bluuebunny/crossref_metadata_2025 huggingface dataset:
Collisional unfolding of multiprotein complexes reveals cooperative stabilization upon ligand binding
Authors: Niu Shuai , Ruotolo Brandon T.
Published: May 2015

Cooperative binding mechanisms are a common feature in biology, enabling a diverse range of protein‐based molecular machines to regulate activities ranging from oxygen uptake to cellular membrane transport. Much, however, is not known about such cooperative binding mechanisms, including how such events typically add to the overall stability of such protein systems. Measurements of such cooperative stabilization events are challenging, as they require the separation and resolution of individual protein complex bound states within a mixture of potential stoichiometries to individually assess protein stabilities. Here, we report ion mobility‐mass spectrometry results for the concanavalin A tetramer bound to a range of polysaccharide ligands. We use collision induced unfolding, a relatively new methodology that functions as a gas‐phase analog of calorimetry experiments in solution, to individually assess the stabilities of concanavalin A bound states. By comparing the differences in activation voltage required to unfold different concanavalin A–ligand stoichiometries, we find evidence suggesting a cooperative stabilization of concanavalin A occurs upon binding most carbohydrate ligands. We critically evaluate this observation by assessing a broad range of ligands, evaluating the unfolding properties of multiple protein charge states, and by comparing our gas‐phase results with those obtained from calorimetry experiments carried out in solution.
Polyglycine hydrolases: Fungal β‐lactamase‐like endoproteases that cleave polyglycine regions within plant class IV chitinases
Authors: Naumann Todd A. , Naldrett Michael J. , Ward Todd J. , Price Neil P. J.
Published: May 2015

Polyglycine hydrolases are secreted fungal proteases that cleave glycine–glycine peptide bonds in the inter‐domain linker region of specific plant defense chitinases. Previously, we reported the catalytic activity of polyglycine hydrolases from the phytopathogens Epicoccum sorghi (Es‐cmp) and Cochliobolus carbonum (Bz‐cmp). Here we report the identity of their encoding genes and the primary amino acid sequences of the proteins responsible for these activities. Peptides from a tryptic digest of Es‐cmp were analyzed by LC‐MS/MS and the spectra obtained were matched to a draft genome sequence of E. sorghi. From this analysis, a 642 amino acid protein containing a predicted β‐lactamase catalytic region of 280 amino acids was identified. Heterologous strains of the yeast Pichia pastoris were created to express this protein and its homolog from C. carbonum from their cDNAs. Both strains produced recombinant proteins with polyglycine hydrolase activity as shown by SDS‐PAGE and MALDI‐MS based assays. Site directed mutagenesis was used to mutate the predicted catalytic serine of Es‐cmp to glycine, resulting in loss of catalytic activity. BLAST searching of publicly available fungal genomes identified full‐length homologous proteins in 11 other fungi of the class Dothideomycetes, and in three fungi of the related class Sordariomycetes while significant BLAST hits extended into the phylum Basidiomycota. Multiple sequence alignment led to the identification of a network of seven conserved tryptophans that surround the β‐lactamase‐like region. This is the first report of a predicted β‐lactamase that is an endoprotease.
Photoluminescence of SiV centers in single crystal CVD diamond in situ doped with Si from silane
Authors: Bolshakov Andrey , Ralchenko Victor , Sedov Vadim , Khomich Andrey , Vlasov Igor , Khomich Alexander , Trofimov Nikolay , Krivobok Vladimir , Nikolaev Sergei , Khmelnitskii Roman , Saraykin Vladimir
Published: May 2015

Homoepitaxial single crystal diamond layers with bright photoluminescence (PL) of silicon‐vacancy (SiV) color centers at 738 nm wavelength have been grown on (100) diamond substrates by a microwave plasma CVD using a controlled Si doping via adding silane to CH4H2 reaction gas mixture in the course of the deposition process. In the range of the silane concentrations SiH4/CH4 explored, from 0 to 2.4%, the SiV PL intensity shows a nonmonotonic behavior with silane addition, with a maximum at 0.6%SiH4/CH4, and a rapid PL quenching at higher Si doping. The maximum SiV concentration of ≈450 ppb in the samples has been determined from optical absorption spectra. It is found that the SiV PL intensity can strongly, an order of magnitude, increase within non‐epitaxial inclusions in single crystal diamond film.
Effect of O2 flow rate on the thermochromic performance of VO2 coatings grown by atmospheric pressure CVD
Authors: Louloudakis Dimitris , Vernardou Dimitra , Spanakis Emmanouel , Dokianakis Spyros , Panagopoulou Marianthi , Raptis Giannis , Aperathitis Elias , Kiriakidis George , Katsarakis Nikolaos , Koudoumas Emmanouel
Published: May 2015

This paper reports the atmospheric pressure chemical vapor deposition of vanadium oxide coatings using vanadyl (IV) acetylacetonate at 500 oC. The as‐grown samples for 0.8 L min‐1 O2 flow rate showed an (022)‐oriented single vanadium dioxide monoclinic phase of low crystallinity. The narrowest hysteresis width is observed for the particular flow rate indicating a dependency on the shape of the grown crystallites. Regarding the difference in transmittance is determined by the enhanced presence of short‐ and long‐range bond ordering of the samples. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Diamond crystals deposited from interacting jets
Authors: Rebrov Aleksey , Emelyanov Aleksey , Kosolobov Sergey , Yudin Ivan
Published: May 2015

