bluuebunny/crossref_metadata_2025 huggingface dataset:
ModView, visualization of multiple protein sequences and
structures
Authors: Ilyin Valentin A. , Pieper Ursula , Stuart Ashley C. , Marti-Renom Marc A. , McMahan Linda , Sali Andrej
Published: December 2002

Summary: We describe ModView, a web application for visualization of multiple protein sequences and structures. ModView integrates a multiple structure viewer, a multiple sequence alignment editor, and a database querying engine. It is possible to interactively manipulate hundreds of proteins, to visualize conservative and variable residues, active and binding sites, fragments, and domains in protein families, as well as to display large macromolecular complexes such as ribosomes or viruses. As a Netscape plug-in, ModView can be included in HTML pages along with text and figures, which makes it useful for teaching and presentations. ModView is also suitable as a graphical interface to various databases because it can be controlled through JavaScript commands and called from CGI scripts.

Availability: ModView is available at http://guitar.rockefeller.edu/modview.

Contact: ilyin@neu.edu, sali@rockefeller.edu

* To whom correspondence should be addressed.
Representation of DNA sequences with virtual potentials and their
processing by (SEQREP) Kohonen self-organizing maps
Authors: Aires-de-Sousa João , Aires-de-Sousa Luisa
Published: December 2002

Motivation: We propose representing individual positions in DNA sequences by virtual potentials generated by other bases of the same sequence. This is a compact representation of the neighbourhood of a base. The distribution of the virtual potentials over the whole sequence can be used as a representation of the entire sequence (SEQREP code). It is a flexible code, with a length independent of the sequence size, does not require previous alignment, and is convenient for processing by neural networks or statistical techniques.

Results: To evaluate its biological significance, the SEQREP code was used for training Kohonen self-organizing maps (SOMs) in two applications: (a) detection of Alu sequences, and (b) classification of sequences encoding for HIV-1 envelope glycoprotein (env) into subtypes A-G. It was demonstrated that SOMs clustered sequences belonging to different classes into distinct regions. For independent test sets, very high rates of correct predictions were obtained (97% in the first application, 91% in the second). Possible areas of application of SEQREP codes include functional genomics, phylogenetic analysis, detection of repetitions, database retrieval, and automatic alignment.

Availability: Software for representing sequences by SEQREP code, and for training Kohonen SOMs is made freely available from http://www.dq.fct.unl.pt/qoa/jas/seqrep

Contact: jas@fct.unl.pt

Supplementary Information: Supplementary material is available at http://www.dq.fct.unl.pt/qoa/jas/seqrep/bioinf2002

* To whom correspondence should be addressed.
Evolutionary algorithms for finding optimal gene sets in microarray prediction
Authors: Deutsch J. M.
Published: December 2002

Motivation: Microarray data has been shown recently to be efficacious in distinguishing closely related cell types that often appear in different forms of cancer, but is not yet practical clinically. However, the data might be used to construct a minimal set of marker genes that could then be used clinically by making antibody assays to diagnose a specific type of cancer. Here a replication algorithm is used for this purpose. It evolves an ensemble of predictors, all using different combinations of genes to generate a set of optimal predictors.

Results: We apply this method to the leukemia data of the Whitehead/MIT group that attempts to differentially diagnose two kinds of leukemia, and also to data of Khan et al. to distinguish four different kinds of childhood cancers. In the latter case we were able to reduce the number of genes needed from 96 to less than 15, while at the same time being able to classify all of their test data perfectly. We also apply this method to two other cases, Diffuse large B-cell lymphoma data (Shipp et al., 2002), and data of Ramaswamy et al. on multiclass diagnosis of 14 common tumor types.

Availability: http://stravinsky.ucsc.edu/josh/gesses/

Contact: josh@physics.ucsc.edu

* To whom correspondence should be addressed.
Language Processing: Functional Organization and Neuroanatomical Basis
Authors: Martin Randi C.
Published: December 2002

Earlier formulations of the relation of language and the brain provided oversimplified accounts of the nature of language disorders, classifying patients into syndromes characterized by the disruption of sensory or motor word representations or by the disruption of syntax or semantics. More recent neuropsychological findings, drawn mainly from case studies, provide evidence regarding the various levels of representations and processes involved in single-word and sentence processing. Lesion data and neuroimaging findings are converging to some extent in providing localization of these components of language processing, particularly at the single-word level. Much work remains to be done in developing precise theoretical accounts of sentence processing that can accommodate the observed patterns of breakdown. Such theoretical developments may provide a means of accommodating the seemingly contradictory findings regarding the neural organization of sentence processing.
Cultural Pathways Through Universal Development
Authors: Greenfield Patricia M. , Keller Heidi , Fuligni Andrew , Maynard Ashley
Published: December 2002

