bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale prediction of protein-protein interactions from structures
Authors: Hue Martial , Riffle Michael , Vert Jean-Philippe , Noble William S 
Published: March 2010

AbstractBackgroundThe prediction of protein-protein interactions is an important step toward the elucidation of protein functions and the understanding of the molecular mechanisms inside the cell. While experimental methods for identifying these interactions remain costly and often noisy, the increasing quantity of solved 3D protein structures suggests thatin silicomethods to predict interactions between two protein structures will play an increasingly important role in screening candidate interacting pairs. Approaches using the knowledge of the structure are presumably more accurate than those based on sequence only. Approaches based on docking protein structures solve a variant of this problem, but these methods remain very computationally intensive and will not scale in the near future to the detection of interactions at the level of an interactome, involving millions of candidate pairs of proteins.ResultsHere, we describe a computational method to predict efficientlyin silicowhether two protein structures interact. This yes/no question is presumably easier to answer than the standard protein docking question, "How do these two protein structures interact?" Our approach is to discriminate between interacting and non-interacting protein pairs using a statistical pattern recognition method known as a support vector machine (SVM). We demonstrate that our structure-based method performs well on this task and scales well to the size of an interactome.ConclusionsThe use of structure information for the prediction of protein interaction yields significantly better performance than other sequence-based methods. Among structure-based classifiers, the SVM algorithm, combined with the metric learning pairwise kernel and the MAMMOTH kernel, performs best in our experiments.
Neuropeptidomic analysis of the embryonic Japanese quail diencephalon
Authors: Scholz Birger , Alm Henrik , Mattsson Anna , Nilsson Anna , Kultima Kim , Savitski Mikhail M , Fälth Maria , Sköld Karl , Brunström Björn , Andren Per E , Dencker Lennart 
Published: March 2010

AbstractBackgroundEndogenous peptides such as neuropeptides are involved in numerous biological processes in the fully developed brain but very little is known about their role in brain development. Japanese quail is a commonly used bird model for studying sexual dimorphic brain development, especially adult male copulatory behavior in relation to manipulations of the embryonic endocrine system. This study uses a label-free liquid chromatography mass spectrometry approach to analyze the influence of age (embryonic days 12 vs 17), sex and embryonic day 3 ethinylestradiol exposure on the expression of multiple endogenous peptides in the developing diencephalon.ResultsWe identified a total of 65 peptides whereof 38 were sufficiently present in all groups for statistical analysis. Age was the most defining variable in the data and sex had the least impact. Most identified peptides were more highly expressed in embryonic day 17. The top candidates for EE2exposure and sex effects were neuropeptide K (downregulated by EE2in males and females), gastrin-releasing peptide (more highly expressed in control and EE2exposed males) and gonadotropin-inhibiting hormone related protein 2 (more highly expressed in control males and displaying interaction effects between age and sex). We also report a new potential secretogranin-2 derived neuropeptide and previously unknown phosphorylations in the C-terminal flanking protachykinin 1 neuropeptide.ConclusionsThis study is the first larger study on endogenous peptides in the developing brain and implies a previously unknown role for a number of neuropeptides in middle to late avian embryogenesis. It demonstrates the power of label-free liquid chromatography mass spectrometry to analyze the expression of multiple endogenous peptides and the potential to detect new putative peptide candidates in a developmental model.
Bilateral occipital lobe infarction with altitudinal field loss following radiofrequency cardiac catheter ablation
Authors: Luu Susie T , Lee Andrew W , Chen Celia S 
Published: March 2010

Abstract

Background
Bilateral stroke following radiofrequency catheter ablation is an unusual complication and may result in bilateral altitudinal visual field defects. Bilateral altitudinal visual field defects usually result from prechiasmal pathology causing damage to both retinas or optic nerves and rarely from bilateral symmetric damage to the post chiasmal visual pathways.

