bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute stimulation of mesenchymal stem cells with cigarette smoke extract affects their migration, differentiation and paracrine potential
Authors: Wahl Elizabeth A. , Schenck Thilo L. , Machens Hans-Günther , Egaña J. Tomás 
Published: March 2016

AbstractMesenchymal stem cells (MSCs) are known to play a key role in tissue regeneration, while smoking cigarettes is described to impair it. This work focuses on the effect cigarette smoke extract (CSE) has on the migration, differentiation and paracrine potential of human adipose derived MSCs (AdMSCs). To mimic native conditions in vitro, AdMSCs were cultured in either monolayer or three-dimensional pellet cultures. While constant exposure to high concentrations of CSE had lethal effects on AdMSCs, lower concentrations of CSE impaired cell migration when compared to control conditions. The secretion of key interleukins was downregulated when CSE was exposed to the cells at low concentrations. Moreover, in this work AdMSCs were exposed to CSE while simultaneously being induced to differentiate into adipocytes, osteoblasts and chondrocytes to determine the effect of CSE on the cells potential to differentiate. While adipogenic differentiation showed no significant variation, AdMSCs exposed to osteogenic and chondrogenic supplements showed both early and late genetic level variation when acutely exposed to low concentrations of CSE. Our results indicate that even a small amount of cigarette smoke can have detrimental effects on the regenerative potential of MSCs.
Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog
Authors: Wang Xiaowen , Hodgkinson Conrad P , Lu Kefeng , Payne Alan J , Pratt Richard E , Dzau Victor J 
Published: March 2016

AbstractWe have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. However, direct reprogramming strategies are inefficient and slow. Moving towards the eventual goal of clinical application it is necessary to develop new methodologies to overcome these limitations. Here, we report the identification of a specific media composition, reprogramming media (RM), which augmented the effect of miR combo by 5–15-fold depending upon the cardiac marker tested. RM alone was sufficient to strongly induce cardiac gene and protein expression in neonatal tail-tip as well as cardiac fibroblasts. Expression of pluripotency markers Nanog, Oct4, Sox2 and Klf4 was significantly enhanced by RM, with miR combo augmenting the effect further. Knockdown of Nanog by siRNA inhibited the effect of RM on cardiac gene expression. Removal of insulin-transferrin-selenium completely inhibited the effect of reprogramming media upon cardiac gene expression and the addition of selenium to standard culture media recapitulated the effects of RM. Moreover, selenium enhanced the reprogramming efficiency of miR combo.
Controlled synthesis of Ni/CuOx/Ni nanowires by electrochemical deposition with self-compliance bipolar resistive switching
Authors: Park Kyuhyun , Lee Jang-Sik 
Published: March 2016

AbstractWe demonstrate synthesis of Ni/CuOx/Ni nanowires (NWs) by electrochemical deposition on anodized aluminum oxide (AAO) membranes. AAO with pore diameter of ~70 nm and pore length of ~50 μm was used as the template for synthesis of NWs. After deposition of Au as the seed layer, NWs with a structure of Ni/CuOx/Ni were grown with a length of ~12 μm. The lengths of 1st Ni, CuOx, and 2nd Ni were ~4.5 μm, ~3 μm, and ~4.5 μm, respectively. The Ni/CuOx/Ni device exhibits bipolar resistive switching behavior with self-compliance characteristics. Due to the spatial restriction of the current path in NW the Ni/CuOx/Ni NW devices are thought to exhibit self-compliance behaviour. Ni/CuOx/Ni NWs showed bipolar resistive changes possibly due to conducting filaments that are induced by oxygen vacancies. The reliability of the devices was confirmed by data retention measurement. The NW-based resistive switching memory has applications in highly scalable memory devices and neuromorphic devices.
Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression
Authors: Miyata Shingo , Taniguchi Manabu , Koyama Yoshihisa , Shimizu Shoko , Tanaka Takashi , Yasuno Fumihiko , Yamamoto Akihide , Iida Hidehiro , Kudo Takashi , Katayama Taiichi , Tohyama Masaya 
Published: March 2016

AbstractRepeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs and that specific white matter abnormalities are closely associated with MDD onset.
The isotype ZnO/SiC heterojunction prepared by molecular beam epitaxy – A chemical inert interface with significant band discontinuities
Authors: Zhang Yufeng , Lin Nanying , Li Yaping , Wang Xiaodan , Wang Huiqiong , Kang Junyong , Wilks Regan , Bär Marcus , Mu Rui 
Published: March 2016

