bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Scheduling and Incentive Compatible Pricing for a Service System with Quality of Service Guarantees
Authors: Hsu Vernon N. , Xu Susan H. , Jukic Boris
Published: September 2008

This paper proposes a resource allocation and pricing mechanism for a service system that serves multiple classes of jobs within an organization. Each class of service request is subject to a class-dependent quality of service (QoS) guarantee on the expected delay bound, which may be imposed by business rules in an organization or other application-specific technical constraints. We develop an extension of a resource allocation and pricing mechanism for an M/M/1 system. In contrast to the system without the QoS guarantee, where a fixed priority scheduling policy—known as the cμ rule—is optimal, we show that the system may need to adopt a more general randomized priority scheduling policy to maximize the overall system profit. We also develop a transfer pricing scheme that is both optimal and incentive compatible, allowing users to act in their self-interests while collectively achieving the system optimum. We show that the pricing scheme with the QoS guarantee depends on the scheduling policy implemented and has different characteristics from that without the QoS guarantee.
Medication Reconciliation at Hospital Discharge: Evaluating Discrepancies
Authors: Wong Jacqueline D , Bajcar Jana M , Wong Gary G , Alibhai Shabbir MH , Huh Jin-Hyeun , Cesta Annemarie , Pond Gregory R , Fernandes Olavo A
Published: September 2008

Background:

Hospital discharge is an interlace of care when patients are at a high risk of medication discrepancies as they transition from hospital to home. These discrepancies are important, as they may contribute to drug-related problems, medication errors, and adverse drug events.

Objective:

To Identify, characterize, and assess the clinical impact of unintentional medication discrepancies at hospital discharge.

Methods:

All consecutive general internal medicine patients admitted for at least 72 hours to a tertiary care teaching hospital were prospectively assessed. Patients were excluded if they were discharged with verbal prescriptions; died during hospitalization; or transferred from or to a nursing home, another institution, or another unit within the same hospital. The primary endpoint was to determine the number of patients with at least one unintended medication discrepancy on hospital discharge. Medication discrepancies were assessed through comparison of a best possible medication discharge list with the actual discharge prescriptions. Secondary objectives were to characterize and assess the potential clinical impact of the unintentional discrepancies.

Results:

From March 14,2006, to June 2,2006,430 patients were screened for eligibility; 150 patients were included in the study. Overall, 106 (70.7%) patients had at least one actual or potential unintentional discrepancy. Sixty-two patients (41.3%) had at least one actual unintentional medication discrepancy al hospital discharge and 83 patients (55.3%) had at least one potential unintentional discrepancy. The most common unintentional discrepancies were an incomplete prescription requiring clarification, which could result in a patient delay in obtaining medications (49.5%), and the omission of medications (22.9%). Of the 105 unintentional discrepancies, 31 (29.5%) had the potential to cause possible or probable patient discomfort and/or clinical deterioration.

Conclusions:

Medication discrepancies occur commonly on hospital discharge. Understanding the type and frequency of discrepancies can help clinicians better understand ways to prevent them. Structured medication reconciliation may help to prevent discharge medication discrepancies.
Communication prompts donation: Exploring the beliefs underlying registration and discussion of the organ donation decision
Authors: Hyde Melissa K. , White Katherine M.
Published: September 2008

Objectives. To use a theory of planned behaviour (TPB) framework to explore the beliefs underlying communication of the donation decision for people who had not previously registered their consent on a donor register or discussed their decision with significant others.

Design. Initially, a focus group study elicited the common TPB (behavioural, normative, and control) beliefs about registering and discussing the organ donation decision. The main study assessed the important TPB belief predictors of intentions to register and discuss the donation decision.

Method. University students and community members from Queensland, Australia (N = 123) completed items assessing their intentions and the TPB behavioural, normative, and control beliefs for registering and discussing their donation decision.

Results. Structural equation modelling (SEM) analyses revealed significant paths between people's intentions to register their donation decisions and underlying behavioural (e.g. enabling efficient donation procedures), normative (e.g. friends, doctors/medical professionals), and control (e.g. lack of motivation, knowing details about transplant recipients) beliefs (R2=.30). There were also significant paths between people's intentions to discuss their donation decision and underlying behavioural (e.g. feeling uncomfortable talking about death related topics) and normative (e.g. partner/spouse, family members) beliefs, but not control beliefs (R2=.33). There was a significant path between intentions to register and intentions to discuss one's donation decision.

