bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enabling Ligand Screening for Palladium‐Catalysed Enantioselective Aza‐Michael Addition Reactions
Authors: Phua Pim Huat , White Andrew J. P. , de Vries Johannes G. , Hii King Kuok (Mimi) 
Published: March 2006

AbstractThe bis(trifluoromethanesulfonate)palladium(II) dihydrate complex, Pd(OTf)2⋅2 H2O (1), is an active palladium(II) precursor for the generation of dicationic palladium(II) catalysts. Parallel ligand screening is enabled for the first time, and twenty‐four chiral ligands were evaluated for the asymmetric aza‐Michael addition of aromatic amines to α,β‐unsaturated N‐alkenoylimides and carbamates. Enantioselectivities of >99% can be obtained. Catalytic precursors generated from 1 using the new protocol have been identified.
Methyltrioxorhenium‐Catalyzed Epoxidation‐Methanolysis of Glycals under Homogeneous and Heterogeneous Conditions
Authors: Goti Andrea , Cardona Francesca , Soldaini Gianluca , Crestini Claudia , Fiani Cinzia , Saladino Raffaele 
Published: March 2006

AbstractThe efficient and high yielding domino epoxidation‐methanolysis of glycals 8–15 has been achieved by oxidation with UHP in MeOH catalyzed by MTO. The products have been conveniently isolated as 2‐acetoxy derivatives 16–23a, b by direct acetylation of the crude mixtures. Homogeneous MTO‐amine complexes 5–7, heterogeneous poly(4‐vinylpyridine)/MTO compounds I–III, and microencapsulated polystyrene/MTO systems IV–VII were also tested and demonstrated their effectiveness as catalysts for the oxidation step. The facial diastereoselectivity of the oxidation ranged from satisfactory to excellent depending on the substrate and could be optimized by ample screening of catalysts. Complete conversions of substrates and nearly quantitative yields of products were obtained under environmentally friendly experimental conditions and with the use of simple work‐up procedures.
Highly Enantioselective Organocatalytic Michael Addition Reactions of Ketones with Chalcones
Authors: Wang Jian , Li Hao , Zu Liansuo , Wang Wei 
Published: March 2006

AbstractA highly enantioselective, organocatalytic Michael addition reaction of unmodified ketones with chalcones has been developed for the first time. The process, catalyzed by (S)‐N‐(pyrrolidin‐2‐ylmethyl)‐trifluoromethanesulfonamide, affords 1,5‐diketones in high yields (73–89%) and with high degrees of enantio‐ and diastereoselectivity (86–97% ee, >30 : 1 dr).
Efficient NADPH Recycling in Enantioselective Bioreduction of a Ketone with Permeabilized Cells of a Microorganism Containing a Ketoreductase and a Glucose 6‐Phosphate Dehydrogenase
Authors: Zhang Jie , Witholt Bernard , Li Zhi 
Published: March 2006

AbstractWe have demonstrated, for the first time, the efficient recycling of NADPH in a bioreduction with permeabilized cells of a single microorganism. Permeabilized cells of Bacillus pumilus Phe‐C3 containing an NADPH‐dependent ketoreductase and a glucose 6‐phosphate dehydrogenase (G‐6‐PDH) were successfully used for the reduction of ethyl 3‐oxo‐4,4,4‐trifluorobutanoate (1) to give (R)‐ethyl 3‐hydroxy‐4,4,4‐trifluorobutanoate (2) in 95% ee with the recycling of NADPH for 4220 times from the externally added NADP+. The permeabilized cells were shown to be stable and active for a long period, allowing for high product concentration with high cofactor TTN by continuing the bioreduction with renewed addition of NADP+. This provides with not only a practical synthesis of (R)‐2 but also a useful method applicable to many microbial oxidoreductions, since G‐6‐PDH is a very common enzyme existing in many microorganisms.
Feasible products in complex batch reactive distillation
Authors: Chin James , Lee Jae W. , Choe Jaehoon 
Published: February 2006

AbstractA new feasibility evaluation procedure for reactive mixtures is presented, where simple homogeneous reactive batch columns cannot produce pure products. Such columns are not feasible for producing pure products if no node products exist that are reachable by residue curves from the reaction equilibrium manifold. Three alternatives are presented. If an unstable node heterogenous azeotrope decants to an almost‐pure product, and that azeotrope is always reachable from the reaction equilibrium manifold, then a batch reactive rectifier can produce pure products with a decanter. If a homogeneous entrainer allows extractive section profiles to connect the reaction equilibrium manifold to an entrainer‐product binary edge, then a homogeneous batch reactive extractive distillation (BRED) column can produce a pure product. If these criteria are not met, then an entrainer that induces an unstable node heterogenous azeotrope between itself and one of the products should be used in a rectifier, a middle‐vessel column, or a BRED column. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Arithmetic difficulties in females with the fragile X premutation
Authors: Lachiewicz Ave M. , Dawson Deborah V. , Spiridigliozzi Gail A. , McConkie‐Rosell Allyn 
Published: February 2006

