bluuebunny/crossref_metadata_2025_split huggingface dataset:
T Cell–Specific Notch Inhibition Blocks Graft-versus-Host Disease by Inducing a Hyporesponsive Program in Alloreactive CD4+ and CD8+ T Cells
Authors: Sandy Ashley R. , Chung Jooho , Toubai Tomomi , Shan Gloria T. , Tran Ivy T. , Friedman Ann , Blackwell Timothy S. , Reddy Pavan , King Philip D. , Maillard Ivan 
Published: May 2013

Abstract
Graft-versus-host disease (GVHD) induced by donor-derived T cells remains the major limitation of allogeneic bone marrow transplantation (allo-BMT). We previously reported that the pan-Notch inhibitor dominant-negative form of Mastermind-like 1 (DNMAML) markedly decreased the severity and mortality of acute GVHD mediated by CD4+ T cells in mice. To elucidate the mechanisms of Notch action in GVHD and its role in CD8+ T cells, we studied the effects of Notch inhibition in alloreactive CD4+ and CD8+ T cells using mouse models of allo-BMT. DNMAML blocked GVHD induced by either CD4+ or CD8+ T cells. Both CD4+ and CD8+ Notch-deprived T cells had preserved expansion in lymphoid organs of recipients, but profoundly decreased IFN-γ production despite normal T-bet and enhanced Eomesodermin expression. Alloreactive DNMAML T cells exhibited decreased Ras/MAPK and NF-κB activity upon ex vivo restimulation through the TCR. In addition, alloreactive T cells primed in the absence of Notch signaling had increased expression of several negative regulators of T cell activation, including Dgka, Cblb, and Pdcd1. DNMAML expression had modest effects on in vivo proliferation but preserved overall alloreactive T cell expansion while enhancing accumulation of pre-existing natural regulatory T cells. Overall, DNMAML T cells acquired a hyporesponsive phenotype that blocked cytokine production but maintained their expansion in irradiated allo-BMT recipients, as well as their in vivo and ex vivo cytotoxic potential. Our results reveal parallel roles for Notch signaling in alloreactive CD4+ and CD8+ T cells that differ from past reports of Notch action and highlight the therapeutic potential of Notch inhibition in GVHD.
Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability
Authors: Marcatili Paolo , Ghiotto Fabio , Tenca Claudya , Chailyan Anna , Mazzarello Andrea N. , Yan Xiao-Jie , Colombo Monica , Albesiano Emilia , Bagnara Davide , Cutrona Giovanna , Morabito Fortunato , Bruno Silvia , Ferrarini Manlio , Chiorazzi Nicholas , Tramontano Anna , Fais Franco 
Published: May 2013

Abstract
Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated.
A Case of Recurrent Tumoral Calcinosis in a Young Female
Authors: Kumar Abhishek , Singh Pawan , Dobhal Heena 
Published: May 2013

ABSTRACT
Tumoral calcinosis, a rare benign clinical condition resembling a neoplasm is characterized by calcium and phosphate deposits, usually located around large joints. It can be primary or secondary to renal failure and hyperparathyroidism. This report describes a rare case of tumoral calcinosis in a 13 years old girl presenting as a huge lump around left shoulder and elbow joint with discharging sinus over left infraclavicular region.

How to cite this article
Kumar A, Singh P, Dobhal H. A Case of Recurrent Tumoral Calcinosis in a Young Female. World J Endoc Surg 2013;5(1):18-20.
Environmental Influences on the Development of Endometriosis
Authors: Carmona Francisco , Martínez-Zamora Angeles , Bassols María L. , Balasch Juan 
Published: May 2013

