bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discriminating response groups in metabolic and regulatory pathway networks
Authors: Van Hemert John L. , Dickerson Julie A. 
Published: February 2012

Abstract
Motivation: Analysis of omics experiments generates lists of entities (genes, metabolites, etc.) selected based on specific behavior, such as changes in response to stress or other signals. Functional interpretation of these lists often uses category enrichment tests using functional annotations like Gene Ontology terms and pathway membership. This approach does not consider the connected structure of biochemical pathways or the causal directionality of events.
Results: The Omics Response Group (ORG) method, described in this work, interprets omics lists in the context of metabolic pathway and regulatory networks using a statistical model for flow within the networks. Statistical results for all response groups are visualized in a novel Pathway Flow plot. The statistical tests are based on the Erlang distribution model under the assumption of independent and identically Exponential-distributed random walk flows through pathways. As a proof of concept, we applied our method to an Escherichia coli transcriptomics dataset where we confirmed common knowledge of the E.coli transcriptional response to Lipid A deprivation. The main response is related to osmotic stress, and we were also able to detect novel responses that are supported by the literature. We also applied our method to an Arabidopsis thaliana expression dataset from an abscisic acid study. In both cases, conventional pathway enrichment tests detected nothing, while our approach discovered biological processes beyond the original studies.
Availability: We created a prototype for an interactive ORG web tool at http://ecoserver.vrac.iastate.edu/pathwayflow (source code is available from https://subversion.vrac.iastate.edu/Subversion/jlv/public/jlv/pathwayflow). The prototype is described along with additional figures and tables in Supplementary Material.
Contact: julied@iastate.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
IDEOM: an Excel interface for analysis of LC–MS-based metabolomics data
Authors: Creek Darren J. , Jankevics Andris , Burgess Karl E. V. , Breitling Rainer , Barrett Michael P. 
Published: February 2012

Abstract
Summary: The application of emerging metabolomics technologies to the comprehensive investigation of cellular biochemistry has been limited by bottlenecks in data processing, particularly noise filtering and metabolite identification. IDEOM provides a user-friendly data processing application that automates filtering and identification of metabolite peaks, paying particular attention to common sources of noise and false identifications generated by liquid chromatography–mass spectrometry (LC–MS) platforms. Building on advanced processing tools such as mzMatch and XCMS, it allows users to run a comprehensive pipeline for data analysis and visualization from a graphical user interface within Microsoft Excel, a familiar program for most biological scientists.
Availability and implementation: IDEOM is provided free of charge at http://mzmatch.sourceforge.net/ideom.html, as a macro-enabled spreadsheet (.xlsb). Implementation requires Microsoft Excel (2007 or later). R is also required for full functionality.
Contact: michael.barrett@glasgow.ac.uk
Supplementary Information: Supplementary data are available at Bioinformatics online.
Improving your target-template alignment with MODalign
Authors: Barbato Alessandro , Benkert Pascal , Schwede Torsten , Tramontano Anna , Kosinski Jan 
Published: February 2012

Abstract
Summary: MODalign is an interactive web-based tool aimed at helping protein structure modelers to inspect and manually modify the alignment between the sequences of a target protein and of its template(s). It interactively computes, displays and, upon modification of the target-template alignment, updates the multiple sequence alignments of the two protein families, their conservation score, secondary structure and solvent accessibility values, and local quality scores of the implied three-dimensional model(s). Although it has been designed to simplify the target-template alignment step in modeling, it is suitable for all cases where a sequence alignment needs to be inspected in the context of other biological information.
Availability and implementation: Freely available on the web at http://modorama.biocomputing.it/modalign. Website implemented in HTML and JavaScript with all major browsers supported.
Contact: jan.kosinski@uniroma1.it
Biophysical assessment of aquaporin‐9 as principal facilitative pathway in mouse liver import of glucogenetic glycerol
Authors: Calamita Giuseppe , Gena Patrizia , Ferri Domenico , Rosito Anna , Rojek Aleksandra , Nielsen Søren , Marinelli Raúl A. , Frühbeck Gema , Svelto Maria 
Published: February 2012