AbstractZnO/SiC heterojunctions show great potential for various optoelectronic applications (e.g., ultraviolet light emitting diodes, photodetectors and solar cells). However, the lack of a detailed understanding of the ZnO/SiC interface prevents an efficient and rapid optimization of these devices. Here, intrinsic (but inherently n-type) ZnO were deposited via molecular beam epitaxy on n–type 6H-SiC single crystalline substrates. The chemical and electronic structure of the ZnO/SiC interfaces were characterized by ultraviolet/x-ray photoelectron spectroscopy and x-ray excited Auger electron spectroscopy. In contrast to the ZnO/SiC interface prepared by radio frequency magnetron sputtering, no willemite-like zinc silicate interface species is present at the MBE-ZnO/SiC interface. Furthermore, the valence band offset at the abrupt ZnO/SiC interface is experimentally determined to be (1.2 ± 0.3) eV, suggesting a conduction band offset of approximately 0.8 eV, thus explaining the reported excellent rectifying characteristics of isotype ZnO/SiC heterojunctions. These insights lead to a better comprehension of the ZnO/SiC interface and show that the choice of deposition route might offer a powerful means to tailor the chemical and electronic structures of the ZnO/SiC interface, which can eventually be utilized to optimize related devices.
Dissection and integration of the autophagy signaling network initiated by bluetongue virus infection: crucial candidates ERK1/2, Akt and AMPK
Authors: Lv Shuang , Xu Qing-Yuan , Sun En-Cheng , Zhang Ji-Kai , Wu Dong-Lai 
Published: March 2016

AbstractBluetongue virus (BTV), a complex double-stranded segmented RNA virus, has been found to initiate cellular autophagy for its own benefit. Here, with a view to understanding the underlying mechanisms, we first systematically dissected the exact signaling network in BTV-induced autophagy. We found that the activity of mTOR, a crucial pivot, was inhibited by BTV1 infection, subsequently leading to downstream p70S6K suppression and autophagy initiation. We then explored the upstream regulators of mTOR and analyzed their activities via a series of assays. We found BTV1-induced autophagy to be independent of the ERK1/2 signaling pathway. However, the BTV1-induced inhibition of PI3K/Akt was found to be partially responsible for mTOR inactivation and subsequent autophagy initiation. Furthermore, we found unexpectedly that AMPK seemed to play a more important role in BTV1-induced autophagy. Elevated [Ca2+]cyto-mediated activation of CaMKKβ exactly managed the activation of AMPK, which then positively regulated autophagy through suppressing mTOR. We must emphasize that TSC2 is a fatal mediator between upstream Akt or AMPK and downstream mTOR through its phosphorylation. Taken together, our data suggested that the BTV1-induced inhibition of the Akt-TSC2-mTOR pathway and the upregulation of the AMPK-TSC2-mTOR pathway both contributed to autophagy initiation and further favored virus replication.
Triggered self-assembly of magnetic nanoparticles
Authors: Ye L. , Pearson T. , Cordeau Y. , Mefford O. T. , Crawford T. M. 
Published: March 2016

AbstractColloidal magnetic nanoparticles are candidates for application in biology, medicine and nanomanufac-turing. Understanding how these particles interact collectively in fluids, especially how they assemble and aggregate under external magnetic fields, is critical for high quality, safe, and reliable deployment of these particles. Here, by applying magnetic forces that vary strongly over the same length scale as the colloidal stabilizing force and then varying this colloidal repulsion, we can trigger self-assembly of these nanoparticles into parallel line patterns on the surface of a disk drive medium. Localized within nanometers of the medium surface, this effect is strongly dependent on the ionic properties of the colloidal fluid but at a level too small to cause bulk colloidal aggregation. We use real-time optical diffraction to monitor the dynamics of self-assembly, detecting local colloidal changes with greatly enhanced sensitivity compared with conventional light scattering. Simulations predict the triggering but not the dynamics, especially at short measurement times. Beyond using spatially-varying magnetic forces to balance interactions and drive assembly in magnetic nanoparticles, future measurements leveraging the sensitivity of this approach could identify novel colloidal effects that impact real-world applications of these nanoparticles.
A cationic tetrapyrrole inhibits toxic activities of the cellular prion protein
Authors: Massignan Tania , Cimini Sara , Stincardini Claudia , Cerovic Milica , Vanni Ilaria , Elezgarai Saioa R. , Moreno Jorge , Stravalaci Matteo , Negro Alessandro , Sangiovanni Valeria , Restelli Elena , Riccardi Geraldina , Gobbi Marco , Castilla Joaquín , Borsello Tiziana , Nonno Romolo , Biasini Emiliano 
Published: March 2016

