bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of a promoter polymorphism on the transcription of nitric oxide synthase 1 and its relevance to Parkinson's disease
Authors: Rife Terrie , Rasoul Bareza , Pullen Nicholas , Mitchell David , Grathwol Kristen , Kurth Janice 
Published: March 2009

AbstractTranscriptional changes of the enzyme nitric oxide synthase I (NOS1) are believed to play a role in the development of many diseases. The gene for NOS1 has 12 alternative first exons (1A–1L). The 1F exon is one of the most highly utilized first exons in the brain and has a polymorphism ((TG)mTA(TG)n) located in its promoter region. The polymorphism's length has been suggested to affect NOS1 transcription and play a role in Parkinson's disease (PD); however, the actual influence of the polymorphism on NOS1 transcription has not been studied. To better characterize the links of the polymorphism with PD, a genotyping study was done comparing polymorphism length among 170 PD patients and 150 age‐matched controls. The pattern of changes between the two group's allele frequencies shows statistical significance (P = 0.0359). The smallest polymorphism sizes are more predominant among PD patients than controls. To study the effects of this polymorphism on NOS1 gene transcription, reporter gene constructs were made by cloning the NOS1 1F promoter with polymorphism lengths of either 42, 54, or 62 bp in front of the luciferase gene and transfecting them into HeLa or Sk‐N‐MC cells. NOS1‐directed reporter gene constructs with the 62‐bp polymorphism increased transcription of luciferase 2.2‐fold in HeLa and 1.8‐fold in Sk‐N‐MC cells compared with reporter gene constructs with the 42‐bp polymorphism. These data suggest that if smaller polymorphism size contributes to the higher NOS1 levels in PD patients, an as yet unknown transcriptional mechanism is required. © 2009 Wiley‐Liss, Inc.
Synergistic effect of low‐frequency ultrasound and low‐dose bradykinin on increasing permeability of the blood–tumor barrier by opening tight junction
Authors: Zhang Zhen , Xia Chunyi , Xue Yixue , Liu Yunhui 
Published: March 2009

AbstractLow‐frequency ultrasound (LFU) and bradykinin (BK) have been shown separately to increase the permeability of the blood–tumor barrier (BTB) in the rat model of C6 glioma. This study examined the hypothesis that the combination of LFU and low‐dose BK has a synergistic effect on increasing the permeability of BTB and explored the possible underlying mechanism including the involvement of tight junction (TJ). The rats were divided into six groups: control group, LFU group, BK group, 2/3LFU + 1/2BK group, 5/6LFU + 2/3BK group, and LFU + BK group. The BTB permeability was assessed by Evans blue extravasation. The mRNA and protein expressions of TJ‐related proteins ZO‐1, occludin, and claudin‐5 were determined by reverse transcriptase–polymerase chain reaction, immunohistochemistry, immunolocalization, and Western blot test. BTB permeability increased in all the experimental groups, accompanied by opening of local TJ of the BTB, observed by transmission electron microscopy, and decreased mRNA and protein expressions of ZO‐1, occludin, and claudin‐5. In addition, there was a further increase in BTB permeability and a further reduction in the expressions of TJ‐related proteins in 5/6LFU + 2/3BK and LFU + BK groups, compared with LFU or BK group. These results indicate that LFU and low‐dose BK applied in combination act in a synergistic manner to increase BTB permeability. The down‐regulation of TJ‐related proteins ZO‐1, occludin, and claudin‐5 may be one of the underlying mechanisms of the increase in BTB permeability induced by LFU and BK. © 2009 Wiley‐Liss, Inc.
NMDA receptors mediate an early up‐regulation of brain‐derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease
Authors: Bustos Gonzalo , Abarca Jorge , Bustos Victor , Riquelme Eduardo , Noriega Viviana , Moya Catherine , Campusano Jorge 
Published: March 2009

