bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal corticosteroid exposure affects hippocampal plasticity and reduces lifespan
Authors: Noorlander C.W. , Visser G.H.A. , Ramakers G.M.J. , Nikkels P.G.J. , de Graan P.N.E.
Published: November 2007

Synthetic corticosteroids, such as dexamethasone, are frequently administered to pregnant women at risk for preterm delivery. Endogenous corticosteroids are essential for normal development, but exposure to therapeutic doses at critical developmental stages may have adverse effects on the central nervous system. Major concern has arisen about long‐term effects of corticosteroid treatment on brain plasticity, particularly in the hippocampus. Therefore, we analyzed the molecular, cellular, and behavioral effects of prenatal dexamethasone treatment on the adult hippocampus. Pregnant mice were treated at embryonic day 15.5 with a single dose of dexamethasone or saline. Adult offspring was analyzed for hippocampal neuron loss, cell proliferation, and NMDA receptor subunit expression. Hippocampal function was assessed in the Morris water maze and synaptic plasticity in the CA1 field by determining frequency dependence of LTP and LTD in hippocampal slices. Prenatal dexamethasone treatment decreased hippocampal cell proliferation in the dentate gyrus. Treated mice showed reduced LTD, impaired spatial learning, and a marked reduction in lifespan. Our data show long‐term adverse effects of prenatal dexamethasone treatment on hippocampal function in mice and suggest accelerated aging. These findings indicate that it is important to be restrictive with corticosteroid administration during fetal development because of the lifelong consequences. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Otoc1: A novel otoconin‐90 ortholog required for otolith mineralization in zebrafish
Authors: Petko Jessica A. , Millimaki Bonny B. , Canfield Victor A. , Riley Bruce B. , Levenson Robert
Published: November 2007

Within the vestibular system of virtually all vertebrate species, gravity and linear acceleration are detected via coupling of calcified masses to the cilia of mechanosensory hair cells. The mammalian ear contains thousands of minute biomineralized particles called otoconia, whereas the inner ear of teleost fish contains three large ear stones called otoliths that serve a similar function. Otoconia and otoliths are composed of calcium carbonate crystals condensed on a core protein lattice. Otoconin‐90 (Oc90) is the major matrix protein of mammalian and avian otoconia, while otolith matrix protein (OMP) is the most abundant matrix protein found in the otoliths of teleost fish. We have identified a novel gene, otoc1, which encodes the zebrafish ortholog of Oc90. Expression of otoc1 was detected in the ear between 15 hpf and 72 hpf, and was restricted primarily to the macula and the developing epithelial pillars of the semicircular canals. Expression of otoc1 was also detected in epiphysis, optic stalk, midbrain, diencephalon, flexural organ, and spinal cord. During embryogenesis, expression of otoc1 mRNA preceded the appearance of omp‐1 transcripts. Knockdown of otoc1 mRNA translation with antisense morpholinos produced a variety of aberrant otolith phenotypes. Our results suggest that Otoc1 may serve to nucleate calcium carbonate mineralization of aragonitic otoliths. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Intranasal HB‐EGF administration favors adult SVZ cell mobilization to demyelinated lesions in mouse corpus callosum
Authors: Cantarella Cristina , Cayre Myriam , Magalon Karine , Pascale Durbec
Published: November 2007

In the adult rodent brain, the subventricular zone (SVZ) represents a special niche for neural stem cells; these cells proliferate and generate neural progenitors. Most of these migrate along the rostral migratory stream to the olfactory bulb, where they differentiate into interneurons. SVZ‐derived progenitors can also be recruited spontaneously to damaged brain areas to replace lost cells, including oligodendrocytes in demyelinated lesions. In this study, we searched for factors able to enhance this spontaneous recruitment of endogenous progenitors. Previous studies have suggested that epidermal growth factor (EGF) could stimulate proliferation, migration, and glial differentiation of SVZ progenitors. In the present study we examined EGF influence on endogenous SVZ cell participation to brain repair in the context of demyelinated lesions. We induced a focal demyelinated lesion in the corpus callosum by lysolecithin injection and showed that intranasal heparin‐binding epidermal growth factor (HB‐EGF) administration induces a significant increase in SVZ cell proliferation together with a stronger SVZ cell mobilization toward the lesions. Besides, HB‐EGF causes a shift of SVZ‐derived progenitor cell differentiation toward the astrocytic lineage. However, due to the threefold increase in cell recruitment by EGF treatment, the absolute number of SVZ‐derived oligodendrocytes in the lesion of treated mice is higher than in controls. These results suggest that enhancing SVZ cell proliferation could be part of future strategies to promote SVZ progenitor cell mobilization toward brain lesions. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Differential regulation of dendrite complexity by AMPA receptor subunits GluR1 and GluR2 in motor neurons
Authors: Prithviraj Ranjini , Kelly Kristen M. , Espinoza‐Lewis Ramon , Hexom Tia , Clark Amy B. , Inglis Fiona M.
Published: November 2007

