bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stakeholder Meeting: Integrated Knowledge Translation Approach to Address the Caregiver Support Gap
Authors: Holroyd-Leduc Jayna M. , McMillan Jacqueline , Jette Nathalie , Brémault-Phillips Suzette C. , Duggleby Wendy , Hanson Heather M. , Parmar Jasneet 
Published: January 2017

RÉSUMÉLes aidants familiaux sont une partie intégrante et de plus en plus débordée du système de soins de santé. Il y a un écart entre ce que les données de recherche démontrent être bénéfique pour les soignants et ce qui est réellement fourni. À l’aide d’une approche basée sur l’application intégrée des connaissances (AC), une réunion des intervenants a inclus des chercheurs, des aidants familiaux, des associations de soignants, des cliniciens, des administrateurs de soins de santé et des décideurs. Les objectifs de la réunion étaient d’examiner les données issues des recherches en cours et de tenir un dialogue entre les intervenants multiples sur les lacunes, les facilitateurs et les obstacles à la fourniture d’un soutien aux aidants naturels. Cent vingt-trois individus ont participé à cette réunion. Trois populations cibles des aidants familiaux ont été identifiées pour discussion: soignants d’aînés atteints de démence, soignants en fin de vie et soignants d’aînés ayant des besoins de santé complexes. Les résultats de cette réunion sont et seront utilisés pour éclairer le développement des efforts visant à mettre en œuvre à la fois des recherches et des politiques afin de fournir un soutien aux aidants familiaux en se basant sur les preuves.
Climate-based prioritization of data collection for monitoring wintering birds in Latin America
Authors: AUER TOM , SOYKAN CANDAN U. , WILSEY CHAD B. , MICHEL NICOLE L. , JENSEN CAITLIN M. , LANGHAM GARY M. , LEBARON GEOFF , SANCHEZ CONNIE C. , TAKEKAWA JOHN 
Published: January 2017

SummaryRecent studies have highlighted the threat that climate change poses to species, as areas of climatic suitability contract or shift across the landscape. North American Neotropical long-distant migrant bird species present a unique problem compared to sedentary species because climate change may differ significantly across their breeding and wintering grounds. Studying the potential future distributions of these birds is challenging on many levels, including the fact that our understanding of the wintering grounds of these species is quite poor. To address this issue, we analyse available eBird data during the winter season in the Western Hemisphere in an effort to further promote and direct citizen science efforts to focus on areas that are climatically undersampled. We used Mobility-Oriented Parity (MOP) to understand the areas where climates are most dissimilar from climates sampled by existing eBird checklists, creating a map that ranks the western hemisphere at a 10 km resolution for climatic sampling during the winter season. We found that parts of Mexico and Central America, areas of Colombia, almost the entire Amazon Basin, coastal Peru and Chile, and northern Argentina are climatically undersampled. As a test case, we then used the map of survey priorities to simulate additional sampling in Colombia and recalculated the rankings. Guiding additional sampling with the priorities reduced climate dissimilarities between sampled and unsampled grid cells more than when additional sampling expanded in proportion to current sampling efforts or based on geographic undersampling. Analyses of sampling coverage in environmental space, such as this, will be a useful tool for targeting monitoring effort for bird species.
CUT TO THE CHEESE – REPLY TO SPIEGEL'S ‘WHY FLATULENCE IS FUNNY’
Authors: Steinert Steffen 
Published: January 2017

In number 35 of Think, James Spiegel presents reasons for why flatulence is funny. In this article I will address five issues that I find problematic in his account:
(1)His claim that laughter always results from a pleasant psychological shift is false.(2)His argumentative move from what makes paradigm cases funny to what makes flatulence funny is unwarranted.(3)His notion of a psychological shift is not specific enough and lacks explanatory power.(4)The claim that funniness of flatulence involves superiority is doubtful.(5)His talk about ‘nervous energy’ is questionable and has implausible implications.
Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration
Authors: Golestaneh Nady , Chu Yi , Xiao Yang-Yu , Stoleru Gianna L , Theos Alexander C 
Published: January 2017