AbstractThe clinical symptoms of Parkinson's disease (PD) appear late and only when the degenerative process at the level of the nigrostriatal dopamine (DA) pathway is quite advanced. An increase in brain‐derived neurotrophic factor (BDNF) expression may be one of the molecular signals associated to compensatory and plastic responses occurring in basal ganglia during presymptomatic PD. In the present study, we used in vivo microdialysis, semiquantitative reverse transcriptase–polymerase chain reaction, and immunohistochemistry to study N‐methyl‐D‐aspartic acid (NMDA) receptor regulation of BDNF expression in substantia nigra (SN) of adult rats after partial lesioning of the nigrostriatal DA pathway with unilateral striatal injections of 6‐hydroxydopamine (6‐OHDA). A time‐dependent partial decrease of striatal DA tissue content as well as parallel and gradual increases in extracellular glutamate and aspartate levels in SN were found 1 to 7 days after unilateral 6‐OHDA intrastriatal injection. Instead, the number of tyrosine hydroxylase–immunoreactive (IR) cells in the ipsilateral SN pars compacta remained statistically unchanged after neurotoxin injection. Intrastriatal administration of 6‐OHDA also produced an early and transient augmentation of pan‐BDNF, exon II–BDNF, and exon III–BDNF transcripts in the ipsilateral SN. The pan‐BDNF and exon II–BDNF transcript increases were completely abolished by the prior systemic administration of MK‐801, a selective antagonist of NMDA receptors. MK‐801 also blocked the increase in BDNF‐IR cells in SN observed 7 days after unilateral 6‐OHDA intrastriatal injections. Our findings suggest that a coupling between glutamate release, NMDA receptor activation, and BDNF expression may exist in the adult SN and represent an important signal in this midbrain nucleus triggered in response to partial DA loss occurring in striatal nerve endings during presymptomatic PD. © 2009 Wiley‐Liss, Inc.
Interaction of estrogen receptor‐α ligand binding domain with nuclear proteins of aging mouse brain
Authors: Ghosh Swati , Thakur M.K. 
Published: March 2009

AbstractAfter the interaction of estrogen with the ligand binding domain (LBD) of mouse estrogen receptor‐α (mERα) and hormone‐responsive elements of target genes, many nuclear proteins are recruited to regulate the expression of specific genes. Because it is not known which brain proteins interact with LBD or whether these proteins vary with age and sex, we used pull‐down assay and far Western blotting to detect five nuclear proteins of 160, 140, 87, 60, and 46 kD in the mouse brain. These interacting proteins were identified as PELP1, RIP140, PGC1α, BAF60, and ADA3, respectively. The level of PELP1, RIP140, PGC1α, and BAF60 decreased drastically in old compared with adult male mice, whereas the ADA3 level showed no significant change. PELP1, PGC1α, and BAF60 levels were lower in old male compared with female mice. Thus we report the identification and interaction of five nuclear proteins with mERα‐LBD, indicating their role in estrogen signaling and brain functions during aging. © 2009 Wiley‐Liss, Inc.
Opposite role of infralimbic and prelimbic cortex in the tachycardiac response evoked by acute restraint stress in rats
Authors: Tavares R.F. , Corrêa F.M.A. , Resstel L.B.M. 
Published: March 2009

AbstractThe ventral medial prefrontal cortex (vMPFC) comprises the prelimbic cortex (PL) and the infralimbic cortex (IL). Conflicting results have been reported from studies aiming to investigate the role played by the vMPFC in behavioral and autonomic responses evoked in rodents exposed to experimental protocols that promote defense responses. Acute restraint is an unavoidable stress situation that evokes marked and sustained cardiovascular changes, which are characterized by elevated blood pressure (BP) and intense heart rate (HR) increases. We report here a comparison between the effects of pharmacological inhibition of IL and PL neurotransmission on BP and HR responses evoked by acute restraint in rats. Bilateral microinjection of 200 nl of the unspecific synaptic blocker CoCl2 (1 mM) into the PL increased HR response associated with restraint, without affecting the restraint‐induced BP response. However, when local synapses in the IL were inhibited by bilateral injection of CoCl2 into that area, the restraint‐induced HR increases were significantly reduced, without a significant effect on the concomitant BP response. No responses were observed when CoCl2 was microinjected into structures surrounding the vMPFC, such as the cingulate cortex area 1, the corpus callosum, or the tenia tecta. The present results confirm the involvement of the vMPFC in modulation of the tachycardiac response evoked by acute restraint but not of the restraint‐evoked blood pressure response. They also indicate that the IL and PL areas have opposite roles in the cardiac response, facilitating and reducing, respectively, restraint‐evoked tachycardiac responses. © 2009 Wiley‐Liss, Inc.
Increased levels of proinflammatory cytokines in the aged rat brain attenuate injury‐induced cytokine response after excitotoxic damage
Authors: Campuzano O. , Castillo‐Ruiz M. M. , Acarin L. , Castellano B. , Gonzalez B. 
Published: March 2009

