bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Thioredoxin-Glutathione Reductase from LarvalTaenia crassiceps(Cysticerci)
Authors: Guevara-Flores Alberto , del Arenal Irene P. , Mendoza-Hernández Guillermo , Pardo Juan Pablo , Flores-Herrera Oscar , Rendón Juan L.
Published: June 2010

Mitochondrial thioredoxin-glutathione reductase was purified from larvalTaenia crassiceps(cysticerci). The preparation showed NADPH-dependent reductase activity with either thioredoxin or GSSG, and was able to perform thiol/disulfide exchange reactions. At25∘Cspecific activities were437  ±  27mU mg-1and840  ±  49mU mg-1with thioredoxin and GSSG, respectively. ApparentKmvalues were0.87  ±  0.04 μM,41  ±  6 μM and19  ±  10 μM for thioredoxin, GSSG and NADPH, respectively. Thioredoxin from eukaryotic sources was accepted as substrate. The enzyme reduced H2O2in a NADPH-dependent manner, although with low catalytic efficiency. In the presence of thioredoxin, mitochondrial TGR showed a thioredoxin peroxidase-like activity. All disulfide reductase activities were inhibited by auranofin, suggesting mTGR is dependent on selenocysteine. The reductase activity with GSSG showed a higher dependence on temperature as compared with the DTNB reductase activity. The variation of the GSSG- and DTNB reductase activities on pH was dependent on the disulfide substrate. Like the cytosolic isoform, mTGR showed a hysteretic kinetic behavior at moderate or high GSSG concentrations, but it was less sensitive to calcium. The enzyme was able to protect glutamine synthetase from oxidative inactivation, suggesting that mTGR is competent to contend with oxidative stress.
The Sensitivity and Specificity of Potassium Hydroxide Smear and Fungal Culture Relative to Clinical Assessment in the Evaluation of Tinea Pedis: A Pooled Analysis
Authors: Levitt Jacob Oren , Levitt Barrie H. , Akhavan Arash , Yanofsky Howard
Published: June 2010

Background. There are relatively few studies published examining the sensitivity and specificity of potassium hydroxide (KOH) smear and fungal culture examination of tinea pedis. Objective. To evaluate the sensitivity and specificity of KOH smear and fungal culture for diagnosing tinea pedis. Methods. A pooled analysis of data from five similarly conducted bioequivalence trials for antifungal drugs was performed. Data from 460 patients enrolled in the vehicle arms of these studies with clinical diagnosis of tinea pedis supported by positive fungal culture were analyzed 6 weeks after initiation of the study to determine the sensitivity and specificity of KOH smear and fungal culture. Results. Using clinical assessment as the gold standard, the sensitivities for KOH smear and culture were 73.3% (95% CI: 66.3 to 79.5%) and 41.7% (34.6 to 49.1%), respectively. The respective specificities for culture and KOH smear were 77.7% (72.2 to 82.5%) and 42.5% (36.6 to 48.6%). Conclusion. KOH smear and fungal culture are complementary diagnostic tests for tinea pedis, with the former being the more sensitive test of the two, and the latter being more specific.
Antidiabetic Activity ofVinca roseaExtracts in Alloxan-Induced Diabetic Rats
Authors: Ahmed Mohammed Fazil , Kazim Syed Mohammed , Ghori Syed Safiullah , Mehjabeen Syeda Sughra , Ahmed Shaik Rasheed , Ali Shaik Mehboob , Ibrahim Mohammed
Published: June 2010

The present study was carried out to evaluate the antidiabetic activity ofVinca roseamethanolic whole plant extracts in alloxan induced diabetic rats for 14 days. The methanolic whole plant extract at high dose (500 mg/kg) exhibited significant anti-hyperglycemic activity than whole plant extract at low dose (300 mg/kg) in diabetic rats. The methanolic extracts also showed improvement in parameters like body weight and lipid profile as well as regeneration ofβ-cells of pancreas in diabetic rats. Histopathological studies reinforce the healing of pancreas, by methanolicVinca roseaextracts, as a possible mechanism of their antidiabetic activity.
Controversies in the Management of Endometrial Carcinoma
Authors: Zhang Ying , Wang Jian
Published: June 2010

Endometrial carcinoma is the most common type of female genital tract malignancy. Although endometrial carcinoma is a low grade curable malignancy, the condition of the disease can range from excellent prognosis with high curability to aggressive disease with poor outcome. During the last 10 years many researches have provided some new valuable data of optimal treatments for endometrial carcinoma. Progression in diagnostic imaging, radiation delivery systems, and systemic therapies potentially can improve outcomes while minimizing morbidity. Firstly, total hysterectomy and bilateral salphingo‐oophorectomy is the primary operative procedure. Pelvic lymhadenectomy is performed in most centers on therapeutic and prognostic grounds and to individualize adjuvant treatment. Women with endometrial carcinoma can be readily segregated intraoperatively into “low‐risk” and “high‐risk” groups to better identify those women who will most likely benefit from thorough lymphadenectomy. Secondly, adjuvant therapies have been proposed for women with endometrial carcinoma postoperatively. Postoperative irradiation is used to reduce pelvic and vaginal recurrences in high risk cases. Chemotherapy is emerging as an important treatment modality in advanced endometrial carcinoma. Meanwhile the availability of new hormonal and biological agents presents new opportunities for therapy.
Spectrum of Disease and Outcome among Patients with Acute Diverticulitis
Authors: Mäkelä Jyrki T. , Kiviniemi Heikki O. , Laitinen Seppo T.
Published: June 2010