AbstractAge-related macular degeneration (AMD) is a devastating neurodegenerative disease and a major cause of blindness in the developed world. Owing to its complexity and the lack of an adequate human model that recapitulates key aspects of the disease, the molecular mechanisms of AMD pathogenesis remain poorly understood. Here we show that cultured human retinal pigment epithelium (RPE) from AMD donors (AMD RPE) are functionally impaired and exhibit distinct phenotypes compared with RPE cultured from normal donors (normal RPE). Accumulation of lipid droplets and glycogen granules, disintegration of mitochondria, and an increase in autophagosomes were observed in AMD RPE cultures. Compared with normal RPE, AMD RPE exhibit increased susceptibility to oxidative stress, produce higher levels of reactive oxygen species (ROS) under stress conditions, and showed reduced mitochondrial activity. Measurement of the ratio of LC3-II/ LC3-I, revealed impaired autophagy in AMD RPE as compared with normal RPE. Autophagic flux was also reduced in AMD RPE as compared with normal RPE, as shown by inability of AMD RPE to downregulate p62 levels during starvation. Impaired autophagic pathways were further shown by analyzing late autophagic vesicles; immunostaining with lysosome-associated membrane protein 1 (LAMP-1) antibody revealed enlarged and annular LAMP-1-positive organelles in AMD RPE as opposed to smaller discrete puncta observed in normal RPE. Our study provides insights into AMD cellular and molecular mechanisms, proposes dysfunctional autophagy as an underlying mechanism contributing to the pathophysiology of the disease, and opens up new avenues for development of novel treatment strategies.
The TAZ–miR-224–SMAD4 axis promotes tumorigenesis in osteosarcoma
Authors: Ma Jianjun , Huang Kangmao , Ma Yan , Zhou Menglu , Fan Shunwu 
Published: January 2017

AbstractTranscriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo signaling pathway that participates in tumorigenesis. The aim of this study was to identify the miRNA counterpart for TAZ and elucidate the mechanism underlying the tumorigenic effect of TAZ. We demonstrated that TAZ is upregulated in osteosarcoma (OS) tissues and cell lines, and that TAZ overexpression can induce cell migration, invasion and proliferation. Moreover, miRNA-224 (miR-224), a TAZ phenocopy that functions downstream of TAZ, was found to be upregulated with TAZ overexpression. Further, a mechanistic study revealed that miR-224 functions by inhibiting the tumor suppressor, SMAD4, to support the proliferation and migration of OS cells. Our findings indicate that targeting TAZ and miR-224 could be a promising approach for the treatment of OS.
Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
Authors: Tahara Yu , Takatsu Yuta , Shiraishi Takuya , Kikuchi Yosuke , Yamazaki Mayu , Motohashi Hiroaki , Muto Aya , Sasaki Hiroyuki , Haraguchi Atsushi , Kuriki Daisuke , Nakamura Takahiro J , Shibata Shigenobu 
Published: January 2017

AbstractThe ability of the circadian clock to adapt to environmental changes is critical for maintaining homeostasis, preventing disease, and limiting the detrimental effects of aging. To date, little is known about age-related changes in the entrainment of peripheral clocks to external cues. We therefore evaluated the ability of the peripheral clocks of the kidney, liver, and submandibular gland to be entrained by external stimuli including light, food, stress, and exercise in young versus aged mice using in vivo bioluminescence monitoring. Despite a decline in locomotor activity, peripheral clocks in aged mice exhibited normal oscillation amplitudes under light–dark, constant darkness, and simulated jet lag conditions, with some abnormal phase alterations. However, age-related impairments were observed in peripheral clock entrainment to stress and exercise stimuli. Conversely, age-related enhancements were observed in peripheral clock entrainment to food stimuli and in the display of food anticipatory behaviors. Finally, we evaluated the hypothesis that deficits in sympathetic input from the central clock located in the suprachiasmatic nucleus of the hypothalamus were in part responsible for age-related differences in the entrainment. Aged animals showed an attenuated entrainment response to noradrenergic stimulation as well as decreased adrenergic receptor mRNA expression in target peripheral organs. Taken together, the present findings indicate that age-related circadian disorganization in entrainment to light, stress, and exercise is due to sympathetic dysfunctions in peripheral organs, while meal timing produces effective entrainment of aged peripheral circadian clocks.
Engineering glucose metabolism of Escherichia coli under nitrogen starvation
Authors: Chubukov Victor , Desmarais John James , Wang George , Chan Leanne Jade G , Baidoo Edward EK , Petzold Christopher J , Keasling Jay D , Mukhopadhyay Aindrila 
Published: January 2017