Conclusions. Results highlight the importance of focusing on behavioural and normative beliefs about communicating the donation decision, specifically for people who have not previously communicated their decision, and suggest potential targets for interventions designed to promote decision communication.
Fast Subplasma Membrane Ca2+Transients Control Exo-Endocytosis of Synaptic-Like Microvesicles in Astrocytes
Authors: Marchaland Julie , Calì Corrado , Voglmaier Susan M. , Li Haiyan , Regazzi Romano , Edwards Robert H. , Bezzi Paola
Published: September 2008

Astrocytes are the most abundant glial cell type in the brain. Although not apposite for long-range rapid electrical communication, astrocytes share with neurons the capacity of chemical signaling via Ca2+-dependent transmitter exocytosis. Despite this recent finding, little is known about the specific properties of regulated secretion and vesicle recycling in astrocytes. Important differences may exist with the neuronal exocytosis, starting from the fact that stimulus-secretion coupling in astrocytes is voltage independent, mediated by G-protein-coupled receptors and the release of Ca2+from internal stores. Elucidating the spatiotemporal properties of astrocytic exo-endocytosis is, therefore, of primary importance for understanding the mode of communication of these cells and their role in brain signaling. We here take advantage of fluorescent tools recently developed for studying recycling of glutamatergic vesicles at synapses (Voglmaier et al., 2006; Balaji and Ryan, 2007); we combine epifluorescence and total internal reflection fluorescence imaging to investigate with unprecedented temporal and spatial resolution, the stimulus-secretion coupling underlying exo-endocytosis of glutamatergic synaptic-like microvesicles (SLMVs) in astrocytes. Our main findings indicate that (1) exo-endocytosis in astrocytes proceeds with a time course on the millisecond time scale (τexocytosis= 0.24 ± 0.017 s; τendocytosis= 0.26 ± 0.03 s) and (2) exocytosis is controlled by local Ca2+microdomains. We identified submicrometer cytosolic compartments delimited by endoplasmic reticulum tubuli reaching beneath the plasma membrane and containing SLMVs at which fast (time-to-peak, ∼50 ms) Ca2+events occurred in precise spatial-temporal correlation with exocytic fusion events. Overall, the above characteristics of transmitter exocytosis from astrocytes support a role of this process in fast synaptic modulation.
Behavioral State Regulation of Dendrodendritic Synaptic Inhibition in the Olfactory Bulb
Authors: Tsuno Yusuke , Kashiwadani Hideki , Mori Kensaku
Published: September 2008

Behavioral states regulate how information is processed in local neuronal circuits. Here, we asked whether dendrodendritic synaptic interactions in the olfactory bulb vary with brain and behavioral states. To examine the state-dependent change of the dendrodendritic synaptic transmission, we monitored changes in field potential responses in the olfactory bulb of urethane-anesthetized and freely behaving rats. In urethane-anesthetized rats, granule-to-mitral dendrodendritic synaptic inhibition was larger and longer when slow waves were present in the electroencephalogram (slow-wave state) than during the fast-wave state. The state-dependent alternating change in the granule-to-mitral inhibition was regulated by the cholinergic system. In addition, the frequency of the spontaneous oscillatory activity of local field potentials and periodic discharges of mitral cells in the olfactory bulb shifted in synchrony with shifts in the neocortical brain state. Freely behaving rats showed multilevel changes in dendrodendritic synaptic inhibition that corresponded to diverse behavioral states; the inhibition was the largest during slow-wave sleep state, and successively smaller during light sleep, awake immobility, and awake moving states. These results provide evidence that behavioral state-dependent global changes in cholinergic tone modulate dendrodendritic synaptic inhibition and the information processing mode in the olfactory bulb.
Role of RhoA in Activity-Dependent Cortical Axon Branching
Authors: Ohnami Soichiro , Endo Mitsuharu , Hirai Satoshi , Uesaka Naofumi , Hatanaka Yumiko , Yamashita Toshihide , Yamamoto Nobuhiko
Published: September 2008

During development, axon branching is influenced by sensory-evoked and spontaneous neural activity. We studied the molecular mechanism that underlies activity-dependent branch formation at horizontally elongating axons (horizontal axons) in the upper cortical layers, focusing on Rho family small GTPases. Axonal labeling with enhanced yellow fluorescent protein showed that horizontal axons formed several branches in organotypic slice cultures. This branch formation was considerably increased by introducing constitutively active RhoA and was slightly inhibited by dominant-negative RhoA. Activators and inhibitors of endogenous RhoA signaling also promoted and inhibited branching, respectively. Daily imaging of horizontal axon growth further demonstrated that constitutively active RhoA increased the dynamic addition and loss of branches. Moreover, the amount of active RhoA relative to the total amount of RhoA was examined by a pull-down assay in cortical slices treated with sodium channel or glutamate receptor blockers to reduce neural activity. Activity blockade significantly decreased active RhoA compared with normal culture conditions, in which spontaneous firing is prominent. These findings suggest that RhoA signaling acts as a positive regulator for activity-dependent axon branching in cortical neurons.
Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus
Authors: Rao Yan , Lu Min , Ge Fei , Marsh Donald J. , Qian Su , Wang Alex Hanxiang , Picciotto Marina R. , Gao Xiao-Bing
Published: September 2008

