bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of quantitative trait loci that influence animal behavior
Authors: Flint Jonathan 
Published: December 2002

AbstractBehavioral differences between inbred strains of mice and rats have a genetic basis that can now be dissected using quantitative trait locus (QTL) analysis. Over the last 10 years, a large number of genetic loci that influence behavior have been mapped. In this article I review what that information has revealed about the genetic architecture of behavior. I show that most behaviors are influenced by QTL of small effect, each contributing to less than 10% of the variance of a behavioral trait. The small effect of each QTL on behavioral variation suggests that the mutational spectrum is different from that which results in Mendelian disorders. Regions of DNA should be appropriately prioritized to find the molecular variants, for instance by looking at sequences that control the level of gene expression rather than variants in coding regions. While the number of allelic loci that can contribute to a trait is large, this is not necessarily the case: the analysis of selected strains shows that a remarkably small number of QTL can explain the bulk of the genetic variation in behavior. I conclude by arguing that genetic mapping has more to offer than a starting point for positional cloning projects. With advances in multivariate analyses, mapping can also test hypotheses about the psychological processes that give rise to behavioral variation. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 46–77, 2003
Molecular approaches to aggregation behavior and social attachment
Authors: de Bono Mario 
Published: December 2002

AbstractIn many animal species individuals aggregate to live in groups. A range of experimental approaches in different animals, including studies of social feeding in nematodes, maternal behavior in rats and sheep, and pair‐bonding in voles, are providing insights into the neural bases for these behaviors. These studies are delineating multiple neural circuits and gene networks in the brain that interact in ways that are as yet poorly understood to coordinate social behavior. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 78–92, 2003
Genetic analysis of the circadian system in Drosophila melanogaster and mammals
Authors: Stanewsky Ralf 
Published: December 2002

AbstractThe fruit fly, Drosophila melanogaster, has been a grateful object for circadian rhythm researchers over several decades. Behavioral, genetic, and molecular studies helped to reveal the genetic bases of circadian time keeping and rhythmic behaviors. Contrary, mammalian rhythm research until recently was mainly restricted to descriptive and physiologic approaches. As in many other areas of research, the surprising similarity of basic biologic principles between the little fly and our own species, boosted the progress of unraveling the genetic foundation of mammalian clock mechanisms. Once more, not only the basic mechanisms, but also the molecules involved in establishing our circadian system are taken or adapted from the fly. This review will try to give a comparative overview about the two systems, highlighting similarities as well as specifics of both insect and murine clocks. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 111–147, 2003
Invertebrate models of drug abuse
Authors: Wolf Fred W. , Heberlein Ulrike 
Published: December 2002

AbstractSusceptibility to drug addiction depends on genetic and environmental factors and their complex interactions. Studies with mammalian models have identified molecular targets, neurochemical systems, and brain regions that mediate some of the addictive properties of abused drugs. Yet, our understanding of how the primary effects of drugs lead to addiction remains incomplete. Recently, researchers have turned to the invertebrate model systems Drosophila melanogaster and Caenorhabditis elegans to dissect the mechanisms by which abused drugs modulate behavior. Due to their sophisticated genetics, relatively simple anatomy, and their remarkable molecular similarity to mammals, these invertebrate models should provide useful insights into the mechanisms of drug action. Here we review recent behavioral and genetic studies in flies and worms on the effects of ethanol, cocaine, and nicotine, three of the most widely abused drugs in the world. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 161–178, 2003
Behavioral plasticity in C. elegans: Paradigms, circuits, genes
Authors: Hobert Oliver 
Published: December 2002

