bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large TCR Diversity of Virus-Specific CD8 T Cells Provides the Mechanistic Basis for Massive TCR Renewal after Antigen Exposure
Authors: Miconnet Isabelle , Marrau Angélique , Farina Alex , Taffé Patrick , Vigano Selena , Harari Alexandre , Pantaleo Giuseppe 
Published: May 2011

Abstract
Ex vivo analysis of virus-specific CD8 T cell populations by anchored PCR has shown that the CD8 TCR repertoire was less oligoclonal (seven to nine clonotypes per individual epitope) than previously thought. In the current study, TCR diversity was investigated by assessing both the overall TCR β-chain variable regions usage as well as the CDR3 regions in ex vivo-isolated CMV- and EBV-specific CD8 T cells from 27 healthy donors. The average number of clonotypes specific to most single viral epitopes comprised between 14 and 77. Changes in the CD8 TCR repertoire were also longitudinally assessed under conditions of HIV-1 chronic infection (i.e., in patients with suppressed virus replication and after treatment interruption and Ag re-exposure). The results showed that a large renewal (≤80%) of the TRB repertoire occurred after Ag re-exposure and was eventually associated with an increased T cell recognition functional avidity. These results demonstrate that the global CD8 TCR repertoire is much more diverse (≤9-fold) than previously estimated and provide the mechanistic basis for supporting massive repertoire renewal during chronic virus infection and Ag re-exposure.
Tumor Cell Programmed Death Ligand 1-Mediated T Cell Suppression Is Overcome by Coexpression of CD80
Authors: Haile Samuel T. , Bosch Jacobus J. , Agu Nnenna I. , Zeender Annette M. , Somasundaram Preethi , Srivastava Minu K. , Britting Sabine , Wolf Julie B. , Ksander Bruce R. , Ostrand-Rosenberg Suzanne 
Published: May 2011

Abstract
Programmed death ligand 1 (PDL1, or B7-H1) is expressed constitutively or is induced by IFN-γ on the cell surface of most human cancer cells and acts as a “molecular shield” by protecting tumor cells from T cell-mediated destruction. Using seven cell lines representing four histologically distinct solid tumors (lung adenocarcinoma, mammary carcinoma, cutaneous melanoma, and uveal melanoma), we demonstrate that transfection of human tumor cells with the gene encoding the costimulatory molecule CD80 prevents PDL1-mediated immune suppression by tumor cells and restores T cell activation. Mechanistically, CD80 mediates its effects through its extracellular domain, which blocks the cell surface expression of PDL1 but does not prevent intracellular expression of PDL1 protein. These studies demonstrate a new role for CD80 in facilitating antitumor immunity and suggest new therapeutic avenues for preventing tumor cell PDL1-induced immune suppression.
Lung Neutrophils Facilitate Activation of Naive Antigen-Specific CD4+ T Cells during Mycobacterium tuberculosis Infection
Authors: Blomgran Robert , Ernst Joel D. 
Published: May 2011

Abstract
Initiation of the adaptive immune response to Mycobacterium tuberculosis occurs in the lung-draining mediastinal lymph node and requires transport of M. tuberculosis by migratory dendritic cells (DCs) to the local lymph node. The previously published observations that 1) neutrophils are a transiently prominent population of M. tuberculosis-infected cells in the lungs early in infection and 2) that the peak of infected neutrophils immediately precedes the peak of infected DCs in the lungs prompted us to characterize the role of neutrophils in the initiation of adaptive immune responses to M. tuberculosis. We found that, although depletion of neutrophils in vivo increased the frequency of M. tuberculosis-infected DCs in the lungs, it decreased trafficking of DCs to the mediastinal lymph node. This resulted in delayed activation (CD69 expression) and proliferation of naive M. tuberculosis Ag85B-specific CD4 T cells in the mediastinal lymph node. To further characterize the role of neutrophils in DC migration, we used a Transwell chemotaxis system and found that DCs that were directly infected by M. tuberculosis migrated poorly in response to CCL19, an agonist for the chemokine receptor CCR7. In contrast, DCs that had acquired M. tuberculosis through uptake of infected neutrophils exhibited unimpaired migration. These results revealed a mechanism wherein neutrophils promote adaptive immune responses to M. tuberculosis by delivering M. tuberculosis to DCs in a form that makes DCs more effective initiators of naive CD4 T cell activation. These observations provide insight into a mechanism for neutrophils to facilitate initiation of adaptive immune responses in tuberculosis.
Rituximab-Associated Progressive Multifocal Leukoencephalopathy in Rheumatoid Arthritis
Authors: Clifford David B. , Ances Beau , Costello Craig , Rosen-Schmidt Shari , Andersson Magnus , Parks Deborah , Perry Arie , Yerra Raju , Schmidt Robert , Alvarez Enrique , Tyler Kenneth L. 
Published: May 2011

