bluuebunny/crossref_metadata_2025 huggingface dataset:
pH‐dependent interaction of an intraluminal loop of inositol 1,4,5‐trisphosphate receptor with chromogranin A
Authors: Yoo Seung Hyun , Lewis Marc S.
Published: July 2002

The inositol 1,4,5‐trisphosphate (IP3)‐sensitive Ca2+ store role of the secretory vesicles of adrenal medullary chromaffin cells is attributed to the presence of high capacity, low affinity Ca2+ binding protein chromogranin A. Chromogranin A has recently been shown to interact with the protein component(s) on the intraluminal side of the secretory vesicle membrane at the intravesicular pH of 5.5 but to dissociate from them at the near physiological pH of 7.5. Further, one of the chromogranin A‐interacting membrane proteins was tentatively identified as the IP3 receptor. Therefore, the pH‐dependent potential interaction of the intraluminal loop domains of the IP3 receptor with chromogranin A was studied by analytical ultracentrifugation utilizing synthetic intraluminal loop peptides of the IP3 receptor labeled with 5‐hydroxy‐tryptophan at the N‐terminus as a chromophore. One of the intraluminal loop domains was found to interact with chromogranin A at pH 5.5 but not at pH 7.5, suggesting the importance of the intraluminal loop domain in transmitting Ca2+ mobilization signals to chromogranin A.
Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver
Authors: de Cavanagh Elena M.V. , Inserra Felipe , Ferder León , Romano Luis , Ercole Liliana , Fraga César G.
Published: July 2002

We have characterized the effect of angiotensin converting enzyme (ACE) inhibitors on the activity of CuZn‐superoxide dismutase (CuZn‐SOD), Mn‐superoxide dismutase (Mn‐SOD), catalase, and selenium‐dependent glutathione peroxidase (Se‐GPx). CF1 mice (4‐month‐old females) were administered water containing enalapril (20 mg/l) or captopril (50 mg/l), during 4 to 11 weeks. After 11 weeks, enalapril treatment caused an increase in the activity of CuZn‐SOD, Mn‐SOD and Se‐GPx, from 19 ± 4 to 46 ± 7, 2.1 ± 0.2 to 3.8 ± 0.2 units/mg protein and 27 ± 3 to 54 ± 3 milliunits/mg protein, respectively. After 11 weeks, captopril treatment increased the activities (P < 0.05) of CuZn‐SOD, MnSOD and Se‐GPx to 35 ± 4, 2.9 ± 0.2 units/mg protein, and 38 ± 2 milliunits/mg protein, respectively. Catalase activity was not affected by the treatments. These results suggest that ACE inhibitors may protect cell components from oxidative damage by increasing the enzymatic antioxidant defenses.
Interaction of a synaptobrevin (VAMP)‐syntaxin complex with presynaptic calcium channels
Authors: El Far Oussama , Charvin Nathalie , Leveque Christian , Martin-Moutot Nicole , Takahashi Masami , Seagar Michael J.
Published: July 2002

Nerve terminal protein complexes implicated in exocytosis were examined by immuno‐isolation from rat brain synaptosomes. Immunoprecipitation with anti‐syntaxin or anti‐VAMP antibodies revealed a syntaxin‐SNAP25‐VAMP‐synaptotagmin complex. Anti‐VAMP antibodies also trapped a distinct VAMP‐synaptophysin complex. A similar fraction (about 70%) of N‐type calcium channels ([125I]ω conotoxin GVIA receptors), was immunoprecipitated by either anti‐syntaxin or anti‐VAMP antibodies, but not by anti‐synaptophysin antibodies (< 4%). The majority of N‐ but not L‐type calcium channels ([3H]PN200‐110 receptors), appear to be associated with a synaptic vesicle prefusion complex.
Membrane traffic motors
Authors: Allan Viki
Published: July 2002

There is a wealth of data suggesting that microtubules and associated motor proteins play important roles in orchestrating membrane traffic within higher eukaryotes, with myosins and actin filaments fulfilling similar functions in organisms such as fungi, algae and plants. In addition, evidence is accumulating that both cytoskeletal systems can co‐operate within one cell. Recent studies have highlighted how individual motor proteins can act at multiple steps in the membrane‐traffic pathways, and in contrast, how more than one motor type may be involved in each transport step and in generating organelle morphology.
Role of the conserved aspartate and phenylalanine residues in prokaryotic and mitochondrial elongation factor Ts in guanine nucleotide exchange
Authors: Zhang Yuelin , Li Xin , Spremulli Linda L.
Published: July 2002

The guanine nucleotide exchange reaction catalyzed by elongation factor Ts is proposed to arise from the intrusion of the side chains of D80 and F81 near the Mg2+ binding site in EF‐Tu. D80A and F81A mutants of E. coli EF‐Ts were 2–3‐fold less active in promoting GDP exchange with E. coli EF‐Tu while the D80AF81A mutant was nearly 10‐fold less active. The D84 and F85 mutants of EF‐Tsmt were 5–10‐fold less active in stimulating the activity of EF‐Tumt. The double mutation completely abolished the activity of EF‐Tsmt.
Targeted delivery of diphtheria toxin via immunoliposomes: efficient antitumor activity in the presence of inactivating anti‐diphtheria toxin antibodies
Authors: Vingerhoeds Monique H , Steerenberg Peter A , Hendriks Jos J.G.W , Crommelin Daan J.A , Storm Gert
Published: July 2002

