bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Single-Cell Analysis Reveals Cell Division-Independent Emergence of Megakaryocytes From Phenotypic Hematopoietic Stem Cells
Authors: Roch Aline , Trachsel Vincent , Lutolf Matthias P. 
Published: July 2015

AbstractDespite increasingly stringent methods to isolate hematopoietic stem cells (HSCs), considerable heterogeneity remains in terms of their long-term self-renewal and differentiation potential. Recently, the existence of long-lived, self-renewing, myeloid-restricted progenitors in the phenotypically defined HSC compartment has been revealed, but these cells remain poorly characterized. Here, we used an in vitro single-cell analysis approach to track the fate of 330 long-term HSCs (LT-HSC; Lin− cKit+ Sca-1+ CD150+ CD48− CD34−) cultured for 5 days under serum-free basal conditions. Our analysis revealed a highly heterogeneous behavior with approximately 15% of all phenotypic LT-HSCs giving rise to megakaryocytes (Mk). Surprisingly, in 65% of these cases, Mk development occurred in the absence of cell division. This observation suggests that myeloid-restricted progenitors may not derive directly from LT-HSCs but instead could share an identical cell surface marker repertoire. Stem Cells 2015;33:3152–3157
Single Cell Analysis Reveals Concomitant Transcription of Pluripotent and Lineage Markers During the Early Steps of Differentiation of Embryonic Stem Cells
Authors: Lanctôt Christian 
Published: July 2015

Abstract
The differentiation of embryonic stem cells is associated with extensive changes in gene expression. It is not yet clear whether these changes are the result of binary switch-like mechanisms or that of continuous and progressive variation. Here, I have used immunostaining and single molecule RNA fluorescence in situ hybridization (FISH) to assess changes in the expression of the well-known pluripotency-associated gene Pou5f1 (also known as Oct4) and early differentiation markers Sox1 and T-brachyury in single cells during the early steps of differentiation of mouse embryonic stem cells. I found extensive overlap between the expression of Pou5f1/Sox1 or Pou5f1/T-brachyury shortly after the initiation of differentiation towards either the neuronal or the mesendodermal lineage, but no evidence of correlation between their respective expression levels. Quantitative analysis of transcriptional output at the sites of nascent transcription revealed that Pou5f1 and Sox1 were transcribed in pulses and that embryonic stem cell differentiation was accompanied by changes in pulsing frequencies. The progressive induction of Sox1 was further associated with an increase in the average size of individual transcriptional bursts. Surprisingly, single cells that actively and simultaneously transcribe both the pluripotency- and the lineage-associated genes could easily be found in the differentiating population. The results presented here show for the first time that lineage priming can occur in cells that are actively transcribing a pluripotent marker. Furthermore, they suggest that this process is associated with changes in transcriptional dynamics. Stem Cells 2015;33:2949–2960
Secure machine‐type communications in LTE networks
Authors: Lai Chengzhe , Lu Rongxing , Li Hui , Zheng Dong , Shen Xuemin (Sherman) 
Published: July 2015

AbstractWith a great variety of potential applications, machine‐type communications (MTC) is gaining a tremendous interest from mobile network operators and research groups. MTC is standardized by the 3rd Generation Partnership Project (3GPP), which has been regarded as the promising solution facilitating machine‐to‐machine communications. In the latest standard, 3GPP proposes a novel architecture for MTC, in which the MTC server is located outside the operator domain. However, the connection between the 3GPP core network and MTC server in this scenario is insecure; consequently, there are distrustful relationships among MTC device, core network, and MTC server. If the security issue is not well addressed, all applications involved in MTC cannot be put into the market. To address this problem, we propose an end‐to‐end security scheme for MTC based on the proxy‐signature technique, called E2SEC. Specifically, both the MTC device and MTC server can establish strong trustful relationships with each other by using the proxy signatures issued by the 3GPP core network. Moreover, we present some implementation considerations of E2SEC and analyze the performance during authentication by comparing the operational cost of three cases that apply three different signature algorithms, that is, ElGamal, Schnorr, and DSA. Through security analysis by using Automatic Cryptographic Protocol Verifier (ProVerif), we conclude that the proposed E2SEC scheme can achieve the security goals and prevent various security threats. Copyright © 2015 John Wiley & Sons, Ltd.
The Alzheimer's Disease Neuroimaging Initiative phase 2: Increasing the length, breadth, and depth of our understanding
Authors: Beckett Laurel A. , Donohue Michael C. , Wang Cathy , Aisen Paul , Harvey Danielle J. , Saito Naomi ,   Alzheimer's Disease Neuroimaging Initiative
Published: July 2015

