bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury
Authors: Luh Clara , Kuhlmann Christoph R. , Ackermann Bianca , Timaru‐Kast Ralph , Luhmann Heiko J. , Behl Christian , Werner Christian , Engelhard Kristin , Thal Serge C. 
Published: November 2009

J. Neurochem. (2009) 112, 1015–1025.AbstractThe role of the endothelial contractile apparatus in the process of brain edema formation after brain trauma is not characterized. Phosphorylation of myosin light chains by myosin light chain kinases (MLCK) activates endothelial contractile elements and results in a rearrangement of the cytoskeleton. This may enhance post‐traumatic blood‐brain barrier dysfunction. In order to investigate the role of the MLCK on brain edema formation and blood‐brain barrier permeability after brain injury, mice were anesthetized and subjected to a controlled cortical impact (CCI). MLCK expression is significantly up‐regulated after CCI with a maximum 12 h post‐injury. Specific inhibition of MLCK by ML‐7 resulted in a reduction of phosphorylation of myosin light chains and improved blood‐brain‐barrier integrity. Accordingly, ML‐7 attenuated post‐traumatic brain edema formation and intracranial hypertension 24 h after CCI. Prevention of brain edema formation did not translate into improved neurological outcome or reduced brain lesion. In conclusion, the results confirm that the endothelial contractile apparatus is activated by CCI and opens the endothelial barrier leading to vasogenic brain edema formation. Lack of neurological and histological improvement suggests that specific targeting of vasogenic brain edema at the endothelial level is not sufficient to limit secondary brain damage and has, therefore, to be combined with other potential neuroprotective strategies.
Positive allosteric modulation of α7 neuronal nicotinic acetylcholine receptors: lack of cytotoxicity in PC12 cells and rat primary cortical neurons
Authors: Hu Min , Gopalakrishnan Murali , Li Jinhe 
Published: November 2009

Background and purpose:  α7‐Nicotinic acetylcholine receptors (α7 nAChRs) play an important role in cognitive function. Positive allosteric modulators (PAMs) amplify effects of α7 nAChR agonist and could provide an approach for treatment of cognitive deficits in neuropsychiatric diseases. PAMs can either predominantly affect the apparent peak current response (type I) or increase both the apparent peak current response and duration of channel opening, due to prolonged desensitization (type II). The delay of receptor desensitization by type II PAMs raises the possibility of Ca2+‐induced toxicity through prolonged activation of α7 nAChRs. The present study addresses whether type I and II PAMs exhibit different cytotoxicity profiles.Experimental approach:  The present studies evaluated cytotoxic effects of type I PAM [N‐(4‐chlorophenyl)]‐α‐[(4‐chloro‐phenyl)‐aminomethylene]‐3‐methyl‐5‐isoxazoleacet‐amide (CCMI) and type II PAM 1‐[5‐chloro‐2,4‐dimethoxy‐phenyl]‐3‐[5‐methyl‐isoxazol‐3‐yl]‐urea (PNU‐120596), or 4‐[5‐(4chloro‐phenyl)‐2‐methyl‐3‐propionyl‐pyrrol‐1‐yl]‐benzenesulphonamide (A‐867744). The studies used cultures of PC12 cells and primary cultures of rat cortical neuronal cells.Key results:  Our results showed that neither type I nor type II PAMs had any detrimental effect on cell integrity or cell viability. In particular, type II PAMs did not affect neuron number and neurite outgrowth under conditions when α7 nAChR activity was measured by Ca2+ influx and extracellular signal‐regulated kinases 1 and 2 phosphorylation, following exposure to α7 nAChR agonists.Conclusions and implications:  This study demonstrated that both type I and type II α7 nAChR selective PAMs, although exhibiting differential electrophysiological profiles, did not exert cytotoxic effects in cells endogenously expressing α7 nAChRs.
Role of the signal peptide in the synthesis and processing of the glucagon‐like peptide‐1 receptor
Authors: Huang Y , Wilkinson GF , Willars GB 
Published: November 2009

