bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetric Mukaiyama Aldol Reactions Using Chiral Diamine–Coordinated Sn(II) Triflate: Development and Application to Natural Product Synthesis
Authors: Shiina Isamu 
Published: January 2014

AbstractIn 1989, the asymmetric Mukaiyama aldol reaction mediated by a Lewis acid consisting of a chiral diamine and Sn(II) triflate was reported. The asymmetric Mukaiyama aldol reaction is now widely used as a versatile tool for the construction of highly advanced, multifunctionalized molecules. In this Personal Account, the history of the development of this powerful methodology and the application of the asymmetric Mukaiyama aldol reaction in the synthesis of natural products are reviewed.
The role of Pten/Akt signaling pathway involved in BPA‐induced apoptosis of rat sertoli cells
Authors: Wang Chengmin , Fu Wenjuan , Quan Chao , Yan Maosheng , Liu Changjiang , Qi Suqin , Yang Kedi 
Published: January 2014

AbstractBisphenol‐A (BPA), one of endocrine‐disrupting chemicals, is a male reproductive toxicant. Previous studies have revealed the direct cytotoxicity of BPA in many cultured cells, such as mitotic aneuploidy in embryonic cells and somatic cells, and apoptosis in neurons and testicular Sertoli cells. To understand the action of BPA and assess its risk, the Pten/Akt pathway was investigated in cultured Sertoli cells to elucidate the mechanism of the reproductive effects of BPA. The results showed that over 50 μM BPA treatment could decrease the viability of Sertoli cells and cause more apoptosis. In addition, BPA could induce the increase in mRNA levels of Pten and Akt. The protein level of Pten was increased; however, the protein levels of phospho‐Akt and procaspase‐3 were decreased after BPA exposure. Taken together, observed results suggested that the Pten/Akt pathway might be involved in the apoptotic effects of BPA on Sertoli cells. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 793–802, 2015.
Brood cover and food resources for wild turkeys following silvicultural treatments in mature upland hardwoods
Authors: McCord John M. , Harper Craig A. , Greenberg Cathryn H. 
Published: January 2014

ABSTRACTClosed‐canopy, upland hardwood forests with limited understory development provide suboptimal habitat for wild turkey (Meleagris gallopavo) broods and may lead to low recruitment. Various forest management practices have been used to stimulate understory development within upland hardwoods, but evaluation of such practices on cover and food resources for wild turkey broods is incomplete. Therefore, we compared effects of 7 silvicultural treatments (repeated fire, shelterwood harvest, shelterwood harvest with one fire, retention cut, retention cut with repeated fire, retention cut with herbicide, and retention cut with herbicide and repeated fire) on cover and food resources for wild turkey broods in mature upland hardwoods of the Ridge and Valley Physiographic Province, Tennessee, USA, during 2000–2009. Canopy reduction treatments enhanced understory conditions for wild turkey broods. Eight years following initial treatment, light infiltration in retention cuts with repeated fire was 6 times greater than that within control, 5 times greater than that within shelterwood harvests, and twice that within shelterwood harvests with one prescribed fire. Woody species dominated understory composition following all treatments and controls. Understory disturbance (prescribed fire and broadcast herbicide treatments) reduced density of stems >1.4 m tall and <11.4 cm diameter at breast height (dbh) and created less visual obstruction above 1 m compared with canopy reduction treatments without understory disturbance. Following canopy reduction without repeated prescribed fire, woody vegetation exceeded ideal height for wild turkey broods after 3 growing seasons and light infiltration returned to control levels within 7 years. Soft mast production was greatest following treatments that included canopy reduction, but varied by year and site. Invertebrate biomass did not increase following any treatment, but all treatment areas contained enough invertebrates to meet the protein requirement for a wild turkey brood (10.1 poults) for 28 days on <30 ha. Where wild turkey is a focal species and understory structure in mature upland hardwoods is limiting for broods, we recommend reducing canopy coverage to 60–70% and using low‐intensity fire every 3–5 years to enhance and maintain brood cover and increase food availability. © 2014 The Wildlife Society.
Evaluating wild Turkey movement ecology: An example using first‐passage time analysis
Authors: Byrne Michael E. , Guthrie Joshua D. , Hardin Jason , Collier Bret A. , Chamberlain Michael J. 
Published: January 2014