AbstractA major aspect of microbial metabolic engineering is the development of chassis hosts that have favorable global metabolic phenotypes, and can be further engineered to produce a variety of compounds. In this work, we focus on the problem of decoupling growth and production in the model bacterium Escherichia coli, and in particular on the maintenance of active metabolism during nitrogen-limited stationary phase. We find that by overexpressing the enzyme PtsI, a component of the glucose uptake system that is inhibited by α-ketoglutarate during nitrogen limitation, we are able to achieve a fourfold increase in metabolic rates. Alternative systems were also tested: chimeric PtsI proteins hypothesized to be insensitive to α-ketoglutarate did not improve metabolic rates under the conditions tested, whereas systems based on the galactose permease GalP suffered from energy stress and extreme sensitivity to expression level. Overexpression of PtsI is likely to be a useful arrow in the metabolic engineer’s quiver as productivity of engineered pathways becomes limited by central metabolic rates during stationary phase production processes.
Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson’s disease
Authors: Hare Dominic J , Cardoso Bárbara Rita , Raven Erika P , Double Kay L , Finkelstein David I , Szymlek-Gay Ewa A , Biggs Beverley-Ann 
Published: January 2017

AbstractIron accumulates gradually in the ageing brain. In Parkinson’s disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson’s diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson’s disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson’s disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson’s diseases and produce a potential biomarker of Parkinson’s disease risk in preclinical individuals.
The emergent role of small-bodied herbivores in pre-empting phase shifts on degraded coral reefs
Authors: Kuempel Caitlin D. , Altieri Andrew H. 
Published: January 2017

AbstractNatural and anthropogenic stressors can cause phase shifts from coral-dominated to algal-dominated states. In the Caribbean, over-fishing of large herbivorous fish and disease among the long-spined urchin, Diadema, have facilitated algal growth on degraded reefs. We found that diminutive species of urchin and parrotfish, which escaped die-offs and fishing pressure, can achieve abundances comparable to total herbivore biomass on healthier, protected reefs, and exert sufficient grazing function to pre-empt macroalgal dominance following mass coral mortality. Grazing was highest on the most degraded reefs, and was driven by small herbivores that made up >93% of the average herbivore biomass (per m2). We suggest that previously marginal species can achieve a degree of functional redundancy, and that their compensatory herbivory may play an important role in ecosystem resilience. Management strategies should consider the potential role of these additional herbivore functional groups in safeguarding natural controls of algal growth in times of increased uncertainty for the world’s reefs.
Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma
Authors: Neira José L. , Bintz Jennifer , Arruebo María , Rizzuti Bruno , Bonacci Thomas , Vega Sonia , Lanas Angel , Velázquez-Campoy Adrián , Iovanna Juan L. , Abián Olga 
Published: January 2017

AbstractIntrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor developmentin vivoon xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the ‘fuzzy’ interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs.
Phosphorylation impact on Spleen Tyrosine kinase conformation by Surface Enhanced Raman Spectroscopy
Authors: Cottat Maximilien , Yasukuni Ryohei , Homma Yo , Lidgi-Guigui Nathalie , Varin-Blank Nadine , Lamy de la Chapelle Marc , Le Roy Christine 
Published: January 2017