AbstractIntroductionThe Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multisite study designed to characterize the trajectories of biomarkers across the aging process. We present ADNI Biostatistics Core analyses that integrate data over the length, breadth, and depth of ADNI.MethodsRelative progression of key imaging, fluid, and clinical measures was assessed. Individuals with subjective memory complaints (SMC) and early mild cognitive impairment (eMCI) were compared with normal controls (NC), MCI, and individuals with Alzheimer's disease. Amyloid imaging and magnetic resonance imaging (MRI) summaries were assessed as predictors of disease progression.ResultsRelative progression of markers supports parts of the amyloid cascade hypothesis, although evidence of earlier occurrence of cognitive change exists. SMC are similar to NC, whereas eMCI fall between the cognitively normal and MCI groups. Amyloid leads to faster conversion and increased cognitive impairment.DiscussionAnalyses support features of the amyloid hypothesis, but also illustrate the considerable heterogeneity in the aging process.
Alzheimer's Disease Neuroimaging Initiative 2 Clinical Core: Progress and plans
Authors: Aisen Paul S. , Petersen Ronald C. , Donohue Michael , Weiner Michael W. ,   Alzheimer's Disease Neuroimaging Initiative
Published: July 2015

AbstractIntroductionThis article reviews the current status of the Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and summarizes planning for the next stage of the project.MethodsClinical Core activities and plans were synthesized based on discussions among the Core leaders and external advisors.ResultsThe longitudinal data in ADNI‐2 provide natural history data on a clinical trials population and continue to inform refinement and standardization of assessments, models of trajectories, and clinical trial methods that have been extended into sporadic preclinical Alzheimer's disease (AD).DiscussionPlans for the next phase of the ADNI project include maintaining longitudinal follow‐up of the normal and mild cognitive impairment cohorts, augmenting specific clinical cohorts, and incorporating novel computerized cognitive assessments and patient‐reported outcomes. A major hypothesis is that AD represents a gradually progressive disease that can be identified precisely in its long presymptomatic phase, during which intervention with potentially disease‐modifying agents may be most useful.
Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans
Authors: Saykin Andrew J. , Shen Li , Yao Xiaohui , Kim Sungeun , Nho Kwangsik , Risacher Shannon L. , Ramanan Vijay K. , Foroud Tatiana M. , Faber Kelley M. , Sarwar Nadeem , Munsie Leanne M. , Hu Xiaolan , Soares Holly D. , Potkin Steven G. , Thompson Paul M. , Kauwe John S.K. , Kaddurah‐Daouk Rima , Green Robert C. , Toga Arthur W. , Weiner Michael W. ,   Alzheimer's Disease Neuroimaging Initiative
Published: July 2015

AbstractIntroductionGenetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) have been crucial in advancing the understanding of Alzheimer's disease (AD) pathophysiology. Here, we provide an update on sample collection, scientific progress and opportunities, conceptual issues, and future plans.MethodsLymphoblastoid cell lines and DNA and RNA samples from blood have been collected and banked, and data and biosamples have been widely disseminated. To date, APOE genotyping, genome‐wide association study (GWAS), and whole exome and whole genome sequencing data have been obtained and disseminated.ResultsADNI genetic data have been downloaded thousands of times, and >300 publications have resulted, including reports of large‐scale GWAS by consortia to which ADNI contributed. Many of the first applications of quantitative endophenotype association studies used ADNI data, including some of the earliest GWAS and pathway‐based studies of biospecimen and imaging biomarkers, as well as memory and other clinical/cognitive variables. Other contributions include some of the first whole exome and whole genome sequencing data sets and reports in healthy controls, mild cognitive impairment, and AD.DiscussionNumerous genetic susceptibility and protective markers for AD and disease biomarkers have been identified and replicated using ADNI data and have heavily implicated immune, mitochondrial, cell cycle/fate, and other biological processes. Early sequencing studies suggest that rare and structural variants are likely to account for significant additional phenotypic variation. Longitudinal analyses of transcriptomic, proteomic, metabolomic, and epigenomic changes will also further elucidate dynamic processes underlying preclinical and prodromal stages of disease. Integration of this unique collection of multiomics data within a systems biology framework will help to separate truly informative markers of early disease mechanisms and potential novel therapeutic targets from the vast background of less relevant biological processes. Fortunately, a broad swath of the scientific community has accepted this grand challenge.
Mediterranean diet and preserved brain structural connectivity in older subjects
Authors: Pelletier Amandine , Barul Christine , Féart Catherine , Helmer Catherine , Bernard Charlotte , Periot Olivier , Dilharreguy Bixente , Dartigues Jean‐François , Allard Michèle , Barberger‐Gateau Pascale , Catheline Gwénaëlle , Samieri Cécilia 
Published: July 2015

IntroductionThe Mediterranean diet (MeDi) has been related to a lower risk of Alzheimer's disease; yet, the underlying mechanisms are unknown. We hypothesized that protection against neurodegeneration would translate into higher gray matter volumes, whereas a specific association with preserved white matter microstructure would suggest alternative mechanisms (e.g., vascular pathways).MethodsWe included 146 participants from the Bordeaux Three‐City study nondemented when they completed a dietary questionnaire and who underwent a 3‐T magnetic resonance imaging at an average of 9 years later, including diffusion tensor imaging.ResultsIn multivariate voxel‐by‐voxel analyses, adherence to the MeDi was significantly associated with preserved white matter microstructure in extensive areas, a gain in structural connectivity that was related to strong cognitive benefits. In contrast, we found no relation with gray matter volumes.DiscussionThe MeDi appears to benefit brain health through preservation of structural connectivity. Potential mediation by a favorable impact on brain vasculature deserves further research.
Targeting the Pim kinases in multiple myeloma
Authors: Keane N A , Reidy M , Natoni A , Raab M S , O'Dwyer M 
Published: July 2015

AbstractMultiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM.
Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1
Authors: Vettorazzi Sabine , Bode Constantin , Dejager Lien , Frappart Lucien , Shelest Ekaterina , Klaßen Carina , Tasdogan Alpaslan , Reichardt Holger M. , Libert Claude , Schneider Marion , Weih Falk , Henriette Uhlenhaut N. , David Jean-Pierre , Gräler Markus , Kleiman Anna , Tuckermann Jan P. 
Published: July 2015

AbstractAcute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition ofSphK1abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulateSphK1expression. Our findings support a critical role forSphK1induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies.
The development and characterization of synthetic minimal yeast promoters
Authors: Redden Heidi , Alper Hal S. 
Published: July 2015

AbstractSynthetic promoters, especially minimally sized, are critical for advancing fungal synthetic biology. Fungal promoters often span hundreds of base pairs, nearly ten times the amount of bacterial counterparts. This size limits large-scale synthetic biology efforts in yeasts. Here we address this shortcoming by establishing a methodical workflow necessary to identify robust minimal core elements that can be linked with minimal upstream activating sequences to develop short, yet strong yeast promoters. Through a series of library-based synthesis, analysis and robustness tests, we create a set of non-homologous, purely synthetic, minimal promoters for yeast. These promoters are comprised of short core elements that are generic and interoperable and 10 bp UAS elements that impart strong, constitutive function. Through this methodology, we are able to generate the shortest fungal promoters to date, which can achieve high levels of both inducible and constitutive expression with up to an 80% reduction in size.
Reduced Graphene Oxide-Based Silver Nanoparticle-Containing Composite Hydrogel as Highly Efficient Dye Catalysts for Wastewater Treatment
Authors: Jiao Tifeng , Guo Haiying , Zhang Qingrui , Peng Qiuming , Tang Yongfu , Yan Xuehai , Li Bingbing 
Published: July 2015

