bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF increases the proliferative capacity and eNOS/NO levels of endothelial progenitor cells through the calcineurin/NFAT signalling pathway
Authors: Yang Long , Guan Hongshan , He Jionghong , Zeng Liqun , Yuan Zhengqiang , Xu Min , Zhang Wenhui , Wu Xiaole , Guan Jing 
Published: September 2011

AbstractWe have investigated whether VEGF (vascular endothelial growth factor) regulates the proliferative capacity and eNOS (endothelial nitric oxide synthase)/NO (nitric oxide) pathway of EPCs (endothelial progenitor cells) by activating CaN (calcineurin)/NFAT (nuclear factor of activated T‐cells) signalling. EPCs were obtained from cultured mononuclear cells isolated from the peripheral blood of healthy adults. Treatment with VEGF (50 ng/ml) potently promoted CaN enzymatic activity, activation of NFAT2, cell proliferation, eNOS protein expression and NO production. Pretreatment with cyclosporin A (10 μg/ml), a pharmacological inhibitor of CaN or 11R‐VIVIT, a special inhibitor of NFAT, completely abrogated the aforementioned effects of VEGF treatment and increased apoptosis. The results indicate that VEGF treatment promotes the proliferative capacity of human EPCs by activating CaN/NFAT signalling leading to increased eNOS protein expression and NO production.
AP‐1 and NF‐κB transcriptionally regulate interleukin‐8 in EA.Hy926 cells under shear stress
Authors: Zhang Yi , Lai Yi , Chen Huai‐Qing , Liu Ying‐Feng 
Published: September 2011

AbstractCardiovascular and cerebrovascular diseases remain the leading cause of death in the world. AS (atherosclerosis) is not only an inflammatory disease in which chemokines play the main role but also a disorder that is related to blood SS (shear stress). We have investigated the action of IL‐8 (interleukin‐8) mRNA expression in human endothelial cells line‐EA.Hy926 under SS at different intensities and duration. Expression increases with time in an intensity dependent manner. With regard to the transcriptional mechanism involved, transient transfection of the human wild‐type IL‐8 promoter (–162/+44)/luciferase reporter plasmid, or site mutation of one of the binding sites [AP‐1 (activator protein 1) or NF‐κB (nuclear factor κB)] in the IL‐8 promoter region was investigated. Both AP‐1 and NF‐κB were essential for SS‐activated transcription, with the cells responding to NF‐κB activation within minutes. After stimulated at low SS (4.20 dyne/cm2) for 30 min, the P65 subunit was translocated from the cytoplasm to nucleus for at least 60 min, while the cytoplasmic level of IκB (inhibitory κB) gradually decreased. The combined activation of NF‐κB and AP‐1 are the upstream regulators of low SS‐induced IL‐8 production in EA.Hy926 cells, which subsequently trigger an inflammatory reaction in endothelium.
Direct measurements of DNA-mediated colloidal interactions and their quantitative modeling
Authors: Rogers W. Benjamin , Crocker John C. 
Published: September 2011

DNA bridging can be used to induce specific attractions between small particles, providing a highly versatile approach to creating unique particle-based materials having a variety of periodic structures. Surprisingly, given the fact that the thermodynamics of DNA strands in solution are completely understood, existing models for DNA-induced particle interactions are typically in error by more than an order of magnitude in strength and a factor of two in their temperature dependence. This discrepancy has stymied efforts to design the complex temperature, sequence and time-dependent interactions needed for the most interesting applications, such as materials having highly complex or multicomponent microstructures or the ability to reconfigure or self-replicate. Here we report high-spatial resolution measurements of DNA-induced interactions between pairs of polystyrene microspheres at binding strengths comparable to those used in self-assembly experiments, up to 6
k
B
T
. We also describe a conceptually straightforward and numerically tractable model that quantitatively captures the separation dependence and temperature-dependent strength of these DNA-induced interactions, without empirical corrections. This model was equally successful when describing the more complex and practically relevant case of grafted DNA brushes with self-interactions that compete with interparticle bridge formation. Together, our findings motivate a nanomaterial design approach where unique functional structures can be found computationally and then reliably realized in experiment.
Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis
Authors: Sartoretto Juliano L. , Kalwa Hermann , Pluth Michael D. , Lippard Stephen J. , Michel Thomas 
Published: September 2011

