bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaffold/Extracellular Matrix Hybrid Constructs for Bone‐Tissue Engineering
Authors: Thibault Richard A. , Mikos Antonios G. , Kasper F. Kurtis 
Published: September 2012

AbstractThe limited natural ability of the body to fully repair large bone defects often necessitates the implantation of a replacement material to promote healing. While the current clinical strategies to address such bone defects generally carry associated limitations, bone‐tissue engineering approaches seek to minimize any adverse effects and facilitate complete regeneration of the lost tissue. Of particular interest are hybrid constructs that incorporate multiple components found within the native bone matrix to enhance the osteogenicity of biocompatible materials, which might otherwise be non‐osteogenic. This Progress Report will focus on such hybrid constructs that incorporate multiple components from native bone matrix for bone‐tissue engineering and will highlight the synthesis and characterization of the hybrid constructs, cellular attachment and proliferation within the constructs, in vitro osteogenicity of the constructs, and the biological response to in vivo implantation of the constructs at ectopic and orthotopic sites.
A Unique Ruthenium Carbyne Complex: A Highly Thermo‐endurable Catalyst for Olefin Metathesis
Authors: Shao Mingbo , Zheng Lu , Qiao Weixia , Wang Jingjing , Wang Jianhui 
Published: September 2012

AbstractA cationic ruthenium carbyne complex was prepared and was found to initiate olefin metathesis reactions with good activities, which throws a new light on the design of a new type of ruthenium catalyst for RCM reactions. More importantly, no double bond isomerized by‐product was observed even at elevated temperatures in reactions catalyzed by the new carbyne complex. A mechanism involving the in situ conversion of the ruthenium carbyne to a ruthenium carbene complex via addition of an iodide to the carbyne carbon was also proposed.
Enantiocontrolled Synthesis of Tertiary α‐Hydroxy‐α‐ynyl Esters by Dimethylzinc‐Mediated Addition of Alkynes to α‐Keto Esters
Authors: Infante Rebeca , Gago Alfonso , Nieto Javier , Andrés Celia 
Published: September 2012

AbstractA perhydro‐1,3‐benzoxazine behaves as an excellent chiral ligand in the nucleophilic addition of alkynylzinc derivatives, prepared from terminal alkynes and dimethylzinc, to α‐keto esters without using other Lewis acids. The enantioselectivity is excellent and homogeneous for a wide variety of aromatic and heteroaromatic α‐keto esters. Aliphatic enolizable α‐keto esters were alkynylated with moderate enantioselection.
Asymmetric Michael Reaction of Acetaldehyde with Nitroolefins Catalyzed by Highly Water‐Compatible Organocatalysts in Aqueous Media
Authors: Qiao Yupu , He Junpeng , Ni Bukuo , Headley Allan D. 
Published: September 2012

AbstractA novel category of diarylprolinol silyl ether catalysts which contain different lengths of alkylamine tags, was designed and synthesized. These catalysts were used, along with benzoic acid as the co‐catalyst, to catalyze the asymmetric Michael reaction of the highly reactive acetaldehyde with nitroolefins. For the reactions studied, this catalytic system exhibited high reactivity in brine without any organic solvents; good yields (30–61%) and high enantioselectivities (80–97% ee) for a wide variety of nitrostyrenes were obtained.
Synthesis of Azocino[5,4‐b]indoles via Gold‐Catalyzed Intramolecular Alkyne Hydroarylation
Authors: Peshkov Vsevolod A. , Pereshivko Olga P. , Eycken Erik V. Van der 
Published: September 2012

