bluuebunny/crossref_metadata_2025 huggingface dataset:
Presentation of Primary Adrenal Insufficiency in Childhood
Authors: Hsieh Susan , White Perrin C.
Published: April 2011

Context:

Primary adrenal insufficiency is usually diagnosed in infancy or adulthood, and cases presenting in childhood have not been systematically reviewed.

Objective:

Our objective was to determine etiologies, signs, and symptoms of primary adrenal insufficiency presenting in childhood.

Design and Setting:

We conducted a retrospective chart review at a tertiary-care pediatric hospital.

Patients:

Patients were children with corticoadrenal insufficiency, glucocorticoid deficiency, or mineralocorticoid deficiency.

Results:

Seventy-seven cases were identified in 1999–2010. Thirty-five had congenital adrenal hyperplasia (CAH) and were not reviewed further. Forty-two patients (20 diagnosed at our institution) had primary adrenal insufficiency. These had etiologies as follows: autoimmune (18), autoimmune polyendocrinopathy syndrome (an additional five), ACTH resistance (four), adrenoleukodystrophy (three), adrenal hypoplasia congenita (two), adrenal hemorrhage (two), IMAGe syndrome (one), and idiopathic (two). Of 20 patients diagnosed at our institution, two were being monitored when adrenal insufficiency developed and were not included in the analysis of presenting signs and symptoms: 13 of 18 patients were hypotensive; 12 of 18 had documented hyperpigmentation. Hyponatremia (<135 mEq/liter) occurred in 16 of 18. However, hyperkalemia (>5.0 mEq/liter) was noted in only nine. Hypoglycemia and ketosis were documented in four of 15 and four of six patients in whom it was sought, respectively. Fifteen patients underwent cosyntropin stimulation testing with median baseline and stimulated cortisol of 1.1 and 1.2 μg/dl, respectively. ACTH and renin were markedly elevated in all patients.

Conclusions:

Hyperkalemia is not a consistent presenting sign of primary adrenal insufficiency in childhood, and its absence cannot rule out this condition. A combination of chronic or subacute clinical symptoms, hypotension, and hyponatremia should raise suspicion of adrenal insufficiency.
The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans
Authors: Huang Xinxin , Zhang Hui , Zhang Hong
Published: April 2011

Like other biological processes, aging is regulated by genetic pathways. However, it remains largely unknown whether aging is determined by an innate programmed timing mechanism and, if so, how this timer is linked to the mechanisms that control developmental timing. Here, we demonstrate that sea-2, which encodes a zinc-finger protein, controls developmental timing in C. elegans larvae by regulating expression of the heterochronic gene lin-28 at the post-transcriptional level. lin-28 is also essential for the autosomal signal element (ASE) function of sea-2 in X:A signal assessment. We also show that sea-2 modulates aging in adulthood. Loss of function of sea-2 slows the aging process and extends the adult lifespan in a DAF-16/FOXO-dependent manner. Mutation of sea-2 promotes nuclear translocation of DAF-16 and subsequent activation of daf-16 targets. We further demonstrate that insulin/IGF-1 signaling functions in the larval heterochronic circuit. Loss of function of the insulin/IGF-1 receptor gene daf-2, which extends lifespan, also greatly enhances the retarded heterochronic defects in sea-2 mutants. Regulation of developmental timing by daf-2 requires daf-16 activity. Our study provides evidence for intricate interplay between the heterochronic circuit that controls developmental timing in larvae and the timing mechanism that modulates aging in adults.
Molybdenum Cluster Halide Compound Mo6Cl12(OH2)2 with Six-Handed Linkage Hydrogen Bonding
Authors: Inumaru Kei , Anzai Atsushi , Kikudome Takashi , Harada Momoko , Sakai Hiroyuki , Ide Yusuke , Sano Tsuneji , Yamanaka Shoji
Published: April 2011

A hexanuclear Mo cluster compound Mo6Cl12(OH2)2 was synthesized for the first time and its crystal structure was analyzed by powder X-ray diffraction and Rietveld analysis. The initial structure model for the Rietveld analysis was developed by a cut and try method of manipulating the hexanuclear molecule(s) in the unit cell using a computer modeling program. In this paper the characteristic network structure of hydrogen bonding is discussed. In the refined structure (I4/m, Z = 2, a = 0.89869(3) nm, c = 1.14471(3) nm), the Mo6Cl12(OH2)2 molecules are connected to form a three-dimensional network by hydrogen-bonding of the aquo ligands. This is a newly reported compound and is isostructural to Mo6Br12(OH2)2 in an earlier report (L. J. Guggenberger et al., Inorg. Chem.1969, 8, 2041) which focused on the skeletal structure of the molecule. The Mo6Cl12(OH2)2 molecule has four terminal Cl atoms at equatorial positions and two aquo ligands at axial positions. The four terminal Cl atoms from four different molecules and two aquo ligands from two different molecules formed a linkage to connect the six molecules via H-bonding, where the two aquo ligands engaged with each other. Infrared absorption in the OH stretching region gave sharp peaks at 3159 and 3235 cm−1, of which the low wavenumbers indicate strong hydrogen bonding of the water molecules. 1H MAS NMR gave a signal at 6.8 ppm as the major species accompanied by well-resolved spinning side bands, indicating that the large cluster molecules separate the water molecules to weaken the dipole–dipole interaction between the protons. The flexible hydrogen-bonding linkages adopt angles such that the cluster molecules contact each other and form the densely packed crystal structure. This compound highlights an example in which molecules at nanometer scale have multisites for bonding that form a unique network structure.
Design and Synthesis of Fluorescent Probe for Polyhistidine Tag Using Macrocyclic Nickel(II) Complex and Fluorescein Conjugate
Authors: Taki Masayasu , Asahi Fumiyoshi , Hirayama Tasuku , Yamamoto Yukio
Published: April 2011

