bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Ape1 Redox Activity Promotes Odonto/osteogenic Differentiation of Dental Papilla Cells
Authors: Chen Tian , Liu Zhi , Sun Wenhua , Li Jingyu , Liang Yan , Yang Xianrui , Xu Yang , Yu Mei , Tian Weidong , Chen Guoqing , Bai Ding
Published: December 2015

Dentinogenesis is the formation of dentin, a substance that forms the majority of teeth and this process is performed by odontoblasts. Dental papilla cells (DPCs), as the progenitor cells of odontoblasts, undergo the odontogenic differentiation regulated by multiple cytokines and paracrine signal molecules. Ape1 is a perfect paradigm of the function complexity of a biological macromolecule with two major functional regions for DNA repair and redox regulation, respectively. To date, it remains unclear whether Ape1 can regulate the dentinogenesis in DPCs. In the present study, we firstly examed the spatio-temporal expression of Ape1 during tooth germ developmental process and found the Ape1 expression was initially high and then gradually reduced along with the tooth development. Secondly, the osteo/odontogenic differentiation capacity of DPCs was up-regulated when treated with either Ape1-shRNA or E3330 (a specific inhibitor of the Ape1 redox function), respectively. Moreover, we found that the canonical Wnt signaling pathway was activated in this process and E3330 reinforced-osteo/odontogenic differentiation capacity was suppressed by Dickkopf1 (DKK1), a potent antagonist of canonical Wnt signaling pathway. Taken together, we for the first time showed that inhibition of Ape1 redox regulation could promote the osteo/odontogenic differentiation capacity of DPCs via canonical Wnt signaling pathway.
Absolute measurement of the 1S0 − 3P0 clock transition in neutral 88Sr over the 330 km-long stabilized fibre optic link
Authors: Morzyński Piotr , Bober Marcin , Bartoszek-Bober Dobrosława , Nawrocki Jerzy , Krehlik Przemysław , Śliwczyński Łukasz , Lipiński Marcin , Masłowski Piotr , Cygan Agata , Dunst Piotr , Garus Michał , Lisak Daniel , Zachorowski Jerzy , Gawlik Wojciech , Radzewicz Czesław , Ciuryło Roman , Zawada Michał
Published: December 2015

We report a stability below 7 × 10−17 of two independent optical lattice clocks operating with bosonic 88Sr isotope. The value (429 228 066 418 008.3(1.9)syst (0.9)stat Hz) of the absolute frequency of the 1S0 – 3P0 transition was measured with an optical frequency comb referenced to the local representation of the UTC by the 330 km-long stabilized fibre optical link. The result was verified by series of measurements on two independent optical lattice clocks and agrees with recommendation of Bureau International des Poids et Mesures.
BIM and mTOR expression levels predict outcome to erlotinib in EGFR-mutant non-small-cell lung cancer
Authors: Karachaliou Niki , Codony-Servat Jordi , Teixidó Cristina , Pilotto Sara , Drozdowskyj Ana , Codony-Servat Carles , Giménez-Capitán Ana , Molina-Vila Miguel Angel , Bertrán-Alamillo Jordi , Gervais Radj , Massuti Bartomeu , Morán Teresa , Majem Margarita , Felip Enriqueta , Carcereny Enric , García-Campelo Rosario , Viteri Santiago , González-Cao María , Morales-Espinosa Daniela , Verlicchi Alberto , Crisetti Elisabetta , Chaib Imane , Santarpia Mariacarmela , Luis Ramírez José , Bosch-Barrera Joaquim , Felipe Cardona Andrés , de Marinis Filippo , López-Vivanco Guillermo , Miguel Sánchez José , Vergnenegre Alain , Sánchez Hernández José Javier , Sperduti Isabella , Bria Emilio , Rosell Rafael
Published: December 2015

BIM is a proapoptotic protein that initiates apoptosis triggered by EGFR tyrosine kinase inhibitors (TKI). mTOR negatively regulates apoptosis and may influence response to EGFR TKI. We examined mRNA expression of BIM and MTOR in 57 patients with EGFR-mutant NSCLC from the EURTAC trial. Risk of mortality and disease progression was lower in patients with high BIM compared with low/intermediate BIM mRNA levels. Analysis of MTOR further divided patients with high BIM expression into two groups, with those having both high BIM and MTOR experiencing shorter overall and progression-free survival to erlotinib. Validation of our results was performed in an independent cohort of 19 patients with EGFR-mutant NSCLC treated with EGFR TKIs. In EGFR-mutant lung adenocarcinoma cell lines with high BIM expression, concomitant high mTOR expression increased IC50 of gefitinib for cell proliferation. We next sought to analyse the signalling pattern in cell lines with strong activation of mTOR and its substrate P-S6. We showed that mTOR and phosphodiesterase 4D (PDE4D) strongly correlate in resistant EGFR-mutant cancer cell lines. These data suggest that the combination of EGFR TKI with mTOR or PDE4 inhibitors could be adequate therapy for EGFR-mutant NSCLC patients with high pretreatment levels of BIM and mTOR.
GLUT3 and PKM2 regulate OCT4 expression and support the hypoxic culture of human embryonic stem cells
Authors: Christensen David R. , Calder Philip C. , Houghton Franchesca D.
Published: December 2015

