bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens
Authors: Pere Helene , Montier Yves , Bayry Jagadeesh , Quintin-Colonna Francoise , Merillon Nathalie , Dransart Estelle , Badoual Cecile , Gey Alain , Ravel Patrice , Marcheteau Elie , Batteux Frederic , Sandoval Federico , Adotevi Olivier , Chiu Christopher , Garcia Sylvie , Tanchot Corinne , Lone Yu-Chun , Ferreira Luis Carlos , Nelson Brad H. , Hanahan Douglas , Fridman Wolf Herman , Johannes Ludger , Tartour Eric 
Published: September 2011

Abstract
Regulatory T cells (Tregs) may impede cancer vaccine efficacy in hematologic malignancies and cancer. CCR4 antagonists, an emergent class of Treg inhibitor, have been shown to block recruitment of Tregs mediated by CCL22 and CCL17. Our aim was to demonstrate the ability of a CCR4 antagonist (a small chemical molecule identified in silico) when combined with vaccines to break peripheral tolerance controlled by Tregs, a prerequisite for the induction of CD8+ T cells against self Ags. Immunization of transgenic or normal mice expressing tumor-associated self Ags (Her2/neu, OVA, gp100) with a CCR4 antagonist combined with various vaccines led to the induction of effector CD8+ T cells and partial inhibition of tumor growth expressing self Ags in both prophylactic and therapeutic settings. The CCR4 antagonist was more efficient than cyclophosphamide to elicit anti-self CD8+ T cells. We also showed that the population of Tregs expressing CCR4 corresponded to memory (CD44high) and activated (ICOS+) Tregs, an important population to be targeted to modulate Treg activity. CCR4 antagonist represents a competitive class of Treg inhibitor able to induce functional anti-self CD8+ T cells and tumor growth inhibition when combined with vaccines. High expression of CCR4 on human Tregs also supports the clinical development of this strategy.
Mutation of L-2,3-diaminopropionic acid synthase genes blocks staphyloferrin B synthesis in Staphylococcus aureus
Authors: Beasley Federico C , Cheung Johnson , Heinrichs David E 
Published: September 2011

Abstract

Background

Staphylococcus aureus synthesizes two siderophores, staphyloferrin A and staphyloferrin B, that promote iron-restricted growth. Previous work on the biosynthesis of staphyloferrin B has focused on the role of the synthetase enzymes, encoded from within the sbnA-I operon, which build the siderophore from the precursor molecules citrate, alpha-ketoglutarate and L-2,3-diaminopropionic acid. However, no information yet exists on several other enzymes, expressed from the biosynthetic cluster, that are thought to be involved in the synthesis of the precursors (or synthetase substrates) themselves.

Results
Using mutants carrying insertions in sbnA and sbnB, we show that these two genes are essential for the synthesis of staphyloferrin B, and that supplementation of the growth medium with L-2,3-diaminopropionic acid can bypass the block in staphyloferrin B synthesis displayed by the mutants. Several mechanisms are proposed for how the enzymes SbnA, with similarity to cysteine synthase enzymes, and SbnB, with similarity to amino acid dehydrogenases and ornithine cyclodeaminases, function together in the synthesis of this unusual nonproteinogenic amino acid L-2,3-diaminopropionic acid.

Conclusions
Mutation of either sbnA or sbnB result in abrogation of synthesis of staphyloferrin B, a siderophore that contributes to iron-restricted growth of S. aureus. The loss of staphyloferrin B synthesis is due to an inability to synthesize the unusual amino acid L-2,3-diaminopropionic acid which is an important, iron-liganding component of the siderophore structure. It is proposed that SbnA and SbnB function together as an L-Dap synthase in the S. aureus cell.
Improving Cry8Ka toxin activity towards the cotton boll weevil (Anthonomus grandis)
Authors: Oliveira Gustavo R , Silva Maria CM , Lucena Wagner A , Nakasu Erich YT , Firmino Alexandre AP , Beneventi Magda A , Souza Djair SL , Gomes José E , de Souza José DA , Rigden Daniel J , Ramos Hudson B , Soccol Carlos R , Grossi-de-Sa Maria F 
Published: September 2011