AbstractFemales with the fragile X full mutation have been reported to have difficulty learning mathematics. Women with the fragile X premutation often give a history of mathematics difficulties in themselves especially with higher level math. In order to evaluate whether women with the premutation have difficulty with math, we asked women with both the fragile X premutation and full mutation to complete the Wide Range Achievement Test‐3. For the group of 39 women with the fragile X premutation, the median standard score on the Arithmetic portion was 93, which was significantly lower (P = 0.001) than the median of the standardized norm of 100. Only nine of the women had Arithmetic scores at or above the 50th centile, while over half of the women had standard scores at or above the 50th centile in Reading and Spelling. The eight women with the full mutation also had lower Arithmetic scores than Reading and Spelling scores. These data suggest that mathematics may be an area of relative weakness for the women with the premutation as well as the full mutation. This possibility should be evaluated further by using other measures. This information is important both for counseling purposes and to understand whether a mathematics deficit is evidence of low expression of the FMR1 gene in the premutation state. © 2006 Wiley‐Liss, Inc.
Haplotype‐based systematic association studies of ATP1A2 in migraine with aura
Authors: Netzer Christian , Todt Unda , Heinze Axel , Freudenberg Jan , Zumbroich Vera , Becker Tim , Goebel Ingrid , Ohlraun Stephanie , Goebel Hartmut , Kubisch Christian 
Published: February 2006

AbstractMutations in ATP1A2 cause familial hemiplegic migraine (FHM) type 2, a rare monogenic form of migraine with aura (MA). Moreover, rare ATP1A2 missense variants are found in familial clustering of common forms of migraine in single pedigrees. To determine whether also common ATP1A2 polymorphisms contribute to MA pathogenesis, we performed systematic case‐control association studies in 284 MA cases and 241 control individuals. By direct sequencing of the 23 coding exons and adjacent intronic regions in 45 MA patients, 16 polymorphisms (12 SNPs, 3 small indels, 1 microsatellite marker) were identified. The sequencing results were used to estimate seven common ATP1A2 haplotypes (with a frequency >5%) covering about 97% of total haplotype diversity for this region. Subsequently, six haplotype‐tagging SNPs/polymorphisms were genotyped in 95 individuals with a family history of MA, in 189 individuals with sporadic MA, and in a gender‐matched control sample. A haplotype analysis was performed using the program FAMHAP. No significant differences in the ATP1A2 haplotype distribution could be detected between MA patients (or patient subgroups) and the control group. In a single‐marker analysis the allele and genotype frequencies of ATP1A2 polymorphisms between cases and controls were compared. Neither the six ht‐SNPs nor a single allele of the microsatellite marker were significantly associated with MA. In summary, we found no evidence for a common contribution of ATP1A2 to the pathogenesis of complex inherited MA. © 2006 Wiley‐Liss, Inc.
Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population
Authors: Washizuka Shinsuke , Kametani Mizue , Sasaki Tsukasa , Tochigi Mamoru , Umekage Tadashi , Kohda Kazuhisa , Kato Tadafumi 
Published: February 2006

AbstractSchizophrenia and bipolar disorder share common genetic background. Several loci such as 18p11, 13q32, and 22q11–13 were commonly linked with these diseases. Since mitochondrial dysfunction has been suggested in both of these disorders, NDUFV2 at 18p11, encoding a subunit of the complex I, NADH ubiquinone oxidoreductase, is a candidate gene for these diseases. We previously reported that single nucleotide polymorphisms (SNPs) in the upstream region of NDUFV2 were associated with bipolar disorder in Japanese. The association of haplotype consisting of two SNPs, −3542G > A and −602G > A, with bipolar disorder was also seen both in Japanese and the National Institute of Mental Health Pedigrees trios. In this study, 2 polymorphisms, −3542G > A and −602G > A, were investigated in 229 schizophrenic patients as compared with controls. Individual genotypes were not associated with schizophrenia. However, the haplotype consisting of these two SNPs were significantly associated with schizophrenia. These results suggested that inter‐individual variation of the genomic sequence of the promoter region of NDUFV2 might be a genetic risk factor common to bipolar disorder and schizophrenia. © 2006 Wiley‐Liss, Inc.
Absence of coding mutations in the X‐linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection
Authors: Blasi Francesca , Bacchelli Elena , Pesaresi Giulia , Carone Simona , Bailey Anthony J. , Maestrini Elena ,   and the International Molecular Genetic Study of Autism Consortium (IMGSAC)
Published: February 2006

