bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective expression of Drebrin in hippocampus improves cognitive function and alleviates lesions of Alzheimer's disease in APP (swe)/PS1 (ΔE9) mice
Authors: Liu Yan , Xu Yan‐Feng , Zhang Ling , Huang Lan , Yu Pin , Zhu Hua , Deng Wei , Qin Chuan 
Published: June 2017

Summary
AimsAlzheimer's disease (AD), a progressive development dementia, is increasingly impacting patients’ living conditions worldwide. Despite medical care and funding support, there are still no highly individualized drugs and practical strategies for clinical prevention and treatment. Developmentally regulated brain protein (abbreviated as Drebrin or Dbn, also known as Dbn1 in mouse) exists in neurons, especially in dendrites, and is an actin‐binding protein that modulates synaptic morphology and long‐term memory. However, the majority of previous studies have focused on its upstream proteins and neglected the impact Drebrin has on behavior and AD in vivo.MethodsHere, we tracked the behavioral performances of 4‐, 8‐, 12‐, and 16‐month‐old AD mice and investigated the expression level of Drebrin in their hippocampi. A Pearson correlation analysis between Drebrin levels and behavioral data was performed. Subsequently, 2‐month‐old AD mice were injected with rAAV‐zsGreen‐Dbn1 vector, composing the APP/PS1‐Dbn1 group, and sex‐ and age‐matched AD mice were injected with rAAV‐tdTomato vector to serve as the control group. All mice were conducted behavioral tests and molecular detection 6 months later.Results(i) The expression of Drebrin is decreased in the hippocampus of aged AD mice compared with that of age‐matched WT and young adult AD mice; (ii) cognitive ability of APP/PS1 mice decreases with age; (iii) Drebrin protein expression in the hippocampus correlates with behavioral performance in different aged AD mice; (iv) cognitive ability improved significantly in APP/PS1‐Dbn1 mice; (v) the expression level of Drebrin in APP/PS1‐Dbn1 mouse hippocampus was significantly increased; (vi) the pathological lesion of AD was alleviated in APP/PS1‐Dbn1 mice; (vii) the filamentous actin (F‐actin) and microtubule‐associated protein 2(MAP‐2) in APP/PS1‐Dbn1 mice were notably more than control mice.ConclusionIn this study, an effective expression of Drebrin improves cognitive abilities and alleviates lesions in an AD mouse model. These results may provide some valid resources for therapy and research of AD.
Downregulation of USP32 inhibits cell proliferation, migration and invasion in human small cell lung cancer
Authors: Hu Wenyu , Wei Haiyan , Li Keming , Li Pei , Lin Jiamao , Feng Rui 
Published: June 2017

AbstractObjectivesUbiquitin specific protease 32 (USP32) is a highly conserved but uncharacterized gene, which has been reported to be associated with growth of breast cancer cells. However, the role of USP32 in human small cell lung cancer (SCLC) has not been uncovered. The aim of this study was to investigate and evaluate the clinical significance of USP32 in patients with SCLC.Materials and methodsExpression of USP32 was firstly investigated using public online data sets and then determined in SCLC tissues and cell lines using quantitative real‐time PCR, Western blotting and immunohistochemical staining. SCLC cells were transfected with a small‐interfering RNA targeting USP32 mRNA and analysed for cell viability, proliferation ability, cell cycle distribution, apoptosis and invasion.ResultsUSP32 was found to be overexpressed in SCLC tissues compared with normal tissues. High USP32 expression was significantly correlated with disease stage and invasion. In vitro experiments demonstrated that silencing of USP32 caused a significant decrease in the proliferation and migration rate of cells. Furthermore, USP32 silencing arrested cell cycle progression at G0/G1 phase via decreasing CDK4/Cyclin D1 complex and elevating p21. In addition, downregulation of USP32 significantly induced cell apoptosis by activating cleaved caspase‐3 and cleaved PARP, as well as inhibiting cell invasiveness via altering epithelial mesenchymal transition expression.ConclusionsOur results suggest for the first time that USP32 is important for SCLC progression and might be a potential target for molecular therapy of SCLC.
Attitudes in Australia on the upscheduling of over‐the‐counter codeine to a prescription‐only medication
Authors: McCoy Jacqui , Bruno Raimondo , Nielsen Suzanne 
Published: June 2017

