bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of hydroelectrical development on the flow regime of the karstic river Cetina
Authors: Bonacci Ognjen , Roje‐Bonacci Tanja
Published: December 2002

The Cetina River is a typical karst watercourse in the deep and well‐developed Dinaric karst. The total length of the Cetina River open streamflow from its spring to the mouth is about 105 km. Estimated mean annual rainfall is 1380 mm. The Cetina catchment is built of Triassic, Jurassic, and Cretaceous carbonate strata. The western part of the catchment by the Cetina River is referred to as the ‘direct’ or topographic catchment. It was defined based on surface morphologic forms, by connection between mountain chain peaks. This part of the catchment is almost entirely situated in the Republic of Croatia. The eastern part of the catchment is referred to as the ‘indirect’ catchment, and is mainly situated in Bosnia‐Herzegovina. Water from the ‘indirect’ catchment emerges from the western ‘direct’ catchment in numerous permanent and temporary karst springs. Since 1960, numerous hydrotechnical works have been carried out on the Cetina River and within its catchment. Five hydroelectric power plants (HEPPs), five reservoirs, and three long tunnels and pipelines have been built. Their operation has significantly altered the natural hydrological regime. The Cetina River is divided into two hydrological reaches. In the 65 km upstream, the hydrological regime was redistributed within the year: low flows had increased and high flows had decreased, although the mean annual discharge remained the same. Part of the Cetina watercourse downstream from the Prančevići Reservoir lost the majority of its flow. The mean annual discharges dropped from 100 m3 s−1 to less than 10 m3 s−1 because of the Zakučac HEPP development. Copyright © 2003 John Wiley & Sons, Ltd.
On the standing wave in coupled non‐linear Klein–Gordon equations
Authors: Zhang Jian
Published: December 2002

This paper is concerned with the standing wave in coupled non‐linear Klein–Gordon equations. By an intricate variational argument we establish the existence of standing wave with the ground state. Then we derive out the sharp criterion for blowing up and global existence by applying the potential well argument and the concavity method. We also show the instability of the standing wave. Copyright © 2003 John Wiley & Sons, Ltd.
Ab initio and DFT studies for accurate description of van der Waals interaction between rare‐gas atoms
Authors: Kurita Noriyuki , Sekino Hideo
Published: December 2002

To evaluate the accuracy of density functional theory (DFT) for describing van der Waals interaction between rare‐gas atoms, we performed coupled‐cluster theory restricted to single, double, and noniterative triple excitations [CCSD(T)], fourth‐order perturbation theory including single, double, and quadruple substitutions [MP4(SDQ)], and several DFT calculations for He, Ne, Ar, and Kr dimers. The results clarified that (1) CCSD(T) and MP4(SDQ) with an “adjusted” diffuse basis‐set reproduce the experimental trend in binding energies as well as equilibrium distances of these dimers, (2) MP3 and MP2 underestimate the binding energies, (3) Becke's three‐parameter exchange functional and the gradient‐corrected functional of Lee, Yang, and Paar (B3LYP) and B3PW91 completely fail to describe the binding, and (4) Perdew–Wang exchange‐correlation functional (PW91PW91) and its modified ones (MPWPW91 and MPW1PW91) can provide the binding states, although the calculated binding energies cannot reproduce the experimental trend in binding energies. Therefore, we conclude that the above DFT functionals cannot quantitatively describe the van der Waals interaction between rare‐gas atoms and that the Perdew‐Wang–type exchange functional needs further improvement to describe the interaction. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
DFT study of methanol conversion to hydrocarbons in a zeolite catalyst
Authors: Andzelm Jan , Govind Niranjan , Fitzgerald George , Maiti Amitesh
Published: December 2002

First‐principles calculations using the density functional theory code DMol3 were performed to investigate important pathways in the methanol‐to‐gasoline conversion process over zeolite catalysts. Reaction paths and energy barriers involving the CO bond cleavage and the first CC bond formation were explored using all‐electron periodic supercell calculations and newly implemented algorithms for the optimization of intermediates and transition states. The simulations indicate that the formation of surface ylide involves prohibitively high barriers, whereas surface methoxyl species can easily react with methanol to form ethanol. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
The use of functional genomics in C. elegans for studying human development and disease
Authors: Kuwabara P. E. , O'Neil N.
Published: December 2002

The 100 MbCaenorhabditis elegansgenome sequence is the first animal genome to be sequenced in its entirety. Many reverse‐genetics tools have been developed to mine the genome sequence and to facilitate the jump between the identification of a gene sequence and the understanding of its function. Here we discuss howC. eleganscan contribute to understanding of the function of genes involved in human development and disease.
Community Coalition Building—Contemporary Practice and Research: Introduction
Authors: Wolff Thomas
Published: December 2002

Over the last 20 years, coalition building has become a prominent intervention employed in communities across America. Coalitions provide community psychologists and those in related fields with a chance to work with whole communities and to better understand how to create community change. As we reflect on the past two decades of community coalition building, there are many questions to be answered about this phenomenon. Why has there been such an upsurge in community coalition building activity? What is the impact of this activity? What have we as students of community learned? What are the questions that we need to be asking to improve the effectiveness of coalition building efforts and their evaluation? This set of articles will review the state of the art of community coalition building in both practice and research. The structure of the articles reflects a collaborative process, with multiple contributors from different disciplines, using a variety of formats. Because this is an evolving phenomenon where the questions asked are as important as the lessons learned, many of the major sections include dialogues with community experts from across the country and from multiple fields, including community psychology, public health, political science, public administration, and grassroots organizing.
A Practitioner's Guide to Successful Coalitions
Authors: Wolff Thomas
Published: December 2002