The lateral hypothalamus (LH) is a central hub that integrates inputs from, and sends outputs to, many other brain areas. Two groups of neurons in the LH, expressing hypocretin/orexin or melanin concentrating hormone (MCH), have been shown to participate in sleep regulation, energy homeostasis, drug addiction, motor regulation, stress response, and social behaviors. The elucidation of crosstalk between these two systems is essential to understand these behaviors and functions because there is evidence that there are reciprocal innervations between hypocretin/orexin and MCH neurons. In this study, we used MCH receptor-1 knock-out (MCHR1 KO) and wild-type (WT) mice expressing green fluorescent protein in hypocretin/orexin-containing neurons to examine the hypothesis that MCH modulates hypocretin/orexin-mediated effects on behavioral state and synaptic transmission in the LH. In MCHR1 KO mice, the efficacy of glutamatergic synapses on hypocretin/orexin neurons is potentiated and hypocretin-1-induced action potential firing is facilitated, potentially explaining an increased effect of modafinil observed in MCHR1 KO mice. In wild-type mice with intact MCHR1 signaling, MCH significantly attenuated the hypocretin-1-induced enhancement of spike frequency in hypocretin/orexin neurons. The MCH effect was dose dependent, pertussis toxin sensitive, and was abolished in MCHR1 KO mice. Consistent with this effect, MCH attenuated hypocretin-1-induced enhancement of the frequency of miniature EPSCs in hypocretin/orexin neurons. These data from MCHR1 KO and WT mice demonstrate a novel interaction between these two systems, implying that MCH may exert a unique inhibitory influence on hypocretin/orexin signaling as a way to fine-tune the output of the LH.
Linking the Response Properties of Cells in Auditory Cortex with Network Architecture: Cotuning versus Lateral Inhibition
Authors: de la Rocha Jaime , Marchetti Cristina , Schiff Max , Reyes Alex D.
Published: September 2008

The frequency-intensity receptive fields (RF) of neurons in primary auditory cortex (AI) are heterogeneous. Some neurons have V-shaped RFs, whereas others have enclosed ovoid RFs. Moreover, there is a wide range of temporal response profiles ranging from phasic to tonic firing. The mechanisms underlying this diversity of receptive field properties are yet unknown. Here we study the characteristics of thalamocortical (TC) and intracortical connectivity that give rise to the individual cell responses. Using a mouse auditory TC slice preparation, we found that the amplitude of synaptic responses in AI varies non-monotonically with the intensity of the stimulation in the medial geniculate nucleus (MGv). We constructed a network model of MGv and AI that was simulated using either rate model cells orin vitroneurons through an iterative procedure that used the recorded neural responses to reconstruct network activity. We compared the receptive fields and firing profiles obtained with networks configured to have either cotuned excitatory and inhibitory inputs or relatively broad, lateral inhibitory inputs. Each of these networks yielded distinct response properties consistent with those documentedin vivowith natural stimuli. The cotuned network produced V-shaped RFs, phasic-tonic firing profiles, and predominantly monotonic rate-level functions. The lateral inhibitory network produced enclosed RFs with narrow frequency tuning, a variety of firing profiles, and robust non-monotonic rate-level functions. We conclude that both types of circuits must be present to account for the wide variety of responses observedin vivo.
Status Epilepticus Induces a Particular Microglial Activation State Characterized by Enhanced Purinergic Signaling
Authors: Avignone Elena , Ulmann Lauriane , Levavasseur Françoise , Rassendren François , Audinat Etienne
Published: September 2008

Microglia cells are the resident macrophages of the CNS, and their activation plays a critical role in inflammatory reactions associated with many brain disorders, including ischemia, Alzheimer's and Parkinson's diseases, and epilepsy. However, the changes of microglia functional properties in epilepsy have rarely been studied. Here, we used a model of status epilepticus (SE) induced by intraperitoneal kainate injections to characterize the properties of microglial cells in hippocampal slices from CX3CR1eGFP/+mice. SE induced within 3 h an increased expression of inflammatory mediators in the hippocampus, followed by a modification of microglia morphology, a microglia proliferation, and a significant neurodegeneration in CA1. Changes in electrophysiological intrinsic membrane properties of hippocampal microglia were detected at 24–48 h after SE with, in particular, the appearance of new voltage-activated potassium currents. Consistent with the observation of an upregulation of purinergic receptor mRNAs in the hippocampus, we also provide pharmacological evidence that microglia membrane currents mediated by the activation of P2 receptors, including P2X7, P2Y6, and P2Y12, were increased 48 h after SE. As a functional consequence of this modification of purinergic signaling, motility of microglia processes toward a source of P2Y12receptor agonist was twice as fast in the epileptic hippocampus. This study is the first functional description of microglia activation in anin vivomodel of inflammation and provides evidence for the existence of a particular microglial activation state after a status epilepticus.
Spatiotemporal Profiles of Field Potentials in Mouse Superior Colliculus Analyzed by Multichannel Recording
Authors: Phongphanphanee Penphimon , Kaneda Katsuyuki , Isa Tadashi
Published: September 2008

