bluuebunny/crossref_metadata_2025 huggingface dataset:
A content analysis of prescription drug information in the UK print news media
Authors: Prosser Helen , Clayson Karen
Published: July 2008

Objective

To determine the frequency and nature of news stories of prescription drugs in a range of widely distributed UK newspapers, and to examine what information is presented.

Setting

UK newsprint media.

Method

Content analysis.

Key findings

Seven-hundred and eighty-five daily and 130 Sunday newspapers were examined. A total of 556 articles mentioning at least one prescription medicine were identified. The majority of news stories (n = 352) present one of two dominant, but conflicting characterisations of modern medicine. On one side, most articles (n = 251) are positive in their portrayal of medicines, with an emphasis on the potential benefits of new drugs. Of these, only 21 (14%) were concerned with new drugs currently available and licensed in the UK. On the other side, a smaller number of articles represented ‘negative news’ about medicines, generally reporting the side-effects or iatrogenic effects of prescription drugs. Positive stories frequently excluded mention of the harmful effects or potential risks of drugs, and equally, ‘negative’ stories frequently excluded any mention of a drug's beneficial effects. Just over one-third of articles (36%, 128/352) included reference to other treatment options. Fifty-six per cent of articles referred to the findings of a specific research study. Of these, 58% cited a specific information source - a journal (66%) or scientific meeting/conference (34%).

Conclusion

The findings indicate that while the news print media are prolific communicators of information about medicines, the information provided is often incomplete and ambiguous, thus constraining the reader's ability to evaluate the risks and benefits of medicines and make informed treatment decisions. It emphasises the benefits of new drugs, particularly those yet to receive a product licence, and the harms of established prescription drugs. Findings highlight the need to make medicines reporting in the UK press more comprehensive.
Development and use of the critical incident technique in evaluating causes of dispensing incidents
Authors: James K Lynette , Barlow David , Hiom Sarah , Roberts Dave , Whittlesea Cate
Published: July 2008

Aims and objectives

The study aimed to evaluate the causes of prevented dispensing incidents reported by hospitals using the critical incident technique developed by key-informant interviews, focus group and observation.

Setting

All Welsh NHS hospitals (n = 20) were invited to participate in the study. Sixteen hospitals agreed to take part; 10 hospitals reported incidents, four hospitals did not report any incidents and two hospitals withdrew from the study.

Method

In June 2005 three key-informant interviews and a focus group were conducted to determine dispensary workflow, which was then validated by a piloted non-participant observational study at three Welsh hospitals. Self-reported critical incident forms were then developed to collect dispensing-incident data involving drugs at high risk of dispensing incidents. Sixteen Welsh hospitals participated in the 4-month study (January-August 2006).

Key findings

Dispensary workflow encompassed the following events: prescription receipt, validating patient information, log of prescription, technical check, clinical check, label generation, stock selection, medicines assembly, product labelling, completion of registers, self-checking/endorsing and final accuracy check. Twenty-four incidents were reported by 10 hospitals involving paediatrics (n = 9, 38%), morphine sulphate (n = 5, 21%), insulin (n = 5, 21%), angiotensin-converting enzyme inhibitors (n = 3, 13%) and nifedipine (n = 2, 8%). Incidents commonly occurred at label generation (n = 9, 43%) and stock selection (n = 9, 43%), caused by error-producing conditions, active and latent failures. Active failures involved dispensing the wrong quantity of medication, interchanging different formulations, and computer and stock-selection errors. Error-producing conditions were reported as high workload, complex prescriptions and interruptions. Latent conditions were inadequate staffing/ skill mix, unclear drug computer selection lists and the storage of drugs on dispensary shelves.

Conclusion

The critical incident technique provided an in-depth understanding of the causes of dispensing incidents. Dispensing incidents arose because of organisational pathologies, error producing conditions and active failures such as inadequate staffing, high workload, interruptions, and computer and drug-selection errors.
Informal learning in the workplace: what are the environmental barriers for junior hospital pharmacists?
Authors: Noble Christy , Hassell Karen
Published: July 2008

Objective

To determine the environmental barriers to informal learning in the workplace of junior hospital pharmacists.

Setting

A pharmacy department within a large teaching hospital in the north west of England.

Method

Twelve semi-structured interviews were conducted with the entire population of junior hospital pharmacists (n = 12). Interviewees were asked about their responsibilities and their learning in the workplace. Questions were also asked about how various aspects of the workplace environment influenced their learning and ability to develop as a pharmacist.

Key findings

Three key environmental barriers to informal learning in the workplace were identified. Firstly, the allocation and structuring of work inhibited the junior hospital pharmacists' informal learning by causing them to work under pressure and in isolation; in addition, the rotational nature of the job created barriers to informal learning. Secondly, lack of feedback and goals inhibited their learning. They also felt that the managers were not fostering an environment conducive to learning. Finally, structural inhibitors such as location of departments, and lack of desk space and computers were perceived to limit their ability to learn.

