bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational augmentation of pro‐matrix metalloproteinase 3 (prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)‐1 mRNAs induced by epidermal growth factor in human uterine cervical fibroblasts
Authors: Hosono Tetsuji , Ito Akira , Sato Takashi , Nagase Hideaki , Mori Yo
Published: April 2003

The mechanisms by which epidermal growth factor (EGF) enhances the production of pro‐matrix metalloproteinase 3 (proMMP‐3/prostromelysin 1) and tissue inhibitor of metalloproteinases (TIMP)‐1 were investigated using human uterine cervical fibroblasts. The treatment of the cells with EGF for 24 h resulted in about 5–6‐fold increase in the production of proMMP‐3 and TIMP‐1 compared with the untreated control cells. This increase was accompanied by an increase of proMMP‐3 and TIMP‐1 mRNAs. However, an about 3‐ and 2‐fold increase in the production of proMMP‐3 and TIMP‐1, respectively, was observed as early as 1 h after the treatment of the cells with EGF, and it was not accompanied by any apparent increase in proMMP‐3 and TIMP‐1 mRNAs. This early effect of EGF on the enhanced production of proMMP‐3 and TIMP‐1 was not inhibited by actinomycin D, even though actinomycin D inhibited the synthesis of the total RNA in both the EGF‐treated and untreated cells. These results indicate that EGF enhances the apparent production of proMMP‐3 and TIMP‐1 by two mechanisms: one by the accelerated translation of their mRNAs; and the other by the enhanced transcription of their genes. The former event takes place much earlier than the latter.
Transformation of Saccharomyces cerevisiae with a cDNA encoding a sterol C‐methyltransferase from Arabidopsis thaliana results in the synthesis of 24‐ethyl sterols
Authors: Husselstein Tania , Gachotte Daniel , Desprez Thierry , Bard Martin , Benveniste Pierre
Published: April 2003

Using an EST‐cDNA probe, a full‐length cDNA (411) sequence of 1411 bp was isolated from A. thaliana. This sequence contained features typical of methyltransferases in general and in particular showed 38% identity with ERG6, a S. cerevisiae gene which encodes the zymosterol‐C‐24‐methyltransferase. A yeast vector containing this ORF (4118‐pYeDP60) was used to transform a wild type S. cerevisiae which accumulates predominantly ergosterol, a 24‐methyl sterol as well as a mutant erg6 null mutant accumulating principally zymosterol, a sterol non‐alkylated at C‐24. In both cases, several 24‐ethyl‐ and 24‐ethylidene sterols were synthetized indicating that the 4118 cDNA encodes a plant sterol C‐methyltransferase able to perform two sequential methylations of the sterol side chain.
In vitro import of pre‐ferredoxin‐NADP+‐oxidoreductase from Cyanophora paradoxa into cyanelles and into pea chloroplasts
Authors: Jakowitsch Johannes , Neumann-Spallart Christoph , Ma Yan , Steiner Jürgen , Schenk Hainfried E.A. , Bohnert Hans J. , Löffelhardt Wolfgang
Published: April 2003

Using a novel cyanelle isolation procedure we showed that pre‐ferredoxin‐NADP+‐oxidoreductase (pre‐FNR) from C. paradoxa is translocated in vitro across the peptidoglycancontaining cyanelle envelope. Efficient import was also observed in a heterologous system with pea chloroplasts as the recipient organelles. These results support the conclusion derived from comparative analysis of plastid genome organization, that all plastids originate from a common semi‐autonomous endosymbiotic ancestor.
Human cone‐specific cGMP phosphodiesterase α′ subunit: Complete cDNA sequence and gene arrangement
Authors: Feshchenko Elena A. , Andreeva Svetlana G. , Suslova Veronika A. , Smirnova Evgeniya V. , Zagranichny Vasily E. , Lipkin Valery M.
Published: April 2003

Four independent phage clones containing the fragments of cone‐specific cGMP phosphodiesterase (PDE) α′ subunit (PDEα′) cDNA were isolated from the human cDNA library. The screening of the genomic library resulted in isolation of four independent phage clones with the fragments of human cone PDEα′ gene including 5′‐flanling region and exons ranged from 1 to 14 (overall 32 kilobases). Structural studies of the clones made it possible to establish the complete human cone PDEα′ cDNA structure (3455 base pairs). The encoding polypeptide consists of 858 amino acid residues with a calculated molecular mass of 99169 Da. The deduced amino acid sequence displays high homology to the earlier analyzed catalytic α, β and α′ subunits of bovine, human, chicken and mouse photoreceptor PDEs.
Enzymatic repair of oxidative damage to human apolipoprotein A‐I
Authors: Sigalov Alexander B. , Stern Lawrence J.
Published: April 2003

Oxidative damage to apolipoprotein A‐I that occurs in vivo commonly involves methionine oxidation, and is accompanied by alterations in structure, lipid association, and cholesterol efflux function. We have used the enzyme peptide methionine sulfoxide reductase (PMSR) to reverse this damage, and shown by a variety of criteria that enzyme treatment restores the primary, secondary, and tertiary structure and lipid association characteristic of the native unoxidized protein. Lipid‐associated as well as lipid‐free apolipoprotein A‐I reacts with PMSR, suggesting that enzymatic reduction of oxidized apolipoprotein A‐I in high density lipoproteins can result in restoration of biological activity and the ability to promote cholesterol efflux from cells.
Drosophila melanogaster acylphosphatase: A common ancestor for acylphosphatase isoenzymes of vertebrate species
Authors: Pieri Alessandro , Magherini Francesca , Liguri Gianfranco , Raugei Giovanni , Taddei Niccolò , Bozzetti Maria Pia , Cecchi Cristina , Ramponi Giampietro
Published: April 2003

