bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrocardiographic left ventricular hypertrophy regression induced by an angiotensin receptor blocker-based regimen in hypertensive patients with diabetes: data from the SARA study
Authors: Barrios Vivencio , Escobar Carlos , Calderón Alberto , Echarri Rocio , Barrios Sara , Navarro-Cid Josefa 
Published: August 2009

Introduction. This study examined the influence of diabetes on left ventricular hypertrophy (LVH) detected by different electrocardiographic (ECG) criteria and its changes induced by a 12-month candesartan-based regimen. Methods. The patients were treated for a 12-month period with a candesartan-based regimen (8/16 mg + hydrochlorothiazide12.5 mg + additional drugs to target blood pressure < 140/90 mmHg [< 130/80 in diabetics]). Cornell voltage index (CorV), Cornell product (CorP), Sokolow-Lyon voltage index (SokV), and Sokolow-Lyon product (SokP) were calculated. In total 276 patients were included, 51 with diabetes. Results. At study end, blood pressure was reduced 19.0±9.2/7.3±3.4 mmHg in diabetic patients and 18.8±9.1/8.0±3.2 mmHg in non-diabetic subjects (both p<0.01 vs. baseline; p=0.85 between groups).At baseline, 37.5% of diabetic and 26.4% of non-diabetic patients fulfilled criteria of ECG-LVH by CorP (p=0.02), 25.7% and 23.2%, respectively, by SokP (p=0.18), 11.8% and 13.7% by CorV (p=0.16), and 14.3% and 11.6% by SokV (p=0.10).At study end, the prevalence of ECG-LVH was reduced to 25.1% (relative risk reduction [RRR] 33.3%, p=0.001) and 18.2% (RRR 29.2%, p=0.001) by CorP and SokP, in diabetic patients, respectively. In non-diabetic patients, only the CorP criterion showed a significant decrease (RRR 18.9%, p=0.01). No significant changes were observed by other criteria.The RRR of ECG-LVH with treatment was significantly higher in diabetics according to CorP and SokP criteria. Conclusions. The prevalence of ECG-LVH detected by CorP was higher in diabetics. Diabetics achieved higher reductions in ECG-LVH prevalence than non-diabetics with a candesartan-based regimen.
Aurora kinase A is a target of Wnt/β-catenin involved in multiple myeloma disease progression
Authors: Dutta-Simmons Jui , Zhang Yunyu , Gorgun Gullu , Gatt Moshe , Mani Mala , Hideshima Teru , Takada Kohichi , Carlson Nicole E. , Carrasco Daniel E. , Tai Yu-Tzu , Raje Noopur , Letai Anthony G. , Anderson Kenneth C. , Carrasco Daniel R. 
Published: August 2009

AbstractMultiple myeloma (MM) is a cancer of plasma cells with complex molecular characteristics that evolves from monoclonal gammopathy of undetermined significance, a highly prevalent premalignant condition. MM is the second most frequent hematologic cancer in the United States, and it remains incurable, thereby highlighting the need for new therapeutic approaches, particularly those targeting common molecular pathways involved in disease progression and maintenance, shared across different MM subtypes. Here we report that Wnt/β-catenin is one such pathway. We document the involvement of β-catenin in cell-cycle regulation, proliferation, and invasion contributing to enhanced proliferative and metastatic properties of MM. The pleiotropic effects of β-catenin in MM correlate with its transcriptional function, and we demonstrate regulation of a novel target gene, Aurora kinase A, implicating β-catenin in G2/M regulation. β-catenin and Aurora kinase A are present in most MM but not in normal plasma cells and are expressed in a pattern that parallels progression from monoclonal gammopathy of undetermined significance to MM. Our data provide evidence for a novel functional link between β-catenin and Aurora kinase A, underscoring a critical role of these pathways in MM disease progression.
Pneumoviruses infect eosinophils and elicit MyD88-dependent release of chemoattractant cytokines and interleukin-6
Authors: Dyer Kimberly D. , Percopo Caroline M. , Fischer Elizabeth R. , Gabryszewski Stanislaw J. , Rosenberg Helene F. 
Published: August 2009