Diphtheria toxin (DT) has attracted considerable attention for anti‐cancer therapy. However, its extensive use is prohibited by (i) its non‐specific action which can result in substantial toxicity, (ii) most patients have low serum levels of anti‐DT antibodies (AT antibodies) which can inactivate DT and (iii) its immunogenicity will boost the circulating AT antibody level, thereby further compromising the antitumor activity. To overcome these limitations, we have developed a new approach for targeted delivery of DT utilizing immunoliposomes. In this approach, protection against the non‐specific action of DT is combined with efficient antitumor activity even in the presence of inactivating AT antibodies.
STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF TENASCIN‐R (RESTRICTIN), AN EXTRACELLULAR MATRIX GLYCOPROTEIN OF GLIAL CELLS AND NEURONS
Authors: Nörenberg Ursel , Hubert Michael , Rathjen Fritz G.
Published: July 2002

Tenascin‐R (TN‐R) is an extracellular matrix protein associated with the surface of neurons and glial cells. Immunohistological studies reveal that TN‐R shows a restricted expression pattern in the developing nervous system. TN‐R is the smallest member of the tenascin family and is composed of four structural motifs: a cysteine‐rich segment at the N‐terminus is followed by 4.5 EGF‐like repeats. This region is followed by 9 consecutive fibronectin type III (FNIII)‐like domains and at the C‐terminus TN‐R is related to the β‐ and γ‐ chains of fibrinogen. TN‐R forms oligomeric structures as revealed by rotary shadowing electron microscopy of immunoaffinity‐purified TN‐R. TN‐R interacts with the axon‐associated F11 protein which results in an enhancement of F11 mediated neurite extension in in vitro assays. In short‐term adhesion assays it was found that neural but not fibroblastic cells attach effectively on immobilized TN‐R. The cell attachment site within TN‐R was allocated to FNIII domain 8 while the site interacting with the F11 protein could be mapped to FNIII domain 2–3.
Retrovirus‐mediated gene delivery into male germ line stem cells
Authors: Nagano Makoto , Shinohara Takashi , Avarbock Mary R , Brinster Ralph L
Published: July 2002

The male germ line stem cell is the only cell type in the adult that can contribute genes to the next generation and is characterized by postnatal proliferation. It has not been determined whether this cell population can be used to deliberately introduce genetic modification into the germ line to generate transgenic animals or whether human somatic cell gene therapy has the potential to accidentally introduce permanent genetic changes into a patient's germ line. Here we report that several techniques can be used to achieve both in vitro and in vivo gene transfer into mouse male germ line stem cells using a retroviral vector. Expression of a retrovirally delivered reporter lacZ transgene in male germ line stem cells and differentiated germ cells persisted in the testis for more than 6 months. At least one in 300 stem cells could be infected. The experiments demonstrate a system to introduce genes directly into the male germ line and also provide a method to address the potential of human somatic cell gene therapy DNA constructs to enter a patient's germ line.
Convergent evolution with combinatorial peptides
Authors: Kay Brian K , Kasanov Jeremy , Knight Stephen , Kurakin Alexei
Published: July 2002

Once the sequence of a genome is in hand, understanding the function of its encoded proteins becomes a task of paramount importance. Much like the biochemists who first outlined different biochemical pathways, many genomic scientists are engaged in determining which proteins interact with which proteins, thereby establishing a protein interaction network. While these interactions have evolved in regard to their specificity, affinity and cellular function over billions of years, it is possible in the laboratory to isolate peptides from combinatorial libraries that bind to the same proteins with similar specificity, affinity and primary structures, which resemble those of the natural interacting proteins. We have termed this phenomenon ‘convergent evolution’. In this review, we highlight various examples of convergent evolution that have been uncovered in experiments dissecting protein–protein interactions with combinatorial peptides. Thus, a fruitful approach for mapping protein–protein interactions is to isolate peptide ligands to a target protein and identify candidate interacting proteins in a sequenced genome by computer analysis.
CD98 induces LFA‐1‐mediated cell adhesion in lymphoid cells via activation of Rap1
Authors: Suga Koji , Katagiri Koko , Kinashi Tatsuo , Harazaki Masashi , Iizuka Tadahiko , Hattori Masakazu , Minato Nagahiro
Published: July 2002

CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well as amino acid transport. We show that CD98 cross‐linking persistently activates Rap1 GTPase in a LFA‐1‐dependent manner and induces LFA‐1/ICAM‐1‐mediated cell adhesion in lymphocytes. Specific phosphatidylinositol‐3‐kinase (PI3K) inhibitors suppressed both LFA‐1 activation and Rap1GTP generation, and abrogation of Rap1GTP by retroviral over‐expression of a specific Rap1 GTPase activating protein, SPA‐1, totally inhibited the LFA‐1/ICAM‐1‐mediated cell adhesion. These results suggest that CD98 cross‐linking activates LFA‐1 via the PI3K signaling pathway and induces accumulation of Rap1GTP in a LFA‐1‐dependent manner, which in turn mediates the cytoskeleton‐dependent cell adhesion process.
Helicobacter mustelae lipid A structure differs from that of Helicobacter pylori
Authors: Thérisod Hélène , Monteiro Mario A , Perry Malcolm B , Caroff Martine
Published: July 2002

