bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal Alzheimer‐like phosphorylation of tau‐protein by cyclin‐dependent kinases cdk2 and cdk5
Authors: Baumann K. , Mandelkow E.-M. , Biernat J. , Piwnica-Worms H. , Mandelkow E.
Published: July 2002

We have shown earlier that certain proline‐directed kinases such as MAP kinase or GSK‐3 can phosphorylate tau protein in an abnormal manner reminiscent of tau from Alzheimer paired helical filaments [Drewes et al. (1992); Mandelkow et al. (1992)]. Both kinases are abundant in brain tissue and associate physically with microtubules through several cycles of assembly and disassembly. In this report we show that cdk2/cyclinA incorporates ≈5 P, into recombinant tau, and that it also induces the M
r
shift and antibody reactivity typical of Alzheimer tau. However, since there is no cdk2 in brain [Meyerson et al. (1992)] we looked for other members of this family of kinases. Using an antibody against the conserved N‐terminus we isolated a cdk‐like kinase from brain which was capable of inducing the Alzheimer‐like characteristics in tau by phosphorylation. Its size (31 kDa), target specificity (proline‐directed), Chromatographic behavior, and abundance in brain suggest that this kinase is similar or identical to the neuronal cdc2‐like kinase nclk alias PSSARLE or cdk5 [Hellmich et al. (1992); Meyerson et al. (1992); Xiong et al. (1992); Tsai et al. (1993)]. This was confirmed by an antibody specific for cdk5. Like MAP kinase and GSK‐3, this kinase is physically associated with microtubules and can be enriched by cycles of microtubule assembly and disassembly. Thus, cdk5 should be regarded as another kinase that could be held responsible for the changes in tau protein during Alzheimer disease progression.
Multiple UDP‐glucuronyltransferases for the glucuronidation of thyroid hormone with preference for 3,3',5'‐triiodothyronine (reverse T3)
Authors: Visser Theo J. , Kaptein Ellen , van Raaij Jeroen A.G.M. , Joe Carol Tjong Tjin , Ebner Thomas , Burchell Brian
Published: July 2002

We have studied the glucuronidation of the thyroid hormones T4, T3 and rT3 by liver microsomes of Wistar, Gunn and WAG rats. Gunn rats have a defect in the gene coding for bilirubin and phenol UDP‐glucuronyltransferase (UGT) isoenzymes; WAG rats have a genetic defect in androsterone UGT. In normal Wistar rats UGT activity was ≈5‐fold higher for rT3 than for T4 or T3. UGT activities for T4 and rT3, but not for T3, were impaired in Gunn rats. Conversely, UGT activity for T3, but not for T4 or rT3, was impaired in WAG rats. Thus, in rat liver rT3 is glucuronidated much more rapidly than T4 and T3. Our results support the view that T4 and rT3 are glucuronidated by bilirubin and phenol UGTs and T3 by androsterone UGT.
Rabbit masseter expresses the cardiac α myosin heavy chain gene
Authors: d'Albis Anne , Anger Marielle , Lompre Anne-Marie
Published: July 2002

The presence of myosin α heavy chain in the rabbit masseter has been previously suggested at the protein level [(1991) Basic Appl. Myol. 1, 23‐34; (1991) Histochem. J. 23, 160‐170]. To confirm this finding, we cloned most of the mRNA corresponding to the myosin heavy chain S2 subfragment. PCR analysis and subsequent nucleotide sequence determination of the amplified cDNA demonstrates the presence of a myosin α heavy chain mRNA in rabbit masticatory muscles.
Identification of the adsorbing site of lysozyme onto the hydroxyapatite surface using hydrogen exchange and 1H NMR
Authors: Nagadome Hatsumi , Kawano Keiichi , Terada Yoshihiro
Published: July 2002

The lysozyme‐hydroxyapatite interaction was studied by measuring individual hydrogen‐deuterium (H‐D) exchange rates of amide protons. The H‐D exchange reaction was initiated by transferring the lysozyme adsorbed on hydroxyapatite powder from H2O into D2O. After various H‐D exchange time periods (pH 7.0, 25°C), the complex was dissociated and the remaining hydrogen label was determined by 2D NMR analysis. The H‐D exchange rate of amide protons of residues 9, 11, 13, and 83 was slowed in the hydroxyapatite‐lysozyme complex compared with free lysozyme. Residues 9, 11 and 13 positioned at the back of the active site would be the location of the binding site.
Molecular cloning of crustacean putative molt‐inhibiting hormone (MIH) precursor
Authors: Klein Jörg M. , Mangerich Sigrid , de Kleijn Dominique P.V. , Keller Rainer , Weidemann Wolfgang M.
Published: July 2002

A cDNA encoding the complete precursor of the putative molt‐inhibiting hormone (MIH) of the shore crab, Carcinus maenas, was isolated and sequenced. The precursor consists of a putative 35 amino acid signal peptide and the 78 amino acid mature MIH. The deduced MIH amino acid sequence is in complete agreement with the sequence previously determined by Edman degradation. In situ hybridization revealed MIH‐expression in a subpopulation of large neurosecretory perikarya of the medulla terminalis X‐organ in the eyestalk.
Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a μ, δ or κ opioid receptor type
Authors: Bunzow James R. , Saez Carmen , Mortrud Marty , Bouvier Claudia , Williams John T. , Low Malcolm , Grandy David K.
Published: July 2002