We report a newly designed polyhistidine tag (His-tag) targeting fluorescent probe, NiLODCF, which we synthesized based on the fluorophore displacement mechanism. A macrocyclic nickel(II) complex (NiLO) was employed as a novel binding site for a His-tag motif, and we chose dichlorofluorescein (DCF) (=2′,7′-dichloro-3′,6′-dihydroxyspiro[isobenzofuran-1(3H),9′-(9H)xanthen]-3-one) as the fluorophore. A hypochromic shift of NiLODCF from the metal-unbound form (LODCF) in the absorption spectrum suggested that the phenolic oxygen atom of DCF interacted directly with the NiLO complex, resulting in efficient fluorescence quenching (Φ = 0.084) in a neutral aqueous solution. When a model peptide having a hexahistidine sequence (H6Y1: YHHHHHH) was added to the solution of NiLODCF, a significant fluorescence enhancement in the emission (Φ = 0.60) was observed. The stoichiometry of the ternary complex between NiLODCF and H6Y1 was 1:1. The fluorescence intensity increased as the concentration of H6Y1 increased, and the dissociation constant (Kd) was determined to be 24 ± 1 µM, consistent with that for the Ni–NTA complex and His6-fused proteins (Kd = 1–20 µM). These results indicate that macrocyclic NiLO can serve as a novel binding site for the polyhistidine sequence and that NiLODCF would be applicable to a switchable fluorescent probe for such His-tagged proteins.
AFM Observation of Stimuli-Responsive Stretching Behavior for Spirobenzopyran/Crown-Ether Copolymer
Authors: Kado Shinpei , Uehara Kunika , Nakahara Yoshio , Kimura Keiichi
Published: April 2011

We have observed stretching behavior of a stimuli-responsive polymer chain bearing two functional groups, spirobenzopyran (SP) and crown ether (CR), at the side chain (SP/CR copolymer) by atomic force microscopy (AFM). The spirobenzopyran side chain can undergo photoisomerization from its electrically neutral spiropyran form to zwitterionic merocyanine by UV irradiation. The crown ether side chain can complex with metal ions. These reactions in the side chains would cause changes in their geometric structure and/or physical properties, resulting in the enhanced bifunctionality of SP/CR copolymer based on their stimuli-responsive ability. In this study, SP/CR copolymer, which was adsorbed on mica substrate, was stretched by AFM tip, when external stimuli (i.e., photoirradiation or metal ion addition) were applied. The force–extension curves of SP/CR copolymer were then analyzed by curve fitting based on a theoretical model of polymer chain elasticity to elucidate the external-stimuli effect on the polymer stretching behavior at the single molecule level.
Highly Efficient Photoinduced Electron Transfer in a Novel Tetrakis(tetraphenylporphyrinatozinc)/Perylenetetracarboxidiimide Array and Its Application to a Photovoltaic Device
Authors: Wang Fuling , Tang Jianguo , Liu Jixian , Wang Yao , Wang Rui , Niu Lin , Huang Linjun , Huang Zhen
Published: April 2011

A novel donor–acceptor array consisting of four 5-(p-substituted phenyl)-10,15,20-triphenylporphyrinatozinc (POR) complexes attached to the 1,6,7,12-positions of perylene-3,4:9,10-tetracarboxidiimide (PDI) was synthesized and characterized. HOMO and LUMO values of the array were aquired by cyclic voltammetry. Photophysical properties were studied by steady-state UV–vis and fluorescence spectroscopy. The results showed that this compound absorbs strongly from 300 to 700 nm, making it an ideal system to harvest polychromatic light. After selective excitation of the POR moiety or PDI moiety, an almost complete fluorescence quenching was observed, indicating that highly efficient photoinduced electron transfer occurs in this array. The predominant quenching process for PDI–POR4 array is electron-transfer yielding POR4+–PDI−. The self-assemblies of this molecular in polar and nonpolar solvents were investigated. Intermolecular π–π interaction in cooperation with the van der Waals interaction between POR and PDI component leads to the formation of spherical nanoparticles and ribbon-like morphological structures in methanol and n-hexane, respectively. Photoelectrochemical studies exhibited prompt and steady photocurrent photovoltage response. Moreover, photovoltaic measurement on this array reveals efficient light energy conversion properties, such as a fill factor of 0.42. These results are of particular relevance for photovoltaic nanodevices and solar energy conversion applications.
Highly Regioselective Double Hydrothiolation of Terminal Acetylenes with Thiols Catalyzed by Palladium Diacetate
Authors: Mitamura Takenori , Daitou Masayuki , Nomoto Akihiro , Ogawa Akiya
Published: April 2011

Treatment of terminal acetylenes 1 with two equivalents of thiols 2 in the presence of Pd(OAc)2 catalyst and H2O causes regioselective double hydrothiolation of 1, leading to the corresponding dithioketals 3 in moderate to good yields.
Temperature Dependence of Structure and Dynamic Properties of Oleic Acid γ and α Phases Studied by FTIR Spectroscopy
Authors: Pi Fuwei , Kaneko Fumitoshi , Shinzawa Hideyuki , Suzuki Masao , Iwahashi Makio , Ozaki Yukihiro
Published: April 2011