The highly complex practice of building successful community coalitions is explored. Key dimensions related to coalition success are identified and best practices are delineated. Nine dimensions are explored that are critical to coalition success: coalition readiness, intentionality, structure and organizational capacity, taking action, membership, leadership, dollars and resources, relationships, and technical assistance. Two coalition case studies follow the discussion of dimensions and illustrate the journey traveled to create successful community coalitions.
Studying the Outcomes of Community‐Based Coalitions
Authors: Berkowitz Bill
Published: December 2002

Community‐based coalitions are popular structures for creating community benefits. But desired effects have been reported only for single cases, the overall documented evidence to date for positive coalition outcomes being weak. Methodological obstacles may account for much of the missing evidence, and research possibilities for addressing these obstacles are suggested. Alternative interpretations include the positions that coalitions in general are not effective intervention mechanisms, that traditional scientific methodology is poorly suited for capturing fine‐grained coalition outcomes, and that coalitions and similar collaborative organizations are too complex to be adequately evaluated by the methodology that is now available.
Individual and Contextual Predictors of Involvement in Twelve‐Step Self‐Help Groups After Substance Abuse Treatment
Authors: Mankowski Eric S. , Humphreys Keith , Moos Rudolf H.
Published: December 2002

Drawing on ecological and narrative theories of self‐help groups, this study tests a multilevel model predicting self‐help group involvement among male veterans who received inpatient substance abuse treatment. Following K. Maton (1993), the study moves beyond the individual‐level of analysis to encompass variables in the treatment and post‐treatment social ecology. Surveys administered to patients (N = 3,018) and treatment staff (N = 329) assessed these predictor domains and self‐help group involvement 1 year after discharge. A hierarchical linear model fit to the data indicates that greater involvement in 12‐step groups after discharge is predicted by the compatibility between personal and treatment belief systems. The implications of these findings for efforts to facilitate transitions between inpatient professional treatment and community‐based self‐help groups are discussed.
p-Nitrophenylphosphatase Activity Catalyzed by Plasma Membrane (Ca2++Mg2+)ATPase: Correlation with Structural Changes Modulated by Glycerol and Ca2+
Authors: Alves Gutemberg G. , Lima Luis Maurício T. R. , Fávero-Retto Maely P. , Lemos Adriana P. , Peres-Sampaio Carlos E. , Meyer-Fernandes José Roberto , Vieyra Adalberto , Sola-Penna Mauro
Published: December 2002

The plasma membrane (Ca2++Mg2+)ATPase hydrolyzes pseudo-substrates such as p-nitrophenylphosphate. Except when calmodulin is present, Ca2+ ions inhibit the p-nitrophenylphosphatase activity. In this report it is shown that, in the presence of glycerol, Ca2+ strongly stimulates phosphatase activity in a dose-dependent manner. The glycerol- and Ca2+-induced increase in activity is correlated with modifications in the spectral center of mass (average emission wavenumber) of the intrinsic fluorescence of the enzyme. It is concluded that the synergistic effect of glycerol and Ca2+ is related to opposite long-term hydration effects on the substrate binding domain and the Ca2+ binding domain.
Decreased Susceptibility of Heart Mitochondria from Diabetic GK Rats to Mitochondrial Permeability Transition Induced by Calcium Phosphate
Authors: Oliveira Paulo J. , Rolo Anabela P. , Seiça R. , Palmeira Carlos M. , Santos M. S. , Moreno António J. M.
Published: December 2002

Type 2 diabetes (or non-insulin dependent diabetes mellitus, NIDDM) is a common metabolic disease in man. The Goto–Kakizaki (GK) rat has been designed as a NIDDM model. Previous studies with this strain have shown differences at the mitochondrial level. The mitochondrial permeability transition (MPT) is a widely studied phenomenon but yet poorly understood, that leads to mitochondrial dysfunction and cell death. The aim of this work was to compare the differences in susceptibility of induction of the MPT with calcium phosphate in GK and Wistar rats. Our results show that heart mitochondria from GK rats are less susceptible to the induction of MPT, and show a larger calcium accumulation before the overall loss of mitochondrial impermeability.
Short-Term Effects of the 21-Aminosteroid Lazaroid Tirilazad Mesylate (PNU-74006F) and the Pyrrolopyrimidine Lazaroid PNU-101033E on Energy Metabolism of Human Peripheral Blood Mononuclear Cells
Authors: Schmid Dirk , Burmester Gerd-Rüdiger , Tripmacher Robert , Fici Greg , von Voigtlander Philip , Buttgereit Frank
Published: December 2002