Background and purpose:  The glucagon‐like peptide‐1 receptor (GLP‐1R) belongs to Family B of the G protein‐coupled receptor superfamily and is a target for treatment of type 2 diabetes. Family B G protein‐coupled receptors contain a putative N‐terminal signal peptide, but its role in receptor synthesis and trafficking are unclear. Further, the signal peptide is not cleaved in at least one family member.Experimental approach:  We examined receptor glycosylation and the role of the signal peptide in GLP‐1R synthesis and trafficking using constructs containing epitope tags at the N‐ and/or C‐terminus and in which the signal peptide sequence was either present or absent.Key results:  The signal peptide was absolutely required for GLP‐1R synthesis but could be substituted to some extent by increasing positive charge in the N‐terminal region of the receptor flanking the signal peptide. The signal peptide is cleaved during synthesis and processing of the receptor. An enhanced GFP‐epitope tag at the N‐terminus of the receptor permitted synthesis of the receptor but blocked signal peptide cleavage and prevented trafficking to the plasma membrane. Cleavage site mutation allowed synthesis of a full‐length receptor, blocked signal peptide cleavage and caused retention within the endoplasmic reticulum.Conclusions and implications:  Signal peptide cleavage was not essential for receptor synthesis but was obligatory for processing and trafficking of receptors to the plasma membrane. Further, the GLP‐1R is subject to N‐linked glycosylation and only the mature, fully glycosylated form of the receptor is present in the plasma membrane. Inhibition of glycosylation prevents processing and cell surface expression of the GLP‐1R.
Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells
Authors: Hanjaya‐Putra Donny , Yee Jane , Ceci Doug , Truitt Rachel , Yee Derek , Gerecht Sharon 
Published: November 2009

AbstractEndothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs break down the extracellular matrix (ECM), migrate, differentiate and undergo tube morphogenesis. Evidently, the ECM plays a critical role by providing biochemical and biophysical cues that regulate cellular behaviour. Using a chemically and mechanically tunable hydrogel to study tube morphogenesis in vitro, we show that vascular endothelial growth factor (VEGF) and substrate mechanics co‐regulate tubulogenesis of EPCs. High levels of VEGF are required to initiate tube morphogenesis and activate matrix metalloproteinases (MMPs), which enable EPC migration. Under these conditions, the elasticity of the substrate affects the progression of tube morphogenesis. With decreases in substrate stiffness, we observe decreased MMP expression while increased cellular elongation, with intracellular vacuole extension and coalescence to open lumen compartments. RNAi studies demonstrate that membrane type 1‐MMP (MT1‐MMP) is required to enable the movement of EPCs on the matrix and that EPCs sense matrix stiffness through signalling cascades leading to the activation of the RhoGTPase Cdc42. Collectively, these results suggest that coupled responses for VEGF stimulation and modulation of substrate stiffness are required to regulate tube morphogenesis of EPCs.
BCR‐ABL‐independent and RAS / MAPK pathway‐dependent form of imatinib resistance in Ph‐positive acute lymphoblastic leukemia cell line with activation of EphB4
Authors: Suzuki Momoko , Abe Akihiro , Imagama Shizuka , Nomura Yuka , Tanizaki Ryohei , Minami Yosuke , Hayakawa Fumihiko , Ito Yoshie , Katsumi Akira , Yamamoto Kazuhito , Emi Nobuhiko , Kiyoi Hitoshi , Naoe Tomoki 
Published: November 2009

Abstract Objective: We investigated the mechanism responsible for imatinib (IM) resistance in Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL) cell lines. Methods: We established cell lines from a patient with Ph+ ALL at the time of first diagnosis and relapsed phase and designated as NPhA1 and NPhA2, respectively. We also derived IM‐resistant cells, NPhA2/STIR, from NPhA2 under gradually increasing IM concentrations. Results: NPhA1 was sensitive to IM (IC50 0.05 μm) and NPhA2 showed mild IM resistance (IC50 0.3 μm). NPhA2/STIR could be maintained in the presence of 10 μm IM. Phosphorylation of MEK and ERK was slightly elevated in NPhA2 and significantly elevated in NPhA2/STIR compared to NPhA1 cells. After treatment with IM, phosphorylation of MEK and ERK was not suppressed but rather increased in NPhA2 and NPhA2/STIR. Active RAS was also increased markedly in NPhA2/STIR after IM treatment. The expression of BCL‐2 was increased in NPhA2 compared to NPhA1, but no further increase in NPhA2/STIR. Proliferation of NPhA2/STIR was significantly inhibited by a combination of MEK inhibitor and IM. Analysis of tyrosine phosphorylation status with a protein tyrosine kinase array showed increased phosphorylation of EphB4 in NPhA2/STIR after IM treatment. Although transcription of EphB4 was suppressed in NPhA1 and NPhA2 after IM treatment, it was not suppressed and its ligand, ephrinB2, was increased in NPhA2/STIR. Suppression of EphB4 transcripts by introducing short hairpin RNA into NPhA2/STIR partially restored their sensitivity to IM. Conclusions: These results suggest a new mechanism of IM resistance mediated by the activation of RAS/MAPK pathway and EphB4.
Epigenetic inactivation of tumour suppressor gene KLF11 in myelodysplastic syndromes*
Authors: Potapova Anna , Hasemeier Britta , Römermann Daniel , Metzig Kathleen , Göhring Gudrun , Schlegelberger Brigitte , Länger Florian , Kreipe Hans , Lehmann Ulrich 
Published: November 2009

