bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Inhibition of interleukin‐6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis
Authors: Samson Maxime , Audia Sylvain , Janikashvili Nona , Ciudad Marion , Trad Malika , Fraszczak Jennifer , Ornetti Paul , Maillefert Jean‐Francis , Miossec Pierre , Bonnotte Bernard 
Published: April 2012

AbstractObjectiveFrom an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti–interleukin‐6 (anti–IL‐6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL‐6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL‐6 blockade on the balance between Th17 cells and Treg cells in patients with active RA.MethodsPatients with active RA for whom TCZ had been prescribed by a rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed, and the Disease Activity Score in 28 joints (DAS28) was assessed. Serum cytokine levels and other parameters of inflammation were measured before the first infusion and after the third infusion of TCZ (8 mg/kg).ResultsCompared to controls, levels of Th17 cells (CD4+IL‐17+) were increased and Treg cells (CD4+CD25highFoxP3+) were decreased in the peripheral blood of patients with active RA. The suppressive function of circulating Treg cells was not impaired in patients with active RA. TCZ treatment induced a significant decrease in the DAS28 associated with a significant decrease in the percentage of Th17 cells (from a median of 0.9% to 0.45%; P = 0.009) and an increase in the percentage of Treg cells (from a median of 3.05% to 3.94%; P = 0.0039) in all patients.ConclusionThis study demonstrates for the first time that inhibition of IL‐6 function by TCZ corrects the imbalance between Th17 cells and Treg cells in patients with RA.
Dkk‐1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice
Authors: Oh Hwanhee , Chun Churl‐Hong , Chun Jang‐Soo 
Published: April 2012

AbstractObjectiveDkk is a family of canonical Wnt antagonists with 4 members (Dkk‐1, Dkk‐2, Dkk‐3, and Dkk‐4). We undertook this study to explore the roles of Dkk‐1 and Dkk‐2 in osteoarthritic (OA) cartilage destruction in mice.MethodsExpression of Dkk and other catabolic factors was determined at the messenger RNA and protein levels in human and mouse OA cartilage. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) or by intraarticular injection of Epas1 adenovirus (AdEPAS‐1). The role of Dkk in OA pathogenesis was examined by intraarticular injection of AdDkk‐1 or by using chondrocyte‐specific Dkk1 (Col2a1‐Dkk1)–transgenic mice and Dkk2 (Col2a1‐Dkk2)–transgenic mice. Primary culture mouse chondrocytes were also treated with recombinant Dkk proteins.ResultsWe found opposite patterns of Dkk1 and Dkk2 expression in human and mouse experimental OA cartilage: Dkk1 was up‐regulated and Dkk2 was down‐regulated. Overexpression of Dkk1 by intraarticular injection of AdDkk‐1 significantly inhibited DMM‐induced experimental OA. DMM‐induced OA was also significantly inhibited in Col2a1‐Dkk1–transgenic mice compared with their wild‐type littermates. However, Col2a1‐Dkk2–transgenic mice showed no significant difference in OA pathogenesis. Wnt‐3a, which activates the canonical Wnt pathway, induced Mmp13 and Adamts4 expression in primary culture chondrocytes, an effect that was significantly inhibited by Dkk‐1 pretreatment or Dkk1 overexpression.ConclusionOur findings indicate that expression of Dkk1, but not Dkk2, in chondrocytes inhibits OA cartilage destruction. The protective effect of Dkk‐1 appears to be associated with its capacity to inhibit Wnt‐mediated expression of catabolic factors, such as Mmp13, providing evidence that Dkk‐1 might serve as a therapeutic target for OA treatment.
Antiinflammatory functions of p38 in mouse models of rheumatoid arthritis: Advantages of targeting upstream kinases MKK‐3 or MKK‐6
Authors: Guma Monica , Hammaker Deepa , Topolewski Katharyn , Corr Maripat , Boyle David L. , Karin Michael , Firestein Gary S. 
Published: April 2012

