bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower bone mass in prepubertal overweight children with prediabetes
Authors: Pollock Norman K , Bernard Paul J , Wenger Karl , Misra Sudipta , Gower Barbara A , Allison Jerry D , Zhu Haidong , Davis Catherine L
Published: July 2010

Childhood studies of the fat-bone relationship are conflicting, possibly reflecting the influence of metabolic abnormalities in some but not all obese children. Bone mass was compared between prepubertal overweight children with (n = 41) and without (n = 99) prediabetes. Associations of bone mass with measures of total and central adiposity, glucose intolerance, insulin sensitivity, lipid profile, systemic inflammation, and osteocalcin also were determined. In 140 overweight children aged 7 to 11 years, an oral glucose tolerance test was used to identify those with prediabetes and for determination of glucose, 2-hour glucose, glucose area under the curve (AUC), insulin, 2-hour insulin, and insulin AUC. Blood samples also were assessed for lipids, C-reactive protein, and osteocalcin. Total-body bone mineral content (BMC), fat-free soft tissue mass (FFST), and fat mass (FM) were measured by dual-energy X-ray absorptiometry (DXA). Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were assessed using MRI. Total-body BMC was 4% lower in overweight children with prediabetes than in those without prediabetes after controlling for sex, race, height, and weight (p = .03). In the total sample, FM was positively related with BMC (β = 0.16, p = .01) after adjusting for sex, race, height, and FFST. However, VAT (β = −0.13, p = .03) and SAAT (β = −0.34, p = .02) were inversely associated with BMC after controlling for sex, race, height, FFST, FM, and SAAT or VAT. No significant associations were found between BMC and the biochemical measurements. Prepubertal overweight children with prediabetes may be at risk for poor skeletal development. In addition, it appears that greater levels of central rather than total adiposity may be deleterious for developing bone. © 2010 American Society for Bone and Mineral Research.
Synthesis, complexation, and biological activity studies of 4‐aminomethyl‐7,8‐dihydroxy coumarines and their crown ether derivatives
Authors: Gümüş Arzu , Karadeniz Şeref , Uğraş Halil İbrahim , Bulut Mustafa , Çakır Ümit , Gören Ahmet Ceyhan
Published: July 2010

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The article focuses synthesis of novel 4‐aminomethyl‐7,8‐dihydroxy coumarins and their crown ether derivatives. The purified novel coumarins and their crown ether derivatives were identified by 1H NMR, 13C NMR, mass spectrometry and elemental analysis. The 1:1 binding constants of Ca2+, Mg2+, Fe2+, Zn2+, Ni2+, Cd2+, Co2+, and Mn2+ ions at 25°C ± 0.1 with the 4‐aminomethyl‐7,8‐dihydroxy coumarins and their crown ether derivatives estimated using extraction procedure with Inductively Coupled Plasma‐Atomic Emission Spectroscopy in dichloromethane/water membrane systems. Synthesized compounds were investigated for complexation and biological activity properties. Best results in biological activity studies were observed for antioxidant activity. J. Heterocyclic Chem., (2010).
Protein PTMs: post‐translational modifications or pesky trouble makers?
Authors: Bradshaw Ralph A. , Medzihradszky Katalin F. , Chalkley Robert J.
Published: July 2010

Analysis of protein post‐translational modifications using mass spectrometry is an intensive area of proteomic research. This perspective discusses the current state of the field with respect to what can be achieved, the challenges encountered, most notably with modification site assignment, the reliability of the published results, consequences of unreliable data and what is needed to be done to improve the situation. Copyright © 2010 John Wiley & Sons, Ltd.
An organization's search for meaning: A humanistic and existential theory of organizational identity and voice
Authors: Hoffman John
Published: July 2010

Drawing on humanistic and existential psychology, the author suggests that organizations are similar to living entities that experience emotions and struggle with questions of meaning and existence and that the work of leading human organizations is similar to the work of counseling human beings. From this foundation, he characterizes organizational development work as the maturing capacity of organizations to create meaning in the context of dynamic and multifaceted change. The author provides summaries of the major components of existential and humanistic psychology and applies them to organization theory. He concludes by presenting a synthesized model for humanistic‐existential organization theory while integrating implications for practice and future research.
Methyl formate oxidation: Speciation data, laminar burning velocities, ignition delay times, and a validated chemical kinetic model
Authors: Dooley S. , Burke M. P. , Chaos M. , Stein Y. , Dryer F. L. , Zhukov V. P. , Finch O. , Simmie J. M. , Curran H. J.
Published: July 2010

The oxidation of methyl formate (CH3OCHO) has been studied in three experimental environments over a range of applied combustion relevant conditions:

A variable‐pressure flow reactor has been used to quantify reactant, major intermediate and product species as a function of residence time at 3 atm and 0.5% fuel concentration for oxygen/fuel stoichiometries of 0.5, 1.0, and 1.5 at 900 K, and for pyrolysis at 975 K.

Shock tube ignition delays have been determined for CH3OCHO/O2/Ar mixtures at pressures of ≈ 2.7, 5.4, and 9.2 atm and temperatures of 1275–1935 K for mixture compositions of 0.5% fuel (at equivalence ratios of 1.0, 2.0, and 0.5) and 2.5% fuel (at an equivalence ratio of 1.0).

Laminar burning velocities of outwardly propagating spherical CH3OCHO/air flames have been determined for stoichiometries ranging from 0.8–1.6, at atmospheric pressure using a pressure‐release‐type high‐pressure chamber.

