bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a clinical examination skills training course in an undergraduate pharmacy programme
Authors: Wearn Andy , Bye Lynne , Bhoopatkar Harsh
Published: July 2008

Objective

To introduce and evaluate a short clinical examination skills course in a BPharm programme. The study objectives were to assess needs, explore attitudes, record perceived competence requirements and assess the value of physical examination skills learning.

Setting

BPharm programme in Auckland, New Zealand. Participants were students enrolled in years 3 and 4 of the programme (2003).

Method

The design was a longitudinal, dual cohort, educational intervention evaluation using a self-completed questionnaire. An examination skills component was added to the fourth year of the pharmacy programme. Year 3 and 4 students were recruited, and completed the questionnaire at two points. Year 3 students were sampled one year before and soon after the skills sessions. Year 4 students were sampled after the sessions and 18 months later (once registered). The questionnaire sought their attitudes towards clinical skills training and practical relevance for future practice, and evaluated their learning experience.

Key findings

Response rates at the four points were 42–67%. Year 3 students identified a similar set of appropriate skills to those actually taught in year 4. Overall, attitudes to introducing examination skills learning were positive at all points. At follow-up, both cohorts agreed more strongly that examination skills training should be core (significantly for registered pharmacists versus year 3, P < 0.006). Measuring manual blood pressure was deemed the most difficult skill. All taught skills were used in practice except for respiratory rate; most used were body mass index (BMI), temperature and peak flow measurement.

Conclusions

There was a close correlation between what was offered in the course, what students felt they needed to learn and what was relevant in practice. Once registered, pharmacists were aware of their limitations and level of competence in relation to clinical skills. The small changes in attitudinal scores appear to reflect maturity and experience. The study design allowed us to adapt the educational component to student need. Health professional educators need to be aware of and respond to changes in professional scopes of practice.
Is there an association between referral population deprivation and antibiotic prescribing in primary and secondary care?
Authors: Curtis Christopher , Marriott John
Published: July 2008

Objective

The study was designed to explore the presence of any relationship between NHS secondary care antibiotic prescribing rates or primary care antibiotic prescribing rates and the levels of deprivation experienced within the referred primary care population. The study also aimed to determine whether the antibiotic prescribing rates for each care sector were correlated.

Method

The study was conducted in 12 English hospital trusts of mixed size and case-mix. Antibiotic usage data (Anatomical Therapeutic Chemical (ATC) category J01) for the financial year, ending March 2001/2002 were used to calculate hospital trust prescribing rates (using the defined daily dose/finished consultant episode indicator). Primary care antibiotic prescribing data were obtained from the Prescription Pricing Authority (antibiotic items prescribed per 1000 residents) for the year 2001/2002. Index of Multiple Deprivation (IMD) 2000 deprivation data were obtained from the regional public health observatory websites for each of the primary care trusts within the relevant study areas.

Key findings

No correlation could be established between the weighted index of multiple deprivation of the treated population and antibiotic prescribing rates at each hospital trust. Primary care antibiotic prescribing rates were not found to correlate with antibiotic prescribing rates in the geographically associated hospital trust. Data from all 12 sites showed that the IMD 2000 measures and primary care prescribing rates were weakly correlated, with higher antibiotic prescribing rates being generally observed in areas of primary care exhibiting the worst levels of deprivation

Conclusions

The likely explanations for the present findings are that deprivation-related illnesses are principally treated within primary care, whereas hospital antibiotic prescribing principally results from procedures isolated within secondary care or through the additional influence of nosocomial infection. Therefore, medicines management measures geared to controlling antibiotic prescribing in secondary care should not focus upon the levels of deprivation in the referred population, whereas those in primary care should.
Involving patients as advisors in pharmacy practice research: what are the benefits?
Authors: Sutton Jane , Weiss Marjorie
Published: July 2008

Objective

To describe the ways in which members of the public with a chronic condition were involved as advisors in a research project exploring pharmacist supplementary prescribing. The primary objective was to be able to reflect upon the benefits and difficulties of this approach so that the patient perspective can be accommodated more fully in future research.

Setting

University of Bath.

Method

Ten individuals were recruited from two clinical areas: a diabetes support group and a chronic lung disease group. None of the individuals had ever seen, or heard of, a pharmacist supplementary prescriber. They joined two members of the research team at each of six meetings held over a period of one year. This paper presents an ethnographic approach to the accounts of these meetings and reflects on the involvement of patients as members of the research team.

Key findings

Initially, the group was unaware of pharmacist prescribing and expressed a range of concerns. After gaining an understanding of pharmacist prescribing, they were able to influence the design and content of interview schedules and offered comments on completed interview transcripts. As the project progressed the patients began to take on a non-lay perspective of pharmacists, becoming more in favour of pharmacist prescribing over time. It may be useful in the future to introduce new patient members to such a group, from time to time, during the life of a project to maintain a lay or ‘outside’ perspective on key research issues. Nonetheless, the use of the patient group contributed to the direction and outcome of the study in a positive way and kept the project grounded in the patient's perspective.

