bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical Epistasis Is a Generic Feature of Gene Regulatory Networks
Authors: Gjuvsland Arne B , Hayes Ben J , Omholt Stig W , Carlborg Örjan 
Published: October 2006

Abstract
Functional dependencies between genes are a defining characteristic of gene networks underlying quantitative traits. However, recent studies show that the proportion of the genetic variation that can be attributed to statistical epistasis varies from almost zero to very high. It is thus of fundamental as well as instrumental importance to better understand whether different functional dependency patterns among polymorphic genes give rise to distinct statistical interaction patterns or not. Here we address this issue by combining a quantitative genetic model approach with genotype–phenotype models capable of translating allelic variation and regulatory principles into phenotypic variation at the level of gene expression. We show that gene regulatory networks with and without feedback motifs can exhibit a wide range of possible statistical genetic architectures with regard to both type of effect explaining phenotypic variance and number of apparent loci underlying the observed phenotypic effect. Although all motifs are capable of harboring significant interactions, positive feedback gives rise to higher amounts and more types of statistical epistasis. The results also suggest that the inclusion of statistical interaction terms in genetic models will increase the chance to detect additional QTL as well as functional dependencies between genetic loci over a broad range of regulatory regimes. This article illustrates how statistical genetic methods can fruitfully be combined with nonlinear systems dynamics to elucidate biological issues beyond reach of each methodology in isolation.
The Cdc34/SCF Ubiquitination Complex Mediates Saccharomyces cerevisiae Cell Wall Integrity
Authors: Varelas Xaralabos , Stuart David , Ellison Michael J , Ptak Christopher 
Published: October 2006

Abstract
To identify novel functions for the Cdc34/SCF ubiquitination complex, we analyzed genomewide transcriptional profiles of cdc53-1 and cdc34-2 Saccharomyces cerevisiae mutants. This analysis revealed altered expression for several gene families, including genes involved in the regulation of cell wall organization and biosynthesis. This led us to uncover a role for the Cdc34/SCF complex in the regulation of cell wall integrity. In support of this, cdc53-1 and cdc34-2 mutants exhibit phenotypes characteristic of cell wall integrity mutants, such as SDS sensitivity and temperature-sensitive suppression by osmotic stabilizers. Examination of these mutants revealed defects in their induction of Slt2 phosphorylation, indicating defects in Pkc1-Slt2 MAPK signaling. Consistent with this, synthetic genetic interactions were observed between the genes encoding the Cdc34/SCF complex and key components of the Pck1-Slt2 MAPK pathway. Further analysis revealed that Cdc34/SCF mutants have reduced levels of active Rho1, suggesting that these defects stem from the deregulated activity of the Rho1 GTPase. Altering the activity of Rho1 via manipulation of the Rho1-GAPs LRG1 or SAC7 affected Cdc34/SCF mutant growth. Strikingly, however, deletion of LRG1 rescued the growth defects associated with Cdc34/SCF mutants, whereas deletion of SAC7 enhanced these defects. Given the differential roles that these GAPs play in the regulation of Rho1, these observations indicate the importance of coordinating Cdc34/SCF activity with specific Rho1 functions.
Contribution of Growth and Cell Cycle Checkpoints to Radiation Survival in Drosophila
Authors: Jaklevic Burnley , Uyetake Lyle , Lemstra Willy , Chang Julia , Leary William , Edwards Anthony , Vidwans Smruti , Sibon Ody , Tin Su Tin 
Published: October 2006