A novel G protein‐coupled receptor was cloned by PCR and homology screening. Its deduced amino acid sequence is 47% identical overall to the μ, δ and κ opioid receptors and 64% identical in the putative transmembrane domains. When transiently expressed in COS‐7 cells this receptor did not bind any of the typical μ, δ or κ opioid receptor ligands with high affinity. In situ hybridization analysis revealed that LC132 mRNA is highly expressed in several rat brain areas, including the cerebral cortex, thalamus, subfornical organ, habenula, hypothalamus, central gray, dorsal raphe, locus coeruleus and the dorsal horn of the spinal cord. Based on this distribution and its high homology with the μ, δ and κ opioid receptors, it is proposed that LC132 is a new member of the opioid receptor family that is involved in analgesia and the perception of pain.
Predominant role of the substituents on the hydroxyl groups of 3‐hydroxy fatty acids of non‐reducing glucosamine in lipid A for the endotoxic and antagonistic activity
Authors: Tanamoto Ken-ichi
Published: July 2002

The synthetic disaccharide precursor of lipid A (406: identical to lipid IVA) was found to reduce its endotoxic activity in mice by an order of 105 or more, by replacing the hydroxyl groups with succinyl or acetyl residues. Both the succinylated and acetylated 406 were also found to antagonize the endotoxic mitogenicity on murine splenocytes. Previous studies demonstrated that the succinylated or acetylated synthetic complete lipid A preparations retained the whole endotoxic activity [1994, Infect. Immunol. 62, 1705]. The drastic contrast in all of these results suggests the importance of the substituents on the hydroxyl groups of 3‐hydroxy fatty acids of non‐reducing glucosamine of lipid A for the activity and for transformation to the antagonistic structure.
Biochemical evidence that the Saccharomyces cerevisiae THR4 gene encodes threonine synthetase
Authors: Ramos Cayo , Calderón Isabel L.
Published: July 2002

In yeast, the assignment of the threonine synthetase activity to the THR4 gene has been inferred from different data, but never really proved enzymatically. In this work, an assay system for threonine synthetase activity in yeast crude extract is reported. The method is based on the quantification by reverse‐phase high‐performance liquid chromatography, of the threonine formed from O‐phosphohomoserine. Using this method we have determined that this activity depends on the presence in the cell of an active form of the THR4 gene, thus demonstrating the univocal relationship between them.
Trypsin induces Ca2+‐activated Cl− currents in X. laevis oocytes
Authors: Durieux Marcel E. , Salafranca Mina N. , Lynch Kevin R.
Published: July 2002

The protease trypsin induces Ca2+‐activated Cl− currents when applied in concentrations as low as 0.1 to defolliculated, voltage clamped X. laevis oocytes. The response is dose‐dependent and specific, as other proteases (chymotrypsin, Lys‐C and Arg‐C), or trypsin pretreated with soybean trypsin inhibitor, did not induce currents. Intracellular trypsin injection did not induce responses. The current does not appear to result from proteolytic activation of the endogenous receptor for lysophosphatidic acid, the only known Ca2+‐mobilizing receptor consistently present in oocytes. These results suggest the presence on the oocyte membrane of a specific receptor for trypsin.
Recombinant soluble urokinase receptor as a scavenger for urokinase‐type plasminogen activator (uPA)
Authors: Wilhelm O. , Weidle U. , Höhl S. , Rettenberger P. , Schmitt M. , Graeff H.
Published: July 2002

A recombinant soluble human urokinase receptor comprising amino acids 1–277 was cloned and transfected into CHO cells. The mutant protein (rec‐uPAR277), purified from the CHO cell supernatant by affinity chromatography on immobilized urokinase (uPA), in a four‐fold excess, completely abolished the binding of FITC‐labeled pro‐uPA to the human ovarian cancer cell line, OV‐MZ‐6. This invasive and tumorigenic cancer cell line expresses uPA, its inhibitor PAI‐1, and the high‐affinity receptor for uPA, uPAR. Rec‐uPAR277 significantly reduced the proliferation of OV‐MZ‐6 cells in a concentration‐dependent manner without altering the viability of the cells. Invasion of OV‐MZ‐6 cells tested in an in vitro Matrigel invasion assay was inhibited by rec‐uPAR277 up to 75%. In conclusion, these results demonstrate that rec‐uPAR277 can function as a scavenger for uPA in vitro by inhibiting proliferation and invasion of human cancer cells.
Identification of a third yeast mitochondrial Tom protein with tetratrico peptide repeats
Authors: Bömer Ulf , Pfanner Nikolaus , Dietmeier Klaus
Published: July 2002

The mitochondrial outer membrane contains a protein complex with at least eight subunits responsible for recognition and translocation of preproteins synthesized in the cytosol. Two subunits, the receptors Tom20 and Tom70, contain tetratrico peptide repeats that are thought to be involved in protein‐protein interactions. We have identified Saccharomyces cerevisiae Tom72, a new Tom protein expressed at a low level. Tom72 is homologous to Tom70, including seven tetratrico peptide repeats. Tom72 is targeted to the mitochondrial outer membrane, forms a large domain exposed to the cytosol and loosely associates with the translocase complex of the outer membrane. These results suggest that Tom72 represents a ninth, weakly expressed component of the preprotein translocase of the mitochondrial outer membrane.
The role of protein structure in genomics
Authors: Domingues Francisco S. , Koppensteiner Walter A. , Sippl Manfred J.
Published: July 2002

