bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a sensitive LC‐MS/MS method with electrospray ionization for quantitation of pramipexole in human plasma: application to a clinical pharmacokinetic study
Authors: Bharathi D. Vijaya , Hotha Kishore Kumar , Sagar P. V. Vidya , Kumar S. Sirish , Naidu A. , Mullangi Ramesh 
Published: September 2008

AbstractA highly sensitive and specific LC‐MS/MS method has been developed and validated for the estimation of pramipexole (PPX) with 500 µL human plasma using memantine as an internal standard (IS). The API‐4000 was operated under multiple‐reaction monitoring mode (MRM) using the electrospray ionization technique. Solid‐phase extraction was used to extract PPX and IS from human plasma. The resolution of peaks was achieved with 0.01 m ammonium acetate buffer (pH 4.4):acetonitrile (30:70, v/v) on a Discovery CN column. The total chromatographic run time was 3.0 min and the elution of PPX and IS occurred at approximately 2.32 and 2.52, respectively. The MS/MS ion transitions monitored were 212.10 → 153.10 for PPX and 180.20 → 107.30 for IS. The method was proved to be accurate and precise at linearity range of 20–3540 pg/mL with a correlation coefficient (r) of ≥0.999. The intra‐ and inter‐day precision and accuracy values found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 0.25 mg PPX tablet. Copyright © 2008 John Wiley & Sons, Ltd.
Correlated waves of actin filaments and PIP3 in Dictyostelium cells
Authors: Asano Yukako , Nagasaki Akira , Uyeda Taro Q.P. 
Published: September 2008

AbstractChemotaxis‐deficient amiB‐null mutant Dictyostelium cells show two distinct movements: (1) they extend protrusions randomly without net displacements; (2) they migrate persistently and unidirectionally in a keratocyte‐like manner. Here, we monitored the intracellular distribution of phosphatidylinositol (3,4,5)‐trisphosphate (PIP3) to gain insight into roles PIP3 plays in those spontaneous motilities. In keratocyte‐like cells, PIP3 showed convex distribution over the basal membrane, with no anterior enrichment. In stalled cells, as well as in wild type cells, PIP3 repeated wave‐like changes, including emergence, expansion and disappearance, on the basal membrane. The waves induced lamellipodia when they approached the cell edge, and the advancing speed of the waves was comparable to the migration speed of the keratocyte‐like cells. LY294002, an inhibitor of PI3 kinase, abolished PIP3 waves in stalled cells and stopped keratocyte‐like cells. These results together suggested that keratocyte‐like cells are “surfing” on the PIP3 waves by coupling steady lamellipodial protrusions to the PIP3 waves. Simultaneous live observation of actin filaments and PIP3 in wild type or stalled amiB− cells indicated that the PIP3 waves were correlated with wave‐like distributions of actin filaments. Most notably, PIP3 waves often followed actin waves, suggesting that PIP3 induces local depolymerization of actin filaments. Consistent with this idea, cortical accumulation of PIP3 was often correlated with local retraction of the periphery. We propose that the waves of PIP3 and actin filaments are loosely coupled with each other and play important roles in generating spontaneous cell polarity. Cell Motil. Cytoskeleton 2008. © 2008 Wiley‐Liss, Inc.
Patterns of p57Kip2 expression in embryonic rat brain suggest roles in progenitor cell cycle exit and neuronal differentiation
Authors: Ye Weizhen , Mairet‐Coello Georges , Pasoreck Elise , DiCicco‐Bloom Emanuel 
Published: September 2008