A detailed chemical kinetic model has been constructed, validated against, and used to interpret these experimental data. The kinetic model shows that methyl formate oxidation proceeds through concerted elimination reactions, principally forming methanol and carbon monoxide as well as through bimolecular hydrogen abstraction reactions. The relative importance of elimination versus abstraction was found to depend on the particular environment. In general, methyl formate is consumed exclusively through molecular decomposition in shock tube environments, while at flow reactor and freely propagating premixed flame conditions, there is significant competition between hydrogen abstraction and concerted elimination channels. It is suspected that in diffusion flame configurations the elimination channels contribute more significantly than in premixed environments. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 527–549, 2010
Temporal changes in vocal functions of human scarred vocal folds after cordectomy
Authors: Kishimoto Yo , Hirano Shigeru , Tateya Ichiro , Kanemaru Shin‐Ichi , Ito Juichi
Published: July 2010

Objectives/Hypothesis:

The maturation process of scarred vocal folds has previously been investigated using animal models. However, in human models the features of scarred vocal folds have rarely been described, and the process by which the scar changes with time is not well known. The present study aimed to investigate the maturation process of human vocal folds scarred by cordectomy in terms of vibratory and aerodynamic functions.

Study Design:

Prospective case series.

Methods:

Eight patients with early glottic carcinoma and two patients with leukoplakia of the vocal fold underwent endoscopic cordectomy at Kyoto University Hospital between 2006 and 2008. The temporal changes in their vocal functions were evaluated using acoustic and aerodynamic analyses and videostroboscopic examination.

Results:

Normalized mucosal wave amplitude, mean flow rate, and the amplitude perturbation quotient appear to stabilize about 6 months after the procedure. Although there were individual variations in the changes in normalized glottal gap and maximum phonation time, it appears to take at least 6 months to reach plateau. The other parameters—pitch perturbation quotient and noise to harmonic ratio—varied by individual, and thus it was difficult to identify commonalities in the healing process.

Conclusions:

Some individual variation was observed in the temporal changes of vocal function of scarred vocal folds after cordectomy. However, in terms of vibratory and aerodynamic functions, this study suggests that it takes at least 6 months for maturation of vocal fold scarring. Laryngoscope, 2010
Concise Review: Polarity in Stem Cells, Disease, and Aging
Authors: Carolina Florian Maria , Geiger Hartmut
Published: July 2010

Adult somatic stem cells are central to homeostasis in tissues that present with a high cellular turnover like the skin, intestine, and the hematopoietic system. It is thought that polarity is particularly important with respect to fate decisions on stem cell division (symmetric or asymmetric) as well as for the maintenance of stem cell adhesion and quiescence (interaction with the niche). Consequently the failure to establish or regulate stem cell polarity might result in disease or tissue attrition. Members of the family of small RhoGTPases are known to exert an important role in regulating cell polarity. We summarize and discuss here recent views on the role of cell polarity in somatic stem cell function, aging, and disease, concluding that targeting cell polarity might be a novel approach to ameliorate or even revert aberrant somatic stem cell function.
Analytical velocity potentials in cells with a rigid spherical wall
Authors: Barnyak M. , Gavrilyuk I. , Hermann M. , Timokha A.
Published: July 2010

By using Kelvin's inversion, we construct analytical harmonic functions satisfying the zero‐Neumann condition on the inner spherical wall everywhere except a single point where the velocity is infinite. This set of functions can be used to construct approximate velocity potentials associated with liquid sloshing in a spherical tank, and in other hydrodynamic problems.
Toxoplasma IgG Expressed in a Patient With Rosai‐Dorfman Disease
Authors: Liao Hung‐Ju , Chiang Ching‐Wen
Published: July 2010

Rosai‐Dorfman Disease (RDD) is a rare benign disease characterized by sinus histiocytosis with massive lymphadenopathy. RDD can be differentiated from other types of histiocytosis by immunochemical analysis, as RDD is positive for S100. Conversely, toxoplasmosis lymphadenitis is characterized by clusters of epithelioid histiocytes in lymphoid tissue, with mixed lymphocytic and immunoblastic cell populations. The serology data could help in diagnosing toxoplasmosis lymphadenitis, as the toxoplasma IgG should be positive. Here we present the rare case of a 73‐year‐old woman who presented with a left parotid mass and multiple neck lymphadenopathy that initially had been diagnosed as toxoplasmosis lymphadenitis from a positive result on serology examination, but was finally proven to be RDD based on immunochemical results. We also discuss the relationship between RDD and toxoplasmosis in this case.
Effective slip boundary conditions for arbitrary periodic surfaces: the surface mobility tensor
Authors: KAMRIN KEN , BAZANT MARTIN Z. , STONE HOWARD A.
Published: July 2010

In a variety of applications, most notably microfluidics design, slip-based boundary conditions have been sought to characterize fluid flow over patterned surfaces. We focus on laminar shear flows over surfaces with periodic height fluctuations and/or fluctuating Navier scalar slip properties. We derive a general formula for the ‘effective slip’, which describes equivalent fluid motion at the mean surface as depicted by the linear velocity profile that arises far from it. We show that the slip and the applied stress are related linearly through a tensorial mobility matrix, and the method of domain perturbation is then used to derive an approximate formula for the mobility law directly in terms of surface properties. The specific accuracy of the approximation is detailed, and the mobility relation is then utilized to address several questions, such as the determination of optimal surface shapes and the effect of random surface fluctuations on fluid slip.
CabaretistasandIndias Bonitas: Gender and Representations of Mexico in the Americas during the Cárdenas Era
Authors: KIDDLE AMELIA M.
Published: July 2010