Nitric oxide (NO) and hydrogen peroxide (H
2
O
2
) are synthesized within cardiac myocytes and play key roles in modulating cardiovascular signaling. Cardiac myocytes contain both the endothelial (eNOS) and neuronal (nNOS) NO synthases, but the differential roles of these NOS isoforms and the interplay of reactive oxygen species and reactive nitrogen species in cardiac signaling pathways are poorly understood. Using a recently developed NO chemical sensor [Cu
2
(FL2E)] to study adult cardiac myocytes from wild-type, eNOS
null
, and nNOS
null
mice, we discovered that physiological concentrations of H
2
O
2
activate eNOS but not nNOS. H
2
O
2
-stimulated eNOS activation depends on phosphorylation of both the AMP-activated protein kinase and kinase Akt, and leads to the robust phosphorylation of eNOS. Cardiac myocytes isolated from mice infected with lentivirus expressing the recently developed H
2
O
2
biosensor HyPer2 show marked H
2
O
2
synthesis when stimulated by angiotensin II, but not following β-adrenergic receptor activation. We discovered that the angiotensin-II-promoted increase in cardiac myocyte contractility is dependent on H
2
O
2
, whereas β-adrenergic contractile responses occur independently of H
2
O
2
signaling. These studies establish differential roles for H
2
O
2
in control of cardiac contractility and receptor-dependent NOS activation in the heart, and they identify new points for modulation of NO signaling responses by oxidant stress.
Correlated evolution of transcription factors and their binding sites
Authors: Yang Shu , Yalamanchili Hari Krishna , Li Xinran , Yao Kwok-Ming , Sham Pak Chung , Zhang Michael Q. , Wang Junwen 
Published: September 2011

Abstract
Motivation:The interaction between transcription factor (TF) and transcription factor binding site (TFBS) is essential for gene regulation. Mutation in either the TF or the TFBS may weaken their interaction and thus result in abnormalities. To maintain such vital interaction, a mutation in one of the interacting partners might be compensated by a corresponding mutation in its binding partner during the course of evolution. Confirming this co-evolutionary relationship will guide us in designing protein sequences to target a specific DNA sequence or in predicting TFBS for poorly studied proteins, or even correcting and rescuing disease mutations in clinical applications.
Results: Based on six, publicly available, experimentally validated TF–TFBS binding datasets for the basic Helix–Loop–Helix (bHLH) family, Homeo family, High-Mobility Group (HMG) family and Transient Receptor Potential channels (TRP) family, we showed that the evolutions of the TFs and their TFBSs are significantly correlated across eukaryotes. We further developed a mutual information-based method to identify co-evolved protein residues and DNA bases. This research sheds light on the dynamic relationship between TF and TFBS during their evolution. The same principle and strategy can be applied to co-evolutionary studies on protein–DNA interactions in other protein families.
Availability: All the datasets, scripts and other related files have been made freely available at: http://jjwanglab.org/co-evo.
Contact: junwen@uw.edu
Supplementary Information: Supplementary data are available at Bioinformatics online.
First Report of Damping-Off of Rhodiola sachalinensis Caused by Rhizoctonia solani AG-4 HG-II in China
Authors: Bai Q. , Xie Y. , Wang X. , Li Y. , Gao J. , Li J. , Li Z. , Li G. , Li H. 
Published: September 2011

