bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipogenic placenta-derived mesenchymal stem cells are not lineage restricted by withdrawing extrinsic factors: developing a novel visual angle in stem cell biology
Authors: Hu C , Cao H , Pan X , Li J , He J , Pan Q , Xin J , Yu X , Li J , Wang Y , Zhu D , Li L 
Published: March 2016

AbstractCurrent evidence implies that differentiated bone marrow mesenchymal stem cells (BMMSCs) can act as progenitor cells and transdifferentiate across lineage boundaries. However, whether this unrestricted lineage has specificities depending on the stem cell type is unknown. Placental-derived mesenchymal stem cells (PDMSCs), an easily accessible and less invasive source, are extremely useful materials in current stem cell therapies. No studies have comprehensively analyzed the transition in morphology, surface antigens, metabolism and multilineage potency of differentiated PDMSCs after their dedifferentiation. In this study, we showed that after withdrawing extrinsic factors, adipogenic PDMSCs reverted to a primitive cell population and retained stem cell characteristics. The mitochondrial network during differentiation and dedifferentiation may serve as a marker of absent or acquired pluripotency in various stem cell models. The new population proliferated faster than unmanipulated PDMSCs and could be differentiated into adipocytes, osteocytes and hepatocytes. The cell adhesion molecules (CAMs) signaling pathway and extracellular matrix (ECM) components modulate cell behavior and enable the cells to proliferate or differentiate during the differentiation, dedifferentiation and redifferentiation processes in our study. These observations indicate that the dedifferentiated PDMSCs are distinguishable from the original PDMSCs and may serve as a novel source in stem cell biology and cell-based therapeutic strategies. Furthermore, whether PDMSCs differentiated into other lineages can be dedifferentiated to a primitive cell population needs to be investigated.
Necroptosis in Niemann–Pick disease, type C1: a potential therapeutic target
Authors: Cougnoux A , Cluzeau C , Mitra S , Li R , Williams I , Burkert K , Xu X , Wassif C A , Zheng W , Porter F D 
Published: March 2016

AbstractNiemann–Pick disease, type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder due to mutation of theNPC1gene. The NPC1 phenotype is characterized by progressive neuronal dysfunction, including cerebellar ataxia and dementia. There is histological evidence of neuroinflammation and progressive neuronal loss, with cerebellar Purkinje cells particularly vulnerable to loss of NPC1 function. Necroptosis was evaluated as a mechanism of neuronal loss. Receptor-interacting protein kinase 1 (RIP1) and RIP3 are key components of the necrosomal complex that regulates necroptotic cell death. We report increased expression of RIP1 and RIP3 in NPC1 fibroblasts, NPC1 iPS cell-derived neuronal precursors, and in cerebellar tissue from both NPC1 mice and patients. Our data suggest a positive correlation between NPC1 neurological disease severity and assembly of the necrosome complex. Furthermore, we demonstrate that pharmacological inhibition of RIP1 decreases cell death bothin vitroandin vivo. Treatment ofNpc1-mutant mice with necrostatin-1, an allosteric inhibitor of RIP1, significantly delayed cerebellar Purkinje cell loss, progression of neurological symptoms, and death. Collectively, our data identified necroptosis as a key component of the molecular network that contributes to neuronal loss in NPC1 and establish that inhibition of necroptosis is a potential therapeutic intervention.
Functional genetics-directed identification of novel pharmacological inhibitors of FAS- and TNF-dependent apoptosis that protect mice from acute liver failure
Authors: Komarov A P , Komarova E A , Green K , Novototskaya L R , Baker P S , Eroshkin A , Osterman A L , Chenchick A A , Frangou C , Gudkov A V 
Published: March 2016