Activity‐dependent developmental mechanisms in many regions of the central nervous system are thought to be responsible for shaping dendritic architecture and connectivity, although the molecular mechanisms underlying these events remain obscure. Since AMPA glutamate receptors are developmentally regulated in spinal motor neurons, we have investigated the role of activation of AMPA receptors in dendritic outgrowth of spinal motor neurons by overexpression of two subunits, GluR1 and GluR2, and find that dendrite outgrowth is differentially controlled by expression of these subunits. Overexpression of GluR1 was associated with greater numbers of filopodia, and an increase in the length and complexity of dendritic arbor. In contrast, GluR2 expression did not alter dendritic complexity, but was associated with a moderate increase in length of arbor, and decreased numbers of filopodia. Neither GluR1 nor GluR2 had any effect on the motility of filopodia. In addition, GluR1 but not GluR2 expression increased the density of dendritic puncta incorporating a GFP‐labeled PSD95, suggesting that GluR1 may mediate its effect in part by augmenting the number of excitatory synapses within motor neuron dendrites. Together these results suggest that in spinal motor neurons, AMPA receptors composed of GluR1 subunits may facilitate neurotrophic mechanisms in these neurons, permitting sustained dendrite outgrowth and synaptogenesis, whereas expression of AMPA receptors containing GluR2 acts to preserve existing dendritic arbor. Thus, the observed downregulation of GluR1 in motor neurons during postnatal development may limit the formation of new dendrite segments and synapses, promoting stabilized synaptic connectivity. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008
CO2 Fixation and Activation by CuII Complexes of 5,5″‐Terpyridinophane Macrocycles
Authors: Verdejo Begoña , Blasco Salvador , González Jorge , García‐España Enrique , Gaviña Pablo , Tatay Sergio , Doménech Antonio , Doménech‐Carbó María Teresa , Jiménez Hermas R. , Soriano Conxa
Published: November 2007

An aza‐terpyridinophane receptor containing the polyamine 4,7,10,13‐tetraazahexadecane‐1,16‐diamine linked through methylene groups to the 5,5″ positions of a terpyridine unit has been prepared and characterized (L). The acid‐base behaviour, CuII speciation and ability to form ternary complexes (CuII‐L‐carbonate) have been explored by potentiometric titrations in 0.15 M NaClO4 and by UV/Vis and paramagnetic NMR spectroscopy. Comparisons are made with a previously reported terpyridinophane containing the polyamine 4,7,10‐triazatridecane‐1,13‐diamine (L1). For this latter receptor, reductive coupling between indigo and carbon dioxide at indigo‐modified electrodes produces carboxylated derivatives via a solid‐state reaction under electrochemical activation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Isolation and physiology of a dimethyl phthalate degrading bacterial strain YZ2
Authors: Wu Dong‐lei , Mahmood Qaisar , Zheng Ping , Hassan Muhammad Jaffar
Published: November 2007

A bacterial strain YZ2 was isolated from digested sludge of Sibao wastewater treatment plant located in Hangzhou, China and was characterized using morphological, biochemical, and physiological characteristics. The microbial colonies on LB medium were yellowish, 3–5 mm in diameter and convex in the center. The individual cells of isolate were short rods, measuring 0.6 × 0.9 – 1.0 × 1.5 μm with small side projections, clubbed ends, and without any filaments. Individual cells were gram‐positive. Based on 16S rDNA (1438 bp) sequence analysis, isolate was identified as Rhodococcus sp. isolate YZ2 capable of dimethyl phthalate (DMP) biodegradation under nitrate‐reducing conditions. Results of batch experiments showed that the degradation of DMP was optimum at pH 7.5 and 31°C. In the range of 70–600 mg l−1, the initial DMP concentrations showed very high correlation with biodegradation rate (0.9773 < r2 < 0.9941), suggesting a first‐order reaction. The half‐life value showed an increase from 0.89 to 2.22 days during biodegradation of various DMP concentrations. HPLC and LC‐MS analysis showed that MMP and PA may be the first and second intermediates, respectively, during DMP biodegradation under anoxic conditions. PA did not accumulate in the culture liquid, while MMP could not be mineralized by Rhodococcus sp. YZ2. © 2007 American Institute of Chemical Engineers Environ Prog, 2007
Application of supercritical fluid extraction to regenerate spent Pd‐active carbon catalyst
Authors: Dąbek Lidia , Świątkowski Andrzej , Dziaduszek Jerzy
Published: November 2007

Pd‐active carbon‐type catalysts are used in a wide variety of processes, typical examples of which are liquid‐phase hydrogenation reactions. In the case of these catalysts, a loss of their catalytic activity is observed. The aim of the present work was to assess the possibility of regenerating spent Pd/AC catalysts using supercritical fluid extraction. The following Pd/AC catalyst samples were investigated and compared: a commercial 10 wt % Pd catalyst (Aldrich) (denoted by CC), a spent catalyst (SC), SC subjected to supercritical fluid–CO2 extraction (SC/SFE/C), SC subjected to supercritical fluid–CO2–ethanol extraction (SC/SFE/C‐Et), and SC subjected to supercritical fluid–ethane–propane extraction (SC/SFE/E‐P). The last three catalysts were additionally subjected to heating in a hydrogen atmosphere at 410 K for 3 h. These were denoted by SC/SFE/C/H, SC/SFE/C‐Et/H, and SC/SFE/E‐P/H, respectively. The spent Pd/AC catalyst (SC) consists of mixed CC samples used in the reduction with hydrogen of various organic compounds. The catalysts CC, SC/SFE/C, SC/SFE/C/H, SC/SFE/C‐Et/H, and SC/SFE/E‐P/H were tested in the reduction of octanoylbenzene with hydrogen. The activity of the catalysts was estimated by measuring the reaction time and also the amount of hydrogen used in relation to the theoretical quantity required for the reaction. XPS and XRD methods were used to evaluate the changes occurring in the form of the palladium present on the Pd/AC catalyst surface during the regeneration processes. It was found that supercritical fluid‐CO2 extraction followed by heating in a hydrogen atmosphere is the most effective method for regenerating that catalyst. The results of our investigations indicate that regeneration of a spent Pd/AC catalyst, irrespective of the reaction in which it has been used, should be based on the complete removal of byproducts, the purification of the catalyst surface, and the restoration of the original form of the palladium. The procedure proposed in this paper, i.e. SFE (CO2) and heating in H2, fulfils both the conditions mentioned above. © 2007 American Institute of Chemical Engineers Environ Prog, 2007
A new programming environment for software defined radio applications
Authors: Hossain Riyadh , Wesseling Matthias , Leopold Claudia
Published: November 2007

