bluuebunny/crossref_metadata_2025 huggingface dataset:
Human mesenchymal stromal cells transplanted into mice stimulate renal tubular cells and enhance mitochondrial function
Authors: Perico Luca , Morigi Marina , Rota Cinzia , Breno Matteo , Mele Caterina , Noris Marina , Introna Martino , Capelli Chiara , Longaretti Lorena , Rottoli Daniela , Conti Sara , Corna Daniela , Remuzzi Giuseppe , Benigni Ariela
Published: October 2017

Mesenchymal stromal cells (MSCs) are renoprotective and drive regeneration following injury, although cellular targets of such an effect are still ill-defined. Here, we show that human umbilical cord (UC)-MSCs transplanted into mice stimulate tubular cells to regain mitochondrial mass and function, associated with enhanced microtubule-rich projections that appear to mediate mitochondrial trafficking to create a reparative dialogue among adjacent tubular cells. Treatment with UC-MSCs in mice with cisplatin-induced acute kidney injury (AKI) regulates mitochondrial biogenesis in proximal tubuli by enhancing PGC1α expression, NAD+ biosynthesis and Sirtuin 3 (SIRT3) activity, thus fostering antioxidant defenses and ATP production. The functional role of SIRT3 in tubular recovery is highlighted by data that in SIRT3-deficient mice with AKI, UC-MSC treatment fails to induce renoprotection. These data document a previously unrecognized mechanism through which UC-MSCs facilitate renal repair, so as to induce global metabolic reprogramming of damaged tubular cells to sustain energy supply.
Tyrosine phosphorylation of the GARU E3 ubiquitin ligase promotes gibberellin signalling by preventing GID1 degradation
Authors: Nemoto Keiichirou , Ramadan Abdelaziz , Arimura Gen-ichiro , Imai Kenichiro , Tomii Kentaro , Shinozaki Kazuo , Sawasaki Tatsuya
Published: October 2017

Gibberellin (GA) is a major hormone for plant growth and development. GA response is derived from the degradation of DELLA repressor proteins after GA-dependent complex formation of the GID1 GA receptor with DELLA. Genistein is a known tyrosine (Tyr) kinase inhibitor and inhibits DELLA degradation. However, the biological role of Tyr phosphorylation on the GA response remains unclear. Here, we demonstrate that GARU (GA receptor RING E3 ubiquitin ligase) mediates ubiquitin-dependent degradation of GID1, and that the TAGK2 plant Tyr-kinase is a target of genistein and inhibits GARU–GID1A interactions by phosphorylation of GARU at Tyr321. Genistein induces degradation of GID1 and accumulation of DELLA. Conversely, Arabidopsis garu mutant and TAGK2-overexpressing plants accelerate GID1 stabilization and DELLA degradation. Under salt stress, GARU suppresses seed germination. We propose that GA response is negatively regulated by GARU-dependent GID1 ubiquitination and positively by Tyr phosphorylation of GARU by TAGK2, and genistein inhibits GA signaling by TAGK2 inhibition.
A new electrode design for ambipolar injection in organic semiconductors
Authors: Kanagasekaran Thangavel , Shimotani Hidekazu , Shimizu Ryota , Hitosugi Taro , Tanigaki Katsumi
Published: October 2017