AbstractAn efficient procedure for the synthesis of the azocino[5,4‐b]indole framework is presented, relying on a cationic gold‐catalyzed intramolecular alkyne hydroarylation of propargylic amides derived from various tryptamines and 3‐substituted 2‐propynoic acids. The triphenylphosphinegold(I) chloride/silver(I) triflate catalytic system was found to be superior to our previously described mercury(II) triflate catalyst, and hence the substrate scope of the process was significantly expanded.
Selective Hydrogenation of Nitroarenes and Olefins over Rhodium Nanoparticles on Hydroxyapatite
Authors: Huang Lei , Luo Pingfei , Pei Weige , Liu Xiaoyun , Wang Yong , Wang Jun , Xing Weihong , Huang Jun 
Published: September 2012

AbstractWe have demonstrated a highly active and selective nanocatalyst, Rh/HAP (rhodium supported on hydroxyapatite), for the reduction of nitroarenes with hydrazine and for the hydrogenation of olefins with hydrogen gas under mild conditions. Nitroarenes were hydrogenated selectively to the corresponding anilines over the Rh/HAP catalyst with hydrazine as reducing agent, and reducible groups, such as halides (fluorine, chlorine, bromine and iodine), cyano and alkene were untouched. Moreover, olefins can be hydrogenated selectively to the corresponding alkanes in good yields over the Rh/HAP catalyst in the presence of reducible nitro, carbonyl and cyano groups when H2 was used.
Tin Tetrachloride‐Catalyzed Regiospecific Allylic Substitution of Quinone Monoketals: An Easy Entry to Benzofurans and Coumestans
Authors: Liu Yingjie , Liu Jingxin , Wang Mang , Liu Jun , Liu Qun 
Published: September 2012

AbstractA highly regioselective allylic substitution of quinone monoketals with α‐oxoketene dithioacetals is achieved under the catalysis of only tin tetrachloride (1 mol%). The advantages of the reaction, including its simplicity, rapidity, low catalyst loading of inexpensive tin tetrachloride, mild conditions and; in particular, the regiospecificity, is proposed to be due to a pseudo‐intramolecular process. This new synthetic method provides a facile [3+2] cycloaddition route to benzofurans and is highlighted by the synthesis of coumestans.
Retropinacol/Cross‐Pinacol Coupling Reactions – A Catalytic Access to 1,2‐Unsymmetrical Diols
Authors: Scheffler Ulf , Stößer Reinhard , Mahrwald Rainer 
Published: September 2012

AbstractA new concept to access unsymmetrical 1,2‐diols with high yields is reported. This new methodology is based on a retropinacol/cross‐pinacol coupling process. This transformation is characterized by its operational simplicity and very mild reaction conditions.
A rare association of fibromuscular dysplasia, renal agenesis, renal arteriovenous fistulae, and vertebral anomalies: Expanding the V in VACTERL association
Authors: Alomari Ahmed K. , Alomari Ahmad I. 
Published: September 2012

AbstractWe report on the association of renal agenesis, renal arteriovenous fistulae, fibromuscular dysplasia and vertebral body anomaly in a young female patient with renovascular hypertension. We believe these vertebral and vascular anomalies can be included under the “V” of the VACTERL association; expanding the vascular spectrum of this complex disorder. © 2012 Wiley Periodicals, Inc.
2q24 deletions: Further characterization of clinical findings and their relation to the SCN cluster
Authors: Nimmakayalu Manjunath , Noble Nathan , Horton V. Kim , Willing Marcia , Copeland Sara , Sheffield Val , Nagy Peter L. , Wassink Tom , Patil Shivanand , Shchelochkov Oleg A. 
Published: September 2012