An open reading frame encoding a putative acylphosphatase was found in Drosophila melanogaster. The corresponding gene product shows 40% identity and 22 additional amino acid residues at the C‐terminus as compared to muscle‐ and common‐type human acylphosphatases. Moreover, all the residues involved in the catalytic mechanism of vertebrate enzymes are conserved in the D. melanogaster acylphosphatase. The D. melanogaster protein and a deletion mutant, similar in length to vertebrate acylphosphatases, were produced by cloning the corresponding cDNA in Escherichia coli. The wild‐type enzyme is a protein with a well‐established three‐dimensional fold and a markedly reduced conformational stability as compared to vertebrate isoenzymes. The specific activity of the enzyme is significantly lower than that found in vertebrate enzymes though the substrate binding capability is basically unaltered. The deletion of 22 residues does not cause a significant change in k
cat, while affecting the apparent binding parameters. This work suggests that the genes encoding the vertebrate enzymes originate from an ancestor gene by duplication and subsequent evolution.
A trypanosome oligopeptidase as a target for the trypanocidal agents pentamidine, diminazene and suramin
Authors: Morty Rory E. , Troeberg Linda , Pike Robert N. , Jones Roy , Nickel Peter , Lonsdale-Eccles John D. , Coetzer Theresa H.T.
Published: April 2003

African trypanosomes contain a cytosolic serine oligopeptidase, called OP‐Tb, that is reversibly inhibited by the active principles of three of the five most commonly used trypanocidal drugs: pentamidine, diminazene and suramin. OP‐Tb was inhibited by pentamidine in a competitive manner, and by suramin in a partial, non‐competitive manner. The inhibition of OP‐Tb by a variety of suramin analogues correlated with the trypanocidal efficacy of these analogues (P = 0.03; by paired Student's t‐test). Since intracellular (therapeutic) concentrations of pentamidine and suramin are reported to reach approximately 206K
i and 15K
i respectively, we suggest that these drugs may exert part of their trypanocidal activity through the inhibition of OP‐Tb.
Identification, functional expression and chromosomal localisation of a sustained human proton‐gated cation channel
Authors: de Weille Jan R. , Bassilana Frédéric , Lazdunski Michel , Waldmann Rainer
Published: April 2003

Non‐inactivating or slowly inactivating proton‐gated cation channels are thought to play an important role in the perception of pain that accompanies tissue acidosis. We have identified a novel human proton‐gated cation channel subunit that has biphasic desensitisation kinetics with both a rapidly inactivating Na+‐selective and a sustained component. The protein shares 84% sequence identity with the proton‐gated cation channel rASIC3 (rDRASIC) from rat sensory neurones. The biphasic desensitisation kinetics and the sequence homology suggest that this novel clone (hASIC3) is the human orthologue of rASIC3 (rDRASIC). While rASIC3 (rDRASIC) requires very acidic pH (pH < 4.5) for activation of the sustained current, the non‐inactivating hASIC3 current starts to be activated when the pH decreases to below pH 6. hASIC3 is an acid sensor and might play an important role in the detection of lasting pH changes in human. We localised the hASIC3 gene to the human chromosome 7q35, 6.4 cRad telomeric from the microsatellite AFMA082XC9.
Apoptosis‐like, reversible changes in plasma membrane asymmetry and permeability, and transient modifications in mitochondrial membrane potential induced by curcumin in rat thymocytes
Authors: Jaruga Ewa , Salvioli Stefano , Dobrucki Jurek , Chrul Sławomir , Bandorowicz-Pikuła Joanna , Sikora Ewa , Franceschi Claudio , Cossarizza Andrea , Bartosz Grzegorz
Published: April 2003

Curcumin (diferuoylmethane) is a natural compound with anticarcinogenic activities which is able to exert either proapoptotic or antiapoptotic effects in different cell types. This paper focuses on the sequence and extent of primary events induced by curcumin, in comparison with those occurring during dexamethasone‐induced apoptosis in rat thymocytes. It also presents annexin VI‐FITC as a new probe for studying membrane asymmetry. Curcumin readily penetrates into the cytoplasm, and is able to accumulate in membranous structures such as plasma membrane, endoplasmic reticulum and nuclear envelope. Curcumin‐treated cells exhibit typical features of apoptotic cell death, including shrinkage, transient phosphatidylserine exposure, increased membrane permeability and decrease in mitochondrial membrane potential. However, nuclei morphology, DNA fragmentation, the extent and time‐course of membrane changes are different from those observed during dexamethasone‐induced apoptosis, suggesting that, despite many similarities, the mode of action and the events triggered by curcumin are different from those occurring during typical apoptosis.
The Ecl18kI restriction‐modification system: cloning, expression, properties of the purified enzymes
Authors: Denjmukhametov M.M. , Brevnov M.G. , Zakharova M.V. , Repyk A.V. , Solonin A.S. , Petrauskene O.V. , Gromova E.S.
Published: April 2003

