bluuebunny/crossref_metadata_2025 huggingface dataset:
An endogenous peptide isolated from the gut, NK‐lysin, stimulates insulin secretion without changes in cytosolic free Ca2+ concentration
Authors: Zaitsev Sergei V , Andersson Mats , Efanov Alexandre M , Efanova Ioulia B , Östenson Claes-Göran , Juntti-Berggren Lisa , Berggren Per-Olof , Mutt Viktor , Efendić Suad
Published: July 2002

We have recently isolated and cloned a novel endogenous peptide from pig intestine, NK‐lysin (NKL). In the present study we show that NKL (1–100 nM) potently and reversibly stimulates insulin secretion in rat pancreatic islets and in the β‐cell line HIT T15. This effect of NKL was not accompanied by changes in cytoplasmic free calcium concentration. The stimulatory activity of NKL on insulin release was also observed in permeabilized islets under Ca2+‐clamped conditions. Preincubation of HIT T15 cells with NKL for 1 h or 24 h did not influence cell viability. Possible mechanisms of insulinotropic activity of NKL are discussed.
VHS domain marks a group of proteins involved in endocytosis and vesicular trafficking
Authors: Lohi Olli , Lehto Veli-Pekka
Published: July 2002

Endocytosis is driven by a mechanism which is characterized by an orderly congregation of a large number of proteins which effectuate, first, formation of a coated vesicles, second, pinching off the vesicle and, third, regulated transport. True to the nature of many other proteins involved in multimolecular complexes, also endocytosis‐associated proteins, such as Eps15, clathrin and AP‐2, are characterized by distinct domains which mediate the protein‐protein interactions. We now report that a group of well‐established endocytosis and/or vesicular trafficking proteins possess a VHS domain, a recently described domain with an unknown function. We suggest that in these proteins VHS serves as a membrane targeting domain which by its specific features together with FYVE, SH3 and/or TAM domains, which are also present in some VHS‐containing proteins, is involved in the stage‐specific assembly of the endocytic machinery.
Alternative splicing generates multiple mRNA forms of the acetylcholine receptor γ‐subunit in rat muscle
Authors: Villarroel Alfredo
Published: July 2002

The fetal type acetylcholine receptor, composed of the αβγδ subunits, has shown a highly variable channel kinetics during postnatal development. We examine the hypothesis whether such a variability could result from multiple channel forms, differing in the N‐terminus of the γ‐subunit. RT‐PCR revealed, in addition to the full‐length mRNA, three new forms lacking exon 4. One of them in addition lacks 19 nucleotides from exon 5, predicting a complete subunit, with a 43 residues shorter N‐terminus. A third one lacking the complete exon 5 predicts a subunit without transmembrane segments. These forms, generated by alternative splicing, may account for the kinetic variability of the acetylcholine receptor channel.
Identification and characterization of ligands for L‐selectin in the kidney. II. Expression of chondroitin sulfate and heparan sulfate proteoglycans reactive with L‐selectin
Authors: Li Yong-Fei , Kawashima Hiroto , Watanabe Norifumi , Miyasaka Masayuki
Published: July 2002

Ligands for the leukocyte adhesion molecule L‐selectin are expressed not only in lymph node high endothelial venules (HEV) but also in the renal distal tubuli. Here we report that L‐selectin‐reactive molecules in the kidney are chondroitin sulfate and heparan sulfate proteoglycans of 500–1000 kDa, unlike those in HEV bearing sialyl Lewis X‐like carbohydrates. Binding of L‐selectin to these molecules was mediated by the lectin domain of L‐selectin and required divalent cations. Binding was inhibited by chondroitinase and/or heparitinase but not sialidase. Thus, L‐selectin can recognize chondroitin sulfate and heparan sulfate glycosaminoglycans structurally distinct from sialyl Lewis X‐like carbohydrates.
Kinetics of transhydrogenase reaction catalyzed by the mitochondrial NADH‐ubiquinone oxidoreductase (Complex I) imply more than one catalytic nucleotide‐binding sites
Authors: Zakharova N.V. , Zharova T.V. , Vinogradov A.D.
Published: July 2002

The steady‐state kinetics of the transhydrogenase reaction (the reduction of acetylpyridine adenine dinucleotide (APAD+) by NADH, DD transhydrogenase) catalyzed by bovine heart submitochondrial particles (SMP), purified Complex I, and by the soluble three‐subunit NADH dehydrogenase (FP) were studied to assess a number of the Complex I‐associated nucleotide‐binding sites. Under the conditions where the proton‐pumping transhydrogenase (EC 1.6.1.1) was not operating, the DD transhydrogenase activities of SMP and Complex I exhibited complex kinetic pattern: the double reciprocal plots of the velocities were not linear when the substrate concentrations were varied in a wide range. No binary complex (ping‐pong) mechanism (as expected for a single substrate‐binding site enzyme) was operating within any range of the variable substrates. ADP‐ribose, a competitive inhibitor of NADH oxidase, was shown to compete more effectively with NADH (K
i=40 μM) than with APAD+ (K
i=150 μM) in the transhydrogenase reaction. FMN redox cycling‐dependent, FP catalyzed DD transhydrogenase reaction was shown to proceed through a ternary complex mechanism. The results suggest that Complex I and the simplest catalytically competent fragment derived therefrom (FP) possess more than one nucleotide‐binding sites operating in the transhydrogenase reaction.
Modelling of a voltage‐dependent Ca2+ channel β subunit as a basis for understanding its functional properties
Authors: Hanlon M.R. , Berrow N.S. , Dolphin A.C. , Wallace B.A.
Published: July 2002