The lipid A structure of the Gram‐negative bacterium Helicobacter mustelae, a ferret gastric pathogen responsible for the onset of gastric diseases in its host, was investigated. Two variant lipid A structures were found in the same strain. One structure contained a bisphosphorylated β‐(1→6)‐linked D‐glucosamine backbone disaccharide with hydroxytetradecanoic acid in amide linkages. Unlike the structure described for the lipid A of the related human Helicobacter pylori gastric pathogen, which contains a C1 phosphate moiety, this lipid A presented phosphate groups at both the C1 and C4′ positions, and contained no octadecanoyl fatty acid, which is present in H. pylori. The second lipid A structure had a different fatty acid composition in that 3‐OH C16 replaced most of the amide‐linked 3‐OH C14.
A new role for vascular endothelial growth factor and fibroblast growth factors: increasing endothelial resistance to oxidative stress
Authors: Yang Weidong , de Bono David P
Published: July 2002

© 1997 Federation of European Biochemical Societies.
Involvement of cyanide‐resistant and rotenone‐insensitive pathways of mitochondrial electron transport during oxidation of glycine in higher plants
Authors: Igamberdiev Abir U , Bykova Natalia V , Gardeström Per
Published: July 2002

Metabolism of glycine in isolated mitochondria and protoplasts was investigated in photosynthetic, etiolated (barley and pea leaves) and fat‐storing (maize scutellum) tissues using methods of [1‐14C]glycine incorporation and counting of 14CO2 evolved, oxymetric measurement of glycine oxidation and rapid fractionation of protoplasts incubated in photorespiratory conditions with consequent determination of ATP/ADP ratios in different cell compartments. The involvement of different paths of electron transport in mitochondria during operation of glycine decarboxylase complex (GDC) was tested in different conditions, using aminoacetonitrile (AAN), the inhibitor of glycine oxidation in mitochondria, rotenone, the inhibitor of Complex I of mitochondrial electron transport, and inhibitors of cytochrome oxidase and alternative oxidase. It was shown that glycine has a preference to other substrates oxidized in mitochondria only in photosynthetic tissue where succinate and malate even stimulated its oxidation. Rotenone had no or small effect on glycine oxidation, whereas the role of cyanide‐resistant path increased in the presence of ATP. Glycine oxidation increased ATP/ADP ratio in cytosol of barley protoplasts incubated in the presence of CO2, but not in the CO2‐free medium indicating that in conditions of high photorespiratory flux oxidation of NADH formed in the GDC reaction passes via the non‐coupled paths. Activity of GDC in fat‐storing tissue correlated with the activity of glyoxylate‐cycle enzymes, glycine oxidation did not reveal preference to other substrates and the involvement of paths non‐connected with proton translocation was not pronounced. It is suggested that the preference of glycine to other substrates oxidized in mitochondria is achieved in photosynthetic tissue by switching to rotenone‐insensitive intramitochrondrial NADH oxidation and by increasing of alternative oxidase involvement in the presence of glycine.
Neuroprotective potential of aromatic alcohols against oxidative cell death
Authors: Moosmann Bernd , Uhr Manfred , Behl Christian
Published: July 2002

Estrogens can protect neurons against oxidative stress‐induced cell death due to their antioxidant potential. Here, we report that other aromatic alcohols with intact phenolic groups and different phenol derivatives can also protect neurons against oxidative cell death induced by glutamate and hydrogen peroxide in vitro. This neuroprotective activity was independent of the time the compound was added before the toxin. Methylation of the phenolic hydroxyl group led to a decrease or loss in neuroprotection. Moreover, the tested compounds directly inhibited peroxidation reactions, suggesting that neuroprotection is mediated by their antioxidant properties.
Trypanosoma cruzi glycosomal glyceraldehyde‐3‐phosphate dehydrogenase: structure, catalytic mechanism and targeted inhibitor design
Authors: Souza D.H.F , Garratt R.C , Araújo A.P.U , Guimarães B.G , Jesus W.D.P , Michels P.A.M , Hannaert V , Oliva G
Published: July 2002

The structure of the enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) from glycosomes of the parasite Trypanosoma cruzi, causative agent of Chagas' disease, is reported. The final model at 2.8 Å includes the bound cofactor NAD+ and 90 water molecules per monomer and resulted in an R
factor of 20.1%, R
free=22.3%, with good geometry indicators. The structure has no ions bound at the active site resulting in a large change in the side chain conformation of Arg249 which as a consequence forms a salt bridge to Asp210 in the present structure. We propose that this conformational change could be important for the reaction mechanism and possibly a common feature of many GAPDH structures. Comparison with the human enzyme indicates that interfering with this salt bridge could be a new approach to specific inhibitor design, as the equivalent to Asp210 is a leucine in the mammalian enzymes.
Kunitz‐type proteinase inhibitors from intact and Phytophthora‐infected potato tubers
Authors: Valueva Tatyana A , Revina Tatyana A , Kladnitskaya Galina V , Mosolov Vladimir V
Published: July 2002

Three protein proteolytic enzyme inhibitors with molecular masses 21, 22, and 23 kDa have been isolated from intact potato tubers (Solanum tuberosum L. cv. Istrinskii). The 21 and 22 kDa proteins denoted as PSPI‐21 and PSPI‐22, respectively, are serine proteinase inhibitors with different specificity. The 23 kDa protein denoted as PCPI‐23 is an inhibitor of plant cysteine proteinases. The PSPI‐21 molecule consists of two disulfide‐linked polypeptide chains with molecular masses of 16.5 kDa and 4.5 kDa. The PSPI‐22 and PCPI‐23 have one polypeptide chain. Their amino‐termini numbered 21–25 amino acid residues have significant homology to other plant inhibitors which are members of the soybean Kunitz inhibitor family. It is found that at least PSPI‐21 and PSPI‐22 can predominantly accumulate in potato tubers infected with Phytophthora infestans zoospores.
Vacuolation induced by cytotoxin from Helicobacter pylori is mediated by the EGF receptor in HeLa cells
Authors: Seto Koichi , Hayashi-Kuwabara Yu , Yoneta Tomoyuki , Suda Hiroshi , Tamaki Hajime
Published: July 2002

