bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting CXCR3-Dependent CD8+ T Cell Trafficking Enhances Tolerance Induction in a Mouse Model of Lung Rejection
Authors: Seung Edward , Cho Josalyn L. , Sparwasser Tim , Medoff Benjamin D. , Luster Andrew D. 
Published: May 2011

Abstract
Lung transplantation remains the only effective therapy for patients with end-stage pulmonary diseases. Unfortunately, acute rejection of the lung remains a frequent complication and is an important cause of morbidity and mortality. The induction of transplant tolerance is thought to be dependent, in part, on the balance between allograft effector mechanisms mediated by effector T lymphocytes (Teff), and regulatory mechanisms mediated by FOXP3+ regulatory T cells (Treg). In this study, we explored an approach to tip the balance in favor of regulatory mechanisms by modulating chemokine activity. We demonstrate in an adoptive transfer model of lung rejection that CXCR3-deficient CD8+ Teff have impaired migration into the lungs compared with wild-type Teff, which results in a dramatic reduction in fatal pulmonary inflammation. The lungs of surviving mice contained tolerized CXCR3-deficient Teff, as well as a large increase in Treg. We confirmed that Treg were needed for tolerance and that their ability to induce tolerance was dependent on their numbers in the lung relative to the numbers of Teff. These data suggest that transplantation tolerance can be achieved by reducing the recruitment of some, but not necessarily all, CD8+ Teff into the target organ and suggest a novel approach to achieve transplant tolerance.
Generation of Human Regulatory γδ T Cells by TCRγδ Stimulation in the Presence of TGF-β and Their Involvement in the Pathogenesis of Systemic Lupus Erythematosus
Authors: Li Xiaoyan , Kang Ning , Zhang Xuan , Dong Xiaoying , Wei Wei , Cui Lianxian , Ba Denian , He Wei 
Published: May 2011

Abstract
As a component of the innate immune cell population, γδ T cells are involved in tumor immunosurveillance and host defense against viral invasion. In this study, we demonstrated a novel function of human γδ T cells as regulatory cells by detecting their suppressive effect on the proliferation of autologous naive CD4+ T cells. These regulatory γδ T cells (γδ Tregs) could be generated in vitro by stimulating with anti-TCRγδ in the presence of TGF-β and IL-2. Similar to CD4+Foxp3+ Tregs, γδ Tregs also expressed Foxp3. Additionally, they primarily belonged to the Vδ1 subset with a CD27+CD25high phenotype. Furthermore, these γδ Tregs showed an immunoregulatory activity mainly through cell-to-cell contact. Importantly, this γδ regulatory population decreased in the peripheral blood of systemic lupus erythematosus patients, suggesting a potential mechanism in understanding the pathogenesis of systemic lupus erythematosus.
Genetic Evidence for an Evolutionarily Conserved Role of IL-7 Signaling in T Cell Development of Zebrafish
Authors: Iwanami Norimasa , Mateos Fernando , Hess Isabell , Riffel Nico , Soza-Ried Cristian , Schorpp Michael , Boehm Thomas 
Published: May 2011

Abstract
In mammals, the cytokine IL-7 is a key regulator of various aspects of lymphocyte differentiation and homeostasis. Because of the difficulty of identifying cytokine homologs in lower vertebrates and the paucity of assay systems and reagents, the degree of functional conservation of cytokine signaling pathways, particularly those pertaining to lymphocyte development, is unclear. In this article, we report on the analysis and characterization of three zebrafish mutants with severely impaired thymopoiesis. The identification of affected genes by positional cloning revealed components of the IL-7 signaling pathway. A presumptive null allele of the zebrafish homolog of the IL-7Rα–chain causes substantially reduced cellularity of the thymus but spares B cell development in the kidney. Likewise, nonsense mutations in the zebrafish homologs of janus kinases JAK1 and JAK3 preferentially affect T cell development. The functional interactions of the cytokine receptor components were examined in the three groups of fish hetero- or homozygous for either il7r and jak1, il7r and jak3, or jak1 and jak3 mutations. The differential effects on T cell development arising from the different genotypes could be explained on the basis of the known structure of the mammalian IL-7R complex. Because IL-7 signaling appears to be a universal requirement for T cell development in vertebrates, the mutants described in this article represent alternative animal models of human immunodeficiency syndromes amenable to large-scale genetic and chemical screens.
Antigen Delivery to Plasmacytoid Dendritic Cells via BST2 Induces Protective T Cell-Mediated Immunity
Authors: Loschko Jakob , Schlitzer Andreas , Dudziak Diana , Drexler Ingo , Sandholzer Nadja , Bourquin Carole , Reindl Wolfgang , Krug Anne B. 
Published: May 2011

