bluuebunny/crossref_metadata_2025 huggingface dataset:
1H NMR spectroscopy and multivariate analysis as possible tool to assess cultivars, from specific geographical areas, in EVOOs
Authors: Girelli Chiara Roberta , Del Coco Laura , Fanizzi Francesco Paolo
Published: December 2015

In this work, we tested a NMR‐based MVA method to assess the authenticity of EVOOs cultivar (from specific origin) declaration by using a total of over a 100 samples coming from different selected areas of Southern Italian Regions (Apulia and Calabria). We built a reference model, by performing unsupervised PCA and supervised PLS‐DA, OPLS‐DA analyses on the 1HNMR spectra of a 40 monovarietal EVOOs training set. These included 10 Coratina (the most popular Apulian cultivar) together with 10 Picholine, 10 Ogliarola Barese, and 10 Carolea samples (the most common Coratina bitterness smoothers cultivars used in Coratina‐based blends). The training set originated PLS‐DA reference model was profitably used to assess the class membership for a series of declared monocultivar EVOO samples and to obtain a clear indication for the composition of Coratina‐based blends. By using the same reference model we analyzed in blind a test set formed by 40 unknown samples coming from the same areas and we predicted their class or blend composition affinity (later confirmed by suppliers as Coratina‐ or Coratina‐based blends). This proposed method could be a simple and quick tool to assess, also for trading purpose, the cultivar (from given geographical areas) declaration of labeled EVOOs.

Practical applications: EVOO is one of the most important element of the Mediterranean diet with its numerous health benefits due to the chemical composition (unsaturated fatty acids and minor components). For this high commercial value in the recent years, EVOO has been processed to adulteration process with seeds oils, refined pomace, and esterified oils with serious damage to its quality. In order to guarantee the quality of this important product, EU Regulation 182 of March 6, 2009, stated the obligatory labeling of EVOO samples with the geographical production area for all European countries. Surprisingly, this regulation lacks of an official methodology to assess the origin and the cultivar of EVOOs. A quick and reproducible method to check the label declaration of commercial EVOOs could be attractive for industry and ensure transparency for consumer choices.

Work flow chart illustrating the procedures sequence to assess cultivars, from specific geographical areas, in EVOOs. A reference model is built and its prediction capability is tested with monovarietal and blend commercial extra virgin olive oil samples.
Impact of Ionomer Content on Proton Exchange Membrane Fuel Cell Performance
Authors: Afsahi F. , Mathieu‐Potvin F. , Kaliaguine S.
Published: December 2015

The effect of Nafion ionomer content on performance of a proton exchange membrane (PEM) fuel cell operated with home‐made anodic and cathodic electrodes fabricated from a novel metal organic framework (MOF) derived Pt‐based electrocatalyst was investigated via numerical simulation and experimental measurement. First, the parameter sensitivity analysis was performed to identify the most influential parameters of the model. Then, these parameters were calibrated for different fuel cell designs investigated in the current study by employing the corresponding experimental data. Afterwards, the calibrated model was used to examine the impact of Nafion content in the catalyst layer of home‐made electrodes. Finally, the qualitative trend predicted by this model was experimentally surveyed by varying the Nafion content between 10–50 wt.% in the catalyst layer of home‐made electrodes. At the anode side, the performance of home‐made electrode in a PEM fuel cell demonstrated small dependency on Nafion content. For the cathodic home‐made electrode, Nafion content was found to affect the PEM fuel cell performance more strongly. Although the model could correctly capture the impact of Nafion content on calculated polarization curves, the model predicted optimum values significantly deviate from the experimental results. This was related to the several simplifications made during model development.
HEALing Higher Education: An Innovative Approach to Preparing HSI Leaders
Authors: Freeman Melissa L.
Published: December 2015

This chapter is a case study of the Higher Education Administration and Leadership (HEAL) program at Adams State University. HEAL focuses on preparing the next generation of leaders at the nation's Hispanic‐serving institutions.
Institutionalizing Support for Undocumented Latino/a Students in American Higher Education
Authors: Gildersleeve Ryan Evely , Vigil Darsella
Published: December 2015

This chapter investigates the institutionalization of support for undocumented students across states that either extend or deny in‐state resident tuition (ISRT) benefits. In their review, the authors highlight promising practices.
Latino Male Ethnic Subgroups: Patterns in College Enrollment and Degree Completion
Authors: Ponjuan Luis , Palomin Leticia , Calise Angela
Published: December 2015

