bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete genome sequence of Treponema pallidum ssp. pallidumstrain SS14 determined with oligonucleotide arrays
Authors: Matějková Petra , Strouhal Michal , Šmajs David , Norris Steven J , Palzkill Timothy , Petrosino Joseph F , Sodergren Erica , Norton Jason E , Singh Jaz , Richmond Todd A , Molla Michael N , Albert Thomas J , Weinstock George M 
Published: May 2008

Abstract

Background
Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently.

Results
The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome.

Conclusion
The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.
A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: A case control study in an Italian population
Authors: Nasri Soroush , More Helen , Graziano Francesco , Ruzzo Annamaria , Wilson Emily , Dunbier Anita , McKinney Cushla , Merriman Tony , Guilford Parry , Magnani Mauro , Humar Bostjan 
Published: May 2008

Abstract

Background
Inherited genetic factors such as E-cadherin (CDH1) promoter variants are believed to influence the risk towards sporadic diffuse gastric cancer (DGC). Recently, a new regulatory region essential for CDH1 transcription has been identified in CDH1 intron 2.

Methods
We genotyped all known polymorphisms located within conserved sequences of CDH1 intron 2 (rs10673765, rs9932686, rs1125557, rs9282650, rs9931853) in an Italian population consisting of 134 DGC cases and 100 healthy controls (55 patient relatives and 45 unrelated, matched individuals). The influence of individual variants on DGC risk was assessed using χ2-tests and logistic regression. The relative contribution of alleles was estimated by haplotype analysis.

Results
We observed a significant (p < 0.0004) association of the CDH1 163+37235G>A variant (rs1125557) with DGC risk. Odds ratios were 4.55 (95%CI = 2.09–9.93) and 1.38 (95%CI = 0.75–2.55) for AA and GA carriers, respectively. When adjusted for age, sex, smoking status, alcohol intake and H. pylori infection, the risk estimates remained largely significant for AA carriers. Haplotype analysis suggested the 163+37235A-allele contributes to disease risk independently of the other variants studied.

Conclusion
The CDH1 163+37235G>A polymorphism may represent a novel susceptibility variant for sporadic DGC if confirmed in other populations. Considering the broad expression of E-cadherin in epithelia, this exploratory study encourages further evaluation of the 163+37235A-allele as a susceptibility variant in other carcinomas.
Construction of a series of vectors for high throughput cloning and expression screening of membrane proteins from Mycobacterium tuberculosis
Authors: Qin Huajun , Hu Jian , Hua Yuanzhi , Challa Shridhar V , Cross Timothy A , Gao Fei P 
Published: May 2008

Abstract

Background
One of the major challenges for membrane protein structural genomics is establishing high-throughput cloning and expression screening methods to obtain enough purified protein in a homogeneous preparation for structural and functional studies. Here a series of ligation independent cloning based vectors were constructed to address this challenge.

Results
The feasibility of these vectors was tested with 41 putative membrane proteins from Mycobacterium tuberculosis. The efficiency for direct cloning of these target genes from PCR products was 95% (39/41). Over 40% of cloned genes were overexpressed in Escherichia coli BL21 (DE3)-RP codon plus strain in the first round of expression screening. For those proteins which showed no expression, three protein fusion partners were prepared and it was found that each of the target proteins could be overexpressed by at least one of these fusions, resulting in the overexpression of two thirds of the cloned genes.

Conclusion
This expression platform features high throughput cloning, high flexibility for different constructs, and high efficiency for membrane protein overexpression, and is expected to be useful in membrane protein structural and functional studies.
Effects of rosiglitazone on contralateral iliac artery after vascular injury in hypercholesterolemic rabbits
Authors: França Neto Olímpio Ribeiro , Precoma Dalton Bertolim , Alessi Alexandre , Prim Camila , da Silva Ruy FernandoKuenzerCaetano , de Noronha Lucia , Baroncini Liz AndréaVillela 
Published: May 2008

Abstract

Background
The objective was to evaluate the effects of rosiglitazone on iliac arteries of hypercholesterolemic rabbits undergoing balloon catheter injury in the contralateral iliac arteries.