Conclusion

We conclude that the benefits of including patients in the research process far outweigh the difficulties. Researchers are encouraged to adopt this approach in the future and listen to the patients but be clear about their role in the research process.
Medicines Use Review: adoption and spread of a service innovation
Authors: Blenkinsopp Alison , Bond Christine , Celino Gianpiero , Inch Jackie , Gray Nicola
Published: July 2008

Background

Research has shown that implementation of community pharmacy Medicines Use Review and Prescription Intervention (MUR) in the first year of the service in England and Wales was less extensive than anticipated. Several barriers to MUR becoming accepted and embedded in the National Health Service (NHS) were identified.

Objective

To evaluate progress in the provision of the MUR service in England and Wales in its second year (April 1, 2006-March 31, 2007) compared with the first year; and to analyse trends from available national data from the third year of provision in 2007–2008.

Methods

The analysis drew on the following data sources: routine data on provision of MURs for community pharmacies in a stratified random sample of 31 primary care organisations in England and Wales, and national datasets on MUR provision from the Pharmaceutical Services Negotiating Committee and NHS Information Centre.

Outcome measures

The percentage of community pharmacies providing the MUR service, the numbers of MURs provided in 2006–2007 at pharmacy and primary care organisation level, and the extent of, and variation in, provision.

Key findings

The percentage of community pharmacies providing the MUR service increased from 38 to 67.2%. Overall, 62 559 MURs were provided (a more than four-fold increase on the previous year), representing 13.8% of the possible maximum. The mean number of MURs provided (per provider) increased from 36 to 85. For existing providers the mean number increased from 36 to 111 (median 78, range 0–423). For new providers the mean number was 52 (median 17, range 1–401). More than half (52%) of the pharmacies in the sample claimed for fewer than 50 MURs. Overall, 82% of MURs were provided by multiples and this percentage was lower among new providers (62%) than existing providers (89%). Thirty-three (8.1%) existing MUR providers had no recorded MURs in the second year: almost two-thirds of these (64%) were independents. Eleven pharmacies (1.5%) provided the maximum number of 400 MURs per year: all but one were branches of multiples. Of the pharmacies not yet providing MURs, 78% were independent.

Conclusions

Both numbers of MURs and numbers of providers of MUR services increased markedly during the service's second year. Those newly providing the service in the second year claimed for more than twice as many MURs as did those who had been ‘new providers' the previous year. Overall just over half of all providing pharmacies claimed for the equivalent of one MUR a week or fewer. Therefore the extent of ‘successful adoption’ of MURs is debatable. Differences in the level of provision continued between independent and multiple pharmacies in terms of both adoption of the service and the number of reviews conducted. As in the previous year, independent pharmacies were less likely to provide the MUR service and when they did the numbers conducted were lower than those provided by multiples.
The secretedDictyosteliumprotein CfaD is a chalone
Authors: Bakthavatsalam Deenadayalan , Brock Debra A. , Nikravan N. Neda , Houston Kevin D. , Hatton R. Diane , Gomer Richard H.
Published: July 2008

Dictyostelium discoideum cells secrete CfaD, a protein that is similar to cathepsin proteases. Cells that lack cfaD proliferate faster and reach a higher stationary-phase density than wild-type cells, whereas cells that overexpress CfaD proliferate slowly and reach the stationary phase when at a low density. On a per-nucleus basis, CfaD affects proliferation but not growth. The drawback of not having CfaD is a reduced spore viability. Recombinant CfaD has no detectable protease activity but, when added to cells, inhibits the proliferation of wild-type and cfaD– cells. The secreted protein AprA also inhibits proliferation. AprA is necessary for the effect of CfaD on proliferation. Molecular-sieve chromatography indicates that in conditioned growth medium, the 60 kDa CfaD is part of a ∼150 kDa complex, and both chromatography and pull-down assays suggest that CfaD interacts with AprA. These results suggest that two interacting proteins may function together as a chalone signal in a negative feedback loop that slows Dictyostelium cell proliferation.
Binding of soluble fibronectin to integrin α5β1 – link to focal adhesion redistribution and contractile shape
Authors: Huveneers Stephan , Truong Hoa , Fässler Reinhard , Sonnenberg Arnoud , Danen Erik H. J.
Published: July 2008

Focal adhesions are randomly distributed across the ventral surface or along the edge of epithelial cells. In fibroblasts they orient centripetally and concentrate at a few peripheral sites connecting long F-actin stress fibers, causing a typical elongated, contractile morphology. Extensive remodeling of adhesions in fibroblasts also takes part in fibronectin fibrillogenesis, a process that depends on Rho-mediated contractility and results in the formation of a fibronectin matrix. Our current study shows that all these fibroblast characteristics are controlled by the ability of integrin α5β1 to bind soluble fibronectin molecules in their compact inactive conformation. The hypervariable region of the ligand-binding I-like domain of integrin α5β1 supports binding of soluble fibronectin. This supports the distribution of centripetally orientated focal adhesions in distinct peripheral sites, Rho activation and fibronectin fibrillogenesis through a mechanism that does not depend on Syndecan-4. Integrin αvβ3, even when locked in high affinity conformations for the RGD recognition motif shows no appreciable binding of soluble fibronectin and, consequently, fails to support the typical fibroblast focal adhesion distribution, Rho activity and fibronectin fibrillogenesis in the absence of integrin α5β1. The ability of α5β1 integrin to interact with soluble fibronectin may thus drive the cell-matrix adhesion and cytoskeletal organization required for a contractile, fibroblast-like morphology, perhaps explaining why α5β1 integrin, similarly to fibronectin, is essential for development.
Burden of Deep Vein Thrombosis in the Outpatient Setting Following Major Orthopedic Surgery
Authors: Nutescu Edith A , Shorr Andrew F , Farrelly Eileen , Horblyuk Ruslan , Happe Laura E , Franklin Meg
Published: July 2008

Background

Venous thromboembolism (VTE) is a known complication of major orthopedic surgery (MOS) with important clinical and economic consequences. Recently published orthopedic guidelines have focused on prevention of pulmonary embolism as a primary outcome, but deep vein thrombosis (DVT) occurrence should not be readily dismissed.

