bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Twinning and Slip in Deformation of a Zr-2.5Nb Tube
Authors: Kim Young S.
Published: May 2008

Tensile tests were conducted from RT to 400°C on tensile specimens taken from the tangential direction (TD) and the longitudinal direction (LD) of a Zr-2.5Nb tube with a strong tangential texture. When tensile stresses were applied to the TD with the tensile axis normal to the basal plane, {101¯2} twinning was activated. With the tensile stresses applied to the LD, however,  slip only was activated. The activation of twinning and slip in the TD and the LD, respectively, caused the tensile properties of the Zr-2.5Nb tube to become anisotropic, leading to higher yield and tensile strengths, and lower uniform and tensile elongations in the TD when compared to those in the LD. Furthermore, twinning promoted softening soon after yielding only in the TD, and localized deformation, while the  slip on the prism plane caused a larger strain hardening after yielding. With increasing temperature, the primary deformation mode changed from twinning to  slip in the TD and  slip to  slip in the LD, resulting in negative temperature dependences for the extent of strain hardening and tensile elongation of the Zr-2.5Nb tube in both directions. The yield stress plateau is discussed in view of the activation of twinning or  slip with a higher critical resolved shear stress that is strongly temperature dependent.
Transient Spine Expansion and Learning-Induced Plasticity in Layer 1 Primary Motor Cortex
Authors: Harms Kimberly J. , Rioult-Pedotti Mengia S. , Carter D. Rosy , Dunaevsky Anna
Published: May 2008

Experience-dependent regulation of synaptic strength in the horizontal connections in layer 1 of the primary motor cortex is likely to play an important role in motor learning. Dendritic spines, the primary sites of excitatory synapses in the brain, are known to change shape in response to various experimental stimuli. We used a rat motor learning model to examine connection strength via field recordings in slices and confocal imaging of labeled spines to explore changes induced solely by learning a simple motor task. We report that motor learning increases response size, while transiently occluding long-term potentiation (LTP) and increasing spine width in layer 1. This demonstrates learning-induced changes in behavior, synaptic responses, and structure in the same animal, suggesting that an LTP-like process in the motor cortex mediates the initial learning of a skilled task.
The Neural Mechanisms Underlying the Influence of Pavlovian Cues on Human Decision Making
Authors: Bray Signe , Rangel Antonio , Shimojo Shinsuke , Balleine Bernard , O'Doherty John P
Published: May 2008

In outcome-specific transfer, pavlovian cues that are predictive of specific outcomes bias action choice toward actions associated with those outcomes. This transfer occurs despite no explicit training of the instrumental actions in the presence of pavlovian cues. The neural substrates of this effect in humans are unknown. To address this, we scanned 23 human subjects with functional magnetic resonance imaging while they made choices between different liquid food rewards in the presence of pavlovian cues previously associated with one of these outcomes. We found behavioral evidence of outcome-specific transfer effects in our subjects, as well as differential blood oxygenation level-dependent activity in a region of ventrolateral putamen when subjects chose, respectively, actions consistent and inconsistent with the pavlovian-predicted outcome. Our results suggest that choosing an action incompatible with a pavlovian-predicted outcome might require the inhibition of feasible but nonselected action–outcome associations. The results of this study are relevant for understanding how marketing actions can affect consumer choice behavior as well as for how environmental cues can influence drug-seeking behavior in addiction.
Accurate Balance of the Polarity Kinase MARK2/Par-1 Is Required for Proper Cortical Neuronal Migration
Authors: Sapir Tamar , Sapoznik Sivan , Levy Talia , Finkelshtein Danit , Shmueli Anat , Timm Thomas , Mandelkow Eva-Maria , Reiner Orly
Published: May 2008

Radial neuronal migration is key in structuring the layered cortex. Here we studied the role of MARK2/Par-1 in this process. The dual name stands for the MAP/microtubule affinity-regulating kinase 2 (MARK2) and the known polarity kinase 1 (Par-1). Reduced MARK2 levels usingin uteroelectroporation resulted in multipolar neurons stalled at the intermediate zone border. Reintroduction of the wild-type kinase postmitotically improved neuronal migration. Our results indicated that reduction in MARK2 affected centrosomal dynamics in migrating neurons of the cerebral cortex. Increased MARK2 has been shown to destabilize microtubules, and here we show for the first time that reduced MARK2 stabilized microtubules in primary cultured neurons. Kinase-independent activity permitted multipolar-to-bipolar transition but did not restore proper migration. Increased MARK2 levels resulted in a different phenotype, which is loss of neuronal polarity. MARK2 kinase activity reduction hindered migration in the developing brain, which was rescued by increasing kinase activity. Our results stress the necessity of maintaining dynamic microtubules for proper neuronal migration. Furthermore, the exact requirements for MARK2 and its kinase activity vary during the course of neuronal migration. Collectively, our results stress the requirements for the different roles of MARK2 during neuronal migration.
Pronounced Reduction of Digit Motor Responses Evoked from Macaque Ventral Premotor Cortex after Reversible Inactivation of the Primary Motor Cortex Hand Area
Authors: Schmidlin Eric , Brochier Thomas , Maier Marc A. , Kirkwood Peter A. , Lemon Roger N.
Published: May 2008