Abstract
Plasmacytoid dendritic cells (PDCs) are capable of presenting Ags to T cells in a tolerogenic or immunogenic manner depending on the formulation of the Ag and the mode of stimulation. It has not been investigated whether effective adaptive immune responses useful for vaccination can be induced by Ab-mediated Ag targeting to PDCs in vivo. In this study, we show that Ag delivered to murine PDCs via bone marrow stromal cell Ag 2 (BST2)/CD317 in combination with TLR agonists as adjuvants is specifically presented by PDCs in vivo and elicits strong cellular and humoral immune responses. These include IFN-γ production by CD4+ T cells and high Ab titers with a broad range of IgG isotypes. In addition, BST2-mediated Ag delivery in the presence of polyinosinic-polycytidylic acid as adjuvant induces cytotoxic T lymphocytes that are functional in vivo. A single immunization with Ag-fused anti-BST2 Ab together with polyinosinic-polycytidylic acid as adjuvant is sufficient to trigger protective immunity against subsequent viral infection and tumor growth. We conclude that despite the potential tolerogenic properties of PDCs, Ag targeting to PDCs in combination with TLR agonists as adjuvants is an effective vaccination strategy.
Effect of Angiogenesis-Related Cytokines on Rotator Cuff Disease: The Search for Sensitive Biomarkers of Early Tendon Degeneration
Authors: Savitskaya Yulia A. , Izaguirre Aldo , Sierra Luis , Perez Francisco , Cruz Francisco , Villalobos Enrique , Almazan Arturo , Ibarra Clemente 
Published: May 2011

BackgroundHallmarks of the pathogenesis of rotator cuff disease (RCD) include an abnormal immune response, angiogenesis, and altered variables of vascularity. Degenerative changes enhance production of pro-inflammatory, anti-inflammatory, and vascular angiogenesis-related cytokines (ARC) that play a pivotal role in the immune response to arthroscopic surgery and participate in the pathogenesis of RCD. The purpose of this study was to evaluate the ARC profile, ie, interleukin (IL): IL-1β, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG), in human peripheral blood serum and correlate this with early degenerative changes in patients with RCD.MethodsBlood specimens were obtained from 200 patients with RCD and 200 patients seen in the orthopedic clinic for nonrotator cuff disorders. Angiogenesis imaging assays was performed using power Doppler ultrasound to evaluate variables of vascularity in the rotator cuff tendons. Expression of ARC was measured by commercial Bio-Plex Precision Pro Human Cytokine Assays.ResultsBaseline concentrations of IL-1β, IL-8, and VEGF was significantly higher in RCD patients than in controls. Significantly higher serum VEGF levels were found in 85% of patients with RCD, and correlated with advanced stage of disease (r = 0.75; P < 0.0005), average microvascular density (r = 0.68, P < 0.005), and visual analog score (r = 0.75, P < 0.0002) in RCD patients. ANG and IL-10 levels were significantly lower in RCD patients versus controls. IL-1β and ANG levels were significantly correlated with degenerative tendon grade in RCD patients. No difference in IL-6 and bFGF levels was observed between RCD patients and controls. Patients with degenerative changes had markedly lower ANG levels compared with controls. Power Doppler ultrasound showed high blood vessel density in patients with tendon rupture.ConclusionThe pathogenesis of RCD is associated with an imbalance between pro-inflammatory, anti-inflammatory, and vascular ARC.
A Monte Carlo Method for Assessing the Quality of Duplication-Aware Alignment Algorithms
Authors: Freschi Valerio , Bogliolo Alessandro 
Published: May 2011

