bluuebunny/crossref_metadata_2025 huggingface dataset:
Early expression of a β1‐adrenergic receptor and catecholamines in Xenopus oocytes and embryos
Authors: Devic E. , Paquereau L. , Steinberg R. , Caput D. , Audigier Y.
Published: July 2002

From a Xenopus stage 11 cDNA library, we have cloned a gene, termed X‐β
1AR, whose sequence is highly homologous to that of the human β1‐adrenergic receptor. As shown by RT‐PCR assay, X‐β
1AR RNA is present in the mature oocyte, decreases after fertilization up to stage 6 and then gradually increases during gastrulation. Binding studies performed with radiolabeled ligands reveal that X‐β
1AR RNA is translated into the receptor protein. Furthermore, noradrenaline and adrenaline are also detected in oocytes and early embryos. The concomitant presence of β1‐adrenergic receptors and catecholamines suggest that this ligand‐receptor couple could play a role in the very early stages of embryonic development.
Cationic lipids destabilize lysosomal membrane in vitro
Authors: Wattiaux Robert , Jadot Michel , Warnier-Pirotte Marie-Thérèse , Wattiaux-De Coninck Simone
Published: July 2002

Addition of cationic lipids to plasmid DNA considerably increases the efficiency of transfection. The mechanism has not yet been elucidated. A possibility is that these compounds destabilize biological membranes (plasma, endosomal, lysosomal), facilitating the transfer of nucleic molecules through these membranes. We have investigated the problem by determining if a cationic lipid N‐(1‐(2,3‐dioleoxy)propyl)‐N,N,N,‐trimethylammonium methyl‐sulfate (DOTAP, Boehringer, Mannheim, Germany) affects the integrity of rat liver lysosomal membrane. We have measured the latency of β‐galactosidase, a lysosomal enzyme, and found that incubation of lysosomes with low concentrations of DOTAP causes a striking increase in free activity of the hydrolase and even a release of the enzyme into the medium. This indicates that lysosomal membrane is deeply destabilized by the lipid. The phenomenon depends on pH, it is less pronounced at pH 5 than at pH 7.4. Anionic compounds, particularly anionic amphipathic lipids, can to some extent prevent this phenomenon. It can be observed with various cationic lipids. A possible explanation is that cationic liposomes interact with anionic lipids of lysosomal membrane, allowing a fusion between the lipid bilayers which results in a destabilization of the organelle membrane.
High resolution methylation analysis of the galectin‐1 gene promoter region in expressing and nonexpressing tissues
Authors: Salvatore Paola , Benvenuto Giovanna , Caporaso Milena , Bruni Carmelo B , Chiariotti Lorenzo
Published: July 2002

We conducted by bisulfite genomic sequencing a high resolution study of the methylation of the galectin‐1 gene in expressing and nonexpressing tissues. We show that: (i) hypomethylation of galectin‐1 promoter correlates with expression; (ii) differences in methylation occur in a small region, which include a CpG cluster; (iii) the density of methyl‐CpGs rather than site‐specific methylation distinguishes the nonexpressing from the expressing alleles; (iv) the modification profiles in nonexpressing tissues are highly heterogeneous; (v) a single CpG within 1300 bp is always methylated both in expressing and nonexpressing tissues; (vi) these features are conserved in rat and mouse.
Human ϵ‐sarcoglycan is highly related to α‐sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene1
Authors: McNally Elizabeth M , Ly Chantal T , Kunkel Louis M
Published: July 2002

The dystrophin‐glycoprotein complex (DGC) is critical for muscle membrane stability. The sarcoglycans are transmembrane proteins within the DGC, and the function of the sarcoglycans is unknown. Mutations in sarcoglycan genes cause autosomal recessive muscular dystrophy. We have identified a new sarcoglycan gene with high homology to α‐sarcoglycan highlighting the redundancy of the DGC. This gene, named ϵ‐sarcoglycan, has an identical intron‐exon structure to α‐sarcoglycan, and is more broadly expressed. The characterization of ϵ‐sarcoglycan should make it possible to determine if it, like the other sarcoglycan genes, is mutated in muscular dystrophy.
Activation of the potato plant uncoupling mitochondrial protein inhibits reactive oxygen species generation by the respiratory chain
Authors: Kowaltowski Alicia J , Costa Alexandre D.T , Vercesi Anibal E
Published: July 2002

A variety of plant tissues contain an uncoupling mitochondrial protein (PUMP), recently described and characterized by our group. In this study we show that the inhibition of PUMP activity in potato tuber mitochondria significantly increases mitochondrial H2O2 generation, while PUMP substrates, such as linoleic acid, reduce mitochondrial H2O2 generation. This H2O2 generation occurred mainly by the dismutation of superoxide radicals formed through monoelectronic reduction of O2 by semiquinone forms of coenzyme Q. The results presented suggest that protection against mitochondrial oxidative stress may be a physiological role of PUMP.
GLUT4 translocation by insulin in intact muscle cells: detection by a fast and quantitative assay
Authors: Wang Qinghua , Khayat Zayna , Kishi Kazuhiro , Ebina Yousuke , Klip Amira
Published: July 2002

We report a rapid and sensitive colorimetric approach to quantitate the amount of glucose transporters exposed at the surface of intact cells, using L6 muscle cells expressing GLUT4 containing an exofacial myc epitope. Unstimulated cells exposed to the surface 5 fmol GLUT4myc per mg protein. This value increased to 10 fmol/mg protein in response to insulin as 2‐deoxyglucose (10 μM) uptake doubled. The results are substantiated by immunofluorescent detection of GLUT4myc in unpermeabilized cells and by subcellular fractionation. We further show that wortmannin and the cytoskeleton disruptors cytochalasin D and latrunculin B completely blocked these insulin effects. The rapid quantitative assay described here could be of high value to study insulin signals and to screen for potential anti‐diabetic drugs.
Procyanidins extracted from pine bark protect α‐tocopherol in ECV 304 endothelial cells challenged by activated RAW 264.7 macrophages: role of nitric oxide and peroxynitrite
Authors: Virgili Fabio , Kim Doran , Packer Lester
Published: July 2002