AbstractLife in the soil is an intellectual and practical challenge that the nematode Caenorhabditis elegans masters by utilizing 302 neurons. The nervous system assembled by these 302 neurons is capable of executing a variety of behaviors, some of respectable complexity. The simplicity of the nervous system, its thoroughly characterized structure, several sets of well‐defined behaviors, and its genetic amenability combined with its isogenic background make C. elegans an attractive model organism to study the genetics of behavior. This review describes several behavioral plasticity paradigms in C. elegans and their underlying neuronal circuits and then goes on to review the forward genetic analysis that has been undertaken to identify genes involved in the execution of these behaviors. Lastly, the review outlines how reverse genetics and genomic approaches can guide the analysis of the role of genes in behavior and why and how they will complement the forward genetic analysis of behavior. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 203–223, 2003
Neural substrates of memory: From synapse to system
Authors: Dubnau Josh , Chiang Ann‐Shyn , Tully Tim 
Published: December 2002

AbstractOne of the fundamental challenges of modern neuroscience is to understand how memories are acquired, stored, and retrieved by the brain. In the broadest terms, attempts to dissect memory can be broken down into four experimental disciplines: (1) identification of molecular components, (2) ex vivo and in vivo cellular analysis of neuronal function, (3) theoretical modeling approaches of neural systems, and (4) organismal‐level behavioral analyses. Our objective here is to offer a conceptually unifying perspective and to discuss this perspective in relation to an experiment analysis of memory in Drosophila. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 238–253, 2003
Cellular bases of behavioral plasticity: Establishing and modifying synaptic circuits in the Drosophila genetic system
Authors: Rohrbough Jeffrey , O'Dowd Diane K. , Baines Richard A. , Broadie Kendal 
Published: December 2002

AbstractGenetic malleability and amenability to behavioral assays make Drosophila an attractive model for dissecting the molecular mechanisms of complex behaviors, such as learning and memory. At a cellular level, Drosophila has contributed a wealth of information on the mechanisms regulating membrane excitability and synapse formation, function, and plasticity. Until recently, however, these studies have relied almost exclusively on analyses of the peripheral neuromuscular junction, with a smaller body of work on neurons grown in primary culture. These experimental systems are, by themselves, clearly inadequate for assessing neuronal function at the many levels necessary for an understanding of behavioral regulation. The pressing need is for access to physiologically relevant neuronal circuits as they develop and are modified throughout life. In the past few years, progress has been made in developing experimental approaches to examine functional properties of identified populations of Drosophila central neurons, both in cell culture and in vivo. This review focuses on these exciting developments, which promise to rapidly expand the frontiers of functional cellular neurobiology studies in Drosophila. We discuss here the technical advances that have begun to reveal the excitability and synaptic transmission properties of central neurons in flies, and discuss how these studies promise to substantially increase our understanding of neuronal mechanisms underlying behavioral plasticity. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 254–271, 2003
Modeling α‐helical coiled‐coil interactions: The axial and azimuthal alignment of 1B segments from vimentin intermediate filaments
Authors: Smith Thomasin A. , Hempstead Paul D. , Palliser Christopher C. , Parry David A.D. 
Published: December 2002

AbstractAttempts at predicting the relative axial alignments of fibrous protein molecules in filamentous structures have relied upon representing the (multichain) molecular structure by a one‐dimensional sequence of amino acids. Potential intermolecular ionic and apolar interactions were counted and determined as a function of the relative axial stagger between the molecules. No attempts were made to consider the azimuthal aspect of the interacting molecules and neither were apolar or ionic energy terms used. Surprisingly, this simple approach proved remarkably informative and yielded accurate predictions of the axial periods present. However, a more comprehensive analysis involving the energetics of aggregation taking due regard for the relative azimuths of the molecules as well as their separation should decrease the noise level in the calculations and reveal other pertinent information. Toward that end, we have modeled the interaction between two α‐helical coiled‐coil segments in intermediate filament molecules (1B segments from human vimentin). The relative axial alignment and polarity of the molecules is already known from detailed crosslinking studies and this provides a criterion against which the success (or otherwise) of the modeling can be judged. The results confirm that an antiparallel alignment of two 1B segments is preferred over any of the parallel options (as observed experimentally). The calculated axial alignment, however, is not identical to that observed from detailed crosslinking studies indicating that other parts of the molecule (probably the head and tail domains as well as other coiled‐coil segments) have a crucial role in determining the precise mode of axial aggregation. The results also show that the apolar interactions seem to be significantly less important in the alignment process than the ionic ones. This is consistent with the observation of a well‐defined period in the linear disposition of the charged (but not apolar) residues along the length of the outer surface of the vimentin molecule. Proteins 2003;50:207–212. © 2002 Wiley‐Liss, Inc.
High‐resolution structure and biochemical properties of a recombinant Proteus mirabilis catalase depleted in iron
Authors: Andreoletti Pierre , Sainz Germaine , Jaquinod Michel , Gagnon Jean , Jouve Hélène Marie 
Published: December 2002