Conclusion

This study highlights the presence of environmental barriers to informal learning for junior hospital pharmacists. While these barriers are contextual and closely related to the workplace setting, their identification will enable those responsible for the development of junior pharmacists in the workplace to take these into consideration when promoting informal learning.
Client and pharmacist factors affecting practice in the management of upper respiratory tract infection presented in community pharmacies: a simulated client study
Authors: Saengcharoen Woranuch , Chongsuvivatwong Virasakdi , Lerkiatbundit Sanguan , Wongpoowarak Payom
Published: July 2008

Objectives

To assess the quality of care provided by community pharmacists for simulated clients (SCs) with upper respiratory tract infection (URI) and to examine the effects of gender and appearance of socioeconomic status (SES) of the SCs on the practice.

Setting

Thirty-two community pharmacies in the south of Thailand with four male and four female SCs.

Method

Each SC visited eight community pharmacies twice, 1month apart, once with moderate and once with an appearance of low SES, in random order. Key outcome variables were history-taking, advice-giving, and antibiotic-dispensing, based on international guidelines. Descriptive statistics and mixed-effects models with nesting of SCs and community pharmacies were conducted.

Key findings

The mean scores for history-taking and advice-giving were low. The proportions of 128 encounters ending up with antibiotics, corticosteroids and nonsteroidal anti-inflammatory drugs were 87.5, 12.5 and 7.8%, respectively. Pharmacist practice did not differ by SC gender or appearance of SES.

Conclusion

Such practice by pharmacists needs improvement. Further studies to confirm the lack of effect of clients' gender and SES are needed.
Progression of meiotic recombination requires structural maturation of the central element of the synaptonemal complex
Authors: Hamer Geert , Wang Hong , Bolcun-Filas Ewelina , Cooke Howard J. , Benavente Ricardo , Höög Christer
Published: July 2008

The synaptonemal complex is an elaborate meiosis-specific supramolecular protein assembly that promotes chromosome synapsis and meiotic recombination. We inactivated the meiosis-specific gene Tex12 and found that TEX12 is essential for progression of meiosis in both male and female germ cells. Structural analysis of the synaptonemal complex in Tex12–/– meiocytes revealed a disrupted central element structure, a dense structure residing between the synapsed homologous chromosomes. Chromosome synapsis is initiated at multiple positions along the paired homologous chromosomes in Tex12–/– meiotic cells, but fails to propagate along the chromosomes. Furthermore, although meiotic recombination is initiated in Tex12–/– meiotic cells, these early recombination events do not develop into meiotic crossovers. Hence, the mere initiation of synapsis is not sufficient to support meiotic crossing-over. Our results show that TEX12 is a component of the central element structure of the synaptonemal complex required for propagation of synapsis along the paired homologous chromosomes and maturation of early recombination events into crossovers.
The Red Queen, Success Bias, and Organizational Inertia
Authors: Barnett William P. , Pontikes Elizabeth G.
Published: July 2008

Why do successful organizations often move in new directions and then fail? We propose that this pattern is especially likely among organizations that have survived a history of competition. Such experience adapts organizations to their environment, through so-called “Red Queen” evolution, but being well adapted for one context makes moving into new contexts more hazardous. Meanwhile, managers in such organizations infer from their histories of competitive success a biased assessment of their organization's ability to change. Consequently, although surviving competition makes organizational change especially hazardous, managers in surviving organizations are especially inclined to such initiatives. We develop these ideas in an empirically testable model, and find supportive evidence in estimates of the model using data from the history of the U.S. computer industry.
Knowledge Sharing Ambidexterity in Long-Term Interorganizational Relationships
Authors: Im Ghiyoung , Rai Arun
Published: July 2008

Although past research has investigated the impact of exploration and exploitation on firm performance, there is limited research on these effects in interorganizational relationships. We examine whether the boundary condition for ambidextrous learning can be extended from firms to long-term interorganizational relationships. Specifically, we focus on a particular aspect of learning—namely, explorative and exploitative knowledge sharing—and examine its impact on the performance of long-term relationships. We also theorize how ambidextrous management of the relationship and ontological commitment to span the syntactic, semantic, and pragmatic knowledge boundaries between partners enable knowledge sharing. Our theoretical predictions are tested using data collected from both account managers at customer firms responsible for the relationship with a leading supply chain vendor and account managers at the vendor firm responsible for relationships with customers. The findings suggest that both exploratory and exploitative knowledge sharing lead to relationship performance gains, that such sharing is enabled by the ambidextrous management of the relationship, and that such sharing is facilitated by ontological commitment. Interesting differences in the enablers and consequences of both forms of knowledge sharing are detected between customers and the vendor.
Computing Virtual Nesting Controls for Network Revenue Management Under Customer Choice Behavior
Authors: van Ryzin Garrett , Vulcano Gustavo
Published: July 2008

We consider a revenue management, network capacity control problem in a setting where heterogeneous customers choose among the various products offered by a firm (e.g., different flight times, fare classes, and/or routings). Customers may therefore substitute if their preferred products are not offered. These individual customer choice decisions are modeled as a very general stochastic sequence of customers, each of whom has an ordered list of preferences. Minimal assumptions are made about the statistical properties of this demand sequence. We assume that the firm controls the availability of products using a virtual nesting control strategy and would like to optimize the protection levels for its virtual classes accounting for the (potentially quite complex) choice behavior of its customers.