AbstractEosinophils are recruited to the lung in response to infection with pneumovirus pathogens and have been associated with both the pathophysiologic sequelae of infection and, more recently, with accelerated virus clearance. Here, we demonstrate that the pneumovirus pathogens, respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM), can infect human and mouse eosinophils, respectively, and that virus infection of eosinophils elicits the release of disease-related proinflammatory mediators from eosinophils. RSV replication in human eosinophils results in the release of infectious virions and in the release of the proinflammatory mediator, interleukin-6 (IL-6). PVM replication in cultured bone marrow eosinophils (bmEos) likewise results in release of infectious virions and the proinflammatory mediators IL-6, IP-10, CCL2, and CCL3. In contrast to the findings reported in lung tissue of RSV-challenged mice, PVM replication is accelerated in MyD88 gene-deleted bmEos, whereas release of cytokines is diminished. Interestingly, exogenous IL-6 suppresses virus replication in MyD88 gene-deleted bmEos, suggesting a role for a MyD88-dependent cytokine-mediated feedback circuit in modulating this response. Taken together, our findings suggest that eosinophils are targets of virus infection and may have varied and complex contributions to the pathogenesis and resolution of pneumovirus disease.
Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced leukemia model
Authors: Hu Xiaoxia , Shen Hongmei , Tian Chen , Yu Hui , Zheng Guoguang , XuFeng Richard , Ju Zhenyu , Xu Jing , Wang Jianmin , Cheng Tao 
Published: August 2009

Abstract
The predominant outgrowth of malignant cells over their normal counterparts in a given tissue is a shared feature for all types of cancer. However, the impact of a cancer environment on normal tissue stem and progenitor cells has not been thoroughly investigated. We began to address this important issue by studying the kinetics and functions of hematopoietic stem and progenitor cells in mice with Notch1-induced leukemia. Although hematopoiesis was progressively suppressed during leukemia development, the leukemic environment imposed distinct effects on hematopoietic stem and progenitor cells, thereby resulting in different outcomes. The normal hematopoietic stem cells in leukemic mice were kept in a more quiescent state but remained highly functional on transplantation to nonleukemic recipients. In contrast, the normal hematopoietic progenitor cells in leukemic mice demonstrated accelerated proliferation and exhaustion. Subsequent analyses on multiple cell-cycle parameters and known regulators (such as p21, p27, and p18) further support this paradigm. Therefore, our current study provides definitive evidence and plausible underlying mechanisms for hematopoietic disruption but reversible inhibition of normal hematopoietic stem cells in a leukemic environment. It may also have important implications for cancer prevention and treatment in general.
MMP/TIMP expression profiles in distinct lung disease models: implications for possible future therapies
Authors: Wong Sissie , Belvisi Maria G , Birrell Mark A 
Published: August 2009

Abstract

Background
There is currently a vast amount of evidence in the literature suggesting that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the pathogenesis of inflammatory airways diseases, such as asthma and COPD. Despite this, the majority of reports only focus on single MMPs, often only in one model system. This study aimed to investigate the profile of an extensive range of MMP/TIMP levels in three different pre-clinical models of airways disease. These models each have a different and very distinct inflammatory profile, each exhibiting inflammatory characteristics that are similar to that observed in asthma or COPD. Since these models have their own characteristic pathophysiological phenotype, one would speculate that the MMP/TIMP expression profile would also be different.

Methods
With the use of designed and purchased MMP/TIMP assays, investigation of rat MMP-2, 3, 7|14 and TIMP-1|4 mRNA expression was undertaken by Real Time PCR. The three rodent models of airways disease investigated were the endotoxin model, elastase model, and the antigen model.

Results
Intriguingly, we demonstrated that despite the distinct inflammatory profile observed by each model, the MMP/TIMP expression profile is similar between the models, in that the same MMPs/TIMPs were observed to be generally increased or decreased in all three models. It could therefore be speculated that in a particular disease, it may be a complex network of MMPs, rather than an individual MMP, together with inflammatory cytokines and other mediators, that results in the distinct phenotype of inflammatory diseases, such as asthma and COPD.