AbstractIntroduction and Aims. In December 2016, the Australian Therapeutic Goods Administration announced that over‐the‐counter (OTC) codeine would be available by prescription‐only in February 2018. Prior to this announcement, the authors aimed to evaluate attitudes among Australian codeine consumers, pharmacists and general medical practitioners (GP) towards the proposed upscheduling of OTC codeine. Design and Methods. Public Therapeutic Goods Administration submissions on codeine upscheduling were assessed, and a brief questionnaire was developed to assess the common issues raised. Participants (354 codeine consumers; 220 pharmacists; 120 GPs) completed a web‐based questionnaire. Comparisons of attitudes on specific statements related to codeine upscheduling were made between consumers who were in support and those who opposed the proposal and between pharmacists and GPs. Regression models were conducted to examine correlates of attitudes towards codeine restriction. Results. Most consumer, pharmacist and a third of GP respondents opposed the upscheduling of codeine. Consumers, on average, questioned whether the proposed intervention would address the intended targets of minimising codeine‐related side effects and risk of codeine dependence. Like consumers, pharmacists indicated concern around whether codeine restriction would address concerns of associated harm and dependence, as well as the burden regular GP appointments would create in terms of finances for consumers and time for GPs. GPs themselves, did not support these views. Discussion and Conclusions. Consumer responses identify key targets for educational campaigns when codeine is rescheduled, particularly around effective alternatives to OTC codeine. Additionally, contrasting views of pharmacists and GPs reinforce the importance of pharmacovigilance in evaluating the effectiveness of codeine restriction, once implemented. [McCoy J, Bruno R, Nielsen S. Attitudes in Australia on the upscheduling of over‐the‐counter codeine to a prescription‐only medication. Drug Alcohol Rev 2017;00:000‐000]
Lexical‐processing efficiency leverages novel word learning in infants and toddlers
Authors: Lany Jill 
Published: June 2017

AbstractChildren who rapidly recognize and interpret familiar words typically have accelerated lexical growth, providing indirect evidence that lexical processing efficiency (LPE) is related to word‐learning ability. Here we directly tested whether children with better LPE are better able to learn novel words. In Experiment 1, 17‐ and 30‐month‐olds were tested on an LPE task and on a simple word‐learning task. The 17‐month‐olds’ LPE scores predicted word learning in a regression model, and only those with relatively good LPE showed evidence of learning. The 30‐month‐olds learned novel words quite well regardless of LPE, but in a more difficult word‐learning task (Experiment 2), their LPE predicted word‐learning ability. These findings suggest that LPE supports word‐learning processes, especially when learning is difficult.
The expanding Empire and spatial distribution of economic activity: the case of Japan's colonization of Korea during the prewar period
Authors: Nakajima Kentaro , Okazaki Tetsuji 
Published: June 2017

AbstractIn 1910, Japan annexed Korea and integrated it into the Empire of Japan. According to its policy of assimilating colonies, the Japanese government intended to remove the tariffs between Japan and Korea, an aim which had almost been realized by 1923. The removal of the tariff barrier was supposed to improve market access between Japan and Korea. This article explores the implications of this event, focusing on the spatial distribution of economic activity in Japan. The regression results suggest that the integration of the Korean market increased population growth rates more in the regions close to the former border between Japan and Korea than in the other regions. Furthermore, after integration, the regions close to Korea that specialized in the fabric industry, whose products were the primary goods exported from Japan to Korea, experienced more population growth than other regions close to Korea did. These results suggest that market accessibility was indeed a determinant of the spatial distribution of economic activity. Our findings also indicate that the economic effect of colonization on the mainland was spatially heterogeneous and that a spatial viewpoint of the history of imperialism is important.
Dispersal enhances beta diversity in nectar microbes
Authors: Vannette Rachel L. , Fukami Tadashi 
Published: June 2017

