bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Kinase D Regulates Trafficking of Dendritic Membrane Proteins in Developing Neurons
Authors: Bisbal Mariano , Conde Cecilia , Donoso Maribel , Bollati Flavia , Sesma Juliana , Quiroga Santiago , Díaz Añel Alberto , Malhotra Vivek , Marzolo Maria Paz , Cáceres Alfredo
Published: September 2008

In non-neuronal cells, inactivation of protein kinase D (PKD) blocks fission oftrans-Golgi network (TGN) transport carriers, inducing the appearance of long tubules filled with cargo. We now report on the function of PKD1 in neuronal protein trafficking. In cultured hippocampal pyramidal cells, the transferrin receptor (TfR) and the low-density receptor-related protein (LRP) are predominantly transported to dendrites and excluded from axons. Expression of kinase-inactive PKD1 or its depletion by RNA interference treatment dramatically and selectively alter the intracellular trafficking and membrane delivery of TfR- and LRP-containing vesicles, without inhibiting exit from the TGN or inducing Golgi tubulation. After PKD1 suppression, dendritic membrane proteins are mispackaged into carriers that transport VAMP2; these vesicles are distributed to both axons and dendrites, but are rapidly endocytosed from dendrites and preferentially delivered to the axonal membrane. A kinase-defective mutant of PKD1 lacking the ability to bind diacylglycerol and hence its Golgi localization does not cause missorting of TfR or LRP. These results suggest that in neurons PKD1 regulates TGN-derived sorting of dendritic proteins and hence has a role in neuronal polarity.
Chip Is Required for Posteclosion Behavior inDrosophila
Authors: Hari Padmanabhan , Deshpande Mugdha , Sharma Neha , Rajadhyaksha Neha , Ramkumar Nitya , Kimura Ken-ichi , Rodrigues Veronica , Tole Shubha
Published: September 2008

Neurons acquire their molecular, neurochemical, and connectional features during development as a result of complex regulatory mechanisms. Here, we show that a ubiquitous, multifunctional protein cofactor, Chip, plays a critical role in a set of neurons inDrosophilathat control the well described posteclosion behavior. Newly eclosed flies normally expand their wings and display tanning and hardening of their cuticle. Using multiple approaches to interfere with Chip function, we find that these processes do not occur without normal activity of this protein. Furthermore, we identified the nature of the deficit to be an absence of Bursicon in the hemolymph of newly eclosed flies, whereas the responsivity to Bursicon in these flies remains normal. Chip interacts with transcription factors of the LIM-HD (LIM-homeodomain) family, and we identified one member, dIslet, as a potential partner of Chip in this process. Our findings provide the first evidence of transcriptional mechanisms involved in the development of the neuronal circuit that regulates posteclosion behavior inDrosophila.
ClC3 Is a Critical Regulator of the Cell Cycle in Normal and Malignant Glial Cells
Authors: Habela Christa W. , Olsen Michelle L. , Sontheimer Harald
Published: September 2008

Although most brain cells are postmitotic, small populations of progenitor or stem cells can divide throughout life. These cells are believed to be the most likely source for primary brain malignancies including gliomas. Such tumors share many common features with nonmalignant glial cells but, because of their insidious growth, form cancers that are typically incurable. In studying the growth regulation of these tumors, we recently discovered that glioma cell division is preceded by a cytoplasmic condensation that we called premitotic condensation (PMC). PMC represents an obligatory step in cell replication and is linked to chromatin condensation. If perturbed, the time required to complete a division is significantly prolonged. We now show that PMC is a feature shared more commonly among normal and malignant cells and that the reduction of cell volume is accomplished by Cl−efflux through ClC3 Cl−channels. Patch-clamp electrophysiology demonstrated a significant upregulation of chloride currents at M phase of the cell cycle. Colocalization studies and coimmunoprecipitation experiments showed the channel on the plasma membrane and at the mitotic spindle. To demonstrate a mechanistic role for ClC3 in PMC, we knocked down ClC3 expression using short hairpin RNA constructs. This resulted in a significant reduction of chloride currents at M phase that was associated with a decrease in the rate of PMC and a similar impairment of DNA condensation. These data suggest that PMC is an integral part of cell division and is dependent on ClC3 channel function.
Dynamic Sculpting of Directional Tuning in the Primate Motor Cortex during Three-Dimensional Reaching
Authors: Merchant Hugo , Naselaris Thomas , Georgopoulos Apostolos P.
Published: September 2008

In the present study, we investigated how directional tuning of putative pyramidal cells is sharpened by inhibition from neighboring interneurons. First, different functional and electrophysiological criteria were used to identify putative pyramidal and interneuronal subtypes in a large database of motor cortical cells recorded during performance of the three-dimensional center-out task. Then we analyzed the relationship between the magnitude of inhibition and the tuning width, and a significant decrease of the latter as a function of the former was found in a population of putative pyramidal cells. In fact, the coupling of inhibition with narrow tuning was observed before and during movement execution on a cell-by-cell basis, indicating an important dynamic role of inhibition during movement control. Overall, these results suggest that local inhibition is involved in sculpting the directional specificity of a group of putative pyramidal neurons in the motor cortex.
Adaptation of Velocity Encoding in Synaptically Coupled Neurons in the Fly Visual System
Authors: Kalb Julia , Egelhaaf Martin , Kurtz Rafael
Published: September 2008