The onset and vector of orienting behaviors, such as saccades, are controlled by commands that descend from a population of neurons in deep layers of the superior colliculus (dSC). In this study, to characterize the role of the collicular local circuitry that generates the spatiotemporal pattern of command activity in the dSC neuronal population, responses evoked by single-pulse electrical stimulation in superficial layers of the superior colliculus (sSC) were analyzed by a 64-channel field potential recording system (planar electrode, 8 × 8 pattern; 150 μm interelectrode spacing) in slices obtained from 16- to 22-d-old mice. A negative field potential with short latency and short duration spatially restricted to the recording sites in sSC was evoked adjacent to the stimulation site. After bath application of 10 μmbicuculline, the same stimulus induced a large negative field response with long duration that spread from sSC to dSC. The dSC potential initially showed a positive response, presumably because of reversal of the negative potential that originated in sSC, and then a long negative response that spread horizontally as far as 1 mm. These responses disappeared after application of an NMDA receptor antagonist, 2-amino-5-phosphonovelarate, indicating that NMDA receptors have an important role in the generation of these responses. Simultaneous whole-cell patch-clamp recordings showed that the long-lasting negative field potentials corresponded to the depolarization accompanying burst spike activity of SC neurons. The present study revealed an extensive excitatory network in the dSC that may contribute to the generation of activity by a large population of neurons that discharge before a saccade.
Hierarchical Organization of Human Cortical Networks in Health and Schizophrenia
Authors: Bassett Danielle S. , Bullmore Edward , Verchinski Beth A. , Mattay Venkata S. , Weinberger Daniel R. , Meyer-Lindenberg Andreas
Published: September 2008

The complex organization of connectivity in the human brain is incompletely understood. Recently, topological measures based on graph theory have provided a new approach to quantify large-scale cortical networks. These methods have been applied to anatomical connectivity data on nonhuman species, and cortical networks have been shown to have small-world topology, associated with high local and global efficiency of information transfer. Anatomical networks derived from cortical thickness measurements have shown the same organizational properties of the healthy human brain, consistent with similar results reported in functional networks derived from resting state functional magnetic resonance imaging (MRI) and magnetoencephalographic data. Here we show, using anatomical networks derived from analysis of inter-regional covariation of gray matter volume in MRI data on 259 healthy volunteers, that classical divisions of cortex (multimodal, unimodal, and transmodal) have some distinct topological attributes. Although all cortical divisions shared nonrandom properties of small-worldness and efficient wiring (short mean Euclidean distance between connected regions), the multimodal network had a hierarchical organization, dominated by frontal hubs with low clustering, whereas the transmodal network was assortative. Moreover, in a sample of 203 people with schizophrenia, multimodal network organization was abnormal, as indicated by reduced hierarchy, the loss of frontal and the emergence of nonfrontal hubs, and increased connection distance. We propose that the topological differences between divisions of normal cortex may represent the outcome of different growth processes for multimodal and transmodal networks and that neurodevelopmental abnormalities in schizophrenia specifically impact multimodal cortical organization.
Ablation of Neurons Expressing Agouti-Related Protein ActivatesFosand Gliosis in Postsynaptic Target Regions
Authors: Wu Qi , Howell Maureen P. , Palmiter Richard D.
Published: September 2008

We have developed a mouse model in which a specific population of inhibitory neurons can be selectively ablated by the action of diphtheria toxin (DT). The model involves targeting the human DT receptor to the agouti-related protein (Agrp) locus so that systemic administration of DT kills all of the AgRP-expressing neurons, resulting in starvation of the mice. Ablation of AgRP neurons results in robust (5- to 10-fold) activation ofFosgene expression in many brain regions that are innervated by AgRP neurons, including the arcuate nucleus (ARC), the paraventricular nucleus, the medial preoptic area, the lateral septum, and nucleus of the solitary tract. As expected, there is robust increase in GFAP staining (astrocytes) as well as IBA1 and CD11b staining (microglia) in the ARC in response to AgRP neuron ablation. There is also a dramatic increase of these markers in most, but not all, postsynaptic targets of AgRP axons. We used a genetic approach to reduce melanocortin signaling, which attenuatedFosactivation in some brain regions after ablation of AgRP neurons. We suggest that loss of inhibitory signaling onto target neurons results in unopposed excitation that is responsible for the activation ofFosand that dysregulation of these neuronal circuits is responsible for starvation. Furthermore, glial cell activation in target areas of AgRP neurons appears to be a result of excitotoxicity.
A Novel Na+Channel Splice Form Contributes to the Regulation of an Androgen-Dependent Social Signal
Authors: Liu He , Wu Ming-ming , Zakon Harold H.
Published: September 2008

Na+channels are often spliced but little is known about the functional consequences of splicing. We have been studying the regulation of Na+current inactivation in an electric fish model in which systematic variation in the rate of inactivation of the electric organ Na+current shapes the electric organ discharge (EOD), a sexually dimorphic, androgen-sensitive communication signal. Here, we examine the relationship between an Na+channel (Nav1.4b), which has two splice forms, and the waveform of the EOD. One splice form (Nav1.4bL) possesses a novel first exon that encodes a 51 aa N-terminal extension. This is the first report of an Na+channel with alternative splicing in the N terminal. This N terminal is present in zebrafish suggesting its general importance in regulating Na+currents in teleosts. The extended N terminal significantly speeds fast inactivation, shifts steady-state inactivation, and dramatically enhances recovery from inactivation, essentially fulfilling the functions of a β subunit. Both splice forms are equally expressed in muscle in electric fish and zebrafish but Nav1.4bL is the dominant form in the electric organ implying electric organ-specific transcriptional regulation. Transcript abundance of Nav1.4bL in the electric organ is positively correlated with EOD frequency and lowered by androgens. Thus, shaping of the EOD waveform involves the androgenic regulation of a rapidly inactivating splice form of an Na+channel. Our results emphasize the role of splicing in the regulation of a vertebrate Na+channel and its contribution to a known behavior.
Altered Sensory Experience Induces Targeted Rewiring of Local Excitatory Connections in Mature Neocortex
Authors: Cheetham Claire E. J. , Hammond Martin S. L. , McFarlane Rachael , Finnerty Gerald T.
Published: September 2008