Structure prediction methods have been used to establish a domain structure for the voltage‐dependent calcium channel β subunit, β1b. One domain was identified from homology searches as an SH3 domain, whilst another was shown, using threading algorithms, to be similar to yeast guanylate kinase. This domain structure suggested relatedness to the membrane‐associated guanylate kinase protein family, and that the N‐terminal domain of the β subunit might be similar to a PDZ domain. Three‐dimensional model structures have been constructed for these three domains. The extents of the domains are consistent with functional properties and mutational assays of the subunit, and provide a basis for understanding its modulatory function.
Delineation of genomic deletion in cardiomyopathic hamster
Authors: Sakamoto Aiji , Abe Makoto , Masaki Tomoh
Published: July 2002

Cardiomyopathic hamster is a representative animal model for autosomal recessive cardiomyopathy. We have previously shown that the transcript of δ‐sarcoglycan is missing in the heart of cardiomyopathic hamster due to genomic deletion. Here we define the normal genomic region deleted in cardiomyopathic hamster, which spans about 30 kb interval and includes the two first exons of the δ‐sarcoglycan gene. RNA blot analysis using genomic DNA fragments covering the entire deletion as probes failed to detect any transcript other than δ‐sarcoglycan in normal hamster heart, suggesting that δ‐sarcoglycan is the only transcript defective in the heart of cardiomyopathic hamster.
Structural requirement of leucine for activation of p70 S6 kinase
Authors: Shigemitsu Kaori , Tsujishita Yosuke , Miyake Hiroshi , Hidayat Sujuti , Tanaka Noriaki , Hara Kenta , Yonezawa Kazuyoshi
Published: July 2002

The addition of leucine induced activation of p70S6k in amino acid‐depleted H4IIE cells. Whereas the activation of p70S6k by leucine was transient, the complete amino acid stimulated p70S6k more persistently. The effect of leucine on p70S6k was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70S6k, indicating that the structural requirement of leucine to induce p70S6k activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70S6k and the other derivatives acted as inhibitors against the leucine‐induced activation of p70S6k.
Evidence against the regulation of caldesmon inhibitory activity by p42/p44erk mitogen‐activated protein kinase in vitro and demonstration of another caldesmon kinase in intact gizzard smooth muscle
Authors: Krymsky Mikhail A. , Chibalina Margarita V. , Shirinsky Vladimir P. , Marston Steven B. , Vorotnikov Alexander V.
Published: July 2002

The effect of direct phosphorylation by recombinant p44erk1 mitogen‐activated protein kinase on the inhibitory activity of caldesmon and its C‐terminal fragment H1 was studied in vitro. Neither inhibition of actin‐tropomyosin activated ATPase of heavy meromyosin by caldesmon or H1, nor inhibition of the actin‐tropomyosin motility over heavy meromyosin by H1 was significantly affected by the phosphorylation while only a moderate effect on the actin‐activated component of heavy meromyosin ATPase inhibition was observed. Phosphopeptide mapping of caldesmon immunoprecipitated from [32P]PO4‐labelled intact gizzard strips revealed that it is predominantly phosphorylated at mitogen‐activated protein kinase sites in unstimulated tissue and that it is stimulated for 1 h with phorbol 12,13‐dibutyrate. We find that phorbol 12,13‐dibutyrate also induces a transitory phosphorylation of caldesmon peaking at 15 min after addition and this phosphorylation is not attributed to mitogen‐activated protein kinase, protein kinase C, Ca2+/calmodulin‐dependent kinase II or casein kinase II. We suggest that a yet unidentified kinase, rather than mitogen‐activated protein kinase, may be involved in regulation of the caldesmon function in vivo.
Localization of the human caveolin‐3 gene to the D3S18/D3S4163/D3S4539 locus (3p25), in close proximity to the human oxytocin receptor gene
Authors: Sotgia Federica , Minetti Carlo , Lisanti Michael P.
Published: July 2002

Caveolin‐3, a muscle‐specific caveolin‐related protein, is the principal structural protein of caveolae membrane domains in striated muscle cell types (cardiac and skeletal). Recently, we identified an autosomal dominant form of limb girdle muscular dystrophy in humans that is due to mutations within exon 2 of the caveolin‐3 gene (3p25). However, the detailed location of the human caveolin‐3 gene and its position with regard to neighboring genes remains unknown. Here, we have isolated three independent BAC clones containing the human caveolin‐3 gene. Using a PCR‐based approach, we determined that these clones contain both exons 1 and 2 of the human caveolin‐3 gene. In addition, we performed microsatellite marker analysis of these BAC clones, using a panel of 13 markers that are known to map within the 3p25 region. Our results indicate that these BAC clones contain the following three markers: D3S18, SHGC‐1079 (also known as D3S4163) and D3S4539. Interestingly, D3S18 is a marker for two known human diseases, von Hippel‐Lindau disease and 3p‐syndrome. As D3S4163 and D3S4539 are known to map in the vicinity of the 3′ end of the human oxytocin receptor gene, we determined if these caveolin‐3 positive BACs also contain the oxytocin receptor gene. We show that (i) these BACs contain all four exons of the oxytocin receptor gene and (ii) that the genes encoding caveolin‐3 and the oxytocin receptor are located ∼7–10 kb apart and in the opposite orientation. As 3p‐syndrome is characterized by cardiac septal defects and caveolin‐3 is expressed primarily in the heart and skeletal muscle, caveolin‐3 is a candidate gene that may be deleted in 3p‐syndrome.
PKC‐β and PKC‐ζ mediate opposing effects on proximal tubule Na+,K+‐ATPase activity
Authors: Efendiev Riad , Bertorello Alejandro M , Pedemonte Carlos H
Published: July 2002

