bluuebunny/crossref_metadata_2025 huggingface dataset:
Eye formation in rotating convection
Authors: Oruba L. , Davidson P. A. , Dormy E.
Published: January 2017

We consider rotating convection in a shallow, cylindrical domain. We examine the conditions under which the resulting vortex develops an eye at its core; that is, a region where the poloidal flow reverses and the angular momentum is low. For simplicity, we restrict ourselves to steady, axisymmetric flows in a Boussinesq fluid. Our numerical experiments show that, in such systems, an eye forms as a passive response to the development of a so-called eyewall, a conical annulus of intense, negative azimuthal vorticity that can form near the axis and separates the eye from the primary vortex. We also observe that the vorticity in the eyewall comes from the lower boundary layer, and relies on the fact the poloidal flow strips negative vorticity out of the boundary layer and carries it up into the fluid above as it turns upward near the axis. This process is effective only if the Reynolds number is sufficiently high for the advection of vorticity to dominate over diffusion. Finally we observe that, in the vicinity of the eye and the eyewall, the buoyancy and Coriolis forces are negligible, and so although these forces are crucial to driving and shaping the primary vortex, they play no direct role in eye formation in a Boussinesq fluid.
Vlasov models for kinetic Weibel-type instabilities
Authors: Ghizzo A. , Sarrat M. , Del Sarto D.
Published: January 2017

The Weibel instability, driven by a temperature anisotropy, is investigated within different kinetic descriptions based on the semi-Lagrangian full kinetic and relativistic Vlasov–Maxwell model, on the multi-stream approach, which is based on a Hamiltonian reduction technique, and finally, with the full pressure tensor fluid-type description. Dispersion relations of the Weibel instability are derived using the three different models. A qualitatively different regime is observed in Vlasov numerical experiments depending on the excitation of a longitudinal plasma electric field driven initially by the combined action of the stream symmetry breaking and weak relativistic effects, in contrast with the existing theories of the Weibel instability based on their purely transverse characters. The multi-stream model offers an alternate way to simulate easily the coupling with the longitudinal electric field and particularly the nonlinear regime of saturation, making numerical experiments more tractable, when only a few moments of the distribution are considered. Thus a numerical comparison between the reduced Hamiltonian model (the multi-stream model) and full kinetic (relativistic) Vlasov simulations has been investigated in that regime. Although nonlinear simulations of the fluid model, including the dynamics of the pressure tensor, have not been carried out here, the model is strongly relevant even in the three-dimensional case.
On Lorentzian surfaces in ℝ2,2
Authors: Bayard Pierre , Patty Victor , Sánchez-Bringas Federico
Published: January 2017

We study the second-order invariants of a Lorentzian surface in ℝ2,2, and the curvature hyperbolas associated with its second fundamental form. Besides the four natural invariants, new invariants appear in some degenerate situations. We then introduce the Gauss map of a Lorentzian surface and give an extrinsic proof of the vanishing of the total Gauss and normal curvatures of a compact Lorentzian surface. The Gauss map and the second-order invariants are then used to study the asymptotic directions of a Lorentzian surface and discuss their causal character. We also consider the relation of the asymptotic lines with the mean directionally curved lines. We finally introduce and describe the quasi-umbilic surfaces, and the surfaces whose four classical invariants vanish identically.
Vision in fossilised eyes
Authors: Schoenemann Brigitte , Clarkson Euan N. K.
Published: January 2017

This paper presents a review of recent developments in the study of vision in fossil arthropods, beginning with a discussion of the origin of visual systems. A report of the eyes of Cambrian arthropods from different Lagerstätten, especially the compound and median arthropod eyes from the Chengjiang fauna of China, is given. Reference is made also to compound eyes from the lower Cambrian Emu Bay Shale fauna of Australia and the Sirius Passet fauna of Greenland; also to the three-dimensionally preserved ‘Orsten’ fauna of Sweden. An understanding of how these eyes functioned is possible by reference to living arthropods and by using physical tools developed by physiologists. The eyes of trilobites (lower Cambrian to Upper Permian) are often very well preserved, and the structure and physiology of their calcite lenses, and the eye as a whole, are summarised here, based upon recent literature. Two main kinds of trilobite eyes have been long known. Firstly, there is the holochroal type, in which the lenses are usually numerous, small and closely packed together; this represents the ancestral kind, first found in lowermost Cambrian trilobites. The second type is the schizochroal eye, in which the lenses are relatively much larger and each is separated from its neighbours. Such eyes are confined to the single suborder Phacopina (Lower Ordovician to Upper Devonian). This visual system has no real equivalents in the animal kingdom. In this present paper, the origin of schizochroal eyes, by paedomorphosis from holochroal precursors, is reviewed, together with subsequent evolutionary transitions in the Early Ordovician. A summary of new work on the structure and mineralogy of phacopid lenses is presented, as is a discussion of the recent discovery of sublensar sensory structures in Devonian phacopids, which has opened up new dimensions in the study of trilobite vision.
When Sufficiently Processed, Semantically Related Distractor Pictures	Hamper Picture Naming
Authors: Matushanskaya Asya , Mädebach Andreas , Müller Matthias M. , Jescheniak Jörg D.
Published: January 2017