We focus our review on three universal tasks of human development: relationship formation, knowledge acquisition, and the balance between autonomy and relatedness at adolescence. We present evidence that each task can be addressed through two deeply different cultural pathways through development: the pathways of independence and interdependence. Whereas core theories in developmental psychology are universalistic in their intentions, they in fact presuppose the independent pathway of development. Because the independent pathway is therefore well-known in psychology, we focus a large part of our review on empirically documenting the alternative, interdependent pathway for each developmental task. We also present three theoretical approaches to culture and development: the ecocultural, the sociohistorical, and the cultural values approach. We argue that an understanding of cultural pathways through human development requires all three approaches. We review evidence linking values (cultural values approach), ecological conditions (ecocultural approach), and socialization practices (sociohistorical approach) to cultural pathways through universal developmental tasks.
The Early Education of Socioeconomically Disadvantaged Children
Authors: Arnold David H. , Doctoroff Greta L.
Published: December 2002

This chapter reviews selected research on the education of lowsocioeconomic status (SES) children from birth through the first years of elementary school. Themes include the importance of early academic skills and interest to later achievement; the benefits of integrating knowledge from research on mental health and other areas; the need to utilize and build children's strengths as well as address their weaknesses; and a call to connect research to practice and policy. Relevant research on race and culture is reviewed because ethnic minority low-SES children are at great risk of poverty. Gender is discussed because low-SES boys have poorer general achievement than girls, while very few low-SES girls pursue careers in math- and science-related fields.
Topology optimization of fluids in Stokes flow
Authors: Borrvall Thomas , Petersson Joakim
Published: December 2002

We consider topology optimization of fluids in Stokes flow. The design objective is to minimize a power function, which for the absence of body fluid forces is the dissipated power in the fluid, subject to a fluid volume constraint. A generalized Stokes problem is derived that is used as a base for introducing the design parameterization. Mathematical proofs of existence of optimal solutions and convergence of discretized solutions are given and it is concluded that no regularization of the optimization problem is needed. The discretized state problem is a mixed finite element problem that is solved by a preconditioned conjugate gradient method and the design optimization problem is solved using sequential separable and convex programming. Several numerical examples are presented that illustrate this new methodology and the results are compared to results obtained in the context of shape optimization of fluids. Copyright © 2003 John Wiley & Sons, Ltd.
Options on bond futures: Isolating the risk premium
Authors: Tompkins Robert G.
Published: December 2002

The introduction of unspanned sources of risk (and frictions) implies that option prices include a
risk premium. Prima facie evidence of the existence of risk premia in option prices is contained in the implied
volatility smile patterns reported in the literature. This article isolates the risk premium (defined as the
simple difference between estimated and observed option prices) on options on U.K. Gilts, German Bunds, and
U.S. Treasury bond futures using models that include price jumps and stochastic volatility. This study finds that
single and multi‐factor stochastic volatility models with jumps may explain the empirical regularities
observed in bond futures. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark 23:169–215, 2003
The economic advantage of learners in a spot/futures market
Authors: Linn Scott C. , Stanhouse Bryan E.
Published: December 2002

This article examines the economic advantage of learners in a futures market. We develop a dynamic model of
learning in which a spot market and futures market both exist for a real good. The economy is composed of
producers who can engage in hedging activities, speculators who trade in the futures market, and consumers who are
described by an inverse demand function for the underlying commodity. Producers and speculators are heterogeneous
and are differentiated based upon the predictive equations they employ when formulating forecasts of next
period's spot price. We derive the dynamic rational‐expectations equilibrium of the model and show
that learners enjoy an economic advantage in the futures market. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark
23:151–167, 2003
Adult day service use and reductions in caregiving hours: effects on stress and psychological well‐being for dementia caregivers
Authors: Gaugler Joseph E. , Jarrott Shannon E. , Zarit Steven H. , Stephens Mary‐Ann Parris , Townsend Aloen , Greene Rick
Published: December 2002

Background

The objective of this study was to determine whether adult day service use interacts with decreases in primary caregiving hours (i.e. the time caregivers spent on activities of daily living/instrumental activities of daily living, memory problems, and behavior problems for patients) to alleviate caregiver stress and negative mental health over time.

Methods

Three‐month longitudinal data from the Adult Day Care Collaborative Study (n=400) were used.

Results

Decreases in memory problem hours among adult day service users were associated with reduced feelings of role overload; decreases in ADL hours among non‐users were associated with decreases in worry and strain over a three‐month period.

Conclusion

The findings suggest that adult day services are potentially effective in restructuring caregiving time and providing respite to family members. Copyright © 2002 John Wiley & Sons, Ltd.
Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration
Authors: Pijnenburg Y. A. L. , Sampson E. L. , Harvey R. J. , Fox N. C. , Rossor M. N.
Published: December 2002

Background

Frontotemporal lobar degeneration (FTLD) is commonly associated with behavioural disturbances such as disinhibition and aggression; these often result in the use of neuroleptic medication.