Rhodiola sachalinensis A. Bor (family Crassulaceae), a perennial herbaceous plant, is distributed mainly in the mountainous areas of China, Japan, Korea, and Russia. It is widely used as a traditional Chinese medicine with adaptogenic properties, cardiopulmonary protective effects, and central nervous system activities (3). Currently, it is extensively cultivated in northeastern China. In August 2010, widespread (>60% of plants were symptomatic) damping-off was observed in a seedling field in Linjiang, China. Leaves and stems near the ground were affected first, with dark lesions forming on the stem and the lowest leaves exhibiting wilt. The wilt spread rapidly over the entire plant with leaves becoming grayish brown and water soaked and then turned black and died. Root rot, defoliation, and damping-off were also observed. Six isolates with morphological characteristics of Rhizoctonia solani Kühn were isolated from symptomatic stems when plated on potato dextrose agar (PDA). Mycelium was branched at right angles with a septum near the branch and a slight constriction at the branch base. Fungal colonies were initially white, turned brown with age, and produced irregularly shaped, brown sclerotia after 8 days on PDA. Hyphal cells removed from cultures grown at 25°C on 2% water agar were determined to be multinucleate when stained with 1% safranin O and 3% KOH solution (1) and examined at ×400 magnification. The internal transcribed spacer (ITS) region of the nuclear rDNA was amplified by using the primers ITS4/ITS5 (2). The ITS sequences (715 bp) were identical in these six isolates (GenBank Accession No. FR878087) and had 100% sequence identity with R. solani AG-4 HG-II (GenBank Accession No. HQ629873) along with numerous other accessions from this AG subgroup. Pathogenicity tests were performed on healthy, potted seedlings of R. sachalinensis. Twenty plants were inoculated near the base of the stem with a 0.6-cm-diameter mycelial plug from 3-day-old PDA cultures for each isolate. Twenty plants inoculated with only PDA plugs served as controls. The plants were covered with plastic bags and kept in a greenhouse at 20 to 25°C for 72 h. All inoculated plants showed characteristic symptoms as previously observed in the seedling field 13 days after inoculation, while control plants remained healthy. R. solani AG-4 HG-II was reisolated from symptomatic tissues on inoculated plants. To our knowledge, this is the first report of R. solani AG-4 HG-II causing damping-off on R. sachalinensis in China. References: (1) R. J. Bandoni. Mycologia 71:873, 1979. (2) D. E. L. Cooke et al. Mycol. Res. 101:667, 1997. (3) T. F. Yan et al. Conserv. Genet. 4:213, 2003.
Multiple Lines of Evidence Localize Signaling, Morphology, and Lipid Biosynthesis Machinery to the Mitochondrial Outer Membrane of Arabidopsis
Authors: Duncan Owen , Taylor Nicolas L. , Carrie Chris , Eubel Holger , Kubiszewski-Jakubiak Szymon , Zhang Botao , Narsai Reena , Millar A. Harvey , Whelan James 
Published: September 2011

Abstract
The composition of the mitochondrial outer membrane is notoriously difficult to deduce by orthology to other organisms, and biochemical enrichments are inevitably contaminated with the closely associated inner mitochondrial membrane and endoplasmic reticulum. In order to identify novel proteins of the outer mitochondrial membrane in Arabidopsis (Arabidopsis thaliana), we integrated a quantitative mass spectrometry analysis of highly enriched and prefractionated samples with a number of confirmatory biochemical and cell biology approaches. This approach identified 42 proteins, 27 of which were novel, more than doubling the number of confirmed outer membrane proteins in plant mitochondria and suggesting novel functions for the plant outer mitochondrial membrane. The novel components identified included proteins that affected mitochondrial morphology and/or segregation, a protein that suggests the presence of bacterial type lipid A in the outer membrane, highly stress-inducible proteins, as well as proteins necessary for embryo development and several of unknown function. Additionally, proteins previously inferred via orthology to be present in other compartments, such as an NADH:cytochrome B5 reductase required for hydroxyl fatty acid accumulation in developing seeds, were shown to be located in the outer membrane. These results also revealed novel proteins, which may have evolved to fulfill plant-specific requirements of the mitochondrial outer membrane, and provide a basis for the future functional characterization of these proteins in the context of mitochondrial intracellular interaction.
Functional Network Construction in Arabidopsis Using Rule-Based Machine Learning on Large-Scale Data Sets
Authors: Bassel George W. , Glaab Enrico , Marquez Julietta , Holdsworth Michael J. , Bacardit Jaume 
Published: September 2011