Abstract. Prominent speech production models view lexical access as a competitive process. According to these models, a semantically related distractor picture should interfere with target picture naming more strongly than an unrelated one. However, several studies failed to obtain such an effect. Here, we demonstrate that semantic interference is obtained, when the distractor picture is sufficiently processed. Participants named one of two pictures presented in close temporal succession, with color cueing the target. Experiment 1 induced the prediction that the target appears first. When this prediction was violated (distractor first), semantic interference was observed. Experiment 2 ruled out that the time available for distractor processing was the driving force. These results show that semantically related distractor pictures interfere with the naming response when they are sufficiently processed. The data thus provide further support for models viewing lexical access as a competitive process.
Three Semantic Serial Position Functions at the Same	Time
Authors: Neath Ian , Kelley Matthew R. , Surprenant Aimée M.
Published: January 2017

Abstract. Serial position functions are so ubiquitous that researchers frequently use buffer items to control for primacy and recency effects regardless of the memory task. However, most theories offer different explanations for different types of tests. In contrast, the relative distinctiveness principle offers one explanation for all tasks: items with fewer close neighbors will generally be more distinct and therefore better remembered than items with more close neighbors. An experiment assessed two predictions of this account. (1) When undergraduates place seven US states in three different orders (by area, year of statehood, and population), serial position functions and error gradients will be observed that resemble those observed in episodic tasks. (2) States that are accurately placed in order because they are an early or late item on one dimension will be placed in order far less accurately when they become mid-list items on a different dimension. The results confirm both predictions.
BMP restricts stemness of intestinal Lgr5+ stem cells by directly suppressing their signature genes
Authors: Qi Zhen , Li Yehua , Zhao Bing , Xu Chi , Liu Yuan , Li Haonan , Zhang Bingjie , Wang Xinquan , Yang Xiao , Xie Wei , Li Baojie , Han Jing-Dong Jackie , Chen Ye-Guang
Published: January 2017

The intestinal epithelium possesses a remarkable self-renewal ability, which is mediated by actively proliferating Lgr5+ stem cells. Bone morphogenetic protein (BMP) signalling represents one major counterforce that limits the hyperproliferation of intestinal epithelium, but the exact mechanism remains elusive. Here we demonstrate that epithelial BMP signalling plays an indispensable role in restricting Lgr5+ stem cell expansion to maintain intestinal homeostasis and prevent premalignant hyperproliferation on damage. Mechanistically, BMP inhibits stemness of Lgr5+ stem cells through Smad-mediated transcriptional repression of a large number of stem cell signature genes, including Lgr5, and this effect is independent of Wnt/β-catenin signalling. Smad1/Smad4 recruits histone deacetylase HDAC1 to the promoters to repress transcription, and knockout of Smad4 abolishes the negative effects of BMP on stem cells. Our findings therefore demonstrate that epithelial BMP constrains the Lgr5+ stem cell self-renewal via Smad-mediated repression of stem cell signature genes to ensure proper homeostatic renewal of intestinal epithelium.
CDK4/6 or MAPK blockade enhances efficacy of EGFR inhibition in oesophageal squamous cell carcinoma
Authors: Zhou Jin , Wu Zhong , Wong Gabrielle , Pectasides Eirini , Nagaraja Ankur , Stachler Matthew , Zhang Haikuo , Chen Ting , Zhang Haisheng , Liu Jie Bin , Xu Xinsen , Sicinska Ewa , Sanchez-Vega Francisco , Rustgi Anil K. , Diehl J. Alan , Wong Kwok-Kin , Bass Adam J.
Published: January 2017

Oesophageal squamous cell carcinoma is a deadly disease where systemic therapy has relied upon empiric chemotherapy despite the presence of genomic alterations pointing to candidate therapeutic targets, including recurrent amplification of the gene encoding receptor tyrosine kinase epidermal growth factor receptor (EGFR). Here, we demonstrate that EGFR-targeting small-molecule inhibitors have efficacy in EGFR-amplified oesophageal squamous cell carcinoma (ESCC), but may become quickly ineffective. Resistance can occur following the emergence of epithelial–mesenchymal transition and by reactivation of the mitogen-activated protein kinase (MAPK) pathway following EGFR blockade. We demonstrate that blockade of this rebound activation with MEK (mitogen-activated protein kinase kinase) inhibition enhances EGFR inhibitor-induced apoptosis and cell cycle arrest, and delays resistance to EGFR monotherapy. Furthermore, genomic profiling shows that cell cycle regulators are altered in the majority of EGFR-amplified tumours and a combination of cyclin-dependent kinase 4/6 (CDK4/6) and EGFR inhibitors prevents the emergence of resistance in vitro and in vivo. These data suggest that upfront combination strategies targeting EGFR amplification, guided by adaptive pathway reactivation or by co-occurring genomic alterations, should be tested clinically.
Hollow boron nitride nanospheres as boron reservoir for prostate cancer treatment
Authors: Li Xia , Wang Xiupeng , Zhang Jun , Hanagata Nobutaka , Wang Xuebin , Weng Qunhong , Ito Atsuo , Bando Yoshio , Golberg Dmitri
Published: January 2017

