bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN-γ Mediates Enhancement of HIV Replication in Astrocytes by Inducing an Antagonist of the β-Catenin Pathway (DKK1) in a STAT 3-Dependent Manner
Authors: Li Wei , Henderson Lisa J. , Major Eugene O. , Al-Harthi Lena 
Published: May 2011

AbstractTypically, IFN-γ is an antiviral cytokine that inhibits the replication of many viruses, including HIV. However, in the CNS, IFN-γ induces HIV-productive replication in astrocytes. Although astrocytes in vitro are refractory to HIV replication, recent in vivo evidence demonstrated that astrocytes are infected by HIV, and their degree of infection is correlated with proximity to activated macrophages/microglia. The ability of IFN-γ to induce HIV replication in astrocytes suggests that the environmental milieu is critical in regulating the permissiveness of astrocytes to HIV infection. We evaluated the mechanism by which IFN-γ relieves restricted HIV replication in astrocytes. We demonstrate that although astrocytes have robust endogenous β-catenin signaling, a pathway that is a potent inhibitor of HIV replication, IFN-γ diminished β-catenin signaling in astrocytes by 40%, as evaluated by both active β-catenin protein expression and β-catenin-mediated T cell factor/lymphoid enhancer reporter (TOPflash) activity. Further, IFN-γ–mediated inhibition of β-catenin signaling was dependent on its ability to induce an antagonist of the β-catenin signaling pathway, Dickkopf-related protein 1, in a STAT 3-dependent manner. Inhibition of STAT3 and Dickkopf-related protein 1 abrogated the ability of IFN-γ to enhance HIV replication in astrocytes. These data demonstrated that IFN-γ induces HIV replication in astrocytes by antagonizing the β-catenin pathway. To our knowledge, this is the first report to point to an intricate cross-talk between IFN-γ signaling and β-catenin signaling that may have biologic and virologic effects on HIV outcome in the CNS, as well as on broader processes where the two pathways interface.
Human Bone Marrow Hosts Polyfunctional Memory CD4+ and CD8+ T Cells with Close Contact to IL-15–Producing Cells
Authors: Herndler-Brandstetter Dietmar , Landgraf Katja , Jenewein Brigitte , Tzankov Alexandar , Brunauer Regina , Brunner Stefan , Parson Walther , Kloss Frank , Gassner Robert , Lepperdinger Günter , Grubeck-Loebenstein Beatrix 
Published: May 2011

Abstract
Recently, a key role in memory T cell homing and survival has been attributed to the bone marrow (BM) in mice. In the human BM, the repertoire, function, and survival niches of CD4+ and CD8+ T cells have not yet been elucidated. In this study, we demonstrate that CD4+ and CD8+ effector memory T cells accumulate in the human BM and are in a heightened activation state as revealed by CD69 expression. BM-resident memory T cells produce more IFN-γ and are frequently polyfunctional. Immunofluorescence analysis revealed that CD4+ and CD8+ T cells are in the immediate vicinity of IL-15–producing BM cells, suggesting a close interaction between these two cell types and a regulatory role of IL-15 on T cells. Accordingly, IL-15 induced an identical pattern of CD69 expression in peripheral blood CD4+ and CD8+ T cell subsets. Moreover, the IL-15–inducible molecules Bcl-xL, MIP-1α, MIP-1β, and CCR5 were upregulated in the human BM. In summary, our results indicate that the human BM microenvironment, in particular IL-15–producing cells, is important for the maintenance of a polyfunctional memory CD4+ and CD8+ T cell pool.
Acids and Acid Catalysis—Homogeneous
Authors: Molnár Árpád 
Published: May 2011

AbstractThe concept of acidity has changed tremendously over the years. It has developed from protic acids in the aqueous phase via Lewis 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 wide variety of transformations ranging from rearrangements of various kinds through 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 laws governing acid‐catalyzed reactions are known to such an extent that mechanistic and quantitative descriptions can be given. In the first part of this review, a general treatment of homogeneous acids and acid catalysis is given through the development of various acid–base theories and acidity scales. This is followed by a short characterization of the most important Brønsted and Lewis acids, including superacids, as well as chiral acids applied in homogeneous catalysis. In the last section, characteristic examples of important acid‐catalyzed processes of organic chemistry, including rearrangements, carbon–carbon bond formation, and breaking and forming of carbon–heteroatom bonds with emphasis on mechanistic and kinetic aspects, are discussed.
Organometallic Catalysts and Catalysis
Authors: Crabtree Robert H. 
Published: May 2011