Ecl18kI is a type II restriction‐modification system isolated from Enterobacter cloaceae 18kI strain. Genes encoding Ecl18kI methyltransferase (M.Ecl18kI) and Ecl18kI restriction endonuclease (R.Ecl18kI) have been cloned and expressed in Escherichia coli. These enzymes recognize the 5′….↓CCNGG….′ sequence in DNA; M.Ecl18kI methylates the C5 carbon atom of the inner dC residue and R.Ecl18kI cuts DNA as shown by the arrow. The restriction endonuclease and the methyltransferase were purified from E. coli B834 [p18Ap1] cells to near homogeneity. The restriction endonuclease is present in the solution as a tetramer, while the methyltransferase is a monomer. The interactions of M.Ecl18kI and R.Ecl18kI with 1,2‐dideoxy‐d‐ribofuranose containing DNA duplexes were investigated. The target base flipping‐out mechanism is applicable in the case of M.Ecl18kI. Correct cleavage of the abasic substrates by R.Ecl18kI is accompanied by non‐canonical hydrolysis of the modified strand.
Impairment of tRNA processing by point mutations in mitochondrial tRNALeu(UUR) associated with mitochondrial diseases
Authors: Rossmanith Walter , Karwan Robert M.
Published: April 2003

Several point mutations in mitochondrial tRNA genes have been linked to distinct clinical subgroups of mitochondrial diseases. A particularly large number of different mutations is found in the tRNALeu(UUR) gene. We show that base substitutions at nucleotide position 3256, 3260, and 3271 of the mitochondrial genome, located in the D and anticodon stem of this tRNA, and mutation 3243 changing a base involved in a tertiary interaction, significantly impair the processing of the tRNA precursor in vitro. In correlation with other studies, our results suggest that inefficient processing of certain mutant variants of mitochondrial tRNALeu(UUR) is a primary molecular impairment leading to mitochondrial dysfunction and consequently to disease.
Dimeric and tetrameric forms of catalytically active transmembrane CD38 in transfected HeLa cells
Authors: Bruzzone Santina , Guida Lucrezia , Franco Luisa , Zocchi Elena , Corte Giorgio , De Flora Antonio
Published: April 2003

CD38, a type II transmembrane glycoprotein, behaves as a catalytically active transporter responsible for ectocellular generation of cyclic ADP‐ribose (cADPR) from NAD+ and for subsequent influx of cADPR across membranes [Franco, L., Guida, L., Bruzzone, S., Zocchi, E., Usai, C. and De Flora, A. (1998) FASEB J. in press]. cADPR regulates intracellular calcium homeostasis by releasing calcium from responsive stores. The cADPR‐transporting function of CD38 requires channel‐generating oligomeric forms of the protein rather than the 46 kDa monomers that have been described so far in CD38+ cells. Here we demonstrate that CD38, both in reconstituted proteoliposomes and in CD38‐transfected HeLa cells, is a mixture of catalytically active monomers, homodimers and homotetramers. A soluble recombinant form of CD38 corresponding to its ectocellular region proved to be monomeric. Thus, association of native CD38 with wither artificial or natural membranes seems to result in a reversible juxtaposition of monomers suitable to cADPR‐transporting activity.
Function and picosecond dynamics of bacteriorhodopsin in purple membrane at different lipidation and hydration
Authors: Fitter J. , Verclas S.A.W. , Lechner R.E. , Seelert H. , Dencher N.A.
Published: April 2003

© 1998 Federation of European Biochemical Societies.
Partial hydatidiform mole with diploid karyotype in a live fetus
Authors: Lembet A , Zorlu C.G , Yalçin H.R , Seçkin B , Ekici E
Published: April 2003

Even though most instances of partial mole are triploid, only a few cases of diploid partial moles have been reported. Prognosis of partial mole is usually better than the complete mole as few cases of partial moles progress to persistent trophoblastic disease. However, the nature and the risks of diploid partial moles are not well established and they seem to be a distinct clinical entity. Here we report a case of partial mole presenting with a 22 weeks live fetus and preeclampsia. Fetal blood sampling was performed for cytogenetic analysis which revealed a diploid (46XY) karyotype. No progression to malignant gestational trophoblastic disease occurred.
The effect of maternal fasting on the fetal biophysical profile
Authors: Mirghani H.M , Weerasinghe D.S.L , Ezimokhai M , Smith J.R
Published: April 2003

Objectives: To determine fetal biophysical profile changes in women observing Ramadan with uncomplicated singleton pregnancy. Methods: In this cross‐sectional observational study healthy women who were observing Ramadan at 30 weeks or more of gestation were recruited as well as a non‐fasting control group matched for age, parity, and gestational age. Ultrasound examination included assessment of amniotic fluid volume, fetal bladder volume, fetal biophysical profile, and umbilical artery Doppler flow. Results: A total of 162 pregnant women were observed. Mean umbilical artery pulsatility index, vertical amniotic pool depth, and fetal bladder volume were similar in the study and control groups. However, there was a significant difference in biophysical scores between the two groups. In the fasting group, 30 of 81 fetuses (37%) had a score of 6/8 compared with 11 of 81 fetuses (13.6%) in the control group (P=0.001). All fetuses in both groups with a biophysical score of 6/8 showed no breathing movements. Conclusions: Fetal breathing movements are reduced during maternal fasting.
HIV infection in critically ill obstetrical patients
Authors: de Groot M.R. , Corporaal L.J. , Cronjé H.S. , Joubert G.
Published: April 2003