AbstractIn developing central nervous system, a variety of mechanisms couple cell cycle exit to differentiation during neurogenesis. The cyclin‐dependent kinase (CDK) inhibitor p57Kip2 controls the transition from proliferation to differentiation in many tissues, but roles in developing brain remain uncertain. To characterize possible functions, we defined p57Kip2 protein expression in embryonic (E) day 12.5 to 20.5 rat brains using immunohistochemistry combined with markers of proliferation and differentiation. The p57Kip2 was localized primarily in cell nuclei and positive cells formed two distinct patterns including wide dispersion and laminar aggregation that were brain region‐specific. From E12.5 to E16.5, p57Kip2 expression was detected mainly in ventricular zone (VZ) and/or mantle zone of hippocampus, septum, basal ganglia, thalamus, hypothalamus, midbrain, and spinal cord. After E18.5, p57Kip2 was detected in select regions undergoing differentiation. The p57Kip2 expression was also compared with regional transcription factors, including Ngn2, Nkx2.1, and Pax6. Time course studies performed in diencephalon showed that p57Kip2 immunoreactivity colocalized with BrdU at 8 hr in nuclei exhibiting the wide dispersion pattern, whereas colocalization in the laminar pattern occurred only later. Moreover, p57Kip2 frequently colocalized with neuronal marker, β‐III tubulin. Finally, we characterized relationships of p57Kip2 to CDK inhibitor p27Kip1: in proliferative regions, p57Kip2 expression preceded p27Kip1 as cells underwent differentiation, though the proteins colocalized in substantial numbers of cells, suggesting potentially related yet distinct functions of Cip/Kip family members during neurogenesis. Our observations that p57Kip2 exhibits nuclear expression as precursors exit the cell cycle and begin expressing neuronal characteristics suggests that the CDK inhibitor contributes to regulating the transition from proliferation to differentiation during brain development. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2009
Matrix metalloproteinase‐2 is involved in myelination of dorsal root ganglia neurons
Authors: Lehmann Helmar C. , Köhne Angelika , Bernal Fabian , Jangouk Parastoo , Meyer Zu Hörste Gerd , Dehmel Thomas , Hartung Hans‐Peter , Previtali Stefano C. , Kieseier Bernd C. 
Published: September 2008

AbstractMatrix metalloproteinases (MMPs) comprise a large family of endopeptidases that are capable of degrading all extracellular matrix components. There is increasing evidence that MMPs are not only involved in tissue destruction but may also exert beneficial effects during axonal regeneration and nerve remyelination. Here, we provide evidence that MMP‐2 (gelatinase A) is associated with the physiological process of myelination in the peripheral nervous system (PNS). In a myelinating co‐culture model of Schwann cells and dorsal root ganglia neurons, MMP‐2 expression correlated with the degree of myelination as determined by immunocytochemistry, zymography, and immunosorbent assay. Modulation of MMP‐2 activity by chemical inhibitors led to incomplete and aberrant myelin formation. In vivo MMP‐2 expression was detected in the cerebrospinal fluid (CSF) of patients with Guillain‐Barré syndrome as well as in CSF and sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy. Our findings suggest an important, previously unrecognized role for MMP‐2 during myelination in the PNS. Endogenous or exogenous modulation of MMP‐2 activity may be a relevant target to enhance regeneration in demyelinating diseases of the PNS. © 2008 Wiley‐Liss, Inc.
Human fetal radial glia cells generate oligodendrocytes in vitro
Authors: Mo Zhicheng , Zecevic Nada 
Published: September 2008

AbstractLimited knowledge about human oligodendrogenesis prompted us to explore the lineage relationship between cortical radial glia (RG) cells and oligodendrocytes (OLs) in the human fetal forebrain. RG cells were isolated from cortical ventricular/subventricular zone and their progeny was followed in vitro. One portion of RG cells differentiated into cells of OL lineage identified by cell‐type specific antibodies, including platelet‐derived growth factor receptor‐alpha (PDGFRα), NG2, O4, myelin basic protein, and myelin oligodendrocyte glycoprotein. Moreover, using Cre Lox fate mapping (brain lipid binding protein‐Cre/Floxed‐yellow fluorescent protein) we established a direct link between RG cells and OL progenitors. In vitro generation of RG‐derived O4+ OL progenitors was enhanced by addition of sonic hedgehog (SHH) and reduced by the SHH inhibitor, cyclopamine, suggesting the role of SHH signaling in this process. In summary, our in vitro experiments revealed that a portion of cortical RG cells isolated from human forebrain at the second trimester of gestation generates OL progenitors and this suggests a role of SHH in this process. © 2008 Wiley‐Liss, Inc.
Persistent apathy in Alzheimer's disease as an independent factor of rapid functional decline: the REAL longitudinal cohort study
Authors: Lechowski L. , Benoit M. , Chassagne P. , Vedel I. , Tortrat D. , Teillet L. , Vellas B. 
Published: September 2008

