bluuebunny/crossref_metadata_2025_split huggingface dataset:
KATP Channel Subunits in Rat Dorsal Root Ganglia: Alterations by Painful Axotomy
Authors: Zoga Vasiliki , Kawano Takashi , Liang Mei-Ying , Bienengraeber Martin , Weihrauch Dorothee , McCallum Bruce , Gemes Geza , Hogan Quinn , Sarantopoulos Constantine 
Published: January 2010

Background: ATP-sensitive potassium (KATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal KATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we characterized the distribution of the KATP channel subunits in rat DRG, and determined their alterations by painful axotomy using RT-PCR, immunohistochemistry and electron microscopy. Results: PCR demonstrated Kir6.1, Kir6.2, SUR1 and SUR2 transcripts in control DRG neurons. Protein expression for all but Kir6.1 was confirmed by Western blots and immunohistochemistry. Immunostaining of these subunits was identified by fluorescent and confocal microscopy in plasmalemmal and nuclear membranes, in the cytosol, along the peripheral fibers, and in satellite glial cells. Kir6.2 co-localized with SUR1 subunits. Kir6.2, SUR1, and SUR2 subunits were identified in neuronal subpopulations, categorized by positive or negative NF200 or CGRP staining. KATP current recorded in excised patches was blocked by glybenclamide, but preincubation with antibody against SUR1 abolished this blocking effect of glybenclamide, confirming that the antibody targets the SUR1 protein in the neuronal plasmalemmal membrane. In the myelinated nerve fibers we observed anti-SUR1 immunostaining in regularly spaced funneled-shaped structures. These structures were identified by electron microscopy as Schmidt-Lanterman incisures (SLI) formed by the Schwann cells. Immunostaining against SUR1 and Kir6.2 colocalized with anti-Caspr at paranodal sites. DRG excised from rats made hyperalgesic by spinal nerve ligation exhibited similar staining against Kir6.2, SUR1 or SUR2 as DRG from controls, but showed decreased prevalence of SUR1 immunofluorescent NF200 positive neurons. In DRG and dorsal roots proximal to axotomy SLI were smaller and showed decreased SUR1 immunofluorescence. Conclusions: We identified Kir6.2/SUR1 and Kir6.2/SUR2 KATP channels in rat DRG neuronal somata, peripheral nerve fibers, and glial satellite and Schwann cells, in both normal state and after painful nerve injury. This is the first report of KATP channels in paranodal sites adjacent to nodes of Ranvier and in the SLI of the Schwann cells. After painful axotomy KATP channels are downregulated in large, myelinated somata and also in SLI, which are also of smaller size compared to controls. Because KATP channels may have diverse functional roles in neurons and glia, further studies are needed to explore the potential of KATP channels as targets of therapies against neuropathic pain and neurodegeneration.
The B-VITAGE trial: A randomized trial of homocysteine lowering treatment of depression in later life
Authors: Ford Andrew H , Flicker Leon , McCaul Kieran , van Bockxmeer Frank , Hegarty Sarah , Hirani Varsha , Fenner Stephen , Almeida Osvaldo P 
Published: January 2010

Abstract

Background
Depression is a leading cause of disability worldwide and depressive symptoms are common in later life. Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine (tHcy), but the results of randomized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6, B12 and folate benefits depressive symptoms. We designed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6, B12 and folate increases the efficacy of standard antidepressant treatment.

Methods/Design
The B-VITAGE trial is a 12-month randomized, double-blind, placebo-controlled trial of daily citalopram (20 to 40 mg) plus B12(0.4 mg), B6 (25 mg) and folic acid (2 mg) or citalopram (20 to 40 mg) plus placebo for the treatment of depression in later life. The trial aims to recruit over 300 older adults with major depression (DSM-IV) and has been powered to detect the impact of an intervention associated with moderate effect size. Depressive symptoms will be rated with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial has two main outcomes of interest: a reduction of 50% or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12, 26 and 52 according to DSM-IV criteria. We hypothesize that subjects randomly allocated to the vitamin arm of the study will be more likely to show a clinically significant improvement and achieve and maintain remission of symptoms at 12, 26 and 52 weeks. Secondary outcomes of interest include compliance with treatment, reduction in the severity of depressive symptoms, switching to different antidepressants, the use of non-pharmacological antidepressant treatments, response to treatment according to MTHFRC677T genotype, and changes in cognitive function over 52 weeks.

