bluuebunny/crossref_metadata_2025 huggingface dataset:
An Empirical Analysis of the Impact of Cash Flow, Stock Returns, and Capital Structure on Investment Decisions in Cigarette Sub-Sector Manufacturing Companies Listed on the Indonesia Stock Exchange
Authors: Amin A. Mustika
Published: February 2025

Aims: This study aims to determine the effect of Cash Flow (CF), Stock Returns (SR) and Capital Structure (CS) on Investment Decisions (ID) in cigarette sub-sector manufacturing companies on IDX.
Study Design: The method used is an associative method with a quantitative approach.
Place and Duration of Study: Indonesia Stock Exchange (IDX) between 2020 to 2024.
Methodology: The population in the study, namely the financial statements of cigarette sub-sector manufacturing companies that have gone public. The number of samples in this study from 5 companies for 5 years using a purposive sampling approach. The type of data used in this study is secondary data using financial statement data for the period 2020-2024. The data analysis method used is multiple linear regression using SPSS.
Results: Sig. value of influence between cash flow toward investment decisions is 0.004 with beta coefficient value of -5.109. It means that the influence of cash flow toward investment decisions is accepted. Furthermore, the Sig. value of the effect between capital structure on investment decisions is 0.010 with a beta coefficient value of -10.421. This provides information that the effect of stock return variables on investment decisions is accepted. However, the Sig. value of the effect between stock returns on investment decisions is 0.547 with a beta coefficient value of 1.105. This indicates that the effect of stock return variables on investment decisions cannot be accepted.
Conclusion: The results showed that cash flow (X1) had a significant effect on investment decisions, stock returns (X2) had no significant effect on investment decisions, capital structure (X3) had a significant effect on investment decisions. Simultaneously, the cash flow, stock return and capital structure variables have a significant effect on investment decisions in cigarette sub-sector manufacturing companies listed on the Indonesia Stock Exchange (IDX) for the period 2020-2024.
The Science Behind Energy Of Mixing Binary Liquid Alloys: Exploring Regular Associated Solutions
Authors: Bhartiam Anjani , Sah Dr. Arvind Kumar
Published: February 2025

The study of binary liquid alloys and the therapies that go with them opens up an interesting world in the areas
of materials science, chemistry, and industrial applications. These materials are the key to enhancing
mechanical characteristics, thermal performance, and sustainability in a number of sectors. They are generated
by the molecular-level interactions between different components. Within the field of metallurgy, binary liquid
alloys are essential for enhancing the mechanical and thermal properties of materials, rendering them fit for use
in high-stress environments such as the aerospace and auto sectors. In an increasingly energy-dependent world,
their remarkable ability to function like efficient coolants and heat transfer fluids throughout thermal
management systems significantly boosts energy production and the cooling of electronic equipment. These
alloys additionally serve important uses in chemical engineering treatments like solvent extraction and
separation, where they enhance industrial productivity while lowering environmental impact and promoting the
growing trend of environmentally friendly and sustainable practices. There are numerous difficulties in studying
binary liquid alloys, despite their enormous potential. Hard challenges include the limited amount of
experimental data and the complex structure of intermolecular interactions. The future, though, is full of
creative possibilities. Future developments in multifaceted research, improved computer modelling, and
environmentally conscious manufacturing techniques might solve the mysteries surrounding the regularly
associated solutions in these alloys. This knowledge will have a big impact on all aspects of materials science
and engineering, as it will make it possible to create materials that have been optimized for cutting-edge
technology and use environmentally friendly techniques. Studying binary liquid alloys and the solutions that go
along with them brings fresh insights into the fields of materials science, chemistry, and industrial applications.
These materials support technical breakthroughs as well as environmental sustainability because of their
special qualities and diverse characteristics. Binary liquid alloys will continue to influence the field of materials science as we traverse the difficult yet creative terrain between innovation and obstacles, advancing technological advancement and sustainable practices
Mobilization of arachidonic acid between diacyl and ether phospholipids in rabbit alveolar macrophages
Authors: Sugiura Takayuki , Katayama Osamu , Fukui Junko , Nakagawa Yasuhito , Waku Keizo
Published: July 2002

The metabolism of 20:4 (arachidonic acid) in alkenylacyl, alkylacyl and diacyl lipid classes in choline glycerophospholipids (CGP) and ethanolamine glycerophospholipids (EGP) in rabbit alveolar macrophages was examined. [3H]20:4 was very rapidly incorporated into diacyl glycerophosphocholine (GPC). After the removal of free 20:4, the radioactivity was gradually lost from diacyl GPC. Concomitantly, the radioactivities in alkylacyl GPC and alkenylacyl glycerophosphoethanolamine (GPE) were increased, indicating that 20:4 was mobilized from diacyl GPC to alkylacyl GPC and alkenylacyl GPE. The mobilization was considered to be a 20:4‐specific event. The gradual accumulation of 20:4 in ether phospholipids leads to a high abundance of 20:4 in these lipids. These results suggest metabolic relationships between 20:4 and ether phospholipids, including platelet‐activating factor (PAF).
Prostaglandin E2‐like activity of 20:3n‐9 platelet lipoxygenase end‐product
Authors: Lagarde M. , Burtin M. , Rigaud M. , Sprecher H. , Dechavanne M. , Renaud S.
Published: July 2002

