bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boundary layer structure in a rough Rayleigh–Bénard cell filled with air
Authors: Liot O. , Salort J. , Kaiser R. , du Puits R. , Chillà F. 
Published: December 2015

In this experimental work, the aim is to understand how turbulent thermal flows are enhanced by the destabilization of the boundary layers. Square-stud roughness elements have been added on the bottom plate of a rectangular Rayleigh–Bénard cell in air, to trigger instabilities in the boundary layers. The top plate is kept smooth. The cell proportions are identical to those of the water cell previously operated and described by Salort et al. (Phys. Fluids, vol. 26, 2014, 015112), but six times larger. The very large size of the Barrel of Ilmenau allows detailed velocity fields to be obtained using particle image velocimetry very close to the roughness elements. We found that the flow is quite different at low Rayleigh numbers, where there is no heat-transfer enhancement, and at high Rayleigh numbers where there is a heat-transfer enhancement due to the roughness. Below the transition, the fluid inside the notch, i.e. between the studs, is essentially at rest, though it is slowly recirculating. The velocity profiles on the top of obstacles and in grooves are fairly compatible with those obtained in the smooth case. Above the transition, on the other hand, we observe large incursions of the bulk inside the notch, and the velocity profiles on the top of obstacles are closer to the logarithmic profiles expected in the case of turbulent boundary layers.
Dropping Out of Rural China's Secondary Schools: A Mixed-methods Analysis
Authors: Shi Yaojiang , Zhang Linxiu , Ma Yue , Yi Hongmei , Liu Chengfang , Johnson Natalie , Chu James , Loyalka Prashant , Rozelle Scott 
Published: December 2015

AbstractStudents in rural China are dropping out of secondary school at troubling rates. While there is considerable quantitative research on this issue, no systematic effort has been made to assess the deeper reasons behind student decision making through a mixed-methods approach. This article seeks to explore the prevalence, correlates and potential reasons for rural dropout throughout the secondary education process. It brings together results from eight large-scale survey studies covering 24,931 rural secondary students across four provinces, as well as analysis of extensive interviews with 52 students from these same study sites. The results show that the cumulative dropout rate across all windows of secondary education may be as high as 63 per cent. Dropping out is significantly correlated with low academic performance, high opportunity cost, low socio-economic status and poor mental health. A model is developed to suggest that rural dropout is primarily driven by two mechanisms: rational cost-benefit analysis or impulsive, stress-induced decision making.
The acceptability of dietary tools to improve maternal and child nutrition in Western Kenya
Authors: Kram Nidal , Melgen Sarah , Kedera Ellah , Collison Deborah Kortso , Colton Jonathan , Blount Wendy , Grant Frederick , Girard Amy Webb 
Published: December 2015

AbstractObjectiveDietary practices in Kenya often fail to provide adequate nutrition during the first 1000 days of life, from conception to 2 years of age. We developed and qualitatively assessed the acceptability of easy-to-use dietary tools consisting of a marked bowl, slotted spoon and illustrated counselling card to support appropriate dietary practices during pregnancy, exclusive breast-feeding and complementary feeding of children aged 6–24 months.DesignWe conducted qualitative research to assess community acceptability and obtain feedback on the design of the dietary tools.SettingThis research took place in urban and rural communities in Western Kenya.SubjectsWe conducted twelve focus group discussions with community members (mothers, husbands, mothers-in-law, community leaders) and five interviews with government nutritionists to assess acceptability and obtain recommendations on design and delivery of the tools. We conducted 24–28 d of user testing with fourteen pregnant women, fourteen breast-feeding women and thirty-two mothers with infants aged 6–18 months.ResultsTools were positively received by communities. Mothers perceived improvements in their own and their children’s food intakes including quantity, frequency, consistency and diversity. Many attributed perceived own and child’s weight gain and/or increased energy to tool use. A minority reported using the bowl for other activities (n 9) or not using the bowl due to food insecurity (n 5).ConclusionsResults suggest that such tools have the potential to positively impact maternal and child dietary practices. Future work should quantitatively assess the impact on diet and nutrition outcomes and the underlying behavioural domains associated with changes.
Genetic ablation of homeodomain-interacting protein kinase 2 selectively induces apoptosis of cerebellar Purkinje cells during adulthood and generates an ataxic-like phenotype
Authors: Anzilotti S , Tornincasa M , Gerlini R , Conte A , Brancaccio P , Cuomo O , Bianco G , Fusco A , Annunziato L , Pignataro G , Pierantoni G M 
Published: December 2015