Abstract
The meta-analysis of large-scale postgenomics data sets within public databases promises to provide important novel biological knowledge. Statistical approaches including correlation analyses in coexpression studies of gene expression have emerged as tools to elucidate gene function using these data sets. Here, we present a powerful and novel alternative methodology to computationally identify functional relationships between genes from microarray data sets using rule-based machine learning. This approach, termed “coprediction,” is based on the collective ability of groups of genes co-occurring within rules to accurately predict the developmental outcome of a biological system. We demonstrate the utility of coprediction as a powerful analytical tool using publicly available microarray data generated exclusively from Arabidopsis thaliana seeds to compute a functional gene interaction network, termed Seed Co-Prediction Network (SCoPNet). SCoPNet predicts functional associations between genes acting in the same developmental and signal transduction pathways irrespective of the similarity in their respective gene expression patterns. Using SCoPNet, we identified four novel regulators of seed germination (ALTERED SEED GERMINATION5, 6, 7, and 8), and predicted interactions at the level of transcript abundance between these novel and previously described factors influencing Arabidopsis seed germination. An online Web tool to query SCoPNet has been developed as a community resource to dissect seed biology and is available at http://www.vseed.nottingham.ac.uk/.
Parallel use of by‐passing agents in haemophilia with inhibitors: a critical review
Authors: Ingerslev Jørgen , Sørensen Benny 
Published: September 2011

SummaryIn the absence of new outbreaks of transfusion‐related infections, the occurrence of neutralizing antibodies currently remains the most prominent complication in haemophilia. Coagulation factor products that may circumvent the inadequate activation of factor X in classical haemophilia, often referred to as bypassing agents, have demonstrated a high degree of efficacy. A smaller number of patients have been described in whom either bypassing agent, or both, demonstrate diminished efficacy. In those cases, the use of both bypassing agents in parallel was attempted, either using simultaneous (combined) or alternating (sequential) infusion of the two drugs, reportedly with successful haemostasis. We speculated whether such treatment might cause thromboembolism. A thorough literature search disclosed 17 reports regarding the parallel use of bypassing agents in the same bleeding episode in 49 patients; reporting nine patients with acquired haemophilia and forty patients with congenital haemophilia with inhibitors. Notable incidences of thromboembolic manifestations were observed: in nine patients with acquired haemophilia, five and in 40 patients with congenital haemophilia five suffered from significant thrombotic complications, and overall four cases were fatal. Although efficacy of parallel treatment was reported excellent in most cases, thromboembolism is rare in haemophilia and parallel treatment with activated prothrombin complex concentrate and activated recombinant human factor VII appears to increase the risk of thrombosis in these patients.
An update on mosquito cell expressed dengue virus receptor proteins
Authors: Smith D. R. 
Published: September 2011

AbstractDengue is the most important mosquito transmitted viral disease of humans worldwide. Despite intensive study over several decades, many of the fine details of the dengue virus (DENV) replication cycle remain unknown, although generally more is known about the phase of the replication cycle in mammalian cells as compared to the phase in mosquito cells. This results from a combination of less research emphasis on the mosquito stage, as well as fewer tools such as specific antibodies against mosquito proteins and insect informatics databases. The binding of a virus to a host cell is a first and critical stage in the infectious process and the mechanism and identity of cellular proteins involved in this process remains largely unknown. This short review aims to provide an update on our current understanding of the proteins expressed by mosquito cells that mediate DENV binding as a prerequisite to DENV entry and replication.
West to east dispersal and subsequent rapid diversification of the mega‐diverse genusBegonia(Begoniaceae) in the Malesian archipelago
Authors: Thomas D. C. , Hughes M. , Phutthai T. , Ardi W. H. , Rajbhandary S. , Rubite R. , Twyford A. D. , Richardson J. E. 
Published: September 2011