ObjectiveTo describe the development of progressive multifocal leukoencephalopathy (PML) in patients with rheumatoid arthritis (RA) treated with rituximab.DesignCase study.SettingClinical care for patients with rheumatologic diseases. Most were referred to academic centers for care after diagnosis (Washington University, St Louis, Missouri; Karolinska Insitute, Stockholm, Sweden; and Royal Melbourne Hospital, Melbourne, Australia) while one was cared for in a neurology practice in Dallas, Texas, with consultation by an academic neurovirologist from the University of Colorado in Denver.PatientsFour patients developing PML in the setting of rituximab therapy for RA.InterventionRituximab therapy.Main Outcome MeasuresClinical and pathological observations.ResultsFour patients from an estimated population of 129 000 exposed to rituximab therapy for RA are reported in whom PML developed after administration of this drug. All were women older than 50 years, commonly with Sjögren syndrome and a history of treatment for joint disease ranging from 3 to 14 years. One case had no prior biologic and minimal immunosuppressive therapy. Progressive multifocal leukoencephalopathy presented as a progressive neurological disorder, with diagnosis confirmed by detection of JC virus DNA in the cerebrospinal fluid or brain biopsy specimen. Two patients died in less than 1 year from PML diagnosis, while 2 remain alive after treatment withdrawal. Magnetic resonance scans and tissue evaluation confirmed the frequent development of inflammatory PML during the course of the disease.ConclusionThese cases suggest an increased risk, about 1 case per 25 000 individuals, of PML in patients with RA being treated with rituximab. Inflammatory PML may occur in this setting even while CD20 counts remain low.
Effect ofAPOEε4 Status on Intrinsic Network Connectivity in Cognitively Normal Elderly Subjects
Authors: Machulda Mary M. , Jones David T. , Vemuri Prashanthi , McDade Eric , Avula Ramesh , Przybelski Scott , Boeve Brad F. , Knopman David S. , Petersen Ronald C. , Jack Clifford R. 
Published: May 2011

ObjectiveTo examine default mode and salience network functional connectivity as a function ofAPOEε4 status in a group of cognitively normal age-, sex-, and education-matched older adults.DesignCase-control study.SubjectsFifty-six cognitively normalAPOEε4 carriers and 56 age-, sex- and education-matched cognitively normalAPOEε4 noncarriers.Main Outcome MeasureAlterations in in-phase default mode and salience network connectivity inAPOEε4 carriers compared withAPOEε4 noncarriers ranging from 63 to 91 years of age.ResultsA posterior cingulate seed revealed decreased in-phase connectivity in regions of the posterior default mode network that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative toAPOEε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus inAPOEε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy.ConclusionsThe observation of functional alterations in default mode and salience network connectivity in the absence of structural changes betweenAPOEε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.
Acids and Acid Catalysis – Homogeneous
Authors: Molnar Arpad 
Published: May 2011

AbstractThe concept of acidity has changed tremendously over the years. It has developed from protic acids in the aqueous phaseviaLewis acids with no proton at all to superacids. Acids are the most frequent catalysts of organic chemistry in the homogeneous phase and they find application as heterogeneous catalysts as well. In solution they catalyze a huge variety of transformations ranging from rearrangements of various kinds to alkylations to Friedel–Crafts reactions. Intermediates are carbenium as well as carbonium ions. In many cases they can be identified and occasionally even isolated. Many of the laws governing acid‐catalyzed reactions are known to such an extent that mechanistic and quantitative descriptions can be given.
Evaluation of group and self‐directed formats of the Arthritis Foundation's Walk With Ease Program
Authors: Callahan Leigh F. , Shreffler Jack H. , Altpeter Mary , Schoster Britta , Hootman Jennifer , Houenou Laura O. , Martin Kathryn R. , Schwartz Todd A. 
Published: May 2011