5,8,11‐Icosatrienoic acid (20:3n‐9), a fatty acid associated with platelet hyperactivity, was oxygenated by platelet lipoxygenase. The end‐product of this pathway was purified by high‐performance liquid chromatography (HPLC) and characterized as 12‐hydroxy‐5,8,10‐icosatrienoic acid [12‐OH‐20:3(5,8,10)] by capillary gas‐liquid mass spectrometry. When tested upon platelet aggregation, 12‐OH‐20:3(5,8,10) exhibited a biphasic effect. At low concentrations (below 5 × 10−7 M) it potentiated aggregation but inhibited it at higher levels, a pattern similar to that obtained with prostaglandin E2. However, since the amounts of 12‐OH‐20:3(5,8,10) generated under thrombin stimulation are in the range of concentrations with potentiating effects, it seems that the 12‐OH derivative is responsible for the hyperaggrebility of 20: 3n‐9‐rich platelets.
Temporal relationships in the effects of protein‐free diet on the activities of rat liver branched‐chain ketoacid dehydrogenase complex and kinase
Authors: Beggs M. , Patel H. , Espinal J. , Randle P.J.
Published: July 2002

Feeding rats 0% casein diet decreased liver activities of branched‐chain ketoacid dehydrogenase complex (active form) and of activator protein (complete within 4 days), and increased activity of branched‐chain ketoacid dehydrogenase kinase (complete within 9–10 days). Refeeding normal diet to rats fed 0% casein diet for 10 days resulted in a rapid and partial (approx. 50%) reversal of the above effects within 24 h; complete reversal required 20–30 days of refeeding.
Ascorbic acid accumulation in plated human neutrophils
Authors: Washko Philip , Rotrosen Daniel , Levine Mark
Published: July 2002

Ascorbic acid uptake was investigated in isolated, plated human neutrophils using high‐performance liquid chromatography with coulometric electrochemical detection. Freshly isolated neutrophils contained 1.3 mM ascorbic acid and accumulated significantly greater amounts when physiologic concentrations of the vitamin were present in the extracellular buffer. In several different buffers uptake was dependent on the presence of calcium and magnesium. Under these conditions, scintillation spectrometry of [14C]ascorbic acid in conjunction with high‐performance liquid chromatography was suited for measuring ascorbic acid transport.
High level expression and characterisation of Plasmepsin II, an aspartic proteinase from Plasmodium falciparum
Authors: Hill Jeffrey , Tyas Lorraine , Phylip Lowri H. , Kay John , Dunn Ben M. , Berry Colin
Published: July 2002

DNA encoding the last 48 residues of the propart and the whole mature sequence of Plasmepsin II was inserted into the T7 dependent vector pET 3a for expression in E. coli. The resultant product was insoluble but accumulated at ∼20 mg/l of cell culture. Following solubilisation with urea, the zymogen was refolded and, after purification by ion‐exchange chromatography, was autoactivated to generate mature Plasmepsin II. The ability of this enzyme to hydrolyse several chromogenic peptide substrates was examined; despite an overall identity of ∼35% to human renin, Plasmepsin II was not inhibited significantly by renin inhibitors.
A possible consensus sequence for VPg of viruses in the family Comoviridae
Authors: Mayoa M.A. , Fritsch C.
Published: July 2002

Alignment of the amino acid sequences of the genome‐linked proteins (VPg) of nepoviruses and comoviruses suggests that viruses within the family Comoviridae have VPg which share a consensus sequence.
Hypo‐osmotic cell swelling activates the p38 MAP kinase signalling cascade
Authors: Tilly Ben C , Gaestel Matthias , Engel Katrin , Edixhoven Marcel J , de Jonge Hugo R
Published: July 2002

Hypo‐osmotic swelling of human Intestine 407 cells leads to a significant increase of intracellular MAPKAP‐kinase 2 activity and Hsp27 phosphorylation. Pre‐treatment of the cells with the p38 MAP kinase inhibitor SB‐203580 blocks this activation, indicating that the hypotonicity‐induced activation of MAPKAP kinase 2 is, similarly to that described for hyper‐osmotic treatment, the result of an activated p38 MAP kinase cascade. The activation of MAPKAP kinase 2 proceeds with kinetics similar to that of one of the first physiological responses of hypo‐osmotic treatment, the opening of compensatory Cl− channels. However, inhibition of the p38 MAP kinase cascade does not block the osmo‐sensitive anion efflux and, vice versa, activation of p38 MAP kinase by cytokines and anisomycin does not increase the efflux. These results indicate that the p38 MAP kinase cascade is not directly involved in Cl− channel activation but instead may play a role in subsequent cellular repair processes.
Eukaryotic selenocysteine tRNA has the 9/4 secondary structure
Authors: Mizutani Takaharu , Goto Chiharu
Published: July 2002

There are two secondary structure models for the eukaryotic selenocysteine (Sec) tRNASec. One model, the 9/4 structure, was experimentally tested and possesses acceptor and T‐stems with 9 and 4 bp, respectively [Sturchler et al., 1993; Hubert et al., 1998]. The other one, the 7/5 secondary structure with a bulge in the T‐stem, was derived from theoretical calculation [Ioudovitch and Steinberg, 1999]. In this report, we show more experimental results supporting the 9/4 secondary structure. Several tRNASec mutants, whose secondary structure can adopt only the 9/4 structure, were active for serylation and selenylation. Some mutants that cannot base‐pair between positions 26 and 44 to provide the 6 bp anticodon stem were still active, inconsistent with the model by Steinberg. We also show that the orientation of the V‐arm directly or indirectly influences the selenylation activity, and that the rigid 6 bp D‐stem is important. Finally, we conclude that all tRNAsSec possess the 13 bp domain II made by the stacking of the colinear AA and T‐stems, whether they present the 9/4 structure in Eukarya and Archaea or the 8/5 structure in bacteria.
Protective roles for ATM in cellular response to oxidative stress
Authors: Takao Noriaki , Li Yingzhu , Yamamoto Ken-ichi
Published: July 2002