A co‐culture system was used to study the effect of reactive nitrogen species (RNS) generated by RAW 264.7 macrophages grown on filters and activated by lipopolysaccharide and interferon‐γ, on the α‐tocopherol levels in ECV 302 endothelial cells. The results indicate that: RNS generated by activated macrophages or by direct administration of peroxynitrite lead to a significant loss of α‐tocopherol in endothelial cells; pre‐incubation with procyanidin extracted from pine bark (Pycnogenol) protects α‐tocopherol of endothelial cells and enhances by about 15% basal endogenous levels of α‐tocopherol. These results demonstrate flavonoids participate in the cellular antioxidant network and suggest that Pycnogenol may play an important role in the protection of endothelium from oxidative stress induced by reactive nitrogen species.
PPARγ3 mRNA: a distinct PPARγ mRNA subtype transcribed from an independent promoter
Authors: Fajas Lluis , Fruchart Jean-Charles , Auwerx Johan
Published: July 2002

PPARγ is a member of the peroxisome proliferator activated receptors (PPAR) subfamily of nuclear receptors. So far two PPARγ isoforms, PPARγ1 and PPARγ2, were known in mammals. We describe the structure of a novel human PPARγ subtype, PPARγ3. The PPARγ3 mRNA is transcribed from a novel promoter localized 5′ of exon A2. PPARγ3 mRNA expression was restricted to adipose tissue and large intestine. Similar to human PPARγ1 and ‐2, PPARγ3 is activated by thiazolidinediones and prostaglandin J derivatives and binds with high affinity to a PPRE.
A p38 MAP kinase inhibitor regulates stability of interleukin‐1‐induced cyclooxygenase‐2 mRNA
Authors: Ridley Simon H. , Dean Jonathon L.E. , Sarsfield Simon J. , Brook Matthew , Clark Andrew R. , Saklatvala Jeremy
Published: July 2002

The mechanism by which p38 mitogen‐activated protein kinase (MAPK) regulates the induction of cyclooxygenase (COX)‐2 by interleukin‐1 (IL‐1) has been investigated in HeLa cells. SB 203580, an inhibitor of p38 MAPK, in the range 0.1–1 μM inhibited IL‐1‐stimulated PGE2 (but not arachidonic acid) release and this was associated with inhibition of induction of COX‐2 protein and mRNA. IL‐1 stimulated COX‐2 transcription in HeLa cells about 2‐fold as judged by both reporter gene and nuclear run‐on assays. The inhibitor had no significant effect on this. However, in cells previously stimulated with IL‐1 it caused rapid destabilisation of COX‐2 mRNA independently of on‐going transcription. The results suggest a novel function for p38 MAPK in the regulation of mRNA stability.
Functional heterodimeric amino acid transporters lacking cysteine residues involved in disulfide bond
Authors: Pfeiffer Rahel , Spindler Benjamin , Loffing Jan , Skelly Patrick J. , Shoemaker Charles B. , Verrey François
Published: July 2002

The protein mediating system L amino acid transport, AmAT‐L, is a disulfide‐linked heterodimer of a permease‐related light chain (AmAT‐L‐lc) and the type II glycoprotein 4F2hc/CD98. The Schistosoma mansoni protein SPRM1 also heterodimerizes with h4F2hc, inducing amino acid transport with different specificity. In this study, we show that the disulfide bond is formed by heavy chain C109 with a Cys residue located in the second putative extracellular loop of the multi‐transmembrane domain light chain (C164 and C137 for XAmAT‐L‐lc and SPRM1, respectively). The non‐covalent interaction of Cys‐mutant subunits is not sufficient to allow coimmunoprecipitation, but cell surface expression of the light chains is maintained to a large extent. The non‐covalently linked transporters display the same transport characteristics as disulfide bound heterodimers, but the maximal transport rates are reduced by 30–80%.
Recent studies of T7 RNA polymerase mechanism
Authors: Kochetkov S.N , Rusakova E.E , Tunitskaya V.L
Published: July 2002

Bacteriophage T7 RNA polymerase (T7 RNAP) is known to be one of the simplest enzymes catalyzing RNA synthesis. In contrast to most RNA polymerases known, this enzyme consists of one subunit and is able to carry out transcription in the absence of additional protein factors. Owing to its molecular properties, the enzyme is widely used for synthesis of specific transcripts, as well as being a suitable model for studying the mechanisms of transcription. In this minireview the recent data on the structure and mechanism of T7 RNAP, including enzyme‐promoter interactions, principal stages of transcription, and the results of functional studies are discussed.
Alpha4 protein as a common regulator of type 2A‐related serine/threonine protein phosphatases1
Authors: Nanahoshi Masakazu , Tsujishita Yosuke , Tokunaga Chiharu , Inui Seiji , Sakaguchi Nobuo , Hara Kenta , Yonezawa Kazuyoshi
Published: July 2002