The bacterial toxin VacA produced by H. pylori induces large vacuoles in several types of cultured cells such as HeLa cells or gastric cells. To determine the mechanism of vacuolation induced by this toxin we employed several inhibitors of membrane trafficking and endocytosis. The development of vacuolation induced by VacA in HeLa cells were prevented by bafilomycin A1 and low temperature conditions that inhibited vesicle transport or endocytosis. Formation of large vacuoles was also inhibited by an antibody against EGF receptor, which was previously shown to be internalized by endocytosis, but not by an anti‐transferrin receptor antibody. Moreover, proteins of 58 and 37 kDa, corresponding to fragments of VacA, were recognized by an anti‐H. pylori antibody after immunoprecipitation with anti‐EGF receptor of cell extracts from HeLa cells treated with VacA, but not from untreated HeLa cells. We suggest that VacA may enter cells by endocytosis mediated by the EGF receptor. These are the first data indicating that the EGF receptor may be significant in the development of vacuolation caused by VacA.
TM7XN1, a novel human EGF‐TM7‐like cDNA, detected with mRNA differential display using human melanoma cell lines with different metastatic potential1
Authors: Zendman Albert J.W , Cornelissen Ine M.H.A , Weidle Ulrich H , Ruiter Dirk J , van Muijen Goos N.P
Published: July 2002

We have identified a novel 3845 bp cDNA differentially expressed in a human melanoma metastasis model. Northern blot analysis showed expression in the poorly and intermediately metastasizing cell lines and a marked downregulation in the highly metastatic cell lines. Using RT‐PCR expression was also seen in several other tumor cell lines and normal cell types of human origin. cDNA sequence analysis revealed an ORF of 687 amino acids containing seven putative transmembrane domains C‐terminally and a long N‐terminus. The gene was mapped to 16q13. Highest homology was observed with members of the EGF‐TM7 subfamily of the secretin/calcitonin receptor family. We propose the delineation of a subfamily of TM7 proteins, LN‐TM7, containing seven transmembrane proteins with a long N‐terminal extracellular part.
Functional identification of ATP‐driven Ca2+ pump in the peribacteroid membrane of broad bean root nodules
Authors: Andreev Igor M. , Dubrovo Pavel N. , Krylova Valeria V. , Izmailov Stanislav F.
Published: July 2002

A Ca2+ indicator arsenazo III was used to demonstrate calcium uptake activity of symbiosomes and the peribacteroid membrane (PBM) vesicles isolated from broad bean root nodules and placed in the medium containing ATP and Mg2+ ions. This process was shown to be rapidly stopped by vanadate, completely reversed in the presence of the calcium ionophore A23187 but insensitive to agents abolishing electrical potential or pH difference across the PBM. The presence of an endogenous calcium pool within isolated symbiosomes and bacteroids was detected using a Ca2+ indicator chlortetracycline. These results prove a primary active transport of Ca2+ through the PBM of legume root nodules and provide the first functional identification of an ATP‐driven Ca2+‐pump, most likely Mg2+‐dependent Ca2+‐translocating ATPase, in this membrane.
Characterisation of a plant 3‐phosphoinositide‐dependent protein kinase‐1 homologue which contains a pleckstrin homology domain
Authors: Deak Maria , Casamayor Antonio , Currie Richard A. , Peter Downes C. , Alessi Dario R.
Published: July 2002

A plant homologue of mammalian 3‐phosphoinositide‐dependent protein kinase‐1 (PDK1) has been identified in Arabidopsis and rice which displays 40% overall identity with human 3‐phosphoinositide‐dependent protein kinase‐1. Like the mammalian 3‐phosphoinositide‐dependent protein kinase‐1, Arabidopsis 3‐phosphoinositide‐dependent protein kinase‐1 and rice 3‐phosphoinositide‐dependent protein kinase‐1 possess a kinase domain at N‐termini and a pleckstrin homology domain at their C‐termini. Arabidopsis 3‐phosphoinositide‐dependent protein kinase‐1 can rescue lethality in Saccharomyces cerevisiae caused by disruption of the genes encoding yeast 3‐phosphoinositide‐dependent protein kinase‐1 homologues. Arabidopsis 3‐phosphoinositide‐dependent protein kinase‐1 interacts via its pleckstrin homology domain with phosphatidic acid, PtdIns3P, PtdIns(3,4,5)P3 and PtdIns(3,4)P2 and to a lesser extent with PtdIns(4,5)P2 and PtdIns4P. Arabidopsis 3‐phosphoinositide‐dependent protein kinase‐1 is able to activate human protein kinase Bα (PKB/AKT) in the presence of PtdIns(3,4,5)P3. Arabidopsis 3‐phosphoinositide‐dependent protein kinase‐1 is only the second plant protein reported to possess a pleckstrin homology domain and the first plant protein shown to bind 3‐phosphoinositides.
Increased expression of the Na+/Ca2+ exchanger in the rat heart after immobilization stress is not induced by cortisol
Authors: Zacikova Lubomira , Kvetnansky Richard , Krizanova Olga
Published: July 2002