AbstractObjectiveInhibitors of p38 demonstrate limited benefit in rheumatoid arthritis (RA), perhaps due to the antiinflammatory functions of p38α. This study was performed to determine if selective deletion of p38α in macrophages affects the severity of arthritis and whether blocking upstream kinases in the p38 pathway, such as MKK‐3 or MKK‐6, avoids some of the limitations of p38 blockade.MethodsWild‐type (WT) mice and mice with selective deletion of p38α in macrophages (p38αΔLysM) were injected with K/BxN sera. Antigen‐induced arthritis was also induced in p38αΔLysM mice. Mouse joint extracts were evaluated by enzyme‐linked immunosorbent assay, quantitative polymerase chain reaction (qPCR), and Western blot analysis. Bone marrow–derived macrophages (BMMs) were stimulated with lipopolysaccharide (LPS) and were evaluated by qPCR and Western blotting. Bone marrow chimeras were generated using MKK‐3−/− and MKK‐6−/− mice, and K/BxN serum was administered to induce arthritis.ResultsCompared to WT mice, p38αΔLysM mice had increased disease severity and delayed resolution of arthritis, which correlated with higher synovial inflammatory mediator expression and ERK phosphorylation. In contrast to WT BMMs cultured in the presence of a p38α/β inhibitor, LPS‐stimulated MKK‐6– and MKK‐3–deficient BMMs had suppressed LPS‐mediated interleukin‐6 (IL‐6) expression but had normal IL‐10 production, dual‐specificity phosphatase 1 expression, and MAPK phosphorylation. WT chimeric mice with MKK‐6– and MKK‐3–deficient bone marrow had markedly decreased passive K/BxN arthritis severity.ConclusionInhibiting p38α in a disease that is dominated by macrophage cytokines, such as RA, could paradoxically suppress antiinflammatory functions and interfere with clinical efficacy. Targeting an upstream kinase that regulates p38 could be more effective by suppressing proinflammatory cytokines while preventing decreased IL‐10 expression and increased MAPK activation.
Synthesis of Optically Pure Norcantharidin Analogue NCA‐01, a Highly Selective Protein Phosphatase 2B Inhibitor, and its Derivatives
Authors: Shimizu Tadashi , Iizuka Masato , Matsukura Hiroko , Hashizume Daisuke , Sodeoka Mikiko 
Published: April 2012

AbstractAn efficient synthetic route to optically pure norcantharidin analogue NCA‐01, a highly selective inhibitor of protein phosphatase 2B (PP2B; calcineurin), has been developed. The absolute stereochemistry of the enantiomers was determined by X‐ray crystallographic analysis. Optically pure NCA derivatives that had various substituents at the C1 position were synthesized in a similar manner. The PP2B‐inhibitory activities of NCA‐01 and its derivatives were independent of the enantiomeric form. NCA‐01 dimethyl ester potently inhibited IL‐2 production in Jurkat cells.
Dietary zinc status reversibly alters both the feeding behaviors of the rats and gene expression patterns in diencephalon
Authors: Okada Shinji , Abuyama Moe , Yamamoto Ryo , Kondo Takashi , Narukawa Masataka , Misaka Takumi 
Published: April 2012

AbstractNutritional status influences feeding behaviors, food preferences, and taste sensations. For example, zinc‐deficient rats have been reported to show reduced and cyclic food intake patterns with increased preferences for NaCl. Although some impairments of the central nervous and endocrine systems have been speculated to be involved in these phenomena, the effects of short‐term zinc deficiency on the brain have not been well examined to date. In this study, we performed a comprehensive analysis of the gene expression patterns in the rat diencephalon, which is a portion of the brain that includes the hypothalamus and thalamus, after short‐term zinc deficiency and also during zinc recovery. The rats showed reduced and cyclic food intake patterns with increased salt preferences after a 10‐day dietary zinc deficiency. A comparative analysis of their diencephalons using cDNA microarrays revealed that approximately 1% of the genes expressed in the diencephalons showed significantly altered expression levels. On the other hand, a 6‐day zinc supplementation following the deprivation allowed for the recovery to initial food intake behaviors and salt preferences. The expression levels of most of the genes that had been altered by exposure to zinc deficient conditions were also recovered. These results show that feeding behaviors, taste preferences and gene expression patterns in the diencephalon respond quickly to changing zinc levels.
Beneficial effect of (–)Schisandrin B against 3‐nitropropionic acid‐induced cell death in PC12 cells
Authors: Lam Philip Y. , Ko Kam Ming 
Published: April 2012