AbstractAs the resolution of molecular cytogenetic methods continues to improve, it has become increasingly possible to refine genotype–phenotype correlations based upon gene involvement. We report three new patients with nonrecurrent deletions involving subbands of 2q24. These patients were referred for evaluation of developmental delay, but were found to have unique, nonoverlapping clinical features. Patient 1 presented with infantile seizures, microcephaly, and brain anomalies, along with facial dysmorphism, growth retardation, neuromuscular scoliosis, and later with developmental regression. Array comparative genomic hybridization (aCGH) detected an 8 Mb interstitial deletion encompassing the neuronal sodium channel (SCN) gene cluster. Patient 2 presented with growth retardation, congenital heart defect, and hypotonia. Patient 3 presented with developmental delay and behavioral problems. Patients 2 and 3 had no history of seizures, microcephaly, or brain anomalies and were found to have deletions of 2q24, ∼8 Mb and <500 kb respectively, centromeric to and outside the SCN cluster. It has been demonstrated that mutations and copy number variants (CNVs) affecting the SCN gene cluster result in severe, early‐onset seizures. It is however, less clear whether haploinsufficiency of regions outside the SCN cluster may result in phenotypically recognizable and clinically significant features. We discuss additional dosage sensitive genes that may exist outside the SCN cluster. Our and published data indicate that 2q24 deletions not involving the SCN cluster are associated with fewer neurobehavioral problems, but may predispose to congenital malformations. © 2012 Wiley Periodicals, Inc.
Apolipoprotein E genotype and neurological disease onset in Niemann–Pick disease, type C1
Authors: Fu Rao , Yanjanin Nicole M. , Elrick Matthew J. , Ware Christopher , Lieberman Andrew P. , Porter Forbes D. 
Published: September 2012

AbstractNiemann–Pick disease, type C1 (NPC1) is a lipid storage disorder that results in progressive neurological impairment. The NPC1 phenotype is extremely variable and at the individual level is likely influenced by other genetic traits. In addition to residual function of NPC1 protein, we hypothesize that modifier genes, as frequently observed with other autosomal recessive diseases, influence the NPC phenotype. The NPC1 phenotype includes progressive dementia, and the NPC pathology has some overlap with the pathology of Alzheimer disease (AD). Thus, we examined apolipoprotein E (ApoE) and microtubule‐associated protein tau (MAPT) polymorphisms in a cohort of 15 NPC1 patients with well characterized longitudinal disease progression. Although we did not find any correlations between disease severity and tau polymorphisms, we found significant associations between ApoE polymorphisms and phenotypic severity. Specifically, ApoE4 and ApoE2 alleles were associated, respectively, with increased and decreased disease severity in this cohort of NPC1 patients. These data support the hypothesis that ApoE may play a role in modulating NPC1 neuropathology. © 2012 Wiley Periodicals, Inc.
Synthesis of Vasorelaxaing 1,4‐Disubstituted 1,2,3‐Triazoles Catalyzed by a 4′‐Phenyl‐2,2′:6′,2′′‐Terpyridine Copper(II) Complex Immobilized on Activated Multiwalled Carbon Nanotubes
Authors: Sharghi Hashem , Ebrahimpourmoghaddam Sakineh , Doroodmand Mohammad Mahdi , Purkhosrow Azar 
Published: September 2012

AbstractA supported catalyst has been prepared by immobilization of a copper(II) complex of 4′‐phenyl‐2,2′:6′,2′′‐terpyridine on activated multiwalled carbon nanotubes [AMWCNTs‐O‐CuII‐PhTPY]. This heterogeneous catalyst was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), inductively coupled plasma (ICP) analysis, UV/vis and FT‐IR techniques. To ensure the efficiency and fidelity of the copper species, the implementation of three‐component strategies in click chemistry was tested. The catalyst enabled the development of one‐pot, two‐step, mild, and environmentally benign syntheses of diversely decorated 1,2,3‐triazoles from alkynes, epoxides or benzyl/alkyl halides, and sodium azide in water. The complex has high catalytic activity, regioselectivity, and was recycled five successive times. In another experiment, the vasorelaxing effect of the triazole products was studied in isolated rat thoracic aorta. All of the selected compounds are vasorelaxants, based on the IC50 values obtained, and the vasorelaxing potency and maximal response for three of the compounds are comparable to acetylcholine.
Synthesis and characterization of chitosan‐graft‐poly(acrylic acid)/nontronite hydrogel composites based on a design of experiments
Authors: Rodrigues Francisco H. A. , Pereira Antonio G. B. , Fajardo André R. , Muniz Edvani C. 
Published: September 2012