Experience-dependent plasticity in adulthood is slower than during development. Previous experience can accelerate adult cortical plasticity. However, the contributions of functional synaptic changes and modifications in neuronal structure to the acceleration of adult cortical plasticity remain unclear. If structural remodeling was important then it should be exhibited by neuronal connections that have altered during plasticity. We trimmed rodents' whiskers to induce experience-dependent plasticity and reconstructed pairs of layer 2/3 (L2/3) pyramidal neurons after electrophysiological recording. We reported recently that local excitatory connections strengthen without a change in synapse number in cortex with retained sensory input (spared) (Cheetham et al., 2007). Here, we show that strengthened connections are rewired. The rewiring involves remodeling of the axonal arbor of excitatory connections with only minor changes in postsynaptic dendritic trees. The axonal remodeling resulted in a greater length of presynaptic axon close to postsynaptic dendrites at existing local excitatory connections in spared cortex. In control cortex, the length of axon close to dendrite in unconnected pairs of L2/3 pyramidal neurons was similar to that in synaptically connected pairs of L2/3 pyramidal neurons. This finding suggests that the probability of forming a synapse and, therefore, establishing a connection, is not driven solely by the length of axon close to dendrite. The axonal remodeling that we describe is not associated with altered synapse number, but instead increases the number of sites where synapses could be formed between synaptically connected neurons with minimal structural changes. This enables rapid and cost-efficient rewiring of local excitatory connections when re-exposed to similarly altered sensory experience in adulthood.
Noggin Expands Neural Stem Cells in the Adult Hippocampus
Authors: Bonaguidi Michael A. , Peng Chian-Yu , McGuire Tammy , Falciglia Gustave , Gobeske Kevin T. , Czeisler Catherine , Kessler John A.
Published: September 2008

New neurons are added to the adult hippocampus throughout life and contribute to cognitive functions, including learning and memory. It remains unclear whether ongoing neurogenesis arises from self-renewing neural stem cells (NSCs) or from multipotential progenitor cells that cannot self-renew in the hippocampus. This is primarily based on observations that neural precursors derived from the subventricular zone (SVZ) can be passaged long term, whereas hippocampal subgranular zone (SGZ) precursors are rapidly depleted by passaging. We demonstrate here that high levels of bone morphogenetic protein (BMP) signaling occur in hippocampal but not SVZ precursorsin vitro, and blocking BMP signaling with Noggin is sufficient to foster hippocampal cell self-renewal, proliferation, and multipotentiality using single-cell clonal analysis. Moreover, NSC maintenance requires continual Noggin exposure, which implicates BMPs as crucial regulators of NSC aging.In vivo, Noggin is expressed in the adult dentate gyrus and limits BMP signaling in proliferative cells of the SGZ. Transgenic Noggin overexpression in the SGZ increases multiple precursor cell populations but proportionally increases the glial fibrillary acidic protein-positive cell population at the expense of other precursors, suggesting that Noggin acts on NSCsin vivo. To confirm this, we used a dual thymidine analog paradigm to repeatedly label slowly dividing cells over a long duration. We find that small populations of label-retaining cells exist in the SGZ and that Noggin overexpression increases their numbers. Thus, we propose that the adult hippocampus contains a population of NSCs, which can be expanded bothin vitroandin vivoby blocking BMP signaling.
Poverty Catchments: Migration, Residential Mobility, and Population Turnover in Impoverished Rural Illinois Communities
Authors: Foulkes Matt , Newbold K. Bruce
Published: September 2008

Abstract  Research has thoroughly documented how out‐migration of the educated and skilled from rural areas leaves behind a poorer population and creates pockets of rural poverty. Recently, studies have recognized that the poor are also geographically mobile and that poverty migration patterns can reinforce rural poverty concentrations. In this process, certain impoverished rural communities in economically depressed regions receive a disproportionate share of poverty migrants, concentrating poverty in certain locations. This paper examines the conditions and processes through which poor rural communities become likely destinations for a highly mobile segment of the rural poor and near‐poor. Utilizing case studies of depressed rural Illinois communities, it investigates how the interplay of community factors and the behavior of migrants transforms rural communities from residentially stable to highly mobile, impoverished places.
Network Framing of Pest Management Knowledge and Practice*
Authors: Moore Keith M.
Published: September 2008

Abstract  Conventional technology transfer is based on the assumption that autonomous individuals independently make behavioral decisions. In contrast, Actor‐Network Theory (ANT) suggests that people and technologies are interconnected in ways that reinforce and reproduce some types of knowledge and consequent behavioral practices, but not others. Research on pest management in Mali shows the extent to which farm‐level decisions are shaped off‐farm through contracts that communicate commercial and regulatory decision‐making information. Findings from the analysis of Ukrainian farmer pest management decision‐making demonstrate the exercise of power of commercial interests. In light of these findings, evidence from Farmer Field School experiences in Indonesia is reinterpreted. This paper concludes that knowledge networks are not monolithic and, furthermore, there is competition between network segments to define appropriate knowledge and practice. It also recommends that agricultural scientists pay more attention to the negotiations framing legitimate knowledge about the networks in which their producer clienteles are embedded.
Does it or Doesn't it? Geographic Differences and the Costs of Living
Authors: Zimmerman Julie N. , Ham Sunny (Seonok) , Frank Sarah Michelle
Published: September 2008