Purpose Several environmental toxicants (ETs), including dioxins and dioxin-like compounds (DLCs), perfluorochemicals, organochlorine pesticides, phthalates, and heavy metals (especially cadmium with its estrogen-like properties in animal models) have been investigated as possibly being related to endometriosis. Methods Systematic review of pertinent literature. Results DLCs have been the most investigated ETs. DLCs are persistent organic pollutants with highly toxic potential and include three types of compounds: polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) or furans, and polychlorinated biphenyls (PCBs). The most toxic is 2, 3, 7, 8- tetrachlorodibenzo-p-dioxin (TCDD). The connection mechanism between dioxins and endometriosis is still unclear. However, dioxins and DLCs are endocrine-disrupting compounds that can affect the pathobiology of endometriosis at multiple levels. Part of the dioxin and DLCs toxic effects can be accounted for by their interaction with the aryl hydrocarbon receptor (AhR). It has been proposed that dioxin can initiate or promote endometriosis by means of interaction with estrogen receptors or by suppressing the expression of progesterone receptors. Furthermore, TCDD alters the expression of cytokines and growth factors, remodeling enzymes and cytochrome P450 expression and activity. Conclusions Studies in rhesus models have revealed a correlation between dioxin exposure and endometriosis. However, evidence from epidemiologic studies is inconclusive.
Effective and Rapid Osteoclast Inhibition by Denosumab, is Reflected in Serum C Telopeptide (CTX), Across Different Tumor Types
Authors: S. Tuyls  , F. Geurs  , Y. Deprest  
Published: May 2013

Denosumab, a monoclonal antibody against RANKL has superior efficacy against bone metastases. Its in vivo activity can be measured recently by dosing of serum C telopeptide, produced by collagen destruction by the osteoclast. We report the first patient series, across several tumor types of the efficacy of denosumab in normalising serum CTX.
Photoacoustic Imaging for Cancer Diagnosis
Authors: Toshihiro Kushibiki  , Miya Ishihara  
Published: May 2013

Photoacoustic imaging (PAI) is a unique modality that overcomes the resolution and depth limitations of optical imaging of tissues while maintaining relatively high contrast. In this article, we reviewthe biomedical applications of PAI, assisted or unassisted by exogenous photoabsorbers (contrast agents). Representative endogenous contrast agents include melanin and hemoglobin, whereas exogenous contrast agents include dyes, metal nanoparticles, and other constructs that absorb strongly in the near-infrared band of the optical spectrum and generate strong photoacoustic responses. These contrast agents, which can be specifically targeted to molecules or cells, have been coupled with photoacoustic imaging for preclinical and clinical applications including detection of cancer cells, sentinel lymph nodes, micrometastases, and monitoring of angiogenesis. Multi-functional agents have also been developed that can carry medicines or simultaneously provide contrast in multiple imaging modalities. Furthermore, contrast agents are used to guide and monitor therapeutic procedures. Overall, photoacoustic imaging has significant potential to assist in diagnosis, therapeutic planning, and monitoring of treatment outcome for cancers and other pathologies.
Biological and Pathological Study of Prostate Cancer at Localized Stage in Western Algeria
Authors: Abdelkrim Berroukche  , Malika Bendahmane-Salmi  , Badreddine Abdelkrim Kandouci  
Published: May 2013

Objective:Toshow the contribution of the pathological examination, associated with prostatic specific antigen (PSA), in the early detection of prostate cancer in Western Algeria.
Methodology:This study focused on 160 cases, old between 50-80 years, with histologically confirmed prostate adenocarcinoma and carried out in urology hospitals in western Algeria during the period from 2007 to 2011. Tumor stage, PSA, Gleason score and the degree of tumor differentiation were analyzed.
Results:135 patients, with a poor prognosis and a Gleason score > 8 index of incurable malignant aggression, have not been the subject of this study. But the other 35 patients were candidates because they had a favorable prognosis with a localized stage that could be curable. Gleason score was between 5-6 in 5 patients with TPSA 10 ng / ml at differential stage, score of 7 in 10 patients with TPSA between 10-20 ng / ml atmoderately differentiated stage and finally a score of 8 in 20 patients with TPSA between 20,1-50 ng / ml at apoorly differentiated stage.
Conclusion:There is a strong correlation between TPSA, Gleason score and the degree of tumor differentiation. Biological and pathological prognosis, established early, can reduce tumor progression.
Nitric Oxide Metabolites Change in Cisplatin-Induced Nephrotoxicity: The Effect of L-Arginine and Losartan
Authors: Zahra Pezeshki  , Mehdi Nematbakhsh  
Published: May 2013