The catalytic activity of the C subunit of serine/threonine phosphatase 2A is regulated by the association with A (PR65) and B subunits. It has been reported that the alpha4 protein, a yeast homolog of the Tap42 protein, binds the C subunit of serine/threonine phosphatase 2A and protein phosphatase 2A‐related protein phosphatases such as protein phosphatase 4 and protein phosphatase 6. In the present study, we showed that alpha4 binds these three phosphatases and the association of alpha4 reduces the activities of these phosphatases in vitro. In contrast, PR65 binds to the C subunit of serine/threonine phosphatase 2A but not to protein phosphatase 4 and protein phosphatase 6. These results suggest that the alpha4 protein is a common regulator of the C subunit of serine/threonine phosphatase 2A and protein phosphatase 2A‐related protein phosphatases.
Molecular cloning and characterization of human AOS1 and UBA2, components of the sentrin‐activating enzyme complex
Authors: Gong Limin , Li Bing , Millas Stefanos , Yeh Edward T.H.
Published: July 2002

Sentrin‐1/SUMO‐1 is a novel ubiquitin‐like protein, which can covalently modify a limited number of cellular proteins. Here we report the identification of the sentrin‐activating enzyme complex, which consists of two proteins AOS1 and UBA2. Human AOS1 is homologous to the N‐terminal half of E1, whereas human UBA2 is homologous to the C‐terminal half of E1. The human UBA2 gene is located on chromosome 19q12. Human UBA2 could form a β‐mercaptoethanol‐sensitive conjugate with members of the sentrin family, but not with ubiquitin of NEDD8, in the presence of AOS1. Identification of human UBA2 and AOS1 should allow a more detailed analysis of the enzymology of the activation of ubiquitin‐like proteins.
Lithium protects cultured neurons against β‐amyloid‐induced neurodegeneration
Authors: Alvarez Gema , Muñoz-Montaño Juan Ramón , Satrústegui Jorgina , Avila Jesús , Bogónez Elena , Dı́az-Nido Javier
Published: July 2002

The deposition of β‐amyloid peptide (Aβ), the hyperphosphorylation of tau protein and the death of neurons in certain brain regions are characteristic features of Alzheimer's disease. It has been proposed that the accumulation of aggregates of Aβ is the trigger of neurodegeneration in this disease. In support of this view, several studies have demonstrated that the treatment of cultured neurons with Aβ leads to the hyperphosphorylation of tau protein and neuronal cell death. Here we report that lithium prevents the enhanced phosphorylation of tau protein at the sites recognized by antibodies Tau‐1 and PHF‐1 which occurs when cultured rat cortical neurons are incubated with Aβ. Interestingly, lithium also significantly protects cultured neurons from Aβ‐induced cell death. These results raise the possibility of using chronic lithium treatment for the therapy of Alzheimer's disease.
The N‐linked glycan of the V3 region of HIV‐1 gp120 and CXCR4‐dependent multiplication of a human immunodeficiency virus type 1 lymphocyte‐tropic variant
Authors: Losman Britt , Biller Marlene , Olofsson Sigvard , Schønning Kristian , Lund Ole Søgaard , Svennerholm Bo , Hansen John-Erik Stig , Bolmstedt Anders
Published: July 2002

We have previously shown that an N‐glycosylation site of N306 of HIV‐1 gp120 is not necessary for the HIV‐1 infectivity but protects HIV‐1 from neutralising antibodies. In contrast Nakayama et al. [FEBS Lett. (1998) 426, 367–372], using a virus with an identical V3 region, suggested that elimination of this particular glycan reduced the ability of T‐tropic HIV to bind to CXCR4 and hence its ability to infect T cell lines. We therefore re‐examined the ability of a mutant virus, lacking the N306 glycan, to replicate in various types of cells and found no change in co‐receptor usage for mutant virus. The ability of mutant virus to replicate or to induce syncytia in infected cells was similar to that of wild type virus. These results corroborate our original observation, confirming that the induced mutation in the N306 glycosylation site neither impairs nor improves the ability of mutant virus to replicate in permissive cells.
In vivo oxidation‐reduction kinetics of OxyR, the transcriptional activator for an oxidative stress‐inducible regulon in Escherichia coli
Authors: Tao Kazuyuki
Published: July 2002

The OxyR protein is a transcriptional activator for a subset of peroxide stress‐inducible genes, most of which are involved in defense systems against oxidative stress. Recently, it was demonstrated that purified OxyR has one intramolecular disulfide bond, which led to the proposal that the reversible disulfide bond formation regulates the activity of OxyR as a transcription factor in response to peroxide stress. In this study, I demonstrated by SDS‐PAGE under non‐reducing conditions that an intramolecular disulfide bond is formed in OxyR upon exposure of the cells to hydrogen peroxide in vivo. Experiments using strains expressing mutant OxyR proteins with Cys to Ser single amino acid substitutions confirmed that the disulfide bond is formed between the Cys‐199 and ‐208. Kinetic analyses indicated that the formation of the disulfide bond is rapid and transient, oxidized within 30 s and re‐reduced within 5 min after the addition of hydrogen peroxide in the wild‐type strain. These results provide evidence for the regulatory role of the reversible oxidation of dithiol to disulfide in sensing peroxide stress in vivo and signal transduction to the transcription apparatus by OxyR.
Up‐regulation of uncoupling protein 3 by thyroid hormone, peroxisome proliferator‐activated receptor ligands and 9‐cis retinoic acid in L6 myotubes
Authors: Nagase Itsuro , Yoshida Shigeru , Canas Xavier , Irie Yukiko , Kimura Kazuhiro , Yoshida Toshihide , Saito Masayuki
Published: July 2002