AbstractThe identification of aberrantly hypermethylated genes may lead to the development of new diagnostic markers and the identification of novel targets of epigenetic therapy in myelodysplastic syndromes (MDS). We therefore investigated the methylation status of transcription factor genes KLF5, KLF11, and MAFB, shown to be aberrantly methylated in myelogeneous leukaemia cells, in a series of 115 MDS patient as well as in 25 control subjects. Using quantitative high‐resolution pyrosequencing methodology, KLF11, MAFB, and KLF5 were shown for the first time to be hypermethylated in 17 (15%), 8 (7%), and 2 (1.7%) cases, respectively, but not in any of the patients with an isolated 5q‐deletion. Patient samples harbouring KLF11 methylation displayed reduced KLF11 mRNA expression and KLF11 hypermethylation correlated with a high International Prognostic Scoring System score (P < 0.05). In conclusion, epigenetic inactivation and subsequent transcriptional repression of the KLF11 gene is quite frequent in MDS. Patients with an isolated 5q‐deletion seem to harbour a distinct epigenetic profile.
Secondary old‐field succession in an ecosystem with restrictive soils: does time from abandonment matter?
Authors: Martínez‐Duro E. , Ferrandis P. , Escudero A. , Luzuriaga A.L. , Herranz J.M. 
Published: November 2009

AbstractQuestion: Our knowledge of secondary old‐field succession in Mediterranean environments is extremely poor and is non‐existent for restrictive soil conditions. How these ecosystems, such as those on semi‐arid gypsum outcrops, recover seems a priority for managing change and for ensuring conservation of specialized and endangered biota. We tested whether reinstallation of gypsum vegetation after cropland abandonment requires: (1) soil physical restructuring and (2) chemical readjustment to enable growth and survival of specialized gypsophilous vegetation, and more specifically how time from abandonment drives such environmental change.Location: We sampled a complete set of old fields on gypsum soils (1–60 yr since abandonment) in Villarrubia de Santiago (Toledo, Spain).Methods: Generalized linear models and model comparisons were used to analyse the effect of several environmental parameters on species abundance and richness. Ordination methods (canonical correspondence analyses and partial canonical correspondence analyses) were undertaken to evaluate compositional variation among the sampled fields.Results: Secondary old‐field succession on semi‐arid Mediterranean gypsum soils was controlled by a complex set of factors acting relatively independently. Surprisingly, time since abandonment explains only a small proportion of compositional variation (3%). Conversely, soil chemical features independently from time since abandonment are important for explaining differences found in old‐field composition.Conclusions: Secondary succession on specialized Mediterranean soils does not follow the widely described “amelioration” process in which soil features and composition are closely related over time. Restrictive soil conditions control both structure and functioning of mature communities and also secondary succession.
Landscape‐scale patterns of alien plant species on coastal dunes: the case of iceplant in central Italy
Authors: Carranza M. Laura , Carboni Marta , Feola Silverio , Acosta Alicia T. R. 
Published: November 2009