The mobile communication market is confronted with an increasing number of communication standards and a corresponding complexity of the mobile terminal applications. To cope with this complexity, the Software Defined Radio (SDR) approach gains more and more attractiveness. Hardware platforms for SDR must meet the conflicting goals of flexibility, that is support for different protocols, and low power consumption. Therefore, upcoming platforms deploy parallelism, which complicates software development and requires specific knowledge about the hardware architecture. To simplify the development process, we suggest to separate the application development process into two steps, such that developers only need experience in either the software or the hardware area. In the first step, the application is specified in a hardware‐independent way, and in the second step, the hardware‐specific implementation is done by application‐independent tools. We developed a new programming environment called Virtual Radio Engine (VRE) that supports this approach. This paper describes the VRE tool chain. Copyright © 2007 John Wiley & Sons, Ltd.
Steady and unsteady laminar flows of Newtonian and generalized Newtonian fluids in a planar T‐junction
Authors: Miranda A. I. P. , Oliveira P. J. , Pinho F. T.
Published: November 2007

An investigation of laminar steady and unsteady flows in a two‐dimensional T‐junction was carried out for Newtonian and a non‐Newtonian fluid analogue to blood. The flow conditions considered are of relevance to hemodynamical applications and the localization of coronary diseases, and the main objective was to quantify the accuracy of the predictions and to provide benchmark data that are missing for this prototypical geometry. Under steady flow, calculations were performed for a wide range of Reynolds numbers and extraction flow rate ratios, and accurate data for the recirculation sizes were obtained and are tabulated. The two recirculation zones increased with Reynolds number, but the behaviour was non‐monotonic with the flow rate ratio. For the pulsating flows a periodic instability was found, which manifests itself by the breakdown of the main vortex into two pieces and the subsequent advection of one of them, while the secondary vortex in the main duct was absent for a sixth of the oscillating period. Shear stress maxima were found on the walls opposite the recirculations, where the main fluid streams impinge onto the walls. For the blood analogue fluid, the recirculations were found to be 10% longer but also short lived than the corresponding Newtonian eddies, and the wall shear stresses are also significantly different especially in the branch duct. Copyright © 2007 John Wiley & Sons, Ltd.
Continuous and discrete adjoint approaches for aerodynamic shape optimization with low Mach number preconditioning
Authors: Asouti V. G. , Zymaris A. S. , Papadimitriou D. I. , Giannakoglou K. C.
Published: November 2007

Discrete and continuous adjoint approaches for use in aerodynamic shape optimization problems at all flow speeds are developed and assessed. They are based on the Navier–Stokes equations with low Mach number preconditioning. By alleviating the large disparity between acoustic waves and fluid speeds, the preconditioned flow and adjoint equations are numerically solved with affordable CPU cost, even at the so‐called incompressible flow conditions. Either by employing the adjoint to the preconditioned flow equations or by preconditioning the adjoint to the ‘standard’ flow equations (under certain conditions the two formulations become equivalent, as proved in this paper), efficient optimization methods with reasonable cost per optimization cycle, even at very low Mach numbers, are derived. During the mathematical development, a couple of assumptions are made which are proved to be harmless to the accuracy in the computed gradients and the effectiveness of the optimization method. The proposed approaches are validated in inviscid and viscous flows in external aerodynamics and turbomachinery flows at various Mach numbers. Copyright © 2007 John Wiley & Sons, Ltd.
MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome
Authors: Wiewrodt Dorothee , Nagel Georg , Dreimüller Nadine , Hundsberger Thomas , Perneczky Axel , Kaina Bernd
Published: November 2007

The DNA repair protein O6‐methylguanine‐DNA methyltransferase (MGMT) plays a pivotal role in alkylating drug resistance. Here, we determined MGMT activity in primary and recurrent glioblastomas (GBM, WHO grade IV) of patients who received radiation therapy (RT) or RT plus chemotherapy with alkylating agents (temozolomide, chloroethylnitrosoureas). The mean MGMT activity of untreated GBM was 37 ± 45 (range 0–205) fmol/mg proteins. In the 1st, 2nd and 3rd recurrences, MGMT activity increased from 66 ± 50 (13–194) to 68 ± 44 (14–143) and 182 ± 163 (64–423) fmol/mg protein, respectively. Comparing patients who received RT only with RT plus chemotherapy, a significant increase of MGMT in 1st recurrences was only found after treatment with RT plus chemotherapy, indicating either selection of MGMT expressing cells or induction of the MGMT gene by alkylating agents. The p53 status was not significantly related to the MGMT expression level, although a trend for lower MGMT activity in p53 positively stained tumors was observed. Patients expressing MGMT activity of ≤30 fmol/mg protein in the pretreatment tumor had a significant better therapeutic response than patients expressing MGMT above this level, which was shown by Kaplan‐Meyer curves and the recurrence free interval after primary tumor resection. In patients who received RT only, this correlation was not found. The data revealed a threshold of MGMT expression (30 fmol/mg protein) below which patients respond better to alkylating agents. Therefore, determination of MGMT activity in the primary tumor appears to be useful in predicting the outcome of GBM therapy. © 2007 Wiley‐Liss, Inc.
The Effect of γ‐Irradiation on the Structure and Properties of Poly(propylene)/Clay Nanocomposites
Authors: Touati Naima , Kaci Mustapha , Ahouari Hania , Bruzaud Stéphane , Grohens Yves
Published: November 2007