AbstractBackground informationLipolytic glycerol, released from adipocytes, flows through the bloodstream to the liver, where its utilisation in supplying hepatocyte gluconeogenesis is rate‐limited by the permeation step. An aquaglyceroporin expressed in hepatocytes, aquaporin‐9 (AQP9), has been often linked to liver uptake of glycerol. However, the truthfulness of this postulation and the potential existence of additional pathways of glycerol import by hepatocytes have never been assessed directly. Here, we define the identity and extent of liver glycerol transport and evaluate the correlation between hepatic AQP9 expression and glycerol permeability (Pgly) in AQP9+/+ wild‐type mice in different nutritional states and circulating insulin levels. The liver Pgly of AQP9 null mice is also assessed.ResultsBy stopped‐flow light scattering, facilitated diffusion of glycerol into hepatocytes was indicated by the low Arrhenius activation energy (3.5 kcal/mol) and strong inhibition by phloretin, an AQP9 blocker, that characterised the transport. Although fasting markedly increased hepatic AQP9, a straight parallelism was seen both in quantitative and time–space terms between Pgly and AQP9 protein in AQP9+/+ mice kept in fed or fasted/refed states. In line with these findings, the highest Pgly (Pgly ≈ 14.0 × 10−6 cm/s at 20°C) at 18‐h fasting coincided with the highest percent of phloretin inhibition (63%). Besides being markedly lower than that in AQP9+/+ mice, the liver Pgly of the AQP9 null mice did not increase during fasting. Reverse‐transcription PCR analysis showed lack of compensation by AQP3 and AQP7, the other known murine glycerol facilitators, in AQP9 null mice.ConclusionsOverall, these results experimentally prove major functional significance for AQP9 in maximising liver glycerol import during states requiring increased glucose production. If any, alternative facilitated pathways would be of minor importance in transporting glucogenetic glycerol into hepatocytes during starvation. Refining the understanding of liver AQP9 in metabolic and energy homeostasis may reveal helpful for therapeutic purposes.
Cancer‐associated orthotopic myofibroblasts stimulates the motility of gastric carcinoma cells
Authors: Fuyuhiro Yuhiko , Yashiro Masakazu , Noda Satoru , Matsuoka Junko , Hasegawa Tsuyoshi , Kato Yukihiro , Sawada Tetsuji , Hirakawa Kosei 
Published: February 2012

Tumor progression has been recognized as the product of evolving crosstalk between cancer cells and the surrounding stromal cells. Cancer‐associated orthotopic myofibroblasts may be linked to the progression of gastric carcinomas. To understand the significance of orthotopic myofibroblasts, we examined the effects of cancer‐associated orthotopic myofibroblasts on the malignant phenotype of gastric cancer cells. Three human gastric cancer cell lines (OCUM‐2MD3, OCUM‐12, MKN‐45) and four human gastric fibroblast cell lines (cancer‐associated orthotopic fibroblast [CaF]‐29, CaF‐33, normal orthotopic fibroblast [NF]‐29, NF‐33) were used. The cancer‐associated orthotopic fibroblast cell lines CaF‐29 and CaF‐33 were established from a tumoral gastric wall, and normal orthotopic fibroblast NF‐29 and NF‐33 were established from a non‐tumoral gastric wall. Fibroblasts that were α‐smooth muscle actin‐positive were defined as myofibroblasts. We examined the effects of cancer‐associated orthotopic myofibroblasts on the aggressiveness of gastric cancer cells by wound‐healing assay, invasion assay, and RT‐PCR. The ratios of myofibroblasts in CaF‐29 (33%) and CaF‐33 (46%) were significantly (P < 0.001) greater than those in NF‐29 (11%) or NF‐33 (13%). Although all four orthotopic fibroblast lines increased the motility of gastric cancer cells, including migration and invasion ability, the motility‐stimulating activity of cancer‐associated fibroblasts (CaF‐29 and CaF‐33) was significantly higher than that of normal fibroblasts (NF‐29 and NF‐33). These motility‐stimulating activities of cancer‐associated orthotopic fibroblasts were downregulated by Smad2 siRNA treatment and anti‐transforming growth factor‐β neutralizing antibody. These findings suggest that cancer‐associated orthotopic myofibroblasts may play an important role in the progression of gastric cancers and that transforming growth factor‐β produced by myofibroblasts may be one of the factors associated with the aggressiveness of gastric carcinoma cells. (Cancer Sci 2012; 103: 797–805)
Epidermal growth factor receptor R521K polymorphism shows favorable outcomes in KRAS wild‐type colorectal cancer patients treated with cetuximab‐based chemotherapy
Authors: Hsieh Yao‐Yu , Tzeng Cheng‐Hwai , Chen Ming‐Huang , Chen Po‐Min , Wang Wei‐Shu 
Published: February 2012