Methods
White male rabbits were fed a hypercholesterolemic diet for 6 weeks and divided into two groups as follows: rosiglitazone group, 14 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) during 6 weeks; and control group, 18 rabbits without rosiglitazone treatment. All animals underwent balloon catheter injury of the right iliac artery on the fourteenth day of the experiment.

Results
There was no significant difference in intima/media layer area ratio between the control group and the rosiglitazone group. Rosiglitazone did not reduce the probability of lesions types I, II, or III (72.73% vs. 92.31%; p = 0.30) and types IV or V (27.27% vs. 7.69%; p = 0.30). There were no differences in the extent of collagen type I and III deposition or in the percentage of animals with macrophages in the intima layer. The percentage of rabbits with smooth muscle cells in the intima layer was higher in rosiglitazone group (p = 0.011).

Conclusion
These findings demonstrate that rosiglitazone given for 6 weeks did not prevent atherogenesis at a vessel distant from the injury site.
Correlation between NK function and response to trastuzumab in metastatic breast cancer patients
Authors: Beano Alessandra , Signorino Elena , Evangelista Andrea , Brusa Davide , Mistrangelo Marinella , Polimeni Maria Antonia , Spadi Rosella , Donadio Michela , Ciuffreda Libero , Matera Lina 
Published: May 2008

Abstract

Background
Trastuzumab is a monoclonal antibody selectively directed against Her2 and approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include mediation of antibody-dependent cellular cytotoxicity (ADCC) by triggering FcγRIII on natural killer (NK) cells. This study addresses the correlation between overall NK function and trastuzumab's clinical activity.

Subjects and methods
Clinical and immunological responses were assessed in 26 patients receiving trastuzumab monotherapy as maintenance management after chemotherapy (8 mg/kg load and then standard doses of 6 mg/kg every 3 weeks). Cytotoxic activity against the MHC class I-negative standard NK target K562 cell line and HER2-specific ADCC against a trastuzumab-coated Her2-positive SKBR3 cell line were assessed in peripheral blood mononuclear cells (PBMC) harvested after the first standard dose. After six months, seventeen patients were scored as responders and nine as non-responders according to the RECIST criteria, while Progression-Free Survival (PFS) was calculated during a 12 months follow-up.

Results
The responders had significantly higher levels of both NK and ADCC activities (p < 0.05) that were not different from those of eleven normal controls. The NK activity of the non-responders was significantly (p < 0.05) lower than that of the normal controls. At twelve months, there was a marked correlation between PFS and NK activity only. PFS was significantly longer in patients with high levels of NK activity, whereas its pattern was unrelated to high or low ADCC activity.

Conclusion
One of the mechanisms of action of trastuzumab is NK cell-mediated ADCC lysis of the Her2-positve target cell. We show here that its potency is correlated with the short-term response to treatment, whereas longer protection against tumor expansion seems to be mediated by pure NK activity.
Proteomics with a pinch of salt: A cyanobacterial perspective
Authors: Pandhal Jagroop , Wright Phillip C , Biggs Catherine A 
Published: May 2008

AbstractCyanobacteria are ancient life forms and have adapted to a variety of extreme environments, including high salinity. Biochemical, physiological and genetic studies have contributed to uncovering their underlying survival mechanisms, and as recent studies demonstrate, proteomics has the potential to increase our overall understanding further. To date, most salt-related cyanobacterial proteomic studies have utilised gel electrophoresis with the model organismSynechocystissp. PCC6803. Moreover, focus has been on 2–4% w/v NaCl concentrations within different cellular compartments. Under these conditions,Synechocystissp. PCC6803 was found to respond and adapt to salt stress through synthesis of general and specific stress proteins, altering the protein composition of extracellular layers, and re-directing control of complex central intermediary pathways. Post-transcriptional control was also predicted through non-correlating transcript level data and identification of protein isoforms.In this paper, we also review technical developments with emphasis on improving the quality and quantity of proteomic data and overcoming the detrimental effects of salt on sample preparation and analysis. Developments in gel-free methods include protein and peptide fractionation workflows, which can increase coverage of the proteome (20% inSynechocystissp. PCC6803). Quantitative techniques have also improved in accuracy, resulting in confidence in quantitation approaching or even surpassing that seen in transcriptomic techniques (better than 1.5-fold in differential expression). Furthermore,in vivometabolic labelling andde novoprotein sequencing software have improved the ability to apply proteomics to unsequenced environmental isolates. The example used in this review is a cyanobacterium isolated from a Saharan salt lake.
APRIL facilitates viral-induced erythroleukemia but is dispensable for T cell immunity and lymphomagenesis
Authors: Hardenberg Gijs , Fernandez Leticia , Hendriks Jenny , Chebli Karim , Jacquet Chantal , Sitbon Marc , Hahne Michel , Medema Jan Paul 
Published: May 2008