Background: This study was designed to evaluate the natural history of patients admitted for acute diverticulitis. Methods: Nine hundred and seventy-seven patients admitted to Oulu University Hospital for acute symptoms of diverticular disease during the 20-year period from 1986 to 2005 were identified using a database. Results: Six hundred and ninety-five patients were admitted for uncomplicated diverticulitis and 282 for complicated diverticulitis. The patients admitted for uncomplicated diverticulitis were younger than the others and 66% of them were admitted only once. The number of admissions preceding perforation was higher in the 1980s, and the number of admissions was unrelated to the degree of perforation or the outcome of the patients. The annual prevalence of sigmoid diverticular perforation increased from 2.6/100,000 in 1986 to 4.2/100,000 in 2005. Seventy (10%) of the 695 patients admitted for the first time for acute diverticulitis underwent urgent surgery during the same admission and 66 (9%) had elective surgery during a later admission. Overall hospital mortality was 2.3%, being 1% among those admitted for acute diverticulitis and 5.5% among those admitted for diverticular perforation. Two hundred and thirty-four (42%) of the 555 nonoperated patients with acute diverticulitis developed a recurrent episode of diverticulitis. The course of recurrent disease was similar to the primary episode. Conclusion: Two or more preceding admissions for acute diverticulitis do not warrant sigmoid resection after diverticulitis. Young patients do not have a greater risk of complicated diverticulitis than older ones.
Effectiveness of Neoadjuvant Radiotherapy in the Treatment of Locally Advanced Rectal Cancer: A Single-Center Experience in 263 Patients
Authors: Bisceglia Giovanni , Mastrodonato Nicola , Rucci Beniamino , Corsa Pietro , Parisi Salvatore , Tardio Berardino , di Sebastiano P.
Published: June 2010

Aim: To determine the frequency of local recurrence (LR) and distant recurrence (DR) with 5-year survival analysis. Methods: Patients with T3–T4 rectal cancer located within 10 cm from the anal verge. Radiotherapy protocol: 36 Gy, delivered in 12 daily doses of 3 Gy each for 5 days/week, followed by surgery after a 2-week break. Results: 263 patients were recruited. Radiotherapy was well tolerated. None of the patients broke off treatment. Complete histological response was 3% and maximum radio-induced downstaging 31.4%. Overall complication rate was 25.8% and direct radio-induced complications 0.4%. Mean duration of treatment was 35.7 days. In 172 patients with a minimum follow-up of 5 years, the rate of LR was 6.0% and DR 24.4%. Five-year overall survival was 70.2%, overall specific survival 78.0%, disease-free survival 70.7%, LR-free specific survival 92.9%, and DR-free specific survival 73.5%. Conclusions: In our experience, local disease control was achieved in 94% of patients. Any changes in our treatment protocols will aim at improving results in terms of LR and DR. In view of the four-fold higher rate of DR as compared to LR, improvement of DR can be defined as the challenge for the future.
Treatment of Metachronous and Simultaneous Liver Metastases of Pancreatic Cancer
Authors: Dünschede F. , Will L. , von Langsdorf C. , Möhler M. , Galle P.R. , Otto G. , Vahl C.F. , Junginger T.
Published: June 2010

Aim: Patients were analyzed who underwent treatment of liver metastases from pancreatic cancer. Methods: Selection criteria were the possibility of R0 resection of the primary and/or the liver metastases, no other sites of metastases, and the presentation of liver metastases. A comparison of treatment by surgery versus chemotherapy regarding overall survival and disease-free interval was performed. Results: Between 1996 and 2008, a total number of 23 patients were retrospectively identified from a prospective database of 193 cases of pancreatic cancer. In 14 cases, liver metastases were found simultaneously, and in 9 cases metachronously, fulfilling the abovementioned selection criteria. Of these, 13 patients underwent surgery and 10 were treated by gemcitabine. There were no differences in survival in patients with synchronous liver metastases of pancreatic cancer treated by resection of the primary combined with partial hepatectomy versus treatment by gemcitabine (8 vs. 11 months). In patients with metachronous liver metastases, the median survival was increased after liver resection compared to patients who were treated with gemcitabine (31 vs. 11 months). Conclusions: Simultaneous resection of pancreatic cancer and liver metastases cannot be recommended. Resection of metachronous liver metastases of pancreatic cancer seems to improve survival in highly selected patients.
Genetic and Pharmacologic Hydrogen Sulfide Therapy Attenuates Ischemia-Induced Heart Failure in Mice
Authors: Calvert John W. , Elston Marah , Nicholson Chad K. , Gundewar Susheel , Jha Saurabh , Elrod John W. , Ramachandran Arun , Lefer David J.
Published: June 2010

Background—

Hydrogen sulfide (H
2
S) is an endogenous signaling molecule with potent cytoprotective effects. The present study evaluated the therapeutic potential of H
2
S in murine models of heart failure.