The oxidative degradation of PP/OMMT nanocomposites under γ‐irradiation was studied. Changes in structure and properties resulting from γ‐exposure in the range 0–100 kGy were investigated. The results were analyzed by comparing the influence of PP‐g‐MA and pristine OMMT on the oxidation kinetics of neat PP. γ‐Irradiation in the presence of air strongly degraded the properties of PP materials, particularly for radiation doses above 20 kGy. The rate of oxidative degradation of PP/OMMT/PP‐g‐MA nanocomposites was much faster than that of neat PP. This suggests that PP‐g‐MA and pristine OMMT components behave as oxidation catalysts, leading to the formation of free radicals in the polymer matrix.

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New Photocleavable Structures, 4
Authors: Ganster Beate , Fischer Urs Karl , Moszner Norbert , Liska Robert
Published: November 2007

As highly reactive acylphosphine oxide‐based photoinitiators (PIs) are limited in the application for dental materials by their absorption behavior, we were interested to prepare acylgermane 1. UV‐Vis absorption maximum of the important n–π* transition was red shifted about 30 nm compared to monoacylphosphine oxides. Photo‐DSC results with a dental LED lamp showed nearly the same reactivity for 1 compared to camphorquinone (CQ), while monoacylphosphine oxides are not reactive. In broadband irradiation experiments, significantly higher reactivity compared to CQ was found. Application‐oriented tests showed sufficient storage stability of the formulation and excellent photobleaching behavior.

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The emerging neuropathology of essential tremor
Authors: Louis Elan D. , Vonsattel Jean Paul G.
Published: November 2007

Essential tremor (ET) is one of the most prevalent neurological disorders. At the same time, it is among the most poorly‐understood of these disorders. The underlying anatomical pathology of ET has been elusive until recently. Postmortem studies have begun to display some of the underlying brain changes in patients with this disease. These types of investigations are likely to lead the way to additional insights into the pathophysiology of ET and guide the development of therapies for this common movement disorder. © 2007 Movement Disorder Society
Interpretation of torsional shear results for nonlinear stress–strain relationship
Authors: Yang Z. X. , Li X. S. , Yang J.
Published: November 2007

Torsional tests are frequently used in material testing to determine shear stress–strain relationships. In the tests, torque is applied to a solid or hollow cylindrical specimen, whose twist angle is recorded as the response. While the raw test results are readily available in terms of torque–twist sets, converting them into intrinsic stress–strain relationships is not always straightforward, owing to the nonlinear stress–strain behavior and the non‐uniform radial distribution of the stress and strain fields. It follows that the approaches currently used to interpret torsional data are essentially empirical based.

The present paper addresses this data interpretation issue from a more rigorous perspective. The paper includes two parts: the first part concerns hollow cylindrical specimens under torsion, where an analytical‐based recursive procedure is developed; and the second part deals with solid torsional specimens, for which an analytical solution given by Nadai is directly employed. Examples pertaining to these two cases are examined and the resulting shear stress–strain curves are compared with those based on a number of popular empirical methods. The proposed analytical approaches can serve as a benchmark for checking the accuracy and validity of those empirical propositions. It is worth noting that, for brittle materials exhibiting softening behavior, only the analytical method gives the correct interpretation. Copyright © 2007 John Wiley & Sons, Ltd.
Variationalr‐adaption in elastodynamics
Authors: Zielonka M. G. , Ortiz M. , Marsden J. E.
Published: November 2007

We develop a variationalr‐adaptive finite element framework for solid dynamic applications and explore its conceptual links with the theory of dynamic configurational forces. The central idea underlying the proposed approach is to allow Hamilton's principle of stationary action to determine jointly the evolution of the displacement field and the discretization of the reference configuration of the body. This is accomplished by rendering the action stationary with respect to the material and spatial nodal coordinates simultaneously. However, we find that a naive consistent Galerkin discretization of the action leads to intrinsically unstable solutions. Remarkably, we also find that this unstable behavior is eliminated when a mixed, multifield version of Hamilton's principle is adopted. Additional features of the proposed numerical implementation include the use of uncoupled space and time discretizations; the use of independent space interpolations for velocities and deformations; the application of these interpolations over a continuously varying adaptive mesh; and the application of mixed variational integrators with independent time interpolations for velocities and nodal parameters. The accuracy, robustness and versatility of the approach are assessed and demonstrated by way of convergence tests and selected examples. Copyright © 2007 John Wiley & Sons, Ltd.
CD‐34 selected hematopoetic stem cell transplantation from HLA identical family members for fanconi anemia
Authors: Balci Yasemin Isik , Akdemir Yasemin , Gumruk Fatma , Cetin Mualla , Arpaci Fikret , Uckan Duygu
Published: November 2007