This article examines the promotion of Mexico's national image in the Americas during the Cárdenas period, using as a starting point a scandal arising from a 1940 performance of Mexican dancers at a cabaret in Panama. Mexican diplomats found the show objectionable because it clashed with the image of women that they used in their efforts to raise the country's reputation abroad. By investigating these efforts, as well as the career of Eva Pérez Caro, the dance troupe's leader, the article contributes to our understanding of the relationship between gender, cultural performance and nationalism, and the role that they played in Mexico's foreign relations.
Segmented Party–Voter Linkages in Latin America: The Case of the UDI
Authors: LUNA JUAN PABLO
Published: July 2010

By analysing the socially segmented party–voter linkages deployed by the Unión Demócrata Independiente (Independent Democratic Union, UDI), a Chilean conservative party, this article demonstrates the usefulness of combining Kitschelt's party–voter linkage framework with Gibson's conceptual approach to conservative party electoral coalition-making. In Latin America, parties take advantage of social fragmentation and the availability of non-state campaign financing to combine multiple linkage types and thus attract socially diverse constituencies. Although it is an opposition party, UDI's historical trajectory and organisation have enabled it to receive private funds from its traditional and party-identified core constituency (business and conservative sectors), whose programmatic preferences and interests it represents, and then use these resources in a ‘charismatic’ mobilisation approach and particularistic exchanges with a non-core constituency (low-income, non-traditional voters of the radical right), in a segmented, but nationally integrated, electoral strategy.
How Can Female Germline Stem Cells Contribute to the Physiological Neo-Oogenesis in Mammals and Why Menopause Occurs?
Authors: Bukovsky Antonin
Published: July 2010

At the beginning of the last century, reproductive biologists have discussed whether in mammalian species the fetal oocytes persist or are replaced by neo-oogenesis during adulthood. Currently the prevailing view is that neo-oogenesis is functional in lower vertebrates but not in mammalian species. However, contrary to the evolutionary rules, this suggests that females of lower vertebrates have a better opportunity to provide healthy offspring compared to mammals with oocytes subjected to environmental threats for up to several decades. During the last 15 years, a new effort has been made to determine whether the oocyte pool in adult mammals is renewed as well. Most recently, Ji Wu and colleagues reported a production of offspring from female germline stem cells derived from neonatal and adult mouse ovaries. This indicates that both neonatal and adult mouse ovaries carry stem cells capable of producing functional oocytes. However, it is unclear whether neo-oogenesis from ovarian somatic stem cells is physiologically involved in follicular renewal and why menopause occurs. Here we review observations that indicate an involvement of immunoregulation in physiological neo-oogenesis and follicular renewal from ovarian stem cells during the prime reproductive period and propose why menopause occurs in spite of persisting ovarian stem cells.
ISUAL far‐ultraviolet events, elves, and lightning current
Authors: Chang S. C. , Kuo C. L. , Lee L. J. , Chen A. B. , Su H. T. , Hsu R. R. , Frey H. U. , Mende S. B. , Takahashi Y. , Lee L. C.
Published: July 2010

The Imager of Sprites and Upper Atmospheric Lightnings (ISUAL) often recorded events that have significant far‐ultraviolet (FUV) emissions in the spectrophotometer but have no discernible transient luminous events (TLEs) in the imager. These FUV events likely are dim TLEs. To confirm the conjecture, lightning emissions were simulated and proved to be completely absorbed by the atmosphere. The FUV emission of the FUV events follows the lightning OI emission within 1 ms, similar to the characteristics of elves. After analyzing the imager‐N21P brightness of the elves and their FUV intensity, a linear correlation was found, which is consistent with the work of Kuo et al. (2007). The intensity of the FUV events ranks among the dimmest elves and is less than 1 × 104 photons/cm2. Combining all the information, the FUV events are identified as dim elves that eluded the detection of the ISUAL imager. Also from the detection limits of the ISUAL spectrophotometer (SP) and the imager, for the before‐the‐limb elves the detection number of SP is found to be nearly 16 times higher than that of the imager. This result is consistent with a related factor of ∼13 that was inferred from the U.S. National Lightning Detection Network (NLDN) peak current distribution for the negative cloud‐to‐ground lightning. Hence the ISUAL spectrophotometer can be used to perform elve survey, to infer the peak current of the elve‐producing lightning, and possibly to be used to deduce other lightning parameters. Evidence is also found for the existence of multielves, which are FUV events from the M‐components or the multiple strokes in lightning flashes.
Nares Strait hydrography and salinity field from a 3‐year moored array
Authors: Rabe B. , Münchow A. , Johnson H. L. , Melling H.
Published: July 2010