Although many adaptation-induced effects on neuronal response properties have been described, it is often unknown at what processing stages in the nervous system they are generated. We focused on fly visual motion-sensitive neurons to identify changes in response characteristics during prolonged visual motion stimulation. By simultaneous recordings of synaptically coupled neurons, we were able to directly compare adaptation-induced effects at two consecutive processing stages in the fly visual motion pathway. This allowed us to narrow the potential sites of adaptation effects within the visual system and to relate them to the properties of signal transfer between neurons. Motion adaptation was accompanied by a response reduction, which was somewhat stronger in postsynaptic than in presynaptic cells. We found that the linear representation of motion velocity degrades during adaptation to a white-noise velocity-modulated stimulus. This effect is caused by an increasingly nonlinear velocity representation rather than by an increase of noise and is similarly strong in presynaptic and postsynaptic neurons. In accordance with this similarity, the dynamics and the reliability of interneuronal signal transfer remained nearly constant. Thus, adaptation is mainly based on processes located in the presynaptic neuron or in more peripheral processing stages. In contrast, changes of transfer properties at the analyzed synapse or in postsynaptic spike generation contribute little to changes in velocity coding during motion adaptation.
Serotonin Hyperinnervation Abolishes Seizure Susceptibility inOtx2Conditional Mutant Mice
Authors: Tripathi Prem Prakash , Di Giovannantonio Luca Giovanni , Viegi Alessandro , Wurst Wolfgang , Simeone Antonio , Bozzi Yuri
Published: September 2008

The homeobox-containing transcription factor Otx2 is crucially involved in fate determination of midbrain neurons. Mutant mice, in whichOtx2was conditionally inactivated by a Cre recombinase expressed under the transcriptional control of the Engrailed1 (En1) gene (En1cre/+;Otx2flox/flox), show a reduced number of dopaminergic neurons and an increased number of serotonergic neurons in the ventral midbrain. Despite these developmental anatomical alterations,En1cre/+;Otx2flox/floxadult mice display normal motor function. Here, we further investigated the neurological consequences ofOtx2inactivation in adultEn1cre/+;Otx2flox/floxmice. AdultEn1cre/+;Otx2flox/floxmice showed increased serotonin (5-HT) levels in the pons, ventral midbrain, hippocampus (CA3 subfield), and cerebral cortex, as indicated by HPLC and immunohistochemistry. Conversely, SERT (5-HT transporter) levels were decreased in conditional mutant brains. As a consequence of this increased 5-HT hyperinnervation,En1cre/+;Otx2flox/floxmice were resistant to generalized seizures induced by the glutamate agonist kainic acid (KA). Indeed, prolonged pretreatment ofEn1cre/+;Otx2flox/floxmice with the 5-HT synthesis inhibitorpara-chlorophenylalanine (pCPA) restored brain 5-HT content to control levels, fully reestablishing KA seizure susceptibility. Accordingly, c-fosmRNA induction after KA was restricted to the hippocampus inEn1cre/+;Otx2flox/floxmice, whereas a widespread c-fosmRNA labeling was observed throughout the brain ofEn1cre/+;Otx2flox/floxmice pretreated with pCPA. These results clearly show that increased brain 5-HT levels are responsible for seizure resistance inEn1cre/+;Otx2flox/floxmice and confirm the important role of 5-HT in the control of seizure spread.
In VivoMetabotropic Glutamate Receptor 5 (mGluR5) Antagonism Prevents Cocaine-Induced Disruption of Postsynaptically Maintained mGluR5-Dependent Long-Term Depression
Authors: Grueter Brad A. , McElligott Zoe A. , Robison Alfred J. , Mathews Gregory C. , Winder Danny G.
Published: September 2008

Metabotropic glutamate receptor 5 (mGluR5) plays a critical role in psychostimulant-induced behavior, yet it is unclear whether mGluR5 is activated by psychostimulant administration, or whether its role is constitutive. We previously reported that activation of mGluR5 with the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) can induce a long-term depression (DHPG-LTD) of glutamatergic transmission in the bed nucleus of the stria terminalis (BNST), and thatex vivoinduction of this LTD is disrupted by repeatedin vivoadministration of cocaine. Here we demonstrate that DHPG-LTD is not maintained by alterations in glutamate release, and that postsynaptic endocytosis is necessary. Furthermore, we find that a single administration of cocaine produces a transient disruption of DHPG-LTD, and the duration of this disruption was increased by repeated days of cocaine administration. The disruption produced by cocaine was not permanent, because DHPG-LTD could be induced 10 d after cocaine administration. To test the role of mGluR5in vivoin the cocaine-induced disruption of DHPG-LTD, we injected mice with the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine before cocaine. mGluR5 antagonism duringin vivococaine administration rescued subsequentex vivoinduction of DHPG-LTD. The effects ofin vivococaine could be mimicked by application of cocaine to BNST-containing slices, suggesting that the actions of cocaine are local. Thus, using a novel strategy ofin vivoantagonist-induced rescue ofex vivoagonist effects for the same receptor, we provide evidence suggesting that mGluR5 activation is actively recruited byin vivococaine.
Identification of a Novel Nurr1-Interacting Protein
Authors: Luo Yu , Xing Feng , Guiliano Rita , Federoff Howard J.
Published: September 2008