Objective

To describe the burden of DVT following hospital discharge for MOS by assessing the impact of DVT on costs and resource utilization from the Third-party payer perspective.

Methods

Retrospective analysis used outpatient medical and pharmacy data from the PharMetrics Patient-Centric Database (January 1, 2002–March 31. 2006). Patients 18 years of age or older with a record of MOS were eligible for inclusion. Included patients were stratified based on the presence of a DVT during the first month after hospital discharge. Characteristics of the samples were described. The impact of DVT on total 6–month costs and resource utilization (readmissions, outpatient, emergency department visits) was assessed through statistical models.

Results:

Of the 32,899 patients in the analysis, 1221 (3.71%) had a record of DVT during the first month following discharge for MOS. Compared with patients who did not develop DVT, patients who developed DVT postdischarge were slightly older (56.5 vs 55.8 y; p = 0.0127), had a higher occurrence of prior VTE (26.2% vs 3.4%; p < 0.0001), and had undergone recent surgical procedures other than MOS (73.0% vs 69.6%; p = 0.0116). After controlling for potential confounders, DVT was associated with a 22% and 74% increase in the average number of expected outpatient and emergency department visits, respectively, during the 6-month postdischarge period but did not significantly impact the number of readmissions. Furthermore, total 6-month costs were significantly higher for patients who developed DVT with an incremental increase of over $2000.

Conclusions:

The burden of DVT following hospital discharge for MOS is substantial. Specifically, DVT increases total costs and outpatient and emergency department visits.
Brand Portfolio Promotions
Authors: Aribarg Anocha , Arora Neeraj
Published: July 2008

Large firms implement brand portfolio promotions (BPPs) that promote multiple brands to targeted consumers at discrete times. Such programs possess unique properties that require a novel model to assess their effectiveness. The authors propose a model that captures the magnitude and shape of the BPP effect for each brand in the portfolio, accounts for diminishing returns of brand exposure, and incorporates the intertemporal effect of BPPs. The model is shown to be general enough to apply to any discrete promotion in which the carryover effect duration is unknown. The authors present several model-based metrics that allow for an objective comparison of a BPP's return on investment with that of other forms of promotion. The results suggest that a BPP, when contrasted with feature, leads to higher sales lift per household for some of the brands. The authors develop an optimal exposure allocation procedure based on the proposed model that informs (1) which assortments of brands to promote across multiple BPPs and (2) the exposure level for each brand.
Attentional Contrast during Sequential Judgments: A Source of the Number-of-Levels Effect
Authors: De Wilde Els , Cooke Alan D.J. , Janiszewski Chris
Published: July 2008

Conjoint analysis is used to measure the importance of attribute-level trade-offs. A methodological anomaly is the number-of-levels effect; that is, as the number of intervening attribute levels increases, the derived importance weight of an attribute increases. The authors use three studies to show that attentional processes contribute to the number-of-levels effect. When there is an inequality in the number of levels across attributes, a given profile may include levels of one attribute that are relatively more novel than levels of the accompanying attributes. A process of attentional contrast directs attention toward the relatively novel attribute levels within each profile. Increased attention toward these attribute levels results in a larger derived importance weight for the attributes defined on those levels.
When 2 + 2 is Not the Same as 1 + 3: Variations in Price Sensitivity across Components of Partitioned Prices
Authors: Hamilton Rebecca W. , Srivastava Joydeep
Published: July 2008

Firms often use a pricing strategy in which the total price of a product and/or service is partitioned into two or more mandatory components. Whereas previous research has compared partitioned with nonpartitioned pricing, this article examines how partitioning the total price differently across the components affects consumer preferences. In four studies, the authors show that consumers' reactions to price partitioning are moderated by the perceived consumption benefit of the components. Specifically, consumers are more sensitive to the price of components that provide low consumption benefits than to the price of components that provide relatively high consumption benefits. Consequently, when evaluating different partitions of the same total price, consumers prefer partitions in which the price of the low-benefit component is lower and the price of the high-benefit component is higher.
Anytime versus Only: Mind-Sets Moderate the Effect of Expansive versus Restrictive Frames on Promotion Evaluation
Authors: Cheema Amar , Patrick Vanessa M.
Published: July 2008