Uncoupling protein 3 (UCP3), expressed abundantly in the skeletal muscle, is one of the carrier proteins dissipating the transmitochondrial electrochemical gradient as heat, and thereby has been implicated in the regulation of energy metabolism. We have investigated UCP3 mRNA expression in the widely used L6 myocyte cell line by Northern blot analysis. UCP3 mRNA was not detected in L6 myoblasts, but appeared after their differentiation to myotubes. The UCP3 mRNA level was increased when L6 myotubes were treated with increasing concentrations of triiodothyronine (T3), oleic acid, α‐bromopalmitate and carbacyclin, a non‐selective ligand of peroxisome proliferator‐activated receptors (PPARs), whereas it was not influenced when treated with selective ligands of PPARα (WY 14 643) and PPARγ (troglitazone). A ligand of retinoid X receptor (RXR), 9‐cis retinoic acid, was also effective by itself and in combination with carbacyclin in stimulating UCP3 mRNA expression. The mRNA analysis of individual PPAR isoforms revealed that L6 cell expressed a significant level of PPARδ but undetectable levels of PPARα and PPARγ. These results suggest that UCP3 expression in myocytes is differentiation‐dependent and regulated by the T3 receptor, RXR and PPARδ.
Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas
Authors: Chuman Yoshiko , Bergman Ann-Charlotte , Ueno Takayuki , Saito Shin'ichi , Sakaguchi Kazuyasu , Alaiya Ayodele A. , Franzén Bo , Bergman Tomas , Arnott David , Auer Gert , Appella Ettore , Jörnvall Hans , Linder Stig
Published: July 2002

A pair of 35 kDa polypeptides (TAO1/TAO2) are expressed in more than 90% of all primary lung adenocarcinomas but not in other major malignancies. Mass spectrometry of tryptic peptides showed that TAO1/TAO2 is identical to napsin A, a recently described member of the aspartic proteinase family. The site of processing of pronapsin A to the mature form was located. Napsin expression was detected in human lung adenocarcinoma tumors, compatible with the marker nature of TAO1/TAO2 in the diagnosis of primary lung adenocarcinoma. This is important since identification of markers which can distinguish primary lung adenocarcinomas from distant metastases is desirable. Northern blot analysis showed expression of napsin also in normal lung and kidney tissue, and in situ hybridization showed expression in type II alveolar cells of the lung. This protease is concluded to have a specific functional role in the normal alveolar epithelium and is a candidate protease for the proteolytic processing of surfactant precursors.
Changes in myosin heavy chain mRNA and protein isoforms in single fibers of unloaded rat soleus muscle
Authors: Stevens Laurence , Gohlsch Bärbel , Mounier Yvonne , Pette Dirk
Published: July 2002

Changes in myosin heavy chain (MHC) mRNA and protein isoforms were investigated in single fibers from rat soleus muscle unloaded by hindlimb suspension for 4 and 7 days. Dramatic changes were seen after 4 days, when all fibers co‐expressed slow and fast MHC mRNAs. Most fibers contained mRNAs for MHCIβ, MHCIIa, MHCIId(x), and MHCIIb. The up‐regulation of the fast isoforms was only partially transmitted to the protein level. Atypical combinations of MHC mRNA isoforms, which deviated from the ‘next‐neighbor rule’, were frequent in fibers from unloaded soleus. These atypical combinations increased with time and were not observed in the controls. The results suggest that hindlimb suspension elicits in soleus muscle pronounced perturbations in the expression of MHC isoforms by disrupting transcriptional and translational activities.
Structure of acetylcholinesterase complexed with (−)‐galanthamine at 2.3 Å resolution
Authors: Greenblatt H.M. , Kryger G. , Lewis T. , Silman I. , Sussman J.L.
Published: July 2002

(−)‐Galanthamine (GAL), an alkaloid from the flower, the common snowdrop (Galanthus nivalis), shows anticholinesterase activity. This property has made GAL the target of research as to its effectiveness in the treatment of Alzheimer's disease. We have solved the X‐ray crystal structure of GAL bound in the active site of Torpedo californica acetylcholinesterase (TcAChE) to 2.3 Å resolution. The inhibitor binds at the base of the active site gorge of TcAChE, interacting with both the choline‐binding site (Trp‐84) and the acyl‐binding pocket (Phe‐288, Phe‐290). The tertiary amine group of GAL does not interact closely with Trp‐84; rather, the double bond of its cyclohexene ring stacks against the indole ring. The tertiary amine appears to make a non‐conventional hydrogen bond, via its N‐methyl group, to Asp‐72, near the top of the gorge. The hydroxyl group of the inhibitor makes a strong hydrogen bond (2.7 Å) with Glu‐199. The relatively tight binding of GAL to TcAChE appears to arise from a number of moderate to weak interactions with the protein, coupled to a low entropy cost for binding due to the rigid nature of the inhibitor.
Connexin43 mRNA contains a functional internal ribosome entry site
Authors: Schiavi Adam , Hudder Alice , Werner Rudolf
Published: July 2002

A reporter gene construct was used to study the regulation of connexin43 (Cx43) expression, the major gap junction protein found in heart and uterus, in transfected cell lines. The construct had the firefly luciferase gene under the control of the Cx43 promoter. Inclusion of the 5′‐untranslated region (UTR) of the mRNA in the construct increased luciferase expression by 70%. A bicistronic vector assay demonstrated that the Cx43 5′‐UTR contains a strong internal ribosome entry site (IRES). Deletion analysis localized the IRES element to the upstream portion of the 5′‐UTR.
Bcl‐2 family: Life‐or‐death switch
Authors: Tsujimoto Yoshihide , Shimizu Shigeomi
Published: July 2002