AbstractHuntington's disease (HD) is characterized by the dysfunction of mitochondrial energy metabolism, which is associated with the functional impairment of succinate dehydrogenase (mitochondrial complex II), and pyruvate dehydrogenase (PDH). Treatment with 3‐nitropropionic acid (3‐NP), a potent irreversible inhibitor of succinate dehydrogenase, replicates most of the pathophysiological features of HD. In the present study, we investigated the effect of (–)schisandrin B [(–)Sch B, a potent enantiomer of schisandrin B] on 3‐NP‐induced cell injury in rat differentiated neuronal PC12 cells. The 3‐NP caused cell necrosis, as assessed by lactate dehydrogenase (LDH) leakage, and mitochondrion‐dependent cell apoptosis, as assessed by caspase‐3 and caspase‐9 activation, in differentiated PC12 cells. The cytotoxicity induced by 3‐NP was associated with a depletion of cellular reduced glutathione (GSH) as well as the activation of redox‐sensitive c‐Jun N‐terminal kinase (JNK) pathway and the inhibition of PDH. (‐)Sch B pretreatment (5 and 15 μM) significantly reduced the extent of necrotic and apoptotic cell death in 3‐NP‐challenged cells. The cytoprotection afforded by (–)Sch B pretreatment was associated with the attenuation of 3‐NP‐induced GSH depletion as well as JNK activation and PDH inhibition. (–)Sch B pretreatment enhanced cellular glutathione redox status and ameliorated the 3‐NP‐induced cellular energy crisis, presumably by suppressing the activated JNK‐mediated PDH inhibition, thereby protecting against necrotic and apoptotic cell death in differentiated PC12 cells.
Synthesis of Fragrance Ingredients by Tandem Hydroformylation‐Cyclization of Limonene Catalyzed by Rhodium Complexes and Pyridinium p‐Toluenesulphonate
Authors: Vieira Camila G. , de Freitas Marina C. , dos Santos Eduardo N. , Gusevskaya Elena V. 
Published: April 2012

AbstractThe rhodium‐catalyzed hydroformylation of limonene (1) in the presence of PPh3 or P(O‐o‐tBuPh)3 as auxiliary ligands and pyridinium p‐toluenesulfonate, as an acid co‐catalyst, gave two diasteroisomers of 4,8‐dimethyl‐bicyclo[3.3.1]non‐7‐en‐2‐ol (3) in nearly quantitative yield. Limonene is a cheap natural product obtained commercially from citrus fruits, in particular, as a sub‐product of the orange juice industry; whereas alcohol 3 is an expensive perfume ingredient. Alcohol 3 is formed through the hydroformylation of 1 giving a corresponding aldehyde (2) followed by the intramolecular carbonyl ene reaction resulting in cyclization of the aldehyde. The cyclization step is highly stereoselective with only one diasteroisomer of 3 being formed from each of two diasteroisomers of 2. The use of the P(O‐o‐tBuPh)3 ligand not only remarkably accelerates the hydroformylation step compared to the system with PPh3, but also increases significantly the cyclization activity of the catalytic system.
Ion Exchange Adsorption Studies of Miglitol in a Fixed Bed
Authors: Zhang J. , Zhang X. L. , Li H. , Zhao B. 
Published: April 2012

AbstractThe adsorption of miglitol on the D001 resin in a fixed bed was studied at different flow rates, temperatures, and height‐to‐diameter ratios (H/D). The exhaustion time decreased and the height of the mass transfer zone (HMTZ) increased with increasing flow rate. The surface area of the adsorbent increased with decreasing solution flow rate. Breakthrough curves at different flows were described by the Thomas, Yoon–Nelson, and Adams‐Bohart models. The rate constants for the kinetic models increased with increasing flow rate. The theoretical and experimental times required for 50 % adsorbate breakthrough slightly differed at varying flow rates. The change trend in the values of the maximum volumetric adsorption capacity was the same as that of the values at the maximum adsorption capacity of the D001 resin. The temperature did not obviously affect the breakthrough curves. The slope of the breakthrough curve decreased and the HMTZ increased with increasing H/D ratio. The adsorption capacities of the fixed bed for H/D = 7.6 and 0.7 were greater than that for H/D = 1.5.
ChemInform Abstract: The Effect of the N‐Mesityl Group in NHC‐Catalyzed Reactions.
Authors: Mahatthananchai Jessada , Bode Jeffrey W. 
Published: April 2012

AbstractThe majority of the NHC‐catalyzed reactions occurs more rapidly with N‐mesityl substituents, whereas less hindered derivatives such as N‐C6F5 are preferred for benzoin and Stetter type reactions.
Knowledge Based Design of Piping and Instrumentation Diagrams
Authors: Uzuner Hülya , Schembecker Gerhard 
Published: April 2012