We formulate a continuous demand and capacity approximation for this problem, which allows for the partial acceptance of requests for products. The model admits an efficient calculation of the sample path gradient of the network revenue function. This gradient is then used to construct a stochastic steepest ascent algorithm. We show the algorithm converges in probability to a stationary point of the expected revenue function under mild conditions. The algorithm is relatively efficient even on large network problems, and in our simulation experiments it produces significant revenue increases relative to traditional virtual nesting methods. On a large-scale, real-world airline example using choice behavior models fit to actual booking data, the method produced an estimated 10% improvement in revenue relative to the controls used by the airline. The examples also provide interesting insights into how protection levels should be adjusted to account for choice behavior. Overall, the results indicate that choice behavior has a significant impact on both capacity control decisions and revenue performance and that our method is a viable approach for addressing the problem.
Real‐time performance monitoring, goal‐setting, and feedback for forklift drivers in a distribution centre
Authors: Ludwig Timothy D. , Goomas David T.
Published: July 2008

In this study conducted in two auto‐parts after‐market distribution centres, immediate performance goals and feedback were delivered to employees in a warehouse on wireless vehicle‐mounted computers. Engineered labour standards (ELS) calculated work‐unit goal times and presented the driver with immediate performance feedback. Ultimately, the ELS feedback was linked to the company's forklift driver team pallet‐per‐hour quota achievement. Replenishment performance for forklift drivers (N=12) was improved by 2.14 pallets per hour when an intervention package that included the depiction of goal times and immediate performance feedback on wireless vehicle‐mounted computers and a newly developed ELS. The implications of these findings, limitations, and safety issues are discussed in terms of operational issues regarding ELS in large industrial settings.
A Bite to Whet the Reward Appetite: The Influence of Sampling on Reward-Seeking Behaviors
Authors: Wadhwa Monica , Shiv Baba , Nowlis Stephen M.
Published: July 2008

In this research, the authors show that sampling a consumption cue (e.g., a flavored beverage) that is high in incentive value (i.e., tastes good) not only enhances subsequent consumption of other similar consumption cues (e.g., Pepsi) but also prompts people to seek anything rewarding (e.g., chocolate, a massage). The authors propose that this phenomenon, which they term “reverse alliesthesia,” occurs as a result of the activation of a general motivational state by cues that are high in incentive value. They test this proposition by showing that the effect is (1) attenuated if the activated motivational state is satiated before the subsequent consumption task and (2) stronger for people who are high rather than low on the behavioral activation system scale. Finally, the authors extend their core findings to nongustatory cues by showing that (un)pleasant odors can also lead to an increase (decrease) in subsequent reward-seeking behaviors.
Gender Jeopardy in Financial Risk Taking
Authors: He Xin , Inman J. Jeffrey , Mittal Vikas
Published: July 2008

This article examines the joint effect of issue capability and gender on risk taking. Across three studies, the authors show that the effect of issue capability is moderated by gender, depending on the compatibility between the goal orientation of the decision maker and the nature of the decision task. For decisions that are mainly driven by achievement of gains (e.g., investment decisions), men's risk-taking propensity is more influenced by their levels of issue capability than women's because the nature of the decision task is consistent with men's agentic orientation focused on the self. Conversely, for decisions that are mainly driven by avoidance of losses (e.g., insurance decisions), women's risk taking is more sensitive to issue capability than men's because the nature of such decisions is consistent with women's communion orientation. The authors analyze the betting data from the Daily Double in the Jeopardy! game show (Study 1). The results show that gender moderates the effect of issue capability on the actual betting behavior in Jeopardy!In Study 2, the authors test the underlying mechanism through mediation analyses of the focus of attention. In Study 3, the authors manipulate the task nature and demonstrate that men's risk taking is more sensitive to issue capability in investment decisions, whereas women's risk taking is more sensitive to issue capability in insurance decisions.
Listening to Strangers: Whose Responses are Valuable, how Valuable are They, and Why?
Authors: Weiss Allen M. , Lurie Nicholas H. , Macinnis Deborah J.
Published: July 2008

Marketing managers and consumers who use the Web as a source of information often use input from strangers to make decisions or gain knowledge. The authors propose that in such contexts, the information provider's current and past behaviors, relative to those of other information providers, influence who the information seeker believes provides a valuable response and how valuable he or she judges the provider's information to be. The authors track information queries, information provider responses, and objective valuation of these responses by information seekers in a Web forum, in which responses to information queries come from multiple information providers with whom the information seeker has not met face-to-face and has had no prior interaction. Among other results, the authors show that a provider's response speed, the extent to which the provider's previous responses within the focal domain have been positively evaluated by others, and the breadth of the provider's previous responses across different domains of knowledge affect objective judgments of information value. Importantly, these effects are moderated by the information seeker's goal orientation. The information provider's experience in responding to questions in different domains of knowledge increases judgments of information value for information seekers with a decision-making orientation, whereas the information provider's reputation for providing valuable contributions within the focal domain increases judgments of information value for information seekers with a learning orientation.
Decomposing Promotional Effects with a Dynamic Structural Model of Flexible Consumption
Authors: Chan Tat , Narasimhan Chakravarthi , Zhang Qin
Published: July 2008