Human embryonic stem cells (hESCs) have the capacity to differentiate into all cell types and thus have great potential for regenerative medicine. hESCs cultured at low oxygen tensions are more pluripotent and display an increased glycolytic rate but how this is regulated is unknown. This study therefore aimed to investigate the regulation of glucose metabolism in hESCs and whether this might impact OCT4 expression. In contrast to the glucose transporter GLUT1, GLUT3 was regulated by environmental oxygen and localised to hESC membranes. Silencing GLUT3 caused a reduction in glucose uptake and lactate production as well as OCT4 expression. GLUT3 and OCT4 expression were correlated suggesting that hESC self-renewal is regulated by the rate of glucose uptake. Surprisingly, PKM2, a rate limiting enzyme of glycolysis displayed a nuclear localisation in hESCs and silencing PKM2 did not alter glucose metabolism suggesting a role other than as a glycolytic enzyme. PKM2 expression was increased in hESCs cultured at 5% oxygen compared to 20% oxygen and silencing PKM2 reduced OCT4 expression highlighting a transcriptional role for PKM2 in hESCs. Together, these data demonstrate two separate mechanisms by which genes regulating glucose uptake and metabolism are involved in the hypoxic support of pluripotency in hESCs.
Flame treatment of graphene oxides: cost-effective production of nanoporous graphene electrode for Lithium-ion batteries
Authors: Jiang Hao-Bo , Zhang Yong-Lai , Zhang Yi , Liu Yan , Fu Xiu-Yan , Liu Yu-Qing , Wang Chun-Dong , Sun Hong-Bo
Published: December 2015

A facile production of highly porous graphene foam by using flame treatment of graphene oxide (GO) is proposed. Highly porous architectures with randomly distributed micro-crack and micro-slit were produced due to the high temperature induced ruinous reduction and rapid expansion of GO. Synchronously, abundant oxygen-containing groups (OCGs) on GO sheets could be effectively removed after flame treatment, which renders significantly increased conductivity to the resultant flame reduced GO (FR-GO). The synergistic effect of micro/nanostructuring and the OCGs removal makes FR-GO a promising candidate for electrode materials. Compared with chemically reduced GO (CR-GO), FR-GO delivers much higher specific capacity. It gives us some hints that flame treatment of graphene-based material is a smart strategy for cost-effective production of anode materials for commercial application.
Antibiotic monensin synergizes with EGFR inhibitors and oxaliplatin to suppress the proliferation of human ovarian cancer cells
Authors: Deng Youlin , Zhang Junhui , Wang Zhongliang , Yan Zhengjian , Qiao Min , Ye Jixing , Wei Qiang , Wang Jing , Wang Xin , Zhao Lianggong , Lu Shun , Tang Shengli , Mohammed Maryam K. , Liu Hao , Fan Jiaming , Zhang Fugui , Zou Yulong , Liao Junyi , Qi Hongbo , Haydon Rex C. , Luu Hue H. , He Tong-Chuan , Tang Liangdan
Published: December 2015

Ovarian cancer is the most lethal gynecologic malignancy with an overall cure rate of merely 30%. Most patients experience recurrence within 12–24 months of cure and die of progressively chemotherapy-resistant disease. Thus, more effective anti-ovarian cancer therapies are needed. Here, we investigate the possibility of repurposing antibiotic monensin as an anti-ovarian cancer agent. We demonstrate that monensin effectively inhibits cell proliferation, migration and cell cycle progression and induces apoptosis of human ovarian cancer cells. Monensin suppresses multiple cancer-related pathways including Elk1/SRF, AP1, NFκB and STAT and reduces EGFR expression in ovarian cancer cells. Monensin acts synergistically with EGFR inhibitors and oxaliplatin to inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Xenograft studies confirm that monensin effectively inhibits tumor growth by suppressing cell proliferation through targeting EGFR signaling. Our results suggest monensin may be repurposed as an anti-ovarian cancer agent although further preclinical and clinical studies are needed.
Formation of Carbonized Polystyrene Sphere/hemisphere Shell Arrays by Ion Beam Irradiation and Subsequent Annealing or Chloroform Treatment
Authors: Song Xianyin , Dai Zhigao , Xiao Xiangheng , Li Wenqing , Zheng Xudong , Shang Xunzhong , Zhang Xiaolei , Cai Guangxu , Wu Wei , Meng Fanli , Jiang Changzhong
Published: December 2015

Heat-resistant two-dimensional (2D) sphere/hemisphere shell array is significant for the fabrication of novel nanostructures. Here large-area, well-ordered arrays of carbonized polystyrene (PS) hollow sphere/hemisphere with controlled size and morphology are prepared by combining the nanosphere self-assembly, kV Ag ion beam modification and subsequent annealing or chloroform treatment. Potential mechanisms for the formation and evolution of the heat-resistant carbonized PS spherical shell with increasing ion fluence and energy are discussed. Combined with noble metal or semiconductor, these modified PS sphere arrays should open up new possibilities for high-performance nanoscale optical sensors or photoelectric devices.
A Wide-angle Multi-Octave Broadband Waveplate Based on Field Transformation Approach
Authors: Zhao Junming , Zhang Lianhong , Li Jensen , Feng Yijun , Dyke Amy , Haq Sajad , Hao Yang
Published: December 2015

