bluuebunny/crossref_metadata_2025 huggingface dataset:
SABIO-RK: Curated Kinetic Data of Biochemical Reactions
Authors: Wittig Ulrike
Published: April 2009

SABIO-RK ("http://sabio.villa-bosch.de/SABIORK/":http://sabio.villa-bosch.de/SABIORK/) is a curated, web-accessible database for modellers and wet-lab scientists to get comprehensive information about biochemical reactions and their kinetic properties. It integrates data from different origin in order to facilitate the access to reaction kinetics data and corresponding information. Since most of the kinetic data is exclusively found in the literature SABIO-RK offers data manually extracted from the literature and related information obtained from other publicly available biological databases. For instance, the kinetic data are related to reactions, organisms, tissues and cellular locations. The type of the kinetic mechanism and corresponding rate equations are presented together with their parameters and experimental conditions. Additionally, SABIO-RK also includes data about the detailed mechanism for some of the reactions based on literature information. This not only includes the graphical representation of the mechanism but also the single reaction steps with their corresponding kinetic data.The data in SABIO-RK are extracted manually from literature and the selection of articles is not restricted to any biological source (e.g. organisms or organism classifications). All the data are curated and annotated by biological experts using a web-based input interface. To support the curation process and data integration we have implemented different constraints in the input interface and offer several controlled vocabularies as lists of values, as well as additional semi-automatic consistency checks to avoid errors and inconsistencies in the database. Controlled vocabularies and annotations to external resources and ontologies were used to identify and relate the data to their biological context. All these efforts to unify and integrate the data augment the content and the semantics of the SABIO-RK database entries to enable a comprehensive understanding and comparison of the data for the user.SABIO-RK can be accessed via a web-based user interface or via web-services. The user interface allows the definition of complex queries by specifying reactions and reaction participants, kinetic parameters, environmental conditions or literature sources. Links to other databases based on the annotations of thedata enable the user to gather further information for example for compounds, reactions or proteins. Selected data about reactions and their kinetics, together with their annotations, can be exported in SBML (Systems Biology Mark-up Language), a widely used standard exchange format in systems biology.
Update On The Zebrafish Genome Project
Authors: Almeida-King J P , Donaldson S , Laird G K , Lloyd D M , Sehra H K , Collins J E , Howe K , Reimholz B , Torrance J , Trevanion S , Stemple D , Barroso I , Gilbert J G R , Griffiths E , Loveland J E , Storey R , Harrow J L , Hubbard T
Published: April 2009

The zebrafish genome, which consists of 25 linkage groups and is ~1.4Gb in size, is being sequenced, finished and analysed in its entirety at the Wellcome Trust Sanger Institute. The manual annotation is provided by the Human and Vertebrate Analysis and Annotation (HAVANA) group and is released at regular intervals onto the Vertebrate Genome Annotation (Vega) database ("http://vega.sanger.ac.uk":http://vega.sanger.ac.uk) and may be viewed as a DAS source in Ensembl ("http://www.ensembl.org/Danio_rerio":http://www.ensembl.org/Danio_rerio). Our annotation is compiled in close collaboration with the Zebrafish Information Network (ZFIN) ("http://zfin.org/":http://zfin.org/), which has enabled us to provide an accurate, dynamic and distinct resource for the zebrafish community as a whole.Annotation is based on the reference genome sequence, which is derived from a minimal tile path assembly composed of clones that have been mapped, sequenced and meticulously finished to a sequence accuracy of over 99.9% per 100Kb. We expect to have 90% of the zebrafish genome to a finished standard by the end of 2009. Our approach to annotation uses two strategies. Firstly, the generation and annotation of gene lists comprising of cDNA (8995 in total) found in ZFIN that maps to our current reference assembly. And, secondly, by using clone by clone annotation, where we have annotated over 3200 genes, 1100 transcripts and 130 pseudogenes across 11 linkage groups and 3530 clones. As well as our on-going genome annotation we also welcome external annotation requests for specific genes and regions, which already include the annotation of 93 genes associated with human obesity and the scheduled annotation of the Major Histocompatability Complex, which will utilise reference sequence taken from libraries of a double haploid fish and complement our previous work on the human and mouse MHC already published. External requests and any feedback, questions or requests can be sent to zfish-help [at] sanger.ac.uk.
Identification of a pancreatic stellate cell population with properties of progenitor cells: new role for stellate cells in the pancreas
Authors: Mato Eugenia , Lucas Maria , Petriz Jordi , Gomis Ramon , Novials Anna
Published: April 2009