AbstractshRNA-mediated gene-silencing technology paired with cell-based functional readouts reveals potential targets directly, providing an opportunity to identify drugs against the target without knowing the precise role of the target in the pathophysiological processes of interest. By screening a lentiviral shRNA library targeting for major components of human signaling pathways and known drug targets, we identified and validated both canonical as well as 52 novel mediators of FAS and TNF ligand-induced apoptosis. Presence of potential therapeutic targets among these mediators was confirmed by demonstration of in vivo activity of siRNAs against four identified target candidates that protected mice from acute liver failure (ALF), a life-threatening disease with known involvement of death receptor (DR)-mediated apoptosis. Network-based modeling was used to predict small-molecule inhibitors for several candidate apoptosis mediators, including somatostatin receptor 5 (SSTR5) and a regulatory subunit of PP2A phosphatase, PPP2R5A. Remarkably, pharmacological inhibition of either SSTR5 or PPP2R5A reduced apoptosis induced by either FASL or TNF in cultured cells and dramatically improved survival in several mouse models of ALF. These results demonstrate the utility of loss-of-function genetic screens and network-based drug-repositioning methods for expedited identification of targeted drug candidates and revealed pharmacological agents potentially suitable for treatment of DR-mediated pathologies.
NORE1A induction by membrane-bound CD40L (mCD40L) contributes to CD40L-induced cell death and G1 growth arrest in p21-mediated mechanism
Authors: Elmetwali T , Salman A , Palmer D H 
Published: March 2016

AbstractMembrane-bound CD40L (mCD40L) but not soluble CD40L (sCD40L) has been implicated in direct cell death induction and apoptosis in CD40-expressing carcinomas. In this study, we show that mCD40L but not sCD40L induces NORE1A/Rassf5 expression in an NFκB-dependant mechanism. NORE1A expression appeared to contribute to mCD40L-induced cell death and enhance cell transition from G1 to S phase of the cell cycle in a p21-dependent mechanism. The upregulation of p21 protein was attributed to NORE1A expression, since NORE1A inhibition resulted in p21 downregulation. p21 upregulation was concomitant with lower p53 expression in the cytoplasmic fraction with no detectable increase at the nuclear p53 level. Moreover, mCD40L-induced cell death mediated by NORE1A expression appeared to be independent of mCD40L-induced cell death mediated by sustained JNK activation since NORE1A inhibition did not affect JNK phosphorylation and vice versa. The presented data allow better understanding of the mechanism by which mCD40L induces cell death which could be exploited in the clinical development of CD40-targeted anti-cancer therapies.
Production of unstable proteins through the formation of stable core complexes
Authors: Levy Nicolas , Eiler Sylvia , Pradeau-Aubreton Karine , Maillot Benoit , Stricher François , Ruff Marc 
Published: March 2016

AbstractPurification of proteins that participate in large transient complexes is impeded by low amounts, heterogeneity, instability and poor solubility. To circumvent these difficulties we set up a methodology that enables the production of stable complexes for structural and functional studies. This procedure is benchmarked and applied to two challenging protein families: the human steroid nuclear receptors (SNR) and the HIV-1 pre-integration complex. In the context of transcriptional regulation studies, we produce and characterize the ligand-binding domains of the glucocorticoid nuclear receptor and the oestrogen receptor beta in complex with a TIF2 (transcriptional intermediary factor 2) domain containing the three SNR-binding motifs. In the context of retroviral integration, we demonstrate the stabilization of the HIV-1 integrase by formation of complexes with partner proteins and DNA. This procedure provides a powerful research tool for structural and functional studies of proteins participating in non-covalent macromolecular complexes.
Collective atomic scattering and motional effects in a dense coherent medium
Authors: Bromley S. L. , Zhu B. , Bishof M. , Zhang X. , Bothwell T. , Schachenmayer J. , Nicholson T. L. , Kaiser R. , Yelin S. F. , Lukin M. D. , Rey A. M. , Ye J. 
Published: March 2016

AbstractWe investigate collective emission from coherently driven ultracold 88Sr atoms. We perform two sets of experiments using a strong and weak transition that are insensitive and sensitive, respectively, to atomic motion at 1 μK. We observe highly directional forward emission with a peak intensity that is enhanced, for the strong transition, by >103 compared with that in the transverse direction. This is accompanied by substantial broadening of spectral lines. For the weak transition, the forward enhancement is substantially reduced due to motion. Meanwhile, a density-dependent frequency shift of the weak transition (∼10% of the natural linewidth) is observed. In contrast, this shift is suppressed to <1% of the natural linewidth for the strong transition. Along the transverse direction, we observe strong polarization dependences of the fluorescence intensity and line broadening for both transitions. The measurements are reproduced with a theoretical model treating the atoms as coherent, interacting radiating dipoles.
Enhanced superconductivity in atomically thin TaS2
Authors: Navarro-Moratalla Efrén , Island Joshua O. , Mañas-Valero Samuel , Pinilla-Cienfuegos Elena , Castellanos-Gomez Andres , Quereda Jorge , Rubio-Bollinger Gabino , Chirolli Luca , Silva-Guillén Jose Angel , Agraït Nicolás , Steele Gary A. , Guinea Francisco , van der Zant Herre S. J. , Coronado Eugenio 
Published: March 2016