Abstract

Background
The cotton boll weevil (Anthonomus grandis) is a serious insect-pest in the Americas, particularly in Brazil. The use of chemical or biological insect control is not effective against the cotton boll weevil because of its endophytic life style. Therefore, the use of biotechnological tools to produce insect-resistant transgenic plants represents an important strategy to reduce the damage to cotton plants caused by the boll weevil. The present study focuses on the identification of novel molecules that show improved toxicity against the cotton boll weevil. In vitro directed molecular evolution through DNA shuffling and phage display screening was applied to enhance the insecticidal activity of variants of the Cry8Ka1 protein of Bacillus thuringiensis.

Results
Bioassays carried out with A. grandis larvae revealed that the LC50 of the screened mutant Cry8Ka5 toxin was 3.15-fold higher than the wild-type Cry8Ka1 toxin. Homology modelling of Cry8Ka1 and the Cry8Ka5 mutant suggested that both proteins retained the typical three-domain Cry family structure. The mutated residues were located mostly in loops and appeared unlikely to interfere with molecular stability.

Conclusions
The improved toxicity of the Cry8Ka5 mutant obtained in this study will allow the generation of a transgenic cotton event with improved potential to control A. grandis.
New approach for T-wave end detection on electrocardiogram: Performance in noisy conditions
Authors: Vázquez-Seisdedos Carlos R , Neto João Evangelista , Marañón Reyes Enrique J , Klautau Aldebaro , Limão de Oliveira Roberto C 
Published: September 2011

Abstract

Background
The detection of T-wave end points on electrocardiogram (ECG) is a basic procedure for ECG processing and analysis. Several methods have been proposed and tested, featuring high accuracy and percentages of correct detection. Nevertheless, their performance in noisy conditions remains an open problem.

Methods
A new approach and algorithm for T-wave end location based on the computation of Trapezium's areas is proposed and validated (in terms of accuracy and repeatability), using signals from the Physionet QT Database. The performance of the proposed algorithm in noisy conditions has been tested and compared with one of the most used approaches for estimating the T-wave end point: the method based on the threshold on the first derivative.

Results
The results indicated that the proposed approach based on Trapezium's areas outperformed the baseline method with respect to accuracy and repeatability. Also, the proposed method is more robust to wideband noise.

Conclusions
The trapezium-based approach has a good performance in noisy conditions and does not rely on any empirical threshold. It is very adequate for use in scenarios where the levels of broadband noise are significant.
Nogo receptor is involved in the adhesion of dendritic cells to myelin
Authors: McDonald Claire L , Steinbach Karin , Kern Florian , Schweigreiter Rüdiger , Martin Roland , Bandtlow Christine E , Reindl Markus 
Published: September 2011

Abstract

Background
Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding proteins for a number of myelin-associated inhibitory factors. After neuronal injury, these inhibitory factors are responsible for preventing axonal outgrowth via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells expressing NgR1/2 are inhibited from adhering to and spreading on a myelin substrate. Neuronal injury also results in the presence of dendritic cells (DCs) in the central nervous system, where they can come into contact with myelin debris. The exact mechanisms of interaction of immune cells with CNS myelin are, however, poorly understood.

Methods
Human DCs were differentiated from peripheral blood monocytes and mouse DCs were differentiated from wild type and NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were determined with quantitative real time PCR and immunoblot, and adhesion of cells to myelin was quantified.

Results
We demonstrate that human immature myeloid DCs express NgR1 and NgR2, which are then down-regulated upon maturation. Human mature DCs also adhere to a much higher extent to a myelin substrate than immature DCs. We observe the same effect when the cells are plated on Nogo-66-His (binding peptide for NgR1), but not on control proteins. Mature DCs taken from Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC differentiation or phenotype.