The temperature dependence of the structure and dynamic properties of oleic acid γ and α phases has been studied by FTIR spectroscopy. By observing the characteristic bands due to the cis-olefin, carboxy, and methyl groups as well as the CH2 rocking–CH2 twisting progression bands, the structural change of each portion of oleic acid corresponding to the γ → α phase transition has been elucidated in detail. For the analysis of the progression bands, the simple-coupled oscillator model has been employed. It has been found that an enhanced mobility of the methyl terminal occurs as the temperature increases in the γ phase, which operates as pre-disordering prior to the sudden and drastic structural changes at the γ → α phase-transition point. Meanwhile, the carboxy group undergoes a gradual and localized structural change in the γ phase. The structural change of carboxy group in the γ phase is likely to be caused by an equilibrium shift between two different states of dimerized carboxy groups. Drastic structural changes at the phase-transition point primarily take place in the portion from the cis-olefin group to the methyl group, which is fully consistent with previous studies by X-ray and Raman spectroscopy. It is clearly shown that the CH2 rocking–CH2 twisting progression bands can be employed as a probe for sensing the states of the methyl-sided and carboxy-sided chains separately, which is applicable for the structural studies of a wide range of fats and lipids systems containing unsaturated acyl chains.
Training and development for radiographers’ extended roles: a case of ad hoc implementation
Authors: Miller Linda , Price Richard , Vosper Martin
Published: April 2011

This paper examines the quality and consistency of postregistration training and development for extended role activities undertaken by radiographers. Although the undergraduate curriculum has changed to some extent to accommodate expanded role requirements, much of the training does not, and cannot, take place until radiographers are qualified and are in post. While undergraduate programmes in radiography must be approved by the Health Professions Council, and are normally accredited by the radiographers’ professional body, the Society and College of Radiographers, much of the training provided for extended role activities is ad hoc and neither validated nor accredited. This paper reports the outcomes of a survey of imaging service managers and follow-up interviews with imaging service managers. Managers’ views of the quality of training and development provided for extended role activities and their approaches to recruiting radiographers with extended role experience, were explored. The research identified concerns among managers regarding the training currently available and indicated potential career disadvantages for radiographers receiving unaccredited development. There is also some evidence of wastage arising from the duplication of training by trusts because of uncertainty about the standards of competence instilled by programmes.
Sandwich Immunoassay for Soluble Glycoprotein VI in Patients with Symptomatic Coronary Artery Disease
Authors: Bigalke Boris , Pötz Oliver , Kremmer Elisabeth , Geisler Tobias , Seizer Peter , Puntmann Valentina O , Phinikaridou Alkystis , Chiribiri Amedeo , Nagel Eike , Botnar Rene M , Joos Thomas , Gawaz Meinrad
Published: April 2011

BACKGROUND

Platelet glycoprotein VI (pGPVI) expression is increased in acute coronary syndrome (ACS), reflecting platelet activation. There is no reliable method available to measure pGPVI. Our aim was to develop a bead-based sandwich immunoassay to measure soluble GPVI (sGPVI).

METHODS

Based on antibodies for sGPVI developed earlier, we established and validated a bead-based sandwich immunoassay in 2438 consecutive patients with stable angina pectoris (SAP; n = 1371), non–ST-elevation myocardial infarction (NSTEMI; n = 724), and ST-elevation MI (STEMI; n = 343). In a subgroup (n = 1011), we measured surface expression of pGPVI using flow cytometry.

RESULTS

The assay revealed a working range of 8–500 ng/L. Intra- and interassay imprecision was <7% and <14%, respectively. Patients with NSTEMI and STEMI showed significantly lower mean sGPVI concentrations than patients with SAP [mean (SD), 8.4 (3.6) μg/L and 8.6 (4.1) μg/L vs 9.8 (4.8) μg/L; P = 0.002], whereas subgroup analysis revealed significantly enhanced pGPVI in NSTEMI (n = 276) and STEMI (n = 80) patients compared with SAP (n = 655) [mean fluorescence intensity (SD), 21.2 (8.1) and 19.8 (6.8) vs 18.5 (7.7); P = 0.002 and P = 0.018]. pGPVI and sGPVI were inversely correlated (r = −0.076; P = 0.023). Area under the ROC curve was 0.716, 95% CI 0.681–0.751, for sGPVI, distinguishing patients with SAP from those with ACS, and was superior (P = 0.044) to the curve of subgroup analysis for pGPVI (0.624, 95% CI 0.586–0.662). sGPVI (P = 0.023) and pGPVI (P = 0.028) had better association with the development of ACS than troponin I (P = 0.055) in the very early stage of disease, based on logistic regression analysis.

CONCLUSIONS

This sandwich immunoassay reliably measures sGPVI and may help to identify patients with ACS earlier than other laboratory markers.
Human Pro–B-Type Natriuretic Peptide Is Processed in the Circulation in a Rat Model
Authors: Semenov Alexander G , Seferian Karina R , Tamm Natalia N , Artem'eva Marina M , Postnikov Alexander B , Bereznikova Anastasiya V , Kara Andrey N , Medvedeva Natalia A , Katrukha Alexey G
Published: April 2011

BACKGROUND

The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides.

METHODS

We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP.

RESULTS

ProBNP was effectively processed in the circulation into BNP (1–32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively.