Methods and Results—

Heart failure was induced by subjecting mice either to permanent ligation of the left coronary artery for 4 weeks or to 60 minutes of left coronary artery occlusion followed by reperfusion for 4 weeks. Transgenic mice with cardiac-restricted overexpression of the H
2
S-generating enzyme cystathione γ-lyase (αMHC-CGL-Tg
+
) displayed a clear protection against left ventricular structural and functional impairment as assessed by echocardiography in response to ischemia-induced heart failure, as well as improved survival in response to permanent myocardial ischemia. Exogenous H
2
S therapy (Na
2
S; 100 μg/kg) administered at the time of reperfusion (intracardiac) and then daily (intravenous) for the first 7 days after myocardial ischemia also protected against the structural and functional deterioration of the left ventricle by attenuating oxidative stress and mitochondrial dysfunction. Additional experiments aimed at elucidating some of the protective mechanisms of H
2
S therapy found that 7 days of H
2
S therapy increased the phosphorylation of Akt and increased the nuclear localization of 2 transcription factors, nuclear respiratory factor 1 and nuclear factor-E2-related factor (Nrf2), that are involved in increasing the levels of endogenous antioxidants, attenuating apoptosis, and increasing mitochondrial biogenesis.

Conclusions—

The results of the present study suggest that either the administration of exogenous H
2
S or the modulation of endogenous H
2
S production may be of therapeutic benefit in the treatment of ischemia-induced heart failure.
Long-Term Localized High-Frequency Electric Stimulation Within the Myocardial Infarct
Authors: Mukherjee Rupak , Rivers William T. , Ruddy Jean Marie , Matthews Robert G. , Koval Christine N. , Plyler Rebecca A. , Chang Eileen I. , Patel Risha K. , Kern Christine B. , Stroud Robert E. , Spinale Francis G.
Published: June 2010

Background—

Disruption of the balance between matrix metalloproteinases (MMP) and MMP inhibitors (TIMPs) within a myocardial infarct (MI) contributes to left ventricular wall thinning and changes in regional stiffness at the MI region. This study tested the hypothesis that a targeted regional approach through localized high-frequency stimulation (LHFS) using low-amplitude electric pulses instituted within a formed MI scar would alter MMP/TIMP levels and prevent MI thinning.

Methods and Results—

At 3 weeks after MI, pigs were randomized for LHFS (n=7; 240 bpm, 0.8 V, 0.05-ms pulses) or were left unstimulated (UNSTIM; n=10). At 4 weeks after MI, left ventricular wall thickness (echocardiography; 0.89±0.07 versus 0.67±0.08 cm;
P
<0.05) and regional stiffness (piezoelectric crystals; 14.70±2.08 versus 9.11±1.24;
P
<0.05) were higher with LHFS than in UNSTIM. In vivo interstitial MMP activity (fluorescent substrate cleavage; 943±59 versus 1210±72 U;
P
<0.05) in the MI region was lower with LHFS than in UNSTIM. In the MI region, MMP-2 levels were lower and TIMP-1 and collagen levels were higher with LHFS than in UNSTIM (all
P
<0.05). Transforming growth factor-β receptor 1 and phosphorylated SMAD-2/3 levels within the MI region were higher with LHFS than in UNSTIM. Electric stimulation (4 Hz) of isolated fibroblasts resulted in reduced MMP-2 and MT1-MMP levels but increased TIMP-1 levels compared with unstimulated fibroblasts.

Conclusions—

These unique findings demonstrate that LHFS of the MI region altered left ventricular wall thickness and material properties, likely as a result of reduced regional MMP activity. Thus, LHFS may provide a novel means to favorably modify left ventricular remodeling after MI.
Reference Values of Pulse Wave Velocity in Healthy Children and Teenagers
Authors: Reusz George S. , Cseprekal Orsolya , Temmar Mohamed , Kis Éva , Cherif Abdelghani Bachir , Thaleb Abddelhalim , Fekete Andrea , Szabó Attila J. , Benetos Athanase , Salvi Paolo
Published: June 2010

Carotid-femoral pulse wave velocity is an established method for characterizing aortic stiffness, an individual predictor of cardiovascular mortality in adults. Normal pulse wave velocity values for the pediatric population derived from a large data collection have yet to be available. The aim of this study was to create a reference database and to characterize the factors determining pulse wave velocity in children and teenagers. Carotid-femoral pulse wave velocity was measured by applanation tonometry. Reference tables from pulse wave velocities obtained in 1008 healthy subjects (aged between 6 and 20 years; 495 males) were generated using a maximum-likelihood curve-fitting technique for calculating SD scores in accordance with the skewed distribution of the raw data. Effects of sex, age, height, weight, blood pressure, and heart rate on pulse wave velocity were assessed. Sex-specific reference tables and curves for age and height are presented. Pulse wave velocity correlated positively (
P
<0.001) with age, height, weight, and blood pressure while correlating negatively with heart rate. After multiple regression analysis, age, height, and blood pressure remained major predictors of pulse wave velocity. This study, involving >1000 children, is the first to provide reference values for pulse wave velocity in children and teenagers, thereby constituting a suitable tool for longitudinal clinical studies assessing subgroups of children who are at long-term risk of cardiovascular disease.
The Climatology of the Middle Atmosphere in a Vertically Extended Version of the Met Office’s Climate Model. Part II: Variability
Authors: Osprey Scott M. , Gray Lesley J. , Hardiman Steven C. , Butchart Neal , Bushell Andrew C. , Hinton Tim J.
Published: June 2010