High global incidence of prostate cancer has led to a focus on prevention and treatment strategies to reduce the impact of this disease in public health. Boron compounds are increasingly recognized as preventative and chemotherapeutic agents. However, systemic administration of soluble boron compounds is hampered by their short half-life and low effectiveness. Here we report on hollow boron nitride (BN) spheres with controlled crystallinity and boron release that decrease cell viability and increase prostate cancer cell apoptosis. In vivo experiments on subcutaneous tumour mouse models treated with BN spheres demonstrated significant suppression of tumour growth. An orthotopic tumour growth model was also utilized and further confirmed the in vivo anti-cancer efficacy of BN spheres. Moreover, the administration of hollow BN spheres with paclitaxel leads to synergetic effects in the suppression of tumour growth. The work demonstrates that hollow BN spheres may function as a new agent for prostate cancer treatment.
Reorientation of the diagonal double-stripe spin structure at Fe1+yTe bulk and thin-film surfaces
Authors: Hänke Torben , Singh Udai Raj , Cornils Lasse , Manna Sujit , Kamlapure Anand , Bremholm Martin , Hedegaard Ellen Marie Jensen , Iversen Bo Brummerstedt , Hofmann Philip , Hu Jin , Mao Zhiqiang , Wiebe Jens , Wiesendanger Roland
Published: January 2017

Establishing the relation between ubiquitous antiferromagnetism in the parent compounds of unconventional superconductors and their superconducting phase is important for understanding the complex physics in these materials. Going from bulk systems to thin films additionally affects their phase diagram. For Fe1+yTe, the parent compound of Fe1+ySe1−xTex superconductors, bulk-sensitive neutron diffraction revealed an in-plane oriented diagonal double-stripe antiferromagnetic spin structure. Here we show by spin-resolved scanning tunnelling microscopy that the spin direction at the surfaces of bulk Fe1+yTe and thin films grown on the topological insulator Bi2Te3 is canted out of the high-symmetry directions of the surface unit cell resulting in a perpendicular spin component, keeping the diagonal double-stripe order. As the magnetism of the Fe d-orbitals is intertwined with the superconducting pairing in Fe-based materials, our results imply that the superconducting properties at the surface of the related superconducting compounds might be different from the bulk.
TRIM14 is a Putative Tumor Suppressor and Regulator of Innate Immune Response in Non-Small Cell Lung Cancer
Authors: Hai Josephine , Zhu Chang-Qi , Wang Tao , Organ Shawna L. , Shepherd Frances A. , Tsao Ming-Sound
Published: January 2017

Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states. We investigated the functional and prognostic role of TRIM14 in NSCLC using in vitro and in vivo perturbation model systems. Firstly, a pooled RNAi screen identified TRIM14 to effect cell proliferation/survival in NSCLC cells. Secondly, silencing of TRIM14 expression significantly enhanced tumor growth in NSCLC xenograft mouse models, while exogenous TRIM14 expression attenuated tumorigenesis. In addition, differences in apoptotic activity between TRIM14-deficient and control tumors suggests that TRIM14 tumor suppressor activity may depend on cell death signaling pathways. TRIM14-deficient cell lines showed both resistance to hypoxia-induced cell death and attenuation of interferon response via STAT1 signaling. Consistent with these phenotypes, multivariate analyses on published mRNA expression datasets of over 600 primary NSCLCs demonstrated that low TRIM14 mRNA levels are significantly associated with poorer prognosis in early stage NSCLC patients. Our functional data therefore establish a novel tumor suppressive role for TRIM14 in NSCLC progression.
A Pilot-scale Benthic Microbial Electrochemical System (BMES) for Enhanced Organic Removal in Sediment Restoration
Authors: Li Henan , Tian Yan , Qu Youpeng , Qiu Ye , Liu Jia , Feng Yujie
Published: January 2017

A benthic microbial electrochemical systems (BMES) of 195 L (120 cm long, 25 cm wide and 65 cm height) was constructed for sediment organic removal. Sediment from a natural river (Ashi River) was used as test sediments in the present research. Three-dimensional anode (Tri-DSA) with honeycomb structure composed of carbon cloth and supporting skeleton was employed in this research for the first time. The results demonstrated that BMES performed good in organic-matter degradation and energy generation from sediment and could be considered for river sediments in situ restoration as novel method. Community analysis from the soil and anode using 16S rDNA gene sequencing showed that more electrogenic functional bacteria was accumulated in anode area when circuit connected than control system.
The Effect of Electronic Structure on the Phases Present in High Entropy Alloys
Authors: Leong Zhaoyuan , Wróbel Jan S. , Dudarev Sergei L. , Goodall Russell , Todd Iain , Nguyen-Manh Duc
Published: January 2017