Transformation optics (TO) offers a geometrical approach in designing optical components of any shapes. Although it has been proven to be a versatile and robust mathematical tool, TO has, however, limited control over electromagnetic (EM) field polarization in the process of coordinate transformation. Such a technique can be extended to a so-called “Field transformation (FT)” which provides direct control over the impedance and polarization signature of an arbitrary object. In this work, we demonstrate a FT application by designing and manufacturing a novel waveplate, which defies the fundamental limit of bandwidth and incident angles and has the ability of converting between TE (transverse electric) and TM (transverse magnetic) as well as LCP (left-handed circular polarization) and RCP (right-handed circular polarization). Such a waveplate can also be applied to different operating modes for both transmitted and reflected waves by adjusting its thickness and adding an optional metallic ground plane. The proposed design approach presents a remarkable degree of advance for designing future devices with arbitrary polarization controls, artificial waveguides or antenna substrates and polarization-enabled resonators with angle-insensitive functionalities. Our approach has far reaching implications applicable from radio to optical frequencies.
Three-dimensional Nitrogen-Doped Graphene Supported Molybdenum Disulfide Nanoparticles as an Advanced Catalyst for Hydrogen Evolution Reaction
Authors: Dong Haifeng , Liu Conghui , Ye Haitao , Hu Linping , Fugetsu Bunshi , Dai Wenhao , Cao Yu , Qi Xueqiang , Lu Huiting , Zhang Xueji
Published: December 2015

An efficient three-dimensional (3D) hybrid material of nitrogen-doped graphene sheets (N-RGO) supporting molybdenum disulfide (MoS2) nanoparticles with high-performance electrocatalytic activity for hydrogen evolution reaction (HER) is fabricated by using a facile hydrothermal route. Comprehensive microscopic and spectroscopic characterizations confirm the resulting hybrid material possesses a 3D crumpled few-layered graphene network structure decorated with MoS2 nanoparticles. Electrochemical characterization analysis reveals that the resulting hybrid material exhibits efficient electrocatalytic activity toward HER under acidic conditions with a low onset potential of 112 mV and a small Tafel slope of 44 mV per decade. The enhanced mechanism of electrocatalytic activity has been investigated in detail by controlling the elemental composition, electrical conductance and surface morphology of the 3D hybrid as well as Density Functional Theory (DFT) calculations. This demonstrates that the abundance of exposed active sulfur edge sites in the MoS2 and nitrogen active functional moieties in N-RGO are synergistically responsible for the catalytic activity, whilst the distinguished and coherent interface in MoS2/N-RGO facilitates the electron transfer during electrocatalysis. Our study gives insights into the physical/chemical mechanism of enhanced HER performance in MoS2/N-RGO hybrids and illustrates how to design and construct a 3D hybrid to maximize the catalytic efficiency.
Hidden symmetry and protection of Dirac points on the honeycomb lattice
Authors: Hou Jing-Min , Chen Wei
Published: December 2015

The honeycomb lattice possesses a novel energy band structure, which is characterized by two distinct Dirac points in the Brillouin zone, dominating most of the physical properties of the honeycomb structure materials. However, up till now, the origin of the Dirac points is unclear yet. Here, we discover a hidden symmetry on the honeycomb lattice and prove that the existence of Dirac points is exactly protected by such hidden symmetry. Furthermore, the moving and merging of the Dirac points and a quantum phase transition, which have been theoretically predicted and experimentally observed on the honeycomb lattice, can also be perfectly explained by the parameter dependent evolution of the hidden symmetry.
Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development
Authors: Wu Yaosen , Chen Linwei , Wang Ye , Li Wanli , Lin Yan , Yu Dongsheng , Zhang Liang , Li Fangcai , Pan Zhijun
Published: December 2015

The aim of our study was to evaluate if Sirt6, a NAD + dependent histone deacetylase, plays a protective role in cartilage degeneration by suppressing cellular senescence and inflammatory responses. The expression level of sirt6 in normal and OA human knee articular cartilage was compared by immunofluorescence and western blotting. The effect of sirt6 overexpression on replicative senescence of chondrocytes and NF-κB target genes expression was evaluated. Histological assessment of OA mice knee joint was carried out to assess the in vivo effects of sirt6 overexpression on mice chondrocytes. We found sirt6 level was significantly decreased in the articular chondrocytes of OA patients compare to normal human. SA-β-gal staining revealed that overexpression of sirt6 suppressed replicative senescence of chondrocytes. Meanwhile, the expression of NF-κB dependent genes were significantly attenuated by sirt6 overxpression. Safranin-O staining and OARSI score of knee joint cartilage in OA mice revealed that Lenti-Sirt6 intraarticular injection could protect mice chondrocytes from degeneration. These data strongly suggest that overexpression of Sirt6 can prevent OA development by reducing both the inflammatory response and chondrocytes senescence. Therefore, the development of specific activators of Sirt6 may have therapeutic potential for the treatment of OA.
Environmental marine pathogen isolation using mesocosm culture of sharpsnout seabream: striking genomic and morphological features of novel Endozoicomonas sp.
Authors: Katharios Pantelis , Seth-Smith Helena M. B. , Fehr Alexander , Mateos José M. , Qi Weihong , Richter Denis , Nufer Lisbeth , Ruetten Maja , Guevara Soto Maricruz , Ziegler Urs , Thomson Nicholas R , Schlapbach Ralph , Vaughan Lloyd
Published: December 2015