The Bcl‐2 family of proteins that consists of anti‐apoptotic and pro‐apoptotic members determines life‐or‐death of a cell by controlling the release of mitochondrial apoptogenic factors, cytochrome c and apoptosis‐inducing factor (AIF), that activate downstream executional phases, including the activation of death proteases called caspases. Cytochrome c release is, thus, central to apoptotic signal transduction in mammals, making study of the mechanism for cytochrome c release a major issue. Several models for cytochrome c release have been proposed, including rupture of mitochondrial outer membrane and involvement of a specific channel. Here, we provide an overview of recent findings on the role of Bcl‐2 family members in the life‐or‐death decision of a cell.
Laminaria, induced fetal demise and misoprostol in late abortion
Authors: Hern W.M
Published: July 2002

Objectives: To analyze and determine the safety and effectiveness of induced fetal demise as an adjunctive method in outpatient abortion for patients with advanced pregnancies and to evaluate the independent effect of intrauterine misoprostol administered after amniotomy in late abortion. Methods: During a 9‐year period, 1677 abortions were performed for patients whose pregnancies ranged from 18 through 34 menstrual weeks in an outpatient facility. Of these, 832 were performed by one physician. Techniques for performing all the abortions included induction of fetal demise by intrauterine fetal injection of digoxin and/or hyperosmolar urea, serial multiple laminaria treatment of the cervix, amniotomy, oxytocin induction of labor, and assisted delivery or surgical evacuation of the fetus and placenta. In the last 411 of the 832 patients whose abortions were performed by one physician, misoprostol was placed in the lower uterine segment following amniotomy in order to enhance labor induction, cervical ripening, and fetal expulsion. Results: Of the entire group of 1677 cases, the median gestational age was 22 menstrual weeks. The median procedure time for all cases was 10 min. Measured median blood loss was 125 ml. Blood loss and procedure time increased with length of gestation, but these were not affected by misoprostol. There were three major complications (0.2%) in the overall series. Among patients seen by one physician (N=832), amniotomy‐to‐procedure time was shorter by 26 min for patients receiving misoprostol, and there was 27% more variability in amniotomy‐to‐procedure time among patients not receiving misoprostol. Complication rates for patients receiving misoprostol were the same as for those not receiving misoprostol. There were no major complications in the 832 patients seen by one physician, no uterine rupture or perforations, and no cervical lacerations. Conclusions: Outpatient abortion may be performed safely from 18 through 34 menstrual weeks using combined surgical and medical procedures. Use of intrauterine post‐amniotomy misoprostol was associated with reduced amniotomy‐to‐procedure time and reduced variability in the amniotomy‐to‐procedure time.
Treatment outcomes for squamous intraepithelial lesions
Authors: Nuovo J. , Melnikow J. , Willan A.R. , Chan B.K.S.
Published: July 2002

Objective: To assess the effectiveness of cone biopsy, cryotherapy, laser ablation and the loop electrosurgical procedure in the treatment of squamous intraepithelial lesions. Method: Systematic review of randomized controlled trials in subjects who underwent treatment of low‐ and high‐grade squamous intraepithelial lesions with these modalities. Main outcome measures included the following: percent resolution and persistence of a lesion and notable complications for each procedure. Result: Pooled rates of resolution for low‐grade, high‐grade, or combined squamous intraepithelial lesions were similar across the different treatment modalities (range 85.2–94.7%), with substantial overlap among the 95% confidence intervals. Significant hemorrhage occurred most frequently in subjects who received cone biopsy (4.6%) (95% CI: 2.15, 6.99), followed by laser ablation (1.75%) (95% CI: 0.70, 2.81), and LEEP (1.35%) (95% CI: 0.24, 2.47). No hemorrhages were reported among subjects who received cryotherapy. Study sample sizes were relatively small. There were no reported cases of progression to invasive cancer, but duration of follow‐up (median follow‐up time for all eligible studies=12 months) was not sufficient to evaluate long‐term outcomes. Conclusions: There were no substantive differences in outcomes regarding persistence and resolution in the treatment of squamous intraepithelial lesions for subjects receiving cone biopsy, cryotherapy, laser ablation, or LEEP.
Quantifying the bullwhip effect in supply chains
Authors: Metters Richard
Published: July 2002

Consider multiple companies operating as a serial supply chain. Within this environment, end users form the demand for the last company in the supply chain, but the demand for upstream companies is formed by the companies in the immediate downstream supply chain link. It has been shown that demand seasonality and forecast error can increase as we proceed up the supply chain. These demand distortions, called the “bullwhip” effect, create inefficiencies for upstream firms. This work seeks to identify the magnitude of the problem by establishing an empirical lower bound on the profitability impact of the bullwhip effect. Results indicate that the importance of the bullwhip effect to a firm differs greatly depending on the specific business environment. Given appropriate conditions, however, eliminating the bullwhip effect can increase product profitability by 10–30%.
Endothelin immunoreactivity and mRNA expression in sensory and sympathetic neurones following selective denervation
Authors: Milner P. , Loesch A. , Burnstock G.
Published: July 2002