Nares Strait to the west of Greenland facilitates the exchange of heat and freshwater between the Arctic and Atlantic Oceans. This study focuses on salinity, temperature, and density measurements from Nares Strait from a mooring array deployed from 2003 to 2006. Innovative moorings requiring novel analysis methods measured seawater properties near 80.5°N, at spacing sufficient to resolve the internal Rossby deformation radius. The 3‐year mean geostrophic velocity has a surface‐intensified southward flow of 0.20 m s−1 against the western side of the strait and a secondary core flowing southward at 0.14 m s−1 in the middle of the strait. Data show warm salty water on the Greenland side and cold fresher water on the Ellesmere Island side, especially in the top layers. There was a clear difference in hydrographic structure between times when sea ice was drifting and when it was land fast. Ice was drifting in late summer, fall, and early winter with a strong surface‐intensified geostrophic flow in the middle of the strait. Ice was land fast in late winter, spring, and early summer, when there was a subsurface core of strong geostrophic flow adjacent to the western side of the strait. Salinity variations of about 2 psu in time and space reflect a variable freshwater outflow from the Arctic Ocean. One particularly strong pulse occurred at the end of July 2005. For several days, steeply sloping isohalines indicated strong geostrophic flow down the middle of the strait coinciding with an amplified ice export from the Arctic due to strong southward winds.
Experimental study on the ice nucleation ability of size‐selected kaolinite particles in the immersion mode
Authors: Lüönd F. , Stetzer O. , Welti A. , Lohmann U.
Published: July 2010

The recently developed immersion mode cooling chamber has been used as an extension of the Zurich ice nucleation chamber (ZINC) in order to measure the ice nucleation efficiency of size‐selected kaolinite particles in the immersion mode. Particles with selected diameters of 200, 400, and 800 nm have been activated as cloud condensation nuclei in order to obtain water droplets with single immersed particles. After continuous cooling of the droplets to the experimental temperature in ZINC, the frozen fraction of the droplets was measured with a recently developed depolarization detector, the ice optical detector (IODE). Temperatures below −30°C were necessary to freeze 50% of the droplets throughout the investigated size range. Although not very strong, a size dependence of the freezing efficiency has been observed. The median freezing temperature increases from −35°C for 200 nm kaolinite particles to −33°C for 800 nm particles. An experiment with 200 nm ammonium sulfate particles in the same temperature range resulted in no significant frozen fraction of the droplets. This suggests that the ice crystals observed in experiments with kaolinite particles nucleated heterogeneously. The temperature‐dependent frozen fraction of water droplets has been fitted with different theoretical models. Comparison of the resulting fit curves with the data suggests that including the concept of active sites in the description of the ice nucleus surface is more appropriate than the approximation of a constant contact angle.
Role of convective heating in the seasonal evolution of the Asian summer monsoon
Authors: Tamura Toru , Koike Toshio
Published: July 2010

The seasonal evolution of the Asian summer monsoon (ASM) is closely related to the reversal of the meridional temperature gradient between the Tibetan Plateau (TP) and the adjacent ocean in the upper troposphere. Sensible heating has been suggested to play a crucial role in tropospheric warming over the TP. More recently, adiabatic subsidence associated with the Matsuno‐Gill type atmospheric response was shown to warm the upper troposphere downward from the tropopause around the TP at the onset phase of the ASM. Here, we suggest the crucial role of convective heating in the seasonal evolution of the ASM, focusing on the seasonal march of the monsoon trough and seasonal upper‐level warming around the TP. Correlation analyses and numerical experiments showed that convective heating around the Maritime Continent, which induces upper tropospheric warming over the southern slope of the TP together with southward extension of the monsoon trough around the Bay of Bengal forming the twin‐cyclone structure, is indispensable to the Southeast Asian summer monsoon onset. Meanwhile, convective heating around the Bay of Bengal, which induces upper tropospheric warming to the southwest of the TP together with westward extension of the monsoon trough from the Bay of Bengal to the Arabian Sea, is necessary for the Indian summer monsoon onset. Thus, although the TP has been emphasized previously, convective heating is a necessary factor in explaining the seasonal upper‐level warming around the TP and the seasonal march of the ASM.
A limited‐memory acceleration strategy for MCMC sampling in hierarchical Bayesian calibration of hydrological models
Authors: Kuczera George , Kavetski Dmitri , Renard Benjamin , Thyer Mark
Published: July 2010

Hydrological calibration and prediction using conceptual models is affected by forcing/response data uncertainty and structural model error. The Bayesian Total Error Analysis methodology uses a hierarchical representation of individual sources of uncertainty. However, it is shown that standard multiblock “Metropolis‐within‐Gibbs” Markov chain Monte Carlo (MCMC) samplers commonly used in Bayesian hierarchical inference are exceedingly computationally expensive when applied to hydrologic models, which use recursive numerical solutions of coupled nonlinear differential equations to describe the evolution of catchment states such as soil and groundwater storages. This note develops a “limited‐memory” algorithm for accelerating multiblock MCMC sampling from the posterior distributions of such models using low‐dimensional jump distributions. The new algorithm exploits the decaying memory of hydrological systems to provide accurate tolerance‐based approximations of traditional “full‐memory” MCMC methods and is orders of magnitude more efficient than the latter.
Precise tremor source locations and amplitude variations along the lower‐crustal central San Andreas Fault
Authors: Shelly David R. , Hardebeck Jeanne L.
Published: July 2010

We precisely locate 88 tremor families along the central San Andreas Fault using a 3D velocity model and numerous P and S wave arrival times estimated from seismogram stacks of up to 400 events per tremor family. Maximum tremor amplitudes vary along the fault by at least a factor of 7, with by far the strongest sources along a 25 km section of the fault southeast of Parkfield. We also identify many weaker tremor families, which have largely escaped prior detection. Together, these sources extend 150 km along the fault, beneath creeping, transitional, and locked sections of the upper crustal fault. Depths are mostly between 18 and 28 km, in the lower crust. Epicenters are concentrated within 3 km of the surface trace, implying a nearly vertical fault. A prominent gap in detectible activity is located directly beneath the region of maximum slip in the 2004 magnitude 6.0 Parkfield earthquake.
Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects
Authors: Wilt T.J. , Howe W. , MacDonald R.
Published: July 2010

Objective To systematically review and evaluate the effectiveness and adverse effects of the α‐antagonist, terazosin, for treating urinary symptoms associated with benign prostatic obstruction (BPO).

