bluuebunny/crossref_metadata_2025 huggingface dataset:
Myosin IIA Associates with NK Cell Lytic Granules to Enable Their Interaction with F-Actin and Function at the Immunological Synapse
Authors: Sanborn Keri B. , Rak Gregory D. , Maru Saumya Y. , Demers Korey , Difeo Analisa , Martignetti John A. , Betts Michael R. , Favier Rémi , Banerjee Pinaki P. , Orange Jordan S.
Published: May 2009

NK cell cytotoxicity requires the formation of an actin-rich immunological synapse (IS) with a target cell and the polarization of perforin-containing lytic granules toward the IS. Following the polarization of lytic granules, they traverse through the actin-rich IS to join the NK cell membrane in order for directed secretion of their contents to occur. We examined the role of myosin IIA as a candidate for facilitating this prefinal step in lytic NK cell IS function. Lytic granules in and derived from a human NK cell line, or ex vivo human NK cells, were constitutively associated with myosin IIA. When isolated using density gradients, myosin IIA-associated NK cell lytic granules directly bound to F-actin and the interaction was sensitive to the presence of ATP under conditions of flow. In NK cells from patients with a truncation mutation in myosin IIA, NK cell cytotoxicity, lytic granule penetration into F-actin at the IS, and interaction of isolated granules with F-actin were all decreased. Similarly, inhibition of myosin function also diminished the penetration of lytic granules into F-actin at the IS, as well as the final approach of lytic granules to and their dynamics at the IS. Thus, NK cell lytic granule-associated myosin IIA enables their interaction with actin and final transit through the actin-rich IS to the synaptic membrane, and can be defective in the context of naturally occurring human myosin IIA mutation.
The UDP-Glucose Receptor P2RY14 Triggers Innate Mucosal Immunity in the Female Reproductive Tract by Inducing IL-8
Authors: Arase Toru , Uchida Hiroshi , Kajitani Takashi , Ono Masanori , Tamaki Kayoko , Oda Hideyuki , Nishikawa Sayaka , Kagami Maki , Nagashima Takashi , Masuda Hirotaka , Asada Hironori , Yoshimura Yasunori , Maruyama Tetsuo
Published: May 2009

Innate mucosal immune responses, including recognition of pathogen-associated molecular patterns through Toll-like receptors, play an important role in preventing infection in the female reproductive tract (FRT). Damaged cells release nucleotides, including ATP and uridine 5′-diphosphoglucose (UDP-glucose), during inflammation and mechanical stress. We show in this report that P2RY14, a membrane receptor for UDP-glucose, is exclusively expressed in the epithelium, but not the stroma, of the FRT in humans and mice. P2RY14 and several proinflammatory cytokines, such as IL-8, are up-regulated in the endometria of patients with pelvic inflammatory disease. UDP-glucose stimulated IL-8 production via P2RY14 in human endometrial epithelial cells but not stromal cells. Furthermore, UDP-glucose enhanced neutrophil chemotaxis in the presence of a human endometrial epithelial cell line in an IL-8-dependent manner. Administration of UDP-glucose into the mouse uterus induced expression of macrophage inflammatory protein-2 and keratinocyte-derived cytokine, two murine chemokines that are functional homologues of IL-8, and augmented endometrial neutrophil recruitment. Reduced expression of P2RY14 by small interfering RNA gene silencing attenuated LPS- or UDP-glucose-induced leukocytosis in the mouse uterus. These results suggest that UDP-glucose and its receptor P2RY14 are key front line players able to trigger innate mucosal immune responses in the FRT bypassing the recognition of pathogen-associated molecular patterns. Our findings would significantly impact the strategic design of therapies to modulate mucosal immunity by targeting P2RY14.
CD40-Independent Engagement of Mammalian hsp70 by Antigen-Presenting Cells
Authors: Binder Robert J.
Published: May 2009

CD40 has been suggested previously to be a receptor for mammalian murine hsc73 (hsp70). We have examined, in vitro and in vivo, the role of CD40 in the interaction of murine dendritic cells and macrophages with hsp70, using several independent parameters including cell surface binding, translocation of NF-κB, stimulation of release of TNF-α, representation of hsp70-chaperoned peptides, and priming of CD8+ T cells. The various consequences of hsp70-APC interaction were compared between CD40+/+ and CD40−/− mice and were found to be identical in kinetics and magnitude. These data strongly indicate that all known effects of mammalian hsp70 on APCs are mediated in a CD40-independent manner. In light of the earlier demonstration that mycobacterial hsp70 binds murine CD40 and stimulates the APCs through it, our data indicate that CD40 can discriminate between self and mycobacterial hsp70 and is thus a receptor for patterns associated with microbial pathogens.
Induction of Distinct TLR2-Mediated Proinflammatory and Proadhesive Signaling Pathways in Response to Porphyromonas gingivalis Fimbriae
Authors: Hajishengallis George , Wang Min , Liang Shuang
Published: May 2009

The oral pathogen Porphyromonas gingivalis, as well as its purified fimbriae, are known to activate TLR2 and induce proinflammatory and proadhesive effects. The TLR2 proinflammatory pathway induces NF-κB-dependent inflammatory cytokines, whereas the TLR2 proadhesive pathway is characterized by inside-out signaling that transactivates β2 integrin adhesive activities. In this article, using dominant-negative or pharmacological approaches, we show that the two pathways bifurcate and proceed independently downstream of TLR2. Whereas the proinflammatory pathway is dependent on the adaptor molecules Toll/IL-1 receptor domain-containing adaptor protein (also known as Mal) and MyD88, the proadhesive pathway is Toll/IL-1 receptor domain-containing adaptor protein/MyD88-independent and proceeds through PI3K-mediated signaling. Although the Ser/Thr kinase Akt is a major downstream target of PI3K and was activated by P. gingivalis fimbriae in a TLR2- and PI3K-dependent way, Akt was shown not to play a role in the proadhesive patway. In contrast, another PI3K downstream target, cytohesin-1, was shown to mediate P. gingivalis fimbria-induced activation of β2 integrin for ICAM-1 binding. Therefore, P. gingivalis fimbriae activate two distinct TLR2 pathways mediating proinflammatory or proadhesive effects. The delineation of these signaling pathways may provide appropriate targets for selectively inhibiting or enhancing specific activities, depending on whether they undermine or promote the host defense.
Cutting Edge: Highly Alloreactive Dual TCR T Cells Play a Dominant Role in Graft-versus-Host Disease
Authors: Morris Gerald P. , Allen Paul M.
Published: May 2009