CONCLUSIONS

In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.
Deutsche Modalverben und deren Übersetzung ins Englische: mögen
Authors: Schmidt Christiane
Published: April 2011

This paper explores the possibilities of translating German modals into English. One objective is to provide translators with a guide on translating modals by making them aware of the wide diversity of meanings and nuances of German modals and by helping them find the best translation possible for a given context. This guide is intended to be a dictionary for translators that is more parole-orientated and user-friendly than standard dictionaries. At the same time the paper also presents a yet undiscussed linguistic approach to analyzing one aspect of two languages in the context of translations. The excerpt starts out with theoretical aspects on the topic and continues with displaying the results of the analysis of one German modal, namely
Korpuslinguistische Analysen zu den Plenardebatten des Deutschen Bundestages zwischen 2005 und 2009
Authors: Bopp Sebastian
Published: April 2011

Political linguistics is underrepresented in contemporary linguistics research for different reasons. In this article, the author outlines how discourse theory and computational linguistics can be applied to political linguistics to make it more relevant again to both linguistics community and the public. To that end, findings concerning the language use of the political parties in the German Bundestag between 2005 and 2009 are presented.
Deutsche und französische Suchmaschinenwerbung: eine linguistisch-kontrastive Studie zu Sponsorenlinks
Authors: Prieto Raul Sanchez
Published: April 2011

This article deals with French and German advertisements on web search engines from a linguistic point of view. It attempts to shed some light on the lexical and morphosyntactic structure of the displayed advertisements by analyzing a corpus of 329 Google ads related to the tourism industry. The most relevant findings concern the higher percentage of foreign words detected in the German ads and the very different phrase structure of the advertisement's body of text.
Glossar Windenergie EN-DE / DE-EN 3. Teil
Authors: Proske Christiane
Published: April 2011

In Zeiten des Kyoto-Protokolls, des beschlossenen deutschen Atomausstiegs und des weltweit wachsenden Hungers nach Energie stellt sich die Frage, wie der Energiebedarf zukünftiger Generationen gedeckt werden kann, ohne dass wir unsere Umwelt weiter belasten. Erneuerbare Energien erscheinen vor diesem Hintergrund als Wunderwaffe, die von Umweltschützern gepriesen und Politikern gefördert wird. Der Windenergie kommt dabei in Deutschland eine besondere Rolle zu. Laut Bundesverband WindEnergie (BWE) deckte sie 2008 etwa sieben Prozent des deutschen Stromverbrauchs und produzierte damit die Hälfte des deutschen „Ökostroms“. Doch wie genau verwandelt das Wunderwerk Windenergieanlage die kinetische Energie des Windes in elektrischen Strom? Und wie wird gewährleistet, dass dieser Strom trotz schwankender Windgeschwindigkeiten von gleichbleibender Qualität ist? Das sind nur zwei von vielen spannenden Fragen aus dem Bereich der Windenergie, denen die im Oktober 2008 am Institut für Linguistik und Translatologie Leipzig eingereichte Diplomarbeit „Windenergieanlagen. Eine terminologische Untersuchung im Deutschen und Englischen unter besonderer Berücksichtigung moderner Antriebskonzepte.“, die in Zusammenarbeit mit der Leipziger Terrawatt Planungsgesellschaft mbH erstellt wurde, nachgeht. Das nachfolgende Glossar ist ein wesentlicher Teil dieser Diplomarbeit und soll sowohl Translatoren als auch Fachleuten aus der Windenergiebranche als zuverlässige Referenz in terminologischen Fragen dienen.
EphB Controls NMDA Receptor Function and Synaptic Targeting in a Subunit-Specific Manner
Authors: Nolt Mark J. , Lin Ying , Hruska Martin , Murphy Jessica , Sheffler-Colins Sean I. , Kayser Matthew S. , Passer Joel , Bennett Michael V. L. , Zukin R. Suzanne , Dalva Matthew B.
Published: April 2011

Dynamic regulation of the localization and function of NMDA receptors (NMDARs) is critical for synaptic development and function. The composition and localization of NMDAR subunits at synapses are tightly regulated and can influence the ability of individual synapses to undergo long-lasting changes in response to stimuli. Here, we examine mechanisms by which EphB2, a receptor tyrosine kinase that binds and phosphorylates NMDARs, controls NMDAR subunit localization and function at synapses. We find that, in mature neurons, EphB2 expression levels regulate the amount of NMDARs at synapses, and EphB activation decreases Ca2+-dependent desensitization of NR2B-containing NMDARs. EphBs are required for enhanced localization of NR2B-containing NMDARs at synapses of mature neurons; triple EphB knock-out mice lacking EphB1–3 exhibit homeostatic upregulation of NMDAR surface expression and loss of proper targeting to synaptic sites. These findings demonstrate that, in the mature nervous system, EphBs are key regulators of the synaptic localization of NMDARs.
Zipcode Binding Protein 1 Regulates the Development of Dendritic Arbors in Hippocampal Neurons
Authors: Perycz Malgorzata , Urbanska Anna S. , Krawczyk Pawel S. , Parobczak Kamil , Jaworski Jacek
Published: April 2011

The pattern of dendritic branching, together with the density of synapses and receptor composition, defines the electrical properties of a neuron. The development of the dendritic arbor and its additional stabilization are highly orchestrated at the molecular level and are guided by intrinsic mechanisms and extracellular information. Although protein translation is known to contribute to these processes, the role of its local component has not been fully explored. For local translation, mRNAs are transported to dendrites in their dormant form as ribonucleoparticles (RNPs). We hypothesized that disturbing spatial mRNA distribution via RNP targeting may result in severe underdevelopment of the dendritic arbor. Zipcode binding protein 1 (ZBP1) controls β-actin mRNA transport and translation in dendrites. We showed that proper cellular levels of ZBP1, its ability to engage in mRNA binding, and Src-dependent release of mRNA cargo from ZBP1 are vital for dendritic arbor development in cultured rat hippocampal neurons. Moreover, β-actin overexpression significantly alleviated the effects of ZBP1 knockdown. These results suggest that ZBP1-dependent dendritic mRNA transport contributes to proper dendritic branching.
Dendrites Have a Rapid Program of Injury-Induced Degeneration That Is Molecularly Distinct from Developmental Pruning
Authors: Tao Juan , Rolls Melissa M.
Published: April 2011

