bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary bladder volumetry by means of a single retrosymphysically implantable ultrasound unit
Authors: Seif C. , Herberger B. , Cherwon E. , Martinez Portillo F.J. , Molitor M. , Stieglitz T. , Böhler G. , Zendler S. , Jünemann K.P. , Braun P.M.
Published: May 2004

Aims

Optimal voiding is a crucial issue for patients with neurogenic bladder dysfunctions to prevent long‐term damage to the urinary tract. In prior studies, implantable ultrasound (US) sensors have proved an appropriate method of measuring the urinary bladder volume. Their disadvantage is that they tend to dislocate in chronic applications as they are fixed directly onto the bladder wall. In the present study, we describe an implantable US volumetry unit that does not require fixing to the bladder wall and consists of a single receiver‐transmitter unit.

Materials and Methods

Six Göttinger minipigs were anesthetized in ITN; a sensor was stitched behind the symphysis into the periosteum and aligned to the bladder so that an US measurement could take place in ventro‐dorsal direction. In steps of 50 ml, the bladder was filled up to 250 ml via a transurethral catheter; after each filling step the volume was measured three times and compared to the instilled volume.

Results

On average the measurements with implanted US differed from the actual bladder filling by 77.4% at a bladder filling of 50 ml (“error” messages were included as 0 ml), 3.8% at 100 ml, 3.8% at 150 ml, and 0.3% at 200 ml, and 3.6% at 250 ml. When the empty bladder (= 0 ml) was measured, the US sensor detected no volume in 73% of the cases.

Conclusions

In our animal model, the above‐described US system proved tantamount with other external US measuring units and presented a precise and low‐artefact system, allowing reliable measuring of the urinary volume with good chances of preserving these positive qualities over time. We expect that clinical application of this system may help to determine the optimal voiding time and thus to avoid bladder overextension and damage to the urinary tract over time. © 2004 Wiley‐Liss, Inc.
Pycnogenol® and vitamin E inhibit ethanol‐induced apoptosis in rat cerebellar granule cells
Authors: Siler‐Marsiglio Kendra I. , Shaw Gerry , Heaton Marieta B.
Published: May 2004

Pycnogenol® (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), scavenges free radicals and promotes cellular health. The protective capacity of PYC against ethanol toxicity of neurons has not previously been explored. The present study demonstrates that in postnatal day 9 (P9) rat cerebellar granule cells the antioxidants vitamin E (VE) and PYC (1) dose dependently block cell death following 400, 800, and 1600 mg/dL ethanol exposure (2) inhibit the ethanol‐induced activation of caspase‐3 in the same model system; and (3) reduce neuronal membrane disruption as assayed by phosphatidylserine translocation to the cell surface. These results suggest that both PYC and VE have the potential to act as therapeutic agents, antagonizing the induction of neuronal cell death by ethanol exposure. © 2004 Wiley Periodicals, Inc. J Neurobiol 59: 261–271, 2004
Expression of functional kainate and AMPA receptors in developing lateral superior olive neurons of the rat
Authors: Vitten Harald , Reusch Margret , Friauf Eckhard , Löhrke Stefan
Published: May 2004

A functional analysis of AMPA and kainate receptors (AMPARs and KARs) in the lateral superior olive (LSO), a major nucleus in the auditory brainstem, has not been performed so far, to our knowledge. Here we investigated the presence and characteristics of such receptors in the rat LSO by means of whole‐cell patch‐clamp recordings in combination with pharmacology. Current responses evoked by 200 μM AMPA were completely blocked by the specific AMPAR antagonist GYKI 52466 (100 μM). Properties of the AMPAR‐mediated currents (latency, activation time constant, and peak amplitude) remained constant between postnatal day 3 (P3) and P10. Current responses evoked by 100 μM KA were not completely blocked by 100 μM GYKI 52466, indicating that the residual component was mediated by KARs. Throughout development, two groups of KAR‐mediated currents (fast IKA and slow IKA) were distinguished because they had significantly different mean activation time constants. Moreover, the mean peak amplitude of fast IKA was significantly higher than that of slow IKA. The differentiation into fast IKA and slow IKA can be explained by the existence of two groups of LSO neurons displaying different KAR densities, distributions, and/or diverse types with differences in conductance. Application of the specific KAR subunit agonists SYM 2081 (10 μM), ATPA (10 μM), or iodowillardiine (1 μM) evoked currents in almost all cells tested, showing that GluR5 subunits are a component of functional KARs in LSO neurons. Electrical stimulation of ipsilateral input fibers in the presence of KAR antagonists (NS‐102 and GAMS), modulators (WGA), or GYKI 52466 revealed the presence of synaptic KARs in LSO neurons. © 2004 Wiley Periodicals, Inc. J Neurobiol 59: 272–288, 2004
Boundary element formulation for 3D transversely isotropic cracked bodies
Authors: Ariza M. P. , Dominguez J.
Published: May 2004

The boundary traction integral representation is obtained in elasticity when the classical displacement representation is differentiated and combined according to Hooke's law. The use of both traction and displacement integral representations leads to a mixed (or dual) formulation of the BEM where the discretization effort for crack problems is much smaller than in the classical formulation. A boundary element analysis of three‐dimensional fracture mechanics problems of transversely isotropic solids based on the mixed formulation is presented in this paper. The hypersingular and strongly singular kernels appearing in the formulation are regularized by using two terms of the displacement series expansion and one term of the traction expansion, at the collocation point. All the remaining integrals are analytically evaluated or transformed by means of Stokes' theorem into regular or weakly singular integrals, which are numerically computed. The method is general and can be used for elements of any shape including quarter‐point crack front elements. No change of co‐ordinates is required for the integration. The formulation as presented in this paper is something as clear, general and easy to handle as the classical BE formulation. It is used in combination with three‐dimensional quadratic and quarter‐point elements to obtain accurate results for several different crack problems. Cracks in boundless and finite transversely isotropic domains are studied. The meshes are simple and include only discretization of the crack and the external boundary. The obtained results are in good agreement with those existing in the literature. Copyright © 2004 John Wiley & Sons, Ltd.
On singularities in the solution of three‐dimensional Stokes flow and incompressible elasticity problems with corners
Authors: Dimitrov A.
Published: May 2004