AbstractA 24–1 fractional factorial design was used to evaluate the effect of some parameters, such as the acrylic acid (AA)/chitosan (CTS) molar ratio, crosslinker concentration, initiator concentration, and filler concentration, in the swelling capacity of superabsorbent hydrogel composites based on CTS‐graft‐poly(acrylic acid) and nontronite clay. The data from wide‐angle X‐ray scattering and Fourier transform infrared spectroscopy confirmed the syntheses of the hydrogel composites. Main and interaction effects were analyzed by analysis of variance, F tests, and p values. We found that the AA/CTS and crosslinker were the most influential effects in the evaluated response. The proposed statistical model presented a high coefficient of determination (R2 = 0.985). In addition to the swelling kinetics, the effects of pH and salt for the both compositions (with and without filler), which presented the best water uptake, were evaluated. Both hydrogels showed responsive behavior in relation to the pH and the salt solution, presenting good potential for application as devices in the controlled release of solutes. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Interleukin‐1β induces differentiation of human mesenchymal stem cells into osteoblasts via the Wnt‐5a/receptor tyrosine kinase–like orphan receptor 2 pathway
Authors: Sonomoto Koshiro , Yamaoka Kunihiro , Oshita Koichi , Fukuyo Shunsuke , Zhang Xiangmei , Nakano Kazuhisa , Okada Yosuke , Tanaka Yoshiya 
Published: September 2012

AbstractObjectiveMesenchymal stem cells (MSCs) are considered to be a novel tool for the treatment of rheumatoid arthritis (RA) because of their multipotency to differentiate into osteoblasts and chondrocytes, their immunosuppressive effects, and availability. The aim of this study was to assess the mechanisms of human MSC differentiation into osteoblasts under inflammatory conditions.MethodsHuman MSCs were cultured in commercialized osteogenic induction medium with inflammatory cytokines for up to 10 days. Osteoblast differentiation was detected by alkaline phosphatase staining and messenger RNA (mRNA) expression of multiple osteoblast markers. Mineralization was assessed by alizarin red S staining.ResultsAmong the various cytokines tested, interleukin‐1β (IL‐1β) induced differentiation of human MSCs into osteoblasts, which was confirmed by alkaline phosphatase activity, expression of RUNX2 mRNA, and strong alizarin red S staining. Among various molecules of the Wnt family, Wnt‐5a and receptor tyrosine kinase–like orphan receptor 2 (Ror2), a major receptor of Wnt‐5a, were significantly induced in human MSCs by IL‐1β. Silencing of either WNT5A or ROR2 by small interfering RNA with 2 different sequences reduced alkaline phosphatase activity, RUNX2 expression, and alizarin red S staining of human MSCs induced by IL‐1β.ConclusionIL‐1β effectively and rapidly induced human MSC differentiation into osteoblasts and mineralization, mainly through the noncanonical Wnt‐5a/Ror2 pathway. These results suggest potential benefits of IL‐1β–treated human MSCs in the treatment of damaged bone as well as in the induction of self‐renewal and self‐repair of damaged tissue, including osseous tissue.
Thrombin induces epidermal growth factor receptor transactivation and CCL2 expression in human osteoblasts
Authors: Huang Chun‐Yin , Chen Shi‐Yann , Tsai Hsiao‐Chi , Hsu Horng‐Chaung , Tang Chih‐Hsin 
Published: September 2012