In this article, the authors offer a methodology to decompose the effects of price promotions into brand switching, stockpiling, and change in consumption by explicitly allowing for consumer heterogeneity in brand preferences and consumption needs. They develop a dynamic structural model of a household that decides when, what, and how much to buy, as well as how much to consume, to maximize its expected utility over an infinite horizon. By making certain simplifying assumptions, the authors reduce the dimensionality of the problem. They estimate the proposed model using household purchase data in the canned tuna and paper towels categories. The results from the model offer insights into the decomposition of promotional effects into its components. This could help managers make inferences about which brand's sales are more responsive to stockpiling or increase in consumption expansion and how temporary price cuts affect future sales. Contrary to previous literature, the authors find that brand switching is not the dominant force for the increase in sales. They show that brand-loyal consumers respond to a price promotion mainly by stockpiling for future consumption, whereas brand switchers do not stockpile at all. The authors also find that heavy users stockpile more, whereas light users mainly increase consumption when there is a price promotion.
Altered Neuron Excitability and Synaptic Plasticity in the Cerebellar Granular Layer of Juvenile Prion Protein Knock-Out Mice with Impaired Motor Control
Authors: Prestori Francesca , Rossi Paola , Bearzatto Bertrand , Lainé Jeanne , Necchi Daniela , Diwakar Shyam , Schiffmann Serge N. , Axelrad Herbert , D'Angelo Egidio
Published: July 2008

Although the role of abnormal prion protein (PrP) conformation in generating infectious brain diseases (transmissible spongiform encephalopathy) has been recognized, the function of PrP in the normal brain remains mostly unknown. In this investigation, we considered the effect of PrP gene knock-out (PrP0/0) on cerebellar neural circuits and in particular on granule cells, which show intense PrP expression during development and selective affinity for PrP. At the third postnatal week, when PrP expression would normally attain mature levels, PrP0/0mice showed low performance in the accelerating rotarod and runway tests and the functioning of 40% of granule cells was abnormal. Spikes were slow, nonovershooting, and nonrepetitive in relation with a reduction in transient inward and outward membrane currents, and also the EPSPs and EPSCs had slow kinetics. Overall, these alterations closely resembled an immature phenotype. Moreover, in slow-spiking PrP0/0granule cells, theta-burst stimulation was unable to induce any long-term potentiation. This profound impairment in synaptic excitation and plasticity was associated with a protracted proliferation of granule cells and disappeared at P40–P50 along with the recovery of normal motor behavior (Büeler et al., 1992). These results suggest that PrP plays an important role in granule cell development eventually regulating cerebellar network formation and motor control.
Anomalous Dopamine Release Associated with a Human Dopamine Transporter Coding Variant
Authors: Mazei-Robison Michelle S. , Bowton Erica , Holy Marion , Schmudermaier Martin , Freissmuth Michael , Sitte Harald H. , Galli Aurelio , Blakely Randy D.
Published: July 2008

Dopamine (DA) signaling at synapses is tightly coordinated through opposing mechanisms of vesicular fusion-mediated DA release and transporter-mediated DA clearance. Altered brain DA signaling is suspected to underlie multiple brain disorders, including schizophrenia, Parkinson's disease, bipolar disorder, and attention-deficit hyperactivity disorder (ADHD). We identified a pedigree containing two male children diagnosed with ADHD who share a rare human DA transporter (DAT;SLC6A3) coding variant, Ala559Val. Among >1000 control and affected subjects, the Val559 variant has only been isolated once previously, in a female subject with bipolar disorder. Although hDAT Ala559Val supports normal DAT protein and cell surface expression, as well as normal DA uptake, the variant exhibits anomalous DA efflux from DA-loaded cells. We also demonstrate that hDAT Ala599Val exhibits increased sensitivity to intracellular Na+, but not intracellular DA, and displays exaggerated DA efflux at depolarized potentials. Remarkably, the two most common ADHD medications, amphetamine and methylphenidate, both block hDAT Ala559Val-mediated DA efflux, whereas these drugs have opposite actions at wild-type hDAT. Our findings reveal that DA efflux, typically associated with amphetamine-like psychostimulants, can be produced through a heritable change in hDAT structure. Because multiple gene products are known to coordinate to support amphetamine-mediated DA efflux, the properties of hDAT Ala559Val may have broader significance in identifying a new mechanism through which DA signaling disorders arise. Additionally, they suggest that block of inappropriate neurotransmitter efflux may be an unsuspected mechanism supporting the therapeutic actions of existing transporter-directed medications.
Role for Subthalamic Nucleus Neurons in Switching from Automatic to Controlled Eye Movement
Authors: Isoda Masaki , Hikosaka Okihide
Published: July 2008

The subthalamic nucleus (STN) of the basal ganglia is an important element of motor control. This is demonstrated by involuntary movements induced by STN lesions and the successful treatment of Parkinson's disease by STN stimulation. However, it is still unclear how individual STN neurons participate in motor control. Here, we report that the STN has a function in switching from automatic to volitionally controlled eye movement. In the STN of trained macaque monkeys, we found neurons that showed a phasic change in activity specifically before volitionally controlled saccades which were switched from automatic saccades. A majority of switch-related neurons were considered to inhibit no-longer-valid automatic processes, and the inhibition started early enough to enable the animal to switch. We suggest that the STN mediates the control signal originated from the medial frontal cortex and implements the behavioral switching function using its connections with other basal ganglia nuclei and the superior colliculus.
Training-Induced Brain Structure Changes in the Elderly
Authors: Boyke Janina , Driemeyer Joenna , Gaser Christian , Büchel Christian , May Arne
Published: July 2008