AbstractThe TNF family member, a proliferation-inducing ligand (APRIL), has been suggested to act as a costimulatory molecule in T cell responses. However, studies addressing this role in vivo are largely lacking. Here, we evaluated the effects of APRIL on physiological T cell responses in vivo. Although receptors for APRIL are expressed on a subset of T cells, neither TCR transgenic (Tg) T cell responses nor endogenous TCR responses were affected by Tg APRIL expression in vivo. Moreover, APRIL did not significantly enhance the induction of T cell lymphomas upon Moloney murine leukemia virus (MLV) infection. This clearly contrasts current belief and indicates that APRIL does not serve a major role in T cell immunity or lymphomagenesis. However, we did observe a strong increase in erythroleukemia formation after MLV inoculation of APRIL Tg mice. Strikingly, this erythroleukemia-facilitating property of APRIL was confirmed using the erythroleukemogenic Friend-MLV. Erythroleukemia in APRIL Tg mice was characterized by low hematocrits and grossly enlarged spleens with an increased percentage of erythroid precursors. Altogether, these results unveil new proerythroleukemogenic properties of APRIL.
Phase II Study of Palifermin and Concurrent Chemoradiation in Head and Neck Squamous Cell Carcinoma
Authors: Brizel David M. , Murphy Barbara A. , Rosenthal David I. , Pandya Kishan J. , Glück Stefan , Brizel Herbert E. , Meredith Ruby F. , Berger Dietmar , Chen Mon-Gy , Mendenhall William 
Published: May 2008

Purpose Acute mucositis is a dose-limiting toxicity of concurrent chemoradiotherapy regimens for locally advanced head and neck cancer. Palifermin (a recombinant human keratinocyte growth factor; ΔN23-KGF) stimulates the proliferation and differentiation of mucosal epithelium to reduce mucositis in patients receiving intensive therapy for hematologic cancers. This study assessed the efficacy and safety of palifermin in patients receiving concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma. Patients and Methods In a phase II trial, standard radiotherapy was delivered in daily 2-Gy fractions to 70 Gy, or hyperfractionated radiotherapy was delivered in 1.25-Gy fractions twice daily to 72 Gy, over 7 weeks. Chemotherapy included cisplatin 20 mg/m2 for 4 days and continuous-infusion fluorouracil 1,000 mg/m2/d for 4 days on weeks 1 and 5 of irradiation. Patients were randomly assigned 2:1 to palifermin 60 μg/kg or placebo once weekly for 10 doses. A follow-up trial evaluated long-term survival. Results Sixty-seven patients received palifermin and 32 received placebo. The median duration of grade ≥ 2 mucositis was 6.5 and 8.1 weeks in the palifermin and placebo groups, respectively (P = .157). Palifermin appeared to reduce mucositis, dysphagia, and xerostomia during hyperfractionated radiotherapy (n = 40) but not standard radiation therapy (n = 59). Adverse events were similar between treatment groups. Palifermin did not alter tumor response or survival. Conclusion Ten once-weekly doses of palifermin at 60 μg/kg were well tolerated. Most patients completed treatment, but palifermin did not reduce the morbidity of concurrent chemotherapy and radiotherapy. Future studies should evaluate higher palifermin doses with longer and more standardized assessment of acute mucositis.
Histologic Results of Para-Aortic Lymphadenectomy in Patients Treated for Stage IB2/II Cervical Cancer With Negative [18F]Fluorodeoxyglucose Positron Emission Tomography Scans in the Para-Aortic Area
Authors: Boughanim Mathias , Leboulleux Sophie , Rey Annie , Tuan Pham Chi , Zafrani Yaelle , Duvillard Pierre , Lumbroso Jean , Haie-Meder Christine , Schlumberger Martin , Morice Philippe 
Published: May 2008