Alloreactivity is the response of T cells to MHC molecules not encountered during thymic development. A small population (1–8%) of peripheral T cells in mice and humans express two TCRs due to incomplete allelic exclusion of TCRα, and we hypothesized they are highly alloreactive. FACS analysis of mouse T cell MLR revealed increased dual TCR T cells among alloreactive cells. Quantitative assessment of the alloreactive repertoire demonstrated a nearly 50% reduction in alloreactive T cell frequency among T cells incapable of expressing a secondary TCR. We directly demonstrated expansion of the alloreactive T cell repertoire at the single cell level by identifying a dual TCR T cell with distinct alloreactivities for each TCR. The importance of dual TCR T cells is clearly demonstrated in a parent-into-F1 model of graft-vs-host disease, where dual TCR T cells comprised up to 60% of peripheral activated T cells, demonstrating a disproportionate contribution to disease.
Sodium and Sodium Alloys
Authors: Eggeman Tim ,   Updated by Staff
Published: May 2009

Of all the alkali metals, sodium has had perhaps the greatest commercial success, owing to its relative ease of manufacture and its important role worldwide in the manufacture of organolead compounds for use as gasoline octane enhancers. The decline of organoleads in North America has greatly affected U.S. production. Other sodium uses exist, but none requiring the massive quantities needed for lead antiknock compounds. Most sodium is made electrolytically. Various electrochemical cells are described.

However, sodium is used to make sodium methylate, herbicides, dyes, rubber, fragrances, vitamins, and ibuprophen. In metal manufacture, sodium is used in tantalum, titanium, silicon and refining metallic lead and grain refining. Newer uses include sodium batteries, flue‐gas cleanup, and alloy surface modification. Safe handling of sodium requires special consideration because of its high reactivity. Sodium alloys are also discussed.
Long‐Term Multilayer Adherent Network (MAN) Expansion, Maintenance, and Characterization, Chemical and Genetic Manipulation, and Transplantation of Human Fetal Forebrain Neural Stem Cells
Authors: Wakeman Dustin R. , Hofmann Martin R. , Redmond D. Eugene , Teng Yang D. , Snyder Evan Y.
Published: May 2009

Human neural stem/precursor cells (hNSC/hNPC) have been targeted for application in a variety of research models and as prospective candidates for cell‐based therapeutic modalities in central nervous system (CNS) disorders. To this end, the successful derivation, expansion, and sustained maintenance of undifferentiated hNSC/hNPC in vitro, as artificial expandable neurogenic micro‐niches, promises a diversity of applications as well as future potential for a variety of experimental paradigms modeling early human neurogenesis, neuronal migration, and neurogenetic disorders, and could also serve as a platform for small‐molecule drug screening in the CNS. Furthermore, hNPC transplants provide an alternative substrate for cellular regeneration and restoration of damaged tissue in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Human somatic neural stem/progenitor cells (NSC/NPC) have been derived from a variety of cadaveric sources and proven engraftable in a cytoarchitecturally appropriate manner into the developing and adult rodent and monkey brain while maintaining both functional and migratory capabilities in pathological models of disease. In the following unit, we describe a new procedure that we have successfully employed to maintain operationally defined human somatic NSC/NPC from developing fetal, pre‐term post‐natal, and adult cadaveric forebrain. Specifically, we outline the detailed methodology for in vitro expansion, long‐term maintenance, manipulation, and transplantation of these multipotent precursors.Curr. Protoc. Stem Cell Biol. 9:2D.3.1‐2D.3.77. © 2009 by John Wiley & Sons, Inc.
Functional Analysis of Adult Stem Cells Using Cre‐Mediated Lineage Tracing
Authors: Carlone Diana L.
Published: May 2009

Lineage‐tracing has been used for decades to establish cell fate maps during development. Recently, with the advent of genetic lineage‐tracing techniques (employing Cre‐lox recombination), it has been possible to permanently mark progenitor/stem cell populations within somatic tissues. In addition, pulse‐chase studies have shown that only stem cells are capable of producing labeled progeny after an extensive period of chase. This unit focuses on the protocols used to target putative adult stem cells in vivo. Using these techniques, one should be able to functionally confirm or deny the stem cell capacity of a given cell population. Curr. Protoc. Stem Cell Biol. 9:5A.2.1‐5A.2.15. © 2009 by John Wiley & Sons, Inc.
Have you made up your story? The effect of suspicion and liars' strategies on reality monitoring
Authors: Gnisci Augusto , Caso Letizia , Vrij Aldert
Published: May 2009

