bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEMOSys: Bioinformatics platform for genome-scale metabolic models
Authors: Pabinger Stephan , Rader Robert , Agren Rasmus , Nielsen Jens , Trajanoski Zlatko 
Published: February 2011

AbstractBackgroundRecent advances in genomic sequencing have enabled the use of genome sequencing in standard biological and biotechnological research projects. The challenge is how to integrate the large amount of data in order to gain novel biological insights. One way to leverage sequence data is to use genome-scale metabolic models. We have therefore designed and implemented a bioinformatics platform which supports the development of such metabolic models.ResultsMEMOSys (MEtabolic MOdel research and development System) is a versatile platform for the management, storage, and development of genome-scale metabolic models. It supports the development of new models by providing a built-in version control system which offers access to the complete developmental history. Moreover, the integrated web board, the authorization system, and the definition of user roles allow collaborations across departments and institutions. Research on existing models is facilitated by a search system, references to external databases, and a feature-rich comparison mechanism. MEMOSys provides customizable data exchange mechanisms using the SBML format to enable analysis in external tools. The web application is based on the Java EE framework and offers an intuitive user interface. It currently contains six annotated microbial metabolic models.ConclusionsWe have developed a web-based system designed to provide researchers a novel application facilitating the management and development of metabolic models. The system is freely available athttp://www.icbi.at/MEMOSys.
Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data
Authors: Krumsiek Jan , Suhre Karsten , Illig Thomas , Adamski Jerzy , Theis Fabian J 
Published: February 2011

Abstract

Background
With the advent of high-throughput targeted metabolic profiling techniques, the question of how to interpret and analyze the resulting vast amount of data becomes more and more important. In this work we address the reconstruction of metabolic reactions from cross-sectional metabolomics data, that is without the requirement for time-resolved measurements or specific system perturbations. Previous studies in this area mainly focused on Pearson correlation coefficients, which however are generally incapable of distinguishing between direct and indirect metabolic interactions.

Results
In our new approach we propose the application of a Gaussian graphical model (GGM), an undirected probabilistic graphical model estimating the conditional dependence between variables. GGMs are based on partial correlation coefficients, that is pairwise Pearson correlation coefficients conditioned against the correlation with all other metabolites. We first demonstrate the general validity of the method and its advantages over regular correlation networks with computer-simulated reaction systems. Then we estimate a GGM on data from a large human population cohort, covering 1020 fasting blood serum samples with 151 quantified metabolites. The GGM is much sparser than the correlation network, shows a modular structure with respect to metabolite classes, and is stable to the choice of samples in the data set. On the example of human fatty acid metabolism, we demonstrate for the first time that high partial correlation coefficients generally correspond to known metabolic reactions. This feature is evaluated both manually by investigating specific pairs of high-scoring metabolites, and then systematically on a literature-curated model of fatty acid synthesis and degradation. Our method detects many known reactions along with possibly novel pathway interactions, representing candidates for further experimental examination.

Conclusions
In summary, we demonstrate strong signatures of intracellular pathways in blood serum data, and provide a valuable tool for the unbiased reconstruction of metabolic reactions from large-scale metabolomics data sets.
A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2
Authors: Thiele Ines , Hyduke Daniel R , Steeb Benjamin , Fankam Guy , Allen Douglas K , Bazzani Susanna , Charusanti Pep , Chen Feng-Chi , Fleming Ronan MT , Hsiung Chao A , De Keersmaecker Sigrid CJ , Liao Yu-Chieh , Marchal Kathleen , Mo Monica L , Özdemir Emre , Raghunathan Anu , Reed Jennifer L , Shin Sook-Il , Sigurbjörnsdóttir Sara , Steinmann Jonas , Sudarsan Suresh , Swainston Neil , Thijs Inge M , Zengler Karsten , Palsson Bernhard O , Adkins Joshua N , Bumann Dirk 
Published: February 2011

Abstract

Background
Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, and genomic (BiGG) knowledge-bases for target organisms by capturing currently available information in a consistent, structured manner. Salmonella enterica subspecies I serovar Typhimurium is a human pathogen, causes various diseases and its increasing antibiotic resistance poses a public health problem.

Results
Here, we describe a community-driven effort, in which more than 20 experts in S. Typhimurium biology and systems biology collaborated to reconcile and expand the S. Typhimurium BiGG knowledge-base. The consensus MR was obtained starting from two independently developed MRs for S. Typhimurium. Key results of this reconstruction jamboree include i) development and implementation of a community-based workflow for MR annotation and reconciliation; ii) incorporation of thermodynamic information; and iii) use of the consensus MR to identify potential multi-target drug therapy approaches.