The localization of endothelin (ET) in perivascular nerve varicosities supports pharmacological evidence that ET is a neurotransmitter in the autonomic nervous system. To examine the potential source of ET previously localized in cerebrovascular nerves, ganglia which send projections to these vessels were immunolabelled for ET and examined at the ultrastructural level. The trigeminal (TG) and superior cervical ganglia (SCG) were examined in control rats and following either sensory denervation or sympathectomy. In control TG, ET immunolabelling was detected throughout the cytoplasm of a subpopulation of neurones whereas in the SCG only the occasional ET‐positive neurone was seen. Following sensory denervation with capsaicin, very few ET‐immunoreactive nerve cell bodies or nerve fibres were detected in the TG compared with control ganglia, suggesting that ET is predominantly localized in primary afferent neurones, although some remaining myelinated nerve fibres stained positively. ET labelling of neurones in the SCG was unaffected by sensory denervation. Following selective damage to sympathetic nerves with 6‐hydroxydopamine, there was a marked increase in intensity of ET‐labelling of nerve fibres in the TG, probably due to increased availability of nerve growth factor for sensory nerves. There was no effect on ET immunoreactivity in the nerve cell bodies and nerve fibres within the SCG. However, in situ hybridization techniques demonstrated that 6‐hydroxydopamine sympathectomy resulted in a marked increase in ET‐1 mRNA expression in the SCG neurones. In conclusion, sensory nerves projecting from the TG are a more likely source of ET‐positive perivascular nerves in cerebral arteries than sympathetic nerves from the SCG. Damaged sympathetic neurones markedly increase ET mRNA expression. In view of the neuroprotective properties of ET, this may represent a compensatory mechanism to promote repair.
Brain‐derived neurotrophic factor and TrkB tyrosine kinase receptor gene expression in zebrafish embryo and larva
Authors: Lum Tom , Huynh Gigi , Heinrich Gerhard
Published: July 2002

The genes that encode the neurotrophin family of secreted polypeptides and the Trk family of high affinity neurotrophin transmembrane protein tyrosine kinase receptors are induced at the time of neurogenesis in mammals and are known to play critical roles in nervous system development. We show here that in contrast to mammals, the genes encoding the neurotrophin brain‐derived neurotrophic factor (BDNF) and the neurotrophin receptor TrkB are expressed throughout embryonic development in the zebrafish. At the embryonic stages preceding transcription of endogenous genes all cells contain BDNF transcripts and immunoreactive BDNF and the trkB transcripts lack the region that encodes a kinase domain. As development proceeds, progressively fewer cells contain BDNF transcripts and by the time of neurogenesis the trkB transcripts encode a kinase‐domain. In the 4‐day‐old larva, a small subset of specialized sensory cells on the surface and cells in deeper structures including the gill arches, fin, and cloaca express the BDNF gene at high levels in a promoter‐specific fashion. This progressive restriction of BDNF gene expression must involve an extinction of BDNF gene transcription in some and induction of high levels of transcription in a promoter‐specific fashion in other cells.
Long‐term behavioural and neuroendocrine changes in roman HIGH‐(RHA/Verh) and LOW‐(RLA‐Verh) avoidance rats following neonatal handling
Authors: Steimer T. , Escorihuela R.M. , Fernández‐teruel A. , Driscoll P.
Published: July 2002

Roman high‐(RHA/Verh) and low‐(RLA/Verh) avoidance rats, originally selected and bred for rapid vs poor acquisition of a two‐way active avoidance response, differ in emotional reactivity and coping style. These differences are associated with particular neuroendocrine and neurochemical characteristics. New data are presented here to show that the behavioural changes specifically induced by neonatal handling, i.e. decreased emotional reactivity, are associated with marked changes in the neuroendocrine responses of (hyperemotional) RLA/Verh rats to a novel environment. Eight months after neonatal handling, self‐grooming behaviour, a reliable marker of emotional reactivity in this line of rats, was significantly decreased in RLA/Verh rats. Defecation scores were also significantly reduced in both lines. Moreover, there was a significant reduction in prolactin and corticosterone release following exposure to a novel environment in neonatally‐handled RLA/Verh rats as compared to control, non‐handled rats. No effects on prolactin and corticosterone release were observed in RHA/Verh rats. There was also no apparent effect of neonatal handling on coping style i.e. RLA/Verh rats did not increase their spontaneous exploration of novel environments. Thus, the phenotypic expression of basic traits of (high) neuroendocrine/emotional reactivity was specifically modulated by neonatal handling in RLA/Verh rats, whereas both the (hypoemotional) RHA/Verh rats as well as coping style in both lines remained unaffected. Changes in emotional reactivity were still apparent at 12 months of age when rats from the same groups were tested for hyponeophagia. These results suggest that psychogenetically selected lines such as RHA/RLA rats are suitable animal models to investigate interactions between genes and the environment in determining individual sensitivity to stress and coping styles, as well as potential vulnerability (or resistance) to the development of maladaptive syndromes similar to anxiety and mood disorders in humans.
Asset allocation decisions in retirement accounts
Authors: Waggle Doug , Englis Basil
Published: July 2002

An examination of survey responses about Individual Retirement Account (IRA) holdings reveals that individuals often take all-or-nothing approaches in their decisions to diversify across the asset categories of cash, bonds, and equity. Two thirds of survey respondents put their entire IRA holdings into a single asset category. A surprisingly large proportion of funds is held in cash, while only a minimal amount is invested in bonds. These findings also contrast with those of Bodie and Crane’s (1997) examination of TIAA-CREF participants, which is heavily weighted with individuals holding fixed income annuities. Our results suggest that there is a compelling need for risk education for investors. © 2000 Elsevier Science Inc. All rights reserved.
Angiotensin converting enzyme (ACE) gene expression in the human left ventricle: effect of ACE gene insertion/deletion polymorphism and left ventricular function
Authors: Davis Gershan K. , Millner Russell W.J. , Roberts David H.
Published: July 2002

Aims:

We investigated the effect of the angiotensin converting enzyme (ACE) I/D polymorphism and left ventricular (LV) function on ACE gene expression in tru‐cut LV myocardial biopsies from 50 consecutive patients (II: 18, ID: 18, DD: 14; 40 males) with ischaemic heart disease undergoing coronary artery bypass grafting (CABG).