In common with other secondary motor areas, the macaque ventral premotor cortex (PMv) gives rise to corticospinal projections; it also makes numerous reciprocal corticocortical connections with the primary motor cortex (M1). Repetitive intracortical microstimulation (rICMS) of the PMv gives rise to movements of the hand and digits. To investigate whether these motor effects are dependent on the corticocortical interactions with M1, the effect of reversible inactivation of the M1 hand area was tested in three macaque monkeys with chronically implanted intracortical electrodes in the hand representations of M1 and PMv (rostral division, area F5). Monkeys were lightly sedated. Test EMG responses to rICMS were recorded from intrinsic hand muscles before and after microinjection of the GABA agonist muscimol in the M1 hand area. This not only greatly reduced EMG responses evoked from M1, but also reduced or abolished responses from F5, over a similar time course (20–50 min). Muscimol in M1 reduced the level of background EMG activity in the contralateral hand, which was paretic for several hours after injection. However, because EMG responses to direct activation of the corticospinal tract were significantly less affected than the responses to F5 stimulation, it is unlikely that reduced motoneuronal excitability explained the loss of the evoked responses from F5. Finally, muscimol injections in M1 greatly reduced the corticospinal volleys evoked by rICMS in F5. The results suggest that the motor effects evoked from F5 depend, at least in part, on corticocortical interactions with M1, leading to activation of M1 corticospinal outputs to hand muscles.
An Essential Role for Frizzled5 in Neuronal Survival in the Parafascicular Nucleus of the Thalamus
Authors: Liu Chunqiao , Wang Yanshu , Smallwood Philip M. , Nathans Jeremy
Published: May 2008

Frizzled5 (Fz5), a putative Wnt receptor, is expressed in the retina, hypothalamus, and the parafascicular nucleus (PFN) of the thalamus. By constructingFz5alleles in which β-galactosidase replaces Fz5 or in which Cre-mediated recombination replaces Fz5 with alkaline phosphatase, we observe that Fz5 is required continuously and in a cell autonomous manner for the survival of adult PFN neurons, but is not required for proliferation, migration, or axonal growth and targeting of developing PFN neurons. A motor phenotype associated with loss of Fz5 establishes a role for the PFN in sensorimotor coordination. Transcripts coding for Wnt9b, the likely Fz5 ligandin vivo, and β-catenin, a mediator of canonical Wnt signaling, are both downregulated in theFz5−/−PFN, implying a positive feedback mechanism in which Wnt signaling is required to maintain the expression of Wnt signaling components. These data suggest that defects in Wnt–Frizzled signaling could be the cause of neuronal loss in degenerative CNS diseases.
Cell-Autonomous Roles of ARX in Cell Proliferation and Neuronal Migration during Corticogenesis
Authors: Friocourt Gaëlle , Kanatani Shigeaki , Tabata Hidenori , Yozu Masato , Takahashi Takao , Antypa Mary , Raguénès Odile , Chelly Jamel , Férec Claude , Nakajima Kazunori , Parnavelas John G.
Published: May 2008

The aristaless-related homeobox (ARX) gene has been implicated in a wide spectrum of disorders ranging from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of X-linked mental retardation without apparent brain abnormalities. To better understand its role in corticogenesis, we usedin uteroelectroporation to knock down or overexpress ARX. We show here that targeted inhibition of ARX causes cortical progenitor cells to exit the cell cycle prematurely and impairs their migration toward the cortical plate. In contrast, ARX overexpression increases the length of the cell cycle. In addition, we report that RNA interference-mediated inactivation of ARX prevents cells from acquiring multipolar morphology in the subventricular and intermediate zones, resulting in decreased neuronal motility. In contrast, ARX overexpression appears to promote the development of tangentially oriented processes of cells in the subventricular and intermediate zones and affects radial migration of pyramidal neurons. We also demonstrate that the level of ARX expression is important for tangential migration of GABA-containing interneurons, because both inactivation and overexpression of the gene impair their migration from the ganglionic eminence. However, our data suggest that ARX is not directly involved in GABAergic cell fate specification. Overall, these results identify multiple and distinct cell-autonomous roles for ARX in corticogenesis.
Methamphetamine Causes Microglial Activation in the Brains of Human Abusers
Authors: Sekine Yoshimoto , Ouchi Yasuomi , Sugihara Genichi , Takei Nori , Yoshikawa Etsuji , Nakamura Kazuhiko , Iwata Yasuhide , Tsuchiya Kenji J. , Suda Shiro , Suzuki Katsuaki , Kawai Masayoshi , Takebayashi Kiyokazu , Yamamoto Shigeyuki , Matsuzaki Hideo , Ueki Takatoshi , Mori Norio , Gold Mark S. , Cadet Jean L.
Published: May 2008

Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [11C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([11C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [11C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [11C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher;p< 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p< 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.
Spine Expansion and Stabilization Associated with Long-Term Potentiation
Authors: Yang Yunlei , Wang Xiao-bin , Frerking Matthew , Zhou Qiang
Published: May 2008