Case presentation
A 48-year-old man complained of visual disturbance on wakening following radiofrequency catheter ablation. The patient had a CHADS score of 1 pre-operatively and no complications were noted intra-operatively. Examination revealed a bilateral superior altitudinal defect and MRI of the brain showed multifocal areas of infarction predominantly involving the occipital lobes which correlated to with the visual deficits.

Conclusion
While the risk of thromboembolism and perioperative stroke during radiofrequency catheter ablation is small, it is not insignificant.
Role of the VEGF ligand to receptor ratio in the progression of mismatch repair-proficient colorectal cancer
Authors: Eppenberger Manuela , Zlobec Inti , Baumhoer Daniel , Terracciano Luigi , Lugli Alessandro 
Published: March 2010

Abstract

Background
The VEGF family of ligands and receptors are intimately involved in tumor angiogenesis, lymphangiogenesis and metastasis. The evaluation of VEGF ligand/receptor ratios may provide a more profound understanding of the involvement of these proteins in colorectal tumour progression. The aim of this study was to elucidate the role of the VEGF ligand/receptor ratios on tumour progression and metastasis in patients with mismatch repair-proficient colorectal cancer.

Methods
Immunohistochemistry for VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR1, VEGFR2 and VEGF3 was carried out on 387 mismatch repair-proficient colorectal cancers using a tissue microarray. Evaluation of immunoreactivity was performed semi-quantitatively and the ligand/receptor expression ratio was obtained.

Results
An increased VEGF-A/VEGFR1 ratio, VEGF-A and VEGFR1 was linked to the presence of peritumoral lymphocytic inflammation at the invasive front (p = 0.032; p = 0.005; p = 0.032, respectively). VEGFR1 expression was related to poorer outcome in multivariable analysis with pT stage, pN stage, vascular invasion, and post-operative therapy. A higher ratio of VEGF-A/VEGFR2 was linked to advanced TNM stage (p = 0.005) while VEGF-A and VEGFR2 were elevated in tumours with an infiltrating tumour growth pattern (p = 0.006; p = 0.014; p = 0.006). No effect of VEGF-A/VEGFR2, VEGF-A or VEGFR2 on survival time was noted.

Conclusions
Our findings highlight an involvement of VEGF-A, VEGR1 and VEGFR2 in events occurring at the invasive tumour front and a potential prognostic role of VEGFR1 expression in mismatch repair-proficient colorectal cancers. The VEGF-A ligand to VEGFR1 or VEGFR2 ratio may represent an alternative evaluation system for identifying patients with poorer clinical outcome.
Socioeconomic deprivation, urban-rural location and alcohol-related mortality in England and Wales
Authors: Erskine Sally , Maheswaran Ravi , Pearson Tim , Gleeson Dermot 
Published: March 2010

Abstract

Background
Many causes of death are directly attributable to the toxic effects of alcohol and deaths from these causes are increasing in the United Kingdom. The aim of this study was to investigate variation in alcohol-related mortality in relation to socioeconomic deprivation, urban-rural location and age within a national context.

Methods
An ecological study design was used with data from 8797 standard table wards in England and Wales. The methodology included using the Carstairs Index as a measure of socioeconomic deprivation at the small-area level and the national harmonised classification system for urban and rural areas in England and Wales. Alcohol-related mortality was defined using the National Statistics definition, devised for tracking national trends in alcohol-related deaths. Deaths from liver cirrhosis accounted for 85% of all deaths included in this definition. Deaths from 1999-2003 were examined and 2001 census ward population estimates were used as the denominators.

Results
The analysis was based on 28,839 deaths. Alcohol-related mortality rates were higher in men and increased with increasing age, generally reaching peak levels in middle-aged adults. The 45-64 year age group contained a quarter of the total population but accounted for half of all alcohol-related deaths. There was a clear association between alcohol-related mortality and socioeconomic deprivation, with progressively higher rates in more deprived areas. The strength of the association varied with age. Greatest relative inequalities were seen amongst people aged 25-44 years, with relative risks of 4.73 (95% CI 4.00 to 5.59) and 4.24 (95% CI 3.50 to 5.13) for men and women respectively in the most relative to the least deprived quintiles. People living in urban areas experienced higher alcohol-related mortality relative to those living in rural areas, with differences remaining after adjustment for socioeconomic deprivation. Adjusted relative risks for urban relative to rural areas were 1.35 (95% CI 1.20 to 1.52) and 1.13 (95% CI 1.01 to 1.25) for men and women respectively.