Calcium homeostasis is crucial for the proper function of cardiac cells. Since the Na+/Ca2+ exchanger is an important modulator of calcium homeostasis especially in the heart, the objective of this study was to investigate the effect of immobilization stress on the high capacity Na+/Ca2+ exchanger in rat heart ventricles and atria. Repeated immobilization stress increased both the mRNA and the protein level and the activity of the Na+/Ca2+ exchanger in the left, but not the right ventricle of rat heart. Since corticosterone is rapidly increased during the stress stimulus, it might be assumed that mRNA of the Na+/Ca2+ exchanger is increased through a glucocorticoid responsive element. However, we have found that cortisol did not change the Na+/Ca2+ exchanger at the mRNA or protein levels. These results clearly show that this effect of stress is not mediated via cortisol.
Identification of proteins that interact with NF‐YA
Authors: Yamada Kazuya , Osawa Haruhiko , Granner Daryl K.
Published: July 2002

We used the yeast two‐hybrid system to show that the serum response factor (SRF) and zinc‐fingers and homeobox 1 (ZHX1) proteins interact with the A subunit of nuclear factor‐Y (NF‐YA). GST pulldown assays revealed that both proteins interact specifically with NF‐YA in vitro. Amino acids located between 272 and 564, a region that contains two homeodomains, are required for the interaction of ZHX1 with NF‐YA. Two different domains of NF‐YA, a glutamine‐rich region and a serine/threonine‐rich region, are necessary for the interactions with ZHX1 and SRF, respectively.
Selection of phage‐displayed Fab antibodies on the active conformation of Ras yields a high affinity conformation‐specific antibody preventing the binding of c‐Raf kinase to Ras
Authors: Horn Ivo R. , Wittinghofer Alfred , de Bruïne Adriaan P. , Hoogenboom Hennie R.
Published: July 2002

The Ras proteins cycle in the cell between an inactive state and an active state. In the active state, Ras signals via the switch I region to effectors like c‐Raf kinase, leading to cell growth. Since Ras mutations in cancer are often associated with the presence of permanently active Ras, molecules that prevent downstream signaling may be of interest. Here, we show that by selection on the active conformation of Ras, using a recently described large phage antibody repertoire [de Haard et al. (1999) J. Biol. Chem. 274, 18218–18230], a Fab antibody (Fab H2) was identified that exclusively binds to active Ras, and not to inactive Ras. Using surface plasmon resonance (SPR) analysis, the interaction was demonstrated to be of high affinity (7.2 nM). In addition, the interaction with Ras is specific, since binding to the homologous Rap1A protein in BIAcore analysis is at least three orders of magnitude lower, and undetectable in an enzyme‐linked immunosorbent assay. The antibody fragment prevents the binding of active Ras to the immobilized Ras‐binding domain of c‐Raf kinase (Raf‐RBD) at an IC50 value of 135 nM. This value compares well to the K
D of active Ras‐binding to immobilized Raf‐RBD using SPR, suggesting identical binding sites. Like the IgG Y13‐259, which does not demonstrate preferential binding to either inactive or active Ras, Fab H2 inhibits intrinsic GTPase activity of Ras in vitro. Mapping studies using SPR analysis demonstrate that the binding sites for the antibodies are non‐identical. This antibody could be used for dissecting functional differences between Ras effectors. Due to its specificity for active Ras, Fab H2 may well be more selective than previously used anti‐Ras antibodies, and thus could be used for gene therapy of cancer with intracellular antibodies.
Mutations in the dystrophin‐like dys‐1 gene of Caenorhabditis elegans result in reduced acetylcholinesterase activity
Authors: Giugia Jean-Bernard , Gieseler Kathrin , Arpagaus Martine , Ségalat Laurent
Published: July 2002

Mutations of the Caenorhabditis elegans dystrophin/utrophin‐like dys‐1 gene lead to hyperactivity and hypercontraction of the animals. In addition dys‐1 mutants are hypersensitive to acetylcholine and acetylcholinesterase inhibitors. We investigated this phenotype further by assaying acetylcholinesterase activity. Total extracts from three different dys‐1 alleles showed significantly less acetylcholinesterase‐specific activity than wild‐type controls. In addition, double mutants carrying a mutation in the dys‐1 gene plus a mutation in either of the two major acetylcholinesterase genes (ace‐1 and ace‐2) display locomotor defects consistent with a strong reduction of acetylcholinesterases, whereas none of the single mutants does. Therefore, in C. elegans, disruption of the dystrophin/utrophin‐like dys‐1 gene affects acetylcholinesterase activity.
Inositol 1,4,5‐trisphosphate receptor associated with focal contact cytoskeletal proteins
Authors: Sugiyama Tomoyasu , Matsuda Yuzuru , Mikoshiba Katsuhiko
Published: July 2002

The linkage between inositol 1,4,5‐trisphosphate (IP3) receptors (IP3Rs) and cytoskeletal proteins is considered to be important in cell function. In the present study, the association of IP3R subtypes with cytoskeletal proteins was examined using monoclonal antibodies specific to each IP3R subtype. We found that IP3R type 2 colocalized with talin, a focal contact cytoskeletal protein. IP3R type 2 exhibited a patchy distribution in the peripheral cytoplasm differently from type 1 and type 3 IP3R. Furthermore, IP3R subtypes co‐immunoprecipitated with talin, vinculin and α‐actin, but not α‐actinin or paxillin.
Ionic currents in regenerating Avian vestibular hair cells
Authors: Masetto Sergio , Correia Manning J.
Published: July 2002