The genome projects produce an enormous amount of sequence data that needs to be annotated in terms of molecular structure and biological function. These tasks have triggered additional initiatives like structural genomics. The intention is to determine as many protein structures as possible, in the most efficient way, and to exploit the solved structures for the assignment of biological function to hypothetical proteins. We discuss the impact of these developments on protein classification, gene function prediction, and protein structure prediction.
STAM2, a new member of the STAM family, binding to the Janus kinases
Authors: Endo Kazuhiro , Takeshita Toshikazu , Kasai Hirotake , Sasaki Yoshiteru , Tanaka Nobuyuki , Asao Hironobu , Kikuchi Kazu , Yamada Mitsuhiro , Chen Min , O'Shea John J. , Sugamura Kazuo
Published: July 2002

We here cloned a cDNA encoding STAM2, a new member of the STAM family, which contains an SH3 domain and ITAM. STAM2 like STAM1 is associated with Jak2 and Jak3, and involved in the signaling for DNA synthesis and c‐myc induction mediated by IL‐2 and GM‐CSF. Co‐expression of the SH3 deletion mutants of STAM1 and STAM2 induces an additive effect on suppressing DNA synthesis upon stimulation with IL‐2 and GM‐CSF, suggesting that STAM1 and STAM2 exhibit compensatory effects on the signaling pathways downstream of Jak2 and Jak3 upon stimulation with GM‐SCF and IL‐2, respectively.
Four years of post‐genomic life with 6000 yeast genes
Authors: Goffeau André
Published: July 2002

Four years after disclosure of the full yeast genome sequence, a series of resources including tens of thousands of mutant strains, plasmids bearing isolated genes and disruption cassettes are becoming publicly available. Deletions of each of the 6000 putative yeast genes are being screened systematically for dozens of phenotypic traits. In addition, new global approaches such as DNA hybridization arrays, quantitative proteomics and two‐hybrid interactions are being steadily improved. They progressively build up an immense computation network of billions of data points which will, within the next decade, characterize all molecular interactions occurring in a simple eukaryotic cell. In this process of acquisition of new basic knowledge, an international community of over 1000 laboratories cooperates with a remarkable willingness to share projects and results.
Gene trap: a way to identify novel genes and unravel their biological function
Authors: Cecconi Francesco , Meyer Barbara I
Published: July 2002

The gene trap methodology is a powerful tool to characterize novel genes and analyze their importance in biological phenomena. It is based on the use of mouse embryonic stem cells and reporter vectors designed to randomly integrate into the genome, tagging an insertion site and generating a mutation. Theoretically, all the 100 000 genes present in the mouse genome could be tagged and functionally inactivated at the same time. Here we describe the basic concepts and perspectives of this methodology and show some results obtained by the gene trap approach used to study molecular cascades in basic cell biology and in developmental processes.
Inhibition of glucocorticoid‐induced apoptosis by the expression of antisense gene of mitochondrial ATPase subunit 6
Authors: Sato Masaki , Matsuki Yasunori , Oguma Takemi , Tsujimoto Kyoko , Takayama Eiji , Tadakuma Takushi
Published: July 2002

To isolate the apoptosis‐linked genes involved in the cell death of thymocytes induced by glucocorticoids, we developed a functional cloning assay. Murine CD4+CD8+ thymic cell line 2‐257‐20 cells were transfected with cDNA expression libraries obtained from a dexamethasone‐resistant cell line. The transfected cells were selected in the presence of dexamethasone, and the plasmids which episomally expanded were then extracted from the surviving cells. One of the rescued cDNAs was found to be an antisense cDNA fragment identical to the mouse mitochondrial ATPase 6 gene. In the stable transfectants with the ATPase 6 antisense gene, the induction of apoptosis by dexamethasone was significantly delayed. Furthermore, the ATP synthesis in these transfectants was also reduced to some extent. ATPase 6 is a subunit of FoF1 ATPase and our results support that ATP synthesis from the mitochondria is necessary for the induction of apoptosis induced by glucocorticoids.
Genomic Exploration of the Hemiascomycetous Yeasts: 21. Comparative functional classification of genes
Authors: Gaillardin Claude , Duchateau-Nguyen Guillemette , Tekaia Fredj , Llorente Bertrand , Casaregola Serge , Toffano-Nioche Claire , Aigle Michel , Artiguenave François , Blandin Gaëlle , Bolotin-Fukuhara Monique , Bon Elisabeth , Brottier Philippe , de Montigny Jacky , Dujon Bernard , Durrens Pascal , Lépingle Andrée , Malpertuy Alain , Neuvéglise Cécile , Ozier-Kalogéropoulos Odile , Potier Serge , Saurin William , Termier Michel , Wésolowski-Louvel Micheline , Wincker Patrick , Souciet Jean-Luc , Weissenbach Jean
Published: July 2002

We explored the biological diversity of hemiascomycetous yeasts using a set of 22 000 newly identified genes in 13 species through BLASTX searches. Genes without clear homologue in Saccharomyces cerevisiae appeared to be conserved in several species, suggesting that they were recently lost by S. cerevisiae. They often identified well‐known species‐specific traits. Cases of gene acquisition through horizontal transfer appeared to occur very rarely if at all. All identified genes were ascribed to functional classes. Functional classes were differently represented among species. Species classification by functional clustering roughly paralleled rDNA phylogeny. Unequal distribution of rapidly evolving, ascomycete‐specific, genes among species and functions was shown to contribute strongly to this clustering. A few cases of gene family amplification were documented, but no general correlation could be observed between functional differentiation of yeast species and variations of gene family sizes. Yeast biological diversity seems thus to result from limited species‐specific gene losses or duplications, and for a large part from rapid evolution of genes and regulatory factors dedicated to specific functions.
Molecular mechanism of stop codon recognition by eRF1: a wobble hypothesis for peptide anticodons
Authors: Muramatsu Tomonari , Heckmann Klaus , Kitanaka Chifumi , Kuchino Yoshiyuki
Published: July 2002