Dopamine (DA) inhibits rodent proximal tubule Na+,K+‐ATPase via stimulation of protein kinase C (PKC). However, direct stimulation of PKC by phorbol 12‐myristate 13‐acetate (PMA) results in increased Na+,K+‐ATPase. LY333531, a specific inhibitor of the PKC‐β isoform, prevents PMA‐dependent activation of Na+,K+‐ATPase, but has no effect on DA inhibition of this activity. A similar result was obtained with a PKC‐β inhibitor peptide. Concentrations of staurosporine, that inhibits PKC‐ζ, prevent DA‐dependent inhibition of Na+,K+‐ATPase and a similar effect was obtained with a PKC‐ζ inhibitor peptide. Thus, PMA‐dependent stimulation of Na+,K+‐ATPase is mediated by activation of PKC‐β, whereas inhibition by DA requires activation of PKC‐ζ.
Identification of residues involved in v‐Src substrate recognition by site‐directed mutagenesis
Authors: Yokoyama Noriko , Miller W.Todd
Published: July 2002

To study the role of the catalytic domain in v‐Src substrate specificity, we engineered three site‐directed mutants (Leu‐472 to Tyr or Trp and Thr‐429 to Met). The mutant forms of Src were expressed in Sf9 cells and purified. We analyzed the substrate specificities of wild‐type v‐Src and the mutants using two series of peptides that varied at residues C‐terminal to tyrosine. The peptides contained either the YMTM motif found in insulin receptor substrate‐1 (IRS‐1) or the YGEF motif identified from peptide library experiments to be the optimal sequence for Src. Mutations at positions Leu‐472 or Thr‐429 caused changes in substrate specificity at positions P+1 and P+3 (i.e. one or three residues C‐terminal to tyrosine). This was particularly evident in the case of the L‐472W mutant, which had pronounced alterations in its preferences at the P+1 position. The results suggest that residue Leu‐472 plays a role in P+1 substrate recognition by Src. We discuss the results in the light of recent work on the roles of the SH2, SH3 and catalytic domains of Src in substrate specificity.
Dynamic re‐distribution of protein kinase D (PKD) as revealed by a GFP‐PKD fusion protein: dissociation from PKD activation
Authors: Matthews Sharon , Iglesias Teresa , Cantrell Doreen , Rozengurt Enrique
Published: July 2002

Protein kinase D (PKD)/protein kinase Cμ (PKCμ), a serine/threonine protein kinase with distinct structural and enzymological properties, is rapidly activated in intact cells via PKC. The amino‐terminal region of PKD contains a cysteine‐rich domain (CRD) that directly binds phorbol esters with a high affinity. Here, we show that treatment of transfected RBL 2H3 cells with phorbol 12,13‐dibutyrate (PDB) induces a striking CRD‐dependent translocation of PKD from the cytosol to the plasma membrane, as shown by real time visualization of a functional green fluorescent protein (GFP)‐PKD fusion protein. A single amino acid substitution in the second cysteine‐rich motif of PKD (P287G) prevented PDB‐induced membrane translocation but did not affect PKD activation. Our results indicate that PKD translocation and activation are distinct processes that operate in parallel to regulate the activity and localization of this enzyme in intact cells.
Effects of acute leptin administration on the differences in proton leak rate in liver mitochondria fromob/obmice compared to lean controls
Authors: Melia H.P. , Andrews J.F. , McBennett S.M. , Porter R.K.
Published: July 2002

In this investigation, the effects on proton leak of leptin administration toob/obmice was measured for liver mitochondria. We and others have shown that proton leak is approximately 3 times greater in liver mitochondria fromob/obmice compared to lean controls at any given membrane potential. The results are consistent with obese mammals having higher lean mass‐specific metabolic rates compared to lean controls. The increase in proton leak rate at any given membrane potential cannot be explained by the presence of free fatty acids associated with mitochondria isolated from the obese animals. The difference in proton leak must therefore represent a real difference in inner membrane permeability. Acute leptin (OB protein) administration restores the liver mitochondrial proton leak rate ofob/obmice to that of lean controls. There was no effect on proton leak rate of liver mitochondria from sham‐treatedob/obmice. These novel results indicate a role for leptin, either directly or indirectly, in regulating the efficiency of oxidative phosphorylation.
Production of fungal fructosyl amino acid oxidase useful for diabetic diagnosis in the peroxisome of Candida boidinii
Authors: Sakai Yasuyoshi , Yoshida Hiroyuki , Yurimoto Hiroya , Yoshida Nobuyuki , Fukuya Hiroshi , Takabe Keiji , Kato Nobuo
Published: July 2002

A high‐level production of fructosyl amino acid oxidase (FAOD), whose production was toxic in Escherichia coli, was investigated through attempts to utilize the peroxisome of Candida boidinii as the place for protein accumulation. The alcohol oxidase‐depleted strain (strain aod1Δ) produced FAOD at a four to five times higher level than the wild type strain in terms of protein amount and enzyme activity, although the transcriptional level was similar. As a result of this study, we could improve FAOD productivity approximately 47‐fold from the original transformant, and FAOD accumulated within membrane‐bound peroxisomes up to 18% of the total soluble proteins.
Transcriptional activation by the Myb proteins requires a specific local promoter structure
Authors: Ganter Brigitte , Chao Samuel T. , Lipsick Joseph S.
Published: July 2002