Conclusions
These results indicate that a lack of NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could be important in neuroinflammatory disorders such as multiple sclerosis in which peripheral immune cells come into contact with myelin debris.
Vascular endothelial growth factor-A and chemokine ligand (CCL2) genes are upregulated in peripheral blood mononuclear cells in Indian amyotrophic lateral sclerosis patients
Authors: Gupta Pawan K , Prabhakar Sudesh , Abburi Chandrika , Sharma Neel K , Anand Akshay 
Published: September 2011

Abstract

Background
We have earlier shown that protein levels of vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian amyotrophic lateral sclerosis (ALS) patients. Here, we report the mRNA levels of VEGF-A and CCL2 in Indian ALS patients since they display extended survival after disease onset.

Methods
VEGF-A and CCL2 mRNA levels were measured in peripheral blood mononuclear cells (PBMCs) of 50 sporadic Indian ALS patients using Real Time Polymerase Chain Reaction (PCR) and compared with normal controls (n = 50). Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption.

Results
VEGF-A and CCL2 mRNA levels were found to be significantly elevated in PBMCs in ALS patients as compared to controls. PBMCs from definite ALS revealed higher VEGF-A mRNA expression as compared to probable and possible ALS. CCL2 mRNA levels were found to be unaltered when definite, probable and possible ALS were compared. PBMCs from patients with respiratory dysfunction showed much higher VEGF-A and CCL2 elevation when compared to patients without respiratory dysfunction. No association of smoking, alcohol and meat consumption with VEGF-A and CCL2 was observed after analyzing the data with univariate and multivariate analysis.

Conclusion
VEGF-A and CCL2 mRNA upregulation in PBMCs may have a clinico-pathological/etiological/epidemiological association with ALS pathogenesis. The cross-cultural and cross-ethnic investigations of these molecules could determine if they have any role in enhancing the mean survival time unique to Indian ALS patients.
Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial
Authors: Menkarios Cathy , Vigneault Éric , Brochet Nicolas , Nguyen David HA , Bahary Jean-Paul , Jolicoeur Marjory , Beauchemin Marie-Claude , Villeneuve Hugo , Van Nguyen Thu , Fortin Bernard , Lambert Carole 
Published: September 2011

Abstract

Background
Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment.

Materials and Methods
We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival.

Results
Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%.

Conclusions
Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.
Adenovirus-mediated delivery of bFGF small interfering RNA reduces STAT3 phosphorylation and induces the depolarization of mitochondria and apoptosis in glioma cells U251
Authors: Liu Jun , Xu Xinnv , Feng Xuequan , Zhang Biao , Wang Jinhuan 
Published: September 2011

Abstract
Glioblastoma multiforme (GBM) carries a dismal prognosis primarily due to its aggressive proliferation in the brain regulated by complex molecular mechanisms. One promising molecular target in GBM is over-expressed basic fibroblast growth factor (bFGF), which has been correlated with growth, progression, and vascularity of human malignant gliomas. Previously, we reported significant antitumor effects of an adenovirus-vector carrying bFGF small interfering RNA (Ad-bFGF-siRNA) in glioma in vivo and in vitro. However, its mechanisms are unknown. Signal transducer and activator of transcription 3 (STAT3) is constitutively active in GBM and correlates positively with the glioma grades. In addition, as a specific transcription factor, STAT3 serves as the convergent point of various signaling pathways activated by multiple growth factors and/or cytokines. Therefore, we hypothesized that the proliferation inhibition and apoptosis induction by Ad-bFGF-siRNA may result from the interruption of STAT3 phosphorylation. In the current study, we found that in glioma cells U251, Ad-bFGF-siRNA impedes the activation of ERK1/2 and JAK2, but not Src, decreases IL-6 secretion, reduces STAT3 phosphorylation, decreases the levels of downstream molecules CyclinD1 and Bcl-xl, and ultimately results in the collapse of mitochondrial membrane potentials as well as the induction of mitochondrial-related apoptosis. Our results offer a potential mechanism for using Ad-bFGF-siRNA as a gene therapy for glioma. To our knowledge, it is the first time that the bFGF knockdown using adenovirus-mediated delivery of bFGF siRNA and its potential underlying mechanisms are reported. Therefore, this finding may open new avenues for developing novel treatments against GBM.
Long-term sickness absence among patients with chronic fatigue syndrome
Authors: Knudsen Ann Kristin , Henderson Max , Harvey Samuel B. , Chalder Trudie 
Published: September 2011