We propose that the amino acid residues 57/58 and 60/61 of eukaryotic release factors (eRF1s) (counted from the N‐terminal Met of human eRF1) are responsible for stop codon recognition in protein synthesis. The proposal is based on amino acid exchanges in these positions in the eRF1s of two ciliates that reassigned one or two stop codons to sense codons in evolution and on the crystal structure of human eRF1. The proposed mechanism of stop codon recognition assumes that the amino acid residues 57/58 interact with the second and the residues 60/61 with the third position of a stop codon. The fact that conventional eRF1s recognize all three stop codons but not the codon for tryptophan is attributed to the flexibility of the helix containing these residues. We suggest that the helix is able to assume a partly relaxed or tight conformation depending on the stop codon recognized. The restricted codon recognition observed in organisms with unconventional eRF1s is attributed mainly to the loss of flexibility of the helix due to exchanged amino acids.
Homeobox gene clusters and the human paralogy map
Authors: Popovici Cornel , Leveugle Magalie , Birnbaum Daniel , Coulier François
Published: July 2002

Homeobox genes encode important developmental control proteins. In vertebrates, those encoding the proteins of the HOX class and their most closely related families, including paraHOX and metaHOX classes, are clustered in paralogous regions (or paralogons). We show that the majority of the other homeobox genes (we called contraHOX) can also be clustered and belong to paralogons in humans. This suggests that they duplicated during vertebrate evolution along the same processes as the HOX genes. We tentatively assembled several paralogons in superparalogons. One of the superparalogons contains the contraHOX genes. These observations were extended to hundreds of genes, and allowed to describe a primary human genome paralogy map.
New polypeptide components purified from mamba venom
Authors: Tytgat Jan , Vandenberghe Isabel , Ulens Chris , Van Beeumen Jozef
Published: July 2002

New polypeptide components have been isolated from Dendroaspis angusticeps venom using chromatography. Two polypeptides containing 59 and 57 amino acids, called ‘DaE1’ and ‘DaE2’ respectively, have been purified to homogeneity and fully sequenced. Spectrometric analysis yielded masses of 6631.5 and 6389.0 Da, respectively. The polypeptides share 98 and 95% identity, respectively, with trypsin inhibitor E (DpE) of Dendroaspis polylepis polylepis. ‘DaE’ polypeptides inhibit Kv1.1 channels with an IC50 value in the range of 300 nM. They can be considered as new dendrotoxins, albeit with fairly low affinity as compared to α‐DTX. ‘DaE’ polypeptides do not affect Kir2.1 channels.
The lysosomal/phagosomal membrane protein h‐lamp‐1 is a target of the IgA1 protease of Neisseria gonorrhoeae
Authors: Hauck Christof R , Meyer Thomas F
Published: July 2002

© 1997 Federation of European Biochemical Societies.
The protein kinase C pseudosubstrate peptide (PKC19–36) inhibits insulin‐stimulated protein kinase activity and insulin‐mediated translocation of the glucose transporter glut 4 in streptolysin‐O permeabilized adipocytes
Authors: Walaas O , Horn R.S , Walaas S.I
Published: July 2002

The effect of insulin on protein kinase activity and plasma membrane translocation of the glucose transporter GLUT 4 has been studied in adipocytes permeabilized by Streptolysin‐O. Insulin increased protein kinase activity, and this was completely inhibited by the PKC pseudosubstrate inhibitor peptide (PKC19–36). Insulin‐mediated translocation of GLUT 4 was also inhibited by the PKC inhibitor peptide. Both these insulin effects were blocked by a PKCβ neutralizing antibody. Our results are consistent with the hypothesis that insulin activates PKCβ activity in adipocytes in situ, and that this PKC activation is a component of the system whereby insulin regulates translocation of GLUT 4 to the plasma membrane.
Affinity and folding properties both influence the selection of antibodies with the selectively infective phage (SIP) methodology
Authors: Pedrazzi Graziella , Schwesinger Falk , Honegger Annemarie , Krebber Claus , Plückthun Andreas
Published: July 2002

We investigated which molecules are selected from a model library by the selectively infective phage (SIP) methodology. As a model system, we used the fluorescein binding single‐chain Fv fragment FITC‐E2, and from a 3D‐model, we identified 11 residues potentially involved in hapten binding and mutated them individually to alanines. The binding constant of each mutant was determined by fluorescence titration, and each mutant was tested individually as well as in competitive SIP experiments for infectivity. After three rounds of SIP, only molecules with KD
values within a factor of 2 of the tightest binder remain, and among those, a mutant no longer carrying an unnecessary exposed tryptophan residue is preferentially selected. SIP is shown to select for the best overall properties of the displayed molecules, including folding behavior, stability and affinity.
Bicarbonate binding to the water‐oxidizing complex in the photosystem II. A Fourier transform infrared spectroscopy study1
Authors: Yruela I , Allakhverdiev S.I , Ibarra J.V , Klimov V.V
Published: July 2002