This paper describes the advancement of hot wire or hot filament CVD methods of diamond synthesis through the use high velocity gas flow activation by multiple collisions with a lengthy hot surface instead of activation by single collisions with hot wires. The possibility of synthesis of diamond crystals from a neutral gas with a high growth rate and a future solution of engineering scaling problems promise that this method will become competitive with others. Interacting jets of hydrogen and mixture of hydrogen with methane were used to synthesize diamond crystals on a molybdenum substrate. The growth rate of crystals about 20 μm/h was attained, which is much higher than in the case of a hot filament CVD. The increase of CH4 concentration essentially increases the diamond crystal growth rate. Depending on local conditions of the interaction of jets with substrates in different points, a completely different morphology of deposit is observed: from a compact film to isolated coarse crystals mostly icosahedral form. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Convergence analysis using the edge Laplacian: Robust consensus of nonlinear multi‐agent systems via ISS method
Authors: Zeng Zhiwen , Wang Xiangke , Zheng Zhiqiang
Published: May 2015

This study develops an original and innovative matrix representation with respect to the information flow for networked multi‐agent system. To begin with, the general concepts of the edge Laplacian of digraph are proposed with its algebraic properties. Benefit from this novel graph‐theoretic tool, we can build a bridge between the consensus problem and the edge agreement problem, we also show that the edge Laplacian sheds a new light on solving the leaderless consensus problem. Based on the edge agreement framework, the technical challenges caused by unknown but bounded disturbances and inherently nonlinear dynamics can be well handled. In particular, we design an integrated procedure for a new robust consensus protocol that is based on a blend of algebraic graph theory and the newly developed cyclic‐small‐gain theorem. Besides, to highlight the intricate relationship between the original graph and cyclic‐small‐gain theorem, the concept of edge‐interconnection graph is introduced for the first time. Finally, simulation results are provided to verify the theoretical analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Local dynamic range compensation for scanning electron microscope imaging system
Authors: Sim K.S. , Huang Y.H.
Published: May 2015

This is the extended project by introducing the modified dynamic range histogram modification (MDRHM) and is presented in this paper. This technique is used to enhance the scanning electron microscope (SEM) imaging system. By comparing with the conventional histogram modification compensators, this technique utilizes histogram profiling by extending the dynamic range of each tile of an image to the limit of 0–255 range while retains its histogram shape. The proposed technique yields better image compensation compared to conventional methods. SCANNING 37:381–388, 2015. © 2015 Wiley Periodicals, Inc.
Analyzing multiple cross‐sectional samples with application to hospitalization time after surgeries
Authors: Mandel Micha
Published: May 2015

Repeated cross‐sectional sampling results in multiple biased samples with possibly different weight functions. The standard non‐parametric maximum likelihood estimator for the lifetime distribution of interest solves a set of nonlinear equations, and its variance has a very complicated form. We suggest a simple closed‐form estimator for the case where entrances to the population of interest follow a Poisson model. The variance of the estimator and confidence intervals are easily calculated. Our motivating example concerns a series of cross‐sectional surveys conducted in Israeli hospitals. We discuss the bias mechanism in our data and suggest a simple design plan that provides valid estimators even when the weight functions are unknown. The new method is applied to estimate the distribution of hospitalization time after bowel and hernia surgeries. Copyright © 2015 John Wiley & Sons, Ltd.
Design and analysis of a wireless monitoring network for transmission lines in smart grid
Authors: Ye Feng , Liang Yun , Zhang Hao , Zhang Xuping , Qian Yi
Published: May 2015

In order to timely and precisely locate a problem over the power lines, the control center needs to monitor the status of the transmissionlines and the towers. In this paper, we design such a monitoring network by taking advantage of the existing optical fiber composite overhead ground wire (OPGW) alongside the transmission lines. Because it is not cost‐effective to have gateway access to the OPGW for every transmission tower, we propose to deploy a multi‐hop wireless sensor network in between two sparsely deployed neighboring OPGW gateways. We mainly study the power allocation for the data transmission of the wireless sensors because of the assumption that such sensors are powered by green energy and a battery with limited capacity for easy deployment and maintenance. Specifically, we propose several centralized schemes with different objectives, for example, the minimum power usage and fast computation. We also propose a distributed scheme so that the sensors can be even more energy efficient dealing with dynamic traffic in field operations. Moreover, we analyze the centralized schemes to study their pros and cons. We also conduct a case study for the distributed scheme to demonstrate its feasibility in field operations. Copyright © 2015 John Wiley & Sons, Ltd.
Mutation of the iron‐sulfur cluster assembly gene IBA57 causes fatal infantile leukodystrophy
Authors: Debray François‐Guillaume , Stümpfig Claudia , Vanlander Arnaud V. , Dideberg Vinciane , Josse Claire , Caberg Jean‐Hubert , Boemer François , Bours Vincent , Stevens René , Seneca Sara , Smet Joél , Lill Roland , van Coster Rudy
Published: May 2015