AbstractObjectiveTo determine the role of persistent apathy in rapid loss of autonomy in Instrumental Activities of Daily Living (IADL) in women with Alzheimer´s disease (AD), taking into account the grade of cognitive decline.MethodsThe study was conducted on 272 women from the French REAL cohort. At inclusion patients had a Mini‐Mental State Examination (MMSE) score between 10–26. A rapid functional decline was defined as a yearly drop of 4 points or more on the 14‐point IADL Lawton scale. Persistent apathy was defined as a frequency score equal to 3 or 4 on the Neuro‐Psychiatric Inventory at the three consecutive 6‐monthly assessments.Results27.6% of women had rapid functional decline in 1 year and 22.1% of them had persistent apathy. A logistic regression analysis showed that, in addition to cognitive decline, persistent apathy plays a role in rapid functional decline in 1 year. For example, for a 3‐point decline in MMSE in 1 year, the probability of a rapid loss in IADL is 0.45 for women with persistent apathy compared with 0.28 for those without persistent apathy.ConlusionsIn this study, a rapid loss in IADL score was partly explained by persistent apathy. Copyright © 2008 John Wiley & Sons, Ltd.
Smell test predicts performance on delayed recall memory test in elderly with depression
Authors: Scalco Monica Z. , Streiner David L. , Rewilak Dmytro , Castel Saulo , Van Reekum Robert 
Published: September 2008

AbstractIntroductionElderly with depression are at increased risk for cognitive dysfunction and dementia. Smell tests are correlated with performance on cognitive tests in the elderly and therefore might serve as a screening test for cognitive impairment in depressed elderly.PurposeTo assess the validity of the CC‐SIT (Cross‐Cultural Smell Identification Test) as a screening test for cognitive impairment in elderly with depression.MethodsForty‐one patients, aged 60 and over, were assessed with the CC‐SIT and CVLT (California Verbal Learning Test) after 3 months treatment of a Major Depressive Episode (DSM‐IV) at the Day Hospital for Depression, Baycrest. Patients already diagnosed with dementia, or other psychiatric and neurological disorders, were excluded. Receiver Operating Characteristics (ROC) analysis was applied to assess the CC‐SIT's accuracy in identifying individuals with impairment (2 SD below the mean for age and education or less) on CVLT delayed recall trials.ResultsForty‐one patients (33 women and eight men) were assessed. Mean age was 76.8 (SD: 6.5), mean HRSD scores before treatment was 22.0 (SD: 5.1). Nine patients had impairment on CVLT delayed recall measures. The area under the ROC curve was 0.776 (95% CI = 0.617–0.936).ConclusionsOur results support the use of the CC‐SIT as a screening tool for cognitive impairment among elderly with depression as an indicator for the need of a comprehensive neuropsychological evaluation. Replication with larger samples is necessary. Copyright © 2008 John Wiley & Sons, Ltd.
Oncogenic NRAS has multiple effects on the malignant phenotype of human melanoma cells cultured in vitro
Authors: Eskandarpour Malihe , Huang Fei , Reeves Karen A. , Clark Edwin , Hansson Johan 
Published: September 2008

AbstractActivating mutations in the NRAS gene, which occur predominantly in codon 61 (Q61R, Q61K) are among the most common genetic events in malignant melanoma. NRAS protein with oncogenic codon 61 mutations may therefore be good therapeutic targets. In the present study, we used gene expression profiling as a method for global characterization of gene expression alterations that resulted from treatment of melanoma cells with siRNA specifically targeting NRASQ61R. Sixteen probe sets representing 15 unique genes were identified whose expression was significantly altered by siRNA against NRASQ61R in 2 melanoma cell lines. The genes with altered expression are involved in several functions, including modulation of cell growth, invasion and migration. The results suggest that downregulation of cyclin E2 and cyclin D1 and also upregulation of the negative cell‐cycle regulator HBP1 in NRASQ61R knockdown cells contribute to the inhibition of cell proliferation. Furthermore, suppression of oncogenic NRAS results in reduced migration and invasion, which is accompanied by downregulation of EphA2 (a receptor tyrosine kinase), uPAR (urokinase receptor) and cytoskeleton proteins such as leupaxin, paxillin and vinculin. These studies support the concept that suppression of oncogenic NRAS by siRNA can induce growth arrest and inhibit invasion of human melanoma cells by modulating the levels of these gene products. © 2008 Wiley‐Liss, Inc.
Phosphoglycerate kinase 1‐overexpressing lung cancer cells reduce cyclooxygenase 2 expression and promote anti‐tumor immunity in vivo
Authors: Tang Shye‐Jye , Ho Ming‐Yi , Cho Huan‐Chieh , Lin Ying‐Chun , Sun Guang‐Huan , Chi Kwan‐Hwa , Wang Yu‐Shan , Jhou Ren‐Shiang , Yang Winnie , Sun Kuang‐Hui 
Published: September 2008