The light‐induced Fourier transform infrared difference (FT‐IR) spectrum originating from the donor side of O2‐evolving photosystem (PS) II was obtained in non‐depleted and CO2‐depleted PSII membrane preparations. The observed spectrum free of contributions from the acceptor side signals was achieved by employing 2 mM/18 mM ferri‐/ferrocyanide as a redox couple. This spectrum showed main positive bands at 1589 and 1365 cm−1 and negative bands at 1560, 1541, 1522 and 1507 cm−1. CO‐depleted PSII preparations showed a quite different spectrum. The main positive and negative bands disappeared after depletion of bicarbonate. The addition of bicarbonate partially restored those bands again. Comparison between difference FT‐IR spectra of untreated and bicarbonate‐depleted PSII membranes indicated that the positive bands at 1589 and 1365 cm−1 can be assigned to COO− stretching modes from bicarbonate. The higher frequency corresponds to uas (COO−) and the lower frequency to us (COO−). 13C‐Labeling FT‐IR measurements confirmed these findings and also suggested that the negative band at 1560 cm−1 can be ascribed to uas (COO−). The data are discussed in the framework of the suggestion that bicarbonate can be a ligand to the Mn‐containing water‐oxidizing complex of PSII.
Chiral DNA packaging in DNA‐cationic liposome assemblies
Authors: Zuidam Nicolaas J , Barenholz Yechezkel , Minsky Abraham
Published: July 2002

Recent studies have indicated that the structural features of DNA‐lipid assemblies, dictated by the lipid composition and cationic lipid‐to‐DNA ratio, critically affect the efficiency of these complexes in acting as vehicles for cellular delivery of genetic material. Using circular dichroism we find that upon binding DNA, positively‐charged liposomes induce a secondary conformational transition of the DNA molecules from the native B form to the C motif. Liposomes composed of positively‐charged and neutral ‘helper’ lipids, found to be particularly effective as transfecting agents, induce – in addition to secondary conformational changes – DNA condensation into a left‐handed cholesteric‐like phase. A structural model is presented according to which two distinct, yet inter‐related modes of DNA packaging coexist within such assemblies. The results underline the notion that subtle changes in the components of a supramolecular assembly may substantially modulate the interplay of interactions which dictate its structure and functional properties.
Discoupling the Ca2+‐activation from the pore‐forming function of the bi‐component Panton‐Valentine leucocidin in human PMNs
Authors: Baba Moussa L. , Werner S. , Colin D.A. , Mourey L. , Pédelacq J.D. , Samama J.P. , Sanni A. , Monteil H. , Prévost G.
Published: July 2002

The consecutive cell activation, including Ca2+‐channel opening, and pore formation leading to human neutrophil lysis were the two functions of the staphylococcal Panton‐Valentine leucocidin attempted to be discoupled by site‐directed mutagenesis. In a first approach consisting in deletions of the cytoplasmic extremity of the transmembranous domain, we produced a LukF‐PV ΔSer125‐Leu128 with a slightly reduced Ca2+ induction but with a significantly lowered lytic activity when combined with its synergistic protein LukS‐PV. The second approach consisted in the modification of charges and/or introduction of a steric hindrance inside the pore, which also led to interesting mutated proteins: LukF‐PV G131D, G131W and G130D. The latter had an intact Ca2+ induction ability while the lytic one was 20‐fold diminished. Binding properties and intrinsic pore diameters of these discoupled toxins remained comparable to the wild‐type protein. The mutated proteins promoted interleukin‐8 secretion, but they were rather inactive in an experimental model. New insights are brought concerning the role of the two functions in the virulence of this bi‐component leucotoxin.
Acyl and alkyl chain length of GPI‐anchors is critical for raft association in vitro
Authors: Benting Jürgen , Rietveld Anton , Ansorge Iris , Simons Kai
Published: July 2002

We determined the acyl and alkyl chain composition of GPI‐anchors isolated from MDCK and Fischer rat thyroid (FRT) cells. Both cell lines synthesize GPI‐anchors containing C16/C18 or C18/C18 saturated acyl and alkyl chains. The GPI‐anchored placental alkaline phosphatase (PLAP) expressed in both cells is raft‐associated and PLAP purified from FRT cells is raft‐associated in vitro when reconstituted into liposomes containing raft lipids. In contrast, the GPI‐anchored variant surface glycoprotein from Trypanosoma brucei which contains C14 acyl and alkyl chains shows no significant raft association after reconstitution in vitro. These data indicate that the acyl and alkyl chain composition of GPI‐anchors determines raft association.
Conservative management of post‐operative peritoneal cysts associated with endometriosis
Authors: Takeuchi K , Kitazawa S , Kitagaki S , Maruo T
Published: July 2002

Objective: To describe the usefulness of fine‐needle aspiration cytology and drainage, followed by long‐acting GnRH‐agonist therapy in the management of post‐operative peritoneal cysts with endometriosis. Methods: In six women who were diagnosed as having post‐operative peritoneal cysts with endometriosis, fine‐needle aspiration cytology and drainage was performed. Thereafter, four patients were treated with long‐acting GnRH‐agonists for 6 months. Two patients refused the treatment. Results: In all patients fine‐needle aspiration yielded specimens which consisted of a population of mesothelial cells. The mean follow‐up time was 4 years (range 3.5–5). The four patients treated with long‐acting GnRH‐agonists show no evidence of recurrence. In two patients who had no additional treatment, the recurrence of the cyst was noted 2 months and 5 months after the drainage. Conclusion: Combination of fine‐needle aspiration cytology and drainage and subsequent long‐acting GnRH‐agonist therapy can be a useful conservative management of post‐operative peritoneal cysts associated with endometriosis.
Human papillomavirus (HPV) DNA assay as an adjunct to liquid‐based Pap test in the diagnostic triage of women with an abnormal Pap smear
Authors: Vassilakos P. , de Marval F. , Muñoz M. , Broquet G. , Campana A.
Published: July 2002