AbstractIn order to evaluate proinflammatory cytokine levels and their producing cell types in the control aged rat brain and after acute excitotoxic damage, both adult and aged male Wistar rats were injected with N‐methyl‐D‐aspartate in the striatum. At different survival times between 6 hr and 7 days after lesioning, interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor alpha (TNF‐α) were analyzed by enzyme‐linked immunosorbent assay and by double immunofluorescence of cryostat sections by using cell‐specific markers. Basal cytokine expression was attributed to astrocytes and was increased in the normal aged brain showing region specificity: TNF‐α and IL‐6 displayed age‐dependent higher levels in the aged cortex, and IL‐1β and IL‐6 in the aged striatum. After excitotoxic striatal damage, notable age‐dependent differences in cytokine induction in the aged vs. the adult were seen. The adult injured striatum exhibited a rapid induction of all cytokines analyzed, but the aged injured striatum showed a weak induction of cytokine expression: IL‐1β showed no injury‐induced changes at any time, TNF‐α presented a late induction at 5 days after lesioning, and IL‐6 was only induced at 6 hr after lesioning. At both ages, in the lesion core, all cytokines were early expressed by neurons and astrocytes, and by microglia/macrophages later on. However, in the adjacent lesion border, cytokines were found in reactive astrocytes. This study highlights the particular inflammatory response of the aged brain and suggests an important role of increased basal levels of proinflammatory cytokines in the reduced ability to induce their expression after damage. © 2009 Wiley‐Liss, Inc.
The mechanisms of collisional activation of ions in mass spectrometry
Authors: Mayer Paul M. , Poon Clement 
Published: March 2009

AbstractThis article is a review of the mechanisms responsible for collisional activation of ions in mass spectrometers. Part I gives a general introduction to the processes occurring when a projectile ion and neutral target collide. The theoretical background to the physical phenomena of curve‐crossing excitation (for electronic and vibrational excitation), impulsive collisions (for direct translational to vibrational energy transfer), and the formation of long‐lived collision intermediates is presented. Part II highlights the experimental and computational investigations that have been made into collisional activation for four experimental conditions: high (>100 eV) and intermediate (1–100 eV) center‐of‐mass collision energies, slow heating collisions (multiple low‐energy collisions) and collisions with surfaces. The emphasis in this section is on the derived post‐collision internal energy distributions that have been found to be typical for projectile ions undergoing collisions in these regimes. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:608–639, 2009
Frequent occurrence of RASSF1A promoter hypermethylation and merkel cell polyomavirus in merkel cell carcinoma
Authors: Helmbold Peter , Lahtz Christoph , Enk Alexander , Herrmann‐Trost Peter , Marsch Wolfgang Ch. , Kutzner Heinz , Dammann Reinhard H. 
Published: March 2009