ATM (ataxia telangiectasia mutated), the gene mutated in ataxia telangiectasia, is related to a family of large phosphatidylinositol 3‐kinase domain‐containing proteins involved in cell cycle control and DNA repair. We found that ATM−/− DT40 cells were more susceptible than wild‐type cells to apoptosis induced not only by ionizing radiation and bleomycin but also by non‐DNA‐damaging apoptotic stimuli such as C2‐ceramide. Furthermore, the apoptosis induced by C2‐ceramide and H2O2 was blocked by anti‐oxidants, indicating that the ATM−/− DT40 cells had a heightened susceptibility to apoptosis induced by reactive oxygen intermediates (ROI), presumably due to defective ROI‐detoxification activities. In support of this hypothesis, we found that more ROI were generated in ATM−/− DT40 cells than in wild‐type cells, following treatment with the above apoptotic stimuli. These results indicate that ATM plays important roles in the maintenance of the cell homeostasis in response to oxidative damage.
Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis
Authors: Kagan Valerian E. , Fabisiak James P. , Shvedova Anna A. , Tyurina Yulia Y. , Tyurin Vladimir A. , Schor Nina F. , Kawai Kazuaki
Published: July 2002

Active maintenance of membrane phospholipid asymmetry is universal in normal cell membranes and its disruption with subsequent externalization of phosphatidylserine is a hallmark of apoptosis. Externalized phosphatidylserine appears to serve as an important signal for targeting recognition and elimination of apoptotic cells by macrophages, however, the molecular mechanisms responsible for phosphatidylserine translocation during apoptosis remain unresolved. Studies have focused on the function of aminophospholipid translocase and phospholipid scramblase as mediators of this process. Here we present evidence that unique oxidative events, represented by selective oxidation of phosphatidylserine, occur during apoptosis that could promote phosphatidylserine externalization. We speculate that selective phosphatidylserine oxidation could affect phosphatidylserine recognition by aminophospholipid translocase and/or directly result in enzyme inhibition. The potential interactions between the anionic phospholipid phosphatidylserine and the redox‐active cationic protein effector of apoptosis, cytochrome c, are presented as a potential mechanism to account for selective oxidation of phosphatidylserine during apoptosis. Thus, cytochrome c‐mediated phosphatidylserine oxidation may represent an important component of the apoptotic pathway.
A suicide‐substrate mechanism for hydrolysis of β‐lactams by an anti‐idiotypic catalytic antibody
Authors: Lefevre Séverine , Debat Hélène , Thomas Daniel , Friboulet Alain , Avalle Bérangère
Published: July 2002

The catalytic mechanism of an anti‐idiotypic antibody, 9G4H9, displaying a β‐lactamase activity was investigated. Kinetics experiments suggest that some penicillinic derivatives behave both as substrates and inactivators. Biochemical and immunological experiments strongly indicate that ampicillin may be regarded as a suicide substrate for hydrolysis by 9G4H9. The anti‐idiotypic network appears as a way to create enzyme mimics with modified catalytic activities.
Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis
Authors: Schweiger Manfred , Hennig Klaus , Lerner Felicitas , Niere Marc , Hirsch-Kauffmann Monica , Specht Thomas , Weise Christoph , Oei Shiao Li , Ziegler Mathias
Published: July 2002

Nicotinamide mononucleotide adenylyl transferase (NMNAT) is an essential enzyme in all organisms, because it catalyzes a key step of NAD synthesis. However, little is known about the structure and regulation of this enzyme. In this study we established the primary structure of human NMNAT. The human sequence represents the first report of the primary structure of this enzyme for an organism higher than yeast. The enzyme was purified from human placenta and internal peptide sequences determined. Analysis of human DNA sequence data then permitted the cloning of a cDNA encoding this enzyme. Recombinant NMNAT exhibited catalytic properties similar to the originally purified enzyme. Human NMNAT (molecular weight 31 932) consists of 279 amino acids and exhibits substantial structural differences to the enzymes from lower organisms. A putative nuclear localization signal was confirmed by immunofluorescence studies. NMNAT strongly inhibited recombinant human poly(ADP‐ribose) polymerase 1, however, NMNAT was not modified by poly(ADP‐ribose). NMNAT appears to be a substrate of nuclear kinases and contains at least three potential phosphorylation sites. Endogenous and recombinant NMNAT were phosphorylated in nuclear extracts in the presence of [γ‐32P]ATP. We propose that NMNAT's activity or interaction with nuclear proteins are likely to be modulated by phosphorylation.
Novel peptides from assassin bugs (Hemiptera: Reduviidae): isolation, chemical and biological characterization
Authors: Corzo Gerardo , Adachi-Akahane Satomi , Nagao Taku , Kusui Yoshihisa , Nakajima Terumi
Published: July 2002

Three novel peptides were isolated from the venomous saliva of predatory reduviids. They were identified by mass spectrometry and HPLC analysis and consist of 34–36 amino acid residues. They are relatively homologous to the calcium channel blockers ω‐conotoxins from marine cone snails and belong to the four‐loop Cys scaffold structural class. Ptu1, the shortest peptide, was chemically synthesized (sPtu1) and co‐eluted with its native form. Circular dichroism spectra of the sPtu1 showed a high content of β‐turns similar to that of ω‐conotoxins GVIA and MVIIA. Electrophysiological experiments demonstrated that sPtu1 reversibly blocks the N‐type calcium channels expressed in BHK cells.
Expression of membrane C1q in human monocyte‐derived macrophages is developmentally regulated and enhanced by interferon‐γ
Authors: Kaul Marcus , Loos Michael
Published: July 2002