Three studies demonstrate that the framing of redemption windows as expansive or restrictive, with the actual length of the window held constant, influences consumers' evaluations of sales promotions. When feasibility concerns are highlighted (i.e., an implemental mind-set), consumers prefer the expansive (“anytime”) to the restrictive (“only”) frame. However, consumers in a deliberative mind-set prefer the restrictive (only) frame to the expansive (anytime) frame. Study 1 reveals that whereas the former consumers attend more to their ability to redeem the offer, the latter are influenced more by the precision of the offer. Study 2 highlights the mediating role of these inferences on consumers' likelihood of taking advantage of the offer. Study 3 demonstrates the impact of these frames on real-world coupon redemption. The authors conclude with a discussion of the scope of this framing effect, the implications of the findings, and directions for further research.
Distribution Intensity and New Car Choice
Authors: Bucklin Randolph E. , Siddarth S. , Silva-Risso Jorge M.
Published: July 2008

The authors develop a new method to assess how changes in the intensity of mature distribution networks—specifically, those in the U.S. automotive industry—might affect consumer choice. They capture distribution intensity by car make (e.g., Honda, Toyota) at the disaggregate level using the exact geographic locations of individual buyers and new car dealers. They develop three buyer-centric measures for the intensity level of each competing make from this information: (1) dealer accessibility (the buyer's distance to the nearest outlet for each make), (2) dealer concentration (the extent to which multiple dealers for each make are located near a given buyer), and (3) dealer spread (the dispersion of the multiple dealers for each make relative to the buyer's location). The authors propose a logit choice model, estimated with Bayesian methods, to study the association of these measures with new car choices. They apply the model to buyer records in the midsize premium sedan category, drawn from an anonymous sample provided by the Power Information Network. All three buyer-centric measures of intensity were significantly related to new car choice. Buyers were more likely to select cars whose dealer networks had shorter distances to the closest outlet (accessibility), more dealers within a given radius from the buyer (concentration), and locations that skewed toward the buyer (spread). Based on the modeling results, the market share elasticity of distribution intensity averages approximately .6 across the new car models included in the study. The approach should help firms evaluate the potential effects of expanding or contracting distribution networks for mature products.
Constitutively Active Akt Induces Enhanced Myelination in the CNS
Authors: Flores Ana I. , Narayanan S. Priyadarshini , Morse Emily N. , Shick H. Elizabeth , Yin Xinghua , Kidd Grahame , Avila Robin L. , Kirschner Daniel A. , Macklin Wendy B.
Published: July 2008

The serine/threonine kinase Akt regulates multiple cellular functions. The current studies identify a new role for Akt in CNS myelination. In earlier studies on cultured oligodendrocytes, we showed that neuregulin signals through phosphatidylinositol-3′-OH kinase and Akt to enhance survival of oligodendrocytes. However, when transgenic animals were generated that overexpressed constitutively active Akt in oligodendrocytes and their progenitor cells, no enhanced survival of oligodendrocytes or progenitors was found. No alteration in the proliferation or death of progenitors was noted. In contrast, the major impact of Akt overexpression in oligodendrocytes was enhanced myelination. Most interestingly, oligodendrocytes in these mice continued actively myelinating throughout life. Thus, expression of constitutively active Akt in oligodendrocytes and their progenitor cells generated no more oligodendrocytes, but dramatically more myelin. The increased myelination continued as these mice aged, resulting in enlarged optic nerves and white matter areas. In older animals with enlarged white matter areas, the density of oligodendrocytes was reduced, but because of the increased area, the total number of oligodendrocytes remained comparable with wild-type controls. Interestingly, in these animals, overexpression of Akt in Schwann cells did not impact myelination. Thus,in vivo, constitutively active Akt enhances CNS myelination but not PNS myelination and has no impact developmentally on oligodendrocyte number. Understanding the unique aspects of Akt signal transduction in oligodendrocytes that lead to myelination rather than uncontrolled proliferation of oligodendrocyte progenitor cells may have important implications for understanding remyelination in the adult nervous system.
Behavioral Impact of Neurotransmitter-Activated G-Protein-Coupled Receptors: Muscarinic and GABABReceptors RegulateCaenorhabditis elegansLocomotion
Authors: Dittman Jeremy S. , Kaplan Joshua M.
Published: July 2008

Neurotransmitter released from presynaptic terminals activates both ligand-gated ion channels (ionotropic receptors) and a variety of G-protein-coupled receptors (GPCRs). These neurotransmitter receptors are expressed on both presynaptic and postsynaptic cells. Thus, each neurotransmitter acts on multiple receptor classes, generating a large repertoire of physiological responses. The impact of many ionotropic receptors on neuronal activity and behavior has been clearly elucidated; however, much less is known about how neurotransmitter-gated GPCRs regulate neurons and circuits. InCaenorhabditis elegans, both acetylcholine (ACh) and GABA are released in the nerve cord and mediate fast neuromuscular excitation and inhibition during locomotion. Here we identify a muscarinic receptor (GAR-2) and the GABABreceptor dimer (GBB-1/2) that detect synaptically released ACh and GABA, respectively. Both GAR-2 and GBB-1/2 inhibited cholinergic motor neurons when ACh and GABA levels were enhanced. Loss of either GPCR resulted in movement defects, suggesting that these receptors are activated during locomotion. When the negative feedback provided by GAR-2 was replaced with positive feedback, animals became highly sensitive to ACh levels and locomotion was severely impaired. Thus, conserved GPCRs act in the nematode motor circuit to provide negative feedback and to regulate locomotory behaviors that underlie navigation.
Erbin Controls Dendritic Morphogenesis by Regulating Localization of δ-Catenin
Authors: Arikkath Jyothi , Israely Inbal , Tao Yanmei , Mei Lin , Liu Xin , Reichardt Louis F.
Published: July 2008