AbstractHomeodomain-interacting protein kinase 2 (HIPK2) is a multitalented coregulator of an increasing number of transcription factors and cofactors involved in cell death and proliferation in several organs and systems. As Hipk2−/− mice show behavioral abnormalities consistent with cerebellar dysfunction, we investigated whether Hipk2 is involved in these neurological symptoms. To this aim, we characterized the postnatal developmental expression profile of Hipk2 in the brain cortex, hippocampus, striatum, and cerebellum of mice by real-time PCR, western blot analysis, and immunohistochemistry. Notably, we found that whereas in the brain cortex, hippocampus, and striatum, HIPK2 expression progressively decreased with age, that is, from postnatal day 1 to adulthood, it increased in the cerebellum. Interestingly, mice lacking Hipk2 displayed atrophic lobules and a visibly smaller cerebellum than did wild-type mice. More important, the cerebellum of Hipk2−/− mice showed a strong reduction in cerebellar Purkinje neurons during adulthood. Such reduction is due to the activation of an apoptotic process associated with a compromised proteasomal function followed by an unpredicted accumulation of ubiquitinated proteins. In particular, Purkinje cell dysfunction was characterized by a strong accumulation of ubiquitinated β-catenin. Moreover, our behavioral tests showed that Hipk2−/− mice displayed muscle and balance impairment, indicative of Hipk2 involvement in cerebellar function. Taken together, these results indicate that Hipk2 exerts a relevant role in the survival of cerebellar Purkinje cells and that Hipk2 genetic ablation generates cerebellar dysfunction compatible with an ataxic-like phenotype.
Akt inhibition attenuates rasfonin-induced autophagy and apoptosis through the glycolytic pathway in renal cancer cells
Authors: Lu Q , Yan S , Sun H , Wang W , Li Y , Yang X , Jiang X , Che Y , Xi Z 
Published: December 2015

AbstractRasfonin is a fungal secondary metabolite with demonstrated antitumor effects. However, the underlying mechanism of the regulatory role in autophagy initiated by rasfonin is largely unknown. Moreover, the function of Akt to positively mediate the induced autophagy remains elusive. In the present study, we observed that rasfonin induced autophagy concomitant with the upregulation of Akt phosphorylation. Both the inhibition of Akt by small molecule inhibitors and genetic modification partially reduced rasfonin-dependent autophagic flux and PARP-1 cleavage. The overexpression of myrAkts (constant active form) promoted rasfonin-induced apoptosis and autophagy in a cell type- and Akt isoform-specific manner. Using quantitative PCR and immunoblotting, we observed that rasfonin increased the expression of glycolytic gene PFKFB3, and this increased expression can be suppressed in the presence of Akt inhibitor. The inhibition of PFKFB3 suppressed rasfonin-activated autophagy with enhanced PARP-1 cleavage. In the case of glucose uptake was disrupted, which mean the glycolytic pathway was fully blocked, the rasfonin-induced autophagy and PARP-1 cleavage were downregulated. Collectively, these results demonstrated that Akt positively regulated rasfonin-enhanced autophagy and caspase-dependent apoptosis primarily through affecting the glycolytic pathway.
NFAT4-dependent miR-324-5p regulates mitochondrial morphology and cardiomyocyte cell death by targeting Mtfr1
Authors: Wang K , Zhang D-l , Long B , An T , Zhang J , Zhou L-Y , Liu C-Y , Li P-F 
Published: December 2015