In this paper, a numerical procedure is presented for the computation of corner singularities in the solution of three‐dimensional Stokes flow and incompressible elasticity problems near corners of various shape. For obtaining the order and mode of singularity, a neighbourhood of the singular point is considered with only local boundary conditions. The weak formulation of this problem is approximated using a mixed u, p Galerkin–Petrov finite element method. Additionally, a separation of variables is used to reduce the dimension of the original problem. As a result, the quadratic eigenvalue problem (P+λQ+λ2R)d=0 is obtained, where the saddle‐point‐type matrices P, Q, R are defined explicitly. For a numerical solution of the algebraic eigenvalue problem an iterative technique based on the Arnoldi method in combination with an Uzawa‐like scheme is used. This technique needs only one direct matrix factorization as well as few matrix–vector products for finding all eigenvalues in the interval 𝓈(λ) ∈ (−0.5, 1.0), as well as the corresponding eigenvectors. Some benchmark tests show that this technique is robust and very accurate. Problems from practical importance are also analysed, for instance the surface‐breaking crack in an incompressible elastic material and the three‐dimensional viscous flow of a Newtonian fluid past a trihedral corner. Copyright © 2004 John Wiley & Sons, Ltd.
The ultraweak time coupling in non‐linear multiphysics modelling and related optimization problems
Authors: Favennec Y. , Labbé V. , Bay F.
Published: May 2004

This paper presents different strategies in order to solve forward direct and backward adjoint problems when dealing with coupled time‐dependent electromagnetic and heat transfer phenomena, as well as related optimization problems. It is shown that the use of the fully discretized gradient method is judicious since the obtained gradient is exact while any other method yield to approximations of the gradient. The use of the ultraweak coupling and of the discretized gradient have been validated through different tests dealing with direct modelling, parameter identification and optimization. Copyright © 2004 John Wiley & Sons, Ltd.
Computational method for atomistic homogenization of nanopatterned point defect structures
Authors: Chung Peter W.
Published: May 2004

The development of an approximation method that rigorously averages small‐scale atomistic physics and embeds them in large‐scale mechanics is the principal aim of this work. This paper presents a general computational procedure based on homogenization to average frozen nanoscale atomistics and couple them to the equations of continuum hyperelasticity. The proposed application is to nanopatterned systems in which complex atomic configurations are organized in a repeating periodic array. The finite element method is used to solve the equations at the large scale, but the small‐scale equation is representative of lattice‐statics. The method is predicated on a quasistatic zero‐temperature assumption and, through homogenization, leads to a coupled set of variational equations. The numerical procedure is presented in detail, and 2‐D examples of ultra thin film layers of carbon one atom thick are shown to illustrate its applicability. Homogenization naturally gives rise to an inner displacement term with which point defects are explicitly modelled and their non‐linear interactions with global states of multiaxial strain are studied. Published in 2004 by John Wiley & Sons, Ltd.
Optimal patterns of glider dynamic soaring
Authors: Zhao Yiyuan J.
Published: May 2004

This paper presents optimal patterns of glider dynamic soaring utilizing wind gradients. A set of three‐dimensional point‐mass equations of motion is used and basic glider performance parameters are identified through normalizations of these equations. In particular, a single parameter is defined that represents the combined effects of air density, glider wing loading, and wind gradient slope. Glider dynamic soaring flights are formulated as non‐linear optimal control problems and three performance indices are considered. In the first formulation, the completion time of one cycle of dynamic soaring is minimized subject to glider equations of motion, limitations on glider flights, and appropriate terminal constraints that enforce a periodic dynamic soaring flight. In the second formulation, the final altitude after one cycle of dynamic soaring is maximized subject to similar constraints. In the third formulation, the least required wind gradient slope that can sustain an energy‐neutral dynamic soaring flight is determined. Different terminal constraints are used to produce basic, travelling, and loiter dynamic soaring patterns. These optimal control problems are converted into parameter optimization via a collocation approach and solved numerically with the software NPSOL. Different patterns of glider dynamic soaring are compared in terms of cycle completion time and altitude‐increasing capability. Effects of wind gradient slope and wind profile non‐linearity on dynamic soaring patterns are examined. Copyright © 2004 John Wiley & Sons, Ltd.
Optimal dynamic irrigation schemes
Authors: Shani Uri , Tsur Yacov , Zemel Amos
Published: May 2004

Optimal control methods are employed to derive irrigation management schemes accounting both for the dynamic response of the biomass yield to soil moisture and for the cost of irrigation water. Moisture dynamics depend on the irrigation rate and on the current biomass and moisture states. We find that the optimal irrigation policy has turnpike characteristics: soil moisture in the root zone should be brought to some optimal target level as rapidly as possible and kept at that level until some time prior to harvest, when irrigation should be ceased. The target moisture level and the stopping time vary across crops, soil types, climatic conditions and economic (price) factors, but the turnpike structure of the optimal irrigation policy persists under general circumstances. An empirical example demonstrates that the optimal scheme significantly outperforms the policy of yield maximization in actual practice. Copyright © 2004 John Wiley & Sons, Ltd.
Polymorphism within the glutathione S‐transferase P1 gene is associated with increased susceptibility to childhood malignant diseases
Authors: Zielińska Elżbieta , Zubowska Małgorzata , Bodalski Jerzy
Published: May 2004