By applying the conventional whole‐cell patch‐clamp technique in combination with the slice procedure, we have investigated the properties of avian semicircular canal hair cells in situ. Passive and active electrical properties of hair cells from control animals have been compared with those of regenerating hair cells following streptomycin treatment (that killed almost all hair cells). Regenerating type II hair cells showed patterns of responses qualitatively similar to those of normal hair cells. However, parameters reflecting the total number of ionic channels and the surface area of type II hair cells changed during recovery—suggesting that new hair cells came from smaller precursors which (with time) reacquired the same electrophysiological properties as normal hair cells. Finally, we have investigated the ionic properties of a small sample of type I hair cells. Ionic currents of regenerating type I hair cells did not show, at least in the temporal window considered (up to 10 weeks from the end of the streptomycin treatment), the typical ionic currents of normal type I hair cells, but expressed instead ionic currents resembling those of type II hair cells. The possibility that regenerating type I hair cells can transdifferentiate from type II hair cells is therefore suggested.
Comparative postnatal development of dopamine D1, D2 and D4 receptors in rat forebrain
Authors: Tarazi Frank I. , Baldessarini Ross J.
Published: July 2002

Postnatal development of dopamine D1, D2 and D4 receptors in the caudate–putamen, nucleus accumbens, frontal cortex and hippocampus was assessed in rat brain between postnatal days 7 and 60. In the caudate–putamen and nucleus accumbens, density of all three receptor subtypes increased to a peak at postnatal day 28, then declined significantly in both regions (postnatal days 35–60) to adult levels. In the frontal cortex and hippocampus, these receptors rose steadily and continuously to stable, maximal adult levels by postnatal day 60. Evidently, D1, D2 and D4 receptors follow a similar course of development in several cortical, limbic and extrapyramidal regions of rat forebrain, with selective elimination of excess dopamine receptors at the time of puberty in the caudate–putamen and accumbens but not other brain regions.
Nosological validity of dysthymia. Part I: historical, epidemiological and clinical data
Authors: Waintraub L , Guelfi JD
Published: July 2002

Dysthymia is the last diagnostic label introduced after a series of precursors to describe a disorder whose nosological status has long been dubious. The results of published epidemiological, as well as clinical studies about its presentation, course and outcome partly support the validity of this construct — although their interpretation is limited by methodological difficulties: same prevalence in many locations in the world, always lower than that of major depression, somewhat specific clinical pattern, course and outcome.
In‐hospital heart failure, first‐year ventricular dilatation and 10‐year survival after acute myocardial infarction
Authors: Gadsbøll Niels , Torp‐Pedersen Christian , Høilund‐Carlsen Poul Flemming
Published: July 2002

Background:

Little is known about the factors that determine long‐term prognosis in patients who have survived the first year after acute myocardial infarction (AMI).

Aims:

To study the influence of left and right ventricular (LV and RV) dilatation during the first year after AMI on subsequent 10‐year survival in comparison with in‐hospital heart failure and other established prognostic indices.

Methods:

Radionuclide ventriculography was performed before the era of thrombolysis and post‐infarction ACE‐inhibition in 57 patients with AMI at hospital discharge and again 1 year later, and compared with survival the ensuing 10 years.

Results:

After 1 year significant LV‐dilatation (> 20%) had occurred in 32 (56%) patients. One year after the re‐investigation the mortality in these was 19% vs. 0% in patients without dilatation (P = 0.02); after 5 years the difference was 38 vs. 12% (P = 0.02), whereafter it declined and became insignificant at 10 years. Neither RV‐dilatation, nor LVEF determined at discharge or at the 1‐year reinvestigation influenced long‐term survival. In contrast, clinical heart failure recorded during the hospital stay had a sustained negative influence on long‐term survival.

Conclusion:

Progressive LV dilatation after discharge and clinical heart failure during the hospital stay are both determinants of late survival after AMI, whereas LV ejection fraction at hospital discharge or 1 year later has little, if any, effect on survival beyond 1‐year post‐AMI.
Discovering altered genomic expression patterns in heart: transcriptome determination by serial analysis of gene expression
Authors: Anisimov Sergey V. , Lakatta Edward G. , Boheler Kenneth R.
Published: July 2002

The development of cardiovascular diseases such as heart failure involve functional changes that are beneficial short‐term, but may be fatal long‐term. Current therapeutic approaches are tailored to limit progression of a disease and to maintain quality of life. At a molecular level, these disease processes involve quantitative and qualitative changes in gene expression. Although some changes in mRNA abundance may not have direct protein correlates, analysis of all the mRNAs present in a cell population (the cells transcriptome) has become a focal point of genomic research. The aim is to provide information about the dynamics of total genome expression in response to environmental changes and point to candidate genes responsible for the cascade of events that result in a disease state. One way of performing these analyses utilizes the technique of Serial Analysis of Gene Expression (SAGE). This method evaluates thousands of expressed transcripts both quantitatively and qualitatively in a single assay. In the first of two reviews on transcriptome analysis, we describe the current state of genomic research for determination of the transcriptome by Serial Analysis of Gene Expression, present the first limited SAGE analysis of rodent heart gene expression, and discuss how results generated with this approach can be applied to the study and treatment of cardiovascular diseases.
The Carvedilol Hibernation Reversible Ischaemia Trial; Marker of Success (CHRISTMAS)
Authors:   The CHRISTMAS Study Steering Committee and Investigators, Cleland John G.F. , Pennel Dudley , Ray Simon , Murray Gordon , MacFarlane Peter , Cowley Allan , Coats Andrew , Lahiri Avijit
Published: July 2002

Background:

Carvedilol improves left ventricular (LV) function when heart failure is due to LV systolic dysfunction, but the magnitude of the response is heterogeneous among patients with coronary disease, possibly reflecting the presence or volume of hibernating myocardium. Aims: The primary objective of the study is to determine whether the presence of hibernating myocardium predicts the magnitude of improvement in LV ejection fraction in response to carvedilol among patients with heart failure and LV systolic dysfunction due to coronary disease.