Leukodystrophies are a heterogeneous group of severe genetic neurodegenerative disorders. A multiple mitochondrial dysfunctions syndrome was found in an infant presenting with a progressive leukoencephalopathy. Homozygosity mapping, whole exome sequencing, and functional studies were used to define the underlying molecular defect. Respiratory chain studies in skeletal muscle isolated from the proband revealed a combined deficiency of complexes I and II. In addition, western blotting indicated lack of protein lipoylation. The combination of these findings was suggestive for a defect in the iron‐sulfur (Fe/S) protein assembly pathway. SNP array identified loss of heterozygosity in large chromosomal regions, covering the NFU1 and BOLA3, and the IBA57 and ABCB10 candidate genes, in 2p15‐p11.2 and 1q31.1‐q42.13, respectively. A homozygous c.436C > T (p.Arg146Trp) variant was detected in IBA57 using whole exome sequencing. Complementation studies in a HeLa cell line depleted for IBA57 showed that the mutant protein with the semi‐conservative amino acid exchange was unable to restore the biochemical phenotype indicating a loss‐of‐function mutation of IBA57. In conclusion, defects in the Fe/S protein assembly gene IBA57 can cause autosomal recessive neurodegeneration associated with progressive leukodystrophy and fatal outcome at young age. In the affected patient, the biochemical phenotype was characterized by a defect in the respiratory chain complexes I and II and a decrease in mitochondrial protein lipoylation, both resulting from impaired assembly of Fe/S clusters.
The Prospective Role of Cognitive Appraisals and Social Support in Predicting Children’s Posttraumatic Stress
Authors: Hitchcock Caitlin , Ellis Alicia A. , Williamson Paul , Nixon Reginald D. V.
Published: May 2015

Although both social support and cognitive appraisals are strong predictors of children’s posttraumatic adjustment, understanding of the interplay between these factors is limited. We assessed whether cognitive appraisals mediated the relationship between social support and symptom development, as predicted by cognitive models of posttraumatic stress disorder (PTSD). Ninety seven children (Mean age = 12.08 years) were assessed at one month and six months following a single incident trauma. We administered self-report measures of cognitive appraisals, social support, and a diagnostic interview for PTSD. Results indicated that cognitive appraisals at one month post-trauma mediated the relationship between social support at one month post-trauma, and PTSD severity at follow-up. Differences in this relationship were observed between child-reported social support and parent-rated ability to provide support. Firm evidence was provided for the application of cognitive models of PTSD to children.
Fish Oil and Olive Oil Supplementation in Late Pregnancy and Lactation Differentially Affect Oxidative Stress and Inflammation in Sows and Piglets
Authors: Shen Yong , Wan Haifeng , Zhu Jiatao , Fang Zhengfeng , Che Lianqiang , Xu Shengyu , Lin Yan , Li Jian , Wu De
Published: May 2015

This study was conducted to compare the effects of fish oil and olive oil supplementation in late pregnancy and during lactation on oxidative stress and inflammation in sows and their piglets. A total of 24 sows were fed a basal diet supplemented with additional corn starch (CON), fish oil (FO) or olive oil (OO). Sows fed an OO diet during late gestation had a higher piglet birth weight compared with CON‐fed and FO‐fed sows (P < 0.05). Furthermore, sows from the OO group had a higher milk fat content than sows from CON and FO groups, and a lower pre‐weaning mortality of piglets was observed in the OO group (P < 0.05). Maternal FO supplementation resulted in increased malondialdehyde concentration in sow plasma, colostrum, milk and piglet plasma than in CON and OO groups (P < 0.05). However, an increased total antioxidant capacity (T‐ACC) and activities of glutathione peroxidase (GSH‐Px) and total superoxide dismutase (T‐SOD) were also observed in the FO group (P < 0.05). Sows fed an OO diet had significantly decreased interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) concentrations in milk compared with CON and FO fed sows (P < 0.05). Moreover, lower plasma IL‐1β and TNF‐α levels were observed in piglets from the OO group compared with the CON group (P < 0.05). Collectively, these results suggest that an OO diet is most beneficial in late gestation and during lactation in sows. However, FO increases the susceptibility to oxidative stress in sows and piglets.
Neuronal responses to stress and injury in C. elegans
Authors: Kim Kyung Won , Jin Yishi
Published: May 2015

The nervous system plays critical roles in the stress response. Animals can survive and function under harsh conditions, and resist and recover from injuries because neurons perceive and respond to various stressors through specific regulatory mechanisms. Caenorhabditis elegans has served as an excellent model to discover fundamental mechanisms underlying the neuronal response to stress. The basic physiological processes that C. elegans exhibits under stress conditions are similar to those observed in higher organisms. Many molecular pathways activated by environmental and cellular stresses are also conserved. In this review, we summarize major findings in examining neuronal responses to hypoxia, oxidative stress, osmotic stress, and traumatic injury. These studies from C. elegans have provided novel insights into our understanding of neuronal responses to stress at the molecular, cellular, and circuit levels.
Viral vector delivery of neurotrophic factors for Parkinson's disease therapy
Authors: Kelly Martin J. , O'Keeffe Gerard W. , Sullivan Aideen M.
Published: May 2015

Parkinson's disease (PD) is a neurodegenerative disorder characterised by the progressive loss of midbrain dopaminergic neurons, which causes motor impairments. Current treatments involve dopamine replacement to address the disease symptoms rather than its cause. Factors that promote the survival of dopaminergic neurons have been proposed as novel therapies for PD. Several dopaminergic neurotrophic factors (NTFs) have been examined for their ability to protect and/or restore degenerating dopaminergic neurons, both in animal models and in clinical trials. These include glial cell line-derived neurotrophic factor, neurturin, cerebral dopamine neurotrophic factor and growth/differentiation factor 5. Delivery of these NTFs via injection or infusion to the brain raises several practical problems. A new delivery approach for NTFs involves the use of recombinant viral vectors to enable long-term expression of these factors in brain cells. Vectors used include those based on adenoviruses, adeno-associated viruses and lentiviruses. Here we review progress to date on the potential of each of these four NTFs as novel therapeutic strategies for PD, as well as the challenges that have arisen, from pre-clinical analysis to clinical trials. We conclude by discussing recently-developed approaches to optimise the delivery of NTF-carrying viral vectors to the brain.
Mean curvature flow by the Allen–Cahn equation
Authors: LEE D. S. , KIM J. S.
Published: May 2015