Stratospheric variability is examined in a vertically extended version of the Met Office global climate model. Equatorial variability includes the simulation of an internally generated quasi-biennial oscillation (QBO) and semiannual oscillation (SAO). Polar variability includes an examination of the frequency of sudden stratospheric warmings (SSW) and annular mode variability. Results from two different horizontal resolutions are also compared. Changes in gravity wave filtering at the higher resolution result in a slightly longer QBO that extends deeper into the lower stratosphere. At the higher resolution there is also a reduction in the occurrence rate of sudden stratospheric warmings, in better agreement with observations. This is linked with reduced levels of resolved waves entering the high-latitude stratosphere. Covariability of the tropical and extratropical stratosphere is seen, linking the phase of the QBO with disturbed NH winters, although this linkage is sporadic, in agreement with observations. Finally, tropospheric persistence time scales and seasonal variability for the northern and southern annular modes are significantly improved at the higher resolution, consistent with findings from other studies.
Coupled Land–Atmosphere Intraseasonal Variability of the West African Monsoon in a GCM
Authors: Lavender Sally L. , Taylor Christopher M. , Matthews Adrian J.
Published: June 2010

Recent observational studies have suggested a role for soil moisture and land–atmosphere coupling in the 15-day westward-propagating mode of intraseasonal variability in the West African monsoon. This hypothesis is investigated with a set of three atmospheric general circulation model experiments. 1) When soil moisture is fully coupled with the atmospheric model, the 15-day mode of land–atmosphere variability is clearly identified. Precipitation anomalies lead soil moisture anomalies by 1–2 days, similar to the results from satellite observations. 2) To assess whether soil moisture is merely a passive response to the precipitation, or an active participant in this mode, the atmospheric model is forced with a 15-day westward-propagating cycle of regional soil moisture anomalies based on the fully coupled mode. Through a reduced surface sensible heat flux, the imposed wet soil anomalies induce negative low-level temperature anomalies and increased pressure (a cool high). An anticyclonic circulation then develops around the region of wet soil, enhancing northward moisture advection and precipitation to the west. Hence, in a coupled framework, this soil moisture–forced precipitation response would provide a self-consistent positive feedback on the westward-propagating soil moisture anomaly and implies an active role for soil moisture. 3) In a final sensitivity experiment, soil moisture is again externally prescribed but with all intraseasonal fluctuations suppressed. In the absence of soil moisture variability there are still pronounced surface sensible heat flux variations, likely due to cloud changes, and the 15-day westward-propagating precipitation signal is still present. However, it is not as coherent as in the previous experiments when interaction with soil moisture was permitted. Further examination of the soil moisture forcing experiment in GCM experiment 2 shows that this precipitation mode becomes phase locked to the imposed soil moisture anomalies. Hence, the 15-day westward-propagating mode in the West African monsoon can exist independently of soil moisture; however, soil moisture and land–atmosphere coupling act to feed back on the atmosphere and further enhance and organize it.
Wake Measurements of a Multi-MW Wind Turbine with Coherent Long-Range Pulsed Doppler Wind Lidar
Authors: Käsler Yvonne , Rahm Stephan , Simmet Rudolf , Kühn Martin
Published: June 2010

Long-range Doppler wind light detection and ranging (lidar) measurements at a wind turbine were carried out for the first time. The turbine was of the type Areva M5000 and is located at a site near the coastline in Bremerhaven, in the northern part of Germany. This wind turbine is the prototype for the German offshore test site “alpha ventus” and has a rated power of 5 MW. Information about the ambient wind field before and after this multimegawatt wind turbine was obtained. In this paper the measurement technique is discussed and the results of measurements in the diurnal layer and in the stable nocturnal boundary layer are shown. The main focus of this work is to determine the reduction of the wind speed at certain distances downstream from the rotor.
The Role of ERK1/2 Signaling Pathway in Nef Protein Upregulation of the Expression of the Intercellular Adhesion Molecule 1 in Endothelial Cells
Authors: Yang Fan  , Chaoqi Liu  , Xiaolin Qin  , Yanlin Wang  , Yu Han  , Yongqin Zhou
Published: June 2010

Human immunodeficiency virus (HIV)-infected patients have increased rates of atherosclerotic cardiovascular diseases because the highly active antiretroviral therapy (HAART) decreased the morbidity and mortality of the disease. Endothelial dysfunction is possibly the most plausible link between HIV infection and related expression of cell adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on the endothelial cells. HIV-1 accessory protein negative regulate factor (Nef) has been shown to be very important for high virus replication and disease progression. Nef could upregulate the expression of ICAM-1 in the pathogenesis of HIV infection. Here, we provide evidence that the HIV-1 Nef can transcriptionally induce the expression of ICAM-1 in stable expressed Nef vascular endothelial cells. Nef-induced ICAM-1 upregulation requires the activation of the downstream kinase extracellular signal-regulated kinase (ERK). Flow cytometry (FCM) results showed that the percentage of ICAM-1 positive cells in Nef-expressed cells and control cells was (35.3% ± 2.2%) and (12.5% ± 0.8%), respectively (P < .01). Furthermore, inhibition of Nef activity by ERK mitogen-activated protein kinase (MAPK) inhibitor effectively blocked ICAM-1 upregulation, suggesting that ERK MAPK activation is an important initiating event in Nef-mediated ICAM-1 expression in Nef-expressed cells. These data demonstrate an important signaling event of Nef in HIV-1 pathogenesis.
Contemporary geographies of exclusion III: To assist or punish?
Authors: Herbert Steve
Published: June 2010

Processes of inclusion and exclusion raise profound questions. As scholars of exclusion, we need to determine where to train our focus; as citizens, we need to determine whether and how exclusion is deleterious. When exclusion is pursued as a form of punishment, it is most readily open to question. This review of recent literature makes clear that scholarship on exclusion is robust, multifaceted, and necessary.
Techniques for Suture Anchor Removal in Shoulder Surgery
Authors: Grutter Paul W. , McFarland Edward G. , Zikria Bashir A. , Dai Zhigang , Petersen Steve A.
Published: June 2010