Objectives: The effect of HIV‐infection on the clinical course of critically ill obstetrical patients by means of a case–control study was evaluated. Methods: Over one calendar year 440 patients were admitted to a high risk obstetrical unit. All patients were tested for HIV‐infection. HIV‐positive patients were included in the study group and two HIV‐negative patients for every HIV‐positive patient were included in the control group. Results: No differences were found between the two groups regarding demographic data, diagnosis, antibiotic use, mode of delivery, duration of hospital stay and mortality. More complications occurred in the HIV‐negative group. Eclampsia recorded for the HIV‐negative group was 17.1% and 4.7% for the HIV‐positive group (P=0.04; 95% CI: −17.1%; −0.9%) and lung edema was 18.2% and 6.2%, respectively (P=0.01; 95% CI: −19.3%; −3.5%). The median CD4/CD8 ratio was significantly lower in the HIV‐positive group (0.43) than the HIV‐negative group (1.37) (P<0.01; 95% CI: −1.04; −0.79). Conclusions: HIV‐infection did not significantly alter the clinical course of critically ill patients in an obstetrical high care unit.
Collagen synthesis during pregnancy, vitamin C availability, and risk of premature rupture of fetal membranes
Authors: Tejero E. , Perichart O. , Pfeffer F. , Casanueva E. , Vadillo‐Ortega F.
Published: April 2003

Objective: To examine the relationship between plasma and leukocyte concentration of ascorbic acid and collagen type I propeptide C during pregnancy and subsequent premature rupture of membranes (PROM). Methods: Fifteen women with PROM and 26 controls were compared for plasma and leukocyte concentration of vitamin C and for Pro‐C during pregnancy. Results: A statistically significant difference in maternal leukocyte ascorbic acid concentration was found between the two groups at week 28 of gestation (P50 was 16.90 for PROM group vs. 21.46 for control group; P>0.05). Increased risk for PROM (odds ratio, 10.99; 95% confidence interval, 2.40–49.91) was found with elevated concentrations of Pro‐C at week 16 of gestation. Conclusions: A higher rate of collagen synthesis early in pregnancy was demonstrated in PROM cases. However, no correlation with ascorbic acid availability was found. This study supports the findings of others that collagen metabolism disturbances are associated with PROM.
Autopsy study of maternal deaths
Authors: Kavatkar A.N , Sahasrabudhe N.S , Jadhav M.V , Deshmukh S.D
Published: April 2003

Objectives: To obtain an insight into the underlying disorder or pathologies in different organs or systems, and to attempt clinicopathologic correlation in maternal deaths. Methods: This is a retrospective study of 95 maternal autopsies done from 1993 to 2000 in Sassoon General Hospital, Pune, India. External examination, in situ examination, gross and microscopic examination was done in each case. The cause of death was arrived at after reviewing clinical details, available investigations, morphological findings, and clinicopathologic correlation. Results: Ninety‐five (45.02%) out of 211 maternal deaths were autopsied. Out of 95, there were 47 (49.5%) direct obstetric deaths, and 33 (34.7%) indirect obstetric deaths. Fifteen (15.8%) deaths were unrelated to pregnancy, 14 of which were due to infections. Conclusions: Hypertensive disorders associated with pregnancy (24.2%) and anemia (14.7%) were most common. In the hypertensive group, important findings were disseminated intravascular coagulation, hemorrhages in different organs and thromboemboli. Two cases were HIV seropositive. The autopsy helped to elucidate factors contributing to death and pathology in different organ systems.
Confirmation of cervical neoplasia using a hand‐held, lighted magnification device
Authors: Winkler J.L. , Tsu V.D. , Bishop A. , Scott R. , Sellors J.W.
Published: April 2003

Objectives: The objective of this study was to estimate the sensitivity and specificity of visual inspection with acetic acid and magnification (VIAM) using the AviScope™ device to confirm high‐grade cervical intraepithelial neoplasia or carcinoma. Methods: VIAM was performed on 142 women aged 18–50 years referred to three colposcopy clinics because of abnormal cervical cytology. Each woman then had a colposcopic examination with cervical biopsy when indicated. Results: The AviScope™ device identified 24 of the 40 women who had CIN 2, 3, or carcinoma, yielding a sensitivity of 60.0% (95% CI 43.4, 74.7). The AviScope™ correctly identified 60 of 87 women negative for dysplasia or cancer, yielding a specificity of 69.0% (95% CI 58.0, 78.2) compared with colposcopy and cervical histology. Conclusion: VIAM using the AviScope™ device was moderately sensitive and specific for the confirmation of high‐grade cervical lesions in women referred with abnormal cervical cytology.
Laparoscopic surgery in the Cameroon
Authors: Raiga J , Kasia J.M , Bruhat M.A
Published: April 2003

A new surgical section of operative laparoscopy was installed in General Hospital of Yaoundé, Cameroon, in April 1992 after many years of collaboration between the University of Clermont–Ferrand and the University of Yaoundé. A total of 735 laparoscopic operations were conducted in the first 5 years. Conditions facilitating such a project are discussed. © 1998 International Federation of Gynecology and Obstetrics
Cost‐effectiveness of IVF in women 38 years and older
Authors: Suchartwatnachai C , Wongkularb A , Srisombut C , Choktanasiri W , Chinsomboon S , Rojanasakul A
Published: April 2003

Objective: To compare the cost per delivery in women younger than 38 years with women equal to or older than 38 years of age attempting IVF. Methods: All couples undergoing IVF treatment between October 1991 and September 1998 were enrolled in this study. A standard protocol of controlled ovarian hyperstimulation was employed throughout the study. Four hundred and seven cases were allocated to two groups — group I composed of patients younger than 38 years of age and group II of patient equal to or older than 38 years of age. The total cost of each successful outcome was the goal of our study. Results: A total of 407 women underwent 722 stimulated cycles for IVF of which 122 cycles (16.89%) did not proceed to oocyte retrieval. We found statistically significant differences in the cancellation rate, the number of hMG ampoules, the number of oocytes retrieved, the number of oocytes fertilized, the number of embryos transferred, the clinical pregnancy rate, the rate of multiple pregnancy, the delivery per initiated cycle and the cost per delivery between the two groups (P<0.05, significant). The cost per delivery in group II was approximately 3.6 times that of group I. Conclusions: Women age 38 years or more have less chance of a successful outcome from IVF treatment. Couples contemplating IVF should be provided with accurate information about prognosis for the pregnancy and the financial costs.
Quantitative and sensitive in vitro assay for osteoinductive activity of demineralized bone matrix
Authors: Han Bo , Tang Baowei , Nimni Marcel E.
Published: April 2003