In this paper, we investigate motion by mean curvature using the Allen–Cahn (AC) equation in two and three space dimensions. We use an unconditionally stable hybrid numerical scheme to solve the equation. Numerical experiments demonstrate that we can use the AC equation for applications to motion by mean curvature. We also study the curve-shortening flow with a prescribed contact angle condition.
Erythropoietin Dampens Injury-Induced Microglial Motility
Authors: Mitkovski Miso , Dahm Liane , Heinrich Ralf , Monnheimer Mathieu , Gerhart Simone , Stegmüller Judith , Hanisch Uwe-Karsten , Nave Klaus-Armin , Ehrenreich Hannelore
Published: May 2015

Traumatic brain injury causes progressive brain atrophy and cognitive decline. Surprisingly, an early treatment with erythropoietin (EPO) prevents these consequences of secondary neurodegeneration, but the mechanisms have remained obscure. Here we show by advanced imaging and innovative analytical tools that recombinant human EPO, a clinically established and neuroprotective growth factor, dampens microglial activity, as visualized also in vivo by a strongly attenuated injury-induced cellular motility.
Arginase I Release from Activated Neutrophils Induces Peripheral Immunosuppression in a Murine Model of Stroke
Authors: Sippel Trisha R , Shimizu Takeru , Strnad Frank , Traystman Richard J , Herson Paco S , Waziri Allen
Published: May 2015

Transient suppression of peripheral immunity is a major source of complication for patients suffering from ischemic stroke. The release of Arginase I (ArgI) from activated neutrophils has recently been associated with T-cell dysfunction in a number of pathologies. However, this pathway has not been previously explored in ischemic stroke. Using the murine model of transient middle cerebral artery occlusion, we explored effects of stroke on peripheral T-cell function and evaluated the role of neutrophils and ArgI. Stimulation of splenic T cells from post-stroke animals with anti-CD3/CD28 resulted in decreased proliferation and interferon-γ production when compared with sham-surgery controls. Flow cytometric analysis of intrasplenic leukocytes exposed the presence of a transient population of activated neutrophils that correlated quantitatively with elevated ArgI levels in culture media. In vitro activation of purified resting neutrophils from unmanipulated controls confirmed the capacity for murine neutrophils to release ArgI from preformed granules. We observed decreased expression of the L-arg-sensitive CD3ζ on T cells, consistent with decreased functional activity. Critically, L-arg supplementation restored the functional response of post-stroke T cells to mitogenic stimulation. Together, these data outline a novel mechanism of reversible, neutrophil-mediated peripheral immunosuppression related to ArgI release following ischemic stroke.
High daytime and nighttime ambulatory pulse pressure predict poor cognitive function and mild cognitive impairment in hypertensive individuals
Authors: Riba-Llena Iolanda , Nafría Cristina , Filomena Josefina , Tovar José L , Vinyoles Ernest , Mundet Xavier , Jarca Carmen I , Vilar-Bergua Andrea , Montaner Joan , Delgado Pilar
Published: May 2015

High blood pressure accelerates normal aging stiffness process. Arterial stiffness (AS) has been previously associated with impaired cognitive function and dementia. Our aims are to study how cognitive function and status (mild cognitive impairment, MCI and normal cognitive aging, NCA) relate to AS in a community-based population of hypertensive participants assessed with office and 24-hour ambulatory blood pressure measurements. Six hundred ninety-nine participants were studied, 71 had MCI and the rest had NCA. Office pulse pressure (PP), carotid–femoral pulse wave velocity, and 24-hour ambulatory PP monitoring were collected. Also, participants underwent a brain magnetic resonance to study cerebral small–vessel disease (cSVD) lesions. Multivariate analysis–related cognitive function and cognitive status to AS measurements after adjusting for demographic, vascular risk factors, and cSVD. Carotid–femoral pulse wave velocity and PP at different periods were inversely correlated with several cognitive domains, but only awake PP measurements were associated with attention after correcting for confounders (beta = −0.22, 95% confidence interval (CI) −0.41, −0.03). All ambulatory PP measurements were related to MCI, which was independently associated with nocturnal PP (odds ratio (OR) = 2.552, 95% CI 1.137, 5.728) and also related to the presence of deep white matter hyperintensities (OR = 1.903, 1.096, 3.306). Therefore, higher day and night ambulatory PP measurements are associated with poor cognitive outcomes.
Beta1-Adrenergic Receptor-Mediated Dilation of Rat Cerebral Artery Requires Shaker-Type KV1 Channels on PSD95 Scaffold
Authors: Moore Christopher L , McClenahan Samantha J , Hanvey Hillary M , Jang Dae-Song , Nelson Piper L , Joseph Biny K , Rhee Sung W
Published: May 2015

