bluuebunny/crossref_metadata_2025_split huggingface dataset:
Panencephalopathic Creutzfeldt‐Jakob Disease with Distinct Pattern of Prion Protein Deposition in a Patient with D178N Mutation and Homozygosity for Valine at Codon 129 of the Prion Protein Gene
Authors: Marcon Gabriella , Indaco Antonio , Di Fede Giuseppe , Suardi Silvia , Finato Nicoletta , Moretti Valentino , Micoli Sandro , Fociani Paolo , Zerbi Pietro , Pincherle Alessandro , Redaelli Veronica , Tagliavini Fabrizio , Giaccone Giorgio 
Published: October 2013

AbstractPrion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53‐year‐old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt‐Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic‐type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrPSc (Parchi classification). These findings underline the clear‐cut distinction between the neuropathological features of Creutzfeldt‐Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.
In vitro and in vivo anti‐tumour effects of MPT0B014, a novel derivative aroylquinoline, and in combination with erlotinib in human non‐small‐cell lung cancer cells
Authors: Tsai An‐Chi , Pai Hui‐Chen , Wang Chih‐Ya , Liou Jing‐Ping , Teng Che‐Ming , Wang Jing‐Chi , Pan Shiow‐Lin 
Published: October 2013

Background and PurposeThe purpose of the current study was to assess a novel anti‐cancer drug, MPT0B014, which is not a substrate for the P‐glycoprotein (P‐gp) transporter, alone and in combination with erlotinib, against human non‐small cell lung cancer (NSCLC).Experimental ApproachCytotoxicity in human NSCLC cell lines was assessed by sulforhodamine B and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays. Cell cycle phase distributions were estimated with FACScan flow cytometry. Protein expression was detected by Western blotting analysis. Efflux of rhodamine 123 or calcein‐acetoxymethylester was used to study the P‐gp profile. The A549 xenograft model in mice was used to assess in vivo anti‐tumour activity.Key ResultsMPT0B014 showed potent anti‐proliferative activity against A549, H1299 and H226 cells. It induced G2/M arrest with down‐regulation of Cdc (Tyr15) and Cdc25C, and up‐regulation of cyclin B1, phospho‐Cdc2 (Thr161) and Aurora A/B. P‐gp‐overexpressing National Cancer Institute/Adriamycin‐Resistant cells were also sensitive to B014. B014‐induced loss of Mcl‐1 was accompanied by activation of caspases‐3, ‐7, ‐8 and ‐9, and initiation of apoptosis. B014 in combination with erlotinib caused significant tumour inhibition in vitro and in vivo.Conclusions and ImplicationsMPT0B014 exerted cytotoxicity against human NSCLC cell lines with little susceptibility to P‐gp. Combined with the EGF receptor inhibitor, erlotinib, MPT0B014 exerted significant growth inhibition of A549 cells both in vitro and in vivo. B014 could be useful as an anti‐cancer agent.
Loop diuretics are open‐channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics
Authors: Ju Min , Scott‐Ward Toby S , Liu Jia , Khuituan Pissared , Li Hongyu , Cai Zhiwei , Husbands Stephen M , Sheppard David N 
Published: October 2013

Background and PurposeLoop diuretics are widely used to inhibit the Na+, K+, 2Cl− co‐transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade.Experimental ApproachUsing the patch‐clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild‐type human CFTR.Key ResultsWhen added to the intracellular solution, loop diuretics inhibited CFTR Cl− currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to loop diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl− channels with ‘very fast’ speed and drug‐induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with ‘intermediate’ speed and drug‐induced blocking events were distinct from channel closures.Conclusions and ImplicationsStructure–activity analysis of the loop diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking loop diuretics within the intracellular vestibule of the CFTR pore. We conclude that loop diuretics are open‐channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity.
Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity
Authors: Tan Xiahui , Sanderson Michael J 
Published: October 2013