Hematopoetic stem cell transplantation, even from an HLA 6/6 identical family member is associated with an increased frequency of complication in fanconi anemia (FA). The increased susceptibility for chromosomal breaks has been suggested as a contributory factor for increased risk of toxicity, graft versus host disease (GVHD) and increased incidence of post‐transplant solid tumors. Therefore, non‐irradiation based preparative regimens usually containing fludarabine and T‐cell depletion of HLA geno‐identical bone marrow cells have increasingly been used in patients with FA. Here, we report three children with FA who underwent CD‐34 selected HSCT from HLA‐identical family donors with reduced intensity fludarabine‐based regimen. Pediatr Blood Cancer 2008;50:1065–1067. © 2007 Wiley‐Liss, Inc.
Sequence analysis of the SRGN, AP3B1, ARF6, and SH2D1A genes in familial hemophagocytic lymphohistiocytosis
Authors: Ma Daoxin , Rudd Eva , Edner Josefine , Gavhed Sofie , Ramme Kim Göransdotter , Fadeel Bengt , Nordenskjöld Magnus , Henter Jan‐Inge , Zheng Chengyun
Published: November 2007

In the present study, DNA sequencing of the genes SRGN, ARF6, AP3B1, and SH2D1A was performed in a well defined cohort of 18 families with familial hemophagocytic lymphohistiocytosis (FHL). A heterozygous nucleotide change (C > T) in the 3′untranslated region of the SRGN gene and a monoallelic 3‐base pair deletion (c.2409_2411delGAA) in exon 21 of the AP3B1 gene were observed in two different families. Additionally, two novel polymorphisms, one in intron 17 of AP3B1 and another in intron 2 of SH2D1A were identified. We conclude that mutations in SRGN, ARF6, and AP3B1 are not likely to be common in patients fulfilling the FHL criteria. Pediatr Blood Cancer 2008;50:1067–1069. © 2007 Wiley‐Liss, Inc.
Awareness and use of complementary therapies for AD
Authors: Larner Andrew J
Published: November 2007

Although complementary and alternative therapies for Alzheimer's disease (AD) are widely available, few studies have been published about patients' knowledge and use of these treatments. Dr Larner reports on a study carried out at his cognitive function clinic to investigate the awareness and use of complementary and alternative therapies for AD by patients and their caregivers. Copyright © 2007 Wiley Interface Ltd
Plasma Process. Polym. 9/2007
Authors: Laroussi Mounir , Akan Tamer
Published: November 2007

Cover: The cover picture shows the plasma pencil in operation (top left). A series of high‐speed photographs taken by an ICCD camera shows the spatial location of fast plasma bullets emitted by a cold plasma jet (right). The plasma pencil can be used to kill bacteria, as can be seen in the pictures of the Petri dishes (bottom left), where the first one corresponds to the control and the others to 30 and 120 s exposure time, respectively. Further details can be found in the article by M. Laroussi* and T. Akan on page 777.
Androgen‐mediated cholesterol metabolism in LNCaP and PC‐3 cell lines is regulated through two different isoforms of acyl‐coenzyme A: Cholesterol Acyltransferase (ACAT)
Authors: Locke Jennifer A. , Wasan Kishor M. , Nelson Colleen C. , Guns Emma S. , Leon Carlos G.
Published: November 2007

BACKGROUND

The objective of this work was to determine the effect of an androgen agonist, R1881, on intracellular cholesterol synthesis and esterification in androgen‐sensitive (AS) prostate cancer (LNCaP) cells.

METHODS

We investigated the activity and expression of cholesterol metabolism enzymes, HMG‐CoA‐reductase and ACAT in the LNCaP and PC‐3 (androgen‐independent control) models.

RESULTS

Microsomal PC‐3 HMG‐CoA‐reductase activity was increased with R1881 despite having similar cholesterol levels while increased cholesterol levels in microsomes from LNCaPs treated with R1881 (L+) were associated with increased HMG‐CoA reductase activity. Increased intracellular cholesteryl esters (CE) found in (L+) were not associated with an increased ACAT1 activity. There was no effect from androgen treatment on ACAT1 protein expression in theses cells; however, ACAT2 expression was induced upon R1881 treatment. In contrast, we found an increase in the in vitro ACAT1 activity in PC‐3 cells treated with androgen (P+). Only ACAT1 expression was induced in P+. We further assessed the expression of STAT1α, a transcriptional activator that modulates ACAT1 expression. STAT1α expression and phosphorylation were induced in P+. To determine the role of the AR on ACAT1 expression and esterification, we treated PC‐3 cells overexpressing the androgen receptor with R1881 (PAR+). AR expression was decreased in PAR+ cells; ACAT1 protein expression and cholesterol ester levels were also decreased, however, ACAT2 remained unchanged. STAT1α expression was decreased in PAR+.

CONCLUSIONS

Overall, these findings support the importance of cholesterol metabolism regulation within prostate cancer cells and unravel a novel role for STAT1α in prostate cancer metabolism. Prostate 68: 20–33, 2008. © 2007 Wiley‐Liss, Inc.
Nonmedical prescribing: managing a hypertension clinic
Authors: Smalley Lorna
Published: November 2007

Our series Nonmedical prescribing gives an overview of the work that can be done by nonmedical prescribers and what can be achieved. Here, a supplementary prescribing pharmacist in Derby describes her role in managing a clinic for patients with newly‐diagnosed hypertension. Copyright © 2007 Wiley Interface Ltd
DiGEM: value of glucose self‐monitoring in type 2 diabetes
Authors: Burrill Peter
Published: November 2007

A randomised controlled trial published in a peer‐reviewed journal is considered to be the ‘gold standard’ of information about the effectiveness of a treatment; however, critical appraisal of trials is required in order to judge the value and implications of the results. Here, the author presents an appraisal of the DiGEM study, which considered the effectiveness of self‐monitoring of blood glucose in patients with noninsulin‐treated diabetes.