AbstractThe title topic is discussed in relation to general principles of organometallic chemistry. The 18e rule is discussed, as are the effects of coordination on ligands, the influence of mechanism on selectivity, and common organometallic reaction steps. These general points are illustrated using alkene isomerization, alkene hydrogenation, alkene hydroformylation, and the Wacker process as examples.
Delay‐dependent filtering for discrete‐time state‐delayed systems with small gain conditions in finite frequency ranges
Authors: Zhang Xiao‐Ni , Yang Guang‐Hong 
Published: May 2011

AbstractThis paper is concerned with the delay‐dependent filtering problem for linear discrete‐time multi‐delay systems with small gain conditions in finite frequency ranges. A new multiplier method is developed to convert the resulting nonconvex filtering synthesis conditions to the ones based on linear matrix inequalities (LMIs). Thus, sufficient conditions for the existence of feasible filters are given in terms of solutions to a set of LMIs. For the entire frequency case, it is shown that the proposed result is less conservative than the relative existing results. Finally, the procedures and the advantages of the proposed approach in comparison with the existing ones in the entire frequency range are illustrated via numerical examples. Copyright © 2011 John Wiley & Sons, Ltd.
Biomimetic Structures: Biological Implications of Dipeptide‐Substituted Polyphosphazene–Polyester Blend Nanofiber Matrices for Load‐Bearing Bone Regeneration
Authors: Deng Meng , Kumbar Sangamesh G. , Nair Lakshmi S. , Weikel Arlin L. , Allcock Harry R. , Laurencin Cato T. 
Published: May 2011

AbstractSuccessful bone regeneration benefits from three‐dimensional (3D) bioresorbable scaffolds that mimic the hierarchical architecture and mechanical characteristics of native tissue extracellular matrix (ECM). A scaffold platform that integrates unique material chemistry with nanotopography while mimicking the 3D hierarchical bone architecture and bone mechanics is reported. A biocompatible dipeptide polyphosphazene‐polyester blend is electrospun to produce fibers in the diameter range of 50–500 nm to emulate dimensions of collagen fibrils present in the natural bone ECM. Various electrospinning and process parameters are optimized to produce blend nanofibers with good uniformity, appropriate mechanical strength, and suitable porosity. Biomimetic 3D scaffolds are created by orienting blend nanofiber matrices in a concentric manner with an open central cavity to replicate bone marrow cavity, as well as the lamellar structure of bone. This biomimicry results in scaffold stress–strain curve similar to that of native bone with a compressive modulus in the mid‐range of values for human trabecular bone. Blend nanofiber matrices support adhesion and proliferation of osteoblasts and show an elevated phenotype expression compared to polyester nanofibers. Furthermore, the 3D structure encourages osteoblast infiltration and ECM secretion, bridging the gaps of scaffold concentric walls during in vitro culture. The results also highlight the importance of in situ ECM secretion by cells in maintaining scaffold mechanical properties following scaffold degradation with time. This study for the first time demonstrates the feasibility of developing a mechanically competent nanofiber matrix via a biomimetic strategy and the advantages of polyphosphazene blends in promoting osteoblast phenotype progression for bone regeneration.
Polystyrene‐Supported Enantiopure 1,2‐Diamines: Development of a Most Practical Catalyst for the Asymmetric Transfer Hydrogenation of Ketones
Authors: Marcos Rocío , Jimeno Ciril , Pericàs Miquel A. 
Published: May 2011

AbstractChlorosulfonylated polystyrene, a commodity resin, reacts with enantiopure 1,2‐diamines to afford, in a single step, high loading catalytic resins involving monosulfonylated 1,2‐diamino moieties. These functional polymers form stable (p‐cymene)ruthenium chloride [RuCl(p‐cymene)] complexes that efficiently catalyze (down to S/C=150) the asymmetric transfer hydrogenation (ATH) of alkyl aryl ketones with formic acid‐triethylamine under essentially solvent‐free (down to 0.25 mL mmol−1) reaction conditions. Among these resins, the immobilized version of TsDPEN stands out as a most practical catalyst for ATH: Uniformly high enantioselectivities are achieved with its use at low catalyst loading, and the resin can be recycled with virtually no limits.
Chiral Squaramide‐Catalyzed Highly Enantioselective Michael Addition of 2‐Hydroxy‐1,4‐naphthoquinones to Nitroalkenes
Authors: Yang Wen , Du Da‐Ming 
Published: May 2011