Postsynaptic density-95 (PSD95) is a scaffolding protein in cerebral vascular smooth muscle cells (cVSMCs), which binds to Shaker-type K+ (KV1) channels and facilitates channel opening through phosphorylation by protein kinase A. β1-Adrenergic receptors (β1ARs) also have a binding motif for PSD95. Functional association of β1AR with KV1 channels through PSD95 may represent a novel vasodilator complex in cerebral arteries (CA). We explored whether a β1AR-PSD95-KV1 complex is a determinant of rat CA dilation. RT-PCR and western blots revealed expression of β1AR in CA. Isoproterenol induced a concentration-dependent dilation of isolated, pressurized rat CA that was blocked by the β1AR blocker CGP20712. Cranial window imaging of middle cerebral arterioles in situ showed isoproterenol- and norepinephrine-induced dilation that was blunted by β1AR blockade. Isoproterenol-induced hyperpolarization of cVSMCs in pressurized CA was blocked by CGP20712. Confocal images of cVSMCs immunostained with antibodies against β1AR and PSD95 indicated strong colocalization, and PSD95 co-immunoprecipitated with β1AR in CA lysate. Blockade of KV1 channels, β1AR or disruption of PSD95-KV1 interaction produced similar blunting of isoproterenol-induced dilation in pressurized CA. These findings suggest that PSD95 mediates a vasodilator complex with β1AR and KV1 channels in cVSMCs. This complex may be critical for proper vasodilation in rat CA.
Reduced Blood Flow in Normal White Matter Predicts Development of Leukoaraiosis
Authors: Bernbaum Manya , Menon Bijoy K , Fick Gordon , Smith Eric E , Goyal Mayank , Frayne Richard , Coutts Shelagh B
Published: May 2015

The purpose of this study was to investigate whether low cerebral blood flow (CBF) is associated with subsequent development of white matter hyperintensities (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging study of minor stroke/transient ischemic attack patients. Images were co-registered and new WMH at 18 months were identified by comparing follow-up imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of-interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up imaging, and (3) regions of normal-appearing white matter at both time points. Registered CBF maps at baseline were used to measure CBF in the ROIs. A multivariable model was developed using mixed-effects logistic regression to determine the effect of baseline CBF on the development on new WMH. Forty patients were included. Mean age was 61 ± 11 years, 30% were female. Low baseline CBF, female sex, and presence of diabetes were independently associated with the presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up imaging reduces by 0.61 (95% confidence interval = 0.57 to 0.65) for each 1 mL/100 g per minute increase in baseline CBF. We conclude that regions of white matter with low CBF develop new WMH on follow-up imaging.
Is Forebrain Neurogenesis a Potential Repair Mechanism after Stroke?
Authors: Inta agos , Gass Peter
Published: May 2015

The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ generates predominantly calretinin (CR)-expressing GABAergic interneurons, which cannot replace the broad spectrum of neuronal subtypes damaged by stroke. Therefore, SVZ neurogenesis may represent a repair mechanism only after genetic manipulation redirecting its differentiation.
Autophagosome–lysosome fusion is independent of V-ATPase-mediated acidification
Authors: Mauvezin Caroline , Nagy Péter , Juhász Gábor , Neufeld Thomas P.
Published: May 2015

The ATP-dependent proton pump V-ATPase ensures low intralysosomal pH, which is essential for lysosomal hydrolase activity. Based on studies with the V-ATPase inhibitor BafilomycinA1, lysosomal acidification is also thought to be required for fusion with incoming vesicles from the autophagic and endocytic pathways. Here we show that loss of V-ATPase subunits in the Drosophila fat body causes an accumulation of non-functional lysosomes, leading to a block in autophagic flux. However, V-ATPase-deficient lysosomes remain competent to fuse with autophagosomes and endosomes, resulting in a time-dependent formation of giant autolysosomes. In contrast, BafilomycinA1 prevents autophagosome–lysosome fusion in these cells, and this defect is phenocopied by depletion of the Ca2+ pump SERCA, a secondary target of this drug. Moreover, activation of SERCA promotes fusion in a BafilomycinA1-sensitive manner. Collectively, our results indicate that lysosomal acidification is not a prerequisite for fusion, and that BafilomycinA1 inhibits fusion independent of its effect on lysosomal pH.
Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters
Authors: Lai Charles P. , Kim Edward Y. , Badr Christian E. , Weissleder Ralph , Mempel Thorsten R. , Tannous Bakhos A. , Breakefield Xandra O.
Published: May 2015

Accurate spatiotemporal assessment of extracellular vesicle (EV) delivery and cargo RNA translation requires specific and robust live-cell imaging technologies. Here we engineer optical reporters to label multiple EV populations for visualization and tracking of tumour EV release, uptake and exchange between cell populations both in culture and in vivo. Enhanced green fluorescence protein (EGFP) and tandem dimer Tomato (tdTomato) were fused at NH2-termini with a palmitoylation signal (PalmGFP, PalmtdTomato) for EV membrane labelling. To monitor EV-RNA cargo, transcripts encoding PalmtdTomato were tagged with MS2 RNA binding sequences and detected by co-expression of bacteriophage MS2 coat protein fused with EGFP. By multiplexing fluorescent and bioluminescent EV membrane reporters, we reveal the rapid dynamics of both EV uptake and translation of EV-delivered cargo mRNAs in cancer cells that occurred within 1-hour post-horizontal transfer between cells. These studies confirm that EV-mediated communication is dynamic and multidirectional between cells with delivery of functional mRNA.
Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency
Authors: Chen Hongwei , Aksoy Irène , Gonnot Fabrice , Osteil Pierre , Aubry Maxime , Hamela Claire , Rognard Cloé , Hochard Arnaud , Voisin Sophie , Fontaine Emeline , Mure Magali , Afanassieff Marielle , Cleroux Elouan , Guibert Sylvain , Chen Jiaxuan , Vallot Céline , Acloque Hervé , Genthon Clémence , Donnadieu Cécile , De Vos John , Sanlaville Damien , Guérin Jean- François , Weber Michael , Stanton Lawrence W , Rougeulle Claire , Pain Bertrand , Bourillot Pierre-Yves , Savatier Pierre
Published: May 2015

Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state characterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. Together, these results show that temporarily increasing STAT3 activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.
Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain
Authors: Eldholm Vegard , Monteserin Johana , Rieux Adrien , Lopez Beatriz , Sobkowiak Benjamin , Ritacco Viviana , Balloux Francois
Published: May 2015

The rise of drug-resistant strains is a major challenge to containing the tuberculosis (TB) pandemic. Yet, little is known about the extent of resistance in early years of chemotherapy and when transmission of resistant strains on a larger scale became a major public health issue. Here we reconstruct the timeline of the acquisition of antimicrobial resistance during a major ongoing outbreak of multidrug-resistant TB in Argentina. We estimate that the progenitor of the outbreak strain acquired resistance to isoniazid, streptomycin and rifampicin by around 1973, indicating continuous circulation of a multidrug-resistant TB strain for four decades. By around 1979 the strain had acquired additional resistance to three more drugs. Our results indicate that Mycobacterium tuberculosis (Mtb) with extensive resistance profiles circulated 15 years before the outbreak was detected, and about one decade before the earliest documented transmission of Mtb strains with such extensive resistance profiles globally.
Contrasting host–pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes
Authors: Desjardins Christopher A. , Sanscrainte Neil D. , Goldberg Jonathan M. , Heiman David , Young Sarah , Zeng Qiandong , Madhani Hiten D. , Becnel James J. , Cuomo Christina A
Published: May 2015

Obligate intracellular pathogens depend on their host for growth yet must also evade detection by host defenses. Here we investigate host adaptation in two Microsporidia, the specialist Edhazardia aedis and the generalist Vavraia culicis, pathogens of disease vector mosquitoes. Genomic analysis and deep RNA-Seq across infection time courses reveal fundamental differences between these pathogens. E. aedis retains enhanced cell surface modification and signalling capacity, upregulating protein trafficking and secretion dynamically during infection. V. culicis is less dependent on its host for basic metabolites and retains a subset of spliceosomal components, with a transcriptome broadly focused on growth and replication. Transcriptional profiling of mosquito immune responses reveals that response to infection by E. aedis differs dramatically depending on the mode of infection, and that antimicrobial defensins may play a general role in mosquito defense against Microsporidia. This analysis illuminates fundamentally different evolutionary paths and host interplay of specialist and generalist pathogens.
Regulation of burstiness by network-driven activation
Authors: García-Pérez Guillermo , Boguñá Marián , Serrano M. Ángeles
Published: May 2015

We prove that complex networks of interactions have the capacity to regulate and buffer unpredictable fluctuations in production events. We show that non-bursty network-driven activation dynamics can effectively regulate the level of burstiness in the production of nodes, which can be enhanced or reduced. Burstiness can be induced even when the endogenous inter-event time distribution of nodes' production is non-bursty. We find that hubs tend to be less susceptible to the networked regulatory effects than low degree nodes. Our results have important implications for the analysis and engineering of bursty activity in a range of systems, from communication networks to transcription and translation of genes into proteins in cells.
Local electrical control of magnetic order and orientation by ferroelastic domain arrangements just above room temperature
Authors: Phillips L. C. , Cherifi R. O. , Ivanovskaya V. , Zobelli A. , Infante I. C. , Jacquet E. , Guiblin N. , Ünal A. A. , Kronast F. , Dkhil B. , Barthélémy A. , Bibes M. , Valencia S.
Published: May 2015

Ferroic materials (ferromagnetic, ferroelectric, ferroelastic) usually divide into domains with different orientations of their order parameter. Coupling between different ferroic systems creates new functionalities, for instance the electrical control of macroscopic magnetic properties including magnetization and coercive field. Here we show that ferroelastic domains can be used to control both magnetic order and magnetization direction at the nanoscale with a voltage. We use element-specific X-ray imaging to map the magnetic domains as a function of temperature and voltage in epitaxial FeRh on ferroelastic BaTiO3. Exploiting the nanoscale phase-separation of FeRh, we locally interconvert between ferromagnetic and antiferromagnetic states with a small electric field just above room temperature. Imaging and ab initio calculations show the antiferromagnetic phase of FeRh is favoured by compressive strain on c-oriented BaTiO3 domains and the resultant magnetoelectric coupling is larger and more reversible than previously reported from macroscopic measurements. Our results emphasize the importance of nanoscale ferroic domain structure and the promise of first-order transition materials to achieve enhanced coupling in artificial multiferroics.
Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis
Authors: Udhane Sameer S. , Pandey Amit V. , Hofer Gaby , Mullis Primus E. , Flück Christa E.
Published: May 2015