AbstractHeme catalases are homotetrameric enzymes with a highly conserved complex quaternary structure, and their functional role is still not well understood. Proteus mirabilis catalase (PMC), a heme enzyme belonging to the family of NADPH‐binding catalases, was efficiently overexpressed in E. coli. The recombinant catalase (rec PMC) was deficient in heme with one‐third heme and two‐thirds protoporphyrin IX as determined by mass spectrometry and chemical methods. This ratio was influenced by the expression conditions, but the enzyme‐specific activity calculated relative to the heme content remained unchanged. The crystal structure of rec PMC was solved to a resolution of 2.0 Å, the highest resolution obtained to date with PMC. The overall structure was quite similar to that of wild‐type PMC, and it is surprising that the absence of iron had no effect on the structure of the active site. Met 53 close to the essential His 54 was found less oxidized in rec PMC than in the wild‐type enzyme. An acetate anion was modeled in an anionic pocket, away from the heme group but important for the enzymatic reaction. An alternate conformation observed for Arg 99 could play a role in the formation of the H‐bond network connecting two symmetrical subunits of the tetramer. Proteins 2003;50:261–271. © 2002 Wiley‐Liss, Inc.
BisANS binding to tubulin: Isothermal titration calorimetry and the site‐specific proteolysis reveal the GTP‐induced structural stability of tubulin
Authors: Gupta Suvroma , Chakraborty Shalmali , Poddar Asim , Sarkar Nabanita , Das Kali P. , Bhattacharyya Bhabatarak 
Published: December 2002

AbstractInteractions of bisANS and ANS to tubulin in the presence and absence of GTP were investigated, and the binding and thermodynamic parameters were determined using isothermal titration calorimetry. Like bisANS binding to tubulin, we observed a large number of lower affinity ANS binding sites (N1 = 1.3, K1 = 3.7 × 105 M−1, N2 = 10.5, K2 = 7 × 104/M−1) in addition to 1–2 higher affinity sites. Although the presence of GTP lowers the bisANS binding to both higher and lower affinity sites (N1 = 4.3, N2 = 11.7 in absence and N1 = 1.8, N2 = 3.6 in presence of GTP), the stoichiometries of both higher and lower affinity sites of ANS remain unaffected in the presence of GTP. BisANS‐induced structural changes on tubulin were studied using site‐specific proteolysis with trypsin and chymotrypsin. Digestion of both α and β tubulin with trypsin and chymotrypsin, respectively, has been found to be very specific in presence of GTP. GTP has dramatic effects on lowering the extent of nonspecific digestion of β tubulin with trypsin and stabilizing the intermediate bands produced from both α and β. BisANS‐treated tubulin is more susceptible to both trypsin and chymotrypsin digestion. At higher bisANS concentration (>20 μM) both α and β tubulins are almost totally digested with enzymes, indicating bisANS‐induced unfolding or destabilization of tubulin structure. Again, the addition of GTP has remarkable effect on lowering the bisANS‐induced enhanced digestion of tubulin as well as stabilizing effect on intermediate bands. These results of isothermal titration calorimetry, proteolysis and the DTNB‐kinetics data clearly established that the addition of GTP makes tubulin compact and rigid and hence the GTP‐induced stabilization of tubulin structure. No such destabilization of tubulin structure has been noticed with ANS, although, like bisANS, ANS possesses a large number of lower affinity binding sites. On the basis of these results, we propose that the unique structure of bisANS, which in absence of GTP can bind tubulin as a bifunctional ligand (through its two ANS moieties), is responsible for the structural changes of tubulin. Proteins 2003;50:283–289. © 2002 Wiley‐Liss, Inc.
Tumour grading from magnetic resonance spectroscopy: a comparison of feature extraction with variable selection
Authors: Huang Y. , Lisboa P. J. G. , El‐Deredy W. 
Published: December 2002