The impact of Veracity, Suspicion (weak or strong) and Strategy (making up a story or using past experiences) on Reality Monitoring (RM) scores was examined. A total of 158 undergraduate students were interviewed twice about the possession of an object. In one interview they were asked to lie, and in the other to tell the truth (Veracity factor). In both conditions, suspicion was raised in the second half of the interview: Participants were accused of lying by the interviewer and asked to repeat their account (Raised Suspicion factor). At the end of the interview participants were asked whether their lies were totally made up or whether they described an event that they had experienced previously (Strategy factor). Results revealed that truth tellers and liars' speech differed from each other in accordance with RM theory, even when the interviewer was suspicious and even when liars fabricated a story by describing events that they had previously experienced. Copyright © 2009 John Wiley & Sons, Ltd.
Congenital skin pedicles with or without amniotic band sequence: Extending the human phenotype resembling mouse disorganization
Authors: Isidor B. , Baujat G. , Le Caignec C. , Pichon O. , Martin‐Coignard D. , Toutain A. , David A.
Published: May 2009

Congenital skin pedicles are very rare and usually described in association with multiple congenital anomalies. Here, we report on six patients with congenital pedicle skin hamartomatous lesions. Two patients showed a single skin pedicle lesion, one of whom was also shown to have 22q11.2 microdeletion syndrome, and four patients also had severe limb anomalies for which they were originally diagnosed with amniotic band sequence (ABS). We propose that all these infants instead show various forms of the phenotype resembling disorganization in the mouse. This article supports previous reports suggesting that “Disorganization‐like” mutations may cause cases with apparent ABS. Owing to these reports, we propose the hypothesis that hamartomatous skin pedicles and “ABS plus” are different phenotypes of the human disorder resembling disorganization. © 2009 Wiley‐Liss, Inc.
Unstable familial transmissions of Huntington disease alleles with 27–35 CAG repeats (intermediate alleles)
Authors: Semaka A. , Collins J.A. , Hayden M.R.
Published: May 2009

There are inconsistent reports regarding the likelihood of repeat instability for alleles with 27–35 CAG repeats in the Huntington disease (HD) gene. We have examined the intergenerational stability of such intermediate alleles in 51 families from the University of British Columbia's DNA and Tissue Bank for Huntington Disease Research (UBC‐HD Databank). A total of 181 transmissions were identified, with 30% (n = 54/181) of the alleles being unstable upon transmission. The unstable transmissions included both expansions (n = 37) and contractions (n = 17) of CAG size. Of the expanded alleles, 68% (n = 25/37) expanded into the HD range (>36 CAG). Therefore, 14% (n = 25/181) of the 27–35 CAG allele transmissions examined expanded into the disease‐associated range resulting in a new mutation for HD. Significantly, of these new mutations, 40% (n = 10/25) originated from an allele with 35 CAG repeats with CAG repeat expansions ranging from +1 CAG to +23 CAG. The proportion of new mutations in the UBC‐HD Databank is consistent with the most recent new mutation rate for HD, estimated to be at least 10%. The observed difference in the stability of HD intermediate allele transmissions in this data set and in other studies may be a reflection of a small sample size. Alternately, these inconsistencies may indicate an underlying difference in genetic factors which influence repeat instability between the different populations examined. Additional studies determining the frequency and magnitude of repeat instability in this CAG repeat range and factors that influence instability are urgently needed. Until we understand the clinical implications of HD alleles with 27–35 CAG repeats and establish reliable risks of instability, we should exercise caution when translating these results to the clinic. © 2009 Wiley‐Liss, Inc.
Association study of the serotoninergic system in migraine in the spanish population
Authors: Corominas R. , Sobrido M.J. , Ribasés M. , Cuenca‐León E. , Blanco‐Arias P. , Narberhaus B. , Roig M. , Leira R. , López‐González J. , Macaya A. , Cormand B.
Published: May 2009

In order to evaluate the contribution of 19 serotonin‐related genes to the susceptibility to migraine in a Spanish population we performed a case–control association study of 122 single nucleotide polymorphisms (SNPs), selected according to genetic coverage parameters, in 528 migraine patients —308 with migraine without aura (MO) and 220 with migraine with aura (MA)— and 528 sex‐matched migraine‐free controls. The single‐marker analysis identified nominal associations with the migraine phenotype or with the MO or MA subtypes. The multiple‐marker analysis revealed risk haplotypes in three genes that remained significantly associated with migraine after correction by permutations. Two‐marker risk haplotypes were identified in the HTR2B (rs16827801T‐rs10194776G) and MAOA (rs3027400G‐rs2072743C) genes conferring susceptibility to MO, and a four‐marker haplotype in DDC was specific of MA (rs2329340A‐rs11974297C‐rs2044859T‐rs11761683G). The present study supports the involvement of HTR2B and MAOA genes in the genetic predisposition to MO, while DDC might confer susceptibility to MA. These results suggest a differential involvement of serotonin‐related genes in the genetic background of MO and MA. © 2009 Wiley‐Liss, Inc.
Epileptic encephalopathy in a girl with an interstitial deletion of Xp22 comprising promoter and exon 1 of the CDKL5 gene
Authors: Bahi‐Buisson Nadia , Girard Benoit , Gautier Agnes , Nectoux Juliette , Fichou Yann , Saillour Yoann , Poirier Karine , Chelly Jamel , Bienvenu Thierry
Published: May 2009