Aquaculture is a burgeoning industry, requiring diversification into new farmed species, which are often at risk from infectious disease. We used a mesocosm technique to investigate the susceptibility of sharpsnout seabream (Diplodus puntazzo) larvae to potential environmental pathogens in seawater compared to control borehole water. Fish exposed to seawater succumbed to epitheliocystis from 21 days post hatching, causing mortality in a quarter of the hosts. The pathogen responsible was not chlamydial, as is often found in epitheliocystis, but a novel species of the γ-proteobacterial genus Endozoicomonas. Detailed characterisation of this pathogen within the infectious lesions using high resolution fluorescent and electron microscopy showed densely packed rod shaped bacteria. A draft genome sequence of this uncultured bacterium was obtained from preserved material. Comparison with the genome of the Endozoicomonas elysicola type strain shows that the genome of Ca. Endozoicomonas cretensis is undergoing decay through loss of functional genes and insertion sequence expansion, often indicative of adaptation to a new niche or restriction to an alternative lifestyle. These results demonstrate the advantage of mesocosm studies for investigating the effect of environmental bacteria on susceptible hosts and provide an important insight into the genome dynamics of a novel fish pathogen.
Podocyte injury in diabetic nephropathy: implications of angiotensin II – dependent activation of TRPC channels
Authors: Ilatovskaya Daria V. , Levchenko Vladislav , Lowing Andrea , Shuyskiy Leonid S. , Palygin Oleg , Staruschenko Alexander
Published: December 2015

Injury to podocytes is considered a major contributor to diabetic kidney disease: their loss causes proteinuria and progressive glomerulosclerosis. Podocyte depletion may result from improper calcium handling due to abnormal activation of the calcium permeant TRPC (Transient Receptor Potential Canonical) channels. Angiotensin II (Ang II) levels are found to be elevated in diabetes; furthermore, it was reported that Ang II causes activation of TRPC6 in podocytes. We hypothesized here that Ang II-mediated calcium influx is aggravated in the podocytes under the conditions of type 1 diabetic nephropathy (DN). Diabetes was induced in the Dahl Salt-Sensitive rats by an injection of streptozotocin (STZ-SS). Eleven weeks post treatment was sufficient for the animals to develop hyperglycemia, excessive urination, weight loss, microalbuminuria, nephrinuria and display renal histological lesions typical for patients with DN. Patch-clamp electrophysiology performed on podocytes of the freshly isolated glomeruli showed enhanced basal TRPC channel activity in the STZ-SS rats and increased response to Ang II; total calcium influx triggered by Ang II application was also augmented in podocytes of these rats. Our studies have a strong potential for advancing the understanding of TRPC-mediated effects on podocytopenia in DN initiation.
Practice reduces task relevant variance modulation and forms nominal trajectory
Authors: Osu Rieko , Morishige Ken-ichi , Nakanishi Jun , Miyamoto Hiroyuki , Kawato Mitsuo
Published: December 2015

Humans are capable of achieving complex tasks with redundant degrees of freedom. Much attention has been paid to task relevant variance modulation as an indication of online feedback control strategies to cope with motor variability. Meanwhile, it has been discussed that the brain learns internal models of environments to realize feedforward control with nominal trajectories. Here we examined trajectory variance in both spatial and temporal domains to elucidate the relative contribution of these control schemas. We asked subjects to learn reaching movements with multiple via-points and found that hand trajectories converged to stereotyped trajectories with the reduction of task relevant variance modulation as learning proceeded. Furthermore, variance reduction was not always associated with task constraints but was highly correlated with the velocity profile. A model assuming noise both on the nominal trajectory and motor command was able to reproduce the observed variance modulation, supporting an expression of nominal trajectories in the brain. The learning-related decrease in task-relevant modulation revealed a reduction in the influence of optimal feedback around the task constraints. After practice, the major part of computation seems to be taken over by the feedforward controller around the nominal trajectory with feedback added only when it becomes necessary.
Heterologous expression of newly identified galectin-8 from sea urchin embryos produces recombinant protein with lactose binding specificity and anti-adhesive activity
Authors: Karakostis Konstantinos , Costa Caterina , Zito Francesca , Matranga Valeria
Published: December 2015

Galectin family members specifically bind beta-galactoside derivatives and are involved in different cellular events, including cell communication, signalling, apoptosis and immune responses. Here, we report a tandem-repeat type galectin from the Paracentrotus lividus sea urchin embryo, referred to as Pl-GAL-8. The 933nt sequence encodes a protein of 34.73 kDa, containing the conserved HFNPRF and WGxExR motifs in the two highly similar carbohydrate-recognition domains (CRD). The three-dimensional protein structure model of the N-CRD confirms the high evolutionary conservation of carbohydrate binding sites. The temporal gene expression is regulated during development and transcripts localize at the tip of the archenteron at gastrula stage, in a subset of the secondary mesenchyme cells that differentiate into blastocoelar (immune) cells. Functional studies using a recombinant Pl-GAL-8 expressed in bacteria demonstrate its hemo-agglutinating activity on human red blood cells through the binding to lactose, as well as its ability in inhibiting the adhesion of human Hep-G2 cells to the substrate. The recent implications in autoimmune diseases and inflammatory disorders make Gal-8 an attractive candidate for therapeutic purposes. Our results offer a solid basis for addressing the use of the new Pl-GAL-8 in functional and applicative studies, respectively in the developmental and biomedical fields.
A Probabilistic Model for Estimating the Depth and Threshold Temperature of C-fiber Nociceptors
Authors: Dezhdar Tara , Moshourab Rabih A. , Fründ Ingo , Lewin Gary R. , Schmuker Michael
Published: December 2015