The LAP [leucine-rich and postsynaptic density-95/Discs large/zona occludens-1 (PDZ)] protein erbin and δ-catenin, a component of the cadherin–catenin cell adhesion complex, are highly expressed in neurons and associate through PDZ-mediated interaction, but have incompletely characterized neuronal functions. We show that short hairpin RNA-mediated knockdown of erbin and knockdown or genetic ablation of δ-catenin severely impaired dendritic morphogenesis in hippocampal neurons. Simultaneous loss of erbin and δ-catenin does not enhance severity of this phenotype. The dendritic phenotype observed after erbin depletion is rescued by overexpression of δ-catenin and requires a domain in δ-catenin that has been shown to regulate dendritic branching. Knockdown of δ-catenin cannot be rescued by overexpression of erbin, indicating that erbin is upstream of δ-catenin. δ-Catenin-null neurons have no alterations in global levels of active Rac1/RhoA. Knockdown of erbin results in alterations in localization of δ-catenin. These results suggest a critical role for erbin in regulating dendritic morphogenesis by maintaining appropriate localization of δ-catenin.
Caspase Inhibitor Infusion Protects an Avian Song Control Circuit from Seasonal-Like Neurodegeneration
Authors: Thompson Christopher K. , Brenowitz Eliot A.
Published: July 2008

Sex steroids such as androgens and estrogens have trophic effects on the brain and can ameliorate neurodegeneration, and the withdrawal of circulating steroids induces neurodegeneration in several hormone-sensitive brain areas. Very little is known about the underlying molecular mechanisms that mediate neuronal regression caused by hormone-withdrawal, however. Here we show that reduction of programmed cell death by local infusion of caspase inhibitors rescues a telencephalic nucleus in the adult avian song control system from neurodegeneration that is induced by hormone withdrawal. This treatment also has trans-synaptic effects that provide some protection of an efferent target region. We found that unilateral infusion of caspase inhibitorsin vivoin adult white-crowned sparrows rescued neurons within the hormone-sensitive song nucleus HVC (used as a proper name) from programmed cell death for as long as seven days after withdrawal of testosterone and a shift to short-day photoperiod and that the activation of caspase-3 was reduced by 59% on average in the ipsilateral HVC compared with the unmanipulated contralateral HVC. Caspase inhibitor infusion near HVC was sufficient to preserve neuron size ipsilaterally in a downstream nucleus, the robust nucleus of the arcopallium. This is the first report that sustained local application of caspase inhibitors can protect a telencephalic brain area from neurodegenerationin vivoand that a degenerating neural circuit rescued with caspase inhibitors produces sufficient trophic support to protect attributes of a downstream target that would otherwise degenerate. These results strengthen the case for the possible therapeutic use of caspase inhibitors under certain neurodegenerative conditions.
P0Protein Is Required for and Can Induce Formation of Schmidt-Lantermann Incisures in Myelin Internodes
Authors: Yin Xinghua , Kidd Grahame J. , Nave Klaus-Amin , Trapp Bruce D.
Published: July 2008

Axons in the PNS and CNS are ensheathed by multiple layers of tightly compacted myelin membranes. A series of cytoplasmic channels connect outer and inner margins of PNS, but not CNS, myelin internodes. Membranes of these Schmidt-Lantermann (S-L) incisures contain the myelin-associated glycoprotein (MAG) but not P0or proteolipid protein (PLP), the structural proteins of compact PNS (P0) and CNS (PLP) myelin. We show here that incisures are present in MAG-null and absent from P0-null PNS internodes. To test the possibility that P0regulates incisure formation, we replaced PLP with P0in CNS myelin. S-L incisures formed in P0-CNS myelin internodes. Furthermore, axoplasm ensheathed by 65% of the CNS incisures examined by electron microscopy had focal accumulations of organelles, indicating that these CNS incisures disrupt axonal transport. These data support the hypotheses that P0protein is required for and can induce S-L incisures and that P0-induced CNS incisures can be detrimental to axonal function.
Folate Deficiency Induces Neurodegeneration and Brain Dysfunction in Mice Lacking Uracil DNA Glycosylase
Authors: Kronenberg Golo , Harms Christoph , Sobol Robert W. , Cardozo-Pelaez Fernando , Linhart Heinz , Winter Benjamin , Balkaya Mustafa , Gertz Karen , Gay Shanna B. , Cox David , Eckart Sarah , Ahmadi Michael , Juckel Georg , Kempermann Gerd , Hellweg Rainer , Sohr Reinhard , Hörtnagl Heide , Wilson Samuel H. , Jaenisch Rudolf , Endres Matthias
Published: July 2008

Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung−/−) versus wild-type controls. Folate depletion increased nuclear mutation rates inUng−/− embryonic fibroblasts, and conferred death of culturedUng−/− hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons inUng−/− but notUng+/+ mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated inUng−/− mice. Independent ofUnggenotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency.
Induction of High-Frequency Oscillations in a Junction-Coupled Network
Authors: Tseng Shin-Hua , Tsai Li-Yun , Yeh Shih-Rung
Published: July 2008

