bluuebunny/crossref_metadata_2025 huggingface dataset:
Parathyroid hormone inhibits phosphorylation of mitogen‐activated protein kinase (MAPK) ERK1/2 through inhibition of c‐Raf and activation of MKP‐1 in osteoblastic cells
Authors: Lai Lick Pui , Mitchell Jane
Published: April 2009

Parathyroid hormone (PTH) regulation of mitogen‐activated protein kinases (MAPK) ERK1/2 contributes to PTH regulation of osteoblast growth and apoptosis. We investigated the mechanisms by which PTH inhibits ERK1/2 activity in osteoblastic UMR 106‐01 cells. Treatment with PTH significantly inhibited phosphorylated ERK1/2 between 5 and 60 min. Transient transfection of cells with a cDNA encoding MAPK phosphatase‐1 (MKP‐1) resulted in 30–40% inhibition of pERK1/2; however MKP‐1 protein levels were only significantly stimulated by PTH after 30 mins, suggesting another mechanism for the early phase of pERK1/2 inhibition. The active upstream kinase c‐Raf phosphorylation at serine 338 (ser338) was significantly inhibited by PTH treatment within 5 min and transfection of the cells with constitutively‐active c‐Raf blocked PTH inhibition of pERK1/2. Inhibition of pERK1/2 and phosphor‐c‐Raf were seen when cells were treated with PTH(1‐34) or PTH(1‐31) analogues that stimulate cAMP, but not with PTH(3‐34), PTH(7‐34) or PTH(18‐48) that do not stimulate cAMP. Stimulation of the cells with forskolin or 8BrcAMP also inhibited pERK1/2 and c‐Raf.p338. Our results suggest that rapid PTH inhibition of ERK1/2 activity is mediated by PKA dependent inhibition of c‐Raf activity and that stimulation of MKP‐1 may contribute to maintaining pERK1/2 inhibition over prolonged time. Copyright © 2009 John Wiley & Sons, Ltd.
Cloning and Sequencing of the Biosynthetic Gene Cluster for Saquayamycin Z and Galtamycin B and the Elucidation of the Assembly of Their Saccharide Chains
Authors: Erb Annette , Luzhetskyy Andriy , Hardter Uwe , Bechthold Andreas
Published: April 2009

Sweet ways: We have investigated the glycosyltransferase genes of the saquayamycin Z (shown) and galtamycin B biosynthetic gene cluster from Micromonospora sp. Tü6368. The results unambiguously show that both compounds are derived from the same cluster. Furthermore, the function of five glycosyltransferases was elucidated, and the results have shed light on the assembly of the sugar chains.

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The Gram‐positive bacterium, Micromonospora sp. Tü6368 produces the angucyclic antibiotic saquayamycin Z and the tetracenequinone galtamycin B. The structural similarity of both compounds suggests a common biosynthetic pathway. The entire biosynthetic gene cluster (saq gene cluster) was cloned and characterized. DNA sequence analysis of a 36.7 kb region revealed the presence of 31 genes that are probably involved in saquayamycin Z and galtamycin B formation. Heterologous expression experiments and targeted gene inactivations were carried out to specifically manipulate the saquayamycin Z and galtamycin B pathways; this demonstrated unambiguously that both compounds are derived from the same cluster. The inactivation of glycosyltransferase genes led to the production of novel saquayamycin and galtamycin derivatives, provided information on the assembly of the sugar chains, and showed that tetracenequinones are formed from angucyclines.
Fragment Formal Concept Analysis Accurately Classifies Compounds with Closely Related Biological Activities
Authors: Krüger Felix , Lounkine Eugen , Bajorath Jürgen
Published: April 2009

Fragment formal concept analysis (FragFCA) for compound classification: Signature fragment combinations for compound classes with closely related biological activity were identified using FragFCA. These combinations are used to accurately classify active test compounds on the basis of fragment mapping. FragFCA can extract class‐specific fragment combinations from compounds active against different target families that have signature character and practical utility in compound classification and database searching.

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Formal concept analysis (FCA), originally developed in information science, has been adapted to identify relationships between fragments of compounds and their biological activity. Here applications of the FragFCA approach with practical utility for medicinal chemistry are explored. Hierarchically derived fragment populations of 24 classes of compounds active against eight target families were subjected to FragFCA analysis, and fragment combinations were identified that distinguished compounds with closely related biological activity from each other. Mapping of signature fragment combinations was carried out to classify active compounds for different target families with high accuracy. The results indicate that compound‐class‐specific structural information and selectivity determinants are predominantly encoded by fragment combinations, rather than individual fragments. Furthermore, class‐specific fragment combinations were successfully applied in similarity searching. The results demonstrate that FragFCA is capable of identifying fragment combinations that differentiate between compound sets with closely related biological activity and that can be used to predict structure–activity relationships.
Relationship between caffeine intake and plasma sex hormone concentrations in premenopausal and postmenopausal women
Authors: Kotsopoulos Joanne , Eliassen A. Heather , Missmer Stacey A. , Hankinson Susan E. , Tworoger Shelley S.
Published: April 2009

BACKGROUND:

Circulating estrogens and androgens are important factors in the development of various female cancers. Caffeine intake may decrease risk of breast and ovarian cancer, although the data are not entirely consistent. Whether or not caffeine affects cancer risk by altering sex hormone levels is currently unknown.

METHODS:

We examined the relationship of caffeine, coffee, decaffeinated coffee, and tea with plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone–binding globulin (SHBG) in 524 premenopausal and 713 postmenopausal women from the Nurses' Health Study (NHS) and NHSII.

RESULTS:

In premenopausal women, caffeine intake was inversely associated with luteal total and free estradiol, and positively associated with luteal progesterone levels (P‐trend = .02, .01, .03, respectively). Coffee intake was significantly associated with lower luteal total and free estradiol levels, but not luteal progesterone levels (P‐trend = .007, .004, .20, respectively). Among the postmenopausal women, there was a positive association between caffeine and coffee intake and SHBG levels (P‐trend = .03 and .06, respectively). No significant associations were detected with the other hormones.