The subjective experience of thermal pain follows the detection and encoding of noxious stimuli by primary afferent neurons called nociceptors. However, nociceptor morphology has been hard to access and the mechanisms of signal transduction remain unresolved. In order to understand how heat transducers in nociceptors are activatedin vivo, it is important to estimate the temperatures that directly activate the skin-embedded nociceptor membrane. Hence, the nociceptor’s temperature threshold must be estimated, which in turn will depend on the depth at which transduction happens in the skin. Since the temperature at the receptor cannot be accessed experimentally, such an estimation can currently only be achieved through modeling. However, the current state-of-the-art model to estimate temperature at the receptor suffers from the fact that it cannot account for the natural stochastic variability of neuronal responses. We improve this model using a probabilistic approach which accounts for uncertainties and potential noise in system. Using a data set of 24 C-fibers recordedin vitro, we show that, even without detailed knowledge of the bio-thermal properties of the system, the probabilistic model that we propose here is capable of providing estimates of threshold and depth in cases where the classical method fails.
An outbreak caused by GII.17 norovirus with a wide spectrum of HBGA-associated susceptibility
Authors: Zhang Xu-Fu , Huang Qiong , Long Yan , Jiang Xi , Zhang Ting , Tan Ming , Zhang Qiao-Li , Huang Zhen-Yu , Li Yue-Huan , Ding Yao-Quan , Hu Gui-Fang , Tang Shixing , Dai Ying-Chun
Published: December 2015

During the past norovirus (NoV) epidemic season, a new GII.17 variant emerged as a predominant NoV strain, surpassed the GII.4 NoVs, causing outbreaks of acute gastroenteritis (AGE) in China. Here we report a study of an AGE outbreak in an elementary school in December 2014 caused by the new GII.17 NoV to explore the potential mechanism behind the sudden epidemics of the GII.17 NoV. A total of 276 individuals were sick with typical NoV infection symptoms of vomiting (93.4%), abdominal pain (90.4%), nausea (60.0%) and diarrhea (10.4%) at an attack rate of 5.7–16.9%. Genotyping of the symptomatic patients showed that individuals with a secretor positive status, including those with A, B and O secretors and Lewis positive blood types, were sensitive to the virus, while the non-secretors and the Lewis negative individual were not. Accordingly, the recombinant capsid P protein of the GII.17 isolate showed a wide binding spectrum to saliva samples of all A, B and O secretors. Thus, the broad binding spectrum of the new GII.17 variant could explain its widely spread nature in China and surrounding areas in the past two years.
Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells
Authors: Huang Kaimeng , Zhang Xiaobai , Shi Jiejun , Yao Mingze , Lin Jiannan , Li Jiao , Liu He , Li Huanhuan , Shi Guang , Wang Zhibin , Zhang Biliang , Chen Jiekai , Pan Guangjin , Jiang Cizhong , Pei Duanqing , Yao Hongjie
Published: December 2015

Nucleosome positioning and histone modification play a critical role in gene regulation, but their role during reprogramming has not been fully elucidated. Here, we determined the genome-wide nucleosome coverage and histone methylation occupancy in mouse embryonic fibroblasts (MEFs), induced pluripotent stem cells (iPSCs) and pre-iPSCs. We found that nucleosome occupancy increases in promoter regions and decreases in intergenic regions in pre-iPSCs, then recovers to an intermediate level in iPSCs. We also found that nucleosomes in pre-iPSCs are much more phased than those in MEFs and iPSCs. During reprogramming, nucleosome reorganization and histone methylation around transcription start sites (TSSs) are highly coordinated with distinctively transcriptional activities. Bivalent promoters gradually increase, while repressive promoters gradually decrease. High CpG (HCG) promoters of active genes are characterized by nucleosome depletion at TSSs, while low CpG (LCG) promoters exhibit the opposite characteristics. In addition, we show that vitamin C (VC) promotes reorganizations of canonical, H3K4me3- and H3K27me3-modified nucleosomes on specific genes during transition from pre-iPSCs to iPSCs. These data demonstrate that pre-iPSCs have a more open and phased chromatin architecture than that of MEFs and iPSCs. Finally, this study reveals the dynamics and critical roles of nucleosome positioning and chromatin organization in gene regulation during reprogramming.
Self-directed exploration provides a Ncs1-dependent learning bonus
Authors: Mun Ho-Suk , Saab Bechara J. , Ng Enoch , McGirr Alexander , Lipina Tatiana V. , Gondo Yoichi , Georgiou John , Roder John C.
Published: December 2015