Objective: The diagnostic performance and clinical value of the combined use of liquid‐based Pap test and human papillomavirus testing were determined in 336 patients with a previous abnormal smear. Method: Subsequent histologic evaluation was used as definitive diagnosis. Result: The combined use of liquid‐based Pap test and HPV DNA testing showed higher rates in sensitivity (99.0%), specificity (59.3%), positive predictive value (89.9%) and negative predictive value (94.5%) than either cytology alone (sensitivity 98.8%, specificity 45.7%, positive predictive value 84.7%, negative predictive value 92.6%) or HPV DNA testing alone (sensitivity 84.9%, specificity 67.4%, positive predictive value 88.8%, negative predictive value 59.5%). Conclusion: The study demonstrated that the diagnostic accuracy for cervical cancer and its precursors was improved by using the liquid‐based Pap test as a primary diagnostic procedure and HPV assay as an adjunctive test. This information may assist the clinicians in triaging patients with equivocal cytologic cervical atypias.
Transvaginal color Doppler ultrasonography and CA‐125 in suspicious adnexal masses
Authors: Alcázar J.L. , Errasti T. , Zornoza A. , Mı́nguez J.A. , Galán M.J.
Published: July 2002

Objective: To compare diagnostic performance of color Doppler ultrasound and CA‐125 in suspicious adnexal masses on B‐mode sonography. Materials and methods: Data on 94 patients (mean age: 47.4 years, range: 17–79 years. Fifty‐two (55.3%) premenopausal and 42 (44.7%) postmenopausal women) managed in our institution because of a suspicious adnexal mass were reviewed. All patients were evaluated by transvaginal color Doppler ultrasonography (CD) and serum CA‐125 level determination prior to surgery. Definitive histopathological diagnosis was obtained in each case. Sonographic morphology evaluation was suspicious in all cases. CD was considered as suspicious when flow was detected and the lowest RI found was ≤0.45. CA‐125 cut‐off was ≥35 UI/ml. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each method and compared. ROC analysis was performed for RI and CA‐125. Areas under curve (AUC) were calculated and compared. Results: Fifty‐six (59.6%) tumors were found to be malignant and 38 (40.4%) benign. Sensitivity, specificity, PPV and NPV for CD were 87.5% (95% CIs: 75.3–94.4), 84.2% (95% CIs: 68.7–94), 89.1% (95% CIs: 77.7–95.9) and 82.1% (95% CIs: 66.5–92.5), respectively. Sensitivity, specificity, PPV and NPV for CA‐125 were 83.9% (95% CIs: 71.7–92.4), 68.4% (95% CIs: 51.3–82.5), 79.7% (95% CIs: 66.2–89) and 74.3% (95% CIs: 56.7–87.5), respectively. Sensitivity, PPV and NPV were not statistically different. CD had higher specificity (P=0.01). AUC curve for Doppler (0.75) was significantly higher than for CA‐125 (0.61) (P=0.0002). Conclusions: Our results indicate that color Doppler ultrasound has a better diagnostic performance as compared with CA‐125, being significantly more specific.
Advanced manufacturing technologies and strategically flexible production
Authors: Cagliano Raffaella , Spina Gianluca
Published: July 2002

This paper deals with the role of advanced manufacturing technologies (AMT) within the context of changes in the basic principles to organize and manage manufacturing systems. In particular, the use and effectiveness of various technologies and their computer‐based integration are investigated in the light of three emerging principles: (i) strategic multi‐focusedness, (ii) process integration across functions, and (iii) process ownership. Together, these principles are referred to as Strategically Flexible Production (SFP). In an international sample of 392 manufacturing units from the metal‐working industry, the use of AMT is analyzed in three groups: core adopters, partial adopters or non‐adopters of SFP. Data show that while core adopters do not use stand‐alone AMT more than the other groups, they have a higher level of computer integration (CI), in particular in their forefront departments. However, the use of integrating technologies varies much within the core adopters, suggesting that SFP does not necessarily require massive information technology (IT) support. This is further confirmed by the analysis of performance improvements. The mere adoption of stand‐alone AMT per se does not provide companies with superior improvements in performance. On the contrary, SFP alone or combined with a higher level of integration of stand‐alone AMT fosters increased time responsiveness.
Expression of amyloid precursor protein mRNA isoforms in rat brain is differentially regulated during postnatal maturation and by cholinergic activity
Authors: Apelt Jenny , Schliebs Reinhard , Beck Mike , Roiner Steffen , Bigl Volker
Published: July 2002

Pathological processing of the amyloid precursor protein (APP) is assumed to be responsible for the amyloid deposits in Alzheimer‐diseased brain tissue, but the physiological function of this protein in the brain is still unclear. The aim of this study is to reveal whether the expression of different splicing variants of APP transcripts in distinct brain regions is driven by postnatal maturation and/or regulated by cortical cholinergic transmission, applying quantitative in situ hybridization histochemistry using 35S‐labeled oligonucleotides as specific probes to differentiate between APP isoforms. In cortical brain regions, the expression of both APP695 and APP751 is high at birth and exhibits nearly adult levels. The developmental expression pattern of cortical APP695 displays a peak value around postnatal day 10, while the age‐related expression of APP751 demonstrates peak values on postnatal days 10 and 25, with the highest steady state levels of APP751 mRNA on day 25. During early development, the cortical laminar distribution of the APP695, but not APP751, mRNA transiently changes from a more homogeneous distribution at birth to a pronounced laminar pattern with higher mRNA levels in cortical layer III/IV detectable at the age of 4 days and persisting until postnatal day 10. The distinct age‐related changes in cortical APP695 and APP751 mRNA levels reflect the functional alterations during early brain maturation and suggest that APP695 might play a role in establishing the mature connectional pattern between neurons, whereas APP751 could play a role in controlling cellular growth and synaptogenesis.Lesion of basal forebrain cholinergic system by the selective cholinergic immunotoxin 192IgG‐saporin resulted in decreased levels of APP695 but not APP751 and APP770 transcripts by about 15–20% in some cortical (cingulate, frontal, parietal, piriform cortex), hippocampal regions (CA1, dentate gyrus), and basal forebrain nuclei (medial septum, vertical limb of diagonal band), detectable not earlier than 30 days after lesion and persisting until 90 days postlesion, suggesting that the nearly complete loss of cortical cholinergic input does not have any significant impact on the expression of APP mRNA isoforms in cholinoceptive cortical target regions.
DSM-IV catatonic features among psychiatric inpatients: a preliminary study
Authors: Oulis P , Lykouras L , Tomaras V , Panayotopoulou V , Gournellis R , Stefanis C
Published: July 2002