AbstractDispersal is considered a key driver of beta diversity, the variation in species composition among local communities, but empirical tests remain limited. We manipulated dispersal of nectar‐inhabiting bacteria and yeasts via flower‐visiting animals to examine how dispersal influenced microbial beta diversity among flowers. Contrary to the prevailing view that dispersal lowers beta diversity, we found beta diversity was highest when dispersal was least limited. Our analysis suggested that this unexpected pattern might have resulted from stronger priority effects under increased dispersal. Dispersal is highly stochastic, generating variability in species arrival history and consequently the potential for community divergence via priority effects, in these and likely many other microbial, plant, and animal communities. Yet most previous experiments eliminated this possibility. We suggest that the positive effects of dispersal on beta diversity, like the one we report here, may have been greatly underappreciated.
The relationship between species richness and ecosystem variability is shaped by the mechanism of coexistence
Authors: Tredennick Andrew T. , Adler Peter B. , Adler Frederick R. 
Published: June 2017

AbstractTheory relating species richness to ecosystem variability typically ignores the potential for environmental variability to promote species coexistence. Failure to account for fluctuation‐dependent coexistence may explain deviations from the expected negative diversity–ecosystem variability relationship, and limits our ability to predict the consequences of increases in environmental variability. We use a consumer‐resource model to explore how coexistence via the temporal storage effect and relative nonlinearity affects ecosystem variability. We show that a positive, rather than negative, diversity–ecosystem variability relationship is possible when ecosystem function is sampled across a natural gradient in environmental variability and diversity. We also show how fluctuation‐dependent coexistence can buffer ecosystem functioning against increasing environmental variability by promoting species richness and portfolio effects. Our work provides a general explanation for variation in observed diversity–ecosystem variability relationships and highlights the importance of conserving regional species pools to help buffer ecosystems against predicted increases in environmental variability.
Acute and long‐term effects of brivaracetam and brivaracetam–diazepam combinations in an experimental model of status epilepticus
Authors: Niquet Jerome , Suchomelova Lucie , Thompson Kerry , Klitgaard Henrik , Matagne Alain , Wasterlain Claude 
Published: June 2017

SummaryObjectiveTo evaluate acute and long‐term effects of intravenous brivaracetam (BRV) and BRV + diazepam (DZP) combination treatment in a rat model of self‐sustaining status epilepticus (SSSE).MethodsRats were treated with BRV (10 mg/kg) 10 min after initiation of perforant path stimulation (PPS) as early treatment; or BRV (10–300 mg/kg), DZP (1 mg/kg), or BRV (0.3–10 mg/kg) + DZP (1 mg/kg) 10 min after the end of PPS (established SSSE). Seizure activity was recorded electrographically for 24 h posttreatment (acute effects), and for 1 week at 6–8 weeks or 12 months' posttreatment (long‐term effects). All treatments were compared with control rats using one‐way analysis of variance (ANOVA) and Bonferroni's test, or Kruskal‐–Wallis and Dunn's multiple comparison tests, when appropriate.ResultsTreatment of established SSSE with BRV (10–300 mg/kg) resulted in dose‐dependent reduction in SSSE duration and cumulative seizure time, achieving statistical significance at doses ≥100 mg/kg. Lower doses of BRV (0.3–10 mg/kg) + low‐dose DZP (1 mg/kg) significantly reduced SSSE duration and number of seizures. All control rats developed spontaneous recurrent seizures (SRS) 6–8 weeks after SSSE, whereas seizure freedom was noted in 2/10, 5/10, and 6/10 rats treated with BRV 200 mg/kg, 300 mg/kg, and BRV 10 mg/kg + DZP, respectively. BRV (10–300 mg/kg) showed a dose‐dependent trend toward reduction of SRS frequency, cumulative seizure time, and spike frequency, achieving statistical significance at 300 mg/kg. Combination of BRV (10 mg/kg) + DZP significantly reduced SRS frequency, cumulative seizure time, and spike frequency. In the 12‐month follow‐up study, BRV (0.3–10 mg/kg) + low‐dose DZP markedly reduced SRS frequency, cumulative seizure time, and spike frequency, achieving statistical significance at some doses. Early treatment of SSSE with BRV 10 mg/kg significantly reduced long‐term SRS frequency.SignificanceThese findings support clinical evaluation of BRV for treatment of status epilepticus or acute repetitive seizures.
Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder: Experience of >100 patients
Authors: Lim Zhan , Wong Kingsley , Olson Heather E. , Bergin Ann M. , Downs Jenny , Leonard Helen 
Published: June 2017