The biological effects of the cellular c‐Myb and the viral v‐Myb proteins are strikingly different. While c‐Myb is indispensable for normal hematopoiesis, v‐Myb induces acute leukemia. The v‐Myb DNA‐binding domain (DBD) differs from that of c‐Myb mainly by deletion of the first of three repeats which correlates with efficient oncogenic transformation and a decrease in DNA‐binding activity. To investigate the difference in DNA‐binding and transcriptional activation, oligonucleotide selection and electrophoretic mobility shift assays were employed. The v‐Myb DBD (R2R3) shows an intrinsic DNA‐binding specificity for an AT‐rich downstream extension of the Myb recognition element (MRE) PyAACT/GG for efficient binding to this site, whereas R1 within the c‐Myb DBD allows for more flexibility for this downstream extension. Therefore, due to the presence of repeat R1, c‐Myb can bind to a greater number of target sites. The intrinsic DNA‐binding specificity of R2R3 is further supported with the results from in vivo transcriptional activation experiments which demonstrated that both the v‐Myb and c‐Myb DBDs require an extension of the MRE (motif #1) by a downstream T‐stretch (motif #2) for full activity. Surprisingly, the T‐stretch improves binding when present on either strand, but is required on a specific strand for transcriptional activation.
Yotiao protein, a ligand for the NMDA receptor, binds and targets cAMP‐dependent protein kinase II1
Authors: Feliciello Antonio , Cardone Luca , Garbi Corrado , Ginsberg Michael D. , Varrone Stelio , Rubin Charles S. , Avvedimento Enrico V. , Gottesman Max E.
Published: July 2002

A yeast two‐hybrid screen revealed that regulatory subunits (RII) of PKAII bind the Yotiao protein. Yotiao interacts with the NR1 subunit of the NMDA receptor. A purified C‐terminal fragment of Yotiao binds PKAII, via an RII binding site constituted by amino acid residues 1452–1469, with a dissociation constant (K
d) between 50 and 90 nM in vitro. A stable complex composed of Yotiao, RII and NR1 was immunoprecipitated from whole rat brain extracts. Immunostaining analysis disclosed that Yotiao, RIIβ and NR1 colocalize in striatal and cerebellar neurons. Co‐assembly of Yotiao/PKAII complexes with NR1 subunits may promote cAMP‐dependent modulation of NMDA receptor activity at synapses, thereby influencing brain development and synaptic plasticity.
Outcome of pregnancy in women with hereditary thrombophilia
Authors: Ogueh O , Chen M.F , Spurll G , Benjamin A
Published: July 2002

Objectives: The aims of this study are to review the outcome of pregnancy in women with thrombophilia, and investigate the possible beneficial effect of heparin therapy in these women. Methods: We reviewed the hospital records of 126 women who were referred to the high‐risk obstetrical hematology clinic between June 1996 and December 1999. The placental histology and outcome of 39 pregnancies in 24 women with hereditary thrombophilia were studied, and pregnancies which were treated with heparin were compared with those without treatment. Results: An adverse pregnancy outcome occurred in 54% of the pregnancies. All seven miscarriages (18%) occurred in pregnancies that were not treated with heparin. However, heparin treatment did not prevent the development of obstetric complications in later pregnancies (odds ratio=0.955, 95% C.I.=I.255–3.577, Fisher's exact test). Excluding miscarriages, 28% of the placentas had thrombotic lesions, and the pregnancies with placental thrombotic lesions were more likely to have complications than those pregnancies without placental abnormalities (P=0.023, C.I.=1.257–5.197, Fisher's exact test). Conclusions: Pregnancy complications in cases of hereditary thrombophilia may be related to placental abnormalities. Heparin therapy is likely to be useful in preventing miscarriage in cases of hereditary thrombophilia.
Human resources for maternity care: the present system in Brazil, Japan, North America, Western Europe and New Zealand
Authors: Page L
Published: July 2002

This article describes the nature of the humanization of birth and the overlapping but distinct role of professionals within the maternity services with an emphasis on the role of the midwife. It describes the status of midwives in different parts of the world, and the common characteristics of work undertaken to restore the role of the midwife. Midwifery is seen as an essential component of effective maternity services. In addition it is important to recognize the important role that traditional birth attendants play in many parts of the world. An appropriate structure including primary and secondary and tertiary care services are important for professionals to play their full part.
American prices embedded in European prices
Authors: Jourdain Benjamin , Martini Claude
Published: July 2002

In this paper, we are interested in American option prices in the Black–Scholes model. For a large class of payoffs, we show that in the region where the European price increases with the time to maturity, this price is equal to the American price of another claim. We give examples in which we explicit the corresponding claims. The characterization of the American claims obtained in this way remains an open question.