Two groups of antioxidant compounds, the 21-aminosteroids and the pyrrolopyrimidines, have been found to act as neuroprotective drugs against lipid peroxidation in the injured CNS. Like glucocorticoids at high doses they are assumed to produce their effects at least in part by direct membrane stabilizing effects. In order to prove this hypothesis, we have investigated in this study the effects of these drugs on the energy metabolism of activated human peripheral blood mononuclear cells (PBMC) since these cells have been shown to serve as a suitable test system for substances affecting processes of ATP turnover. We compared the in vitro effects of (i) the 21-aminosteroid lazaroid tirilazad, (ii) the pyrrolopyrimidine lazaroid PNU-101033E and (iii) the glucocorticoid methylprednisolone on mitogen-induced respiration rate and ATP-consumption. We show that tirilazad inhibits concanavalin A-stimulated respiration rate and sodium cycling across the plasma membrane. The effect of methylprednisolone is similar indicating corresponding cellular mechanisms. However, unlike methylprednisolone, tirilazad produced no significant effect on calcium cycling across the plasma membrane. PNU-101033E in our test system caused cytotoxic effects on PBMC that did not allow us to quantify cellular actions on energy metabolism. Our results underline the view that tirilazad, first, is mimicking the high-dose immunosuppressive pharmacology of glucocorticoids such as methylprednisolone and, second, is likely to produce its therapeutic effects by direct physicochemical interactions with cellular membranes.
Intermediates of unsaturated fatty acid oxidation are incorporated in triglycerides but not in phospholipids in tissues from patients with mitochondrial β‐oxidation defects
Authors: Onkenhout W. , Venizelos V. , Scholte H. R. , de Klerk J. B. C. , Poorthuis B. J. H. M.
Published: December 2002

The fatty acid composition was determined of liver, skeletal muscle and heart obtained post mortem from patients with medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD), multiple acyl‐CoA dehydrogenase deficiency (MADD) and very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD). Increased amounts of 4‐decenoic acid 10:1(n−6), 5‐dodecenoic acid 12:1(n−7), 5‐tetradecenoic acid 14:1(n−9), 5,8‐tetradecadienoic acid 14:2(n−6) and 7,10‐hexadecadienoic acid 16:2(n−6)—intermediates of unsaturated fatty acid oxidation—were found. Fractionation into different lipid classes showed that these fatty acids were exclusively present in the triglyceride fraction. They could not be detected in the free fatty acid fraction or in the phospholipid fraction. Our results suggest that intermediates of unsaturated fatty acid oxidation that accumulate as a consequence of MCADD, MADD and VLCADD are transported to the endoplasmic reticulum for esterification into neutral glycerolipids. The pattern of accumulation is characteristic for each disease, which makes fatty acid analysis of total lipid of post‐mortem tissues a useful tool in the detection of mitochondrial fatty acid oxidation defects in patients who died unexpected, for example with sudden infant death syndrome.
Working memory in posttraumatic stress disorder—an event‐related potential study
Authors: Galletly Cherrie , Clark C. Richard , McFarlane Alexander C. , Weber Darren L.
Published: December 2002

This study examined ERP topography during the updating and the utilization of working memory in subjects with PTSD. Event‐related potentials of 18 participants with PTSD and 18 controls were recorded from 32 scalp electrodes during an auditory target detection task requiring the constant updating of target identity. Midline N2 and P3 abnormalities previously noted in PTSD during target detection were replicated. Scalp topographic data revealed sustained reduction in activity over the right hemisphere during working memory updating. Executive processes were associated with brief but widespread right hemisphere reductions during the P3, followed by sustained, bilateral reduction frontally. This study identifies an abnormal pattern of cortical network function during both the updating and use of working memory in PTSD.
Development of a depersonalization severity scale
Authors: Simeon Daphne , Guralnik Orna , Schmeidler James
Published: December 2002

Our aim was to develop a clinician‐rated scale assessing depersonalization severity for use in clinical trials of Depersonalization Disorder and trauma‐related disorders in general. The 6‐item Depersonalization Severity Scale (DSS) was administered to 63 participants with DSM‐IV Depersonalization Disorder as diagnosed by the SCID‐D, and its psychometric properties were examined. The sensitivity of the DSS and of the Dissociative Experiences Scale (DES) to treatment change was assessed in blinded, controlled settings. Individual items were widely distributed across the severity range. Interrater reliability was excellent and internal consistency was moderate. The DSS had high convergent and discriminant validity and was sensitive to treatment change. The DES was also sensitive to treatment change. We recommend piloting the DSS in future treatment trials of trauma‐spectrum disorders.
Bifurcations and Periodic Orbits in Chaotic Maps
Authors: Stefański Krzysztof
Published: December 2002

A hierarchy of universalities in families of 1-D maps is discussed. Breakdown of universalities in families of 3-D maps is shown on selected examples of such families.
Coherence, Teleportation, and Open Systems: Comments on Interpretation of Quantum Mechanics
Authors: Ingarden Roman S.
Published: December 2002

A physical and philosophical discussion of quantum phenomena of coherence, teleportation and open systems is given. We attempt to show that modern physics can give some impulses for new solutions or new tendencies in philosophy. One of the questions is the problem of what is basic in quantum physics: “substances” or “situations”, the problem of an observer or two observers at least, of a whole and a part, or distributive or collective sets, of particle-wave complementarity, and of modalities such as possibility, necessity, probability, potentiality, etc.
Cooling Load Density Analysis and Optimization for an Endoreversible Air Refrigerator
Authors: Zhou Shengbing , Chen Lingen , Sun Fengrui , Wu Chih
Published: December 2002

