bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Flexible Asymmetric Approach to Methyl 5‐Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A
Authors: Lan Hong‐Qiao , Ye Jian‐Liang , Wang Ai‐E , Ruan Yuan‐Ping , Huang Pei‐Qiang 
Published: November 2010

AbstractBy using a methyl tetramate derivative (R)‐ or (S)‐9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)‐ or (S)‐5‐alkyltetramates (2) is disclosed. Among the synthesized methyl 5‐alkyltetramates 2, methyl 5‐methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5‐benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)‐9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)‐belamide A (7) been confirmed, but also the solvent used for recording the 13C NMR spectrum, the 13C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised.
Domino Pd‐Catalyzed Heck Cyclization and Bismuth‐Catalyzed Hydroamination: Formal Synthesis of Elacomine and Isoelacomine
Authors: Kamisaki Haruhi , Nanjo Takeshi , Tsukano Chihiro , Takemoto Yoshiji 
Published: November 2010

AbstractThe formal synthesis of hemiterpene spirooxindole alkaloids elacomine (1) and isoelacomine (2) is described. Heck reaction of protected iodoanilines with 5,6‐dihydro‐2H‐pyran‐2‐one or six‐membered unsaturated lactams was investigated. The coupling product was readily converted to a carbamoyl chloride with an incorporated diene unit. The spiro(pyrrolidine‐3,3′‐oxindole) skeleton, which corresponds to the carbon skeleton of1and2, was efficiently constructed from this intermediate by using a domino palladium‐catalyzed Heck reaction and bismuth‐catalyzed hydroamination. An isolated byproduct of the reaction could also be converted to the spirooxindole skeleton.
Design of Polymeric Porous Adsorbent Media and the Dynamic Behavior of Transport and Adsorption of Bioactive Molecules in Such Media
Authors: Liapis Athanasios I. , Wang Jee‐Ching 
Published: November 2010

AbstractA systematic methodology based on molecular dynamics (MD) modeling and simulation was developed to study ion exchange chromatography (IEC) that utilizes polymeric porous adsorbent media in which charged affinity ligands are linked to the base matrix of the porous media via a grafted polysaccharide extender. During its transport in a porous polymeric medium, a charged adsorbate biomolecule is found to exhibit decreased mass transport coefficients, changes in shape, orientation and lateral position, and to displace the counterions in the proximity of the adsorption site in order to become adsorbed. The ligand density distributions from the MD studies as well as other ligand density distributions of interest are considered in macroscopic continuum models and this leads to a multiscale modeling study of adsorption systems.
New cis‐Configured Aziridine‐2‐carboxylates as Aspartic Acid Protease Inhibitors
Authors: Büchold Christian , Hemberger Yasmin , Heindl Cornelia , Welker Armin , Degel Björn , Pfeuffer Thomas , Staib Peter , Schneider Sabrina , Rosenthal Philip J. , Gut Jiri , Morschhäuser Joachim , Bringmann Gerhard , Schirmeister Tanja 
Published: November 2010

AbstractA series of 52 cis‐configured 1‐alkyl‐3‐phenylaziridine‐2‐carboxylates were synthesized as new pseudo‐irreversible inhibitors of Candida albicans secreted aspartic acid protease 1 (SAP1), SAP2, SAP3, and SAP8. Some of the compounds, which were obtained as diastereomers with S,S‐ and R,R‐configured aziridine rings by Cromwell synthesis of racemic (2R,3S+2S,3R)‐dibromophenylpropionic acid ester with amines, followed by ester hydrolysis and coupling to hydrophobic amino acid esters, were separated by preparative HPLC. The absolute configuration of the aziridine ring was assigned by a combination of experimental circular dichroism (CD) investigations and quantum chemical CD calculations. In agreement with previous docking studies, the diastereomers all exhibit similar activity. The compounds were found to be more active against the related mammalian enzyme cathepsin D, presumably due to productive interactions of the N‐alkyl substituent with the highly lipophilic S2 pocket. The most active inhibitors (5, 9, 10, 21, and 28), characterized by benzyl, cyclohexylmethyl, tert‐butyl, or 1,4‐dimethylpentyl moieties at the aziridine nitrogen atom, exhibit k2nd values between 500 and 900×103 M−1 min−1 and Ki values near or below 1 μM for cathepsin D.
Galectin‐9 ameliorates acute GVH disease through the induction of T‐cell apoptosis
Authors: Sakai Kazuki , Kawata Eri , Ashihara Eishi , Nakagawa Yoko , Yamauchi Akira , Yao Hisayuki , Nagao Rina , Tanaka Ruriko , Yokota Asumi , Takeuchi Miki , Hirai Hideyo , Kimura Shinya , Hirashima Mitsuomi , Yoshimura Norio , Maekawa Taira 
Published: November 2010