Numerous studies conducted in a diversity of adult tissues have shown that certain stem cells are characterized by the expression of a protein known as the ABCG2 transporter (where ABC is ATP- binding cassette). In the adult pancreas, although various multipotent progenitors have been proposed, the ABCG2 marker has only been detected in the so-called ‘side population’ (a primitive haematopoietic cell population with a multipotential capacity). In the present study we sought to identify new ABCG2+ pancreatic cell populations and to explore whether they exhibit the properties of progenitor cells. We isolated and expanded mitoxantrone-resistant cells from pancreata of lactating rats by drug selection. These cells were characterized and maintained in different stages of differentiation using several media ‘cocktails’ plus Matrigel™ (BD Biosciences). Differentiation was assessed by RT–PCR (reverse transcription–PCR), immunocytochemistry, electron microscopy and ELISA. The expanded cell population demonstrated a phenotype of PaSCs (pancreatic stellate cells). Spontaneous cell clusters occurred during cell expansion and they showed weak expression of the transcription factor Pdx1 (pancreatic and duodenal homeobox 1). Moreover, the presence of inductive factors in the Matrigel plus exendin-4 led to an increase in Pdx1 and endocrine genes, such as insulin, islet amyloid polypeptide, glucagon, the glucose transporter GLUT2, chromogranin A and the convertases PC1/3 and PC2 were also detected. Immunocytochemical analysis showed co-localization of insulin and C-peptide, whereas ultrastructural studies revealed the presence of granules. Insulin secretion from cell clusters was detected in the cell culture medium. We identified a population of PaSCs that express the ABCG2+ transporter and have the capacity to transdifferentiate into insulin-producing cells. Although the potential therapeutic application remains to be tested, PaSCs could represent a future option for insulin replacement in diabetes research.
Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function
Authors: Wang Dairong , Patel Vickas V. , Ricciotti Emanuela , Zhou Rong , Levin Mark D. , Gao Ehre , Yu Zhou , Ferrari Victor A. , Lu Min Min , Xu Junwang , Zhang Hualei , Hui Yiqun , Cheng Yan , Petrenko Nataliya , Yu Ying , FitzGerald Garret A.
Published: April 2009

Nonsteroidal anti-inflammatory drugs selective for inhibition of COX-2 increase heart failure and elevate blood pressure. The
COX-2
gene was floxed and crossed into merCremer mice under the α-myosin heavy-chain promoter. Tamoxifen induced selective deletion of COX-2 in cardiomyocytes depressed cardiac output, and resulted in weight loss, diminished exercise tolerance, and enhanced susceptibility to induced arrhythmogenesis. The cardiac dysfunction subsequent to pressure overload recovered progressively in the knockouts coincident with increasing cardiomyocyte hypertrophy and interstitial and perivascular fibrosis. Inhibition of COX-2 in cardiomyocytes may contribute to heart failure in patients receiving nonsteroidal anti-inflammatory drugs specific for inhibition of COX-2.
PPARα blocks glucocorticoid receptor α-mediated transactivation but cooperates with the activated glucocorticoid receptor α for transrepression on NF-κB
Authors: Bougarne Nadia , Paumelle Réjane , Caron Sandrine , Hennuyer Nathalie , Mansouri Roxane , Gervois Philippe , Staels Bart , Haegeman Guy , De Bosscher Karolien
Published: April 2009

Glucocorticoid receptor α (GRα) and peroxisome proliferator-activated receptor α (PPARα) are transcription factors with clinically important immune-modulating properties. Either receptor can inhibit cytokine gene expression, mainly through interference with nuclear factor κB (NF-κB)-driven gene expression. The present work aimed to investigate a functional cross-talk between PPARα- and GRα-mediated signaling pathways. Simultaneous activation of PPARα and GRα dose-dependently enhances transrepression of NF-κB-driven gene expression and additively represses cytokine production. In sharp contrast and quite unexpectedly, PPARα agonists inhibit the expression of classical glucocorticoid response element (GRE)-driven genes in a PPARα-dependent manner, as demonstrated by experiments using PPARα wild-type and knockout mice. The underlying mechanism for this transcriptional antagonism relies on a PPARα-mediated interference with the recruitment of GRα, and concomitantly of RNA polymerase II, to GRE-driven gene promoters. Finally, the biological relevance of this phenomenon is underscored by the observation that treatment with the PPARα agonist fenofibrate prevents glucocorticoid-induced hyperinsulinemia of mice fed a high-fat diet. Taken together, PPARα negatively interferes with GRE-mediated GRα activity while potentiating its antiinflammatory effects, thus providing a rationale for combination therapy in chronic inflammatory disorders.
Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease
Authors: Dikeakos Jimmy D. , Di Lello Paola , Lacombe Marie-Josée , Ghirlando Rodolfo , Legault Pascale , Reudelhuber Timothy L. , Omichinski James G.
Published: April 2009

Several peptide hormones are initially synthesized as inactive precursors. It is only on entry of these prohormones and their processing proteases into dense core secretory granules (DCSGs) that the precursors are cleaved to generate their active forms. Prohormone convertase (PC)1/3 is a processing protease that is targeted to DCSGs. The signal for targeting PC1/3 to DCSGs resides in its carboxy-terminal tail (PC1/3
617–753
), where 3 regions (PC1/3
617–625
, PC1/3
665–682
, and PC1/3
711–753
) are known to aid in sorting and membrane association. In this article, we have determined a high-resolution structure of the extreme carboxy-terminal sorting domain, PC1/3
711–753
in micelles by NMR spectroscopy. PC1/3
711–753
contains 2 alpha helices located between residues 722–728 and 738–750. Functional assays demonstrate that the second helix (PC1/3
738–750
) is necessary and sufficient to target a constitutively secreted protein to granules, and that L
745
anchors a hydrophobic patch that is critical for sorting. Also, we demonstrate that calcium binding by the second helix of PC1/3
711–753
promotes aggregation of the domain via the hydrophobic patch centered on L
745
. These results provide a structure-function analysis of a DCSG-sorting domain, and reveal the importance of a hydrophobic patch and calcium binding in controlling the sorting of proteins containing alpha helices to DCSGs.
Statistical estimation of cell-cycle progression and lineage commitment in
Plasmodium falciparum
reveals a homogeneous pattern of transcription in ex vivo culture
Authors: Lemieux Jacob E. , Gomez-Escobar Natalia , Feller Avi , Carret Celine , Amambua-Ngwa Alfred , Pinches Robert , Day Felix , Kyes Sue A. , Conway David J. , Holmes Chris C. , Newbold Chris I.
Published: April 2009