A sensitive, rapid, reliable and quantitative method to check the bone forming potential of demineralized bone matrix (DBM) has been developed. The osteoinductivity of the bone morphogenetic proteins (BMPs), present in DBM, can be measured in vitro using a pluripotent myoblast C2C12 cell line. Alkaline phosphatase activity induced by co‐incubation of DBM with C2C12 cells was dose‐responsive and corresponds to the amount of active BMPs in DBM. Bone forming potential was simultaneously tested in vivo by implanting DBM intra‐muscularly in nude rats. ALP activity induced in C2C12 cells, correlated with bone formation in vivo (r= 0.88), determined by alkaline phosphatase activity, mineralization density and histomorphology of the DBM explants. Results from DBM batches, originating from five established Bone Banks, showed good consistency between in vitro and in vivo assays. However, DBM activity varied widely from bank to bank as well as from batch to batch within the same bank. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Disseminated melioidosis in two cats
Authors: O'Brien CR , Krockenberger MB , Martin P , Parkes H , Kidd M , Malik R
Published: April 2003

Melioidosis was diagnosed in two cats at necropsy. The first cat presented with jaundice and anaemia but died of overwhelming sepsis soon after admission, despite blood transfusion and other supportive measures. The second cat died several days after developing neurological signs; an infected digital wound may have been the primary focus of infection in this patient. The cats had presumably acquired the infection in Malaysia and northern Australia, respectively, and in both cases disease may have represented reactivation of a latent infection brought on by the stress of relocation. The epidemiology, clinical presentation, diagnosis and treatment of melioidosis are discussed from a feline perspective.
Eligibility for biventricular pacing in patients with an implantable cardioverter defibrillator
Authors: Molhoek S.G. , Bax J.J. , van Erven L. , Steendijk P. , van der Wall E.E. , Schalij M.J.
Published: April 2003

Implantable cardioverter defibrillator (ICD)‐therapy prevents sudden death in patients at high risk, but incidence of death due to heart failure remains unaltered. Recent data suggest that biventricular (BV) pacing is useful in patients with heart failure. It is unclear, how many patients with an ICD indication may have an indication for BV pacing. Therefore all patients who received an ICD were analyzed for eligibility of BV pacing using the following criteria: NYHA class III or IV, QRS duration >120 ms, depressed LVEF. Three hundred and ninety consecutive patients received an ICD from June 1996 to March 2001. Underlying disease was ischemic heart disease in 66%. In the 390 patients the mean LVEF was 36±17%, 20% were in NYHA class III–IV and 16% were in NYHA class II with an LVEF <30%. Of these 140 patients, 79 had a QRS duration >120 ms. Thus, 79 (20%) patients were eligible for BV pacing in addition to ICD‐therapy. Patients who received a BV pacemaker in addition to ICD‐therapy had a superior survival, improved in NYHA class and showed a significantly lower hospitalization rate as compared to patients who received an ICD only. Screening for eligibility of BV pacing may be considered in patients with CHF scheduled for ICD implantation.
Alleviatory effects of calcium on the toxicity of sodium, potassium and magnesium chlorides to seed germination in three non-halophytes
Authors: Tobe Kazuo , Zhang Liping , Omasa Kenji
Published: April 2003

Saline soils contain numerous salts with varying impact on seed germination. Seeds of three non-halophytic species found in Chinese sandy deserts (Artemisia ordosica, Aristida adscensionis and Bassia dasyphylla) were incubated in salt solutions (NaCl, KCl or MgCl2, each with or without CaCl2) at 20°C in the dark. The effects of each salt on the percentage of seeds from which visibly detectable radicles emerged, and the percentage of seeds with emerging radicles surviving to a length of at least 4 mm, were examined. NaCl, KCl and MgCl2 were toxic to emerging radicles in all three species, but before radicle emergence these salts reduced seed germinability only in A. ordosica. The toxic effects of each salt on the radicles were alleviated in all three species by the addition of low concentrations of CaCl2. MgCl2 was more toxic than NaCl and KCl, and the concentration of CaCl2 needed to alleviate the toxicity of MgCl2 was several times higher than that required for alleviation of NaCl or KCl toxicity. These results suggest that Ca2+ present in saline soils alleviates the toxic effects of other salt components on seed germination, and that the results of germination experiments with a single salt are not always applicable to field conditions.
Seed size, shape and persistence in soil: a test on Italian flora from Alps to Mediterranean coasts
Authors: Cerabolini Bruno , Ceriani Roberta M. , Caccianiga Marco , Andreis Rossella De , Raimondi Barbara
Published: April 2003