Conclusion
Taken together, with the growing number of parallel MRs a structured, community-driven approach will be necessary to maximize quality while increasing adoption of MRs in experimental design and interpretation.
Gastric cancers of Western European and African patients show different patterns of genomic instability
Authors: Buffart Tineke E , Louw Melanie , van Grieken Nicole CT , Tijssen Marianne , Carvalho Beatriz , Ylstra Bauke , Grabsch Heike , Mulder Chris JJ , van de Velde Cornelis JH , van der Merwe Schalk W , Meijer Gerrit A 
Published: February 2011

Abstract

Background
Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.

Methods
DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.

Results
Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.

Conclusions
Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.
The role of proboscis of the malaria vector mosquito Anopheles stephensi in host-seeking behavior
Authors: Maekawa Emi , Aonuma Hiroka , Nelson Bryce , Yoshimura Aya , Tokunaga Fumio , Fukumoto Shinya , Kanuka Hirotaka 
Published: February 2011

Abstract

Background
The proboscis is an essential head appendage in insects that processes gustatory code during food intake, particularly useful considering that blood-sucking arthropods routinely reach vessels under the host skin using this proboscis as a probe.

Results
Here, using an automated device able to quantify CO2-activated thermo (35°C)-sensing behavior of the malaria vector Anopheles stephensi, we uncovered that the protruding proboscis of mosquitoes contributes unexpectedly to host identification from a distance. Ablation experiments indicated that not only antennae and maxillary palps, but also proboscis were required for the identification of pseudo-thermo targets. Furthermore, the function of the proboscis during this behavior can be segregated from CO2 detection required to evoke mosquito activation, suggesting that the proboscis of mosquitoes divide the proboscis into a "thermo-antenna" in addition to a "thermo-probe".

Conclusions
Our findings support an emerging view with a possible role of proboscis as important equipment during host-seeking, and give us an insight into how these appendages likely evolved from a common origin in order to function as antenna organs.
The modulation of TRPM7 currents by nafamostat mesilate depends directly upon extracellular concentrations of divalent cations
Authors: Chen Xuanmao , Numata Tomohiro , Li Minghua , Mori Yasuo , Orser Beverley A , Jackson Michael F , Xiong Zhi-Gang , MacDonald John F 
Published: February 2011

Abstract
Concentrations of extracellular divalent cations (Ca2+ and Mg2+) fall substantially during intensive synaptic transmission as well as during some pathophysiological conditions such as epilepsy and brain ischemia. Here we report that a synthetic serine protease inhibitor, nafamostat mesylate (NM), and several of its analogues, block recombinant TRPM7 currents expressed in HEK293T cells in inverse relationship to the concentration of extracellular divalent cations. Lowering extracellular Ca2+ and Mg2+ also evokes a divalent-sensitive non-selective cation current that is mediated by TRPM7 expression in hippocampal neurons. In cultured hippocampal neurons, NM blocked these TRPM7-mediated currents with an apparent affinity of 27 μM, as well as the paradoxical Ca2+ influx associated with lowering extracellular Ca2+. Unexpectedly, pre-exposure to NM strongly potentiated TRPM7 currents. In the presence of physiological concentrations of extracellular divalent cations, NM activates TRPM7. The stimulating effects of NM on TRPM7 currents are also inversely related to extracellular Ca2+ and Mg2+. DAPI and HSB but not netropsin, blocked and stimulated TRPM7. In contrast, mono-cationic, the metabolites of NM, p-GBA and AN, as well as protease inhibitor leupeptin and gabexate failed to substantially modulate TRPM7. NM thus provides a molecular template for the design of putative modulators of TRPM7.
Properties of Contextual Memory Formed in the Absence of αCaMKII Autophosphorylation
Authors: Irvine Elaine E , Danhiez Arthur , Radwanska Kasia , Nassim Charlotte , Lucchesi Walter , Godaux Emile , Ris Laurence , Giese K Peter 
Published: February 2011