The orphan nuclear receptor Nurr1 is required for the development of ventral mesencephalic dopaminergic neurons in mice. One of the possible mechanisms that might contribute to the regulation activity of Nurr1 is through interaction with other proteins. To identify potential partners of Nurr1, we screened a yeast two-hybrid library from developing mouse embryonic mesencephalon with the Nurr1 ligand-binding domain (NLBD). We identified a novel interacting protein, termed the Nurr1-interacting protein (NuIP). We demonstrate that it specifically interacts with NLBD using the mammalian two-hybrid assay and coimmunoprecipitation studies in MN9D cells. In addition, we show that NuIP interacts with Nurr1 in lysates from substantia nigra. Coexpression of NuIP with Nurr1 results in potentiation of the transcriptional activity of Nurr1 on an nerve growth factor inducible-B response element reporter, as well as reporters driven by the endogenous tyrosine hydroxylase promoter. The mechanism underlying the regulatory action of NuIP on Nurr1 is demonstrated to be through assembly of distinct helical domains of the NLBD. Using a NuIP specific antibody, we show that expression of NuIP protein is mainly colocalized with Nurr1 in adult midbrain dopaminergic neurons. Finally, we demonstrate that suppression of NuIP expression in MN9D cells by NuIP-specific small interfering RNA leads to decreased cell division and decreased expression of a Nurr1 target gene, the dopamine transporter. These results suggest NuIP interacts with and positively regulates the activity of Nurr1 protein and modulates the phenotype of dopaminergic cells.
Complete Rescue of Cerebrovascular Function in Aged Alzheimer's Disease Transgenic Mice by Antioxidants and Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist
Authors: Nicolakakis Nektaria , Aboulkassim Tahar , Ongali Brice , Lecrux Clotilde , Fernandes Priscilla , Rosa-Neto Pedro , Tong Xin-Kang , Hamel Edith
Published: September 2008

Accumulating evidence suggests that cerebrovascular dysfunction is an important factor in the pathogenesis of Alzheimer's disease (AD). Using aged (∼16 months) amyloid precursor protein (APP) transgenic mice that exhibit increased production of the amyloid-β (Aβ) peptide and severe cerebrovascular and memory deficits, we examined the capacity ofin vivotreatments with the antioxidantsN-acetyl-l-cysteine (NAC) and tempol, or the peroxisome proliferator-activated receptor γ agonist pioglitazone to rescue cerebrovascular function and selected markers of AD neuropathology. Additionally, we tested the ability of pioglitazone to normalize the impaired increases in cerebral blood flow (CBF) and glucose uptake (CGU) induced by whisker stimulation, and to reverse spatial memory deficits in the Morris water maze. All compounds fully restored cerebrovascular reactivity of isolated cerebral arteries concomitantly with changes in proteins regulating oxidative stress, without reducing brain Aβ levels or Aβ plaque load. Pioglitazone, but not NAC, significantly attenuated astroglial activation and improved, albeit nonsignificantly, the reduced cortical cholinergic innervation. Furthermore, pioglitazone completely normalized the CBF and CGU responses to increased neuronal activity, but it failed to improve spatial memory. Our results are the first to demonstrate that late pharmacological intervention with pioglitazone not only overcomes cerebrovascular dysfunction and altered neurometabolic coupling in aged APP mice, but also counteracts cerebral oxidative stress, glial activation, and, partly, cholinergic denervation. Although early or combined therapy may be warranted to improve cognition, these findings unequivocally point to pioglitazone as a most promising strategy for restoring cerebrovascular function and counteracting several AD markers detrimental to neuronal function.
The Effects of Violence and Internal Displacement on Rural‐Agrarian Change in Turkey*
Authors: Sonmez Abdulkerim
Published: September 2008

Abstract  This paper addresses two interrelated issues that have assumed major political significance in the handling of the Kurdish question in Turkey. The first is the impact of violence and resulting internal displacement in Eastern and Southeastern Turkey on rural‐agrarian change. The second concerns the implications of the structural change and social transformation of the displaced population for their return to rural life. Analysis of national agricultural census data indicates that violence and displacement, in combination with a general process of agrarian change, have given rise to a new agrarian structure in the affected provinces, which leaves no room for the permanent return of most of the displaced population. On the other hand, the displaced population has undergone a social transformation that makes such a return less desirable for them.
A Place to Call Home: Cultural Understandings of Heir Property among Rural African Americans*
Authors: Dyer Janice F. , Bailey Conner
Published: September 2008

Abstract  Heir property is land held communally by family members of a landowner who has died intestate. Because this informal arrangement does not fit neatly into the individualist‐centered, integrated property rights system of the United States, it is viewed by most as a hindrance to economic development and capitalism. We present an alternative framework for analyzing the significance of heir property in the African American community and its constraints. While the consequences of owning land with clouded title are clear‐ineligibility for housing programs, inability to secure a mortgage or sell timber, and vulnerability to land loss through partition and tax sales‐we argue that a culturally‐based understanding of heir property provides insight to why it persists among rural African Americans. Based on personal interviews with heir property owners, lawyers, housing counselors, and county officials, the authors illustrate how heir property is supportive of certain cultural values and meets the needs of a subset of rural populations in ways that other forms of property ownership cannot.
Transforming growth factor-β: its role in ovarian follicle development
Authors: Rosairo Davina , Kuyznierewicz Ileana , Findlay Jock , Drummond Ann
Published: September 2008