Methods:

The study is a prospective, randomised, parallel‐group, double‐blind, multi‐centre study comparing carvedilol and placebo over a period of approximately 6 months in the above patient population. The primary end‐point is the comparison of the mean change, from baseline to the final visit, in radionuclide‐determined LV ejection fraction among patients on placebo with those on carvedilol stratified according to the presence of hibernating myocardium. Hibernating status will be determined by a combination of echocardiographic and myocardial perfusion (technetium‐99m sestamibi) imaging.

Results:

255 patients have undergone screening tests of which 207 have been randomised so far. The study intends to randomise 400 patients and the first report of results is expected in 2000.

Conclusions:

As far as we are aware this is the first randomised controlled trial to investigate the effects of treatment in patients stratified according to the presence of hibernating myocardium. The study will provide insights into the prevalence of myocardial hibernation, its natural history, and its influence on prognosis as well as the interaction between the presence of hibernating myocardium and the effects of treatment with carvedilol.
Genetic aspects of heart failure
Authors: Komajda Michel , Charron Philippe , Tesson Frédérique
Published: July 2002

Heart failure is a major health problem and is associated with a high mortality and morbidity. Recently, the role of the genetic background in the onset and the development of the disease has been evidenced in both heart failure with and without systolic dysfunction and in familial and non‐familial forms of this condition. Preliminary studies suggest that the I/D polymorphism of the Angiotensin Converting Enzyme gene influence the development of left ventricular hypertrophy, a major determinant of heart failure. Familial hypertrophic cardiomyopathy (FHC) is a highly heterogenous autosomal dominant disease. Seven genes have been identified which all encode proteins of the sarcomere or proteins involved in the regulation of contraction. More than one hundred mutations have been evidenced. Modifier genes such as the I/D polymorphism seem to play a role in the expression of the disease. Susceptibility genes have been searched for in sporadic forms of dilated cardiomyopathy and conflicting results have been published with regard to the I/D polymorphism. Finally, familial forms of dilated cardiomyopathy (FDC) are frequent. Various modes of inheritance and phenotypes have been reported and this condition appears genetically highly heterogenous. It has been postulated that the molecular defect involved in FDC is an abnormality in the transmission of contractile force. The analysis of genetic factors that predispose to heart failure looks promising: it should allow better understanding of the underlying mechanisms that promote the progression of the disease, to identify subjects at risk of the disease who would benefit from early medical management and promote the development of pharmacogenetics.
Drug interactions as a cause of overanticoagulation on phenprocoumon or acenocoumarol predominantly concern antibacterial drugs
Authors: Penning‐van Beest Fernie J. A. , van Meegen Erik , Rosendaal Frits R. , Stricker Bruno H.
Published: July 2002

Background

The risk of hemorrhage when coumarin anticoagulants are used sharply increases when the international normalized ratio (INR) is ≥6.0. Such overanticoagulation may be caused by drug interactions. We performed a case‐control study among previously stable outpatients of an anticoagulation clinic using phenprocoumon or acenocoumarol to identify changes in the use of potentially interacting drugs related to overanticoagulation.

Methods

Three hundred case patients with INR values ≥6.0 were compared with 302 randomly selected matched control subjects with INR values within the target zone. Information on changes in the use of 87 potentially interacting drugs in the 4 weeks before the index day was collected by interviewing patients and by reviewing the anticoagulant medical record.

Results

Forty‐five potentially interacting drugs were not used in the 4‐week study period, and only 15 drugs were used by at least 10 patients. For a number of drugs, too few patients had a relevant change in use to judge their association with overanticoagulation. A course of a combination product of sulfamethoxazole and trimethoprim strongly increased the risk of overanticoagulation (adjusted odds ratio, 24.2; 95% confidence interval [CI], 2.8 to 209.1; population attributable risk percentage [PAR%], 5.7%), especially in patients receiving acenocoumarol. Penicillins were associated with a risk of overanticoagulation of 2.4 (95% CI, 1.00 to 5.5); the corresponding PAR% was 3.4%. The effect was confined to amoxicillin (INN, amoxicilline) plus clavulanic acid.

Conclusion

Drug interactions as a cause of overanticoagulation predominantly concerned antibacterial drugs. If possible, the use of sulfamethoxazole‐trimethoprim and amoxicillin plus clavulanic acid should be avoided in patients receiving coumarins. If there is no therapeutic alternative available, increased monitoring of INR values is warranted to prevent overanticoagulation and potential bleeding complications.