We have cultured
Plasmodium falciparum
directly from the blood of infected individuals to examine patterns of mature-stage gene expression in patient isolates. Analysis of the transcriptome of
P. falciparum
is complicated by the highly periodic nature of gene expression because small variations in the stage of parasite development between samples can lead to an apparent difference in gene expression values. To address this issue, we have developed statistical likelihood-based methods to estimate cell cycle progression and commitment to asexual or sexual development lineages in our samples based on microscopy and gene expression patterns. In cases subsequently matched for temporal development, we find that transcriptional patterns in ex vivo culture display little variation across patients with diverse clinical profiles and closely resemble transcriptional profiles that occur in vitro. These statistical methods, available to the research community, assist in the design and interpretation of
P. falciparum
expression profiling experiments where it is difficult to separate true differential expression from cell-cycle dependent expression. We reanalyze an existing dataset of in vivo patient expression profiles and conclude that previously observed discrete variation is consistent with the commitment of a varying proportion of the parasite population to the sexual development lineage.
Role of
Filia
, a maternal effect gene, in maintaining euploidy during cleavage-stage mouse embryogenesis
Authors: Zheng Ping , Dean Jurrien
Published: April 2009

During oogenesis, mammalian eggs accumulate proteins required for early embryogenesis. Although limited data suggest a vital role of these maternal factors in chromatin reprogramming and embryonic genome activation, the full range of their functions in preimplantation development remains largely unknown. Here we report a role for maternal proteins in maintaining chromosome stability and euploidy in early-cleavage mouse embryogenesis.
Filia
, expressed in growing oocytes, encodes a protein that binds to MATER and participates in a subcortical maternal complex essential for cleavage-stage embryogenesis. The depletion of maternal stores of Filia impairs preimplantation embryo development with a high incidence of aneuploidy that results from abnormal spindle assembly, chromosome misalignment, and spindle assembly checkpoint (SAC) inactivation. In helping to ensure normal spindle morphogenesis, Filia regulates the proper allocation of the key spindle assembly regulators (i.e., AURKA, PLK1, and γ-tubulin) to the microtubule-organizing center via the RhoA signaling pathway. Concurrently, Filia is required for the placement of MAD2, an essential component of the SAC, to kinetochores to enable SAC function. Thus, Filia is central to integrating the spatiotemporal localization of regulators that helps ensure euploidy and high-quality cell cycle progression in preimplantation mouse development. Defects in the well-conserved human homologue could play a similar role and account for recurrent human fetal wastage.
Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication
Authors: Berger Kristi L. , Cooper Jacob D. , Heaton Nicholas S. , Yoon Rosa , Oakland Todd E. , Jordan Tristan X. , Mateu Guaniri , Grakoui Arash , Randall Glenn
Published: April 2009

Hepatitis C virus (HCV) reorganizes cellular membranes to establish sites of replication. The required host pathways and the mechanism of cellular membrane reorganization are poorly characterized. Therefore, we interrogated a customized small interfering RNA (siRNA) library that targets 140 host membrane-trafficking genes to identify genes required for both HCV subgenomic replication and infectious virus production. We identified 7 host cofactors of viral replication, including Cdc42 and Rock2 (actin polymerization), EEA1 and Rab5A (early endosomes), Rab7L1, and PI3-kinase C2gamma and PI4-kinase IIIalpha (phospholipid metabolism). Studies of drug inhibitors indicate actin polymerization and phospholipid kinase activity are required for HCV replication. We found extensive co-localization of the HCV replicase markers NS5A and double-stranded RNA with Rab5A and partial co-localization with Rab7L1. PI4K-IIIalpha co-localized with NS5A and double-stranded RNA in addition to being present in detergent-resistant membranes containing NS5A. In a comparison of type II and type III PI4-kinases, PI4Ks were not required for HCV entry, and only PI4K-IIIalpha was required for HCV replication. Although PI4K-IIIalpha siRNAs decreased HCV replication and virus production by almost 100%, they had no effect on initial HCV RNA translation, suggesting that PI4K-IIIalpha functions at a posttranslational stage. Electron microscopy identified the presence of membranous webs, which are thought to be the site of HCV replication, in HCV-infected cells. Pretreatment with PI4K-IIIalpha siRNAs greatly reduced the accumulation of these membranous web structures in HCV-infected cells. We propose that PI4K-IIIalpha plays an essential role in membrane alterations leading to the formation of HCV replication complexes.
Insulin Resistance Impairs Endothelial Function but not Adrenergic Reactivity or Vascular Structure in Fructose‐fed Rats
Authors: ROMANKO OLGA P. , ALI M. IRFAN , MINTZ JAMES D. , STEPP DAVID W.
Published: April 2009