Methods Studies were sought and included in the review if they were randomized trials of at least 1 month duration, involved men with symptomatic BPO and compared terazosin with placebo or active controls. The study, patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol.

Results Seventeen studies involving 5151 men met the inclusion criteria, i.e. placebo‐controlled (10), α‐blockers (seven), finasteride alone or combined with terazosin and placebo (one), and microwave therapy (one). The study duration was 4–52 weeks; the mean age of the men was 65 years and 82% were white. Baseline urological symptom scale scores and flow rates showed that men had moderate BPO. Efficacy outcomes were rarely reported in a way that allowed for data pooling, but indicated that terazosin improved symptom scores and flow rates more than did placebo or finasteride, and similarly to other α‐antagonists. The pooled mean percentage improvement for the Boyarsky symptom score was 37% for terazosin and 15% for placebo (four studies). The mean percentage improvement for the American Urological Association symptom score was 38%, compared with 17% and 20% for placebo and finasteride, respectively (two studies). The pooled mean improvement in the International Prostate Symptom Score of 40% was similar to that with tamsulosin (43%). Peak urinary flow rates improved more with terazosin (22%) than with placebo (11%) and finasteride (15%), but did not differ significantly from the other α‐antagonists. The percentage of men discontinuing terazosin was comparable with those receiving placebo and finasteride, but greater than with other α‐antagonists. Adverse effects were greater than with placebo and included dizziness, asthenia, headache and postural hypotension.

Conclusions The available evidence indicates that terazosin improves the symptoms and flow rates associated with BPO; it was more effective than placebo or finasteride and similar to other α‐antagonists. Adverse effects were generally mild but more frequent than with other α‐antagonists and associated with a two‐ to four‐fold increase in treatment discontinuation.
Phorbol Ester‐ and Retinoic Acid‐Induced Regulation of the Protein Kinase C Substrate MARCKS in Immortalized Hippocampal Cells
Authors: Watson D. G. , Wainer B. H. , Lenox R. H.
Published: July 2010

Abstract: The expression of MARCKS, a major protein kinase C (PKC) substrate, was examined in the immortalized hippocampal cell line HN33, following differentiation using phorbol esters or retinoic acid. In cells exposed to phorbol esters, MARCKS protein levels were reduced through an apparent PKC‐dependent mechanism. Exposure to 1 µM phorbol 12‐myristate 13‐acetate (PMA) for 10 min resulted in a rapid loss of PKC activity in the soluble fraction with a concurrent increase in membrane‐associated PKC activity. PKC activity was reduced to <20% of control values in both soluble and membrane fractions following 1 h of PMA exposure. Significant reductions in MARCKS protein levels were initially observed in membrane and soluble fractions following PMA exposure for 4 and 8 h, respectively. The reduction in MARCKS protein levels was maximal following 24 h of PMA exposure. MARCKS protein expression was also down‐regulated in a dose‐dependent manner on exposure of HN33 cells to retinoic acid. In cells exposed to 10 µM retinoic acid, the MARCKS protein level was reduced in the membrane fraction within 4 h. Reduction of MARCKS protein levels was maximal (>90%) by 12 h with no evidence for any alteration in PKC activity. Reduced levels of MARCKS protein were also observed in the soluble fraction of retinoic acid‐exposed cells, but to a significantly lesser extent. Addition of the PKC inhibitor GF109203X blocked the down‐regulation of MARCKS protein in PMA‐treated cultures but not in retinoic acid‐treated cells. These findings suggest that the down‐regulation of MARCKS may play an important role in both phorbol ester‐ and retinoic acid‐induced differentiation in cells of neuronal origin.
Nitric Oxide Implication in the Control of Neurosecretion by Chromaffin Cells
Authors: Oset‐Gasque M. J. , Parramón M. , Hortelano S. , Boscá L. , González M. P.
Published: July 2010

Abstract: In this work, we have studied the effects of pure nitric oxide (NO) on the regulation of catecholamine (CA) secretion by chromaffin cells, as well as the possible presence of its synthesizing enzyme l‐arginine:NO synthase (NOS) in these cells. Our results show that NO produces a large stimulation of basal CA secretion. This effect was calcium‐ and concentration‐dependent (EC50 = 64 ± 8 µM) and was not due to nonspecific damage of the tissue by NO. NO also modulates the CA secretion evoked by nicotine in a dose‐dependent manner. Although it has a stimulatory effect on the CA secretion evoked by low doses of nicotine (<3 µM; EC50 = 16 ± 3 µM), it produces a dose‐dependent inhibition of the CA secretion induced by high doses of nicotine (≥30 µM; IC50 = 52 ± 6 µM). The mechanism by which NO modulates CA secretion seems to be through the increase in the cyclic GMP levels, because there was a close correlation between the CA secretion and the cyclic GMP levels. The presence of a specific activity of NOS in chromaffin cells has been demonstrated by two independent methods: release of [14C]citruiline from [14C]arginine and formation of an NO‐hemoglobin complex. NOS activity was about 0.5 pmol/min/mg of protein. It was calcium‐ and mainly calmodulin‐dependent and could be specifically blocked by the NOS inhibitor N‐methyl‐l‐arginine. These results suggest that NO could be an important intracellular messenger in the regulation of neurosecretion in chromaffin cells.
Platelet‐Activating Factor: Diminished Acetylcholine Release from Rat Brain Slices Is Mediated by a Gi Protein
Authors: Wang Hoau‐Yan , Yue Tian‐Li , Feuerstein Giora , Friedman Eitan
Published: July 2010