Multicomponent systems, termed High Entropy Alloys (HEAs), with predominantly single solid solution phases are a current area of focus in alloy development. Although different empirical rules have been introduced to understand phase formation and determine what the dominant phases may be in these systems, experimental investigation has revealed that in many cases their structure is not a single solid solution phase, and that the rules may not accurately distinguish the stability of the phase boundaries. Here, a combined modelling and experimental approach that looks into the electronic structure is proposed to improve accuracy of the predictions of the majority phase. To do this, the Rigid Band model is generalised for magnetic systems in prediction of the majority phase most likely to be found. Good agreement is found when the predictions are confronted with data from experiments, including a new magnetic HEA system (CoFeNiV). This also includes predicting the structural transition with varying levels of constituent elements, as a function of the valence electron concentration, n, obtained from the integrated spin-polarised density of states. This method is suitable as a new predictive technique to identify compositions for further screening, in particular for magnetic HEAs.
A late-lineage murine neutrophil precursor population exhibits dynamic changes during demand-adapted granulopoiesis
Authors: Kim Min-Hyeok , Yang Dongchan , Kim Mirang , Kim Seon-Young , Kim Dongsup , Kang Suk-Jo
Published: January 2017

Homeostasis of neutrophils—the blood cells that respond first to infection and tissue injury—is critical for the regulation of immune responses and regulated through granulopoiesis, a multi-stage process by which neutrophils differentiate from hematopoietic stem cells. Granulopoiesis is a highly dynamic process and altered in certain clinical conditions, such as pathologic and iatrogenic neutropenia, described as demand-adapted granulopoiesis. The regulation of granulopoiesis under stress is not completely understood because studies of granulopoiesis dynamics have been hampered by technical limitations in defining neutrophil precursors. Here, we define a population of neutrophil precursor cells in the bone marrow with unprecedented purity, characterized by the lineage−CD11b+Ly6GloLy6BintCD115−, which we call NeuPs (Neutrophil Precursors). We demonstrated that NeuPs differentiate into mature and functional neutrophils bothin vitroandin vivo. By analyzing the gene expression profiles of NeuPs, we also identified NeuP stage-specific genes and characterized patterns of gene regulation throughout granulopoiesis. Importantly, we found that NeuPs have the potential to proliferate, but the proliferation decreased in multiple different hematopoietic stress settings, indicating that proliferating NeuPs are poised at a critical step to regulate granulopoiesis. Our findings will facilitate understanding how the hematopoietic system maintains homeostasis and copes with the demands of granulopoiesis.
The OPRM1 A118G polymorphism modulates the descending pain modulatory system for individual pain experience in young women with primary dysmenorrhea
Authors: Wei Shyh-Yuh , Chen Li-Fen , Lin Ming-Wei , Li Wei-Chi , Low Intan , Yang Ching-Ju , Chao Hsiang-Tai , Hsieh Jen-Chuen
Published: January 2017

The mu-opioid receptor (OPRM1) A118G polymorphism underpins different pain sensitivity and opioid-analgesic outcome with unclear effect on the descending pain modulatory system (DPMS). Primary dysmenorrhea (PDM), the most prevalent gynecological problem with clear painful and pain free conditions, serves as a good clinical model of spontaneous pain. The objective of this imaging genetics study was therefore to explore if differences in functional connectivity (FC) of the DPMS between the OPRM1 A118G polymorphisms could provide a possible explanation for the differences in pain experience. Sixty-one subjects with PDM and 65 controls participated in the current study of resting-state functional magnetic resonance imaging (fMRI) during the menstruation and peri-ovulatory phases; blood samples were taken for genotyping. We studied 3 aspects of pain experience, namely, mnemonic pain (recalled overall menstrual pain), present pain (spontaneous menstrual pain), and experimental pain (thermal pain) intensities. We report that G allele carriers, in comparison to AA homozygotes, exhibited functional hypo-connectivity between the anterior cingulate cortex (ACC) and periaqueductal gray (PAG). Furthermore, G allele carriers lost the correlation with spontaneous pain experience and exhibited dysfunctional DPMS by means of PAG-seeded FC dynamics. This OPRM1 A118G-DPMS interaction is one plausible neurological mechanism underlying the individual differences in pain experience.
Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions
Authors: Rood Mark T. M. , Spa Silvia J. , Welling Mick M. , ten Hove Jan Bart , van Willigen Danny M. , Buckle Tessa , Velders Aldrik H. , van Leeuwen Fijs W. B.
Published: January 2017

The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or “training” of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings.
Incommensurate Graphene Foam as a High Capacity Lithium Intercalation Anode
Authors: Paronyan Tereza M. , Thapa Arjun Kumar , Sherehiy Andriy , Jasinski Jacek B. , Jangam John Samuel Dilip
Published: January 2017

Graphite’s capacity of intercalating lithium in rechargeable batteries is limited (theoretically, 372 mAh g−1) due to low diffusion within commensurately-stacked graphene layers. Graphene foam with highly enriched incommensurately-stacked layers was grown and applied as an active electrode in rechargeable batteries. A 93% incommensurate graphene foam demonstrated a reversible specific capacity of 1,540 mAh g−1 with a 75% coulombic efficiency, and an 86% incommensurate sample achieves above 99% coulombic efficiency exhibiting 930 mAh g−1 specific capacity. The structural and binding analysis of graphene show that lithium atoms highly intercalate within weakly interacting incommensurately-stacked graphene network, followed by a further flexible rearrangement of layers for a long-term stable cycling. We consider lithium intercalation model for multilayer graphene where capacity varies with N number of layers resulting LiN+1C2N stoichiometry. The effective capacity of commonly used carbon-based rechargeable batteries can be significantly improved using incommensurate graphene as an anode material.
Cigarette smoke extract profoundly suppresses TNFα-mediated proinflammatory gene expression through upregulation of ATF3 in human coronary artery endothelial cells
Authors: Teasdale Jack E. , Hazell Georgina G. J. , Peachey Alasdair M. G. , Sala-Newby Graciela B. , Hindmarch Charles C. T. , McKay Tristan R. , Bond Mark , Newby Andrew C. , White Stephen J.
Published: January 2017