Obesity and diabetes are major risk factors for the development of vascular disease in the lower limbs. Previous studies have demonstrated reduced nitric oxide (NO)‐mediated vasodilation, increased adrenergic constriction, and inward, atrophic remodeling in the limb circulation of obese Zucker rats, but the component of the “metabolic syndrome” driving these changes is unclear. Because insulin resistance precedes the state of frank diabetes, the current study hypothesized that insulin resistance independent of obesity induced by fructose feeding would impair microvascular function in the skeletal muscle circulation in lean Zucker rats (LZR). A 66% fructose diet impaired glucose tolerance and induced moderate insulin resistance with no changes in whole‐body hemodynamics of anesthetized rats (FF‐LZR), compared to control LZR. NO‐mediated vasodilation of isolated gracilis arteries, assessed in vitro with acetylcholine and sodium nitroprusside, was reduced ∼20% in FF‐LZR vs. LZR. NO‐independent cGMP‐mediated vasodilation was unimpaired. Pretreatment of isolated vessels with the superoxide scavenger, tempol, improved responses to both vasodilators. Reactivity to adrenergic stimulation was unaltered in FF‐LZR vs. LZR, although constriction to endothelin was increased. Structural and passive mechanical characteristics of isolated gracilis arteries were similar in both LZR and FF‐LZR. Taken together, these findings indicate that moderate insulin resistance is sufficient to impair endothelial function in an oxidant‐dependent manner in the rat hindlimb circulation. Other aspects of skeletal muscle vascular function documented in obese models, specifically adrenergic tone and inward remodeling, must reflect either severe insulin resistance or other aspects of obesity. The factors accounting for nonendothelial vasculopathies remain unknown.
Association between aerobic fitness, body composition, and physical activity in 9‐ and 15‐year‐olds
Authors: Sveinsson Thorarinn , Arngrimsson Sigurbjorn A. , Johannsson Erlingur
Published: April 2009

The aim of this study was to examine the interrelationship between aerobic fitness, body composition, and physical activity in 9‐ and 15‐year‐olds. The 270 participants were randomly selected from 18 primary and secondary schools in Iceland. Aerobic fitness was assessed by a graded exercise test on a bicycle ergometer. Body composition was estimated via: logarithm of sum of four skinfolds (loge skinfolds), waist adjusted for height, and body mass index (BMI). Physical activity was measured with Actigraph activity monitors using total activity each day as the physical activity variable. Aerobic fitness was chosen as the primary outcome variable, body composition as the secondary variable, and physical activity as the tertiary variable. All the full models explained a similar proportion of fitness variance for both age groups (45–65%). Among the 15‐year‐olds, loge skinfolds explained a significantly larger proportion of the fitness variance (54%) than waist adjusted for height (29%) and BMI (15%), but all the body composition variables explained a similar proportion of the fitness variance (35–42%) among the 9‐year‐olds. Physical activity explained a smaller proportion (0%) of the unadjusted variance in fitness for the 9‐year‐olds than for the 15‐year‐olds (19%). This group difference became non‐significant (0% vs. 4%) when adjusting for loge skinfolds but remained significant when controlling for waist adjusted for height (0% vs. 15%) and BMI (0% vs. 18%). Gender differences in aerobic fitness after puberty can largely be explained by gender differences in loge skinfolds and physical activity. In conclusion, the interrelationship between fitness, body composition, physical activity, and gender is not the same among 9‐ and 15‐year‐olds.
Development of a performance assessment tool for rock climbers
Authors: Brent Simon , Draper Nick , Hodgson Christopher , Blackwell Gavin
Published: April 2009

Rock climbing is a popular adventure sport for which there is a growing body of scientific knowledge. There is, however, a lack of sport‐specific assessment tools to monitor performance. The aim of this study was to examine the potential of the rock‐over climbing test (ROCT) as a measure of climbing performance. The ROCT was conducted on a climbaflex board and involved the climber making a rock‐over move for which the height gained from lower to upper handhold was measured. Results indicated there was a significant relationship between scaled (to the height of the climber) ROCT scores and climbing ability (r=0.67, P<0.0005). Regression modelling revealed that the ROCT explained 45% of the variance in scores between climbers. The ROCT differentiated between climber ability levels. Mean ROCT scores for novice, intermediate, advanced, and elite climbers were 59.5%, 71%, 82%, and 90% of participant height respectively. Results of analysis of variance revealed that these differences were significant (F 3,42=13.38, P<0.0005). Limits of agreement and intra‐class correlation indicated that the ROCT is a reliable performance measure. Our findings suggest that the ROCT is a useful measure of climbing performance.
Evaluation of body composition using three different methods compared to dual‐energy X‐ray absorptiometry
Authors: Duz Serkan , Kocak Mehmet , Korkusuz Feza
Published: April 2009