Background

Glutathione S‐transferases (GSTs) are involved in the metabolism of carcinogens and anticancer drugs. Functional polymorphisms exist in at least three genes that code for the GSTs, such as the GSTM1 and GSTT1 gene deletions or the A–G transition within the GSTP1 gene, which represents distinct GSTP1a and GSTP1b alleles. In the present case‐control study, we aimed at estimation of the relationship between the GSTM1, GSTT1, and GSTP1 genotypes and the susceptibility to various types of childhood malignancies and the early relapses of diseases.

Procedure

Using the polymerase chain reaction on the DNA extracted from peripheral blood leukocytes, we identified the GSTM1, GSTT1, and GSTP1 genotypes in 234 children at the initial stage of a childhood malignancy as well as in 460 age‐and sex‐matched healthy subjects who served as controls. The follow‐up period for the effects of the anticancer therapy ranged from 11 to 43 months.

Results

Compared to the controls, a significant increase in the frequency of the GSTP1b/GSTP1b genotype (odds ratio (OR) 5.7; 95% confidence limit (CL) from 2.4 to 13.8; Pearsons Chi‐square P = 0.0001) was detected in the children with neoplasms. The GSTM1 and GSTT1 genotypes did not show any correlation with the risk of the de novo diagnosed neoplasms. During the observation, 62 children (26%) were found to be present with a local or disseminated recurrence of the diseases. The analysis indicated a trend in increasing risk of relapse for carriers of the GSTP1a allele (OR = 3.29; 95% CL from 0.73 to 14.67 P = 0.03).

Conclusions

Our results support the hypothesis that GST genotype affects etiology and outcome of a variety of childhood malignancies. © 2004 Wiley‐Liss, Inc.
On the non‐monotonic lateral size dependence of the height of GaAs nanowhiskers grown by molecular beam epitaxy at high temperature
Authors: Dubrovskii V. G. , Soshnikov I. P. , Cirlin G. E. , Tonkikh A. A. , Samsonenko Yu. B. , Sibirev N. V. , Ustinov V. M.
Published: May 2004

GaAs nanowhiskers were grown by molecular beam epitaxy on the GaAs(111)B surface activated by Au at the surface temperature of 585 °C. The dependence of nanowhisker height on the size of Au–GaAs alloy drops was investigated. It has been found that the height of GaAs nanowhiskers is zero at a certain minimum diameter of drop, then increases with size, has a pronounced maximum at a certain size, decreases for thicker whiskers and finally goes to a certain asymptotic value. The theoretical model for the growth kinetics of nanowhiskers was developed in order to explain the observed size dependence. The results of comparison of theoretical and experimental data for the height of GaAs nanowhiskers are presented and analyzed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Post‐source decay matrix‐assisted laser desorption/ionization mass spectrometric study of tetracyclic 2,3‐dihydro‐1,5‐benzothiazepines
Authors: Kéki Sándor , Nagy Lajos , Deák György , Lévai Albert , Zsuga Miklós
Published: May 2004

The fragmentation behavior of six tetracyclic 2,3‐dihydro‐1,5‐benzothiazepine derivatives cationized with protons and silver ions under post‐source decay (PSD) matrix‐assisted laser desorption/ionization (MALDI) conditions is reported. The protonated adduct ions decompose into several structurally important fragment ions, including substituted cyclopropane and benzohydrothiazole cations. Elimination of Ag and H and/or AgH from the silver‐cationized adduct ions of these ([M+Ag]+) compounds was observed. It was also found that [M+Ag]+ produced silver‐depleted fragment ions exclusively. Based on the PSD results a fragmentation pathway is proposed for the [M+H]+ and [M+Ag]+ precursor ions. Copyright © 2004 John Wiley & Sons, Ltd.
Semi‐automated quantification of ivermectin in rat and human plasma using protein precipitation and filtration with liquid chromatography/tandem mass spectrometry
Authors: Pereira Tony , Chang Steve W
Published: May 2004

Ivermectin is a parasiticide commonly used in humans and livestock. It is currently under development for the treatment of pediculosis of humans (head lice) that does not respond to established treatments. A liquid chromatography/turbo ion spray tandem mass spectrometry (LC/TIS‐MS/MS) method for the determination of ivermectin in rat and human plasma has been developed that uses emamectin [4″‐epi‐(methylamino)‐4″‐deoxyavermectin] as the internal standard. Sample preparation involved protein precipitation and filtration of fortified plasma in the 96‐well format. Chromatographic separation was accomplished using fast gradient conditions on a C8 stationary phase. The analytes were detected with the mass spectrometer operated in the positive ion, multiple reaction monitoring mode. The method exhibited good intra‐ and interday accuracy and precision, and was linear over a dynamic range of 1–2000 ng/mL. In rat plasma, intraday accuracy ranged between 84–93% for the low quality control (QC) sample (1.5 ng/mL), and between 91–109% for the remaining QCs. Intraday precision ranged between 4.9–15% for the low QC, and 0.8–6.3% for the remaining QCs. Interday accuracy ranged between 88–107%, and precision between 4.1–11%. Similar data was obtained using human plasma. An investigation of matrix effects indicated that the ionization efficiency of ivermectin was favored by the presence of an ammonium ion in an aqueous environment. The implications of this observation toward assay sensitivity are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Quadratic form of stable sub‐manifold for power systems
Authors: Cheng Daizhan , Ma Jin , Lu Qiang , Mei Shengwei
Published: May 2004

