coincides well with the native co-crystallized human Sac and inhibitor AZDO530 complex. Thus, Fisetin, identified as Lead ‘1’ in the present study would be highly useful for developing potential drug molecules for treatment of advanced prostate cancer.
Deciphering the genome structure and paleohistory of Theobroma cacao
Authors: Chaparro Cristian , Murat Florent , Carlson John , Guignon Valentin , Tahi Mathias , Guiderdoni Emmanuel , Legavre Thierry , Fouet Olivier , Sallet Erika , Sabau Xavier , Akaza Joseph Moroh , Quetier Francis , Guiltinan Mark , Poulain Julie , T. Schiex , Axtell Michael , Pitollat Bertrand , Panaud Olivier , Maximova Siela , Ruiz Manuel , Dievart Anne , Ma Zhaorong , Gramacho Karina , Wincker Patrick , Roguet Yolande , Kramer Melissa , Zhang Yufan , D’Hont Angélique , Sidibe-Bocs Stephanie , Lanaud Claire , Argout Xavier , Rodier-Goud Maguy , Gelley Laura , Brown Spencer , Brunel Dominique , Infante Diogenes , Salse Jerome , Barbosa-Neto Jose Fernandes , Sh Zi , Bourge Mickael , Golser Wolfgang , Kebe Ismael , Aury Jean Marc , Sabot Francois , Bérard Aurélie , Viot Christopher , Song Xiang , Costet Pierre , Droc Gaetan , Kudrna Dave , Ammiraju Jetty Siva , Boccara Michel , Clement Didier , Wing Rod , Gouzy Jerome , Abrouk Michael , Schuster Stephan , Risterucci Ange Marie , Rivalan Ronan , McCombie W. Richard , Allegre Mathilde 
Published: October 2010

AbstractWe sequenced and assembled the genome of Theobroma cacao, an economically important tropical fruit tree crop that is the source of chocolate. The assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of them anchored on the 10 T. cacao chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example flavonoid-related genes. It also provides a major source of candidate genes for T. cacao disease resistance and quality improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten T. cacao chromosomes were shaped from an ancestor through eleven chromosome fusions. The T. cacao genome can be considered as a simple living relic of higher plant evolution.
The activating receptors 2B4 and NTB-A, but not CRACC are subject to ligand-induced down-regulation on human natural killer cells
Authors: Meinke Stephan , Böhm Carolin , Durlanik Sibel , Watzl Carsten 
Published: October 2010

AbstractActivation of natural killer cells can be mediated by different receptors. Stimulation of the receptors 2B4, NTB-A and CRACC, members of the SLAM-related receptor family, induces cytotoxicity and cytokine production. The surface expression of 2B4 and other activating natural killer cell receptors is down-modulated after receptor engagement, which results in a weaker response to consecutive stimulation. We tested whether this regulatory mechanism applies to all SLAM-related receptors expressed by primary human natural killer cells. After co-culture with target cells expressing the respective ligands different effects on receptor surface expression were observed. While 2B4 ex-pression was strongly reduced, NTB-A showed less prominent down-modulation and the expression level of CRACC remained unchanged. The expression levels of the receptor-proximal signaling molecules SAP, EAT-2 and FynT did not change after receptor engagement. Co-culture with target cells expressing the ligands for NTB-A or CRACC had no impact on subsequent NTB-A or CRACC-mediated NK cell activation.
Diabetes and kidney cancer: A direct or indirect association?
Authors: Ojha Rohit , Evans Eva , Powell Tabatha , Nuwayhid Bahij , Mulla Zuber 
Published: October 2010

AbstractA positive association between diabetes and kidney cancer has been reported in several investigations, but it is unclear whether diabetes or its complications account for this association. Recent advances in estimating direct associations may be useful for elucidating the association between diabetes and kidney cancer. Therefore, we performed a case-control analysis to evaluate whether the direct association between diabetes and kidney cancer is the primary concern in this exposure-outcome relation. Discharge data (with International Classification of Diseases – 9 codes) from 2001 for hospitals throughout Florida were used to construct a case-control population of inpatients aged ≥45 years. Cases (n=1,909) were inpatients with malignant kidney cancer and controls (n=6,451) were inpatients with motor vehicle injuries. Diabetes status was ascertained for cases and controls. Covariates that required adjustment to estimate the total (age, gender, ethnicity, obesity, and smoking) and direct (age, gender, ethnicity, obesity, smoking, hypertension, and kidney disease) associations were identified in a directed acyclic graph. Binary logistic regression was used to estimate the adjusted total and direct odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of kidney cancer for diabetics. The odds of kidney cancer were higher for inpatients with diabetes than inpatients without diabetes when estimating the total association (OR=1.27, 95%CI: 1.10, 1.47) but attenuated when estimating the direct association (OR=1.08, 95%CI: 0.93, 1.25). Our findings provide preliminary insight that the direct association between diabetes and kidney cancer may not be the primary concern in this exposure-outcome relation; indirect pathways (i.e. diabetic complications) may have greater influence on this relation. A similar analysis using longitudinal data with appropriately measured covariates may provide more definitive conclusions and could have implications for kidney cancer prevention among diabetics.
PERSPECTIVES OF NANODIAMOND FORMATION FROM THE ORGANIC MATTER AT LOW P-T PARAMETERS
Authors: Simakov Sergei 
Published: October 2010