In this study, we compared the simple methods of skinfolds, ultrasound, and bioelectrical impedance analysis (BIA) against the standard of dual‐energy X‐ray absorptiometry (DEXA) in the assessment of body fat in normoactive Turkish male and female university students. We wished to develop new regression equations to more accurately predict percent body fat from skinfolds and ultrasound for this group of individuals. One hundred and four male (age 22.2±2.5 years; height 1.77±0.06 m; mass 74.9±10.4 kg) and one hundred and four female (age 21.9±1.9 years; height 1.65±0.06 m; mass 55.6±7.9 kg) students aged 18–26 years participated in the study. Analysis of variance and confidence intervals were used to compare mean percent body fat derived from skinfolds, ultrasound, BIA, and DEXA measurements, while intra‐class correlation coefficients and Pearson correlation coefficients were used to evaluate the strength of the relationship between the methods. Bland and Altman plot analysis was used to evaluate the strength of agreement of the three methods with DEXA. Moreover, multiple regression analyses were conducted to develop new regression equations to predict percent body fat from subcutaneous fat thickness measured at three sites. The accuracy of the predictive equations was assessed by a cross‐validation test. Mean percent body fat derived from DEXA (18.5±6.2% for males, 28.4±1.3% for females) was found to be significantly (p<0.01) greater than that derived from skinfolds (12.4±5.5% for males, 20.8±1.0% for females), ultrasound (12.0±7.8% for males, 25.0±1.4% for females), and BIA (13.7±4.9% for males, 19.2±1.0% for females) in both males and females. According to the Bland and Altman plot analysis, ultrasound gave the closest results to DEXA for females and males and females combined, whereas BIA gave the closest results to DEXA for males. Skinfolds were the second closest measure to DEXA for all groups. Results of the regression analysis showed that measurement of subcutaneous fat thickness at three sites by skinfolds and ultrasound best predicted percent body fat for males and females respectively. Multiple correlations using three sites simultaneously in the skinfold measurements were r=0.92 ( =2.4) and r=0.91 ( =2.8), and in the ultrasound measurements were r=0.93 ( =2.3) and r=0.90 ( =3.0), for males and females respectively. In conclusion, comparison of the methods revealed that the three techniques could not be used interchangeably in this population. However, with these new regression equations, ultrasound and skinfolds are confirmed to be accurate, portable, and non‐invasive tools for use in field studies. As a result, ultrasound can be used accurately on all individuals, regardless of whether they are obese or thin.
FDR made easy in differential feature discovery and correlation analyses
Authors: Ling Xuefeng Bruce , Cohen Harvey , Jin Joseph , Lau Irwin , Schilling James
Published: April 2009

Summary: Rapid progress in technology, particularly in high-throughput biology, allows the analysis of thousands of genes or proteins simultaneously, where the multiple comparison problems occurs. Global false discovery rate (gFDR) analysis statistically controls this error, computing the ratio of the number of false positives over the total number of rejections. Local FDR (lFDR) method can associate the corrected significance measure with each hypothesis testing for its feature-by-feature interpretation. Given the large feature number and sample size in any genomics or proteomics analysis, FDR computation, albeit critical, is both beyond the regular biologists' specialty and computationally expensive, easily exceeding the capacity of desktop computers. To overcome this digital divide, a web portal has been developed that provides bench-side biologists easy access to the server-side computing capabilities to analyze for FDR, differential expressed genes or proteins, and for the correlation between molecular data and clinical measurements.

Availability:  http://translationalmedicine.stanford.edu/Mass-Conductor/FDR.html

Contacts:  xuefeng_ling@yahoo.com; jschill@stanford.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A local multiple alignment method for detection of non-coding RNA sequences
Authors: Tabei Yasuo , Asai Kiyoshi
Published: April 2009

Motivation: Non-coding RNAs (ncRNAs) show a unique evolutionary process in which the substitutions of distant bases are correlated in order to conserve the secondary structure of the ncRNA molecule. Therefore, the multiple alignment method for the detection of ncRNAs should take into account both the primary sequence and the secondary structure. Recently, there has been intense focus on multiple alignment investigations for the detection of ncRNAs; however, most of the proposed methods are designed for global multiple alignments. For this reason, these methods are not appropriate to identify locally conserved ncRNAs among genomic sequences. A more efficient local multiple alignment method for the detection of ncRNAs is required.

Results: We propose a new local multiple alignment method for the detection of ncRNAs. This method uses a local multiple alignment construction procedure inspired by ProDA, which is a local multiple aligner program for protein sequences with repeated and shuffled elements. To align sequences based on secondary structure information, we propose a new alignment model which incorporates secondary structure features. We define the conditional probability of an alignment via a conditional random field and use a γ-centroid estimator to align sequences. The locally aligned subsequences are clustered into blocks of approximately globally alignable subsequences between pairwise alignments. Finally, these blocks are multiply aligned via MXSCARNA. In benchmark experiments, we demonstrate the high ability of the implemented software, SCARNA_LM, for local multiple alignment for the detection of ncRNAs.

Availability: The C++ source code for SCARNA_LM and its experimental datasets are available at http://www.ncrna.org/software/scarna_lm/download.

Contact:  scarna@m.aist.go.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
CATMAID: collaborative annotation toolkit for massive amounts of image data
Authors: Saalfeld Stephan , Cardona Albert , Hartenstein Volker , Tomančák Pavel
Published: April 2009

Summary: High-resolution, three-dimensional (3D) imaging of large biological specimens generates massive image datasets that are difficult to navigate, annotate and share effectively. Inspired by online mapping applications like GoogleMaps™, we developed a decentralized web interface that allows seamless navigation of arbitrarily large image stacks. Our interface provides means for online, collaborative annotation of the biological image data and seamless sharing of regions of interest by bookmarking. The CATMAID interface enables synchronized navigation through multiple registered datasets even at vastly different scales such as in comparisons between optical and electron microscopy.