Farmer A, Wade A, Goyder E, et al. Impact of self‐monitoring of blood glucose in the management of patients with non‐insulin treated diabetes: open parallel group randomised trial. BMJ 2007;335:132‐6. Copyright © 2007 Wiley Interface Ltd
Effectiveness of interventions to improve adherence
Authors: Chaplin Steve
Published: November 2007

Steve Chaplin reports on a systematic review of various interventions to improve adherence that showed only modest improvements and little effect on clinical outcomes. Copyright © 2007 Wiley Interface Ltd
Optimal QSAR Analysis of the Carcinogenic Activity of Aromatic and Heteroaromatic Amines
Authors: Fang Yaping , Feng Yi , Li Menglong
Published: November 2007

Aromatic and heteroaromatic amines are widely used in industrial chemicals and can be found in cooked foods and in tobacco smoke. In this study, Quantitative Structure–Activity Relationships (QSARs) are developed that correlate the observed carcinogenic activities of 80 aromatic and heteroaromatic amines. Principal Component Regression and stepwise linear regression techniques have been applied to construct the QSAR models. The performance of these two models is slightly superior compared to the previous reported based on the same dataset by multiple linear regression techniques. To improve the performance, Support Vector Regression (SVR) has been used to construct the QSARs and Genetic Algorithm (GA) has been used to select the most informational descriptors. Additionally, by introducing the concept of the weighting technique into the model, a new SVR, optimized sample‐weighted SVR is proposed. The optimal weighted coefficient is 0.2. The results suggest that approaches using GA selecting descriptors and weighting the descriptors can effectively improve the performance of the SVR models. The optimal Root Mean Square Error in Prediction is 0.799, which is relative smaller than other models. Jackknife‐testing procedure has been used to validate the models. The results indicate that the selected descriptors by GA and weighting technique are important and necessary to improve the performance of QSAR models by SVR.
Complete profiling and characterization of in vitro nefazodone metabolites using two different tandem mass spectrometric platforms
Authors: Li Austin C. , Shou Wilson Z. , Mai Ting T. , Jiang Xiang‐yu
Published: November 2007

This paper describes the complete profiling and characterization of in vitro metabolites of the antidepressant agent nefazodone (NEF) generated by human liver microsome (HLM). Two new metabolic pathways (biotransformation) for NEF have been discovered by the characterization of three new metabolites, including two new metabolites (M24, M25) formed due to the N‐dealkylation reaction that occurred between the triazolone and propyl units, and one new metabolite (M26) formed due to the O‐dearylation reaction that occurred on the phenoxyethyl unit. These metabolites were initially detected by a 4000 Q‐Trap instrument and then confirmed by exact mass measurement using an LTQ‐Orbitrap. Both instruments proved to be capable of providing complete in vitro metabolite information in a single liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis, although each had its advantages and disadvantages. One noticeable disadvantage of the 4000 Q‐Trap was the reduced quality of isotopic pattern in the enhanced mass scan (EMS) spectrum when it was used as survey scan to trigger multiple dependent product ion scans. The problem was especially exacerbated for minor metabolites with low signal intensity. On the other hand, the LTQ‐Orbitrap maintained excellent isotopic pattern when used as a full scan survey scan. Twenty‐six metabolites were detected and identified. The formation of these new metabolites was also confirmed by analyzing duplicate incubations at different time points. Copyright © 2007 John Wiley & Sons, Ltd.
MHC I expression and synaptic plasticity in different mice strains after axotomy
Authors: Sabha Mario , Emirandetti Amanda , Cullheim Staffan , De Oliveira Alexandre Leite Rodrigues
Published: November 2007

The success of axonal regeneration has been attributed to a co‐operation between the severed neurons and the surrounding environment, including non‐neuronal cells and the extracellular matrix. Important differences regarding the regeneration potential after injury have been described among inbred mice strains. To date, there is only limited knowledge of how such variation can be linked with the genetic background. It has recently been demonstrated that MHC class I molecules have an influence on the spinal cord synaptic plasticity elicited by a peripheral lesion, and the regenerative capacity following such a lesion. Therefore, in the present work we compared the MHC I expression after axotomy in three isogenic mice strains, namely C57BL/6J, Balb/cJ, and A/J, and investigated the fine ultrastructure of the synaptic elimination process that follows such lesion. The results show that C57BL/6J mice, that have a comparatively poor regenerative potential, display a lower upregulation of MHC I in the spinal cord, coupled with a slower synaptic stripping. On the other hand, A/J mice, which have been shown to have a stronger axonal regrowth potential, showed a clear upregulation of MHC I and a sharp acute loss of afferents, at 1 week after lesion. Our results suggest that a more prominent expression of MHC I in the first week after lesion may positively influence the regenerative outcome associated with a more effective axonal regrowth. Synapse 62:137–148, 2008. © 2007 Wiley‐Liss, Inc.
CART receptor binding in primary cell cultures of the rat nucleus accumbens
Authors: Jones Douglas C. , Kuhar Michael J.
Published: November 2007