We report a 2‐year‐old girl with early onset seizures variant of Rett syndrome with a deletion at Xp22 detected by multiplex ligation‐dependent probe amplification (MLPA) technique. This patient presented with tonic seizures at 7 days of life. Subsequently, she developed infantile spasms at three months and finally refractory myoclonic epilepsy. She demonstrated severe encephalopathy with hypotonia, deceleration of head growth, with eye gaze but limited eye pursuit, no language, limited hand use, and intermittent hand stereotypies. This combination of clinical features, suggestive of early onset variant of Rett syndrome led us to screen the CDKL5 gene. In a first step, screening of the whole coding sequence of the CDKL5 gene revealed no point mutations. In a second step, we searched gross rearrangements by MLPA and identified a microdeletion affecting both the promoter and exon 1 in CDKL5. Subsequent analysis on a Nimblegen HD2 microarray confirmed a deletion of approximately 300 kb at Xp22, including the BEND2, SCML2, and CDKL5 genes. In conclusion, our report suggests that searching for large rearrangements in CDKL5 should be considered in girls with early onset seizures and Rett‐like features. © 2009 Wiley‐Liss, Inc.
Nucleotide variation in central nervous system genes among male suicide attempters
Authors: Baca‐Garcia Enrique , Vaquero‐Lorenzo Concepción , Perez‐Rodriguez M. Mercedes , Gratacòs Mònica , Bayés Mònica , Santiago‐Mozos Ricardo , Leiva‐Murillo Jose Miguel , de Prado‐Cumplido Mario , Artes‐Rodriguez Antonio , Ceverino Antonio , Diaz‐Sastre Carmen , Fernandez‐Navarro Pablo , Costas Javier , Fernandez‐Piqueras José , Diaz‐Hernandez Montserrat , de Leon Jose , Baca‐Baldomero Enrique , Saiz‐Ruiz Jeronimo , Mann J. John , Parsey Ramin V. , Carracedo Angel , Estivill Xavier , Oquendo Maria A.
Published: May 2009

Despite marked morbidity and mortality associated with suicidal behavior, accurate identification of individuals at risk remains elusive. The goal of this study is to identify a model based on single nucleotide polymorphisms (SNPs) that discriminates between suicide attempters and non‐attempters using data mining strategies. We examined functional SNPs (n = 840) of 312 brain function and development genes using data mining techniques. Two hundred seventy‐seven male psychiatric patients aged 18 years or older were recruited at a University hospital psychiatric emergency room or psychiatric short stay unit. The main outcome measure was history of suicide attempts. Three SNPs of three genes (rs10944288, HTR1E; hCV8953491, GABRP; and rs707216, ACTN2) correctly classified 67% of male suicide attempters and non‐attempters (0.50 sensitivity, 0.82 specificity, positive likelihood ratio = 2.80, negative likelihood ratio = 1.64). The OR for the combined three SNPs was 4.60 (95% CI: 1.31–16.10). The model's accuracy suggests that in the future similar methodologies may generate simple genetic tests with diagnostic utility in identification of suicide attempters. This strategy may uncover new pathophysiological pathways regarding the neurobiology of suicidal acts. © 2009 Wiley‐Liss, Inc.
A sequencing‐based survey of functional APAF1 alleles in a large sample of individuals with affective illness and population controls
Authors: Amin Zenab , Kanarek Katarzyna , Krupitsky Evgeny , Walderhaug Espen , Ilomäki Risto , Blumberg Hilary , Price Lawrence H. , Bhagwagar Zubin , Carpenter Linda L. , Tyrka Audrey R. , Magnusson Andres , Landrø Nils Inge , Zvartau Edwin , Gelernter Joel , Epperson C. Neill , Räsänen Pirkko , Siironen Jari , Lappalainen Jaakko
Published: May 2009

Rare apoptosis‐promoting functional variants in the apoptosis protease activating factor 1 (APAF1) gene were recently reported to co‐segregate with major depression in male members of families from Utah. In order to estimate the impact of these variants on risk for major depressive disorder (MDD) in the general population, we surveyed the frequency of the APAF1 putative MDD risk alleles using re‐sequencing in a large sample of northern European and European‐American subjects, including a large number of males with MDD. The E777K and N782T APAF1 variants previously described by Harlan et al. [Harlan et al. (2006) Mol Psychiatry 11(1):76–85] were found at low frequencies in affected individuals and population controls. The C450W and Q465R variants were not detected in any of the 632 subjects sequenced. These results show that the APAF1 variants associated with risk for MDD in the Utah pedigrees are very rare in Northern European and European‐American populations. In addition, the E777K and N782T variants were found at low frequencies both in patients and population controls, suggesting that these variants have limited impact on risk for MDD. © 2009 Wiley‐Liss, Inc.
Tin Chemistry.Fundamentals, Frontiers, and Applications. Herausgegeben von Alwyn G. Davies, Marcel Gielen, Keith H. Pannell und Edward R. T. Tiekink.
Authors: Dehnen Stefanie
Published: May 2009

John Wiley & Sons, Chichester 2008. 752 S., geb., 199.00 €.—ISBN 978‐0470517710

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Indirect Optical Analysis of a Dynamic Chemical System
Authors: Gasparini Giulio , Bettin Federico , Scrimin Paolo , Prins Leonard J.
Published: May 2009

Versteckspiel: Die Gleichgewichtszusammensetzung einer dynamischen kovalenten Reaktion wird bestimmt, indem man die Restkonzentration einer Bezugsverbindung ermittelt (blau, siehe Bild). Das Abfangen dieser Bezugsverbindung führt zu einem charakteristischen UV/Vis‐Signal, das nicht von der Molekülstruktur der Zielverbindung abhängt.

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Mirror‐Image Photoswitching of Individual Single‐Walled Carbon Nanotube Transistors Coated with Titanium Dioxide
Authors: Liu Song , Li Jianming , Shen Qian , Cao Yang , Guo Xuefeng , Zhang Guoming , Feng Chaoqun , Zhang Jin , Liu Zhongfan , Steigerwald Michael L. , Xu Dongsheng , Nuckolls Colin
Published: May 2009

Stimuliresponsive optoelektronische Einheiten werden aus den mit photoaktiven Quantenpunkten funktionalisierten Titeltransistoren erhalten. Bei den p‐Halbleiterröhren nimmt der Stromfluss unter UV‐Licht rasch ab und beim Abschalten der Bestrahlung reversibel wieder zu. Dagegen zeigen ambipolare Röhren spiegelbildliche Photoschalteffekte, wenn negative und positive Gatter‐Vorspannungen angewendet werden.