AbstractAim The complex palaeogeography of the Malesian archipelago, characterized by the evolution of an ever‐changing mosaic of terrestrial and marine areas throughout the Cenozoic, provides the geographic backdrop for the remarkable diversification of MalesianBegonia(> 450 species). This study aimed to investigate the origin of MalesianBegonia, the directionality of dispersal events within the Malesian archipelago and the impact of ancient water gaps on colonization patterns, and to identify drivers of diversification.Location Asia, Southeast Asia, Malesia.Methods Plastid DNA sequence data of representatives of all families of the Cucurbitales and Fagales (matK,rbcL,trnL intron,trnL–F spacer, 4076 aligned positions, 92 taxa) and a sample of all major AsianBegoniasections (ndhA intron,ndhF–rpl32 spacer,rpl32–trnL spacer, 4059 aligned positions, 112 taxa) were analysed under an uncorrelated‐rates relaxed molecular clock model to estimate the age of theBegoniacrown group divergence and divergence ages within AsianBegonia. Ancestral areas were reconstructed using a likelihood approach implementing a dispersal–extinction–cladogenesis model, and with a Bayesian approach to dispersal–vicariance analysis.Results The results indicated an initial diversification of AsianBegoniain continental Asia in the Miocene, and subsequent colonization of Malesia by multiple lineages. There was support for at least six independent dispersal events from continental Asia and western Malesia to Wallacea dating from the late Miocene to the Pleistocene.BegoniasectionPetermannia(> 270 species) originated in Western Malesia, and subsequently dispersed to Wallacea, New Guinea and the Philippines. Lineages within this section diversified rapidly since the Pliocene, coinciding with rapid orogenesis on Sulawesi and New Guinea.Main conclusions The predominant trend ofBegoniadispersals between continental Asia and Malesia, and also within Malesia, has been from west to east. The water bodies separating the Sunda Shelf region from Wallacea have been porous barriers to dispersal inBegoniafollowing the emergence of substantial land in eastern Malesia from the late Miocene onwards. We hypothesize two major drivers of the diversification of MalesianBegonia: (1) the formation of topographical heterogeneity and the promotion of microallopatry by orogenesis in the Pliocene and Pleistocene; and (2) cyclic vicariance by frequent habitat fragmentations and amalgamations due to climate and sea‐level fluctuations during the Pleistocene.
Range shift promotes the formation of stable range edges
Authors: Phillips Ben L. 
Published: September 2011

AbstractAim I investigate the counter‐intuitive possibility that range shift promotes the formation of stable range edges. This might be expected because: (1) range‐shifting populations typically evolve increased dispersal on the expanding range edge; (2) increased dispersal steepens the relative slope of environmental gradients (gradients appear steeper to a more dispersive population); and (3) environmental gradients that are steep relative to dispersal encourage the formation of stable range edges (when gradients appear steep, adaptation on the range edge is swamped by maladapted genes).Methods I test the idea that populations take longer to evolve across an environmental gradient when those populations have already undergone a period of spread. I do this using an individual‐based coupled map lattice simulation, in which individuals carry heritable traits for dispersal probability and environment‐specific fitness.Results Numerous simulations across parameter space confirm that a period of range shift almost always results in a longer time to evolve through an environmental gradient. This occurs because of both the mechanism described above and the erosion of adaptive variation resulting from the serial foundering that occurs during range advance.Main conclusions This result suggests that species may often shift their range due to intrinsic changes in the population rather than extrinsic changes in the environment. The result also suggests a new mechanism regulating the speed of invasion, and sounds a cautionary note for climate change impacts: the longer a species tracks climate change, the less able it may be to track that change into the future.
Diversification in temporally heterogeneous environments: effect of the grain in experimental bacterial populations
Authors: VENAIL P. A. , KALTZ O. , OLIVIERI I. , POMMIER T. , MOUQUET N. 
Published: September 2011

AbstractAlthough theory established the necessary conditions for diversification in temporally heterogeneous environments, empirical evidence remains controversial. One possible explanation is the difficulty of designing experiments including the relevant range of temporal grains and the appropriate environmental trade‐offs. Here, we experimentally explore the impact of the grain on the diversification of the bacterium Pseudomonas fluorescens SBW25 in a temporally fluctuating environment by including 20 different pairs of environments and four temporal grains. In general, higher levels of diversity were observed at intermediate temporal grains. This resulted in part from the enhanced capacity of disruptive selection to generate negative genotypic correlations in performance at intermediate grains. However, the evolution of reciprocal specialization was an uncommon outcome. Although the temporal heterogeneity is in theory less powerful than the spatial heterogeneity to generate and maintain the diversity, our results show that diversification under temporal heterogeneity is possible provided appropriate environmental grains.