Abstract
Cell cycle checkpoints contribute to survival after exposure to ionizing radiation (IR) by arresting the cell cycle and permitting repair. As such, yeast and mammalian cells lacking checkpoints are more sensitive to killing by IR. We reported previously that Drosophila larvae mutant for grp (encoding a homolog of Chk1) survive IR as well as wild type despite being deficient in cell cycle checkpoints. This discrepancy could be due to differences either among species or between unicellular and multicellular systems. Here, we provide evidence that Grapes is needed for survival of Drosophila S2 cells after exposure to similar doses of IR, suggesting that multicellular organisms may utilize checkpoint-independent mechanisms to survive irradiation. The dispensability of checkpoints in multicellular organisms could be due to replacement of damaged cells by regeneration through increased nutritional uptake and compensatory proliferation. In support of this idea, we find that inhibition of nutritional uptake (by starvation or onset of pupariation) or inhibition of growth factor signaling and downstream targets (by mutations in cdk4, chico, or dmyc) reduced the radiation survival of larvae. Further, some of these treatments are more detrimental for grp mutants, suggesting that the need for compensatory proliferation is greater for checkpoint mutants. The difference in survival of grp and wild-type larvae allowed us to screen for small molecules that act as genotype-specific radiation sensitizers in a multicellular context. A pilot screen of a small molecule library from the National Cancer Institute yielded known and approved radio-sensitizing anticancer drugs. Since radiation is a common treatment option for human cancers, we propose that Drosophila may be used as an in vivo screening tool for genotype-specific drugs that enhance the effect of radiation therapy.
The Puente Génave-Castelo de Vide shear zone (southern Central Iberian Zone, Iberian Massif): geometry, kinematics and regional implications
Authors: Parra Luis Miguel Martín , Lodeiro Francisco González , Poyatos David Martínez , Matas Jerónimo 
Published: October 2006

Abstract
This paper is concerned with the existence and the salient characteristics of an extensional shear zone (the Puente Génave-Castelo de Vide shear zone) along 400 km in the southern Central Iberian Zone. This shear zone is almost parallel to the previous Variscan structures, but it is slightly cross-cut by the discontinuous late Carboniferous Alburquerque-Pedroches batholithic alignment (which has been considered by some authors to be a fundamental feature for the sub-zonation of the Iberian Massif). The shear zone dips towards the S or SW, showing a top-to-the-S sense of movement. Early ductile deformation was concentrated along a band of andalusite-rich carbonaceous shales in the shear zone, but this can also be recognized in the footwall, particularly in the eastern sector, where the southern border of the (pre- to syn-kinematic) Santa Elena stock was intensely sheared; later intrusion of dyke-swarms agrees with the extensional stress field. Finally the shear zone appears brecchiated and bounded by two brittle faults. From a regional point of view, the shear zone described separates rocks with some differences regarding their stratigraphic, igneous and structural characteristics. These differences, and their precise limits, have been the basis for numerous subdivisions of this part of the Iberian Massif during the last decades. It is our contention that if any subzonation of the southern Central Iberian Zone is to be made (namely eg : Obejo-Valsequillo Domain, Lusitan-Marianic Domain), its northern boundary should be the Puente Génave-Castelo de Vide shear zone. As for the southern boundary, it is located in the Badajoz-Córdoba suture that separates the Central Iberian Zone from the Ossa-Morena Zone.
Earwitness identification performance: the effect of language, target, deliberate strategies and indirect measures
Authors: Philippon Axelle C. , Cherryman Julie , Bull Ray , Vrij Aldert 
Published: October 2006

AbstractThe present study examined whether voice identification performance is influenced by language comprehension (i.e. familiar vs. non‐familiar language) and target presence (target‐present (TP) vs. target‐absent line‐ups (TA)). It also looked at the relationship of deliberate strategies and indirect measures (i.e. confidence, difficulty and pressure) with performance. Sixty Native English speakers were exposed to an auditory event involving 45 to 50 seconds of speech. After 30 minutes delay, participants listened to a voice line‐up (TP or TA) in either a familiar (i.e. English) or unfamiliar language (i.e. French) according to the language spoken during the event, and were then asked to identify the original speaker's voice. Participants demonstrated significantly better performance for the familiar language/TP line‐ups. Participants who reported using the ‘elimination’ strategy were significantly more accurate than participants who reported using either a ‘matching’ strategy or no strategy. Indirect measures were not found to be good predictors of performance, except for confidence regarding TA accuracy. Copyright © 2006 John Wiley & Sons, Ltd.
The impact of experienced versus non‐experienced suggestions on children's recall of repeated events
Authors: Powell Martine B. , Roberts Kim P. , Thomson Donald M. , Ceci Stephen J. 
Published: October 2006