Understanding the mechanisms of memory formation is fundamental to establishing optimal educational practices and restoring cognitive function in brain disease. Here, we show for the first time in a non-primate species, that spatial learning receives a special bonus from self-directed exploration. In contrast, when exploration is escape-oriented, or when the full repertoire of exploratory behaviors is reduced, no learning bonus occurs. These findings permitted the first molecular and cellular examinations into the coupling of exploration to learning. We found elevated expression of neuronal calcium sensor 1 (Ncs1) and dopamine type-2 receptors upon self-directed exploration, in concert with increased neuronal activity in the hippocampal dentate gyrus and area CA3, as well as the nucleus accumbens. We probed further into the learning bonus by developing a point mutant mouse (Ncs1P144S/P144S) harboring a destabilized NCS-1 protein and found this line lacked the equivalent self-directed exploration learning bonus. Acute knock-down of Ncs1 in the hippocampus also decoupled exploration from efficient learning. These results are potentially relevant for augmenting learning and memory in health and disease and provide the basis for further molecular and circuit analyses in this direction.
Atomically precise semiconductor—graphene and hBN interfaces by Ge intercalation
Authors: Verbitskiy N. I. , Fedorov A. V. , Profeta G. , Stroppa A. , Petaccia L. , Senkovskiy B. , Nefedov A. , Wöll C. , Usachov D. Yu. , Vyalikh D. V. , Yashina L. V. , Eliseev A. A. , Pichler T. , Grüneis A.
Published: December 2015

The full exploration of the potential, which graphene offers to nanoelectronics requires its integration into semiconductor technology. So far the real-world applications are limited by the ability to concomitantly achieve large single-crystalline domains on dielectrics and semiconductors and to tailor the interfaces between them. Here we show a new direct bottom-up method for the fabrication of high-quality atomically precise interfaces between 2D materials, like graphene and hexagonal boron nitride (hBN) and classical semiconductor via Ge intercalation. Using angle-resolved photoemission spectroscopy and complementary DFT modelling we observed for the first time that epitaxially grown graphene with the Ge monolayer underneath demonstrates Dirac Fermions unaffected by the substrate as well as an unperturbed electronic band structure of hBN. This approach provides the intrinsic relativistic 2D electron gas towards integration in semiconductor technology. Hence, these new interfaces are a promising path for the integration of graphene and hBN into state-of-the-art semiconductor technology.
Electron beam irradiated silver nanowires for a highly transparent heater
Authors: Hong Chan-Hwa , Oh Seung Kyu , Kim Tae Kyoung , Cha Yu-Jung , Kwak Joon Seop , Shin Jae-Heon , Ju Byeong-Kwon , Cheong Woo-Seok
Published: December 2015

Transparent heaters have attracted increasing attention for their usefulness in vehicle windows, outdoor displays and periscopes. We present high performance transparent heaters based on Ag nanowires with electron beam irradiation. We obtained an Ag-nanowire thin film with 48 ohm/sq of sheet resistance and 88.8% (substrate included) transmittance at 550 nm after electron beam irradiation for 120 sec. We demonstrate that the electron beam creates nano-soldering at the junctions of the Ag nanowires, which produces lower sheet resistance and improved adhesion of the Ag nanowires. We fabricated a transparent heater with Ag nanowires after electron beam irradiation and obtained a temperature of 51 °C within 1 min at an applied voltage of 7 V. The presented technique will be useful in a wide range of applications for transparent heaters.
Superdiffusive motion of membrane-targeting C2 domains
Authors: Campagnola Grace , Nepal Kanti , Schroder Bryce W. , Peersen Olve B. , Krapf Diego
Published: December 2015

Membrane-targeting domains play crucial roles in the recruitment of signalling molecules to the plasma membrane. For most peripheral proteins, the protein-to-membrane interaction is transient. After proteins dissociate from the membrane they have been observed to rebind following brief excursions in the bulk solution. Such membrane hops can have broad implications for the efficiency of reactions on membranes. We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported lipid bilayers. The ensemble-averaged mean square displacement (MSD) exhibits superdiffusive behaviour. However, traditional time-averaged MSD analysis of individual trajectories remains linear and does not reveal superdiffusion. Our observations are explained in terms of bulk excursions that introduce jumps with a heavy-tail distribution. These hopping events allow proteins to explore large areas in a short time. The experimental results are shown to be consistent with analytical models of bulk-mediated diffusion and numerical simulations.
Exploring the automaticity of language-perception interactions: Effects of attention and awareness
Authors: Francken Jolien C. , Meijs Erik L. , Hagoort Peter , van Gaal Simon , de Lange Floris P.
Published: December 2015

Previous studies have shown that language can modulate visual perception, by biasing and/or enhancing perceptual performance. However, it is still debated where in the brain visual and linguistic information are integrated and whether the effects of language on perception are automatic and persist even in the absence of awareness of the linguistic material. Here, we aimed to explore the automaticity of language-perception interactions and the neural loci of these interactions in an fMRI study. Participants engaged in a visual motion discrimination task (upward or downward moving dots). Before each trial, a word prime was briefly presented that implied upward or downward motion (e.g., “rise”, “fall”). These word primes strongly influenced behavior: congruent motion words sped up reaction times and improved performance relative to incongruent motion words. Neural congruency effects were only observed in the left middle temporal gyrus, showing higher activity for congruent compared to incongruent conditions. This suggests that higher-level conceptual areas rather than sensory areas are the locus of language-perception interactions. When motion words were rendered unaware by means of masking, they still affected visual motion perception, suggesting that language-perception interactions may rely on automatic feed-forward integration of perceptual and semantic material in language areas of the brain.
Cytoplasmic hnRNPK interacts with GSK3β and is essential for the osteoclast differentiation
Authors: Fan Xiaoqin , Xiong Haiting , Wei Jinmei , Gao Xuejuan , Feng Yuan , Liu Xiaohui , Zhang Gong , He Qing-Yu , Xu Jiake , Liu Langxia
Published: December 2015