AbstractSpleen Tyrosine Kinase (Syk) plays a crucial role in immune cell signalling and its altered expression or activation are involved in several cancers. Syk activity relies on its phosphorylation status and its multiple phosphorylation sites predict several Syk conformations. In this report, we characterized Syk structural changes according to its phosphorylation/activation status by Surface Enhanced Raman Spectroscopy (SERS). Unphosphorylated/inactive and phosphorylated/active Syk forms were produced into two expression systems with different phosphorylation capability. Syk forms were then analysed by SERS that was carried out in liquid condition on a lithographically designed gold nanocylinders array. Our study demonstrated that SERS signatures of the two Syk forms were drastically distinct, indicating structural modifications related to their phosphorylation status. By comparison with the atomic structure of the unphosphorylated Syk, the SERS peak assignments of the phosphorylated Syk nearest gold nanostructures revealed a differential interaction with the gold surface. We finally described a model for Syk conformational variations according to its phosphorylation status. In conclusion, SERS is an efficient technical approach for studying in vitro protein conformational changes and might be a powerful tool to determine protein functions in tumour cells.
Hepatic MiR-291b-3p Mediated Glucose Metabolism by Directly Targeting p65 to Upregulate PTEN Expression
Authors: Guo Jun , Dou Lin , Meng Xiangyu , Chen Zhenzhen , Yang Weili , Fang Weiwei , Yang Chunxiao , Huang Xiuqing , Tang Weiqing , Yang Jichun , Li Jian 
Published: January 2017

AbstractSeveral studies have suggested an important role of miR-291b-3p in the development of embryonic stem cells. In previous study, we found that the expression of miR-291b-3p was significantly upregulated in the liver of db/db mice. However, the role of miR-291b-3p in glucose metabolism and its underlying mechanisms remain unknown. In the present study, we demonstrated that miR-291b-3p was abundantly expressed in the liver. Of note, hepatic miR-291b-3p expression was upregulated in HFD-fed mice and induced by fasting in C57BL/6 J normal mice. Importantly, hepatic inhibition miR-291b-3p expression ameliorated hyperglycemia and insulin resistance in HFD-fed mice, whereas hepatic overexpression of miR-291b-3p led to hyperglycemia and insulin resistance in C57BL/6 J normal mice. Further study revealed that miR-291b-3p suppressed insulin-stimulated AKT/GSK signaling and increased the expression of gluconeogenic genes in hepatocytes. Moreover, we identified that p65, a subunit of nuclear factor-κB (NF-κB), is a target of miR-291b-3p by bioinformatics analysis and luciferase reporter assay. Silencing of p65 significantly augmented the expression of PTEN and impaired AKT activation. In conclusion, we found novel evidence suggesting that hepatic miR-291b-3p mediated glycogen synthesis and gluconeogenesis through targeting p65 to regulate PTEN expression. Our findings indicate the therapeutic potential of miR-291b-3p inhibitor in hyperglycemia and insulin resistance.
Evaluation of 10-Nitro Oleic Acid Bio-Elimination in Rats and Humans
Authors: Salvatore Sonia R. , Vitturi Dario A. , Fazzari Marco , Jorkasky Diane K. , Schopfer Francisco J. 
Published: January 2017

AbstractNitrated fatty acids are endogenously present in human and animal tissues, as well as in plant-derived oils. In particular, 10-nitro oleic acid (10-NO2-OA) potently induces Nrf2-dependent antioxidant gene expression and inhibits TLR4/NF-κB signaling, thus promoting an overall cyto-protective and anti-inflammatory response. 10-NO2-OA has been extensively tested in animal models and is currently undergoing clinical evaluation in humans. Bio-elimination pathways for 10-NO2-OA were evaluated in rats (30 mg/kg·day) and in humans (0.34 mg/kg) using samples obtained from a double-blind, dose-rising clinical trial. Quantitative radiochromatographic/MS analysis indicated that the renal and fecal pathways are the main routes for 10-NO2-OA excretion in rats, and allowed the identification of 4-nitro-octanedioic acid (NO2-8:0-diCOOH) as the most abundant metabolite in rat urine. In addition, high resolution LC-MS/MS analysis revealed the presence of a novel series of urinary metabolites including ω-carboxylation and β-oxidation products, as well as N-acetylcysteine, taurine and sulfo-conjugates in both rats and humans. Overall, the findings reported herein not only provide valuable tools for the experimental evaluation of 10-NO2-OA levels in vivo, but importantly they also set the basis for monitoring its metabolism during potential clinical interventions in humans.
Asymmetric interaction of point defects and heterophase interfaces in ZrN/TaN multilayered nanofilms
Authors: Lao Yuanxia , Hu Shuanglin , Shi Yunlong , Deng Yu , Wang Fei , Du Hao , Zhang Haibing , Wang Yuan 
Published: January 2017