The R521K polymorphism of epidermal growth factor receptor has attenuated affinity in ligand binding and proto‐oncogene induction, which may affect the efficacy of cetuximab. We analyzed the effect of this polymorphism on the outcome of 112 patients with KRAS wild‐type metastatic colorectal carcinoma treated with first‐line cetuximab plus FOLFOX‐4. The associations of this polymorphism with vascular endothelial growth factor (VEGF) expression and clinicopathologic characteristics were also examined. The results showed that the frequencies of the G/G, G/A, and A/A genotypes were 32.1% (n = 36), 42.9% (n = 48), and 25.0% (n = 28), respectively. A marked decrease in VEGF expression levels (66.7% vs 28.9%, P < 0.01) was observed in patients with 521A allele variants (Arg/Lys or Lys/Lys), which were associated with a decreased tumor size (55.6% vs 31.6%, P = 0.02), good histological differentiation (63.9% vs 85.5%, P = 0.01), decreased lymphovascular invasion (69.4% vs 39.5%, P < 0.01), and a higher response rate to cetuximab plus FOLFOX treatment (55.6% vs 78.9%, P = 0.01). In addition, this polymorphism was associated with a longer progression‐free period (P = 0.001) and overall survival (P = 0.001). By multivariate analysis, this polymorphism was also identified as an independent prognostic factor. These data suggest that the R521K polymorphism of epidermal growth factor receptor, by reducing its activation and a consequential downregulation of its target genes, including VEGF, could be a key determinant of an increased response to cetuximab‐based chemotherapy and a longer survival for KRAS wild‐type colorectal carcinoma patients. (Cancer Sci 2012; 103: 791–796)
Ability of non‐invasive intermittent blood pressure monitoring and a continuous non‐invasive arterial pressure monitor (CNAP™) to provide new readings in each 1‐min interval during elective caesarean section under spinal anaesthesia
Authors: McCarthy T. , Telec N. , Dennis A. , Griffiths J. , Buettner A. 
Published: February 2012

SummaryWe compared the ability of automated non‐invasive intermittent oscillometric blood pressure monitoring with a new device, CNAPTM (continuous non‐invasive arterial pressure) to provide a new blood pressure reading in each 1‐min interval between spinal anaesthesia and delivery during caesarean section. We also compared the accuracy of continuous non‐invasive arterial pressure readings with non‐invasive blood pressure measurements before spinal anaesthesia. Fifty‐nine women participated. The non‐invasive and continuous non‐invasive monitors displayed new blood pressure readings in a mean of 82% (11%) and 83% (13%) (p = 0.97) of the one‐minute intervals between spinal anaesthesia and delivery, respectively. Continuous non‐invasive arterial pressure was more likely to fail on two or more consecutive minutes (p = 0.001). From the pre‐spinal readings, the mean bias, defined as non‐invasive – continuous non‐invasive arterial pressure, and limits of agreement (±2SD mean bias) for systolic, diastolic and mean blood pressure respectively were +1.3 (±26.0), −2.9 (±21.8) and +2.6 (±20.4) mmHg. The new monitor has disadvantages compared with conventional non‐invasive intermittent blood pressure monitoring.
Investigation of the haemodynamic effects of exenatide in healthy male subjects
Authors: Mendis Buddhike , Simpson Elizabeth , MacDonald Ian , Mansell Peter 
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Large clinical trials show that chronic use of GLP‐1 agonists cause a fall in blood pressure independent of weight loss. Animal studies have shown acute haemodynamic and vasodilator effects of these drugs. The exact mechanism of the blood pressure drop and acute cardiovascular effects has not been studied in humans.WHAT THIS STUDY ADDS• This study shows that exenatide also has acute haemodynamic effects in humans. This study demonstrates direct vascular effects and potentially direct cardiac effects. This will enable future studies to look at GLP‐1 agonists as aids in the treatment of cardiovascular disease in type 2 diabetes.AIMS In clinical studies of glucagon‐like peptide‐1 (GLP‐1) agonists used in the management of patients with type 2 diabetes, there is often a small accompanying fall in blood pressure. The mechanism underlying this effect is not known, although exenatide, a GLP‐1 mimetic, has acute regional vasodilator properties in rats. We have therefore studied the haemodynamic effects of exenatide in healthy male volunteers.METHODS We compared the effects of a single 10 µg subcutaneous injection of exenatide with placebo in a double‐blind, randomized, crossover study. For 2 h after dosing, haemodynamic measurements were made using a Finometer, venous occlusion plethysmography and Doppler ultrasound. The urine sodium : creatinine excretion ratio was determined.RESULTS At the end of the study when exenatide was compared with placebo, heart rate had risen by a mean of 8.2 (95% CI 4.2, 12.2, P < 0.01) beats min−1, cardiac output by a mean of 1.2 (95% CI 0.42, 20.3, P < 0.05) l min−1 and total peripheral resistance had fallen by 120 (95% CI −8, −233, P < 0.05) dyn s cm−5.There were no differences in blood pressure. The urinary sodium : creatinine ratio was increased by mean 12.4 (95% CI 4.6, 20.2, P < 0.05) mmol mmol−1 when exenatide was compared with placebo.CONCLUSIONS Exenatide has significant haemodynamic effects in healthy volunteers. The results of this study are consistent with exenatide having both vasodilator and natriuretic properties. The vascular changes may contribute to the hypotensive effect of exenatide when used chronically in patients with diabetes.
Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma
Authors: Huang Congfa , Sun Zhijun , Sun Yan , Chen Xinming , Zhu Xiaojie , Fan Chengchao , Liu Bing , Zhao Yifang , Zhang Wenfeng 
Published: February 2012

