bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasorelaxation induced by prostaglandin E2in human pulmonary vein: role of the EP4receptor subtype
Authors: Foudi N , Kotelevets L , Louedec L , Leséche G , Henin D , Chastre E , Norel X
Published: June 2008

Background and purpose:

PGE2has been shown to induce relaxations in precontracted human pulmonary venous preparations, while in pulmonary arteries this response was not observed. We investigated and characterized the prostanoid receptors which are activated by PGE2in the human pulmonary veins.

Experimental approach:

Human pulmonary arteries and veins were cut as rings and set up in organ baths in presence of a TP antagonist. A pharmacological study was performed using selective EP1−4ligands. The cellular localization of the EP4receptors by immunohistochemistry and their corresponding transcripts were also investigated in these vessels.

Key results:

PGE2and the EP4agonists (L‐902688, ONO‐AE1‐329) induced potent vasodilatation of the human pulmonary vein, pEC50values: <7.22±0.20, 8.06±0.12 and 7.80±0.09, respectively. These relaxations were inhibited by the EP4antagonist GW627368X and not modified in presence of the DP antagonist L‐877499. Higher concentrations (1 μM) of the EP2agonist ONO‐AE1‐259 induced relaxations of the veins. The EP4agonists had no effect on the precontracted arteries. Finally, the EP1antagonists ONO‐8713 and SC‐51322 potentiated the relaxation of the veins induced by PGE2. EP4and EP1receptors were detected by immunohistochemistry in the veins but not in the arteries. EP4mRNA accumulation was also greater in the veins when compared with the arterial preparations.

Conclusions and implications:

Of the 4 EP receptor subtypes, smooth muscle cells in the human pulmonary vein express the EP4and EP1receptor subtypes. The relaxations induced by PGE2in this vessel result from the activation of the EP4receptor.

British Journal of Pharmacology(2008)154, 1631–1639; doi:10.1038/bjp.2008.214; published online 2 June 2008
Use of a Hearing and Balance Screening Survey With Local Primary Care Physicians
Authors: Danhauer Jeffrey L. , Celani Kristina E. , Johnson Carole E.
Published: June 2008

Purpose

This investigation is a follow-up to a national survey of hearing/balance screening and referrals in elderly patients by primary care physicians (PCPs). This local study focused on PCPs who actually treated elderly patients and could be contacted and followed in a single community.

Method

PCPs in Santa Barbara, CA, were surveyed with a 35-item questionnaire via mailings, phone calls, and hand delivery to determine their participation in, knowledge of, and attitudes toward hearing/balance screening and referrals for the elderly. Potential respondents were 154 PCPs obtained from WebMD, Google, and telephone and provider directories for Santa Barbara. Of the 154 surveys mailed/delivered, 33 were returned undeliverable or unusable, and 32 were returned usable, producing an overall response rate of 26.5%.

Results

Results were similar to those of the national study; PCPs were unlikely to screen for hearing/balance problems unless patients complained. The PCPs were unaware of patient self-report screening methods and probably would not use them in the future.

Conclusions

These PCPs acknowledged the importance of hearing/balance problems in the elderly, but their responses demonstrated insufficiencies in knowledge and potential attitudinal, time, and reimbursement obstacles that could interfere with their screening for hearing/balance problems. Audiologists should partner with PCPs to improve ways of meeting patients' needs but must consider resource/payoff implications for such endeavours.
Establishing a Tinnitus Clinic in Your Practice
Authors: Tyler Richard S. , Haskell George B. , Gogel Stephanie A. , Gehringer Anne K.
Published: June 2008

Purpose

While tinnitus is very common among the hearing impaired population, specific treatment for tinnitus is not provided in most clinics. This article provides a plan for establishing a tinnitus treatment program that can be implemented in stages at most audiology clinics.

Method

Preparation for establishing a tinnitus clinic includes having an overall plan regarding the type and degree of tinnitus management. Assessment involves a measurement of tinnitus and of the reaction a patient has to the tinnitus, including the use of handicap questionnaires. Management typically involves some form of counseling and sound therapy. Four problematic areas in tinnitus management are thoughts and emotions, hearing and communication, sleep, and concentration.

Conclusions

Licensed audiologists generally have the essential training necessary to provide counseling and sound therapy to treat tinnitus patients. We introduce 3 levels of treatment implementation, depending on whether the patient is curious, concerned, or distressed. Follow-up and referrals might be necessary in more severe cases. Finally, the development of a tinnitus clinic centers around establishing a need for individual treatment, creating a treatment plan, estimating the need for additional staff and resources, reimbursement options, and assessing the effectiveness of the program.
The Effect of Room Acoustics and Sound-Field Amplification on Word Recognition Performance in Young Adult Listeners in Suboptimal Listening Conditions
Authors: Larsen Jeffery B. , Vega Alison , Ribera John E.
Published: June 2008

Purpose

To compare the speech recognition performance of young adult listeners with normal hearing in 2 college classrooms, only 1 of which met American National Standards Institute (ANSI) S12.60-2002 acoustic standards. Also, differences in speech recognition performance were compared in both classrooms with and without the use of a classroom amplification system. The speech was presented at low intensity to simulate listening in the rear seats of a large college classroom.