Methods

All available case notes of patients attending a specialist cognitive disorders clinic with a diagnosis of FTLD were selected. This gave 100 subjects (62 male, 38 female).

Results

In 61 patients significant behavioural disturbances were present. Of these patients, 24 had been prescribed neuroleptics. Significant extrapyramidal side effects were reported in eight patients (33%); in five patients these were severe enough to cause severe mobility problems and in one patient resulted in impaired consciousness. In some instances the extrapyramidal side effects took weeks to wear off.

Conclusion

These results suggest that patients with FTLD may, as in Lewy body dementia, be particularly sensitive to the extrapyramidal side effects of neuroleptics. We suggest that neuroleptics should be used cautiously in FTLD and treatment should be started at low doses avoiding depot preparations until further prospective studies have been performed. Copyright © 2002 John Wiley & Sons, Ltd.
On the vibrations of a plate with a concentrated mass and very small thickness
Authors: Gómez D. , Lobo M. , Pérez E.
Published: December 2002

We consider the vibrations of an elastic plate that contains a small region whose size depends on a small parameter ε. The density is of order O(ε–m) in the small region, the concentrated mass, and it is of order O(1) outside; m is a positive parameter. The thickness plate h being fixed, we describe the asymptotic behaviour, as ε→O, of the eigenvalues and eigenfunctions of the corresponding spectral problem, depending on the value of m: Low‐ and high‐frequency vibrations are studied for m>2. We also consider the case where the thickness plate h depends on ε; then, different values of m are singled out. Copyright © 2003 John Wiley & Sons, Ltd.
Ab initio and experimental study on thermally degradable polycarbonates: Effect of structure on reactivity
Authors: Van Speybroeck V. , Waroquier M. , Martelé Y. , Schacht E.
Published: December 2002

The thermal degradation process of some new synthesized polycarbonates is studied both from theoretical and experimental points of view to obtain microscopic insight into the factors that govern the reaction rates. Ab initio density functional theory calculations are performed on a set of carbonates, which are model systems for the polycarbonates. Kinetic parameters are determined by transition‐state theory and compared with experimental‐derived degradation temperatures. The study as presented here gives evidence of the existence of a correlation between these degradation temperatures and the reaction rates resulting from static ab initio calculations on small model systems that are representative for the active area of the degradation process. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Oligothiophene radical cations: Polaron structure in hybrid DFT and MP2 calculations
Authors: Geskin V. M. , Dkhissi A. , Brédas J. L.
Published: December 2002

We investigate the geometric and electronic structure of radical cations in oligothiophene chains by performing hybrid DFT (BHandHLYP) calculations on chains with up to 13 thiophene rings and ab initio MP2 calculations. The BHandHLYP‐optimized structures indicate a self‐localization of charge, spin, and geometric distortion around the middle of the chain, i.e., the formation of a polaron even in the case of the longer chains. This result contrasts with previous pure DFT findings that indicate complete delocalization of the radical cation over the whole chain. The MP2‐optimized structure of octathiophene, an oligomer long enough to allow for possible polaron formation, confirms the presence of a well‐localized polaron structure, similar to that obtained at the Hartree–Fock level. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Density functional study of nitroprusside: Mechanism of the photochemical formation and deactivation of the metastable states
Authors: Buchs M. , Daul C. A. , Manoharan P. T. , Schläpfer C. W.
Published: December 2002

In this article, we present a theoretical investigation about the mechanism of the photochemical formation and deactivation of the metastable states observed in nitroprusside ions. The quantum chemical calculations are based on density functional theory. The peculiar photochemical and photophysical behavior of this molecule has attracted chemists' interest for a while. Due to this interest, many details on the nature of nitroprusside's ground state and its two metastable states were known. However, a clear picture of the reaction pathways between the three minima on the ground‐state potential energy curve was still missing. By studying the excited states corresponding to all three minima, we could set up, in this work, a model explaining the photochemistry and photophysics responsible for the population of the three different states on the ground‐state potential energy curve. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Breathing modes of 2‐D quantum dots with elliptical shape in magnetic fields
Authors: Serra Llorenç , Puente Antonio , Lipparini Enrico
Published: December 2002

The characteristics of the breathing modes of 2‐D dots are theoretically investigated as a function of the dot elliptical deformation and intensity of an applied perpendicular magnetic field. Analytic results obtained by neglecting the interelectron Coulomb interaction are compared with numerical results including interactions within the time‐dependent local spin density approximation. The existence of four characteristic E0 modes and the evolution of their oscillator strength with both deformation and magnetic field are discussed. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
DFT analysis of fluctuations in electronegativity and hardness of a molecular oscillator
Authors: Komorowski Ludwik , Ordon Piotr
Published: December 2002