Conclusions
The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to standard antidepressant treatment. We anticipate that our findings will have implications for clinical practice and health policy development.

Trial Registration
The trial is registered with the Australian Clinical Trials Registry, trial number (())ACTRN12609000256279.
Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa
Authors: Shibeko Alexey M , Lobanova Ekaterina S , Panteleev Mikhail A , Ataullakhanov Fazoil I 
Published: January 2010

Abstract

Background
Blood coagulation is a complex network of biochemical reactions, which is peculiar in that it is time- and space-dependent, and has to function in the presence of rapid flow. Recent experimental reports suggest that flow plays a significant role in its regulation. The objective of this study was to use systems biology techniques to investigate this regulation and to identify mechanisms creating a flow-dependent switch in the coagulation onset.

Results
Using a detailed mechanism-driven model of tissue factor (TF)-initiated thrombus formation in a two-dimensional channel we demonstrate that blood flow can regulate clotting onset in the model in a threshold-like manner, in agreement with existing experimental evidence. Sensitivity analysis reveals that this is achieved due to a combination of the positive feedback of TF-bound factor VII activation by activated factor X (Xa) and effective removal of factor Xa by flow from the activating patch depriving the feedback of "ignition". The level of this trigger (i.e. coagulation sensitivity to flow) is controlled by the activity of tissue factor pathway inhibitor.

Conclusions
This mechanism explains the difference between red and white thrombi observed in vivo at different shear rates. It can be speculated that this is a special switch protecting vascular system from uncontrolled formation and spreading of active coagulation factors in vessels with rapidly flowing blood.
Chronic constipation due to presacral teratoma in a 36-year-old woman: a case report
Authors: Paramythiotis Daniel , Papavramidis Theodossis S , Michalopoulos Antonios , Papadopoulos Vassilios N , Apostolidis Stylianos , Televantou Despoina , Hytiroglou Prodromos 
Published: January 2010

Abstract

Introduction
Teratomas of the sacrococcygeal area are usually diagnosed in infancy and are rarely seen in adults.

Case presentation
We report the case of a 36-year-old Greek woman experiencing chronic constipation due to a benign presacral teratoma. Imaging examinations showed a pelvic mass without evidence of malignancy. An ovoid tumour with a maximum dimension of 6 cm was surgically removed. A histologic examination revealed a mature cystic teratoma. Two years after surgery, the patient is well, with no evidence of recurrence and no constipation.

Conclusion
Sacrococcygeal teratomas are rare in adults. A high index of suspicion is important in making an early diagnosis. Rectal examination and radiologic evaluation are also valuable.
Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus
Authors: Voisin Veronique , Legault Philippe , Ospina Diana Paulina Salazar , Ben-David Yaacov , Rassart Eric 
Published: January 2010

Abstract

Background
Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias.

Methods
To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus.

Results
The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines.
We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease.

Conclusions
Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.
RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis
Authors: Zheng Xiufen , Suzuki Motohiko , Zhang Xusheng , Ichim Thomas E , Zhu Fei , Ling Hong , Shunnar Aminah , Wang Michael H , Garcia Bertha , Inman Robert D , Min Wei-Ping 
Published: January 2010

Abstract
Introduction
We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40.

Methods
Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses.

Results
Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells.

Conclusions
These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity.
Phase II Trial of a Trimodality Regimen for Stage III Non–Small-Cell Lung Cancer Using Chemotherapy As Induction Treatment With Concurrent Hyperfractionated Chemoradiation With Carboplatin and Paclitaxel Followed by Subsequent Resection: A Single-Center Study
Authors: Friedel Godehard , Budach Wilfried , Dippon Juergen , Spengler Werner , Eschmann Susanne Martina , Pfannenberg Christina , Al-Kamash Fawaz , Walles Thorsten , Aebert Hermann , Kyriss Thomas , Veit Stefanie , Kimmich Martin , Bamberg Michael , Kohlhaeufl Martin , Steger Volker , Hehr Thomas 
Published: January 2010