AbstractNeuroligin abnormalities have been recently implicated in the aetiology of autism spectrum disorders (ASD), given the finding of point mutations in the two X‐linked genes NLGN3 and NLGN4X and the important role of neuroligins in synaptogenesis. To enquire on the relevance and frequency of neuroligin mutations in ASD, we performed a mutation screening of NLGN3 and NLGN4X in a sample of 124 autism probands from the International Molecular Genetic Study of Autism Consortium (IMGSAC). We identified a new non‐synonymous variant in NLGN3 (Thr632Ala), which is likely to be a rare polymorphism. Our data indicate that coding mutations in these genes are very rarely associated to ASD. © 2006 Wiley‐Liss, Inc.
Synthesis and characterization of organotin complexes with dithiocarbamates and crystal structures of (4‐NCC6H4CH2)2Sn(S2CNEt2)2 and (2‐ClC6H4CH2)2 Sn(Cl)S2CNBz2
Authors: Yin Han Dong , Xue Sheng Cai 
Published: March 2006

AbstractTen organotin derivatives with dithiocarbamates of the formulae (4‐NCC6H4CH2)2Sn(S2CNEt2)2 (1), (4‐NCC6H4CH2)2Sn(S2CNBz2)2 (2), (4‐NCC6H4CH2)2Sn[S2CN(CH2CH2)2NCH3]2 (3), (2‐ClC6H4CH2)2 Sn(S2CNEt2)2 (4), (2‐ClC6H4CH2)2Sn(S2CNBz2)2 (5), (4‐NCC6H4CH2)2Sn(Cl)S2CNEt2 (6), (4‐NCC6H4CH2)2Sn(Cl)S2CNBz2 (7), (4‐NCC6H4CH2)2Sn(Cl)S2CN(CH2CH2)2NCH3 (8), (2‐ClC6H4CH2)2 Sn(Cl)S2CNEt2 (9) and (2‐ClC6H4CH2)2Sn(Cl)S2CNBz2 (10) have been prepared. All complexes were characterized by elemental analyses, IR and NMR. The crystal structures of complexes 1 and 10 were determined by X‐ray single crystal diffraction. For complex 1, the central tin atom exists in a skew‐trapezoidal planar geometry defined by two asymmetrically coordinated dithiocarbamate ligands and two 4‐cyanobenzyl groups. In addition, because of the presence of close intermolecular non‐bonded contacts, complex 1 is a weakly‐bridged dimer. In complex 10, the central tin atom is rendered pentacoordinated in a distorted trigonal bipyramidal configuration by coordinating with S atoms derived from the dithiocarbamate ligand. In vitro assays for cytotoxicity against five human tumor cell lines (MCF‐7, EVSA‐T, WiDr, IGROV and M226) furnished the significant toxicities of the title complexes. Copyright © 2006 John Wiley & Sons, Ltd.
Critical comparative analyses of anti–α‐actinin and glomerulus‐bound antibodies in human and murine lupus nephritis
Authors: Kalaaji Manar , Sturfelt Gunnar , Mjelle Janne Erikke , Nossent Hans , Rekvig Ole Petter 
Published: February 2006