AbstractObjectiveTo evaluate the effects of a revised 6‐week walking program for adults with arthritis, Walk With Ease (WWE), delivered in 2 formats, instructor‐led group or self‐directed.MethodsIn an observational pre‐post study design, 462 individuals with self‐reported arthritis selected either a group format (n = 192) or a self‐directed (n = 270) format. Performance and self‐reported outcomes were assessed at baseline and at 6 weeks. Self‐reported outcomes were assessed at 1 year. Adjusted mean outcome values for group and self‐directed participants were determined using regression models, adjusting for covariates.ResultsAt 6 weeks, significant adjusted mean improvements (P < 0.05) were seen for nearly all self‐report and performance measures in both formats. Modest to moderate effect sizes (ES) were seen for disability (ES 0.16–0.23), pain, fatigue, and stiffness (ES 0.21–0.40), and helplessness (ES 0.24–0.28). The Arthritis Self‐Efficacy (ASE) pain and symptom scales had modest improvements (ES 0.09–0.21). The performance measures of strength (ES 0.29–0.35), balance (ES 0.12–0.36), and walking pace (ES 0.12–0.32) all showed modest to moderate improvements. No adverse events were reported for either format. At 1 year, both formats showed modest improvement in ASE pain, but there were 5 outcomes where self‐directed participants showed significant improvement, while the group participants did not.ConclusionThe revised WWE program decreases disability and improves arthritis symptoms, self‐efficacy, and perceived control, balance, strength, and walking pace in individuals with arthritis, regardless of whether they are taking a group class or doing the program as self‐directed walkers. At 1 year, some benefits are maintained, particularly among the self‐directed. This is a safe, easy, and inexpensive program to promote community‐based physical activity.
Additional features of unique Primrose syndrome phenotype
Authors: Carvalho Daniel Rocha , Speck‐Martins Carlos Eduardo 
Published: May 2011

AbstractPrimrose syndrome is a unique condition of intellectual disability, dysmorphic facial features, and specific minor abnormalities including large calcified ear auricles. Only six patients have been previously reported. We describe a Brazilian boy with the striking similar facies and the main clinical findings that reinforced the singular phenotype of this rare disorder. The key features of all patients already published were compared. Our young patient has abnormalities that were not observed in preceding reports: nail dysplasia and hyperuricemia. © 2011 Wiley‐Liss, Inc.
Familial 9q22.3 microduplication spanning PTCH1 causes short stature syndrome with mild intellectual disability and dysmorphic features
Authors: Izumi Kosuke , Hahn Amanda , Christ Laurie , Curtis Christine , Neilson Derek E 
Published: May 2011

AbstractPartial trisomy 9q involving the duplication of band 9q22 is manifested by a constellation of symptoms including short stature, intellectual disability, microcephaly, pyloric stenosis, facial dysmorphism, and various defects of the heart, distal extremities, eyes, thyroid, and esophagus. In three family members with growth retardation, mild intellectual disability, and mild facial dysmorphism, array‐based comparative genomic hybridization analyses showed a familial microduplication at 9q22.3. On the basis of the described functions of the duplicated genes, PTCH1 represents a candidate gene that may be responsible for the phenotypic findings, although the 14 other genes in this duplicated segment may also contribute to the phenotype. The current report provides evidence to support a specific phenotype associated with a 9q22.3 microduplication and confirm localization of a subset of the trisomy 9q phenotype to this chromosomal region. © 2011 Wiley‐Liss, Inc.
Ritscher–Schinzel (cranio‐cerebello‐cardiac, 3C) syndrome: Report of four new cases with renal involvement
Authors: Seidahmed Mohammed Zein , Alkuraya Fowzan S. , Shaheed Meeralebbae , Al Zahrani Mohammed , Al Manea Waleed , Mansour Fayzeh , Mustafa Tareq , Farid Gehan , Salih Mustafa A. 
Published: May 2011

AbstractRitscher–Schinzel (cranio‐cerebello‐cardiac, 3C) syndrome is a multiple congenital anomaly syndrome that is considered to be autosomal recessive although no genetic defect has yet been identified. In a consanguineous Saudi family, we have identified four patients who meet the diagnostic criteria of 3C syndrome and who also have alopecia, camptodactaly and significant renal involvement. Interestingly, two otherwise normal female siblings have unilateral renal agenesis only. This report expands the phenotypic spectrum of 3C syndrome. © 2011 Wiley‐Liss, Inc.
Clinical and molecular description of a Wilms tumor in a patient with tuberous sclerosis complex
Authors: Spreafico Filippo , Notarangelo Lucia Dora , Schumacher Richard Fabian , Savoldi Gianfranco , Gamba Beatrice , Terenziani Monica , Collini Paola , Fasoli Silvia , Giordano Lucio , Luisa Bercich , Porta Fulvio , Massimino Maura , Radice Paolo , Perotti Daniela 
Published: May 2011