SummaryChronic fatigue syndrome is associated with high levels of occupational disability. Consecutive out-patients at a chronic fatigue syndrome treatment service were studied for associations between occupational status, symptom severity and cognitive and behavioural responses to symptoms. All patients had high symptom levels; however, those on long-term sickness absence had significantly more physical fatigue (β = 0.098, P<0.05) and worse sleep (β = 0.075, P<0.05). Patients with long-term sickness absence also demonstrated more embarrassment avoidance cognitions (β = 0.086, P<0.05) and avoidance resting behavioural responses (β = 0.078, P<0.05). Identifying and addressing avoidance behaviours and cognitions regarding embarrassment in interventions may enhance the chances of individuals returning to work.
Relationship of orthostatic blood pressure to white matter hyperintensities and subcortical volumes in late-life depression
Authors: Colloby Sean J. , Vasudev Akshya , O'Brien John T. , Firbank Michael J. , Parry Steve W. , Thomas Alan J. 
Published: September 2011

BackgroundStructural brain abnormalities are associated with late-life major depression, with numerous studies reporting increased white matter hyperintensities (WMH) and reduced cortical/subcortical grey matter volumes. There is strong evidence linking vascular disease to WMH, but limited evidence on its association with subcortical volumes.AimsTo investigate the relationship of orthostatic blood pressure changes to WMH and subcortical grey matter volumes in late-life depression.MethodThirty-eight people with depression and a similarly aged comparison group (n = 30) underwent fluid attenuated inversion recovery (FLAIR) and T1-weighted magnetic resonance imaging as well as systematic orthostatic blood pressure assessments. Volumetric estimates of WMH and subcortical grey matter were obtained for each participant and the relationship to blood pressure drop on active stand was examined.ResultsAn association between orthostatic systolic blood pressure drop and WMH volumes in temporal and parietal regions was found in the depression group (age-corrected partial correlation r’ = 0.31–0.35, P<0.05). Subcortical volumes were not related to blood pressure changes or WMH volumes in either group.ConclusionsWe found evidence for an association between the degree of orthostatic systolic blood pressure drop and WMH volume in the depression group. Since blood pressure drops lead to WMH in animals our findings suggest systolic blood pressure drops may be a factor contributing to these lesions in late-life depression.
Preliminary study of whole-body diffusion-weighted imaging in detecting pulmonary metastatic lesions from clear cell renal cell carcinoma: comparison with CT
Authors: Liu Jing , Yang Xuedong , Li Feiyu , Wang Xiaoying , Jiang Xuexiang 
Published: September 2011

Background Whole-body diffusion-weighted imaging (DWI) has been widely used in detecting malignant metastases, including pulmonary metastases. Purpose To evaluate the possible utility of whole-body DWI in detecting pulmonary metastases of patients with clear cell renal cell carcinoma (ccRCC) and compare the exact differences between MR and CT in detecting pulmonary lesions. Material and Methods Whole-body DWI and chest CT examinations were performed on nine consecutive patients (8 men and 1 woman) with histologically confirmed ccRCC and possible metastatic lesions before chemotherapy. Results CT and MR demonstrated pulmonary metastases in seven patients and no metastatic lesions in two patients. The numbers of pulmonary metastases detected on CT, DWI-only, T1WI-only and DWI in combination with T1WI were 83, 35, 34 and 39, respectively. Metastases with a diameter above 1.0 cm could all be detected by DWI and a diameter above 0.7 cm could all be detected by DWI in combination with T1WI. Significant differences were obtained both for correlationship between diameter and detection rates of DWI and T1WI by using Spearman rank correlation analysis. Conclusion Although MR cannot be considered a replacement for CT in pulmonary metastases from ccRCC, whole-body DWI, with the combination of T1 dual echo, might be helpful for the evaluation of tumor response to chemotherapy in the follow-up of patients when the diameter of the pulmonary metastases is over 1.0 cm.
Progression of reflux patterns in saphenous veins of women with chronic venous valvular insufficiency
Authors: Engelhorn C A , Manetti R , Baviera M M , Bombonato G M , Lonardoni M , Cassou M F , Engelhorn A L , Salles-Cunha S X 
Published: September 2011