Conclusion
We believe our data may provide key information necessary to understand the role of various MMPs/TIMPs in different inflammatory airway diseases, and aid the development of more selective therapeutics without the side effect profile of current broad-spectrum MMP inhibitors.
MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening
Authors: Sauton Nicolas , Lagorce David , Villoutreix Bruno O , Miteva Maria A 
Published: August 2009

Abstract

Background
The number of protein targets with a known or predicted tri-dimensional structure and of drug-like chemical compounds is growing rapidly and so is the need for new therapeutic compounds or chemical probes. Performing flexible structure-based virtual screening computations on thousands of targets with millions of molecules is intractable to most laboratories nor indeed desirable. Since shape complementarity is of primary importance for most protein-ligand interactions, we have developed a tool/protocol based on rigid-body docking to select compounds that fit well into binding sites.

Results
Here we present an efficient multiple conformation rigid-body docking approach, MS-DOCK, which is based on the program DOCK. This approach can be used as the first step of a multi-stage docking/scoring protocol. First, we developed and validated the Multiconf-DOCK tool that generates several conformers per input ligand. Then, each generated conformer (bioactives and 37970 decoys) was docked rigidly using DOCK6 with our optimized protocol into seven different receptor-binding sites. MS-DOCK was able to significantly reduce the size of the initial input library for all seven targets, thereby facilitating subsequent more CPU demanding flexible docking procedures.

Conclusion
MS-DOCK can be easily used for the generation of multi-conformer libraries and for shape-based filtering within a multi-step structure-based screening protocol in order to shorten computation times.
easyExon – A Java-based GUI tool for processing and visualization of Affymetrix exon array data
Authors: Chang Ting-Yu , Li Yin-Yi , Jen Chih-Hung , Yang Tsun-Po , Lin Chi-Hung , Hsu Ming-Ta , Wang Hsei-Wei 
Published: August 2009

Abstract

Background
Alternative RNA splicing greatly increases proteome diversity and thereby contribute to species- or tissue-specific functions. The possibility to study alternative splicing (AS) events on a genomic scale using splicing-sensitive microarrays, including the Affymetrix GeneChip Exon 1.0 ST microarray (exon array), has appeared very recently. However, the application of this new technology is hindered by the lack of free and user-friendly software devoted to these novel platforms.

Results
In this study we present a Java-based freeware, easyExon http://microarray.ym.edu.tw/easyexon, to process, filtrate and visualize exon array data with an analysis pipeline. This tool implements the most commonly used probeset summarization methods as well as AS-orientated filtration algorithms, e.g. MIDAS and PAC, for the detection of alternative splicing events. We include a biological filtration function according to GO terms, and provide a module to visualize and interpret the selected exons and transcripts. Furthermore, easyExon can integrate with other related programs, such as Integrate Genome Browser (IGB) and Affymetrix Power Tools (APT), to make the whole analysis more comprehensive. We applied easyExon on a public accessible colon cancer dataset as an example to illustrate the analysis pipeline of this tool.

Conclusion
EasyExon can efficiently process and analyze the Affymetrix exon array data. The simplicity, flexibility and brevity of easyExon make it a valuable tool for AS event identification in genomic research.
Extended Newick: it is time for a standard representation of phylogenetic networks
Authors: Cardona Gabriel , Rosselló Francesc , Valiente Gabriel 
Published: August 2009

Abstract

Background
Phylogenetic trees resulting from molecular phylogenetic analysis are available in Newick format from specialized databases but when it comes to phylogenetic networks, which provide an explicit representation of reticulate evolutionary events such as recombination, hybridization or lateral gene transfer, the lack of a standard format for their representation has hindered the publication of explicit phylogenetic networks in the specialized literature and their incorporation in specialized databases. Two different proposals to represent phylogenetic networks exist: as a single Newick string (where each hybrid node is splitted once for each parent) or as a set of Newick strings (one for each hybrid node plus another one for the phylogenetic network).