Availability:  http://fly.mpi-cbg.de/catmaid

Contact:  tomancak@mpi-cbg.de
Royal Jelly Facilitates Restoration of the Cognitive Ability in Trimethyltin‐Intoxicated Mice
Authors: Hattori Noriko , Ohta Shozo , Sakamoto Takashi , Mishima Satoshi , Furukawa Shoei
Published: April 2009

Trimethyltin (TMT) is a toxic organotin compound that induces acute neuronal death selectively in the hippocampal dentate gyrus (DG) followed by cognition impairment; however the TMT‐injured hippocampal DG itself is reported to regenerate the neuronal cell layer through rapid enhancement of neurogenesis. Neural stem/progenitor cells (NS/NPCs) are present in the adult hippocampal DG, and generate neurons that can function for the cognition ability. Therefore, we investigated whether royal jelly (RJ) stimulates the regenerating processes of the TMT‐injured hippocampal DG, and found that orally administered RJ significantly increased the number of DG granule cells and simultaneously improved the cognitive impairment. Furthermore, we have already shown that RJ facilitates neurogenesis of cultured NS/NPCs. These present results, taken together with previous observations, suggest that the orally administered RJ may be a promising avenue for ameliorating neuronal function by regenerating hippocampal granule cells that function in the cognition process.
Analyzing Serum‐Stimulated Prostate Cancer Cell Lines After Low‐Fat, High‐Fiber Diet and Exercise Intervention
Authors: Soliman Sherry , Aronson William J. , Barnard R. James
Published: April 2009

Serum from men undergoing a low‐fat, high‐fiber diet and exercise intervention has previously been shown to decrease growth and increase apoptosis in serum‐stimulated, androgen‐dependent LNCaP cells associated with a reduction in serum IGF‐I. Here we sought to determine the underlying mechanisms for these anticancer effects. Again, the intervention slowed growth and increased apoptosis in LNCaP cells; responses that were eliminated when IGF‐I was added back to the post‐intervention samples. The p53 protein content was increased and NFκB activation reduced in the post serum‐stimulated LNCaP cells. Similar results were observed when the IGF‐I receptor was blocked in the pre‐intervention serum. In androgen‐independent PC‐3 cells, growth was reduced while none of the other factors were changed by the intervention. We conclude that diet and exercise intervention might help prevent clinical PCa as well as aid in the treatment of PCa during the early stages of development.
Numerical modelling of the shoulder for clinical applications
Authors: Favre Philippe , Snedeker Jess G. , Gerber Christian
Published: April 2009

Research activity involving numerical models of the shoulder is dramatically increasing, driven by growing rates of injury and the need to better understand shoulder joint pathologies to develop therapeutic strategies. Based on the type of clinical question they can address, existing models can be broadly categorized into three groups: (i) rigid body models that can simulate kinematics, collisions between entities or wrapping of the muscles over the bones, and which have been used to investigate joint kinematics and ergonomics, and are often coupled with (ii) muscle force estimation techniques, consisting mainly of optimization methods and electromyography-driven models, to simulate muscular action and joint reaction forces to address issues in joint stability, muscular rehabilitation or muscle transfer, and (iii) deformable models that account for stress–strain distributions in the component structures to study articular degeneration, implant failure or muscle/tendon/bone integrity. The state of the art in numerical modelling of the shoulder is reviewed, and the advantages, limitations and potential clinical applications of these modelling approaches are critically discussed. This review concentrates primarily on muscle force estimation modelling, with emphasis on a novel muscle recruitment paradigm, compared with traditionally applied optimization methods. Finally, the necessary benchmarks for validating shoulder models, the emerging technologies that will enable further advances and the future challenges in the field are described.
Simulation of cardiac electrophysiology on next-generation high-performance computers
Authors: Bordas Rafel , Carpentieri Bruno , Fotia Giorgio , Maggio Fabio , Nobes Ross , Pitt-Francis Joe , Southern James
Published: April 2009

Models of cardiac electrophysiology consist of a system of partial differential equations (PDEs) coupled with a system of ordinary differential equations representing cell membrane dynamics. Current software to solve such models does not provide the required computational speed for practical applications. One reason for this is that little use is made of recent developments in adaptive numerical algorithms for solving systems of PDEs. Studies have suggested that a speedup of up to two orders of magnitude is possible by using adaptive methods. The challenge lies in the efficient implementation of adaptive algorithms on massively parallel computers. The finite-element (FE) method is often used in heart simulators as it can encapsulate the complex geometry and small-scale details of the human heart. An alternative is the spectral element (SE) method, a high-order technique that provides the flexibility and accuracy of FE, but with a reduced number of degrees of freedom. The feasibility of implementing a parallel SE algorithm based on fully unstructured all-hexahedra meshes is discussed. A major computational task is solution of the large algebraic system resulting from FE or SE discretization. Choice of linear solver and preconditioner has a substantial effect on efficiency. A fully parallel implementation based on dynamic partitioning that accounts for load balance, communication and data movement costs is required. Each of these methods must be implemented on next-generation supercomputers in order to realize the necessary speedup. The problems that this may cause, and some of the techniques that are beginning to be developed to overcome these issues, are described.
A mathematical approach to bone tissue engineering
Authors: Sanz-Herrera J.A. , García-Aznar J.M. , Doblaré M.
Published: April 2009

Tissue engineering is becoming consolidated in the biomedical field as one of the most promising strategies in tissue repair and regenerative medicine. Within this discipline, bone tissue engineering involves the use of cell-loaded porous biomaterials, i.e. bioscaffolds, to promote bone tissue regeneration in bone defects or diseases such as osteoporosis, although it has not yet been incorporated into daily clinical practice. The overall success of a particular bone tissue engineering application depends strongly on scaffold design parameters, which do away with long and expensive clinical protocols. Computer simulation is a useful tool that may reduce animal experiments and help to identify optimal patient-specific designs after concise model validation. In this paper, we present a novel mathematical approach to bone regeneration within scaffolds, based on a multiscale framework. Results are presented over an actual scaffold microstructure, showing the potential of computer simulation, and how it can aid in the task of making bone tissue engineering a reality in clinical practice.
Disruption ofOsYSL15Leads to Iron Inefficiency in Rice Plants
Authors: Lee Sichul , Chiecko Jeff C. , Kim Sun A. , Walker Elsbeth L. , Lee Youngsook , Guerinot Mary Lou , An Gynheung
Published: April 2009