The performance analysis and optimization of an endoreversible air refrigerator is carried out by taking the cooling load density, which is defined as the ratio of cooling load to the maximum specific volume in the cycle, as the optimization objective in this paper. The results obtained are different from those with the cooling load objective. Numerical examples show the effects of pressure ratio and allocation of heat exchanger inventory on the cooling load density of the refrigerator.
Optimal Choice of Prices and Flows in a Complex Open Industrial System
Authors: Amelkin Sergey , Tsirlin Anatolii
Published: December 2002

Production processes are very important subject of economic study. These processes are irreversible. Processes in non homogenious systems are considered taking into account restrictions on the finite intensities of the resources flows. The problem on determination of optimal prices is considered for a firm with given internal structure.
Entropy Approach to Comparison of Images
Authors: Kirsanova E. N. , Sadovsky M. G.
Published: December 2002

Basically new pattern recognition method is implemented to compare two (or several) digital images. The method has neither feature alphabet, nor pattern dictionary recovery stages. It compares input images due to a special object called palette built from fragments of images. The measures to estimate the distances between images are based on a determination of the specific entropy of the frequency dictionary of an image with respect to the palette; that latter presents the statistical ancestor of the group of the images under comparison. The palette is defined as the frequency dictionary with frequencies of the fragments equal to arithmetic mean of the frequencies of the same fragments from the images to be compared. Such definition yields a minimum of the sum of specific entropies of the compared images with respect to the palette. Some preliminary results in the application of the method in pattern recognition and synergistics problems are presented. The limitations and basic properties of the method are discussed.
Neonatal hypoglycaemia in severe succinyl‐CoA:3‐oxoacid CoA‐transferase deficiency
Authors: Berry G. T. , Fukao T. , Mitchell G. A. , Mazur A. , Ciafre M. , Gibson J. , Kondo N. , Palmieri M. J.
Published: December 2002

Succinyl‐CoA:3‐oxoacid CoA‐transferase (SCOT) deficiency is an inborn error of ketone body utilization, characterized by intermittent ketoacidotic crises and persistent ketosis. The diagnosis was suspected in a patient who presented with hypoglycaemia, ketoacidosis and coma at 4 days of age. The hypoglycaemic tendency was only observed during the first month of life. A novel macromolecular labelling assay in cultured skin fibroblasts using D‐3‐hydroxy[3‐14C]butyrate supported the diagnosis. Subsequently, 9% residual SCOT activity and undetectable cross‐reactive protein were noted in fibroblasts and the patient was found to be homozygous for the G324E SCOT gene mutation. By 7 years of age, recurrent episodes of ketoacidosis superimposed on persistent hyperketonaemia had resulted in over 25 hospitalizations requiring intravenous fluid, glucose and sodium bicarbonate therapy. He has had normal growth but developmental delay and attention deficit–hyperactivity disorder. A continuous intravenous glucose infusion at 38 μmol (6.8 mg)/kg per min reduced plasma total ketone levels from greater than 1.5 mmol/L to less than 0.5 mmol/L after 48 h. This indicates that patients with SCOT deficiency do not always manifest ketosis with administration of a sufficient amount of carbohydrates, but that even under such conditions hyperketonaemia is difficult to eliminate completely. The presence of hypoglycaemia does not exclude the diagnosis of SCOT deficiency in infancy.
Renal pathological changes in Fabry disease
Authors: Sessa A. , Meroni M. , Battini G. , Maglio A. , Brambilla P. L. , Bertella M. , Nebuloni M. , Pallotti F. , Giordano F. , Bertagnolio B. , Tosoni A.
Published: December 2002

Fabry disease is a rare X‐linked disorder, characterized by deficient activity of the lysosomal enzyme α‐galactosidase A. This leads to systemic accumulation of the glycosphingolipid globotriaosylceramide (Gb3) in all body tissues and organs, including the kidney. Renal manifestations are less evident in female heterozygotes than in male hemizygotes, according to the Lyon hypothesis. Accumulation of Gb3 occurs mainly in the epithelial cells of Henle's loop and distal tubule, inducing early impairment in renal concentrating ability; involvement of the proximal tubule induces Fanconi syndrome. All types of glomerular cells are involved, especially podocytes, and glomerular proteinuria may occur at a young age. The evolution of renal Fabry disease is characterized by progressive deterioration of renal function to end‐stage renal failure (ESRF). Ultrastructural study of kidney biopsies reveals typical bodies in the cytoplasm of all types of renal cells, characterized byconcentric lamellation of clear and dark layers with a periodicity of 35–50 Å.Management of progressive renal disease requires dietetic and therapeutic strategies, usually indicated in developing chronic renal failure, with dialysis and renal transplantation required for patients with ESRF. The recent development of enzyme replacement therapy, however, should make it possible to prevent or reverse the progressive renal dysfunction associated with Fabry disease.
Increased fertility in a woman with classic galactosaemia
Authors: Kimonis V.
Published: December 2002