Abstract  The relative cost of living in rural areas has long been of interest to rural sociologists. Today, the popular perception is that rural prices are lower. This study examines geographic differences in the costs of living in Kentucky. The results indicate that, contrary to the popular perception, when prices of the same products and services were compared, there was no consistent pattern of lower prices in the rural counties. Furthermore, differences in the material conditions of rural living meant that there were additional costs that price comparisons alone did not capture.
Rural Parentage and Labor Market Disadvantage in a Sub‐Saharan Setting: Sources and Trends
Authors: Giroux Sarah C.
Published: September 2008

Abstract  High unemployment in many developing countries is intensifying job competition and raising concern for the employment prospects of vulnerable groups, including children of rural parents. This paper examines the trends and sources in employment disadvantage associated with rural parentage in Cameroon. In documenting the sources of inequality, the study moves beyond a “consensus versus conflict” dichotomy, and instead uses regression decomposition to estimate the relative contributions of both perspectives. It also uses fixed‐effects methods to examine the importance of unobserved family influences that have been understudied in previous research. In documenting historical change in rural disadvantage, the study distinguishes between long‐term trends and shorter‐term economic fluctuations. Findings show that although rural parentage does not create a disadvantage in off‐farm employment as a whole, it does so within the formal sector. This disadvantage is predominantly due to rural‐urban differences in returns to schooling rather than levels of schooling. Disadvantage in schooling has been declining over time but, interestingly, these gains may stall during prosperous times, as these tend to inordinately benefit urban children.
Positive Selection at the Binding Sites of the Male-Specific Lethal Complex Involved in Dosage Compensation in Drosophila
Authors: Bachtrog Doris
Published: September 2008

In many taxa, males and females differ with respect to their sex chromosomes, and dosage compensation mechanisms have evolved to equalize X-linked gene transcription. In Drosophila, the male-specific lethal (MSL) complex binds to hundreds of sites along the male X chromosome and mediates twofold hypertranscription of the single male X. Two recent studies found evidence for lineage-specific adaptive evolution in all five core protein-coding genes of the MSL complex in Drosophila melanogaster. In particular, dramatic positive selection was detected in domains shown to be responsible for their specific targeting to the X chromosome. Here I use population genetics to show that three previously characterized MSL-binding DNA segments on the X themselves underwent adaptive evolution in D. melanogaster, but not in its close relatives D. simulans and D. yakuba. MSL components have been shown to not correctly target the D. melanogaster X chromosome in hybrids between D. melanogaster and D. simulans. My finding supports the idea of selection-driven coevolution among DNA-protein interactions of the dosage compensation machinery and suggests that misregulated dosage compensation could contribute to male hybrid inviability in Drosophila.
A Two-Stage Pruning Algorithm for Likelihood Computation for a Population Tree
Authors: RoyChoudhury Arindam , Felsenstein Joseph , Thompson Elizabeth A
Published: September 2008

We have developed a pruning algorithm for likelihood estimation of a tree of populations. This algorithm enables us to compute the likelihood for large trees. Thus, it gives an efficient way of obtaining the maximum-likelihood estimate (MLE) for a given tree topology. Our method utilizes the differences accumulated by random genetic drift in allele count data from single-nucleotide polymorphisms (SNPs), ignoring the effect of mutation after divergence from the common ancestral population. The computation of the maximum-likelihood tree involves both maximizing likelihood over branch lengths of a given topology and comparing the maximum-likelihood across topologies. Here our focus is the maximization of likelihood over branch lengths of a given topology. The pruning algorithm computes arrays of probabilities at the root of the tree from the data at the tips of the tree; at the root, the arrays determine the likelihood. The arrays consist of probabilities related to the number of coalescences and allele counts for the partially coalesced lineages. Computing these probabilities requires an unusual two-stage algorithm. Our computation is exact and avoids time-consuming Monte Carlo methods. We can also correct for ascertainment bias.
AMBIENCE: A Novel Approach and Efficient Algorithm for Identifying Informative Genetic and Environmental Associations With Complex Phenotypes
Authors: Chanda Pritam , Sucheston Lara , Zhang Aidong , Brazeau Daniel , Freudenheim Jo L , Ambrosone Christine , Ramanathan Murali
Published: September 2008