Although suture anchor complications after arthroscopic shoulder surgery are uncommon, they can be devastating, such as articular cartilage or bone loss secondary to a dislodged or prominent suture anchor. Proper insertion of the anchor is the most important factor in the prevention of this complication, but if a complication occurs, prompt recognition and treatment are important to prevent damage to the shoulder. The goals were to (1) discuss strategies for preventing or dealing with dislodged or prominent suture anchors and (2) introduce techniques for removal of these implants.
Korean Apparel Manufacturing Industry: Exploration From the Industry Life Cycle Perspective
Authors: Ha-Brookshire Jung E. , Lee Yuri
Published: June 2010

Under the industry life cycle framework, the study (a) explored Korean apparel manufacturing firms’ business activity profiles (what firms do) and competitive advantages (what they have or do to compete) as described by firms; and (b) examined the relationships between business activity profiles and competitive advantages. Based on content analysis, canonical correlation analysis, and correspondence analysis of 200 Korean apparel manufacturing firms’ Web sites, the study found that the Korean apparel manufacturing industry showed consistent characteristics of the mature or declining phase of the industry life cycle. The majority of these firms were engaged in value-added activities such as retailing and product development with an emphasis on brand, quality, and customer service. Results also showed the three clusters of Korean apparel manufacturing firms, Domestic Manufacturers, Foreign Manufacturers, and Retailers, all of which had different competitive advantages. The study concluded with contributions and implications of the results.
Facts, Fiction, and Figures of the Sarcoptes scabiei Infection
Authors: Orrico, Josephine A. , Krause-Parello Cheryl A.
Published: June 2010

Today scabies, an ectoparasitic skin disease caused by the mite Sarcoptes scabiei variety hominis, is estimated to infect over 300 million humans worldwide. Scabies most frequently occurs among children and young adults. Outbreaks in child care facilities and schools are common. Scabies affects all socioeconomic classes and races. Students presenting with a possible outbreak of scabies in the school setting must be referred by the school nurse to a medical provider for diagnosis and treatment because scabies is highly contagious and can be spread by skin contact. This article will provide school nurses with the history, etiology, mode of transmission, symptoms, and the recommended treatment of a S. scabiei infection. Implications for school nursing practice will be discussed.
A very popular blog: The internet and the possibilities of publicity
Authors: Malin Brenton J.
Published: June 2010

This article outlines two modes of publicity, a publicity of promotion and a publicity of openness, and then considers their implications for traditional broadcast versus online communications. Although the structure of the internet makes it particularly good at developing a publicity of openness, the economics, regulatory structure and technology of the traditional broadcast media make them far better at developing promotional publicity. I trace a series of examples that demonstrate this inequality and discuss the implications of this disparity for the economics of attention. Ultimately, I argue, discussions of the democratic possibilities of the internet must take account of the relative lack of promotional publicity online.
Prediction of GTP interacting residues, dipeptides and tripeptides in a protein from its evolutionary information
Authors: Chauhan Jagat S , Mishra Nitish K , Raghava Gajendra PS
Published: June 2010

Background

Guanosine triphosphate (GTP)-binding proteins play an important role in regulation of G-protein. Thus prediction of GTP interacting residues in a protein is one of the major challenges in the field of the computational biology. In this study, an attempt has been made to develop a computational method for predicting GTP interacting residues in a protein with high accuracy (Acc), precision (Prec) and recall (Rc).

Result

All the models developed in this study have been trained and tested on a non-redundant (40% similarity) dataset using five-fold cross-validation. Firstly, we have developed neural network based models using single sequence and PSSM profile and achieved maximum Matthews Correlation Coefficient (MCC) 0.24 (Acc 61.30%) and 0.39 (Acc 68.88%) respectively. Secondly, we have developed a support vector machine (SVM) based models using single sequence and PSSM profile and achieved maximum MCC 0.37 (Prec 0.73, Rc 0.57, Acc 67.98%) and 0.55 (Prec 0.80, Rc 0.73, Acc 77.17%) respectively. In this work, we have introduced a new concept of predicting GTP interacting dipeptide (two consecutive GTP interacting residues) and tripeptide (three consecutive GTP interacting residues) for the first time. We have developed SVM based model for predicting GTP interacting dipeptides using PSSM profile and achieved MCC 0.64 with precision 0.87, recall 0.74 and accuracy 81.37%. Similarly, SVM based model have been developed for predicting GTP interacting tripeptides using PSSM profile and achieved MCC 0.70 with precision 0.93, recall 0.73 and accuracy 83.98%.

Conclusion

These results show that PSSM based method performs better than single sequence based method. The prediction models based on dipeptides or tripeptides are more accurate than the traditional model based on single residue. A web server "GTPBinder"http://www.imtech.res.in/raghava/gtpbinder/based on above models has been developed for predicting GTP interacting residues in a protein.
Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation
Authors: Peng Shih Chi , Wong David Shan Hill , Tung Kai Che , Chen Yan Yu , Chao Chun Cheih , Peng Chien Hua , Chuang Yung Jen , Tang Chuan Yi
Published: June 2010

Background

Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Diverse cellular stimuli create a wide variety of transcription factor activities through signal transduction pathways, resulting in different gene expression patterns. Understanding the relationship between external stimuli and the corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach is needed to integrate experimental data and theoretical hypotheses to identify the physiological consequences of environmental stimuli.