Seed size is a good predictor of seed persistence in soil for British, Argentinean, Iranian and – to some extent – New Zealand species. It has been suggested that seed shape should also be linked to the ease of burial and, thus, to seed persistence, even if some studies failed to show this. The relationship between seed size and shape and persistence in soil was analysed for 259 species of the Italian flora, belonging to a wide range of habitats, from alpine pasture to limestone prairies and meadows of the Prealps, and from woodlands to Mediterranean maquis and garigues. Seed size was related to persistence in soil in the same way as in most other floras examined. Furthermore, seed shape was highly related to persistence in soil among the species analysed, when considered both altogether and divided among the different habitats. Our results suggest that not only seed size, but also seed shape, are key factors in determining seed fate and seed persistence in soil.
Seed size, shape and persistence in dry Mediterranean grass and scrublands
Authors: Peco Begoña , Traba Juan , Levassor Catherine , Sánchez Ana M. , Azcárate Francisco M.
Published: April 2003

Seed size and shape, measured as the variance of the three main dimensions, have been proposed as good indicators for predicting seed persistence. We tested whether these variables were robust predictors of seed persistence in the soil for 58 abundant herbaceous species, primarily annuals, in grass and scrubland of central Spain. Seed persistence was estimated from data on germinable seed banks, while seed weight and shape were measured using fresh seeds collected in the study area. There was a significant tendency for species with persistent seeds to have smaller seeds than species with transient seeds. Seed shape was not, however, related to persistence and we did not find any clear seed weight/shape threshold for predicting persistence. The binary logistic model of seed bank type as a function of seed weight was significant and explained 67% of total variability. Supplementary information about dormancy, environmental conditions of habitat, predation and attack by pathogens has to be used to elaborate more accurate general predictive models of seed persistence.
Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response
Authors: Kao Gary D. , McKenna W. Gillies , Guenther Matthew G. , Muschel Ruth J. , Lazar Mitchell A. , Yen Tim J.
Published: March 2003

Anumber of proteins are recruited to nuclear foci upon exposure to double-strand DNA damage, including 53BP1 and Rad51, but the precise role of these DNA damage–induced foci remain unclear. Here we show in a variety of human cell lines that histone deacetylase (HDAC) 4 is recruited to foci with kinetics similar to, and colocalizes with, 53BP1 after exposure to agents causing double-stranded DNA breaks. HDAC4 foci gradually disappeared in repair-proficient cells but persisted in repair-deficient cell lines or cells irradiated with a lethal dose, suggesting that resolution of HDAC4 foci is linked to repair. Silencing of HDAC4 via RNA interference surprisingly also decreased levels of 53BP1 protein, abrogated the DNA damage–induced G2 delay, and radiosensitized HeLa cells. Our combined results suggest that HDAC4 is a critical component of the DNA damage response pathway that acts through 53BP1 and perhaps contributes in maintaining the G2 cell cycle checkpoint.
Nuclear envelope breakdown in starfish oocytes proceeds by partial NPC disassembly followed by a rapidly spreading fenestration of nuclear membranes
Authors: Lénárt Péter , Rabut Gwénaël , Daigle Nathalie , Hand Arthur R. , Terasaki Mark , Ellenberg Jan
Published: March 2003

Breakdown of the nuclear envelope (NE) was analyzed in live starfish oocytes using a size series of fluorescently labeled dextrans, membrane dyes, and GFP-tagged proteins of the nuclear pore complex (NPC) and the nuclear lamina. Permeabilization of the nucleus occurred in two sequential phases. In phase I the NE became increasingly permeable for molecules up to ∼40 nm in diameter, concurrent with a loss of peripheral nuclear pore components over a time course of 10 min. The NE remained intact on the ultrastructural level during this time. In phase II the NE was completely permeabilized within 35 s. This rapid permeabilization spread as a wave from one epicenter on the animal half across the nuclear surface and allowed free diffusion of particles up to ∼100 nm in diameter into the nucleus. While the lamina and nuclear membranes appeared intact at the light microscopic level, a fenestration of the NE was clearly visible by electron microscopy in phase II. We conclude that NE breakdown in starfish oocytes is triggered by slow sequential disassembly of the NPCs followed by a rapidly spreading fenestration of the NE caused by the removal of nuclear pores from nuclear membranes still attached to the lamina.
An essential role for hGle1 nucleocytoplasmic shuttling in mRNA export
Authors: Kendirgi Frederic , Barry Dianne M. , Griffis Eric R. , Powers Maureen A. , Wente Susan R.
Published: March 2003

Gle1 is required for mRNA export in yeast and human cells. Here, we report that two human Gle1 (hGle1) isoforms are expressed in HeLa cells (hGle1A and B). The two encoded proteins are identical except for their COOH-terminal regions. hGle1A ends with a unique four–amino acid segment, whereas hGle1B has a COOH-terminal 43–amino acid span. Only hGle1B, the more abundant isoform, localizes to the nuclear envelope (NE) and pore complex. To test whether hGle1 is a dynamic shuttling transport factor, we microinjected HeLa cells with recombinant hGle1 and conducted photobleaching studies of live HeLa cells expressing EGFP–hGle1. Both strategies show that hGle1 shuttles between the nucleus and cytoplasm. An internal 39–amino acid domain is necessary and sufficient for mediating nucleocytoplasmic transport. Using a cell-permeable peptide strategy, we document a role for hGle1 shuttling in mRNA export. An hGle1 shuttling domain (SD) peptide impairs the export of both total poly(A)+ RNA and the specific dihydrofolate reductase mRNA. Coincidentally, SD peptide–treated cells show decreased endogenous hGle1 localization at the NE and reduced nucleocytoplasmic shuttling of microinjected, recombinant hGle1. These findings pinpoint the first functional motif in hGle1 and link hGle1 to the dynamic mRNA export mechanism.
The Ulp1 SUMO isopeptidase
Authors: Li Shyr-Jiann , Hochstrasser Mark
Published: March 2003