AbstractThe perspectives of nanosized diamond particles formation at metastable P-T parameters from organic matter at hydrothermal conditions is discussed. From the known data it’s possible to conclude that we could provide the hydrothermal syntheses of nanodiamonds from the water-oil or water-alcohol-oil solutions.
SC1/PRDM4 recruits PRMT5 to control the timing of neural precursor differentiation in developing neural stem cells
Authors: Chittka Alexandra , Grazini Ursula 
Published: October 2010

AbstractDuring cortical development, neural stem cells (NSCs) switch from proliferative to neuron-generating asymmetric divisions. Here we investigated the role of Schwann cell factor 1 (SC1/PRDM4), a transcriptional repressor highly expressed in the developing nervous system, during NSCs development. We found that SC1 protein levels were down-regulated in newly differentiating neurons, while remaining high in undifferentiated NSCs, suggesting an asymmetric inheritance of SC1. Knockdown of SC1 in the NSCs led to precocious differentiation of neurons and its overexpression led to an increase in Nestin-expressing precursors. We found that SC1, through its amino-terminus, recruits the chromatin modifier PRMT5, a histone arginine methyltransferase that catalyses histone H4R3 symmetric dimethylation (H4R3me2s). Mutations disrupting SC1/PRMT5 interaction resulted in loss of SC1-mediated increase in undifferentiated neural precursor cells. Our data demonstrate that SC1 and PRMT5 are components of an epigenetic regulatory complex that provides an epigenetic signature of a “stem-like” cellular state in the NSCs and which may be asymmetrically inherited during neurogenic divisions.
Molecular evidence for Toxoplasma gondii in the brain of striped dolphins (Stenella coeruleoalba) stranded along the Ligurian Sea coast of Italy
Authors: Traversa Donato , Di Cesare Angela , Casalone Cristina , Iulini Barbara , Mignone Walter , Tittarelli Cristiana , Proietto Umberto , Meloni Silvana , Buffatello Giulia , Forster Fiona , Kennedy Seamus , Di Guardo Giovanni 
Published: October 2010

AbstractToxoplasma gondii is a protozoan agent of increasing concern for both free-ranging and captive cetaceans. Nonetheless, information on epidemiology, biology, genetics and pathogenic potential of T. gondii for aquatic mammals is incomplete. This work provides molecular evidence for T. gondii in the brain tissue from five striped dolphins (Stenella coeruleoalba) found stranded in 2007-2008 along the Ligurian Sea coast of Italy. These animals showed a more or less severe, subacute to chronic, non purulent, multifocal meningo-encephalitis. Additionally, the cerebral parenchyma of 3 animals harboured protozoan cysts and zoites which were immunohistochemically linked to T. gondii. Consequently, a preliminary molecular investigation was undertaken to confirm the presence of the protozoan in these dolphins. Genomic DNA was extracted from the brain tissue of the animals and the extracts were examined with a nested PCR specific for the B1 gene of T. gondii. Three out of the 5 animals scored positive upon B1-PCR. Sequences were subsequently searched against the GenBankTM Database using the Basic Local Alignment Search Tool. The three sequences were identical to each other and showed 100% homology with the corresponding B1 sequence of T. gondii, with no insertions/deletions nor substitutions. The other 2 dolphins were negative upon B1-specific PCRs and also upon PCRs targeting other T. gondii genes (i.e. GRA and UPRT). To explore more in depth the genetic make-up of this protozoan, complementary studies are presently ongoing on GRA and UPRT genes of the 3 animals which were molecularly confirmed (i.e. B1-PCR) as infected by T. gondii. In conclusion, further studies are needed to elucidate a number of epidemiological and biological features of T. gondii infection in free-ranging cetaceans, with special emphasis on “pelagic” species such as striped dolphins.
A unique avenue to control drug resistant pathogens: Experimental evidences
Authors: Sen Sribir 
Published: October 2010

