bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular plant species richness and composition in two types of post‐cultivation tropical secondary forest
Authors: Neo Louise , Yee Alex T.K. , Chong Kwek Yan , Kee Carmen Y. , Tan Hugh T.W.
Published: June 2017

Question

How are plant communities in forests regenerating on post‐cultivation land structured along environmental gradients, landscape context and past land use? We investigated this for two types of post‐agricultural fates: plantations abandoned with trees intact (abandoned land forest) versus land that was cleared and left to regenerate into a forest (waste woodland).

Location

The tropical city‐state of Singapore, Southeast Asia.

Methods

Five 20 m × 20 m plots were surveyed for vascular plants in each of 11 patches of abandoned land forest and nine patches of waste woodland. For each plot, we estimated soil nutrient levels (N, K, P), canopy cover, leaf litter depth, distance to old‐growth forest and the size of the forest patch.

Results

For both forest types, increasing leaf litter and distance to old‐growth forest is associated with lower species richness. Increasing soil N in abandoned land forest and increasing soil K in waste woodland is associated with lower total and native species richness, but not exotic species richness. Overall community composition is correlated with leaf litter, canopy cover, soil P and K and distance to old‐growth forest.

Conclusions

Different forms of land abandonment resulted in different successional trajectories that led to separate sets of environmental drivers of community patterns. Restoring such degraded forms of vegetation to native‐rich communities may require management of soil nutrient levels and enrichment planting.
How restudy decisions affect overall comprehension for seventh‐grade students
Authors: Thiede Keith W. , Redford Joshua S. , Wiley Jennifer , Griffin Thomas D.
Published: June 2017

Background

Self‐regulated learning requires accurate monitoring and effective regulation of study. Little is known about how effectively younger readers regulate their study.

Aims

We examined how decisions about which text to restudy affect overall comprehension for seventh‐grade students. In addition to a Participant's Choice condition where students were allowed to pick texts for restudy on their own, we compared learning gains in two other conditions in which texts were selected for them. The Test‐Based Restudy condition determined text selection using initial test performance – presenting the text with the lowest initial test performance for restudy, thereby circumventing potential problems associated with inaccurate monitoring and ineffective regulation. The Judgement‐Based Restudy condition determined text selection using metacognitive judgements of comprehension – presenting the text with the lowest judgement of comprehension, thereby circumventing potential problems associated with ineffective regulation.

Sample

Four hundred and eighty seventh‐grade students participated.

Method

Students were randomly assigned to conditions in an experimental design.

Results and conclusions

Gains in comprehension following restudy were larger for the Test‐Based Restudy condition than for the Judgement‐Based Restudy condition or the Participant's Choice condition. No differences in comprehension were seen between the Judgement‐Based Restudy and Participant's Choice conditions. These results suggest seventh graders can systematically use their monitoring to make decisions about what to restudy. However, the results highlight how inaccurate monitoring is one reason why younger students fail to benefit from self‐regulated study opportunities.
Exposure to Bordetella pertussis adenylate cyclase toxin affects integrin‐mediated adhesion and mechanics in alveolar epithelial cells
Authors: Angely Christelle , Nguyen Ngoc‐Minh , Andre Dias Sofia , Planus Emmanuelle , Pelle Gabriel , Louis Bruno , Filoche Marcel , Chenal Alexandre , Ladant Daniel , Isabey Daniel
Published: June 2017

Background Information

The adenylate cyclase (CyaA) toxin is a major virulent factor of Bordetella pertussis, the causative agent of whooping cough. CyaA toxin is able to invade eukaryotic cells where it produces high levels of cyclic adenosine monophosphate (cAMP) affecting cellular physiology. Whether CyaA toxin can modulate cell matrix adhesion and mechanics of infected cells remains largely unknown.

Results

In this study, we use a recently proposed multiple bond force spectroscopy (MFS) with an atomic force microscope to assess the early phase of cell adhesion (maximal detachment and local rupture forces) and cell rigidity (Young's modulus) in alveolar epithelial cells (A549) for toxin exposure <1 h. At 30 min of exposure, CyaA toxin has a minimal effect on cell viability (>95%) at CyaA concentration of 0.5 nM, but a significant effect (≈81%) at 10 nM. MFS performed on A549 for three different concentrations (0.5, 5 and 10 nM) demonstrates that CyaA toxin significantly affects both cell adhesion (detachment forces are decreased) and cell mechanics (Young's modulus is increased). CyaA toxin (at 0.5 nM) assessed at three indentation/retraction speeds (2, 5 and 10 μm/s) significantly affects global detachment forces, local rupture events and Young modulus compared with control conditions, while an enzymatically inactive variant CyaAE5 has no effect. These results reveal the loading rate dependence of the multiple bonds newly formed between the cell and integrin‐specific coated probe as well as the individual bond kinetics which are only slightly affected by the patho‐physiological dose of CyaA toxin. Finally, theory of multiple bond force rupture enables us to deduce the bond number N which is reduced by a factor of 2 upon CyaA exposure (N ≈ 6 versus N ≈ 12 in control conditions).