AbstractEmerging evidence suggest that the abnormal mitochondrial fission participates in pathogenesis of cardiac diseases, including myocardial infarction and heart failure. However, the molecular components regulating mitochondrial network in heart remain largely unidentified. Here we report that NFAT4, miR-324-5p and mitochondrial fission regulator 1 (Mtfr1) function in one signaling axis that regulates mitochondrial morphology and cardiomyocyte cell death. Knocking down Mtfr1 suppresses mitochondrial fission, apoptosis and myocardial infarction. Mtfr1 is a direct target of miR-324-5p, and miR-324-5p attenuates mitochondrial fission, cardiomyocyte apoptosis and myocardial infarction by suppressing Mtfr1 translation. Finally, we show that transcription factor NFAT4 inhibits miR-324-5p expression. Knockdown of NFAT4 suppresses mitochondrial fission and protects cardiomyocyte from apoptosis and myocardial infarction. Our study defines the NFAT4/ miR-324-5p/Mtfr1 axis, which participates in the regulation of mitochondrial fission and cardiomyocyte apoptosis, and suggests potential new treatment avenues for cardiac diseases.
Neuroblastoma: oncogenic mechanisms and therapeutic exploitation of necroptosis
Authors: Nicolai S , Pieraccioli M , Peschiaroli A , Melino G , Raschellà G 
Published: December 2015

AbstractNeuroblastoma (NB) is the most common extracranial childhood tumor classified in five stages (1, 2, 3, 4 and 4S), two of which (3 and 4) identify chemotherapy-resistant, highly aggressive disease. High-risk NB frequently displays MYCN amplification, mutations in ALK and ATRX, and genomic rearrangements in TERT genes. These NB subtypes are also characterized by reduced susceptibility to programmed cell death induced by chemotherapeutic drugs. The latter feature is a major cause of failure in the treatment of advanced NB patients. Thus, proper reactivation of apoptosis or of other types of programmed cell death pathways in response to treatment is relevant for the clinical management of aggressive forms of NB. In this short review, we will discuss the most relevant genomic rearrangements that define high-risk NB and the role that destabilization of p53 and p73 can have in NB aggressiveness. In addition, we will propose a strategy to stabilize p53 and p73 by using specific inhibitors of their ubiquitin-dependent degradation. Finally, we will introduce necroptosis as an alternative strategy to kill NB cells and increase tumor immunogenicity.
The effect of soil-borne pathogens depends on the abundance of host tree species
Authors: Liu Yu , Fang Suqin , Chesson Peter , He Fangliang 
Published: December 2015

AbstractThe overarching issue for understanding biodiversity maintenance is how fitness advantages accrue to a species as it becomes rare, as this is the defining feature of stable coexistence mechanisms. Without these fitness advantages, average fitness differences between species will lead to exclusion. However, empirical evidence is lacking, especially for forests, due to the difficulty of manipulating density on a large-enough scale. Here we took advantage of naturally occurring contrasts in abundance between sites of a subtropical tree species, Ormosia glaberrima, to demonstrate how low-density fitness advantages accrue by the Janzen–Connell mechanism. The results showed that soil pathogens suppressed seedling recruitment of O. glaberrima when it is abundant but had little effect on the seedlings when it is at low density due to the lack of pathogens. The difference in seedling survival between abundant and low-density sites demonstrates strong dependence of pathogenic effect on the abundance of host species.
PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype
Authors: Duan Shunlei , Yuan Guohong , Liu Xiaomeng , Ren Ruotong , Li Jingyi , Zhang Weizhou , Wu Jun , Xu Xiuling , Fu Lina , Li Ying , Yang Jiping , Zhang Weiqi , Bai Ruijun , Yi Fei , Suzuki Keiichiro , Gao Hua , Esteban Concepcion Rodriguez , Zhang Chuanbao , Belmonte Juan Carlos Izpisua , Chen Zhiguo , Wang Xiaomin , Jiang Tao , Qu Jing , Tang Fuchou , Liu Guang-Hui 
Published: December 2015