Stable expression of long-term synaptic plasticity is critical for the developmental refinement of neural circuits and for some forms of learning and memory. Although structural remodeling of dendritic spines is associated with the stable expression of long-term potentiation (LTP), the relationship between structural and physiological plasticity remains unclear. To define whether these two processes are related or distinct, we simultaneously monitored EPSPs and dendritic spines, using combined patch-clamp recording and two-photon time-lapse imaging in the same CA1 pyramidal neurons in acute hippocampal slices. We found that theta burst stimulation paired with postsynaptic spiking, which reliably induced LTP, also induced a rapid and persistent expansion of dendritic spines. Like LTP, this expansion was NMDA receptor dependent. Spine expansion occurred even when LTP was inhibited by postsynaptic inhibition of exocytosis or PKA (protein kinase A); however, under these conditions, the spine expansion was unstable and collapsed spontaneously. Furthermore, similar changes in LTP and spine expansion were observed when hippocampal neurons were treated with protein synthesis inhibitors. Like LTP, spine expansion was reversed by low-frequency stimulation (LFS) via a phosphatase-dependent mechanism, but only if the LFS was applied in a critical time window after induction. These results indicate that the initial expression of LTP and spine expansion is dissociable, but there is a high degree of mechanistic overlap between the stabilization of structural plasticity and LTP.
Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway
Authors: Chen Yong , Geis Christian , Sommer Claudia
Published: May 2008

Tolerance to the analgesic effects of opioids occurs after their chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we investigated the role of TRPV1, which is crucial for the transduction of noxious chemical and thermal stimuli, in morphine tolerance and tolerance-associated thermal hyperalgesia. After chronic morphine treatment, a marked increase in TRPV1 immunoreactivity (IR) was detected in L4 dorsal root ganglion (DRG) neurons, spinal cord dorsal horn, and sciatic nerve. Real-time reverse transcription (RT)-PCR demonstrated that TRPV1 mRNA was upregulated in spinal cord and sciatic nerve but not in the DRG. Intrathecal pretreatment with SB366791 [N-(3-methoxyphenyl)-4-chlorocinnamide], a selective antagonist of TRPV1, attenuated both morphine tolerance and associated thermal hyperalgesia. Chronic morphine exposure induced increases in phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK-IR, extracellular signal-regulated protein kinase (ERK)-IR, and c-Jun N-terminal kinase (JNK)-IR, in L4 DRG neurons. Intrathecal administration of the selective p38, ERK, or JNK inhibitors not only reduced morphine tolerance and associated thermal hyperalgesia but also suppressed the morphine-induced increase of TRPV1-IR in DRG neurons, spinal cord, and sciatic nerve and of mRNA levels in spinal cord and sciatic nerve. Together, we have identified a novel mechanism by which sustained morphine treatment results in tolerance and tolerance-associated thermal hyperalgesia, by regulating TRPV1 expression, in a MAPK-dependent manner. Thus, blocking TRPV1 might be a way to reduce morphine tolerance.
Out-of-equilibrium charge density distribution of spin crossover complexes from steady-state photocrystallographic measurements: experimental methodology and results
Authors: Pillet Sébastien , Legrand Vincent , Weber Hans-Peter , Souhassou Mohamed , Létard Jean-François , Guionneau Philippe , Lecomte Claude
Published: May 2008

The electron density distribution of a light-induced molecular excited state, i.e. the high spin metastable state of [Fe(phen)2(NCS)2], was determined from steady-state photocrystallographic measurements. We defined the experimental conditions under which the accuracy of the measured diffraction data is compatible with an electron density analysis. These include: (i) a large structural and electronic contrast between high spin (HS) and low spin (LS) states, (ii) an efficient photoconversion under light irradiation and (iii) slow relaxation of the HS metastable state. Multipolar modeling of the electron density yielded a deformation density and 3d-orbital populations for Fe(II) characteristic of a high spin (t
2g
4
e
g
2) electron configuration and support the assumption of significant σ-donation and π-backbonding of the Fe—N interactions. The electron density distribution in the intermolecular regions confirms anisotropic intermolecular interactions with possibly a layer topology parallel to the orthorhombic (ab) plane, related to the system cooperativity.
Light-induced phase separation (LIPS) into like-spin phases observed by Laue neutron diffraction on a single crystal of [Fe(ptz)6](BF4)2
Authors: Varret François , Boukheddaden Kamel , Goujon Antoine , Gillon Béatrice , McIntyre Garry J.
Published: May 2008

We have followed the photo-transformation, the light-induced thermal hysteresis, and the light-induced phase separation (LIPS) into like-spin phases on a [Fe(ptz)6](BF4)2 single crystal, in the quenched rhombohedral phase, through the analysis of neutron Laue diffraction patterns. In agreement with the analysis of previous magnetic measurements, phase separation was observed in the close vicinity of the static light-induced instability, but not otherwise. The positions of the Laue spots were analysed in terms of variation in the a/c lattice-parameter ratio which is well correlated with the variation of the high-spin fraction predicted by a simple homogeneous mean-field model. Using a mapped version of the same model, we analyzed the line shapes of the Laue spots during photo-excitation and relaxation experiments so as to determine the width of the distribution of irradiation intensities, a crucial parameter in phase separation. The predictions of the mapped model failed to reproduce the rapid initial kinetics of the phase separation process, but were in agreement with the further evolution. These features are attributed to a nucleation and growth process, for which the crossover from microscopic to macroscopic regimes has been observed.
State of the art and opportunities in probing photoinduced phase transitions in molecular materials by conventional and picosecond X-ray diffraction
Authors: Collet Eric , Buron-Le Cointe Marylise , Lorenc Maciej , Cailleau Hervé
Published: May 2008