Conclusions
Large inequalities in alcohol-related mortality exist between sub-groups of the population in England and Wales. These should be considered when designing public health policies to reduce alcohol-related harm.
Antibodies against multiple merozoite surface antigens of the human malaria parasite Plasmodium falciparum inhibit parasite maturation and red blood cell invasion
Authors: Woehlbier Ute , Epp Christian , Hackett Fiona , Blackman Michael J , Bujard Hermann 
Published: March 2010

AbstractBackgroundPlasmodium falciparummerozoites expose at their surface a large protein complex, which is composed of fragments of merozoite surface protein 1 (MSP-1; called MSP-183, MSP-130, MSP-138, and MSP-142) plus associated processing products of MSP-6 and MSP-7. During erythrocyte invasion this complex, as well as an integral membrane protein called apical membrane antigen-1 (AMA-1), is shed from the parasite surface following specific proteolysis. Components of the MSP-1/6/7 complex and AMA-1 are presently under development as malaria vaccines.MethodsThe specificities and effects of antibodies directed against MSP-1, MSP-6, MSP-7 on the growth of blood stage parasites were studied using ELISA and the pLDH-assay. To understand the mode of action of these antibodies, their effects on processing of MSP-1 and AMA-1 on the surface of merozoites were investigated.ResultsAntibodies targeting epitopes located throughout the MSP-1/6/7 complex interfere with shedding of MSP-1, and as a consequence prevent erythrocyte invasion. Antibodies targeting the MSP-1/6/7 complex have no effect on the processing and shedding of AMA-1 and, similarly, antibodies blocking the shedding of AMA-1 do not affect cleavage of MSP-1, suggesting completely independent functions of these proteins during invasion. Furthermore, some epitopes, although eliciting highly inhibitory antibodies, are only poorly recognized by the immune system when presented in the structural context of the intact antigen.ConclusionsThe findings reported provide further support for the development of vaccines based on MSP-1/6/7 and AMA-1, which would possibly include a combination of these antigens.
Cytosolic group IVa phospholipase A2 mediates IL-8/CXCL8-induced transmigration of human polymorphonuclear leukocytes in vitro
Authors: Meliton Angelo Y , Muñoz Nilda M , Meliton Lucille N , Binder David C , Osan Christopher M , Zhu Xiangdong , Dudek Steven M , Leff Alan R 
Published: March 2010

AbstractBackgroundCytosolic gIVaPLA2is a critical enzyme in the generation of arachidonate metabolites and in induction of β2-integrin adhesion in granulocytes. We hypothesized that gIVaPLA2activation also is an essential downstream step forpost adhesivemigration of PMNin vitro.MethodsMigration of PMNs caused by IL-8/CXCL8 was assessed using a transwell migration chamber. PMNs were pretreated with two structurally unrelated inhibitors of gIVaPLA2, arachidonyl trifluoromethylketone (TFMK) or pyrrophenone, prior to IL-8/CXCL8 exposure. The fraction of migrated PMNs present in the lower chamber was measured as total myeloperoxidase content. GIVaPLA2enzyme activity was analyzed using [14C-PAPC] as specific substrate F-actin polymerization and cell structure were examined after rhodamine-phalloidin staining.ResultsIL-8/CXCL8-induced migration of PMNs was elicited in concentration- and time-dependent manner. Time-related phosphorylation and translocation of cytosolic gIVaPLA2to the nucleus was observed for PMNs stimulated with IL-8/CXCL8 in concentration sufficient to cause upstream phosphorylation of MAPKs (ERK-1/2 and p38) and Akt/PKB. Inhibition of gIVaPLA2corresponded to the magnitude of blockade of PMN migration. Neither AA nor LTB4secretion was elicited following IL-8/CXCL8 activation. In unstimulated PMNs, F-actin was located diffusely in the cytosol; however, a clear polarized morphology with F-actin-rich ruffles around the edges of the cell was observed after activation with IL-8/CXCL8. Inhibition of gIVaPLA2blocked change in cell shape and migration caused by IL-8/CXCL8 but did not cause F-actin polymerization or translocation of cytosolic F-actin to inner leaflet of the PMN membrane.ConclusionWe demonstrate that IL-8/CXCL8 causes a) phosphorylation and translocation of cytosolic gIVaPLA2to the nucleus, b) change in cell shape, c) polymerization of F-actin, and d) chemoattractant/migration of PMN in vitro. Inhibition of gIVaPLA2blocks the deformability and subsequent migration of PMNs caused by IL-8/CXCL8. Our data suggest that activation of gIVaPLA2is an essential step in PMN migrationin vitro.
Kimura's disease with eosinophilic panniculitis - treated with cyclosporine: a case report
Authors: Maleki Davood , Sayyah Alireza , Rahimi-Rad Mohammad Hossein , Gholami Nasrin 
Published: March 2010