Abstract: The effect of platelet‐activating factor (PAF) on neurotransmitter release from rat brain slices prelabeled with [3H]acetylcholine ([3H]ACh), [3H]norepinephrine ([3H]NE), or [3H]serotonin ([3H]5‐HT) was studied. PAF inhibited K+ depolarization‐induced [3H]ACh release in slices of brain cortex and hippocampus by up to 59% at 10 nM but did not inhibit [3H]ACh release in striatal slices. PAF did not affect 5‐HT or NE release from cortical brain slices. The inhibition of K+‐evoked [3H]ACh release induced by PAF was prevented by pretreating tissues with several structurally different PAF receptor antagonists. The effect of PAF was reversible and was not affected by pretreating brain slices with tetrodotoxin. PAF‐induced inhibition of [3H]ACh release was blocked 90 ± 3 and 86 ± 2% by pertussis toxin and by anti‐Gαi1/2 antiserum incorporated into cortical synaptosomes, respectively. The results suggest that PAF inhibits depolarization‐induced ACh release in brain slices via a Gαi1/2 protein‐mediated action and that PAF may serve as a neuromodulator of brain cholinergic system.
Bimodal Opioid Regulation of Cyclic AMP Formation: Implications for Positive and Negative Coupling of Opiate Receptors to Adenylyl Cyclase
Authors: Wang Lin , Gintzler Alan R.
Published: July 2010

Abstract: A μ‐selective opiate receptor agonist, sufentanil, can either increase or decrease the stimulated formation of cyclic AMP (cAMP) in the myenteric plexus. The direction of the opioid modulation of this second messenger depends on the concentration of opioid used. Low doses of opioid enhance, whereas higher concentrations inhibit, the magnitude of cAMP that is formed in response to electrical stimulation. Opioids exert this dual regulation on only stimulated cAMP formation. Basal levels are not affected. Opioid facilitation and inhibition of stimulated cAMP formation are blocked by naloxone, indicating mediation by opiate receptors. Because all experiments were conducted in the presence of a phosphodiesterase inhibitor, it is highly unlikely that opioid regulation of stimulated cAMP formation is due to changes in the rate of its degradation. Positive and negative coupling of μ‐opiate receptors to adenylyl cyclase is the most plausible explanation for the bimodal opioid effects on cAMP content. The marked parallel between the current observations and the previously reported bimodal opioid regulation of evoked enkephalin release is consistent with the hypothesis that adenylyl cyclase is one biochemical substrate for the bimodal opiate receptor‐coupled regulatory mechanism governing the stimulated release of this opioid peptide.
On the Role of Extracellular ATP in the Induction of Long‐Term Potentiation in the Hippocampus
Authors: Wieraszko A. , Ehrlich Y. H.
Published: July 2010

Abstract: The involvement of a purinergic system in the mechanisms of ATP‐ and electrically induced long‐term potentiation (LTP) has been investigated in mouse hippocampal slices. Extracellular ATP (500 nM) and its slowly hydrolyzable analogue adenosine 5′‐O‐(3‐thiotriphosphate) (ATP‐γ‐S; 2.5 µM) amplified permanently the magnitude of the population spike. This effect was antagonized by adenylimidodiphosphate (AMPPNP), a non‐hydrolyzable analogue of ATP. AMPPNP, other ATP analogues [2‐methylthioadenosine triphosphate (2‐MeSATP) and α,β‐methyleneadenosine 5′‐triphosphate (α,β‐methyleneATP)], or a purinergic receptor antagonist (Cibacron Blue 3G) tested in the concentration range of 3–40 µM did not exert agonistic activity similar to that of ATP or ATP‐γ‐S, suggesting that ATP hydrolysis is required to exert this effect. All the tested nonhydrolyzable analogues reduced or prevented the establishment of stable, nondecremental LTP without blocking the short‐lasting increase in the magnitude of the population spike immediately after electrical stimulation (short‐term potentiation). These results indicate that ATP released by high‐frequency stimulation contributes to the maintenance of stable LTP. The underlying mechanism operating in this process may involve a new type of ATP receptors or hydrolysis by ecto‐ATPase. However, the findings that ATP‐γ‐S is less potent than ATP and that other ATP analogues known to act as agonists of purinergic receptors did not induce LTP but rather inhibited its maintenance are more consistent with the possibility that ecto‐protein kinase, using extracellular ATP as a cosubstrate, plays a role in mechanisms underlying synaptic plasticity.
Extracellular Ionic Composition Alters Kinetics of Vesicular Release of Catecholamines and Quantal Size During Exocytosis at Adrenal Medullary Cells
Authors: Jankowski Jeffrey A. , Finnegan Jennifer M. , Wightman R. Mark
Published: July 2010