Results
The standard we advocate as extended Newick format describes a whole phylogenetic network with k hybrid nodes as a single Newick string with k repeated nodes, and this representation is unique once the phylogenetic network is drawn or the ordering among children nodes is fixed. The extended Newick format facilitates phylogenetic data sharing and exchange, and also allows for the practical use of phylogenetic networks in computer programs and scripts. This standard has been recently agreed upon by a number of computational biologists, is already supported by several phylogenetic tools, and avoids the different drawbacks of using an a priori unknown number of Newick strings without any additional mark-up to represent a phylogenetic network.

Conclusion
The adoption of the extended Newick format as a standard for the representation of phylogenetic network is an important step towards the publication of explicit phylogenetic networks in peer-reviewed journals and their incorporation in a future database of published phylogenetic networks.
Developmental genetics of the C. eleganspharyngeal neurons NSML and NSMR
Authors: Axäng Claes , Rauthan Manish , Hall David H , Pilon Marc 
Published: August 2009

Abstract

Background
We are interested in understanding how the twenty neurons of the C. elegans pharynx develop in an intricate yet reproducible way within the narrow confines of the embryonic pharyngeal primordium. To complement an earlier study of the pharyngeal M2 motorneurons, we have now examined the effect of almost forty mutations on the morphology of a bilateral pair of pharyngeal neurosecretory-motor neurons, the NSMs.

Results
A careful description of the NSM morphology led to the discovery of a third, hitherto unreported process originating from the NSM cell body and that is likely to play a proprioceptive function. We found that the three NSM processes are differently sensitive to mutations. The major dorsal branch was most sensitive to mutations that affect growth cone guidance and function (e.g. unc-6, unc-34, unc-73), while the major sub-ventral branch was more sensitive to mutations that affect components of the extracellular matrix (e.g. sdn-1). Of the tested mutations, only unc-101, which affects an adaptin, caused the loss of the newly described thin minor process. The major processes developed synaptic branches post-embryonically, and these exhibited activity-dependent plasticity.

Conclusion
By studying the effects of nearly forty different mutations we have learned that the different NSM processes require different genes for their proper guidance and use both growth cone dependent and growth cone independent mechanisms for establishing their proper trajectories. The two major NSM processes develop in a growth cone dependent manner, although the sub-ventral process relies more on substrate adhesion. The minor process also uses growth cones but uniquely develops using a mechanism that depends on the clathrin adaptor molecule UNC-101. Together with the guidance of the M2 neuron, this is the second case of a pharyngeal neuron establishing one of its processes using an unexpected mechanism.
Genetic evidence from Indian red jungle fowl corroborates multiple domestication of modern day chicken
Authors: Kanginakudru Sriramana , Metta Muralidhar , Jakati RD , Nagaraju J 
Published: August 2009

Abstract

Background
Domestication of chicken is believed to have occurred in Southeast Asia, especially in Indus valley. However, non-inclusion of Indian red jungle fowl (RJF), Gallus gallus murghi in previous studies has left a big gap in understanding the relationship of this major group of birds. In the present study, we addressed this issue by analyzing 76 Indian birds that included 56 G. g. murghi (RJF), 16 G. g. domesticus (domestic chicken) and 4 G. sonneratii (Grey JF) using both microsatellite markers and mitochondrial D-loop sequences. We also compared the D-loop sequences of Indian birds with those of 779 birds obtained from GenBank.

Results
Microsatellite marker analyses of Indian birds indicated an average FST of 0.126 within G. g. murghi, and 0.154 within G. g. domesticus while it was more than 0.2 between the two groups. The microsatellite-based phylogenetic trees showed a clear separation of G. g. domesticus from G. g. murghi, and G. sonneratii. Mitochondrial DNA based mismatch distribution analyses showed a lower Harpending's raggedness index in both G. g. murghi (0.001515) and in Indian G. g. domesticus (0.0149) birds indicating population expansion. When meta analysis of global populations of 855 birds was carried out using median joining haplotype network, 43 Indian birds of G. g. domesticus (19 haplotypes) were distributed throughout the network sharing haplotypes with the RJFs of different origins.