This work extends application of the density functional theory apparatus to the analysis of thermal fluctuations. It focuses on expectations concerning the role of molecular deformation in changing the global hardness and electronegativity (chemical potential), and hence, the affinity for an intermolecular electron exchange. Molecular harmonic oscillations, the most common molecular deformations, have been analyzed in detail to discover the circumstances, leading to significant modifications in electronegativity and hardness of the molecule. The mean fluctuations of electronegativity and global hardness have been analyzed for a harmonic oscillator. The nuclear reactivity and nuclear stiffness indices have been explored in calculation of thermal fluctuations for any system, harmonic as well as anharmonic. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Ab initio electrical conductance of a molecular wire
Authors: Baer Roi , Neuhauser Daniel
Published: December 2002

A method is developed for computing the direct current and alternating current conductance of molecular wires at small bias. The basic ingredients are: linear response theory, time‐dependent density functional theory, imaginary potentials, and a jellium model for the metallic leads. The theory is capable of incorporating the effect of realistic charge distributions in the system and electron–electron correlation. We demonstrate the method on the jellium–C3–jellium system. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
A non‐standard J‐spectral factorization of rational matrices via zero compensator approach
Authors: Kawamoto Atsushi , Katayama Tohru
Published: December 2002

This paper deals with a non‐standard J‐spectral factorization problem (NS‐J‐SFP) that arises in he non‐standard H∞ control problem for a descriptor system. We derive the solvability conditions for the NS‐J‐SFP by adapting the zero compensation technique due to Copeland and Safonov (Internat. J. Robust Nonlinear Control 1992; 2:139) to the descriptor system. It is also shown that the solvability conditions of the NS‐J‐SFP are equivalent to the existence of a semi‐stabilizing solution of a generalized algebraic Riccati equation. Copyright © 2002 John Wiley & Sons, Ltd.
Can Home Visitation Enhance Maternal Social Support?
Authors: McCurdy Karen
Published: December 2002

This study investigates the impacts of Healthy Start, a statewide, home visitation program, on the social support systems of 212 disadvantaged mothers in Oahu, Hawaii. Maternal support was assessed at the time these mothers gave birth and 12 months later with the Maternal Social Support Index. Comparisons of mothers randomly assigned to visited (n = 108) or nonvisited (n = 104) conditions uncover few differences on structural or affiliational aspects of support after 12 months. Visited mothers, however, are significantly less likely to report a decline in satisfaction with a close adult than nonvisited mothers do. The discussion examines the challenges of fostering social support and the ability of home visitation efforts to achieve this outcome.
The role of chaperone‐assisted folding and quality control in inborn errors of metabolism: Protein folding disorders
Authors: Gregersen N. , Bross P. , Andresen B. S. , Pedersen C. B. , Corydon T. J. , Bolund L.
Published: December 2002

Molecular chaperones are present in the various compartments of the cell and assist the folding of newly synthesized proteins. Compared to wild‐type proteins, missense mutant proteins are generally synthesized in a normal fashion, but may be impaired in their folding. A broad array of diseases that are due to misfolding of mutant proteins may be labelled conformational diseases: aggregation diseases, such as Alzheimer disease; diseases caused by negative dominance from misfolded structural proteins, such as hypertrophic cardiomyopathy; and disorders where the misfolded protein is degraded by intracellular proteases. Many metabolic disorders belong to this last category, where the so‐called protein quality control systems, comprising chaperones and proteases, attempt to eliminate folding intermediates or misfolded proteins. On the basis of in vitro experiments with a limited number of missense mutations identified in patients with phenylalanine hydroxylase and fatty acid oxidation deficiencies, we discuss the cellular fate of missense mutant proteins. We find that the balance between folding to functional conformers, retention (holding) and degradation of folding intermediates or misfolded proteins is dependent on the nature of the mutation and on the efficiency of the quality control. For example, low temperature may promote formation of functional conformers, while elevated temperature usually promotes retention and degradation. We conclude that disorders caused by many missense mutations are complex diseases in which the mutation itself is a necessary major primary component, but that its effect may be modified by cellular conditions and possibly by genetic variations in the quality control systems. We suggest that this new knowledge about cell handling may open new avenues of understanding of the cell pathology and treatment of patients with metabolic disorders.
fMLP Receptor Stimulated Activation of Macrophage: Its Effect on Killing of Intracellular Leishmania donovani
Authors: Dasgupta Dalia , Chakraborty Prasanta , Basu Mukul K.
Published: December 2002

The fMLP receptor of peritoneal macrophages stimulated by fMLP graftedliposomes as ligand, was analysed and compared with respective controlsfor its ability to promote killing of intracellular Leishmaniaparasites. fMLP grafted liposomes show greater efficacy in killingintracellular L. donovani (MHOM/IN/1983/AG83) parasites in a timedependent manner than free fMLP. fMLP grafted liposomes also releasemore active oxygen intermediates and reactive nitrogen intermediates(O−2, H2O2, NO) than free fMLP. The key enzymes PKCand PTK for the respiratory burst and nitric oxide generation werefound to be important in this fMLP receptor mediated signaling processas the enzyme specific inhibitors viz. staurosporine, genistein andAG126 suppressed the leishmanicidal effect of fMLP graftedliposomes. The above findings suggest that the fMLP receptorof macrophages activates PKC and PTK mediated signalling thatis responsible for the intracellular parasite killing.
The Psychological Sense of Economic Hardship: Measurement Models, Validity, and Cross‐Ethnic Equivalence for Urban Families
Authors: Barrera Manuel , Caples Heather , Tein Jenn-Yun
Published: December 2002