Neurons have two types of processes: axons and dendrites. Axons have an active disassembly program activated by severing. It has not been tested whether dendrites have an analogous program. We severDrosophiladendritesin vivoand find that they are cleared within 24 h. Morphologically, this clearance resembles developmental dendrite pruning and, to some extent, axon degeneration. Like axon degeneration, both injury-induced dendrite degeneration and pruning can be delayed by expression of Wld(s) or UBP2. We therefore hypothesized that they use common machinery. Surprisingly, comparison of dendrite pruning and degeneration in the same cell demonstrated that none of the specific machinery used to prune dendrites is required for injury-induced dendrite degeneration. In addition, we show that the rapid program of dendrite degeneration does not require mitochondria. Thus, dendrites do have a rapid program of degeneration, as do axons, but this program does not require the machinery used during developmental pruning.
Acute Inhibition of 11β-Hydroxysteroid Dehydrogenase Type-1 Improves Memory in Rodent Models of Cognition
Authors: Mohler Eric G. , Browman Kaitlin E. , Roderwald Victoria A. , Cronin Elizabeth A. , Markosyan Stella , Scott Bitner R. , Strakhova Marina I. , Drescher Karla U. , Hornberger Wilfried , Rohde Jeffrey J. , Brune Michael E. , Jacobson Peer B. , Rueter Lynne E.
Published: April 2011

Mounting evidence suggests excessive glucocorticoid activity may contribute to Alzheimer's disease (AD) and age-associated memory impairment. 11β-hydroxysteroid dehydrogenase type-1 (HSD1) regulates conversion of glucocorticoids from inactive to active forms. HSD1 knock-out mice have improved cognition, and the nonselective inhibitor carbenoxolone improved verbal memory in elderly men. Together, these data suggest that HSD1 inhibition may be a potential therapy for cognitive deficits, such as those associated with AD. To investigate this, we characterized two novel and selective HSD1 inhibitors, A-918446 and A-801195. Learning, memory consolidation, and recall were evaluated in mouse 24 h inhibitory avoidance. Inhibition of brain cortisol production and phosphorylation of cAMP response element-binding protein (CREB), a transcription factor involved in cognition, were also examined. Rats were tested in a short-term memory model, social recognition, and in a separate group cortical and hippocampal acetylcholine release was measured viain vivomicrodialysis. Acute treatment with A-801195 (10–30 mg/kg) or A-918446 (3–30 mg/kg) inhibited cortisol production in theex vivoassay by ∼35–90%. Acute treatment with A-918446 improved memory consolidation and recall in inhibitory avoidance and increased CREB phosphorylation in the cingulate cortex. Acute treatment with A-801195 significantly improved short-term memory in rat social recognition that was not likely due to alterations of the cholinergic system, as acetylcholine release was not increased in a separate set of rats. These studies suggest that selective HSD1 inhibitors work through a novel, noncholinergic mechanism to facilitate cognitive processing.
DrosophilaMmp2 Regulates the Matrix Molecule Faulty Attraction (Frac) to Promote Motor Axon Targeting inDrosophila
Authors: Miller Crystal M. , Liu Nan , Page-McCaw Andrea , Broihier Heather T.
Published: April 2011

Matrix metalloproteinases (MMPs) are widely hypothesized to regulate signaling events through processing of extracellular matrix (ECM) molecules. We previously demonstrated that membrane-associated Mmp2 is expressed in exit glia and contributes to motor axon targeting. To identify possible substrates, we undertook a yeast interaction screen for Mmp2-binding proteins and identified the novel ECM protein faulty attraction (Frac). Frac encodes a multidomain extracellular protein rich in epidermal growth factor (EGF) and calcium-binding EGF domains, related to the vertebrate Fibrillin and Fibulin gene families. It is expressed in mesodermal domains flanking Mmp2-positive glia. The juxtaposition of Mmp2 and Frac proteins raises the possibility that Frac is a proteolytic target of Mmp2. Consistent with this hypothesis, levels of full-length Frac are increased in Mmp2 loss-of-function (LOF) and decreased in Mmp2 gain-of-function (GOF) embryos, indicating that Frac cleavage is Mmp2 dependent. To test whetherfracis necessary for axon targeting, we characterized guidance infracLOF mutants. Motor axons infracLOF embryos are loosely associated and project ectopically, a phenotype essentially equivalent to that ofMmp2LOF. The phenotypic similarity between enzyme and substrate mutants argues that Mmp2 activates Frac. In addition,Mmp2overexpression pathfinding phenotypes depend onfracactivity, indicating thatMmp2is genetically upstream offrac. Last, overexpression experiments suggest that Frac is unlikely to have intrinsic signaling activity, raising the possibility that an Mmp2-generated Frac fragment acts as a guidance cue cofactor. Indeed, we present genetic evidence that Frac regulates a non-canonical LIM kinase 1-dependent bone morphogenetic protein signaling pathway in motoneurons necessary for axon pathfinding during embryogenesis.
Sexually Dimorphic Shaping of Interneuron Dendrites Involves the Hunchback Transcription Factor
Authors: Goto Junpei , Mikawa Yoshitaka , Koganezawa Masayuki , Ito Hiroki , Yamamoto Daisuke
Published: April 2011