We studied DSM-IV catatonic features in 120 psychiatric inpatients with a main diagnosis of acute psychotic, affective or cognitive disorder. Individual catatonic features were highly intercorrelated, although diagnostically nonspecific. A single factor, accounting for 85% of the variance, was extracted and interpreted as representing both types (excited and retarded) of catatonic syndrome.
Discriminant cognitive factors in responder and non-responder patients with schizophrenia
Authors: Stip E. , Lussier I. , Ngan E. , Mendrek A. , Liddle P.
Published: July 2002

To identify which improvements in cognitive function are associated with symptom resolution in schizophrenic patients treated with atypical antipsychotics. Design: a prospective open trial with atypical neuroleptics (risperidone, clozapine, quetiapine). Setting: Inpatient and outpatient units, Institute of Psychiatry. Patients: Thirty-nine patients with schizophrenia according to DSM-IV criteria were included. Clinical and cognitive assessment were done at baseline (T0) and again after six months of treatment (T2). Twenty-five patients completed the trial. Interventions: New-generation antipsychotics during six months. Patients were considered as responders if their PANSS score decreased at least 20% (n= 15) and non-responders if it did not (n= 10). Outcome measures: a computerized cognitive assessment comprised tests of short-term-memory (digit span), explicit long-term memory (word pair learning), divided attention, selective attention and verbal fluency (orthographic and semantic). Clinical assessment included PANSS and ESRS. Results: A discriminant function analysis was performed to determine which changes in cognitive performance predicted symptomatic response status. Semantic fluency and orthographic fluency were significant predictors. Together they correctly predicted responder status in 88% of cases. Memory was not a significant predictor of symptomatic response. Conclusion: Verbal fluency discriminated the responder from the non-responder group during a pharmacological treatment.
Fascism and the New Russian Nationalism
Authors: Gregor A. James
Published: July 2002

This article provides a broad comparison between Italian Fascism and the new nationalism that has arisen in post-Soviet Russia. The focus is on that nationalism which has, in the immediate past, merged with what used to be the Marxism-Leninism of the Communist Party of the Russian Federation. The ideas of Gennadii Ziuganov, leader of the CPRF, are traced to Sergei Kurginian and Alexander Prokhanov-and compared to those of the ideologues of historic Fascism.
Cognitive Screening Tools
Authors: Gulick Sarah H. , Mandel Steven , Maitz Edward A. , Brigham Christopher R. , Direnfeld Lorne K.
Published: May 2021

Physicians performing impairment evaluations on patients with cognitive complaints and possible central nervous system disorders should perform a clinical mental status assessment. Assessing cognitive complaints efficiently, in a systematic and supportable way, can be challenging. The AMA Guides to the Evaluation of Permanent Impairment specifies that objective criteria are important to consider when assessing impairment. Physicians may choose to use standardized cognitive screening tests (cognitive screeners) as a relatively quick, practical tool to initially assess patients and aid in decision making. Several cognitive screeners will be discussed in detail below. A patient's performance on such tests may indicate that more comprehensive testing is needed. Cognitive screeners have limitations and are not designed to assess symptom validity or the extent to which psychological factors may contribute to cognitive complaints. Comprehensive neuropsychological assessment may be indicated in these situations and when the screeners demonstrate findings of potential concern help define MMI.
Environmental Impact and Aging Properties of Natural and Synthetic Transformer Oils under Electrical Stress Conditions
Authors: Kurzweil Peter , Schell Christian , Haller Rainer , Trnka Pavel , Hornak Jaroslav
Published: May 2021

Against the background of environmental compatibility and unrestricted technical usability, synthetic, and natural transformer oils are critically compared in long‐term tests under high voltage using electrical and instrumental analytical methods. Synthetic alkyl esters of pentaerythrol appear to be sustainable and sometimes superior substitutes for mineral oils in terms of chemical stability, viscosity, permittivity, and heat transport. Natural esters of unsaturated fatty acids are found to be unsuitable for equipment exposed to moist air. Adsorbed water appears to be a general problem in transformer oils. The aging mechanisms and molecular changes during long‐term operation include radical reactions, and the formation, isomerization and cleavage of CC bonds. Extensive material data are provided.
Hypothesis: JNK signaling is a therapeutic target of neurodegenerative diseases
Authors: Zhao Yingying , Kuca Kamil , Wu Wenda , Wang Xu , Nepovimova Eugenie , Musilek Kamil , Wu Qinghua
Published: May 2021