A 27‐year‐old caucasian female with classical galactosaemia due to Q188R homozygous mutation is reported. At 18 years she had triplets and at 23 years a further pregnancy. All infants are well.
Novel exon 11 skipping mutation in a patient with glycogen storage disease type IIId
Authors: Sugie H. , Fukuda T. , Ito M. , Sugie Y , Kojoh T. , Nonaka I.
Published: December 2002

We report the molecular genetic abnormalities of a patient with GSD IIId presenting with progressive myopathy and cardiopathy leading to a fatal outcome. We identified two independent deletions including a 4 bp deletion (1117–1120) and a 98 bp deletion (1135–1232) in cDNA. Sequencing of the genomic DNA of the corresponding region revealed a 4 bp deletion in exon 10; however, the other 98 bp deletion corresponding to exon 11, which was deleted in cDNA, was present in genomic DNA. We therefore concluded that skipping of exon 11 occurred in the cDNA of the patient. Intron/exon boundary analysis of the skipped exon 11 revealed no mutation in the consensus splice‐site sequence. If normal splicing had occurred, a stop codon would have appeared within exon 11 due to frameshift mutation. The mechanism of exon skipping observed in our patient is as yet unknown, and it is still not clear whether intraexonal mutation of the preceding exon can influence splice‐site selection. It is possible that a unique exon skipping occurred, preventing the appearance of a stop codon in our patient
Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses
Authors: Cox T. M.
Published: December 2002

Gaucher disease is a typical lysosomal storage disease, resulting from an inborn deficiency of glucocerebrosidase. This leads to the accumulation of glycolipidsin macrophages, particularly those in the liver, bone marrow, spleen and lung. In addition, disease of the nervous system can arise as a result of the accumulation of endogenous glycosphingolipid metabolites in brain tissue. About 150 mutations of the glucocerebrosidase gene have been identified in patients with Gaucher disease, some of which are predictive of phenotype. However, even patients and siblings with the same mutation, including monozygotic twins, may exhibit marked variability in disease expression and severity, illustrating our lack of understanding of thephenotype–genotype relationship in the sphingolipidoses. Massive organomegaly, particularly of the spleen, is a frequent feature of the disease. Although the liver and spleen may increase greatly in size, the amount of pathological lipid stored in the affected macrophages (Gaucher cells) accounts for less than 2% of the additional tissue mass. It is therefore clear that an inflammatory response occurs in affected individuals and that the clinical phenotype is due to an effect of macrophage storage beyond the physical presence of the Gaucher cells. Factors released by Gaucher cells, including pro‐inflammatory cytokines and perhaps cathepsins, provide a mechanistic link between lysosomal storage and the diverse clinical manifestations of Gaucher disease. Emerging proteomic technology and gene expression profiling should not only improve our understanding of pathogenesis but also offer the prospect of identifying novel biomarkers that can be used as surrogate measures of disease activity and responses to treatment.
Natural history of Fabry disease in males: preliminary observations
Authors: Schiffmann R.
Published: December 2002

A large cohort of patients with Fabry disease is being studied to determine the natural history of the disease and how this relates to the specific mutation involved and the amount of residual α‐galactosidase A activity. To date, we have investigated the progression of cerebral lesions and stroke, as identified by magnetic resonance imaging, and renal disease. Results have shown that cerebral lesions do not appear until 23 years of age, but are present in all patients by55 years of age. The peak onset of proteinuria occurred in the fourth decade, and the peak onset of chronic renal insufficiency and end‐stage renal disease occurred in the fifth decade of life. Renal outcome was related to the type of mutation and residual enzyme activity. Data from these studies in untreated patients will be important when assessing the long‐term efficacy of enzyme replacement therapy.
Cerebrotendinous xanthomatosis: Heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings
Authors: Dotti M. T. , Rufa A. , Federico A.
Published: December 2002

Cerebrontendinous xanthomatosis (CTX) is a rare autosomal recessive neurometabolic disease involving lipid metabolism. The classical phenotype is characterized by neurological dysfunction, tendon xanthomas and juvenile cataracts. Other ophthalmological findings have occasionally been reported. To gain more insight into the type and frequency of ophthalmological alterations in this multisystem metabolic disorder, we examined 13 CTX patients. Besides cataracts, found in all cases, the second most frequent ocular abnormality was paleness of the optic disk, which was found in 6 patients and was probably previously underestimated. Signs of premature retinal senescence were also observed. We discuss the possible relation between these ocular manifestations and the metabolic defect.
Does everyone have a name? Psychological distress and quality of life among child Holocaust survivors with lost identity
Authors: Amir Marianne , Lev‐Wiesel Rachel
Published: December 2002

Knowing one's identity, name, and biological parents is considered essential to personality development and psychological well‐being. This study assessed post‐traumatic stress disorder (PTSD) symptoms, subjective quality of life (QoL), psychological distress, and potency in a group of adults who were children during the Holocaust (child Holocaust survivors) and who did not know their true identity. Twenty‐three such survivors were compared to 23 child Holocaust survivors who knew their identity. Results showed that survivors with lost identity had lower physical, psychological, and social QoL and higher somatization, depression, and anxiety scores than did survivors with known identity. The findings suggest that the psychological consequences of not knowing one's identity are long‐lasting.
Rape and physical violence: Comparison of assault characteristics in older and younger adults in the national women's study
Authors: Acierno Ron , Gray Matt , Best Connie , Resnick Heidi , Kilpatrick  , Saunders Ben , Brady Kristine
Published: December 2002