Sexual dimorphism of the brain has been well characterized anatomically inDrosophila melanogasterat the single neuron level, yet little is known about the molecular mechanism whereby cellular sex differences are generated except that the neural sex determination genefruitless (fru) plays a key role. Thefru-expressing mAL interneuron cluster is sexually dimorphic in three aspects: the number of cells composing the cluster is 5 in females and 30 in males; the ipsilateral neurite is absent in females and present in males; the contralateral neurite forms Y-shaped branches in the subesophageal ganglion in females while it ends with a simple horsetail-like structure in males. By screens in the compound eye for modifiers of roughness induced byfru+overexpression, we identified a loss-of-function allele ofhunchback(hb) to be a suppressor of this phenotype. Hb was expressed in most of thefru-expressing neurons in the pupal and adult stages. Knocking downhbin mAL MARCM (Mosaic Analysis with a Repressible Cell Marker) clones in the male brain resulted in partial demasculinization of the branching pattern of the contralateral neurites without affecting the cell number and the ipsilateral neurite formation. The present results suggest that Hb is essential for male-typical shaping of the contralateral neurites by Fru.
Previous Ethanol Experience Enhances Synaptic Plasticity of NMDA Receptors in the Ventral Tegmental Area
Authors: Bernier Brian E. , Whitaker Leslie R. , Morikawa Hitoshi
Published: April 2011

Alcohol addiction (alcoholism) is one of the most prevalent substance abuse disorders worldwide. Addiction is thought to arise, in part, from a maladaptive learning process in which enduring memories of drug experiences are formed. However, alcohol (ethanol) generally interferes with synaptic plasticity mechanisms in the CNS and thus impairs various types of learning and memory. Therefore, it is unclear how powerful memories associated with alcohol experience are formed during the development of alcoholism. Here, using brain slice electrophysiology in mice, we show that repeatedin vivoethanol exposure (2 g/kg, i.p., three times daily for 7 d) causes increased susceptibility to the induction of long-term potentiation (LTP) of NMDA receptor (NMDAR)-mediated transmission in mesolimbic dopamine neurons, a form of synaptic plasticity that may drive the learning of stimuli associated with rewards, including drugs of abuse. Enhancement of NMDAR plasticity results from an increase in the potency of inositol 1,4,5-trisphosphate (IP3) in producing facilitation of action potential-evoked Ca2+signals, which is critical for LTP induction. This increase in IP3effect, which lasts for a week but not a month after ethanol withdrawal, occurs through a protein kinase A (PKA)-dependent mechanism. Corticotropin-releasing factor, a stress-related neuropeptide implicated in alcoholism and other addictions, further amplifies the PKA-mediated increase in IP3effect in ethanol-treated mice. Finally, we found that ethanol-treated mice display enhanced place conditioning induced by the psychostimulant cocaine. These data suggest that repeated ethanol experience may promote the formation of drug-associated memories by enhancing synaptic plasticity of NMDARs in dopamine neurons.
Dopamine D2Receptor Activity Modulates Akt Signaling and Alters GABAergic Neuron Development and Motor Behavior in Zebrafish Larvae
Authors: Souza Bruno Rezende , Romano-Silva Marco Aurelio , Tropepe Vincent
Published: April 2011

An imbalance in dopamine-mediated neurotransmission is a hallmark physiological feature of neuropsychiatric disorders, such as schizophrenia. Recent evidence demonstrates that dopamine D2receptors, which are the main target of antipsychotics, modulate the activity of the protein kinase Akt, which is known to be downregulated in the brain of patients with schizophrenia. Akt has an important role in the regulation of cellular processes that are critical for neurodevelopment, including gene transcription, cell proliferation, and neuronal migration. Thus, it is possible that during brain development, altered Akt-dependent dopamine signaling itself may lead to defects in neural circuit formation. Here, we used a zebrafish model to assess the direct impact of altered dopamine signaling on brain development and larval motor behavior. We demonstrate that D2receptor activation acutely suppresses Akt activity by decreasing the level of pAkt(Thr308) in the larval zebrafish brain. This D2-dependent reduction in Akt activity negatively regulates larval movement and is distinct from a D1-dependent pathway with opposing affects on motor behavior. In addition, we show that D2-dependent suppression of Akt activity causes a late onset change in GSK3b activity, a known downstream target of Akt signaling. Finally, altered D2receptor signaling, or direct inhibition of Akt activity, causes a significant decrease in the size of the GABAergic neuron population throughout most of the brain. Our observations suggest that D2receptor signaling suppresses Akt-GSK3b activity, which regulates GABAergic neuron development and motor behavior.
Bilateral Plasticity of Vibrissae SII Representation Induced by Classical Conditioning in Mice
Authors: Debowska Weronika , Liguz-Lecznar Monika , Kossut Malgorzata
Published: April 2011