Ce travail met en évidence un lien entre prix d’options européennes et prix d’options américaines dans le modèle de Black–Scholes. Nous montrons que pour une large classe de fonctions de payoff

\varphi

, dans la zone où il augmente avec la maturité, le prix de l’option européenne est égal au prix américain correspondant à une fonction de payoff modifiée

\widehat \varphi

. Nous donnons des exemples où il est possible d’expliciter

\widehat \varphi

. Mais la caractérisation de l’image de

\varphi→\widehat \varphi

reste un problème ouvert.
Hölder continuity conditions for the solvability of Dirichlet problems involving functionals with free discontinuities
Authors: Solimini S , Lops F.A , Maddalena F
Published: July 2002

The paper deals with the problem of minimizing a free discontinuity functional under Dirichlet boundary conditions. An existence result was known so far for

C^1(∂Ω)

boundary data

\hat u

. We show here that the same result holds for

\hat u \in C^{0,μ}(∂Ω)

if

μ> \frac 1 2

and it cannot be extended to cover the case

μ=\frac 1 2

. The proof is based on some geometric measure theoretic properties, in part introduced here, which are proved
a priori
to hold for all the possible minimizers.

On savait que le minimum d’une fonctionnelle à discontinuité libre avec condition de Dirichlet sur le bord était atteint quand la donnée de bord

\hat u

est

C^1(∂Ω)

. Nous étendons ce résultat à

\hat u\in C^{0,μ}(∂Ω)

si

μ>\frac 1 2

et montrons qu’il n’est plus vrai pour

μ=\frac 1 2

. Pour cela, nous démontrons des propriétés de théorie de la mesure géométrique
a priori
valides pour tout minimiseur de la fonctionnelle.
Regularity properties of free discontinuity sets
Authors: Maddalena Francesco , Solimini Sergio
Published: July 2002

This paper is concerned with the problem of estimating the dimension, expected to be

N−2

, of the singular set of a minimizer of a functional with free discontinuities in

N

dimensions. The best result already known, namely the

(N−1)

-negligibility, is improved here.

On s’attend à ce que la dimension de l’ensemble singulier d’un minimum d’une fonctionnelle à discontinuité libre soit

N−2

. Selon le meilleur résultat connu jusqu’à présent, cet ensemble est

N−1

négligeable. Nous améliorons ce résultat.
Polysialic acid in the cochlea of the developing mouse
Authors: Whitlon Donna S. , Zhang Xueli
Published: July 2002

Polysialic acid (PSA), an unusual molecule covalently attached to the neural cell adhesion molecule, NCAM, has been shown to regulate cell‐to‐cell and cell‐to‐matrix interactions by interfering with the binding of cell‐surface adhesion molecules. We used immunocytochemistry to map the temporospatial distribution of PSA in the mouse cochlea between embryonic day 16 and postnatal day 32 and compared it to the known timetable of neural growth and development. Polysialic acid immunoreactivity develops along a temporospatial gradient beginning in the basal turn and progressing to the apical turn. The expression is transitory on spiral ganglion neurons, intraganglionic bundles, radial bundles, and outer hair cells. Immunoreactivity diminishes progressively from the basal turn to the apical turn. Immunolabeling is maintained to adulthood on fibers in the inner spiral and inner pillar bundles, bundles which have been suggested to sprout continually and grow even in older animals. Inner hair cells are never immunolabeled. The temporo‐spatial expression of PSA suggests its involvement in neural growth, whereas its extinction correlates with the time of onset of nerve‐receptor interactions.
The effects of apolipoprotein e deficiency on braincholinergic neurons
Authors: Kleifeld Oded , Diebler Marie‐francoise , Chapman Shira , Oron Lea , Michaelson Daniel M.
Published: July 2002

Previous studies utilizing apolipoprotein E (apoE)‐deficient mice revealed distinctdecreases in the levels of cholinergic synaptic markers of projecting basal forebrain cholinergicneurons and no such alterations in other brain cholinergic systems. In order to investigate themechanisms underlying these neuron‐specific cholinergic effects, primary neuronal cultures fromapoE‐deficient and control mice were prepared and characterized. These include basal forebraincultures, which are enriched in projecting cholinergic neurons, and cortical cultures, which containcholinergic interneurons. The levels of cholinergic nerve terminals in these cultures were assessedby ligand binding measurements of the levels of the vesicular acetylcholine transporter (VAChT).This revealed that basal forebrain cultures of apoE‐deficient mice contain markedly lower VAChTlevels (∼50%) than do control cultures, but that VAChT levels of the corresponding corticalcultures of the apoE‐deficient and control mice were the same. Time course studies revealed thatVAChT levels of the basal forebrain cultures increased with culture age, but that the relativereduction in VAChT levels of the apoE‐deficient cholinergic neurons was unaltered and was thesame for freshly prepared and for 96 h old cultures. Thesein vitroobservations are inaccordance with thein vivofindings and suggest that projecting basal forebraincholinergic neurons, but not cholinergic interneurons, are markedly dependent on apoE and thatsimilar mechanisms mediate thein vivoandin vitroeffects of apoE deficiencyon cholinergic function.
IL‐1β increases intracellular calcium through an IL‐1 type 1 receptor mediated mechanism in C6 astrocytic cells
Authors: Pita Ignacio , Jelaso Anna M. , Ide Charles F.
Published: July 2002