Ovarian follicular growth and differentiation in response to transforming growth factor-β (TGFB) was investigated using postnatal and immature ovarian models. TGFB ligand and receptor mRNAs were present in the rat ovary 4–12 days after birth and at day 25. In order to assess the impact of TGFB1 on follicle growth and transition from the primordial through to the primary and preantral stages of development, we established organ cultures with 4-day-old rat ovaries. After 10 days in culture with FSH, TGFB1, or a combination of the two, ovarian follicle numbers were counted and an assessment of atresia was undertaken using TUNEL. Preantral follicle numbers declined significantly when treated with the combination of FSH and TGFB1, consistent with our morphological appraisal suggesting an increase in atretic primary and preantral follicles. To investigate the mechanisms behind the actions of TGFB1, we isolated granulosa cells and treated them with FSH and TGFB1. Markers of proliferative, steroidogenic, and apoptotic capacity were measured by real-time PCR. Cyclin D2 mRNA expression by granulosa cells was significantly increased in response to the combination of FSH and TGFB. The expression of forkhead homolog in rhabdomyosarcoma (Foxo1) mRNA by granulosa cells was significantly reduced in the presence of both FSH and TGFB1, individually and in combination regimes. By contrast, the expression of steroidogenic enzymes/proteins was largely unaffected by TGFB1. These data suggest an inhibitory role for TGFB1 (in the presence of FSH) in follicle development and progression.
End Joining atCaenorhabditis elegansTelomeres
Authors: Lowden Mia Rochelle , Meier Bettina , Lee Teresa Wei-sy , Hall Julie , Ahmed Shawn
Published: September 2008

Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage–fusion–bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapped telomeres rely on PCR assays that typically capture fusion breakpoints created by direct ligation of chromosome ends. Here we use independent approaches that rely on distinctive features of Caenorhabditis elegans to study the frequency of direct end-to-end chromosome fusion in telomerase mutants: (1) holocentric chromosomes that allow for genetic isolation of stable end-to-end fusions and (2) unique subtelomeric sequences that allow for thorough PCR analysis of samples of genomic DNA harboring multiple end-to-end fusions. Surprisingly, only a minority of end-to-end fusion events resulted from direct end joining with no additional genome rearrangements. We also demonstrate that deficiency for the C. elegans Ku DNA repair heterodimer does not affect telomere length or cause synthetic effects in the absence of telomerase.
Patterns of Amino Acid Evolution in the Drosophila ananassae Chimeric Gene, siren, Parallel Those of Other Adh-Derived Chimeras
Authors: Shih Hung-Jui , Jones Corbin D
Published: September 2008

siren1 and siren2 are novel alcohol dehydrogenase (Adh)-derived chimeric genes in the Drosophila bipectinata complex. D. ananassae, however, harbors a single homolog of these genes. Like other Adh-derived chimeric genes, siren evolved adaptively shortly after it was formed. These changes likely shifted the catalytic activity of siren.
Domain-Specific Regulation of Recombination inCaenorhabditis elegansin Response to Temperature, Age and Sex
Authors: Lim Jaclyn G Y , Stine Rachel R W , Yanowitz Judith L
Published: September 2008

It is generally considered that meiotic recombination rates increase with temperature, decrease with age, and differ between the sexes. We have reexamined the effects of these factors on meiotic recombination in the nematode Caenorhabditis elegans using physical markers that encompass >96% of chromosome III. The only difference in overall crossover frequency between oocytes and male sperm was observed at 16°. In addition, crossover interference (CI) differs between the germ lines, with oocytes displaying higher CI than male sperm. Unexpectedly, our analyses reveal significant changes in crossover distribution in the hermaphrodite oocyte in response to temperature. This feature appears to be a general feature of C. elegans chromosomes as similar changes in response to temperature are seen for the X chromosome. We also find that the distribution of crossovers changes with age in both hermaphrodites and females. Our observations indicate that it is the oocytes from the youngest mothers—and not the oldest—that showed a different pattern of crossovers. Our data enhance the emerging hypothesis that recombination in C. elegans, as in humans, is regulated in large chromosomal domains.
Pnc1p-Mediated Nicotinamide Clearance Modifies the Epigenetic Properties of rDNA Silencing in Saccharomyces cerevisiae
Authors: McClure Julie M , Gallo Christopher M , Smith Daniel L , Matecic Mirela , Hontz Robert D , Buck Stephen W , Racette Frances G , Smith Jeffrey S
Published: September 2008