This study compared characteristics of recently occurring assaults against younger adults (age 18–34 years) with those of distant‐past assaults against older adults (age 55–89 years) when they were younger. Responses of a subset of participants in the National Women's Study were the source of data for this study. With the exception of perceived life threat during assault (more prevalent in younger women), assault characteristics did not vary greatly by age in terms of proportions reporting that they had seen the perpetrator before; the event was one in a series; they or the perpetrator were under the influence of a substance; they actually experienced injury; and they reported the assault to authorities. Consistent with previous research, younger women reported greater prevalences of assault than older women.
Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity
Authors: Le Bouteiller Philippe , Barakonyi Aliz , Giustiniani Jérome , Lenfant Françoise , Marie-Cardine Anne , Aguerre-Girr Maryse , Rabot Magali , Hilgert Ivan , Mami-Chouaib Fathia , Tabiasco Julie , Boumsell Laurence , Bensussan Armand
Published: December 2002

Circulating human natural killer (NK) lymphocytes have been functionally defined by their ability to exert cytotoxic activity against MHC class I-negative target cell lines, including K562. Therefore, it was proposed that NK cells recognized the “missing self.” We show here that the Ig-like CD160 receptor expressed by circulating CD56dim+NK cells or IL-2-deprived NK cell lines is mainly involved in their cytotoxic activity against K562 target cells. Further, we report that HLA-C molecules that are constitutively expressed by K562 trigger NK cell lysis through CD160 receptor engagement. In addition, we demonstrate, with recombinant soluble HLA-Cw3 and CD160 proteins, direct interaction of these molecules. We also find that CD158b inhibitory receptors partially interfere with CD160-mediated cytotoxicity, whereas CD94/CD159a and CD85j have no effect on engagement with their respective ligands. Thus, CD160/HLA-C interaction constitutes a unique pathway to trigger NK cell cytotoxic activity.
Increased level of hemoglobin 1 enhances survival of hypoxic stress and promotes early growth in
Arabidopsis thaliana
Authors: Hunt P. W. , Klok E. J. , Trevaskis B. , Watts R. A. , Ellis M. H. , Peacock W. J. , Dennis E. S.
Published: December 2002

Overexpression of a class 1 Hb (GLB1) protects
Arabidopsis thaliana
plants from the effects of severe hypoxia. Overexpression of the bifunctional symbiotic Hb (GLB1S) from
Parasponia andersonii
in
A. thaliana
also increases survival after hypoxia. Plants overexpressing the Hb 1 protein, mutated to have a low oxygen affinity, are as susceptible to hypoxia as WT plants, suggesting that the protection against hypoxia depends on the ability of the Hb to bind ligands, such as oxygen, with high affinity. A mild hypoxia pretreatment (5%) induces the Hb gene and increases the survival of plants after severe hypoxic treatment (0.1%). These results with Hb 1 show that plant Hbs have a role other than in nitrogen-fixing root nodules. Plants overexpressing the GLB1 protein show early vigorous growth in nonhypoxic conditions and are 50% larger in weight than the controls at 14 days. The constitutive expression of GLB1 also resulted in a reduced number of root hairs and increased number of laterals in the root system.
Transcription defines the embryonic domains of cis-regulatory activity at the
Drosophila
bithorax complex
Authors: Drewell Robert A. , Bae Esther , Burr John , Lewis Edward B.
Published: December 2002

The extensive
infraabdominal
(
iab
) region contains a number of cis-regulatory elements, including enhancers, silencers, and insulators responsible for directing the developmental expression of the
abdominal-A
and
Abdominal-B
homeotic genes at the
Drosophila
bithorax complex. It is unclear how these regulatory elements are primed for activity early in embryogenesis, but the 100-kb intergenic region is subject to a complex transcriptional program. Here, we use molecular and genetic methods to examine the functional activity of the RNAs produced from this region and their role in cis regulation. We show that a subset of these transcripts demonstrates a distinct pattern of cellular localization. Furthermore, the transcripts from each
iab
region are discrete and the transcripts do not spread across the insulator elements that delineate the
iab
regions. In embryos carrying a
Mcp
deletion, the intergenic transcription pattern is disrupted in the
iab4
region and the fourth abdominal segment is transformed into the fifth. We propose that intergenic transcription is required early in embryogenesis to initiate the activation of the
Drosophila
bithorax complex and define the domains of activity for the
iab
cis-regulatory elements. We also discuss a possible mechanism by which this may occur.
Imaging direct, dynamin-dependent recapture of fusing secretory granules on plasma membrane lawns from PC12 cells
Authors: Holroyd Phillip , Lang Thorsten , Wenzel Dirk , De Camilli Pietro , Jahn Reinhard
Published: December 2002