AbstractMerkel cell carcinoma (MCC) is one of the most aggressive cancers of the skin. It has recently been reported that integration of a Merkel cell polyomavirus (MCPyV) in receptor tyrosine phosphates type G (PTPRG) gene occurs in MCC, and that viral infections are associated with epigenetic silencing of tumor suppressor genes (TSG) in cancer. To examine whether a correlation between TSG inactivation and viral infection can be found in MCC, we investigated the promoter hypermethylation of RASSF1A, TP73, PTPRG, FHIT, and CDKN2A and the presence of MCPyV and SV40 in 98 MCC by PCR. Hypermethylation of RASSF1A was frequently found in 42 of 83 (51%) of MCC. Methylation of CDKN2A was present in 9 of 41 (22%) of MCC. Hypermethylation of TP73 (0%), PTPRG (4%), and FHIT (0%) was infrequent in MCC. Interestingly, MCPyV was found in 90 of 98 (92%) MCC, however, no SV40 signal was detected. No correlation between TSG hypermethylation and viral infection was found. Our results show frequent hypermethylation of RASSF1A and the presence of MCPyV in primary MCC, and that these events may contribute to the pathogenesis of MCC. © 2009 Wiley‐Liss, Inc.
Generalized finite element method using proper orthogonal decomposition
Authors: Aquino W. , Brigham J. C. , Earls C. J. , Sukumar N. 
Published: March 2009

AbstractA methodology is presented for generating enrichment functions in generalized finite element methods (GFEM) using experimental and/or simulated data. The approach is based on the proper orthogonal decomposition (POD) technique, which is used to generate low‐order representations of data that contain general information about the solution of partial differential equations. One of the main challenges in such enriched finite element methods is knowing how to choose, a priori, enrichment functions that capture the nature of the solution of the governing equations. POD produces low‐order subspaces, that are optimal in some norm, for approximating a given data set. For most problems, since the solution error in Galerkin methods is bounded by the error in the best approximation, it is expected that the optimal approximation properties of POD can be exploited to construct efficient enrichment functions. We demonstrate the potential of this approach through three numerical examples. Best‐approximation studies are conducted that reveal the advantages of using POD modes as enrichment functions in GFEM over a conventional POD basis. Copyright © 2009 John Wiley & Sons, Ltd.
A combined finite volume–finite element scheme for the discretization of strongly nonlinear convection–diffusion–reaction problems on nonmatching grids
Authors: Eymard Robert , Hilhorst Danielle , Vohralík Martin 
Published: March 2009

AbstractWe propose and analyze in this paper a numerical scheme for nonlinear degenerate parabolic convection–diffusion–reaction equations in two or three space dimensions. We discretize the time evolution, convection, reaction, and source terms on a given grid, which can be nonmatching and can contain nonconvex elements, by means of the cell‐centered finite volume method. To discretize the diffusion term, we construct a conforming simplicial mesh with the vertices given by the original grid and use the conforming piecewise linear finite element method. In this way, the scheme is fully consistent and the discrete solution is naturally continuous across the interfaces between the subdomains with nonmatching grids, without introducing any supplementary equations and unknowns or using any interpolation at the interfaces. We allow for general inhomogeneous and anisotropic diffusion–dispersion tensors, propose two variants corresponding respectively to arithmetic and harmonic averaging, and use the local Péclet upstream weighting in order to only add the minimal numerical diffusion necessary to avoid spurious oscillations in the convection‐dominated case. The scheme is robust, efficient since it leads to positive definite matrices and one unknown per element, locally conservative, and satisfies the discrete maximum principle under the conditions on the simplicial mesh and the diffusion tensor usual in the finite element method. We prove its convergence using a priori estimates and the Kolmogorov relative compactness theorem and illustrate its behavior on a numerical experiment. © 2009 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2010
Who benefits from demand‐driven distribution of HIV/AIDS services? An analysis of the emerging CBO sector in Malawi
Authors: Schou Arild 
Published: March 2009

AbstractCommunity‐based organisations (CBOs) play a key role in Malawi's multi‐sector programme for responding to the HIV/AIDS pandemic. In this programme they are funded in a demand‐driven manner—which means that only those areas that apply for funds to CBO services are blessed with programme benefits. This paper argues that this funding mechanism is not conducive to either distributing CBO services to areas most in need or enhancing downward accountability. Because areas most in need of services generally also lacked the capacity to attract project funding, the programme did not reach them. Instead, it tended to reach those areas with the greatest capacity to attract funding, though not necessarily the greatest need for it. Furthermore, those CBOs that were funded were unable to facilitate collective action in their communities because of elite capture of decision making. The programme, however, was relatively responsive to the communities' thematic demands. Thus, all in all, the elites were relatively more successful in representing the communities' wishes than in caring for all geographical areas in their constituencies. Copyright © 2009 John Wiley & Sons, Ltd.
Dealing with sectoral corruption in Bangladesh: Developing citizen involvement
Authors: Knox Colin 
Published: March 2009