ABSTRACTRecent advances in animal tracking technology have increased interest in the field of animal movement ecology. Numerous methods have been developed to extract information from animal movement paths that can be used to link movement behavior to external stimuli such as habitat and climatic conditions. Given the recent development of Global Positioning System (GPS) technology suitable for use on wild turkeys (Meleagris gallapavo), we advocate the adoption of new methodologies to design novel research on wild turkey ecology. Here we provide a worked example using first‐passage time on male Rio Grande wild turkeys (M. g. intermedia) tracked via GPS in South Texas, USA, during April 2009 to illustrate one methodological option on which research can be based. From our example, we infer behavioral decisions in response to habitat variables that varied during the diurnal cycle; turkeys were more likely to exhibit localized movements during midday in open areas near food and water resources. We contend that by taking advantage of GPS technology and focusing research questions on movement behavior, wild turkey research can progress toward answering mechanistic questions regarding turkey habitat use. This shift in research focus will provide much‐needed information to managers that is currently lacking at both local and regional scales. © 2014 The Wildlife Society.
Molecular correlates of platinum response in human high‐grade serous ovarian cancer patient‐derived xenografts
Authors: Topp Monique D. , Hartley Lynne , Cook Michele , Heong Valerie , Boehm Emma , McShane Lauren , Pyman Jan , McNally Orla , Ananda Sumitra , Harrell Marisol , Etemadmoghadam Dariush , Galletta Laura , Alsop Kathryn , Mitchell Gillian , Fox Stephen B. , Kerr Jeffrey B. , Hutt Karla J. , Kaufmann Scott H. ,   Australian Ovarian Cancer Study, Swisher Elizabeth M. , Bowtell David D. , Wakefield Matthew J. , Scott Clare L. 
Published: January 2014

IntroductionImprovement in the ability to target underlying drivers and vulnerabilities of high‐grade serous ovarian cancer (HG‐SOC) requires the development of molecularly annotated pre‐clinical models reflective of clinical responses.MethodsWe generated patient‐derived xenografts (PDXs) from consecutive, chemotherapy‐naïve, human HG‐SOC by transplanting fresh human HG‐SOC fragments into subcutaneous and intra‐ovarian bursal sites of NOD/SCID IL2Rγnull recipient mice, completed molecular annotation and assessed platinum sensitivity.ResultsThe success rate of xenografting was 83%. Of ten HG‐SOC PDXs, all contained mutations in TP53, two were mutated for BRCA1, three for BRCA2, and in two, BRCA1 was methylated. In vivo cisplatin response, determined as platinum sensitive (progression‐free interval ≥100 d, n = 4), resistant (progression‐free interval <100 d, n = 3) or refractory (n = 3), was largely consistent with patient outcome. Three of four platinum sensitive HG‐SOC PDXs contained DNA repair gene mutations, and the fourth was methylated for BRCA1. In contrast, all three platinum refractory PDXs overexpressed dominant oncogenes (CCNE1, LIN28B and/or BCL2).ConclusionsBecause PDX platinum response reflected clinical outcome, these annotated PDXs will provide a unique model system for preclinical testing of novel therapies for HG‐SOC.
Coarse-grained simulations of the gating current in the voltage-activated Kv1.2 channel
Authors: Kim Ilsoo , Warshel Arieh 
Published: January 2014

Significance
Structure-based modeling of gating currents in voltage activation of ion channels presents a major challenge. A part of the challenge involves the difficulties of modeling explicitly the charge motion in the electrolytes between the membrane and the electrodes. The present work overcomes some of the above challenge by using a coarse-grained model in simulating the activation of the Kv1.2 channel. The model yields realistic gating charges and free energy landscapes and allows us to simulate the time dependence of the fast gating current and to elucidate its relationship to the landscape involved in the activation process.
Comparison of approaches for parameter identifiability analysis of biological systems
Authors: Raue Andreas , Karlsson Johan , Saccomani Maria Pia , Jirstrand Mats , Timmer Jens 
Published: January 2014

AbstractMotivation: Modeling of dynamical systems using ordinary differential equations is a popular approach in the field of Systems Biology. The amount of experimental data that are used to build and calibrate these models is often limited. In this setting, the model parameters may not be uniquely determinable. Structural or a priori identifiability is a property of the system equations that indicates whether, in principle, the unknown model parameters can be determined from the available data.Results: We performed a case study using three current approaches for structural identifiability analysis for an application from cell biology. The approaches are conceptually different and are developed independently. The results of the three approaches are in agreement. We discuss strength and weaknesses of each of them and illustrate how they can be applied to real world problems.Availability and implementation: For application of the approaches to further applications, code representations (DAISY, Mathematica and MATLAB) for benchmark model and data are provided on the authors webpage.Contact: andreas.raue@fdm.uni-freiburg.de
ECplot: an online tool for making standardized plots from large datasets for bioinformatics publications
Authors: Fok Alex Chun-Hong , Mok Sunny Siu-Nam , Lee Sau Dan , Yip Kevin Y. 
Published: January 2014