Method

Listeners were randomly assigned seats in the 2 classrooms, and Northwestern University Auditory Test No. 6 (NU-6) words were presented via a loudspeaker from the front of the classroom for all listening conditions as well as through a sound-field infrared system with ceiling-mounted speakers during the amplified condition.

Results

Results showed statistically significant differences in speech recognition performance between classrooms, with and without classroom amplification, and across the rows of each classroom when the classroom amplification system was not used.

Conclusions

These results demonstrate how meeting the ANSI S12.60-2002 standard, which was written for elementary school classrooms, can benefit young adult listeners in postsecondary classrooms. Also, classroom amplification was shown to improve speech recognition for students across the classroom in both acoustically poor and acoustically sound classroom environments.
Increased efficiency of short-pulse laser-generated proton beams from novel flat-top cone targets
Authors: Flippo K. A. , d’Humières E. , Gaillard S. A. , Rassuchine J. , Gautier D. C. , Schollmeier M. , Nürnberg F. , Kline J. L. , Adams J. , Albright B. , Bakeman M. , Harres K. , Johnson R. P. , Korgan G. , Letzring S. , Malekos S. , Renard-LeGalloudec N. , Sentoku Y. , Shimada T. , Roth M. , Cowan T. E. , Fernández J. C. , Hegelich B. M.
Published: June 2008

Ion-driven fast ignition (IFI) may have significant advantages over electron-driven FI due to the potentially large reduction in the amount of energy required for the ignition beam and the laser driver. Recent experiments at the Los Alamos National Laboratory’s Trident facility employing novel Au flat-top cone targets have produced a fourfold increase in laser-energy to ion-energy efficiency, a 13-fold increase in the number of ions above 10MeV, and a few times increase in the maximum ion energy compared to Au flat-foil targets. Compared to recently published scaling laws, these gains are even greater. If the efficiency scales with intensity in accordance to flat-foil scaling, then, with little modification, these targets can be used to generate the pulse of ions needed to ignite thermonuclear fusion in the fast ignitor scheme. A proton energy of at least 30MeV was measured from the flat-top cone targets, and particle-in-cell (PIC) simulations show that the maximum cutoff energy may be as high as 40–45MeV at modest intensity of 1×1019W∕cm2 with 20J in 600fs. Simulations indicate that the observed energy and efficiency increase can be attributed to the cone target’s ability to guide laser light into the neck to produce hot electrons and transport these electrons to the flat-top of the cone where they can be heated to much higher temperatures, creating a hotter, denser sheath. The PIC simulations also elucidate the critical parameters for obtaining superior proton acceleration such as the dependence on laser contrast/plasma prefill, as well as longitudinal and transverse laser pointing, and cone geometry. These novel cones have the potential to revolutionize inertial confinement fusion target design and fabrication via their ability to be mass produced. In addition, they could have an impact on the general physics community studying basic electron and radiation transport phenomena or as better sources of particle beams to study equations of state and warm dense matter, or for hadron therapy, as new radioisotope generators, or for compact proton radiography sources.
Observation of ion-acoustic shock wave transition due to enhanced Landau damping
Authors: Bailung H. , Nakamura Y. , Saitou Y.
Published: June 2008

Ion-acoustic shock waves are observed experimentally introducing strong Landau damping by increasing the ion temperature in a double plasma device. An oscillatory ion-acoustic shock wave undergoes transition with enhanced Landau damping and forms a monotonic shock wave. Numerical results of the Korteweg–de Vries equation with an additional integral term to account for the strength of Landau damping are compared with the experimental findings. Enhancement of Landau damping is found to increase the dissipation of the wave, which manifests in quenching of the oscillatory structure behind the shock front.
Limitation of cross-excitation instability in a relativistic Cerenkov generator with coaxial slow wave structure
Authors: Xiao Renzhen , Zhang Lijun , Liang Tiezhu , Teng Yan , Chen Changhua , Shao Hao , Liu Guozhi , Lin Yuzheng
Published: June 2008

The operation in the cross-excitation instability regimes for relativistic backward wave oscillators has been reported and studied in some earlier papers. In the experiment of a relativistic Cerenkov generator with coaxial slow wave structure (CRCG), the cross-excitation instability has also been observed by us. In this paper, experimental results for the CRCG operating in this regime are given, and an explanation is provided to account for the appearance of the instability. Based on this explanation, two types of reflectors, i.e., coaxial Bragg reflectors and cutoff necks, are adopted to restrain the cross-excitation instability by increasing the reflection coefficient at the entrance of the coaxial slow wave structure.
Photoinduced electron transfer reaction in polymer-surfactant aggregates: Photoinduced electron transfer between N,N-dimethylaniline and 7-amino coumarin dyes
Authors: Chakraborty Anjan , Seth Debabrata , Setua Palash , Sarkar Nilmoni
Published: June 2008