AbstractNew reduced graphene oxide-based silver nanoparticle-containing composite hydrogels were successfully prepared in situ through the simultaneous reduction of GO and noble metal precursors within the GO gel matrix. The as-formed hydrogels are composed of a network structure of cross-linked nanosheets. The reported method is based on the in situ co-reduction of GO and silver acetate within the hydrogel matrix to form RGO-based composite gel. The stabilization of silver nanoparticles was also achieved simultaneously within the gel composite system. The as-formed silver nanoparticles were found to be homogeneously and uniformly dispersed on the surface of the RGO nanosheets within the composite gel. More importantly, this RGO-based silver nanoparticle-containing composite hydrogel matrix acts as a potential catalyst for removing organic dye pollutants from an aqueous environment. Interestingly, the as-prepared catalytic composite matrix structure can be conveniently separated from an aqueous environment after the reaction, suggesting the potentially large-scale applications of the reduced graphene oxide-based nanoparticle-containing composite hydrogels for organic dye removal and wastewater treatment.
Renormalization group approach to the Fröhlich polaron model: application to impurity-BEC problem
Authors: Grusdt F. , Shchadilova Y. E. , Rubtsov A. N. , Demler E. 
Published: July 2015

AbstractWhen a mobile impurity interacts with a many-body system, such as a phonon bath, a polaron is formed. Despite the importance of the polaron problem for a wide range of physical systems, a unified theoretical description valid for arbitrary coupling strengths is still lacking. Here we develop a renormalization group approach for analyzing a paradigmatic model of polarons, the so-called Fröhlich model and apply it to a problem of impurity atoms immersed in a Bose-Einstein condensate of ultra cold atoms. Polaron energies obtained by our method are in excellent agreement with recent diagrammatic Monte Carlo calculations for a wide range of interaction strengths. They are found to be logarithmically divergent with the ultra-violet cut-off, but physically meaningful regularized polaron energies are also presented. Moreover, we calculate the effective mass of polarons and find a smooth crossover from weak to strong coupling regimes. Possible experimental tests of our results in current experiments with ultra cold atoms are discussed.
Magnetic multi-granule nanoclusters: A model system that exhibits universal size effect of magnetic coercivity
Authors: Sung Lee Ji , Myung Cha Jin , Young Yoon Ha , Lee Jin-Kyu , Keun Kim Young 
Published: July 2015

AbstractIt is well known that the coercivity of magnetic nanomaterials increases up to a maximum and then decreases to zero with decreasing particle size. However, until now, no single synthesis method has been able to produce magnetic nanoparticles with a wide range of sizes, i.e., from 10 to 500 nm, in order to uncover the coercivity evolution. Here we report the characterization of magnetite (Fe3O4) multi-granule nanoclusters (MGNCs) to demonstrate the transitional behaviour of coercivity. The M–H curves indicate that our samples had a relatively high saturation magnetization (MS) value of ~70 emu/g and that the coercivity (Hc) increased to the maximum value of ~48 Oe until the nanoclusters reached a size of ~120 nm; the coercivity then gradually decreased to zero.
Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Cystic Fibrosis Mutation
Authors: Tomati Valeria , Sondo Elvira , Armirotti Andrea , Caci Emanuela , Pesce Emanuela , Marini Monica , Gianotti Ambra , Ju Jeon Young , Cilli Michele , Pistorio Angela , Mastracci Luca , Ravazzolo Roberto , Scholte Bob , Ronai Ze’ev , Galietta Luis J. V. , Pedemonte Nicoletta 
Published: July 2015