Cisplatin (CP) is an anticancer drug with the most common side effect of nephrotoxicity. CP also alters the level of nitric oxide (NO), and NO itself may promote CP-induced nephrotoxicity. In this short report, we measured the serum levels of NO metabolites in an animal model of CP-induced nephrotoxicity, and tested the effect of two nephroprotectant agents; l-arginine and losartan on serum levels of NO metabolites. The results indicated that CP increased the serum concentration of nitrite but not nitrate. However, l-arginine and losartan significantly decreased the serum level of nitrite. It seems that l-arginine and losartan provide their nephroprotectant effect against CP-induced nephrotoxicity by reducing the serum level of nitrite.
Association of aggression with a novel microRNA binding site polymorphism in the wolframin gene
Authors: Kovacs‐Nagy Reka , Elek Zsuzsanna , Szekely Anna , Nanasi Tibor , Sasvari‐Szekely Maria , Ronai Zsolt 
Published: May 2013

AbstractRare mutations in the WFS1 gene lead to Wolfram syndrome, a severe multisystem disorder with progressive neurodegeneration and diabetes mellitus causing life‐threatening complications and premature death. Only a few association studies using small clinical samples tested the possible effects of common WFS1 gene variants on mood disorders and suicide, the non‐clinical spectrum has not been studied yet. Self‐report data on Aggression, Impulsiveness, Anxiety, and Depression were collected from a large (N = 801) non‐psychiatric sample. Single nucleotide polymorphisms (SNPs) were selected to provide an adequate coverage of the entire WFS1 gene, as well as to include putative microRNA binding site polymorphisms. Molecular analysis of the assumed microRNA binding site variant was performed by an in vitro reporter‐gene assay of the cloned 3′ untranslated region with coexpression of miR‐668. Among the 17 WFS1 SNPs, only the rs1046322, a putative microRNA (miR‐668) binding site polymorphism showed significant association with psychological dimensions after correction for multiple testing: those with the homozygous form of the minor allele reported higher aggression on the Buss–Perry Aggression Questionnaire (P = 0.0005). Functional effect of the same SNP was also demonstrated in a luciferase reporter system: the minor A allele showed lower repression compared to the major G allele, if co‐expressed with miR‐668. To our knowledge, this is the first report describing a microRNA binding site polymorphism of the WFS1 gene and its association with human aggression based on a large, non‐clinical sample. © 2013 Wiley Periodicals, Inc.
Lymphangiogenesis in abdominal aortic aneurysm
Authors: Scott D J A , Allen C J , Honstvet C A , Hanby A M , Hammond C , Johnson A B , Perry S L , Jones P F 
Published: May 2013

AbstractBackgroundOngoing angiogenesis is implicated in the inflammatory environment that characterizes abdominal aortic aneurysm (AAA). Although lymphangiogenesis has been associated with chronic inflammatory conditions, it has yet to be demonstrated in AAA. The aim was to determine the presence of lymphangiogenesis and to delineate the relationship between inflammation and neovascularization in AAA tissue.MethodsAAA samples and preoperative computed tomography images were obtained from patients undergoing elective AAA repair. Control samples were age-matched abdominal aortic tissue. Specific immunostains for blood vessels (CD31, CD105), lymphatic vessels (D2-40), vascular endothelial growth factor (VEGF) A and VEGF receptor (VEGFR) 3 allowed characterization and quantitation of vasculature.ResultsThe AAA wall contained high levels of inflammatory infiltrate; microvascular densities of blood (P &lt; 0·001) and lymphatic (P = 0·003) vessels were significantly increased in AAA samples compared with controls. Maximal AAA vascularity was observed in inflammatory areas, with vessels that stained positively for CD31 (ρ = 0·625, P = 0·017), CD105 (ρ = 0·692, P = 0·009) and D2-40 (ρ = 0·675, P = 0·008) correlating positively with the extent of inflammation. Increased VEGFR-3 and VEGF-A expression was also evident within inflammatory AAA areas.ConclusionThese findings demonstrated lymphatic vessel involvement in end-stage AAA disease, which was associated with the degree of inflammation, and confirmed the involvement of neovascularization.
Forecasting deforestation and carbon emissions in tropical developing countries facing demographic expansion: a case study in Madagascar
Authors: Vieilledent Ghislain , Grinand Clovis , Vaudry Romuald 
Published: May 2013