The present study investigated when during ‘in vitro’ maturation macrophages (MΦ) express membrane C1q (mC1q), and whether cell activation affects expression and function of mC1q. Although C1q mRNA was repeatedly detected in freshly isolated monocytes using reverse transcriptase‐polymerase chain reaction, C1q protein was observed only in developing MΦ from day 1 to 4 on using immunodetection and flow cytometry. However, the quantity of mC1q and other MΦ membrane proteins differed strikingly in cells from different donors. We report here for the first time that CD14+ and CD14− mC1q‐bearing MΦ can develop, and that interferon‐γ increases mC1q display at the cell surface, and mC1q‐mediated phagocytosis.
Redox FTIR difference spectroscopy using caged electrons reveals contributions of carboxyl groups to the catalytic mechanism of haemcopper oxidases
Authors: Lübben Mathias , Gerwert Klaus
Published: July 2002

Redox spectra of the haem‐copper oxidases cytochrome aa
3 of Rhodobacter sphaeroides and cytochrome bo
3 of Escherichia coli were recorded in the visible and infrared spectral regions. The reduction of oxidases was initiated after light activation of the ‘caged electron’ donor riboflavin. Infrared redox difference spectra exhibit absorbance changes in the amide I region, which are indicative of very small redox‐finked conformational movements in the polypeptide backbone. A reproducible redox‐dependent pattern of positive and negative absorption changes is found in the carbonyl region (1680–1750 cm−1). The carbonyl bands shift to lower frequencies due to isotope exchange of the solvent H2O to D2O. This common feature of cytochrome c and quinol oxidases indicates that at least (i) one redox‐sensitive carboxyl group is in the protonated state in the oxidized form and (ii) one carboxylic acid is involved at a catalytic step — presumably in proton translocation — of haem‐copper oxidases.
Cytosolic NAD+ content strictly depends on ATP concentration in isolated liver cells
Authors: Devin Anne , Guérin Bernard , Rigoulet Michel
Published: July 2002

By focusing on the question of the thermodynamic relationships involved in the regulation of biological energy conversion, bioenergetic studies usually consider the free pyridine and adenine nucleotide rather than their total pools, in either cytosol or mitochondria. In this study, we report a new observation that, at steady state, nicotinamide nucleotide content is increased by a rise in the ATP content of the whole cell under physiological conditions. It is a straight line relationship when only NAD+ and ATP are considered. When regarding the compartmentation of this phenomenon, it appears that the linear relationship between [NAD+] and [ATP] occurs only in the cytosol. Such a dependence could be a supplementary mechanism of regulation between various metabolic pathways in the liver cell.
3‐Methoxynaltrexone, a selective heroin/morphine‐6β‐glucuronide antagonist
Authors: Brown George P , Yang Ke , King Michael A , Rossi Grace C , Leventhal Liza , Chang Albert , W. Pasternak Gavril
Published: July 2002

Recent work has suggested that heroin and morphine‐6β‐glucuronide (M6G) both act through a novel mu opioid receptor subtype distinct from those mediating morphine's actions. This very high affinity3H‐M6G site is selectively competed by 3‐methoxynaltrexone. In vivo, 3‐methoxynaltrexone (2.5 ng, i.c.v.) selectively antagonizes the analgesic actions of heroin and M6G without interfering with mu (morphine and [d‐Ala2,MePhe4,Gly(ol)5]enkephalin), delta ([d‐Pen2,d‐Pen5]enkephalin), kappa1(U50,488H) or kappa3(naloxone benzoylhydrazone) analgesia. In dose–response studies, 3‐methoxynaltrexone (2.5 ng, i.c.v.) significantly shifted the ED50values for heroin and its active metabolite, 6‐acetylmorphine, without affecting the morphine curve. These results indicate that 3‐methoxynaltrexone selectively blocks a novel3H‐M6G binding site which is responsible for the analgesic actions of heroin and M6G. This ability to selectively antagonize heroin actions opens new possibilities in the development of therapeutics for the treatment of opioid abuse.
Gly166 in the NK1 receptor regulates tachykinin selectivity and receptor conformation1
Authors: Ciucci Alessandra , Palma Carla , Riitano Daniela , Manzini Stefano , Werge Thomas M
Published: July 2002

We have studied the pharmacological properties of genetically engineered human NK1 tachykinin receptors in which residues at the extracellular surface of the fourth transmembranal domain were substituted with the corresponding amino acids from the NK2 receptor. We show that substitution of G166C:Y167F in the human NK1 receptor induces high affinity binding of a group of tachykinin ligands, known as `septides' (i.e. neurokinin A, neurokinin B, [pGlu6,Pro9]‐substance P6‐11 and substance P‐methylester). In contrast, binding of substance P and non‐peptide antagonists is unaffected by these mutations. This effect parallels that found on the rat receptor and is therefore species specific. Second, we demonstrate that mutation of Gly166 to Cys alone is both necessary and sufficient to create this pan‐reactive tachykinin receptor, whereas replacement of Tyr167 by Phe has no detectable effect on the pharmacological properties of the receptor. Furthermore, analysis of the effect of N‐ethylmaleimide and dithiothreitol on binding of radiolabelled substance P documents differences in the mode in which this ligand interacts with wild‐type and mutant receptors and supports the existence of a mutational induced change in the conformational status of the NK1 receptor.
DDC‐4, an apoptosis‐associated gene, is a secreted frizzled relative
Authors: Wolf Vladimir , Ke Guo , Dharmarajan A.M , Bielke Wolfgang , Artuso Livia , Saurer Susanne , Friis Robert
Published: July 2002