AbstractCystic fibrosis (CF) is caused by mutations in the CFTR chloride channel. Deletion of phenylalanine 508 (F508del), the most frequent CF mutation, impairs CFTR trafficking and gating. F508del-CFTR mistrafficking may be corrected by acting directly on mutant CFTR itself or by modulating expression/activity of CFTR-interacting proteins, that may thus represent potential drug targets. To evaluate possible candidates for F508del-CFTR rescue, we screened a siRNA library targeting known CFTR interactors. Our analysis identified RNF5 as a protein whose inhibition promoted significant F508del-CFTR rescue and displayed an additive effect with the investigational drug VX-809. Significantly, RNF5 loss in F508del-CFTR transgenic animals ameliorated intestinal malabsorption and concomitantly led to an increase in CFTR activity in intestinal epithelial cells. In addition, we found that RNF5 is differentially expressed in human bronchial epithelia from CF vs. control patients. Our results identify RNF5 as a target for therapeutic modalities to antagonize mutant CFTR proteins.
Hidden non-Fermi liquid behavior caused by magnetic phase transition in Ni-doped Ba-122 pnictides
Authors: Lee Seokbae , Choi Ki-Young , Jung Eilho , Roh Seulki , Shin Soohyeon , Park Tuson , Hwang Jungseek 
Published: July 2015

AbstractWe studied two BaFe2−xNixAs2 (Ni-doped Ba-122) single crystals at two different doping levels (underdoped and optimally doped) using an optical spectroscopic technique. The underdoped sample shows a magnetic phase transition around 80 K. We analyze the data with a Drude-Lorentz model with two Drude components (D1 and D2). It is known that the narrow D1 component originates from electron carriers in the electron-pockets and the broad D2 mode is from hole carriers in the hole-pockets. While the plasma frequencies of both Drude components and the static scattering rate of the broad D2 component show negligible temperature dependencies, the static scattering rate of the D1 mode shows strong temperature dependence for the both samples. We observed a hidden quasi-linear temperature dependence in the scattering rate of the D1 mode above and below the magnetic transition temperature while in the optimally doped sample the scattering rate shows a more quadratic temperature dependence. The hidden non-Fermi liquid behavior in the underdoped sample seems to be related to the magnetic phase of the material.
Resilience and receptivity worked in tandem to sustain a geothermal mat community amidst erratic environmental conditions
Authors: Ghosh Wriddhiman , Roy Chayan , Roy Rimi , Nilawe Pravin , Mukherjee Ambarish , Haldar Prabir Kumar , Chauhan Neeraj Kumar , Bhattacharya Sabyasachi , Agarwal Atima , George Ashish , Pyne Prosenjit , Mandal Subhrangshu , Rameez Moidu Jameela , Bala Goutam 
Published: July 2015

AbstractTo elucidate how geothermal irregularities affect the sustainability of high-temperature microbiomes we studied the synecological dynamics of a geothermal microbial mat community (GMMC) vis-à-vis fluctuations in its environment. Spatiotemporally-discrete editions of a photosynthetic GMMC colonizing the travertine mound of a circum-neutral hot spring cluster served as the model-system. In 2010 a strong geyser atop the mound discharged mineral-rich hot water, which nourished a GMMC continuum from the proximal channels (PC) upto the slope environment (SE) along the mound’s western face. In 2011 that geyser extinguished and consequently the erstwhile mats disappeared. Nevertheless, two relatively-weaker vents erupted in the southern slope and their mineral-poor outflow supported a small GMMC patch in the SE. Comparative metagenomics showed that this mat was a relic of the 2010 community, conserved via population dispersal from erstwhile PC as well as SE niches. Subsequently in 2012, as hydrothermal activity augmented in the southern slope, ecological niches widened and the physiologically-heterogeneous components of the 2011 “seed-community” split into PC and SE meta-communities, thereby reclaiming either end of the thermal gradient. Resilience of incumbent populations and the community’s receptiveness towards immigrants, were the key qualities that ensured the GMMC’s sustenance amidst habitat degradation and dispersal to discrete environments.