The optical control of the macroscopic physical properties (magnetic, optical …) of a material by laser irradiation is gaining interest through the emerging field of photoinduced phase transitions. Light-induced changes of the macroscopic state of a material involves subtle coupling between the electronic and structural degrees of freedom, which are essential to stabilize the photo-excited state, different in nature from the stable state. Therefore the new experimental field of photocrystallography plays a key role. It goes far beyond simple structural analysis under laser excitation. By playing on different physical parameters and developing the techniques and analysis, one can investigate new out of equilibrium physics through light-driven cooperative dynamics and transformations in materials. This paper is reviewing different aspects of the use of photocrystallography to investigate the nature, the mechanisms and the dynamics of photoinduced phase transitions for photo-steady or long-lived states, as well as transformations driven by an ultra-short light pulse. We also give a brief overview on recent advances in time-resolved crystallography with 100 ps resolution.
Real-time studies of reversible lattice dynamics by femtosecond X-ray diffraction
Authors: v. Korff Schmising Clemens , Bargheer Matias , Woerner Michael , Elsaesser Thomas
Published: May 2008

Ultrafast X-ray diffraction allows for observing structural dynamics of condensed matter in real-time, in this way directly probing reversible and irreversible geometry changes on atomic length and time scales. This article reports recent progress in this rapidly developing field, focusing on experimental work performed with laser-driven X-ray sources. After an introduction into the state-of-the-art methods for generation and measurement, we discuss coherent lattice motions of ferroelectric nanolayered systems and structural dynamics related to polar dipole solvation in bulk molecular crystals.
Exploiting EXAFS and XANES for time-resolved molecular structures in liquids
Authors: Bressler Christian , Abela Rafael , Chergui Majed
Published: May 2008

Time-resolved X-ray absorption fine structure (XAFS) spectroscopy with picosecond temporal resolution is a new method to observe electronic and geometric structures of short-lived reaction intermediates. It combines an intense femtosecond laser source synchronized to the X-ray pulses delivered by a synchrotron Swiss light source (SLS). We present key experiments on charge transfer reactions as well as spin-crossover processes in coordination chemistry compounds next to solvation dynamics studies of photogenerated atomic radicals. These examples emphasize the observables at hand using ultrafast XAFS techniques, which include the density of states, full and even partial changes in oxidation state, and internuclear distances with milli-Angström accuracy. An outlook towards femtosecond studies and biologically relevant systems stresses the high potential of XAFS methods using new femtosecond X-ray sources like free electron lasers (XFELs).
Home-based time-resolved photo small angle X-ray diffraction and its applications
Authors: Quevedo Wilson , Petri Marcel , Techert Simone
Published: May 2008

An experimental outline will be given for home-based time-resolved photo small angle X-ray diffraction apparatus. Depending on the time-resolution of the optical laser excitation source, the readout time of the detector and their relative time jitter, time resolutions down to some hundred microseconds might be achieved. Even though the X-ray flux might be low, as expected for sealed tube kind of sources, experiments with a sufficient signal/noise ratio can be performed by applying a stroboscopic mode. The method of photo small angle X-ray scattering will be applied to photo-sensitized liquid crystal systems demonstrating the possibility of photo-inducing a phase transition between a liquid crystal and a microemulsion phase in this type of material.
DFT study of crystalline nitrosyl compounds
Authors: Delley Bernard
Published: May 2008

Nitrosyl linkage isomer compounds are investigated with density functional theory for realistic crystal structures. As compared to free anion models, significant differences are found for various properties. At the metastable state S1, a crystal environment contribution of 30–40 cm−1 to the red shift exists. The barrier against thermal decomposition of S1 in SNP is significantly lowered by 300 meV.
DFT study of metastable linkage isomers of six-coordinate ruthenium nitrosyl complexes
Authors: Sizova Olga V. , Lubimova Olga O. , Sizov Vladimir V. , Ivanova Nina V.
Published: May 2008

The linkage isomers of the [M(NO)(CN)5]2− (M = Fe, Ru, Os), [Ru(NO)Cl5]2−, trans-[Ru(NO)(NH3)4(L)]q+ (L = NH3, H2O, nicotinamide, imidazole, pyridine, pyrazine, NO2
−, OH−, Cl−), and trans-[Ru(NO)L4(OH)]q (L = pyridine, NO2
−) ions are studied by density functional theory. DFT calculations show that the electronic ground-state potential surface of these nitrosyl complexes has the local minima corresponding to η
2-NO and η
1-O linkage isomers, of which the former is characterized by lower energy. The stationary points on the ground state potential energy surface along the GS → MS2 → MS1 path for the [M(NO)(CN)5]2− (M = Fe, Ru, Os) and [Ru(NO)Cl5]2− complexes were found. The calculations of infrared spectra of linkage isomers [Ru(NO)Cl5]2− and [Ru(NO)(CN)5]2− are carried out. The analysis of quantum chemical bond orders indicates a noticeable delocalization of π-electron density along the Ltrans—M—NO axis and a possibility of direct interactions between NO and equatorial ligands in the structures with the bent {MNO} group.
Applications of photocrystallography: a future perspective
Authors: Cole Jacqueline M.
Published: May 2008