AbstractMotivation and results: We have implemented ECplot, an online tool for plotting charts from large datasets. This tool supports a variety of chart types commonly used in bioinformatics publications. In our benchmarking, it was able to create a Box-and-Whisker plot with about 67 000 data points and 8 MB total file size within several seconds. The design of the tool makes common formatting operations easy to perform. It also allows more complex operations to be achieved by advanced XML (Extensible Markup Language) and programming options. Data and formatting styles are stored in separate files, such that style templates can be made and applied to new datasets. The text-based file formats based on XML facilitate efficient manipulation of formatting styles for a large number of data series. These file formats also provide a means to reproduce published figures from raw data, which complement parallel efforts in making the data and software involved in published analysis results accessible. We demonstrate this idea by using ECplot to replicate some complex figures from a previous publication.Availability and implementation: ECplot and its source code (under MIT license) are available at https://yiplab.cse.cuhk.edu.hk/ecplot/.Contact: kevinyip@cse.cuhk.edu.hk
Combinatorial therapy discovery using mixed integer linear programming
Authors: Pang Kaifang , Wan Ying-Wooi , Choi William T. , Donehower Lawrence A. , Sun Jingchun , Pant Dhruv , Liu Zhandong 
Published: January 2014

AbstractMotivation: Combinatorial therapies play increasingly important roles in combating complex diseases. Owing to the huge cost associated with experimental methods in identifying optimal drug combinations, computational approaches can provide a guide to limit the search space and reduce cost. However, few computational approaches have been developed for this purpose, and thus there is a great need of new algorithms for drug combination prediction.Results: Here we proposed to formulate the optimal combinatorial therapy problem into two complementary mathematical algorithms, Balanced Target Set Cover (BTSC) and Minimum Off-Target Set Cover (MOTSC). Given a disease gene set, BTSC seeks a balanced solution that maximizes the coverage on the disease genes and minimizes the off-target hits at the same time. MOTSC seeks a full coverage on the disease gene set while minimizing the off-target set. Through simulation, both BTSC and MOTSC demonstrated a much faster running time over exhaustive search with the same accuracy. When applied to real disease gene sets, our algorithms not only identified known drug combinations, but also predicted novel drug combinations that are worth further testing. In addition, we developed a web-based tool to allow users to iteratively search for optimal drug combinations given a user-defined gene set.Availability: Our tool is freely available for noncommercial use at http://www.drug.liuzlab.org/.Contact: zhandong.liu@bcm.eduSupplementary information: Supplementary data are available at Bioinformatics online.
G-BLASTN: accelerating nucleotide alignment by graphics processors
Authors: Zhao Kaiyong , Chu Xiaowen 
Published: January 2014

AbstractMotivation: Since 1990, the basic local alignment search tool (BLAST) has become one of the most popular and fundamental bioinformatics tools for sequence similarity searching, receiving extensive attention from the research community. The two pioneering papers on BLAST have received over 96 000 citations. Given the huge population of BLAST users and the increasing size of sequence databases, an urgent topic of study is how to improve the speed. Recently, graphics processing units (GPUs) have been widely used as low-cost, high-performance computing platforms. The existing GPU-BLAST is a promising software tool that uses a GPU to accelerate protein sequence alignment. Unfortunately, there is still no GPU-accelerated software tool for BLAST-based nucleotide sequence alignment.Results: We developed G-BLASTN, a GPU-accelerated nucleotide alignment tool based on the widely used NCBI-BLAST. G-BLASTN can produce exactly the same results as NCBI-BLAST, and it has very similar user commands. Compared with the sequential NCBI-BLAST, G-BLASTN can achieve an overall speedup of 14.80X under ‘megablast’ mode. More impressively, it achieves an overall speedup of 7.15X over the multithreaded NCBI-BLAST running on 4 CPU cores. When running under ‘blastn’ mode, the overall speedups are 4.32X (against 1-core) and 1.56X (against 4-core). G-BLASTN also supports a pipeline mode that further improves the overall performance by up to 44% when handling a batch of queries as a whole. Currently G-BLASTN is best optimized for databases with long sequences. We plan to optimize its performance on short database sequences in our future work.Availability: http://www.comp.hkbu.edu.hk/∼chxw/software/G-BLASTN.htmlContact: chxw@comp.hkbu.edu.hkSupplementary information: Supplementary data are available at Bioinformatics online.
MLL fusion proteins link transcriptional coactivators to previously active CpG-rich promoters
Authors: Okuda Hiroshi , Kawaguchi Marie , Kanai Akinori , Matsui Hirotaka , Kawamura Takeshi , Inaba Toshiya , Kitabayashi Issay , Yokoyama Akihiko 
Published: January 2014