Specific cocaine‐amphetamine regulated transcript (CART) receptor binding has been reported in AtT20 and PC12 cells. In this study, receptor binding has been examined in primary cell cultures of several rat brain regions. Utilizing125I‐CART 61–102 as a ligand and CART 55–102 as a displacer, significant levels of specific binding compared with nonspecific binding were found in the nucleus accumbens. Specific CART binding was substantially lower in hippocampal, hypothalamic, and pituitary cells. The specific binding was saturable with aKdof 1.43 ± 0.25 nM and aBmaxof 49.03 ± 2.33 fmol/mg protein. The binding was also highly specific for CART 55–102 as other inactive CART peptide fragments, unrelated peptides, γ‐aminobutyric acid, or cocaine showed no affinity for the receptor at 10 μM concentrations. Furthermore, addition of the GTP analog, Gpp(NH)p, significantly decreased specific binding but addition of an ATP analog did not, suggesting that the receptor is a g‐protein coupled receptor. This is the first demonstration of CART peptide receptor binding in primary cell cultures of the rat brain. Synapse 62:122–127, 2008. © 2007 Wiley‐Liss, Inc.
Dopamine partial agonist actions of the glutamate receptor agonists LY 354,740 and LY 379,268
Authors: Seeman Philip , Caruso Carla , Lasaga Mercedes
Published: November 2007

Because glutamate compounds alter the release of dopamine and prolactin, the present study examined whether group II metabotropic receptor agonists, LY 354,740 and LY 379,268, had any direct in vitro action on dopamine D2 receptors on rat striatal tissue, cloned D2Long receptors, and prolactin release from anterior pituitary cells. In competition versus the D2‐specific ligand [3H]domperidone, LY 354,740 had a dissociation constant of 24 nM at D2High(the functional high‐affinity state of dopamine D2 receptors), while the value for LY 379,268 was 21 nM. LY 354,740 also stimulated by 50% the incorporation of [35S]‐GTP‐γ‐S at a concentration of 120 nM, but its maximal stimulation was only 22% of the maximum elicited by dopamine. LY 379,268 stimulated by 50% the incorporation of [35S]‐GTP‐γ‐S at 280 nM, but its maximal stimulation was also only 22% of the maximum elicited by dopamine. However, both LY 354,740 and LY 379,268 potently inhibited the dopamine‐induced incorporation of [35S]‐GTP‐γ‐S with inhibitory Ki values of 43 nM and 30 nM, respectively. The release of prolactin from rat isolated anterior pituitary cells in culture was 50% inhibited by 20 nM LY 379,268 and by 100 nM LY 354,740. These Ki values are similar to those known for the mGluR II receptor, suggesting that these compounds may have both glutamate and dopamine actions in vivo. The dopamine agonist and antagonist actions of these compounds indicate that these drugs have properties of a dopamine partial agonist, and may, therefore, have antipsychotic action. Synapse 62:154–158, 2008. © 2007 Wiley‐Liss, Inc.
In vivo effects of fenthion on oxidative processes by the modulation of glutathione metabolism in the brain of Oreochromis niloticus
Authors: Piner Petek , Sevgiler Yusuf , Üner Nevin
Published: November 2007

The present study was designed to understand the oxidative stress potential of fenthion, an organophosphate (OP) pesticide and its involvement in glutathione metabolism modulated buthionine sulfoximine (BSO, 50 mg/kg) and N‐acetylcysteine (NAC, 100 mg/kg) in the brain of fish, Oreochromis niloticus. A sublethal fenthion concentration (0.45 mg/L) was applied for 24, 48, and 96 h together with injection with BSO or NAC; following treatment, recovery periods for 24, 48, and 96 h were allowed. Total glutathione (tGSH), oxidized glutathione (GSSG), lipid peroxidation, protein level, and GSH‐related enzyme activities were analyzed by using spectrophotometric methods. Fenthion in applied concentration did not change GSH levels, but increased GSSG levels. BSO application in fenthion exposure caused a depletion in GSH, while increasing the GSSG levels. Glutathione peroxidase (GPx; EC 1.11.1.9) specific activity increased in fenthion‐applied groups at 24‐h treatment. γ‐Glutamylcysteinyl synthetase (γ‐GCS; EC 6.3.2.2) was not detected in the brain. NAC injection in fenthion treatment decreased GSH and increased GSSG levels and GST activity. In conclusion, fenthion in sublethal concentration induced an oxidative stress processes in brain. BSO application provided an evidence for the involvement of fenthion in GSH metabolism. NAC elevated the fenthion‐induced effects in spite of its antioxidant properties. Recovery period for 96 h was not adequate to eliminate the fenthion‐induced changes. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 605–612, 2007.
Influence of intracellular Ca2+, mitochondria membrane potential, reactive oxygen species, and intracellular ATP on the mechanism of microcystin‐LR induced apoptosis in Carassius auratus lymphocytes in vitro
Authors: Zhang H. , Zhang J. , Chen Y. , Zhu Y.
Published: November 2007

Microcystin‐LR (MCLR), the most toxic microcystin up to date, could induce apoptosis in many kinds of fish and mammalian cells. For the fish immunotoxicity, it was found that MCLR could induce apoptosis in Carassius auratus lymphocytes in vitro. So this study focused on the role of intracellular Ca2+, mitochondrial membrane potential, reactive oxygen species (ROS), and intracellular ATP in response to the mechanisms of MCLR‐induced apoptosis in fish lymphocytes. MCLR (10 nM) administration resulted in a massive elevation in ROS, intracellular Ca2+, decreased ATP, and rapid mitochondrial membrane potential (ΔΨm) disruption. When compared to controls, both a fourfold significant (P < 0.001) elevation in O2− in 1.5 h and an approximately twofold increase in Ca2+ in 0.5 h were observed. After 6 h of treatment, an approximately 30% decrease for ΔΨm but about 75% decline for ATP were found. Together, the results demonstrated that MCLR‐induced apoptosis was associated with a massive calcium influx, resulting in O2− elevation, ΔΨm disruption, and ATP depletion. This study provided a possible cytotoxic mechanism of fish lymphocytes caused by MCLR. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 559–564, 2007.
New targeted therapies for treatment of thrombosis in antiphospholipid syndrome
Authors: Pierangeli Silvia S. , Vega-Ostertag Mariano E. , González Emilio B.
Published: November 2007