AbstractPrion diseases are rare neurodegenerative conditions associated with the conformational conversion of the cellular prion protein (PrPC) into PrPSc, a self-replicating isoform (prion) that accumulates in the central nervous system of affected individuals. The structure of PrPSc is poorly defined and likely to be heterogeneous, as suggested by the existence of different prion strains. The latter represents a relevant problem for therapy in prion diseases, as some potent anti-prion compounds have shown strain-specificity. Designing therapeutics that target PrPC may provide an opportunity to overcome these problems. PrPC ligands may theoretically inhibit the replication of multiple prion strains, by acting on the common substrate of any prion replication reaction. Here, we characterized the properties of a cationic tetrapyrrole [Fe(III)-TMPyP], which was previously shown to bind PrPC and inhibit the replication of a mouse prion strain. We report that the compound is active against multiple prion strains in vitro and in cells. Interestingly, we also find that Fe(III)-TMPyP inhibits several PrPC-related toxic activities, including the channel-forming ability of a PrP mutant and the PrPC-dependent synaptotoxicity of amyloid-β (Aβ) oligomers, which are associated with Alzheimer’s Disease. These results demonstrate that molecules binding to PrPC may produce a dual effect of blocking prion replication and inhibiting PrPC-mediated toxicity.
Suppression of Spry1 inhibits triple-negative breast cancer malignancy by decreasing EGF/EGFR mediated mesenchymal phenotype
Authors: He Qing , Jing Hongyu , Liaw Lucy , Gower Lindsey , Vary Calvin , Hua Shucheng , Yang Xuehui 
Published: March 2016

AbstractSprouty (Spry) proteins have been implicated in cancer progression, but their role in triple-negative breast cancer (TNBC), a subtype of lethal and aggressive breast cancer, is unknown. Here, we reported that Spry1 is significantly expressed in TNBC specimen and MDA-MB-231 cells. To understand Spry1 regulation of signaling events controlling breast cancer phenotype, we used lentiviral delivery of human Spry1 shRNAs to suppress Spry1 expression in MDA-MB-231, an established TNBC cell line. Spry1 knockdown MDA-MB-231 cells displayed an epithelial phenotype with increased membrane E-cadherin expression. Knockdown of Spry1 impaired MDA-MB-231 cell migration, Matrigel invasion, and anchorage-dependent and -independent growth. Tumor xenografts originating from Spry1 knockdown MDA-MB-231 cells grew slower, had increased E-cadherin expression, and yielded fewer lung metastases compared to control. Furthermore, suppressing Spry1 in MDA-MB-231 cells impaired the induction of Snail and Slug expression by EGF, and this effect was associated with increased EGFR degradation and decreased EGFR/Grb2/Shp2/Gab1 signaling complex formation. The same phenotype was also observed in the TNBC cell line MDA-MB-157. Together, our results show that unlike in some tumors, where Spry may mediate tumor suppression, Spry1 plays a selective role in at least a subset of TNBC to promote the malignant phenotype via enhancing EGF-mediated mesenchymal phenotype.
Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents
Authors: Reis R S , Dalle Molle R , Machado T D , Mucellini A B , Rodrigues D M , Bortoluzzi A , Bigonha S M , Toazza R , Salum G A , Minuzzi L , Buchweitz A , Franco A R , Pelúzio M C G , Manfro G G , Silveira P P 
Published: March 2016

AbstractThe goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.
Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder
Authors: Mocking R J T , Harmsen I , Assies J , Koeter M W J , Ruhé H G , Schene A H 
Published: March 2016

AbstractOmega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants’ age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114–0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I2=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009–0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017–0.01144), P=0.044) and earlier publication year (β=−0.0735 (−0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.
Fiber networks amplify active stress
Authors: Ronceray Pierre , Broedersz Chase P. , Lenz Martin 
Published: March 2016