Osteoclast differentiation is a complex and finely regulated physiological process that involves a variety of signaling pathways and factors. Recent studies suggested that the Ser9 phosphorylation of Glycogen synthase kinase-3β (GSK3β) is required for the osteoclast differentiation. However, the precise underlying mechanism remains unclear. We have previously identified the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a putative GSK3β interactor. In the present study, we demonstrate that, during the RANKL-induced osteoclast differentiation, the PI3K/Akt-mediated Ser9 phosphorylation of GSK3β provokes the nuclear-cytoplasmic translocation of hnRNPK in an ERK-dependent manner, enhancing the cytoplasmic co-localization and interaction of GSK3β and hnRNPK. We show that hnRNPK is essential for the osteoclast differentiation and is involved in several reported functions of GSK3β, including the activation of NF-κB, the expression of NFATc1 and the acetylation of tubulin, all known to be critical for osteoclast differentiation and functions. We find that hnRNPK is localized in the actin belt and is important for the mature osteoclast formation. Taken together, we demonstrate here the critical role of hnRNPK in osteoclast differentiation and depict a model in which the cytoplasmic hnRNPK interacts with GSK3β and regulates its function.
Pure spin-Hall magnetoresistance in Rh/Y3Fe5O12 hybrid
Authors: Shang T. , Zhan Q. F. , Ma L. , Yang H. L. , Zuo Z. H. , Xie Y. L. , Li H. H. , Liu L. P. , Wang B. M. , Wu Y. H. , Zhang S. , Li Run-Wei
Published: December 2015

We report an investigation of anisotropic magnetoresistance (AMR) and anomalous Hall resistance (AHR) of Rh and Pt thin films sputtered on epitaxial Y3Fe5O12 (YIG) ferromagnetic insulator films. For the Pt/YIG hybrid, large spin-Hall magne toresistance (SMR) along with a sizable conventional anisotropic magnetoresistance (CAMR) and a nontrivial temperature dependence of AHR were observed in the temperature range of 5–300 K. In contrast, a reduced SMR with negligible CAMR and AHR was found in Rh/YIG hybrid. Since CAMR and AHR are characteristics for all ferromagnetic metals, our results suggest that the Pt is likely magnetized by YIG due to the magnetic proximity effect (MPE) while Rh remains free of MPE. Thus the Rh/YIG hybrid could be an ideal model system to explore physics and devices associated with pure spin current.
Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage
Authors: Luo Hanwen , Li Jing , Cao Hong , Tan Yang , Magdalou Jacques , Chen Liaobin , Wang Hui
Published: December 2015

Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway.
Observation of Bloch oscillations in complex PT-symmetric photonic lattices
Authors: Wimmer Martin , Miri Mohammed-Ali , Christodoulides Demetrios , Peschel Ulf
Published: December 2015

Light propagation in periodic environments is often associated with a number of interesting and potentially useful processes. If a crystalline optical potential is also linearly ramped, light can undergo periodic Bloch oscillations, a direct outcome of localized Wannier-Stark states and their equidistant eigenvalue spectrum. Even though these effects have been extensively explored in conservative settings, this is by no means the case in non-Hermitian photonic lattices encompassing both amplification and attenuation. Quite recently, Bloch oscillations have been predicted in parity-time-symmetric structures involving gain and loss in a balanced fashion. While in a complex bulk medium, one intuitively expects that light will typically follow the path of highest amplification, in a periodic system this behavior can be substantially altered by the underlying band structure. Here, we report the first experimental observation of Bloch oscillations in parity-time-symmetric mesh lattices. We show that these revivals exhibit unusual properties like secondary emissions and resonant restoration of PT symmetry. In addition, we present a versatile method for reconstructing the real and imaginary components of the band structure by directly monitoring the light evolution during a cycle of these oscillations.
Buckling assisted and lithographically micropatterned fully flexible sensors for conformal integration applications
Authors: Maji Debashis , Das Debanjan , Wala Jyoti , Das Soumen
Published: December 2015

Development of flexible sensors/electronics over substrates thicker than 100 μm is of immense importance for its practical feasibility. However, unlike over ultrathin films, large bending stress hinders its flexibility. Here we have employed a novel technique of fabricating sensors over a non-planar ridge topology under pre-stretched condition which not only helps in spontaneous generation of large and uniform parallel buckles upon release, but also acts as stress reduction zones thereby preventing Poisson’s ratio induced lateral cracking. Further, we propose a complete lithography compatible process to realize flexible sensors over pre-stretched substrates thicker than 100 μm that are released through dissolution of a water soluble sacrificial layer of polyvinyl alcohol. These buckling assisted flexible sensors demonstrated superior performance along different flexible modalities. Based on the above concept, we also realized a micro thermal flow sensor, conformally wrapped around angiographic catheters to detect flow abnormalities for potential applications in interventional catheterization process.
Copy number variation and microdeletions of the Y chromosome linked genes and loci across different categories of Indian infertile males
Authors: Kumari Anju , Yadav Sandeep Kumar , Misro Man Mohan , Ahmad Jamal , Ali Sher
Published: December 2015