AbstractQuestion: We investigated the spatial pattern of coastal landscapes invaded by iceplant (Carpobrotus aff. acinaciformis) focusing on two questions: (1) Does the spatial structure of iceplant patches differ from that of native natural costal dune cover types?; (2) Is the distribution of iceplant patches related to other cover types?Location: Tyrrhenian coast of Central Italy.Method: On the basis of a detailed land‐cover map, we calculated structural metrics for iceplant patches and for each native coastal dune cover category (mean patch size and patch shape index) and compared them by means of anova. To assess the spatial association between iceplant patches and the different cover types, we implemented an electivity analysis which analyses the frequency of common borders.Results: The mapped coastal dune cover types included beaches, dunes and sand plain variants, related to the typical Tyrrhenian coastal dune vegetation zonation. Iceplant‐dominated vegetation presented elongated and irregularly shaped patches, which were not significantly different from most of the natural cover types suggesting a natural spread along the territory analysed. Iceplant patches were positively associated with beach, mobile and inter‐dune cover types indicating that these habitats are exposed to further alien spread. Iceplant patches were also positively associated with artificial surfaces highlighting this cover type as a possible source of propagule pressure.Conclusions: The proposed landscape approach combining patch‐based metrics with edge‐based metrics provided a comprehensive description of the invaded coastal landscape. From an applied research perspective, this landscape approach could be useful in identifying the correct management strategies for alien‐invaded areas.
Policy Attitudes, Ideological Values and Social Representations
Authors: Staerklé Christian 
Published: November 2009

AbstractThis article reviews research on policy attitudes and ideological values from the perspective of social representations theory. In the first part of the paper, key features of lay political thinking are presented, its pragmatic imperative, its focus on communication and the social functions of shared knowledge.Objectificationtransforms abstract and group‐neutral ideological values into concrete and socially useful knowledge, in particular stereotypes of value‐conforming and value‐violating groups. Such shared understandings of intergroup relations provide citizens with common reference knowledge which provides the cognitive and cultural basis of policy attitudes. Social representations theory further suggests that lay knowledge reflects the social context in which it has been elaborated (anchoring), an aspect which allows conceptualising aggregate‐level differences in policy attitudes. In the second part of the paper, a model of lay conceptions of social order is outlined which organises four shared conceptions of social order, along with the stereotype‐based thinking associated with each conception: Moral order, Free Market, Social diversity and Structural inequality. We conclude by arguing that policy attitudes are symbolic devices expressed to justify or to challenge existing social arrangements.
Assessment of referral patterns for CT KUB in a tertiary setting
Authors: Jo H , Buckley BT 
Published: November 2009

SummaryThe purpose of this study was to assess the referral patterns and the use of unenhanced renal tract CT (CT KUB) for investigating patients presenting with clinically suspected renal colic. We retrospectively reviewed 500 consecutive CT KUB studies requested for suspected renal colic carried out at a single institution between December 2006 and July 2007. Follow‐up radiology reports and discharge summaries on the hospital clinical Intranet were also reviewed. Studies were analysed for characteristics including patient demographics, referring clinical team, time of referral, final diagnosis and requirement for further imaging. The majority of requests were from Emergency (ED) or Urology Departments (49%, 245 out of 500, and 37%, 186 out of 500, respectively). The positive rate for urolithiasis was 67% (337 out of 500), the negative rate was 25% (123 out of 500), and 8% (40 out of 500) of patients had alternative significant findings. Female patients were more likely to have a negative study than male patients (35 versus 20%, P < 0.0001) and more likely to have alternative significant pathology (12 versus 6%, P < 0.0001). Patients referred by specialities other than Urology and ED were more likely to be female and have a negative or alternative finding (P < 0.0001). CT KUB is a widely used first method of investigation for patients with suspected renal colic with a high positive predictive value allowing rapid diagnosis and intervention. However, given the high rate of negative or alternative findings on CT KUB in young women, especially those referred by specialities other than ED or Urology, ultrasound should be considered as an alternative imaging method to minimise unnecessary radiation exposure.
Use of deodorants during adjuvant breast radiotherapy: A survey of compliance with standard advice, impact on patients and a literature review on safety
Authors: Graham PH , Graham JL 
Published: November 2009