The applied potential of photocrystallography is discussed herein. In particular, its ability to help realise new generation ‘smart’ materials for the opto-electronics industry, alternative photovoltaic solar cells, and health science, is discussed. Where relevant photocrystallographic studies have already been reported, examples are given and put into the context of potential device applicability. In certain areas of photonics research, there are no current photocrystallographic results specifically pertaining to the perceived application described. Here, the likely type of results is projected since this perspective is designed deliberately to look ahead as to what advances photo-crystallography could bring to the photonics research area that continues to develop so rapidly. Brief reference to global economic, environmental and health considerations are also made in relevant places in order to put the subject onto a world setting.
Schizosaccharomyces pombeBub3 Is Dispensable for Mitotic Arrest Following Perturbed Spindle Formation
Authors: Tange Yoshie , Niwa Osami
Published: May 2008

The core proteins of the spindle assembly checkpoint (SAC), Mads, Bubs, and Mps1, first identified in the budding yeast, are thought to be functionally and structurally conserved through evolution. We found that fission yeast Bub3 is dispensable for SAC, as bub3 null mutants blocked mitotic progression when spindle formation was disrupted. Consistently, the bub3 mutation only weakly affected the stability of minichromosome Ch16 compared with other SAC mutants. Fission yeast Rae1 has sequence homology with Bub3. The bub3 rae1 double mutant and rae1 single mutant did not have defective SAC, suggesting that these genes do not have overlapping roles for SAC. Observations of living cells revealed that the duration of the mitotic prometaphase/metaphase was longer in the bub3 mutant and was Mad2 dependent. Further, the bub3 mutant was defective in sister centromere association during metaphase. Together, these findings suggest that fission yeast Bub3 is required for normal spindle dynamics, but not for SAC.
Positional Cloning of a Bombyx Wingless Locus flügellos (fl) Reveals a Crucial Role for fringe That Is Specific for Wing Morphogenesis
Authors: Sato Kaoru , Matsunaga Tomoko Matsuoka , Futahashi Ryo , Kojima Tetsuya , Mita Kazuei , Banno Yutaka , Fujiwara Haruhiko
Published: May 2008

Mutations at the flügellos (fl) locus in Bombyx mori produce wingless pupae and moths because of the repressed response of wing discs to ecdysteroid. Four recessive fl alleles occurred spontaneously and were mapped at 13.0 of the silkworm genetic linkage group 10. By positional cloning, we confirmed that the gene responsible for fl is fringe (fng) encoding Fng glycosyltransferase, which is involved in regulating the Notch signaling pathway. In four different fl alleles, we detected a large deletion of the fng gene in flk and nonsense mutations in fl, flo, and fln. In the wild-type (WT) silkworm, fng is expressed actively in the wing discs, brain, and reproductive organs from the fourth to final instars but barely in the other tissues tested. In situ hybridization showed that fng mRNA is expressed in the dorsal layer of the WT wing discs. The wingless (wg) mRNA, a downstream marker of Fng-mediated Notch signaling, is localized at the dorsoventral boundary in the WT wing discs but repressed markedly in the fl wing discs. Although null mutants of Drosophila fng result in postembryonic lethality, loss of fng function in Bombyx affects only wing morphogenesis, suggesting different essential roles for fng in tissue differentiation among insects.
Identification of Mutations in Caenorhabditis elegans That Cause Resistance to High Levels of Dietary Zinc and Analysis Using a Genomewide Map of Single Nucleotide Polymorphisms Scored by Pyrosequencing
Authors: Bruinsma Janelle J , Schneider Daniel L , Davis Diana E , Kornfeld Kerry
Published: May 2008

Zinc plays many critical roles in biological systems: zinc bound to proteins has structural and catalytic functions, and zinc is proposed to act as a signaling molecule. Because zinc deficiency and excess result in toxicity, animals have evolved sophisticated mechanisms for zinc metabolism and homeostasis. However, these mechanisms remain poorly defined. To identify genes involved in zinc metabolism, we conducted a forward genetic screen for chemically induced mutations that cause Caenorhabditis elegans to be resistant to high levels of dietary zinc. Nineteen mutations that confer significant resistance to supplemental dietary zinc were identified. To determine the map positions of these mutations, we developed a genomewide map of single nucleotide polymorphisms (SNPs) that can be scored by the high-throughput method of DNA pyrosequencing. This map was used to determine the approximate chromosomal position of each mutation, and the accuracy of this approach was verified by conducting three-factor mapping experiments with mutations that cause visible phenotypes. This is a generally applicable mapping approach that can be used to position a wide variety of C. elegans mutations. The mapping experiments demonstrate that the 19 mutations identify at least three genes that, when mutated, confer resistance to toxicity caused by supplemental dietary zinc. These genes are likely to be involved in zinc metabolism, and the analysis of these genes will provide insights into mechanisms of excess zinc toxicity.
An Approximate Bayesian Computation Approach to Overcome Biases That Arise When Using Amplified Fragment Length Polymorphism Markers to Study Population Structure
Authors: Foll Matthieu , Beaumont Mark A , Gaggiotti Oscar
Published: May 2008