Interleukin‐1β (IL‐1β) is a cytokine that regulates a variety of biological processes. In addition to its traditional role in the immune system, IL‐1β plays an integral role in neural‐immune and developmental processes in the nervous system. The pleiotropic ability of IL‐1β may be due to the activation of different signal transduction mechanisms in specific cell types or under certain cellular conditions. We have previously demonstrated that IL‐1β regulates healing and repair in the developing, mammalian nervous system. In the damaged perinatal mouse brain, IL‐1β is expressed in astrocytes that change from a stellate to a spindle‐shaped morphology. The spindle‐shaped astrocytes enclose the wound, separating the healthy from damaged neural tissue. The shape change and subsequent repair processes are IL‐1β activity‐dependent, acting through the IL‐1 type 1 receptor (IL‐1R1), as co‐application of the IL‐1type 1 receptor antagonist protein (IL‐1ra) blocks IL‐1β induced effects. In the C6 astrocytic cell line, IL‐1β induced similar shape changes and upregulated expression of the cytoskeletal protein, glial fibrillary acidic protein (GFAP). Since cytoskeletal changes, as well as specific signal transduction mechanisms, are associated with increases in intracellular calcium ([Ca2+]i), studies were carried out to determine if increases in [Ca2+]i induced by IL‐1β occurred through activation of the IL‐1R1 in C6 cells. Cells were treated with IL‐1β and/or IL‐1ra, followed by measurement of relative changes in [Ca2+]i using fura‐2 fluorescence imaging methods. IL‐1β increased [Ca2+]i levels in a dose and time dependent manner. Treatment with IL‐1ra blocked IL‐1β induced increases in [Ca2+]i, indicating that IL‐1β acts through the IL‐1R1. Immunocytochemistry experiments showed that untreated C6 cells normally express IL‐1β, IL‐1ra, and IL‐1R1. Thus, IL‐1 system molecules may play a role in normal C6 astrocyte physiology.
Evaluation of thyroid function in lithium-naive bipolar patients
Authors: Valle J. , Ayuso-Gutierrez J.L. , Abril A. , Ayuso-Mateos J.L.
Published: July 2002

A high prevalence of thyroid hypofunction has been found in bipolar patients. However, the samples used in previous studies included a high percentage of patients in treatment with lithium and carbamazepine. Since the use of these drugs may explain the high prevalence of thyroid disturbances found in bipolar patients, we designed the present study to assess thyroid function in a sample of bipolar patients who had not been treated previously with lithium or carbamazepine. Patients included in the sample met Research Diagnostic Criteria for bipolar affective disorder. Assessment included determination of serum levels for total tyroxine (T4), total triiodothyronine (T3), and thyrotropin both basally and in response to infusion of 500 mg of Protilerin. The rate of thyroid hypofunction in the total sample (9.2%) was considerably lower than that reported in other studies with bipolar patients undergoing lithium therapy. Five patients (9.2%) showed some thyroid hyperfuncion parameter. Our results do not show significant differences in thyroid function indices between long-term and short-term duration of illness, between outpatients and inpatients, between high and low number of episodes, and between rapid- and non-rapid-cycling cases. Comparison between bipolar I and bipolar II patients shows a statistically significant difference in the values of TSH levels, with the bipolar II group having a higher mean value. Our data suggest that thyroid dysfunction is not related to gender, duration of illness, number of episodes, or rapid-cycling course of illness. The higher TRH-stimulated TSH levels in the bipolar II group could be considered a differential biological feature.
An analysis on the relationship between safety awareness and safety behaviors of healthcare professionals, Ankara/Turkey
Authors: Uzuntarla Fatma , Kucukali Serhat , Uzuntarla Yasin
Published: June 2020

Objectives

This descriptive study aims to examine the relationship between the safety awareness of healthcare professional and their safety behaviors.

Methods

The study was carried out on 418 healthcare professionals working in a training and research hospital in Ankara/Turkey. The survey method was used as data collection tool. The questionnaire consisted of 3 sections and 18 questions. First section consisted of questions on sociodemographic characteristics and, second section consisted of the awareness scale and third section consisted of safety behaviors scale.

Results

The safety awareness and safety behaviors are scored on a scale from 1 (completely disagree) to 5 (completely agree). The safety awareness and safety behaviors has an average score of 3.85 ± 0.81 and 3.56 ± 0.82, respectively. The safety awareness and safety behavior levels of healthcare professionals were found to be high.

Conclusion

A significant positive correlation was found between safety awareness and safety behaviors and it was concluded that the increase in safety awareness led to an increase in safety behavior.
Comparison of the complete mitochondrial genome of Phyllophorus liuwutiensis (Echinodermata: Holothuroidea: Phyllophoridae) to that of other sea cucumbers
Authors: Yang Fuyuan , Zhou Chen , Tran Ngoc Tuan , Sun Zaiqiao , Wu Jianshao , Ge Hui , Lu Zhen , Zhong Chenhui , Zhu Zhihuang , Yang Qiuhua , Lin Qi
Published: June 2020

Sea cucumber species are abundant (>1400 species) and widely distributed globally. mtDNA sequencing is frequently used to identify the phylogenetic and evolutionary relationships among species. However, there are no reports on the mitochondrial genome of Phyllophorus liuwutiensis. Here, we performed mtDNA sequencing of P. liuwutiensis to examine its phylogenetic relationships with other echinoderms. Its mitochondrial genome (15 969 bp) contains 37 coding genes, including 13 protein‐coding genes, 22 tRNA genes and 2 rRNA genes. Except for one protein‐coding gene (nad6) and five tRNA genes encoded on the negative strand, all other genes were encoded on the positive strand. The mitochondrial bases of P. liuwutiensis were composed of 29.55% T, 22.16% C, 35.64% A and 12.64% G. The putative control region was 703 bp in length. Seven overlapping regions (1–10 bp) were found. The noncoding region between the genes ranged from 1 to 130 bp in length. One putative control region has been found in the P. liuwutiensis mitogenome. All of the tRNA genes were predicted to fold into a cloverleaf structure. In addition, we compared the gene arrangements of six echinoderms, revealing that the gene order of P. liuwutiensis was a new arrangement.
Hierarchical structure‐based adaptive fault‐tolerant consensus control for multiple 3‐DOF laboratory helicopters
Authors: Liu Chun , Jiang Bin , Patton Ron J. , Zhang Ke
Published: June 2020