AbstractPTEN is a tumour suppressor frequently mutated in many types of cancers. Here we show that targeted disruption of PTEN leads to neoplastic transformation of human neural stem cells (NSCs), but not mesenchymal stem cells. PTEN-deficient NSCs display neoplasm-associated metabolic and gene expression profiles and generate intracranial tumours in immunodeficient mice. PTEN is localized to the nucleus in NSCs, binds to the PAX7 promoter through association with cAMP responsive element binding protein 1 (CREB)/CREB binding protein (CBP) and inhibits PAX7 transcription. PTEN deficiency leads to the upregulation of PAX7, which in turn promotes oncogenic transformation of NSCs and instates ‘aggressiveness’ in human glioblastoma stem cells. In a large clinical database, we find increased PAX7 levels in PTEN-deficient glioblastoma. Furthermore, we identify that mitomycin C selectively triggers apoptosis in NSCs with PTEN deficiency. Together, we uncover a potential mechanism of how PTEN safeguards NSCs, and establish a cellular platform to identify factors involved in NSC transformation, potentially permitting personalized treatment of glioblastoma.
DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression
Authors: Wingo Aliza P. , Almli Lynn M. , Stevens Jennifer S. , Klengel Torsten , Uddin Monica , Li Yujing , Bustamante Angela C. , Lori Adriana , Koen Nastassja , Stein Dan J. , Smith Alicia K. , Aiello Allison E. , Koenen Karestan C. , Wildman Derek E. , Galea Sandro , Bradley Bekh , Binder Elisabeth B. , Jin Peng , Gibson Greg , Ressler Kerry J. 
Published: December 2015

AbstractDICER1is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that bloodDICER1expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower bloodDICER1expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region ofDICER1, rs10144436, is significantly associated withDICER1expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggestDICER1plays a role in molecular mechanisms of PTSD&Dep through theDICER1and the miRNA regulation pathway.
microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus
Authors: Jimenez-Mateos Eva M. , Arribas-Blazquez Marina , Sanz-Rodriguez Amaya , Concannon Caoimhin , Olivos-Ore Luis A. , Reschke Cristina R. , Mooney Claire M. , Mooney Catherine , Lugara Eleonora , Morgan James , Langa Elena , Jimenez-Pacheco Alba , Silva Luiz Fernando Almeida , Mesuret Guillaume , Boison Detlev , Miras-Portugal M. Teresa , Letavic Michael , Artalejo Antonio R. , Bhattacharya Anindya , Diaz-Hernandez Miguel , Henshall David C. , Engel Tobias 
Published: December 2015

AbstractThe ATP-gated ionotropic P2X7 receptor (P2X7R) modulates glial activation, cytokine production and neurotransmitter release following brain injury. Levels of the P2X7R are increased in experimental and human epilepsy but the mechanisms controlling P2X7R expression remain poorly understood. Here we investigated P2X7R responses after focal-onset status epilepticus in mice, comparing changes in the damaged, ipsilateral hippocampus to the spared, contralateral hippocampus. P2X7R-gated inward currents were suppressed in the contralateral hippocampus and P2rx7 mRNA was selectively uploaded into the RNA-induced silencing complex (RISC), suggesting microRNA targeting. Analysis of RISC-loaded microRNAs using a high-throughput platform, as well as functional assays, suggested the P2X7R is a target of microRNA-22. Inhibition of microRNA-22 increased P2X7R expression and cytokine levels in the contralateral hippocampus after status epilepticus and resulted in more frequent spontaneous seizures in mice. The major pro-inflammatory and hyperexcitability effects of microRNA-22 silencing were prevented in P2rx7−/− mice or by treatment with a specific P2X7R antagonist. Finally, in vivo injection of microRNA-22 mimics transiently suppressed spontaneous seizures in mice. The present study supports a role for post-transcriptional regulation of the P2X7R and suggests therapeutic targeting of microRNA-22 may prevent inflammation and development of a secondary epileptogenic focus in the brain.
Cross-modal and modality-specific expectancy effects between pain and disgust
Authors: Sharvit Gil , Vuilleumier Patrik , Delplanque Sylvain , Corradi-Dell’Acqua Corrado 
Published: December 2015