There is great interest in using amplified fragment length polymorphism (AFLP) markers because they are inexpensive and easy to produce. It is, therefore, possible to generate a large number of markers that have a wide coverage of species genomes. Several statistical methods have been proposed to study the genetic structure using AFLPs but they assume Hardy–Weinberg equilibrium and do not estimate the inbreeding coefficient, FIS. A Bayesian method has been proposed by Holsinger and colleagues that relaxes these simplifying assumptions but we have identified two sources of bias that can influence estimates based on these markers: (i) the use of a uniform prior on ancestral allele frequencies and (ii) the ascertainment bias of AFLP markers. We present a new Bayesian method that avoids these biases by using an implementation based on the approximate Bayesian computation (ABC) algorithm. This new method estimates population-specific FIS and FST values and offers users the possibility of taking into account the criteria for selecting the markers that are used in the analyses. The software is available at our web site (http://www-leca.ujf-grenoble.fr/logiciels.htm). Finally, we provide advice on how to avoid the effects of ascertainment bias.
Delimiting the Frequency of Paternal Leakage of Mitochondrial DNA in Chinook Salmon
Authors: Wolff Jonci N , Gandre Sandra , Kalinin Aleksander , Gemmell Neil J
Published: May 2008

We analyzed embryos of a wild-return hatchery population of chinook salmon for the presence of paternal mtDNA. None of the 10,082 offspring examined revealed paternally transmitted DNA, delimiting the maximum frequency of paternal leakage in this system to 0.03% (power of 0.95) and 0.05% (power of 0.99).
High DNA Sequence Diversity in Pericentromeric Genes of the Plant Arabidopsis lyrata
Authors: Kawabe Akira , Forrest Alan , Wright Stephen I , Charlesworth Deborah
Published: May 2008

Differences in neutral diversity at different loci are predicted to arise due to differences in mutation rates and from the “hitchhiking” effects of natural selection. Consistent with hitchhiking models, Drosophila melanogaster chromosome regions with very low recombination have unusually low nucleotide diversity. We compared levels of diversity from five pericentromeric regions with regions of normal recombination in Arabidopsis lyrata, an outcrossing close relative of the highly selfing A. thaliana. In contrast with the accepted theoretical prediction, and the pattern in Drosophila, we found generally high diversity in pericentromeric genes, which is consistent with the observation in A. thaliana. Our data rule out balancing selection in the pericentromeric regions, suggesting that hitchhiking is more strongly reducing diversity in the chromosome arms than the pericentromere regions.
Bayesian LASSO for Quantitative Trait Loci Mapping
Authors: Yi Nengjun , Xu Shizhong
Published: May 2008

The mapping of quantitative trait loci (QTL) is to identify molecular markers or genomic loci that influence the variation of complex traits. The problem is complicated by the facts that QTL data usually contain a large number of markers across the entire genome and most of them have little or no effect on the phenotype. In this article, we propose several Bayesian hierarchical models for mapping multiple QTL that simultaneously fit and estimate all possible genetic effects associated with all markers. The proposed models use prior distributions for the genetic effects that are scale mixtures of normal distributions with mean zero and variances distributed to give each effect a high probability of being near zero. We consider two types of priors for the variances, exponential and scaled inverse-χ2 distributions, which result in a Bayesian version of the popular least absolute shrinkage and selection operator (LASSO) model and the well-known Student's t model, respectively. Unlike most applications where fixed values are preset for hyperparameters in the priors, we treat all hyperparameters as unknowns and estimate them along with other parameters. Markov chain Monte Carlo (MCMC) algorithms are developed to simulate the parameters from the posteriors. The methods are illustrated using well-known barley data.
Schizosaccharomyces pombe Histone Acetyltransferase Mst1 (KAT5) Is an Essential Protein Required for Damage Response and Chromosome Segregation
Authors: Gómez Eliana B , Nugent Rebecca L , Laria Sebastián , Forsburg Susan L
Published: May 2008

Schizosaccharomyces pombe Mst1 is a member of the MYST family of histone acetyltransferases and is the likely ortholog of Saccharomyces cerevisiae Esa1 and human Tip60 (KAT5). We have isolated a temperature-sensitive allele of this essential gene. mst1 cells show a pleiotropic phenotype at the restrictive temperature. They are sensitive to a variety of DNA-damaging agents and to the spindle poison thiabendazole. mst1 has an increased frequency of Rad22 repair foci, suggesting endogenous damage. Two-hybrid results show that Mst1 interacts with a number of proteins involved in chromosome integrity and centromere function, including the methyltransferase Skb1, the recombination mediator Rad22 (Sc Rad52), the chromatin assembly factor Hip1 (Sc Hir1), and the Msc1 protein related to a family of histone demethylases. mst1 mutant sensitivity to hydroxyurea suggests a defect in recovery following HU arrest. We conclude that Mst1 plays essential roles in maintenance of genome stability and recovery from DNA damage.
Recurrent Events of Positive Selection in Independent Drosophila Lineages at the Spermatogenesis Gene roughex
Authors: Llopart Ana , Comeron Josep M
Published: May 2008