Abstract
Kimura's disease is a rare, benign, slow growing chronic inflammatory swelling with a predilection for the head and neck region and almost always with peripheral blood eosinophilia and elevated serum IgE levels. Here, we report a 25-year-old male patient with asthma, Reynaud phenomenon, eosinophilic panniculitis, bilateral inguinal lymphadenopathy and peripheral blood eosinophilia.
He responded initially to oral prednisolone with the subsidence of peripheral blood eosinophilia, asthma and the Reynaud phenomenon. But with tapering of prednisolone symptoms reappeared and hereby he was treated with cyclosporine. He has been symptom free for 6 months of follow up while taking cyclosporine 25 mg orally per day. Eosinophilia has resolved. This case shows that in addition to previously reported associations, Kimura disease may be associated with eosinophilic panniculitis and that cyclosporine could be effective in its treatment.
Choline PET based dose-painting in prostate cancer - Modelling of dose effects
Authors: Niyazi Maximilian , Bartenstein Peter , Belka Claus , Ganswindt Ute 
Published: March 2010

Abstract

Background
Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed.

Methods
Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed.

Results
Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition).

Discussion
Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the assumption of high detection rates and low initial TCP values the TCP gain has been shown to be relevant.

Conclusions
Based on the employed assumptions, specific dose escalation to choline PET positive areas within the prostate may increase the local control rates. Due to the lack of exact PET sensitivity and prostate α/β parameter, no firm conclusions can be made. Small variations may completely abrogate the clinical benefit of a SIB based on choline PET imaging.
The internal state of medium spiny neurons varies in response to different input signals
Authors: Qi Zhen , Miller Gary W , Voit Eberhard O 
Published: March 2010

Abstract

Background
Parkinson's disease, schizophrenia, Huntington's chorea and drug addiction are manifestations of malfunctioning neurons within the striatum region at the base of the human forebrain. A key component of these neurons is the protein DARPP-32, which receives and processes various types of dopamine and glutamate inputs and translates them into specific biochemical, cellular, physiological, and behavioral responses. DARPP-32's unique capacity of faithfully converting distinct neurotransmitter signals into appropriate responses is achieved through a complex phosphorylation-dephosphorylation system that evades intuition and predictability.

Results
To gain deeper insights into the functioning of the DARPP-32 signal transduction system, we developed a dynamic model that is robust and consistent with available clinical, pharmacological, and biological observations. Upon validation, the model was first used to explore how different input signal scenarios are processed by DARPP-32 and translated into distinct static and dynamic responses. Secondly, a comprehensive perturbation analysis identified the specific role of each component on the system's signal transduction ability.