AbstractThe ability to exfoliate layered materials down to the single layer limit has presented the opportunity to understand how a gradual reduction in dimensionality affects the properties of bulk materials. Here we use this top–down approach to address the problem of superconductivity in the two-dimensional limit. The transport properties of electronic devices based on 2H tantalum disulfide flakes of different thicknesses are presented. We observe that superconductivity persists down to the thinnest layer investigated (3.5 nm), and interestingly, we find a pronounced enhancement in the critical temperature from 0.5 to 2.2 K as the layers are thinned down. In addition, we propose a tight-binding model, which allows us to attribute this phenomenon to an enhancement of the effective electron–phonon coupling constant. This work provides evidence that reducing the dimensionality can strengthen superconductivity as opposed to the weakening effect that has been reported in other 2D materials so far.
Quantitative thermophoretic study of disease-related protein aggregates
Authors: Wolff Manuel , Mittag Judith J. , Herling Therese W. , Genst Erwin De , Dobson Christopher M. , Knowles Tuomas P. J. , Braun Dieter , Buell Alexander K. 
Published: March 2016

AbstractAmyloid fibrils are a hallmark of a range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. A detailed understanding of the physico-chemical properties of the different aggregated forms of proteins, and of their interactions with other compounds of diagnostic or therapeutic interest, is crucial for devising effective strategies against such diseases. Protein aggregates are situated at the boundary between soluble and insoluble structures, and are challenging to study because classical biophysical techniques, such as scattering, spectroscopic and calorimetric methods, are not well adapted for their study. Here we present a detailed characterization of the thermophoretic behavior of different forms of the protein α-synuclein, whose aggregation is associated with Parkinson’s disease. Thermophoresis is the directed net diffusional flux of molecules and colloidal particles in a temperature gradient. Because of their low volume requirements and rapidity, analytical methods based on this effect have considerable potential for high throughput screening for drug discovery. In this paper we rationalize and describe in quantitative terms the thermophoretic behavior of monomeric, oligomeric and fibrillar forms of α-synuclein. Furthermore, we demonstrate that microscale thermophoresis (MST) is a valuable method for screening for ligands and binding partners of even such highly challenging samples as supramolecular protein aggregates.
Acute Kidney Injury Classification for Critically Ill Cirrhotic Patients: A Comparison of the KDIGO, AKIN and RIFLE Classifications
Authors: Pan Heng-Chih , Chien Yu-Shan , Jenq Chang-Chyi , Tsai Ming-Hung , Fan Pei-Chun , Chang Chih-Hsiang , Chang Ming-Yang , Tian Ya-Chung , Fang Ji-Tseng , Yang Chih-Wei , Chen Yung-Chang 
Published: March 2016

AbstractCritically ill cirrhotic patients have high mortality rates, particularly when they present with acute kidney injury (AKI) on admission. The Kidney Disease: Improving Global Outcomes (KDIGO) group aimed to standardize the definition of AKI and recently published a new AKI classification. However, the efficacy of the KDIGO classification for predicting outcomes of critically ill cirrhotic patients is unclear. We prospectively enrolled 242 cirrhotic patients from a 10-bed specialized hepatogastroenterology intensive care unit (ICU) in a 2000-bed tertiary-care referral hospital. Demographic parameters and clinical variables on day 1 of admission were prospectively recorded. The overall in-hospital mortality rate was 62.8%. Liver diseases were usually attributed to hepatitis B viral infection (26.9%). The major cause of ICU admission was upper gastrointestinal bleeding (38.0%). Our result showed that the KDIGO classification had better discriminatory power than RIFLE and AKIN criteria in predicting in-hospital mortality. Cumulative survival rates at the 6-month after hospital discharge differed significantly between patients with and without AKI on ICU admission day. In summary, we identified that the outcome prediction performance of KDIGO classification is superior to that of AKIN or RIFLE classification in critically ill cirrhotic patients.
Study of flux pinning mechanism under hydrostatic pressure in optimally doped (Ba,K)Fe2As2 single crystals
Authors: Shabbir Babar , Wang Xiaolin , Ma Y. , Dou S. X. , Yan S. S. , Mei L. M. 
Published: March 2016