AbstractGalectins comprise a family of animal lectins that differ in their affinity for β‐galactosides. Galectin‐9 (Gal‐9) is a tandem‐repeat‐type galectin that was recently shown to function as a ligand for T‐cell immunoglobin domain and mucin domain‐3 (Tim‐3) expressed on terminally differentiated CD4+ Th1 cells. Gal‐9 modulates immune reactions, including the induction of apoptosis in Th1 cells. In this study, we investigated the effects of Gal‐9 in murine models of acute GVH disease (aGVHD). First, we demonstrated that recombinant human Gal‐9 inhibit MLR in a dose‐dependent manner, involving both Ca2+ influx and apoptosis in T cells. Next, we revealed that recombinant human Gal‐9 significantly inhibit the progression of aGVHD in murine BM transplantation models. In conclusion, Gal‐9 ameliorates aGVHD, possibly by inducing T‐cell apoptosis, suggesting that gal‐9 may be an attractive candidate for the treatment of aGVHD.
Negative regulation of Toll‐like receptor signaling plays an essential role in homeostasis of the intestine
Authors: Biswas Amlan , Wilmanski Jeanette , Forsman Huamei , Hrncir Tomas , Hao Liming , Tlaskalova‐Hogenova Helena , Kobayashi Koichi S. 
Published: November 2010

AbstractA healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria‐dependent colitis model in IL‐10‐deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL‐10−/−MyD88−/− mice, IL‐10−/−TLR4−/− mice exhibited reduced colitis compared to IL‐10−/− mice, indicating that TLR4 signaling plays an important role in inducing colitis. Interestingly, the expression of IRAK‐M, a negative regulator of TLR signaling, is dependent on intestinal commensal flora, as IRAK‐M expression was reduced in mice re‐derived into a germ‐free environment, and introduction of commensal bacteria into germ‐free mice induced IRAK‐M expression. IL‐10−/−IRAK‐M−/− mice exhibited exacerbated colitis with increased inflammatory cytokine gene expression. Therefore, this study indicates that intestinal microflora stimulate the colitogenic immune system through TLR and negative regulation of TLR signaling is essential in maintaining intestinal homeostasis.
CD68‐expressing cells can prime T cells and initiate autoimmune arthritis in the absence of reactive oxygen species
Authors: Pizzolla Angela , Gelderman Kyra A. , Hultqvist Malin , Vestberg Mikael , Gustafsson Kenth , Mattsson Ragnar , Holmdahl Rikard 
Published: November 2010

AbstractIt is widely believed that DC, but not macrophages, prime naïve T cells in vivo. Here, we investigated the ability of CD68‐expressing cells (commonly defined as macrophages) in priming autoreactive T cells and initiating collagen‐induced arthritis (CIA) in the mouse. For this purpose, a transgenic mouse was developed (MBQ mouse) where macrophages exclusively expressed the MHC class II H2‐Aq (Aq) on an H2‐Ap (Ap) background. Aq, but not Ap expression mediates susceptibility to CIA through presentation of type II collagen (CII) to T cells. CIA severity is enhanced by a mutation in the Ncf1 gene, impairing reactive oxygen species (ROS) production by the phagocyte NADPH oxidase (NOX2) complex. Expression of functional Ncf1 on macrophages was previously shown to protect from severe CIA. To study the effect of ROS on macrophage‐mediated priming of T cells, the Ncf1 mutation was introduced in the MBQ mouse. Upon CII immunization, Ncf1‐mutated MBQ mice, but not Ncf1 wild‐type MBQ mice nor Ncf1‐mutated Ap mice, activated autoreactive T cells and developed CIA. These findings demonstrate for the first time that macrophages can initiate arthritis and that the process is negatively regulated by ROS produced via the NOX2 complex.
Overexpression of phospholipase Cε in keratinocytes upregulates cytokine expression and causes dermatitis with acanthosis and T‐cell infiltration
Authors: Takenaka Nobuyuki , Edamatsu Hironori , Suzuki Noboru , Saito Hiromitsu , Inoue Yukiko , Oka Masahiro , Hu Lizhi , Kataoka Tohru 
Published: November 2010

