bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localization of mature neprilysin in lipid rafts
Authors: Sato Kimihiko , Tanabe Chiaki , Yonemura Yoji , Watahiki Haruhiko , Zhao Yimeng , Yagishita Sosuke , Ebina Maiko , Suo Satoshi , Futai Eugene , Murata Masayuki , Ishiura Shoichi 
Published: December 2011

AbstractAlzheimer's disease (AD) is characterized by senile plaques caused by amyloid‐β peptide (Aβ) accumulation. It has been reported that Aβ generation and accumulation occur in membrane microdomains, called lipid rafts, which are enriched in cholesterol and glycosphingolipids. Moreover, the ablation of cholesterol metabolism has been implicated in AD. Neprilysin (NEP), a neutral endopeptidase, is one of the major Aβ‐degrading enzymes in the brain. Activation of NEP is a possible therapeutic target. However, it remains unknown whether the activity of NEP is regulated by its association with lipid rafts. Here we show that only the mature form of NEP, which has been glycosylated in the Golgi, exists in lipid rafts, where it is directly associated with phosphatidylserine. Moreover, the localization of NEP in lipid rafts is enhanced by its dimerization, as shown using the NEP E403C homodimerization mutant. However, the protease activities of the mature form of NEP, as assessed by in vitro peptide hydrolysis, did not differ between lipid rafts and nonlipid rafts. We conclude that cholesterol and other lipids regulate the localization of mature NEP to lipid rafts, where the substrate Aβ accumulates but does not modulate the protease activity of NEP. © 2011 Wiley Periodicals, Inc.
Pituitary adenylate cyclase‐activating polypeptide counteracts the impaired adult neural stem cell viability induced by palmitate
Authors: Mansouri Shiva , Ortsäter Henrik , Pintor Gallego Otto , Darsalia Vladimer , Sjöholm Åke , Patrone Cesare 
Published: December 2011

AbstractDiabetes and obesity are characterized by hyperlipidemia and represent risk factors for premature neurological disorders. Diabetic/obese animals have impaired adult neurogenesis. We hypothesize that lipotoxicity leading to neurogenesis impairment plays a role in the development of neurological complications. If so, normalizing neurogenesis in diabetes/obesity could be therapeutically useful in counteracting neurological dysfunction. The goal of this study was to determine the potential of pituitary adenylate cyclase‐activating polypeptide (PACAP) to protect adult neural stem cells (NSCs) from lipotoxicity and to study the expression of PACAP receptors in NSCs under lipotoxic conditions in vitro and in the subventricular zone in vivo. The viability of NSCs isolated from the adult mouse brain subventricular zone was assessed in the presence of a high‐fat milieu, as mimicked by palmitate, which characterizes diabetic lipotoxicity. Regulation studies of PACAP receptors were performed by quantitative PCR on NSCs in vitro or on subventricular tissues isolated from obese ob/ob mice and their lean littermates. We show that palmitate impairs NSC viability by promoting lipoapoptosis. We also show that PACAP counteracts lipotoxicity via PAC‐1 receptor activation. Studies on PACAP receptor expression revealed that PAC‐1 and VPAC‐2 are expressed by NSC in vitro and are upregulated by palmitate treatment and that PAC‐1, VPAC‐1, and VPAC‐2 are expressed in the subventricular zone/striatum in vivo and are upregulated in ob/ob mice. The present study reveals a previously uncharacterized role of PACAP to protect NSC from lipotoxicity and suggests a potential therapeutic role for PACAP receptor agonists in the treatment of neurological complications in obesity and diabetes. © 2011 Wiley Periodicals, Inc.
Effect of chronic administration of estradiol, progesterone, and tibolone on the expression and phosphorylation of glycogen synthase kinase‐3β and the microtubule‐associated protein tau in the hippocampus and cerebellum of female rat
Authors: Pinto‐Almazán Rodolfo , Calzada‐Mendoza Claudia C. , Campos‐Lara María G. , Guerra‐Araiza Christian 
Published: December 2011