This chapter examines Latino male ethnic subgroups and their college enrollment and degree completion patterns. The chapter also offers recommendations to improve Latino male ethnic subgroups’ educational achievement.
Socio‐economic Inequality in the Use of Procedures and Mortality Among AMI Patients: Quantifying the Effects Along Different Paths
Authors: Hagen Terje P. , Häkkinen Unto , Iversen Tor , Klitkou Søren Toksvig , Moger Tron Anders ,   on behalf of the EuroHOPE study group
Published: December 2015

It is not known whether inequality in access to cardiac procedures translates into inequality in mortality. In this paper, we use a path analysis model to quantify both the direct effect of socio‐economic status on mortality and the indirect effect of socio‐economic status on mortality as mediated by the provision of cardiac procedures. The study links microdata from the Finnish and Norwegian national patient registers describing treatment episodes with data from prescription registers, causes‐of‐death registers and registers covering education and income. We show that socio‐economic variables affect access to percutaneous coronary intervention in both countries, but that these effects are only moderate and that the indirect effects of the socio‐economic factors on mortality through access to percutaneous coronary intervention are minor. The direct effects of income and education on mortality are significantly larger. We conclude that the socio‐economic gradient in the use of percutaneous coronary intervention adds to socio‐economic differences in mortality to little or no extent. Copyright © 2015 John Wiley & Sons, Ltd.
On a nonlocal problem for the Laplace equation in the unit ball with fractional boundary conditions
Authors: Kirane Mokhtar , Torebek Berikbol T.
Published: December 2015

In this paper, we investigate the correct solvability for the Laplace equation with a nonlocal boundary condition in the unit ball. The considered boundary operator is of fractional order. This problem is a generalization of the well‐known Bitsadze–Samarskii problem. Copyright © 2015 John Wiley & Sons, Ltd.
Numerical investigations of microscopic characteristic influences on the mechanical properties of polymer‐matrix composites
Authors: Ye Junjie , Qiu Yuanying , Chen Xuefeng , Zhai Zhi , Huang Changlong , Zhang Xinglong
Published: December 2015

In this study, an isoparametric micro‐mechanical model is developed to study the failure behaviors under biaxial loadings for composites with different fiber arrangements. For validating the method, the numerical results of the unidirectional (UD) composite lamina with consideration of two different failure criteria (the constituent failure criterion and UD failure criterion) are compared with the experimental results. On this basis, the fiber arrangements and fiber off‐axis angles influence on the failure envelopes for the UD composite lamina are studied. Furthermore, the failure strength of a typical composite laminates is also investigated. The results show that the failure strength of composite laminates is closely dependent on the fiber arrangements. Compared with the hexagonal packing, the square diagonal packing provides the higher failure strengths. POLYM. COMPOS., 38:2734–2742, 2017. © 2015 Society of Plastics Engineers
Link adaptation in mobile satellite links: schemes for different degrees of CSI knowledge
Authors: Rico‐Alvariño Alberto , Arnau Jesus , Mosquera Carlos
Published: December 2015

We consider the problem of modulation and coding scheme selection in the return link of a mobile satellite system. We propose to use an affine combination of both open loop and closed loop signal quality indicators to perform this selection. The combination weights are dynamically adapted according to the acknowledgement/negative acknowledgement (ACK/NAK) exchange between both ends, without making any assumptions on the channel distribution; this adaptation procedure is obtained as a stochastic programming solution to an optimization problem. We further extend our analysis to the particular case of not having information on the channel state, exploiting only ACK/NAK exchange for the rate selection problem. Simulation results will show the good performance of the proposed affine‐combination method compared with previous algorithms, and its robustness to environment changes. Copyright © 2015 John Wiley & Sons, Ltd.
Security approach to controlling access to personal health records in healthcare service
Authors: Chen Tzer‐Long , Liao Yu‐Ting , Chang Yi‐Fan , Hwang Jen‐Hung
Published: December 2015

The changing information technology and the constant progress of medical technologies have gradually changed traditional paper‐based medical records into low‐cost electronic health records. The broad application of electronic health records allows a medical information exchange model being developed, called personal health records (PHR), which are the personal health medical information managed and maintained by the user. In consideration of PHR being a patient's health medical information, the privacy setting and the access authority have to be strictly controlled. In addition to providing users with reasonable access authorities, the PHR system has to avoid the illegal access of unauthorized single users or groups. The idea of public‐key cryptosystems and Lagrange interpolating polynomial is applied to construct a high‐security and efficient encryption scheme so that PHR users could execute the access system in a secure environment. Copyright © 2015 John Wiley & Sons, Ltd.
Porphyrin Nanodroplets: Sub‐micrometer Ultrasound and Photoacoustic Contrast Imaging Agents
Authors: Paproski Robert J. , Forbrich Alexander , Huynh Elizabeth , Chen Juan , Lewis John D. , Zheng Gang , Zemp Roger J.
Published: December 2015