AbstractA chiral squaramide‐organocatalyzed, highly enantioselective Michael addition of 2‐hydroxy‐1,4‐naphthoquinones to nitroalkenes has been developed. This reaction afforded the chiral naphthoquinones in excellent yields (up to 99%) and excellent enantioselectivity (up to 98% ee) under very low catalyst loading (0.25 mol%). This organocatalytic asymmetric Michael addition provides an efficient alternative route toward the synthesis of chiral functionalized naphthoquinones.
Reversed clinical phenotype due to a microduplication of Sotos syndrome region detected by array CGH: Microcephaly, developmental delay and delayed bone age
Authors: Zhang Han , Lu Xianglan , Beasley Julie , Mulvihill John J , Liu Ruizhi , Li Shibo , Lee Ji‐Yun 
Published: May 2011

AbstractHaploinsufficiency of the NSD1 gene due to 5q35 microdeletions or intragenic mutations is the major cause of Sotos syndrome characterized by generalized overgrowth, large hands and feet with advanced bone age, craniofacial dysmorphic features, learning disability, and possible susceptibility to tumors. Here, we report on a 14‐month‐old boy with a reverse phenotype of Sotos syndrome due to the reciprocal duplication of the 5q35.3 region, including the NSD1 gene, detected by array CGH. The phenotype includes delayed bone age, microcephaly, seizures, and failure to thrive. Our case suggests that the gene dosage effect of the NSD1 gene is the likely cause for the reversed phenotype of Sotos syndrome in this patient. © 2011 Wiley‐Liss, Inc.
11p14.1 microdeletions associated with ADHD, autism, developmental delay, and obesity
Authors: Shinawi Marwan , Sahoo Trilochan , Maranda Bruno , Skinner S.A. , Skinner Cindy , Chinault Craig , Zascavage Roxanne , Peters Sarika U. , Patel Ankita , Stevenson Roger E. , Beaudet Arthur L. 
Published: May 2011

AbstractGenomic copy number imbalances are being increasingly identified as an important cause of intellectual disability and behavioral abnormalities. The typical deletion in WAGR syndrome encompasses the PAX6 and WT1 genes, but larger deletions have been associated with neurobehavioral abnormalities and obesity. We identified four patients with overlapping interstitial deletions on 11p14.1 and extending telomeric to the WAGR critical domain. The minimal overlapping critical chromosomal region was 2.3 Mb at 11p14.1. The deletions encompass the BDNF and LIN7C genes that are implicated in the regulation of development and differentiation of neurons and synaptic transmission. All patients with this deletion exhibit variable degrees of developmental delay, behavioral problems, and obesity. Our data show that ADHD, autism, developmental delay, and obesity are highly associated with deletion involving 11p14.1 and provide additional support for a significant role of BDNF in obesity and neurobehavioral problems. © 2011 Wiley‐Liss, Inc.
A novel mutation in PYCR1 causes an autosomal recessive cutis laxa with premature aging features in a family
Authors: Lin Dar‐Shong , Yeung Chun‐Yan , Liu Hsuan‐Liang , Ho Che‐Sheng , Shu Chyong‐Hsin , Chuang Chih‐Kuang , Huang Yu‐Wen , Wu Tsu‐Yen , Huang Zon‐Darr , Jian Yuan‐Ren , Lin Shuan‐Pei 
Published: May 2011