AbstractBangladesh has had a troubled political history since gaining independence in 1971 and is also beleaguered by poverty and natural environmental disasters. In particular however, corruption is blighting its prospects for economic growth, undermining the rule of law and damaging the legitimacy of the political process. This article adopts a sectoral approach to the study of corruption by examining people's experiences of using health and education services in Bangladesh through a large scale quantitative survey. It also presents case study research which assesses the impact of anti‐corruption work by Transparency International Bangladesh (TIB) in the areas of health and education. The article concludes that: the poorest in Bangladesh are most penalised by corruption; there are significant benefits for health and education service users resulting from TIB's interventions and there is a need for committed political leadership if ongoing efforts to tackle corruption are to be effective and sustainable. Copyright © 2009 John Wiley & Sons, Ltd.
Modes of influence: Participation in publicly administered development programmes
Authors: Parkinson Sarah 
Published: March 2009

AbstractThis article considers the way that farmers within a national agricultural advisory programme in Uganda were able to exert influence over that programme's policy and practice. Although the literature has tended to focus on engagement within formal programme structures as a major mode of participation, the analysis of the NAADS case reveals that farmers were able to exert an important influence over programme policy through their roles as political constituents. The brokerage role of supportive programme staff also worked to allow farmers' views to influence the programme, as did the collective weight of decisions commonly made by farmers, and to a lesser extent, the lobbying efforts of national NGOs. Copyright © 2009 John Wiley & Sons, Ltd.
False‐photosensitivity and transient hemiparesis following high‐dose intravenous and intrathecal methotrexate for treatment of acute lymphoblastic leukemia
Authors: Shah Nilay , Zambidis Elias T. 
Published: March 2009

AbstractWe describe a patient who was treated with high‐dose intravenous and intrathecal methotrexate for acute lymphoblastic leukemia, and who manifested a false photosensitivity reaction with no prior evidence of sun exposure. This patient later experienced delayed transient hemiparesis following methotrexate administration, although without long‐term sequelae. The etiology of these events is obscure, but suggestive of a vasculitic or immune‐mediated reaction to methotrexate. Pediatr Blood Cancer 2009;53:103–105. © 2009 Wiley‐Liss, Inc.
Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib
Authors: Janeway Katherine A. , Albritton Karen H. , Van Den Abbeele Annick D. , D'Amato Gina Z. , Pedrazzoli Paolo , Siena Salvatore , Picus Joel , Butrynski James E. , Schlemmer Marcus , Heinrich Michael C. , Demetri George D. 
Published: March 2009

AbstractBackgroundSunitinib inhibits KIT and other members of the split‐kinase‐domain family of receptor tyrosine kinases. Sunitinib prolongs survival in adult patients with imatinib‐resistant gastrointestinal stromal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib.ProcedureSunitinib therapy was provided through a treatment‐use protocol. Patients were 10–17 years old at enrollment. All patients had GIST resistant to imatinib therapy. Sunitinib was administered daily for 4 weeks in 6‐week treatment cycles. KIT and platelet‐derived growth factor receptor alpha (PDGFRA) genotyping of tumor tissue were performed.ResultsOne patient achieved a partial response, five patients had stable disease and one patient had progressive disease on sunitinib. The duration of disease stabilization was between 7 and 21+ months, with a mean of 15 months. Time to tumor progression was longer on sunitinib than on prior imatinib treatment for five of six patients. Two patients experienced grade 3 adverse events. All other adverse events were grade 1–2. None of the five patients tested had mutations in KIT or PDGFRA.ConclusionSunitinib treatment was associated with substantial initial antitumor activity and acceptable tolerability in this group of pediatric patients with imatinib‐resistant GIST. Pediatr Blood Cancer 2009;52:767–771. © 2009 Wiley‐Liss, Inc.