Photoinduced electron transfer between coumarin dyes and N,N-dimethylaniline has been investigated by using steady state and picosecond time resolved fluorescence spectroscopy in sodium dodecyl sulphate (SDS) micelles and PVP–polyvinyl pyrrolidone (SDS) polymer-surfactant aggregates. A slower rate of electron transfer is observed in PVP-SDS aggregates than in polymer-free SDS micelles. A Marcus type inversion is observed in the correlation of free energy change in comparison with the electron transfer rate. The careful investigation reveals that C-151 deviates from the normal Marcus inverted region compared to its analogs C-152 and C-481 due to slower rotational relaxation and smaller translational diffusion coefficient.
Transition metal oxides as charge injecting layer for admittance spectroscopy
Authors: Hoping M. , Schildknecht C. , Gargouri H. , Riedl T. , Tilgner M. , Johannes H.-H. , Kowalsky W.
Published: June 2008

Admittance spectroscopy is a simple yet powerful tool to determine the carrier mobility of organic compounds. One requirement is to have an Ohmic contact for charge injection. By employing a thin interfacial layer of tungsten oxide, or molybdenum oxide we have found a possibility to efficiently inject holes into organic materials with a deep highest occupied molecular orbital level down to 6.3eV. These results considerably enhance the application range of the admittance spectroscopy method. The measured data are in excellent agreement with data obtained by the time-of-flight technique.
Room-temperature, intraband, infrared absorption in CdSe∕poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4-(1-cyanovinylene)phenylene] nanocomposites drop cast on GaAs
Authors: Stiff-Roberts Adrienne D. , Lantz Kevin R.
Published: June 2008

We have previously demonstrated a method for achieving room-temperature, intraband, midinfrared (3–5μm) absorption in CdSe colloidal quantum dot∕poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4- phenylenevinylene] conducting polymer nanocomposites deposited on GaAs substrates. In this work, theoretical and experimental evidence are presented to further verify that the observed infrared sensitivity is due to intraband transitions.
Distribution of frequencies of a single precessing spin detected by scanning tunneling microscope
Authors: Komeda Tadahiro , Manassen Yishay
Published: June 2008

We have measured high frequency signals in the tunneling current of scanning tunneling microscopy for a submonolayer oxide thin film on the Si(111)-7×7 surface. We demonstrate that the signal is related to the Larmor precession of the electron spin associated with a dangling bond. The detected precession frequency possesses a broad distribution (linewidth is comparable to that observed by conventional electron spin resonance) and a split near the maxima, both of which are attributed to the inhomogeneity of the g factor of a single spin.
Effectively enhanced oxygen sensitivity of individual ZnO tetrapod sensor by water preadsorption
Authors: Zheng K. H. , Zhao Y. C. , Deng K. , Liu Z. , Sun L. F. , Zhang Z. X. , Song L. , Yang H. F. , Gu C. Z. , Xie S. S.
Published: June 2008

In this letter, individual ZnO tetrapod was designed as a multiterminal sensor. The gas-sensing properties of water and oxygen of the device have been investigated. We found that if water was preadsorbed on the device, the sensitivity of oxygen can be effectively enhanced; meanwhile, the response time can also be remarkably shortened. The mechanism of these phenomena, we propose, is the adsorption competition of the two kinds of molecules. Our results show that the preadsorption of appropriate gas can enhance the performance of the sensors, which is helpful for sensor designing.
Composition anisotropy compensation and magnetostriction in Pr(Fe1−xCox)1.9 (⩽x⩽0.5) cubic Laves alloys
Authors: Shi Y. G. , Tang S. L. , Zhai L. , Huang H. B. , Wang R. L. , Yu J. Y. , Du Y. W.
Published: June 2008

Polycrystalline magnetostrictive alloys Pr(Fe1−xCox)1.9 (0⩽x⩽0.5) with cubic Laves phase were synthesized by high-pressure annealing. Measurements of Curie temperature, easy magnetic direction (EMD), and magnetostriction were made on these alloys. The EMD of the alloys rotates continuously from ⟨111⟩ for x=0.0 to ⟨110⟩ for x=0.3 and then shows a tendency to ⟨111⟩ with further increasing x. Two magnetostriction peaks at low fields are observed around x=0.2 and x=0.4 due to the lower anisotropy of these two alloys, which is consistent with the variation of EMD. This work demonstrates that the composition anisotropy compensation can be realized in Pr(Fe1−xCox)1.9 system.
Bond strength and electronic structures of coherent Ir∕Ir3Zr interfaces
Authors: Gong H. R. , Liu Yong , Tang Hui Ping , Xiang Chang Shu
Published: June 2008