Results

We proposed a systematic approach that combines forward and reverse engineering to link the signal transduction cascade with the gene responses. To demonstrate the feasibility of our strategy, we focused on linking the NF-κB signaling pathway with the inflammatory gene regulatory responses because NF-κB has long been recognized to play a crucial role in inflammation. We first utilized forward engineering (Hybrid Functional Petri Nets) to construct the NF-κB signaling pathway and reverse engineering (Network Components Analysis) to build a gene regulatory network (GRN). Then, we demonstrated that the corresponding IKK profiles can be identified in the GRN and are consistent with the experimental validation of the IKK kinase assay. We found that the time-lapse gene expression of several cytokines and chemokines (TNF-α, IL-1, IL-6, CXCL1, CXCL2 and CCL3) is concordant with the NF-κB activity profile, and these genes have stronger influence strength within the GRN. Such regulatory effects have highlighted the crucial roles of NF-κB signaling in the acute inflammatory response and enhance our understanding of the systemic inflammatory response syndrome.

Conclusion

We successfully identified and distinguished the corresponding signaling profiles among three microarray datasets with different stimuli strengths. In our model, the crucial genes of the NF-κB regulatory network were also identified to reflect the biological consequences of inflammation. With the experimental validation, our strategy is thus an effective solution to decipher cross-talk effects when attempting to integrate new kinetic parameters from other signal transduction pathways. The strategy also provides new insight for systems biology modeling to link any signal transduction pathways with the responses of downstream genes of interest.
Chromosome phylogeny of the subfamily Pitheciinae (Platyrrhini, Primates) by classic cytogenetics and chromosome painting
Authors: Finotelo Liane FM , Amaral Paulo JS , Pieczarka Julio C , de Oliveira Edivaldo HC , Pissinati Alcides , Neusser Michaela , Müller Stephan , Nagamachi Cleusa Y
Published: June 2010

Background

The New World monkey (Platyrrhini) subfamily Pitheciinae is represented by the genera Pithecia, Chiropotes and Cacajao. In this work we studied the karyotypes of Pithecia irrorata (2n = 48) and Cacajao calvus rubicundus (2n = 45 in males and 2n = 46 in females) by G- and C-banding, NOR staining and chromosome painting using human and Saguinus oedipus whole chromosome probes. The karyotypes of both species were compared with each other and with Chiropotes utahicki (2n = 54) from the literature.

Results

Our results show that members of the Pitheciinae have conserved several chromosome forms found in the inferred ancestral Platyrrhini karyotype (associations of human homologous segments 3a/21, 5/7a, 2b/16b, 8a/18, 14/15a and 10a/16a). Further, the monophyly of this subfamily is supported by three chromosomal synapomorphies (2a/10b, an acrocentric 15/14 and an acrocentric human 19 homolog). In addition, each species presents several autapomorphies. From this data set we established a chromosomal phylogeny of Pitheciinae, resulting in a single most parsimonious tree.

Conclusions

In our chromosomal phylogeny, the genus Pithecia occurred in a more basal position close to the inferred ancestor of Platyrrhini, while C. c. rubicundus and C. utahicki are closely related and are linked by exclusive synapomorphies.
High resolution mapping of trypanosomosis resistance loci Tir 2 and Tir 3 using F12 advanced intercross lines with major locus Tir 1 fixed for the susceptible allele
Authors: Nganga Joseph K , Soller Morris , Iraqi Fuad A
Published: June 2010

Background

Trypanosomosis is the most economically important disease constraint to livestock productivity in Africa. A number of trypanotolerant cattle breeds are found in West Africa, and identification of the genes conferring trypanotolerance could lead to effective means of genetic selection for trypanotolerance. In this context, high resolution mapping in mouse models are a promising approach to identifying the genes associated with trypanotolerance. In previous studies, using F2 C57BL/6J × A/J and C57BL/6J × BALB/cJ mouse resource populations, trypanotolerance QTL were mapped within a large genomic intervals of 20-40 cM to chromosomes MMU17, 5 and 1, and denoted Tir 1, Tir 2 and Tir 3 respectively. Subsequently, using F6 C57BL/6J × A/J and C57BL/6J × BALB/cJ F6 advanced intercross lines (AIL), Tir 1 was fine mapped to a confidence interval (CI) of less than 1 cM, while Tir 2 and Tir 3, were mapped within 5-12 cM. Tir 1 represents the major trypanotolerance QTL.

Results

In order to improve map resolutions of Tir 2 and Tir 3, an F12 C57BL/6J × A/J AIL population fixed for the susceptible alleles at Tir 1 QTL was generated. An F12 C57BL/6J × A/J AIL population, fixed for the resistant alleles at Tir 1 QTL was also generated to provide an additional estimate of the gene effect of Tir 1. The AIL populations homozygous for the resistant and susceptible Tir 1 alleles and the parental controls were challenged with T. congolense and followed for survival times over 180 days. Mice from the two survival extremes of the F12 AIL population fixed for the susceptible alleles at Tir 1 were genotyped with a dense panel of microsatellite markers spanning the Tir 2 and Tir 3 genomic regions and QTL mapping was performed. Tir 2 was fine mapped to less than 1 cM CI while Tir 3 was mapped to three intervals named Tir 3a, Tir 3b and Tir 3c with 95% confidence intervals (CI) of 6, 7.2 and 2.2 cM, respectively.