Purpose We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. Patients and Methods Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. Conclusion Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.
Overall Survival Analysis of a Phase II Randomized Controlled Trial of a Poxviral-Based PSA-Targeted Immunotherapy in Metastatic Castration-Resistant Prostate Cancer
Authors: Kantoff Philip W. , Schuetz Thomas J. , Blumenstein Brent A. , Glode L. Michael , Bilhartz David L. , Wyand Michael , Manson Kelledy , Panicali Dennis L. , Laus Reiner , Schlom Jeffrey , Dahut William L. , Arlen Philip M. , Gulley James L. , Godfrey Wayne R. 
Published: January 2010

Purpose Therapeutic prostate-specific antigen (PSA) –targeted poxviral vaccines for prostate cancer have been well tolerated. PROSTVAC-VF treatment was evaluated for safety and for prolongation of progression-free survival (PFS) and overall survival (OS) in a randomized, controlled, and blinded phase II study. Patients and Methods In total, 125 patients were randomly assigned in a multicenter trial of vaccination series. Eligible patients had minimally symptomatic castration-resistant metastatic prostate cancer (mCRPC). PROSTVAC-VF comprises two recombinant viral vectors, each encoding transgenes for PSA, and three immune costimulatory molecules (B7.1, ICAM-1, and LFA-3). Vaccinia-based vector was used for priming followed by six planned fowlpox-based vector boosts. Patients were allocated (2:1) to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor or to control empty vectors plus saline injections. Results Eighty-two patients received PROSTVAC-VF and 40 received control vectors. Patient characteristics were similar in both groups. The primary end point was PFS, which was similar in the two groups (P = .6). However, at 3 years post study, PROSTVAC-VF patients had a better OS with 25 (30%) of 82 alive versus 7 (17%) of 40 controls, longer median survival by 8.5 months (25.1 v 16.6 months for controls), an estimated hazard ratio of 0.56 (95% CI, 0.37 to 0.85), and stratified log-rank P = .0061. Conclusion PROSTVAC-VF immunotherapy was well tolerated and associated with a 44% reduction in the death rate and an 8.5-month improvement in median OS in men with mCRPC. These provocative data provide preliminary evidence of clinically meaningful benefit but need to be confirmed in a larger phase III study.
Understanding the role of coping in the development of depressive symptoms: Symptom specificity, gender differences, and cross‐cultural applicability
Authors: Auerbach Randy P. , Abela John R. Z. , Zhu Xiongzhao. , Yao Shuqiao. 
Published: January 2010

Objectives. The primary aim examined whether coping deficits, a greater tendency to utilize maladaptive as opposed to adaptive coping strategies, was associated with increases in depressive symptoms following negative events. The secondary goals examined: the common vulnerability hypothesis, sex differences, and the cross‐cultural generalizability.Design. Following the initial assessment, Canadian adolescents completed three follow‐up assessments every 6 weeks. The Chinese adolescents completed an initial assessment and six follow‐up assessments occurring monthly.Methods. At Time 1, 150 Canadian and 397 Chinese adolescents completed self‐report measures assessing depressive symptoms, anxious symptoms, negative events, and coping. During each of the follow‐up assessments, participants completed self‐report measures assessing depressive symptoms, anxious symptoms, and negative events.Results. In both samples, higher levels of coping deficits were associated with increases in depressive, but not anxious, symptoms following negative events. Gender differences did not emerge.Conclusions. The present study provides a theoretically driven model to examine the impact of broad‐based coping on the development of depressive symptoms.
Differences of Multiple Fibonacci Numbers
Authors: Alpert Hannah 
Published: January 2010

AbstractWe show that every integer can be written uniquely as a sum of Fibonacci numbers and their additive inverses, such that every two terms of the same sign differ in index by at least 4 and every two terms of different sign differ in index by at least 3. Furthermore, there is no way to use fewer terms to write a number as a sum of Fibonacci numbers and their additive inverses. This is an analogue of the Zeckendorf representation.
An Interspecific Plant Hybrid Shows Novel Changes in Parental Splice Forms of Genes for Splicing Factors
Authors: Scascitelli Moira , Cognet Marie , Adams Keith L 
Published: January 2010