AbstractMagnetic resonance spectroscopy (MRS) provides a non‐invasive measurement of the biochemistry of living tissue. However, signal variation due to tissue heterogeneity causes considerable mixing between different disease categories, making accurate class assignments difficult. This paper compares a systematic methodology for classifier design using multivariate bayesian variable selection (MBVS), with one based on feature extraction using independent component analysis (ICA). We illustrate the methodology and assess the classification performance using a data set comprising 41 magnetic resonance spectra acquired in vivo from two grades of brain tumour, namely low‐ and medium‐grade astrocytic tumours, labelled astrocytomas (AST), and high‐grade gliomas and glioblastomas labelled glioblastomas (GL). The aim of this study is threefold. First, to describe the application of the alternative methodologies to MRS, then to benchmark their classification performance, and finally to interpret the classification models in terms of biologically relevant signals derived from the spectra. The classification performance is assessed using the bootstrap method and by application to a test sample in a retrospective study. Copyright © 2003 John Wiley & Sons, Ltd.
In vitro bioequivalence testing
Authors: Chow Shein‐Chung , Shao Jun , Wang Hansheng 
Published: December 2002

Abstract A statistical test is proposed for in vitro bioequivalence testing between drug products such as nasal aerosols and nasal sprays. The proposed test generalizes the one recommended in the FDA 1999 guidance to the situation where replicated observations obtained from each sampled canister or bottle of the drug product are available. The technique developed by Hyslop, Hsuan and Holder is used so that the proposed test is asymptotically accurate. The type I error probability and power of the proposed test are investigated through a simulation study. A method for determining the required sample size to achieve a desired power is also proposed. A numerical example is given for illustration. Copyright © 2003 John Wiley & Sons, Ltd.
Migration of DCE applications into CORBA and SOAP environments
Authors: Fatoohi R. , Jensen D. 
Published: December 2002

AbstractLegacy applications based on the Distributed Computing Environment (DCE) are subject to several significant limitations. As the development and support of DCE wanes, object‐oriented development becomes more desirable, and transmission over HTTP is established as the preferred protocol over the Internet, DCE application managers and developers are pressed to find extensions and alternatives to DCE. This paper briefly discusses several alternative targets for migration of DCE systems, then proceeds to detail, compare, and contrast two preferred candidates: CORBA and SOAP. Although we have found that developing a general migration solution for legacy DCE applications to CORBA or SOAP to be a non‐trivial, long‐term project, developing specific solutions that are based on a general architecture is feasible. Given a short list of reasonable premises, many DCE applications may be ported to technologies such as CORBA and SOAP. Copyright © 2002 John Wiley & Sons, Ltd.
Decorating tokens to facilitate recognition of ambiguous language constructs
Authors: Malloy Brian A. , Gibbs Tanton H. , Power James F. 
Published: December 2002

AbstractSoftware tools are fundamental to the comprehension, analysis, testing and debugging of application systems. A necessary first step in the development of many tools is the construction of a parser front‐end that can recognize the implementation language of the system under development. In this paper, we describe our use of token decoration to facilitate recognition of ambiguous language constructs. We apply our approach to the C++ language since its grammar is replete with ambiguous derivations such as the declaration/expression and template‐declaration/expression ambiguity. We describe our implementation of a parser front‐end for C++, keystone, and we describe our results in decorating tokens for our test suite including the examples from Clause Three of the C++ standard. We are currently exploiting the keystone front‐end to develop a taxonomy for implementation‐based class testing and to reverse‐engineer Unified Modeling Language (UML) class diagrams. Copyright © 2002 John Wiley & Sons, Ltd.
Conjoined twins in a monozygotic triplet pregnancy: Prenatal diagnosis and X‐inactivation
Authors: Zeng She Min , Yankowitz Jerome , Murray Jeffrey C. 
Published: December 2002