The increasing availability of high throughput sequencing technologies poses several challenges concerning the analysis of genomic data. Within this context, duplication-aware sequence alignment taking into account complex mutation events is regarded as an important problem, particularly in light of recent evolutionary bioinformatics researches that highlighted the role of tandem duplications as one of the most important mutation events. Traditional sequence comparison algorithms do not take into account these events, resulting in poor alignments in terms of biological significance, mainly because of their assumption of statistical independence among contiguous residues. Several duplication-aware algorithms have been proposed in the last years which differ either for the type of duplications they consider or for the methods adopted to identify and compare them. However, there is no solution which clearly outperforms the others and no methods exist for assessing the reliability of the resulting alignments. This paper proposes a Monte Carlo method for assessing the quality of duplication-aware alignment algorithms and for driving the choice of the most appropriate alignment technique to be used in a specific context. The applicability and usefulness of the proposed approach are demonstrated on a case study, namely, the comparison of alignments based on edit distance with or without repeat masking.
Efficient Reduction of Ethyl 2‐Oxo‐4‐phenylbutyrate at 620 g⋅L−1 by a Bacterial Reductase with Broad Substrate Spectrum
Authors: Ni Yan , Li Chun‐Xiu , Zhang Jie , Shen Nai‐Dong , Bornscheuer Uwe T. , Xu Jian‐He 
Published: May 2011

AbstractA β‐ketoacyl‐ACP reductase (FabG) gene from Bacillus sp. ECU0013 was heterologously overexpressed in Escherichia coli and the encoded protein was purified to homogeneity. The recombinant reductase could reduce a broad spectrum of prochiral ketones including aromatic ketones and keto esters and showed the highest activity in the asymmetric reduction of ethyl 2‐oxo‐4‐phenylbutyrate (OPBE). Using E. coli cells coexpressing both FabG and glucose dehydrogenase (GDH) genes, as much as 620 g⋅L−1 of OPBE was almost stoichiometrically converted to ethyl (S)‐2‐hydroxy‐4‐phenylbutyrate [(S)‐HPBE] with excellent (>99%) enantiomeric excess. More importantly, the process could be performed smoothly without external addition of an expensive cofactor as usually done and could be scaled up very easily. All these positive features demonstrate the applicability of this reductase for the large‐scale production of optically active α‐hydroxy acids/esters.
Synthesis and Catalysis in China
Authors: Zhou Qi‐Lin 
Published: May 2011

AbstractIn 2000 China ranked 5th in the world (7.9%) in the publication of SCI papers on organic synthesis and catalysis; by 2008 China had become 1st (21.6%), followed by the USA, Germany and Japan. Major contributions made by Chinese research groups in the last decade in the areas of total synthesis of complex natural products, cross‐coupling, asymmetric catalysis, and heterogeneous catalysis are highlighted. The output and quality of the research on synthesis and catalysis from China continue to increase, so that with the rapid development of China’s economy, Chinese chemists will make greater contributions to organic synthesis and catalysis in the future.
GM2 gangliosidosis in Saudi Arabia: Multiple mutations and considerations for future carrier screening
Authors: Kaya Namik , Owain Mohammad Al‐ , AbuDheim Nada , Zahrani Jawaher Al‐ , Colak Dilek , Sayed Moeen Al‐ , Milanlioglu Aysel , Ozand Pinar T. , Alkuraya Fowzan S. 
Published: May 2011

AbstractThe GM2 gangliosidose, Tay–Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population. Consistent with our previous observation of allelic heterogeneity in consanguineous populations, we show here that these diseases are largely caused by private mutations which present a major obstacle in replicating the Ashkenazi success story. Alternative solutions are proposed which can also be implemented for other autosomal recessive diseases in our population. © 2011 Wiley‐Liss, Inc.
Age related change in social behavior in children with Angelman syndrome
Authors: Adams Dawn , Horsler Kate , Oliver Chris 
Published: May 2011

AbstractWe investigated the relationship between age and laughing and smiling in children with Angelman syndrome. Twenty‐four children with Angelman syndrome were exposed to three experimentally manipulated conditions: proximity only, restricted social interaction, and social interaction. Children smiled the most in the social interaction condition and the least in the proximity only condition confirming the effect of social interaction on these behaviors. There was a decline in smiling and laughing in the oldest group (13.4–15.9 years) only in the social interaction condition. This trajectory of a decline in resource soliciting behaviors with age is consistent with predictions based on kinship theory. © 2011 Wiley‐Liss, Inc.
Extending the phenotype of lethal skeletal dysplasia type al Gazali
Authors: Grigelioniene Giedre , Papadogiannakis Nikos , Conner Peter , Geiberger Stefan , Nishikawa Masanori , Nakayama Masahiro 
Published: May 2011