AbstractThe alpha-isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is a major synaptic kinase that undergoes autophosphorylation after NMDA receptor activation, switching the kinase into a calcium-independent activity state. This αCaMKII autophosphorylation is essential for NMDA receptor-dependent long-term potentiation (LTP), induced by a single tetanus, in hippocampal area CA1 and in neocortex. Furthermore, the αCaMKII autophosphorylation is essential for contextual long-term memory (LTM) formation after a single training trial but not after a massed training session. Here, we show that in the absence of αCaMKII autophosphorylation contextual fear conditioning is hippocampus dependent and that multi-tetanus-dependent late-LTP cannot be induced in hippocampal area CA1. Furthermore, we show that in the absence of αCaMKII autophosphorylation contextual LTM persists for 30 days, the latest time point tested. Additionally, contextual, but not cued, LTM formation in the absence of αCaMKII autophosphorylation appears to be impaired in 18 month-old mice. Taken together, our findings suggest that αCaMKII autophosphorylation-independent plasticity in the hippocampus is sufficient for contextual LTM formation and that αCaMKII autophosphorylation may be important for delaying age-related impairments in hippocampal memory formation. Furthermore, they propose that NMDA receptor-dependent LTP in hippocampal area CA1 is essential for contextual LTM formation after a single trial but not after massed training. Finally, our results challenge the proposal that NMDA receptor-dependent LTP in neocortex is required for remote contextual LTM.
Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors
Authors: Xu BingHe , Wu YiLong , Shen Lin , Ye DingWei , Jappe Annette , Cherfi Azzeddine , Wang Hui , Yuan RuiRong 
Published: February 2011

Abstract

Background
This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors.

Methods
A total of 24 patients with advanced breast cancer (n = 6), gastric cancer (n = 6), non-small cell lung cancer (n = 6), or renal cell carcinoma (n = 6) who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued.

Results
Everolimus was absorbed rapidly; median Tmax was 3 h (range, 1-4) and 2 h (range, 0.9-6) in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7%) and fatigue (16.7% and 33.3%) in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83%) and 6 (50%) patients in the 5 and 10 mg/day groups, respectively.

Conclusions
Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies.

Trial registration
Chinese Health Authorities 2008L09346
Bostrycin inhibits proliferation of human lung carcinoma A549 cells via downregulation of the PI3K/Akt pathway
Authors: Chen Wei-Sheng , Hou Jun-Na , Guo Yu-Biao , Yang Hui-Ling , Xie Can-Mao , Lin Yong-Cheng , She Zhi-Gang 
Published: February 2011

Abstract

Background
Bostrycin is a novel compound isolated from marine fungi that inhibits proliferation of many cancer cells. However, the inhibitory effect of bostrycin on lung cancers has not been reported. This study is to investigate the inhibitory effects and mechanism of bostrycin on human lung cancer cells in vitro.

Methods
We used MTT assay, flow cytometry, microarray, real time PCR, and Western blotting to detect the effect of bostrycin on A549 human pulmonary adenocarcinoma cells.

Results
We showed a significant inhibition of cell proliferation and induction of apoptosis in bostrycin-treated lung adenocarcinoma cells. Bostrycin treatment caused cell cycle arrest in the G0/G1 phase. We also found the upregulation of microRNA-638 and microRNA-923 in bostrycin-treated cells. further, we found the downregulation of p110α and p-Akt/PKB proteins and increased activity of p27 protein after bostrycin treatment in A549 cells.

Conclusions
Our study indicated that bostrycin had a significant inhibitory effect on proliferation of A549 cells. It is possible that upregulation of microRNA-638 and microRNA-923 and downregulaton of the PI3K/AKT pathway proteins played a role in induction of cell cycle arrest and apoptosis in bostrycin-treated cells.
Changes in joint coupling and variability during walking following tibialis posterior muscle fatigue
Authors: Ferber Reed , Pohl Michael B 
Published: February 2011

AbstractBackgroundThe tibialis posterior muscle is believed to play a key role in controlling foot mechanics during the stance phase of gait. However, an experiment involving localised tibialis posterior muscle fatigue, and analysis of discrete rearfoot and forefoot kinematic variables, indicated that reduced force output of the tibialis posterior muscle did not alter rearfoot and forefoot motion during gait. Thus, to better understand how muscle fatigue affects foot kinematics and injury potential, the purpose of this study was to reanalyze the data and investigate shank, rearfoot and forefoot joint coupling and coupling variability during walking.MethodsTwenty‐nine participants underwent an exercise fatigue protocol aimed at reducing the force output of tibialis posterior. An eight camera motion analysis system was used to evaluate 3 D shank and foot joint coupling and coupling variability during treadmill walking both pre‐ and post‐fatigue.ResultsThe fatigue protocol was successful in reducing the maximal isometric force by over 30% and a concomitant increase in coupling motion of the shank in the transverse plane and forefoot in the sagittal and transverse planes relative to frontal plane motion of the rearfoot. In addition, an increase in joint coupling variability was measured between the shank and rearfoot and between the rearfoot and forefoot during the fatigue condition.ConclusionsThe reduced function of the tibialis posterior muscle following fatigue resulted in a disruption in typical shank and foot joint coupling patterns and an increased variability in joint coupling. These results could help explain tibialis posterior injury aetiology.
At the frontiers of surgery: review
Authors: Upile Tahwinder , Jerjes Waseem K , Sterenborg Henricus J , Wong Brian J , El-Naggar Adel K , Ilgner Justus F , Sandison Ann , Witjes Max J , Biel Merrill A , van Veen Robert , Hamdoon Zaid , Gillenwater Ann , Mosse Charles A , Robinson Dominic J , Betz Christian S , Stepp Herbert , Bolotine Lina , McKenzie Gordon , Barr Hugh , Chen Zhongping , Berg Kristian , D'Cruz Anil K , Sudhoff Holger , Stone Nicholas , Kendall Catherine , Fisher Sheila , MacRobert Alexander J , Leunig Andreas , Olivo Malini , Richards-Kortum Rebecca , Soo Khee C , Bagnato Vanderlei , Choo-Smith Lin-Ping , Svanberg Katarina , Tan I Bing , Wilson Brian C , Wolfsen Herbert , Bigio Irving , Yodh Arjun G , Hopper Colin 
Published: February 2011