Conclusions

MFS measurements demonstrate that adhesion and mechanical properties of A549 are deeply affected by exposure to the CyaA toxin but not to an enzymatically inactive variant. This indicates that the alteration of cell mechanics triggered by CyaA is a consequence of the increase in intracellular cAMP in these target cells.

Significance

These results suggest that mechanical and adhesion properties of the cells appear as pertinent markers of cytotoxicity of CyaA toxin.
Rational design of peptide derivatives for inhibition of MyD88‐mediated toll‐like receptor signaling in human peripheral blood mononuclear cells and epithelial cells exposed to Francisella tularensis
Authors: Ryan Daniel A. , Degardin Melissa , Alam Shahabuddin , Kissner Teri L. , Hale Martha , Cameron Michael D. , Rebek Mitra , Ajami Dariush , Saikh Kamal U. , Rebek Julius
Published: June 2017

Small molecules were developed to attenuate proinflammatory cytokines resulting from activation of MyD88‐mediated toll‐like receptor (TLR) signaling by Francisella tularensis. Fifty‐three tripeptide derivatives were synthesized to mimic a key BB‐loop region involved in toll‐like/interleukin‐1 receptor recognition (TIR) domain interactions. Compounds were tested for inhibition of TNF‐α, IFN‐γ, IL‐6, and IL‐1β in human peripheral blood mononuclear cells (PBMCs) and primary human bronchial epithelial cells exposed to LPS extracts from F. tularensis. From 53 compounds synthesized and tested, ten compounds were identified as effective inhibitors of F. tularensisLPS‐induced cytokines. Compound stability testing in the presence of human liver microsomes and human serum resulted in the identification of tripeptide derivative 7 that was a potent, stable, and drug‐like small molecule. Target corroboration using a cell‐based reporter assay and competition experiments with MyD88 TIR domain protein supported that the effect of 7 was through MyD88 TIR domain interactions. Compound 7 also attenuated proinflammatory cytokines in human peripheral blood mononuclear cells and bronchial epithelial cells challenged with a live vaccine strain of F. tularensis at a multiplicity of infection of 1:5. Small molecules that target TIR domain interactions in MyD88‐dependent TLR signaling represent a promising strategy toward host‐directed adjunctive therapeutics for inflammation associated with biothreat agent‐induced sepsis.
The Impact of Parenting on Emotion Regulation During Childhood and Adolescence
Authors: Morris Amanda S. , Criss Michael M. , Silk Jennifer S. , Houltberg Benjamin J.
Published: June 2017

Regulating emotions well is critical for promoting social and emotional health among children and adolescents. Parents play a prominent role in how children develop emotion regulation. In 2007, Morris et al. proposed a tripartite model suggesting that parents influence children's emotion regulation through three mechanisms: children's observation of parents' emotion regulation, emotion‐related parenting practices, and the emotional climate of the family. Over the past decade, we have conducted many studies that support this model, which we summarize here along with other research related to parenting and emotion regulation. We also discuss recent research on the effects of parenting on the neural circuitry involved in emotion regulation and highlight potential directions for research. Finally, we suggest how this research can aid prevention and intervention efforts to help families.
Pattern Understanding: Relationships With Arithmetic and Reading Development
Authors: Burgoyne Kelly , Witteveen Kate , Tolan Anne , Malone Stephanie , Hulme Charles
Published: June 2017