Protein modification by the ubiquitin-like SUMO protein contributes to many cellular regulatory mechanisms. In Saccharomyces cerevisiae, both sumoylating and desumoylating activities are essential for viability. Of its two known desumoylating enzymes, Ubl-specific protease (Ulp)1 and Ulp2/Smt4, Ulp1 is specifically required for cell cycle progression. A ∼200-residue segment, the Ulp domain (UD), is conserved among Ulps and includes a core cysteine protease domain that is even more widespread. Here we demonstrate that the Ulp1 UD by itself can support wild-type growth rates and in vitro can cleave SUMO from substrates. However, in cells expressing only the UD of Ulp1, many SUMO conjugates accumulate to high levels, indicating that the nonessential Ulp1 NH2-terminal domain is important for activity against a substantial fraction of sumoylated targets. The NH2-terminal domain also includes sequences necessary and sufficient to concentrate Ulp1 at nuclear envelope sites. Remarkably, NH2-terminally deleted Ulp1 variants are able, unlike full-length Ulp1, to suppress defects of cells lacking the divergent Ulp2 isopeptidase. Thus, the NH2-terminal regulatory domain of Ulp1 restricts Ulp1 activity toward certain sumoylated proteins while enabling the cleavage of others. These data define key functional elements of Ulp1 and strongly suggest that subcellular localization is a physiologically significant constraint on SUMO isopeptidase specificity.
Dictyostelium cell death
Authors: Levraud Jean-Pierre , Adam Myriam , Luciani Marie-Françoise , de Chastellier Chantal , Blanton Richard L. , Golstein Pierre
Published: March 2003

Cell death in the stalk of Dictyostelium discoideum, a prototypic vacuolar cell death, can be studied in vitro using cells differentiating as a monolayer. To identify early events, we examined potentially dying cells at a time when the classical signs of Dictyostelium cell death, such as heavy vacuolization and membrane lesions, were not yet apparent. We observed that most cells proceeded through a stereotyped series of differentiation stages, including the emergence of “paddle” cells showing high motility and strikingly marked subcellular compartmentalization with actin segregation. Paddle cell emergence and subsequent demise with paddle-to-round cell transition may be critical to the cell death process, as they were contemporary with irreversibility assessed through time-lapse videos and clonogenicity tests. Paddle cell demise was not related to formation of the cellulose shell because cells where the cellulose-synthase gene had been inactivated underwent death indistinguishable from that of parental cells. A major subcellular alteration at the paddle-to-round cell transition was the disappearance of F-actin. The Dictyostelium vacuolar cell death pathway thus does not require cellulose synthesis and includes early actin rearrangements (F-actin segregation, then depolymerization), contemporary with irreversibility, corresponding to the emergence and demise of highly polarized paddle cells.
A perfect funeral with no corpse
Authors: Earnshaw William C. , Carmena Mar
Published: March 2003

“Indeed, the role in mitosis of the chromosome arms, which carry most of the genetic material, may be compared with that of a corpse at a funeral: they provide the reason for the proceedings but do not take an active part in them.” (Mazia, 1961)
Mechanism of Rectification in Inward-rectifier K+ Channels
Authors: Guo Donglin , Ramu Yajamana , Klem Angela M. , Lu Zhe
Published: March 2003

Rectification in inward-rectifier K+ channels is caused by the binding of intracellular cations to their inner pore. The extreme sharpness of this rectification reflects strong voltage dependence (apparent valence is ∼5) of channel block by long polyamines. To understand the mechanism by which polyamines cause rectification, we examined IRK1 (Kir2.1) block by a series of bis-alkyl-amines (bis-amines) and mono-alkyl-amines (mono-amines) of varying length. The apparent affinity of channel block by both types of alkylamines increases with chain length. Mutation D172N in the second transmembrane segment reduces the channel's affinity significantly for long bis-amines, but only slightly for short ones (or for mono-amines of any length), whereas a double COOH-terminal mutation (E224G and E299S) moderately reduces the affinity for all bis-amines. The apparent valence of channel block increases from ∼2 for short amines to saturate at ∼5 for long bis-amines or at ∼4 for long mono-amines. On the basis of these and other observations, we propose that to block the channel pore one amine group in all alkylamines tested binds near the same internal locus formed by the COOH terminus, while the other amine group of bis-amines, or the alkyl tail of mono-amines, “crawls” toward residue D172 and “pushes” up to 4 or 5 K+ ions outwardly across the narrow K+ selectivity filter. The strong voltage dependence of channel block therefore reflects the movement of charges carried across the transmembrane electrical field primarily by K+ ions, not by the amine molecule itself, as K+ ions and the amine blocker displace each other during block and unblock of the pore. This simple displacement model readily accounts for the classical observation that, at a given concentration of intracellular K+, rectification is apparently related to the difference between the membrane potential and the equilibrium potential for K+ ions rather than to the membrane potential itself.
Simulation of Calcium Sparks in Cut Skeletal Muscle Fibers of the Frog
Authors: Chandler W.K. , Hollingworth S. , Baylor S.M.
Published: March 2003