AbstractThree experiments were conducted to test the proposition that children's suggestibility about an occurrence of a repeated event is heightened when an interviewer suggests false details that were experienced in non‐target occurrences of the event as opposed to new details that never occurred. In each experiment, children participated in a repeated event during which specific items varied each time (e.g. the children always got a sticker but the theme of the sticker was different in each occurrence). Separate biasing and memory interviews were then conducted. In Experiment 1, the interviewer merely suggested that the false details might have occurred in the event. In the remaining experiments, the suggested details were clearly linked to the target occurrence with either a contextual or temporal cue. The potential moderating effect of the child's age (Experiment 1) and the retention interval (Experiments 1 and 2) were also examined. Consistent with the initial hypothesis, suggestions about experienced (non‐target) details were more likely to be repeated by the children compared to suggestions about non‐experienced details. In Experiments 2 and 3, experienced suggestions were also more likely to inhibit children's recall of the target occurrence. The relevance and generalizability of these findings to the legal setting are discussed. Copyright © 2006 John Wiley & Sons, Ltd.
“Pocket Dendrimers” as Nanoscale Receptors for Bimolecular Guest Accommodation
Authors: Shinoda Satoshi , Ohashi Masakazu , Tsukube Hiroshi 
Published: October 2006

AbstractA new series of dendrimer receptors was prepared by combining a (tetraphenylporphinato)zinc(II) core and benzyl ether type dendritic substituents. Since one direction of the (tetraphenylporphinato)zinc(II) was not substituted by a dendritic residue, the resulting unsymmetrical dendrimers have “pockets” available for access of external substrates. Molecular modeling, NMR measurements, and zinc‐coordination experiments revealed that the third‐generation dendrimer of this type exhibited characteristic inclusion of coordinative pyridine guests. When diamidopyridine moiety was introduced into the dendrimer pocket, a thymine derivative was bound through complementary hydrogen bonding. Two different kinds of substrates, pyridine and thymine derivatives, were simultaneously accommodated in the nanoscale pocket and bimolecular guest accommodation was realized with the designed dendrimer receptor.
Myosin16b: The COOH‐tail region directs localization to the nucleus and overexpression delays S‐phase progression
Authors: Cameron Richard S. , Liu Changdan , Mixon April S. , Pihkala Jeanene P. S. , Rahn Rebecca J. , Cameron Patricia L. 
Published: October 2006

AbstractRat Myo16a and Myo16b comprise the founding members of class XVI myosin and are characterized by an N‐terminal ankyrin repeat domain thought to mediate an association with protein phosphatase 1 catalytic subunits 1α and 1γ. Myo16b is the principal isoform and reveals predominant expression in developing neural tissue. Here, we use COS‐7 cells as a model system to develop an understanding of Myo16b function. We find that Myo16b displays predominant localization in the nucleus of cells transitioning through interphase, but is not associated with processes of mitosis. Using a panel of EGFP‐Myo16b‐expression plasmids in transient transfection studies, we identified the COOH‐terminal residues 1616–1912 as necessary and solely sufficient to target Myo16b to the nucleus. We show that the Myo16b‐tail region directs localization to a nuclear compartment containing profilin and polymerized actin, which appears to form a three‐dimensional meshwork through the depth of the nucleus. Further, we demonstrate that this compartment localizes within euchromatic regions of the genome and contains proliferating cell nuclear antigen (PCNA) and cyclin A, both markers of S‐phase of the cell cycle. Cells transiently expressing Myo16b or Myo16b‐tail region show limited incorporation of BrdU, delayed progression through S‐phase of the cell cycle, and curtailed cellular proliferation. Cell Motil. Cytoskeleton 2006. © 2006 Wiley‐Liss, Inc.
Periventricular efferent neurons in the optic tectum of rainbow trout
Authors: Kinoshita Masae , Ito Etsuro , Urano Akihisa , Ito Hironobu , Yamamoto Naoyuki 
Published: October 2006