The differential display method has been used in our laboratory as a coincidence analysis to isolate genes expressed in common in each of three different rat tissues undergoing physiological apoptosis: mammary gland, ovarian corpus luteum and ventral prostate. The most interesting of these isolates, DDC‐4, shows a clear association with apoptosis, its expression being confined to these three organs, and only during their involution. Using DDC‐4 as probe, we screened a rat ovarian cDNA library to obtain full‐length isolates. One isolate, Y81 clone 40, gives rise to a protein of approximately 40 kDa with coupled in vitro transcription/translation. Sequencing of this clone indicates an open reading frame of 1044 nucleotides encoding a protein of 39.7 kDa with a putative signal sequence. This clone exhibits a high homology with the cysteine‐rich domain, i.e. the ligand‐binding domain, of the frizzled gene family originally defined as tissue polarity genes in Drosophila. The homology of Y81 clone 40 is most extensive with the newly described secreted frizzled relatives, the frzb subfamily.
Interaction of Oct‐1 and automodification domain of poly(ADP‐ribose) synthetase
Authors: Nie Jing , Sakamoto Shuji , Song Demao , Qu Zhiqiang , Ota Katsuya , Taniguchi Taketoshi
Published: July 2002

We isolated several clones from a matchmaker two‐hybrid system human lymphocyte cDNA library using an automodification domain of poly(ADP‐ribose) synthetase (PARS) as a probe. A DNA sequence (∼1 kbp) of the clone was identical to part of the Oct‐1 DNA sequence. We then constructed either a His‐tagged or GST fusion protein of the inserted cDNA from the clone and the fusion protein was shown to interact with PARS by far‐Western blot analysis and co‐precipitation with affinity resin. Furthermore, the His‐tagged Oct‐1/POU‐homeo fusion protein interacted weakly with the octamer motif of the DRa promoter and the addition of PARS fusion protein greatly increased the DNA binding activity. These results suggest that PARS interacts with Oct‐1 and stabilizes the binding of Oct‐1 to the octamer motif.
Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin alterations
Authors: Paradies Giuseppe , Ruggiero Francesca Maria , Petrosillo Giuseppe , Quagliariello Ernesto
Published: July 2002

Rat heart mitochondrial membranes exposed to the free radicals generating system tert‐butylhydroperoxide/Cu2+ undergo lipid peroxidation as evidenced by the accumulation of thyobarbituric acid reactive substances. Mitochondrial lipid peroxidation resulted in a marked loss of both cytochrome c oxidase activity and cardiolipin content. The alterations in the properties of cytochrome c oxidase were confined to a decrease in the maximal activity (V
max) with no change in the affinity (K
m) with respect to the substrate cytochrome c. Various lipid soluble antioxidants could prevent the lipid peroxidation reaction and the associated loss of cytochrome c oxidase activity. External added cardiolipin but no other phospholipids, nor peroxidized cardiolipin was able to prevent the loss of cytochrome oxidase activity induced by lipid peroxidation. These results establish a close correlation between oxidative damage to cardiolipin and alterations in the cytochrome oxidase activity and may prove useful in probing molecular mechanism of free radicals induced peroxidative damage of mitochondria which has been proposed to contribute to aging and to chronic degenerative diseases.
Perpetually mobile footprints of ancient infections in human genome
Authors: Sverdlov Eugene D
Published: July 2002

Up to 1% of the human genome is represented by human endogenous retroviruses (HERVs) and their fragments that are likely footprints of ancient primate germ‐cell infections by retroviruses that occurred 10–60 million years ago. HERV solitary long terminal repeats (LTRs) can be often met in close vicinity to functional genes. The LTRs comprise a set of regulatory sequences like promoters, enhancers, hormone responsive elements and polyadenylation signals that might come out as new regulatory signals to resident genes and thus change their regulation in evolution. Moreover, the LTRs have a potential for chromatin remodeling that can also modulate gene expression. This review describes the integration specificity and distribution of the HERVs and LTRs in the human genome and discusses possible functional consequences of their integration in the vicinity of genes.
Trypanosoma brucei tryparedoxin, a thioredoxin‐like protein in African trypanosomes
Authors: Lüdemann Heike , Dormeyer Matthias , Sticherling Christian , Stallmann Dirk , Follmann Hartmut , Krauth-Siegel R.Luise
Published: July 2002

A gene has been cloned from Trypanosoma brucei which encodes a protein of 144 amino acid residues containing the thioredoxin‐like motif WCPPCR. Overexpression of the gene in E. coli resulted in 4 mg pure protein from 100 ml bacterial cell culture. Recombinant T. brucei tryparedoxin acts as a thiol‐disulfide oxidoreductase. It is spontaneously reduced by trypanothione. This dithiol, exclusively found in parasitic protozoa, also reduces E. coli glutaredoxin but not thioredoxin. The trypanothione/tryparedoxin couple is an effective reductant of T. brucei ribonucleotide reductase. Like thioredoxins it has a poor GSH:disulfide transhydrogenase activity. The catalytic properties of tryparedoxin are intermediate between those of classical thioredoxins and glutaredoxins which indicates that these parasite proteins may form a new class of thiol‐disulfide oxidoreductases.
Site‐specific regulatory interaction between spinach leaf sucrose‐phosphate synthase and 14‐3‐3 proteins
Authors: Toroser Dikran , Athwal Gurdeep S. , Huber Steven C.
Published: July 2002