Spark mass, the volume integral of ΔF/F, was investigated theoretically and with simulations. These studies show that the amount of Ca2+ bound to fluo-3 is proportional to mass times the total concentration of fluo-3 ([fluo-3T]); the proportionality constant depends on resting Ca2+ concentration ([Ca2+]R). In the simulation of a Ca2+ spark in an intact frog fiber with [fluo-3T] = 100 μM, fluo-3 captures approximately one-fourth of the Ca2+ released from the sarcoplasmic reticulum (SR). Since mass in cut fibers is several times that in intact fibers, both with similar values of [fluo-3T] and [Ca2+]R, it seems likely that SR Ca2+ release is larger in cut fiber sparks or that fluo-3 is able to capture a larger fraction of the released Ca2+ in cut fibers, perhaps because of reduced intrinsic Ca2+ buffering. Computer simulations were used to identify these and other factors that may underlie the differences in mass and other properties of sparks in intact and cut fibers. Our spark model, which successfully simulates calcium sparks in intact fibers, was modified to reflect the conditions of cut fiber measurements. The results show that, if the protein Ca2+-buffering power of myoplasm is the same as that in intact fibers, the Ca2+ source flux underlying a spark in cut fibers is 5–10 times that in intact fibers. Smaller source fluxes are required for less buffer. In the extreme case in which Ca2+ binding to troponin is zero, the source flux needs to be 3–5 times that in intact fibers. An increased Ca2+ source flux could arise from an increase in Ca2+ flux through one ryanodine receptor (RYR) or an increase in the number of active RYRs per spark, or both. These results indicate that the gating of RYRs, or their apparent single channel Ca2+ flux, is different in frog cut fibers—and, perhaps, in other disrupted preparations—than in intact fibers.
Leadership lessons from the African tree
Authors: van der Colff Linda
Published: April 2003

This paper explores meaning of leadership and management in the context of South Africa. It does this by clarifying the way in which Ubuntu – traditional African leadership values – may impact an organisation. It explains how this tradition‐based concept could be integrated into the organisation to enable the leadership to dismantle the past organisational culture, promote the development of a new and more inclusive culture, and, finally, create a set of leadership skills and competencies that enable globalisation processes.
On the internal drivers of export performance among Nigerian firms: empirical findings and implications
Authors: Ibeh Kevin I.N.
Published: April 2003

This paper discusses the export behaviour of firms from Nigeria against the backdrop of the aggregate findings from previous empirical studies, which originate mainly from the economically advanced countries. Based on the analysis of survey data from 78 Nigerian‐based manufacturing firms (34 exporters and 44 non‐exporters), a number of internal factors were identified as influential drivers of positive export performance. Among these are decision makers’ previous experience, international contacts and orientation, and firm‐specific competencies relating to planning orientation, adoption of innovative technologies, foreign market information search, and managing channel relationships. The remarkable consistency between these findings and previous evidence from studies undertaken in more developed economies is discussed. Also highlighted is the need to improve the overall effectiveness with which appropriate competence‐enhancing support is targeted at firms, mainly SMEs, in less performing developing regions.
Transnational law and technology as potential forces against corruption in Africa
Authors: Schroth Peter W. , Sharma Preeti
Published: April 2003

Africa is the only continent none of whose states have joined the conventions against international bribery and very few African countries have national laws attempting to fill the gap. South Africa has taken promising steps internally and now should accept a leadership role in the development of transnational law against corruption. Meanwhile, the Internet and other new technologies are developing as parallel, mostly non‐governmental tools against corruption. Unlike transnational and most national laws, their impact has already been clearly visible in Africa and they offer at least the possibility of substantial interference with corruption in the short to medium term.
The “Indian” supply chain architecture
Authors: Sahay B.S. , Cavale Vasant , Mohan Ramneesh
Published: April 2003

With close to 22 percent of aggregate industry sales tied up in inventories in the entire supply chain network, what is it that ails Indian industry? Is it the way Indian supply chains are configured – their orientation to processes to streamline business activities; their fusion of information technology to speed up business transactions; their approach to supply chain strategy to improve bottom line results – that has restricted them from achieving global standards? The article, based on a recently concluded nationwide study titled “Supply chain management practices in Indian Industry: 2000”, throws up glaring facts about the current architecture of supply chains in India. The article concludes that though some Indian organizations are moving fast towards improving supply chain efficiencies, most of them are still far from realising its effect on business performance.
The inevitability of conflict between buyers and sellers
Authors: Emiliani M.L.
Published: April 2003

Examines the source of conflict between buyers and sellers as it relates to the price of goods purchased for use in production. Focuses on management’s understanding and application of the term “maximize shareholder value”, which is found to result in business decisions that marginalize suppliers’ capabilities and interests. Concludes that conflict between buyers and sellers is an inevitable outcome when buyers make decisions principally centered upon the literal interpretation of management’s role as agents of the board whose primary responsibility is to maximize shareholder value. This finding has widespread implications for both academics and practitioners, as making this linkage explicit defines the challenge for improving purchasing and supply chain management practices in a new way.
Corporate ethics as a factor for success – the measurement instrument of the University of Agricultural Sciences (BOKU), Vienna
Authors: Schiebel Walter , Pöchtrager Siegi
Published: April 2003

Over the past decade, a growing number of companies have recognized the business benefits of corporate social responsibilities policies and practices. Their experiences are bolstered by a growing body of empirical studies which demonstrate that corporate social responsibility (CSR) has a positive impact on business economic performance, and is not harmful to shareholder value. There are six key responsibilities or dimensions of CSR and CSR is really how to manage these six responsibilities. Companies employing such a new values‐based business approach have found that it can improve financial performance, increase employees’ motivation and commitment to work, and enhance customer loyalty and corporate reputation. The model in use (theoretical language), is able to explain the impact of CSR with the help of a bundle of dependent variables. Measuring CSR also affects additional benefits. The “BOKU approach” defines the independent variables (objective language) for the CSR working model and shows the way to measure (correspondential language) the independent variables by auditing using a “reduced design”, Austriacism and a “mystery” shift to enhance the acceptance rate.