AbstractThe autosomal recessive form of type II cutis laxa (ARCL II) is characterized by the appearance of redundant, inelastic skin with wrinkling, an aged look and additional variable systemic involvement including intrauterine growth retardation, failure to thrive, developmental delay, dysmorphism, osseous abnormality, and CNS manifestations. Several genetic defects have been found in patients and families with the clinical manifestations of ARCL II. Recently, mutations in PYCR1 have been linked to cutis laxa with progeroid features. We ascertained two siblings with of ARCL II born to non‐consanguineous parents. Mutation analysis of PYCR1 revealed a novel single‐base deletion (c.345delC) in exon 4 leading to frame‐shift and premature stop of translation. The effect of this mutation results in a strong reduction of PYCR1 expression in skin fibroblasts from affected siblings. These two cases extend the genotypic spectrum of PYCR1‐related ARCL II. © 2011 Wiley‐Liss, Inc.
Lethal presentation of neurofibromatosis and Noonan syndrome
Authors: Prada Carlos E. , Zarate Yuri A. , Hagenbuch Sean , Lovell Anne , Schorry Elizabeth K. , Hopkin Robert J. 
Published: May 2011

AbstractNeurofibromatosis type 1 and Noonan syndrome are both common genetic disorders with autosomal dominant inheritance. Similarities between neurofibromatosis type 1 and Noonan syndrome have been noted for over 20 years and patients who share symptoms of both conditions are often given the diagnosis of neurofibromatosis–Noonan syndrome (NFNS). The molecular basis of these combined phenotypes was poorly understood and controversially discussed over several decades until the discovery that the syndromes are related through disturbances of the Ras pathway. We present an infant male with coarse facial features, severe supravalvar pulmonic stenosis, automated atrial tachycardia, hypertrophic cardiomyopathy, airway compression, severe neurological involvement, and multiple complications that lead to death during early infancy. The severity of clinical presentation and significant dysmorphic features suggested the possibility of a double genetic disorder in the Ras pathway instead of NFNS. Molecular analysis showed a missense mutation in exon 25 of the NF1 gene (4288A>G, p.N1430D) and a pathogenic mutation on exon 8 (922A>G, p.N308D) of the PTPN11 gene. Cardiovascular disease has been well described in patients with Noonan syndrome with PTPN11 mutations but the role of haploinsufficiency for neurofibromin in the heart development and function is not yet well understood. Our case suggests that a double genetic defect resulting in the hypersignaling of the Ras pathway may lead to complex cardiovascular abnormalities, cardiomyopathy, refractory arrhythmia, severe neurological phenotype, and early death. © 2011 Wiley‐Liss, Inc.
Mutation in SAM domain of TP63 is associated with nonsyndromic cleft lip and palate and cleft palate
Authors: Kantaputra Piranit N. , Malaivijitnond Sutti , Vieira Alexandre R. , Heering Jan , Dötsch Volker , Khankasikum Theerapong , Sripathomsawat Warissara 
Published: May 2011

AbstractMutations in sterile alpha motif (SAM) domain of TP63 have been reported to be associated with ankyloblepharon‐ectodermal dysplasia‐cleft lip/palate syndrome and Rapp‐Hodgkin syndrome. SAM domain, a protein–protein interaction module, is found in cytoplasmic signaling proteins and several transcriptional regulatory proteins which are involved in development and differentiation. Here, we report on a SAM domain mutation (p.Asp564His) in TP63 that predisposed the patients to have nonsyndromic cleft palate and nonsyndromic cleft lip and palate. © 2011 Wiley‐Liss, Inc.
High prevalence of carpal tunnel syndrome in children with mucopolysaccharidosis type II (Hunter syndrome)
Authors: Kwon Jeong‐Yi , Ko Kiljun , Sohn Young Bae , Kim Su Jin , Park Sung Won , Kim Se‐Hwa , Cho Sung‐Yoon , Jin Dong‐Kyu 
Published: May 2011

AbstractAlthough carpal tunnel syndrome (CTS) is the most common compressive neuropathy seen in the upper extremity of adults, it is rarely seen in children. Several reports have shown that mucopolysaccharidosis type II (Hunter syndrome), a rare genetic disorder, is one of the causes of CTS in children. Usual symptoms of CTS are pain, weakness, and paresthesias in the hand and digits. However, the diagnosis of CTS in Hunter syndrome is often delayed or unrecognized because of atypical symptoms and cognitive impairment. Here, we report the prevalence, clinical manifestation, and nerve conduction profiles of CTS in 45 Hunter syndrome patients. The mean age of the study participants was 117.1 (74.9) months (range: 4–408 months); all patients were male. Forty‐three (96.0%) of the 45 patients with Hunter syndrome had CTS. Bilateral CTS was observed in all patients; 73 (82.0%) of the patients' hands had severe degree of CTS. Intriguingly, in contrast with other nerve velocities, decreases in forearm conduction velocities of the median nerve were observed in 28 (31.5%) of 89 hands with CTS. There was a significant difference in age (P < 0.001) between hands with normal, mild, moderate, and severe grades of CTS. The compound muscle action potential and sensory nerve action potential amplitudes of the median nerves decreased with age (CMAP, r = −0.526, P < 0.001; SNAP, r = −0.564, P < 0.001). Early recognition and intervention to ameliorate the symptoms of CTS are important in improving the quality of life of Hunter syndrome patients. © 2011 Wiley‐Liss, Inc.
Significance of marrow‐derived nicotinamide adenine dinucleotide phosphate oxidase in experimental ischemic stroke
Authors: Tang Xian N. , Zheng Zhen , Giffard Rona G. , Yenari Midori A. 
Published: May 2011