AbstractIn this study, we describe the clinical and radiological phenotype of two patients with a rare skeletal dysplasia type al Gazali. The phenotype is characterized by brachycephaly, flat face, hypertelorism, low‐set ears, hypertrichosis, hypoplastic thorax, as well as short extremities with brachydactyly. Further characteristics are severe fetal hydrops, radiologic signs of increased bone density and short, poorly modeled tubular bones with wide diaphysis and smooth, rounded metaphyses. Cortical bones as well as vertebral endplates are thick and the skull is sclerotic with prominent parietal bones and a large anterior fontanel. Our cases suggest that skeletal dysplasia type al Gazali is a lethal condition and provide further evidence that it is inherited in an autosomal recessive manner. Both morphological and radiological features of these patients are very similar, which together with the previous report may indicate the presence of a new clinical entity in the group of skeletal dysplasias with increased bone density and metaphyseal and diaphyseal involvement. Surprisingly, histological analysis of the bone tissue and the growth plate shows completely normal structure, which suggests that the skeletal dysplasia type al Gazali is a systemic disorder resulting in increased bone density and restricted growth of the skeleton. © 2011 Wiley‐Liss, Inc.
Type 1 collagenopathy presenting with a Russell–Silver phenotype
Authors: Parker Michael J. , Deshpande Charulata , Rankin Julia , Wilson Louise C. , Balasubramanian Meena , Hall Christine M. , Wagner Bart E. , Pollitt Rebecca , Dalton Ann , Bishop Nicholas J. 
Published: May 2011

AbstractOsteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It exhibits a broad spectrum of clinical severity, ranging from multiple fractures in utero and perinatal death, to normal adult stature and low fracture incidence. Extra‐skeletal features of OI include blue sclera, hearing loss, skin hyperlaxity, joint hyperextensibility, and dentinogenesis imperfecta. The proα1(I) and proα2(I) chains of collagen 1 are encoded by theCOL1A1andCOL1A2genes, respectively; quantitative or qualitative defects in type I collagen synthesis usually manifest as types of OI or some sub‐types of EDS. The majority of patients (about 90%) with a clinical diagnosis of OI have a mutation in theCOL1A1orCOL1A2genes, which shows an autosomal dominant pattern of inheritance. Six other genes,CRTAP,LEPRE1,FKBP10,PP1B,SP7/Osterix(OSX), andSERPINH1, are associated with autosomal recessive forms of OI. However, other, rare phenotypes have also been described. There are many differential diagnoses of the short, syndromic child, including chromosomal, single gene, and multifactorial causes. However, one condition of particular relevance in the context of this report is the Russell–Silver syndrome (RSS). As originally described, the RSS is a very specific condition. However, it has subsequently become an umbrella term for a heterogeneous group of conditions presenting with short stature and triangular shape to the face. A significant proportion of these are now believed to be due to imprinting defects at 11p15. However, the cause in many cases remains unknown. We describe two cases with a phenotypic overlap between OI and RSS who both haveCOL1A1mutations. Thus, a type 1 collagenopathy should be considered in the differential diagnosis of syndromic short stature. © 2011 Wiley‐Liss, Inc.
NOA‐05 phase 2 trial of procarbazine and lomustine therapy in gliomatosis cerebri
Authors: Glas Martin , Bähr Oliver , Felsberg Jörg , Rasch Katja , Wiewrodt Dorothee , Schabet Martin , Simon Matthias , Urbach Horst , Steinbach Joachim P. , Rieger Johannes , Fimmers Rolf , Bamberg Michael , Nägele Thomas , Reifenberger Guido , Weller Michael , Herrlinger MD Ulrich , Group of the German Cancer Society for the Neuro‐Oncology 
Published: May 2011

AbstractObjective:The NOA‐05 multicenter trial was performed to analyze the efficacy of primary chemotherapy with procarbazine and lomustine (PC) in patients with gliomatosis cerebri (GC) and to define clinical, imaging, and molecular factors influencing outcome.Methods:Thirty‐five patients with previously untreated GC were treated with up to six 56‐day courses of 110mg/m2 lomustine on day 1 and 60mg/m2 procarbazine on days 8 to 21. The primary endpoint was the rate of patients without therapy failure (defined as progressive disease, death from any cause, or termination of PC therapy before the end of course 4) at 8 months after the beginning of PC chemotherapy.Results:The failure‐free survival rate at 8 months was 50.3%. Median progression‐free survival was 14 months. At progression, 12 patients received salvage radiotherapy. Median overall survival was 30 months. Multivariate analysis revealed isocitrate dehydrogenase 1 (IDH1) gene mutation (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.02–0.58) and initial presentation without a bilateral symmetrical infiltration pattern on magnetic resonance imaging (HR 0.07, 95%CI 0.01‐0.54) as independent prognostic factors associated with prolonged survival. IDH1 mutation was significantly associated with MGMT promoter methylation and an oligodendroglial tumor component.Interpretation:PC chemotherapy is effective in GC. With the NOA‐05 trial being the first prospective multicenter trial in GC, PC chemotherapy can be regarded as a promising option for the primary therapy of these tumors. Ann Neurol 2011;
Biodegradable amphiphiles of grafted poly(lactide) onto 2‐hydroxyethyl methacrylate‐co‐N‐vinylpyrrolidone copolymers as drug carriers
Authors: Fares Mohammad M. , Assaf Shereen M. , Jaber Anees A. 
Published: May 2011