AbstractDer Designprozess des Rohrleitungs‐ und Instrumentierungsfließbildes (R&I‐Fließbild), das aufgrund seiner auftragsspezifischen Unikaterstellung einen enormen Aufwand und hohe Kosten für jedes Chemieanlagenprojekt bedeutet, bietet ein erhebliches Einsparungspotenzial innerhalb des Planungsprozesses chemischer Anlagen. Der Beitrag thematisiert die Verkürzung von Projektdurchlaufzeiten durch Beschleunigung der Entwicklungsphase von R&I‐Fließbildern. Es wird ein modulbasierter Ansatz zur Erstellung wissensbasierter R&I‐Fließbilder in der frühen Basic‐Engineering‐Phase vorgestellt und gezeigt, wie eine verfahrenstechnische Anlage systematisch aus vorgefertigten, flexiblen Planungseinheiten rechnergestützt zusammengesetzt werden kann.
The dynamic role of bone morphogenetic proteins in neural stem cell fate and maturation
Authors: Bond Allison M. , Bhalala Oneil G. , Kessler John A. 
Published: April 2012

AbstractThe bone morphogenetic proteins (BMPs) are a group of powerful morphogens that are critical for development of the nervous system. The effects of BMP signaling on neural stem cells are myriad and dynamic, changing with each stage of development. During early development inhibition of BMP signaling differentiates neuroectoderm from ectoderm, and BMP signaling helps to specify neural crest. Thus modulation of BMP signaling underlies formation of both the central and peripheral nervous systems. BMPs secreted from dorsal structures then form a gradient which helps pattern the dorsal–ventral axis of the developing spinal cord and brain. During forebrain development BMPs sequentially induce neurogenesis and then astrogliogenesis and participate in neurite outgrowth from immature neurons. BMP signaling also plays a critical role in maintaining adult neural stem cell niches in the subventricular zone (SVZ) and subgranular zone (SGZ). BMPs are able to exert such diverse effects through closely regulated temporospatial expression and interaction with other signaling pathways. © 2012 Wiley Periodicals, Inc. Develop Neurobiol 72: 1068–1084, 2012
Rhodium‐Catalyzed Allylic Substitution Reactions with Indium(III) Organometallics
Authors: Riveiros Ricardo , Tato Rubén , Pérez Sestelo José , Sarandeses Luis A. 
Published: April 2012

AbstractA novel rhodium‐catalyzed allylic substitution reaction using indium organometallics is reported. Aryl‐ and heteroarylindium reagents reacted in THF at 80 °C with primary and secondary allyl halides and their derivatives under rhodium(I) catalysis to afford the α‐substituted products in good yields and with high regio‐ and stereoselectivity. The reaction takes place with substoichiometric amounts of the triorganoindium reagents, which demonstrates the efficiency of the indium–rhodium transmetallation process in carbon–carbon bond‐forming reactions.
Interaction between the controls on fluvial system development: tectonics, climate, base level and river capture – Rio Alias, Southeast Spain
Authors: Whitfield (née Maher) Elizabeth , Harvey Adrian M. 
Published: April 2012

ABSTRACTFluvial systems in uplifting terrain respond to tectonic, climatic, eustatic and local base‐level controls modified by specific local factors, such as river capture. The Rio Alias in southeast Spain is an ephemeral, transverse‐to‐structure fluvial system. The river drains two interconnected Neogene sedimentary basins, the Sorbas and Almeria basins, and crosses two major geological structures, the Sierras de Alhamilla/Cabrera and the Carboneras Fault Zone. Regional epeirogenic uplift resulted in sustained fluvial incision during the Quaternary, punctuated by major climatically driven periods of aggradation and dissection, which created a suite of five river terraces. The river terrace sequence was radically modified in the late Pleistocene by a major river capture (itself a response to regional tectonics), localized tectonic activity and eustatic base‐level change. The Rio Alias is defined by four reaches; within each the climatically‐generated, region‐wide, fluvial response was modified by tectonics, base‐level change or river capture to varying degrees. In the upper part of the basin (Lucainena reach), climate was the dominant control on river development, with limited modification of the sequence by uplift of the Sierra Alhamilla and local drainage reorganization by a local river capture. Downstream of the Sierra Alhamilla in the Polopus reach, the climatic signal is dominant, but its expression is radically modified by the response to a major river capture whereby the Alias system lost up to 70% of its pre‐capture drainage area. In the reach adjacent to the Carboneras Fault Zone (Argamason reach), modification of the terrace sequence by local tectonic activity and a resultant local base‐level fall led to a major local incisional event (propagating c. 3–4 km upstream from the area of tectonic disturbance). At the seaward end of the system (El Saltador reach) Quaternary sea‐level changes modified the patterns of erosion and incision and have resulted in steep incisional terrace profiles. The signals generated by regional tectonics and the Quaternary climate change can be identified throughout the basin but those generated by ongoing local tectonics, river capture and sea‐level change are spatially restricted and define the four reaches. The connectivity of the system from the headwaters to the coast decreased through time as incision progressed, resulting in changes in local coupling characteristics. Copyright © 2012 John Wiley & Sons, Ltd.
Acute toxicity of cadmium, lead, zinc, and their mixtures to stream-resident fish and invertebrates
Authors: Mebane Christopher A. , Dillon Frank S. , Hennessy Daniel P. 
Published: April 2012