AbstractBackgroundThe etiology of monozygotic twinning is not known. Some investigators have implicated abnormal X‐inactivation, which could also be related to the increased female:male ratio in higher order multiple gestations in general, and in monozygotic and conjoined twins (CTS) in particular. CTS are rare, and even more unusual when part of a triplet pregnancy.MethodsDNA polymorphism analysis using 13 markers in the buccal cells of the triplets and the lymphocytes of the parents were used to evaluate zygosity. We investigated the X‐inactivation pattern of the triplets by analyzing methylation at the androgen receptor gene.ResultsWe found a female triplet gestation consisting of CTS and a normal singleton. The thoracopagus CTS were joined from the clavicles to the umbilicus. Congenital heart disease was suspected antenatally, but the precise delineation of the heart defects required extensive postnatal evaluation. There was a single placental mass with a thin dividing membrane. Cesarean section was carried out at 32 weeks after the onset of labor. Histologically, the placenta was diamniotic monochorionic. The normal singleton did well after delivery; the CTS died at 35 days from cardiopulmonary collapse. The babies were monozygotic (>99.99% probability). Each baby in this triplet set exhibited a random and symmetric X‐inactivation pattern. The degree of X‐inactivation skewing fell in the range of 50–65%.ConclusionGenetic or environmental factors other than abnormal X‐inactivation must be involved in causing monozygous multiple gestation or CTS. Despite prenatal diagnosis, shared myocardium or cardiac anomalies in CTS often determine the prognosis. Teratology 66:278–281, 2002. © 2002 Wiley‐Liss, Inc.
Effect of sera from women with systemic lupus erythematosus or antiphospholipid syndrome and recurrent abortions on human placental explants in culture
Authors: Yacobi Sarah , Ornoy Asher , Blumenfeld Zeev , Miller Richard K. 
Published: December 2002

AbstractBackgroundSystemic lupus erythematosus (SLE) with or without evidence of antiphospholipid antibodies (aPA) and antiphospholipid syndrome (APS) is associated with a high rate of spontaneous abortions. The placenta is thought to be the site of pathological damage in many of these abortions. To test this hypothesis, we studied the effects of sera obtained from women with SLE with or without treatment on human placental explants in culture.MethodsWe cultured 5.5‐ to 7.5‐week‐old human placental explants in a culture medium containing F‐12 DMEM and 10% FCS or in 90% human serum obtained from nonpregnant women with SLE prior to or after treatment. Culture was carried out for 96 hr. At the end of the culture period, we studied the secretion of the placental hormones estrogen (E2), progesterone (PGN), and human chorionic gonadotropin (hCG). In addition, we studied the proliferation rate (using PCNA staining) and the rate of apoptosis (using ApoTag) of the trophoblastic cells.ResultsPlacentae grew better in normal human serum than in a chemically defined medium of F‐12 DMEM and 10% FCS. Enhanced growth and higher secretion rates for hCG and estradiol (E2) were manifested in placentae cultured in control sera with no change in PGN secretion. Secretion rates of hCG and PGN (but not of E2in the treated group) by placental explants were similar to that of controls. However, the serum levels prior to culture were not measured. Further, explants in serum from untreated women with SLE produced a significant decrease in the proliferation rate of the trophoblastic cells and an increase of apoptosis. Treatment significantly reduced the apoptotic rate and increased cell proliferation, but the cell proliferation rate was still lower than that noted in controls.ConclusionsWe conclude that sera from women with SLE may directly damage the developing placenta reducing proliferation and enhancing apoptosis. Successful treatment of the women reduces that damage. Teratology 66:300–308, 2002. © 2002 Wiley‐Liss, Inc.