AbstractPain sensitivity increases when a noxious stimulus is preceded by cues predicting higher intensity. However, it is unclear whether the modulation of nociception by expectancy is sensory-specific (“modality based”) or reflects the aversive-affective consequence of the upcoming event (“unpleasantness”), potentially common with other negative events. Here we compared expectancy effects for pain and disgust by using different, but equally unpleasant, nociceptive (thermal) and olfactory stimulations. Indeed both pain and disgust are aversive, associated with threat to the organism and processed in partly overlapping brain networks. Participants saw cues predicting the unpleasantness (high/low) and the modality (pain/disgust) of upcoming thermal or olfactory stimulations and rated the associated unpleasantness after stimuli delivery. Results showed that identical thermal stimuli were perceived as more unpleasant when preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was found for olfactory disgust. Critically, cross-modal expectancy effects were observed on inconsistent trials when thermal stimuli were preceded by high-disgust cues or olfactory stimuli preceded by high-pain cues. However, these effects were stronger in consistent than inconsistent conditions. Taken together, our results suggest that expectation of an unpleasant event elicits representations of both its modality-specific properties and its aversive consequences.
High-density linkage map construction and mapping of seed trait QTLs in chickpea (Cicer arietinum L.) using Genotyping-by-Sequencing (GBS)
Authors: Verma Subodh , Gupta Shefali , Bandhiwal Nitesh , Kumar Tapan , Bharadwaj Chellapilla , Bhatia Sabhyata 
Published: December 2015

AbstractThis study reports the use of Genotyping-by-Sequencing (GBS) for large-scale SNP discovery and simultaneous genotyping of recombinant inbred lines (RILs) of an intra-specific mapping population of chickpea contrasting for seed traits. A total of 119,672 raw SNPs were discovered, which after stringent filtering revealed 3,977 high quality SNPs of which 39.5% were present in genic regions. Comparative analysis using physically mapped marker loci revealed a higher degree of synteny with Medicago in comparison to soybean. The SNP genotyping data was utilized to construct one of the most saturated intra-specific genetic linkage maps of chickpea having 3,363 mapped positions including 3,228 SNPs on 8 linkage groups spanning 1006.98 cM at an average inter marker distance of 0.33 cM. The map was utilized to identify 20 quantitative trait loci (QTLs) associated with seed traits accounting for phenotypic variations ranging from 9.97% to 29.71%. Analysis of the genomic sequence corresponding to five robust QTLs led to the identification of 684 putative candidate genes whose expression profiling revealed that 101 genes exhibited seed specific expression. The integrated approach utilizing the identified QTLs along with the available genome and transcriptome could serve as a platform for candidate gene identification for molecular breeding of chickpea.
Properties of skyrmions and multi-quanta vortices in chiral p-wave superconductors
Authors: Garaud Julien , Babaev Egor 
Published: December 2015

AbstractChiral p-wave superconducting state supports a rich spectrum of topological excitations different from those in conventional superconducting states. Besides domain walls separating different chiral states, chiral p-wave state supports both singular and coreless vortices also interpreted as skyrmions. Here, we present a numerical study of the energetic properties of isolated singular and coreless vortex states as functions of anisotropy and magnetic field penetration length. In a given chiral state, single quantum vortices with opposite winding have different energies and thus only one kind is energetically favoured. We find that with the appropriate sign of the phase winding, two-quanta (coreless) vortices are always energetically preferred over two isolated single quanta (singular) vortices. We also report solutions carrying more flux quanta. However those are typically more energetically expensive/metastable as compared to those carrying two flux quanta.
Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse
Authors: Liu Yuchen , Li Dameng , Liu Zhengya , Zhou Yu , Chu Danping , Li Xihan , Jiang Xiaohong , Hou Dongxia , Chen Xi , Chen Yuda , Yang Zhanzhao , Jin Ling , Jiang Waner , Tian Chenfei , Zhou Geyu , Zen Ke , Zhang Junfeng , Zhang Yujing , Li Jing , Zhang Chen-Yu 
Published: December 2015

AbstractCell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools. In the present study, we employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface to deliver opioid receptor mu (MOR) siRNA into the brain to treat morphine addiction. We found that MOR siRNA could be efficiently packaged into RVG exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered MOR siRNA into Neuro2A cells and the mouse brain. Functionally, siRNA-loaded RVG exosomes significantly reduced MOR mRNA and protein levels. Surprisingly, MOR siRNA delivered by the RVG exosomes strongly inhibited morphine relapse via the down-regulation of MOR expression levels. In conclusion, our results demonstrate that targeted RVG exosomes can efficiently transfer siRNA to the central nervous system and mediate the treatment of morphine relapse by down-regulating MOR expression levels. Our study provides a brand new strategy to treat drug relapse and diseases of the central nervous system.