Significance
Living organisms generate forces to move, change shape, and maintain their internal functions. These forces are typically produced by molecular motors embedded in networks of fibers. Although these motors are traditionally regarded as the defining elements of biological force generation, here we show that the surrounding network also plays a central role in this process. Indeed, rather than merely propagating forces like a simple elastic medium, fiber networks produce emergent, dramatically amplified stresses and can go so far as reversing small-scale extensile forces into large-scale contraction. Our theory quantitatively accounts for experimental measurements of contraction.
Protein networks identify novel symbiogenetic genes resulting from plastid endosymbiosis
Authors: Méheust Raphaël , Zelzion Ehud , Bhattacharya Debashish , Lopez Philippe , Bapteste Eric 
Published: March 2016

Significance
Endosymbiotic gene transfer from the plastid genome to the nucleus comprises the most significant source of horizontal gene transfer in photosynthetic eukaryotes. We investigated genomic data at the infragenic level to determine whether the cyanobacterial endosymbiont also contributed gene fragments (i.e., domains) to create novel nuclear-encoded proteins. We found 67 such gene families that are expressed as RNA and widely distributed among plants and algae. At least 23 genes are putatively involved in redox regulation and light response, namely the maintenance of a photodynamic organelle. Our results add a new layer of complexity to plastid integration and point to the role of fused proteins as key players in this process.
SARS-like WIV1-CoV poised for human emergence
Authors: Menachery Vineet D. , Yount Boyd L. , Sims Amy C. , Debbink Kari , Agnihothram Sudhakar S. , Gralinski Lisa E. , Graham Rachel L. , Scobey Trevor , Plante Jessica A. , Royal Scott R. , Swanstrom Jesica , Sheahan Timothy P. , Pickles Raymond J. , Corti Davide , Randell Scott H. , Lanzavecchia Antonio , Marasco Wayne A. , Baric Ralph S. 
Published: March 2016

Significance
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV highlights the continued risk of cross-species transmission leading to epidemic disease. This manuscript describes efforts to extend surveillance beyond sequence analysis, constructing chimeric and full-length zoonotic coronaviruses to evaluate emergence potential. Focusing on SARS-like virus sequences isolated from Chinese horseshoe bats, the results indicate a significant threat posed by WIV1-CoV. Both full-length and chimeric WIV1-CoV readily replicated efficiently in human airway cultures and in vivo, suggesting capability of direct transmission to humans. In addition, while monoclonal antibody treatments prove effective, the SARS-based vaccine approach failed to confer protection. Together, the study indicates an ongoing threat posed by WIV1-related viruses and the need for continued study and surveillance.
Artificial eye for scotopic vision with bioinspired all-optical photosensitivity enhancer
Authors: Liu Hewei , Huang Yinggang , Jiang Hongrui 
Published: March 2016

Significance
Although biological eyes ingeniously adopt diverse optical approaches to improve their scotopic vision, enhancement of the photosensitivity in artificial imaging systems still clings to electronic methods. Here we present an all-optical strategy to significantly improve the low-light imaging capability of manmade sensors, which is inspired by the optical concept of superposition eyes and elephantnose fish eye. Besides showing an artificial eye whose scotopic vision is largely improved by a bioinspired photosensitivity enhancer, we also demonstrate a complete solution to acquire high-resolution images under low-light conditions with our device. More importantly, our purely optical approach can be used on top of other electronic technologies, which can boost the most state-of-the-art imaging sensor whose photosensitivity is gaining on the physical limitations.
Inhibition of SCF ubiquitin ligases by engineered ubiquitin variants that target the Cul1 binding site on the Skp1–F-box interface
Authors: Gorelik Maryna , Orlicky Stephen , Sartori Maria A. , Tang Xiaojing , Marcon Edyta , Kurinov Igor , Greenblatt Jack F. , Tyers Mike , Moffat Jason , Sicheri Frank , Sidhu Sachdev S. 
Published: March 2016

Significance
The ubiquitin proteasome components are often misregulated in numerous diseases, encouraging the search for drug targets and inhibitors. E3 ligases that specify ubiquitination targets are of particular interest. Multimeric Skp1–Cul1–F-box (SCF) E3 ligases constitute one of the largest E3 families connected to every cellular process and multiple diseases; however, their characterization as therapeutic targets is impeded by functional diversity and poor characterization of its members. Herein we describe a strategy to inhibit SCF E3 ligases using engineered ubiquitin-based binders. We identify a previously uncharacterized inhibitory site and design ubiquitin-based libraries targeting this site. Our strategy to target SCF E3 ligases with small-molecule–like agents will have broad applications for basic research and drug development relating to SCF E3 ligase function.