Clinical Pharmacology & Therapeutics (2001) 69, 451–457; doi: 10.1067/mcp.2001.115723
Evaluation and modulation of DNA lesion bypass in an SV40 large T antigen‐based in vitro replication system
Authors: Szeltner Zoltán , Póti Ádám , Harami Gábor M. , Kovács Mihály , Szüts Dávid
Published: January 2021

DNA damage removal by nucleotide excision repair (NER) and replicative bypass via translesion synthesis (TLS) and template switch (TSw) are important in ensuring genome stability. In this study, we tested the applicability of an SV40 large T antigen‐based replication system for the simultaneous examination of these damage tolerance processes. Using both Sanger and next‐generation sequencing combined with lesion‐specific qPCR and replication efficiency studies, we demonstrate that this system works well for studying NER and TLS, especially its one‐polymerase branch, while it is less suited to investigations of homology‐related repair processes, such as TSw. Cis‐syn cyclobutane pyrimidine dimer photoproducts were replicated with equal efficiency to lesion‐free plasmids in vitro, and the majority of TLS on this lesion could be inhibited by a peptide (PIR) specific for the polη‐PCNA interaction interface. TLS on 6–4 pyrimidine–pyrimidone photoproduct proved to be inefficient and was slightly facilitated by PIR as well as by a recombinant ubiquitin‐binding zinc finger domain of polη in HeLa extract, possibly by promoting polymerase exchange. Supplementation of the extract with recombinant PCNA variants indicated the dependence of TLS on PCNA ubiquitylation. In contrast to active TLS and NER, we found no evidence of successful TSw in cellular extracts. The established methods can promote in vitro investigations of replicative DNA damage bypass.
Unconventional Image‐Sensing and Light‐Emitting Devices for Extended Reality
Authors: Park Jinhong , Seung Hyojin , Kim Dong Chan , Kim Min Sung , Kim Dae‐Hyeong
Published: January 2021

Extended reality (XR) refers to a space where physical and digital elements coexist and comprises three elements, namely, environment, human, and computer, which interact with each other. Image sensors and displays are the core elements of XR systems because visual information is important for recognizing and judging objects. Recently, new features of image sensors and displays that are useful for developing next‐generation XR systems have been reported. For example, a miniaturized version of image sensors with the superb object detection and recognition capability offers new opportunities for machine vision technology. Furthermore, transparent and deformable displays are the key components of XR systems because they not only provide highly realistic virtual image information but also serve as efficient user interfaces. Herein, the recent progresses in such unconventional image sensors and display technologies are reviewed. First, image sensors with features of wavelength‐selective photodetection for color discrimination, neuromorphic image acquisition for facile pattern recognition, and curved image sensor designs inspired by biological eyes for miniaturization and unconventional imaging performances are discussed. Then, light‐emitting device technologies focusing on devices with transparency and deformable form factors are described. Finally, the review is concluded with a brief summary and a future outlook.
Hierarchical Interface Engineering for Advanced Nanocellulosic Hybrid Aerogels with High Compressibility and Multifunctionality
Authors: Zhang Junyan , Cheng Yanhua , Xu Chengjian , Gao Mengyue , Zhu Meifang , Jiang Lei
Published: January 2021

The hierarchical combination of mineral and biopolymer building blocks is advantageous for the notable properties of structural materials. Integrating silane and cellulose nanofibers into high‐performance hybrid aerogels is promising yet remains challenging due to the unsatisfied interface connections. Here, an interfacial engineering strategy is introduced via freeze–drying‐induced wetting and mineralization to reinforce the hierarchical porous cellulose network, resulting in mineral‐coated nanocellulose hybrid aerogels in a simple and consecutive bottom‐up assembly process. With optimized multiscale interfacial engineering between the stiff and soft components, the resulting cellulose‐based hybrid aerogels are endowed with lightweight (>0.7 mg cm−3), superior enhanced mechanical compressibility (>99% strain) within a wide temperature range, as well as super‐hydrophobicity (≈168°) and moisture stability under high humidity (95% relative humidity). Benefiting from these superior characters, the multifunctional hybrid aerogels as effective oil/water absorbents with excellent recyclability, thermal insulators in extreme conditions, and sensitive strain sensors are demonstrated. This assembly approach with optimized interfacial features is scalable and efficient, affording high‐performance cellulose‐based aerogels for various applications.
Broadband Bi2O2Se Photodetectors from Infrared to Terahertz
Authors: Chen Yunfeng , Ma Wanli , Tan Congwei , Luo Man , Zhou Wei , Yao Niangjuan , Wang Hao , Zhang Lili , Xu Tengfei , Tong Tong , Zhou Yong , Xu Yongbing , Yu Chenhui , Shan Chongxin , Peng Hailin , Yue Fangyu , Wang Peng , Huang Zhiming , Hu Weida
Published: January 2021

2D Bi2O2Se has shown great potential in photodetector from visible to infrared (IR) owing to its high mobility, ambient stability, and layer‐tunable bandgaps. However, for the terahertz (THz) band with longer wavelength and richer spectral information, there are few reports on the research of THz detection based on 2D materials. Herein, an antenna‐assisted Bi2O2Se photodetector is constructed to achieve broadband photodetection from IR to THz ranges driven by multi‐mechanism of electromagnetic waves to electrical conversion. The good tradeoff between the bandgap and high mobility results in a broad spectral detection. In the IR region, the nonequilibrium carriers result from photo‐induced electron‐hole pairs in the Bi2O2Se body. While in the THz region, the carriers are caused by the injected electrons from the metal electrodes by the electromagnetic‐induced well. The Bi2O2Se photodetector achieves a broadband responsivity of 58 A W‐1 at 1550 nm, 2.7 × 104 V W‐1 at 0.17 THz, and 1.9 × 108 V W‐1 at 0.029 THz, respectively. Surprisingly, an ultrafast response time of 476 ns and a quite low noise equivalent power of 0.2 pW Hz−1/2 are acquired at room temperature. Our researches exhibit promising prospects of Bi2O2Se in broadband detection, THz imaging, and ultrafast sensing.