AbstractWe report on a girl affected with tuberous sclerosis, carrying a germline de novo TSC2 mutation, c.4934‐4935delTT, leading to a p.F1645CfsX7, who developed a unilateral Wilms tumor (WT). Molecular investigation of the tumor biopsy at diagnosis revealed the loss of the constitutional wild‐type TSC2 allele, and loss of heterozygosity for the WT1 gene. Deletion of the WTX gene was also present, but it involved the functionally inactive X chromosome. No mutation affecting the remaining WT1 and WTX alleles, as well as the CTNNB1 gene was found. Pathological examination of the surgical specimen documented the presence of diffuse anaplasia and p53 immunoreactivity. To the best of our knowledge, this is the second report of a patient with tuberous sclerosis who developed a WT, and it represents the first case in which a detailed clinical and molecular description is provided. © 2011 Wiley‐Liss, Inc.
TGFBR2 deletion in a 20‐month‐old female with developmental delay and microcephaly
Authors: Campbell Ian M. , Kolodziejska Katarzyna E. , Quach Michael M. , Wolf Varina Louise , Cheung Sau Wai , Lalani Seema R. , Ramocki Melissa B. , Stankiewicz Pawel 
Published: May 2011

AbstractTo date, over 70 mutations in the TGFBR2 gene have been reported in patients with Loeys–Dietz syndrome (LDS), Marfan syndrome type 2 (MFS2), or other hereditary thoracic aortic aneurysms and dissections. Whereas almost all of mutations analyzed thus far are predicted to disrupt the constitutively active C‐terminal serine/threonine kinase domain of TGFBR2, mounting evidence suggests that the molecular mechanism underlying these diseases is more complex than simple haploinsufficiency. Using exon‐targeted oligonucleotide array comparative genomic hybridization, we identified an ∼896 kb deletion of TGFBR2 in a 20‐month‐old female with microcephaly and global developmental delay, but no stigmata of LDS. FISH analysis showed no evidence of this deletion in the parental peripheral blood samples; however, somatic mosaicism was detected using PCR in the paternal DNA from peripheral blood lymphocytes and lymphoblasts. Our data suggest that TGFBR2 haploinsufficiency may cause a phenotype, which is distinct from LDS. Moreover, we propose that somatic mosaicism below the detection threshold of FISH analysis in asymptomatic parents of children with genomic disorders may be more common than previously recognized. © 2011 Wiley‐Liss, Inc.
Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans
Authors: Shaheen Ranad , Al‐Owain Mohammed , Faqeih Eissa , Al‐Hashmi Nadia , Awaji Ali , Al‐Zayed Zayed , Alkuraya Fowzan S 
Published: May 2011

AbstractBruck syndrome (BS) is an autosomal recessive syndromic form of osteogenesis imperfecta (OI) that is characterized by the additional presence of pterygium formation. We have recently shown that FKBP10 previously reported as a novel autosomal recessive OI gene also defines a novel Bruck syndrome locus (BKS3). In this manuscript, we extend our analysis to describe a mutation previously described in isolated OI patients and show that it results in BS phenotype in a Saudi family. More interestingly, we describe a novel FKBP10 mutation that results in isolated OI as well as BS phenotype in the same family. These results, combined with recently published work, confirm that FKBP10 is a bonafide BS locus and lay the foundation for future research into modifiers that underlie the phenotypic heterogeneity of FKBP10 mutations. © 2011 Wiley‐Liss, Inc.
Delayed cortical impairment following lipopolysaccharide exposure in preterm fetal sheep
Authors: Dean Justin M. , van de Looij Yohan , Sizonenko Stephane V. , Lodygensky Gregory A. , Lazeyras Francois , Bolouri Hayde , Kjellmer Ingemar , Huppi Petra S. , Hagberg Henrik , Mallard Carina 
Published: May 2011