Background and PurposeWhile selective, bitter tasting, TAS2R agonists can relax agonist‐contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca2+ signalling and Ca2+ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinine and denotonium regulate contractile agonist‐induced Ca2+ signalling and sensitivity.Experimental ApproachAirways in mouse lung slices were contracted with either methacholine (MCh) or 5HT and bronchodilation assessed using phase‐contrast microscopy. Ca2+ signalling was measured with 2‐photon fluorescence microscopy of ASM cells loaded with Oregon Green, a Ca2+‐sensitive indicator (with or without caged‐IP3). Effects on Ca2+ sensitivity were assessed on lung slices treated with caffeine and ryanodine to permeabilize ASM cells to Ca2+.Key ResultsThe TAS2R10 agonists dilated airways constricted by either MCh or 5HT, accompanied by inhibition of agonist‐induced Ca2+ oscillations. However, in non‐contracted airways, TAS2R10 agonists, at concentrations that maximally dilated constricted airways, did not evoke Ca2+ signals in ASM cells. Ca2+ increases mediated by the photolysis of caged‐IP3 were also attenuated by chloroquine, quinine and denotonium. In Ca2+‐permeabilized ASM cells, the TAS2R10 agonists dilated MCh‐ and 5HT‐constricted airways.Conclusions and ImplicationsTAS2R10 agonists reversed bronchoconstriction by inhibiting agonist‐induced Ca2+ oscillations while simultaneously reducing the Ca2+ sensitivity of ASM cells. Reduction of Ca2+ oscillations may be due to inhibition of Ca2+ release through IP3 receptors. Further characterization of bronchodilatory TAS2R agonists may lead to the development of novel therapies for the treatment of bronchoconstrictive conditions.
Temperate mountain grasslands: a climate‐herbivore hypothesis for origins and persistence
Authors: Weigl Peter D. , Knowles Travis W. 
Published: October 2013

ABSTRACTTemperate montane grasslands and their unique biotas are declining worldwide as they are increasingly being invaded by forests. The origin and persistence of these landscapes have been the focus of such controversy that in many areas their conservation is in doubt. In the USA some biologists have largely dismissed the grass balds of the Southern Appalachians as human artifacts or anomalous and transitory elements of regional geography, worthy of only limited preservation efforts. On the basis of information from biogeography, community ecology, regional history and palaeontology and from consideration of two other montane grassland ecosystems—East Carpathian poloninas and Oregon Coast Range grass balds—we hypothesize that these landscapes are more widespread than was formerly recognized; they are, in many cases, natural and ancient and largely owe their origin and persistence to past climatic extremes and the activities of large mammalian herbivores.
Seed‐swallowing Toucans are Less Effective Dispersers of Guettarda viburnoides (Rubiaceae) than Pulp‐feeding Jays
Authors: Loayza Andrea P. , Rios Rodrigo S. 
Published: October 2013

AbstractFor many tropical plants, birds are the most important seed dispersers. Not all birds, however, will provide equally effective dispersal services. Behavioral differences, during and after feeding, can result in different establishment probabilities of new individuals. During 3 yr, we examined species‐specific quantitative and qualitative aspects of Guettarda viburnoides seed dispersal by avian frugivores, focusing on how these aspects modify seed dispersal effectiveness. Fruits of G. viburnoides were consumed by ten species of birds, two of which, Cyanocorax cyanomelas and Pteroglossus castanotis, removed 80 percent of the fruits. These two species differ in qualitative aspects of seed dispersal. First, they select for fruits of different sizes; C. cyanomelas feeds on larger fruits than P. castanotis, which results in the former dispersing larger endocarps than the latter. Second, they differ in their fruit handling treatment; C. cyanomelas are pulp consumers, whereas P. castanotis swallow the fruit whole, and are thus traditionally considered ‘legitimate’ dispersers. The probability of seedling emergence, the temporal pattern of emergence, the number of emerged seedlings per endocarp, and the probability of post‐dispersal seed predation differs between endocarps dispersed by C. cyanomelas and P. castanotis; endocarps dispersed by the former have higher emergence probabilities, higher number of seedlings, faster emergence times, and lower predation probabilities than those dispersed by the latter. Finally, these birds differ in their landscape patterns of endocarp deposition; C. cyanomelas disperses endocarps to habitats with higher recruitment probabilities. Ultimately, the pulp consumer C. cyanomelas is a more effective disperser of G. viburnoides than P. castanotis.
Therapeutic role of EF24 targeting glucose transporter 1‐mediated metabolism and metastasis in ovarian cancer cells
Authors: Zhang Dandan , Wang Yan , Dong Lina , Huang Yangang , Yuan Jing , Ben Wei , Yang Yang , Ning Ning , Lu Meisong , Guan Yongmei 
Published: October 2013

Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells, increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer. However, it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis. In the present research, we found that EF24, a HIF‐1α inhibitor, could significantly block glucose uptake, the rate of glycolysis, and lactate production compared with vehicle treatment in SKOV‐3, A2780 and OVCAR‐3 cells. These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays. Furthermore, as an important mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to contribute to the function of EF24 in both energy metabolism and metastasis. To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model were introduced. Our results indicated that EF24 treatment could inhibit tumor growth, intraperitoneal metastasis and lung metastasis of SKOV‐3 cells, and Glut1 is a possible mediator for the role of EF24. In conclusion, our results highlight that an anti‐cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis, and EF24 is a possible candidate for anti‐metastasis therapeutic applications for ovarian cancer.
p53 accumulation is a strong predictor of recurrence in estrogen receptor‐positive breast cancer patients treated with aromatase inhibitors
Authors: Yamamoto Mitsugu , Hosoda Mitsuchika , Nakano Kiichiroh , Jia Shusheng , Hatanaka Kanako C. , Takakuwa Emi , Hatanaka Yutaka , Matsuno Yoshihiro , Yamashita Hiroko 
Published: October 2013