SummaryObjectivePathogenic variants involving the CDKL5 gene result in a severe epileptic encephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its influences on seizures.MethodsThe International CDKL5 Disorder Database, established in 2012, collects information on individuals with the CDKL5 disorder. Families have provided information regarding seizure characteristics, use, and side effects of the KD treatment. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided on patients attending Boston Children's Hospital.ResultsData regarding KD use were available for 204 individuals with a pathogenic CDKL5 variant. Median age of inclusion in the database was 4.8 years (range = 0.3–33.9 years), with median age of 6 weeks (range = 1 day–65 weeks) at seizure onset. History of KD use was reported for 51% (104 of 204) of individuals, with a median duration of use of 17 months (95% confidence interval = 9–24). Changes in seizure activity after commencing KD were reported for two‐thirds (69 of 104), with improvements in 88% (61 of 69). Nearly one‐third (31.7%) experienced side effects during the diet. At ascertainment, only one‐third (32%) remained on the diet, with lack of long‐term efficacy as the main reason for diet cessation (51%, 36 of 70).SignificanceBenefits of KD in the CDKL5 disorder are in keeping with previous trials on refractory epilepsies. However, poor long‐term efficacy remains as a significant barrier. In view of its side effect profile, KD administration should be supervised by a pediatric neurologist and specialist dietician.
Inherent vulnerabilities in monoaminergic pathways predict the emergence of depressive impairments in an animal model of chronic epilepsy
Authors: Medel‐Matus Jesús‐Servando , Shin Don , Sankar Raman , Mazarati Andrey 
Published: June 2017

SummaryThe objective was to determine whether the depression comorbid with epilepsy could be predicted based on inherent premorbid patterns of monoaminergic transmission. In male Wistar rats, despair‐like and anhedonia‐like behaviors were examined using forced swimming and taste preference tests, respectively. Serotonergic raphe nucleus (RN)–prefrontal cortex (PFC) and dopaminergic ventral tegmental area (VTA)–nucleus accumbens (NAcc) pathways were interrogated by fast scan cyclic voltammetry (FSCV). The assays were performed before and 2 months after pilocarpine status epilepticus. In a subset of naive rats, FSCV, coupled with the intensity‐dependent stimulation paradigm, detected specific deviations in each pathway (six rats for RN‐PFC and seven rats for VTA‐NAcc, with overlap in two, of 19 total subjects) in the absence of behavioral impairments. During epilepsy, animals with preexisting deviations in RN‐PFC invariably developed despair, and rats with deviations in VTA‐NAcc developed anhedonia. Serotonergic and dopaminergic pathways, respectively, showed signs of explicit deterioration. We suggest that epilepsy triggers decompensations in the already vulnerable depression‐relevant neuronal circuits, which culminate in depression. The established connection between the identified specific signatures in monoamine transmission in naive rats and specific symptoms of epilepsy‐associated depression may help in understanding causes of comorbidity and in developing its early biomarkers.
Alarm call‐based discrimination between common cuckoo and Eurasian sparrowhawk in a Chinese population of great tits
Authors: Yu Jiangping , Xing Xiaoying , Jiang Yunlei , Liang Wei , Wang Haitao , Møller Anders Pape 
Published: June 2017