Abstract: The temporal resolution of carbon‐fiber microelectrodes has been exploited to examine the plasticity of quantal secretory events at individual adrenal medullary cells. The size of individual quantal events, monitored by amperometric oxidation of released catecholamines, was found to be dependent on the extracellular ionic composition, the secretagogue, and the order of depolarization delivery. Release was observed with either exposure to 60 mM K+ in the presence of Ca2+ or exposure to 3 mM Ba2+ in solutions of different pH, with and without external Ca2+. Ba2+ was demonstrated to induce Ca2+‐independent exocytotic release for an extended period of time (>4 min) relative to release induced by K+ (∼30 s), which is Ca2+ dependent. In all cases, simultaneous changes of intracellular divalent cations, monitored by fura‐2 fluorescence, accompanied quantal release and had a similar time course. Exocytosis caused by Ba2+ in Ca2+‐free medium had a larger mean spike area at pH 8.2 than at pH 7.4. When Ba2+‐induced spikes measured at pH 7.4 were compared, the spikes in Ca2+‐free medium were found to be broader and shorter but had the same area. Release induced by K+ after exposure to Ba2+ was comprised of larger quantal events when compared with preceding K+ stimulations. Finally, spikes obtained with Ba2+ exposure at an extracellular pH of 5.5 had a different shape than those obtained in more basic solutions. These changes in spike size and shape are consistent with the interactions between catecholamines and other intravesicular components.
Annexin VI Binds to a Synaptic Vesicle Protein, Synapsin I
Authors: Inui Makoto , Watanabe Tatsuo , Sobue Kenji
Published: July 2010

Abstract: Annexin VI bound to >14 species of proteins in the whole homogenate of rat forebrain in a Ca2+/phosphatidylserine‐ or phosphatidic acid‐dependent manner. When the subcellular fractions of rat forebrain were examined with a blot from a sodium dodecyl sulfate‐polyacrylamide gel, each annexin VI‐binding protein showed a different distribution, suggesting that annexin VI is a multifunctional protein. Of these proteins, the doublets of Mr 80,000 were enriched in the purified synaptic vesicles and were identified as synapsin I. Annexin VI bound to the head domain of synapsin I. When the binding of annexin VI to synapsin I was characterized in the native state, the affinity of the binding for Ca2+ (KCa) was 12.6 µM, and the affinity for annexin VI (KD) was ∼270 nM. Phosphorylation of synapsin I by cyclic AMP‐dependent protein kinase and by Ca2+/calmodulin‐dependent protein kinase II inhibited the annexin VI binding. The mode of the inhibition was different between the two kinases. These results indicate that annexin VI may modulate the function of synapsin I in a Ca2+‐ and phospholipid‐dependent manner.
Molecular and Pharmacological Characterization of GABAA Receptors in the Rat Pituitary
Authors: Berman Joshua A. , Roberts James L. , Pritchett Dolan B.
Published: July 2010

Abstract: Levels of mRNA for the major subunits of the GABAA receptor were assayed in the rat pituitary anterior and neurointermediate lobes by ribonuclease protection assay. α1, β1, β2, β3, and γ2s were found to be the predominant subunits in the anterior lobe, whereas α2, α3, β1, β3, γ2s, and γ1 were the predominant subunits expressed in the neurointermediate lobe. α5, α6, and δ subunits were not detectable. Hill and Scatchard analysis of [3H]muscimol binding to anterior and neurointermediate lobe membranes showed high‐affinity binding sites with dissociation constants of 5.6 and 4.5 nM, respectively, and Hill coefficients near 1. Muscimol sites were present at a maximum of 126 fmol/mg in the anterior lobe and 138 fmol/mg in the neurointermediate lobe. The central‐type benzodiazepine antagonist [3H]Ro 15‐1788 bound to a high‐affinity site with a dissociation constant of 1.5 nM in both tissues, at a maximum of 60 fmol/mg in anterior pituitary and 72 fmol/mg in neurointermediate lobe. A Hill coefficient of 1 was measured for this site in both tissues. Assays of CL 218 872 displacement of Ro 15‐1788 were consistent with a pure type I benzodiazepine site in the anterior lobe and a pure type II site in the intermediate lobe. These results are consistent with both tissue‐specific expression of particular GABAA receptor subunits and receptor heterogeneity within individual cells in the pituitary.
K‐252a Promotes Survival and Choline Acetyltransferase Activity in Striatal and Basal Forebrain Neuronal Cultures
Authors: Glicksman M. A. , Forbes M. E. , Prantner J. E. , Neff N. T.
Published: July 2010

Abstract: The organic molecule K‐252a promoted cell survival, neurite outgrowth, and increased choline acetyltransferase (ChAT) activity in rat embryonic striatal and basal forebrain cultures in a concentration‐dependent manner. A two‐ to threefold increase in survival was observed at 75 nM K‐252a in both systems. A single application of K‐252a at culture initiation prevented substantial (>60%) cell death that otherwise occurred after 4 days in striatal or basal forebrain cultures. A 5‐h exposure of striatal or basal forebrain cells to K‐252a, followed by its removal, resulted in survival equivalent to that observed in cultures continually maintained in its presence. This is in contrast to results found with a 5‐h exposure of basal forebrain cultures to nerve growth factor (NGF). Acute exposure of basal forebrain cultures to K‐252a, but not to NGF, increased ChAT activity, indicating that NGF was required the entire culture period for maximum activity. Striatal cholinergic and GABAergic neurons were among the neurons rescued by K‐252a. Of the protein growth factors tested in striatal cultures (ciliary neurotrophic factor, neurotrophin‐3, NGF, brain‐derived neurotrophic factor, interleukin‐2, basic fibroblast growth factor), only brain‐derived neurotrophic factor promoted survival. The enhancement of survival and ChAT activity of basal forebrain and striatal neurons by K‐252a defines additional populations of neurons in which survival and/or differentiation is regulated by a K‐252a‐responsive mechanism. The above results expand the potential therapeutic targets for these molecules for the treatment of neurodegenerative diseases.
Estimating Hydroxyl Radical Content in Rat Brain Using Systemic and Intraventricular Salicylate: Impact of Methamphetamine
Authors: Giovanni Andrew , Liang Li Ping , Hastings Teresa G. , Zigmond Michael J.
Published: July 2010