Abstract
The authors conducted 150 tests of the acute toxicity of resident fish and invertebrates to Cd, Pb, and Zn, separately and in mixtures, in waters from the South Fork Coeur d'Alene River watershed, Idaho, USA. Field-collected shorthead sculpin (Cottus confusus), westslope cutthroat trout (Oncorhynchus clarkii lewisi), two mayflies (Baetis tricaudatus and Rhithrogena sp.), a stonefly (Sweltsa sp.), a caddisfly (Arctopsyche sp.), a snail (Gyraulus sp.), and hatchery rainbow trout (Oncorhynchus mykiss), were tested with all three metals. With Pb, the mayflies (Drunella sp., Epeorus sp., and Leptophlebiidae), a Simuliidae black fly, a Chironomidae midge, a Tipula sp. crane fly, a Dytiscidae beetle, and another snail (Physa sp.), were also tested. Adult westslope cutthroat trout were captured to establish a broodstock to provide fry of known ages for testing. With Cd, the range of 96-h median effect concentrations (EC50s) was 0.4 to &gt;5,329 µg/L, and the relative resistances of taxa were westslope cutthroat trout ≈ rainbow trout ≈ sculpin &lt;&lt; other taxa; with Pb, EC50s ranged from 47 to 3,323 µg/L, with westslope cutthroat trout &lt; rainbow trout &lt; other taxa; and with Zn, EC50s ranged from 21 to 3,704 µg/L, with rainbow trout &lt; westslope cutthroat trout ≈ sculpin &lt;&lt; other taxa. With swim-up trout fry, a pattern of decreasing resistance with increasing fish size was observed. In metal mixtures, the toxicities of the three metals were less than additive on a concentration-addition basis. Environ. Toxicol. Chem. 2012;31:1334–1348. © 2012 SETAC
Hexabromocyclododecane in consumer fish from South China: Implications for human exposure via dietary intake
Authors: Meng Xiang-Zhou , Xiang Nan , Duan Yan-Ping , Chen Ling , Zeng Eddy Y. 
Published: April 2012

Abstract
Levels of hexabromocyclododecane (HBCD) were determined in 12 consumer fish species from South China. The concentrations of the sum of HBCD diastereoisomers (ΣHBCD) ranged from nondetectable to 194 pg/g wet weight, with a detectable frequency of 70%. This was at the low end of the concentration range globally observed. Carnivorous fish species contained higher HBCD concentrations than herbivorous and detritivorous ones, suggesting the potential for biomagnification of HBCDs via the trophic chain. Moreover, ΣHBCD concentrations were higher in both freshwater and seawater farmed fish than in wild marine fish, indicating that human activities were probably an important input source of HBCD in aquaculture. Among the three diastereoisomers, α-HBCD dominated in most samples, with a mean relative abundance of 70%. In agreement with previous studies, a difference in the diastereomer patterns was observed from commercial products and several environmental media to biota samples. For farm-raised snubnose pompano, the concentrations of ΣHBCD were moderately linearly correlated with lipid contents but were not significantly correlated with fish body lengths and weights. In the worst-case exposure, the mean estimated daily intake of ΣHBCD via fish consumption for residents of South China ranged from 13 to 16 pg/kg body weight/d for various age groups, much lower than its lowest observed adverse effect level derived from a two-generation reproductive toxicity study on rats. Environ. Toxicol. Chem. 2012; 31: 1424–1430. © 2012 SETAC