CONCLUSIONS:

Data from this cross‐sectional study suggest that caffeine may alter circulating levels of luteal estrogens and SHBG, representing possible mechanisms by which coffee or caffeine may be associated with pre‐ and postmenopausal malignancies, respectively. Future studies evaluating how caffeine‐mediated alterations in sex hormones and binding protein levels affect the risk of female cancers are warranted. Cancer 2009. © 2009 American Cancer Society.
Remarks on some properties of conic yield restrictions in limit analysis
Authors: Makrodimopoulos Athanasios
Published: April 2009

A major difficulty when applying the kinematic theorem in limit analysis is the derivation of expressions of the dissipation functions and the set of plastically admissible strains. At present, no standard methodology exists. Here, it is shown that they can be readily obtained, provided that the yield restriction can be rewritten as an intersection of cones, and that the expression defining the dual cones is available. This is always possible for the case of self‐dual cones and some other classes, and covers many of the well‐known criteria. Therefore, a difficult obstacle with respect to the use of the kinematic theorem in conjunction with any numerical method can be overcome. The methodology is illustrated by giving the expressions of the dissipation functions for various conic yield restrictions. A special emphasis is given on upper bound finite element limit analysis. Taking advantage of duality in conic programming, we can obtain the dual problem, where knowledge of the dual cone is not necessary. Therefore, this formulation is feasible for any cone. Finally, it is interesting that the form of the dual problem, for varying yield strength within the finite element, differs from that presented in other papers. Copyright © 2009 John Wiley & Sons, Ltd.
Gibt es durch die harmonisierten europäischen Prüfnormen Auswirkungen auf das Brandverhalten von Mauerwerk?
Authors: Hahn Christiane , Nause Peter
Published: April 2009

Die deutsche Mauerwerksindustrie ist in Europa führend. Nicht nur in der Vielfältigkeit der Mauerwerksarten, sondern insbesondere auch hinsichtlich der Brandschutznachweise. Aufgrund des hohen deutschen Sicherheitsniveaus wurde jede Neuerung im Mauerwerksbau zeitnah brandschutztechnisch nach DIN 4102 nachgewiesen. Da in Deutschland im Brandschutz hinsichtlich der Prüfverfahren eine umfangreiche Erfahrung vorlag, wurde in den 1990‐er Jahren intensiv an der Entwicklung der europäischen Prüfnormen mitgearbeitet. Bei der Erarbeitung der europäischen Extrapolationsregeln zu den Prüfnormen im Bereich Mauerwerk ist die Industrie aktiv eingebunden. Aufgrund der Privatisierung der Prüfanstalten ist dies in vielen anderen Bereichen nicht der Fall. Im Gegensatz zu Deutschland wird in anderen europäischen Ländern, insbesondere Großbritannien, die Mitarbeit in europäischen Normungsgremien als nationales und damit politisches Interesse eingestuft und daher staatlich finanziert. Für Mauerwerk kann zusammenfassend festgestellt werden, dass die bereits in den 90‐er Jahren harmonisierten europäischen Prüfnormen den deutschen Normenstandard sowie das deutsche Sicherheitsniveau widerspiegeln. Dadurch lässt sich die eingangs gestellte Frage, ob die harmonisierten europäischen Prüfnormen Auswirkungen auf das Brandverhalten von Mauerwerk haben, kurz mit nein beantworten. Lediglich der sich aus der europäischen Normung ergebende Formalismus im bauaufsichtlichen Verfahren hat massive Auswirkung auf den Aufwand beim Einsatz von Mauerwerk. Insofern sind die nachfolgenden Informationen und Einblicke für den Anwender sinnvoll und notwendig.
Pericellular matrix of decidua‐derived mesenchymal cells: A potent human‐derived substrate for the maintenance culture of human ES cells
Authors: Nagase Tomoko , Ueno Morio , Matsumura Michiru , Muguruma Keiko , Ohgushi Masatoshi , Kondo Naomi , Kanematsu Daisuke , Kanemura Yonehiro , Sasai Yoshiki
Published: April 2009

In routine culture, human embryonic stem (hES) cells are maintained on either feeder cells or special culture substrates such as Matrigel. However, to expand hES cells for clinical applications, it is desirable to minimize animal‐derived materials in the culture for safety reasons. In this report, we show that the pericellular matrix prepared from human decidua‐derived mesenchymal cells (PCM‐DM) is a potent substrate material that supports the growth and pluripotency of hES cells as efficiently as Matrigel does. This supporting activity of PCM‐DM is stable and can be preserved for several months in the refrigerator. PCM‐DM‐based culture is compatible with non‐conditioned commercial defined medium, and with the maintenance of dissociated hES cells in the presence of ROCK inhibitor. Since decidual mesenchymal cells can be prepared and expanded in a large quantity, PCM‐DM is a practical human‐derived substitute for the animal‐derived substrates for use in clinical‐grade culture of hES cells. Developmental Dynamics 238:1118–1130, 2009. © 2009 Wiley‐Liss, Inc.
Fgf signaling components are associated with muscles and tendons during limb development
Authors: Eloy‐Trinquet Sophie , Wang Hui , Edom‐Vovard Fréderic , Duprez Delphine
Published: April 2009

Muscle‐tendon interactions are important for the establishment of a functional musculoskeletal system. Fgf4 and Fgf8 are expressed in muscle and tendon boundary regions during limb development, suggesting a potential role for Fgf signaling pathway in muscle and tendon interactions. We have examined the expression of Fgf syn‐expression group components during muscle and tendon formation of vertebrate limb development. We observed that the transcriptional effector of Fgf signaling, Pea3, and the modulators of Fgf signal, Sprouty1 and 2, were expressed in muscles and tendons and that their expression was enhanced at the myotendinous junctions in chick and mouse limbs. Analysis of Pea3 and Sprouty gene expression in muscleless limbs of Pax3 mutant mice indicated a major expression in muscles but also revealed that the Pea3 and Sprouty expression in tendons depended on muscles. Finally, our data showed that Fgf4 positively regulated Pea3, Sprouty1, and 2 expression in chick limb mesenchyme. Developmental Dynamics 238:1195–1206, 2009. © 2009 Wiley‐Liss, Inc.
Increased Hox activity mimics the teratogenic effects of excess retinoic acid signaling
Authors: Waxman Joshua S. , Yelon Deborah
Published: April 2009

Excess retinoic acid (RA) signaling can be teratogenic and result in cardiac birth defects, but the cellular and molecular origins of these defects are not well understood. Excessive RA signaling can completely eliminate heart formation in the zebrafish embryo. However, atrial and ventricular cells are differentially sensitive to more modest increases in RA signaling. Increased Hox activity, downstream of RA signaling, causes phenotypes similar to those resulting from excess RA. These results suggest that Hox activity mediates the differential effects of ectopic RA on atrial and ventricular cardiomyocytes and may underlie the teratogenic effects of RA on the heart. Developmental Dynamics 238:1207–1213, 2009. © 2009 Wiley‐Liss, Inc.
Tissue selective expression of conditionally‐regulated ROCK by gene targeting to a defined locus
Authors: Samuel Michael S. , Munro June , Bryson Sheila , Forrow Stephen , Stevenson David , Olson Michael F.
Published: April 2009

ROCK kinases regulate actin‐myosin structures downstream of Rho GTPases. We generated mice expressing 4‐hydroxytamoxifen (4HT)‐regulated human ROCK II (ROCKII:mER™) under the transcriptional control of the cytokeratin14 (K14) promoter. The K14‐ROCKII:mER™ minigene was recombineered into a novel cloning vector containing the promoter and first exon of the human HPRT gene, and second and third exons of the mouse Hprt gene. Homologous recombination into the Hprt locus, which is deleted for the promoter and first two exons in HM1 embryonic stem cells, reconstitutes a functional Hprt gene, allowing for growth in HAT (hypoxanthine‐aminopterin‐thymidine) medium. K14‐promoter‐driven ROCKII:mER™ expression was restricted to a superficial cell layer in embryoid bodies, with increased ROCK substrate phosphorylation induced by 4HT. ROCKII:mER™‐expressing primary murine keratinocytes responded to 4HT with increased substrate phosphorylation and cytoskeleton rearrangements, indicating that ROCKII:mER™ activity is regulated by 4HT in the target tissue. K14‐ROCKII:mER™ mice will be valuable for examining the role of ROCK in skin development and cancer. genesis 47:440–446, 2009. © 2009 Wiley‐Liss, Inc.
Prostaglandin E2 enhances Th17 responses via modulation of IL‐17 and IFN‐γ production by memory CD4+ T cells
Authors: Napolitani Giorgio , Acosta‐Rodriguez Eva V. , Lanzavecchia Antonio , Sallusto Federica
Published: April 2009

The contribution of Th1 and Th17 cells in chronic inflammatory conditions leading to autoimmunity remains highly controversial. In inflamed tissues, production of prostaglandins by COX‐2 has been proposed to favor Th17 responses indirectly by increasing IL‐23 and blocking IL‐12 release from APC. We report here that prostaglandin E2 (PGE2) can directly modulate cytokine production by human memory CD4+ T cells. TCR triggering in the presence of PGE2 increased IL‐17 and reduced IFN‐γ production by freshly isolated memory T cells or T‐cell clones. PGE2 triggered the EP2 and EP4 receptors expressed on T cells leading to a rapid increase of retinoic‐acid‐related orphan receptor‐γt (ROR‐γt) and decrease of T‐cell‐specific T‐box transcription factor 21 (T‐bet) mRNA. Moreover, PGE2 promoted the selective enrichment of IL‐17‐producing cells by differentially modulating the proliferation of memory T‐cell subsets in vitro. Taken together our results indicate that T‐cell effector function is a direct target for PGE2 modulation and suggest a novel mechanism by which inhibitors of prostaglandin synthesis, such as COX‐2 inhibitors, exert their anti‐inflammatory effect.
Interleukin‐10‐secreting T cells define a suppressive subset within the HIV‐1‐specific T‐cell population
Authors: Torheim Eirik A. , Ndhlovu Lishomwa C. , Pettersen Frank O. , Larsen Trine‐Lise , Jha Aashish R. , Torgersen Knut M. , Kvale Dag , Nixon Douglas F. , Taskén Kjetil , Aandahl Einar M.
Published: April 2009

Recent studies have indicated that Treg contribute to the HIV type 1 (HIV‐1)‐related immune pathogenesis. However, it is not clear whether T cells with suppressive properties reside within the HIV‐1‐specific T‐cell population. Here, PBMC from HIV‐1‐infected individuals were stimulated with a 15‐mer Gag peptide pool, and HIV‐1‐specific T cells were enriched by virtue of their secretion of IL‐10 or IFN‐γ using immunomagnetic cell‐sorting. Neither the IL‐10‐secreting cells nor the IFN‐γ‐secreting cells expressed the Treg marker FOXP3, yet the IL‐10‐secreting cells potently suppressed anti‐CD3/CD28‐induced CD4+ as well as CD8+ T‐cell proliferative responses. As shown by intracellular cytokine staining, IL‐10‐ and IFN‐γ‐producing T cells represent distinct subsets of the HIV‐1‐specific T cells. Our data collectively suggest that functionally defined HIV‐1‐specific T‐cell subsets harbor potent immunoregulatory properties that may contribute to HIV‐1‐associated T‐cell dysfunction.
γδ T cells in EAE: Early trafficking events and cytokine requirements
Authors: Wohler Jillian E. , Smith Sherry S. , Zinn Kurt R. , Bullard Dan C. , Barnum Scott R.
Published: April 2009

We have previously shown that γδ T cells traffic to the CNS during EAE with concurrently increased expression of β2‐integrins and production of IFN‐γ and TNF‐α. To extend these studies, we transferred bioluminescent γδ T cells to WT mice and followed their movement through the acute stages of disease. We found that γδ T cells rapidly migrated to the site of myelin oligodendrocyte glycoprotein peptide injection and underwent massive expansion. Within 6 days after EAE induction, bioluminescent γδ T cells were found in the spinal cord and brain, peaking in number between days 10 and 12 and then rapidly declining by day 15. Reconstitution of γδ T cell−/− mice with γδ T cells derived from β2‐integrin‐deficient mice (CD11a, ‐b or ‐c) demonstrated that γδ T‐cell trafficking to the CNS during EAE is independent of this family of adhesion molecules. We also examined the role of γδ T‐cell‐produced IFN‐γ and TNF‐α in EAE and found that production of both cytokines by γδ T cells was required for full development of EAE. These results indicate that γδ T cells are critical for the development of EAE and suggest a therapeutic target in demyelinating disease.
Synthesis and Characterization of Single‐Crystalline Lanthanum Fluoride with a Ring‐Like Nanostructure
Authors: Tian Yang , Wen Jing , Liu Bin , Sui Ning , Jin Qionghua , Jiao Xiuling
Published: April 2009

LaF3 ring‐like nanostructures with a diameter of less than 2 μm have been fabricated by a facile, effective, and environmentally friendly molten salt synthesis route in which NaNO3 and KNO3 (2:1 molar ratio) act as reaction media and the rare‐earth nitrate and NaF as precursor. X‐ray diffraction, TEM, HR‐TEM, energy dispersive X‐ray spectroscopy, and photoluminescence spectroscopy are all used to characterize the as‐prepared samples. Experiments peformed with different reaction times indicate that a central‐etching of the plates from the inner part towards the edge during nanocrystal growth plays a key role in the formation of LaF3 nanorings since no other templates/surfactants are present in our system. Additionally, the luminescence properties of LaF3 nanorings doped with Eu3+ cation have been investigated andcompared with those of bulk materials and nanoparticles with a size of approximately 50 nm. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
31Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depression
Authors: Forester Brent P. , Harper David G. , Jensen J. Eric , Ravichandran Caitlin , Jordan Brittany , Renshaw Perry F. , Cohen Bruce M.
Published: April 2009

Introduction

We investigated tissue specific differences in markers of energy metabolism, including high energy phosphate compounds (beta and total NTP, PCr) and pH, in older adults with depression compared with healthy controls, before and after a 12‐week treatment trial of sertraline.

Methods

Thirteen older adults, age ≥55, with Major Depressive Disorder (HAMD17 score of ≥18) were recruited along with ten age‐matched controls. The depression subjects had a pre‐ and post‐treatment 4T 31P‐MRS scan using a three‐dimensional chemical shift imaging sequence. The extracted brain images were segmented into white matter (WM), gray matter (GM) and CSF. A linear mixed effects model analyzed the effects of pre‐treatment and post‐treatment depression on phosphorus metabolite concentration estimates (including calculated pH and Mg++).

Results

Total tissue beta‐NTP (−8%, t(18.66) = 3.50; p = 0.0024) and total tissue total NTP (−6%, t(17.41) = 2.68; p = 0.0156) were lower in subjects with geriatric depression compared with healthy controls. Total tissue levels of total‐NTP changed significantly with treatment (−2%, t(14.84) = −2.47; p = 0.0259). Total NTP was reduced in the WM, but not the GM, in the pre‐treatment depression group (t(51.65) = 4.02; p = 0.0002). Intracellular pH was higher in the GM of subjects with pre‐treatment depression (t(1133.84) = −2.10; p = 0.0353) and decreased to approximate control levels after treatment (t(648.86) = −2.53; p = 0.0115).

Discussion

These findings demonstrate bioenergetic changes including tissue specific differences in 31P‐MRS metabolites in geriatric depression. Decreased white matter total NTP may reflect alterations in white matter function. Copyright © 2009 John Wiley & Sons, Ltd.
Dissociation between phase‐locked and nonphase‐locked alpha oscillations in a working memory task
Authors: Freunberger Roman , Fellinger Robert , Sauseng Paul , Gruber Walter , Klimesch Wolfgang
Published: April 2009

The functions of human alpha oscillations (∼10 Hz) were related to cognitive processes such as memory and top‐down control. Recent models suggest that alpha phase serves as a mechanism especially relevant for the timing of neural activity, whereas alpha amplitude is important for the inhibition of task‐irrelevant brain areas. This study investigates directly the influence of top‐down modulation on phase‐locked and nonphase‐locked alpha rhythms. We conducted an EEG experiment where subjects performed a working memory task. In the encoding phase of the task subjects had to learn presented pictures of nonliving objects that could later be asked to be retrieved. We varied the top‐down modulation by including cues indicating either to remember or to forget (not to remember) the next following item. Spectral analyses showed that nonremember cues elicited pronounced alpha amplitude increase compared to remember cues. Furthermore, phase‐locking in low frequencies, especially in the alpha range (7–12 Hz), was stronger for remember as opposed to not‐to‐remember items. In conclusion, we propose that alpha amplitude reflects top‐down modulated inhibition and that alpha phase is important for the exact timing of neural activity and can be related to binding processes. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Contingency learning in human fear conditioning involves the ventral striatum
Authors: Klucken Tim , Tabbert Katharina , Schweckendiek Jan , Merz Christian Josef , Kagerer Sabine , Vaitl Dieter , Stark Rudolf
Published: April 2009

The ability to detect and learn contingencies between fearful stimuli and their predictive cues is an important capacity to cope with the environment. Contingency awareness refers to the ability to verbalize the relationships between conditioned and unconditioned stimuli. Although there is a heated debate about the influence of contingency awareness on conditioned fear responses, neural correlates behind the formation process of contingency awareness have gained only little attention in human fear conditioning. Recent animal studies indicate that the ventral striatum (VS) could be involved in this process, but in human studies the VS is mostly associated with positive emotions. To examine this question, we reanalyzed four recently published classical fear conditioning studies (n = 117) with respect to the VS at three distinct levels of contingency awareness: subjects, who did not learn the contingencies (unaware), subjects, who learned the contingencies during the experiment (learned aware) and subjects, who were informed about the contingencies in advance (instructed aware). The results showed significantly increased activations in the left and right VS in learned aware compared to unaware subjects. Interestingly, this activation pattern was only found in learned but not in instructed aware subjects. We assume that the VS is not involved when contingency awareness does not develop during conditioning or when contingency awareness is unambiguously induced already prior to conditioning. VS involvement seems to be important for the transition from a contingency unaware to a contingency aware state. Implications for fear conditioning models as well as for the contingency awareness debate are discussed. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Modulation of preparatory volitional motor cortical activity by paired associative transcranial magnetic stimulation
Authors: Lu Ming‐Kuei , Bliem Barbara , Jung Patrick , Arai Noritoshi , Tsai Chon‐Haw , Ziemann Ulf
Published: April 2009

Paired associative transcranial magnetic stimulation (PAS) has been shown to induce long‐term potentiation (LTP)‐like or long‐term depression (LTD)‐like change in excitability of human primary motor cortex (M1), as probed by motor evoked potential (MEP) amplitude. In contrast, little is known about PAS effects on volitional motor cortical activity. In 10 healthy subjects, movement related cortical potentials (MRCP) were recorded to index volitional motor cortical activity during preparation of simple thumb abduction (prime mover: abductor pollicis brevis, APB) or wrist extension movements (prime mover: extensor carpi radialis, ECR). PASLTP increased, PASLTD decreased, and PAScontrol did not change MEPAPB, while MEPECR, not targeted by PAS, remained unchanged in all PAS conditions. PASLTP decreased MRCP negativity during the late Bereitschaftspotential (−500 to 0 ms before movement onset), only in the APB task, and predominantly over central scalp electrodes contralateral to the thumb movements. This effect correlated negatively with the PASLTP induced increase in MEPAPB. PASLTD and PAScontrol did not affect MRCP amplitude. Findings indicate a specific interference of PAS with preparatory volitional motor cortical activity, suggestive of a net result caused by increased M1 excitability and disrupted effective connectivity between premotor areas and M1. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Highly efficient and chemoselective acetalization of carbonyl compounds catalyzed by new and reusable zirconyl triflate, ZrO(OTf)2
Authors: Moghadam Majid , Mohammadpoor‐Baltork Iraj , Tangestaninejad Shahram , Mirkhani Valiollah , Yazdani Parvin , Ghorjipoor Saeedeh
Published: April 2009

Various types of aromatic aldehydes were efficiently converted to their corresponding 1,3‐dioxanes and 1,3‐dioxolane with 1,3‐propanediol and ethylene glycol, respectively, in the presence of catalytic amount of ZrO(OTf)2 in acetonitrile at room temperature. The catalyst can be reused several times without loss of its catalytic activity. Very short reaction times, selective acetalization of aromatic aldehydes in the presence of aliphatic aldehydes and ketones, very mild reaction conditions, reusability of the catalyst, and easy workup are noteworthy advantages of this method. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:131–135, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20523
Convenient synthesis of symmetrical diketosulfides from enolizable ketones using [hydroxy(tosyloxy)iodo]benzene and na2S ⋅ 9H2O
Authors: Karade Nandkishor N. , Tiwari Girdharilal B. , Gampawar Sumit V. , Shinde Sandeep V.
Published: April 2009

An efficient method for the preparation of symmetrical diketosulfides of the type ArCOCH2SCH2COAr has been developed from the reaction of [hydroxy(tosyloxy)iodo]benzene with various acetophenones, followed by treatment with Na2S ⋅ 9H2O. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:172–176, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20524
Crystal and molecular structures of some six‐coordinate tin(IV) halogeno complexes with phosphorus‐containing ligands
Authors: Batsanov Andrei S. , Deng Robert M. K. , Dillon Keith B. , Goeta Andrés E. , Howard Judith A. K. , Meldrum James , Monks Philippa K. , Puschmann Horst , Shepherd Helena J.
Published: April 2009

Six new complexes of tin(IV) halides with phosphorus‐containing ligands have been fully characterized by single‐crystal X‐ray diffraction at low temperature. Three of the compounds, derived from the diphosphanes bis‐(diphenylphosphino)methane or bis‐(dicyclohexylphosphino)methane, have a novel zwitterionic structure, with five Cl ligands and one unidentate phosphorus‐containing ligand on tin, together with a proton on the second phosphorus atom of the potentially bidentate ligand; these are Cl5Sn−P(Ph2)CH2PPh2H+ (1), Cl5Sn−OP(Ph2)CH2‐PPh2H+ (2), and Cl5Sn−OP(cy2)CH2Pcy2H+ (3). The other three complexes have a bidentate donor attached to the SnX4 moiety; they comprise Cl4SnOP(Ph2)‐(CH2)2PPh2O (4), a derivative of bis‐(diphenylphosphino)ethane dioxide, I4SnOP(Ph2)CH2PPh2O (5), a similar derivative of bis‐(diphenylphosphino)‐methane dioxide, and the very unusual Br4SnAs‐(Ph2)(CH2)2PPh2O (6), with coordination to tin by As and O. Since the starting material for the last compound was Ph2As(CH2)2PPh2, this result illustrates well the more facile oxidation of P(III) than As(III). © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:136–143, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20525
Microwave‐assisted synthesis of some 2,4‐thiazolidinedione derivatives
Authors: Mahalle Shital , Ligampalle Dinesh , Mane Ramrao
Published: April 2009

The condensation of 5‐[4′‐(2″‐halo‐ethoxy)benzylidenyl]‐2,4‐thiazolidinediones 2 when separately carried with different 2‐amino thiazoles 3 and different sulphanilamides 4 in DMF, using potassium hydroxide in the presence of a catalytic amount of a phase transfer catalyst, gave new 5‐[4′‐(4″‐aryl‐thiazol‐2″‐yl‐aminoethoxy)‐3′/5′‐substituted benzylidenyl]‐2,4‐thiazolidinediones 5 and 5‐[4′‐(2″/4″‐sulphonamidophenyl aminoethoxy)‐3′/5′‐substituted benzylidenyl]‐2,4‐thiazolidinediones 6 derivatives in good yields, respectively. The structures of all new compounds were established from analytical and spectral data. All the reaction sequences were carried under microwave irradiation, as an efficient tool. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:151–156, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20528
Shoulder morbidity after pectoralis major flap reconstruction for head and neck cancer
Authors: Merve Ashirwad , Mitra Indu , Swindell Ric , Homer Jarrod J.
Published: April 2009

Background.