The stable sub‐manifold of type‐1 unstable equilibrium point is fundamental in determining the region of attraction of a stable working point for power systems, because such sub‐manifolds form the boundary of the region (IEEE Trans. Automat. Control 1998; 33(1):16–27; IEEE Trans. Circuit Syst. 1988; 35(6):712–728). The quadratic approximation has been investigated in some recent literatures (Automatica 1997; 33(10):1877–1883; IEEE Trans. Power Syst. 1997; 12(2):797–802). First, the paper reports our recent result: a precise formula is obtained, which provides the unique quadratic approximation with the error of 0(∣∣x∣∣3). Then the result is applied to differential–algebraic systems. The real form of practical large scale power systems are of this type. A detailed algorithm is obtained for the quadratic approximation of the stable sub‐manifold of type‐1 unstable equilibrium points of such systems. Some examples are presented to illustrate the algorithm and the application of the approximation to stability analysis of power systems. Copyright © 2004 John Wiley & Sons, Ltd.
Brief report: Construct validity of two identity status measures: the EIPQ and the EOM‐EIS‐II
Authors: Schwartz Seth J.
Published: May 2004

The present study was designed to examine construct validity of two identity status measures, the Ego Identity Process Questionnaire (EIPQ; J. Adolescence 18 (1995) 179) and the Extended Objective Measure of Ego Identity Status II (EOM‐EIS‐II; J. Adolescent Res. 1 (1986) 183). Construct validity was operationalized in terms of how identity status classifications generated by the EIPQ and EOM‐EIS related to a measure of psychological agency, the Multi‐Measure Agentic Personality Scale (MAPS; J. Adolescence 20 (1997) 421). Results indicated that, for the most part, the agentic personality scales differentiated the EIPQ diffused and moratorium statuses from the foreclosed and achieved statuses, whereas the agentic personality scales differentiated the EOM‐EIS‐II achieved status from the other three statuses. The EIPQ is recommended as the preferred instrument for making contrasts between or among identity statuses, whereas the EOM‐EIS‐II is recommended when the objective is to consider continuous measures of the identity statuses.
Personality trait risk factors for attempted suicide among young women with eating disorders
Authors: Youssef G. , Plancherel B. , Laget J. , Corcos M. , Flament M.F. , Halfon O.
Published: May 2004

Objective

Clinical observations and a review of the literature led us to hypothesize that certain personality and character traits could provide improved understanding, and thus improved prevention, of suicidal behaviour among young women with eating disorders.

Method

The clinical group consisted of 152 women aged between 18 and 24 years, with DSM-IV anorexia nervosa/restrictive type (AN-R = 66), anorexia nervosa/purging type (AN-P = 37), bulimia nervosa/non-purging type (BN-NP = 9), or bulimia nervosa/purging type (BN-P = 40). The control group consisted of 140 subjects. The assessment measures were the Minnesota Multiphasic Personality Inventory—second version (MMPI-2) scales and subscales, the Beck Depression Inventory (BDI) used to control for current depressive symptoms, plus a specific questionnaire concerning suicide attempts.

Results

Suicide attempts were most frequent in subjects with purging behaviour (30.0% for BN-P and 29.7% for AN-P). Those attempting suicide among subjects with eating disorders were mostly students (67.8%). For women with AN-R the scales for ‘Depression’ and ‘Antisocial practices’ represented significant suicidal risk, for women with AN-P the scales for ‘Hysteria’, ‘Psychopathic deviate’, ‘Shyness/Self-consciousness’, ‘Antisocial Practices’, ‘Obsessiveness’ and ‘Low self-esteem’ were risk indicators and for women with BN-P the ‘Psychasthenia’, ‘Anger’ and ‘Fears’ scales were risk indicators.

Conclusion

This study provides interesting results concerning the personality traits of young women with both eating disorders and suicidal behaviour. Students and those with purging behaviour are most at risk. Young women should be given more attention with regard to the risk of suicide attempts if they: (a) have AN-R with a tendency to self-punishment and antisocial conduct, (b) have AN-P with multiple physical complaints, are not at ease in social situations and have antisocial behaviour, or (c) if they have BN-P and tend to be easily angered with obsessive behaviour and phobic worries. The MMPI-2 is an interesting assessment method for the study of traits indicating a risk of suicidal behaviour in young subjects, after controlling for current depressive pathology.
Attempted suicide and psychiatric consultation
Authors: Suominen Kirsi H. , Isometsä Erkki T. , Lönnqvist Jouko K.
Published: May 2004

This study investigated the differences in clinical characteristics between suicide attempters referred or not referred to psychiatric consultation after a suicide attempt and factors affecting such referral to psychiatric aftercare after attempted suicide. All 1198 consecutive suicide attempters treated in hospital emergency rooms in Helsinki during a 12-month period were identified. Data were gathered on any psychiatric consultation after the attempt and on all health care contacts 1 year before and after the index attempt. We found that half of the suicide attempters who were not referred to psychiatric consultation were without any aftercare recommendation and treatment contact soon after their attempt. Factors predicting referral to psychiatric consultation were age, psychotic disorder, lack of substance use disorder and, most strongly, the hospital where the suicide attempt was treated. Although the characteristics of a patient attempting suicide do play a role in determining whether a psychiatric consultation will take place or not, the most important factor is the consultation practices of the particular hospital. This in turn influences the probability of adequate aftercare.
The role of protein phosphatase‐1 in the modulation of synaptic and structural plasticity
Authors: Munton Richard P. , Vizi Sándor , Mansuy Isabelle M.
Published: May 2004