First principles calculation reveals that the coherent Ir∕Ir3Zr interfaces possess high values of bond strength and that interface orientation and atomic configuration have important effects on interface bonding and interface energy. Calculation also shows that the interface dipole is formed in the Ir∕Ir3Zr interface due to an unequal loss of the electrons from Ir and Ir3Zr atoms, and density of states suggests that a stronger covalent bonding is formed in the interface than corresponding Ir or Ir3Zr bulks, which results in the strengthening effect of the Ir3Zr precipitation in the Ir-base superalloys from experimental observations in the literature.
Transportation: The Bottleneck of Regional Competitiveness in Toronto
Authors: Keil Roger , Young Douglas
Published: June 2008

The reconciliation of global trade interests, regional transportation necessities, and urban everyday life and politics is at the centre of the emergence of new infrastructures in general, and new transportation networks in particular. In Toronto recent rescaling and restructuring of regional government provide a potential opportunity for new modes of regional governance. Will transportation in the Toronto region remain bifurcated into a premium network of transport infrastructure systems, on the one hand, and underserved community-based systems, on the other hand? We argue that the existing transportation situation has become a bottleneck for the continued globalization of the region, because global and local circuits of mobility are not well coordinated and various scales of decision making do not visibly interact for the regional good. At this point we ask whether there is an emerging collective actor (or collective actors) to remedy the situation, or whether we can instead expect the anarchic governance model of the recent past, with its biases towards suburban road building, to continue. We are particularly interested in casting light on the institutions that have been created (or dismantled) to deal with comprehensive transportation planning in the region. We posit that, in the context of recent institutional reforms, transportation agencies had to adjust, and we pose a series of research questions as a means of exploring and understanding those adjustments.
Organizational Environments and Public-Service Failure: An Empirical Analysis
Authors: Andrews Rhys , Boyne George A
Published: June 2008

Organizational failure in the public sector is an increasingly topical issue. Media attention to high-profile cases of dysfunction has been matched by vigorous government determination to identify and remedy perceived weaknesses in the provision of public services. Research on organizational environments suggests that poor public-service performance may be the result of external pressures. However, few studies have systematically investigated the effects of the environment on public-service failure. We formalize and test a comprehensive model of the impact of environmental constraints on organizational failure across the public sector in England between 2002 and 2004. The results show that the munificence, complexity, and dynamism of organizational environments are significant predictors of the extent of public-service failure.
Inventing Seed: The Nature(s) of Intellectual Property in Plants
Authors: van Dooren Thom
Published: June 2008

This paper explores some of the inequities in the ways in which intellectual property has been applied to agricultural plant genetic resources, focusing primarily on patents. In particular, it is concerned with the importance of what counts as ‘nature’ in making the distinction between something that is ‘invented’ and something that is merely ‘discovered’—a distinction that is at the heart of patent law (although not always made in these terms). While discoveries are understood to be mere revealings of nature, genuine inventions are considered to be human products, and therefore eligible for patent protection. What counts as nature in this discourse, and which kinds of human labour are taken to be genuinely inventive, is, therefore, a highly consequential issue. Ultimately, I argue for both the exposure of the noninnocent and highly political way in which ‘nature’ is formed, and the importance of more honest ways of characterising the coming-into-being of new plant varieties. The final section points to some existing proposals and projects that might help us to build systems of property in this area that are both more equitable and that acknowledge the contributions and needs of all of the diverse actors—human and not—involved in the ‘emergence’ of agricultural biodiversity.
Trend in HIV incidence in a cohort of homosexual men in Sydney: data from the Health in Men Study
Authors: Jin Fengyi , Prestage Garrett P. , McDonald Ann , Ramacciotti Tim , Imrie John C. , Kippax Susan C. , Kaldor John M. , Grulich Andrew E.
Published: June 2008

Objectives: To determine the incidence of HIV seroconversion in a community-based cohort of homosexual men in Sydney from 2002 to 2006. Methods: Participants were recruited between 2001 and 2004 from community-based events and venues. They were tested for HIV annually at follow-up interviews. Each year, the study database was matched against the national HIV register to identify additional HIV seroconversions among men lost to active follow up. The trend in HIV incidence over time was examined using Cox regression. Results: Among 1426 participants, 52 cases of HIV seroconversion were identified between 2002 and 2006, an incidence of 0.87 per 100 person-years (95% CI: 0.65–1.14). HIV incidence varied from 1.67 per 100 person-years in 2002 to 0.39 in 2006 (P trend = 0.282). The median age of HIV seroconversion was 36.9 years, ranging from 22 to 63 years. Conclusion: In this community-based cohort of highly sexually active homosexual men in Sydney, HIV incidence was close to 1% each year and declined non-significantly between 2002 and 2006. These data are consistent with surveillance data suggesting no increase in recent HIV incidence in homosexual men in New South Wales.
Trends in HIV incidence in homosexual men in developed countries
Authors: Grulich Andrew E. , Kaldor John M.
Published: June 2008