It has been suggested that learning is associated with a transient and highly selective increase in brain gray matter in healthy young volunteers. It is not clear whether and to what extent the aging brain is still able to exhibit such structural plasticity. We built on our original study, now focusing on healthy senior citizens. We observed that elderly persons were able to learn three-ball cascade juggling, but with less proficiency compared with 20-year-old adolescents. Similar to the young group, gray-matter changes in the older brain related to skill acquisition were observed in area hMT/V5 (middle temporal area of the visual cortex). In addition, elderly volunteers who learned to juggle showed transient increases in gray matter in the hippocampus on the left side and in the nucleus accumbens bilaterally.
Emotion-Induced Retrograde Amnesia Is Determined by a 5-HTT Genetic Polymorphism
Authors: Strange Bryan A. , Kroes Marijn C. W. , Roiser Jonathan P. , Tan Geoffrey C. Y. , Dolan Raymond J.
Published: July 2008

A polymorphism in the human serotonin transporter (5-HTT) gene is implicated in susceptibility to anxiety and depression and in enhanced emotion-induced activation in the amygdala. A role for 5-HTT polymorphism in the emotional modulation of human episodic memory has yet to be demonstrated. Here, we demonstrate that whereas emotional memory for aversive events per se is not influenced by 5-HTT polymorphism, an emotion-induced retrograde amnesia is expressed solely in the presence of the short allele. The findings indicate a critical role for the serotonin system in emotion-mediated memory disruption.
Roles of Endocannabinoids in Heterosynaptic Long-Term Depression of Excitatory Synaptic Transmission in Visual Cortex of Young Mice
Authors: Huang Yan , Yasuda Hiroki , Sarihi Abdolrahman , Tsumoto Tadaharu
Published: July 2008

Tetanic stimulation of one of two afferent pathways converging to neurons in the visual cortex induces long-term depression (LTD) of synaptic transmission in the other, nonactivated pathway under a certain condition. This form of synaptic plasticity called heterosynaptic LTD (hetero-LTD) was not systematically investigated in previous studies, whereas homosynaptic LTD has been extensively studied. To determine whether hetero-LTD is induced in visual cortical slices of mice and, if so, through what mechanisms, we recorded EPSPs evoked in layer II/III neurons by alternating test stimulation of two sites in layer IV at 0.05 Hz. After theta-burst stimulation of one site, EPSPs evoked by test stimulation of the other site were depressed for a long time in most of the neurons, whereas homosynaptic long-term potentiation was induced at activated synapses. Such a hetero-LTD was induced in most mice at postnatal day 7–20 (P7–P20), but not induced in mice at P35–P41. Tests using the paired-pulse stimulation protocol and coefficient of variation analysis suggested that hetero-LTD was expressed at presynaptic sites. Pharmacological analysis indicated that this form of LTD was induced through activation of the type 5 of metabotropic glutamate receptors, not through the NMDA type of glutamate receptors. Additional analysis using a cannabinoid type 1 receptor agonist and an antagonist suggested that endocannabinoids (eCBs) are involved in this type of LTD. Moreover, results suggest that brain-derived neurotrophic factor, which may be released from strongly activated presynaptic sites, prevents eCBs from suppressing the release of transmitters from these sites.
Mecp2 Organizes Juvenile Social Behavior in a Sex-Specific Manner
Authors: Kurian Joseph R. , Bychowski Meaghan E. , Forbes-Lorman Robin M. , Auger Catherine J. , Auger Anthony P.
Published: July 2008

Methyl-CpG-binding protein 2 (MeCP2) binds methylated DNA and recruits corepressor proteins to modify chromatin and alter gene transcription. Mutations of theMECP2gene can cause Rett syndrome, whereas subtle reductions of MeCP2 expression may be associated with male-dominated social and neurodevelopmental disorders. We report that transiently decreased amygdala Mecp2 expression during a sensitive period of brain sexual differentiation disrupts the organization of sex differences in juvenile social play behavior. Interestingly, neonatal treatment with Mecp2 small interfering RNA within the developing amygdala reduced juvenile social play behavior in males but not females. Reduced Mecp2 expression did not change juvenile sociability or anxiety-like behavior, suggesting that this disruption is associated with subtle behavioral modification. This suggests that Mecp2 may have an overlooked role in the organization of sexually dimorphic behaviors and that male juvenile behavior is particularly sensitive to Mecp2 disruption during this period of development.
The Role of Hypothalamic Mammalian Target of Rapamycin Complex 1 Signaling in Diet-Induced Obesity
Authors: Cota Daniela , Matter Emily K. , Woods Stephen C. , Seeley Randy J.
Published: July 2008