Aromatase inhibitors have played a central role in endocrine therapy for estrogen receptor (ER)‐positive breast cancer in postmenopausal women. However, factors predictive of the efficacy of aromatase inhibitors, and prognostic factors, both for early and late recurrence in women treated with adjuvant aromatase inhibitors have not been identified. Whole genome analysis identified that a TP53 gene mutation exists in ER‐positive breast cancers, although the frequency of TP53 gene mutation in luminal tumors is lower compared with basal‐like or human epidermal growth factor receptor type 2 (HER2)‐positive breast cancers. We examined expression of p53, as well as ER, progesterone receptor, HER2 and Ki‐67 using immunohistochemistry in postmenopausal ER‐positive breast cancer patients who were treated with aromatase inhibitors as adjuvant endocrine therapy. There were 53 (21%) tumors that contained 10% or more p53‐positive cells. High p53 expression was positively correlated with tumor grade, HER2 score and Ki‐67 expression. Significant association was observed between disease‐free survival and high p53 expression in multivariate analysis (P < 0.0001). Compared with women without recurrence, women with early recurrence had significantly higher p53 expression (P < 0.0001), as did women with late recurrence (P = 0.037). The present study demonstrates that p53 accumulation is a strong predictor of both early and late recurrence in ER‐positive breast cancer patients treated with aromatase inhibitors as adjuvant endocrine therapy. TP53 gene alteration might be a key biological characteristic of ER‐positive breast cancer.
Family environment and attention‐deficit/hyperactivity disorder in adopted children: associations with family cohesion and adaptability
Authors: Crea T. M. , Chan K. , Barth R. P. 
Published: October 2013

AbstractBackgroundPositive family environments are crucial in promoting children's emotional and behavioural well‐being, and may also buffer development of attention‐deficit/hyperactivity disorder (ADHD). ADHD is highly heritable, but psychosocial factors in the family environment, particularly family cohesion and communication, may mediate genetic predispositions. The purpose of the current study is to examine the mediating influence of the adoptive family environment between pre‐adoptive risk factors and youths' ADHD symptomatology at 14 years post adoption.MethodsThe data used in this study were obtained from the fourth wave of the California Long‐Range Adoption Study (CLAS) (n = 449). Using structural equation modelling (SEM), family sense of coherence and family adaptability were tested as possible mediators between environmental and biological predictors and ADHD symptomatology. Predictors included birthweight, gender, age at adoption, adoption from foster care, transracial adoption status, ethnicity and having a previous diagnosis of ADHD.ResultsResults show that, while adoption from foster care is negatively associated with family functioning, higher family cohesion and adaptability mediate this influence on children's ADHD symptomatology. Older age of adoption directly predicts greater ADHD symptoms with no mediating influence of the family environment.ConclusionsThe mediating influence of the family environment between children's risk factors and ADHD symptoms suggests that family intervention strategies may be helpful in improving adopted children's outcomes. Once children are adopted, targeting family communication patterns and dynamics may be an additional part of developing an evidence‐based, post‐adoption services toolkit.
Pollution and Infant Health
Authors: Currie Janet 
Published: October 2013

AbstractIn this article, I review recent research showing that even relatively low levels of pollution can affect infants' health. This research attempts to go beyond documenting correlations by using sharp changes in pollution levels, carefully selecting control groups (including unexposed siblings as controls for exposed children), and considering behavioral responses to pollution such as maternal mobility. Poor and minority children are more likely to be affected, and differential exposure could be responsible for some of the observed group‐level differences in health at birth. Policy makers concerned about the roots of inequality should consider the role played by environmental exposures of pregnant mothers.
Toddlers Default to Canonical Surface‐to‐Meaning Mapping When Learning Verbs
Authors: Dautriche Isabelle , Cristia Alejandrina , Brusini Perrine , Yuan Sylvia , Fisher Cynthia , Christophe Anne 
Published: October 2013