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9,10‐Dihydro‐9,10‐diboraanthracene: Supramolecular Structure and Use as a Building Block for Luminescent Conjugated Polymers
Authors: Lorbach Andreas , Bolte Michael , Li Haiyan , Lerner Hans‐Wolfram , Holthausen Max C. , Jäkle Frieder , Wagner Matthias
Published: May 2009

Dreizentren‐Zweielektronen‐B‐H‐B‐Brücken kennzeichnen die neuartige polymere Struktur der Titelverbindung im Festkörper. Dieses Organoboran dient als effiziente Vorstufe für die Herstellung bordotierter π‐konjugierter Polymere durch Hydroborierungspolymerisation mit einem funktionalisierten 1,4‐Diethinylbenzol (siehe Bild). Diese Polymere bilden dünne Filme, die sich durch intensive grüne Lumineszenz auszeichnen.

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Self‐Healing Colloidal Crystals
Authors: Iyer Ashlee St. John , Lyon L. Andrew
Published: May 2009

Heilende Hände: Ein komplexes Zusammenspiel kolloidaler und polymerer Energetik bei der Selbstorganisation von Mikrogelen führt zur Bildung weicher kolloidaler Anordnungen mit Selbstheilungseigenschaften. Repulsive weiche Kugeln können in kolloidalen kristallinen Gittern stark komprimierte Konformationen ohne direkten Kontakt zu den nächsten Nachbarn annehmen (siehe Bild). Diese Fernwirkung ist direkte Ursache für die Selbstheilung der Assoziate.

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Titelbild: Selectivity Control in Gold‐Mediated Esterification of Methanol (Angew. Chem. 23/2009)
Authors: Xu Bingjun , Liu Xiaoying , Haubrich Jan , Madix Robert J. , Friend Cynthia M.
Published: May 2009

Auf Gold adsorbierte Sauerstoffatome erleichtern die Umwandlung von Methanol zu Methylformiat, Formaldehyd und Ameisensäure bei tiefen Temperaturen. Die Reaktionen finden an sauerstoffhaltigen Goldnanopartikeln mit ca. 2 nm Durchmesser statt, die bei der Oxidation einer Au(111)‐Oberfläche mit Ozon entstehen. Der genaue Reaktionsmechanismus wird von C. M. Friend und Mitarbeitern in ihrer Zuschrift auf S. 4270 ff. besprochen.

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From Metal Binding to Nanoparticle Formation: Monitoring Biomimetic Iron Oxide Synthesis within Protein Cages using Mass Spectrometry
Authors: Kang Sebyung , Jolley Craig C. , Liepold Lars O. , Young Mark , Douglas Trevor
Published: May 2009

Mass measurements of metal‐mineralized protein cages allowed quantitative examination of the effects of metal‐ion concentration on the final nanoparticle size. Modeling using a kinetic master equation suggests that particle growth involves both a binding phase and a growth phase (see picture; I: relative abundance; LiDps: a DNA binding protein; nFe: number of Fe atoms).

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Cooperative Molecular Motion within a Self‐Assembled Liquid‐Crystalline Molecular Wire: The Case of a TEG‐Substituted Perylenediimide Disc
Authors: Hansen Michael Ryan , Schnitzler Tobias , Pisula Wojciech , Graf Robert , Müllen Klaus , Spiess Hans Wolfgang
Published: May 2009

Always on the move: Molecular dynamics of perylene cores in columnar structures influences the processability and self‐healing of these materials. A combination of X‐ray scattering and advanced solid‐state NMR methods show that these systems have restricted angular mobility of the cores even in the frozen phase, and a cooperative spiral type of motion in the liquid crystalline phase (see picture).

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Phosphonium Salts as Chiral Phase‐Transfer Catalysts: Asymmetric Michael and Mannich Reactions of 3‐Aryloxindoles
Authors: He Rongjun , Ding Changhua , Maruoka Keiji
Published: May 2009

It′s a PTC: A highly efficient reaction of 3‐aryloxindoles in an asymmetric Michael addition was achieved by using a quaternary tetraalkylphosphonium salt as a chiral phase‐transfer catalyst (PTC). The products were obtained in quantitative yields highee values. The reaction of 3‐aryloxindoles in an asymmetric Mannich reaction using the same catalyst also proved to be feasible.

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Oxidative Carbocation Formation in Macrocycles: Synthesis of the Neopeltolide Macrocycle
Authors: Tu Wangyang , Floreancig Paul E.
Published: May 2009

Macrocyclic oxocarbenium ions can be formed from macrolactones that contain benzylic or allylic ether groups through oxidative carbon–hydrogen‐bond activation mediated by 2,3‐dichloro‐4,5‐dicyanoquinone (DDQ). The applicability of this efficient reaction to complex‐molecule synthesis was demonstrated by its use in a brief formal synthesis of neopeltolide (see retrosynthetic scheme) to form the tetrahydropyrone ring.

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Self‐Healing Colloidal Crystals
Authors: Iyer Ashlee St. John , Lyon L. Andrew
Published: May 2009

Healing hands: A complex interplay between colloidal and polymeric energetics in microgel self‐assembly behavior results in soft colloidal assemblies with self‐healing properties. Repulsive soft spheres can adopt highly compressed conformations in colloidal crystalline lattices without directly contacting the nearest neighbors (see picture). This distant action is directly responsible for the self‐healing of the assemblies.

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Practical Synthesis of the Dendralene Family Reveals Alternation in Behavior
Authors: Payne Alan D. , Bojase Gomotsang , Paddon‐Row Michael N. , Sherburn Michael S.
Published: May 2009

Back from obscurity: The practical synthesis of the first six members of the fundamental class of acyclic branched oligoalkenes has been achieved. The syntheses allow access to the target compounds on multigram scales in good yields. Members of the family with even numbers of double bonds are significantly more stable than those with odd numbers (see picture), and exhibit different chemical reactivities in Diels–Alder reactions.