Rhythmic oscillations of up to 600 Hz in grouped neurons frequently occur in the brains of animals. These high-frequency oscillations can be sustained in calcium-free conditions and may be blocked by gap junction blockers, implying a key role for electrical synapses in oscillation generation. Mathematical theories have been developed to demonstrate oscillations mediated by electrical synapses without chemical modulation; however, these models have not been verified in animals. Here we report that oscillations of up to 686 Hz are induced by paired spikes of short spike intervals (SIs) in a junction-coupled network. To initiate oscillations, it was essential that the second spike was elicited during the relative refractory period. The second spike suffered from slow propagation speed and failure to transmit through a low-conductance junction. Thus, at the spike initiation site, paired spikes of short SIs triggered one transjunctional spike in the postsynaptic neuron. At distant synaptic sites, two transjunctional spikes were produced as the SI increased during spike propagation. Consequently, spike collision of these asymmetrical transjunctional spikes occurred in the interconnected network. The remaining single spike reverberated in a network serving as an oscillator center. Paired-spike-induced oscillations were modeled by computer simulation and verified electrophysiologically in a network that mediates the tail-flip escape response of crayfish.
Sleep Deprivation Effects on Circadian Clock Gene Expression in the Cerebral Cortex Parallel Electroencephalographic Differences among Mouse Strains
Authors: Wisor Jonathan P. , Pasumarthi Ravi K. , Gerashchenko Dmitry , Thompson Carol L. , Pathak Sayan , Sancar Aziz , Franken Paul , Lein Ed S. , Kilduff Thomas S.
Published: July 2008

Sleep deprivation (SD) results in increased electroencephalographic (EEG) delta power during subsequent non-rapid eye movement sleep (NREMS) and is associated with changes in the expression of circadian clock-related genes in the cerebral cortex. The increase of NREMS delta power as a function of previous wake duration varies among inbred mouse strains. We sought to determine whether SD-dependent changes in circadian clock gene expression parallel this strain difference described previously at the EEG level. The effects of enforced wakefulness of incremental durations of up to 6 h on the expression of circadian clock genes (bmal1,clock,cry1,cry2,csnk1ε,npas2,per1, andper2) were assessed in AKR/J, C57BL/6J, and DBA/2J mice, three strains that exhibit distinct EEG responses to SD. Cortical expression of clock genes subsequent to SD was proportional to the increase in delta power that occurs in inbred strains: the strain that exhibits the most robust EEG response to SD (AKR/J) exhibited dramatic increases in expression ofbmal1,clock,cry2,csnkIε, andnpas2, whereas the strain with the least robust response to SD (DBA/2) exhibited either no change or a decrease in expression of these genes andcry1. The effect of SD on circadian clock gene expression was maintained in mice in which both of thecryptochromegenes were genetically inactivated.cry1andcry2appear to be redundant in sleep regulation as elimination of either of these genes did not result in a significant deficit in sleep homeostasis. These data demonstrate transcriptional regulatory correlates to previously described strain differences at the EEG level and raise the possibility that genetic differences underlying circadian clock gene expression may drive the EEG differences among these strains.
Evidence for Segregated and Integrative Connectivity Patterns in the Human Basal Ganglia
Authors: Draganski Bogdan , Kherif Ferath , Klöppel Stefan , Cook Philip A. , Alexander Daniel C. , Parker Geoff J. M. , Deichmann Ralf , Ashburner John , Frackowiak Richard S. J.
Published: July 2008

Detailed knowledge of the anatomy and connectivity pattern of cortico-basal ganglia circuits is essential to an understanding of abnormal cortical function and pathophysiology associated with a wide range of neurological and neuropsychiatric diseases. We aim to study the spatial extent and topography of human basal ganglia connectivityin vivo. Additionally, we explore at an anatomical level the hypothesis of coexistent segregated and integrative cortico-basal ganglia loops. We use probabilistic tractography on magnetic resonance diffusion weighted imaging data to segment basal ganglia and thalamus in 30 healthy subjects based on their cortical and subcortical projections. We introduce a novel method to define voxel-based connectivity profiles that allow representation of projections from a source to more than one target region. Using this method, we localize specific relay nuclei within predefined functional circuits. We find strong correlation between tractography-based basal ganglia parcellation and anatomical data from previously reported invasive tracing studies in nonhuman primates. Additionally, we showin vivothe anatomical basis of segregated loops and the extent of their overlap in prefrontal, premotor, and motor networks. Our findings in healthy humans support the notion that probabilistic diffusion tractography can be used to parcellate subcortical gray matter structures on the basis of their connectivity patterns. The coexistence of clearly segregated and also overlapping connections from cortical sites to basal ganglia subregions is a neuroanatomical correlate of both parallel and integrative networks within them. We believe that this method can be used to examine pathophysiological concepts in a number of basal ganglia-related disorders.
STAT3 is a Critical Regulator of Astrogliosis and Scar Formation after Spinal Cord Injury
Authors: Herrmann Julia E. , Imura Tetsuya , Song Bingbing , Qi Jingwei , Ao Yan , Nguyen Thu K. , Korsak Rose A. , Takeda Kiyoshi , Akira Shizuo , Sofroniew Michael V.
Published: July 2008