The histone deacetylase activity of Sir2p is dependent on NAD+ and inhibited by nicotinamide (NAM). As a result, Sir2p-regulated processes in Saccharomyces cerevisiae such as silencing and replicative aging are susceptible to alterations in cellular NAD+ and NAM levels. We have determined that high concentrations of NAM in the growth medium elevate the intracellular NAD+ concentration through a mechanism that is partially dependent on NPT1, an important gene in the Preiss–Handler NAD+ salvage pathway. Overexpression of the nicotinamidase, Pnc1p, prevents inhibition of Sir2p by the excess NAM while maintaining the elevated NAD+ concentration. This growth condition alters the epigenetics of rDNA silencing, such that repression of a URA3 reporter gene located at the rDNA induces growth on media that either lacks uracil or contains 5-fluoroorotic acid (5-FOA), an unusual dual phenotype that is reminiscent of telomeric silencing (TPE) of URA3. Despite the similarities to TPE, the modified rDNA silencing phenotype does not require the SIR complex. Instead, it retains key characteristics of typical rDNA silencing, including RENT and Pol I dependence, as well as a requirement for the Preiss–Handler NAD+ salvage pathway. Exogenous nicotinamide can therefore have negative or positive impacts on rDNA silencing, depending on the PNC1 expression level.
Lethal Mutagenesis of Bacteria
Authors: Bull James J , Wilke Claus O
Published: September 2008

Lethal mutagenesis, the killing of a microbial pathogen with a chemical mutagen, is a potential broad-spectrum antiviral treatment. It operates by raising the genomic mutation rate to the point that the deleterious load causes the population to decline. Its use has been limited to RNA viruses because of their high intrinsic mutation rates. Microbes with DNA genomes, which include many viruses and bacteria, have not been considered for this type of treatment because their low intrinsic mutation rates seem difficult to elevate enough to cause extinction. Surprisingly, models of lethal mutagenesis indicate that bacteria may be candidates for lethal mutagenesis. In contrast to viruses, bacteria reproduce by binary fission, and this property ensures their extinction if subjected to a mutation rate >0.69 deleterious mutations per generation. The extinction threshold is further lowered when bacteria die from environmental causes, such as washout or host clearance. In practice, mutagenesis can require many generations before extinction is achieved, allowing the bacterial population to grow to large absolute numbers before the load of deleterious mutations causes the decline. Therefore, if effective treatment requires rapid population decline, mutation rates ≫0.69 may be necessary to achieve treatment success. Implications for the treatment of bacteria with mutagens, for the evolution of mutator strains in bacterial populations, and also for the evolution of mutation rate in cancer are discussed.
Chromosome Segmental Dosage Analysis of Maize Morphogenesis Using B–A–A Translocations
Authors: Sheridan William F , Auger Donald L
Published: September 2008

The B–A–A translocations have enabled us to simultaneously assess the possible dosage-sensitive interactions of two nonhomologous chromosome segments in affecting maize plant development. Maize B–A–A translocations contain segments of two nonhomologous essential A chromosomes in tandem arrangement attached to a segment of the long arm of a supernumerary B chromosome. By utilizing the frequent nondisjunction of the B centromere at the second pollen mitosis we produced plants containing an extra copy of the two A chromosome segments. We compared these hyperploid plants with nonhyperploid plants by measuring leaf width, plant height, ear height, internode length, stalk circumference, leaf length, and tassel-branch number in 20 paired families that involved one of the chromosome arms 1S, 1L, 4L, 5S, and 10L. One or more of the seven measured traits displayed dosage sensitivity among 17 of the 20 B–A–A translocations, which included the involvement of chromosome arms 2L, 3L, 5L, 6L, and 7L. The most obvious effect of an increased dosage of the B–A–A translocation was a significant decrease in the traits in the hyperploid plants. These effects may be either the additive effects of hyperploidy for the two chromosome segments or a result of gene interaction between them.
FST andQST Under Neutrality
Authors: Miller Judith R , Wood Bryan P , Hamilton Matthew B
Published: September 2008

A commonly used test for natural selection has been to compare population differentiation for neutral molecular loci estimated by FST and for the additive genetic component of quantitative traits estimated by QST. Past analytical and empirical studies have led to the conclusion that when averaged over replicate evolutionary histories, QST = FST under neutrality. We used analytical and simulation techniques to study the impact of stochastic fluctuation among replicate outcomes of an evolutionary process, or the evolutionary variance, of QST and FST for a neutral quantitative trait determined by n unlinked diallelic loci with additive gene action. We studied analytical models of two scenarios. In one, a pair of demes has recently been formed through subdivision of a panmictic population; in the other, a pair of demes has been evolving in allopatry for a long time. A rigorous analysis of these two models showed that in general, it is not necessarily true that mean QST = FST (across evolutionary replicates) for a neutral, additive quantitative trait. In addition, we used finite-island model simulations to show there is a strong positive correlation between QST and the difference QST − FST because the evolutionary variance of QST is much larger than that of FST. If traits with relatively large QST values are preferentially sampled for study, the difference between QST and FST will also be large and positive because of this correlation. Many recent studies have used tests of the null hypothesis QST = FST to identify diversifying or uniform selection among subpopulations for quantitative traits. Our findings suggest that the distributions of QST and FST under the null hypothesis of neutrality will depend on species-specific biology such as the number of subpopulations and the history of subpopulation divergence. In addition, the manner in which researchers select quantitative traits for study may introduce bias into the tests. As a result, researchers must be cautious before concluding that selection is occurring when QST ≠ FST.
A Genome-Scan Method to Identify Selected Loci Appropriate for Both Dominant and Codominant Markers: A Bayesian Perspective
Authors: Foll Matthieu , Gaggiotti Oscar
Published: September 2008