AbstractObjectiveAlthough anti–double‐stranded DNA (anti‐dsDNA) antibodies are important in lupus nephritis, the question regarding which glomerular structures (α‐actinin, nucleosomes, or others) are recognized by nephritogenic anti‐dsDNA antibodies is still controversial. In this study, we determined which glomerular structures are recognized by monoclonal and in vivo–bound nephritogenic antibodies.MethodsWestern blotting was used to analyze the ability of nephritogenic anti‐dsDNA antibodies to recognize glomerular and nucleosomal structures. Sera from patients with lupus nephritis, sera from random antinuclear antibody–positive patients, and paired antibodies from sera and kidney eluates from nephritic (NZB × NZW)F1 mice were analyzed for activity against proteins identified by monoclonal nephritogenic antibodies, and against α‐actinin, dsDNA, nucleosomes, histone H1, heparan sulfate, DNase I, and type IV collagen. Immunoelectron microscopy was used to determine the glomerular localization of α‐actinin and in vivo–bound autoantibodies in nephritic (NZB × NZW)F1 mouse kidneys.ResultsAnti–α‐actinin antibodies were observed in human and murine lupus nephritis sera and in sera from patients without systemic lupus erythematosus and were not detected in kidney eluates from nephritic mice. Antibodies to dsDNA and histone H1 were detected in all eluates. Western blot analyses revealed that nephritogenic anti‐dsDNA antibodies recognized a 32‐kd band, identified as histone H1. Competitive enzyme‐linked immunosorbent assay demonstrated that nephritogenic monoclonal antibodies, and dominant antibodies eluted from nephritic kidneys, cross‐reacted with dsDNA and H1. This cross‐reactive anti‐H1 specificity was largely absent in sera from those mice. Immunoelectron microscopic analysis of nephritic (NZB × NZW)F1 mouse kidneys revealed that antibodies eluted from kidneys, but not anti–α‐actinin antibodies, bound to distinct nephritis‐associated electron‐dense structures linked to glomerular basement membranes.ConclusionCross‐reactive anti‐dsDNA/anti–histone H1 antibodies, but not anti–α‐actinin antibodies, are central among those deposited in nephritic glomeruli.
Sphingosine kinase 1–mediated inhibition of Fas death signaling in rheumatoid arthritis B lymphoblastoid cells
Authors: Pi Xiujun , Tan Shi‐Yu , Hayes Michael , Xiao Liqun , Shayman James A. , Ling Song , Holoshitz Joseph 
Published: February 2006

AbstractObjectiveIt is becoming increasingly apparent that B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). Due to the scarcity of B cells in RA, it has been technically difficult to functionally characterize B cell apoptosis in this disease. As a necessary first step to identify candidate aberrations, we investigated Fas‐mediated signaling events in immortalized peripheral blood B lymphoblastoid cell lines (LCLs) from patients with RA and controls.MethodsCell death was determined by the MTS assay, and apoptosis was detected by the TUNEL assay and DNA laddering. Proteolytic activation of caspase 3 was determined by immunoblotting, and its enzymatic activity was determined by a fluorometric technique. Messenger RNA (mRNA) expression was quantified by real‐time polymerase chain reaction (PCR) analysis. The functional role of sphingosine kinase (SPHK) was determined by measuring its enzymatic activity, by quantifying the levels of its product, sphingosine 1‐phosphate (S1P), and by investigating the ability of the SPHK inhibitor N,N‐dimethylsphingosine and isozyme‐specific small interfering RNA (siRNA) oligonucleotides to reverse signaling aberrations.ResultsLCLs from patients with RA displayed disease‐specific Fas‐mediated signal transduction impairment with consequent resistance to cell death. RA LCLs displayed high constitutive SPHK activity and increased levels of S1P. Real‐time PCR analysis showed higher SPHK‐1 mRNA expression levels in RA patients compared with paired controls. Increased SPHK‐1 (but not SPHK‐2) mRNA levels were observed in synovial tissue from RA patients. Competitive inhibitors of SPHK reversed the resistance of RA LCLs to Fas‐induced apoptosis. Additionally, resistance to Fas‐mediated signaling was reversed by siRNA oligonucleotides specific for SPHK‐1 but not by oligonucleotides specific for SPHK‐2.ConclusionThese findings demonstrate disease‐specific resistance to Fas‐mediated death signaling in patients with RA and implicate increased SPHK‐1 activity as the cause of this aberration.
Effects of a novel tylophorine analog on collagen‐induced arthritis through inhibition of the innate immune response
Authors: You Xin , Pan Meng , Gao Wenli , Shiah Her‐Shyong , Tao Jian , Zhang Dongqing , Koumpouras Fotios , Wang Shuang , Zhao Hongyu , Madri Joseph A. , Baker David , Cheng Yung‐Chi , Yin Zhinan 
Published: February 2006

AbstractObjectiveTo test the effects of a novel tylophorine analog, DCB 3503, on the prevention and treatment of collagen‐induced arthritis (CIA) and to elucidate its underlying mechanisms.MethodsDBA/1J mice were immunized with type II collagen, and in some cases, lipopolysaccharide (LPS) was used to boost the development of arthritis. DCB 3503 was injected intraperitoneally before or after the onset of CIA. Mice were monitored to assess the effects of DCB 3503 on the clinical severity of the disease, and pathologic changes in the joints were examined histologically. Levels of tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) in serum and joint tissues were measured by enzyme‐linked immunosorbent assay and by cytometric bead array analysis. The effect of DCB 3503 on LPS‐induced proinflammatory cytokines from bone marrow–derived dendritic cells was determined by flow cytometry.ResultsDCB 3503 significantly suppressed the development and progression of CIA. Moreover, DCB 3503 completely blocked the LPS‐triggered acceleration of joint inflammation and destruction. Consistent with its effects in vivo, DCB 3503 significantly suppressed the synthesis of proinflammatory cytokines in inflamed joints as well as cytokine synthesis by macrophages examined ex vivo. Treatment also reduced the levels of inflammatory cytokines (IL‐6, IL‐12, TNFα, and monocyte chemotactic protein 1) produced by bone marrow–derived dendritic cells in vitro. However, DCB 3503 showed no direct effects on T cell proliferation and B cell antibody response.ConclusionBecause of its ability to specifically suppress innate immune responses, DCB 3503 may be a novel therapeutic agent for inflammatory arthritis in humans.
DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti–topoisomerase I autoantibodies from systemic sclerosis patients
Authors: Hénault Jill , Robitaille Geneviève , Senécal Jean‐Luc , Raymond Yves 
Published: February 2006

AbstractObjectiveSystemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis due to excessive and dysregulated collagen production by fibroblasts. Previously, we reported that anti–DNA topoisomerase I (anti–topo I) antibodies bound specifically to fibroblast surfaces; however, we had not identified their antigenic target. We undertook this study to characterize the target of anti–topo I antibodies on fibroblasts and the effects of their binding.MethodsPurified topo I or topo I released from apoptotic cells was tested for surface binding to a number of human cell types by cell‐based enzyme‐linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. Antibodies purified from SSc patient and normal control sera were used to detect topo I binding. The consequences of topo I and anti–topo I binding to fibroblasts were assessed by coculture with THP‐1 monocytes.ResultsThe autoantigen topo I itself was found to bind specifically to fibroblasts in a dose‐dependent and saturable manner, where it was recognized by anti–topo I from SSc patients. The binding of anti–topo I subsequently stimulated adhesion and activation of cocultured monocytes. Topo I released from apoptotic endothelial cells was also found to bind specifically to fibroblasts.ConclusionThe findings of this study thus confirm and extend the findings of our previous study by showing that topo I binding to fibroblast surfaces is both necessary and sufficient for anti–topo I binding. Second, topo I–anti–topo I complex binding can then trigger the adhesion and activation of monocytes, thus providing a plausible model for the amplification of the fibrogenic cascade in anti–topo I–positive SSc patients.
Antigen‐induced, tolerogenic CD11c+,CD11b+ dendritic cells are abundant in Peyer's patches during the induction of oral tolerance to type II collagen and suppress experimental collagen‐induced arthritis
Authors: Min So‐Youn , Park Kyung‐Su , Cho Mi‐La , Kang Jung‐Won , Cho Young‐Gyu , Hwang Sue‐Yun , Park Min‐Jung , Yoon Chong‐Hyeon , Min Jun‐Ki , Lee Sang‐Heon , Park Sung‐Hwan , Kim Ho‐Youn 
Published: February 2006

AbstractObjectiveAlthough oral tolerance is a well‐known phenomenon, the role of dendritic cells (DCs) is not well characterized. This study was conducted to better understand the differential role played by each Peyer's patch DC subset in the induction of oral tolerance to type II collagen (CII) in murine collagen‐induced arthritis (CIA).MethodsCII was fed 6 times to DBA/1 mice beginning 2 weeks before immunization, and the effect on arthritis was assessed. We compared the proportion of CD11c+,CD11b+ DCs and CD11c+,CD8α+ DCs in the Peyer's patches of CII‐fed tolerized and phosphate buffered saline–fed nontolerized mice after the induction of CIA. The immunosuppressive properties of each DC subset were determined using fluorescence‐activated cell sorter analysis for intracellular interleukin‐10 (IL‐10) and IL‐12 and mixed lymphocyte culture. The ability of each DC subset to induce CD4+,CD25+ T regulatory cells was also examined. Mice were injected with CII‐pulsed CD11c+,CD11b+ DCs isolated from Peyer's patches of tolerized mice, and the effect on CIA was examined.ResultsThe severity of arthritis was significantly lower in tolerized mice. The proportion of CD11c+,CD11b+ DCs was increased in the Peyer's patches of tolerized mice and those DCs exhibited immunosuppressive characteristics, such as increased IL‐10 production, inhibition of T cell proliferative responses to CII, and CD4+,CD25+ regulatory T cell induction. Furthermore, the CD11c+,CD11b+ DCs suppressed the severity of arthritis upon adoptive transfer.ConclusionOur observations demonstrate that CD11c+,CD11b+ DCs, which are abundant in Peyer's patches during the induction of oral tolerance to CII, are crucial for the suppression of CIA and could be exploited for immunotherapy of autoimmune diseases.