Conclusions

The mapped QTL regions encompass genes that are vital to innate immune response and can be potential candidate genes for the underlying QTL.
Does D3 surgery offer a better survival outcome compared to D1 surgery for gastric cancer? A result based on a hospital population of two decades as taking D2 surgery for reference
Authors: Zhang Hao , Liu Caigang , Wu Di , Meng Yi , Song Ruonan , Lu Ping , Wang Shubao
Published: June 2010

Background

We conducted a retrospective study in our hospital in which we compared D1 with D3 through D2 lymphadenectomy for gastric cancer in terms of morbidity, postoperative mortality, long-term survival after surgery.

Methods

567 patients who were performed curative intent between 1980 and 2003 were enrolled. 187 in the D1 group, 189 in the D2 group and 191 in the D3 group. Every procedure was verified by pathological analyses. The primary endpoints were 5-year overall survival.

Results

Median follow-up periods were 36 months and 60 months for D1 group and D3 group. Overall 5-year survival rate was significantly higher in patients underwent D3 surgery than in those performed D1 surgery (37.4% vs 48.7%; log-rank, p = 0.027). For the cases followed up to 120 months, the 10-year overall survival rate was 29% (95% CI, 22.1% to 35.9%) for the D1 group and 33.7% (95% CI, 26.6% to 40.8%) for the D3 group (log-rank, p = 0.005).

Conclusions

D1 surgery should be operated only for patients with Borrmann I disease. As D3 gastrectomy is associated with low mortality and adequate survival times when performed in selected institutions that have had sufficient experience with the operation and with postoperative management, we recommend D3 lymphadenectomy for patients with curable gastric cancer.
Peri-operative chemotherapy for the treatment of resectable liver metastases from colorectal cancer: A systematic review and meta-analysis of randomized trials
Authors: Wieser Martina , Sauerland Stefan , Arnold Dirk , Schmiegel Wolff , Reinacher-Schick Anke
Published: June 2010

Background

The role of peri-operative chemotherapy in patients with resected stage IV colorectal cancer (CRC) remains to be defined. This study was aimed at evaluating the effectiveness of peri-operative chemotherapy in patients with resected stage IV CRC by performing a meta-analysis of relevant trials.

Methods

We performed a literature search to identify trials comparing patients with stage IV CRC receiving peri-operative chemotherapy and surgery with patients undergoing surgery alone. The hazard ratio (HR) was estimated to assess any survival advantage of peri-operative chemotherapy.

Results

Eight trials conducted on a total of 1174 patients were identified by a literature search. In these trials, HR estimates suggested that peri-operative chemotherapy yielded no survival advantage over surgery alone (HR, 0.94; 95%CI, 0.8-1.10; p = 0.43). In a subset analysis on intra-arterial chemotherapy alone, no survival benefit was evident (HR, 1.0; 95% CI, 0.84-1.21; p = 0.96; I2 = 30%), whereas in the trials involving systemic chemotherapy, the difference between the groups approached statistical significance (HR, 0.74; 95% CI, 0.53-1.04; p = 0.08; I2 = 0%). Both peri-operative treatment groups had a significant recurrence-free survival benefit (HR, 0.78; 95% CI, 0.65-0.95; P = 0.01 for hepatic arterial infusion; and HR, 0.75; 95% CI, 0.62-0.91; p = 0.003 for systemic therapy). The toxicities of chemotherapy were acceptable in most trials.

Conclusions

This is the first meta-analysis demonstrating the importance of peri-operative chemotherapy in the treatment of resected stage IV CRC. Although the results must be carefully interpreted because of some limitations, critical issues were identified that must be resolved by future studies.
Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer
Authors: Gjerde Jennifer , Geisler Jürgen , Lundgren Steinar , Ekse Dagfinn , Varhaug Jan Erik , Mellgren Gunnar , Steen Vidar M , Lien Ernst A
Published: June 2010

Background

The cytochrome P450 (CYP) enzymes 2C19, 2D6, and 3A5 are responsible for converting the selective estrogen receptor modulator (SERM), tamoxifen to its active metabolites 4-hydroxy-tamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen). Inter-individual variations of the activity of these enzymes due to polymorphisms may be predictors of outcome of breast cancer patients during tamoxifen treatment. Since tamoxifen and estrogens are both partly metabolized by these enzymes we hypothesize that a correlation between serum tamoxifen and estrogen levels exists, which in turn may interact with tamoxifen on treatment outcome. Here we examined relationships between the serum levels of tamoxifen, estrogens, follicle-stimulating hormone (FSH), and also determined the genotypes of CYP2C19, 2D6, 3A5, and SULT1A1 in 90 postmenopausal breast cancer patients.

Methods

Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Estrogen and FSH levels were determined using a sensitive radio- and chemiluminescent immunoassay, respectively.

Results

We observed significant correlations between the serum concentrations of tamoxifen,N-dedimethyltamoxifen, and tamoxifen-N-oxide and estrogens (p < 0.05). The genotype predicted CYP2C19 activity influenced the levels of both tamoxifen metabolites and E1.