SummaryProscription of antiperspirant or deodorant use during adjuvant breast radiotherapy is common. The investigators were seeking an information base to facilitate design of an appropriate controlled trial of the use of deodorants during radiotherapy.The first component consisted of a survey of women after adjuvant breast radiotherapy seeking information about routine deodorant use and potential concern if deodorants were not permitted during radiotherapy. The second component comprised a literature search for any existing controlled evidence regarding harm from deodorant use during radiotherapy.Four hundred fourteen women completed surveys. Two hundred eighty recalled advice against deodorants. Two hundred ninety‐nine women routinely used deodorants, 70% of whom used roll‐on products. Forty‐five continued deodorant use during radiation, 20 of these despite recalling advice not to wear a deodorant. Of the 233 women who routinely wore a deodorant but abstained during radiotherapy, 19% expressed a lot of concern about body odour and 45% were slightly concerned. Three controlled studies totalling 310 patients report specific deodorants versus no deodorant use which did not show statistically significantly increased skin reactions, but had only a small subset with axillary irradiation.The proscription of deodorant use during radiotherapy is of unproven benefit and causes body odour concern to the majority of women who are usual deodorant users. The next most appropriate trial would compare use of the usual deodorant versus no deodorant, would encompass a significant number of women with radiotherapy to the axilla or application of deodorant to irradiated skin areas, and include endpoints other than skin reaction alone.
Prospective development of an individualised predictive model for treatment coverage using offline cone beam computed tomography surrogate measures in post‐prostatectomy radiotherapy
Authors: Tran PK , Haworth A , Foroudi F , Paneghel A , Herschtal AG , Tai KH , Williams SG , Soteriou S , Laferlita M , Duchesne GM 
Published: November 2009

SummaryThe aim of this study is to prospectively evaluate and model surrogate explanatory variables (SEVs) of target coverage and rectal dose pertaining to soft tissue anatomy visualised on cone beam computed tomography (CBCT) for incorporation into post‐prostatectomy treatment coverage verification protocols. Twenty post‐prostatectomy patients treated with conformal prostate bed radiotherapy (64–74 Gy) underwent CBCT daily at fractions 1 to 5, and then weekly. Treatment coverage was defined on each CBCT using ‘PTV95’, percentage of the CBCT PTV covered by original treatment fields, and ‘RECTD50’, dose delivered to 50% of CBCT rectal volume by original treatment fields. Three candidate SEVs for treatment coverage were defined for each scan: anterior rectal wall movement, change in bladder length and bladder base movement. Both anterior rectal wall movement and increase in bladder length predicted for the decreased PTV95 (P < 0.001 for each). Anterior movement of the anterior rectal wall predicted for increased RECTD50 (P < 0.001). Predictive models for the PTV95 and RECTD50 that accept the significant SEVs as inputs were developed. We developed simple CBCT‐acquired soft tissue anatomic surrogate measures that signal changes in target coverage and rectal dose during post‐prostatectomy radiotherapy. Conventional bony anatomy patient position verification protocols were inadequate in accounting for soft tissue target and organ variation seen with CBCT.
Partial mid-portion Achilles tendon ruptures: new sonographic findings helpful for diagnosis
Authors: Alfredson Håkan , Masci Lorenzo , Öhberg Lars 
Published: November 2009

BackgroundPartial Achilles tendon ruptures are not always easy to diagnose. A history including a sudden onset of pain and/or relative weakness in plantar flexion force is an indicator. The most loaded side of the Achilles tendon is the dorsal side (skin side).ObjectiveThe aim of this study was to evaluate the ultrasound (US) and colour Doppler (CD) findings in patients with a suspected partial rupture in the Achilles tendon.Materials and MethodsSeventeen patients (16 men and 1 woman) with a mean age of 36 years (range 23–71 years) were examined clinically and by US+CD because of mid-portion Achilles tendon pain. There was an acute onset in 14 of 17 patients, and all had painful weakness during tendon loading activity.ResultsIn all patients, the US examination showed a partial Achilles tendon rupture, presented as a disrupted dorsal (skin side) tendon line and an irregular tendon structure mainly located in the dorsal and mid-tendon. The size of the rupture varied from 1/3 to 2/3 of the tendon thickness. In the dorsal part of the tendon, corresponding to the region with disrupted tendon line and irregular structure, CD examination showed high blood flow—most often of a longitudinal character. Six of the patients were surgically treated, and macroscopical examination verified the US findings showing disruption on the dorsal side and a partial rupture in the dorsal and mid-tendon.ConclusionsUS and Doppler examination can be helpful tools to diagnose partial mid-portion Achilles tendon ruptures. The characteristic findings of a disrupted dorsal tendon line and high blood flow in the structurally abnormal dorsal tendon indicate a partial rupture.