Pattern understanding (patterning) is commonly taught in preschool and early elementary classrooms. However, the relationship between patterning and academic attainment is not well understood. In this article, we review studies of children's pattern understanding. Some evidence suggests that pattern understanding is related causally to acquiring math and reading skills. However, much of the evidence is weak and these conclusions remain tentative. Research on the relationship between patterning and other skills needs to use psychometrically robust measures and analytic techniques that control for the effects of measurement error. Recent studies suggest that teaching young children patterning skills can improve their attainment in math and reading, but we need larger, methodologically robust, randomized controlled trials to confirm such claims.
The Effectiveness of a Large‐Scale Language and Preliteracy Intervention: The SPELL Randomized Controlled Trial in Denmark
Authors: Bleses Dorthe , Højen Anders , Justice Laura M. , Dale Philip S. , Dybdal Line , Piasta Shayne B. , Markussen‐Brown Justin , Clausen Marit , Haghish E. F.
Published: June 2017

The present article reports results of a real‐world effectiveness trial conducted in Denmark with six thousand four hundred eighty‐three 3‐ to 6‐year‐olds designed to improve children's language and preliteracy skills. Children in 144 child cares were assigned to a control condition or one of three planned variations of a 20‐week storybook‐based intervention: a base intervention and two enhanced versions featuring extended professional development for educators or a home‐based program for parents. Pre‐ to posttest comparisons revealed a significant impact of all three interventions for preliteracy skills (= .21–.27) but not language skills (d = .04–.16), with little differentiation among the three variations. Fidelity, indexed by number of lessons delivered, was a significant predictor of most outcomes. Implications for real‐world research and practice are considered.
Nutritional role of folate
Authors: Ebara Shuhei
Published: June 2017

Folate functions as a coenzyme to transfer one‐carbon units that are necessary for deoxythymidylate synthesis, purine synthesis, and various methylation reactions. Ingested folate becomes a functional molecule through intestinal absorption, circulation, transport to cells, and various modifications to its structure. Associations between nutritional folate status and chronic diseases such as cardiovascular disease, cancer, and cognitive dysfunction have been reported. It has also been reported that maternal folate nutritional status is related to the risk of neural tube defects (NTDs) in the offspring. It has also been recommended that folate be consumed in the diet to promote the maintenance of good health. To reduce the risk of NTDs, supplementation with folic acid (a synthetic form of folate) during the periconceptional period has also been recommended. This paper describes the basic features and nutritional role of folate.
The State of the Art in Sentiment Visualization
Authors: Kucher Kostiantyn , Paradis Carita , Kerren Andreas
Published: June 2017

Visualization of sentiments and opinions extracted from or annotated in texts has become a prominent topic of research over the last decade. From basic pie and bar charts used to illustrate customer reviews to extensive visual analytics systems involving novel representations, sentiment visualization techniques have evolved to deal with complex multidimensional data sets, including temporal, relational and geospatial aspects. This contribution presents a survey of sentiment visualization techniques based on a detailed categorization. We describe the background of sentiment analysis, introduce a categorization for sentiment visualization techniques that includes 7 groups with 35 categories in total, and discuss 132 techniques from peer‐reviewed publications together with an interactive web‐based survey browser. Finally, we discuss insights and opportunities for further research in sentiment visualization. We expect this survey to be useful for visualization researchers whose interests include sentiment or other aspects of text data as well as researchers and practitioners from other disciplines in search of efficient visualization techniques applicable to their tasks and data.
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

Aims

Alzheimer'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.

Methods

Here, 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.

Conclusion

In 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

Objectives

Ubiquitin 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 methods

Expression 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.

Results

USP32 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.

Conclusions

Our 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

Introduction 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

Children 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

In 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

Dispersal 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

Theory 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

Objective

To 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).

Methods

Rats 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.

Results

Treatment 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.

Significance

These 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

Objective

Pathogenic 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.

Methods

The 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.

Results

Data 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).

Significance

Benefits 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

The 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

Morphological 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.
Proteases as antimalarial targets: strategies for genetic, chemical, and therapeutic validation
Authors: Deu Edgar
Published: June 2017

Malaria is a devastating parasitic disease affecting half of the world's population. The rapid emergence of resistance against new antimalarial drugs, including artemisinin‐based therapies, has made the development of drugs with novel mechanisms of action extremely urgent. Proteases are enzymes proven to be well suited for target‐based drug development due to our knowledge of their enzymatic mechanisms and active site structures. More importantly, Plasmodium proteases have been shown to be involved in a variety of pathways that are essential for parasite survival. However, pharmacological rather than target‐based approaches have dominated the field of antimalarial drug development, in part due to the challenge of robustly validating Plasmodium targets at the genetic level. Fortunately, over the last few years there has been significant progress in the development of efficient genetic methods to modify the parasite, including several conditional approaches. This progress is finally allowing us not only to validate essential genes genetically, but also to study their molecular functions. In this review, I present our current understanding of the biological role proteases play in the malaria parasite life cycle. I also discuss how the recent advances in Plasmodium genetics, the improvement of protease‐oriented chemical biology approaches, and the development of malaria‐focused pharmacological assays, can be combined to achieve a robust biological, chemical and therapeutic validation of Plasmodium proteases as viable drug targets.
Non‐oscillatory and non‐singular asymptotic solutions to stress fields at interface cracks
Authors: Lei W.‐S.
Published: June 2017