We report an Mg2+‐dependent interaction between spinach leaf sucrose‐phosphate synthase (SPS) and endogenous 14‐3‐3 proteins, as evidenced by co‐elution during gel filtration and co‐immunoprecipitation. The content of 14‐3‐3s associated with an SPS immunoprecipitate was inversely related to activity, and was specifically reduced when tissue was pretreated with 5‐aminoimidazole‐4‐carboxamide riboside, suggesting metabolite control in vivo. A synthetic phosphopeptide based on Ser‐229 was shown by surface plasmon resonance to bind a recombinant plant 14‐3‐3, and addition of the phosphorylated SPS‐229 peptide was found to stimulate the SPS activity of an SPS:14‐3‐3 complex. Taken together, the results suggest a regulatory interaction of 14‐3‐3 proteins with Ser‐229 of SPS.
Hairpin‐shaped DNA duplexes with disulfide bonds in sugar‐phosphate backbone as potential DNA reagents for crosslinking with proteins
Authors: Dolinnaya Nina , Metelev Valeri , Oretskaya Tatiana , Tabatadze David , Shabarova Zoe
Published: July 2002

Convenient approaches were described to incorporate ‐OP(=O)O−‐SS‐O−(O=)PO‐ bridges in hairpin‐shaped DNA duplexes instead of regular phosphodiester linkages: (i) H2O2‐ or 2,2′‐dipyridyldisulfide‐mediated coupling of 3′‐ and 5′‐thiophosphorylated oligonucleotides on complementary template and (ii) more selective template‐guided autoligation of a preactivated oligonucleotide derivative with an oligomer carrying a terminal thiophosphoryl group. Dithiothreitol was found to cleave completely modified internucleotide linkage releasing starting oligonucleotides. The presence of complementary template as an intrinsic element of the molecule protects the hairpin DNA analog from spontaneous exchange of disulfide‐linked oligomer fragments and makes it a good candidate for auto‐crosslinking with cysteine‐containing proteins.
The interaction of ubiquinone‐3 with phospholipid membranes
Authors: Asai Yasuyuki , Watanabe Sumio
Published: July 2002

The effects of ubiquinone‐3 (UQ) on dipalmitoylphosphatidylcholine (DPPC) membrane were studied by surface monolayer, differential scanning calorimetry (DSC) and fluorescence techniques. DPPC and UQ are proved to be freely miscible in the mixed monolayer at an air/water interface, and to be partially miscible in bulk phase, i.e. bilayer and solid phase. There is a condensing interaction between UQ and DPPC in the UQ/DPPC mixed monolayers. The solubility of UQ in the DPPC is about 20 mole% and the solubility of DPPC in UQ is about 10 mole%. The membrane fluidity of DPPC was increased by the addition of UQ and the phase transition temperature was decreased.
p24 and p23, the major transmembrane proteins of COPI‐coated transport vesicles, form hetero‐oligomeric complexes and cycle between the organelles of the early secretory pathway
Authors: Gommel D , Orci L , Emig E.M , Hannah M.J , Ravazzola M , Nickel W , Helms J.B , Wieland F.T , Sohn K
Published: July 2002

COPI‐coated vesicles that bud off the Golgi complex contain two major transmembrane proteins, p23 and p24. We have localized the protein at the Golgi complex and at COPI‐coated vesicles. Transport from the intermediate compartment (IC) to the Golgi can be blocked at 15°C, and under these conditions p24 accumulates in peripheral punctated structures identified as IC. Release from the temperature block leads to a redistribution of p24 to the Golgi, showing that p24, similar to p23, cycles between the IC and Golgi complex. Immunoprecipitations of p24 from cell lysates and from detergent‐solubilized Golgi membranes and COPI‐coated vesicles show that p24 and p23 interact with each other to form a complex. Transient transfection of p23 in HeLa cells shows that p23 and p24 colocalize in structures induced by the overexpression of p23. Taken together p24 interacts with p23 and constitutively cycles between the organelles of the early secretory pathway.
Novel BNIP1 variants and their interaction with BCL2 family members
Authors: Zhang Hong , Heim Jutta , Meyhack Bernd
Published: July 2002

By PCR and EST database searches we have identified three novel BNIP1 splice variants, and found that one of them, BNIP1‐b, contains a highly conserved BH3 domain. The BNIP1 gene has been assigned to chromosome 5q33–34. Using in vitro protein‐protein interaction assays, all BNIP1 variants were shown to interact with BCL2 and also with BCL2L1 (previously Bcl‐xL). These interactions are BH3‐independent. Furthermore, the BNIP1 variants cannot interact with BAX. The results suggest that the BNIP1 variants are novel members of the BCL2 family but function through a mechanism different from other BH3‐only members.
Identification and characterization of GABA, proline and quaternary ammonium compound transporters from Arabidopsis thaliana
Authors: Breitkreuz Kevin E. , Shelp Barry J. , Fischer Wolf N. , Schwacke Rainer , Rentsch Doris
Published: July 2002

Arabidopsis thaliana grows efficiently on GABA as the sole nitrogen source, thereby providing evidence for the existence of GABA transporters in plants. Heterologous complementation of a GABA uptake‐deficient yeast mutant identified two previously known plant amino acid transporters, AAP3 and ProT2, as GABA transporters with Michaelis constants of 12.9±1.7 and 1.7±0.3 mM at pH 4, respectively. The simultaneous transport of [1‐14C]GABA and [2,3‐3H]proline by ProT2 as a function of pH, provided evidence that the zwitterionic state of GABA is an important parameter in substrate recognition. ProT2‐mediated [1‐14C]GABA transport was inhibited by proline and quaternary ammonium compounds.
Novel reactions involved in energy conservation by methanogenic archaea
Authors: Deppenmeier Uwe , Lienard Tanja , Gottschalk Gerhard
Published: July 2002