Abstract
Mixed-lineage leukemia (MLL) maintains the expression of cellular memory genes during development, while leukemic MLL fusion proteins aberrantly maintain expression of hematopoietic stem cell program genes such as HOXA9 to cause leukemia. However, the molecular mechanism of gene activation is unclear. Here we show that only two functional modules are necessary and sufficient for target recognition: those that bind to non-methylated CpGs and di-/tri-methylated histone H3 lysine 36 (H3K36me2/3). An artificial protein composed of the two targeting modules and an interaction domain for AF4-family coactivators can functionally substitute for MLL fusion proteins. Because H3K36me2/3 markers are indicative of active transcription, MLL fusion proteins target previously active CpG-rich genes and activate transcription by recruiting coactivators thereto. Our results indicate that such chromatin context-dependent gene activation is the fundamental mechanism by which MLL fusion proteins maintain the expression of the cellular memory/hematopoietic stem cell program genes.
MLV integration site selection is driven by strong enhancers and active promoters
Authors: LaFave Matthew C. , Varshney Gaurav K. , Gildea Derek E. , Wolfsberg Tyra G. , Baxevanis Andreas D. , Burgess Shawn M. 
Published: January 2014

Abstract
Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized &gt;3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in &lt;2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors.
Interplay between pre-mRNA splicing and microRNA biogenesis within the supraspliceosome
Authors: Agranat-Tamir Lily , Shomron Noam , Sperling Joseph , Sperling Ruth 
Published: January 2014

Abstract
MicroRNAs (miRNAs) are central regulators of gene expression, and a large fraction of them are encoded in introns of RNA polymerase II transcripts. Thus, the biogenesis of intronic miRNAs by the microprocessor and the splicing of their host introns by the spliceosome require coordination between these processing events. This cross-talk is addressed here. We show that key microprocessor proteins Drosha and DGCR8 as well as pre-miRNAs cosediment with supraspliceosomes, where nuclear posttranscriptional processing is executed. We further show that inhibition of splicing increases miRNAs expression, whereas knock-down of Drosha increases splicing. We identified a novel splicing event in intron 13 of MCM7, where the miR-106b-25 cluster is located. The unique splice isoform includes a hosted pre-miRNA in the extended exon and excludes its processing. This indicates a possible mechanism of altering the levels of different miRNAs originating from the same transcript. Altogether, our study indicates interplay between the splicing and microprocessor machineries within a supraspliceosome context.
The RNase H-like superfamily: new members, comparative structural analysis and evolutionary classification
Authors: Majorek Karolina A. , Dunin-Horkawicz Stanislaw , Steczkiewicz Kamil , Muszewska Anna , Nowotny Marcin , Ginalski Krzysztof , Bujnicki Janusz M. 
Published: January 2014

Abstract
Ribonuclease H-like (RNHL) superfamily, also called the retroviral integrase superfamily, groups together numerous enzymes involved in nucleic acid metabolism and implicated in many biological processes, including replication, homologous recombination, DNA repair, transposition and RNA interference. The RNHL superfamily proteins show extensive divergence of sequences and structures. We conducted database searches to identify members of the RNHL superfamily (including those previously unknown), yielding &gt;60 000 unique domain sequences. Our analysis led to the identification of new RNHL superfamily members, such as RRXRR (PF14239), DUF460 (PF04312, COG2433), DUF3010 (PF11215), DUF429 (PF04250 and COG2410, COG4328, COG4923), DUF1092 (PF06485), COG5558, OrfB_IS605 (PF01385, COG0675) and Peptidase_A17 (PF05380). Based on the clustering analysis we grouped all identified RNHL domain sequences into 152 families. Phylogenetic studies revealed relationships between these families, and suggested a possible history of the evolution of RNHL fold and its active site. Our results revealed clear division of the RNHL superfamily into exonucleases and endonucleases. Structural analyses of features characteristic for particular groups revealed a correlation between the orientation of the C-terminal helix with the exonuclease/endonuclease function and the architecture of the active site. Our analysis provides a comprehensive picture of sequence-structure-function relationships in the RNHL superfamily that may guide functional studies of the previously uncharacterized protein families.
Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion
Authors: Luisier Raphaëlle , Unterberger Elif B. , Goodman Jay I. , Schwarz Michael , Moggs Jonathan , Terranova Rémi , van Nimwegen Erik 
Published: January 2014

Abstract
Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis.