bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of New 3‐Substituted‐5‐(2‐hydroxyethyl)‐3,4,5,6‐tetrahydro‐2H‐l,3,5‐thiadiazine‐2‐thione Derivatives with Potential Antimicrobial Activity
Authors: Hussein Mostafa A. , Hashem Mohammed
Published: May 2008

The purpose of this study is based upon design and synthesis of a new series of flexible molecules of 3,4,5,6‐tetrahydro‐2H‐1,3,5‐thiadiazine‐2‐thione (THTT) derivatives depending upon incorporation of 2‐aminoethanol as a part of the polar moiety in this nucleus. Thirteen derivatives of 3‐substituted‐5‐(2‐hydroxyethyl)‐3,4,5,6‐tetrahydro‐2H‐1,3,5‐thiadiazine‐2‐thione were synthesized by reaction of the appropriate alkyl, cycloalkyl, aralkyl amine, or glycine with carbon disulphide, formaldehyde, and 2‐aminoethanol. The structures of the target compounds were elucidated using spectral methods as well as elemental analyses. A mass‐spectrometry study was carried out on representatives of the synthesized derivatives. The title compounds were tested for their antibacterial activity in vitro against some gram positive and gram negative bacteria. The in‐vitro antifungal activity was tested against dermatophytic, saprophytic, phytopathogenic, and antagonistic fungi. In most cases, the newly synthesized compounds 4–16 exhibited a considerable inhibitory effect on the growth of some of the tested organisms in comparison to that of ampicillin or muconazole as reference drugs. Moreover, the results indicated that the polar hydroxyethyl group at the N5‐ and the lipophilic one at the N3‐positions are essential for the antimicrobial activity of the tested compounds.
Anatomy: Spotlight on Africa
Authors: Kramer Beverley , Pather Nalini , Ihunwo Amadi O.
Published: May 2008

Anatomy departments across Africa were surveyed regarding the type of curriculum and method of delivery of their medical courses. While the response rate was low, African anatomy departments appear to be in line with the rest of the world in that many have introduced problem based learning, have hours that are within the range of western medical schools and appear to be well resourced. Human body dissection is a constant and strong aspect of the majority of the courses surveyed. The staff to student ratio appears to be relatively high in Africa, but in many of the responding African institutions, there appears to be little difficulty in attracting suitable faculty (including those who are medically qualified) to teach anatomy. Retaining this faculty, in some cases, may be difficult because of a global demand for anatomy educators. Anat Sci Ed 1:111–118, 2008. © 2008 American Association of Anatomists.
Intradisciplinary differences in database coverage and the consequences for bibliometric research
Authors: Frandsen Tove Faber , Nicolaisen Jeppe
Published: May 2008

Bibliographic databases (including databases based on open access) are routinely used for bibliometric research. The value of a specific database depends to a large extent on the coverage of the discipline(s) under study. A number of studies have determined the coverage of databases in specific disciplines focusing on interdisciplinary differences; however, little is known about the potential existence of intradisciplinary differences in database coverage. Focusing on intradisciplinary differences, the article documents large database‐coverage differences within two disciplines (economics and psychology). The point extends to include both the uneven coverage of specialties and research traditions. The implications for bibliometric research are discussed, and precautions which need to be taken are outlined.
Evaluating a dual‐process model of risk: affect and cognition as determinants of risky choice
Authors: van Gelder Jean‐Louis , de Vries Reinout E. , van der Pligt Joop
Published: May 2008

In three studies we addressed the impact of perceived risk and negative affect on risky choice. In Study 1, we tested a model that included both perceived risk and negative affect as predictors of risky choice. Study 2 and Study 3 replicated these findings and examined the impact of affective versus cognitive processing modes. In all the three studies, both perceived risk and negative affect were shown to be significant predictors of risky choice. Furthermore, Study 2 and Study 3 showed that an affective processing mode strengthened the relation between negative affect and risky choice and that a cognitive processing mode strengthened the relation between perceived risk and risky choice. Together, these findings show support for the idea of a dual‐process model of risky choice. Copyright © 2008 John Wiley & Sons, Ltd.
Morphometric analysis of metacarpophalangeal and proximal interphalangeal palmar plates
Authors: Kömürcü Mahmut , Kirici Yalçin , Korkmaz Cem , Alemdaroğlu Kadir Bahadir , Sanısoğlu Yavuz , Başbozkurt Mustafa
Published: May 2008

Palmar plates are being used as a source of graft in radial or ulnar collateral ligament reconstruction, pulley reconstruction, and volar plate arthroplasty. The purpose of this study is to determine morphometric and major histological differences of palmar plates in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints among fingers, and supply sufficient data which would be useful in reconstruction procedures. Ninety‐six MCP and 96 PIP palmar plates of 12 well‐preserved formalin‐fixed cadavers were measured focusing on their length, width, central thickness, and lateral thickness and statistically analyzed using ANOVA. Randomized three male and three female cadavers' specimens were examined histologically after staining with Masson's trichrome. For central thickness of the PIP joint level, there was significant difference among fingers, caused by the middle and little fingers. For lateral thickness of the PIP joint level, there was significant difference which was originated from little fingers. MCP palmar plates were significantly thicker than PIP joint levels for most of the fingers. There were thicker and denser collagen bands in MCP than PIP palmar plates. The relation of size‐related parameters was not close with the thickness parameters. The predicted sizes and thicknesses of palmar plates vary according to fingers. The data collected for each finger in this study should be used as a guide in reconstructive procedures that use palmar plates as source of graft. Clin. Anat. 21:433–438, 2008. © 2008 Wiley‐Liss, Inc.
Inter‐professional working in child protection with families with long‐term and complex needs
Authors: Devaney John
Published: May 2008

Within the United Kingdom there is growing awareness of the need to identify and support the small number of children who are living in families experiencing multiple problems. Research indicates that adverse experiences in childhood can result in poor outcomes in adulthood in terms of lack of employment, poorer physical and mental health and increases in social problems experienced. It is acknowledged that most of these children are known to child welfare professionals and that some are referred to social services, subsequently entering the child protection system. This paper reports research conducted with 28 experienced child welfare professionals. It explores their views about families known to the child protection system with long‐term and complex needs in relation to the characteristics of children and their families; the process of intervention with families; and the effects of organisational arrangements on practice. The research indicates that these families are characterised by the range and depth of the problems experienced by the adults, such as domestic violence, mental health difficulties and substance misuse problems, and the need for professionals to have good inter‐personal skills and access to specialist therapeutic services if families are to be supported to address their problems. Copyright © 2008 John Wiley & Sons, Ltd.
Ecdysteroids from Vitex Species: Distribution and Compilation of Their 13C‐NMR Spectral Data
Authors: Sena Filho José G. , Duringer Jennifer , Maia Gabriela L. A. , Tavares Josean F. , Xavier Haroudo S. , Sobral da Silva Marcelo , da‐Cunha Emídio V. L. , Barbosa‐Filho José M.
Published: May 2008

Iridoids and ecdysteroids are found in some genera of the family Verbenaceae. In such cases, they are used as chemotaxonomic markers for the difficult task of taxonomic identification by using morphological characteristics of plants belonging to this family. The present work describes the distribution of ecdysteroids in plants from the genus Vitex from a review of previous work on seventeen Vitex species. In addition, 13C‐NMR data of the main ecdysteroids found in this genus are described. This study attempted to summarize previous research on ecdysteroids distribution in Vitex species with the addition of 13C‐NMR analysis to further refine the characterization of these compounds in the Verbenaceae family.
Chemical Constituents of Stereum subtomentosum and Two Other Birch‐Associated Basidiomycetes: An Interspecies Comparative Study
Authors: Hybelbauerová Simona , Sejbal Jan , Dračínský Martin , Hahnová Alice , Koutek Bohumír
Published: May 2008

Metabolites of the wood‐rotting fungus Stereum subtomentosum Pouzar (Basidiomycetes, order Russulales, family Stereaceae) occuring on birch (Betula pendula Roth) trees were phytochemically investigated for the first time. Three main metabolite chemotypes present in MeOH extracts of the fruit bodies, viz. steroids, fatty acids, and water‐soluble sugars, were fractionated, isolated, and identified by 1D/2D NMR‐spectroscopic analyses, NMR data comparisons, and chemical correlations combined with GC/MS experiments. Thirteen compounds including two 5α,8α‐epidioxy steroids, α,α′‐trehalose, D‐arabinitol, D‐mannitol, and saturated/unsaturated fatty acids, were identified. Differences among S. subtomentosum and two other birch‐associated fungal species, Trametes versicolor (L.: Fr.) Pilát, and Piptoporus betulinus (Bull.: Fr.) P. Karst (Basidiomycetes, order Polyporales, family Polyporaceae) were evaluated as regards the richness and abundance relationships in metabolite profiling.
Two New Megastigmane Glycosides, Physanosides A and B, from Physalis alkekengi L. var. franchetii, and Their Effect on NO Release in Macrophages
Authors: Qiu Li , Zhao Feng , Liu Hongwei , Chen Lixia , Jiang Zhihu , Liu Hongxia , Wang Naili , Yao Xinsheng , Qiu Feng
Published: May 2008

Two new megastigmane glycosides, physanosides A and B (1 and 2, resp.), were isolated from Physalis alkekengi L. var. franchetii, together with four known compounds (6S,9R)‐roseoside (3), (6S,9S)‐roseoside (4), (6R,9S)‐3‐oxo‐α‐ionol β‐D‐glucopyranoside (5), and citroside A (6). Their structures were elucidated on the basis of physicochemical evidence, in‐depth NMR spectroscopic analysis, high‐resolution mass spectrometry, and CD spectroscopy, and their inhibitory effect on NO production was also examined. Compounds 2 and 3 exhibited strong inhibition on lipopolysaccharide‐induced NO release by macrophages with IC50 values of 9.93 and 7.31 μM, respectively.
Alkaloids from Corydalis saxicola and Their Anti‐Hepatitis B Virus Activity
Authors: Li Hui‐Liang , Han Ting , Liu Run‐Hui , Zhang Chuan , Chen Hai‐Sheng , Zhang Wei‐Dong
Published: May 2008

Eight protoberberine‐type alkaloids and two indole alkaloids were isolated from the MeOH extracts of the herb Corydalis saxicola Bunting (Papaveraceae). Their structures were identified as dehydrocavidine (1), dehydroapocavidine (2), dehydroisoapocavidine (3), berberine (4), dehydroisocorypalmine (5), coptisine (6), tetradehydroscoulerine (7), berbinium (8), 1‐formyl‐5‐methoxy‐6‐methylindoline (9), and 1‐formyl‐2‐hydroxy‐5‐methoxy‐6‐methylindoline (10). Compounds 3, 9, and 10 are new alkaloids. All compounds were tested for anti‐HBV activity against the 2.2.15 cell line in vitro. Dehydrocavidine (1), dehydroapocavidine (2), and dehydroisoapocavidine (3) exhibited inhibitory activity against HBsAg and HBeAg, but no cytotoxicity against the 2.2.15 cell line.
New Polyphenolic β‐Lactams with Antioxidant Activity
Authors: Cainelli Gianfranco , Angeloni Cristina , Cervellati Rinaldo , Galletti Paola , Giacomini Daria , Hrelia Silvana , Sinisi Riccardo
Published: May 2008

Novel 4‐alkylidene‐β‐lactams with a polyphenolic side chain were synthesized and evaluated as radical scavengers. We have undertaken a detailed study of the antioxidant activity in vitro with chemical and biological testing of the new β‐lactams and of the corresponding methyl polyhydroxy benzoates. Antioxidant activity of β‐lactams and methyl benzoates was measured with the Briggs–Rauscher oscillating reaction, the TEAC (Trolox® Equivalent Antioxidant Capacity) assay, and as ability to inhibit ROS (=Reactive Oxygen Species) production on myoblast H9c2 cells. The results were discussed with regard to mechanism and correlated with structural parameters.
Microwave‐Assisted Synthesis of 4′‐Azaflavones and Their N‐Alkyl Derivatives with Biological Activities
Authors: Yaşar Ahmet , Akpınar Kurtuluş , Burnaz Nesibe Arslan , Küçük Murat , Karaoğlu Şengül Alpay , Doğan Neşe , Yaylı Nurettin
Published: May 2008

4′‐Azaflavone (=2‐(pyridin‐4‐yl)‐4H‐1‐benzopyran‐4‐one; 4) and 3‐[(pyridin‐4‐yl)methyl]‐4′‐azaflavone (5) were synthesized by a simple environmentally friendly microwave‐assisted one‐pot method through the cyclization of 3‐hydroxy‐1‐(2‐hydroxyphenyl)‐3‐(pyridin‐4‐yl)propan‐1‐one (1), (E)‐2′‐hydroxy‐4‐azachalcone (2; chalcone=1,3‐diphenylprop‐2‐en‐1‐one), and 2′‐hydroxy‐2‐[(hydroxy)(pyridin‐4‐yl)methyl]‐4″‐azachalcone (3) under solventless conditions using silica‐supported NaHSO4, followed by treatment with base. In addition, N‐alkyl‐substituted 4′‐azaflavonium bromides 6 and 7 were prepared from compounds 4 and 5, respectively. The antimicrobial and antioxidant activities of compounds 1–7 were tested. The N‐alkyl‐substituted 4′‐azaflavonium bromides 6 and 7 showed high antimicrobial activity against the Gram‐positive bacteria and the fungus tested, with MIC values close to those of reference antimicrobials ampicilline and fluconazole. The alkylated compounds 6 and 7 also showed a good antioxidant character in the two antioxidant methods, DPPH (=1,1‐diphenyl‐2‐picrylhydrazyl) radical‐scavenging and ferric reducing/antioxidant power (FRAP) tests.
Synthesis and Characterization of Chiral Benzylic Ether‐Bridged Periodic Mesoporous Organosilicas
Authors: Morell Jürgen , Chatterjee Sangam , Klar Peter J. , Mauder Daniel , Shenderovich Ilja , Hoffmann Frank , Fröba Michael
Published: May 2008

The first synthesis of a chiral periodic mesoporous organosilica (PMO) carrying benzylic ether bridging groups is reported. By hydrolysis and condensation of the new designed chiral organosilica precursor 1,4‐bis(triethoxysilyl)‐2‐(1‐methoxyethyl)benzene (BTEMEB) in the presence of the non‐ionic oligomeric surfactant Brij 76 as supramolecular structure‐directing agent under acidic conditions, an ordered mesoporous chiral benzylic ether‐bridged hybrid material with a high specific surface area was obtained. The chiral PMO precursor was synthesized in a four‐step reaction from 1,4‐dibromobenzene as the starting compound. The evidence for the presence of the chiral units in the organosilica precursor as well as inside the PMO material is provided by optical activity measurements.
Bis(guanidinate) Alkoxide Complexes of Lanthanides: Synthesis, Structures and Use in Immortal and Stereoselective Ring‐Opening Polymerization of Cyclic Esters
Authors: Ajellal Noureddine , Lyubov Dmitrii M. , Sinenkov Mikhail A. , Fukin Georgii K. , Cherkasov Anton V. , Thomas Christophe M. , Carpentier Jean‐François , Trifonov Alexander A.
Published: May 2008

A series of new bis(guanidinate) alkoxide Group 3 metal complexes [Ln{(Me3Si)2NC(NiPr)2}2(OR)] (R=OtBu, Ln=Y, Nd, Sm, Lu; R=OiPr, Ln=Y, Nd, Lu) has been synthesized. X‐ray structural determinations revealed that bis(guanidinate) tert‐butoxides are monomeric complexes. The isopropoxide complex [Y{(Me3Si)2NC(NiPr)2}2(OiPr)] undergoes slow decomposition in solution, to afford the unusual dimeric amido complex [(Y{(Me3Si)2NC(NiPr)2}2{μ‐N(iPr)CN})2]. Complexes [Ln{(Me3Si)2NC(NiPr)2}2(OR)] (R=OtBu, Ln=Y, Nd, Sm, Lu; R=OiPr, Ln=Y, Nd, Lu) are active catalysts/initiators for the ROP of rac‐lactide and rac‐β‐butyrolactone under mild conditions. Most of those polymerizations proceed with a significant degree of control. Bis(guanidinate) alkoxides appear to be well suited for achieving immortal polymerization of lactide, through the introduction of large amounts of isopropanol as a chain‐transfer agent. The synthesized complexes are able to promote the stereoselective ROP of rac‐β‐butyrolactone to afford syndiotactic poly(hydrobutyrate) through a chain‐end control mechanism, while they are surprisingly non‐stereoselective for the ROP of lactide under strictly similar conditions.
Supramolecular Sensing with Phosphonate Cavitands
Authors: Melegari Monica , Suman Michele , Pirondini Laura , Moiani Davide , Massera Chiara , Ugozzoli Franco , Kalenius Elina , Vainiotalo Pirjo , Mulatier Jean‐Christophe , Dutasta Jean‐Pierre , Dalcanale Enrico
Published: May 2008

Phosphonate cavitands are an emerging class of synthetic receptors for supramolecular sensing. The molecular recognition properties of the third‐generation tetraphosphonate cavitands toward alcohols and water at the gas–solid interface have been evaluated by means of three complementary techniques and compared to those of the parent mono‐ and diphosphonate cavitands. The combined use of ESI‐MS and X‐ray crystallography defined precisely the host–guest association at the interface in terms of type, number, strength, and geometry of interactions. Quartz crystal microbalance (QCM) measurements then validated the predictive value of such information for sensing applications. The importance of energetically equivalent multiple interactions on sensor selectivity and sensitivity has been demonstrated by comparing the molecular recognition properties of tetraphosphonate cavitands with those of their mono‐ and diphosphonate counterparts.
Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors
Authors: Insinna Christine , Besharse Joseph C.
Published: May 2008

Analysis of the other segments of rod and cone photoreceptors in vertebrates has provided a rich molecular understanding of how light absorbed by a visual pigment can result in changes in membrane polarity that regulate neurotransmitter release. These events are carried out by a large group of phototransduction proteins that are enriched in the outer segment. However, the mechanisms by which phototransduction proteins are sequestered in the outer segment are not well defined. Insight into those mechanisms has recently emerged from the findings that outer segments arise from the plasma membrane of a sensory cilium, and that intraflagellar transport (IFT), which is necessary for assembly of many types of cilia and flagella, plays a crucial role. Here we review the general features of outer segment assembly that may be common to most sensory cilia as well those that may be unique to the outer segment. Those features illustrate how further analysis of photoreceptor IFT may provide insight into both IFT cargo and the role of alternative IFT kinesins. Developmental Dynamics 237:1982–1992, 2008. © 2008 Wiley‐Liss, Inc.
Expression of the semaphorins Sema 3D and Sema 3F in the developing parathyroid and thymus
Authors: Takahashi Kaoru , Ishida Mami , Hirokawa Katsuiku , Takahashi Hiroshi
Published: May 2008

We have identified two Semaphorin genes, Sema 3D and Sema 3F, as being specifically expressed in the developing parathyroid and thymus. The thymus and parathyroid originate from a common primordium that develops from the third pharyngeal pouch in mice. The expression of Sema 3D and Sema 3F was compared with that of gcm2, Pax1, and Neuropilin‐1 and ‐2, and genes encoding a variety of Plexins by in situ hybridization during mouse pharyngeal development. Sema 3D was specifically expressed in the dorsal and cranial portions of the primordium developing from the third pouch at mouse embryonic day (E) 10.5. That the expression pattern of Sema 3D was consistent with that of gcm2 indicates that Sema 3D was expressed in the parathyroid‐specific domains of the developing third pouch. The parathyroid‐specific pattern of Sema 3D expression continued until E17.5. By contrast, Sema 3F was expressed in both the parathyroid and thymic domains of the common primordium at E10.5, and the expression levels in both tissues were decreased during development. The Semaphorin receptors were expressed in the blood vessels, nerves, and mesenchymal cells adjacent to the common primordium or the separated parathyroid and thymus during development. Our results show that Sema 3D and Sema 3F genes were overlappingly and distinctly expressed in the developing parathyroid and thymus, respectively, and that Semaphorin signaling might play roles in the interactions between these organs and surrounding tissues such as nerves and blood vessels, and in the recruitment of lymphoid cells. Developmental Dynamics 237:1699–1708, 2008. © 2008 Wiley‐Liss, Inc.
The germ plasm component vasa allows tracing of the interstitial stem cells in the cnidarian Hydractinia echinata
Authors: Rebscher Nicole , Volk C. , Teo R. , Plickert G.
Published: May 2008

Germ cells in hydrozoans arise lifelong from multipotent interstitial stem cells. To discover if a true germline‐soma segregation exists in these species, we studied gametogenesis in Hydractinia echinata using in situ hybridization and immunohistochemistry for the germ cell marker Vasa. We could show that Hevas is a zygotic transcript, present in embryos from the gastrula stage onward. In the planula larva, Hevas is expressed in the interstitial stem cells located in the endoderm. During metamorphosis, Hevas‐expressing cells appear in the ectoderm in the lower half of the polyp. While the Hevas transcript is not detectable in developing gametes, the protein accumulates during oogenesis. Vasa containing granules are detectable at the polar‐body‐forming pole after fertilization. These results suggest that, in Hydractinia, maternal Vasa protein, but not the mRNA, is a maternal constituent of a germ plasm and might be involved in the specification and maintenance of interstitial stem cells. Developmental Dynamics 237:1736–1745, 2008. © 2008 Wiley‐Liss, Inc.
Investigation of Frizzled‐5 during embryonic neural development in mouse
Authors: Burns Carole J. , Zhang Jianmin , Brown Erinn C. , Van Bibber Alyssa M. , Van Es Johan , Clevers Hans , Ishikawa Tomo‐o , Taketo M. Mark , Vetter Monica L. , Fuhrmann Sabine
Published: May 2008

Recent studies revealed that the Wnt receptor Frizzled‐5 (Fzd5) is required for eye and retina development in zebrafish and Xenopus, however, its role during mammalian eye development is unknown. In the mouse embryo, Fzd5 is prominently expressed in the pituitary, distal optic vesicle, and optic stalk, then later in the progenitor zone of the developing retina. To elucidate the role of Fzd5 during eye development, we analyzed embryos with a germline disruption of the Fzd5 gene at E10.25, just before embryos die due to defects in yolk sac angiogenesis. We observed severe defects in optic cup morphogenesis and lens development. However, in embryos with conditional inactivation of Fzd5 using Six3‐Cre, we observed no obvious early eye defects. Analysis of Axin2 mRNA expression and TCF/LEF‐responsive reporter activation demonstrate that Fzd5 does not regulate the Wnt/β‐catenin pathway in the eye. Thus, the function of Fzd5 during eye development appears to be species‐dependent. Developmental Dynamics 237:1614–1626, 2008. © 2008 Wiley‐Liss, Inc.
Phonological and orthographic spelling in high‐functioning adult dyslexics
Authors: Kemp Nenagh , Parrila Rauno K. , Kirby John R.
Published: May 2008

Despite a history of reading or spelling difficulties, some adults attain age‐appropriate spelling skills and succeed at university. We compared the spelling of 29 such high‐functioning dyslexics with that of 28 typical students, matched on general spelling ability, and controlling for vocabulary and non‐verbal intelligence. Participants wrote derived real and pseudo words, whose spelling relationship to their base forms was categorized as phonologically simple (apt‐aptly), orthographically simple (deceit‐deceitful), phonologically complex (ash‐ashen), or orthographically complex (plenty‐plentiful). Dyslexic participants spelled all word and pseudoword categories more poorly than controls. Both groups spelled simple phonological words best. Dyslexics were particularly poor at spelling simple orthographic words, whose letter patterns and rules must likely be memorized. In contrast, dyslexics wrote more plausible spellings of orthographic than phonological pseudowords, but this might be an artefact of their more variable spelling attempts. These results suggest that high‐functioning dyslexics make some use of phonological skills to spell familiar words, but they have difficulty in memorizing orthographic patterns, which makes it difficult to spell unfamiliar words consistently in the absence of sufficient phonological cues or orthographic rules. Copyright © 2008 John Wiley & Sons, Ltd.
Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α‐chain CDR3 loop
Authors: Exley Mark A. , Hou Runhua , Shaulov Angela , Tonti Elena , Dellabona Paolo , Casorati Giulia , Akbari Omid , Akman H. Orhan , Greenfield Edward A. , Gumperz Jenny E. , Boyson Jonathan E. , Balk Steven P. , Wilson S. Brian
Published: May 2008

A significant fraction of CD1d‐restricted T cells express an invariant T cell receptor (TCR) α‐chain. These highly conserved invariant NKT (iNKT) populations are important regulators of a wide spectrum of immune responses. The ability to directly identify and manipulate iNKT cells is essential to understanding their function and to exploit their therapeutic potential. To this end, we sought monoclonal and polyclonal antibodies specific for iNKT cells by immunizing CD1d KO mice, which lack iNKT cells, with a cyclic peptide modeled after the TCRα CDR3 loop. One mAb (6B11) was specific for cloned and primary human but not rodent iNKT cells and the human invariant TCRα, as shown by transfection and reactivity with human invariant TCRα transgenic T cells ex vivo and in situ. 6B11 was utilized to identify, purify, and expand iNKT cells from an otherwise minor component of human peripheral blood lymphocytes and to specifically identify human iNKT cells in tissue. Thus, we report a novel and general strategy for the generation of mAb specific for the CDR3 loop encoded by the TCR of interest. Specifically, an anti‐Vα24Jα18 CDR3 loop clonotypic TCR mAb is available for the enumeration and therapeutic manipulation of human and non‐human primate iNKT populations.
IL‐15 acts as a potent inducer of CD4+CD25hi cells expressing FOXP3
Authors: Imamichi Hiromi , Sereti Irini , Lane H. Clifford
Published: May 2008

IL‐15 is a member of the γ chain‐dependent cytokines and known to affect innate and CD8+ adaptive immune responses. Despite a growing interest in the use of IL‐15 as an immunotherapeutic agent, the broad spectrum of immunoregulatory functions exerted by IL‐15 has not been fully elucidated. Here, we demonstrate that IL‐15 increases expression of CD25 and forkhead box transcription factor P3 (FOXP3), a master transcriptional regulator of regulatory T cells, in human peripheral CD4+CD25– T cells in the absence of antigenic stimulation. Comparisons involving IL‐2 and IL‐7 revealed that the induction of CD25hi and FOXP3 expression was most prominent with IL‐15 and IL‐2. More modest effects were seen with IL‐7. Despite levels of FOXP3 expression comparable to that of conventional regulatory T cells, cytokine‐induced CD4+CD25hiFOXP3+ cells exerted only weak suppressor activity. Thus, the current study has demonstrated that IL‐15 acts as a potent inducer of CD4+CD25hiFOXP3+ cells in the periphery, and suggests a potential role for IL‐15 in blunting immune activation. This study has provided further insights into the pleiotropic nature of IL‐15 beyond the regulation of CD8+ T cells.

Supporting Information for this article is available at www.wiley‐vch.de/contents/jc_2040/2008/37607_s.pdf
DNA methylation controls Foxp3 gene expression
Authors: Polansky Julia K. , Kretschmer Karsten , Freyer Jennifer , Floess Stefan , Garbe Annette , Baron Udo , Olek Sven , Hamann Alf , von Boehmer Harald , Huehn Jochen
Published: May 2008

Compelling evidence suggests that Foxp3‐expressing CD25+CD4+ regulatory T cells (Treg) are generated within the thymus as a separate lineage. However, Foxp3+CD4+ Treg can also be generated de novo in a TGF‐β‐dependent process from naive T cells by TCR triggering. Recently, we have shown that naturally occurring, but not in vitro TGF‐β‐induced Foxp3+ Treg display stable Foxp3 expression that was associated with selective demethylation of an evolutionarily conserved element within the Foxp3 locus named TSDR (Treg‐specific demethylated region). Here, we report that inhibition of DNA methylation by azacytidine, even in absence of exogenous TGF‐β, not only promoted de novo induction of Foxp3 expression during priming, but also conferred stability of Foxp3 expression upon restimulation. Most notably, such stable Foxp3 expression was found only for cells displaying enhanced TSDR demethylation. In contrast, in vitro TSDR methylation diminished its transcriptional activity. Foxp3+ Treg generated in vivo by DEC‐205‐mediated targeting of agonist ligands to dendritic cells showed long‐term survival in the absence of the inducing antigen and exhibited efficient TSDR demethylation. Together, our data suggest that TSDR is an important methylation‐sensitive element regulating Foxp3 expression and demonstrate that epigenetic imprinting in this region is critical for establishment of a stable Treg lineage.

Supporting Information for this article is available at www.wiley‐vch.de/contents/jc_2040/2008/38105_s.pdf
Lamina propria dendritic cells: For whom the bell TOLLs?
Authors: Rescigno Maria , Matteoli Gianluca
Published: May 2008

One of the major tasks of the mucosal immune system is to discriminate between dangerous and harmless antigens that are encountered daily at mucosal sites. In the gastrointestinal tract, immune cells have to tolerate food antigens and commensal microbes but at the same time have to induce a prompt response against invasive pathogens, when needed. In this issue of the European Journal of Immunology, it is shown that intestinal dendritic cell (DC) populations can be distinguished based on the expression level of Toll‐like receptors (TLR) and on the response of these TLR to their microbial ligands. DC either do not express TLR or they express them but respond in a non‐inflammatory mode. In this commentary, these findings are discussed in the context of available knowledge on lamina propria DC.

See accompanying article http://dx.doi.org/10.1002/eji.200737909
Synthesis and Reactivity of Monocyclopentadienyltantalum(V) Siloxide Complexes
Authors: Conde Ana , Fandos Rosa , Otero Antonio , Rodríguez Ana , Terreros Pilar
Published: May 2008

The new tantalum siloxide complex [TaCp*Me3(OSiPh3)] (1; Cp* = η5‐C5Me5) has been synthesized. The reaction of complex 1 with isocyanides yields the respective azatantalacyclopropanes [TaCp*(η2‐Me2CNxylyl)Me(OSiPh3)] (2; xylyl = 2,6‐dimethylphenyl) and [TaCp*(η2‐Me2CNtBu)Me(OSiPh3)] (3). The molecular structure of complex 2 has been established by X‐ray diffraction. Complex 2 reacts with a second mol‐equiv. of 2,6‐xylyl isocyanide to yield [TaCp*(Nxylyl)[N(xylyl)CMe=CMe2)(OSiPh3)] (4). The reaction of 1 with carbon monoxide gives [TaCp*(O)(OCMe=CMe2)(OSiPh3)] (5), whereas 1 reacts with B(C6F5)3 to give the corresponding cationic compound [TaCp*Me2(OSiPh3)][MeB(C6F5)3] (6). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Self‐Assembled Azaphthalocyanine Dimers with Higher Fluorescence and Singlet Oxygen Quantum Yields than the Corresponding Monomers
Authors: Novakova Veronika , Zimcik Petr , Kopecky Kamil , Miletin Miroslav , Kuneš Jiří , Lang Kamil
Published: May 2008

In this work, we describe diethylamino‐substituted metalazaphthalocyanines that form self‐assembled J‐dimers in noncoordinating solvents. The dimers are formed by the coordination of the free electron pair of one diethylamino group with the central metal of the adjacent molecule. The addition of pyridine leads to monomerization and considerable quenching of fluorescence and singlet oxygen formation as a result of intramolecular photoinduced singlet electron transfer (PET). PET is efficiently inhibited in dimers; therefore, dimers have higher fluorescence and singlet oxygen quantum yields than the corresponding monomers.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Electrochemiluminescence of Tris(2,2′‐bipyridine)ruthenium with Various Co‐reactants under Ultrasound Irradiation
Authors: Takahashi Fumiki , Jin Jiye
Published: May 2008

Electrochemiluminescence (ECL) of tris(2,2′‐bipyridine)ruthenium, Ru(bpy)32+ in the presence of various co‐reactants, such as tripropylamine (TPA), oxalate ion (C2O42−), ascorbic acid (H2A) and dehydroascorbic acid (DHA), were investigated under ultrasound irradiation. In sono‐ECL experiments, an indium‐thin‐oxide (ITO) was used as working electrode, and a titanium tipped sonic horn probe (diameter 2 mm) which operated at a frequency of 20 kHz was set in the front of the ITO electrode. Under the ultrasound irradiation, ECL signals were found to be significantly enhanced when TPA and C2O42− were used as co‐reactants, only slightly enhanced in Ru(bpy)32+/DHA system, but total quenched in Ru(bpy)32+/H2A system. The difference of Ru(bpy)32+ ECL behaviors for various co‐reactant could to be due to the different kinetics of catalytic reactions associated in ECL schemes. ECL quenching effect observed in Ru(bpy)32+/H2A system was suggested to be due to electron transfer (ET) route between the excited state *Ru(bpy)32+ and ascorbate anion HA− diffused from the bulk solution, where the diffusional HA− species served as electron donor. The effect becomes more pronounced upon sonication because the effective collision frequency between *Ru(bpy)32+ and HA− would be significantly increased by the enhanced mass transport effect of ultrasound.
Risk‐reducing effect of education in Alzheimer's disease
Authors: Sando Sigrid Botne , Melquist Stacey , Cannon Ashley , Hutton Michael , Sletvold Olav , Saltvedt Ingvild , White Linda R. , Lydersen Stian , Aasly Jan
Published: May 2008

Objective

To estimate the effect of education on the risk of Alzheimer's disease (AD).

Methods

373 patients diagnosed with AD and 559 healthy control individuals without first degree relatives with known dementia, were included in a case‐control study (2003–2006). All individuals were genotyped for APOE alleles. Odds ratio (OR) for developing AD was calculated by binary logistic regression, with the number of APOE ε4 alleles and educational level as covariates. Analyses were carried out separately for men and women and for different age groups.

Results

Carriers of one APOE ε4 allele had OR of 4.2, and carriers of two APOE ε4 alleles OR of 12.4 for developing AD. When adjusted for the number of APOE ε4 alleles, OR for developing AD was significantly reduced in participants with 8–9 years of education compared to those with only 6–7 years, and was reduced further for those with 10–18 years of education. These findings were obtained for all the age groups studied and for both men and women.

Conclusions

Education had a consistently protective effect on the risk of developing clinical AD in a dose‐dependent manner in both men and women, and in all age groups, also when adjusting for the number of APOE ε4 alleles. Male gender was protective, probably at least in part because of a higher educational level. Copyright © 2008 John Wiley & Sons, Ltd.
A double dissociation of subcortical hippocampal efferents for encoding and consolidation/retrieval of spatial information
Authors: Hunsaker Michael R. , Tran Giang T. , Kesner Raymond P.
Published: May 2008

CA3 lesions impair encoding, whereas CA1 lesions impair retrieval during learning of a Hebb‐Williams maze. CA3 efferents in the fimbria were transected, taking care to spare cholinergic and GABAergic afferents. CA1 efferents in the dorsal fornix were similarly transected. Fimbria transections, but not dorsal fornix transections, resulted in deficits for the encoding of spatial information during learning of a Hebb‐Williams maze. Dorsal fornix, but not fimbria, transections resulted in deficits for retrieval of spatial memory during learning of a Hebb‐Williams maze. These results reveal a double dissociation for the roles of CA3 and CA1 subcortical efferents in encoding and retrieval processes that mirror the double dissociation seen after excitotoxic lesions of CA1 and CA3. These data provide support for the theory that the cholinergic projections from the septal nuclei modulate the dynamics for encoding and consolidation/retrieval in the hippocampus. © 2008 Wiley‐Liss, Inc.
Changes of hippocampal signaling protein levels during postnatal brain development in the rat
Authors: Weitzdörfer Rachel , Höger Harald , Shim Ki‐Shuk , Cekici Leyla , Pollak Arnold , Lubec Gert
Published: May 2008

Developmental regulation of individual signaling proteins in the brain has been reported, although no systematic approach to study postnatal signaling protein expression in the rat has been described. This formed the rationale to compare hippocampal protein levels in rat hippocampus at different developmental time points. Sprague‐Dawley rats at 3 days, 3 weeks, and 3 months of age were used, hippocampi were extirpated, proteins extracted and run on two‐dimensional gel electrophoresis with subsequent identification of protein spots by mass spectrometry. Identified signaling proteins were quantified by specific software and for between group comparison Fisher's exact or Mann–Whitney U tests were applied. Annexin A3, GTP‐binding nuclear protein RAN, phosphatidylethanolamine‐binding protein, adenylyl cyclase associated protein 1, Rho‐associated protein kinase 1, nucleoside diphosphate kinase A, LIM, and SH3 domain protein 1 were developmentally regulated. High‐abundance hippocampal signaling proteins from several cascades in three different postnatal stages are presented, showing temporal regulation of signaling protein levels that have not been described in literature so far. Results are relevant for design and interpretation of further studies at the protein level and, moreover, an analytical tool concomitantly determining regulation of a large series of signaling proteins in the hippocampus is provided. These data contribute to the understanding that different time points may use different signaling cascades. © 2008 Wiley‐Liss, Inc.
Alterations in mossy fiber physiology and GAP‐43 expression and function in transgenic mice overexpressing HuD
Authors: Tanner Daniel C. , Qiu Shenfeng , Bolognani Federico , Partridge L. Donald , Weeber Edwin J. , Perrone‐Bizzozero Nora I
Published: May 2008

HuD is a neuronal RNA‐binding protein associated with the stabilization of mRNAs for GAP‐43 and other neuronal proteins that are important for nervous system development and learning and memory mechanisms. To better understand the function of this protein, we generated transgenic mice expressing human HuD (HuD‐Tg) in adult forebrain neurons. We have previously shown that expression of HuD in adult dentate granule cells results in an abnormal accumulation of GAP‐43 mRNA via posttranscriptional mechanisms. Here we show that this mRNA accumulation leads to the ectopic expression of GAP‐43 protein in mossy fibers. Electrophysiological analyses of the mossy fiber to CA3 synapse of HuD‐Tg mice revealed increases in paired‐pulse facilitation (PPF) at short interpulse intervals and no change in long‐term potentiation (LTP). Presynaptic calcium transients at the same synapses exhibited faster time constants of decay, suggesting a decrease in the endogenous Ca2+ buffer capacity of mossy fiber terminals of HuD‐Tg mice. Under resting conditions, GAP‐43 binds very tightly to calmodulin sequestering it and then releasing it upon PKC‐dependent phosphorylation. Therefore, subsequent studies examined the extent of GAP‐43 phosphorylation and its association to calmodulin. We found that despite the increased GAP‐43 expression in HuD‐Tg mice, the levels of PKC‐phosphorylated GAP‐43 were decreased in these animals. Furthermore, in agreement with the increased proportion of nonphosphorylated GAP‐43, HuD‐Tg mice showed increased binding of calmodulin to this protein. These results suggest that a significant amount of calmodulin may be trapped in an inactive state, unable to bind free calcium, and activate downstream signaling pathways. In conclusion, we propose that an unregulated expression of HuD disrupts mossy fiber physiology in adult mice in part by altering the expression and phosphorylation of GAP‐43 and the amount of free calmodulin available at the synaptic terminal. © 2008 Wiley‐Liss, Inc.
Sleep to find your way: The role of sleep in the consolidation of memory for navigation in humans
Authors: Ferrara Michele , Iaria Giuseppe , Tempesta Daniela , Curcio Giuseppe , Moroni Fabio , Marzano Cristina , De Gennaro Luigi , Pacitti Claudio
Published: May 2008

Although a large body of evidence indicates that sleep plays an important role in learning and memory processes, the actual existence of a sleep‐dependent spatial memory consolidation has been not firmly established. Here, by using a computerized 3D virtual navigation tool, we were able to show that topographical orientation in humans largely benefits from sleep after learning, while 10 h of wakefulness during the daytime do not exert similar beneficial effects. In particular, navigation performance enhancement needs sleep in the first post‐training night, and no further improvements were seen after a second night of sleep. On the other hand, sleep deprivation hinders any performance enhancement and exerts a proactive disruption of spatial memory consolidation, since recovery sleep do not revert its effects. Spatial memory performance does not benefit from the simple passage of time, and a period of wakefulness between learning and sleep does not seem to have the role of stabilizing memory traces. In conclusion, our results indicate that spatial performance improvement is observed only when learning is followed by a period of sleep, regardless of the retention interval length. © 2008 Wiley‐Liss, Inc.
Biotransformation of Vermitaline by Cunninghamella echinulata
Authors: Lü Yi‐Feng , Chen Ke‐Yu , Li Hui‐Liang , Pei Yue‐Hu , Liu Run‐Hui , Zhang Wei‐Dong
Published: May 2008

Biotransformation of vermitaline (1) by Cunninghamella echinulata (ACCC 30369) was carried out. Four biotransformation products were obtained and three of them were characterized as new compounds. On the basis of their NMR and mass‐spectral data, their structures were characterized as 7α‐hydroxyrubijervine (2), 7α‐hydroxyrubijervine‐7‐O‐β‐D‐galactofuranoside (3), 7α‐hydroxyvermitaline (4), and 7α‐hydroxyvermitaline‐7‐O‐β‐D‐galactofuranoside (5).
A One‐Pot Synthesis of 1,2‐Dihydroisoquinoline Derivatives from Isoquinoline via a Four‐Component Reaction
Authors: Alizadeh Abdolali , Zohreh Nasrin
Published: May 2008

A four‐component reaction for the synthesis of 1,2‐dihydroisoquinoline derivatives is described. The Huisgen 1,4‐dipolar intermediate, which is produced from isoquinoline and an electron‐deficient acetylene compound 1, reacts with H2O in the presence of diketene to produce 1,2‐dihydroisoquinoline derivatives 2 (Scheme 1). In addition, reaction of isoquinoline, dibenzoylacetylene (=1,4‐diphenylbut‐2‐yne‐1,4‐dione), and diketene in the presence of H2O leads to pyrroloisoquinoline derivative 7. The structures of the compounds 2a–f and 7 were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, EI‐MS) and by elemental analyses. A plausible mechanism for the reaction is proposed (Schemes 2 and 3).
Efficient Iminophosphorane‐Mediated Preparation of Benzofuro[3,2‐d]pyrimidin‐4(3H)‐ones and Unexpected Ring Opening Products
Authors: Hu Yang‐Gen , Liu Ming‐Guo , Ding Ming‐Wu
Published: May 2008

The carbodiimides 4, obtained from aza‐Wittig reactions of iminophosphorane 3 with aromatic isocyanates, reacted with secondary amines, phenols or alcohols in the presence of catalytic amounts of K2CO3 or sodium alkoxide to give 2‐substituted benzofuro[3,2‐d]pyrimidin‐4(3H)‐ones 6. However, when 2,2′‐iminobis[ethanol] was used, the unexpected ring opening product 7 was formed instead of 6. Reaction of 4 with primary amines RNH2 (R=Et, Pr, Bu, etc.) gave guanidine intermediates 8, which were further treated with EtONa to give only one regioisomer 9 via a base catalyzed cyclization. However, another regioisomer 11 was obtained when NH3 or ‘small’ amines RNH2 (R=Me, NH2) were used in the absence of EtONa via a spontaneous cyclization of 8.
Expression and enzyme activity of α(1,6)fucosyltransferase in human colorectal cancer
Authors: Muinelo‐Romay Laura , Vázquez‐Martín Cristina , Villar‐Portela Susana , Cuevas Elisa , Gil‐Martín Emilio , Fernández‐Briera Almudena
Published: May 2008

Changes in enzyme activity and the expression levels of α(1,6)fucosyltransferase [α(1,6)FT] have been reported in certain types of malignant transformations. To develop a better understanding of the role of α(1,6)FT in human colorectal carcinoma (CRC), we analysed the enzyme activity in healthy and tumour tissues. α(1,6)FT activity was considerably higher in tumour tissue than in healthy tissue and was related to gender, lymph node metastasis, type of growth and tumour stage. We also observed a significant increase in the α(1,6)FT expression in tumour tissues as compared to healthy and transitional tissues, inflammatory lesions and adenomas. The immunohistochemical expression in tumour tissues was correlated with the degree of infiltration through the intestinal wall. Finally, a statistical correlation was found between enzyme activity and expression obtained by Western blot in colorectal tumours when compared in the same patient. All these findings demonstrate an alteration of α(1,6)FT activity and expression in CRC. © 2008 Wiley‐Liss, Inc.
What controls TOR?
Authors: Jacinto Estela
Published: May 2008

The target of rapamycin (TOR) is a protein kinase with numerous functions in cell growth control. Some of these functions can be potently inhibited by rapamycin, an immunosuppressive and potential anticancer drug. TOR exists as part of two functionally distinct protein complexes. The functions of TOR complex 1 (TORC1) are effectively inhibited by rapamycin, but the mechanism for this inhibition remains elusive. The identification of TORC2 and recent reports that rapamycin can inhibit TORC2 functions, in some cases, challenge current models of TOR regulation. This review discusses the latest findings in yeast and mammals on the possible mechanisms that control TOR activity leading to its many cellular functions. © 2008 IUBMB IUBMB Life, 60(8): 483–496, 2008