AbstractAnthropogenic deforestation in tropical countries is responsible for a significant part of global carbon dioxide emissions in the atmosphere. To plan efficient climate change mitigation programs (such as REDD+, Reducing Emissions from Deforestation and forest Degradation), reliable forecasts of deforestation and carbon dioxide emissions are necessary. Although population density has been recognized as a key factor in tropical deforestation, current methods of prediction do not allow the population explosion that is occurring in many tropical developing countries to be taken into account. Here, we propose an innovative approach using novel computational and statistical tools, including R/GRASS scripts and the new phcfM R package, to model the intensity and location of deforestation including the effect of population density. We used the model to forecast anthropogenic deforestation and carbon dioxide emissions in five large study areas in the humid and spiny‐dry forests of Madagascar. Using our approach, we were able to demonstrate that the current rapid population growth in Madagascar (+3.39% per year) will significantly increase the intensity of deforestation by 2030 (up to +1.17% per year in densely populated areas). We estimated the carbon dioxide emissions associated with the loss of aboveground biomass to be of 2.24 and 0.26 tons per hectare and per year in the humid and spiny‐dry forest, respectively. Our models showed better predictive ability than previous deforestation models (the figure of merit ranged from 10 to 23). We recommend this approach to reduce the uncertainty associated with deforestation forecasts. We also underline the risk of an increase in the speed of deforestation in the short term in tropical developing countries undergoing rapid population expansion.
High resolution 13CNMR detection of short‐ and medium‐chain synthetic triacylglycerols used in butterfat adulteration
Authors: Picariello Gianluca , Sacchi Raffaele , Fierro Olga , Melck Dominique , Romano Raffaele , Paduano Antonello , Motta Andrea , Addeo Francesco 
Published: May 2013

Recently in European countries, control laboratories have revealed real cases of deceptive practices in which synthetic triacylglycerols (TAGs) were used for adulterating butterfat. The complex fat blends are difficult to detect with the classical methods of analysis, especially when the adulterating TAGs contain fatty acids (FAs) in the proportions similar to that of genuine butter. Nevertheless, because butyric acid (C4) exclusively occurs at the sn‐3 position in milk fat TAGs, the determination of its distribution on the glycerol backbone provides a diagnostic indicator to differentiate genuine butter from mixtures with synthetic TAGs. Herein, we have demonstrated the straightforward application of mono‐dimensional 13C NMR spectroscopy for detecting synthetic TAGs in mixtures with authentic butterfat. The method is based on the 13C NMR determination of the regioisomeric distribution of C4 between the sn‐1,3‐ and sn‐2‐positions and boasts several analytical advantages, such as specificity, robustness and minimal sample handling. The limit of detection (LOD) and limit of quantification (LOQ) of the synthetic fats, estimated to be 1 and 2.5% w/w, respectively, easily surpass the limit of 10% at which a fraudulent practice might be economically attractive.Practical applications We have developed a robust and efficient method, based on high resolution 13C NMR spectroscopy, for detecting the adulteration of butterfat with synthetic low‐ and medium‐carbon number TAG mixtures. In milk fat TAGs, butyric acid is esterified exclusively at the sn‐3 position of the glycerol backbone. Thus, the method relies on 13C NMR monitoring of the carbonyl resonance of butyric acid at the sn‐2 glycerol position, which is diagnostic of synthetic or interesterified TAGs. The 13C NMR‐based analysis overcomes the pitfalls of traditional pattern recognition methodologies for the assessment of butter authenticity, which can be ineffective when butter is adulterated with synthetic TAGs obtained from FA in proportions similar to those of natural milk fat. The method achieves reliable quantification up to 2.5% w/w of adulterating fats (LOQ) and can detect quantities as low as 1% w/w of synthetic TAGs blended with butter (LOD).
Hybrid in silico models for drug‐induced liver injury using chemical descriptors and in vitro cell‐imaging information
Authors: Zhu Xiang‐Wei , Sedykh Alexander , Liu Shu‐Shen 
Published: May 2013