Objectives: To describe trends in HIV notifications and in other measures of HIV incidence in homosexual men in developed countries. Methods: A literature search was conducted using PubMed. In addition to the peer-reviewed literature, data on HIV surveillance trends were sought by searching websites of surveillance authorities in developed countries. Results: The availability of long-term HIV surveillance data varied considerably. However, in almost all jurisdictions in which such data were available, notifications of new HIV diagnoses among homosexual men have increased, mostly since the late 1990s. The magnitude of this increase varied, but was more than 50% in many countries. There were much fewer data available on trends in direct measures of HIV incidence in homosexual men, and increases in HIV testing rates may have contributed to the increases in HIV diagnoses in many countries. However, since the late 1990s, several clinic- and community-based cohort studies in Europe and North America reported increasing incidence. Conclusion: There were increases in HIV notifications in homosexual men in almost all developed countries, starting in the late 1990s and continuing to 2006. Although increases in HIV testing probably contributed to the increases in some settings, limited cohort data do support the existence of a true increase in HIV incidence in European and North American countries. Improved monitoring of HIV incidence in homosexual men at the population level is required to allow more timely assessment of the drivers underlying such trends.
Effective partnership and adequate investment underpin a successful response: key factors in dealing with HIV increases
Authors: Bernard Diana , Kippax Susan , Baxter Don
Published: June 2008

Background: Australia has mounted an effective response to HIV and AIDS by investing in evidence-informed policy. Recently, in response to increases in HIV in some states in Australia, the New South Wales Department of Health set up a ‘think tank’ to examine differences in epidemiological and behavioural data, policies, strategies and community responses in order to account for state-based differences and ensure an effective ongoing response to HIV. Methods: The National Centre in HIV Social Research undertook key informant interviews with major stakeholders to help understand differences in responses by the three states most affected by HIV in Australia – Queensland, New South Wales and Victoria. In parallel, the Australian Federation of AIDS Organisations completed an analysis of the investments in HIV-prevention activities targeting gay men in all jurisdictions in Australia. The Australian Federation of AIDS Organisations also analysed the strategic contexts and government responses to HIV in the three states. Results: There were significant differences between New South Wales, Queensland and Victoria in the way the HIV partnership functions. Type of prevention strategy and level of financial investment in prevention activities appear to be related to the effectiveness of the ongoing response to HIV. Conclusions: An active commitment to and adequate resourcing of HIV prevention by all stakeholders in the HIV partnership – government and non-government departments, researchers and gay community organisations – is crucial if Australia is to respond effectively to HIV among gay and other men who have sex with men.
Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment
Authors: Falster Kathleen , Gelgor Linda , Shaik Ansari , Zablotska Iryna , Prestage Garrett , Grierson Jeffrey , Thorpe Rachel , Pitts Marian , Anderson Jonathan , Chuah John , Mulhall Brian , Petoumenos Kathy , Kelleher Anthony , Law Matthew
Published: June 2008

Objectives: To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006. Methods: We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts. Results: We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81–92%) and two large, community-based surveys in Australia (69–85% and 49–83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria; however, the sample size was very small. Conclusions: For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.
Health Care Services for men who have sex with men in different Australian states and territories since the emergence of HIV
Authors: Pell Cathy , Donohoe Simon , Conway Damian
Published: June 2008

The purpose of this article is to describe sexual health services available in Australia across the different states and territories for gay men and men who have sex with men (MSM) and their utilisation. An assessment of services available in different states is made, then the evidence about how MSM and people living with HIV/AIDS access health care in Australia is presented. This demonstrates that the number and location of sexual health services has changed over time. It also demonstrates that services available differ by state and territory. The availability of non-occupational post-exposure prophylaxis for HIV infection has been different in each state and territory, as has its utilisation. The majority of care for sexual health-related issues and for MSM and people living with HIV/AIDS is delivered in general practice settings in Australia, with hospital outpatient settings, including sexual health clinics, utilised commonly.
Social and physiological influences of robot therapy in a care house
Authors: Wada Kazuyoshi , Shibata Takanori
Published: June 2008

This article presents research on robot therapy for elderly residents in a care house. Experiments were conducted from June 2005, lasting more than 2 months. Two therapeutic baby seal robots were introduced to the residents, and activated for over 9 hours daily. To investigate the psychological and social effects of the robots, the residents’ activities in public areas were recorded using video cameras, during the daytime (8:30–18:00) for over 2 months. In addition, urinalysis of the residents was performed for 17-ketosteroid sulfate and 17-hydroxycorticosteroid. Results of the video analysis indicated that social interaction increased through interaction with the seal robots. Results of the urine tests showed that the reactions of the subjects’ vital organs to stress improved after the introduction of the robots.
P2X7 receptors on osteoblasts couple to production of lysophosphatidic acid: a signaling axis promoting osteogenesis
Authors: Panupinthu Nattapon , Rogers Joseph T. , Zhao Lin , Solano-Flores Luis Pastor , Possmayer Fred , Sims Stephen M. , Dixon S. Jeffrey
Published: June 2008