During exocytosis, secretory granules fuse with the plasma membrane and discharge their content into the extracellular space. The exocytosed membrane is then reinternalized in a coordinated fashion. A role of clathrin-coated vesicles in this process is well established, whereas the involvement of a direct retrieval mechanism (often called kiss and run) is still debated. Here we report that a significant population of docked secretory granules in the neuroendocrine cell line PC12 fuses with the plasma membrane, takes up fluid-phase markers, and is retrieved at the same position. Fusion allows for complete discharge of small molecules, whereas GFP-labeled neuropeptide Y (molecular mass ≈35 kDa) is only partially released. Retrieved granules were preferentially associated with dynamin. Furthermore, recapture is inhibited by guanosine 5′-[γ-thio]triphosphate and peptides known to block dynamin function. We conclude that secretory granules can be recaptured immediately after formation of an exocytotic opening by an endocytic reaction that is spatially and temporally coupled to soluble
N
-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent fusion, but is not a reversal of the fusion reaction.
Dynamics of microtubule asters in microfabricated chambers: The role of catastrophes
Authors: Faivre-Moskalenko Cendrine , Dogterom Marileen
Published: December 2002

Recent
in vivo
as well as
in vitro
experiments have indicated that microtubule pushing alone is sufficient to position a microtubule-organizing center within a cell. Here, we investigate the effect of catastrophes on the dynamics of microtubule asters within microfabricated chambers that mimic the confining geometry of living cells. The use of a glass bead as the microtubule-organizing center allows us to manipulate the aster by using optical tweezers. In the case in which microtubules preexist, we show that because of microtubule buckling, repositioning almost never occurs after relocation with the optical tweezers, although initial microtubule growth always leads the aster to the geometrical center of the chamber. When a catastrophe promoter is added, we find instead that the aster is able to efficiently explore the chamber geometry even after being relocated with the optical tweezers. As predicted by theoretical calculations, the results of our
in vitro
experiments clearly demonstrate the need for catastrophes for proper positioning in a confining geometry. These findings correlate with recent observations of nuclear positioning in fission yeast cells.
Disruption of T helper 2-immune responses in Epstein–Barr virus-induced gene 3-deficient mice
Authors: Nieuwenhuis Edward E. S. , Neurath Markus F. , Corazza Nadia , Iijima Hideki , Trgovcich Joanne , Wirtz Stefan , Glickman Jonathan , Bailey Dan , Yoshida Masaru , Galle Peter R. , Kronenberg Mitchell , Birkenbach Mark , Blumberg Richard S.
Published: December 2002

Epstein–Barr virus-induced gene 3 (EBI3) is a widely expressed IL-12p40-related protein that associates as a heterodimer with either IL-12p35 or an IL-12p35 homologue, p28, to create a new cytokine (IL-27). To define the function of EBI3in vivo, we generated knockout mice in which theebi3gene was targeted by homologous recombination. EBI3−/−mice exhibited normal numbers of both naive and mature CD4+and CD8+T cells and B cells, but markedly decreased numbers of invariant natural killer T cells (iNKT) as defined by staining with an α-galactosylceramide (αGalCer)-loaded CD1d-tetramer. iNKT cells from EBI3−/−mice exhibited decreased IL-4 and, to a lesser extent, IFN-γ production after αGalCer stimulationin vitro. A sustained decrease in IL-4 production was also observed in EBI3−/−mice after αGalCer stimulationin vivoin contrast to IFN-γ production, which was only transiently decreased under such stimulation. Notably, EBI3−/−mice were resistant to the induction of immunopathology associated with oxazolone-induced colitis, a colitis model mediated primarily by T helper (Th) 2-type cytokine production by iNKT cells. In contrast, trinitrobenzene sulfonic acid-induced colitis, a predominantly Th1-mediated colitis model, was unaffected. Thus, EBI3 plays a critical regulatory role in the induction of Th2-type immune responses and the development of Th2-mediated tissue inflammationin vivo, which may be mediated through the control of iNKT cell function.
Common denominator of Cu/Zn superoxide dismutase mutants associated with amyotrophic lateral sclerosis: Decreased stability of the apo state
Authors: Lindberg Mikael J. , Tibell Lena , Oliveberg Mikael
Published: December 2002

More than 100 point mutations of the superoxide scavenger Cu/Zn superoxide dismutase (SOD; EC

) have been associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). However, these mutations are scattered throughout the protein and provide no clear functional or structural clues to the underlying disease mechanism. Therefore, we undertook to look for folding-related defects by comparing the unfolding behavior of five ALS-associated mutants with distinct structural characteristics: A4V at the interface between the N and C termini, C6F in the hydrophobic core, D90A at the protein surface, and G93A and G93C, which decrease backbone flexibility. With the exception of the disruptive replacements A4V and C6F, the mutations only marginally affect the stability of the native protein, yet all mutants share a pronounced destabilization of the metal-free apo state: the higher the stability loss, the lower the mean survival time for ALS patients carrying the mutation. Thus organism-level pathology may be directly related to the properties of the immature state of a protein rather than to those of the native species.
A polyphosphate kinase (PPK2) widely conserved in bacteria
Authors: Zhang Haiyu , Ishige Kazuya , Kornberg Arthur
Published: December 2002