AbstractGonadal hormones regulate expression and activation of protein tau. Tibolone is a drug used as first‐ choice comprehensive treatment for the relief of menopausal symptoms, because it and its various metabolites have estrogenic properties and progestogenic/androgenic effects; however, the effect on the activation of tau protein and its signaling cascade in the brain is unknown. We studied the effect of chronic administration of estradiol (E2), progesterone (P4), and tibolone (TIB) on the expression and phosphorylation of microtubule‐associated protein tau and glycogen synthase kinase‐3β (GSK3β) in the hippocampus and cerebellum of ovariectomized rats. Ovariectomized adult female rats were implanted with pellets of vehicle, E2, or P4 or were treated with TIB by oral administration for 60 days. The animals were sacrificed, and tissue proteins were analyzed by Western blot. We observed that, in the hippocampus, administration of E2, P4, or TIB significantly decreased the protein content of hyperphosphorylated tau and increased the tau dephosphorylated form, whereas only treatment with TIB increased the content of the phosphorylated form of GSK3β. In the cerebellum, E2 and TIB treatments resulted in a significant decrease in the expression of hyperphosphorylated tau, whereas E2 and TIB increased phosphorylated GSK3β; P4 had no effect. These results indicate that chronic administration of gonadal hormones and tibolone modulates tau and GSK3β phosphorylation in hippocampus and cerebellum of the rat and may exert a neuroprotective effect in these tissues. © 2011 Wiley Periodicals, Inc.
Development of colour and firmness in strawberry crops is UV light sensitive, but colour is not a good predictor of several quality parameters
Authors: Ordidge Matthew , García‐Macías Paulina , Battey Nicholas H , Gordon Michael H , John Philip , Lovegrove Julie A , Vysini Eleni , Wagstaffe Alexandra , Hadley Paul 
Published: December 2011

AbstractBACKGROUND: Strawberry (Fragaria × ananassa Duchesne var. Elsanta) plants were grown in polytunnels covered with three polythene films that transmitted varying levels of ultraviolet (UV) light. Fruit were harvested under near‐commercial conditions and quality and yield were measured. During ripening, changes in the colour parameters of individual fruit were monitored, and the accuracy of using surface colour to predict other quality parameters was determined by analysing the correlation between colour and quality parameters within UV treatments.RESULTS: Higher exposure to UV during growth resulted in the fruit becoming darker at harvest and developing surface colour more quickly; fruit were also firmer at harvest, but shelf life was not consistently affected by the UV regime. Surface colour measurements were poorly correlated to firmness, shelf life or total phenolics, anthocyanins and ellagic acid contents.CONCLUSION: Although surface colour of strawberry fruits was affected by the UV regime during growth, and this parameter is an important factor in consumer perception, we concluded that the surface colour at the time of harvest was, contrary to consumer expectations, a poor indicator of firmness, potential shelf life or anthocyanin content. Copyright © 2011 Society of Chemical Industry
Impacts of climate change and inter‐annual variability on cereal crops in China from 1980 to 2008
Authors: Zhang Tianyi , Huang Yao 
Published: December 2011

AbstractBACKGROUND: Negative climate impacts on crop yield increase pressures on food security in China. In this study, climatic impacts on cereal yields (rice, wheat and maize) were investigated by analyzing climate‐yield relationships from 1980 to 2008.RESULTS: Results indicated that warming was significant, but trends in precipitation and solar radiation were not statistically significant in most of China. In general, maize is particularly sensitive to warming. However, increase in temperature was correlated with both lower and higher yield of rice and wheat, which is inconsistent with the current view that warming results in decline in yields. Of the three cereal crops, further analysis suggested that reduction in yields with higher temperature is accompanied by lower precipitation, which mainly occurred in northern parts of China, suggesting droughts reduced yield due to lack of water resources. Similarly, a positive correlation between temperature and yield can be alternatively explained by the effect of solar radiation, mainly in the southern part of China where water resources are abundant.CONCLUSION: Overall, our study suggests that it is inter‐annual variations in precipitation and solar radiation that have driven change in cereal yields in China over the last three decades. Copyright © 2011 Society of Chemical Industry
Who Pays More for a Cultural Festival, Tourists or Locals? A Certainty Analysis of a Contingent Valuation Application
Authors: Herrero Luis César , Sanz José Ángel , Bedate Ana , del Barrio María José 
Published: December 2011

ABSTRACTCultural festivals are one of the most common representations of diversification strategies in tourist demand in cities boasting abundant historical heritage. The goal of this work is to estimate the economic value allocated by tourists and local residents to a classical music festival in the emblematic city of Santiago de Compostela (Spain). The contingent valuation method is used to ascertain whether there are any significant differences between the value declared and to study the sensitivity of the findings in a range of socio‐economic variables. Finally, the problems of hypothetical bias are explored, as are the possible implications for management of pricing policies. Copyright © 2011 John Wiley & Sons, Ltd.
Habitat selection by northern spotted owls in mixed‐coniferous forests
Authors: Irwin Larry L. , Rock Dennis F. , Rock Suzanne C. 
Published: December 2011