Abstract: Free radicals have been implicated in the etiology of many neurodegenerative conditions. Yet, because these species are highly reactive and thus short‐lived it has been difficult to test these hypotheses. We adapted a method in which hydroxyl radicals are trapped by salicylate in vivo, resulting in the stable and quantifiable products, 2,3‐dihydroxybenzoic acid (DHBA) and 2,5‐DHBA. After systemic (100 mg/kg i.p.) or intraventricular (4 µmol) administration of salicylate, the amount of DHBA in striatal tissue correlated with tissue levels of salicylate. After systemic salicylate, the ratio of total DHBA to salicylate in neostriatum was at least 10‐fold higher than that observed after central salicylate. In addition, systemic salicylate resulted in considerably higher concentrations of 2,3‐ and 2,5‐DHBA in plasma than in brain. Therefore, a large portion of the DHBA present in brain after systemic salicylate may have been formed in the periphery. A neurotoxic regimen of methamphetamine increased the concentration of DHBA in neostriatum after either central or systemic administration of salicylate. The increase in 2,3‐DHBA after the central administration of salicylate was significant at 2 h, but not at 4 h, after the last dose of methamphetamine. These results suggest that (1) when assessing specific events in brain, it is preferable to administer salicylate centrally, and (2) neurotoxic doses of methamphetamine increase the hydroxyl radical content in brain in a time‐dependent manner.
Endopeptidase‐24.11 Is the Integral Membrane Peptidase Initiating Degradation of Somatostatin in the Hippocampus
Authors: Barnes Kay , Doherty Sean , Turner Anthony J.
Published: July 2010

Abstract: The membrane metalloenzyme endopeptidase‐24.11 has been localized by immunocytochemistry in the porcine hippocampus in the stratum oriens and stratum radiatum. Endopeptidase‐24.11 was found to be ∼10‐fold more abundant in a striatal than a hippocampal membrane preparation. Both somatostatin‐28 and somatostatin‐14 were metabolized by endopeptidase‐24.11, but the kinetics of hydrolysis markedly favoured the smaller form of the neuropeptide. After phase separation with Triton X‐114 of striatal and hippocampal membrane preparations, and by using selective inhibitors, the major (>80%) somatostatin‐metabolizing activity was found to partition into the detergent‐rich phase and was attributable predominantly to endopeptidase‐24.11. The residual activity observed in the presence of the selective endopeptidase‐24.11 inhibitor phosphoramidon was blocked by Pro‐Ile or N‐[1‐(RS)‐carboxy‐3‐phenylpropyl]‐Ala‐Ala‐Phe‐p‐aminobenzoate, inhibitors of endopeptidase‐24.16 and endopeptidase‐24.15, respectively. However, Pro‐Ile, at comparable concentrations, was shown to inhibit endopeptidase‐24.11, challenging the validity of its use as a selective inhibitor of endopeptidase‐24.16. The immunocytochemical and Triton X‐114 phase‐separation data implicate endopeptidase‐24.11, rather than endopeptidase‐24.16 or endopeptidase‐24.15, as the major physiological somatostatin‐degrading neuropeptidase in the striatum and hippocampus.
Melanocyte‐Stimulating Hormone Release‐Inhibiting Factor‐1 (MIF‐1) Can Be Formed from Tyr‐MIF‐1 in Brain Mitochondria but Not in Brain Homogenate
Authors: Kastin Abba J. , Hahn Kathy , Zadina James E. , Banks William A. , Hackler Laszlo
Published: July 2010

Abstract: Two samples of the peptide tyrosine‐melanocyte‐stimulating hormone release‐inhibiting factor‐1 (Tyr‐MIF‐1; Tyr‐Pro‐Leu‐Gly‐NH2) were tritiated on different amino acids (Tyr or Pro) and incubated together at 37°C with fractions of rat brain. The amount of intact tetrapeptide remaining was determined by HPLC. By 3 min, most of the Tyr‐MIF‐1 was degraded. Because similar amounts of [3H]Pro and [3H]Tyr appeared after incubation of the Tyr‐MIF‐1 peptides in brain homogenate, even as early as 30 s, examination of only this crude preparation would misleadingly indicate that Tyr‐MIF‐1 is not a precursor of melanocyte‐stimulating hormone release‐inhibiting factor‐1 (MIF‐1; Pro‐Leu‐Gly‐NH2) in brain tissue. However, incubation of the mitochondrial fractions of brain under the same conditions resulted in more than three times as much [3H]Tyr being formed as [3H]Pro, with accompanying accumulation of MIF‐1. Addition of excess MIF‐1 to the mitochondrial fraction completely suppressed the formation of MIF‐1 and more than doubled the amount of Tyr‐MIF‐1 remaining intact. When Tyr‐MIF‐1 tritiated only on the Tyr was added to the mitochondrial fraction, the main peaks of radioactivity appeared only at the positions of Tyr and Tyr‐MIF‐1, not at the position of Tyr‐Pro. The results indicate that Tyr‐MIF‐1 can serve as a precursor of MIF‐1 in brain mitochondria, an effect not evident when crude brain homogenate is used.