The mammalian target of rapamycin (mTOR) kinase is a key regulator of several cellular functions, including cell growth and differentiation. Because hypothalamic mTOR complex 1 (mTORC1) signaling has been implicated as a target of leptin in the regulation of energy balance, we investigated its role in obesity-induced leptin resistance. In contrast to rats maintained on a low-fat (LF) diet for 3 weeks, rats maintained on a high-fat (HF)-diet had no anorexic response to intracerebroventricular leptin. Western blot analysis revealed that leptin was unable to modulate hypothalamic mTORC1 signaling in the HF group, whereas it significantly induced phosphorylation of both S6 kinase 1 (S6K1) and S6 ribosomal protein (S6) in the LF group. Similar to leptin, the cytokine ciliary neurotrophic factor (CNTF) induces hypophagia and increases signal transduction activator of transcription 3 phosphorylation. However, CNTF and its analog CNTFAx15activate leptin-like pathways in the hypothalamus, even in leptin-resistant states, including diet-induced obesity. Intracerebroventricular CNTFAx15decreased 24 h food intake and body weight in rats on HF or LF diets and increased the phosphorylation of hypothalamic S6K1 and S6 in a comparable way in both diets. Importantly, mice lacking the expression ofS6K1(S6K1−/−) did not respond to the anorectic action of either leptin or CNTFAx15, implying a crucial role for S6K1 in modulating the actions of these two cytokines. Finally, exposure to HF diet decreased mTORC1 signaling within the hypothalamus. Overall, these findings point strongly to the possibility that reduced hypothalamic mTORC1 signaling contributes to the development of hyperphagia, weight gain, and leptin resistance during diet-induced obesity.
Bone Morphogenetic Proteins, Eye Patterning, and Retinocollicular Map Formation in the Mouse
Authors: Plas Daniel T. , Dhande Onkar S. , Lopez Joshua E. , Murali Deepa , Thaller Christina , Henkemeyer Mark , Furuta Yasuhide , Overbeek Paul , Crair Michael C.
Published: July 2008

Patterning events during early eye formation determine retinal cell fate and can dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward central brain targets. The temporally and spatially regulated expression of bone morphogenetic proteins (BMPs) and their receptors in the retina are thought to play a key role in this process, initiating gene expression cascades that distinguish different regions of the retina, particularly along the dorsoventral axis. Here, we examine the role of BMP and a potential downstream effector, EphB, in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior colliculus (SC). RGC axon behaviors during retinotopic map formation in wild-type mice are compared with those in several strains of mice with engineered defects of BMP and EphB signaling. Normal RGC axon sorting produces axon order in the optic tract that reflects the dorsoventral position of the parent RGCs in the eye. A dramatic consequence of disrupting BMP signaling is a missorting of RGC axons as they exit the optic chiasm. This sorting is not dependent on EphB. When BMP signaling in the developing eye is genetically modified, RGC order in the optic tract and targeting in the LGN and SC are correspondingly disrupted. These experiments show that BMP signaling regulates dorsoventral RGC cell fate, RGC axon behavior in the ascending optic tract, and retinotopic map formation in the LGN and SC through mechanisms that are in part distinct from EphB signaling in the LGN and SC.
Differences between Dorsal and Ventral Striatum in Drd1a Dopamine Receptor Coupling of Dopamine- and cAMP-Regulated Phosphoprotein-32 to Activation of Extracellular Signal-Regulated Kinase
Authors: Gerfen Charles R. , Paletzki Ronald , Worley Paul
Published: July 2008

Dopamine receptor signaling exhibits prominent plasticity that is important for the pathogenesis of both addictive and movement disorders. Psychoactive stimulants that activate the dopamine D1receptor (Drd1a) induce the rapid phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in neurons of the nucleus accumbens and ventral striatum. This response is known to be dependent on the phosphatase inhibitor dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) and appears critical for the sensitization of Drd1a responses that contributes to addiction. Loss of dopamine input to the striatum, as in models of Parkinson's disease (PD), also results in a sensitization of responses to dopamine agonists that is manifest by increased activation of ERK1/2 in the dorsal striatum. Here, we test whether DARPP-32 is required for sensitization of Drd1a responses in a PD model. In the normal dorsal striatum, there is minimal Drd1a-mediated activation of ERK1/2; however, in the PD model there is robust Drd1a-mediated activation of ERK1/2. In both wild-type and DARPP-32 knock-out mice, Drd1a robustly induces pERK1/2 throughout the dopamine-depleted striatum. These findings indicate that Drd1a sensitization relevant for PD occurs by a novel mechanism that does not require DARPP-32.
Sound-Intensity-Dependent Compensation for the Small Interaural Time Difference Cue for Sound Source Localization
Authors: Nishino Eri , Yamada Rei , Kuba Hiroshi , Hioki Hiroyuki , Furuta Takahiro , Kaneko Takeshi , Ohmori Harunori
Published: July 2008