Poverty is a community stressor that disproportionally affects ethnic minority families. One aspect of programmatic research on poverty focuses on the psychological sense of economic hardship. In a study of 319 African American, European American, and Mexican American urban families, parents completed objective measures of economic status and scales of perceived economic hardship that were adapted from previous research. Measurement models identified a coherent construct of psychological sense of economic hardship that was essentially equivalent for mothers and fathers, English‐ and Spanish‐speaking Mexican Americans, and the 3 ethnic groups. In support of the validity of this construct, relations between objective indicators of economic status and perceived economic hardship showed equivalence across these same groups.
Inhibition of the Ecto-ATPdiphosphohydrolase of Schistosoma mansoni by Thapsigargin
Authors: Martins Samantha M. , Torres Christiane R. , Ferreira Sérgio T.
Published: December 2002

ATPdiphosphohydrolases (ATPDases) are ubiquitous enzymes capable ofhydrolyzing nucleoside di- and triphosphates. Although a number ofpossible physiological roles have been proposed for ATPDases, detailedstudies on structure-function relationships have generally been hamperedby the lack of specific inhibitors of these enzymes. We have previouslycharacterized a Ca2+-activated ATPDase on the external surface ofthe tegument of Schistosoma mansoni, the etiologic agent of humanschistosomiasis. In the present work, we have examined the effectsof thapsigargin, a sesquiterpene lactone known as a high affinityinhibitor of sarco-endoplasmic reticulum calcium transport (SERCA)ATPase, on ATPDase activity. Whereas other lactones tested had littleor no inhibitory action, thapsigargin inhibited ATP hydrolysis by the ATPDase (Ki∼20 μM). Interestingly, hydrolysis of ADP was notinhibited by thapsigargin. The lack of inhibition of ATPase activityby orthovanadate, a specific inhibitor of P-type ATPases, and theinhibition of the Mg2+-stimulated ATP hydrolysis by thapsigarginruled out the possibility that the observed inhibition of the ATPDaseby thapsigargin could be due to the presence of contaminating SERCAATPases in our preparation. Kinetic analysis indicated that a singleactive site in the ATPDase is responsible for hydrolysis of both ATPand ADP. Thapsigargin caused changes in both Vmax and Km for ATP, indicating a mixed type of inhibition. Inhibition by thapsigarginwas little or not affected by changes in free Ca2+ or Mg2+concentrations. These results suggest that interaction of thapsigarginwith the S. mansoni ATPDase prevents binding of ATP or its hydrolysisat the active site, while ADP can still undergo catalysis.
Diagnosis of mitochondrial disorders: Clinical and biochemical approach
Authors: Thorburn D. R. , Smeitink J.
Published: December 2002

The topic of Workshop W3‐1 was clinical and biochemical approaches to the diagnosis of mitochondrial respiratory chain disorders. Four main questions were addressed in an attempt to make some progress towards a consensus diagnostic approach: What are the major limitations in diagnosis of respiratory chain dysfunction? What is the ideal approach to investigating children with a suspected respiratory chain disorder? Can we begin to develop consensus diagnostic criteria? Can we develop a quality assurance (QA) scheme for respiratory chain enzyme assays? The workshop demonstrated strong consensus on recognizing the limitations of current diagnostic approaches, on the ideal diagnostic approach and on the desirability of an enzyme QA scheme. There was also support for the desirability of consensus diagnostic criteria, albeit with some concerns about the practicality of gaining consensus. Two potential approaches to developing consensus criteria were described.
Life Stressors, Social Support, and Depressive Symptoms Among First‐Time Welfare Recipients
Authors: Kalil Ariel , Born Catherine E. , Kunz James , Caudill Pamela J.
Published: December 2002

This paper examines the associations among stressful life events, social support, and depressive symptoms in a sample of 580 first‐time welfare recipients. Self‐reported number of depressive symptoms was greater than in corresponding community samples. Stressors and social supports made independent main effect contributions to depressive symptoms in a multiple regression analysis. Women with transportation barriers to employment, those experiencing greater numbers of stressful life events, and those who were less satisfied with their housing situation reported greater numbers of depressive symptoms. In contrast, women who were more satisfied with their social support and those with higher attendance at religious services reported fewer depressive symptoms. Implications for welfare reform policy and programs are discussed.
Applications of mass spectrometry in the study of inborn errors of metabolism
Authors: Clayton P. T.
Published: December 2002