AbstractStrong pinning depends on the pinning force strength and number density of effective defects. Using the hydrostatic pressure method, we demonstrate here that hydrostatic pressure of 1.2 GPa can significantly enhance flux pinning or the critical current density (Jc) of optimally doped Ba0.6K0.4Fe2As2 crystals by a factor of up to 5 in both low and high fields, which is generally rare with other Jc enhancement techniques. At 4.1 K, high pressure can significantly enhance Jc from 5 × 105A/cm2 to nearly 106A/cm2 at 2 T, and from 2 × 105A/cm2 to nearly 5.5 × 105A/cm2 at 12 T. Our systematic analysis of the flux pinning mechanism indicates that both the pinning centre number density and the pinning force are greatly increased by the pressure and enhance the pinning. This study also shows that superconducting performance in terms of flux pinning or Jc for optimally doped superconducting materials can be further improved by using pressure.
Metabolic role of dipeptidyl peptidase 4 (DPP4) in primary human (pre)adipocytes
Authors: Zilleßen Pia , Celner Jennifer , Kretschmann Anita , Pfeifer Alexander , Racké Kurt , Mayer Peter 
Published: March 2016

AbstractDipeptidyl peptidase 4 (DPP4) is the target of the gliptins, a recent class of oral antidiabetics. DPP4 (also called CD26) was previously characterized in immune cells but also has important metabolic functions which are not yet fully understood. Thus, we investigated the function of DPP4 in human white preadipocytes and adipocytes. We found that both cell types express DPP4 in high amounts; DPP4 release markedly increased during differentiation. In preadipocytes, lentiviral DPP4 knockdown caused significant changes in gene expression as determined by whole-genome DNA-array analysis. Metabolic genes were increased, e.g. PDK4 18-fold and PPARγC1α (=PGC1α) 6-fold and proliferation-related genes were decreased (e.g. FGF7 5-fold). These effects, contributing to differentiation, were not inhibited by the PPARγ antagonist T0070907. Vice versa, the PPARγ agonist pioglitazone induced a different set of genes (mainly FABP4). DPP4 knockdown also affected growth factor signaling and, accordingly, retarded preadipocyte proliferation. In particular, basal and insulin-induced ERK activation (but not Akt activation) was markedly diminished (by around 60%). This indicates that DPP4 knockdown contributes to adipocyte maturation by mimicking growth factor withdrawal, an early step in fat cell differentiation. In mature adipocytes, DPP4 becomes liberated so that adipose tissue may constitute a relevant source of circulating DPP4.
Design of Advanced Photocatalysis System by Adatom Decoration in 2D Nanosheets of Group-IV and III–V Binary Compounds
Authors: Jin Hao , Dai Ying , Huang Bai-Biao 
Published: March 2016

AbstractSearching for novel photocatalysts is one of the most important topic in photocatalytic fields. In the present work, we propose a feasible approach to improve the photocatalytic activities of 2D bilayers through surface decoration, i.e. hydrogenation, halogenation and hydroxylation. Our investigations demonstrate that after surface modification, the optical adsorption expands into the visible region, while a built-in electric field is induced due to the interlayer coupling, which can promote the charge separation for photogenerated electron-hole pairs. Our results show that the indirect-direct band gap transition of SiC, SnC, BN and GaN can be realised through adatom decoration. Furthermore, the surface-modified 2D bilayers have suitable VBM and CBM alignments with the oxidation and reduction potentials for water splitting, suggesting powerful potentials in energy and environmental applications.
Reconstruction of thermotolerant yeast by one-point mutation identified through whole-genome analyses of adaptively-evolved strains
Authors: Satomura Atsushi , Miura Natsuko , Kuroda Kouichi , Ueda Mitsuyoshi 
Published: March 2016