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Photometric monitoring of the young star Par 1724 in Orion
Authors: Neuhäuser R. , Koeltzsch A. , Raetz St. , Schmidt T. O. B. , Mugrauer M. , Young N. , Bertoldi F. , Roell T. , Eisenbeiss T. , Hohle M. M. , Vaňko M. , Ginski C. , Rammo W. , Moualla M. , Broeg C.
Published: May 2009

We report new photometric observations of the ∼200 000 year old naked weak‐line run‐away T Tauri star Par 1724, located north of the Trapezium cluster in Orion. We observed in the broad band filters B, V, R, and I using the 90 cm Dutch telescope on La Silla, the 80 cm Wendelstein telescope, and a 25 cm telescope of the University Observatory Jena in Großschwabhausen near Jena. The photometric data in V and R are consistent with a ∼5.7 day rotation period due to spots, as observed before between 1960ies and 2000. Also, for the first time, we present evidence for a long‐term 9 or 17.5 year cycle in photometric data (V band) of such a young star, a cycle similar to that to of the Sun and other active stars (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Automated classification of Plasmodium sporozoite movement patterns reveals a shift towards productive motility during salivary gland infection
Authors: Hegge Stephan , Kudryashev Mikhail , Smith Ashley , Frischknecht Friedrich
Published: May 2009

The invasive stages of malaria and other apicomplexan parasites use a unique motility machinery based on actin, myosin and a number of parasite‐specific proteins to invade host cells and tissues. The crucial importance of this motility machinery at several stages of the life cycle of these parasites makes the individual components potential drug targets. The different stages of the malaria parasite exhibit strikingly diverse movement patterns, likely reflecting the varied needs to achieve successful invasion. Here, we describe a Tool for Automated Sporozoite Tracking (ToAST) that allows the rapid simultaneous analysis of several hundred motile Plasmodium sporozoites, the stage of the malaria parasite transmitted by the mosquito. ToAST reliably categorizes different modes of sporozoite movement and can be used for both tracking changes in movement patterns and comparing overall movement parameters, such as average speed or the persistence of sporozoites undergoing a certain type of movement. This allows the comparison of potentially small differences between distinct parasite populations and will enable screening of drug libraries to find inhibitors of sporozoite motility. Using ToAST, we find that isolated sporozoites change their movement patterns towards productive motility during the first week after infection of mosquito salivary glands.
Commercially viable resolution of ibuprofen
Authors: Chávez‐Flores David , Salvador James M.
Published: May 2009

Ibuprofen belongs to the non‐steroidal anti‐inflammatory drug (NSAID) family known as profens. Studies demonstrate that (S‐ibuprofen is 160 times more potent than (R‐ibuprofen in vitro, while the accumulation of (R‐ibuprofen can cause serious side effects such as gastrointestinal pain. Candida rugosa lipase was used to enantioselectively esterify racemic ibuprofen with decan‐1‐ol and butan‐1‐ol in cyclohexane with an enantiomeric ratio (E) of 130 and 46, respectively, in up to 46% conversion. Separation by bulb‐to‐bulb distillation of (R)‐ibuprofen and unreacted alcohol from the corresponding (S)‐alkyl ibuprofen ester was possible for the decyl but not the butyl case. The enantioselective hydrolysis of (S)‐alkyl ibuprofen esters with the same biocatalyst in aqueous phosphate buffer was twice as slow for the decyl alcohol versus the butyl example. The combined environmentally friendly enantioselective esterification and hydrolysis of ibuprofen insured the isolation of (S)‐ibuprofen with a greater than 99% enantiomeric excess.
Differentiation rather than aging of muscle stem cells abolishes their telomerase activity
Authors: O'Connor Matthew S. , Carlson Morgan E. , Conboy Irina M.
Published: May 2009

A general feature of stem cells is the ability to routinely proliferate to build, maintain, and repair organ systems. Accordingly, embryonic and germline, as well as some adult stem cells, produce the telomerase enzyme at various levels of expression. Our results show that, while muscle is a largely postmitotic tissue, the muscle stem cells (satellite cells) that maintain this biological system throughout adult life do indeed display robust telomerase activity. Conversely, primary myoblasts (the immediate progeny of satellite cells) quickly and dramatically downregulate telomerase activity. This work thus suggests that satellite cells, and early transient myoblasts, may be more promising therapeutic candidates for regenerative medicine than traditionally utilized myoblast cultures. Muscle atrophy accompanies human aging, and satellite cells endogenous to aged muscle can be triggered to regenerate old tissue by exogenous molecular cues. Therefore, we also examined whether these aged muscle stem cells would produce tissue that is “young” with respect to telomere maintenance. Interestingly, this work shows that the telomerase activity in muscle stem cells is largely retained into old age wintin inbred “long” telomere mice and in wild‐derived short telomere mouse strains, and that age‐specific telomere shortening is undetectable in the old differentiated muscle fibers of either strain. Summarily, this work establishes that young and old muscle stem cells, but not necessarily their progeny, myoblasts, are likely to produce tissue with normal telomere maintenance when used in molecular and regenerative medicine approaches for tissue repair. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Lowering oxygen tension enhances the differentiation of mouse embryonic stem cells into neuronal cells
Authors: Mondragon‐Teran Paul , Lye Gary J. , Veraitch Farlan S.
Published: May 2009