Interaural time difference (ITD) is a major cue for sound source localization. However, animals with small heads experience small ITDs, making ITD detection difficult, particularly for low-frequency sound. Here, we describe a sound-intensity-dependent mechanism for compensating for the small ITD cues in the coincidence detector neurons in the nucleus laminaris (NL) of the chicken aged from 3 to 29 d after hatching. The hypothesized compensation mechanisms were confirmed by simulation.In vivosingle-unit recordings revealed an improved contrast of ITD tuning in low-best-frequency (<1 kHz) NL neurons by suppressing the firing activity at the worst ITD, whereas the firing rate was increased with increasing sound intensity at the best ITD. In contrast, level-dependent suppression was so weak in the middle- and high-best-frequency (≥1 kHz) NL neurons that loud sounds led to increases in firing rate at both the best and the worst ITDs. The suppression of firing activity at the worst ITD in the low-best-frequency neurons required the activation of the superior olivary nucleus (SON) and was eliminated by electrolytic lesions of the SON. The frequency-dependent suppression reflected the dense projection from the SON to the low-frequency region of NL. Thus, the small ITD cues available in low-frequency sounds were partly compensated for by a sound-intensity-dependent inhibition from the SON.
Mesolimbic Dopamine in Desire and Dread: Enabling Motivation to Be Generated by Localized Glutamate Disruptions in Nucleus Accumbens
Authors: Faure Alexis , Reynolds Sheila M. , Richard Jocelyn M. , Berridge Kent C.
Published: July 2008

An important issue in affective neuroscience concerns the role of mesocorticolimbic dopamine systems in positive-valenced motivation (e.g., reward) versus negative-valenced motivation (e.g., fear). Here, we assessed whether endogenous dopamine receptor stimulation in nucleus accumbens contributes to both appetitive behavior and fearful behavior that is generated in keyboard manner by local glutamate disruptions at different sites in medial shell. 6,7-Dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) microinjections (450 ng) locally disrupt glutamate signals in <4 mm3of nucleus accumbens, and generate either desire or fear (or both) depending on precise rostrocaudal location in medial shell. At rostral shell sites, local AMPA/kainate blockade generates positive ingestive behavior, but the elicited motivated behavior becomes incrementally more fearful as the same microinjection is moved caudally. A dopamine-blocking mixture of D1and D2antagonists (raclopride and SCH-23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine hydrochloride]) was combined here in the same microinjection with DNQX to assess the role of endogenous local dopamine in mediating the DNQX-motivated behaviors. We report that local dopamine blockade prevented DNQX microinjections from generating appetitive behavior (eating) in rostral shell, and equally prevented DNQX from generating fearful behavior (defensive treading) in caudal shell. We conclude that local dopamine is needed to enable disruptions of corticolimbic glutamate signals in shell to generate either positive incentive salience or negative fearful salience (valence depending on site and other conditions). Thus, dopamine interacts with localization of valence-biased glutamate circuits in medial shell to facilitate keyboard stimulation of both appetitive and fearful motivations.
Die Seuche im Heerlager der Achäer vor Troia. Orakel und magische Rituale im hethiterzeitlichen Kleinasien und im archaischen Griechenland1
Authors: Högemann Peter , Oettinger Norbert
Published: July 2008

Das zentrale Anliegen dieses Aufsatzes besteht in dem Versuch, den Iliasdichter als realen Menschen darzustellen, der in der Lebenswelt Westkleinasiens um 700 v. Chr. wurzelte. Hier hat der Dichter hethiterzeitliche Traditionen noch in praxi erlebt und so auch die Art, Orakel zu befragen und magische Rituale zur Abwehr von Seuchen im Heer anzuwenden. Im ersten Gesang der Ilias lassen sich auf Grund erhaltener Spuren ein in hethitischer Tradition stehendes Vogelflugorakel und ein Seuchenritual rekonstruieren, für die es keine Parallelen im griechischen Mutterland gibt. Das anatolische Orakel unterscheidet sich fundamental von der Orakelpraxis Delphis und Dodonas. Das ist der Grund, warum Kroisos, der in anatolischer Tradition stand, in Delphi scheiterte.
Lepreon and Phyrkos in 421–420
Authors: Paradiso Annalisa , Roy James
Published: July 2008

This paper examines the tension between Sparta and Elis in 421–420 over Lepreon and the fort at Phyrkos, reported principally by Thucydides. Sparta sent Brasideioi and neodamodeis to garrison Lepreon some months before the Olympic Games of 420. The Eleans objected to this garrison as a breach of the hieromenia (rather than the shorter ekecheiria) of the Games, and both the garrisoning and an attack on the fort at Phyrkos seem to have been part of a single military operation. Phyrkos was situated in the territory of Lepreon, probably near the River Neda. Thucydides presents as parallel Mantinean control of southern Parrhasia with a fort at Kypsela near the Lakonian frontier, and Elis' desire to control Lepreon with a fort at Phyrkos near the Messenian frontier. He shows Sparta acting in 421 to remove unfriendly control of access to Sparta's frontiers and to neutralise forts posted near the frontiers.
Democracia frente a populismo en Isócrates
Authors: Rocher Laura Sancho
Published: July 2008

Tradicionalmente la posición política de Isócrates ha sido tachada de conservadora. Como maestro de la elite ateniense a lo largo de un periodo que abarca casi por entero la IVa centuria ha sido considerado ideólogo del llamado proyecto político moderado cuyo objetivo sería abolir la democracia real a través de reformas institucionales que tendrían por meta la exclusión del pueblo del control político. En este artículo se plantea una interpretación alternativa: Isócrates pretendería salvar la democracia mejorando la dirección política por lo que su crítica pone especial énfasis en el engaño demagógico y su exhortación se orienta al desarrollo de la libertad de criterio de los hombres educados.
M. Titius, Menas and the insignia scutorum
*
Authors: Tansey Patrick
Published: July 2008