Previous work has shown that toddlers readily encode each noun in the sentence as a distinct argument of the verb. However, languages allow multiple mappings between form and meaning that do not fit this canonical format. Two experiments examined French 28‐month‐olds' interpretation of right‐dislocated sentences (nouni‐verb, nouni) where the presence of clear, language‐specific cues should block such a canonical mapping. Toddlers (N = 96) interpreted novel verbs embedded in these sentences as transitive, disregarding prosodic cues to dislocation (Experiment 1) but correctly interpreted right‐dislocated sentences containing well‐known verbs (Experiment 2). These results suggest that toddlers can integrate multiple cues in ideal conditions, but default to canonical surface‐to‐meaning mapping when extracting structural information about novel verbs in semantically impoverished conditions.
Parent–Child Discrepancies in Educational Expectations: Differential Effects of Actual Versus Perceived Discrepancies
Authors: Wang Yijie , Benner Aprile D. 
Published: October 2013

This study explored how discrepancies between parents' and adolescents' educational expectations influenced adolescents' achievement using a nationally representative, longitudinal sample of 14,041 students (14 years old at baseline). Actual discrepancies (i.e., those between parents' and adolescents' actual educational expectations) and perceived discrepancies (i.e., those between adolescents' perceptions of their parents' educational expectations and adolescents' own) were examined. Achievement was higher when parents actually held higher expectations than adolescents held or when adolescents perceived that their parents' expectations were lower than their own. In contrast, achievement was lower when parents actually held lower expectations than adolescents held or when adolescents believed that their parents' expectations exceeded their own. Implications for identifying adolescents at risk and promoting adaptive parent–child educational expectations are discussed.
Highly expressed cytoplasmic FcεRIβ in human mast cells functions as a negative regulator of the FcRγ‐mediated cell activation signal
Authors: Okayama Y. , Matsuda A. , Kashiwakura J.‐I. , Sasaki‐Sakamoto T. , Nunomura S. , Shimokawa T. , Yamaguchi K. , Takahashi S. , Ra C. 
Published: October 2013

SummaryBackgroundWe recently reported that the interaction between Lyn and FcεRIβ is indispensable for FcεRI‐mediated human mast cell (MC) activation and that FcεRIβ functions as an amplifier of FcεRI‐mediated activation signal. Some of FcεRIβ in cytoplasm appeared not to be co‐localized with FcεRIα. The function of FcεRIβ in the cytoplasm remains unknown.MethodsThe localization of FcεRIβ and FcεRIα in giant papillae specimens from patients with allergic keratoconjunctivitis and of FcεRIβ, FcεRIα, and Lyn in cultured human MCs was examined using confocal microscopy. FcεRIβ was overexpressed using an adenovirus vector system. Mediators were measured by enzyme immunoassays or enzyme‐linked immunosorbent assays.ResultsIn the subepithelial region, FcεRIβ was mainly localized in the cell membrane of MCs. In the perivascular region, FcεRIβ expression was scattered throughout the cytoplasm and in the cell membrane of MCs. Overexpression of FcεRIβ in MCs mainly increased its cytoplasmic expression and slightly up‐regulated cell surface FcεRI expression. However, overexpression of FcεRIβ in MCs resulted in down‐regulation of the tyrosine phosphorylation levels of FcεRIβ and Syk and down‐regulation of the Ca2+ influx soon after FcεRI aggregation and then resulted in down‐regulation of degranulation, PGD2 synthesis, and production of a set of cytokines. This negative regulatory effect may be due to inhibition of the redistribution of Lyn to small patches within the plasma membrane.ConclusionCytoplasmic FcεRIβ, which is not co‐localized with FcεRIα, may function as a negative regulator, as it can capture important signalling molecules such as Lyn.
VB-201, an oxidized phospholipid small molecule, inhibits CD14- and Toll-like receptor-2-dependent innate cell activation and constrains atherosclerosis
Authors: Mendel I , Feige E , Yacov N , Salem Y , Levi I , Propheta-Meiran O , Shoham A , Ishai E , George J , Harats D , Breitbart E 
Published: October 2013

Summary
Atherosclerosis is an inflammatory disease of the vascular wall. Activated monocytes and dendritic cells (DC) in the intima layer of the vasculature promote atherogenesis. Toll-like receptor (TLR)-2 and TLR-4, which are predominantly expressed on these cells and mediate their activation, are essential for atherosclerosis development. In this study we demonstrate that VB-201, an oxidized phospholipid (Ox-PL) small molecule, inhibits TLR signalling restricted to TLR-2 and TLR-4 in human and mouse monocytes and DC. Mechanistically, we show that VB-201 binds directly to TLR-2 and CD14, the TLR-4 co-receptor, to impair downstream cues and cytokine production. In a rabbit model, oral administration of VB-201 constrained atherosclerosis progression. This effect was not due to reduced cholesterol abundance, as hyperlipidaemia was sustained. We suggest that VB-201 may counter inflammation where TLR-2 and/or CD14 complicity is essential, and is therefore beneficial for the treatment of atherosclerosis.