Methods:

The polymerase chain reaction was used for ACE genotyping. LV function [normal (n = 22) or impaired] was determined by left ventriculography at cardiac catheterisation prior to bypass surgery. ACE expression was determined (n = 46) by a competitive quantitative reverse transcription PCR assay using 5×105, 12.5×105 and 20×105 copies of a mutant DNA internal standard (IS). PCR products were analysed by negative film photography and laser densitometry to determine the number of ACE transcripts present.

Results:

Mean age was similar (II: 59.1±10.4, ID: 57.0±10.6, DD: 61.4±6.2; P = NS) with no differences between groups in sex (P = 0.25); hypertension, P = 0.31; previous myocardial infarction, P = 0.44; LV function, P = 0.23; and ACE inhibitor therapy, P = 0.06. ACE expression per 100 ng of total RNA varied with genotype [< 5×105 copies in II: 6, 5–12.5×105 copies in II: 6, ID: 16, DD: 4; and >12.5×105 (II: 4, ID: 2, DD: 8), Kendall's tau‐b coefficient (τb) = 0.43, P = 0.003]. Impaired LV function also correlated with higher levels of ACE expression, Kendall's τb = 0.40, P = 0.001.

Conclusion:

ACE gene expression in the left ventricle varied with ACE genotype and LV function in IHD patients undergoing CABG.
Baseline demographics of the Valsartan Heart Failure Trial
Authors: Cohn Jay N. , Tognoni Gianni , Glazer Robert , Spormann Dirk ,   Val‐HeFT Investigators
Published: July 2002

Background

The Valsartan Heart Failure Trial (Val‐HeFT) is the first large‐scale randomized, multinational clinical study to assess the efficacy and safety of valsartan, an angiotensin II receptor blocker, added to conventional therapy, including angiotensin‐converting enzyme inhibitors, in heart failure patients. A total of 5010 patients with an ejection fraction <40% have been randomized to either valsartan titrated to 160 mg b.i.d. or to placebo.

Aims

Baseline characteristics of patients in Val‐HeFT are presented and compared with other major clinical trials in heart failure.

Methods

Baseline data were collected and summary statistics calculated.

Results

The study population has a mean age of 62.7 years and is 80% male, 90.3% white, 6.9% black, and 2.8% Asian. Antecedent coronary heart disease is reported in 57.2% of patients. Angiotensin‐converting enzyme inhibitors are prescribed for 92.7% of patients, diuretics for 85.8%, digoxin for 67.3%, and β‐blockers for 35.6%. Subgroup comparisons by age, sex, race and ejection fraction quartile show small differences in baseline characteristics.

Conclusion

Overall the Val‐HeFT population is generally representative of the population of patients with mild to moderate heart failure in industrialized countries.
Incidence of serious adverse drug reactions in general practice: A prospective study
Authors: Lacoste‐Roussillon Caroline , Pouyanne Pierre , Haramburu Françoise , Miremont Ghada , Bégaud Bernard
Published: July 2002

Background

Many studies have been conducted to estimate the incidence and economic impact of adverse drug reactions. Most of these studies used historical data or were based on single hospital units. Little is known, however, about the frequency of serious adverse drug reactions in general practice.

Objective

To estimate the incidence of serious adverse drug reactions in the community.

Methods

A prospective study during 5 consecutive working days between March 1 and April 30, 1998, was conducted among a random representative sample of 254 general practitioners in Aquitaine, France. The main outcome measure was the number of serious adverse drug reactions (ie, resulting in death, life‐threatening condition, hospitalization, incapacity, or sequel) observed by each general practitioner during the study period and validated by an expert panel.

Results

Thirteen validated serious adverse drug reactions, 2 of which were fatal (1 subarachnoidal hemorrhage with oral anticoagulant and 1 aplastic anemia with antineoplastics), were observed, resulting in an incidence density of 10.2 (95% confidence interval [CI], 5.4 to 17.5) per 1000 days of practice. Eleven case subjects (84.6%) were hospitalized. This represents an average of 2.6 cases per general practitioner per year, and 123,000 adverse drug reaction cases (95% CI, 65,400 to 210,000) for the 60,000 general practitioners in France. Antineoplastics and anticoagulants were the drugs most frequently involved, and blood dyscrasia and bleeding were the most frequent adverse drug reactions.

Conclusion

This study, which is one of the few available that has prospectively measured the incidence of serious adverse drug reactions in general practice settings, confirms that serious adverse drug reactions are a major public health concern.

Clinical Pharmacology & Therapeutics (2001) 69, 458–462; doi: 10.1067/mcp.2001.116145
Einsatz eines Online‐Methanol‐Messsystems zur Regelung von Zulaufsatzkultur‐Fermentationen
Authors: Schumbera Eric , Schmüser Malte , Hinderer Daniel , Schlegel Konstantin , Kampeis Percy
Published: April 2020

Zur Optimierung von Zulaufsatzkultur‐Fermentationen von methylotrophen Organismen wird eine Online‐Messmethode vorgestellt, mit der die Methanol‐Konzentration im Medium während einer Fermentation durch ein Spülgaspervaporations‐Prinzip bestimmt werden kann. Im Gegensatz zu anderen Analysemethoden bietet die Messmethode die Möglichkeit, die Substratkonzentration bei Prozessen mit Methanol als zentralem Substrat über eine Regelung auf einem definierten Wert zu halten. Es werden Schwierigkeiten, aber auch deren Überwindung bei der Adaption der Messmethode auf Fermentationsprozesse dargestellt.
Guanidiniocarbonyl‐Pyrroles (GCP) – 20 Years of the Schmuck Binding Motif
Authors: Giese Michael , Niemeyer Jochen , Voskuhl Jens
Published: April 2020