AbstractObjective:Reperfusion after stroke leads to infiltration of inflammatory cells into the ischemic brain. Nicotinamide adenine dinucleotide phosphate oxidase (NOX2) is a major enzyme system that generates superoxide in immune cells. We studied the effect of NOX2 derived from the immune cells in the brain and in blood cells in experimental stroke.Methods:To establish whether NOX2 plays a role in brain ischemia, strokes were created in mice, then mice were treated with the NOX2 inhibitor apocynin or vehicle and compared to mice deficient in NOX2's gp91 subunit and their wild‐type littermates. To determine whether NOX2 in circulating cells versus brain resident cells contribute to ischemic injury, bone marrow chimeras were generated by transplanting bone marrow from wild‐type or NOX2‐deficient mice into NOX2 or wild‐type hosts, respectively.Results:Apocynin and NOX2 deletion both significantly reduced infarct size, blood–brain barrier disruption, and hemorrhagic transformation of the infarcts, compared to untreated wild‐type controls. This was associated with decreased matrix metalloproteinase 9 expression and reduced loss of tight junction proteins. NOX2‐deficient mice receiving wild‐type marrow had better outcomes compared to the wild‐type mice receiving wild‐type marrow. Interestingly, wild‐type mice receiving NOX2‐deficient marrow had even smaller infarct sizes and less hemorrhage than NOX2‐deficient mice receiving wild‐type marrow.Interpretation:This indicates that NOX2, whether present in circulating cells or brain resident cells, contributes to ischemic brain injury and hemorrhage. However, NOX2 from the circulating cells contributed more to the exacerbation of stroke than that from brain resident cells. These data suggest the importance of targeting the peripheral immune system for treatment of stroke. Ann Neurol 2011;70:606–615
A randomized, pilot trial of etanercept in dermatomyositis
Authors:   The Muscle Study Group
Published: May 2011

AbstractObjective:The aims of this pilot study were to assess (1) the safety and tolerability of etanercept in dermatomyositis (DM); (2) the feasibility and safety of a forced prednisone taper; and (3) outcome measures, including those recommended by the International Myositis Assessment Clinical Study (IMACS) group.Methods:We conducted a randomized, double‐blind, placebo‐controlled trial of etanercept (50mg subcutaneously weekly) for 52 weeks in DM subjects. Subjects were tapered off prednisone in a standardized schedule as tolerated over the initial 24 weeks of the study. Principal outcomes included adverse events, time from randomization to treatment failure (inability to wean off prednisone on schedule), and average prednisone dosage after week 24.Results:Sixteen subjects were randomized, 11 to etanercept and 5 to placebo. There were no significant differences in adverse event rates between the treatment groups, although 5 etanercept‐treated and 1 placebo‐treated subjects developed worsening rash. All 5 subjects receiving placebo were treatment failures (median time to treatment failure 148 days). In contrast, 5 of 11 subjects in the etanercept arm were successfully weaned off prednisone; the median time to treatment failure in this group was 358 days (p = 0.0002). The median of the average prednisone dosage after week 24 was 29.2mg/day in the placebo group and 1.2mg/day in the etanercept group (p = 0.02). IMACS and other outcome measures demonstrated excellent test–retest reliability (intraclass correlation coefficients 0.79–0.99). There was no significant treatment effect on functional outcome.Interpretation:The findings of no major safety concerns and a steroid‐sparing effect in our study suggest that further investigation of etanercept as a treatment for DM is warranted. Ann Neurol 2011;