Our understanding of the role of positive selection in the evolution of genes with male-biased expression can be hindered by two observations. First, male-biased genes tend to be overrepresented among lineage-specific genes. Second, novel genes are prone to experience bursts of adaptive evolution shortly after their formation. A thorough study of the forces acting on male-biased genes therefore would benefit from phylogenywide analyses that could distinguish evolutionary trends associated with gene formation and later events, while at the same time tackling the interesting question of whether adaptive evolution is indeed idiosyncratic. Here we investigate the roughex (rux) gene, a dose-dependent regulator of Drosophila spermatogenesis with a C-terminal domain responsible for nuclear localization that shows a distinct amino acid sequence in the melanogaster subgroup. We collected polymorphism and divergence data in eight populations of six Drosophila species, for a total of 99 rux sequences, to study rates and patterns of evolution at this male-biased gene. Our results from two phylogeny-based methods (PAML and HyPhy) as well as from population genetics analyses (McDonald–Kreitman-based tests) indicate that amino acid replacements have contributed disproportionately to divergence, consistent with adaptive evolution at the Rux protein. Analyses based on extant variation show also the signature of recent selective sweeps in several of the populations surveyed. Most important, we detect the significant and consistent signature of positive selection in several independent Drosophila lineages, which evidences recurrent and concurrent events of adaptive evolution after rux formation.
Phenotypic Plasticity and Genotype by Environment Interaction for Olfactory Behavior inDrosophila melanogaster
Authors: Sambandan Deepa , Carbone Mary Anna , Anholt Robert R H , Mackay Trudy F C
Published: May 2008

Genotype by environment interactions (GEI) play a major part in shaping the genetic architecture of quantitative traits and are confounding factors in genetic studies, for example, in attempts to associate genetic variation with disease susceptibility. It is generally not known what proportion of phenotypic variation is due to GEI and how many and which genes contribute to GEI. Behaviors are complex traits that mediate interactions with the environment and, thus, are ideally suited for studies of GEI. Olfactory behavior in Drosophila melanogaster presents an opportunity to systematically dissect GEI, since large numbers of genetically identical individuals can be reared under defined environmental conditions and the olfactory system of Drosophila and its behavioral response to odorants have been well characterized. We assessed variation in olfactory behavior in a population of 41 wild-derived inbred lines and asked to what extent different larval-rearing environments would influence adult olfactory behavior and whether GEI is a minor or major contributing source of phenotypic variation. We found that ∼50% of phenotypic variation in adult olfactory behavior is attributable to GEI. In contrast, transcriptional analysis revealed that only 20 genes show GEI at the level of gene expression [false discovery rate (FDR) < 0.05], some of which are associated with physiological responses to environmental chemicals. Quantitative complementation tests with piggyBac-tagged mutants for 2 of these genes (CG9664 and Transferrin 1) demonstrate that genes that show transcriptional GEI are candidate genes for olfactory behavior and that GEI at the level of gene expression is correlated with GEI at the level of phenotype.
A Fast and Reliable Computational Method for Estimating Population Genetic Parameters
Authors: Vasco Daniel A
Published: May 2008

The estimation of ancestral and current effective population sizes in expanding populations is a fundamental problem in population genetics. Recently it has become possible to scan entire genomes of several individuals within a population. These genomic data sets can be used to estimate basic population parameters such as the effective population size and population growth rate. Full-data-likelihood methods potentially offer a powerful statistical framework for inferring population genetic parameters. However, for large data sets, computationally intensive methods based upon full-likelihood estimates may encounter difficulties. First, the computational method may be prohibitively slow or difficult to implement for large data. Second, estimation bias may markedly affect the accuracy and reliability of parameter estimates, as suggested from past work on coalescent methods. To address these problems, a fast and computationally efficient least-squares method for estimating population parameters from genomic data is presented here. Instead of modeling genomic data using a full likelihood, this new approach uses an analogous function, in which the full data are replaced with a vector of summary statistics. Furthermore, these least-squares estimators may show significantly less estimation bias for growth rate and genetic diversity than a corresponding maximum-likelihood estimator for the same coalescent process. The least-squares statistics also scale up to genome-sized data sets with many nucleotides and loci. These results demonstrate that least-squares statistics will likely prove useful for nonlinear parameter estimation when the underlying population genomic processes have complex evolutionary dynamics involving interactions between mutation, selection, demography, and recombination.
When Parameters in Dynamic Models Become Phenotypes: A Case Study on Flesh Pigmentation in the Chinook Salmon (Oncorhynchus tshawytscha)
Authors: Rajasingh Hannah , Gjuvsland Arne B , Våge Dag Inge , Omholt Stig W
Published: May 2008