AbstractObjectiveThrombin is a key factor involved in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA). The aim of this study was to investigate the intracellular signaling pathways involved in thrombin‐induced CCL2 expression in human osteoblasts.MethodsThrombin‐mediated CCL2 expression was assessed by quantitative polymerase chain reaction and enzyme‐linked immunosorbent assay. The mechanisms of action of thrombin in different signaling pathways were studied using Western blotting. Knockdown of protease‐activated receptor (PAR) protein was achieved by small interfering RNA (siRNA) transfection. Chromatin immunoprecipitation assays were used to study in vivo binding of c‐Jun to the CCL2 promoter. Transient transfection was used to examine activator protein 1 (AP‐1) activity.ResultsStimulation of human primary osteoblasts and MG‐63 cells with thrombin induced CCL2 expression. PAR‐1–specific siRNA (but not other PAR siRNA) was involved in thrombin‐mediated up‐regulation of CCL2. Thrombin‐mediated CCL2 production was attenuated by the thrombin inhibitor PPACK, the protein kinase Cδ (PKCδ) inhibitor rottlerin, the c‐Src inhibitor PP2, epidermal growth factor receptor (EGFR) inhibitor AG‐1478, MEK inhibitors PD98059 and U0126, or AP‐1 inhibitors curcumin and tanshinone IIA. Stimulation of cells with thrombin increased PKCδ, c‐Src, EGFR, MEK, and ERK activation. Treatment of osteoblasts with thrombin also increased c‐Jun phosphorylation, AP‐1 luciferase activity, and c‐Jun binding to the AP‐1 element on the CCL2 promoter.ConclusionOur results suggest that the interaction between thrombin and PAR‐1 increases CCL2 expression in human osteoblasts via the PKCδ/c‐Src/ EGFR transactivation/MEK/ERK/c‐Jun/AP‐1 pathway.
Expression of HLA–B27 causes loss of migratory dendritic cells in a rat model of spondylarthritis
Authors: Utriainen Lotta , Firmin Dawn , Wright Pamela , Cerovic Vuk , Breban Maxime , McInnes Iain , Milling Simon 
Published: September 2012

AbstractObjectiveIn rats transgenic for human HLA–B27 and β2‐microglobulin (B27‐transgenic rats), colitis and peripheral inflammation develop spontaneously. Therefore, B27‐transgenic rats provide a model of spondylarthritis. Because inflammation in these rats requires CD4+ T lymphocytes and involves intestinal pathology, we hypothesized that dendritic cells (DCs) that migrate from the intestine and control CD4+ T cell differentiation would be aberrant in B27‐transgenic rats.MethodsMigrating intestinal lymph DCs were collected via thoracic duct cannulation from B27‐transgenic and control (HLA–B7–transgenic or nontransgenic) rats. The phenotypes of these DCs and of mesenteric lymph node DCs were assessed by flow cytometry. The ability of DCs to differentiate from bone marrow precursors in vitro was also assessed.ResultsLymph DCs showed increased activation and, strikingly, lacked the specific DC population that is important for maintaining tolerance to self‐antigens. This population of DCs was also depleted from the mesenteric lymph nodes of B27‐transgenic rats. Furthermore, in vitro culture of DCs from bone marrow precursors revealed a defect in the ability of B27‐transgenic rats to produce DCs of the migratory phenotype, although the DCs that were generated induced enhanced interleukin‐17 (IL‐17) production from naive CD4+ T cells.ConclusionWe describe 2 different mechanisms by which HLA–B27 may contribute to inflammatory disease: increased apoptotic death of B27‐transgenic DCs that normally function to maintain immunologic tolerance and enhanced IL‐17 production from CD4+ T cells stimulated by the surviving B27‐transgenic DCs.
Chondrocyte‐intrinsic Smad3 represses Runx2‐inducible matrix metalloproteinase 13 expression to maintain articular cartilage and prevent osteoarthritis
Authors: Chen Carol G. , Thuillier Daniel , Chin Emily N. , Alliston Tamara 
Published: September 2012