This study investigates the consensus problem of multiple 3‐DOF laboratory helicopters modeled with system nonlinearity, uncertainty, and actuator faults. The simultaneous additives and partial loss of effectiveness actuator faults are considered. The fault detection hierarchy, the healthy control hierarchy, and the fault‐tolerant control hierarchy constitute the hierarchical structure of multihelicopter systems. The fault‐tolerant consensus protocol is switched from the healthy control hierarchy once the actuator fault is detected in the fault detection hierarchy. An adaptive fault‐tolerant consensus control scheme is developed on the basis of the instantaneous and integral estimations to compensate simultaneously for system nonlinearity, uncertainty, and actuator faults and to guarantee the mean‐square consensus in a completely distributed form. Simulation results are presented to validate the effectiveness of the proposed adaptive fault‐tolerant consensus control algorithm.
Electrochemical Nonacidic N‐Nitrosation/N‐Nitration of Secondary Amines through a Biradical Coupling Reaction
Authors: Zhao Ji‐Ping , Ding Lu‐jia , Wang Peng‐Cheng , Liu Ying , Huang Min‐Jun , Zhou Xin‐Li , Lu Ming
Published: June 2020

An acid‐free N‐nitrosation/nitration of the N−H bonds in secondary amines with Fe(NO3)3 ⋅ 9H2O as the nitroso/nitro source through an electrocatalyzed radical coupling reaction was developed. Cyclic aliphatic amines and N‐heteroaromatic compounds were N‐nitrosated and N‐nitrated, respectively, under mild conditions. Control and competition experiments, as well as kinetic studies, demonstrate that N‐nitrosation and N‐nitration involve two different radical reaction pathways involving N+ and N. radicals. Moreover, the electrocatalysis method enables the preferential activation of the N−H bond over the electrode and thus provides high selectivity for specific N atoms. Finally, this strategy exhibits a broad scope and provides a green and straightforward approach to generate useful N‐nitroso/nitro compounds in good yields.

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Energy Level Alignment in Ternary Organic Solar Cells
Authors: Lami Vincent , Hofstetter Yvonne J. , Butscher Julian F. , Vaynzof Yana
Published: June 2020

Ternary organic solar cells (TOSC) are currently under intensive investigation, recently reaching a record efficiency of 17.1%. The origin of the device open‐circuit voltage (VOC), already a multifaceted issue in binary OSC, is even more complex in TOSCs. Herein, two ternary systems are investigated with one donor (D) and two acceptor materials (A1, A2) including fullerene and nonfullerene acceptors. By varying the ratio between the two acceptors, VOC is found to be gradually tuned between those of the two binary systems, D:A1 and D:A2. To investigate the origin of this change, ultraviolet photoemission spectroscopy (UPS) depth profiling is employed, which is used to estimate the photovoltaic gap in the ternary systems. The results reveal an excellent agreement between the estimated photovoltaic gap and the VOC for all mixing ratios, suggesting that the energetic alignment between the blend components varies depending on the ratio D:A1:A2. Furthermore, the results indicate that the sum of radiative and nonradiative losses in these ternary systems is independent of the blend composition. Finally, the superiority of UPS over X‐ray photoemission spectroscopy (XPS) depth profiling is demonstrated in resolving compositional profiles for material combinations with very similar chemical, but dissimilar electronic structures, as common in TOSCs.
Correlating the Structural and Photophysical Properties of Ortho, Meta, and Para‐Carboranyl–Anthracene Dyads
Authors: Marsh Adam V. , Dyson Matthew J. , Cheetham Nathan J. , Bidwell Matthew , Little Mark , White Andrew J. P. , Warriner Colin N. , Swain Anthony C. , McCulloch Iain , Stavrinou Paul N. , Meskers Stefan C. J. , Heeney Martin
Published: June 2020

The role of the carborane isomer is investigated on the structural and photophysical properties of molecules comprising a carborane cluster and a conjugated organic moiety is investigated by synthesizing isomeric o‐, m‐, and p‐carboranyl‐anthracene donor–acceptor dyads. While appending a carborane leads to emission from a low energy intramolecular charge transfer state for the o‐isomer, as well as emission from an excited state localized on the anthracene, this is not the case for the m‐ and p‐carborane derivatives. This difference is attributed to a lower electron affinity for the latter two isomers. However, adding both m‐ and p‐ deforms the aromatic backbone and increases its structural rigidity, reducing non‐radiative decay pathways and hence enhancing photoluminescence quantum efficiency relative to anthracene.
Assessment of Professionalism During the Emergency Medicine Clerkship Using the National Clinical Assessment Tool for Medical Students in Emergency Medicine
Authors: Emery Matt , Parsa Michael D. , Watsjold Bjorn K. , Franzen Doug
Published: June 2020

Objectives

In 2016, a national consensus conference created the National Clinical Assessment Tool for Medical Students in Emergency Medicine (NCAT‐EM), a standardized end‐of‐shift assessment tool. We report the first large‐scale analysis of professionalism concerns collected from May 2017 through December 2018 by a multisite consortium using the NCAT‐EM. Our primary objective was to characterize the nature and frequency of professionalism concerns. Our secondary objective was to identify characteristics associated with giving or receiving a professionalism flag.