The Pacific chinook salmon occurs as both white- and red-fleshed populations, with the flesh color type (red or white) seemingly under strong genetic influence. Previously published data on crosses between red- and white-fleshed individuals cannot be reconciled with a simple Mendelian two-locus, two-allele model, pointing to either a more complex inheritance pattern or the existence of gene interactions. Here we show that a standard single-locus, three-allele model can fully explain these data. Moreover, by implementing the single-locus model at the parameter level of a previously developed mathematical model describing carotenoid dynamics in salmon, we show that variation at a single gene involved in the muscle uptake of carotenoids is able to explain the available data. This illustrates how such a combined approach can generate biological understanding that would not be possible in a classical population genetic explanatory structure. An additional asset of this approach is that by allowing parameters to become phenotypes obeying a given genetic model, biological interpretations of mechanisms involved at a resolution level far beyond what is built into the original dynamic model are made possible. These insights can in turn be exploited in experimental studies as well as in construction of more detailed models.
The T-Box Gene tbx-2, the Homeobox Gene egl-5 and the Asymmetric Cell Division Gene ham-1 Specify Neural Fate in the HSN/PHB Lineage
Authors: Singhvi Aakanksha , Frank C Andrew , Garriga Gian
Published: May 2008

Understanding how neurons adopt particular fates is a fundamental challenge in developmental neurobiology. To address this issue, we have been studying a Caenorhabditis elegans lineage that produces the HSN motor neuron and the PHB sensory neuron, sister cells produced by the HSN/PHB precursor. We have previously shown that the novel protein HAM-1 controls the asymmetric neuroblast division in this lineage. In this study we examine tbx-2 and egl-5, genes that act in concert with ham-1 to regulate HSN and PHB fate. In screens for mutants with abnormal HSN development, we identified the T-box protein TBX-2 as being important for both HSN and PHB differentiation. TBX-2, along with HAM-1, regulates the migrations of the HSNs and prevents the PHB neurons from adopting an apoptotic fate. The homeobox gene egl-5 has been shown to regulate the migration and later differentiation of the HSN. While mutations that disrupt its function show no obvious role for EGL-5 in PHB development, loss of egl-5 in a ham-1 mutant background leads to PHB differentiation defects. Expression of EGL-5 in the HSN/PHB precursor but not in the PHB neuron suggests that EGL-5 specifies precursor fate. These observations reveal a role for both EGL-5 and TBX-2 in neural fate specification in the HSN/PHB lineage.
Overdispersion of the Molecular Clock Varies Between Yeast, Drosophila and Mammals
Authors: Bedford Trevor , Wapinski Ilan , Hartl Daniel L
Published: May 2008

Although protein evolution can be approximated as a “molecular evolutionary clock,” it is well known that sequence change departs from a clock-like Poisson expectation. Through studying the deviations from a molecular clock, insight can be gained into the forces shaping evolution at the level of proteins. Generally, substitution patterns that show greater variance than the Poisson expectation are said to be “overdispersed.” Overdispersion of sequence change may result from temporal variation in the rate at which amino acid substitutions occur on a phylogeny. By comparing the genomes of four species of yeast, five species of Drosophila, and five species of mammals, we show that the extent of overdispersion shows a strong negative correlation with the effective population size of these organisms. Yeast proteins show very little overdispersion, while mammalian proteins show substantial overdispersion. Additionally, X-linked genes, which have reduced effective population size, have gene products that show increased overdispersion in both Drosophila and mammals. Our research suggests that mutational robustness is more pervasive in organisms with large population sizes and that robustness acts to stabilize the molecular evolutionary clock of sequence change.
Genetic variation for stomatal conductance in upland cotton as influenced by heat-stressed and non-stressed growing regimes
Authors: Rahman H. , Murtaza N. , Shah K. , Qayyum A. , Ullah I. , Malik W.
Published: May 2008

Stomatal conductance is an important heat avoidance mechanism and its association with higher yield and heat resistance has been established in Pima cotton. Experiments were carried out on upland cotton under heat-stressed and non-stressed greenhouse and field regimes, to understand the impact of heat-stressed and non-stressed environments on the genetic and combining ability variations for stomatal conductance. The experimental material comprised 8 upland cotton cultivars and their 15 F
1
cross combinations obtained in a line × tester mating arrangement. The results showed high genetic variability for stomatal conductance in a single environment, but low genetic variability across environments, due to the higher magnitude of the environmental interaction, especially that caused by temperature regimes. The interaction effect of temperature regimes also substantially modified general and specific combining ability variations for stomatal conductance. The relative contributions of general and specific combining abilities to total phenotypic variation for stomatal conductance also underwent a great change across field temperature regimes. The non-stressed regime favoured the expression of genes causing the additive type of genetic variability. The heat-stressed field regime, however, favoured the expression of both additive and non-additive types of genetic variation for stomatal conductance in upland cotton. Recurrent selection for the accumulation of favourable genes for general combining ability under non-stressed conditions was suggested for improving stomatal conductance in applied cotton breeding programmes.