Huang C, Sun Z, Sun Y, Chen X, Zhu X, Fan C, Liu B, Zhao Y & Zhang W  (2012) Histopathology 60, 793–803Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinomaAims:  We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC).Methods and results:  We studied the expression of CypA, CD147, hypoxia‐inducible factor 1α (HIF‐1α), vascular endothelial growth factor A and C (VEGF‐A and VEGF‐C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF‐1α, VEGF‐A and VEGF‐C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P < 0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF‐1α, VEGF‐A and VEGF‐C. A significant relationship between VEGF‐A and VEGF‐C was also detected (P < 0.01). Patients with overexpression of CypA, CD147, HIF‐1α and VEGF‐C had significantly worse overall survival (P < 0.05) using Kaplan–Meier analysis. Multivariate Cox regression analysis showed that HIF‐1α, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients.Conclusions:  The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC.
Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease
Authors: Soltani Amir , Muller Hans Konrad , Sohal Sukhwinder S , Reid David W , Weston Steve , Wood‐Baker Richard , Walters Eugene Haydn 
Published: February 2012

Soltani A, Muller H K, Sohal S S, Reid D W, Weston S, Wood‐Baker R & Walters E H  (2012) Histopathology 60, 964–970Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same diseaseAims:  This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.Methods and results:  Bronchoscopic biopsies were stained with anti‐collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non‐smoking controls were studied. The Rbm in COPD was fragmented, non‐homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls. Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4–68.5) versus 5.3% (0.0–21.7) versus 1.5% (0.0–15.1), P < 0.001]. The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6–23.0) versus 4.5 (0.0–26.4) versus 4.4 (0.4–8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115–2456) versus 462 (0–3263) versus 426 (32–2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.Conclusions:  The characteristics of Rbm remodelling are quite different in asthma and COPD.
Bcl‐2 and BLIMP‐1 expression predict worse prognosis in gastric diffuse large B cell lymphoma (DLCBL) while other markers for nodal DLBCL are not useful
Authors: Martin‐Arruti Maialen , Vaquero Manuel , Díaz de Otazu Ramón , Zabalza Iñaki , Ballesteros Javier , Roncador Giovanna , García‐Orad Africa 
Published: February 2012