Organic semiconductors have attracted much attention for low-cost, flexible and human-friendly optoelectronics. However, achieving high electron-injection efficiency is difficult from air-stable electrodes and cannot be equivalent to that of holes. Here, we present a novel concept of electrode composed of a bilayer of tetratetracontane (TTC) and polycrystalline organic semiconductors (pc-OSC) covered by a metal layer. Field-effect transistors of single-crystal organic semiconductors with the new electrodes of M/pc-OSC/TTC (M: Ca or Au) show both highly efficient electron and hole injection. Contact resistance for electron injection from Au/pc-OSC/TTC and hole injection from Ca/pc-OSC/TTC are comparable to those for electron injection from Ca and hole injection from Au, respectively. Furthermore, the highest field-effect mobilities of holes (22 cm2 V–1 s–1) and electrons (5.0 cm2 V–1 s–1) are observed in rubrene among field-effect transistors with electrodes so far proposed by employing Ca/pc-OSC/TTC and Au/pc-OSC/TTC electrodes for electron and hole injection, respectively.
Sensory TRP channels contribute differentially to skin inflammation and persistent itch
Authors: Feng Jing , Yang Pu , Mack Madison R. , Dryn Dariia , Luo Jialie , Gong Xuan , Liu Shenbin , Oetjen Landon K. , Zholos Alexander V. , Mei Zhinan , Yin Shijin , Kim Brian S. , Hu Hongzhen
Published: October 2017

Although both persistent itch and inflammation are commonly associated with allergic contact dermatitis (ACD), it is not known if they are mediated by shared or distinct signaling pathways. Here we show that both TRPA1 and TRPV1 channels are required for generating spontaneous scratching in a mouse model of ACD induced by squaric acid dibutylester (SADBE), a small molecule hapten, through directly promoting the excitability of pruriceptors. TRPV1 but not TRPA1 channels protect the skin inflammation, as genetic ablation of TRPV1 function or pharmacological ablation of TRPV1-positive sensory nerves promotes cutaneous inflammation in the SADBE-induced ACD. Our results demonstrate that persistent itch and inflammation are mediated by distinct cellular and molecular mechanisms in a mouse model of ACD. Identification of distinct roles of TRPA1 and TRPV1 in regulating itch and inflammation may provide new insights into the pathophysiology and treatment of chronic itch and inflammation in ACD patients.
Three-dimensional context rather than NLS amino acid sequence determines importin α subtype specificity for RCC1
Authors: Sankhala Rajeshwer S. , Lokareddy Ravi K. , Begum Salma , Pumroy Ruth A. , Gillilan Richard E. , Cingolani Gino
Published: October 2017

Active nuclear import of Ran exchange factor RCC1 is mediated by importin α3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin α3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin α1, although the two isoforms share an identical NLS-binding groove. Importin α3 uses its greater conformational flexibility to wedge the RCC1 β-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core. Removing the β-propeller, or inserting a linker between NLS and β-propeller, disrupts specificity for importin α3, demonstrating the structural context rather than NLS sequence determines selectivity for isoform 3. We propose importin α3 evolved to recognize topologically complex NLSs that lie next to bulky domains or are masked by quaternary structures.
Anomalous quantization trajectory and parity anomaly in Co cluster decorated BiSbTeSe2 nanodevices
Authors: Zhang Shuai , Pi Li , Wang Rui , Yu Geliang , Pan Xing-Chen , Wei Zhongxia , Zhang Jinglei , Xi Chuanying , Bai Zhanbin , Fei Fucong , Wang Mingyu , Liao Jian , Li Yongqing , Wang Xuefeng , Song Fengqi , Zhang Yuheng , Wang Baigeng , Xing Dingyu , Wang Guanghou
Published: October 2017

Dirac Fermions with different helicities exist on the top and bottom surfaces of topological insulators, offering a rare opportunity to break the degeneracy protected by the no-go theorem. Through the application of Co clusters, quantum Hall plateaus were modulated for the topological insulator BiSbTeSe2, allowing an optimized surface transport. Here, using renormalization group flow diagrams, we show the extraction of two sets of converging points in the conductivity tensor space, revealing that the top surface exhibits an anomalous quantization trajectory, while the bottom surface retains the 1/2 quantization. Co clusters are believed to induce a sizeable Zeeman gap ( > 4.8 meV) through antiferromagnetic exchange coupling, which delays the Landau level hybridization on the top surface for a moderate magnetic field. A quasi-half-integer plateau also appears at −7.2 Tesla. This allows us to study the interesting physics of parity anomaly, and paves the way for further studies simulating exotic particles in condensed matter physics.
Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
Authors: Albayram Onder , Kondo Asami , Mannix Rebekah , Smith Colin , Tsai Cheng-Yu , Li Chenyu , Herbert Megan K. , Qiu Jianhua , Monuteaux Michael , Driver Jane , Yan Sandra , Gormley William , Puccio Ava M. , Okonkwo David O. , Lucke-Wold Brandon , Bailes Julian , Meehan William , Zeidel Mark , Lu Kun Ping , Zhou Xiao Zhen
Published: October 2017

Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and associated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer’s disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology and functional impairment in an animal model of severe TBI. Here we found that in human samples obtained post TBI due to a variety of causes, cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Using mouse models of severe or repetitive TBI, we showed that cis P-tau elimination with a specific neutralizing antibody administered immediately or at delayed time points after injury, attenuates the development of neuropathology and brain dysfunction during acute and chronic phases including CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau contributes to short-term and long-term sequelae after TBI, but is effectively neutralized by cis antibody treatment.
Mechanocaloric effects in superionic thin films from atomistic simulations
Authors: Sagotra Arun K. , Errandonea Daniel , Cazorla Claudio
Published: October 2017

Solid-state cooling is an energy-efficient and scalable refrigeration technology that exploits the adiabatic variation of a crystalline order parameter under an external field (electric, magnetic, or mechanic). The mechanocaloric effect bears one of the greatest cooling potentials in terms of energy efficiency owing to its large available latent heat. Here we show that giant mechanocaloric effects occur in thin films of well-known families of fast-ion conductors, namely Li-rich (Li3OCl) and type-I (AgI), an abundant class of materials that routinely are employed in electrochemistry cells. Our simulations reveal that at room temperature AgI undergoes an adiabatic temperature shift of 38 K under a biaxial stress of 1 GPa. Likewise, Li3OCl displays a cooling capacity of 9 K under similar mechanical conditions although at a considerably higher temperature. We also show that ionic vacancies have a detrimental effect on the cooling performance of superionic thin films. Our findings should motivate experimental mechanocaloric searches in a wide variety of already known superionic materials.
Remote light-controlled intracellular target recognition by photochromic fluorescent glycoprobes
Authors: Zhang Junji , Fu Youxin , Han Hai-Hao , Zang Yi , Li Jia , He Xiao-Peng , Feringa Ben L. , Tian He
Published: October 2017

Development of powerful fluorescence imaging probes and techniques sets the basis for the spatiotemporal tracking of cells at different physiological and pathological stages. While current imaging approaches rely on passive probe–analyte interactions, here we develop photochromic fluorescent glycoprobes capable of remote light-controlled intracellular target recognition. Conjugation between a fluorophore and spiropyran produces the photochromic probe, which is subsequently equipped with a glycoligand “antenna” to actively localize a target cell expressing a selective receptor. We demonstrate that the amphiphilic glycoprobes that form micelles in water can selectively enter the target cell to operate photochromic cycling as controlled by alternate UV/Vis irradiations. We further show that remote light conversion of the photochromic probe from one isomeric state to the other activates its reactivity toward a target intracellular analyte, producing locked fluorescence that is no longer photoisomerizable. We envision that this research may spur the use of photochromism for the development of bioimaging probes.
Mechanoresponsive lipid-protein nanoglobules facilitate reversible fibre formation in velvet worm slime
Authors: Baer Alexander , Schmidt Stephan , Haensch Sebastian , Eder Michaela , Mayer Georg , Harrington Matthew J.
Published: October 2017