Identifying loci under natural selection from genomic surveys is of great interest in different research areas. Commonly used methods to separate neutral effects from adaptive effects are based on locus-specific population differentiation coefficients to identify outliers. Here we extend such an approach to estimate directly the probability that each locus is subject to selection using a Bayesian method. We also extend it to allow the use of dominant markers like AFLPs. It has been shown that this model is robust to complex demographic scenarios for neutral genetic differentiation. Here we show that the inclusion of isolated populations that underwent a strong bottleneck can lead to a high rate of false positives. Nevertheless, we demonstrate that it is possible to avoid them by carefully choosing the populations that should be included in the analysis. We analyze two previously published data sets: a human data set of codominant markers and a Littorina saxatilis data set of dominant markers. We also perform a detailed sensitivity study to compare the power of the method using amplified fragment length polymorphism (AFLP), SNP, and microsatellite markers. The method has been implemented in a new software available at our website (http://www-leca.ujf-grenoble.fr/logiciels.htm).
Secondary Mutations Correct Fitness Defects inToxoplasma gondiiWith Dinitroaniline Resistance Mutations
Authors: Ma Christopher , Tran Johnson , Li Catherine , Ganesan Lakshmi , Wood David , Morrissette Naomi
Published: September 2008

Dinitroanilines (oryzalin, trifluralin, ethafluralin) disrupt microtubules in protozoa but not in vertebrate cells, causing selective death of intracellular Toxoplasma gondii parasites without affecting host cells. Parasites containing α1-tubulin point mutations are dinitroaniline resistant but show increased rates of aberrant replication relative to wild-type parasites. T. gondii parasites bearing the F52Y mutation were previously demonstrated to spontaneously acquire two intragenic mutations that decrease both resistance levels and replication defects. Parasites bearing the G142S mutation are largely dependent on oryzalin for viable growth in culture. We isolated 46 T. gondii lines that have suppressed microtubule defects associated with the G142S or the F52Y mutations by acquiring secondary mutations. These compensatory mutations were α1-tubulin pseudorevertants or extragenic suppressors (the majority alter the β1-tubulin gene). Many secondary mutations were located in tubulin domains that suggest that they function by destabilizing microtubules. Most strikingly, we identified seven novel mutations that localize to an eight-amino-acid insert that stabilizes the α1-tubulin M loop, including one (P364R) that acts as a compensatory mutation in both F52Y and G142S lines. These lines have reduced dinitroaniline resistance but most perform better than parental lines in competition assays, indicating that there is a trade-off between resistance and replication fitness.
Impact of Transgene Inheritance on the Mitigation of Gene Flow Between Crops and Their Wild Relatives: The Example of Foxtail Millet
Authors: Shi Yunsu , Wang TianYu , Li Yu , Darmency Henri
Published: September 2008

Developing genetically modified crop plants that are biologically contained could reduce significantly the potential spread of transgenes to conventional and organic crop plants and to wild or weedy relatives. Among several strategies, the hereditary mode of transmission of transgenes, whether dominant, recessive, or maternal, could play a major role in interspecific gene flow. Here we report on the gene flow between foxtail millet (Setaria italica), an autogamous crop, and its weedy relative, S. viridis, growing within or beside fields containing the three kinds of inherited herbicide resistance. Over the 6-year study, in the absence of herbicide selection, the maternal chloroplast-inherited resistance was observed at a 2 × 10−6 frequency in the weed populations. Resistant weed plants were observed 60 times as often, at 1.2 × 10−4 in the case of the nuclear recessive resistance, and 190 times as often, at 3.9 × 10−4 in the case of the dominant resistance. Because the recessive gene was not expressed in the first-generation hybrids, it should be more effective than dominant genes in reducing gene flow under normal agricultural conditions where herbicides are sprayed because interspecific hybrids cannot gain from beneficial genes.
Sequential Elimination of Major-Effect Contributors Identifies Additional Quantitative Trait Loci Conditioning High-Temperature Growth in Yeast
Authors: Sinha Himanshu , David Lior , Pascon Renata C , Clauder-Münster Sandra , Krishnakumar Sujatha , Nguyen Michelle , Shi Getao , Dean Jed , Davis Ronald W , Oefner Peter J , McCusker John H , Steinmetz Lars M
Published: September 2008

Several quantitative trait loci (QTL) mapping strategies can successfully identify major-effect loci, but often have poor success detecting loci with minor effects, potentially due to the confounding effects of major loci, epistasis, and limited sample sizes. To overcome such difficulties, we used a targeted backcross mapping strategy that genetically eliminated the effect of a previously identified major QTL underlying high-temperature growth (Htg) in yeast. This strategy facilitated the mapping of three novel QTL contributing to Htg of a clinically derived yeast strain. One QTL, which is linked to the previously identified major-effect QTL, was dissected, and NCS2 was identified as the causative gene. The interaction of the NCS2 QTL with the first major-effect QTL was background dependent, revealing a complex QTL architecture spanning these two linked loci. Such complex architecture suggests that more genes than can be predicted are likely to contribute to quantitative traits. The targeted backcrossing approach overcomes the difficulties posed by sample size, genetic linkage, and epistatic effects and facilitates identification of additional alleles with smaller contributions to complex traits.
The R2R3 MYB Transcription Factor GhMYB109 Is Required for Cotton Fiber Development
Authors: Pu Li , Li Qun , Fan Xiaoping , Yang Weicai , Xue Yongbiao
Published: September 2008