During the twentieth century, and particularly in its last decade, there have been major advances in mass spectrometry (MS). As a result, MS remains one of the most powerful tools for the investigation of genetic metabolic disease. Analysis of organic acids by gas chromatography–mass spectrometry (GC‐MS) and analysis of acylcarnitines by tandem mass spectrometry are still leading to the discovery of new disorders. Tandem mass spectrometry is increasingly being used for neonatal screening. New methods for lipid analysis have opened up the fields of inborn errors of cholesterol synthesis, of bile acid synthesis and of leukotriene synthesis. The latest developments in MS allow it to be used for determination of the amino acid sequence and posttranslational modifications of proteins. There are still some major hurdles to be overcome, but soon it should be possible to detect mutant proteins directly rather than by cDNA or genomic DNA analysis. Measurement of which proteins are overexpressed and underexpressed (‘proteomics’) should provide further information on the pathogenesis of complications of inborn errors, e.g. hepatic cirrhosis. The use of stable isotopes in conjunction with MS allows us to probe metabolic pathways. As an example, evidence is presented to support the contention that vitamin E and its oxidation product are catabolized by peroxisomal β‐oxidation. Mass spectrometry also has a major role in monitoring new forms of treatment for inborn errors.
A structural hypothesis for BH4 responsiveness in patients with mild forms of hyperphenylalaninaemia and phenylketonuria
Authors: Erlandsen H. , Stevens R. C.
Published: December 2002

Deficiencies in the human enzyme phenylalanine hydroxylase (PAH) due to mutations in the PAH gene (PAH) result in the inborn error of metabolism phenylketonuria (PKU). The clinical symptom of this disease is an elevated concentration of L‐phenylalanine (L‐Phe) in blood serum. To prevent mental retardation due to the buildup of neurotoxic metabolites of L‐Phe, patients with severe PKU must be treated with a low‐L‐Phe diet starting early in their life. Owing to extensive newborn screening programmes and genotyping efforts, more than 400 different mutations have been identified in the PAH gene. Recently, there have been several reports of PKU patients showing a normalization of their L‐Phe concentrations upon oral administration of the natural cofactor to PAH, (6R)‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4). In an attempt to correlate the clinical responsiveness to BH4 administration with PKU genotype, we propose specific structural consequences for this subset of PAH mutations. Based on the location and proximity of this subset of mutations to the cofactor‐binding site in the three‐dimensional structure of PAH, a hypothesis for BH4 responsiveness in PKU patients is presented. It is believed that some of these mutations result in expressed mutant enzymes that are Km variants (with a lower binding affinity for BH4) of the standard PAH enzyme phenotype. Oral administration of excess BH4 thus makes it possible for these mutant enzymes to suppress their low binding affinity for BH4, enabling this subset of PAH mutations to perform the L‐Phe hydroxylation reaction. Most of the BH4‐responsive PAH mutations map to the catalytic domain of PAH in either of two categories. Residues are located in cofactor‐binding regions or in regions that interact with the secondary structural elements involved in cofactor binding. Based on the series of known mutations that have been found to be responsive to BH4, we propose that other subsets of PAH mutations will have a high likelihood of being responsive to oral BH4 administration.
Effects of Two Highly Monounsaturated Oils on Lipid Composition and Enzyme Activities in Rat Jejunum
Authors: Vázquez Carmen M. , Zanetti Rosana , Santa-María Consuelo , Ruíz-Gutiérrez Valentina
Published: December 2002

The effects of two monounsaturated fatty acid (MUFA) oils, olive oil (OO)and high-oleic sunflower oil (HOSO), with high content in oleic acid butdiffering in their non-fatty acid fraction, on brush-border membrane(BBM) lipid composition and fluidity and on mucosal enzyme activitiesof rat jejunum were studied. Animals were given semipurified diet withlinoleic acid to prevent essential fatty acid deficiency (control group)or semipurified diet containing 10% of either OO or HOSO for 12weeks. There was a significant decrease in the content of jejunalBBM phospholipids together with an increase in the level of freecholesterol in both oil-fed rats, when compared to controlgroup. Although the increase in the BBM free cholesterol levelwas not statistically significant in HOSO-fed rats, a significantdecrease in the phospholipid/free cholesterol ratio was found inboth OO and HOSO-fed animals compared to control group. Rat jejunalBBM had a high level of free fatty acids which was increased in BBMisolated from OO and HOSO-fed animals. There was no statisticalsignificant difference in the phospholipid distribution between thecontrol and the OO group. However, HOSO-fed animals showed the lowestlevel of phosphatidylethanolamine together with the highestphosphatidylcholine content and the phosphatidylcholine/sphingomyelinratio. The fatty acid pattern of jejunal BBM lipids was modifiedaccording to the major fatty acids in the oils. There was a decreasein both stearic acid (18:0) and linoleic acid (18:2 n-6), togetherwith an increase in oleic acid (18:1 n-9) in jenunal BBM isolatedfrom both oil experimental groups. All these results were accompaniedby a significant increase in the BBM fluidity (as assessed bysteady-state fluorescence polarization of diphenylhexatriene) isolatedfrom oil-fed rat, when compared to control group. OO and HOSO-fedanimals had the lowest activities of sucrase and maltase, whilealkaline phosphatase activity only was decreased in HOSO-fedanimals. The specific activity of maltase was not modified in anyexperimental rats. In summary, both MUFA oils induced similar effectson jejunal BBM lipid composition, fluidity, sucrase, maltase andlactase activities. Furthermore, HOSO intake resulted in a lowestalkaline phosphatase activity which was accompanied by changes inindividual phospholipid composition. All these results suggest thateffects of MUFA oils on jejunal BBM lipid composition and hydrolaseactivities are most likely due to the presence of high content ofoleic acid rather than other components contained in the non-fattyacid of olive oil.
Mechanisms of Initiation of Membrane Fusion: Role of Lipids
Authors: Kinnunen Paavo K. J. , Holopainen Juha M.
Published: December 2002