Endothelial dysfunction caused by the combined action of disturbed flow, inflammatory mediators and oxidants derived from cigarette smoke is known to promote coronary atherosclerosis and increase the likelihood of myocardial infarctions and strokes. Conversely, laminar flow protects against endothelial dysfunction, at least in the initial phases of atherogenesis. We studied the effects of TNFα and cigarette smoke extract on human coronary artery endothelial cells under oscillatory, normal laminar and elevated laminar shear stress for a period of 72 hours. We found, firstly, that laminar flow fails to overcome the inflammatory effects of TNFα under these conditions but that cigarette smoke induces an anti-oxidant response that appears to reduce endothelial inflammation. Elevated laminar flow, TNFα and cigarette smoke extract synergise to induce expression of the transcriptional regulator activating transcription factor 3 (ATF3), which we show by adenovirus driven overexpression, decreases inflammatory gene expression independently of activation of nuclear factor-κB. Our results illustrate the importance of studying endothelial dysfunction in vitro over prolonged periods. They also identify ATF3 as an important protective factor against endothelial dysfunction. Modulation of ATF3 expression may represent a novel approach to modulate proinflammatory gene expression and open new therapeutic avenues to treat proinflammatory diseases.
Structural Effects of Lanthanide Dopants on Alumina
Authors: Patel Ketan , Blair Victoria , Douglas Justin , Dai Qilin , Liu Yaohua , Ren Shenqiang , Brennan Raymond
Published: January 2017

Lanthanide (Ln3+) doping in alumina has shown great promise for stabilizing and promoting desirable phase formation to achieve optimized physical and chemical properties. However, doping alumina with Ln elements is generally accompanied by formation of new phases (i.e. LnAlO3, Ln2O3), and therefore inclusion of Ln-doping mechanisms for phase stabilization of the alumina lattice is indispensable. In this study, Ln-doping (400 ppm) of the alumina lattice crucially delays the onset of phase transformation and enables phase population control, which is achieved without the formation of new phases. The delay in phase transition (θ → α), and alteration of powder morphology, particle dimensions, and composition ratios between α- and θ-alumina phases are studied using a combination of solid state nuclear magnetic resonance, electron microscopy, digital scanning calorimetry, and high resolution X-ray diffraction with refinement fitting. Loading alumina with a sparse concentration of Ln-dopants suggests that the dopants reside in the vacant octahedral locations within the alumina lattice, where complete conversion into the thermodynamically stable α-domain is shown in dysprosium (Dy)- and lutetium (Lu)-doped alumina. This study opens up the potential to control the structure and phase composition of Ln-doped alumina for emerging applications.
Non-invasive, Focused Ultrasound-Facilitated Gene Delivery for Optogenetics
Authors: Wang Shutao , Kugelman Tara , Buch Amanda , Herman Mathieu , Han Yang , Karakatsani Maria Eleni , Hussaini S. Abid , Duff Karen , Konofagou Elisa E.
Published: January 2017

Optogenetics, a widely used technique in neuroscience research, is often limited by its invasive nature of application. Here, we present a noninvasive, ultrasound-based technique to introduce optogenetic channels into the brain by temporarily opening the blood-brain barrier (BBB). We demonstrate the efficiency of the method developed and evaluate the bioactivity of the non-invasively introduced channelrhodopsin channels by performing stimulation in freely behaving mice.
Meprin β contributes to collagen deposition in lung fibrosis
Authors: Biasin V. , Wygrecka M. , Marsh L. M. , Becker-Pauly C. , Brcic L. , Ghanim B. , Klepetko W. , Olschewski A. , Kwapiszewska G.
Published: January 2017

Lung fibrosis is a severe disease characterized by epithelial cell injury, inflammation and collagen deposition. The metalloproteases meprinα and meprinβ have been shown to enhance collagen maturation and inflammatory cell infiltration via cleavage of cell-cell contact molecules; therefore we hypothesized that meprins could play a role in lung fibrosis. An exhaustive characterization of bleomycin-treated meprinα, meprinβ and the double meprinsαβ knock-out (KO) with respective wt-littermates was performed by using several different methods. We observed no difference in lung function parameters and no change in inflammatory cells infiltrating the lung between wt and all meprins KO mice after 14 days bleomycin. No difference in epithelial integrity as assessed by e-cadherin protein level was detected in bleomycin-treated lungs. However, morphological analysis in the bleomycin-treated mice revealed decrease collagen deposition and tissue density in meprinβ KO, but not in meprinα and meprinαβ KO mice. This finding was accompanied by localization of meprinβ to epithelial cells in regions with immature collagen in mice. Similarly, in human IPF lungs meprinβ was mostly localized in epithelium. These findings suggest that local environment triggers meprinβ expression to support collagen maturation. In conclusion, our data demonstrate the in vivo relevance of meprinβ in collagen deposition in lung fibrosis.
Neuronal apoptosis inhibitory protein (NAIP) localizes to the cytokinetic machinery during cell division
Authors: Abadía-Molina Francisco , Morón-Calvente Virginia , Baird Stephen D. , Shamim Fahad , Martín Francisco , MacKenzie Alex
Published: January 2017