AbstractObjective:Preterm infants exhibit chronic deficits in white matter (WM) and cortical maturation. Although fetal infection/inflammation may contribute to WM pathology, the factors contributing to cortical changes are largely unknown. We examined the effect of fetal lipopolysaccharide (LPS) exposure on WM and cortical development as assessed by magnetic resonance imaging (MRI), electroencephalography (EEG), and histopathology in fetal sheep at preterm human equivalent age.Methods:LPS was administered to fetal sheep at 102.5 ± 0.5 days of gestation. Continuous biophysical recordings were analyzed for 10 days after LPS. At postmortem, measurement of cerebral WM and cortical tissue volumes was achieved by stereological techniques. Specific effects of LPS on MRI‐assessed T1‐weighted and T2‐weighted images, and immunohistochemical expression of oligodendrocytes, proliferating cells, cortical NeuN‐positive and Nurr1‐positive neurons (subplate marker), and cell death mechanisms were examined.Results:We observed reductions in WM (∼21%; LPS, 1.19 ± 0.04 vs control, 1.51 ± 0.07cm3; p < 0.001) and cortical (∼18%; LPS, 2.34 ± 0.10 vs control, 2.85 ± 0.07cm3; p < 0.001) volumes, associated with overt and diffuse WM injury, T1‐/T2‐weighted signal alterations, and reduced numbers of WM oligodendrocytes (LPS, 485 ± 31 vs control, 699 ± 69 cells/mm2; p = 0.0189) and NeuN‐positive (LPS, 421 ± 71 vs control 718 ± 92 cells/mm2; p = 0.04) and Nurr1‐positive (control, 2.5 ± 0.6 vs LPS, 0.6 ± 0.1 cells/mm2; p = 0.007) cortical neurons after LPS. Moreover, there was loss of the normal maturational increase in cortical EEG amplitude, which correlated with reduced cortical volumes.Interpretation:Fetal exposure to LPS prior to myelination onset can impair both white matter and cortical development in a preclinical large animal model, supporting a role for maternal/fetal infection in the pathogenesis of preterm brain injury. ANN NEUROL 2011
Microencapsulation of sulfur in poly(urea–formaldehyde)
Authors: Li Jie , Wang Shu‐Jun , Liu Hong‐Yan , Wang Su‐Kai , You Long 
Published: May 2011

AbstractPoly(urea–formaldehyde) (PUF) microcapsules loaded with sulfur were prepared by in situ polymerization. Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry and thermogravimetric (TG) analysis were used for the characterization of the obtained microcapsules. The chemical structure of the microcapsules was determined by FTIR. SEM analysis showed that the microcapsules were spherical and that the mean diameter of microcapsules was 42 ± 1 μm. Thermal analysis showed that the microcapsules were thermally stable below 247°C. The release properties of sulfur from the PUF microcapsules during the vulcanization of acrylonitrile–butadiene rubber (NBR) were studied by analysis of the vulcanization properties. The results show that at a vulcanizing temperature of 160°C, all of the sulfur entrapped in PUF was released out through the microcracks and pores of the shell, and the curing time of the microcapsule curing system compared with that of the sulfur curing system was longer. The mechanical properties of the NBR vulcanized by sulfur microcapsules were better than those of the NBR vulcanized by sulfur. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Synthesis and characterization of bis‐triethoxysilane endcapped polyurethane/urea
Authors: Gao Feng , Ku Bin , Huang Shiqiang 
Published: May 2011

AbstractA type of bistriethoxysilane endcapped polyurethane/ureas (SPU) with well‐defined structure was synthesized from bis(triethoxysiylpropyl) amine and purified prepolymers, which were obtained from the reaction of 2,4‐toluene diisocyanate (TDI) and polyoxyethylene glycol (PEG) with different molecular weight. Then, fourier transform infrared spectroscopy (FTIR), hydrogen nuclearmagnetic resonance (1H‐NMR) and standard dibutylamine back‐titration method were used to confirm the structures of prepolymers and SPUs. Moreover, the properties of SPU were investigated by wide angle X‐ray diffraction (WAXD), differential scanning calorimetry (DSC), thermogravimetric analyses (TGA), and percentage of water uptake. Results indicated that these polyurethanes were amorphous, and the percentage of water uptake and thermal stability of these polyurethanes went up with the increase of Mn of SPU, accompanying with the glass transition temperature (Tg) values decreased with the increase of Mn. This study provides us with a method to synthesize well‐defined end‐functionalized polyurethane. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011