Conclusion
Our results suggest that the domestication of chicken has occurred independently in different locations of Asia including India. We found evidence for domestication of Indian birds from G. g. spadiceus and G. g. gallus as well as from G. g. murghi, corroborating multiple domestication of Indian and other domestic chicken. In contrast to the commonly held view that RJF and domestic birds hybridize in nature, the present study shows that G. g. murghi is relatively pure. Further, the study also suggested that the chicken populations have undergone population expansion, especially in the Indus valley.
Mitochondrial genomes reveal an explosive radiation of extinct and extant bears near the Miocene-Pliocene boundary
Authors: Krause Johannes , Unger Tina , Noçon Aline , Malaspinas Anna-Sapfo , Kolokotronis Sergios-Orestis , Stiller Mathias , Soibelzon Leopoldo , Spriggs Helen , Dear Paul H , Briggs Adrian W , Bray Sarah CE , O'Brien Stephen J , Rabeder Gernot , Matheus Paul , Cooper Alan , Slatkin Montgomery , Pääbo Svante , Hofreiter Michael 
Published: August 2009

Abstract

Background
Despite being one of the most studied families within the Carnivora, the phylogenetic relationships among the members of the bear family (Ursidae) have long remained unclear. Widely divergent topologies have been suggested based on various data sets and methods.

Results
We present a fully resolved phylogeny for ursids based on ten complete mitochondrial genome sequences from all eight living and two recently extinct bear species, the European cave bear (Ursus spelaeus) and the American giant short-faced bear (Arctodus simus). The mitogenomic data yield a well-resolved topology for ursids, with the sloth bear at the basal position within the genus Ursus. The sun bear is the sister taxon to both the American and Asian black bears, and this clade is the sister clade of cave bear, brown bear and polar bear confirming a recent study on bear mitochondrial genomes.

Conclusion
Sequences from extinct bears represent the third and fourth Pleistocene species for which complete mitochondrial genomes have been sequenced. Moreover, the cave bear specimen demonstrates that mitogenomic studies can be applied to Pleistocene fossils that have not been preserved in permafrost, and therefore have a broad application within ancient DNA research. Molecular dating of the mtDNA divergence times suggests a rapid radiation of bears in both the Old and New Worlds around 5 million years ago, at the Miocene-Pliocene boundary. This coincides with major global changes, such as the Messinian crisis and the first opening of the Bering Strait, and suggests a global influence of such events on species radiations.
Meiosis genes in Daphnia pulexand the role of parthenogenesis in genome evolution
Authors: Schurko Andrew M , Logsdon John M , Eads Brian D 
Published: August 2009

AbstractBackgroundThousands of parthenogenetic animal species have been described and cytogenetic manifestations of this reproductive mode are well known. However, little is understood about the molecular determinants of parthenogenesis. TheDaphnia pulexgenome must contain the molecular machinery for different reproductive modes: sexual (both male and female meiosis) and parthenogenetic (which is either cyclical or obligate). This feature makesD. pulexan ideal model to investigate the genetic basis of parthenogenesis and its consequences for gene and genome evolution. Here we describe the inventory of meiotic genes and their expression patterns during meiotic and parthenogenetic reproduction to help address whether parthenogenesis uses existing meiotic and mitotic machinery, or whether novel processes may be involved.ResultsWe report an inventory of 130 homologs representing over 40 genes encoding proteins with diverse roles in meiotic processes in the genome ofD. pulex. Many genes involved in cell cycle regulation and sister chromatid cohesion are characterized by expansions in copy number. In contrast, most genes involved in DNA replication and homologous recombination are present as single copies. Notably,RECQ2(which suppresses homologous recombination) is present in multiple copies whileDMC1is the only gene in our inventory that is absent in theDaphniagenome. Expression patterns for 44 gene copies were similar during meiosisversusparthenogenesis, although several genes displayed marked differences in expression level in germline and somatic tissues.ConclusionWe propose that expansions in meiotic gene families inD. pulexmay be associated with parthenogenesis. Taking into account our findings, we provide a mechanistic model of parthenogenesis, highlighting steps that must differ from meiosis including sister chromatid cohesion and kinetochore attachment.