AbstractObjectiveTo identify mechanisms by which Smad3 maintains articular cartilage and prevents osteoarthritis.MethodsA combination of in vivo and in vitro approaches was used to test the hypothesis that Smad3 represses Runx2‐inducible gene expression to prevent articular cartilage degeneration. Col2‐Cre;Smad3fl/fl mice allowed study of the chondrocyte‐intrinsic role of Smad3 independently of its role in the perichondrium or other tissues. Primary articular cartilage chondrocytes from Smad3fl/fl mice and ATDC5 chondroprogenitor cells were used to evaluate Smad3 and Runx2 regulation of matrix metalloproteinase 13 (MMP‐13) messenger RNA (mRNA) and protein expression.ResultsChondrocyte‐specific reduction of Smad3 caused progressive articular cartilage degeneration due to imbalanced cartilage matrix synthesis and degradation. In addition to reduced type II collagen mRNA expression, articular cartilage from Col2‐Cre;Smad3fl/fl mice was severely deficient in type II collagen and aggrecan protein due to excessive MMP‐13–mediated proteolysis of these key cartilage matrix constituents. Normally, transforming growth factor β (TGFβ) signals through Smad3 to confer a rapid and dynamic repression of Runx2‐inducible MMP‐13 expression. However, we found that in the absence of Smad3, TGFβ signals through p38 and Runx2 to induce MMP‐13 expression.ConclusionOur findings elucidate a mechanism by which Smad3 mutations in humans and mice cause cartilage degeneration and osteoarthritis. Specifically, Smad3 maintains the balance between cartilage matrix synthesis and degradation by inducing type II collagen expression and repressing Runx2‐inducible MMP‐13 expression. Selective activation of TGFβ signaling through Smad3, rather than p38, may help to restore the balance between matrix synthesis and proteolysis that is lost in osteoarthritis.
Brief Report: To squeeze or not to squeeze, that is the question! Optimizing the Disease Activity Score in 28 joints by adding the squeeze test of metatarsophalangeal joints in early rheumatoid arthritis
Authors: de Jong P. H. , Weel A. E. , de Man Y. A. , Huisman A. M. , Gerards A. H. , van Krugten M. V. , Luime J. J. , Hazes J. M. 
Published: September 2012

AbstractObjectiveTo optimize use of the Disease Activity Score in 28 joints (DAS28) in early rheumatoid arthritis (RA) by adding the “squeeze test” of forefeet.MethodsThe squeeze test is used to examine bilateral compression pain (BCP) across the metatarsophalangeal (MTP) joints. For this study, data for patients participating in the Treatment in the Rotterdam Early Arthritis Cohort study, an ongoing clinical trial that evaluates different induction therapies in patients with early RA, were randomly divided into 2 subsets. In subset 1 (149 patients and 819 disease activity assessments), the mathematical function of the DAS28‐squeeze was constructed using a linear regression model with the DAS as the dependent variable and the DAS28 and squeeze test as the independent variables. A DAS28‐BCP disease state was also constructed, in which DAS28 disease state categorizations were upgraded one state if the result of the squeeze test was positive. In subset 2 (153 patients and 754 assessments), concordance in disease states between the DAS28, DAS28‐squeeze, and DAS28‐BCP disease states was compared, using both the DAS and Boolean‐defined remission criteria as reference.ResultsAgreement between the DAS and the DAS28‐squeeze (82%) was significantly higher than agreement between the DAS and the DAS28 (76%). When we assessed the group of patients who had arthritis of the forefeet only (22 patients and 46 assessments), overall agreement between the DAS and the DAS28 was 40%, while agreement between the DAS and the DAS28‐squeeze was 59% and that between the DAS and the DAS28‐BCP disease state was 65%. Furthermore, the specificities of the DAS28‐squeeze and the DAS28‐BCP (80% and 81%, respectively) were higher than that of the DAS28 (76%), while the sensitivities of the DAS28, DAS28‐squeeze, and DAS28‐BCP to identify true remission according to the Boolean criteria were 88%, 87%, and 81%, respectively.ConclusionAdding the squeeze test of forefeet to the DAS28 has value for dependably classifying the disease state in patients with early RA.