AbstractPhospholipase Cε (PLCε) is an effector of Ras and Rap small GTPases. We showed previously using PLCε‐deficient mice that PLCε plays a critical role in activation of cytokine production in non‐immune skin cells in a variety of inflammatory reactions. For further investigation of its role in inflammation, we created transgenic mice overexpressing PLCε in epidermal keratinocytes. The resulting transgenic mice spontaneously developed skin inflammation as characterized by formation of adherent silvery scales, excessive growth of keratinocytes, and aberrant infiltration of immune cells such as T cells and DC. Development of the skin symptoms correlated well with increased expression of factors implicated in human inflammatory skin diseases, such as IL‐23, in keratinocytes, and with the accumulation of CD4+ T cells producing IL‐22, a potent inducer of keratinocyte proliferation. Intradermal injection of a blocking antibody against IL‐23 as well as treatment with the immunosuppressant FK506 reversed these skin phenotypes, which was accompanied by suppression of the IL‐22‐producing T‐cell infiltration. These results reveal a crucial role of PLCε in the development of skin inflammation and suggest a mechanism in which PLCε induces the production of cytokines including IL‐23 from keratinocytes, leading to the activation of IL‐22‐producing T cells.
Generation of human Th1‐like regulatory CD4+ T cells by an intrinsic IFN‐γ‐ and T‐bet‐dependent pathway
Authors: Zheng Jian , Liu Yinping , Qin Gang , Lam Kwok‐Tai , Guan Jing , Xiang Zheng , Lewis David B. , Lau Yu‐Lung , Tu Wenwei 
Published: November 2010

AbstractMurine Foxp3+ Treg have recently been shown to express T‐bet, a transcription factor characteristic of Th1 effector cells. A human Treg phenotype equivalent has not been reported. Here, we show that naïve human CD4+ T cells incubated with low numbers of CD40‐activated allogeneic B cells preferentially differentiate into alloantigen‐specific CD4hiCD25hi Treg. These differentiated cells potently suppress effector T‐cell responses and express T‐bet, IFN‐γ, and CXCR3, the features of Th1 effector cells. In contrast, co‐culture of naïve CD4+ T cells with high numbers of allogeneic B cells results in CD4+CD25+ T cells that promote, rather than inhibit, effector T‐cell responses, demonstrating the plasticity of CD4+ T‐cell differentiation in response to alloantigen‐presenting B cells. The optimal accumulation of CD4hiCD25hi Treg induced using higher T cell:B cell co‐culture ratios was dependent on the expression of T‐bet and endogenously produced IFN‐γ. Induction of Treg‐mediated suppression function in the Treg population was not. As CXCR3 confers the preferential trafficking of T cells to tissue sites of IFN‐γ, these human Th1‐like Treg might be useful for modulating pathological Th1 effector responses, such as that occurring during graft‐versus‐host disease or graft rejection.
CD4+T‐cell immunity to theBurkholderia pseudomalleiABC transporter LolC in melioidosis
Authors: Chu Karen K. , Tippayawat Patcharaporn , Walker Nicola J. , Harding Sarah V. , Atkins Helen S. , Maillere Bernard , Bancroft Gregory J. , Lertmemongkolchai Ganjana , Altmann Daniel M. 
Published: November 2010

AbstractBurkholderia pseudomalleicauses melioidosis, a disease with a wide range of possible outcomes, from seroconversion and dormancy to sepsis and death. This spectrum of host–pathogen interactions poses challenging questions about the heterogeneity in immunity toB. pseudomallei. Models show protection to be dependent on CD4+cells and IFN‐γ, but little is known about specific target antigens. Having previously implicated the ABC transporter, LolC, in protective immunity, we here use epitope prediction, HLA‐binding studies, HLA‐transgenic models and studies of T cells from seropositive individuals to characterize HLA‐restricted LolC responses. Immunized mice showed long‐lasting memory to the protein, whereas predictive algorithms identified epitopes within LolC that subsequently demonstrated strong HLA class II binding. Immunization of HLA‐DR transgenics with LolC stimulated T‐cell responses to four of these epitopes. Furthermore, the responsiveness of HLA transgenics to LolC revealed a hierarchy supportive of HLA polymorphism‐determined differential susceptibility. Seropositive human donors of diverse HLA class II types showed T‐cell responses to LolC epitopes, which are conserved amongBurkholderiaspecies includingBurkholderia cenocepacia, associated with life‐threateningcepaciacomplex in cystic fibrosis patients andBurkholderia mallei, which causes glanders. These findings suggest a role for LolC epitopes in multiepitope vaccine design for melioidosis and related diseases.
Space–time regression modeling of tree growth using the skew‐t distribution
Authors: Nathoo F. S. 
Published: November 2010