A novel class of all‐organic nanoscale porphyrin nanodroplet agents is presented which is suitable for multimodality ultrasound and photoacoustic molecular imaging. Previous multimodality photoacoustic‐ultrasound agents are either not organic, or not yet demonstrated to exhibit enhanced accumulation in leaky tumor vasculature, perhaps because of large diameters. In the current study, porphyrin nanodroplets are created with a mean diameter of 185 nm which is small enough to exhibit the enhanced permeability and retention effect. Porphyrin within the nanodroplet shell has strong optical absorption at 705 nm with an estimated molar extinction coefficient >5 × 109 m−1 cm−1, allowing both ultrasound and photoacoustic contrast in the same nanoparticle using all organic materials. The potential of nanodroplets is that they may be phase‐changed into microbubbles using high pressure ultrasound, providing ultrasound contrast with single‐bubble sensitivity. Multispectral photoacoustic imaging allows visualization of nanodroplets when injected intratumorally in an HT1080 tumor in the chorioallantoic membrane of a chicken embryo. Intravital microscopy imaging of Hep3‐GFP and HT1080‐GFP tumors in chicken embryos determines that nanodroplets accumulated throughout or at the periphery of tumors, suggesting that porphyrin nanodroplets may be useful for enhancing the visualization of tumors with ultrasound and/or photoacoustic imaging.
Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders—review and meta‐analysis of observational studies published over more than 35 years
Authors: Burgard Peter , Kölker Stefan , Haege Gisela , Lindner Martin , Hoffmann Georg F.
Published: December 2015

Background

For urea cycle disorders (UCD), proportions and mortality of early onset (EO) patients, as well as outcome at one year of life show large variability. We aimed to integrate available evidence to create benchmarks for new diagnostic and therapeutic strategies.

Methods

Medline search for reports published between 1978 and Dec 22, 2014 was completed by hand search. Random effects meta‐analysis was done for four UCDs, deficiency of carbamylphosphate synthetase 1 (CPS1D), male/female ornithine transcarbamylase (OTCDm/f), argininosuccinate synthetase (ASSD) and lyase (ASLD). Effects of publication year and geographic area were analysed by meta‐regression.

Results

Twenty‐four publications report onset time (n = 1542 patients), survival of EO (n = 665 patients) and outcome at one year of life (n = 172 patients). Proportions for EO manifestation (95 % confidence interval) were: CPS1D = 0.75 (0.61;0.88); OTCDm = 0.52 (0.39;0.65); OTCDf = 0.07 (0.03;0.11); ASSD = 0.65 (0.57;0.73); ASLD = 0.60 (0.44;0.77); for surviving EO patients: CPS1D = 0.64 (0.50;0.79); OTCDm = 0.40 (0.16;0.64); OTCDf = 0.57 (0.29;0.85); ASSD = 0.67 (0.48;0.86); ASLD = 0.81 (0.68;0.94); and for normal outcome at one year for survivors: CPS1D = 0.20 (0.07;0.38); OTCDm = 0.15 (0.00;0.39); OTCDf no data; ASSD = 0.36 (0.13;0.60); ASLD = 0.36 (0.17;0.58). Between study variation was large. Year of publication had no effect. Studies from Europe showed lower survival rates than those from Japan or USA.

Conclusions

UCDs, except for OTCDf, have high risks of EO disease manifestation and, except for ASLD, of neonatal death. No improvement of survival was observed over more than three decades. Geographic variation remains to be explained. This comprehensive description of the natural history of EO UCDs should be considered by scientists, clinicians, health policy makers and guideline developers.
Mikrozephalie bei psychomotorischen Entwicklungsstörungen und geistiger Behinderung
Authors: Zweier Christiane
Published: December 2015