Purpose Histologic results of complete para-aortic lymphadenectomy were studied in patients treated for stage IB2/II cervical carcinoma who had no para-aortic uptake on [18F]fluorodeoxyglucose positron emission tomography combined with integrated computed tomography (FDG-PET/CT). Patients and Methods Patients were treated between 2004 and 2006 for stage IB2/II cervical cancer. Magnetic resonance imaging of the abdomen and pelvis and FDG-PET/CT were initially performed. Patients with no para-aortic abnormalities were treated with external pelvic radiation therapy and concomitant chemotherapy followed by utero-vaginal brachytherapy. Para-aortic lymphadenectomy was then performed. FDG-PET/CT images were reviewed by two nuclear medicine specialists. Results Thirty-eight patients were studied. Three patients had histologically proven para-aortic involvement (metastatic nodes with capsular rupture in the para-aortic area), leading to a negative predictive value of 92% for para-aortic nodal involvement. Conclusion In this study, three of 38 patients with no para-aortic uptake on [18F]FDG-PET/CT imaging had histologically proven para-aortic node involvement. PET/CT imaging without histologic examination of the para-aortic area used to determine radiation therapy fields in stage IB2/II cervical cancer would overlook 8% of patients with histologic para-aortic nodal involvement.
Surveillance of the Fracture Behavior of Zircaloy-4 Welds Using the Small Punch Test
Authors: Wei T. , Carr D. G. , Li H. , Smith K. , Harrison R. P. 
Published: May 2008

Abstract
Zircaloy-4 (Zr-4) is a zirconium alloy that has been used extensively within the nuclear industry in both power generation and research reactors. The potential for welded reactor core components to undergo embrittlement during neutron irradiation is an important materials property issue to be considered throughout the service life of the reactor. Of particular interest is the performance of welded joints which depend on the properties of both the weld heat-affected zone (HAZ) and the parent metal. For this work Zr-4 HAZ was simulated using a Gleeble weld simulator to rapidly bring the material into the β-Zr zone at peak temperatures of 1200 and 1400°C. The small punch (SP) test was then used to investigate the variation in fracture behavior of these narrow zones of the weld and compare them with the parent metal. A finite element analysis (FEA) model of the SP test was developed which can be used to predict the deformation and fracture behavior of Zr-4 welds and is compared with the experimental data obtained.
Measurement of Physical Environmental Parameters and Apparent Ventilation Rates Aboard Passenger Aircraft
Authors: Murphy Michael J. 
Published: May 2008

Abstract
As part of the ASHRAE RP-1262 Phase 1 study of the airliner cabin environment, measurements were made of physical environmental parameters aboard four passenger aircraft in revenue service. The objectives of these measurements were to measure physical environmental parameters and ventilation rates on board commercial airliners in revenue service and to correlate those measurements with self-reported health effects and complaints. The measurements included temperature, relative humidity, total pressure, air velocity, sound level, light level, and motion. These measurements were recorded each second throughout the flight. In addition, measurements of carbon dioxide levels in the cabin were made that, along with passenger loadings and assumed metabolic rates, allowed the calculation of an apparent air change rate. Because as another part of the study, passengers filled-out written surveys on their comfort and health experience, this study provides unique simultaneous measurement of both physical environmental parameters in an aircraft cabin and the human response. Results of these measurements are presented as temporal graphs for the duration of the flight and are compared to various benchmarks. Among the results, air change rates ranged from 10 to 16 air changes per hour, noise levels varied from 68 to 80 dBA, according to the location in the cabin. Relative humidity values declined from 30 to 35 % during the boarding process to as low as 7 to 8 % during the cruise portion of the flights. The temperature variation was greatest during the boarding process and was generally near 25°C, during the cruise portion of the flights. Over all four flights, the cabin pressure varied from 562 to 740 torr. There was a wide variation in light levels: from over 8000 lux if sunlight was present, to about 250 lux if the window shades were in use.
The post partum period and the onset of Graves' disease: an overestimated risk factor
Authors: Rotondi Mario , Pirali Barbara , Lodigiani Sara , Bray Simona , Leporati Paola , Chytiris Spyridon , Balzano Simona , Magri Flavia , Chiovato Luca 
Published: May 2008