AbstractConservation planning for the federally threatened northern spotted owl (Strix occidentalis caurina) requires an ability to predict their responses to existing and future habitat conditions. To inform such planning we modeled habitat selection by northern spotted owls based upon fine‐scale (approx. 1.0 ha) characteristics within stands comprised primarily of mixed‐aged, mixed coniferous forests of southwestern Oregon and north‐central California. We sampled nocturnal (i.e., primarily foraging) habitat use by 71 radio‐tagged spotted owls over 5 yr in 3 study areas and sampled vegetative and physical environmental conditions at inventory plots within 95% utilization distributions of each bird. We compared conditions at available forest patches, represented by the inventory plots, with those at patches used by owls using discrete‐choice regressions, the coefficients from which were used to construct exponential resource selection functions (RSFs) for each study area and for all 3 areas combined. Cross‐validation testing indicated that the combined RSF was reasonably robust to local variation in habitat availability. The relative probability that a fine‐scale patch was selected decreased nonlinearly with distances from nests and streams; varied unimodally with increasing average diameter of coniferous trees and also with increasing basal area of Douglas‐fir (Pseudotsuga menziesii) trees; increased linearly with increasing basal areas of sugar pine (Pinus lambertiana) and hardwood trees and with increasing density of understory shrubs. Large‐diameter trees (>66 cm) appeared important <400 m from nest sites. The RSF can support comparative risk assessments of the short‐ versus long‐term effects of silvicultural alternatives designed to integrate forest ecosystem restoration and habitat improvement for northern spotted owls. Results suggest fine‐scale factors may influence population fitness among spotted owls. © 2011 The Wildlife Society.
In Silico Models to Discriminate Compounds Inducing and Noninducing Toxic Myopathy
Authors: Hu Xiaoying , Yan Aixia 
Published: December 2011

AbstractToxic myopathy is a muscular disease in which the muscle fibers do not function and which results in muscular weakness. Some drugs, such as lipid‐lowering drugs and antihistamines, can cause toxic myopathy. In this work, a dataset containing 232 chemical compounds inducing toxic myopathy (IM‐compounds) and 117 drugs not inducing toxic myopathy (notIM‐compounds) was collected. The dataset was split into a training set (containing 270 compounds) and a test set (containing 79 compounds). A Kohonen’s self‐organizing map (SOM) and a support vector machine (SVM) were applied to develop classification models to differentiate IM‐compounds and notIM‐compounds. Polarizibity related descriptors, electronegativity related descriptors, atom charges related descriptors, H‐bonding related descriptor, atom identity and molecular shape descriptors were used to build models. Using the SOM method, classification accuracies of 88.4 % for the training set and 88.2 % for the test set were achieved; using the SVM method, classification accuracies of 95.6 % for the training set and 86.1 % for the test set were achieved. In addition, extended connectivity fingerprints (ECFP_4) were calculated and analyzed to find important substructures of molecules relating to toxic myopathy.
Influence of severity of anemia on clinical findings in infants with sickle cell anemia: Analyses from the BABY HUG study
Authors: Lebensburger Jeffrey D. , Miller Scott T. , Howard Thomas H. , Casella James F. , Brown R. Clark , Lu Ming , Iyer Rathi V. , Sarnaik Sharada , Rogers Zora R. , Wang Winfred C. ,   for the BABY HUG Investigators
Published: December 2011

AbstractBackgroundClinical complications of sickle cell anemia begin in infancy. BABY HUG (ClinicalTrials.gov, NCT00006400) was a NHLBI‐NICHD supported randomized phase III placebo‐controlled trial of hydroxyurea (HU) in infants (recruited at 9–18 months) unselected for clinical severity with sickle cell anemia. This secondary analysis of data from BABY HUG examines the influence of anemia on the incidence of sickle cell related complications, and the impact of hydroxyurea therapy in altering these events by comparing children with lower (<25th percentile) and higher (>75th percentile) hemoglobin concentrations at study entry.ProcedureInfants were categorized by: (1) age‐adjusted hemoglobin quartiles as determined by higher (Hi) and lower (Lo) hemoglobin concentrations at study entry (9–12 months old: <8.0 and >10.0 gm/dL; 12–18 months old: <8.1 and >9.9 gm/dL) and (2) treatment arm (hydroxyurea or placebo). Four subgroups were created: placebo (PL) LoHb (n = 25), PL HiHb (n = 27), hydroxyurea (HU) LoHb (n = 21), and HU HiHb (n = 18). The primary and secondary endpoints of BABY HUG were analyzed by subgroup.ResultsInfants with lower hemoglobin at baseline were more likely to have a higher incidence of clinical events (acute chest syndrome, pain crisis, fever) as well as higher TCD velocities and lower neuropsychological scores at study exit. Hydroxyurea reduced the incidence of these findings.ConclusionInfants with more severe anemia are at risk for increased clinical events that may be prevented by early initiation of hydroxyurea. Pediatr Blood Cancer 2012;59:675–678. © 2011 Wiley Periodicals, Inc.
Tumor necrosis predicts survival following neo‐adjuvant chemotherapy for hepatoblastoma
Authors: Venkatramani Rajkumar , Wang Larry , Malvar Jemily , Dias Dennis , Sposto Richard , Malogolowkin Marcio H. , Mascarenhas Leo 
Published: December 2011