Methods

The consortium database includes assessments for all students on EM clerkships at participating sites. This report presents descriptive statistics about the frequency of different flags, the distribution of flags among different student categories, assessor and student characteristics, and distribution of global assessment scores on assessments citing concerns. We used Fisher's exact test to look for associations between the frequency of professionalism flags and the sex of the students and assessors and across student categories. We used logistic regression to look for relationships between professionalism concerns and global assessment scores as well as intent to apply in EM.

Results

We screened 6,768 assessments of 784 students by 719 assessors from 13 sites. After excluding assessments without flags and assessments with apparent data entry errors, we analyzed 57 (0.8%) assessments containing 79 flags. The most frequent flags were punctuality (25/79, 31.6%) and initiative (20/79, 25.3%). Few students received flags (42/784, 5.4%). Few assessors flagged concerns (41/719, 5.7%). We detected no correlation between the frequency of flags and whether a student was applying in EM or between the sex of students and assessors. Global scores of lower one‐third appeared more often in assessments with a flag (30/57, 52.6% vs. 233/6,711, 3.5%).

Conclusions

Only 5.4% of students received flags. Punctuality and initiative accounted for a majority of citations. Professionalism flags correlated strongly with lower global assessment scores.
Effects of selenium hyperaccumulators on soil selenium distribution and vegetation properties
Authors: Reynolds R. Jason B. , Jones Rachel R. , Heiner Jake , Crane Kelsey M. , Pilon‐Smits Elizabeth A.H.
Published: June 2020

Premise

The ecological implications of hyperaccumulation have been investigated at the organismal level, but are poorly understood at the plant community level. Questions addressed here were: Does the presence of selenium (Se) hyperaccumulators affect Se distribution and concentration in their native soil, and do hyperaccumulators affect overall vegetation properties and species composition?

Methods

Plant survey and soil Se mapping were performed at three seleniferous sites in Colorado. In season one, plots with and without hyperaccumulators were compared for (1) bare ground, canopy cover, and species richness; (2) relative species abundance; (3) soil Se distribution and concentration. In season two, a smaller‐scale design was implemented, focusing on areas 3 m in diameter around hyperaccumulators versus nonhyperaccumulators in 44 paired plots on one site.

Results

Plots with hyperaccumulators generally showed more bare ground, less canopy cover, higher species richness, and 2–3‐fold higher soil Se levels. These patterns were not consistently significant across all sites; the effects of hyperaccumulators may have been diluted by their low abundance and the relatively large area of survey. In the smaller‐scale study, highly significant results were obtained, showing more bare ground, less canopy cover, and higher species richness in plots with hyperaccumulators; soil Se concentration was also higher in plots with hyperaccumulators.

Conclusions

Hyperaccumulators may significantly affect local soil Se concentration and vegetation over at least a 3 m diameter area, or 4× their canopy. These differences may result from the combined positive and negative allelopathic effects observed earlier at the organismal level.
Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia
Authors: Rohanizadegan Mersedeh , Tracy Sarah , Galarreta Carolina I. , Poorvu Tabitha , Buchmiller Terry L. , Bird Lynne M. , Estroff Judy A. , Tan Wen‐Hann
Published: June 2020

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.
Chemodivergent Dehydrative Nucleophilic Substitutions of Diarylmethanols with 1‐Phenyl‐1H‐tetrazole‐5‐thiol Catalyzed by FeCl3
Authors: Oda Ryoga , Nakata Kenya
Published: June 2020

Chemodivergent dehydrative nucleophilic substitutions of diarylmethanols with 1‐phenyl‐1H‐tetrazole‐5‐thiol were achieved using FeCl3 as a catalyst in MeNO2 by changing reaction temperature. It was found that sulfur nucleophilic attack occurred to afford kinetically controlled products that rearranged into thermodynamically controlled products. A variety of diarylmethanols could be applied to the reaction, irrespective of the substituents on the aromatic rings of the substrates. It was also revealed that the reactions of several kinds of alkyl‐ and heteroaryl‐substituted benzyl alcohols gave moderate to good product yields. The controlled experiments performed revealed that both reactions proceeded in an SN1 fashion and heating with a Lewis acid was necessary for rearrangement.
Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum
Authors: Milà‐Alomà Marta , Salvadó Gemma , Gispert Juan Domingo , Vilor‐Tejedor Natalia , Grau‐Rivera Oriol , Sala‐Vila Aleix , Sánchez‐Benavides Gonzalo , Arenaza‐Urquijo Eider M. , Crous‐Bou Marta , González‐de‐Echávarri José Maria , Minguillon Carolina , Fauria Karine , Simon Maryline , Kollmorgen Gwendlyn , Zetterberg Henrik , Blennow Kaj , Suárez‐Calvet Marc , Molinuevo José Luis ,   for the ALFA study
Published: June 2020

Introduction

The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood.

Methods

We used NeuroToolKit and Elecsys® immunoassays to measure cerebrospinal fluid (CSF) amyloid‐β (Aβ)42, Aβ40, phosphorylated tau (p‐tau), total tau (t‐tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and α‐synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum.

Results

CSF t‐tau, p‐tau, and neurogranin increase throughout aging only in Aβ‐positive individuals, whereas NfL and glial biomarkers increase with aging regardless of Aβ status. We modelled biomarker changes as a function of CSF Aβ42/40, p‐tau and p‐tau/Aβ42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF Aβ42/40 ratio. This is followed by a steep increase in CSF p‐tau; t‐tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers.

Discussion

Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.