Androgens are essential for sexual development and reproduction. However, androgen regulation in health and disease is poorly understood. We showed that human adrenocortical H295R cells grown under starvation conditions acquire a hyperandrogenic steroid profile with changes in steroid metabolizing enzymes HSD3B2 and CYP17A1 essential for androgen production. Here we studied the regulatory mechanisms underlying androgen production in starved H295R cells. Microarray expression profiling of normal versus starved H295R cells revealed fourteen differentially expressed genes; HSD3B2, HSD3B1, CYP21A2, RARB, ASS1, CFI, ASCL1 and ENC1 play a role in steroid and energy metabolism and ANGPTL1, PLK2, DUSP6, DUSP10 and FREM2 are involved in signal transduction. We discovered two new gene networks around RARB and ANGPTL1 and show how they regulate androgen biosynthesis. Transcription factor RARB stimulated the promoters of genes involved in androgen production (StAR, CYP17A1 and HSD3B2) and enhanced androstenedione production. For HSD3B2 regulation RARB worked in cooperation with Nur77. Secretory protein ANGPTL1 modulated CYP17A1 and DUSP6 expression by inducing ERK1/2 phosphorylation. By contrast, our studies revealed no evidence for hormones or cell cycle involvement in regulating androgen biosynthesis. In summary, these studies establish a firm role for RARB and ANGPTL1 in the regulation of androgen production in H295R cells.
Conductivity-limiting bipolar thermal conductivity in semiconductors
Authors: Wang Shanyu , Yang Jiong , Toll Trevor , Yang Jihui , Zhang Wenqing , Tang Xinfeng
Published: May 2015

Intriguing experimental results raised the question about the fundamental mechanisms governing the electron-hole coupling induced bipolar thermal conduction in semiconductors. Our combined theoretical analysis and experimental measurements show that in semiconductors bipolar thermal transport is in general a “conductivity-limiting” phenomenon and it is thus controlled by the carrier mobility ratio and by the minority carrier partial electrical conductivity for the intrinsic and extrinsic cases, respectively. Our numerical method quantifies the role of electronic band structure and carrier scattering mechanisms. We have successfully demonstrated bipolar thermal conductivity reduction in doped semiconductors via electronic band structure modulation and/or preferential minority carrier scatterings. We expect this study to be beneficial to the current interests in optimizing thermoelectric properties of narrow gap semiconductors.
Effect of targeted estrogen delivery using glucagon-like peptide-1 on insulin secretion, insulin sensitivity and glucose homeostasis
Authors: Tiano Joseph P. , Tate Chandra R. , Yang Bin S. , DiMarchi Richard , Mauvais-Jarvis Franck
Published: May 2015

The female estrogen 17β-estradiol (E2) enhances pancreatic β-cell function via estrogen receptors (ERs). However, the risk of hormone dependent cancer precludes the use of general estrogen therapy as a chronic treatment for diabetes. To target E2 to β-cells without the undesirable effects of general estrogen therapy, we created fusion peptides combining active or inactive glucagon-like peptide-1 (GLP-1) and E2 in a single molecule (aGLP1-E2 and iGLP1-E2 respectively). By combining the activities of GLP-1 and E2, we envisioned synergistic insulinotropic activities of these molecules on β-cells. In cultured human islets and in C57BL/6 mice, both aGLP1 and aGLP1-E2 enhanced glucose-stimulated insulin secretion (GSIS) compared to vehicle and iGLP1-E2 without superior efficacy of aGLP1-E2 compared to GLP-1 alone. However, aGLP1-E2 decreased fasting and fed blood glucose to a greater extent than aGLP1 and iGLP1-E2 alone. Further, aGLP1-E2 exhibited improved insulin sensitivity compared to aGLP1 and iGLP1-E2 alone (HOMA-IR and insulin tolerance test). In conclusion, targeted estrogen delivery to non-diabetic islets in the presence of GLP-1 does not enhance GSIS. However, combining GLP-1 to estrogen delivers additional efficacy relative to GLP-1 alone on insulin sensitivity and glucose homeostasis in non-diabetic mice.
Improving the activity of Lycium barbarum polysaccharide on sub-health mice
Authors: Zhao Rui , Cai Yaping , Shao Xingyue , Ma Baoling
Published: May 2015

Anti-fatigue activity of Lycium barbarum polysaccharide on sub-health mice: LBP-4a exhibited anti-fatigue activity on sub-health mice, and the mechanism was closely correlated with the reduction of lipid peroxidation levels and an increase of antioxidant enzyme activities in skeletal muscle tissue, in addition to the improvement in intracellular calcium homeostasis imbalance of skeletal muscle and an increase in mitochondrial membrane potential.
Sensitive and direct electrochemical detection of double-stranded DNA utilizing alkaline phosphatase-labelled zinc finger proteins
Authors: Noh Soodong , Ha Dat Thinh , Yang Haesik , Kim Moon-Soo
Published: May 2015

We report sensitive and direct detection of specific bacterial dsDNA sequences using (i) the zinc finger protein labelled with alkaline phosphatase and (ii) electrochemical measurement at the ITO electrode.
A drug formulation using an alginate hydrogel matrix for efficient oral delivery of the manganese porphyrin-based superoxide dismutase mimic
Authors: Aikawa T. , Ito S. , Shinohara M. , Kaneko M. , Kondo T. , Yuasa M.
Published: May 2015

In order for patients to avail of the therapeutic benefits of antioxidant drugs efficiently and conveniently, a robust oral delivery system needs to be developed.
Hyperbranched PEG-based supramolecular nanoparticles for acid-responsive targeted drug delivery
Authors: Chen Xiaofei , Yao Xuemei , Wang Chunran , Chen Li , Chen Xuesi
Published: May 2015

In this article acid-sensitive hyperbranched PEG-based supramolecular nanoparticles were designed and used for targeted drug delivery.
Using RecA protein to enhance kinetic rates of DNA circuits
Authors: Milligan J. N. , Ellington A. D.
Published: May 2015