Synaptic plasticity is a phenomenon contributing to changes in the efficacy of neuronal transmission. These changes are widely believed to be a major cellular basis for learning and memory. Protein phosphorylation is a key biochemical process involved in synaptic plasticity that operates through a tight balance between the action of protein kinases and protein phosphatases (PPs). Although the majority of research in this field has concentrated primarily on protein kinases, the significant role of PPs is becoming increasingly apparent. This review examines one such phosphatase, PP1, and highlights recent advances in the understanding of its intervention in synaptic and structural plasticity and the mechanisms of learning and memory.
Of flies and men; p53, a tumour suppressor
Authors: Sutcliffe Josephine E. , Brehm Alexander
Published: May 2004

The completion of the Drosophila genome sequencing project [Science 287 (2000) 2185] has reconfirmed the fruit fly as a model organism to study human disease. Comparison studies have shown that two thirds of genes implicated in human cancers have counterparts in the fly [Curr. Opin. Genet. Dev. 11 (2001) 274; J. Cell Biol. 150 (2000) F23], including the tumour suppressor, p53. The suitability of the fruit fly to study the function of the tumour suppressor p53 is further exemplified by the lack of p53 family members within the fly genome, i.e., no homologues to p63 and p73 have been identified. Hence, there is no redundancy between family members greatly facilitating the analysis of p53 function. In addition, studying p53 in Drosophila provides an opportunity to learn about the evolution of tumour suppressors. Here, we will discuss what is known about Drosophila p53 in relation to human p53.
Involvement of GSK‐3β in TWEAK‐mediated NF‐κB activation
Authors: De Ketelaere Adelheid , Vermeulen Linda , Vialard Jorge , Van De Weyer Inez , Van Wauwe Jean , Haegeman Guy , Moelans Inge
Published: May 2004

Glycogen synthase kinase‐3β (GSK‐3β) is a key component of several signaling pathways. We found that a short variant of `TNF‐like weak inducer of apoptosis' (shortTWEAK) formed a complex with GSK‐3β in a yeast two‐hybrid system. We demonstrate that shortTWEAK and GSK‐3β colocalize in the nucleus of human neuroblastoma cells. We also show that TWEAK is internalized in different cell lines and that it translocates to the nucleus. This event causes the degradation of IκBα, the nuclear translocation of both GSK‐3β and p65, and the induction of NF‐κB‐driven gene expression. We demonstrate that the induction of IL‐8 expression by TWEAK can be counteracted by LiCl. Taken together, these data suggest that GSK‐3β plays an important role in the signal transduction pathway between TWEAK and NF‐κB.
Cytoplasmic localization of calcium/calmodulin‐dependent protein kinase I‐α depends on a nuclear export signal in its regulatory domain
Authors: Stedman Diann R. , Uboha Nataliya V. , Stedman Timothy T. , Nairn Angus C. , Picciotto Marina R.
Published: May 2004

Calcium/calmodulin‐dependent protein kinase I‐α (CaMKI‐α) is a ubiquitous cytosolic enzyme that phosphorylates a number of nuclear proteins in vitro and has been implicated in transcriptional regulation. We report that cytoplasmic localization of CaMKI‐α depends on CRM1‐mediated nuclear export mediated through a Rev‐like nuclear export signal in the CaMKI‐α regulatory domain. Interaction of CaMKI‐α with a CRM1 complex in vitro is enhanced by incubation with calcium/calmodulin. Translocation of CaMKI‐α into the nucleus involves a conserved sequence located within the catalytic core. Mutation of this sequence partially blocks nuclear entry of an export‐impaired mutant of CaMKI‐α.
Effectiveness of RNA interference in transgenic plants
Authors: Kerschen Arthur , Napoli Carolyn A. , Jorgensen Richard A. , Müller Andreas E.
Published: May 2004

RNA interference (RNAi) can be used to study gene function by effecting degradation of the targeted transcript. However, the effectiveness of transgene‐induced RNAi among multiple target genes has not been compared systematically. To this end, we developed a relative quantitative RT‐PCR protocol that allows use of a single internal standard over a wide range of target gene expression levels. Using this method in an analysis of transgenic Arabidopsis thaliana RNAi lines targeting 25 different endogenes revealed that independent, homozygous, single‐copy (sc) T4 lines targeting the same gene generally reduce transcript levels to the same extent, whereas multi‐copy RNAi lines differed in the degree of target reduction and never exceeded the effect of sc transgenes. The maximal reduction of target transcript levels varied among targets. These observations suggest that each target sequence possesses an inherent degree of susceptibility to dsRNA‐mediated degradation.
Monoglucosylated glycans in the secreted human complement component C3: implications for protein biosynthesis and structure
Authors: Max Crispin M.D. , Ritchie Gayle E. , Critchley Alison J. , Paul Morgan B. , Wilson Ian A. , Dwek Raymond A. , Sim Robert B. , Rudd Pauline M.
Published: May 2004

The monoglucosylated oligomannose N‐linked oligosaccharide (Glc1Man9GlcNAc2) is a retention signal for the calnexin–calreticulin quality control pathway in the endoplasmic reticulum. We report here the presence of such monoglucosylated N‐glycans on the human complement serum glycoprotein C3. This finding represents the first report of monoglucosylated glycans on a human serum glycoprotein from non‐diseased individuals. The presence of the glucose moiety in 5% of the human C3 glycoprotein suggests that this glycosylation site is sequestered within the protein and is consistent with previous studies identifying a cryptic conglutinin binding site on C3 that becomes exposed upon its conversion to iC3b.
Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration
Authors: Li Liang , Sengupta Amitabha , Haque Niloufar , Grundke-Iqbal Inge , Iqbal Khalid
Published: May 2004