Martin‐Arruti M, Vaquero M, Díaz de Otazu R, Zabalza I, Ballesteros J, Roncador G & García‐Orad A  (2012) Histopathology 60, 785–792Bcl‐2 and BLIMP‐1 expression predict worse prognosis in gastric diffuse large B cell lymphoma (DLCBL) while other markers for nodal DLBCL are not usefulAims:  Previous studies have identified clinicopathological and immunohistochemical differences among diffuse large B cell lymphomas (DLBCL) as a function of disease location. Nevertheless, there is a continuing tendency to generalize the prognostic value of various identified markers without taking into account tumour site. Accordingly, we analysed the prognostic value of several of the immunohistochemical markers that have been proposed for nodal DLBCL in a group of patients with gastric DLBCL.Methods and results:  Using histochemical methods, CD10, Bcl‐6, Gcet1, MUM‐1, Bcl‐2 and BLIMP‐1 expression was investigated in 43 cases of gastric DBLCL. As in nodal DLBCLs, expression of BLIMP‐1, and of Bcl‐2 in non‐germinal centre B cell‐like (non‐GCB) patients, was associated with a worse prognosis. However, unlike nodal DBLCL, there was no significant association of prognosis with expression of CD10, Bcl‐6, Gcet1 or MUM‐1, or with categorization according to Hans or Muris algorithms.Conclusions:  Although most markers of prognosis in nodal DLBCL are not useful indicators for gastric DLBCL, Bcl‐2 or BLIMP‐1 expression does correlate with worse prognosis. These data support the notion that clinicopathological features in DLBCL vary according to the disease location.
Cumulative risk assessment of phthalate exposure of Danish children and adolescents using the hazard index approach
Authors: Søeborg T. , Frederiksen H. , Andersson A. M. 
Published: February 2012

SummaryHuman risk assessment of chemicals is traditionally presented as the ratio between the actual level of exposure and an acceptable level of exposure, with the acceptable level of exposure most often being estimated by appropriate authorities. This approach is generally sound when assessing the risk of individual chemicals. However, several chemicals may concurrently target the same receptor, work through the same mechanism or in other ways induce the same effect(s) in the body. In these cases, cumulative risk assessment should be applied. The present study uses biomonitoring data from 129 Danish children and adolescents and resulting estimated daily intakes of four different phthalates. These daily intake estimates are used for a cumulative risk assessment with anti‐androgenic effects as the endpoint using Tolerable Daily Intake (TDI) values determined by the European Food Safety Authorities (EFSA) or Reference Doses for Anti‐Androgenicity (RfD AA) determined by Kortenkamp and Faust [Int J Androl 33 (2010) 463] as acceptable levels of exposure. United States Environmental Protection Agency Reference Doses (US EPA RfD) could not be used as none of them identifies anti‐androgenic effects as the most sensitive endpoint for the phthalates included in this article. Using the EFSA TDI values, 12 children exceeded the hazard quotient for the sum of di‐n‐butyl phthalate and di‐iso‐butyl phthalate (∑DBP(i+n)) and one child exceeded the hazard quotient for di‐(2‐ethylhexyl)phthalate (DEHP). Nineteen children exceeded the cumulated hazard index for three phthalates. Using the RfD AA values, one child exceeded the hazard quotient for DEHP and the same child exceeded the cumulated hazard index for four phthalates. The EFSA TDI approach thus is more restrictive and identifies ∑DBP(i+n) as the compound(s) associated with the greatest risk, while DEHP is the compound associated with the greatest risk when using the RfD AA approach.
Effect of fermentation on the nutritive value of maize
Authors: Cui Li , Li Da‐jing , Liu Chun‐quan 
Published: February 2012

SummaryThe effects of fermentation on protein, in vitro protein digestibility (IVPD), amino acid, total phenolics, phytic acid and colour values of four maize cultivars (two bi‐colour waxy corn and two super sweet corn), namely Jing Tian Zi Hua Nuo NO. 2, Jing Tian NO. 3, Bright Jean and Su Ke Hua Nuo 2008, were determined and compared with those of their unfermented counterparts. Results showed that fermentation caused significant increase in protein (43.5% largest increase), most kind of amino acid (131.5% largest increase in lysine content) and total phenolic content (23.4% largest increase), but significant reduction in phytic acid content (24.3% largest reduction) of four maize cultivars. The IVPD of four maize cultivars, except Suke2008, did not change significantly. Colour values of two waxy corn were resulted in the increase in a‐values and reduction in L‐values.