Signaling mechanisms that regulate astrocyte reactivity and scar formation after spinal cord injury (SCI) are not well defined. We used the Cre recombinase (Cre)-loxPsystem under regulation of the mouse glial fibrillary acidic protein (GFAP) promoter to conditionally delete the cytokine and growth factor signal transducer, signal transducer and activator of transcription 3 (STAT3), from astrocytes. After SCI in GFAP-Cre reporter mice, >99% of spinal cord cells that exhibited Cre activity as detected by reporter protein expression were GFAP-expressing astrocytes. Conditional deletion (or knock-out) of STAT3 (STAT3-CKO) from astrocytes in GFAP-Cre-loxPmice was confirmedin vivoandin vitro. In uninjured adult STAT3-CKO mice, astrocytes appeared morphologically similar to those in STAT3+/+ mice except for a partially reduced expression of GFAP. In STAT3+/+ mice, phosphorylated STAT3 (pSTAT3) was not detectable in astrocytes in uninjured spinal cord, and pSTAT3 was markedly upregulated after SCI in astrocytes and other cell types near the injury. Mice with STAT3-CKO from astrocytes exhibited attenuated upregulation of GFAP, failure of astrocyte hypertrophy, and pronounced disruption of astroglial scar formation after SCI. These changes were associated with increased spread of inflammation, increased lesion volume and partially attenuated motor recovery over the first 28 d after SCI. These findings indicate that STAT3 signaling is a critical regulator of certain aspects of reactive astrogliosis and provide additional evidence that scar-forming astrocytes restrict the spread of inflammatory cells after SCI.
A NewDrosophilaPOU Gene,pdm3, Acts in Odor Receptor Expression and Axon Targeting of Olfactory Neurons
Authors: Tichy Andrea L. , Ray Anandasankar , Carlson John R.
Published: July 2008

Olfaction depends on the differential activation of olfactory receptor neurons (ORNs) and on the proper transmission of their activities to the brain. ORNs select individual receptors to express, and they send axons to particular targets in the brain. Little is known about the molecular mechanisms underlying either process. We have identified a newDrosophilaPOU gene,pdm3, that is expressed in ORNs. Genetic analysis shows thatpdm3is required for odor response in one class of ORNs. We find thatpdm3acts in odor receptor expression in this class, and that the odor response can be rescued by the receptor. Another POU gene,acj6, is required for receptor expression in the same class, and we find a genetic interaction between the two POU genes. The results support a role for a POU gene code in receptor gene choice.pdm3is also expressed in other ORN classes in which it is not required for receptor expression. For two of these classes,pdm3is required for normal axon targeting. Thus, this mutational analysis, the first for a POU class VI gene, demonstrates a role forpdm3in both of the processes that define the functional organization of ORNs in the olfactory system.
Translocation of GluR1-Containing AMPA Receptors to a Spinal Nociceptive Synapse during Acute Noxious Stimulation
Authors: Larsson Max , Broman Jonas
Published: July 2008

Potentiation of spinal nociceptive transmission by synaptic delivery of AMPA receptors, via an NMDA receptor- and Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway, has been proposed to underlie certain forms of hyperalgesia, the enhanced pain sensitivity that may accompany inflammation or tissue injury. However, the specific synaptic populations that may be subject to such plasticity have not been identified. Using neuronal tracing and postembedding immunogold labeling, we show that a model of acute inflammatory hyperalgesia is associated with an elevated density of GluR1-containing AMPA receptors, as well as an increased synaptic ratio of GluR1 to GluR2/3 subunits, at synapses established by C-fibers that lack the neuropeptide substance P. A more subtle increase in GluR1 immunolabeling was noted at synapses formed by substance P-containing nociceptors. No changes in either GluR1 or GluR2/3 contents were observed at synapses formed by low-threshold mechanosensitive primary afferent fibers. These results contrast with our previous observations in the same pain model of increased and decreased levels of activated CaMKII at synapses formed by peptidergic and nonpeptidergic nociceptive fibers, respectively, suggesting that the observed redistribution of AMPA receptor subunits does not depend on postsynaptic CaMKII activity. The present ultrastructural evidence of topographically specific, activity-dependent insertion of GluR1-containing AMPA receptors at a central synapse suggests that potentiation of nonpeptidergic C-fiber synapses by this mechanism contributes to inflammatory pain.
Considerazioni su Clutorio Prisco e il suo processo (Tac. ann. III 49–51, Cass. Dio LVII 20,3–4).*
Authors: Petrini Francesco Maria
Published: July 2008