We developed a computationally efficient algorithm AMBIENCE, for identifying the informative variables involved in gene–gene (GGI) and gene–environment interactions (GEI) that are associated with disease phenotypes. The AMBIENCE algorithm uses a novel information theoretic metric called phenotype-associated information (PAI) to search for combinations of genetic variants and environmental variables associated with the disease phenotype. The PAI-based AMBIENCE algorithm effectively and efficiently detected GEI in simulated data sets of varying size and complexity, including the 10K simulated rheumatoid arthritis data set from Genetic Analysis Workshop 15. The method was also successfully used to detect GGI in a Crohn's disease data set. The performance of the AMBIENCE algorithm was compared to the multifactor dimensionality reduction (MDR), generalized MDR (GMDR), and pedigree disequilibrium test (PDT) methods. Furthermore, we assessed the computational speed of AMBIENCE for detecting GGI and GEI for data sets varying in size from 100 to 105 variables. Our results demonstrate that the AMBIENCE information theoretic algorithm is useful for analyzing a diverse range of epidemiologic data sets containing evidence for GGI and GEI.
Selection at Work in Self-Incompatible Arabidopsis lyrata. II. Spatial Distribution of S Haplotypes in Iceland
Authors: Schierup Mikkel H , Bechsgaard Jesper S , Christiansen Freddy B
Published: September 2008

We survey the distribution of haplotypes at the self-incompatibility (SI) locus of Arabidopsis lyrata (Brassicaceae) at 12 locations spread over the species' natural distribution in Iceland. Previous investigations of the system have identified 34 functionally different S haplotypes maintained by frequency-dependent selection and arranged them into four classes of dominance in their phenotypic expression. On the basis of this model of dominance and the island model of population subdivision, we compare the distribution of S haplotypes with that expected from population genetic theory. We observe 18 different S haplotypes, recessive haplotypes being more common than dominant ones, and dominant ones being shared by fewer populations. As expected, differentiation, although significant, is very low at the S locus even over distances of up to 300 km. The frequency of the most recessive haplotype is slightly larger than expected for a panmictic population, but consistent with a subdivided population with the observed differentiation. Frequencies in nature reflect effects of segregation distortion previously observed in controlled crosses. The dynamics of the S-locus variation are, however, well represented by a 12-island model and our simplified model of dominance interactions.
Patterns of Molecular Evolution Associated With Two Selective Sweeps in the Tb1–Dwarf8 Region in Maize
Authors: Camus-Kulandaivelu Letizia , Chevin Luis-Miguel , Tollon-Cordet Christine , Charcosset Alain , Manicacci Domenica , Tenaillon Maud I
Published: September 2008

We focused on a region encompassing a major maize domestication locus, Tb1, and a locus involved in the flowering time variation, Dwarf8 (D8), to investigate the consequences of two closely linked selective sweeps on nucleotide variation and gain some insights into maize geographical diffusion, through climate adaptation. First, we physically mapped D8 at ∼300 kb 3′ of Tb1. Second, we analyzed patterns of nucleotide variation at Tb1, D8, and seven short regions (400–700 bp) located in the Tb1–D8 region sequenced on a 40 maize inbred lines panel encompassing early-flowering temperate and late-flowering tropical lines. The pattern of polymorphism along the region is characterized by two valleys of depleted polymorphism while the region in between exhibits an appreciable amount of diversity. Our results reveal that a region ∼100 kb upstream of the D8 gene exhibits hallmarks of divergent selection between temperate and tropical lines and is likely closer than the D8 gene to the target of selection for climate adaptation. Selection in the tropical lines appears more recent than in the temperate lines, suggesting an initial domestication of early-flowering maize. Simulation results indicate that the polymorphism pattern is consistent with two interfering selective sweeps at Tb1 and D8.
From Hypo- to Hypersuppression: Effect of Amino Acid Substitutions on the RNA-Silencing Suppressor Activity of the Tobacco etch potyvirus HC-Pro
Authors: Torres-Barceló Clara , Martín Susana , Daròs José-Antonio , Elena Santiago F
Published: September 2008

RNA silencing participates in several important functions: from the regulation of cell metabolism and organism development to sequence-specific antiviral defense. Most plant viruses have evolved proteins that suppress RNA silencing and that in many cases are multifunctional. Tobacco etch potyvirus (TEV) HC-Pro protein suppresses RNA silencing and participates in aphid-mediated transmission, polyprotein processing, and genome amplification. In this study, we have generated 28 HC-Pro amino acid substitution mutants and quantified their capacity as suppressors of RNA silencing in a transient expression assay. Most mutations either had no quantitative effect or completely abolished silencing suppression (10 in each class), 3 caused a significant decrease in the activity, and 5 significantly increased it, revealing an unexpected high frequency of mutations conferring hypersuppressor activity. A representative set of the mutant alleles, containing both hypo- and hypersuppressors, was further analyzed for their effect on TEV accumulation and the strength of induced symptoms. Whereas TEV variants with hyposuppressor mutants were far less virulent than wild-type TEV, those with hypersuppressor alleles induced symptoms that were not more severe than those characteristic of the wild-type virus, suggesting that there is not a perfect match between suppression and virulence.
Interactions Between Markers Can Be Caused by the Dominance Effect of Quantitative Trait Loci
Authors: Zhang Luyan , Li Huihui , Li Zhonglai , Wang Jiankang
Published: September 2008