Background Venous ultrasonography identifies reflux patterns of the great and small saphenous veins (GSV, SSV), allowing evaluation of lower extremities for treatment planning and patient follow-up. Objective To determine progression of saphenous vein reflux patterns in women with primary venous valvular insufficiency. Methods Venous ultrasonography was performed in the extremities of 92 women, 43 ± 12 (23–77) years old, CEAP (clinical, aetiological, anatomical and pathological elements) clinical classes C1–C2. Two examinations were performed 33 ± 19 (8–89) months apart in patients without saphenous vein treatment. GSV and SSV reflux patterns were classified as segmental, multisegmental, distal, proximal, diffuse and normal. Prevalence was determined for each examination, separately for right and left extremities, and jointly. Prevalence was compared using χ2 statistics. Results Reflux prevalence was higher for the GSV, 89% (164/184) and 88% ( n = 162), than for the SSV, 24% ( n = 45) and 30% ( n = 56), respectively for first and second examinations ( P < 0.001). Reflux pattern prevalence was not significantly different in the right and left extremities (1.0 > P > 0.14). Most prevalent patterns were (a) GSV segmental reflux initially, 41% (76/184), decreasing to 28% (52/184) ( P = 0.009), and (b) GSV multisegmental reflux at the second examination, increasing from 26% (48/184) to 40% (73/184) ( P = 0.006). Prevalence of other GSV or SSV reflux patterns did not change significantly (0.88 > P > 0.19). Conclusions We documented early findings and venous reflux progression in a specific population of women with varicose veins, reticular veins and telangiectasias. GSV segmental reflux was most prevalent initially, progressing to GSV multisegmental reflux.
Morphological and haemodynamic abnormalities in the jugular veins of patients with multiple sclerosis
Authors: Radak D , Kolar J , Tanaskovic S , Sagic D , Antonic Z , Mitrasinovic A , Babic S , Nenezic D , Ilijevski N 
Published: September 2011

Objectives Multiple areas of stenosis and different levels of obstruction of internal jugular and azygous veins (a condition known as cronic cerebrospinal venous insufficiency) recently emerged as an additional theory to the well-known autoimmune concept, explaining etiology of multiple sclerosis (MS). The aim of our study was to evaluate internal jugular vein (IJV) morphology and haemodynamic characteristics in patients with MS and compare it with well-matched healthy individuals and to evaluate the prevalence of venous flow abnormalities in both groups. Methods Sixty-four patients with clinically proven MS and 37 healthy individuals were included in our study. In all patients, IJV morphology and haemodynamic characteristics were evaluated by colour Doppler sonography as well as venous flow disorder. The patients were classified into four groups according to MS clinical form presentation. The prevalence of morphological and haemodynamic abnormalities in the IJV were assessed. Results The presence of stenosing lesion, mostly intraluminal defects like abnormal IJV valves, were observed in 28 patients (43%) in the MS group, and in 17 patients (45.9%) in the control group ( P = NS). By adding haemodynamic Doppler information in the IJV venous outflow was significantly different in 42% of MS patients showing flow abnormalities (27/64), as compared with 8.1% of the controls (3/37), P < 0.001. Conclusion In our group of patients, patients suffering from MS had significantly more IJV morphological changes and haemodynamic abnormalities when compared with healthy individuals not suffering from MS. These findings can be well demonstrated by non-invasive and cost-effective Doppler ultrasound.