Cotton (Gossypium hirsutum L.) fibers are single highly elongated cells derived from the outer epidermis of ovules. A large number of genes are required for fiber differentiation and development, but so far, little is known about how these genes control and regulate the process of fiber development. Here we examine the role of the cotton-fiber-specific R2R3 MYB gene GhMYB109 in cotton fiber development. Transgenic reporter gene analysis revealed that a 2-kb GhMYB109 promoter was sufficient to confirm its fiber-specific expression. Antisense-mediated suppression of GhMYB109 led to a substantial reduction in fiber length. Consistently, several genes related to cotton fiber growth were found to be significantly reduced in the transgenic cotton. Our results showed that GhMYB109 is required for cotton fiber development and reveal a largely conserved mechanism of the R2R3 MYB transcription factor in cell fate determination in plants.
ADBP-1 Regulates an ADAR RNA-Editing Enzyme to Antagonize RNA-Interference-Mediated Gene Silencing in Caenorhabditis elegans
Authors: Ohta Hiromitsu , Fujiwara Manabi , Ohshima Yasumi , Ishihara Takeshi
Published: September 2008

Small interfering RNAs (siRNAs) and microRNAs (miRNAs) mediate gene silencing through evolutionarily conserved pathways. In Caenorhabditis elegans, the siRNA/miRNA pathways are also known to affect transgene expression. To identify genes that regulate the efficiencies of the siRNA/miRNA pathways, we used the expression level of a transgene as an indicator of gene silencing and isolated a transgene-silencing mutant, adbp-1 (ADR-2 binding protein). The adbp-1 mutation caused transgene silencing in hypodermal and intestinal cells in a cell-autonomous manner, depending on the RNA interference (RNAi) machinery. The adbp-1 gene encodes a protein with no conserved domains that is localized in the nucleus. Yeast two-hybrid screening and co-immunoprecipitation analysis demonstrated that ADBP-1 physically interacts with ADR-2, an RNA-editing enzyme from the ADAR (adenosine deaminase acting on dsRNA) family. In the adbp-1 mutant, as previously shown in adr-2 mutants, A-to-I RNA editing was not detected, suggesting that ADBP-1 is required for the RNA-editing activity of ADR-2. We found that ADBP-1 facilitates the nuclear localization of ADR-2. ADBP-1 may regulate ADR-2 activity and the consequent RNA editing and thereby antagonize RNAi-mediated transgene silencing in C. elegans.
A Computational Approach to the Functional Clustering of Periodic Gene-Expression Profiles
Authors: Kim Bong-Rae , Zhang Li , Berg Arthur , Fan Jianqing , Wu Rongling
Published: September 2008

DNA microarray analysis has emerged as a leading technology to enhance our understanding of gene regulation and function in cellular mechanism controls on a genomic scale. This technology has advanced to unravel the genetic machinery of biological rhythms by collecting massive gene-expression data in a time course. Here, we present a statistical model for clustering periodic patterns of gene expression in terms of different transcriptional profiles. The model incorporates biologically meaningful Fourier series approximations of gene periodic expression into a mixture-model-based likelihood function, thus producing results that are likely to be closer to biological relevance, as compared to those from existing models. Also because the structures of the time-dependent means and covariance matrix are modeled, the new approach displays increased statistical power and precision of parameter estimation. The approach was used to reanalyze a real example with 800 periodically expressed transcriptional genes in yeast, leading to the identification of 13 distinct patterns of gene-expression cycles. The model proposed can be useful for characterizing the complex biological effects of gene expression and generate testable hypotheses about the workings of developmental systems in a more precise quantitative way.
R. H. Wood's ‘The stability of tall buildings’: a contemporary view
Authors: King C.
Published: September 2008

Randal Wood's 1958 paper on the stability of tall buildings is valuable reading for all today's designers of medium-rise steel buildings, and especially those using either BS 5950-1 or Eurocode 3, Part 1.1. The paper describes the fundamentals of stability of buildings with rigid beam–column joints, explains the origins of design methods available in current codes of practice, advises on how best to proportion frames for stability and warns about the need for stability of traditional steel frames. The main focus of the paper was on steel frames in which the beam–column connections were stiff moment-resisting joints. Its effect on design can be judged from its effect on codes of practice. Its effect on construction practice can be seen by the extent that rigidly jointed frames have been used since the paper was written.
A new lateral force distribution formula for base-isolated structures
Authors: Khoshnoudian F. , Esrafili S.
Published: September 2008