Riassunto

Il presente elaborato ha inteso ricostruire quanto più compiutamente possibile la figura e la vicenda di Clutorio Prisco, poeta processato e condannato a morte nel 21, al culmine della sua popolarità; la sua rovina, scaturita — come quella ovidiana di pochi anni anteriore — da una singola e fatale composizione poetica, venne decisa, assenti Druso e Tiberio, dalla sola assemblea senatoria. L’indagine si è in primis concentrata sulla questione onomastica del personaggio come sulla considerazione dei relativi dati prosopografici e del contesto culturale, socio-relazionale e clientelare di appartenenza (§ 1), pervenendo, attraverso una necessaria regestazione documentaria, ad alcune nuove proposte interpretative; la seconda parte del contributo (§§ 2–3) è invece volta all'analisi specifica del processo a Clutorio, delle sue dinamiche ed implicazioni, della sua incidenza storica e della sua memoria nella tradizione storiografica. Contestualmente all'indagine è stata inoltre operata (§ 3.1) una breve rilettura degli ultimi anni della vita di Druso Minore (21–23 E. C.), evidenziando la sospetta lacuna documentaria gravante sul personaggio fin dalla prima tradizione storiografica altoimperiale
Held oder Harlekin? Der sterbende Seneca bei Tacitus
Authors: Schmal Stephan
Published: July 2008

Tacitus schildert den Freitod des Philosophen Seneca (65 n. Chr.) sehr ausführlich und, wie es scheint, wohlwollend als einen Akt der Seelenstärke und der philosophischen Läuterung (Tac. ann. 15.60.2–64). Doch wer Tacitus und dessen Hang zur Ironie kennt, der merkt, daß der Historiker dem Philosophen eitle Phrasen und hohles Pathos in den Mund legt. Nicht umsonst läßt er wenig später den Dichter Petronius ganz anders sterben, nämlich unter gezielter Vermeidung jeglicher Inszenierung (Tac. ann. 16.19.2 f.).

Seneca war als Politiker, als Lehrer Neros und als einer der reichsten Männer Roms höchst umstritten. Sein theatralischer Tod paßt für Tacitus zu einem Menschen und Literaten, dem der schöne Schein immer wichtiger war als Wahrheit und echter Anstand.
Constantinus rerum nouator: dal comitatus dioclezianeo ai palatini di Valentiniano I
Authors: Colombo Maurizio
Published: July 2008

Sommario

Il mio articolo affronta principalmente quattro questioni, che riguardano l'evoluzione dell'esercito romano nel corso del IV secolo d.C.: 1) la relazione tra l'istituzione dei comites rei militaris e la creazione ufficiale dei comitatenses, entrambe innovazioni di Costantino; 2) l'ascesa della cavalleria scelta e la creazione degli auxilia sotto il regno di Costantino; 3) le dimensioni e la composizione dei comitatenses; 4) l'evoluzione ulteriore dell'esercito romano sotto i successori di Costantino. Questo studio esamina anche altri punti, ma mira soprattutto a confutare le tesi vulgate sull'esercito romano del IV secolo d.C.; alla fine del mio articolo risulterà chiaro che soltanto gli anni Sessanta di quel secolo videro gli auxilia palatina raggiungere una posizione di rilievo nell'esercito romano della Tarda Antichità.
Ansichten eines Zivilisierten über die unzivilisierte Welt: Das Sāsāniden-Bild des Georgios Pisides und sein historischer Wert für den spätantiken Iran*
Authors: Huber Irene
Published: July 2008

Georgios Pisides, Hofpanegyrist des Kaisers Herakleios, überliefert in seinen angeblich auf Autopsie beruhenden Carmina Details über die byzantinischen Perserfeldzüge in den zwanziger Jahren des siebten Jahrhunderts. Der Aufsatz untersucht, welches Bild der Sāsāniden in den Gedichten vermittelt wird und welche Intentionen des Dichters sich dahinter verbergen. Weiter werden die Anspielungen auf Ereignisse der iranischen Geschichte vorgestellt. Dabei wird deutlich, daß der Dichter im Dienste der Kaiserideologie steht und von zeitgenössischer Kriegspropaganda beeinflußt ist. Zudem sind weitere Faktoren wie die Unterhaltung seines Publikums sowie der Rekurs auf die klassische Literatur bestimmend. Im gesamten zeigt Pisides indes mehr Interesse, sein religiös fundiertes Kaiserbild zu bestärken als historische Informationen über den Kriegsgegner zu liefern.
TEC : A RESOURCE FOR STUDYING WHAT IS "IN" AND "OF" TRANSLATIONAL ENGLISH
Authors: Laviosa Sara
Published: July 2008

The Translational English Corpus (TEC) held at the Centre
for Translation Studies at UMIST is a full-text, synchronic, general,
monolingual, written, single, translational corpus of English. It is also a
direct, multi-source-language, mono-translation-mode (written mode), mono-translation-method
(human translation), largely into-mother-tongue, professional, published
corpus. At the time of writing TEC represents four text categories: newspapers,
biography, fiction, and inflight magazines. Hatim (1999) has argued that so far
in translation studies an important distinction has been ignored. This
distinction is between what is "in" and what is "of" the
text. "In" refers to the language itself, which can be ana-lyzed
through text analysis, while "of" refers to the text in its entirety,
its overall effect in terms of ideology. In this paper, I will argue that TEC
can indeed be a valuable, self-contained, single resource for studying
precisely the "of" of translational language, that is, its
ideological impact in the target language and culture. To this purpose, I will
discuss some methodological issues as well as the methods for carrying out
critical linguistic analy-sis. I will also suggest ways of investigating norms
of lexical use in TEC and their possible ideological implications through the
lexico-grammatical and collocational analysis of a set of key words relating to
Europe in translated newspaper articles.