F2 populations are commonly used in genetic studies of animals and plants. For simplicity, most quantitative trait locus or loci (QTL) mapping methods have been developed on the basis of populations having two distinct genotypes at each polymorphic marker or gene locus. In this study, we demonstrate that dominance can cause the interactions between markers and propose an inclusive linear model that includes marker variables and marker interactions so as to completely control both additive and dominance effects of QTL. The proposed linear model is the theoretical basis for inclusive composite-interval QTL mapping (ICIM) for F2 populations, which consists of two steps: first, the best regression model is selected by stepwise regression, which approximately identifies markers and marker interactions explaining both additive and dominance variations; second, the interval mapping approach is applied to the phenotypic values adjusted by the regression model selected in the first step. Due to the limited mapping population size, the large number of variables, and multicollinearity between variables, coefficients in the inclusive linear model cannot be accurately determined in the first step. Interval mapping is necessary in the second step to fine tune the QTL to their true positions. The efficiency of including marker interactions in mapping additive and dominance QTL was demonstrated by extensive simulations using three QTL distribution models with two population sizes and an actual rice F2 population.
Dynamics and Differential Proliferation of Transposable Elements During the Evolution of the B and A Genomes of Wheat
Authors: Charles Mathieu , Belcram Harry , Just Jérémy , Huneau Cécile , Viollet Agnès , Couloux Arnaud , Segurens Béatrice , Carter Meredith , Huteau Virginie , Coriton Olivier , Appels Rudi , Samain Sylvie , Chalhoub Boulos
Published: September 2008

Transposable elements (TEs) constitute >80% of the wheat genome but their dynamics and contribution to size variation and evolution of wheat genomes (Triticum and Aegilops species) remain unexplored. In this study, 10 genomic regions have been sequenced from wheat chromosome 3B and used to constitute, along with all publicly available genomic sequences of wheat, 1.98 Mb of sequence (from 13 BAC clones) of the wheat B genome and 3.63 Mb of sequence (from 19 BAC clones) of the wheat A genome. Analysis of TE sequence proportions (as percentages), ratios of complete to truncated copies, and estimation of insertion dates of class I retrotransposons showed that specific types of TEs have undergone waves of differential proliferation in the B and A genomes of wheat. While both genomes show similar rates and relatively ancient proliferation periods for the Athila retrotransposons, the Copia retrotransposons proliferated more recently in the A genome whereas Gypsy retrotransposon proliferation is more recent in the B genome. It was possible to estimate for the first time the proliferation periods of the abundant CACTA class II DNA transposons, relative to that of the three main retrotransposon superfamilies. Proliferation of these TEs started prior to and overlapped with that of the Athila retrotransposons in both genomes. However, they also proliferated during the same periods as Gypsy and Copia retrotransposons in the A genome, but not in the B genome. As estimated from their insertion dates and confirmed by PCR-based tracing analysis, the majority of differential proliferation of TEs in B and A genomes of wheat (87 and 83%, respectively), leading to rapid sequence divergence, occurred prior to the allotetraploidization event that brought them together in Triticum turgidum and Triticum aestivum, <0.5 million years ago. More importantly, the allotetraploidization event appears to have neither enhanced nor repressed retrotranspositions. We discuss the apparent proliferation of TEs as resulting from their insertion, removal, and/or combinations of both evolutionary forces.
Muller's Ratchet and the Degeneration of Y Chromosomes: A Simulation Study
Authors: Engelstädter Jan
Published: September 2008

A typical pattern in sex chromosome evolution is that Y chromosomes are small and have lost many of their genes. One mechanism that might explain the degeneration of Y chromosomes is Muller's ratchet, the perpetual stochastic loss of linkage groups carrying the fewest number of deleterious mutations. This process has been investigated theoretically mainly for asexual, haploid populations. Here, I construct a model of a sexual population where deleterious mutations arise on both X and Y chromosomes. Simulation results of this model demonstrate that mutations on the X chromosome can considerably slow down the ratchet. On the other hand, a lower mutation rate in females than in males, background selection, and the emergence of dosage compensation are expected to accelerate the process.
Retention of Induced Mutations in a Drosophila Reverse-Genetic Resource
Authors: Cooper Jennifer L , Greene Elizabeth A , Till Bradley J , Codomo Christine A , Wakimoto Barbara T , Henikoff Steven
Published: September 2008

Targeting induced local lesions in genomes (TILLING) is a reverse-genetic method for identifying point mutations in chemically mutagenized populations. For functional genomics, it is ideal to have a stable collection of heavily mutagenized lines that can be screened over an extended period of time. However, long-term storage is impractical for Drosophila, so mutant strains must be maintained by continual propagation of live cultures. Here we evaluate a strategy in which ethylmethane sulfonate (EMS) mutagenized chromosomes were maintained as heterozygotes with balancer chromosomes for >100 generations before screening. The strategy yielded a spectrum of point mutations similar to those found in previous studies of EMS-induced mutations, as well as 2.4% indels (insertions and deletions). Our analysis of 1887 point mutations in 148 targets showed evidence for selection against deleterious lesions and differential retention of lesions among targets on the basis of their position relative to balancer breakpoints, leading to a broad distribution of mutational densities. Despite selection and differential retention, the success of a user-funded service based on screening a large collection several years after mutagenesis indicates sufficient stability for use as a long-term reverse-genetic resource. Our study has implications for the use of balancer chromosomes to maintain mutant lines and provides the first large-scale quantitative assessment of the limitations of using breeding populations for repositories of genetic variability.