This paper explores an intriguing episode in Cass. Dio 48.30.4–6 in the light of the literary and archaeological evidence for shield blazons in the Roman legions. The statement of Menas, reported by Dio, that the soldiers of M. Titius carried the name of Sextus (Pompeius) on their shields is usually taken literally. It is argued, however, that the passage may involve an unrecognized pun and that some of the soldiers of M. Titius may have been veterans of Caesar's legio VI who carried shields emblazoned with their former legion's unit number.
Kanopos oder Menouthis?1 Zur Identifikation einer Ruinenstätte in der Bucht von Abuqir in Ägypten
Authors: Stolz Yvonne
Published: July 2008

Bevor endgültige Beweise unter Wasser gefunden worden sind, kann die Identifikation der in der Bucht von Abuqir gelegenen Ruinenstätte nur durch einen Indizienbeweis erfolgen. Für einen solchen bieten sich die Lage der Ruinenstätte und die dort zutage geförderten Kleinfunde an. Beide legen nahe, daß es sich bei der Ruinenstätte nicht um Kanopos, wie zunächst angenommen, sondern um Menouthis handelt. Die Umfassungsmauer TW4 wäre dann die Temenosmauer des berühmten Isieions von Menouthis und die byzantinische Anlage Teil des Pilgerheiligtums von Kyros und Ioannes.
REPORTING THAT IN TRANSLATED ENGLISH. EVIDENCE FOR SUBCONSCIOUS PROCESSES OF EXPLICITATION?
Authors: Olohan Maeve , Baker Mona
Published: July 2008

This paper sets out to provide evidence of explicitation in
translation into English through an analysis of patterns of inclusion and
omission of optional that with the reporting verbs SAY and TELL. The notion of
explicitation in the context of translation is first introduced and explained.
An overview of the literature relating to that-clauses in English is then
given, and this forms the basis for subsequent data analysis. The sources of
the data to be analysed are briefly described: the TEC (Translational English
Corpus) providing us with translated English, and the BNC (British National
Corpus) containing original English. On the basis of a comparison of
concordance data from the two corpora, quantitative results serve to illustrate
the marked differences in use of that and zero with forms of SAY and TELL. Thus
it is shown that the that-connective is far more frequent in TEC than in BNC,
and conversely that the zero-connective is more frequent for all forms of both
verbs in the BNC corpus than in TEC. A detailed investigation of the instances
of occurrence of that/zero constructions in both corpora attempts to
categorise, compare and contrast patterns of occurrence, and provides potential
starting points for further research of this nature.
TRANSLATION POLICIES IN PRE-COMMUNIST AND COMMUNIST ROMANIA. THE CASE OF ALDOUS HUXLEY
Authors: Dimitriu Rodica
Published: July 2008

The paper draws on the perspectives provided by the
polysystem theory in Translation Studies and the "ideological" trends
in the discipline in order to detect preliminary and textual translation norms
that operated in Pre-Communist (Inter-War and World War II period) and
Communist Romania. However, translation-related issues are examined in a wider
historical, literary, cultural and political context. The "case of Aldous
Huxley" is thus illustrative for more general tendencies that were
manifest in terms of translation policies, textual norms and translators'
status during the two distinct periods under discussion. In the paper we also
emphasize the importance of translation studies for reception studies in
general, as well as the necessity for translation criticism both to improve
transla-tion standards at a given time and to highlight the translators'
remarkable achievements that frequently tend to be overlooked.
Conference Reports Gender and Literary Translation. International Symposium. The University of East Anglia, Norwich, United Kingdom, 17-19 December, 1999
Authors: Sergia Adamo , Károly Krisztina
Published: July 2008

The link between gender issues and translation in recent
years has developed into an intertwining of theory and practice. For instance,
feminist writing has given a deep insight into the questions of how to
translate from one culture to another the issues at stake; new attention to
traditionally neglected historical subjects has led us to consider the role
women played in the past in all the proc-esses involved with translation (a
role often hidden behind traditional historical reconstructions) whilst bearing
in mind the present; the need to reflect upon specifically feminist translation
strategies has increasingly been highlighted; the notion of gender as a
cultural construction has started to be seen as a tool of in-vestigation in
Translation Studies.
Book Reviews Theo Hermans: Translation in Systems. Descriptive and System-Oriented Approaches Explained. Manchester: St. Jerome Publishing, 1999, 197 pp. ISBN 1-900650-11-8 (pbk)
Authors: Millán-Varela Carmen , Sohár Anikó , Zlateva Palma , Dróth Júlia
Published: July 2008

It is hardly necessary to emphasise how important role the
Manipulation School played in making the discipline, we now call Translation
Studies, acknowledged in the seventies-eighties. Translation in Systems
provides a good overview of its history, leading figures, key concepts, and
limitations, anddoes not try to cover all descriptive approaches, only this
one.