Uptake and translocation of metal nutrients are essential processes for plant growth. Graminaceous species release phytosiderophores that bind to Fe3+; these complexes are then transported across the plasma membrane. We have characterized OsYSL15, one of the rice (Oryza sativa) YS1-like (YSL) genes that are strongly induced by iron (Fe) deficiency. The OsYSL15 promoter fusion to β-glucuronidase showed that it was expressed in all root tissues when Fe was limited. In low-Fe leaves, the promoter became active in all tissues except epidermal cells. This activity was also detected in flowers and seeds. The OsYSL15:green fluorescent protein fusion was localized to the plasma membrane. OsYSL15 functionally complemented yeast strains defective in Fe uptake on media containing Fe3+-deoxymugineic acid and Fe2+-nicotianamine. Two insertional osysl15 mutants exhibited chlorotic phenotypes under Fe deficiency and had reduced Fe concentrations in their shoots, roots, and seeds. Nitric oxide treatment reversed this chlorosis under Fe-limiting conditions. Overexpression of OsYSL15 increased the Fe concentration in leaves and seeds from transgenic plants. Altogether, these results demonstrate roles for OsYSL15 in Fe uptake and distribution in rice plants.
A Mobile Secretory Vesicle Cluster Involved in Mass Transport from the Golgi to the Plant Cell Exterior
Authors: Toyooka Kiminori , Goto Yumi , Asatsuma Satoru , Koizumi Masato , Mitsui Toshiaki , Matsuoka Ken
Published: April 2009

Secretory proteins and extracellular glycans are transported to the extracellular space during cell growth. These materials are carried in secretory vesicles generated at the trans-Golgi network (TGN). Analysis of the mammalian post-Golgi secretory pathway demonstrated the movement of separated secretory vesicles in the cell. Using secretory carrier membrane protein 2 (SCAMP2) as a marker for secretory vesicles and tobacco (Nicotiana tabacum) BY-2 cell as a model cell, we characterized the transport machinery in plant cells. A combination of analyses, including electron microscopy of quick-frozen cells and four-dimensional analysis of cells expressing fluorescent-tagged SCAMP2, enabled the identification of a clustered structure of secretory vesicles generated from TGN that moves in the cell and eventually fuses with plasma membrane. This structure was termed the secretory vesicle cluster (SVC). The SVC was also found in Arabidopsis thaliana and rice (Oryza sativa) cells and moved to the cell plate in dividing tobacco cells. Thus, the SVC is a motile structure involved in mass transport from the Golgi to the plasma membrane and cell plate in plant cells.
The RNA Binding Protein ELF9 Directly ReducesSUPPRESSOR OF OVEREXPRESSION OF CO1Transcript Levels inArabidopsis, Possibly via Nonsense-Mediated mRNA Decay
Authors: Song Hae-Ryong , Song Ju-Dong , Cho Jung-Nam , Amasino Richard M. , Noh Bosl , Noh Yoo-Sun
Published: April 2009

SUPPRESSOR OF OVEREXPRESSION OF CO1 (SOC1) is regulated by a complex transcriptional regulatory network that allows for the integration of multiple floral regulatory inputs from photoperiods, gibberellin, and FLOWERING LOCUS C. However, the posttranscriptional regulation of SOC1 has not been explored. Here, we report that EARLY FLOWERING9 (ELF9), an Arabidopsis thaliana RNA binding protein, directly targets the SOC1 transcript and reduces SOC1 mRNA levels, possibly through a nonsense-mediated mRNA decay (NMD) mechanism, which leads to the degradation of abnormal transcripts with premature translation termination codons (PTCs). The fully spliced SOC1 transcript is upregulated in elf9 mutants as well as in mutants of NMD core components. Furthermore, a partially spliced SOC1 transcript containing a PTC is upregulated more significantly than the fully spliced transcript in elf9 in an ecotype-dependent manner. A Myc-tagged ELF9 protein (MycELF9) directly binds to the partially spliced SOC1 transcript. Previously known NMD target transcripts of Arabidopsis are also upregulated in elf9 and recognized directly by MycELF9. SOC1 transcript levels are also increased by the inhibition of translational activity of the ribosome. Thus, the SOC1 transcript is one of the direct targets of ELF9, which appears to be involved in NMD-dependent mRNA quality control in Arabidopsis.
Pausing of Golgi Bodies on Microtubules Regulates Secretion of Cellulose Synthase Complexes in Arabidopsis
Authors: Crowell Elizabeth Faris , Bischoff Volker , Desprez Thierry , Rolland Aurélia , Stierhof York-Dieter , Schumacher Karin , Gonneau Martine , Höfte Herman , Vernhettes Samantha
Published: April 2009