AbstractIn this paper, we present new statistical methodology for the analysis of repeated measures of spatially correlated growth data. Our motivating application, a 10 year study of height growth in a plantation of even‐aged white spruce, presents several challenges for statistical analysis. Here, the growth measurements arise from an asymmetric distribution, with heavy tails, and thus standard longitudinal regression models based on a Gaussian error structure are not appropriate. We seek more flexibility for modeling both skewness and fat tails, and achieve this within the class of skew‐elliptical distributions. Within this framework, robust space–time regression models are formulated using random effect growth curves, with coefficients arising from an underlying multivariate spatial process. Computational difficulties arise when data are collected at a large number of locations, and we consider two approaches for spatial modeling in the large data context. Both approaches are compared within the context of our application, and inference is conducted in a Bayesian framework, with implementation based on hybrid Monte Carlo. Copyright © 2010 John Wiley & Sons, Ltd.
Impact of gavage dosing procedure and gastric content on adverse respiratory effects and mortality in rat toxicity studies
Authors: Eichenbaum G. , Damsch S. , Looszova A. , Vandenberghe J. , Van den Bulck K. , Roels K. , Megens A. , Knight E. , Hillsamer V. , Feyen B. , Kelley M. F. , Tonelli A. , Lammens L. 
Published: November 2010

AbstractUnscheduled mortality preceded by adverse respiratory clinical signs in rats dosed by oral gavage may not only be caused by technical gavage error or systemic toxicity but may also be caused by gastro‐esophageal reflux and subsequent aspiration of high concentrations of drug formulation. In a 3 week oral gavage rat toxicity study for an early drug development compound, preterminal deaths (approximately 20% of animals) at high doses (≥1000 mg kg−1) and concentrations (≥60 mg ml−1) were preceded by recurrent dyspnea, rales or excessive salivation, without evidence of accidental intrapulmonary gavage error. Histological evaluation revealed extensive necrosis and inflammatory changes in the upper respiratory tract, especially in the nasal turbinates and/or nasopharynx. The presence of food particles in inflammatory exudates suggested a retrograde aspiration of stomach content with test formulation via the nasopharyngeal duct into the posterior region of the nose. In contrast, no mortality or adverse respiratory effects were observed in rats following 2 week intravenous administration at comparable exposures or oral gavage administration at lower concentrations (≤20 mg ml−1). In a pharmacology study, the compound caused a dose‐dependent increase in gastric content (partly due to inhibition of gastric emptying), providing a pharmacological basis for the suspected gavage‐mediated gastroesophageal reflux. Reducing the dose volume and dosing fasted animals substantially reduced or eliminated the respiratory effects and mortality at the high test article concentrations, demonstrating that the adverse effects are related to the gavage method. Copyright © 2010 John Wiley & Sons, Ltd.
Different reaction patterns of dopamine content to prenatal exposure to chlorpyrifos in different periods
Authors: Chen Xiao‐Ping , Wang Xiang , Dong Jing‐Yin 
Published: November 2010