The neuronal apoptosis inhibitory protein (NAIP) is a constituent of the inflammasome and a key component of the innate immune system. Here we use immunofluorescence to position NAIP within the cytokinetic apparatus, contiguous to chromosomal passenger complex (CPC), Centralspindlin, PRC1 and KIF4A. During metaphase, NAIP accumulates in the mitotic spindle poles and is shown in spindle microtubules; in anaphase NAIP is detected in the middle of the central spindle. At the end of cytokinesis, NAIP is localized in the outlying region of the stem body, the center of the intercellular bridge formed between daughter cells prior to cellular abscission. We also describe the sustained presence of NAIP mRNA and protein throughout the cell cycle with a significant increase observed in the G2/M phase. Consistent with a role for NAIP in cytokinesis, NAIP overexpression in HeLa cells promotes the acquisition of a multinuclear phenotype. Conversely, NAIP siRNA gene silencing results in an apoptotic lethal phenotype. Our confocal and super resolution stimulated-emission-depletion (STED) examination of mammalian cell cytokinesis demonstrate a potential new role for NAIP in addition to anti-apoptotic and innate immunology functions.
Dynamics of ferrofluidic flow in the Taylor-Couette system with a small aspect ratio
Authors: Altmeyer Sebastian , Do Younghae , Lai Ying-Cheng
Published: January 2017

We investigate fundamental nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined be-tween two concentric independently rotating cylinders - consider small aspect ratio by solving the ferro-hydrodynamical equations, carrying out systematic bifurcation analysis. Without magnetic field, we find steady flow patterns, previously observed with a simple fluid, such as those containing normal one- or two vortex cells, as well as anomalous one-cell and twin-cell flow states. However, when a symmetry-breaking transverse magnetic field is present, all flow states exhibit stimulated, finite two-fold mode. Various bifurcations between steady and unsteady states can occur, corresponding to the transitions between the two-cell and one-cell states. While unsteady, axially oscillating flow states can arise, we also detect the emergence of new unsteady flow states. In particular, we uncover two new states: one contains only the azimuthally oscillating solution in the configuration of the twin-cell flow state, and an-other a rotating flow state. Topologically, these flow states are a limit cycle and a quasiperiodic solution on a two-torus, respectively. Emergence of new flow states in addition to observed ones with classical fluid, indicates that richer but potentially more controllable dynamics in ferrofluidic flows, as such flow states depend on the external magnetic field.
Online games: a novel approach to explore how partial information influences human random searches
Authors: Martínez-García Ricardo , Calabrese Justin M. , López Cristóbal
Published: January 2017

Many natural processes rely on optimizing the success ratio of a search process. We use an experimental setup consisting of a simple online game in which players have to find a target hidden on a board, to investigate how the rounds are influenced by the detection of cues. We focus on the search duration and the statistics of the trajectories traced on the board. The experimental data are explained by a family of random-walk-based models and probabilistic analytical approximations. If no initial information is given to the players, the search is optimized for cues that cover an intermediate spatial scale. In addition, initial information about the extension of the cues results, in general, in faster searches. Finally, strategies used by informed players turn into non-stationary processes in which the length of e ach displacement evolves to show a well-defined characteristic scale that is not found in non-informed searches.
An exploratory study of predisposing genetic factors for DiGeorge/velocardiofacial syndrome
Authors: Vergés Laia , Vidal Francesca , Geán Esther , Alemany-Schmidt Alexandra , Oliver-Bonet Maria , Blanco Joan
Published: January 2017

DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a disorder caused by a 22q11.2 deletion mediated by non-allelic homologous recombination (NAHR) between low-copy repeats (LCRs). We have evaluated the role of LCR22 genomic architecture and PRDM9 variants as DGS/VCFS predisposing factors. We applied FISH using fosmid probes on chromatin fibers to analyze the number of tandem repeat blocks in LCR22 in two DGS/VCFS fathers-of-origin with proven 22q11.2 NAHR susceptibility. Results revealed copy number variations (CNVs) of L9 and K3 fosmids in these individuals compared to controls. The total number of L9 and K3 copies was also characterized using droplet digital PCR (ddPCR). Although we were unable to confirm variations, we detected an additional L9 amplicon corresponding to a pseudogene. Moreover, none of the eight DGS/VCFS parents-of-origin was heterozygote for the inv(22)(q11.2) haplotype. PRDM9 sequencing showed equivalent allelic distributions between DGS/VCFS parents-of-origin and controls, although a new PRDM9 allele (L50) was identified in one case. Our results support the hypothesis that LCR22s variations influences 22q11.2 NAHR events, however further studies are needed to confirm this association and clarify the contribution of pseudogenes and rare PDRM9 alleles to NAHR susceptibility.
Conserved role of Ovo in germline development in mouse and Drosophila
Authors: Hayashi Makoto , Shinozuka Yuko , Shigenobu Shuji , Sato Masanao , Sugimoto Michihiko , Ito Seiji , Abe Kuniya , Kobayashi Satoru
Published: January 2017