AbstractInterspecific hybridization plays an important role in plant adaptive evolution and speciation, and the process often results in phenotypic novelty. Hybrids can show changes in genome structure and gene expression compared with their parents including chromosomal rearrangments, changes in cytosine methylation, up- and downregulation of gene expression, and gene silencing. Alternative splicing (AS) is a fundamental aspect of the expression of many genes. However alternative splicing patterns have not been examined in multiple genes in an interspecific plant hybrid compared with its parents. Here we studied alternative splicing patterns in an interspecific Populus hybrid and its parents by assaying 40 genes using reverse transcription PCR. Most of the genes showed identical alternative splicing patterns between the parents and the hybrid. We found new alternative splicing variants present in the hybrid in two SR genes involved in the regulation of splicing and alternative splicing. The novel alternative splicing patterns included changes in donor and acceptor sites to create a new exon in one allele of PtRSZ22 in the hybrid and retention of an intron in both alleles of PtSR34a.1 in the hybrid, with effects on the function of the corresponding truncated proteins, if present. Our results suggest that novel alternative splicing patterns are present in a small percentage of genes in hybrids, but they could make a considerable impact on the expression of some genes. Changes in alternative splicing are likely to be an important component of the genetic changes that occur upon interspecific hybridization.
Cyclin Y Is a Novel Conserved Cyclin Essential for Development in Drosophila
Authors: Liu Dongmei , Finley Russell L 
Published: January 2010

Abstract
The Drosophila gene CG14939 encodes a member of a highly conserved family of cyclins, the Y-type cyclins, which have not been functionally characterized in any organism. Here we report the generation and phenotypic characterization of a null mutant of CG14939, which we rename Cyclin Y (CycY). We show that the null mutant, CycYE8, is homozygous lethal with most mutant animals arresting during pupal development. The mutant exhibits delayed larval growth and major developmental defects during metamorphosis, including impaired gas bubble translocation, head eversion, leg elongation, and adult tissue growth. Heat-shock-induced expression of CycY at different times during development resulted in variable levels of rescue, the timing of which suggests a key function for zygotic CycY during the transition from third instar larvae to prepupae. CycY also plays an essential role during embryogenesis since zygotic null embryos from null mothers fail to hatch into first instar larvae. We provide evidence that the CycY protein (CycY) interacts with Eip63E, a cyclin-dependent kinase (Cdk) for which no cyclin partner had previously been identified. Like CycY, the Eip63E gene has essential functions during embryogenesis, larval development, and metamorphosis. Our data suggest that CycY/Eip63E form a cyclin/Cdk complex that is essential for several developmental processes.
Estimated Burden of Rotavirus-Associated Diarrhea in Ambulatory Settings in the United States
Authors: Flores Anthony R. , Szilagyi Peter G. , Auinger Peggy , Fisher Susan G. 
Published: January 2010

BACKGROUND:
Two vaccines to prevent disease from rotavirus among young children were recently approved in the United States. Although previous studies of the burden of rotaviral disease have focused on hospitalizations, the assessment of baseline disease burden in ambulatory settings is useful for evaluating the overall impact of the vaccine.

METHODS:
Outpatient and emergency department (ED) data for 1994–2006 were analyzed from 2 nationally representative databases: the National Ambulatory Medical Care Survey and the National Hospital Medical Care Survey. Visits by children (younger than 5 years) with acute gastroenteritis (AGE) were identified by using a defined set of International Classification of Diseases, Ninth Revision, Clinical Modification codes. Two previously described methods (the winter-residual-excess [WRE] and Brandt methods) were used to estimate the proportion of AGE attributable to rotavirus and to determine the annual number of visits, annual average visits, and annual visit rates in each setting.

RESULTS:
The estimated average annual number of rotavirus-associated visits over the 13-year period was 782 453 outpatient visits and 164 261 ED visits from the WRE method and 665 773 outpatient visits and 205 206 ED visits from the Brandt method. This resulted in an average of 39.1 and 33.3 outpatient visits per 1000 children and 8.2 and 10.3 ED visits per 1000 children for both the WRE and Brandt methods, respectively. The average annual proportion of visits for AGE attributed to rotavirus was 34.2% (29.1% from the Brandt method) in the outpatient setting and 21.8% (27.1% from the Brandt method) in the ED, with wide variations in individual years.

CONCLUSIONS:
Before the rotavirus vaccine, rotavirus seemed to be associated with a large number of outpatient and ED visits among young children. Rotavirus vaccine has the potential to reduce many outpatient and ED visits.