AbstractDrug resistant bacterial pathogens are increasing in the environment due to multiple reasons. If any drug resistant pathogen grows in a host, the host will face death treat because there is no way to resist their growth in the host system. Eventuality is death in almost all cases. Reports on the mechanisms of drug resistance in bacteria are many. However, there is no solution for these cases. The present work is providing an important understanding to fight against drug resistant pathogens and that can be used in gastrointestinal diseases.
Cluster Analysis of Breast Cancer Microarray Data
Authors: Dave Kirtan 
Published: October 2010

AbstractHigh-throughput genomic technology has rapidly become a major tool for the study of breast cancer. The recent development gene expression microarray and related technology provide to an opportunity to perform more detail profiling of the disease However, whole-genome approaches are still relatively new and critics have been quick to highlight, non-overlapping results from groups testing similar hypotheses. In this canopy, cluster analysis helps to reduce complex multivariate data and may be used to devise in the development of classification systems or taxonomies by gene ontology.
The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core
Authors: Smith Lucian , Wilkinson Darren , Hucka Michael , Bergmann Frank , Hoops Stefan , Keating Sarah , Sahle Sven , Schaff James 
Published: October 2010

AbstractThis is the final specification for Release 1 of *SBML Level 3 Version 1 Core*, an electronic model representation format for systems biology.SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. SBML is defined neutrally with respect to programming languages and software encoding; however, it is oriented primarily towards allowing models to be encoded using XML. This document contains many examples of SBML models written in XML.More information about SBML and this specification is available online at "http://sbml.org/Documents/Specifications/":http://sbml.org/Documents/Specifications/.
Context-based generation of kinetic equations with SBMLsqueezer 1.3
Authors: Dräger Andreas , Nitschmann Sandra , Dörr Alexander , Eichner Johannes , Ziller Michael , Zell Andreas 
Published: October 2010

AbstractThe development of predictive, quantitative models constitutes a common task in today‘s systems biology. To obtain a mathematical model description for the simulation of gene-regulatory, signaling, and metabolic networks, kinetic equations are required for each reaction within the network. Deriving and assembling these formulas is a complicated, time-consuming, and error-prone process that requires knowledge about the structure of interactions, consistently choosing a rate law for each type of reaction, and assignment of appropriate units to all parameters. In many cases, thermodynamic dependencies between the parameters have to be taken into account. For multi compartment models, the concentration units of reacting species have to be converted into molecular amounts. Here we present version 1.3 of the program SBMLsqueezer that generates kinetic equations for SBML models based on the definition of the network's topology and annotations of the elements therein, i.e., Systems Biology Ontology (SBO) and Minimal Information Requested In the Annotation of Models (MIRIAM) annotations.
JSBML
Authors: Rodriguez Nicolas , Dräger Andreas 
Published: October 2010

AbstractThe XML-based Systems Biology Markup Language (SBML) is the de facto standard file format for the storage and exchange of biochemical network models, and is supported by more than 180 software packages to date. Much of this success is due to SBML's clearly defined specifications and the availability of libSBML, a portable, robust and easy-to-use library.LibSBML provides many methods for manipulating and validating SBML files through its Application Programming Interface (API). Originally written in C and C++, libSBML also provides automatically-generated language bindings for Java, MATLAB, Perl, Python, and many more. However, the platform independence of Java is compromised in libSBML due to the fact that the language binding is a wrapper around the C/C++ core. The real-world experiences of many software developers has been that the deployment of portable libSBML-based Java applications is difficult. Further, the libSBML API and type hierarchy are not sufficiently intuitive from a Java programmer's perspective simply because they were not designed directly for Java.For these reasons, several groups in the SBML community have mounted an open-source effort to develop a pure Java library for SBML. Here we present the JSBML project, whose products are freely available at the website "http://jsbml.sourceforge.net/":http://jsbml.sourceforge.net/. The JSBML project's aim is to provide an SBML parser and programming library that maps all SBML elements to a flexible and extended type hierarchy. Where possible, JSBML strives to attain 100% API compatibility with the libSBML Java API, to facilitate a switch from one library to the other for those who desire it.Currently, JSBML supports all constructs for SBML up to the latest Level 3 Version 1 release candidate specification, including an API to add SBML extensions. There are no plans to re-implement some of the more complex functions of libSBML, since separate community efforts are expected to make them available to JSBML via web services. These more complex functions include model consistency checking, SBML validation, and the conversion between different SBML Levels and Versions.In summary, JSBML is a young, ongoing software project that provides comprehensive and entirely Java-based data structures to read, write, and manipulate SBML files. Its layered architecture allows for the creation of Java web start applications and CellDesigner plug-ins based on stand-alone programs with very little effort. One program, SBMLsqueezer 1.3, has already been re-implemented and released using JSBML, and many others are planned.
Phantom Pain Reduction by Non-ionizing Electromagnetic Treatment
Authors: Bokkon Istvan 
Published: October 2010