Main emphasis in studies on the mechanisms of fusion of cellular membranes has been in the roles of various proteins, with far less interest in the properties of lipids. Yet, on a molecular level fusion involves the merging of lipid bilayers. Studies so far have revealed lipids forming inverted non-lamellar phases to be important in controlling membrane fusion. However, the underlying molecular level mechanisms have remained controversial. While this review is focused on presenting one possible mechanism, involving so-called extended lipid conformation, we are also advocating the view, that in order to obtain a more complete understanding of this process it is necessary to merge the relevant physicochemical properties of lipids with the models describing the specific functions of proteins. To this end, taking into account the central importance of fusion in a wide range of cellular processes, we may anticipate its control to open novel possibilities also for therapeutic intervention.
Building Value‐Based Partnerships: Toward Solidarity With Oppressed Groups
Authors: Nelson Geoffrey , Prilleltensky Isaac , MacGillivary Heather
Published: December 2002

We propose a value‐based conceptualization of partnership, defining partnership as relationships between community psychologists, oppressed groups, and other stakeholders, which strive to achieve key community psychology values (caring, compassion, community, health, self‐determination, participation, power‐sharing, human diversity, and social justice). These values guide partnership work related to the development of services or supports, coalitions and social action, and community research and program evaluation. We prescribe guidelines for building such partnerships and conclude by considering some of the challenges in implementing value‐based partnerships.
The Role of the Transmembrane and of the Intraviral Domain of Glycoproteins in Membrane Fusion of Enveloped Viruses
Authors: Schroth-Diez Britta , Ludwig Kai , Baljinnyam Bolormaa , Kozerski Christine , Huang Qiang , Herrmann Andreas
Published: December 2002

Fusion of enveloped viruses with their target membrane is mediated by viral integral glycoproteins. A conformational change of their ectodomain triggers membrane fusion. Several studies suggest that an extended, triple-stranded rod-shaped α-helical coiled coil resembles a common structural and functional motif of the ectodomain of fusion proteins. From that, it is believed that essential features of the fusion process are conserved among the various enveloped viruses. However, this has not been established so far for the highly conserved transmembrane and intraviral sequences of fusion proteins. The article will focus on the role of both sequences in the fusion process. Recent studies from various enveloped viruses strongly imply that a transmembrane domain with a minimum length is required for later steps of membrane fusion, i.e., the formation and enlargement of the aqueous fusion pore. Although no specific sequence of the TM is necessary for pore formation, distinct properties and motifs of the domain may be obligatory to ascertain full fusion activity. However, with some exceptions, the intraviral domain seems to be not required for fusion activity of viral fusion proteins.
How Urban African American Young Adolescents Spend Their Time: Time Budgets for Locations, Activities, and Companionship
Authors: Larson Reed W. , Richards Maryse H. , Sims Belinda , Dworkin Jodi
Published: December 2002

The time budgets of a population of youth provide important information about their daily experience and socialization. This study reports data on the time budgets of a sample of 253 urban African American poor to working‐ and middle‐class 5th–8th graders in Chicago. These youth were found to spend less time in school than other postindustrial adolescent populations, but spent no less time doing homework than White suburban U.S. young adolescents. They spent large quantities of time at home and with their families—at rates comparable to rates for young adolescents in a society with collectivist values like India. Unlike with other populations, early adolescence was not associated with major age changes in time allocations. Amount of time in schoolwork did not differ by grade, and amount of time with family did not show the decline with age that has been found for European American suburban adolescents.
Quantitative Analysis of Phospholipid Peroxidation and Antioxidant Protection in Live Human Epidermal Keratinocytes
Authors: Shvedova Anna A. , Tyurina Yulia Y. , Tyurina Vladimir A. , Kikuchi Yoko , Kagan Valerian E. , Quinn Peter J.
Published: December 2002