Embryonic stem cells (ESC) are capable of proliferating indefinitely in vitro whilst retaining their ability to differentiate into cells of every adult lineage. Efficient, high yield processes, which direct differentiation of ESC to specific lineages, will underpin the development of cost‐effective drug screening and cell therapy products. The aim of this study was to investigate whether laboratory oxygen tension currently used for the neuronal differentiation of ESC was suboptimal resulting in inefficient process yields. An adherent monolayer protocol for the neuronal differentiation of mouse ESC (mESC) was performed in oxygen controlled chambers using a chemically defined media over an 8 day period of culture. When exposed to oxygen tensions more appropriate to in vivo neuronal development (2% O2), there was a 34‐fold increase in the yield of viable cells from the differentiation process. Low oxygen tension inhibited cell death during an early phase (48 to 96 h) and toward the end (120 to 192 h) of the process. The percentage of cells expressing neuronal markers was determined by flow cytometry, revealing a small rise in the βIII tubulin and a threefold increase in the MAP2 populations at 2% O2. The total increase in the yield of viable cells expressing neuronal markers was shown to be 55‐fold for βIII tubulin and 114‐fold for MAP2. In conclusion, this study revealed that low oxygen tension can be used to enhance the yield of neuronal cells derived from ESCs and has implications for the development of efficient, cost‐effective production processes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
A robust method for the joint estimation of yield coefficients and kinetic parameters in bioprocess models
Authors: Vastemans V. , Rooman M. , Bogaerts Ph.
Published: May 2009

Bioprocess model structures that require nonlinear parameter estimation, thus initialization values, are often subject to poor identification performances because of the uncertainty on those initialization values. Under some conditions on the model structure, it is possible to partially circumvent this problem by an appropriate decoupling of the linear part of the model from the nonlinear part of it. This article provides a procedure to be followed when these structural conditions are not satisfied. An original method for decoupling two sets of parameters, namely, kinetic parameters from maximum growth, production, decay rates, and yield coefficients, is presented. It exhibits the advantage of requiring only initialization of the first subset of parameters. In comparison with a classical nonlinear estimation procedure, in which all the parameters are freed, results show enhanced robustness of model identification with regard to parameter initialization errors. This is illustrated by means of three simulation case studies: a fed‐batch Human Embryo Kidney cell cultivation process using a macroscopic reaction scheme description, a process of cyclodextrin‐glucanotransferase production by Bacillus circulans, and a process of simultaneous starch saccharification and glucose fermentation to lactic acid by Lactobacillus delbrückii, both based on a Luedeking‐Piret model structure. Additionally, perspectives of the presented procedure in the context of systematic bioprocess modeling are promising. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Adaptive remodeling of hypoplastic hemodialysis fistulas salvaged with angioplasty
Authors: Bittl John A. , von Mering Gregory O. , Feldman Robert L.
Published: May 2009

Objectives: The aim of this study was to determine whether immature hemodialysis fistulas undergo flow‐induced adaptive remodeling after successful percutaneous angioplasty. Background: Approximately 50% of radiocephalic fistulas remain immature after surgery and cannot be used for hemodialysis. Small fistulas with anastomotic inflow stenoses may undergo salvage angioplasty, but the time course of outward remodeling after successful treatment has not been defined. Methods: Thirty‐two of 39 patients (82%) with inaccessible, hypoplastic radiocephalic fistulas underwent attempted salvage angioplasty of inflow stenoses involving the arteriovenous anastomoses. Twenty patients experienced salvage of their fistulas and successfully underwent hemodialysis (51%). Results: Eleven patients had serial angiographic procedures, which allowed paired sequential quantitative angiographic measurements of the fistulas to be made during a median follow‐up of 200 days (range 5–2,298 days). Fistula diameters increased from 4.5 ± 1.3 mm to 8.0 ± 2.5 mm (mean ± S.D.). The mean growth of the fistulas was 1.0 ± 0.9 mm per year. Conclusions: The mechanism of adaptive remodeling transforms nonmaturing hypoplastic autogenous fistulas into functioning accessible dialysis accesses after successful percutaneous transluminal angioplasty of inflow anastomotic stenoses. © 2009 Wiley‐Liss, Inc.
Catheter‐based closure of atrial septal defects in the oval fossa with the Amplatzer® device in patients in their first or second year of life
Authors: Fischer G. , Smevik B. , Kramer H.H. , Bjørnstad P.G.
Published: May 2009

Objective: To assess feasibility, safety, and efficacy of the use of Amplatzer® occluders in closure of atrial septal defects (ASD) in children in the first 2 years of life. Background: Although scattered reports on such closure have been published, no agreement consists on the policy. Methods: In 654 patients of all ages, closure was achieved in 632 (96.6%). Data were analyzed retrospectively in all 71 children where an attempt had been made to close the ASD before their second birthday. Results: Median age and body weight were 17.2 months (range 3.9–23.8) and 10.0 kg (range 3.8–14.5), respectively. Median fluoroscopy time was 13.6 min and median device size 15 mm. Successful closure was achieved in 68 children (95.8%). Three times the procedure was aborted: in one, the device repeatedly straddled the septum; in the other two, a small left atrium restricted the movement of the left‐sided disc. One device embolized and was reimplanted after retrieval. One infant with multiple disorders died 6 days after closure from acute sepsis probably unrelated to the procedure. No other complications occurred. Only trivial shunts closing with time were registered during follow‐up. Symptomatic patients profited markedly from closure. Conclusion: The results and complications of ASD closure with the Amplatzer® device in patients in their first 2 years of life compare favorably with procedures in older patients, provided that the size of the septum and the dimensions in the left atrium are taken into consideration when selecting the size of the device. © 2009 Wiley‐Liss, Inc.
Impact of day versus night as intervention time on the outcomes of primary angioplasty for acute myocardial infarction
Authors: Uyarel Huseyin , Ergelen Mehmet , Akkaya Emre , Ayhan Erkan , Demirci Deniz , Gul Mehmet , Isık Turgay , Cicek Gokhan , Gunaydın Zeki Yuksel , Ugur Murat , Demirci Duygu Ersan , Turkkan Ceyhan , Erer Hatice Betul , Ozturk Recep , Yekeler Ibrahim
Published: May 2009