The effect of pectoralis major flap (PMF) harvest on shoulder function, allowing for the effects of neck dissection, has not previously been objectively measured.

Methods.

Twenty‐two patients who underwent PMF reconstruction were studied. The control group comprised 35 patients with neck dissection (without PMF). Neck dissections in both groups were classified into 3 grades; grade 1: no neck dissection/selective neck dissection; grade 2: modified radical neck dissection; grade 3: radical neck dissection/extended radical neck dissection. Objective shoulder assessments were carried out using Constant score.

Results.

Constant score deteriorated with grade of neck dissection (p < .005). The median Constant score for PMF group and neck dissection only group were 82 and 90, respectively (p = .40). Subgroup analysis within neck dissection grade did not show any significant difference, but the effect of PMF was noted to be greatest in grade 2 patients (p = .064).

Conclusions.

There is minimal or low shoulder morbidity, additional to neck dissection, caused by PMF reconstruction in head and neck surgery. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Immunohistochemical studies on early stage of hepatic damage induced by subacute inhalation of toluene vapor in rats
Authors: Gotohda Takako , Nishimura Akiyoshi , Morita Kyoji
Published: April 2009

Toluene is one of the most widely used organic solvents and is commonly recognized as a noxious substance inducing chronically toxic damage to neural, hepatic and renal functions in the workers engaged in printing and painting. Although hepatic cells are generally considered to be vulnerable and susceptible to various organic solvents, particularly chloroform and other halogenated hydrocarbons, the hepatotoxic effects of aromatic hydrocarbons including toluene have not yet been sufficiently characterized. In particular, it still seems unclear whether toluene itself can directly act on hepatic cells, inducing toxic damage to their metabolism and function. To assess the toxic effect of toluene inhalation on rat liver, immunohistochemical analyses of the histological markers for hepatic damage were carried out in animals exposed subacutely to toluene vapor. The immunoreactivities of heat shock proteins (HSP‐70 and HSP‐90) and cytochrome P4502E1 (CYP2E1) in the liver were analyzed to assess the hepatotoxic damage induced by toluene inhalation, and the expression of these histological markers was shown to be substantially enhanced by the subacute exposure to toluene vapor. Toluene inhalation was furthermore shown to enhance the immunoreactivities of α‐smooth muscle actin (α‐SMA), collagen, glucocorticoid receptors (GR) and leptin receptors (Ob‐R) in the liver. Additional studies using human hepatoma HepG2 cells showed that toluene can directly induce toxic damage to cells. These findings suggest that toluene inhalation may primarily induce hepatic damage, which may be secondarily exacerbated by the activation of systemic processes possibly connected with glucocorticoids and leptin. Copyright © 2009 John Wiley & Sons, Ltd.
Stringent testing identifies highly potent and escape‐proof anti‐HIV short hairpin RNAs
Authors: von Eije Karin J. , ter Brake Olivier , Berkhout Ben
Published: April 2009

Background

RNA interference (RNAi) is a cellular mechanism that can be induced by small interfering RNAs to mediate sequence‐specific gene silencing by cleavage of the targeted mRNA. RNAi can be used as an antiviral approach to silence the human immunodeficiency virus type 1 (HIV‐1) through stable expression of short hairpin RNAs (shRNAs). Previously, we used a co‐transfection assay in which shRNA constructs were transfected with an HIV‐1 molecular clone to identify 20 shRNA inhibitors that target highly conserved HIV‐1 sequences.

Methods

In the present study, we selected the most potent shRNAs to formulate a combinatorial shRNA therapy and determine the best and easiest method for antiviral shRNA selection. We performed transient inhibition assays with either a luciferase reporter or HIV‐1 molecular clone and also infected shRNA‐expressing T cell lines with HIV‐1 and monitored virus replication. The latter assay allows detection of viral escape. In addition, we also tested shRNA‐expressing T cells upon challenge with increasing dosages of HIV‐1, and measured the dose required to result in massive virus‐induced syncytia formation in this 2‐week assay.

Results

Extended culturing selected three highly effective shRNAs that do not allow viral replication for more than 100 days. This difference in potency was not observed in the transient co‐transfection assays. The use of increased dosages of HIV‐1 selected the same highly potent shRNAs as the laborious and extended escape study.

Conclusions

These highly potent shRNAs could be used for a clinical vector and the comparison of the developed assays might help other researchers in their search for antiviral shRNAs. Copyright © 2009 John Wiley & Sons, Ltd.
The preparation and nuclear magnetic resonance study of 5‐ and 7‐nitrocoumarans
Authors: Raulins N. Rebecca , Kruggel William G. , Titus Donald D. , Van Landuyt Dennis C.
Published: April 2009

Mononitration of coumaran has been achieved by the use of acetyl chloride and silver nitrate in acetonitrile solution. Nmr decoupling experiments have served to establish the structures of the two products as the 5‐ and 7‐nitrocoumarans. Attempted nitration with nitronium tetrafluoroborate resulted in extensive ring opening.
Biselenienyl series. II. Synthesis and resolution of 2,2′‐dinitro‐3,3′‐biselenienyl‐4,4′‐dicarboxylic acid
Authors: Dell'Erba Carlo , Spinelli Domenico , Garbarino Giacomo , Leandri Giuseppe
Published: April 2009

2,2′‐Dinitro‐3,3′‐biselenienyl‐4,4′‐dicarboxylic acid (VI), the first recorded compound of the 3,3′‐biselenienyl series, has been prepared and resolved into its optical antipodes by fractional crystallization of its brucine salt.