Ovo, which encodes a transcription factor with Zn-finger domains, is evolutionarily conserved among animals. InDrosophila, in addition to its zygotic function for egg production, maternalovoactivity is required in primordial germ cells (PGCs) for expression of germline genes such asvasaandnanos. In this study, we found that maternal Ovo accumulates in PGC nuclei during embryogenesis. In these cells,ovoserves a dual function: activation of genes expressed predominantly in PGCs, and conversely suppression of somatic genes. Reduction ofovoactivity in PGCs makes them unable to develop normally into germ cells of both sexes. In mice, knockout of theovoortholog,Ovol2, which is expressed in PGCs, decreases the number of PGCs during early embryogenesis. These data strongly suggest thatovoacts as part of an evolutionarily conserved mechanism that regulates germline development in animals.
ABCG2-overexpressing H460/MX20 cell xenografts in athymic nude mice maintained original biochemical and cytological characteristics
Authors: Zhang Wei , Chen Zhen , Chen Likun , Wang Fang , Li Furong , Wang Xiaokun , Fu Liwu
Published: January 2017

H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone’s induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro. Importantly, xH460/MX20 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan as H460/MX20 cells did. Furthermore, lapatinib, the inhibitor of ABCG2, potently reversed mitoxantrone- and topotecan-resistance of xH460/MX20 cells. Taken together, these results suggest that H460/MX20 cell xenografts in athymic nude mice still retain their original cytological characteristics and MDR phenotype. Thus, the H460/MX20 cell xenografts model could serve as a sound model in vivo for study on reversal MDR.
A Markov State-based Quantitative Kinetic Model of Sodium Release from the Dopamine Transporter
Authors: Razavi Asghar M. , Khelashvili George , Weinstein Harel
Published: January 2017

The dopamine transporter (DAT) belongs to the neurotransmitter:sodium symporter (NSS) family of membrane proteins that are responsible for reuptake of neurotransmitters from the synaptic cleft to terminate a neuronal signal and enable subsequent neurotransmitter release from the presynaptic neuron. The release of one sodium ion from the crystallographically determined sodium binding site Na2 had been identified as an initial step in the transport cycle which prepares the transporter for substrate translocation by stabilizing an inward-open conformation. We have constructed Markov State Models (MSMs) from extensive molecular dynamics simulations of human DAT (hDAT) to explore the mechanism of this sodium release. Our results quantify the release process triggered by hydration of the Na2 site that occurs concomitantly with a conformational transition from an outward-facing to an inward-facing state of the transporter. The kinetics of the release process are computed from the MSM, and transition path theory is used to identify the most probable sodium release pathways. An intermediate state is discovered on the sodium release pathway, and the results reveal the importance of various modes of interaction of the N-terminus of hDAT in controlling the pathways of release.
Panoramic lens designed with transformation optics
Authors: Wang Huaping , Deng Yangyang , Zheng Bin , Li Rujiang , Jiang Yuyu , Dehdashti Shahram , Xu Zhiwei , Chen Hongsheng
Published: January 2017

The panoramic lens is a special kind of lens, which is applied to observe full view. In this letter, we theoretically present a panoramic lens (PL) using transformation optics method. The lens is designed with inhomogeneous and anisotropic constitutive parameters, which has the ability to gather light from all directions and confine light within the visual angle of observer. Simulation results validate our theoretical design.
Comparison of sputum microbiome of legionellosis-associated patients and other pneumonia patients: indications for polybacterial infections
Authors: Mizrahi Hila , Peretz Avi , Lesnik René , Aizenberg-Gershtein Yana , Rodríguez-Martínez Sara , Sharaby Yehonatan , Pastukh Nina , Brettar Ingrid , Höfle Manfred G. , Halpern Malka
Published: January 2017

Bacteria of the genus Legionella cause water-based infections resulting in severe pneumonia. Here we analyze and compare the bacterial microbiome of sputum samples from pneumonia patients in relation to the presence and abundance of the genus Legionella. The prevalence of Legionella species was determined by culture, PCR, and Next Generation Sequencing (NGS). Nine sputum samples out of the 133 analyzed were PCR-positive using Legionella genus-specific primers. Only one sample was positive by culture. Illumina MiSeq 16S rRNA gene sequencing analyses of Legionella-positive and Legionella-negative sputum samples, confirmed that indeed, Legionella was present in the PCR-positive sputum samples. This approach allowed the identification of the sputum microbiome at the genus level, and for Legionella genus at the species and sub-species level. 42% of the sputum samples were dominated by Streptococcus. Legionella was never the dominating genus and was always accompanied by other respiratory pathogens. Interestingly, sputum samples that were Legionella positive were inhabited by aquatic bacteria that have been observed in an association with amoeba, indicating that amoeba might have transferred Legionella from the drinking water together with its microbiome. This is the first study that demonstrates the sputum major bacterial commensals and pathogens profiles with regard to Legionella presence.
Identification of a novel missense mutation of MIP in a Chinese family with congenital cataracts by target region capture sequencing
Authors: Jiang Bo , chen Yanhua , Xu Baisheng , Hong Nan , Liu Rongrong , Qi Ming , Shen Liping
Published: January 2017