ABSTRACTDrug‐induced liver injury (DILI) is a major adverse drug reaction that accounts for one‐third of post‐marketing drug withdrawals. Several classifiers for human hepatotoxicity using chemical descriptors with limited prediction accuracies have been published. In this study, we developed predictive in silico models based on a set of 156 DILI positive and 136 DILI negative compounds for DILI prediction. First, models based on a chemical descriptor (CDK, Dragon and MOE) and in vitro cell‐imaging endpoints [human hepatocyte imaging assay technology (HIAT) descriptors] were built using random forest (RF) and five‐fold cross‐validation procedure. Then three hybrid models were built using HIAT and a single type of chemical descriptors. Generally, the models based only on chemical descriptors were poor, with a correct classification rate (CCR) around 0.60 when the default threshold value (i.e. threshold = 0.50) was used. The hybrid models afforded a CCR of 0.73 with a specificity of 0.74 and a better true positive rate (sensitivity of 0.71), which is crucial in drug toxicity screening for the purpose of patient safety. The benefit of hybrid models was even more drastic when stricter classification thresholds were employed (e.g. CCR would be 0.83 when double thresholds (non‐toxic < 0.40 and toxic > 0.60) were used for the hybrid model). We have developed rigorously validated hybrid models which can be used in virtual screening of lead compounds with potential hepatotoxicity. Our study also showed a chemical structure and in vitro biological data can be complementary in enhancing the prediction accuracy of human hepatotoxicity and can afford rational mechanistic interpretation. Copyright © 2013 John Wiley & Sons, Ltd.
Delivery of S1P receptor‐targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect
Authors: Das Anusuya , Tanner Shaun , Barker Daniel A. , Green David , Botchwey Edward A. 
Published: May 2013

AbstractBiodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic‐co‐glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1‐phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow‐degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro‐computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in‐growth and an increase in new bone formation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1210‐1218, 2014.
ATF4 promotes bone angiogenesis by increasing vegf expression and release in the bone environment
Authors: Zhu Ke , Jiao Hongli , Li Shuai , Cao Huiling , Galson Deborah L , Zhao Zhongfang , Zhao Xi , Lai Yumei , Fan Jie , Im Hee-Jeong , Chen Di , Xiao Guozhi 
Published: May 2013

ABSTRACT

Activating transcription factor 4 (ATF4) is a critical transcription factor for bone remodeling; however, its role in bone angiogenesis has not been established. Here we show that ablation of the Atf4 gene expression in mice severely impaired skeletal vasculature and reduced microvascular density of the bone associated with dramatically decreased expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in osteoblasts located on bone surfaces. Results from in vivo studies revealed that hypoxia/reoxygenation induction of HIF-1α and VEGF expression leading to bone angiogenesis, a key adaptive response to hypoxic conditions, was severely compromised in mice lacking the Atf4 gene. Loss of ATF4 completely prevented endothelial sprouting from embryonic metatarsals, which was restored by addition of recombinant human VEGF protein. In vitro studies revealed that ATF4 promotion of HIF-1α and VEGF expression in osteoblasts was highly dependent upon the presence of hypoxia. ATF4 interacted with HIF-1α in hypoxic osteoblasts, and loss of ATF4 increased HIF-1α ubiquitination and reduced its protein stability without affecting HIF-1α mRNA stability and protein translation. Loss of ATF4 increased the binding of HIF-1α to prolyl hydroxylases, the enzymes that hydroxylate HIF-1a protein and promote its proteasomal degradation via the pVHL pathway. Furthermore, parathyroid hormone-related protein (PTHrP) and receptor activator of NF-κB ligand (RANKL), both well-known activators of osteoclasts, increased release of VEGF from the bone matrix and promoted angiogenesis through the protein kinase C- and ATF4-dependent activation of osteoclast differentiation and bone resorption. Thus, ATF4 is a new key regulator of the HIF/VEGF axis in osteoblasts in response to hypoxia and of VEGF release from bone matrix, two critical steps for bone angiogenesis.