It has been suggested that the static lateral response procedure for a base-isolated structure presented in the International Building Code (IBC) somewhat overestimates the seismic storey force. In this paper an IBC-equivalent static method for base-shear distribution of seismic isolated structures is evaluated. The results of the equivalent static procedure in the vertical distribution of base shear are compared with results obtained from dynamic linear and nonlinear analysis and the efficiency of its application is studied. In general, the results of the equivalent lateral response procedure in the proposed triangular distribution of base shear are somewhat conservative. Based on linear and nonlinear analysis results of isolated structures, therefore, two new formulae are proposed for the vertical distribution of the base shear. The proposed linear formula is based on the first mode shape of the isolated structure and the nonlinear formula follows three first mode shapes, which imply contribution of higher modes in a more realistic nonlinear analysis. The accuracy of the new formulae is examined by comparing the results obtained from this study with those calculated from linear and nonlinear time history analysis.
Improving bridge afflux prediction for overbank flows
Authors: Seckin G. , Knight D. W. , Atabay S. , Seckin N.
Published: September 2008

Tests were carried out to investigate bridge afflux phenomena for bridge constrictions in a compound channel flume. The flume had different roughness configurations in the main channel and floodplains. All tests were undertaken for the condition of no eccentricity and no entrance rounding. The normal crossing (ø = 0°) and two different skew angles (ø = 30° and 45°) were tested for different arch and flat soffit type bridge models. For each set of experiments, the Froude number for normal depth, afflux ratio and blockage ratio (area of bridge below water level to total flow area) were obtained based on an analogical method developed previously. These quantities were analysed to obtain a simple practical afflux equation. This afflux equation was also applied to field data collected by the US Geological Survey and the results were compared with those obtained using the more complex methods such as HEC-2, WSPRO and USBPR.
Flood risk management strategies using multi-criteria analysis
Authors: Yazdandoost F. , Bozorgy B.
Published: September 2008

Flood risk management is investigated in the context of a decision making problem. Various flood risk management strategies are considered the alternatives; the evaluation criteria of such strategies, previously defined in other research, are considered the decision criteria. The concept of ‘resilience’, also introduced in other research, is appropriately addressed in this regard. The application of multi-criteria decision making in flood risk management is demonstrated in a case study of the lower Rhine River. Flood risk management strategies other than the current strategy are defined based on the concept of resilience, and ranking of the strategies based on the flood risk management evaluation criteria is presented. The results are supported by uncertainty analyses to show the effect of uncertainties on the ranking order of the strategies.
Laboratory study of maximum scour depth downstream of sills
Authors: Chinnarasri C. , Kositgittiwong D.
Published: September 2008

Bed sills have been widely used as a sequence of grade-control structures in mountain streams where incision has to be prevented. Major local scouring downstream of these structures is, however, often observed. In order to investigate the characteristics of local scouring, a number of experiments have been carried out with 105 cases in different situations. The initial bed slopes were 0·176 and 0·268; sediments were coarse sand, fine gravel and medium gravel. The sill spacings were 0·4, 0·6, 0·8 and 0·9 m, and the sill heights above initial stream bed level were 0, 0·02, 0·04 and 0·06 m, respectively. Three stages of scour evolution could be classified. The size of scour hole depends on the bed slope, sediment diameter, sill height and sill spacing. The slope of the stream bed was found to be the most important parameter affecting the maximum scour depth. Using dimensional analysis, the relative maximum scour depth at the equilibrium stage was formulated as functions of the relative morphological jump to mobility of sediment and the relative energy loss to flow energy. Compared with the measured data at the Maso di Spinelle River in the Italian Alps, the proposed formulae showed satisfactory results.
The Efficacy of Female Condom Skills Training in HIV Risk Reduction Among Women: A Randomized Controlled Trial
Authors: Choi Kyung-Hee , Hoff Colleen , Gregorich Steven E. , Grinstead Olga , Gomez Cynthia , Hussey Wendy
Published: September 2008

Objectives. We evaluated the efficacy of skills training designed to increase female condom use among women.

Methods. We conducted a randomized controlled trial of 409 women, recruited from family planning clinics in northern California, who were randomly assigned to the experimental 4-session female condom skills training intervention or the comparison 4-session women's general health promotion intervention. Participants received condom use instructions at baseline and male and female condoms during the study. They completed audio computer-assisted self-interviews at baseline and at 3 and 6 months.

Results. At 3 and 6 months, women in the experimental group were more likely than those in the comparison group to have used the female condom at least once in the prior 3 months. The increase in the percentage of sexual acts protected by female condoms from baseline to the 6-month follow-up was greater for the experimental group. The percentage of sexual acts during which any condom was employed was higher in the experimental group at 6 months. There were no group differences in male condom use.

Conclusions. Outcomes suggest that skills training can increase female condom use and protected sexual acts without reducing male condom use among women.
Pleasure, Power, and Inequality: Incorporating Sexuality Into Research on Contraceptive Use
Authors: Higgins Jenny A. , Hirsch Jennifer S.
Published: September 2008

We know surprisingly little about how contraception affects sexual enjoyment and functioning (and vice versa), particularly for women. What do people seek from sex, and how do sexual experiences shape contraceptive use? We draw on qualitative data to make 3 points. First, pleasure varies. Both women and men reported multiple aspects of enjoyment, of which physical pleasure was only one.

Second, pleasure matters. Clear links exist between the forms of pleasure respondents seek and their contraceptive practices. Third, pleasure intersects with power and social inequality. Both gender and social class shape sexual preferences and contraceptive use patterns. These findings call for a reframing of behavioral models that explain why people use (or do not use) contraception.