Memantine, an N‐methyl‐d‐aspartate (NMDA) receptor antagonist, reduces the clinical deterioration in moderate‐to‐severe Alzheimer disease (AD) for which other treatments are not available. The activity of protein phosphatase (PP)‐2A is compromised in AD brain and is believed to be a cause of the abnormal hyperphosphorylation of tau and the consequent neurofibrillary degeneration. Here we show that memantine inhibits and reverses the PP‐2A inhibition‐induced abnormal hyperphosphorylation and accumulation of tau in organotypic culture of rat hippocampal slices. Such restorative effects of memantine were not detected either with 5,7‐dichlorokynurenic acid or with d(−)‐2‐amino‐5‐phosphopentanoic acid, NMDA receptor antagonists active at the glycine binding site and at the glutamate binding site, respectively. These findings show (1) that memantine inhibits and reverses the PP‐2A inhibition‐induced abnormal hyperphosphorylation of tau/neurofibrillary degeneration and (2) that this drug might be useful for the treatment of AD and related tauopathies.
ADP‐ribosylation factor (ARF)‐like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI‐dependent cholesterol export
Authors: Engel Thomas , Lueken Aloys , Bode Günther , Hobohm Uwe , Lorkowski Stefan , Schlueter Bernhard , Rust Stephan , Cullen Paul , Pech Michael , Assmann Gerd , Seedorf Udo
Published: May 2004

Here, we identify ADP‐ribosylation factor (ARF)‐like 7 (ARL7) as the only ARF‐ and ARL‐family member whose mRNA‐expression is induced by liver X‐receptor/retinoid X‐receptor agonists or cholesterol loading in human macrophages. Moreover, subcellular distribution of mutant and wild type ARL7‐enhanced green fluorescent protein (EGFP) supports that ARL7 may be involved in a vesicular transport step between a perinuclear compartment and the plasma membrane. Therefore, we investigated the effect of ARL7 over‐expression on the cholesterol secretory pathway. We found that expression of wild type and dominant active ARL7‐EGFP stimulated the rate of apolipoprotein AI‐specific cholesterol efflux 1.7‐ and 2.8‐fold. In contrast, expression of the dominant negative form of ARL7‐EGFP led to ∼50% inhibition of cholesterol efflux. This data is consistent with a model in which ARL7 is involved in transport between a perinuclear compartment and the plasma membrane apparently linked to the ABCA1‐mediated cholesterol secretion pathway.
Glucocorticoid activation of the neuronal nicotinic acetylcholine receptor α7 subunit gene: involvement of transcription factor Egr‐1
Authors: Carrasco-Serrano Carmen , Criado Manuel
Published: May 2004

The α7 subunit is a component of nicotinic acetylcholine receptors expressed in bovine chromaffin cells. The peculiar localization of these receptors at adrenomedullary areas adjacent to the adrenal cortex suggests that factors, probably glucocorticoids, arising from the cortex might diffuse and regulate α7 receptor expression. In reporter gene transfection experiments, dexamethasone increased α7 promoter activity by up to fivefold in a concentration‐ and time‐dependent manner despite the absence of consensus glucocorticoid receptor elements at the α7 promoter. Transcriptional activation induced by glucocorticoids was abolished through simultaneous mutation of at least two of the three sites for the immediate early transcription factor Egr‐1, present in the proximal promoter region of the α7 subunit gene. Therefore, glucocorticoids activate the α7 subunit gene through Egr‐1 in an indirect way.
Characterization of splice variants of human caspase‐activated DNase with CIDE‐N structure and function
Authors: Bayascas José R. , Yuste Vı́ctor J. , Solé Carme , Sánchez-López Isabel , Segura Miquel F. , Perera Remei , Comella Joan X.
Published: May 2004

Internucleosomal DNA fragmentation is an apoptotic event that depends on the activity of different nucleases. Among them, the DNA fragmentation factor B, better known as caspase‐activated DNase (CAD), is mainly responsible for this DNA fragmentation in dying cells. CAD is an endonuclease that is chaperoned and inhibited by inhibitor of CAD (ICAD). Activation of CAD needs the cleavage of ICAD by activated caspase‐3. During the characterization of the staurosporine‐induced apoptotic process in human neuroblastoma cell lines, we have found three novel splice variants of CAD. In all three messengers, the open reading frame is truncated after the second exon of the CAD gene. This truncated open reading frame codifies the CAD protein amino terminal part corresponding to the cell death‐inducing DFF45‐like effector‐N (CIDE‐N) domain. We have detected these splicing variants in human tissues and in peripheral white blood cells from 10 unrelated individuals, and their products have been showed to be expressed in certain mouse tissues. We demonstrate that these truncated forms of CAD are soluble proteins that interact with ICAD. We also provided evidences that these CIDE‐N forms of CAD promote apoptosis in a caspase‐dependent manner.
The N‐terminal sequence directs import of mitochondrial alanine aminotransferase into mitochondria
Authors: Metón Isidoro , Egea Miriam , Fernández Felipe , Eraso Marı́a C. , Baanante Isabel V.
Published: May 2004