AbstractSaccharomyces cerevisiae is used as a host strain in bioproduction, because of its rapid growth, ease of genetic manipulation, and high reducing capacity. However, the heat produced during the fermentation processes inhibits the biological activities and growth of the yeast cells. We performed whole-genome sequencing of 19 intermediate strains previously obtained during adaptation experiments under heat stress; 49 mutations were found in the adaptation steps. Phylogenetic tree revealed at least five events in which these strains had acquired mutations in the CDC25 gene. Reconstructed CDC25 point mutants based on a parental strain had acquired thermotolerance without any growth defects. These mutations led to the downregulation of the cAMP-dependent protein kinase (PKA) signaling pathway, which controls a variety of processes such as cell-cycle progression and stress tolerance. The one-point mutations in CDC25 were involved in the global transcriptional regulation through the cAMP/PKA pathway. Additionally, the mutations enabled efficient ethanol fermentation at 39 °C, suggesting that the one-point mutations in CDC25 may contribute to bioproduction.
Superconducting H5S2 phase in sulfur-hydrogen system under high-pressure
Authors: Ishikawa Takahiro , Nakanishi Akitaka , Shimizu Katsuya , Katayama-Yoshida Hiroshi , Oda Tatsuki , Suzuki Naoshi 
Published: March 2016

AbstractRecently, hydrogen sulfide was experimentally found to show the high superconducting critical temperature (Tc) under high-pressure. The superconducting Tc shows 30–70 K in pressure range of 100–170 GPa (low-Tc phase) and increases to 203 K, which sets a record for the highest Tc in all materials, for the samples annealed by heating it to room temperature at pressures above 150 GPa (high-Tc phase). Here we present a solid H5S2 phase predicted as the low-Tc phase by the application of the genetic algorithm technique for crystal structure searching and first-principles calculations to sulfur-hydrogen system under high-pressure. The H5S2 phase is thermodynamically stabilized at 110 GPa, in which asymmetric hydrogen bonds are formed between H2S and H3S molecules. Calculated Tc values show 50–70 K in pressure range of 100–150 GPa within the harmonic approximation, which can reproduce the experimentally observed low-Tc phase. These findings give a new aspect of the excellent superconductivity in compressed sulfur-hydrogen system.
Carbonate Doping in TiO2 Microsphere: The Key Parameter Influencing Others for Efficient Dye Sensitized Solar Cell
Authors: Seddigi Zaki S. , Ahmed Saleh A. , Sardar Samim , Pal Samir Kumar 
Published: March 2016

AbstractFour key parameters namely light trapping, density of light harvesting centre, photoinduced electron injection and electron transport without self-recombination are universally important across all kinds of solar cells. In the present study, we have considered the parameters in the context of a model Dye Sensitized Solar Cell (DSSC). Our experimental studies reveal that carbonate doping of TiO2 mesoporous microspheres (doped MS) makes positive influence to all the above mentioned key parameters responsible for the enhanced solar cell efficiency. A simple method has been employed to synthesize the doped MS for the photoanode of a N719 (ruthenium dye)-based DSSC. A detail electron microscopy has been used to characterize the change in morphology of the MS upon doping. The optical absorption spectrum of the doped MS reveals significant shift of TiO2 (compared to that of the MS without doping) towards maximum solar radiance (~500 nm) and the excellent scattering in the entire absorption band of the sensitizing dye (N719). Finally and most importantly, for the first time we have demonstrated that the solar cells with doped MS offers better efficiency (7.6%) in light harvesting compared to MS without doping (5.2%) and also reveal minimum self recombination of photoelectrons in the redox chain.
Vertical Microcavity Organic Light-emitting Field-effect Transistors
Authors: Hu Yongsheng , Lin Jie , Song Li , Lu Qipeng , Zhu Wanbin , Liu Xingyuan 
Published: March 2016

AbstractOrganic light-emitting field-effect transistors (OLEFETs) are regarded as a novel kind of device architecture for fulfilling electrical-pumped organic lasers. However, the realization of OLEFETs with high external quantum efficiency (EQE) and high brightness simultaneously is still a tough task. Moreover, the design of the resonator structure in LED is far from satisfactory. Here, OLEFETs with EQE of 1.5% at the brightness of 2600 cdm−2 and the corresponding ON/OFF ratio and current efficiency reaches above 104 and 3.1 cdA−1, respectively, were achieved by introducing 1,4,5,8,9,12-hexaazatriphenylene-hexacarbonitrile (HAT-CN) as a charge generation layer. Moreover, a vertical microcavity based on distributed Bragg reflector (DBR) and Ag source/drain electrodes is successfully introduced into the high performance OLEFETs, which results in electroluminescent spectrum linewidth narrowing from 96 nm to 6.9 nm. The results manifest the superiority of the vertical microcavity as an optical resonator in OLEFETs, which sheds some light on achieving the electrically pumped organic lasers.