AbstractBackgroundTumor response to chemotherapy has been shown to predict outcome in children with acute lymphoblastic leukemia, osteosarcoma, and Ewing Sarcoma. We evaluated whether tumor necrosis following neo‐adjuvant chemotherapy is prognostic for survival in hepatoblastoma (HB).ProcedurePrimary tumors from children with newly diagnosed stage III and IV HB who underwent surgical resection following neo‐adjuvant chemotherapy were evaluated histologically for the extent of tumor necrosis (total diameter of necrotic and fibrotic tissue divided by total diameter of tumor). Clinical features, laboratory values, pathological features, treatment delivered, and vital status were recorded. Univariate and multivariate Cox regression analyses were performed to evaluate prognostic factors.ResultsThirty‐two patients were evaluable. After a median of four cycles of neo‐adjuvant chemotherapy gross total surgical resection was achieved in 29 patients and complete resection documented by histology in 22 patients. Three‐year event free survival (EFS) and overall survival (OS) of the evaluable patients were 70.3 ± 8.3% and 76.8 ± 7.6%, respectively. Extent of tumor necrosis, platelet count at diagnosis, decline in serum alpha fetoprotein, and surgical margin status (positive vs. negative) were statistically significant predictors for both EFS and OS by univariate analysis. Multivariate analyses revealed that extent of tumor necrosis and surgical margin status predicted improved EFS (P < 0.001) and OS (P < 0.0001).ConclusionsExtent of tumor necrosis following neo‐adjuvant chemotherapy is an independent prognostic factor in patients with newly diagnosed HB. Histological response may potentially be used in strategies to modify post‐surgical therapy to improve survival in HB. Pediatr Blood Cancer 2012;59:493–498. © 2011 Wiley Periodicals, Inc.
SUV‐measurements and patient‐specific corrections in pediatric Hodgkin‐lymphoma: Is there a benefit for PPV in early response assessment by FDG‐PET?
Authors: Furth Christian , Meseck Robert M. , Steffen Ingo G. , Schoenberger Stefan , Denecke Timm , Henze Günter , Hautzel Hubertus , Hofheinz Frank , Großer Oliver , Hundsdoerfer Patrick , Amthauer Holger , Ruf Juri 
Published: December 2011

AbstractBackgroundTo evaluate the influence of different SUV‐measurements and patient‐specific corrections thereof on the positive predictive value (PPV) of FDG‐PET in pediatric Hodgkin lymphoma (pHL) using SUV‐based response assessment.MethodsPET‐datasets of 33 children [female, n = 13, male, n = 20; range of age, 8.0–17.8 (mean, 15.0) years; follow‐up, 44.5–83.3 (mean 63.0) months] with HL were analyzed retrospectively. PET‐scans were obtained baseline (PET1) and after two cycles of chemotherapy (PET2). Within the leading lesion maximal SUV (SUVmax) and mean SUVs were generated by using isocontur‐thresholds for different volumes of interest: Absolute, SUV2.5; relative to SUVmax, SUVmean40% to SUVmean70%. Generated SUVs were adjusted to body weight (SUV) and corrected for body surface area (SUV_BSA), patient's blood glucose and a combination thereof. The decrease in SUV or respective derivates thereof between PET1 and PET2 (ΔSUV) was assessed for response prediction using receiver operating characteristics (ROC)‐analysis.ResultsThree patients had recurrence of disease. ROC‐analysis showed the most accurate differentiation of responders and non‐responders for ΔSUVmax_BSA [AUC, 0.97; P = 0.0026; sensitivity, 100%; specificity, 93.3%; PPV, 60.0%; negative predictive value (NPV), 100%; accuracy, 93.3%]. However, comparable results were obtained for conventional ΔSUVmax‐determination (AUC, 0.96; P = 0.0112; sensitivity, 100%; specificity, 90.0%; PPV, 50.0%; NPV, 100%; accuracy, 90.9%). Threshold‐based approaches were less effective or technically not performable in all patients.ConclusionsAt early response assessment by FDG‐PET, patient‐specific correction of ΔSUVmax by BSA improves PPV without impairment of excellent NPV in pHL. However, it is not statistically superior to simple ΔSUVmax‐analyses. Larger cohorts are needed to investigate this observation. Pediatr Blood Cancer 2012;59:475–480. © 2011 Wiley Periodicals, Inc.
Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma
Authors: Grill Jacques , Puget Stephanie , Andreiuolo Felipe , Philippe Cathy , MacConaill Laura , Kieran Mark W. 
Published: December 2011