To characterize oxidative stress in phospholipids of normal human epidermal keratinocytes we metabolically labeled their membrane phospholipids with a natural oxidation-sensitive fluorescent fatty acid, cis-parinaric acid, and exposed the cells to two different sources of oxidants–a lipid-soluble azo-initiator of peroxyl radicals, 2,2′-azobis(2,4-dimethyl-valeronitrile), AMVN, and a superoxide generator, xanthine oxidase/xanthine. We demonstrated that both oxidants induced pronounced oxidation of four major classes of cis-parinaric acid-labeled phospholipids–phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol–in normal human epidermal keratinocytes that was not detectable as any significant change of their phospholipid composition. Vitamin E was effective in protecting the cells against phospholipid peroxidation. Since viability of normal human epidermal keratinocytes was not changed either by labeling or exposure to oxidants the labeling protocol and oxidative stress employed are compatible with the quantitative analysis of phospholipid peroxidation in viable cells.
Common Properties of Fusion Peptides from Diverse Systems
Authors: Martin Isabelle , Ruysschaert Jean-Marie
Published: December 2002

Although membrane fusion occurs ubiquitously and continuously in alleukaroytic cells, little is known about the mechanism that governs lipidbilayer fusion associated with any intracellular fusion reactions. Recentstudies of the fusion of enveloped viruses with host cell membranes havehelped to define the fusion process. The identification and characterizationof key proteins involved in fusion reactions have mainly driven recent advancesin our understanding of membrane fusion. The most important denominator amongthe fusion proteins is the fusion peptide. In this review, work done in thelast few years on the molecular mechanism of viral membrane fusion will behighlighted, focusing in particular on the role of the fusion peptide and themodification of the lipid bilayer structure. Much of what is known regardingthe molecular mechanism of viral membrane fusion has been gained using liposomesas model systems in which the molecular components of the membrane and the environmentare strictly controlled. Many amphilphilic peptides have a high affinity forlipid bilayers, but only a few sequences are able to induce membrane fusion. Thepresence of α-helical structure in at least part of the fusion peptideis strongly correlated with activity whereas, γ-structure tends to beless prevalent, associated with non-native experimental conditions, and morerelated to vesicle aggregation than fusion. The specific angle of insertionof the peptides into the membrane plane is also found to be an importantcharacteristic for the fusion process. A shallow penetration, extending onlyto the central aliphatic core region, is likely responsible for the destabilization ofthe lipids required for coalescence of the apposing membranes and fusion.
Hydrophobic-at-Interface Regions in Viral Fusion Protein Ectodomains
Authors: Nieva José L. , Suárez Tatiana
Published: December 2002

In this chapter we shall describe how to apply the hydrophobicity-at-interface scale, as proposed by Wimley and White [Wimley, W. C. and White, S. H. (1996) Nature Struct. Biol. 3:842–848], to the detection of amino acid sequences of viral envelope glycoproteins putatively engaged in interactions with the target membranes. In addition, a new approach will be briefly introduced to infer the bilayer location at equilibrium of membrane-partitioning sequences. The use of these new procedures may be important in describing the molecular mechanism leading to the formation of a fusion pore by viral glycoproteins.
Insights into a Structure-Based Mechanism of Viral Membrane Fusion
Authors: LeDuc Danika L. , Shin Yeon-Kyun
Published: December 2002

A number of different viral spike proteins, responsible for membrane fusion, show striking similarities in their core structures. The prospect of developing a general structure-based mechanism seems plausible in light of these newly determined structures. Influenza hemagglutinin (HA) is the best-studied fusion machine, whose action has previously been described by a hypothetical “spring-loaded” model. This model has recently been extended to explain the mechanism of other systems, such as HIV gp120–gp41. However, evidence supporting this idea is insufficient, requiring re-examination of the mechanism of HA-induced membrane fusion. Recent experiments with a shortened construct of HA, which is able to induce lipid mixing, have provided evidence for an alternative scenario for HA-induced membrane fusion and perhaps that of other viral systems.
Collaborating for Social Change: The Black Psychologist and the Black Community
Authors: Jordan Lisa C. , Bogat G. Anne , Smith Gloria
Published: December 2002

Several prominent Black scholars have argued that the predicament of Black intellectuals is inseparable from that of Black communities (C. West, 1994), and that Black psychologists should be at the forefront in developing culturally relevant psychological interventions (J. A. Baldwin, 1989). Yet, for Black psychologists there are a number of challenges to conducting successful interventions in Black communities, including historical abuses of Black communities by the “helping” professions and divergences in values, goals, and behaviors of professionals as compared to community members. In order for community psychologists to design interventions that are respectful of the cultural traditions and norms of Black communities, these obstacles to collaboration need to be addressed. This paper outlines some of the challenges faced by Black community psychologists, as well as the unique strengths they can mobilize when collaborating on research and interventions in Black communities. The paper also addresses methods of empowering Black communities and improving the training of community psychologists.