ObjectiveAggravation of autoimmune diseases due to a rebound reaction to the pregnancy-associated immune changes is common during the post partum (PP) period. Previous studies demonstrated that up to 45% of women developing Graves' disease (GD) in the childbearing age had a PP onset of disease. Thus, the PP period was identified as a major risk factor for GD onset.DesignThe aim of this study was to evaluate the role of the PP period as a risk factor for GD occurrence.MethodsThe reproductive histories of 291 consecutive GD patients (165 patients in the childbearing age and 126 in the non-childbearing age) were retrospectively collected.ResultsThe rate of PP onset of GD in all patients with at least one successful pregnancy was 9.8 and 20.0% when only patients in the childbearing age were considered. In the entire cohort of GD women, independent of their age and parity status (i.e., the number of successful pregnancies), the rate of PP onset of GD was 7.2%. The relative frequencies of the rate of PP onset of GD were similar in relation with increasing parity. The rates of false negative (nulliparous) and false positive (parous non-childbearing+childbearing with a non-PP onset of GD) were estimated. The positive predictive value of the PP period for the onset of GD was less than 10%.ConclusionsThe results of the current study would not support a role for the PP period as a major risk factor for de novo occurrence of GD.
Calcium Handling in Human Embryonic Stem Cell-Derived Cardiomyocytes
Authors: Satin Jonathan , Itzhaki Ilanit , Rapoport Sophia , Schroder Elizabeth A. , Izu Leighton , Arbel Gil , Beyar Rafael , Balke C. William , Schiller Jackie , Gepstein Lior 
Published: May 2008

Abstract
The objective of the current study was to characterize calcium handling in developing human embryonic stem cell-derived cardiomyocytes (hESC-CMs). To this end, real-time polymerase chain reaction (PCR), immunocytochemistry, whole-cell voltage-clamp, and simultaneous patch-clamp/laser scanning confocal calcium imaging and surface membrane labeling with di-8-aminonaphthylethenylpridinium were used. Immunostaining studies in the hESC-CMs demonstrated the presence of the sarcoplasmic reticulum (SR) calcium release channels, ryanodine receptor-2, and inositol-1,4,5-trisphosphate (IP3) receptors. Store calcium function was manifested as action-potential-induced calcium transients. Time-to-target plots showed that these action-potential-initiated calcium transients traverse the width of the cell via a propagated wave of intracellular store calcium release. The hESC-CMs also exhibited local calcium events (“sparks”) that were localized to the surface membrane. The presence of caffeine-sensitive intracellular calcium stores was manifested following application of focal, temporally limited puffs of caffeine in three different age groups: early-stage (with the initiation of beating), intermediate-stage (10 days post-beating [dpb]), and late-stage (30–40 dpb) hESC-CMs. Calcium store load gradually increased during in vitro maturation. Similarly, ryanodine application decreased the amplitude of the spontaneous calcium transients. Interestingly, the expression and function of an IP3-releasable calcium pool was also demonstrated in the hESC-CMs in experiments using caged-IP3 photolysis and antagonist application (2 μM 2-Aminoethoxydiphenyl borate). In summary, our study establishes the presence of a functional SR calcium store in early-stage hESC-CMs and shows a unique pattern of calcium handling in these cells. This study also stresses the importance of the functional characterization of hESC-CMs both for developmental studies and for the development of future myocardial cell replacement strategies.
Disclosure of potential conflicts of interest is found at the end of this article.