Abstract
The complete surgical removal of disease is a desirable outcome particularly in oncology. Unfortunately much disease is microscopic and difficult to detect causing a liability to recurrence and worsened overall prognosis with attendant costs in terms of morbidity and mortality. It is hoped that by advances in optical diagnostic technology we could better define our surgical margin and so increase the rate of truly negative margins on the one hand and on the other hand to take out only the necessary amount of tissue and leave more unaffected non-diseased areas so preserving function of vital structures. The task has not been easy but progress is being made as exemplified by the presentations at the 2nd Scientific Meeting of the Head and Neck Optical Diagnostics Society (HNODS) in San Francisco in January 2010. We review the salient advances in the field and propose further directions of investigation.
Statistical structure of lateral connections in the primary visual cortex
Authors: Hunt Jonathan J , Bosking William H , Goodhill Geoffrey J 
Published: February 2011

Abstract

Background
The statistical structure of the visual world offers many useful clues for understanding how biological visual systems may understand natural scenes. One particularly important early process in visual object recognition is that of grouping together edges which belong to the same contour. The layout of edges in natural scenes have strong statistical structure. One such statistical property is that edges tend to lie on a common circle, and this 'co-circularity' can predict human performance at contour grouping. We therefore tested the hypothesis that long-range excitatory lateral connections in the primary visual cortex, which are believed to be involved in contour grouping, display a similar co-circular structure.

Results
By analyzing data from tree shrews, where information on both lateral connectivity and the overall structure of the orientation map was available, we found a surprising diversity in the relevant statistical structure of the connections. In particular, the extent to which co-circularity was displayed varied significantly.

Conclusions
Overall, these data suggest the intriguing possibility that V1 may contain both co-circular and anti-cocircular connections.
Genetic visualization of the secondary olfactory pathway in Tbx21 transgenic mice
Authors: Mitsui Sachiko , Igarashi Kei M , Mori Kensaku , Yoshihara Yoshihiro 
Published: February 2011

Abstract

Background
Mitral and tufted cells are the projection neurons in the olfactory bulb, conveying odour information to various regions of the olfactory cortex. In spite of their functional importance, there are few molecular and genetic tools that can be used for selective labelling or manipulation of mitral and tufted cells. Tbx21 was first identified as a T-box family transcription factor regulating the differentiation and function of T lymphocytes. In the brain, Tbx21 is specifically expressed in mitral and tufted cells of the olfactory bulb.

Results
In this study, we performed a promoter/enhancer analysis of mouse Tbx21 gene by comparing nucleotide sequence similarity of Tbx21 genes among several mammalian species and generating transgenic mouse lines with various lengths of 5' upstream region fused to a fluorescent reporter gapVenus. We identified the cis-regulatory enhancer element (~300 nucleotides) at ~ 3.0 kb upstream of the transcription start site of Tbx21 gene, which is both necessary and sufficient for transgene expression in mitral and tufted cells. In contrast, the 2.6-kb 5'-flanking region of mouse Tbx21 gene induced transgene expression with variable patterns in restricted populations of neurons predominantly located along the olfactory pathway. Furthermore, we generated transgenic mice expressing the genetically-encoded fluorescent exocytosis indicator, synaptopHluorin, in mitral and tufted cells for visualization of presynaptic neural activities in the piriform cortex.

Conclusions
The transcriptional enhancer of Tbx21 gene provides a powerful tool for genetic manipulations of mitral and tufted cells in studying the development and function of the secondary olfactory pathways from the bulb to the cortex.