Herein, we report cloning and subcellular localization of two alanine aminotransferase (ALT) isozymes, cALT and mALT, from liver of gilthead sea bream (Sparus aurata). CHO cells transfected with constructs expressing cALT or mALT as C‐ or N‐terminal fusion with the enhanced green fluorescent protein (EGFP) showed that cALT is cytosolic, whereas mALT localized to mitochondria. Fusion of EGFP to mALT N‐terminus or removal of amino acids 1–83 of mALT avoided import into mitochondria, supporting evidence that the mALT N‐terminus contains a mitochondrial targeting signal. The amino acid sequence of mALT is the first reported for a mitochondrial ALT in animals.
Bioimaging TOF‐SIMS: localization of cholesterol in rat kidney sections
Authors: Nygren Håkan , Malmberg Per , Kriegeskotte Christian , Arlinghaus Heinrich F.
Published: May 2004

Rat kidneys were sectioned by cryoultramicrotomy and dried at room temperature. The samples were covered with a thin silver layer and analyzed in an imaging TOF‐SIMS instrument equipped with a Ga+‐source. The cholesterol signal showed a high concentration in the nuclear areas of the epithelial cells and a lower concentration over areas representing the basal lamina of renal tubules. A more diffuse distribution of cholesterol was also found over areas representing the cytoplasm or plasma membrane of the epithelial cells.
Protein phosphatase 1, but not protein phosphatase 2A, dephosphorylates DNA‐damaging stress‐induced phospho‐serine 15 of p53
Authors: Haneda Masataka , Kojima Eiji , Nishikimi Akihiko , Hasegawa Tadao , Nakashima Izumi , Isobe Ken-ichi
Published: May 2004

Okadaic acid (OA) is a protein phosphatase (PP) inhibitor and induces hyperphosphorylation of p53. We investigated whether the inhibition of PP1 by OA promotes the phosphorylation of the serine 15 of p53. In vitro dephosphorylation assay showed that PP1 dephosphorylated ultraviolet C (UVC)‐induced phospho‐ser15 of p53, and that OA treatment inhibited it. One of the PP1 regulators, growth arrest and DNA damage 34 (GADD34), disturbed PP1 binding with p53, interfered with the dephosphorylation of p53 and increased the amount of phospho‐p53 after UVC‐treatment. This report provides the first evidence that PP1, but not PP2A, dephosphorylates phospho‐serine 15 of p53.
A carotenoid‐binding protein (CBP) plays a crucial role in cocoon pigmentation of silkworm (Bombyx mori) larvae
Authors: Tabunoki Hiroko , Higurashi Satoshi , Ninagi Osamu , Fujii Hiroshi , Banno Yutaka , Nozaki Masashi , Kitajima Mika , Miura Nami , Atsumi Shogo , Tsuchida Kozo , Maekawa Hideaki , Sato Ryoichi
Published: May 2004

We examined the role of carotenoid‐binding protein (CBP) in yellow cocoon pigmentation. First, using yellow or white cocoon races, we investigated the linkage between the yellow pigmentation and CBP expression. CBP was expressed only in the silk gland of the yellow cocoon races, which utilize carotenoids for cocoon pigmentation. Furthermore, CBP expression in the silk glands of day 1–7 fifth instar larvae matched the period of carotenoid uptake into the silk gland. Finally, we gave double‐stranded CBP RNA to Bombyx mori (B. mori) larvae to induce RNA interference. The significantly reduced expression of CBP in the silk gland of fifth instar larva was confirmed on day 4 and a decrease in yellow pigmentation was observed in the cocoon. We showed that CBP plays a key role in the yellow cocoon pigmentation caused by carotenoids.
Rac1 and PAK1 are upstream of IKK‐ε and TBK‐1 in the viral activation of interferon regulatory factor‐3
Authors: Ehrhardt Christina , Kardinal Christian , Wurzer Walter J. , Wolff Thorsten , von Eichel-Streiber Christoph , Pleschka Stephan , Planz Oliver , Ludwig Stephan
Published: May 2004

The anti‐viral type I interferon (IFN) response is initiated by the immediate induction of IFNβ, which is mainly controlled by the IFN‐regulatory factor‐3 (IRF‐3). The signaling pathways mediating viral IRF‐3 activation are only poorly defined. We show that the Rho GTPase Rac1 is activated upon virus infection and controls IRF‐3 phosphorylation and activity. Inhibition of Rac1 leads to reduced IFNβ promoter activity and to enhanced virus production. As a downstream mediator of Rac signaling towards IRF‐3, we have identified the kinase p21‐activated kinase (PAK1). Furthermore, both Rac1 and PAK1 regulate the recently described IRF‐3 activators, IκB kinase‐ε and TANK‐binding kinase‐1, establishing a first canonical virus‐induced IRF‐3 activating pathway.
Miniaturized proteomics and peptidomics using capillary liquid separation and high resolution mass spectrometry
Authors: Ramström Margareta , Bergquist Jonas
Published: May 2004

Knowledge of the protein and peptide content in a tissue or a body fluid is vital in many areas of medical and biomedical sciences. Information from proteomic and peptidomic studies may reveal alterations in expression due to, e.g., a disease and facilitate the understanding of the pathophysiology and the identification of biological markers. In this minireview, we discuss miniaturized proteomic and peptidomic approaches that have been applied in our laboratory in order to investigate the protein and peptide contents of body fluids (such as plasma, cerebrospinal and amniotic fluid), as well as extracted tissues. The methods involve miniaturized liquid separation, i.e., capillary liquid chromatography and capillary electrophoresis, combined with high resolution mass spectrometry (MS), i.e., Fourier transform ion cyclotron resonance MS. These approaches provide the opportunity to analyze samples of small volumes with high throughput, high sensitivity, good dynamic range and minimal sample handling. Also, the experiments are relatively easy to automate.
Structural commonalities among integral membrane enzymes
Authors: Bracey Michael H. , Cravatt Benjamin F. , Stevens Raymond C.
Published: May 2004