Nucleotides are released from cells in response to mechanical stimuli and signal in an autocrine/paracrine manner through cell surface P2 receptors. P2rx7−/− mice exhibit diminished appositional growth of long bones and impaired responses to mechanical loading. We find that calvarial sutures are wider in P2rx7−/− mice. Functional P2X7 receptors are expressed on osteoblasts in situ and in vitro. Activation of P2X7 receptors by exogenous nucleotides stimulates expression of osteoblast markers and enhances mineralization in cultures of rat calvarial cells. Moreover, osteogenesis is suppressed in calvarial cell cultures from P2rx7−/− mice compared with the wild type. P2X7 receptors couple to production of the potent lipid mediators lysophosphatidic acid (LPA) and prostaglandin E2. Either an LPA receptor antagonist or cyclooxygenase (COX) inhibitors abolish the stimulatory effects of P2X7 receptor activation on osteogenesis. We conclude that P2X7 receptors enhance osteoblast function through a cell-autonomous mechanism. Furthermore, a novel signaling axis links P2X7 receptors to production of LPA and COX metabolites, which in turn stimulate osteogenesis.
Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis
Authors: Leal-Ortiz Sergio , Waites Clarissa L. , Terry-Lorenzo Ryan , Zamorano Pedro , Gundelfinger Eckart D. , Garner Craig C.
Published: June 2008

Active zones are specialized regions of the presynaptic plasma membrane designed for the efficient and repetitive release of neurotransmitter via synaptic vesicle (SV) exocytosis. Piccolo is a high molecular weight component of the active zone that is hypothesized to participate both in active zone formation and the scaffolding of key molecules involved in SV recycling. In this study, we use interference RNAs to eliminate Piccolo expression from cultured hippocampal neurons to assess its involvement in synapse formation and function. Our data show that Piccolo is not required for glutamatergic synapse formation but does influence presynaptic function by negatively regulating SV exocytosis. Mechanistically, this regulation appears to be calmodulin kinase II–dependent and mediated through the modulation of Synapsin1a dynamics. This function is not shared by the highly homologous protein Bassoon, which indicates that Piccolo has a unique role in coupling the mobilization of SVs in the reserve pool to events within the active zone.
Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth
Authors: Shimada Tadayuki , Toriyama Michinori , Uemura Kaori , Kamiguchi Hiroyuki , Sugiura Tadao , Watanabe Naoki , Inagaki Naoyuki
Published: June 2008

Actin polymerizes near the leading edge of nerve growth cones, and actin filaments show retrograde movement in filopodia and lamellipodia. Linkage between actin filament retrograde flow and cell adhesion molecules (CAMs) in growth cones is thought to be one of the mechanisms for axon outgrowth and guidance. However, the molecular basis for this linkage remains elusive. Here, we show that shootin1 interacts with both actin filament retrograde flow and L1-CAM in axonal growth cones of cultured rat hippocampal neurons, thereby mediating the linkage between them. Impairing this linkage, either by shootin1 RNA interference or disturbing the interaction between shootin1 and actin filament flow, inhibited L1-dependent axon outgrowth, whereas enhancing the linkage by shootin1 overexpression promoted neurite outgrowth. These results strengthen the actin flow–CAM linkage model (“clutch” model) for axon outgrowth and suggest that shootin1 is a key molecule involved in this mechanism.
Original CIN: reviewing roles for APC in chromosome instability
Authors: Rusan Nasser M. , Peifer Mark
Published: June 2008

You may have seen the bumper sticker “Eve was framed.” Thousands of years of being blamed for original sin and still many wonder, where's the evidence? Today, the tumor suppressor adenomatous polyposis coli (APC) may have the same complaint about accusations of a different type of CIN, chromosome instability. A series of recent papers, including three in this journal, propose that loss of APC function plays an important role in the CIN seen in many colon cancer cells. However, a closer look reveals a complex story that raises more questions than answers.
ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1
Authors: Nishitoh Hideki , Kadowaki Hisae , Nagai Atsushi , Maruyama Takeshi , Yokota Takanori , Fukutomi Hisashi , Noguchi Takuya , Matsuzawa Atsushi , Takeda Kohsuke , Ichijo Hidenori
Published: June 2008

Mutation in Cu/Zn-superoxide dismutase (SOD1) is a cause of familial amyotrophic lateral sclerosis (ALS). Mutant SOD1 protein (SOD1mut) induces motor neuron death, although the molecular mechanism of SOD1mut-induced cell death remains controversial. Here we show that SOD1mut specifically interacted with Derlin-1, a component of endoplasmic reticulum (ER)-associated degradation (ERAD) machinery and triggered ER stress through dysfunction of ERAD. SOD1mut-induced ER stress activated the apoptosis signal-regulating kinase 1 (ASK1)-dependent cell death pathway. Perturbation of binding between SOD1mut and Derlin-1 by Derlin-1-derived oligopeptide suppressed SOD1mut-induced ER stress, ASK1 activation, and motor neuron death. Moreover, deletion of ASK1 mitigated the motor neuron loss and extended the life span of SOD1mut transgenic mice. These findings demonstrate that ER stress-induced ASK1 activation, which is triggered by the specific interaction of Derlin-1 with SOD1mut, is crucial for disease progression of familial ALS.
Akt-dependent regulation of NF-κB is controlled by mTOR and Raptor in association with IKK
Authors: Dan Han C. , Cooper Matthew J. , Cogswell Patricia C. , Duncan Joseph A. , Ting Jenny P.-Y. , Baldwin Albert S.
Published: June 2008