The somatosensory cortex in mice contains primary (SI) and secondary (SII) areas, differing in somatotopic precision, topographic organization, and function. The role of SII in somatosensory processing is still poorly understood. SII is activated bilaterally during attentional tasks and is considered to play a role in tactile memory and sensorimotor integration. We measured the plasticity of SII activation after associative learning based on classical conditioning, in which unilateral stimulation of one row of vibrissae was paired with a tail shock. The training consisted of three daily 10 min sessions, during which 40 pairings were delivered. Cortical activation driven by stimulation of vibrissae was mapped with 2-[14C]deoxyglucose (2DG) autoradiography 1 d after the end of conditioning. We reported previously that the conditioning procedure resulted in unilateral enlargement of 2DG-labeled cortical representation of the “trained” row of vibrissae in SI. Here, we measured the width and intensity of the labeled region in SII. We found that both measured parameters in SII increased bilaterally. The increase was observed in cortical layers II/III and IV. Apparently, plasticity in SII is not a simple reflection of changes in SI. It may be attributable to bilateral integrative role of SII, its lesser topographical specificity, and strong involvement in attentional processing.
Double Dissociation between Hippocampal and Parahippocampal Responses to Object–Background Context and Scene Novelty
Authors: Howard Lorelei R. , Kumaran Dharshan , Ólafsdóttir Hauður F. , Spiers Hugo J.
Published: April 2011

Several recent models of medial temporal lobe (MTL) function have proposed that the parahippocampal cortex processes context information, the perirhinal cortex processes item information, and the hippocampus binds together items and contexts. While evidence for a clear functional distinction between the perirhinal cortex and other regions within the MTL has been well supported, it has been less clear whether such a dissociation exists between the hippocampus and parahippocampal cortex. In the current study, we use a novel approach applying a functional magnetic resonance imaging adaptation paradigm to address these issues. During scanning, human subjects performed an incidental target detection task while viewing trial-unique sequentially presented pairs of natural scenes, each containing a single prominent object. We observed a striking double dissociation between the hippocampus and parahippocampal cortex, with the former showing a selective sensitivity to changes in the spatial relationship between objects and their background context and the latter engaged only by scene novelty. Our findings provide compelling support for the hypothesis that rapid item–context binding is a function of the hippocampus, rather than the parahippocampal cortex, with the former acting to detect relational novelty of this nature through its function as a match–mismatch detector.
Dose-Dependent Nonlinear Effect of l-DOPA on Paired Associative Stimulation-Induced Neuroplasticity in Humans
Authors: Thirugnanasambandam Nivethida , Grundey Jessica , Paulus Walter , Nitsche Michael A.
Published: April 2011

Dopamine is one of the major neuromodulators in the CNS, which is involved in learning and memory processes. A nonlinear, inverted U-shaped dose–response curve of its effects on cognition has been observed in animal studies. The basis for this nonlinear effect might be a similar effect of dopamine on neuroplasticity. Whereas it has been shown that dopamine affects paired associative stimulation (PAS)-induced plasticity, which might reflect learning-related processes to a larger degree than other noninvasive plasticity induction protocols in the human motor cortex in principle, its dose-dependency has not been explored previously. We studied the effect of different dosages of the dopamine precursorl-DOPA on motor cortex plasticity induced by facilitatory and inhibitory PAS of the motor cortex in 12 healthy humans. They received 25, 100, or 200 mg ofl-DOPA or placebo medication combined with either excitability-enhancing or -diminishing PAS. Cortical excitability level was monitored before and for up to 2 d after plasticity induction by assessment of transcranial magnetic stimulation-induced motor-evoked potentials. Low-dosel-DOPA abolished the aftereffects of PAS and medium-dosel-DOPA prolonged facilitatory plasticity. High-dosel-DOPA reversed the excitability enhancement accomplished by facilitatory PAS to diminution. Thus, the results show a clear nonlinear effect ofl-DOPA dosage on associative plasticity, different from that on nonfocal plasticity. This might help to explain dopaminergic effect on cognition and could be relevant for understanding the pathophysiology and treatment of neuropsychiatric diseases accompanied by alterations of the dopaminergic system.
The Influence of Short-Day Photoperiods on Bone Composition of Hamsters: a Raman Spectroscopic Investigation
Authors: Shen Jing , Lerchl Alexander , Donfack Patrice , Hu Jiming , Materny Arnulf
Published: April 2011

Biological rhythms, which regulate the biological cycles of life, are of great interest in biomedicine. The effect of biological rhythms on bone is controversial at the moment. Raman spectroscopy was applied to assess the bone compositional information of hamsters under different photoperiods, designed as long day photoperiod of 16 h light and 8 h dark (LD, 16L : 8D) and short day photoperiod of 8 h light and 16 h dark (SD, 8L : 16D). After three months under such well-defined conditions, the hamsters in the two groups exhibited differences in body weight, fur color and testis size. In addition, for the first time to our knowledge bone compositional variations were observed in both mineral constituents and collagen secondary structures in hamsters conditioned under the different photoperiods. The collagen secondary structure in the SD hamsters was characterized by a higher ratio of mature intra-fibril cross-links indicating a more stable form of collagen. It is hypothesized that increased bone turnover rate and resorption led to the alteration of collagen cross-links in the SD group.
Checking and Improving Calibration of Raman Spectra using Chemometric Approaches
Authors: Dörfer Thomas , Bocklitz Thomas , Tarcea Nicolae , Schmitt Michael , Popp Jürgen
Published: April 2011

A wavenumber and intensity calibration procedure of Raman spectra by using chemometric techniques is presented. This approach allows the fine tuning of calibration parameters and routines with the final goal to eliminate setup dependent differences within experimentally recorded Raman spectra. This seems to be necessary since more and more Raman databases are needed for different analytical tasks, like identification of minerals or bacteria. Minimizing the impact of the applied experimental Raman setup on the reference (database stored) Raman spectra allows the databases to be enlarged very easily by feeding the database with Raman spectra recorded with different setups. Furthermore the chemometric analysis performance increases due to the larger number and better quality of reference spectra.
Ultrafast Charge Separation at the CdSe Quantum Dot/Methylviologen Interface: Dependence on Electron Acceptor Concentration
Authors: Dworak Lars , Wachtveitl Josef
Published: April 2011