Conclusions

We have shown an association between tamoxifen and its metabolites and estrogen serum levels. An impact of CYP2C19 predicted activity on tamoxifen, as well as estrogen kinetics may partly explain the observed association between tamoxifen and its metabolites and estrogen serum levels. Since the role of estrogen levels during tamoxifen therapy is still a matter of debate further prospective studies to examine the effect of tamoxifen and estrogen kinetics on treatment outcome are warranted.
Prevention of mother-to-child transmission of HIV infection: Views and perceptions about swallowing nevirapine in rural Lilongwe, Malawi
Authors: O'Gorman Deirdre A , Nyirenda Lot J , Theobald Sally J
Published: June 2010

Background

In 2006 the World Health Organization described the status of prevention of mother to child transmission (PMTCT) service implementation as unacceptable, with an urgent need for a renewed public health approach to improve access. For PMTCT to be effective it needs to be accessible, acceptable and affordable; however research in Africa into accessibility, uptake and acceptability of PMTCT services has been predominately urban based and usually focusing on women who deliver in hospitals. The importance of involving other community members to strengthen both PMTCT uptake and adherence, and to support women emotionally, has been advocated. Urban men's and rural traditional birth attendants' (TBAs) involvement have improved uptake of HIV testing and of nevirapine.

Methods

A qualitative study was carried out in a rural district of Malawi's central region to explore the views about and perceptions of PMTCT antiretroviral treatment. Semi-structured interviews and focus group discussions were held with antenatal and postnatal women, fathers, grandmothers, TBAs, community leaders and PMTCT health workers.

Results

Two broad themes of findings emerged: those that relate to the hospital PMTCT service, and those that relate to the community. Trust in the hospital was strong, but distance, transport costs and perceived harsh, threatening health worker attitudes were barriers to access. Grandmothers were perceived to have influence on the management of labour, unlike fathers, but both were suggested as key people to ensure that babies are brought to the hospital for nevirapine syrup. TBAs were seen as powerful, local, and important community members, but some as uneducated.

Conclusion

PMTCT was seen as a community issue in which more than the mother alone can be involved. To support access to PMTCT, especially for rural women, there is need for further innovation and implementation research on involving TBAs in some aspects of PMTCT services, and in negotiating with women which community members, if any, they would like to support them in ensuring that newborn babies receive nevirapine.
Primary care capitation payments in the UK. An observational study
Authors: Rhys Gwion , Beerstecher Hendrik J , Morgan Claire L
Published: June 2010

Background

In 2004 an allocation formula for primary care services was introduced in England and Wales so practices would receive equitable pay. Modifications were made to this formula to enable local health authorities to pay practices.

Similar pay formulae were introduced in Scotland and Northern Ireland, but these are unique to the country and therefore could not be included in this study.

Objective

To examine the extent to which the Global Sum, and modifications to the original formula, determine practice funding.

Methods

The allocation formula determines basic practice income, the Global Sum. We compared practice Global Sum entitlements using the original and the modified allocation formula calculations.

Practices receive an income supplement if Global Sum payments were below historic income in 2004. We examined current overall funding levels to estimate what the effect will be when the income supplements are removed.

Results

Virtually every Welsh and English practice (97%) received income supplements in 2004. Without the modifications to the formula only 72% of Welsh practices would have needed supplements. No appreciable change would have occurred in England.

The formula modifications increased the Global Sum for 99.5% of English practices, while it reduced entitlement for every Welsh practice.

In 2008 Welsh practices received approximately £6.15 (9%) less funding per patient per year than an identical English practice. This deficit will increase to 11.2% when the Minimum Practice Income Guarantee is abolished.

Conclusions

Identical practices in different UK countries do not receive equitable pay. The pay method disadvantages Wales where the population is older and has higher health needs.
The approximate entropy of the electromyographic signals of tremor correlates with the osmotic fragility of human erythrocytes
Authors: Mansur Paulo HG , Cury Lacordaire KP , Leite José OB , Pereira Adriano A , Penha-Silva Nilson , Andrade Adriano O
Published: June 2010

Background

The main problem of tremor is the damage caused to the quality of the life of patients, especially those at more advanced ages. There is not a consensus yet about the origins of this disorder, but it can be examined in the correlations between the biological signs of aging and the tremor characteristics.

Methods

This work sought correlations between the osmotic fragility of erythrocytes and features extracted from electromyographic (EMG) activity resulting from physiological tremor in healthy patients (N = 44) at different ages (24-87 years). The osmotic fragility was spectrophotometrically evaluated by the dependence of hemolysis, provided by the absorbance in 540 nm (A

54

o), on the concentration of NaCl. The data were adjusted to curves of sigmoidal regression and characterized by the half transition point (H

50
), amplitude of lysis transition (dx) and values of A

540
in the curve regions that characterize the presence of lysed (A

1
) and preserved erythrocytes (A

2
). The approximate entropy was estimated from EMG signals detected from the extensor carpi ulnaris muscle during the movement of the hand of subjects holding up a laser pen towards an Archimedes spiral, fixed in a whiteboard. The evaluations were carried out with the laser pen at rest, at the center of the spiral, and in movement from the center to the outside and from outside to the center. The correlations among the parameters of osmotic fragility, tremor and age were tested.

Results

Negative correlations with age were found for A

1
and dx. With the hand at rest, a positive correlation with H

50
was found for the approximate entropy. Negative correlations with H

50
were found for the entropy with the hand in movement, as from the center to the outside or from the outside to the center of the spiral.

Conclusion

In healthy individuals, the increase in the erythrocyte osmotic fragility was associated with a decrease in the approximate entropy for rest tremor and with an increase of the entropy for movement tremor. This suggests that the neuromuscular degeneration associated with tremor entails also the mechanisms involved in the breakdown of structural homeostasis of the erythrocyte membrane.