AbstractMorphological resemblance of the common cuckoo Cuculus canorus to the Eurasian sparrowhawk Accipiter nisus has been regarded as an example of predator mimicry. Common hosts could distinguish parasites as the result of coevolution, while rare hosts or non‐hosts may mistake cuckoos for hawks because rare hosts or non‐hosts behave similarly when faced with these two species. Birds usually produce alarm calls in addition to showing behavioral responses when in danger. However, previous studies of identification by rare hosts or non‐hosts of sparrowhawks usually lacked experimental evidence of alarm calls. Great tits Parus major, a rare cuckoo host, perform similar behaviors and usually produce alarm calls in response to sparrowhawks and common cuckoos. Here, we tested whether great tits could distinguish common cuckoo from sparrowhawk based on analysis of their alarm calls and the effects of playback of alarm calls on conspecific behavior. Previous studies showed that great tits have a complex communication system that conveys information about predators, and they could perform different kinds of response behavior to different alarm calls. If great tits have not made the ability to distinguish between common cuckoo and sparrowhawk, then their acoustic responses to these two species and their response behaviors in playback experiments should be similar. Specimens of a common cuckoo (parasite), a sparrowhawk (predator) and an Oriental turtle dove Streptopelia orientalis (harmless control) were used to elicit and subsequently record the response behavior and alarm calls of great tits. There was no significant difference in behavioral response among great tits when exposed to the dummy of cuckoo, sparrowhawk and dove. In contrast, they differed significantly in alarm calls. Great tits produced more notes per call that contained increasing D‐type and decreasing I‐type notes when responding to sparrowhawk as compared to cuckoo or dove. In playback experiments, we found that great tits responded more strongly to great tit hawk than to great tit cuckoo or great tit dove alarm calls. Our study suggests that great tits are able to distinguish sparrowhawks from common cuckoos and convey relevant information in alarm calls by adjusting the number and combinations of notes of a single call type.
Non‐oscillatory and non‐singular asymptotic solutions to stress fields at interface cracks
Authors: Lei W.‐S. 
Published: June 2017

AbstractThis work concerns the complex oscillatory singularities revealed in Williams's asymptotic solutions to stress fields around arbitrary interface cracks, which are the foundation of phenomenological interface fracture mechanics. First, we highlight the fatal discrepancy between the asymptotic stress fields for cracks in a homogeneous material obtained by assigning an identical material on both regions embracing an interface crack, and the solutions directly derived from cracks in a single material. Next, following a brief introduction to Williams's formulation process, we adopt the method of repeatedly eliminating variables instead of solving the determinant equation for the coefficient matrix to reformulate the asymptotic analysis of stress fields at arbitrary interface cracks. The resultant stresses get rid of oscillatory character. Further, under two specific loading conditions, namely, remotely uniaxial tension or shear, non‐oscillatory and non‐singular asymptotic solutions to stress fields around interface cracks are obtained.
Biomass production and water use efficiency in perennial grasses during and after drought stress
Authors: Kørup Kirsten , Lærke Poul Erik , Baadsgaard Helle , Andersen Mathias N. , Kristensen Kristian , Münnich Cora , Didion Thomas , Jensen Erik Steen , Mårtensson Linda‐Maria , Jørgensen Uffe 
Published: June 2017

AbstractDrought is a great challenge to agricultural production, and cultivation of drought‐tolerant or water use‐efficient cultivars is important to ensure high biomass yields for bio‐refining and bioenergy. Here, we evaluated drought tolerance of four C3 species, Dactylis glomerata cvs. Sevenop and Amba, Festuca arundinacea cvs. Jordane and Kora, Phalaris arundinacea cvs. Bamse and Chieftain and Festulolium pabulare cv. Hykor, and two C4 species Miscanthus × giganteus and M. lutarioriparius. Control (irrigated) and drought‐treated plants were grown on coarse and loamy sand in 1 m2 lysimeter plots where rain was excluded. Drought periods started after harvest and lasted until 80% of available soil water had been used. Drought caused a decrease in dry matter yield (DM; P < 0.001) for all species and cultivars during the drought period. Cultivars Sevenop, Kora and Jordane produced DM at equal levels and higher than the other C3 cultivars in control and drought‐treated plots both during and after the drought period. Negative correlations were observed between stomatal conductance (gs) and leaf water potential (P < 0.01) and positive correlations between gs and DM (P < 0.05) indicating that gs might be suitable for assessment of drought stress. There were indications of positive associations between plants carbon isotope composition and water use efficiency (WUE) as well as DM under well‐watered conditions. Compared to control, drought‐treated plots showed increased growth in the period after drought stress. Thus, the drought events did not affect total biomass production (DMtotal) of the whole growing season. During drought stress and the whole growing season, WUE was higher in drought‐treated compared to control plots, so it seems possible to save water without loss of biomass. Across soil types, M. lutarioriparius had the highest DMtotal (15.0 t ha−1), WUEtotal (3.6 g L−1) and radiation use efficiency (2.3 g MJ−1) of the evaluated grasses.