Conclusions
Our study investigated the effects of various patterns of neurotransmission on signal integration and interpretation by DARPP-32 and showed that the DARPP-32 system has the capability of discerning surprisingly many neurotransmission scenarios. We also screened out potential mechanisms underlying this capability of the DARPP-32 system. This type of insight deepens our understanding of neuronal signal transduction in normal medium spiny neurons, sheds light on neurological disorders associated with the striatum, and might aid the search for intervention targets in neurological diseases and drug addiction.
Limited educational attainment and radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis using data from the Johnston County (North Carolina) Osteoarthritis Project
Authors: Callahan Leigh F , Shreffler Jack , Siaton Bernadette C , Helmick Charles G , Schoster Britta , Schwartz Todd A , Chen Jiu-Chiuan , Renner Jordan B , Jordan Joanne M 
Published: March 2010

Abstract
Introduction
Applying a cross-sectional analysis to a sample of 2,627 African-American and Caucasian adults aged ≥ 45 years from the Johnston County Osteoarthritis Project, we studied the association between educational attainment and prevalence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis.

Methods
Age- and race-adjusted associations between education and osteoarthritis outcomes were assessed by gender-stratified logistic regression models, with additional models adjusting for body mass index, knee injury, smoking, alcohol use, and occupational factors.

Results
In an analysis of all participants, low educational attainment (<12 years) was associated with higher prevalence of four knee osteoarthritis outcomes (unilateral and bilateral radiographic and symptomatic osteoarthritis). Women with low educational attainment had 50% higher odds of having radiographic knee osteoarthritis and 65% higher odds of symptomatic knee osteoarthritis compared with those with higher educational attainment (≥ 12 years), by using fully adjusted models. In the subset of postmenopausal women, these associations tended to be weaker but little affected by adjustment for hormone replacement therapy. Men with low educational attainment had 85% higher odds of having symptomatic knee osteoarthritis by using fully adjusted models, but the association with radiographic knee osteoarthritis was explained by age.

Conclusions
After adjustment for known risk factors, educational attainment, as an indicator of socioeconomic status, is associated with symptomatic knee osteoarthritis in both men and women and with radiographic knee osteoarthritis in women.
Mechanical ventilation with high tidal volume induces inflammation in patients without lung disease
Authors: Pinheiro de Oliveira Roselaine , Hetzel Marcio Pereira , dos Anjos Silva Mauro , Dallegrave Daniele , Friedman Gilberto 
Published: March 2010

Abstract
Introduction
Mechanical ventilation (MV) with high tidal volumes may induce or aggravate lung injury in critical ill patients. We compared the effects of a protective versus a conventional ventilatory strategy, on systemic and lung production of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in patients without lung disease.

Methods
Patients without lung disease and submitted to mechanical ventilation admitted to one trauma and one general adult intensive care unit of two different university hospitals were enrolled in a prospective randomized-control study. Patients were randomized to receive MV either with tidal volume (VT) of 10 to 12 ml/kg predicted body weight (high VT group) (n = 10) or with VT of 5 to 7 ml/kg predicted body weight (low VT group) (n = 10) with an oxygen inspiratory fraction (FIO2) enough to keep arterial oxygen saturation >90% with positive end-expiratory pressure (PEEP) of 5 cmH2O during 12 hours after admission to the study. TNF-α and IL-8 concentrations were measured in the serum and in the bronchoalveolar lavage fluid (BALF) at admission and after 12 hours of study observation time.

Results
Twenty patients were enrolled and analyzed. At admission or after 12 hours there were no differences in serum TNF-α and IL-8 between the two groups. While initial analysis did not reveal significant differences, standardization against urea of logarithmic transformed data revealed that TNF-α and IL-8 levels in bronchoalveolar lavage (BAL) fluid were stable in the low VT group but increased in the high VT group (P = 0.04 and P = 0.03). After 12 hours, BALF TNF-α (P = 0.03) and BALF IL-8 concentrations (P = 0.03) were higher in the high VT group than in the low VT group.

Conclusions
The use of lower tidal volumes may limit pulmonary inflammation in mechanically ventilated patients even without lung injury.

Trial Registration
Clinical Trial registration: NCT00935896