AbstractThe efferent connections and axonal and dendritic morphologies of periventricular neurons were examined in the optic tectum of rainbow trout to classify periventricular efferent neurons in salmonids. Among the target nuclei of tectal efferents, tracer injections to the following four structures labeled periventricular neurons: the area pretectalis pars dorsalis (APd), nucleus pretectalis superficialis pars magnocellularis (PSm), nucleus ventrolateralis of torus semicircularis (TS), and nucleus isthmi (NI). Two types of periventricular neurons were labeled by injections to the APd. One of them had an apical dendrite ramifying at the stratum fibrosum et griseum superficiale (SFGS), with an axon that bifurcated into two branches at the stratum griseum centrale (SGC), and the other had an apical dendrite ramifying at the SGC. Two types of periventricular neurons were labeled after injections to the TS. One of them had an apical dendrite ramifying at the boundary between the stratum opticum (SO) and the SFGS, and the other had dendritic branches restricted to the stratum album centrale or stratum periventriculare. Injections to the PSm and NI labeled periventricular neurons of the same type with an apical dendrite ramifying at the SO and a characteristic axon that split into superficial and deep branches projecting to the PSm and NI, respectively. This cell type also possessed axonal branches that terminated within the tectum. These results indicate that periventricular efferent neurons can be classified into at least five types that possess type‐specific axonal and dendritic morphologies. We also describe other tectal neurons labeled by the present injections. J. Comp. Neurol. 499:546–564, 2006. © 2006 Wiley‐Liss, Inc.
Distribution and differentiation of microglia in the human encephalon during the first two trimesters of gestation
Authors: Monier Anne , Evrard Philippe , Gressens Pierre , Verney Catherine 
Published: October 2006

AbstractWe describe the topographical distribution of microglial subpopulations during development of the human diencephalon and telencephalon. Brains from embryos and fetuses age 5–23.5 gestational weeks (gw) were subjected to single‐ and double‐immunolabeling for lectin RCA‐1 (Ricinus Communis Agglutinin 1), Iba1 (a microglial marker), CD68 (specific of macrophages), CD45 (marker for mononucleate cells of hematopoietic lineage), CD34 (expressed on endothelial cells), and MIB1 and Ki67 (markers for cell proliferation). At 5.5 gw the first intracerebral microglial cells were seen close to the meninges and choroid plexus near the di‐telencephalic fissure. They were amoeboid and positive for Iba1, CD45, and RCA‐1, whereas cells in the deep parenchyma expressed Iba1/CD68/RCA‐1 and constituted clusters. In the developing diencephalon, microglial clusters were located in junctional regions of the white matter anlagen, most notably at the junctions of the internal capsule with the thalamic projections, the external capsule, and the cerebral peduncle. In the cortical anlagen, Iba1+/RCA‐1/CD68+/CD45+ cells accumulated at 10–12 gw, constituting a tangential band at the junction between the cortical plate and the subplate. Between 10 and 16 gw microglial clusters increased markedly in size and cellular density. Contact between Iba1+ microglia and CD34+ blood vessels was clearly visible from 10–12 gw onward, first in microglial clusters of the white matter anlagen and subsequently throughout the parenchyma. From the middle of the second trimester onward microglial cells colonized the entire cerebral parenchyma, developed a ramified morphology, and downregulated their surface antigens, but remained more numerous in the white matter. J. Comp. Neurol. 499:565–582, 2006. © 2006 Wiley‐Liss, Inc.
Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic vesicular transporter and postsynaptic scaffolding proteins
Authors: Henny Pablo , Jones Barbara E. 
Published: October 2006

AbstractOrexin/hypocretin (Orx) neurons are critical for the maintenance of waking in association with behavioral arousal and postural muscle tone, since with their loss narcolepsy with cataplexy occurs. Given that basal forebrain (BF) neurons project to the hypothalamus and play important diverse roles in sleep/wake states, we sought to determine whether acetylcholine (ACh), glutamate (Glu), and/or GABA‐releasing BF neurons innervate and could thereby differentially regulate the Orx neurons. From discrete injections of biotinylated dextran amine (BDA, 10,000 MW) into the magnocellular preoptic nucleus (MCPO) and substantia innominata (SI) in the rat, BDA‐labeled fibers projected to the lateral hypothalamus (LH), perifornical area (PF), and dorsomedial hypothalamus (DMH), where ∼41%, ∼11%, and 9% of Orx‐positive (+) neurons were respectively contacted in each region. Employing triple fluorescent staining for Orx, BDA, and presynaptic vesicular (V) transporters (T), we found that only 4% of the innervated Orx+ neurons in the LH were contacted by BDA+[VAChT+] terminals, whereas ∼31% and ∼67% were respectively contacted by BDA+[VGluT2+] and BDA+[VGAT+] terminals. In 3D‐rendered and rotated confocal images, we confirmed the latter contacts and examined staining for postsynaptic proteins PSD‐95, a marker for glutamatergic synapses, and gephyrin, a marker for GABAergic synapses, that were located on Orx+ neurons facing BDA‐labeled terminals in ∼20% and ∼50% of contacts, respectively. With such synaptic input, BF glutamatergic neurons can excite Orx neurons and thus act to maintain behavioral arousal with muscle tone, whereas GABAergic neurons can inhibit Orx neurons and thus promote behavioral quiescence and sleep along with muscle atonia. J. Comp. Neurol. 499:645–661, 2006. © 2006 Wiley‐Liss, Inc.
Modular neuropile organization in the Drosophila larval brain facilitates identification and mapping of central neurons
Authors: Iyengar Balaji G. , Chou C. Jennifer , Sharma Abhinav , Atwood Harold L. 
Published: October 2006