RecA, a recombination enzyme that catalyzes sequence specific strand exchange, increases the rate of DNA circuitry up to 9-fold.
Neutral amine based alcohol-soluble interface materials for inverted polymer solar cells: realizing high performance and overcoming solvent erosion
Authors: Zhang Qu , Zhang Dawei , Li Xiaodong , Liu Xiaohui , Zhang Wenjun , Han Lei , Fang Junfeng
Published: May 2015

We realized high performance and simultaneously solved the solvent erosion problem using neutral electron transport materials for inverted polymer solar cells.
Tunable emission in lanthanide coordination polymer gels based on a rationally designed blue emissive gelator
Authors: Sutar Papri , Suresh Venkata M. , Maji Tapas Kumar
Published: May 2015

A new blue emissive gelator has been synthesized and its self-assembly with TbIII and EuIII results in coordination polymer gels, which show tunable emission based on stoichiometric control over LMWG:TbIII:EuIII.
Gold-catalyzed selective oxidation of 4-oxahepta-1,6-diynes to 2H-pyran-3(6H)-ones and chromen-3(4H)-ones via β-gold vinyl cation intermediates
Authors: Ji Kegong , Liu Xiang , Du Bowen , Yang Fang , Gao Jinming
Published: May 2015

α-Oxo gold carbenes generated in situ via the gold-catalyzed selective oxidation of 4-oxahepta-1,6-diynes were effectively trapped by internal alkynes, resulting in the formation of 2H-pyran-3(6H)-ones, 3, and chromen-3(4H)-ones, 4, upon facile trapping the vinyl cation intermediates.
The total chemical synthesis of the monoglycosylated GM2 ganglioside activator using a novel cysteine surrogate
Authors: Sato Kohei , Kitakaze Keisuke , Nakamura Takahiro , Naruse Naoto , Aihara Keisuke , Shigenaga Akira , Inokuma Tsubasa , Tsuji Daisuke , Itoh Kohji , Otaka Akira
Published: May 2015

We describe a novel peptide ligation/desulfurization strategy using a β-mercapto-N-glycosylated asparagine derivative. The strategy is successfully applied to the total chemical synthesis of GM2 ganglioside activator protein.
Reversible thermo-sensitivity induced from varying the hydrogen bonding between the side residues of rationally designed polypeptides
Authors: Liu Hong , Xiao Yan , Xu Heng , Guan Yebin , Zhang Jun , Lang Meidong
Published: May 2015

Balancing the ratio of the hydrogen bond acceptor/donor in the side residues of poly(l-glutamate) derivatives endows the copolypeptide obtained with reversible thermosensitivity.
Strong electronic polarization of the C60 fullerene by imidazolium-based ionic liquids: accurate insights from Born–Oppenheimer molecular dynamic simulations
Authors: Chaban Vitaly V. , Fileti Eudes Eterno
Published: May 2015

Fullerenes are known to be polarizable due to their strained carbon–carbon bonds and high surface curvature.
Visible room-temperature phosphorescence of pure organic crystals via a radical-ion-pair mechanism
Authors: Kuno Shinichi , Akeno Hiroshi , Ohtani Hiroyuki , Yuasa Hideya
Published: May 2015

Hyperfine coupling of a radical ion pair in metal free organic crystals is responsible for room temperature, second-persisting phosphorescence.
Magnetic and noble metal nanocomposites for separation and optical detection of biological species
Authors: Bagga K. , Brougham D. F. , Keyes T. E. , Brabazon D.
Published: May 2015

Nanoalloys and nanocomposites are widely studied classes of nanomaterials within the context of biological systems. This article presents an overview of methods currently used for nanoalloy and nanocomposite synthesis and characterization, focusing on Au-Ag and FexOy@Au structures as primary components in detection platforms for plasmonic and magnetically enabled plasmonic bio-sensing.
Dielectric, thermal and mechanical properties of zirconium silicate reinforced high density polyethylene composites for antenna applications
Authors: Varghese Jobin , Nair Dinesh Raghavan , Mohanan Pezholil , Sebastian Mailadil Thomas
Published: May 2015

Dielectric, thermal and mechanical properties of ZrSiO4reinforced high density polyethylene composites and their device prototype.
Anomalous lattice vibrations of monolayer MoS2 probed by ultraviolet Raman scattering
Authors: Liu Hsiang-Lin , Guo Huaihong , Yang Teng , Zhang Zhidong , Kumamoto Yasuaki , Shen Chih-Chiang , Hsu Yu-Te , Li Lain-Jong , Saito Riichiro , Kawata Satoshi
Published: May 2015

Raman scattering spectrum of monolayer MoS2 shows anomalous enhanced peaks from 500 to 900 cm−1 for the 354 nm laser excitation, which can be explained by the double resonance Raman scattering process.
Photoswitching in nanoporous, crystalline solids: an experimental and theoretical study for azobenzene linkers incorporated in MOFs
Authors: Wang Zhengbang , Heinke Lars , Jelic Jelena , Cakici Murat , Dommaschk Marcel , Maurer Reinhard J. , Oberhofer Harald , Grosjean Sylvain , Herges Rainer , Bräse Stefan , Reuter Karsten , Wöll Christof
Published: May 2015

By using UV-vis-spectroscopy and uptake experiments combined with DFT-calculations, the photoswitching of azobenzene-side groups in MOFs is precisely investigated.