On the basis of the quasi‐racemate method of Fredga and the O.R.D. spectra, to the dextrorotatory acid is assigned the R configuration.
Ring closure reactions with nitriles. II. Formation of pyrrolo[1,2‐a] quinazolines and thiazolo[3,2‐a] quinazolines
Authors: Bell Stanley C. , Wei Peter H. L.
Published: April 2009

2‐Quinazolinepropionic acids have been obtained from the reactions of potassium cyanide with o‐carboxy‐ or o‐acyl‐3‐chloropropionanilides. Some of these compounds have been cyclized to pyrrolo [1,2‐a] quinazolines. The reaction of an o‐carbethoxy‐2‐chloroacetanilide with potassium thiocyanate formed a 2‐quinazolinylthioacetic acid, which was cyclized to a thiazolo‐[3,2‐a]quinazoline. A mechanism is presented for the formation of these compounds.
Oxazolidine formation in the attempted eschweiler‐clarke reductive methylation of cis‐3‐aminobicyclo[2.2.2] octan‐2‐ol
Authors: Nelson Wendel L.
Published: April 2009

Evidence is presented confirming the formation of N‐methyl‐cis‐bicyclo[2.2.2]octyl[2,3‐d]‐oxazolidine as the product of Eschweiler‐Clarke reductive alkylation of cis‐3‐amino‐bicyclo‐[2.2.2]octan‐2‐ol.
Studies on heteroaromaticity. XV . the 1,3‐dipolar cycloaddition reaction of 5‐nitro‐2‐furyldiazomethane
Authors: Sasaki Tadashi , Eguchi Shoji , Kojima Atsuyuki
Published: April 2009

The 1,3‐dipolar cycloaddition reaction of 5‐nitro‐2‐furyldiazomethane (1) with acrylonitrile, acrylamide, methyl acrylate, diethyl fumarate, methyl methacrylate and methyl cinnamate afforded the corresponding 3‐substituted pyrazolines. (2a‐f). Similarly the pyrazoles (3b‐d) were prepared by addition of 1 to acetylenic compounds such as diethyl acetylenedicarboxylate, methyl phenylpropiolate and cyanoacetylene. Reaction of 1 with fumaronitrile and ω‐nitro‐styrene gave also the corresponding pyrazoles (3a and 3e) instead of the pyrazolines. 3‐(5′‐Nitro‐2′‐furyl)‐4‐phenyl‐5‐carbomethoxypyrazoline (2f) was oxidized with lead tetraacetate to the corresponding pyrazole (3f), which was different from 3c, an addition product of 1 with methyl phenylpropiolate. 3‐(5′‐Nitro‐2′‐furyl)‐5‐carbamidopyrazoline (2b) was pyrolyzed to the corresponding cyclopropane derivative 4 in low yield.
Diazonia hexacyclic aromatic systems from bis(bromomethyl)naphthalenes
Authors: Bradsher C. K. , Sherer J. P.
Published: April 2009

Starting with the appropriate bis(bromomethyl)naphthalenes, 14a,16a‐diazoniaanthra[1,2‐a]‐anthracene salts (6), and the 4a,12a‐ (13, 14) 4a,8a‐(15) and 8a,16a‐diazoniadibenzo[b,k]‐chrysene (16) salts have been prepared for the first time.
Further heterocyclic analogs of polyaryls
Authors: Buu‐Hoi N. P. , Delcey M. , Jacquignon P. , P'erin F.
Published: April 2009

A series of indoles, indolizines, imidazo[1,2‐a]pyridines, and quinolines, all of them heterocyclic analogs of polyaryls, have been prepared from diacetyl derivatives of aromatic hydrocarbons.
Etude en spectrométrie de masse. III. Phénothiazines à chaine hétérocyclique sur l'Azote en 10
Authors: Audier L. , Cambon A. , Guedj R. , Azzaro M.
Published: April 2009

Les spectres de masse‡ de sept phénothiazines homologues présentant une substitution en 2 et une chaine hétérocyclique sur l'azote en 10 ont été realisés et interprétés.

Des mécanismes plausibles, simples, permettant de rationaliser les processus de fragmentation de cette classe de composés (I‐VII) sont proposés.
Synthesis of 2,3‐disubstituted‐1,3‐oxazolidines
Authors: King George G. , Babiec John S. , Karabinos J. V.
Published: April 2009

A series of 2‐aryl‐3‐alkyl or aryl carbamoyl‐ and thiocarbamoyl‐1,3‐oxazolidines was prepared by the reactions of alkyl and aryl isocyanates and isothiocyanates with N‐(2‐hydroxyethyl)‐benzalamincs. The nuclear magnetic resonance spectra of these compounds are discussed.
The synthesis of 2‐chloro‐1‐β‐D‐ribofuranosyl‐5,6‐dimethylbenzimidazole and (certain related derivatives
Authors: Revankar Ganapathi R. , Townsend Leroy H.
Published: April 2009

The synthesis of 2‐chloro‐1‐(β‐D‐ribofuranosyl)‐5,6‐dimethylbenzimidazole (3b) has been accomplished by a condensation of 1‐trimethylsilyl‐2‐chloro‐5,6‐dimethylbenzimidazole (1) with 2,3,5‐tri‐O‐acetyl‐D‐ribofuranosyl bromide (2) followed by subsequent deacetylation. Nucleophilic displacement of the 2‐chloro group from 3b has furnished several interesting 2‐substituted‐1‐(β‐D‐ribofuranosyl)‐5,6‐dimethylbenzimidazoles. 1‐(β‐D‐Ribofuranosyl)‐5,6‐dimethylbenzimidazole (5) and 1‐(β‐D‐ribofuranosyl)‐5,6‐dimethylbenzimidazole‐2‐thione (4) were prepared from 3b. Alkylation of 4 furnished certain 2‐alkylthio‐1‐(β‐D‐ribofuranosyl)‐5,6‐dirnethylbenzimidazoles and oxidation of 4 with alkaline hydrogen peroxide produced 1‐(β‐D‐ribofuranosyl)‐5,6‐dimethylbenzimidazole‐2‐one D The assignment of anomeric configuration for all nucleosides reported is discussed.
5‐vinylisoxazole
Authors: Bertini Vincenzo , De Munno Angela , Pelosi Paolo , Pino Piero
Published: April 2009