Methanogenic archaea of the order Methanosarcinales which utilize C1 compounds such as methanol, methylamines or H2+CO2, employ two novel membrane‐bound electron transport systems generating an electrochemical proton gradient: the H2:heterodisulfide oxidoreductase and the F420H2:heterodisulfide oxidoreductase. The systems are composed of the heterodisulfide reductase and either a membrane‐bound hydrogenase or a F420H2 dehydrogenase which is functionally homologous to the proton‐translocating NADH dehydrogenase. Cytochromes and the novel electron carrier methanophenazine are also involved. In addition, the methyl‐H4MPT:HS‐CoM methyltransferase is bioenergetically relevant. The enzyme couples methyl group transfer with the translocation of sodium ions and seems to be present in all methanogens. The proton‐translocating systems with the participation of cytochromes and methanophenazine have been found so far only in the Methanosarcinales.
Core α1→3‐fucose is a common modification of N‐glycans in parasitic helminths and constitutes an important epitope for IgE from Haemonchus contortus infected sheep
Authors: van Die Irma , Gomord Veronique , Kooyman Frans N.J. , van den Berg Timo K. , Cummings Richard D. , Vervelde Lonneke
Published: July 2002

Synthesis of parasite specific IgE plays a critical role in the defence against helminth infections. We report here that IgE from serum from Schistosoma mansoni infected mice and Haemonchus contortus infected sheep recognizes complex‐type N‐glycans from Arabidopsis thaliana, which contain R‐GlcNAcβ1→4(Fucα1→3)GlcNAcβ1‐Asn (core α1→3‐Fuc) and Xylβ1→2Manβ1→4GlcNAcβ1‐R (core β1→2‐Xyl) modifications, and honeybee phospholipase A2, which carries N‐glycans that contain the core α1→3‐Fuc epitope. Evidence is presented that core α1→3‐fucosylated N‐glycans bind a substantial part of the parasite specific IgE in serum of H. contortus infected sheep. These results suggest that the core α1→3‐Fuc antigen may contribute to induction of a Th2 response leading to the production of IgE. In addition we show here that N‐glycans carrying core α1→3‐Fuc and β1→2‐Xyl antigens are synthesized by many parasitic helminths and also by the free living nematode Caenorhabditis elegans. Since N‐glycans containing the core α1→3‐Fuc have also been implicated in honeybee and plant induced allergies, this conserved glycan might represent an important common IgE epitope.
A novel glycosyltransferase with a polyglutamine repeat; a new candidate for GD1α synthase (ST6GalNAc V)1
Authors: Ikehara Yuzuru , Shimizu Nobuyuki , Kono Mari , Nishihara Shoko , Nakanishi Hayao , Kitamura Tabito , Narimatsu Hisashi , Tsuji Shuichi , Tatematsu Masae
Published: July 2002

The fifth type GalNAcα2,6‐sialyltransferase (mST6GalNAc V) was cloned from a mouse brain cDNA library. mST6GalNAc V exhibited type II transmembrane topology containing a polyglutamine repeat, which showed 42.6% and 44.8% identity to mouse ST6GalNAc III and IV, respectively. Northern blot analysis revealed that the mST6GalNAc V gene was specifically expressed in forebrain and cerebellum. mST6GalNAc V exhibited GD1α synthetic activity from GM1b the same as mST6GalNAc III and IV. The activity ratio of GM1b toward fetuin and the expression pattern were completely different among the three ST6GalNAcs. Interestingly, the polyglutamine repeat number was different from that of inbred mice. We report the first glycosyltransferase with a polymorphic polyglutamine repeat.
Plant MAP kinase pathways: how many and what for?
Authors: Wrzaczek Michael , Hirt Heribert
Published: July 2002

Summry— Mitogen activated protein kinases (MAPK) are important mediators in signal transmission, connecting the perception of external stimuli to cellular responses. MAPK cascades are involved in signalling various biotic and abiotic stresses, like wounding and pathogen infection, temperature stress or drought, but also some plant hormones, such as ethylene and auxin. Moreover, MAPKs have been implicated in cell cycle and developmental processes. In Arabidopsis mutant screens and in vivo assays several components of plant MAPK cascades have been identified. This review compares results obtained from functional analyses of MAPK cascades in plants with recent data obtained from searching the complete Arabidopsis genome.  This analysis reveals that plants have an overall of 24 MAPK pathways of which only a small subset has been studied so far.
A tutorial on business process improvement
Authors: Rohleder Thomas R. , Silver Edward A.
Published: July 2002

Considering the strategic importance of business process improvement, it is imperative that educators, students, and practitioners be familiar with this topic. Thus, the intention of this tutorial is to provide a guiding framework for carrying out improvements of business processes. We present numerous illustrative examples, taken from our personal experiences and those of our students, as well as from the literature. An extensive reference list is provided, thus pointing the interested reader to sources of further detail on specific topics.
Existence of solutions for compressible fluid models of Korteweg type
Authors: Danchin Raphaël , Desjardins Benoı̂t
Published: July 2002

The purpose of this work is to prove existence and uniqueness results of suitably smooth solutions for an isothermal model of capillary compressible fluids derived by J.E. Dunn and J. Serrin (1985), which can be used as a phase transition model.

We first study the well-posedness of the model in spaces with critical regularity indices with respect to the scaling of the associated equations. In a functional setting as close as possible to the physical energy spaces, we prove global existence of solutions close to a stable equilibrium, and local in time existence for solutions when the pressure law may present spinodal regions. Uniqueness is also obtained.

Assuming a lower and upper control of the density, we also show the existence of weak solutions in dimension 2 near equilibrium. Finally, referring to the work of Z. Xin (1998) in the non-capillary case, we describe some blow-up properties of smooth solutions with finite total mass.