AbstractIn addition to the known function in the glycolytic pathway, phosphoglycerate kinase 1 (PGK‐1) promotes reduction of plasmin disulfide bonds leading to angiostatin formation and inhibition of tumor angiogenesis. In this study, the effects of PGK‐1 on anti‐ tumor immunity against lung cancer were evaluated using the Tet‐Off control of PGK‐1 expression in the Lewis lung carcinoma (LLC‐1). There was no significant difference in cell proliferation between parental LLC‐1 and LLC‐1 transduced with PGK‐1 (PGK‐LLC‐1). However, expression of PGK‐1 was found to limit tumor growth in mice subcutaneously injected with the cell lines and tumor growth was restored after doxycycline treatment. In addition, the cell invasion ability of PGK‐LLC‐1 became weaker than that of LLC‐1. Expressions of COX‐2, TGF‐β1 and PGE2 were all found to be down‐regulated in PGK‐LLC‐1. PGK‐LLC‐1 cells treated with doxycycline recovered their COX‐2 protein expression. In the presence of conditioned medium from PGK‐LLC‐1, the endothelial cell migration was reduced. Moreover, PGK‐LLC‐1 also stimulated T lymphocytes to express higher levels of Th1 cytokine (IFN‐γ) and lower levels of IL‐10 in comparison with parental LLC‐1. PGK‐LLC‐1 cells restored the growth rate in immunodeficient mice when compared with the growth rate in normal mice. In the tissue sections, reduced COX‐2 expressions and marked infiltrated CD3 T lymphocytes were observed in the PGK‐LLC‐1 injected group. These findings indicate that overexpression of PGK‐1 in LLC‐1 reduces the COX‐2 expression, and, in turn, affect PGE2, cell invasion, angiogenesis, and the immune functions, and finally inhibit the tumor progression. © 2008 Wiley‐Liss, Inc.
A prospective analysis of the association between dietary fiber intake and prostate cancer risk in EPIC
Authors: Suzuki Reiko , Allen Naomi E. , Key Timothy J. , Appleby Paul N. , Tjønneland Anne , Johnsen Nina Føns , Jensen Majken K. , Overvad Kim , Boeing Heiner , Pischon Tobias , Kaaks Rudolf , Rohrmann Sabine , Trichopoulou Antonia , Misirli Gesthimani , Trichopoulos Dimitrios , Bueno‐de‐Mesquita H. Bas , van Duijnhoven Fränzel , Sacerdote Carlotta , Pala Valeria , Palli Domenico , Tumino Rosario , Ardanaz Eva , Quirós José Ramón , Larrañaga Nerea , Sánchez Maria‐José , Tormo María‐José , Jakszyn Paula , Johansson Ingegerd , Stattin Pär , Berglund Göran , Manjer Jonas , Bingham Sheila , Khaw Kay‐Tee , Egevad Lars , Ferrari Pietro , Jenab Mazda , Riboli Elio 
Published: September 2008