AbstractDiffuse intrinsic pontine gliomas (DIPG) can not be cured with current treatment modalities. Targeted therapy in this disease would benefit from advanced technologies detecting relevant drugable mutations. Twenty patients with classic newly diagnosed DIPG underwent stereotactic biopsies and were analyzed for the presence of 983 different mutations in 115 oncogenes and tumor‐suppressor genes using OncoMap, a mass spectrometric method of allele detection. Our results identified oncogenic mutations in TP53 (40%), PI3KCA (15%), and ATM/MPL (5%) while none were identified in a large number of other genes commonly mutated in malignant gliomas. The identification of oncogenic mutations in the PI3K pathway offers the potential of a therapeutic target at initial diagnosis in this devastating disease. Pediatr Blood Cancer 2012; 58: 489–491. © 2011 Wiley Periodicals, Inc.
Strigolactones—intriguing biologically active compounds: perspectives for deciphering their biological role and for proposing practical application
Authors: Vurro Maurizio , Yoneyama Koichi 
Published: December 2011

AbstractStrigolactones are a class of bioactive natural metabolites produced by plant roots and released into the rhizosphere. They were discovered as signals indispensable for the induction of germination of seeds of root parasitic weeds, but since then, interestingly, many other biological, physiological and ecological roles have been described. This has suddenly provoked huge scientific interest in these compounds within different research fields. In this short perspective the attention is focused mainly on the ongoing and future research aimed at deciphering the biological roles of strigolactones that could positively affect, more or less directly, the management of parasitic weeds. Copyright © 2012 Society of Chemical Industry
‘A Place to Stay in Pakistan’: Why Migrants Build Houses in their Country of Origin
Authors: Erdal Marta Bivand 
Published: December 2011

ABSTRACTMigrants' houses are a common feature of many regions of emigration globally and are one manifestation of migrants' transnational ties. This paper explores why migrants' build houses in their country of origin, even when migrants are not planning to return. The paper aims to analyze migrants' houses as relational places located in transnational social space. This is done through an analysis of the reasons for building migrants' houses, which shows the significance of these houses as relational places, in practical and symbolic ways. This is supported by a transnational perspective that includes the different views on migrants' houses among involved actors across transnational social space: the migrants, their relatives, the local communities the houses are built in, and societies where migrants have settled. The data for this paper consist of 45 semi‐structured interviews with Pakistani migrants in Norway and non‐migrant relatives in Pakistan, informal conversations with local Pakistanis, and analysis of media reports in Norway. Copyright © 2011 John Wiley & Sons, Ltd.
Hydrogen bond networks: Structure and dynamics via first‐principles spectroscopy
Authors: Schiffmann Christoph , Sebastiani Daniel 
Published: December 2011

AbstractDifferent hydrogen bonding networks, same principle: hydrogen bonds are the most common fundamental structural driving forces, which determine structural and dynamical properties of numerous functional materials. First‐principles calculations of spectroscopic parameters can help to understand local geometric motifs, but also more complex processes such as hydrogen bond lifetimes and ion transport processes in condensed phases. In this feature article, we review the relevance of structure–spectroscopy‐relationships, we discuss recent ab initio calculations eludicating the structure of supramolecular assemblies, and highlight the importance of incorporating atomic and molecular mobility by means of molecular dynamics (MD) simulations.magnified imageComplex hydrogen bonding networks: vinyl‐phosphonic acid polymers (left) and aqueous hydrochloric acid (right).