AbstractBased on our years of experience testing a technique called non-ionizing Electromagnetic-Own-Signal-Treatment (EMOST), here, we present our preliminary results for phantom pain reduction by this method under clinical circumstances. Our preliminary results showed not only a reduction in phantom pain in patients but also a marked improvement in their sleep and mood quality after the treatments. Here, we also suggest that some of the important effects of our method may be achieved via the redox balance of the body and redox-related neural plasticity. However, low-frequency and intensity electromagnetic fields can potentially provide useful methods for the treatment of various problematic disorders and can play important roles in public health of the 21st century medicine.
Towards reproducible MSMS data preprocessing, quality control and quantification
Authors: Gatto Laurent , Lilley Kathryn 
Published: October 2010

AbstractThe development of MSnbase aims at providing researchers dealing with labelled quantitative proteomics data with a transparent, portable, extensible and open-source collaborative framework to easily manipulate and analyse MS2-level raw tandem mass spectrometry data. The implementation in R gives users and developers a great variety of powerful tools to be used in a controlled and reproducible way. Furthermore, MSnbase has been developed following an object-oriented programming paradigm: all information that is manipulated by the user is encapsulated in ad hoc data containers to hide it's underlying complexity. We illustrate the usage and achievements of our software using a published spiked-in data set in which varying quantities of test proteins have been labelled with four different iTRAQ tags. In addition to providing raw MSMS data, MSnbase also stores meta-data and logs processing steps in the data object itself for optimal traceability. We provide graphics on how to inspect precursor data for quality control and how individual or merged MSMS spectra can subsequently be processed, plotted and extracted using a variety of methods. We also demonstrate how reporter ions (or any peaks of interest defined by the user) can easily be quantified and normalised using several build-in alternative strategies and how the effect of each transformation can be recorded, examined and reproduced. MSnbase constitutes a unique versatile working and development environment to process labelled MSMS data and provides in turn important feedback for data acquisition optimisation. We conclude by presenting future extensions of MSnbase and highlight its usage in reproducible proteomics research.
The pancreatic islet β-cell-enriched transcription factor Pdx-1 regulates Slc30a8 gene transcription through an intronic enhancer
Authors: Pound Lynley D. , Hang Yan , Sarkar Suparna A. , Wang Yingda , Milam Laurel A. , Oeser James K. , Printz Richard L. , Lee Catherine E. , Stein Roland , Hutton John C. , O'Brien Richard M. 
Published: October 2010

The SLC30A8 gene encodes the zinc transporter ZnT-8, which provides zinc for insulin-hexamer formation. Genome-wide association studies have shown that a polymorphic variant in SLC30A8 is associated with altered susceptibility to Type 2 diabetes and we recently reported that glucose-stimulated insulin secretion is decreased in islets isolated from Slc30a8-knockout mice. The present study examines the molecular basis for the islet-specific expression of Slc30a8. VISTA analyses identified two conserved regions in Slc30a8 introns 2 and 3, designated enhancers A and B respectively. Transfection experiments demonstrated that enhancer B confers elevated fusion gene expression in both βTC-3 cells and αTC-6 cells. In contrast, enhancer A confers elevated fusion gene expression selectively in βTC-3 and not αTC-6 cells. These data suggest that enhancer A is an islet β-cell-specific enhancer and that the mechanisms controlling Slc30a8 expression in α- and β-cells are overlapping, but distinct. Gel retardation and ChIP (chromatin immunoprecipitation) assays revealed that the islet-enriched transcription factor Pdx-1 binds enhancer A in vitro and in situ respectively. Mutation of two Pdx-1-binding sites in enhancer A markedly reduces fusion gene expression suggesting that this factor contributes to Slc30a8 expression in β-cells, a conclusion consistent with developmental studies showing that restriction of Pdx-1 to pancreatic islet β-cells correlates with the induction of Slc30a8 gene expression and ZnT-8 protein expression in vivo.