Eine geistige Behinderung kommt bei ca. 2–3 % der Bevölkerung vor. Sowohl die klinischen Erscheinungsbilder als auch die genetischen Ursachen sind extrem heterogen. Es können sowohl chromosomale als auch monogene Veränderungen ursächlich sein. Eine Mikrozephalie ist ein häufiges Symptom bei psychomotorischen Entwicklungsstörungen und geistiger Behinderung, was auf überlappende Pathomechanismen hindeutet. Etwa 23 % der bekannten, mit geistiger Behinderung assoziierten Gene sind auch mit Mikrozephalie assoziiert. Weitere häufige Komorbiditäten sind Krampfanfälle, Kleinwuchs oder Fehlbildungen. In einer Kohorte von über 700 Patienten mit psychomotorischer Entwicklungsstörung, die in der genetischen Sprechstunde des Humangenetischen Instituts in Erlangen gesehen wurden, waren 22,5 % auch mikrozephal. Dabei korrelierte die Schwere der Mikrozephalie mit der Schwere der kognitiven Einschränkung und dem Auftreten von Krampfanfällen.

In dieser Übersichtsarbeit werden genetische Ursachen für psychomotorische Entwicklungsstörungen mit Mikrozephalie sowie die Häufigkeit einer Mikrozephalie in einer Kohorte von Patienten mit ungeklärter Entwicklungsstörung und ihre Bedeutung bei der Diagnosefindung bei geistiger Behinderung diskutiert.
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.
Selflessness and the Loss of Self
Authors: Hampton Jean
Published: December 2015

The biggest danger, that of losing oneself, can pass off in the world as quietly as if it were nothing; every other loss, an arm, a leg, five dollars, a wife, etc. is bound to be noticed.

Soren Kierkegaard, The Sickness Unto Death
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

Students 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 Murdoch Early Intervention Program After 2 Years
Authors: Birnbrauer Jay S. , Leach David J.
Published: December 2015

The goal of the Murdoch Early Intervention Program (MEIP) was to replicate the intensive early intervention program designed by Lovaas for children with severe developmental disability and autism. This paper describes the objectives, methods, and the results as of 24 months. Although MEIP differs from Lovaas's model in several respects, and the children have been generally less capable at the outset, results are interpreted tentatively as being as predicted. Four of 9 experimental children have shown signs of approaching normal levels of functioning whereas 1 of 5 control children has made significant progress. Improvements in the remainder of the children are rated as moderate to minimal. These preliminary results are presented to encourage others working with children with autism and other difficult-to-teach children to publish their methods and results. The small number of children in any one locality, and the high cost of controlled studies indicates the necessity for accumulating findings across service providers.
Using Questions in Cognitive Therapy with People with Intellectual Disabilities
Authors: Dagnan Dave , Pulford Helen , Cathers Rebecca , Jahoda Andrew
Published: December 2015

Background: There is increasing interest in the provision of cognitive behaviour therapy (CBT) to people with intellectual disabilities. A small number of studies have begun to address therapy process issues. Aims: The aim of this paper is to contribute to process research through the development of a taxonomy of question types for use in analysing therapy interactions in CBT for people with intellectual disabilities. Method: A taxonomy of CBT question types was adapted and applied to the transcriptions of session 4 and 9 of 15 CBT therapy dyads. Results: The taxonomy was reliably applied to the data. Therapists used significantly more questions in session 4 than in session 9, therapists used fewer questions in the final quarter of all sessions, and therapists used more questions with people with higher IQ scores in session 4 but not in session 9. Conclusions: The taxonomy of questions is reliable and may be used in future studies of CBT therapy process with people with intellectual disabilities.
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

Objective

Dietary 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.

Design

We conducted qualitative research to assess community acceptability and obtain feedback on the design of the dietary tools.

Setting

This research took place in urban and rural communities in Western Kenya.

Subjects

We 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.

Results

Tools 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).

Conclusions

Results 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.
Atom Probe Tomography Analysis of a Gallium-Nitride-Based Commercial Light-Emitting Diode
Authors: Prosa T.J. , Olson D. , Giddings A.D. , Lefebvre W. , Clifton P.H. , Larson D.J.
Published: December 2015

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Aerosols May Play a Big Part in Atmospheric Absorption
Authors: Strelich Lily
Published: December 2015

A new study shows that aerosols have a strong impact on the reflectivity of the Earth's atmosphere, absorbing more solar radiation within the atmospheric layers than previously thought.
Taking the Pulse of the Earth's Surface Systems
Authors: Larsen Laurel , Hajek Elizabeth , Maher Kate , Paola Chris , Merritts Dorothy , Bralower Timothy , Montañez Isabel , Wing Scott , Snyder Noah , Hochella Jr. Michael , Kump Lee , Person Mark
Published: December 2015