AbstractThis article describes the synthesis and characterization of 2‐hydroxylethyl methacrylate‐co‐N‐vinylpyrrolidone copolymers, (HEMA‐co‐NVP), via free radical polymerization followed by grafting of poly(lactide) onto (HEMA‐co‐NVP) copolymers, via ring opening polymerization using tin octoate as a catalyst. The copolymers and the grafted copolymers (i.e., amphiphiles) were subjected to sustained release studies using salicylic acid, as a model drug. Characterization of the formed copolymers was performed using 1H‐NMR, 13C‐NMR, FTIR, TGA, DSC, and SEM techniques. Derivative of TGA thermogram was used to determine %hydrophilicity and %hydrophobicity in the grafted and ungrafted copolymers. The SEM morphology revealed porous layers with crispy structure that were most likely due to the presence of poly(lactide) chains. At lower content of poly(lactide) moiety, grafted copolymers showed non‐Fickian diffusion release rate, whereas Fickian diffusion release rate at higher content of poly(lactide) was observed. The increase of poly(lactide) content (i.e., larger %hydrophobicity) in the copolymer increased the drug‐sustainability, due to the consistent but porous amphiphilic degradable structures that allow controllable release of drug in time interval. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
The influence of membrane formation parameters on structural morphology and performance of PES/PDMS composite membrane for gas separation
Authors: Madaeni Sayed S. , Enayati Enayat , Vatanpour Vahid 
Published: May 2011

AbstractIn this study, influence of membrane preparation parameters on structural morphology and performance of polyethersulfone/polydimethylsiloxane (PES/PDMS) composite membrane was investigated for gas separation. Asymmetric PES flat sheet membranes were composed by phase inversion method and used as supports. PES composite membranes were fabricated by coating silicone rubber as selective layer on the top surface of support. Effects of different concentrations of PES and PDMS, solvent type, and support thickness on membrane performance were investigated for separation of oxygen from nitrogen. The optimized superior membrane was further modified using polyvinylidenfluoride, methanol and ethanol as additives in PES solutions and/or in water coagulation bath to promote the membrane capability. The results showed that addition of ethanol and methanol in cast solution and coagulation bath can greatly affect the morphology and hence the performance of the prepared membranes. The permeance changes have the contrary trend with solubility parameter difference between solvent and nonsolvent mixture, for instance when this parameter difference was lowest, higher permeance was obtained. Support and coating polymer concentration can control the permeance. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Association of accelerated switch from vertebral end‐plate Modic I to Modic 0 signal changes with clinical benefit of intradiscal corticosteroid injection for chronic low back pain
Authors: Nguyen Christelle , Bénichou Marc , Revel Michel , Poiraudeau Serge , Rannou François 
Published: May 2011

AbstractModic I vertebral end‐plate signal changes detected by magnetic resonance imaging (MRI) are associated with chronic low back pain. Typically, Modic I signal changes in untreated patients switch to non–Modic I signal changes within 3 years, which reflect spontaneous healing. Recent findings suggest that Modic I signal changes may be related to local inflammatory changes, providing a rationale for treatment with intradiscal injections of antiinflammatory drugs. In the present report, we describe a 31‐year‐old man with 1‐year history of chronic low back pain associated with vertebral end‐plate Modic I signal changes, who received 1 intradiscal corticosteroid injection in L5–S1. Local treatment led to rapid pain relief and was associated with an accelerated switch from Modic I to Modic 0 signal changes, as seen on lumbar MRI at 1‐month followup. This is the first report of an effective local treatment for both the symptoms and the structural changes of chronic low back pain that are associated with Modic I signal changes. Additionally, this case reinforces the hypothesis that local inflammation has a pathogenic role.