The X‐ray crystal structures of five distinct enzymes (prostaglandin H2 synthase, squalene cyclase, fatty acid amide hydrolase, microsomal cytochrome P450, and estrone sulfatase) challenge contemporary descriptions of integral membrane proteins. This structurally divergent group represents an important component of the integral membrane proteome that lies at the bilayer's aqueous interface. We summarize here what is collectively understood about the membrane insertion of these proteins, what roles they may play in lipid biology, and their relationship to soluble structural homologs.
Zooplankton volume trends off Peru between 1964 and 2001
Authors: Ayón Patricia , Purca Sara , Guevara-Carrasco Renato
Published: May 2004

Zooplankton samples were collected by Hensen net (300 μm) vertical hauls from a depth of 50 m in 57 surveys along the Peruvian coast during winter and summer from 1961 to 2001. In general, the latitudinal distribution of total zooplankton volumes showed highest values within 60 nmi (111 km) of the coast. Predominantly during the 1960s, high zooplankton volumes were found between 4°S–6°S and 14°S–16°S, coinciding with narrow continental shelf areas. Strong declines of zooplankton volumes were observed in these regions in the 1990s. In the long term, zooplankton volumes off Peru were higher during “cold” decades, particularly in the 1960s, than during “warm” decades. This research supports the regime-shift previously observed in the Peruvian coastal upwelling, and is in agreement with global changes observed in lower and upper trophic levels elsewhere in the Pacific and North Atlantic basins.
Perinatal exposure to GABA‐transaminase inhibitor impaired psychomotor function in the developing and adult mouse
Authors: Levav T. , Saar T. , Berkovich L. , Golan H.
Published: May 2004

Antiepileptic drugs acting through the potentiation of GABA‐ergic pathways have harmful effects on brain development. Increased risk of impaired intellectual development was reported in children born to women treated for epilepsy during pregnancy. Here we examined the vulnerability of the developing brain to treatment with one of the new antiepileptic drugs—vigabatrin—during two time periods in newborn mice (postnatal days 1–7 and 4–14) which parallel the third trimester of human embryo brain development. Delayed development of sensory and motor reflexes, reduced mobility in the open field, impaired object recognition and deficient spatial learning and memory were observed independently of the treatment period. On the contrary, specific susceptibility to the age of exposure was detected in various motor functions. A number of morphological correlates may explain these behavioral alterations; a transient increase in CA1 pyramidal cell layer (P<0.001) and decrease in granular cell layer (P<0.05) in hippocampus were detected at postnatal day 7. In addition, a significantly lower cell density was observed in the adult mouse brain in all layers of the M2 cerebral cortex of mice treated during days 4–14, compared to the controls (P<0.05). Our findings demonstrated short‐ and long‐term deleterious effects of vigabatrin treatment and suggest a specific vulnerability of the developing motor system to GABA enhancement during the first postnatal week.
Restricted utility of δ13C of bulk organic matter as a record of paleovegetation in some loess–Paleosol sequences in the Chinese Loess Plateau
Authors: Xie Shucheng , Guo Jianqiu , Huang Junhua , Chen Fahu , Wang Haibin , Farrimond Paul
Published: May 2004

Molecular stratigraphic analyses using gas chromatograph-mass spectrometry have been performed in the upper section (S0, L1, S1) of the Yuanbo loess–paleosol sequences in northwest China, with a record extending from the last interglaciation through the present interglaciation. The CPI (Carbon Preference Index) values of both n-alkanols and n-alkan-2-ones display variations between loess deposits and paleosols, showing a correlation with the magnetic susceptibility record, an indicator of the East Asian summer monsoon. The observed variations in the indexes in relation to changes in lithology/paleoclimate are proposed to result from microbial degradation of higher plant lipids in the paleosols. The CPI values of n-alkanes, n-alkanols, and n-alkan-2-ones are negatively correlated with δ13C of bulk organic matter. The correlations suggest that the observed glacial–interglacial variations of δ13C data in the loess stratigraphy reflect the relative importance of the contribution of paleovegetation compared with microorganisms (including both the degradation and the addition of organic matter) and allochthonous loess/soil parent materials. It is thus necessary to evaluate the contributions of the latter two before the paleovegetation can be reconstructed based on the δ13C analysis of bulk organic matter in some loess–paleosol sequences of the Chinese Loess Plateau.
On the prediction of simultaneous inbreeding coefficients at multiple loci
Authors: HERNÁNDEZ-SÁNCHEZ JULES , HALEY CHRIS S. , WOOLLIAMS JOHN A.
Published: May 2004

A new deterministic method for predicting simultaneous inbreeding coefficients at three and four loci is presented. The method involves calculating the conditional probability of IBD (identical by descent) at one locus given IBD at other loci, and multiplying this probability by the prior probability of the latter loci being simultaneously IBD. The conditional probability is obtained applying a novel regression model, and the prior probability from the theory of digenic measures of Weir and Cockerham. The model was validated for a finite monoecious population mating at random, with a constant effective population size, and with or without selfing, and also for an infinite population with a constant intermediate proportion of selfing. We assumed discrete generations. Deterministic predictions were very accurate when compared with simulation results, and robust to alternative forms of implementation. These simultaneous inbreeding coefficients were more sensitive to changes in effective population size than in marker spacing. Extensions to predict simultaneous inbreeding coefficients at more than four loci are now possible.