Plant growth and organ formation depend on the oriented deposition of load-bearing cellulose microfibrils in the cell wall. Cellulose is synthesized by plasma membrane–bound complexes containing cellulose synthase proteins (CESAs). Here, we establish a role for the cytoskeleton in intracellular trafficking of cellulose synthase complexes (CSCs) through the in vivo study of the green fluorescent protein (GFP)-CESA3 fusion protein in Arabidopsis thaliana hypocotyls. GFP-CESA3 localizes to the plasma membrane, Golgi apparatus, a compartment identified by the VHA-a1 marker, and, surprisingly, a novel microtubule-associated cellulose synthase compartment (MASC) whose formation and movement depend on the dynamic cortical microtubule array. Osmotic stress or treatment with the cellulose synthesis inhibitor CGA 325'615 induces internalization of CSCs in MASCs, mimicking the intracellular distribution of CSCs in nongrowing cells. Our results indicate that cellulose synthesis is coordinated with growth status and regulated in part through CSC internalization. We find that CSC insertion in the plasma membrane is regulated by pauses of the Golgi apparatus along cortical microtubules. Our data support a model in which cortical microtubules not only guide the trajectories of CSCs in the plasma membrane, but also regulate the insertion and internalization of CSCs, thus allowing dynamic remodeling of CSC secretion during cell expansion and differentiation.
Misexpression of FATTY ACID ELONGATION1 in theArabidopsisEpidermis Induces Cell Death and Suggests a Critical Role for Phospholipase A2 in This Process
Authors: Reina-Pinto José J. , Voisin Derry , Kurdyukov Sergey , Faust Andrea , Haslam Richard P. , Michaelson Louise V. , Efremova Nadia , Franke Benni , Schreiber Lukas , Napier Johnathan A. , Yephremov Alexander
Published: April 2009

Very-long-chain fatty acids (VLCFAs) are important functional components of various lipid classes, including cuticular lipids in the higher plant epidermis and lipid-derived second messengers. Here, we report the characterization of transgenic Arabidopsis thaliana plants that epidermally express FATTY ACID ELONGATION1 (FAE1), the seed-specific β-ketoacyl-CoA synthase (KCS) catalyzing the first rate-limiting step in VLCFA biosynthesis. Misexpression of FAE1 changes the VLCFAs in different classes of lipids but surprisingly does not complement the KCS fiddlehead mutant. FAE1 misexpression plants are similar to the wild type but display an essentially glabrous phenotype, owing to the selective death of trichome cells. This cell death is accompanied by membrane damage, generation of reactive oxygen species, and callose deposition. We found that nuclei of arrested trichome cells in FAE1 misexpression plants cell-autonomously accumulate high levels of DNA damage, including double-strand breaks characteristic of lipoapoptosis. A chemical genetic screen revealed that inhibitors of KCS and phospholipase A2 (PLA2), but not inhibitors of de novo ceramide biosynthesis, rescue trichome cells from death. These results support the functional role of acyl chain length of fatty acids and PLA2 as determinants for programmed cell death, likely involving the exchange of VLCFAs between phospholipids and the acyl-CoA pool.
Genome-Wide and Organ-Specific Landscapes of Epigenetic Modifications and Their Relationships to mRNA and Small RNA Transcriptomes in Maize
Authors: Wang Xiangfeng , Elling Axel A. , Li Xueyong , Li Ning , Peng Zhiyu , He Guangming , Sun Hui , Qi Yijun , Liu X. Shirley , Deng Xing Wang
Published: April 2009

Maize (Zea mays) has an exceptionally complex genome with a rich history in both epigenetics and evolution. We report genomic landscapes of representative epigenetic modifications and their relationships to mRNA and small RNA (smRNA) transcriptomes in maize shoots and roots. The epigenetic patterns differed dramatically between genes and transposable elements, and two repressive marks (H3K27me3 and DNA methylation) were usually mutually exclusive. We found an organ-specific distribution of canonical microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs), indicative of their tissue-specific biogenesis. Furthermore, we observed that a decreasing level of mop1 led to a concomitant decrease of 24-nucleotide siRNAs relative to 21-nucleotide miRNAs in a tissue-specific manner. A group of 22-nucleotide siRNAs may originate from long-hairpin double-stranded RNAs and preferentially target gene-coding regions. Additionally, a class of miRNA-like smRNAs, whose putative precursors can form short hairpins, potentially targets genes in trans. In summary, our data provide a critical analysis of the maize epigenome and its relationships to mRNA and smRNA transcriptomes.
Autosomal recessive type 2 pseudoxanthoma elasticum presenting with generalized skin laxity
Authors: LEE Woo Jin , BAK Hana , CHANG Sung Eun , LEE Mi Woo , CHOI Jee Ho , MOON Kee Chan , KOH Jai Kyoung
Published: April 2009

Herein, we describe a sporadic case of recessive type 2 pseudoxanthoma elasticum. A 26‐year‐old woman without family history presented with cutis laxa‐like marked wrinkling involving the whole‐body and a serpiginous streak on the upper left arm. She denied any other systemic problems related to difficulty with visual acuity or vascular disease. A skin biopsy specimen from the loose skin showed the accumulation of calcified degenerated elastic fibers and foci of ossification in the dermis. Histopathological study from a serpiginous streak revealed mineralized debris that was eliminated through the epidermis, the finding consistent with elastosis perforans serpiginosa. Recessive type 2 pseudoxanthoma elasticum is very rare and the presenting case is interesting in that this patient presented with lesions of secondary ossification and elastosis perforans serpiginosa in association with pseudoxanthoma elasticum.