Antiphospholipid (aPL) antibodies (Abs) are associated with thrombosis and pregnancy loss in antiphospholipid syndrome (APS), a disorder initially characterised in patients with systemic lupus erythematosus (SLE) but now known to occur in the absence of other autoimmune disease. There is strong evidence that aPL Abs are pathogenic in vivo, from studies of animal models of thrombosis, endothelial cell activation and pregnancy loss. In recent years, progress has been made in characterising the molecular basis of this pathogenicity, which includes direct effects on platelets, endothelial cells and monocytes as well as activation of complement. This review summarises the clinical manifestations of APS and current modalities of treatment, and explains recent advances in understanding the molecular events triggered by aPL Abs on target cells in coagulation pathways as well as effects of aPL Abs on complement activation. Based on this information and on additional scientific evidence using in vitro and in vivo models, new potential targeted therapies for treatment and/or prevention of thrombosis in APS are proposed and discussed.
Arctic Ice Dynamics Joint Experiment (AIDJEX) assumptions revisited and found inadequate
Authors: Coon Max , Kwok Ron , Levy Gad , Pruis Matthew , Schreyer Howard , Sulsky Deborah
Published: November 2007

This paper revisits the Arctic Ice Dynamics Joint Experiment (AIDJEX) assumptions about pack ice behavior with an eye to modeling sea ice dynamics. The AIDJEX assumptions were that (1) enough leads were present in a 100 km by 100 km region to make the ice isotropic on that scale; (2) the ice had no tensile strength; and (3) the ice behavior could be approximated by an isotropic yield surface. These assumptions were made during the development of the AIDJEX model in the 1970s, and are now found inadequate. The assumptions were made in part because of insufficient large‐scale (10 km) deformation and stress data, and in part because of computer capability limitations. Upon reviewing deformation and stress data, it is clear that a model including deformation on discontinuities and an anisotropic failure surface with tension would better describe the behavior of pack ice. A model based on these assumptions is needed to represent the deformation and stress in pack ice on scales from 10 to 100 km, and would need to explicitly resolve discontinuities. Such a model would require a different class of metrics to validate discontinuities against observations.
Fast evaluation of zero‐offset Green's function for layered media with application to ground‐penetrating radar
Authors: Lambot Sébastien , Slob Evert , Vereecken Harry
Published: November 2007

We propose an efficient integration path for the fast evaluation of the three‐dimensional spatial‐domain Green's function for electromagnetic wave propagation in layered media for the particular case of zero‐offset, source‐receiver proximal ground‐penetrating radar (GPR) applications. The integration path is deformed in the complex plane of the integration variable kρ so that the oscillations of the dominant exponential term in the spectral Green's function are minimized. The contour does not need to be closed back on the real kρ axis as the complex integrand rapidly damps. The accuracy and efficiency of the technique have been confirmed by comparison with traditional elliptic integration contours. The proposed algorithm appears to be promising development for fast, full‐wave modeling and inversion of GPR data.
On the evolution of the snow surface during snowfall
Authors: Löwe H. , Egli L. , Bartlett S. , Guala M. , Manes C.
Published: November 2007

The deposition and attachment mechanism of settling snow crystals during snowfall dictates the very initial structure of ice within a natural snowpack. In this letter we apply ballistic deposition as a simple model to study the structural evolution of the growing surface of a snowpack during its formation. The roughness of the snow surface is predicted from the behaviour of the time dependent height correlation function. The predictions are verified by simple measurements of the growing snow surface based on digital photography during snowfall. The measurements are in agreement with the theoretical predictions within the limitations of the model which are discussed. The application of ballistic deposition type growth models illuminates structural aspects of snow from the perspective of formation which has been ignored so far. Implications of this type of growth on the aerodynamic roughness length, density, and the density correlation function of new snow are discussed.
Scotia arc kinematics from GPS geodesy
Authors: Smalley R. , Dalziel I. W. D. , Bevis M. G. , Kendrick E. , Stamps D. S. , King E. C. , Taylor F. W. , Lauría E. , Zakrajsek A. , Parra H.
Published: November 2007

GPS crustal velocity data from the Scotia and South Sandwich plates, transform azimuths, spreading data, and an updated earthquake slip vector catalog provide the first Scotia and South Sandwich plate Euler vector estimates not dependent on closure as the GPS data tie them to the global plate circuit. Neither the GPS data, which sample limited portions of the plates, nor the geologic data, which are not tied to the global spreading circuit, are sufficient individually to define the Euler vectors. As Scotia plate GPS measurements do not sample the stable plate interior, plate boundary deformation field modeling is necessary for Euler vector estimation. Our South America‐Antarctic and Scotia‐South Sandwich Euler pole estimates agree with previous estimates from either GPS or geologic data. Our South America‐Scotia Euler vector, however, is significantly different and near the South America‐Antarctic Euler vector producing an approximately coaxial motion of Scotia between South America and Antarctica.