While NF-κB is considered to play key roles in the development and progression of many cancers, the mechanisms whereby this transcription factor is activated in cancer are poorly understood. A key oncoprotein in a variety of cancers is the serine–threonine kinase Akt, which can be activated by mutations in PI3K, by loss of expression/activity of PTEN, or through signaling induced by growth factors and their receptors. A key effector of Akt-induced signaling is the regulatory protein mTOR (mammalian target of rapamycin). We show here that mTOR downstream from Akt controls NF-κB activity in PTEN-null/inactive prostate cancer cells via interaction with and stimulation of IKK. The mTOR-associated protein Raptor is required for the ability of Akt to induce NF-κB activity. Correspondingly, the mTOR inhibitor rapamycin is shown to suppress IKK activity in PTEN-deficient prostate cancer cells through a mechanism that may involve dissociation of Raptor from mTOR. The results provide insight into the effects of Akt/mTOR-dependent signaling on gene expression and into the therapeutic action of rapamycin.
Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas
Authors: Dong P. Duc Si , Provost Elayne , Leach Steven D. , Stainier Didier Y.R.
Published: June 2008

The mechanisms regulating pancreatic endocrine versus exocrine fate are not well defined. By analyzing the effects of Ptf1a partial loss of function, we uncovered novel roles for this transcription factor in determining pancreatic fates. In a newly identified hypomorphic ptf1a mutant, pancreatic cells that would normally express ptf1a and become exocrine cells, express the endocrine marker Isl1, indicating a cell fate switch. Surprisingly, a milder reduction of Ptf1a leads to an even greater increase of ectopic endocrine cells, suggesting that Ptf1a also plays a role in promoting endocrine development. We propose that low levels of Ptf1a promote endocrine fate, whereas high levels repress endocrine fate and promote exocrine fate.
How ATR turns on: TopBP1 goes on ATRIP with ATR: Figure 1.
Authors: Burrows Anna E. , Elledge Stephen J.
Published: June 2008

In this issue of Genes & Development, Mordes and colleagues (pp. 1478–1489) reveal intriguing mechanistic insights into activation of the ATR (ATM and Rad3-related) kinase critical for DNA damage resistance. They identify conserved regulatory domains within ATR and its binding partner ATRIP (ATR-interacting protein), which are contacted by the ATR activator TopBP1. These discoveries expand on our understanding of the regulation of other PIKK family members, which also contain these domains, and illustrate how functional diversity has been achieved among these kinases.
Lego clocks: building a clock from parts
Authors: Brunner Michael , Simons Mirre J.P. , Merrow Martha
Published: June 2008

A new finding opens up speculation that the molecular mechanism of circadian clocks in Synechococcus elongatus is composed of multiple oscillator systems (Kitayama and colleagues, this issue, pp. 1513–1521), as has been described in many eukaryotic clock model systems. However, an alternative intepretation is that the pacemaker mechanism—as previously suggested—lies primarily in the rate of ATP hydrolysis by the clock protein KaiC.
VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertasePcsk5
Authors: Szumska Dorota , Pieles Guido , Essalmani Rachid , Bilski Michal , Mesnard Daniel , Kaur Kulvinder , Franklyn Angela , El Omari Kamel , Jefferis Joanna , Bentham Jamie , Taylor Jennifer M. , Schneider Jurgen E. , Arnold Sebastian J. , Johnson Paul , Tymowska-Lalanne Zuzanna , Stammers Dave , Clarke Kieran , Neubauer Stefan , Morris Andrew , Brown Steve D. , Shaw-Smith Charles , Cama Armando , Capra Valeria , Ragoussis Jiannis , Constam Daniel , Seidah Nabil G. , Prat Annik , Bhattacharya Shoumo
Published: June 2008

We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, renal and palatal agenesis, and pulmonary hypoplasia. It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5Vcc/null) completely recapitulate thePcsk5Vcc/Vccphenotype, as does an epiblast-specific conditional deletion ofPcsk5. The C470R mutation ablates a disulfide bond in the P domain, and blocks export from the endoplasmic reticulum and proprotein convertase activity. We show that GDF11 is cleaved and activated by PCSK5A, but not by PCSK5A-C470R, and thatGdf11-deficient embryos, in addition to having anteroposterior patterning defects and renal and palatal agenesis, also have a presacral mass, anorectal malformation, and exomphalos.Pcsk5mutation results in abnormal expression of several paralogousHoxgenes (Hoxa,Hoxc, andHoxd), and ofMnx1(Hlxb9). These include knownGdf11targets, and are necessary for caudal embryo development. We identified nonsynonymous mutations inPCSK5in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation. We propose thatPcsk5, at least in part via GDF11, coordinately regulates caudalHoxparalogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development.
Accurate forced-choice recognition without awareness of memory retrieval
Authors: Voss Joel L. , Baym Carol L. , Paller Ken A.
Published: June 2008