On s’intéresse ici à des résultats d’existence et d’unicité de solutions pour un modèle de fluides compressibles isothermes avec capillarité. Ce modèle de transition de phase a été dérivé par J.E. Dunn et J. Serrin (1985).

Pour commencer, on montre que le problème de Cauchy est bien posé dans des espaces à régularité critique pour le
scaling
des équations. Pour des données initiales proches d’un état d’équilibre stable, on obtient l’existence globale (et l’unicité) de solutions dans un cadre fonctionnel aussi proche que possible de l’espace d’énergie physique. Pour des lois de pression plus générales (pouvant être décroissantes), on prouve des résultats locaux en temps.

En supposant que l’on dispose d’un minorant strictement positif et d’une borne supérieure pour la densité, on obtient l’existence de solutions faibles en dimension 2 pour des données initiales proches de l’équilibre. Enfin, en adaptant un travail de Z. Xin pour les fluides sans capillarité, on établit l’explosion de solutions régulières à masse totale finie.
Multi-peak bound states for nonlinear Schrödinger equations
Authors: Del Pino Manuel , Felmer Patricio L.
Published: July 2002

In this paper we consider the study of
standing wave solutions
for a nonlinear Schrödinger equation. This problem reduces to that of finding nonnegative solutions of

\begin{matrix} ɛ^{2}\Delta u - V\left(x\right)u + f\left(u\right) = 0 & \text{in} & \Omega , \\ \end{matrix}

with finite energy. Here ɛ is a small parameter, ω is a smooth, possibly unbounded domain,
f
is an appropriate superlinear function, and
V
is a positive potential, bounded away from zero.

It is the purpose of this article to obtain multi-peak solutions in the “multiple well case”. We find solutions exhibiting concentration at any prescribed finite set of local minima, possibly degenerate, of the potential.

The proof relies on variational arguments, where a penalization-type method is developed for the identification of the desired solutions.

Dans cet article, on considère l’étude des solutions de
ondes permanentes
d’une équation de Schrödinger nonlinéaire. Ce problème se réduit à la recherche de solutions non négatives de

\begin{matrix} ɛ^{2}\Delta u - V\left(x\right)u + f\left(u\right) = 0 & \text{dans} & \Omega , \\ \end{matrix}

avec une énergie finie. Ici ɛ est un paramètre petit, ω est un domaine lisse qui peut être non borné,
f
est une fonction superlinéaire appropriée et
V
est un potentiel positif borné hors de zéro.

L’objectif de cet article consiste à obtenir des solutions à pics multiples dans le cas de puits multiples. Nous trouvons des solutions qui montrent une concentration pour tout ensemble choisi fini de minima locaux du potentiel, qui peuvent être dégénérés.

La démonstration se base sur des arguments variationnels, où une méthode de pénalisation est développée pour identifier les solutions cherchées.
Localization and pharmacological characterization of voltage dependent calcium channels in cultured neocortical neurons
Authors: Timmermann Daniel B. , Lund Trine M. , Belhage Bo , Schousboe Arne
Published: July 2002

The physiological significance and subcellular distribution of voltage dependent calcium channels was defined using calcium channel blockers to inhibit potassium induced rises in cytosolic calcium concentration in cultured mouse neocortical neurons. The cytosolic calcium concentration was measured using the fluorescent calcium chelator fura‐2. The types of calcium channels present at the synaptic terminal were determined by the inhibitory action of calcium channel blockers on potassium‐induced [3H]GABA release in the same cell preparation. L‐, N‐, P‐, Q‐ and R‐/T‐type voltage dependent calcium channels were differentially distributed in somata, neurites and nerve terminals. ω‐conotoxin MVIIC (ω‐CgTx MVIIC) inhibited approximately 40% of the Ca2+‐rise in both somata and neurites and 60% of the potassium induced [3H]GABA release, indicating that the Q‐type channel is the quantitatively most important voltage dependent calcium channel in all parts of the neuron. After treatment with thapsigargin the increase in cytosolic calcium was halved, indicating that calcium release from thapsigargin sensitive intracellular calcium stores is an important component of the potassium induced rise in cytosolic calcium concentration. The results of this investigation demonstrate that pharmacologically distinct types of voltage dependent calcium channels are differentially localized in cell bodies, neurites and nerve terminals of mouse cortical neurons but that the Q‐type calcium channel appears to predominate in all compartments.
Role of Ca2+‐stimulated adenylyl cyclases in LTP and memory formation
Authors: Poser Steve , Storm Daniel R.
Published: July 2002

Studies with invertebrates and vertebrates have strongly implicated the CREB/CRE transcriptional pathway in long‐term memory (LTM) and transcriptionally‐dependent L‐LTP. It is hypothesized that LTM and L‐LTP are both dependent upon a Ca2+ signal generated through activation of NMDA receptors. This review discusses evidence that Ca2+ signals generated through activation of NMDA receptors coactivate the Erk/MAP kinase and cAMP signal transduction pathways. It is hypothesized that activation of these two regulatory pathways increases the transcription of a family of genes through the CREB/CRE transcriptional pathway. Gene disruption studies have shown that Ca2+ activated adenylyl cyclases play a critical role in generating the cAMP signal required for LTM and L‐LTP. Although cAMP may be required for several events in this complex signal transduction cascade, one of the major roles of cAMP may be to support nuclear translocation of Erk/MAP kinase in hippocampal neurons.
Genetic vulnerability to drug abuse
Authors: Duaux E. , Krebs M.O. , Loo H. , Poirier M.F.
Published: July 2002

Addiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.