As human activity alters the Earth's surface environment in unprecedented ways, a comprehensive survey campaign is necessary to predict future impacts.
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

Homeodomain-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

Rasfonin 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

Emerging 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

Neuroblastoma (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

The 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

PTEN 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

DICER1is 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

The 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

Pain 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

This 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

Chiral 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

Cell-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.
Ultrafine ferroferric oxide nanoparticles embedded into mesoporous carbon nanotubes for lithium ion batteries
Authors: Gao Guo , Zhang Qiang , Cheng Xin-Bing , Shapter Joseph G. , Yin Ting , Sun Rongjin , Cui Daxiang
Published: December 2015

An effective one-pot hydrothermal method for in situ filling of multi-wall carbon nanotubes (CNT, diameter of 20–40 nm, length of 30–100 μm) with ultrafine ferroferric oxide (Fe3O4) nanoparticles (8–10 nm) has been demonstrated. The synthesized Fe3O4@CNT exhibited a mesoporous texture with a specific surface area of 109.4 m2 g−1. The loading of CNT, in terms of the weight ratio of Fe3O4 nanoparticles, can reach as high as 66.5 wt%. Compared to the conventional method of using a Al2O3 membrane as template to fill CNT with iron oxides nanoparticles, our strategy is facile, effective, low cost and easy to scale up to large scale production (~1.42 g per one-pot). When evaluated for lithium storage at 1.0 C (1 C = 928 mA g−1), the mesoporous Fe3O4@CNT can retain at 358.9 mAh g−1 after 60 cycles. Even when cycled at high rate of 20 C, high capacity of 275.2 mAh g−1 could still be achieved. At high rate (10 C) and long life cycling (500 cycles), the cells still exhibit a good capacity of 137.5 mAhg−1.
TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma
Authors: Damo Martina , Wilson David S. , Simeoni Eleonora , Hubbell Jeffrey A.
Published: December 2015

Dendritic cell (DC)-derived exosomes (Dexo) contain the machinery necessary to activate potent antigen-specific immune responses. As promising cell-free immunogens, Dexo have been tested in previous clinical trials for cancer vaccine immunotherapy, yet resulted in limited therapeutic benefit. Here, we explore a novel Dexo vaccine formulation composed of Dexo purified from DCs loaded with antigens and matured with either the TLR-3 ligand poly(I:C), the TLR-4 ligand LPS or the TLR-9 ligand CpG-B. When poly(I:C) was used to produce exosomes together with ovalbumin (OVA), the resulting Dexo vaccine strongly stimulated OVA-specific CD8+ and CD4+ T cells to proliferate and acquire effector functions. When a B16F10 melanoma cell lysate was used to load DCs with tumor antigens during exosome production together with poly(I:C), we obtained a Dexo vaccine capable of inducing robust activation of melanoma-specific CD8+ T cells and the recruitment of cytotoxic CD8+ T cells, NK and NK-T cells to the tumor site, resulting in significantly reduced tumor growth and enhanced survival as compared to a Dexo vaccine formulation similar to the one previously tested on human patients. Our results indicate that poly(I:C) is a particularly favorable TLR agonist for DC maturation during antigen loading and exosome production for cancer immunotherapy.
A small molecule inhibitor for ATPase activity of Hsp70 and Hsc70 enhances the immune response to protein antigens
Authors: Baek Kyung-Hwa , Zhang Haiying , Lee Bo Ryeong , Kwon Young-Guen , Ha Sang-Jun , Shin Injae
Published: December 2015

The ATPase activities of Hsp70 and Hsc70 are known to be responsible for regulation of various biological processes. However, little is known about the roles of Hsp70 and Hsc70 in modulation of immune responses to antigens. In the present study, we investigated the effect of apoptozole (Az), a small molecule inhibitor of Hsp70 and Hsc70, on immune responses to protein antigens. The results show that mice administered with both protein antigen and Az produce more antibodies than those treated with antigen alone, showing that Az enhances immune responses to administered antigens. Treatment of mice with Az elicits production of antibodies with a high IgG2c/IgG1 ratio and stimulates the release of Th1 and Th2-type cytokines, suggesting that Az activates the Th1 and Th2 immune responses. The observations made in the present study suggest that inhibition of Hsp70 and Hsc70 activities could be a novel strategy designing small molecule-based adjuvants in protein vaccines.