The exact signaling leading to neurological dysfunction in neurodegenerative diseases is currently unknown. We hypothesize that the c‐Jun N‐terminal kinase (JNK) signaling pathway is a potential therapeutic target for neurodegenerative diseases. This postulate rests on extensive data from cell and animal experimental studies, demonstrating that JNK signaling plays a crucial role in the pathogenesis of neurodegenerative diseases. The sustained activation of JNK leads to synaptic dysfunction and even neuronal apoptosis, ultimately resulting in memory deficits and neurodegeneration. JNK phosphorylates the amyloid precursor protein and tau, ultimately resulting in the formation of extraneuronal senile plaques and intraneuronal neurofibrillary tangles. Our hypothesis could be validated by investigating the cerebral cortex of elderly chimpanzees injected with phosphorylated JNK or transgenic pig and chimpanzee models established using gene editing technology including CRISPR. This hypothesis provides clues for further understanding the molecular mechanisms of neurodegenerative diseases and the development of potential target therapeutic drugs.
Tau pathologies mediate the association of blood pressure with cognitive impairment in adults without dementia: The CABLE study
Authors: Hu Hao , Meng Li , Bi Yan‐Lin , Zhang Wei , Xu Wei , Shen Xue‐Ning , Ou Ya‐Nan , Ma Ya‐Hui , Dong Qiang , Tan Lan , Yu Jin‐Tai
Published: May 2021

Introduction

This study delineated the interrelationships among blood pressure (BP), cerebrospinal fluid (CSF) core biomarkers of Alzheimer's disease (AD), and cognition.

Methods

The linear regression analyses were conducted in 1546 non‐demented participants (mean age of 61.58 years, range 40 to 89 years; 40% female; average days of BP measurement, 9.10 days). Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects.

Results

A clear age‐related pattern of BP was delineated. Mid‐life hypertension (especially systolic BP), late‐life lower diastolic BP, as well as mid‐ and late‐life higher pulse pressure were associated with cognitive impairment and tau‐related biomarkers. BP variability was associated only with cognition but not with CSF biomarkers. Overall, the associations between BP and cognition were partially mediated (proportion: 11% to 30%) by tau pathologies, independently of amyloid pathology.

Discussion

Tau pathologies might play important roles in the relationship between BP and cognition, with significant age‐ and BP‐type dependences.
Inorganic Synthesis Based on Reactions of Ionic Liquids and Deep Eutectic Solvents
Authors: Zhang Tao , Doert Thomas , Wang Hui , Zhang Suojiang , Ruck Michael
Published: May 2021

Ionic liquids and deep eutectic solvents are of growing interest as solvents for the resource‐efficient synthesis of inorganic materials. This Review covers chemical reactions of various deep eutectic solvents and types of ionic liquids, including metal‐containing ionic liquids, [BF4]−‐ or [PF6]−‐based ionic liquids, basic ionic liquids, and chalcogen‐containing ionic liquids. Cases in which cations, anions, or both are incorporated into the final products are also included. The purpose of this Review is to raise caution about the chemical reactivity of ionic liquids and deep eutectic solvents and to establish a guide for their proper use.
Conductive Two‐Dimensional Phthalocyanine‐based Metal–Organic Framework Nanosheets for Efficient Electroreduction of CO2
Authors: Yi Jun‐Dong , Si Duan‐Hui , Xie Ruikuan , Yin Qi , Zhang Meng‐Di , Wu Qiao , Chai Guo‐Liang , Huang Yuan‐Biao , Cao Rong
Published: May 2021

The electrocatalytic conversion of CO2 into value‐added chemicals is a promising approach to realize a carbon‐energy balance. However, low current density still limits the application of the CO2 electroreduction reaction (CO2RR). Metal–organic frameworks (MOFs) are one class of promising alternatives for the CO2RR due to their periodically arranged isolated metal active sites. However, the poor conductivity of traditional MOFs usually results in a low current density in CO2RR. We have prepared conductive two‐dimensional (2D) phthalocyanine‐based MOF (NiPc‐NiO4) nanosheets linked by nickel‐catecholate, which can be employed as highly efficient electrocatalysts for the CO2RR to CO. The obtained NiPc‐NiO4 has a good conductivity and exhibited a very high selectivity of 98.4 % toward CO production and a large CO partial current density of 34.5 mA cm−2, outperforming the reported MOF catalysts. This work highlights the potential of conductive crystalline frameworks in electrocatalysis.
Selective Separation of Hexachloroplatinate(IV) Dianions Based on Exo‐Binding with Cucurbit[6]uril
Authors: Wu Huang , Wang Yu , Jones Leighton O. , Liu Wenqi , Zhang Long , Song Bo , Chen Xiao‐Yang , Stern Charlotte L. , Schatz George C. , Stoddart J. Fraser
Published: May 2021

The recognition and separation of anions attracts attention from chemists, materials scientists, and engineers. Employing exo‐binding of artificial macrocycles to selectively recognize anions remains a challenge in supramolecular chemistry. We report the instantaneous co‐crystallization and concomitant co‐precipitation between [PtCl6]2−dianions and cucurbit[6]uril, which relies on the selective recognition of these dianions through noncovalent bonding interactions on the outer surface of cucurbit[6]uril. The selective [PtCl6]2−dianion recognition is driven by weak [Pt−Cl⋅⋅⋅H−C] hydrogen bonding and [Pt−Cl⋅⋅⋅C=O] ion–dipole interactions. The synthetic protocol is highly selective. Recognition is not observed in combinations between cucurbit[6]uril and six other Pt‐ and Pd‐ or Rh‐based chloride anions. We also demonstrated that cucurbit[6]uril is able to separate selectively [PtCl6]2−dianions from a mixture of [PtCl6]2−, [PdCl4]2−, and [RhCl6]3−anions. This protocol could be exploited to recover platinum from spent vehicular three‐way catalytic converters and other platinum‐bearing metal waste.