Photoinduced charge transfer dynamics between CdSe semiconductor quantum dots (QDs) and the molecular acceptor methylviologen (MV2+) were investigated by time resolved absorption spectroscopy. Biexponential behavior of the charge separation is observed and explained by different donor states involved in the electron transfer reaction. Furthermore, we found a linear dependence of the amplitude weighted average electron transfer rate <k
ET> on the electron acceptor concentration until a methylviologen saturation limit is reached.
Reactions between Cold CH
x

+ and Slow H and H2
Authors: Gerlich Dieter , Borodi Gheorge , Luca Alfonz , Mogo Cesar , Smith Mark A.
Published: April 2011

Using the combination of a linear 22-pole ion trap (22 PT) and a coaxial beam of hydrogen atoms, H abstraction from CH
x

+ (x=1, 4 and 5) has been studied. The temperature of the trap, T
22 PT, can be varied between 10 K and 300 K. The velocity distribution of the neutral target beam can be changed by cooling the accommodator (T
ACC=10–300 K) and using the focusing features of one or two hexapole magnets. The resulting velocity distributions are characterized by time-of-flight measurements. With the same setup, reactions of mass selected stored ions with a cold effusive beam of H2 molecules have been measured with the discharge turned off. At temperatures of interstellar space, H-abstraction from CH+ is efficient. CH4
+ reacts five times faster with H than with H2 at 50 K. In contradiction to ab initio calculations and to the established proton affinity of methane, CH5
+ is slowly destroyed in collisions with H in our trap, even at 10 K. Some first results for collisions between CH
x

+ and D atoms are reported. For x=1, H–D exchange is quite efficient, even though it is in competition with the exothermic abstraction reaction. For x=4, H-abstraction, i.e. formation of HD molecules, dominates. Deuteration of CH5
+ is measured to be very slow.
Short-term continuous subcutaneous insulin infusion decreases the plasma vaspin levels in patients with type 2 diabetes mellitus concomitant with improvement in insulin sensitivity
Authors: Li Ke , Li Ling , Yang Mengliu , Liu Hua , Liu Dongfang , Yang Hao , Boden Guenther , Yang Gangyi
Published: April 2011

Objective

To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma vaspin levels in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Method

Thirty patients with severe newly diagnosed T2DM, 37 subjects with impaired glucose tolerance (IGT) and 38 gender-, age- and body mass index (BMI)-matched normal GT (NGT) controls participated in the study. The T2DM group was treated with CSII for 2 weeks. Euglycemic–hyperinsulinemic clamps were performed in 16 subjects of the T2DM group. Plasma vaspin concentrations were measured with a commercial ELISA kit. The relationship between plasma vaspin levels and metabolic parameters was also analyzed.

Results

Fasting plasma vaspin levels were higher in the T2DM group than in IGT and NGT groups (1.83±0.55 vs 0.51±0.21 vs 0.53±0.24 μg/l, P<0.05), but there was no difference between IGT and NGT groups. In T2DM patients, fasting plasma vaspin concentrations were significantly decreased after CSII treatment for 2 weeks (1.83±0.55 vs 1.19±0.57 μg/l, P<0.05), accompanied by significant amelioration of insulin sensitivity and glucose control. The changes in plasma vaspin levels were positively associated with the amelioration of insulin resistance (IR) shown by the changes in homeostasis model assessment of IR.

Conclusion

Plasma vaspin level is associated with IR and is significantly reduced following short-term CSII treatment.
Drug transporters and blood–testis barrier function
Authors: Su Linlin , Mruk Dolores D , Lee Will M , Cheng C Yan
Published: April 2011

The blood–testis barrier (BTB) creates an immunological barrier that segregates the seminiferous epithelium into the basal and apical compartment. Thus, meiosis I/II and post-meiotic germ cell development take place in a specialized microenvironment in the apical compartment behind the BTB and these events are being shielded from the host immune system. If unwanted drugs and/or chemicals enter the apical compartment from the microvessels in the interstitium via the basal compartment, efflux pumps (e.g. P-glycoprotein) located in Sertoli cells and/or spermatids can actively transport these molecules out of the apical compartment. However, the mechanism(s) by which influx pumps regulate the entry of drugs/chemicals into the apical compartment is not known. In this study, a solute carrier (SLC) transporter organic anion transporting polypeptide 3 (Oatp3, Slco1a5) was shown to be an integrated component of the N-cadherin-based adhesion complex at the BTB. However, a knockdown of Oatp3 alone or in combination with three other major Sertoli cell drug influx pumps, namely Slc22a5, Slco6b1, and Slco6c1, by RNAi using corresponding specific siRNA duplexes failed to perturb the Sertoli cell tight junction (TJ) permeability barrier function. Yet, the transport of [3H]adjudin, a potential male contraceptive that is considered a toxicant to spermatogenesis, across the BTB was impeded following the knockdown of either Oatp3 or all the four SLC transporters. In short, even though drug transporters (e.g. influx pumps) are integrated components of the adhesion protein complexes at the BTB, they are not involved in regulating the Sertoli cell TJ permeability barrier function, instead they are only involved in the transport of drugs, such as adjudin, across the immunological barrier at the BTB.