Cycloaddition of fulminic acid to 1‐butyn‐3‐ol gave a mixture of 5‐α‐hydroxyethylisoxazole (I) and 4‐α‐hydroxyethylisoxazole (II) in the ratio 9:1. By the dehydration of 1, 5‐vinylisoxazole (III) was obtained. Compound III has also been prepared by cyclization of 4‐penten‐2‐ynal as well as its diethylacetal with hydroxylamine hydrochloride; in both instances no isomers have been obtained. Compound III spontaneously polymerizes even at room temperature yielding a polymer still containing isoxazole rings.
Crystal and molecular structure of 1‐azabicyclo[3.2.0]heptane‐1‐methyl chloride
Authors: Majeste Richard , Trefonas L. M.
Published: April 2009

The structure of the compound, 1‐azabicyclo[3.2.0]heptane‐1‐methyl chloride has been determined by a single crystal x‐ray diffraction study. The compound crystallizes in space group Cmcm with four formula weights in a unit cell of dimensions a = 8.53, b = 10.30, c = 9.27 ± .01 Å. The molecular cations fit in large holes between the chloride anions and consequently are disordered about the cation positions. The five‐membered ring portion is non‐planar and bears a strong resemplance to other five‐membered rings in bicyclic‐fused compounds. The azetidine portion of the molecule is planar. The basic fused ring structure is contrasted to that found in penicillin salts. A final value of R = 0.106 for the 305 independent reflections was obtained.
A modified synthesis of codamine under eschweiler‐clarke conditions
Authors: Kametani T. , Terui T. , Agui H. , Fukumoto K.
Published: April 2009

Codamine (1) was obtained in 88.4% yield by Eschweiler‐Clarke reaction of X with formalin and formic acid, whereas it formed in 46.2% yield in case of Mannich reaction of X with formalin and hydrochloric acid.
Preparation of 2,6‐bis(l‐menthopyrzol‐3‐yl)pyridines and their catalytic activity for asymmetric diels alder reaction
Authors: Kashima Choji , Shibata Saori , Yokoyama Hiroyo , Nishio Takehiko
Published: April 2009

3‐Aryl‐l‐menthopyrazoles 1 and 2 and related compounds were prepared from l‐menthone, and their enantioselective activities were discussed as chiral ligands. In this series of compounds, 2,6‐bis(2‐methyl‐l‐menthopyrazol‐3‐yl)pyridine (8a), which had both structural features of 3‐phenyl‐l‐menthopyrazole (1b) and C2 symmetric ligand in the molecule, should form the C2 symmetric complex in situ with Zn(OTf)2 or Ni(ClO4)2•6H2O. The subsequent complex catalyzed the Diels Alder reaction of 1‐acryloyl‐3,5‐dimethylpyrazole (11a) with cyclopentadiene (12) enantioselectively up to 75 % ee.
Ruthenium‐catalyzed formation of quinolines via reductive cyclization of nitroarenes with tris(3‐hydroxypropyl)amine in an aqueous medium
Authors: Cho Chan Sik , Lee Na Young , Choi Heung‐Jin , Kim Tae‐Jeong , Shim Sang Chul
Published: April 2009

Nitroarenes react with tris(3‐hydroxypropyl)amine in an aqueous medium (dioxane/H2O) at 180° in the presence of a catalytic amount of a ruthenium catalyst and tin(II) chloride along with isopropanol as hydrogen donor to afford the corresponding quinolines in good yields. The presence of tin(II) chloride is essential for the formation of quinolines. A reaction pathway involving initial reduction of nitroarenes to anilines, propanol group transfer from tris(3‐hydroxypropyl)amine to anilines to form 3‐anilino‐1‐propanols, N‐alkylation of anilines by 3‐anilino‐1‐propanol to form 1,3‐dianilinopropane and intramolecular heteroannulation of 1,3‐dianilinopropane is proposed for this catalytic process.
2‐Pyrazolines from 1,3 ‐ dipolar cycloaddition of diazomethane to arylsulfonylethenes
Authors: Padmavathi Venkatapuram , Sarma Mudigonda Rajagopala , Padmaja Adivireddy , Reddy Dandu Bhaskar
Published: April 2009

Novel 2‐pyrazolines were obtained by the cycloaddition of diazomethane to bis(arylsulfonylethenyl)‐sulfones (3) and 1‐arylsulfonyl‐2‐styrylsulfonylethenes (7). Dehydrogenation of 2‐pyrazolines with chloranil gave pyrazoles.
Synthesis and reactions of 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]‐quinazolin‐9‐one and 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one
Authors: Saleh Mohamed A. , Hafez Yehia A. , Abdel‐Hay Foad E. , Gad Wagdy I.
Published: April 2009

The reaction of 3‐N‐(2‐mercapto‐4‐oxo‐4H‐quinazolin‐3‐yl)acetamide (1) with hydrazine hydrate yielded 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one (2). The reaction of 2 with o‐chlorobenzaldehyde and 2‐hydroxy‐naphthaldehyde gave the corresponding 3‐arylidene amino derivatives 3 and 4, respectively. Condensation of 2 with 1‐nitroso‐2‐naphthol afforded the corresponding 3‐(2‐hydroxy‐naphthalen‐1‐yl‐diazenyl)‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one (5), which on subsequent reduction by SnCl2 and HCl gave the hydrazino derivative 6. Reaction of 2 with phenyl isothiocyanate in refluxing ethanol yielded thiourea derivative 7. Ring closure of 7 subsequently cyclized on refluxing with phencyl bromide, oxalyl dichloride and chloroacetic acid afforded the corresponding thiazolidine derivatives 8, 9 and 10, respectively. Reaction of 2‐mercapto‐3‐phenylamino‐3H‐quinazolin‐4‐one (11) with hydrazine hydrate afforded 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one (12). The reactivity 12 towards carbon disulphide, acetyl acetone and ethyl acetoacetate gave 13, 14 and 15, respectively. Condensation of 12 with isatin afforded 2‐[N‐(2‐oxo‐1,2‐dihydroindol‐3‐ylidene)hydrazino]‐3‐phenylamino‐3H‐quinazolin‐4‐one (16). 2‐(4‐Oxo‐3‐phenylamino‐3,4‐dihydroquinazolin‐2‐ylamino)isoindole‐1,3‐dione (17) was synthesized by the reaction of 12 with phthalic anhydride. All isolated products were confirmed by their ir, 1H nmr, 13C nmr and mass spectra.