Congenital cataract is both clinically diverse and genetically heterogeneous. To investigate the underlying genetic defect in three-generations of a Chinese family with autosomal dominant congenital cataracts, we recruited family members who underwent comprehensive ophthalmic examinations. A heterozygous missense mutation c.634G > C (p.G212R) substitution was identified in the MIP gene through target region capture sequencing. The prediction results of PolyPhen-2 and SIFT indicated that this mutation was likely to damage the structure and function of MIP. Confocal microscopy images showed that the intensity of the green fluorescent signal revealed much weaker signal from the mutant compared to the wild-type MIP. The expressed G212R-MIP was diminished and almost exclusively cytoplasmic in the HeLa cells; whereas the WT-MIP was stable dispersed throughout the cytoplasm, and it appeared to be in the membrane structure. Western blot analysis indicated that the protein expression level of the mutant form of MIP was remarkably reduced compared with that of the wild type, however, the mRNA levels of the wild-type and mutant cells were comparable. In conclusion, our study presented genetic and functional evidence for a novel MIP mutation of G212R, which leads to congenital progressive cortical punctate with or without Y suture.
Preparation and electrochemical performances of carbon sphere@ZnO core-shell nanocomposites for supercapacitor applications
Authors: Xiao Xuechun , Han Bingqian , Chen Gang , Wang Lihong , Wang Yude
Published: January 2017

Carbon sphere (CS)@ZnO core-shell nanocomposites were successfully prepared through facile low-temperature water-bath method without annealing treatment. The morphology and the microstructure of samples were characterized by transition electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), respectively. ZnO nanoparticles with several nanometers in size decorated on the surface of the carbon sphere and formed a core-shell structure. Electrochemical performances of the CS@ZnO core-shell nanocomposites electrodes were investigated by cyclic voltammetry (CV) and galvanostatic charge/discharge (GDC). The CS@ZnO core-shell nanocomposite electrodes exhibit much larger specific capacitance and cycling stability is improved significantly compared with pure ZnO electrode. The CS@ZnO core-shell nanocomposite with mole ratio of 1:1 achieves a specific capacitance of 630 F g−1 at the current density of 2 A g−1. Present work might provide a new route for fabricating carbon sphere and transition metal oxides composite materials as electrodes for the application in supercapacitors.
Splicing imbalances in basal-like breast cancer underpin perturbation of cell surface and oncogenic pathways and are associated with patients’ survival
Authors: Gracio Filipe , Burford Brian , Gazinska Patrycja , Mera Anca , Mohd Noor Aisyah , Marra Pierfrancesco , Gillett Cheryl , Grigoriadis Anita , Pinder Sarah , Tutt Andrew , de Rinaldis Emanuele
Published: January 2017

Despite advancements in the use of transcriptional information to understand and classify breast cancers, the contribution of splicing to the establishment and progression of these tumours has only recently starting to emerge. Our work explores this lesser known landscape, with special focus on the basal-like breast cancer subtype where limited therapeutic opportunities and no prognostic biomarkers are currently available. Using ExonArray analysis of 176 breast cancers and 9 normal breast tissues we demonstrate that splicing levels significantly contribute to the diversity of breast cancer molecular subtypes and explain much of the differences compared with normal tissues. We identified pathways specifically affected by splicing imbalances whose perturbation would be hidden from a conventional gene-centric analysis of gene expression. We found that a large fraction of them involve cell-to-cell communication, extracellular matrix and transport, as well as oncogenic and immune-related pathways transduced by plasma membrane receptors. We identified 247 genes in which splicing imbalances are associated with clinical patients’ outcome, whilst no association was detectable at the gene expression level. These include the signaling gene TGFBR1, the proto-oncogene MYB as well as many immune-related genes such as CCR7 and FCRL3, reinforcing evidence for a role of immune components in influencing breast cancer patients’ prognosis.
Enhanced thermoelectric performance of a chalcopyrite compound CuIn3Se5−xTex (x = 0~0.5) through crystal structure engineering
Authors: Lu Yufu , Chen Shaoping , Wu Wenchang , Du Zhengliang , Chao Yimin , Cui Jiaolin
Published: January 2017

In this work the chalcopyrite CuIn3Se5−xTex (x = 0~0.5) with space group "Equation missing" through isoelectronic substitution of Te for Se have been prepared, and the crystal structure dilation has been observed with increasing Te content. This substitution allows the anion position displacement ∆u = 0.25-u to be zero at x ≈ 0.15. However, the material at x = 0.1 (∆u = 0.15 × 10−3), which is the critical Te content, presents the best thermoelectric (TE) performance with dimensionless figure of merit ZT = 0.4 at 930 K. As x value increases from 0.1, the quality factor B, which informs about how large a ZT can be expected for any given material, decreases, and the TE performance degrades gradually due to the reduction in nH and enhancement in κL. Combining with the ZTs from several chalcopyrite compounds, it is believable that the best thermoelectric performance can be achieved at a certain ∆u value (∆u ≠ 0) for a specific space group if their crystal structures can be engineered.