Background: Conflicting datas exist regarding the outcomes of primary percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI) when the intervention is performed during night hours. Methods and Results: 2,644 consecutive patients with STEMI (mean age 56.7 ± 11.9, years, 2,188 male) undergoing primary PCI between October 2003 and March 2008 were retrospectively enrolled into this study (single high‐volume center: >3,000 PCIs/year). Day time was defined according to intervention between 08:00 am and 06:00 pm and night as intervention time between 06:00 pm and 08:00 am. 1,141 patients (43.2%) were treated during the day and 1,503 (56.8%) at night. The baseline characteristics of both groups were similar except for more frequent hypertension (42.6 vs. 36.5%; P = 0.002), women (19.7 vs. 15.4%; P = 0.003), and old (≥75y) patients (9.6 vs. 7.4; P = 0.046) in the day time group. Compared with those treated during night time, day time patients had longer angina‐reperfusion times (mean, 205 vs. 188 minutes, P = 0.016). Door‐to‐balloon times were similar (P = 0.87), and less than 90 minutes in both groups. There were no differences concerning clinical events and PCI success between the two groups. Hospital mortality was 6.1% during the day and 5.2% during the night (OR 0.98, 95% CI 0.7–1.36; P = 0.89). The median follow‐up time was 21 months. The Kaplan‐Meier survival plot for long‐term cardiovascular death was not different for both groups (P = 0.78). In‐hospital and long‐term cardiovascular mortality was also similar in shock and nonshock subgroups. Conclusions: Primary PCI can be performed safely during the night at a high‐volume PCI center with suitable and effective organization of cardiology department and catheterisation laboratory with 24 hours per day, 7 days per week onsite staffing. © 2009 Wiley‐Liss, Inc.
Comparison of the angiographic myocardial blush grade with delayed‐enhanced cardiac magnetic resonance for the assessment of microvascular obstruction in acute myocardial infarctions
Authors: Vicente J. , Mewton N. , Croisille P. , Staat P. , Bonnefoy‐Cudraz E. , Ovize M. , Revel, D.
Published: May 2009

Background: Both myocardial blush grade (MBG) and cardiac magnetic resonance (CMR) are imaging tools that can assess myocardial reperfusion after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Objectives: We studied the relation between MBG and gadolinium‐enhanced CMR for the assessment of microvascular obstruction (MVO) in patients with acute ST‐elevated myocardial infarction (STEMI) treated by primary PCI. Material and Methods: MBG was assessed in 39 patients with initial TIMI 0 STEMI successfully treated by PCI, resulting in TIMI 3 flow grade and complete ST‐segment resolution. These MBG values were related to MVO determined by CMR, performed between 2 and 7 days after PCI. Left ventricular (LV) volumes were determined at baseline and at 6‐month follow‐up. Results: No statistical relation was found between MBG and MVO extent at CMR (P = 0.63). Regarding MBG 0 and 1 as a sign of MVO, the sensitivity and specificity of these scores were 53.8 and 75%, respectively. In this study, CMR determined MVO was the only significant LV remodeling predicting factor (β = 31.8; P = 0.002), whatever the MBG status was. Conclusion: MBG underestimates MVO after an optimal revascularization in AMI compared with CMR. This study suggests the superior accuracy of delayed‐enhanced magnetic resonance over MBG for the assessment of myocardial reperfusion injury that is needed in clinical trials, where the principal endpoint is the reduction of infarct size and MVO. © 2009 Wiley‐Liss, Inc.
Telescoping catheter technique for enlarged aortas
Authors: Anantharaman Rajaram , Obaid Daniel , Chase Alexander
Published: May 2009

Selective coronary angiography in severely dilated ascending aorta is technically challenging and sometimes impossible. The Terumo “five‐in‐six” system uses an extra long 5Fr guide catheter in a standard 6Fr guide catheter, so that the tip of the 5Fr guide catheter protrudes beyond the tip of the 6Fr catheter allowing an extra reach. This system has been used successfully to advance balloon catheters across chronic total occlusions (Takahashi et al, Catheter Cardiovasc Interv 2004;63:452–456) and stent delivery beyond proximal obstruction point (Mamas et al, Catheter Cardiovasc Interv 2008;71:358–363). We describe the successful use of this system in an atraumatic manner for selective coronary angiography in a patient with a severely dilated ascending aorta. © 2009 Wiley‐Liss, Inc.
The Role of Water in Platinum‐Catalyzed Cycloisomerization of 1,6‐Enynes: A Combined Experimental and Theoretical Gas Phase Study
Authors: Baumgarten Sigrid , Lesage Denis , Gandon Vincent , Goddard Jean‐Philippe , Malacria Max , Tabet Jean‐Claude , Gimbert Yves , Fensterbank Louis
Published: May 2009

PtII‐catalyzed cycloisomerization of a 1,6‐enyne proceeds quickly in CHCl3 at room temperature, and also in the gas phase. However, calculations predict a slow reaction, because of the formation of a very stable chelate that undergoes oxidative cyclization at a high energy cost. The electrophilic activation of the alkyne followed by nucleophilic attack of the double bond to generate a cyclopropyl carbene would lead to a faster reaction, but the decomplexation of the double bond to generate an unsaturated platinum species is also energetically disfavored. However, decomplexation can be envisaged if an adventitious molecule of water enters the coordination sphere of the metal. This crucial role of water in PtII‐catalyzed cycloisomerization of enynes, initially sensed some years ago (Echavarren et al., J. Am. Chem. Soc. 2001, 123, 10511) is now supported by mass spectrometry studies.