AbstractMaterials with a high density of heterophase interfaces, which are capable of absorbing and annihilating radiation-induced point defects, can exhibit a superior radiation tolerance. In this paper, we investigated the interaction behaviors of point defects and heterophase interfaces by implanting helium atoms into the ZrN/TaN multilayered nanofilms. It was found that the point defect-interface interaction on the two sides of the ZrN/TaN interface was asymmetric, likely due to the difference in the vacancy formation energies of ZrN and TaN. The helium bubbles could migrate from the ZrN layers into the TaN layers through the heterophase interfaces, resulting in a better crystallinity of the ZrN layers and a complete amorphization of the TaN layers. The findings provided some clues to the fundamental behaviors of point defects near the heterophase interfaces, which make us re-examine the design rules of advanced radiation-tolerant materials.
Large-scale synthesis of uniform hexagonal boron nitride films by plasma-enhanced atomic layer deposition
Authors: Park Hamin , Kim Tae Keun , Cho Sung Woo , Jang Hong Seok , Lee Sang Ick , Choi Sung-Yool 
Published: January 2017

AbstractHexagonal boron nitride (h-BN) has been previously manufactured using mechanical exfoliation and chemical vapor deposition methods, which make the large-scale synthesis of uniform h-BN very challenging. In this study, we produced highly uniform and scalable h-BN films by plasma-enhanced atomic layer deposition, which were characterized by various techniques including atomic force microscopy, transmission electron microscopy, Raman spectroscopy, and X-ray diffraction. The film composition studied by X-ray photoelectron spectroscopy and Auger electron spectroscopy corresponded to a B:N stoichiometric ratio close to 1:1, and the band-gap value (5.65 eV) obtained by electron energy loss spectroscopy was consistent with the dielectric properties. The h-BN-containing capacitors were characterized by highly uniform properties, a reasonable dielectric constant (3), and low leakage current density, while graphene on h-BN substrates exhibited enhanced electrical performance such as the high carrier mobility and neutral Dirac voltage, which resulted from the low density of charged impurities on the h-BN surface.
Associations among executive function, cardiorespiratory fitness, and brain network properties in older adults
Authors: Kawagoe Toshikazu , Onoda Keiichi , Yamaguchi Shuhei 
Published: January 2017

AbstractAging is associated with deterioration in a number of cognitive functions. Previous reports have demonstrated the beneficial effect of physical fitness on cognitive function, especially executive function (EF). The graph theoretical approach models the brain as a complex network represented graphically as nodes and edges. We analyzed several measures of EF, an index of physical fitness, and resting-state functional magnetic resonance imaging data from healthy older volunteers to elucidate the associations among EF, cardiorespiratory fitness, and brain network properties. The topological neural properties were significantly related to the level of EF and/or physical fitness. Global efficiency, which represents how well the whole brain is integrated, was positively related, whereas local efficiency, which represents how well the brain is functionally segregated, was negatively related, to the level of EF and fitness. The associations among EF, physical fitness and topological resting-state functional network property appear related to compensation and dedifferentiation in older age. A mediation analysis showed that high-fit older adults gain higher global efficiency of the brain at the expense of lower local efficiency. The results suggest that physical fitness may be beneficial in maintaining EF in healthy aging by enhancing the efficiency of the global brain network.