We analyzed 34 azoospermic (AZ), 43 oligospermic (OS) and 40 infertile males with normal spermiogram (INS) together with 55 normal fertile males (NFM) from the Indian population. AZ showed more microdeletions in the AZFa and AZFb regions whereas oligospermic ones showed more microdeletions in the AZFc region. Frequency of the AZF partial deletions was higher in males with spermatogenic impairments than in INS. Significantly, SRY, DAZ and BPY2 genes showed copy number variation across different categories of the patients and much reduced copies of the DYZ1 repeat arrays compared to that in normal fertile males. Likewise, INS showed microdeletions, sequence and copy number variation of several Y linked genes and loci. In the context of infertility, STS deletions and copy number variations both were statistically significant (p = 0.001). Thus, semen samples used during in vitro fertilization (IVF) and assisted reproductive technology (ART) must be assessed for the microdeletions of AZFa, b and c regions in addition to the affected genes reported herein. Present study is envisaged to be useful for DNA based diagnosis of different categories of the infertile males lending support to genetic counseling to the couples aspiring to avail assisted reproductive technologies.
Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma
Authors: Zhu Yitan , Li Hui , Guo Wentian , Drukker Karen , Lan Li , Giger Maryellen L. , Ji Yuan
Published: December 2015

Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status.
Pseudo-immortalization of postnatal cochlear progenitor cells yields a scalable cell line capable of transcriptionally regulating mature hair cell genes
Authors: Walters Brandon J. , Diao Shiyong , Zheng Fei , Walters Bradley J. , Layman Wanda S. , Zuo Jian
Published: December 2015

The mammalian cochlea is a highly specialized organ within the inner ear. Sensory hair cells (HC) in the cochlea detect and transduce sound waves into electrical impulses that are sent to the brain. Studies of the molecular pathways regulating HC formation are hindered by the very sparse nature of HCs, where only ~3300 are found within an entire mouse cochlea. Current cell lines mimic certain aspects of HCs but lack terminal HC marker expression. Here we successfully “pseudo-immortalized” cochlear progenitor cells using the “conditional reprogramming” technique. These cells, termed “Conditionally Reprogrammed Otic Stem Cells” (CR-OSC), are able to bypass the senescence inherent to cochlear progenitor cells without genetic alterations, allowing for the generation of over 15 million cells from a single cochlea. These cells can be differentiated and up-regulate both early and terminal differentiation genes associated with HCs, including the terminal HC differentiation marker prestin. CR-OSCs also respond to known HC cues, including upregulation of HC genes in response to Atoh1 overexpression and upregulation of prestin expression after thyroid hormone application. Overall, we describe the creation of a HC line capable of regulated expression of HC genes that can easily be recreated in any laboratory from any mouse of interest.
Molecular Assembly of Clostridium botulinum progenitor M complex of type E
Authors: Eswaramoorthy Subramaniam , Sun Jingchuan , Li Huilin , Singh Bal Ram , Swaminathan Subramanyam
Published: December 2015

Clostridium botulinum neurotoxin (BoNT) is released as a progenitor complex, in association with a non-toxic-non-hemagglutinin protein (NTNH) and other associated proteins. We have determined the crystal structure of M type Progenitor complex of botulinum neurotoxin E [PTC-E(M)], a heterodimer of BoNT and NTNH. The crystal structure reveals that the complex exists as a tight, interlocked heterodimer of BoNT and NTNH. The crystal structure explains the mechanism of molecular assembly of the complex and reveals several acidic clusters at the interface responsible for association at low acidic pH and disassociation at basic/neutral pH. The similarity of the general architecture between the PTC-E(M) and the previously determined PTC-A(M) strongly suggests that the progenitor M complexes of all botulinum serotypes may have similar molecular arrangement, although the neurotoxins apparently can take very different conformation when they are released from the M complex.
RESOLFT nanoscopy with photoswitchable organic fluorophores
Authors: Kwon Jiwoong , Hwang Jihee , Park Jaewan , Han Gi Rim , Han Kyu Young , Kim Seong Keun
Published: December 2015

Far-field optical nanoscopy has been widely used to image small objects with sub-diffraction-limit spatial resolution. Particularly, reversible saturable optical fluorescence transition (RESOLFT) nanoscopy with photoswitchable fluorescent proteins is a powerful method for super-resolution imaging of living cells with low light intensity. Here we demonstrate for the first time the implementation of RESOLFT nanoscopy for a biological system using organic fluorophores, which are smaller in size and easier to be chemically modified. With a covalently-linked dye pair of Cy3 and Alexa647 to label subcellular structures in fixed cells and by optimizing the imaging buffer and optical parameters, our RESOLFT nanoscopy achieved a spatial resolution of ~74 nm in the focal plane. This method provides a powerful alternative for low light intensity RESOLFT nanoscopy, which enables biological imaging with small organic probes at nanoscale resolution.