In this Minireview, an overview about the past 20 years of the guanidiniocarbonyl‐pyrrole (GCP) binding motif, which was designed, investigated and applied by Prof. Dr. Carsten Schmuck, is presented. Here we highlight the first steps from design and discovery, initial binding studies, applications in material science to advanced biomedical use in protein modulation and delivery of genetic material.
Mixed Oil–Based Lipid Emulsions vs Soybean Oil–Based Lipid Emulsions on Incidence and Severity of Intestinal Failure–Associated Liver Disease in a Neonatal Intensive Care Unit
Authors: Ferguson Chelsea L. , Perry Courtney , Subramanian Mary , Gillette Chris , Ayers Kathleen , Welch Cherrie
Published: April 2020

Background

Neonates requiring long‐term parenteral nutrition (PN) are at risk for developing intestinal failure–associated liver disease (IFALD). The purpose of this study was to compare the incidence and severity of IFALD in a highly surgical neonatal population receiving mixed oil–based lipid emulsions (MOLEs) vs soybean oil–based lipid emulsions (SOLEs) for long‐term PN.

Methods

This retrospective cohort study evaluated patients admitted to a neonatal intensive care nursery that received PN for ≥14 days. Patients were separated into 2 cohorts; those who received SOLE and those who received MOLE. The primary outcome of this study was the occurrence of IFALD. Secondary outcomes included time to IFALD, peak bilirubin level during therapy, incidence of hypertriglyceridemia, bronchopulmonary dysplasia, and retinopathy of prematurity.

Results

A total of 107 patients were included in the study, IFALD occurred in 44.8% of patients receiving SOLE compared with 30% of patients receiving MOLE (relative risk, 0.67; 95% CI, 0.39–1.15). In the multivariable analysis, adjusting for the known confounders (prematurity, necrotizing enterocolitis, presence of ostomy, and duration of PN and lipids), the type of lipids was not a significant predictor for development of IFALD. Duration of PN and duration of lipids were determined to be significant risk factors for IFALD, regardless of type of lipid emulsion (odds ratio, 1.03; 95% CI, 1.01–1.05).

Conclusions

Use of MOLE resulted in no significant difference in the outcomes studied when compared with SOLE. Duration of PN and duration of lipids were significant risk factors for development of IFALD.
Synthesis of well‐defined norbornenyl‐terminated poly(alkyl methacrylate)s by group transfer polymerization and their grafting‐through ring‐opening metathesis polymerization
Authors: Lee Gue Seon , Kim Jeung Gon
Published: April 2020

Highly efficient syntheses of poly(alkyl methacrylate)‐based brush polymers were accomplished via a facile group transfer polymerization (GTP) and a consecutive grafting‐through ring‐opening metathesis polymerization. The GTP system, composed of the norbornenyl‐methyl trimethylsilyl ketene acetal initiator and the N‐(trimethylsilyl) bis(trifluoromethanesulfonyl)imide catalyst, rapidly and quantitatively generates norbornenyl‐terminated poly(alkyl methacrylate) macromonomers with very narrow polydispersities (Mw/Mn < 1.10). The ring‐opening metathesis polymerization of methacrylate macromonomers using Grubbs third generation catalyst successfully generated a group of methacrylate‐based brush polymers, which assured the high quality of the macromonomers obtained from GTP.
Climate change in the Chinese mind: An overview of public perceptions at macro and micro levels
Authors: Wang Binbin , Zhou Qinnan
Published: April 2020

This paper summarizes the current literature on public responses to climate change in China. The paper first provides a “macro view” by reviewing what we know about public climate change knowledge, risk perceptions, policy preferences, and behaviors based on large‐scale survey research. The paper also examines what sociodemographic, psychological, and cultural variables – such as age, gender, rural/urban status, and income – can best predict public understanding and responses to climate change. Second, it provides a “micro view” by presenting findings from place‐based and contextualized research projects in China. The review concludes by suggesting next steps to advance the understanding of public engagement with climate change in China.

This article is categorized under:

Perceptions, Behavior, and Communication of Climate Change > Perceptions of Climate Change
A Subglacial Lake in Antarctica Churns Out Nutrients
Authors: Kornei Katherine
Published: April 2020

Eight hundred meters below the West Antarctic Ice Sheet, microbes in subglacial Lake Whillans create organic carbon that helps power the Southern Ocean’s vast food chain.
Highly efficient surface-emitting semiconductor lasers exploiting quasi-crystalline distributed feedback photonic patterns
Authors: Biasco Simone , Ciavatti Andrea , Li Lianhe , Giles Davies A. , Linfield Edmund H. , Beere Harvey , Ritchie David , Vitiello Miriam S.
Published: April 2020

Quasi-crystal distributed feedback lasers do not require any form of mirror cavity to amplify and extract radiation. Once implemented on the top surface of a semiconductor laser, a quasi-crystal pattern can be used to tune both the radiation feedback and the extraction of highly radiative and high-quality-factor optical modes that do not have a defined symmetric or anti-symmetric nature. Therefore, this methodology offers the possibility to achieve efficient emission, combined with tailored spectra and controlled beam divergence. Here, we apply this concept to a one-dimensional quantum cascade wire laser. By lithographically patterning a series of air slits with different widths, following the Octonacci sequence, on the top metal layer of a double-metal quantum cascade laser operating at THz frequencies, we can vary the emission from single-frequency-mode to multimode over a 530-GHz bandwidth, achieving a maximum peak optical power of 240 mW (190 mW) in multimode (single-frequency-mode) lasers, with record slope efficiencies for multimode surface-emitting disordered THz lasers up to ≈570 mW/A at 78 K and ≈720 mW/A at 20 K and wall-plug efficiencies of η ≈ 1%.