Recognition confidence and the explicit awareness of memory retrieval commonly accompany accurate responding in recognition tests. Memory performance in recognition tests is widely assumed to measure explicit memory, but the generality of this assumption is questionable. Indeed, whether recognition in nonhumans is always supported by explicit memory is highly controversial. Here we identified circumstances wherein highly accurate recognition was unaccompanied by hallmark features of explicit memory. When memory for kaleidoscopes was tested using a two-alternative forced-choice recognition test with similar foils, recognition was enhanced by an attentional manipulation at encoding known to degrade explicit memory. Moreover, explicit recognition was most accurate when the awareness of retrieval was absent. These dissociations between accuracy and phenomenological features of explicit memory are consistent with the notion that correct responding resulted from experience-dependent enhancements of perceptual fluency with specific stimuli—the putative mechanism for perceptual priming effects in implicit memory tests. This mechanism may contribute to recognition performance in a variety of frequently-employed testing circumstances. Our results thus argue for a novel view of recognition, in that analyses of its neurocognitive foundations must take into account the potential for both (1) recognition mechanisms allied with implicit memory and (2) recognition mechanisms allied with explicit memory.
Increasing CREB in the auditory thalamus enhances memory and generalization of auditory conditioned fear
Authors: Han Jin-Hee , Yiu Adelaide P. , Cole Christina J. , Hsiang Hwa-Lin , Neve Rachael L. , Josselyn Sheena A.
Published: June 2008

Although the lateral nucleus of the amygdala (LA) is essential for conditioned auditory fear memory, an emerging theme is that plasticity in multiple brain regions contributes to fear memory formation. The LA receives direct projections from the auditory thalamus, specifically the medial division of the medial geniculate nucleus (MGm) and adjacent posterior intralaminar nucleus (PIN). While traditionally viewed as a simple relay structure, mounting evidence implicates the thalamus in diverse cognitive processes. We investigated the role of plasticity in the MGm/PIN in auditory fear memory. First we found that auditory fear conditioning (but not control manipulations) increased the levels of activated CREB in both the MGm and PIN. Next, using viral vectors, we showed that exogenously increasing CREB in this region specifically enhanced formation of an auditory conditioned fear memory without affecting expression of an auditory fear memory, formation of a contextual fear memory, or basic auditory processing. Interestingly, mice with increased CREB levels in the MGm/PIN also showed broad auditory fear generalization (in contrast to control mice, they exhibited fear responses to tones of other frequencies). Together, these results implicate CREB-mediated plasticity in the MGm/PIN in both the formation and generalization of conditioned auditory fear memory. Not only do these findings refine our knowledge of the circuitry underlying fear memory but they also provide novel insights into the neural substrates that govern the degree to which acquired fear of a tone generalizes to other tones.
Studies of Varying Alignment Algorithm, Amino Acid Scoring Matrix, and Gap Penalties
Authors: Mount David W.
Published: June 2008

INTRODUCTION

Comparing different amino acid scoring matrix-gap penalty combinations poses several problems. For example, the analysis often overlooks the purposes of different matrices; e.g., protein family or domain searching, evolutionary analysis, or structural alignment. In the past, gap penalties were usually not published or well known, thus throwing a level of uncertainty into the results. More recently, when investigators publish a new scoring matrix, they usually provide suitable choices for gap penalties that may be used for comparisons with other matrices. This article summarizes a number of reports that have examined combinations of alignment algorithm, scoring matrix, and gap penalties used to align sequences for various purposes.
Reduction of Contamination of Epithelial Cultures by Fibroblasts
Authors: Jones Jonathan C.R.
Published: June 2008

INTRODUCTION

This protocol describes a method to reduce the numbers of fibroblasts from adherent populations of epithelial cells by using differential trypsinization.
Phenotypic Analysis of Arabidopsis Mutants: Ethylene Hormone Response: Figure 1.
Authors: Larsen Paul B. , Chang Caren
Published: June 2008

Ethylene is one of the five classic plant hormones, having profound effects at all stages of plant growth and development from seed germination to tissue senescence. Tremendous strides have been made in our understanding of the molecular components of the ethylene signal transduction pathway through the identification of mutants having altered responses to ethylene. These mutants were isolated by screening for seedlings with an altered triple-response phenotype, which is manifested upon exposure to high levels of ethylene in the dark. The triple response consists of the formation of a pronounced apical hook, along with a shortening and thickening of both the hypocotyl and root and a proliferation of root hairs. This is unlike an untreated seedling, which normally has a long etiolated hypocotyl, normal root, and no apical hook formation. To carry out an ethylene gas treatment, seedlings must be grown in an enclosed system to maintain the levels of ethylene desired. This protocol describes ethylene treatment of seedlings in wide-mouth Mason jars sealed with canning jar lids.