Synthesis of inorganic polyphosphate (poly P) from the terminal phosphate of ATP is catalyzed reversibly by poly P kinase (PPK, now designated PPK1) initially isolated from
Escherichia coli
. PPK1 is highly conserved in many bacteria, including some of the major pathogens such as
Pseudomonas aeruginosa
. In a null mutant of
P. aeruginosa
lacking
ppk1
, we have discovered a previously uncharacterized PPK activity (designated PPK2) distinguished from PPK1 by the following: synthesis of poly P from GTP or ATP, a preference for Mn
2+
over Mg
2+
, and a stimulation by poly P. The reverse reaction, a poly P-driven nucleoside diphosphate kinase synthesis of GTP from GDP, is 75-fold greater than the forward reaction, poly P synthesis from GTP. The gene encoding PPK2 (
ppk2
) was identified from the amino acid sequence of the protein purified near 1,000-fold, to homogeneity. The 5′-end is 177 bp upstream of the annotated genome sequence of a “conserved hypothetical protein”;
ppk2
(1,074 bp) encodes a protein of 357 aa with a molecular mass of 40.8 kDa. Sequences homologous to PPK2 are present in two other proteins in
P. aeruginosa
, in two Archaea, and in 32 other bacteria (almost all with PPK1 as well); these include rhizobia, cyanobacteria,
Streptomyces
, and several pathogenic species. Distinctive features of the poly P-driven nucleoside diphosphate kinase activity and structural aspects of PPK2 are among the subjects of an accompanying report.
A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage
Authors: Chang Michael , Bellaoui Mohammed , Boone Charles , Brown Grant W.
Published: December 2002

We performed a systematic screen of the set of ≈5,000 viable
Saccharomyces cerevisiae
haploid gene deletion mutants and have identified 103 genes whose deletion causes sensitivity to the DNA-damaging agent methyl methanesulfonate (MMS). In total, 40 previously uncharacterized alkylation damage response genes were identified. Comparison with the set of genes known to be transcriptionally induced in response to MMS revealed surprisingly little overlap with those required for MMS resistance, indicating that transcriptional regulation plays little, if any, role in the response to MMS damage. Clustering of the MMS response genes on the basis of their cross-sensitivities to hydroxyurea, UV radiation, and ionizing radiation revealed a DNA damage core of genes required for responses to a broad range of DNA-damaging agents. Of particular significance, we identified a subset of genes that show a specific MMS response, displaying defects in S phase progression only in the presence of MMS. These genes may promote replication fork stability or processivity during encounters between replication forks and DNA damage.
Dual role for phosphoinositides in regulation of yeast and mammalian phospholipase D enzymes
Authors: Sciorra Vicki A. , Rudge Simon A. , Wang Jiyao , McLaughlin Stuart , Engebrecht JoAnne , Morris Andrew J.
Published: December 2002

Phospholipase D (PLD) generates lipid signals that coordinate membrane trafficking with cellular signaling. PLD activity in vitro and in vivo is dependent on phosphoinositides with a vicinal 4,5-phosphate pair. Yeast and mammalian PLDs contain an NH2-terminal pleckstrin homology (PH) domain that has been speculated to specify both subcellular localization and regulation of PLD activity through interaction with phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2). We report that mutation of the PH domains of yeast and mammalian PLD enzymes generates catalytically active PI(4,5)P2-regulated enzymes with impaired biological functions. Disruption of the PH domain of mammalian PLD2 results in relocalization of the protein from the PI(4,5)P2-containing plasma membrane to endosomes. As a result of this mislocalization, mutations within the PH domain render the protein unresponsive to activation in vivo. Furthermore, the integrity of the PH domain is vital for yeast PLD function in both meiosis and secretion. Binding of PLD2 to model membranes is enhanced by acidic phospholipids. Studies with PLD2-derived peptides suggest that this binding involves a previously identified polybasic motif that mediates activation of the enzyme by PI(4,5)P2. By comparison, the PLD2 PH domain binds PI(4,5)P2 with lower affinity but sufficient selectivity to function in concert with the polybasic motif to target the protein to PI(4,5)P2-rich membranes. Phosphoinositides therefore have a dual role in PLD regulation: membrane targeting mediated by the PH domain and stimulation of catalysis mediated by the polybasic motif.
Mps3p is a novel component of the yeast spindle pole body that interacts with the yeast centrin homologue Cdc31p
Authors: Jaspersen Sue L. , Giddings Thomas H. , Winey Mark
Published: December 2002

Accurate duplication of the Saccharomyces cerevisiae spindle pole body (SPB) is required for formation of a bipolar mitotic spindle. We identified mutants in SPB assembly by screening a temperature-sensitive collection of yeast for defects in SPB incorporation of a fluorescently marked integral SPB component, Spc42p. One SPB assembly mutant contained a mutation in a previously uncharacterized open reading frame that we call MPS3 (for monopolar spindle). mps3-1 mutants arrest in mitosis with monopolar spindles at the nonpermissive temperature, suggesting a defect in SPB duplication. Execution point experiments revealed that MPS3 function is required for the first step of SPB duplication in G1. Like cells containing mutations in two other genes required for this step of SPB duplication (CDC31 and KAR1), mps3-1 mutants arrest with a single unduplicated SPB that lacks an associated half-bridge. MPS3 encodes an essential integral membrane protein that localizes to the SPB half-bridge. Genetic interactions between MPS3 and CDC31 and binding of Cdc31p to Mps3p in vitro, as well as the fact that Cdc31p localization to the SPB is partially dependent on Mps3p function, suggest that one function for Mps3p during SPB duplication is to recruit Cdc31p, the yeast centrin homologue, to the half-bridge.