AbstractDevelopmental exposure to chlorpyrifos (CPF) induces abnormalities in neurotransmission. In the present study, we evaluated the dopamine reaction patterns in brain regions after CPF exposure during different prenatal periods. Animals were exposed on gestational days (GD) 7.5–11.5 or 13–17 and assessed at GD17, and at postnatal days (PN) 14 and 60. CPF exposure during GD7.5–11.5 elicited a decrease in dopamine content at each measurement stages, with more changes in the hippocampus than in the cerebral cortex. In contrast, CPF exposure in GD13–17 elicited a decrease in dopamine content at PN14 and PN60, with more changes in the cerebral cortex than in the hippocampus. These results suggest that the two key brain regions involved in learning and memory, the cerebral cortex and hippocampus, react differently to CPF exposure in different prenatal periods. The abnormalities did not recover long after cessation of CPF exposure and deficiencies persisted into pre‐puberty and adulthood. Copyright © 2010 John Wiley & Sons, Ltd.
Application of dosimetry systems and cytogenetic status of the child population exposed to diagnostic X‐rays by use of the cytokinesis‐block micronucleus cytome assay
Authors: Gajski Goran , Milković Đurđica , Ranogajec‐Komor Mária , Miljanić Saveta , Garaj‐Vrhovac Vera 
Published: November 2010

ABSTRACTLow‐dose ionizing radiation used for medical purposes is one of the definite risk factors for cancer development, and children exposed to ionizing radiation are at a relatively greater cancer risk as they have more rapidly dividing cells than adults and have longer life expectancy. Since cytokinesis‐block micronucleus cytome (CBMN Cyt) assay has become one of the standard endpoints for radiation biological dosimetry, we used that assay in the present work for the assessment of different types of chromosomal damage in children exposed to diagnostic X‐ray procedures. Twenty children all with pulmonary diseases between the ages of 4 and 14 years (11.30 ± 2.74) were evaluated. Absorbed dose measurements were conducted for posterior–anterior projection on the forehead, thyroid gland, gonads, chest and back. Doses were measured using thermoluminescence and radiophotoluminescent dosimetry systems. It was shown that, after diagnostic X‐rays, the mean total number of CBMN Cyt assay parameters (micronucleus, nucleoplasmic bridges and nuclear buds) was significantly higher than prior to diagnostic procedure and that interindividual differences existed for each monitored child. For the nuclear division index counted prior and after examination, no significant differences were noted among mean group values. These data suggest that even low‐dose diagnostic X‐ray exposure may induce damaging effect in the somatic DNA of exposed children, indicating that immense care should be given in both minimizing and optimizing radiation exposure to diminish the radiation burden, especially in the youngest population. Copyright © 2010 John Wiley & Sons, Ltd.
THE GENDERED BURDEN OF LIBERALISATION: THE IMPACT OF INDIA'S ECONOMIC REFORMS ON ITS FEMALE AGRICULTURAL LABOUR
Authors: Garikipati Supriya , Pfaffenzeller Stephan 
Published: November 2010

AbstractIndia has experienced unprecedented growth in the last two decades—a development largely attributed to economic reforms initiated in the early 1990s. India's approach to liberalisation has been commended for its gradual implementation and its sympathy for poor rural workers. Studies examining the relevance of this claim generally use national survey data, which are seriously limited. So far little effort has been focussed on understanding what reforms actually mean for the rural poor using primary data. In this paper, we use data from a household survey carried out in the villages of Andhra Pradesh. We ask what impact India's reforms have had on its female agricultural labour—who are arguably among its poorest. Specifically, we investigate the impact of three developments considered fundamental to India's economic transformation: a sectoral shift in favour of industry, credit market reforms and poverty alleviation strategies. We argue that despite having a beneficial impact overall, economic reforms have resulted in further marginalising rural women into badly paid and socially debasing waged work. Copyright © 2010 John Wiley & Sons, Ltd.
Surgical preparation of bone–scaffold interface is critical for bone regeneration inside tissue engineering scaffold
Authors: Roshan‐Ghias Alireza , Pioletti Dominique P. 
Published: November 2010

AbstractThe goal of this study was to investigate if the preparation of implantation site affects bone formation inside tissue engineering scaffolds. For this purpose, two different drilling techniques were used to create a hole in distal femurs of rats before the insertion of a bone scaffold: a manually driven wood drill bit and an electrically driven metal drill bit. The size and the position of the hole were identical for the two cases. The bone volume, bone mineral density, and callus formation were assessed noninvasively using micro‐CT tomography at several time points after implantation. The formation of bone and soft tissue inside scaffold were evaluated by histology. The bone structure around the holes made by the two techniques was compared ex vivo. The long‐term study of bone formation showed that when a wood drill bit was used, the bone formation is accelerated by 3 weeks compared to when a metal drill bit was used. The ex vivo studies suggest that this result is due to the drilling methods differentially affecting the structure of the bone surrounding the generated defects. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:767–772, 2011