AbstractFew studies have examined the association between dietary fiber intake and prostate cancer risk. We evaluated the association between dietary fiber intake and the risk of prostate cancer among 142,590 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Consumption of dietary fiber (total, cereal, fruit and vegetable fiber) was estimated by validated dietary questionnaires and calibrated using 24‐hr dietary recalls. Incidence rate ratios were estimated using Cox regression and adjusted for potential confounding factors. During an average of 8.7 years follow‐up, prostate cancer was diagnosed in 2,747 men. Overall, there was no association between dietary fiber intake (total, cereal, fruit or vegetable fiber) and prostate cancer risk, although calibrated intakes of total fiber and fruit fiber were associated with nonstatistically significant reductions in risk. There was no association between fiber derived from cereals or vegetables and risk and no evidence for heterogeneity in any of the risk estimates by stage or grade of disease. Our results suggest that dietary fiber intake is not associated with prostate cancer risk. © 2008 Wiley‐Liss, Inc.
Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF‐coated electrodes
Authors: Evans Alison J. , Thompson Brianna C. , Wallace Gordon G. , Millard Rodney , O'Leary Stephen J. , Clark Graeme M. , Shepherd Robert K. , Richardson Rachael T. 
Published: September 2008

AbstractRelease of neurotrophin‐3 (NT3) and brain‐derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para‐toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3‐coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3‐coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3‐day SGN explant assay found that neurite outgrowth from explants was 12.3‐fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve‐electrode interactions is discussed for specialized applications such as cochlear implants. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Seafloor glacial features reveal the extent and decay of the last British Ice Sheet, east of Scotland
Authors: Graham Alastair G. C. , Lonergan Lidia , Stoker Martyn S. 
Published: September 2008

AbstractThree‐dimensional (3D) seismic datasets, 2D seismic reflection profiles and shallow cores provide insights into the geometry and composition of glacial features on the continental shelf, offshore eastern Scotland (58° N, 1–2° W). The relic features are related to the activity of the last British Ice Sheet (BIS) in the Outer Moray Firth. A landsystem assemblage consisting of four types of subglacial and ice marginal morphology is mapped at the seafloor. The assemblage comprises: (i) large seabed banks (interpreted as end moraines), coeval with the Bosies Bank moraine; (ii) morainic ridges (hummocky, push and end moraine) formed beneath, and at the margins of the ice sheet; (iii) an incised valley (a subglacial meltwater channel), recording meltwater drainage beneath former ice sheets; and (iv) elongate ridges and grooves (subglacial bedforms) overprinted by transverse ridges (grounding line moraines). The bedforms suggest that fast‐flowing grounded ice advanced eastward of the previously proposed terminus of the offshore Late Weichselian BIS, increasing the size and extent of the ice sheet beyond traditional limits. Complex moraine formation at the margins of less active ice characterised subsequent retreat, with periodic stillstands and readvances. Observations are consistent with interpretations of a dynamic and oscillating ice margin during BIS deglaciation, and with an extensive ice sheet in the North Sea basin at the Last Glacial Maximum. Final ice margin retreat was rapid, manifested in stagnant ice topography, which aided preservation of the landsystem record. Copyright © 2008 John Wiley & Sons, Ltd.
The definition, source, manifestation and assessment of unintended effects in genetically modified plants
Authors: Deng Ping‐Jian , Zhou Xiang‐Yang , Yang Dong‐Yan , Hou Hong‐Li , Yang Xiao‐Ke , Li Yong‐Hong , Yang Yong‐Cun , Wang Xue‐Lin , Fang Shi‐Song , Wu Shui‐Qing , Liu Jin 
Published: September 2008

AbstractAt present, there is consensus among many relevant international agencies that unintended effects should be paid particular attention in the process of edible safety assessment of genetically modified plants (GMPs) and their products, especially in regard to some long‐term and potential food safety issues. However, with respect to the current risk assessment of GMPs, serious dissension on the apprehension of unintended effects exists. The present paper interprets and systematically analyses this dissension in order to review development on the definition, source and manifestation of unintended effects in GMPs. First, differences in the various concepts of unintended effect are discussed and compared. Then the mechanisms whereby unintended effects may arise during GMP breeding are analysed and the main unexpected variation manifestations in GMPs are presented. With regard to the safety assessment of unintended effects in GMPs, the current evaluation strategy, detection methods and several assessment cases are expounded. In addition, the unique assessment standard for unintended effects in GMPs in China is outlined. Copyright © 2008 Society of Chemical Industry