This 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

Drought 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.
Determination of AsSI‐SbSI glasses short‐range structure via Raman spectroscopy, XPS and XRD
Authors: Kurushkin Mikhail V. , Markov Viktor A. , Semencha Alexandr V. , Mikhailov Mikhail D. , Tverjanovich Andrey S. , Shakhmin Aleksandr L. , Larionova Tatiana V. , Andreeva Valentina D.
Published: June 2017

The ability to predict the influence of dopants (such as antimony) on the short‐range structure of As‐S‐I glasses has the potential to help design glasses with modified properties. In the present work, the short‐range structure of As‐Sb‐S‐I glasses has been investigated along AsSI‐SbSI section of fixed sulfur and iodine concentrations and equivalent arsenic by antimony substitution. At high arsenic content (As:Sb≥2:1) antimony substitutes arsenic in AsI3 molecules justified by Raman spectroscopy and XPS. Further antimony introduction (As:Sb<2:1) leads to the substitution of arsenic by antimony in ‐S‐As‐S‐ polymeric chains, leading to SbSI crystallization justified by XRD. The resulting two‐dimensional schematic diagrams represent the AsSI‐SbSI glasses short‐range structure and show the mechanism of arsenic by antimony substitution.
Formation of Core‐Shell Mesoporous Ceramic Fibers
Authors: Elishav Oren , Beilin Vadim , Shter Gennady E. , Dinner Omry , Halperin Victor , Grader Gideon S.
Published: June 2017

Ceramic Fe–Al–O nanofibers with a core‐shell architecture were obtained by electrospinning. The fibers consist of an Fe–Al–O core with novel lamellar‐like mesopores and an Fe‐rich shell. A mechanism of this unique core and shell formation is outlined and confirmed. The described mesoporous nanofibers are highly promising for new research and applications involving catalysis, sensing and absorption of mobile components on the accessible porous core surface.
Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer
Authors: Mazouffre Clément , Geyl Sophie , Perraud Aurélie , Blondy Sabrina , Jauberteau Marie‐Odile , Mathonnet Muriel , Verdier Mireille
Published: June 2017

Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathways—neurotrophic factors (TrkB/BDNF) and autophagy—on cell fate and tumour evolution. In vitro studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages. On the basis of our previous study (which demonstrated that TrkB overexpression is associated with prosurvival signaling in CRC cells), we pharmacologically inhibited NTs pathways with K252a. As expected, an inactivation of the PI3K/AKT pathway was observed and CRC cells initiated autophagy. Conversely, blocking the autophagic flux with chloroquine or with ATG5‐siRNA overactivated TrkB/BDNF signaling. In vitro, dual inhibition improved the effectiveness of single treatment by significantly reducing metabolic activity and enhancing apoptotic cell death. These findings were accentuated in vivo, in which dual inhibition induced a spectacular reduction in tumour volume following long‐term treatment (21 days for K252a and 12 days for CQ). Finally, significant amounts of phospho‐TrkB and LC3II were found in the patients’ tissues, highlighting their relevance in CRC tumour biology. Taken together, our results show that targeting NTs and autophagy pathways potentially constitutes a new therapeutic approach for CRC.
Nintedanib reduces ventilation‐augmented bleomycin‐induced epithelial–mesenchymal transition and lung fibrosis through suppression of the Src pathway
Authors: Li Li‐Fu , Kao Kuo‐Chin , Liu Yung‐Yang , Lin Chang‐Wei , Chen Ning‐Hung , Lee Chung‐Shu , Wang Chih‐Wei , Yang Cheng‐Ta
Published: June 2017

Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)‐β1‐induced epithelial–mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear. In this study, we suggested hypothesized that nintedanib can suppress MV‐augmented bleomycin‐induced EMT and pulmonary fibrosis by inhibiting the Src pathway. Five days after administrating bleomycin to mimic acute lung injury (ALI), C57BL/6 mice, either wild‐type or Src‐deficient were exposed to low tidal volume (VT) (6 ml/kg) or high VT (30 ml/kg) MV with room air for 5 hrs. Oral nintedanib was administered once daily in doses of 30, 60 and 100 mg/kg for 5 days before MV. Non‐ventilated mice were used as control groups. Following bleomycin exposure in wild‐type mice, high VT MV induced substantial increases in microvascular permeability, TGF‐β1, malondialdehyde, Masson's trichrome staining, collagen 1a1 gene expression, EMT (identified by colocalization of increased staining of α‐smooth muscle actin and decreased staining of E‐cadherin) and alveolar epithelial apoptosis (P < 0.05). Oral nintedanib, which simulated genetic downregulation of Src signalling using Src‐deficient mice, dampened the MV‐augmented profibrotic mediators, EMT profile, epithelial apoptotic cell death and pathologic fibrotic scores (P < 0.05). Our data indicate that nintedanib reduces high VT MV‐augmented EMT and pulmonary fibrosis after bleomycin‐induced ALI, partly by inhibiting the Src pathway.
Morphology and Phylogenetic Analyses of Three Novel Naegleria Isolated from Freshwaters on Jeju Island, Korea, During the Winter Period
Authors: Khwon Woo Jun , Park Jong Soo
Published: June 2017

The genus Naegleria is one of the best known heterolobosean groups, and is the causative agent of primary amoebic meningoencephalitis. This group is rarely studied in temperate regions during winter. Here, three novel Naegleria were isolated from freshwaters on Jeju Island, Korea, during winter. Two isolates were amoeboflagellates, and one of the three amoebae did not undergo enflagellation. All amoebae had eruptive pseudopodia, and the layer of refractile granules around a large nucleus. They formed a cyst with ~2 pores in the cyst stage. The amoeboflagellate form had two flagella and no division in the flagellate stage, and no cytostome. These features are very similar to typical Naegleria. Furthermore, our isolates were able to grow at > 30 °C, suggesting that they had different thermophilicity from Naegleria in polar regions. All amoebae were largely encysted at 5 or 10 °C, indicating that they were likely encysted during winter. Based on the 18S rRNA gene and the ITS1‐5.8S rRNA gene‐ITS2 sequences, the phylogenetic analyses consistently revealed that the isolates are members of the Naegleria group. However, the isolates differ from other species in both phylogenetic trees. Thus, Naegleria in cold habitats appeared to have a high degree of novelty, but their thermophilicity may be dependent on locality.
Functional Impairment and Risk of Venous Thrombosis in Older Adults
Authors: Engbers Marissa J. , Blom Jeanet W. , Cushman Mary , Rosendaal Frits R. , van Hylckama Vlieg Astrid
Published: June 2017

Objectives

To determine the role of age‐specific risk factors for thrombosis in older age, such as functional impairment.

Design

Case‐control study.

Setting

The Age and Thrombosis—Acquired and Genetic risk factors in the Elderly Study, a two‐center study conducted in the Netherlands and the United States from 2008 to 2011.

Participants

Individuals aged 70 and older with a first‐time deep venous thrombosis in the leg or pulmonary embolism (n = 401) and controls aged 70 and older (n = 431) without a history of thrombosis. Exclusion criteria were active malignancy and severe cognitive disorders.

Measurements

The thrombotic risk associated with functional impairment, defined as impairment in two or more activities of daily living (ADLs), impaired mobility (inability to walk outside), sedentary lifestyle (≥20 h/d sleeping or sitting), and low handgrip strength (<15th percentile), was assessed. Odds ratios (ORs) adjusted for age, sex, and study center with 95% confidence intervals (95% CI) and population attributable risks (PAR) were calculated.

Results

Risk of venous thrombosis was 2.9 times greater (OR = 2.9, 95% CI = 1.6–5.3) in individuals with impairment in ADLs, three times as great (OR = 3.0, 95% CI = 1.9–4.7) in those with impaired mobility, four times as great (OR = 4.0, 95% CI = 2.5–6.3) in those with a sedentary life style, and 2.3 times as great (OR = 2.3, 95% CI = 1.5–3.4) in those with weak handgrip strength. PARs were 8% for ADL disability, 13% for inability to walk outside for 15 minutes, 29% for sedentary lifestyle, and 13% for weak hand grip strength.

Conclusion

In individuals aged 70 and older, functional impairments are a major risk factor for venous thrombosis. These findings may help providers caring for older people be more aware of venous thrombosis risk.