AbstractElucidating how neuronal networks process information requires identification of critical individual neurons and their connectivity patterns. For this purpose, we used the third‐instar Drosophila larval brain and applied reverse‐genetic tools, immunolabeling procedures, and 3D digital reconstruction software. Consistent topological definition of neuropile compartments in the larval brain can be obtained through simple fluorescence‐immunolabeling methods. The modular neuropiles can be used as a fiducial framework for mapping the projection patterns of individual neurons labeled with green fluorescent protein (GFP). GFP‐labeled neurons often exhibit dendrite‐like arbors as well as clustered varicose terminals on neurite branches that innervate identifiable neuropile compartments. We identified candidate cholinergic interneurons in genetic mosaic brains that overlap with the larval optic nerve terminus. By using the neuropile framework, we demonstrate that the candidate visual interneurons are not a subset of the previously identified circadian pacemaker neurons that also contact the larval optic nerve terminus; they may represent parallel pathways in the processing of visual inputs. Thus, in the Drosophila larval brain, modular neuropiles can be used as a framework for systematically identifying, mapping, and classifying interneurons; understanding their roles in behavior can then be pursued further. J. Comp. Neurol. 499:583–602, 2006. © 2006 Wiley‐Liss, Inc.
Perceived criticism, marital interaction and relapse in unipolar depression—findings from a Korean sample
Authors: Kwon Jung‐Hye , Lee Yuri , Lee Min‐Soo , Bifulco Antonia 
Published: October 2006

AbstractPerceived criticism by partner (PC) has been demonstrated to be a powerful predictor of depressive relapse. The purpose of this prospective 11‐month study was to replicate this finding in an outpatient series of married women in Korea, but also to further explore the nature of PC in terms of qualities of the marital relationship and dysfunctional attitudes. The subjects consisted of 27 married female outpatients who had all been treated for major depression, but were in recovery at time of first contact or shortly after. All were interviewed at time 1 and then again after 11 months at time 2 to ascertain major depressive episode using the Korean version of SADS as well as completing the BDI. At first contact, questionnaire and interview assessments were used for marital quality and dysfunctional attitudes denoting dependency. There was a significant relationship between the single‐item PC and depressive relapse at follow‐up as predicted. This relationship was not enhanced by using the expanded item scale. PC and/or PC‐E were significantly correlated with marital quality variables, specifically lack of emotional support from partner, negative interaction and dependence on partner. The study shows that perceived criticism by spouse is a predictor of depressive relapse in Korean outpatients and that this appears to reflect actual negative characteristics of the marital relationship as well as the depressed person's high dependence on the relationship. These results support the importance of improving marital interactions in preventing relapse in depression. Copyright © 2006 John Wiley & Sons, Ltd.
Factors influencing levels of research activity in clinical psychologists: a new model
Authors: Holttum Sue , Goble Laura 
Published: October 2006

AbstractThere are concerns in the USA and UK about low levels of research activity amongst clinical psychologists emerging from doctoral level training. The authors explore existing evidence and theory pertaining to this phenomenon. Three relevant theoretical strands are identified, along with related empirical studies and commentaries in practitioner journals. These different sources are integrated to suggest a more complete model of factors influencing clinical psychologists' research intentions, and in turn research activity itself: vocational preferences, research training experienced during qualifying training, practice context, value placed on expected outcomes of doing research, perceived norms for clinical psychologists in relation to doing research, research self‐efficacy, professional identity and, most tentatively, sex role identity. Our new model points to training interventions, either pre‐ or post‐qualification, that may increase the likelihood of clinical psychologists carrying out clinical research that will contribute to their profession's knowledge base, beyond their time in qualifying training. Copyright © 2006 John Wiley & Sons, Ltd.