Velvet worms eject a fluid capture slime that can be mechanically drawn into stiff biopolymeric fibres. Remarkably, these fibres can be dissolved by extended exposure to water, and new regenerated fibres can be drawn from the dissolved fibre solution—indicating a fully recyclable process. Here, we perform a multiscale structural and compositional investigation of this reversible fabrication process with the velvet worm Euperipatoides rowelli, revealing that biopolymeric fibre assembly is facilitated via mono-disperse lipid-protein nanoglobules. Shear forces cause nanoglobules to self-assemble into nano- and microfibrils, which can be drawn into macroscopic fibres with a protein-enriched core and lipid-rich coating. Fibre dissolution in water leads to re-formation of nanoglobules, suggesting that this dynamic supramolecular assembly of mechanoresponsive protein-building blocks is mediated by reversible non-covalent interactions. These findings offer important mechanistic insights into the role of mechanochemical processes in bio-fibre formation, providing potential avenues for sustainable material fabrication processes.
AUNIP/C1orf135 directs DNA double-strand breaks towards the homologous recombination repair pathway
Authors: Lou Jiangman , Chen Hongxia , Han Jinhua , He Hanqing , Huen Michael S. Y. , Feng Xin-hua , Liu Ting , Huang Jun
Published: October 2017

DNA double-strand breaks (DSBs) are mainly repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). Here, we identify AUNIP/C1orf135, a largely uncharacterized protein, as a key determinant of DSB repair pathway choice. AUNIP physically interacts with CtIP and is required for efficient CtIP accumulation at DSBs. AUNIP possesses intrinsic DNA-binding ability with a strong preference for DNA substrates that mimic structures generated at stalled replication forks. This ability to bind DNA is necessary for the recruitment of AUNIP and its binding partner CtIP to DSBs, which in turn drives CtIP-dependent DNA-end resection and HR repair. Accordingly, loss of AUNIP or ablation of its ability to bind to DNA results in cell hypersensitivity toward a variety of DSB-inducing agents, particularly those that induce replication-associated DSBs. Our findings provide new insights into the molecular mechanism by which DSBs are recognized and channeled to the HR repair pathway.
Topological quantum phase transition from mirror to time reversal symmetry protected topological insulator
Authors: Mandal Partha S. , Springholz Gunther , Volobuev Valentine V. , Caha Ondrej , Varykhalov Andrei , Golias Evangelos , Bauer Günther , Rader Oliver , Sánchez-Barriga Jaime
Published: October 2017

Topological insulators constitute a new phase of matter protected by symmetries. Time-reversal symmetry protects strong topological insulators of the Z2 class, which possess an odd number of metallic surface states with dispersion of a Dirac cone. Topological crystalline insulators are merely protected by individual crystal symmetries and exist for an even number of Dirac cones. Here, we demonstrate that Bi-doping of Pb1−x
Sn
x
Se (111) epilayers induces a quantum phase transition from a topological crystalline insulator to a Z2 topological insulator. This occurs because Bi-doping lifts the fourfold valley degeneracy and induces a gap at $$\bar \Gamma $$

Γ

̄

, while the three Dirac cones at the $${\bar{\rm M}}$$

M

̄

points of the surface Brillouin zone remain intact. We interpret this new phase transition as caused by a lattice distortion. Our findings extend the topological phase diagram enormously and make strong topological insulators switchable by distortions or electric fields.
Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma
Authors: Ducie Jennifer , Dao Fanny , Considine Michael , Olvera Narciso , Shaw Patricia A. , Kurman Robert J. , Shih Ie-Ming , Soslow Robert A. , Cope Leslie , Levine Douglas A.
Published: October 2017

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.
Investigating the relationship between Aerosol Optical Depth and Precipitation over Southeast Asia with Relative Humidity as an influencing factor
Authors: Ng Daniel Hui Loong , Li Ruimin , Raghavan Srivatsan V. , Liong Shie-Yui
Published: October 2017

Atmospheric aerosols influence precipitation by changing the earth’s energy budget and cloud properties. A number of studies have reported correlations between aerosol properties and precipitation data. Despite previous research, it is still hard to quantify the overall effects that aerosols have on precipitation as multiple influencing factors such as relative humidity (RH) can distort the observed relationship between aerosols and precipitation. Thus, in this study, both satellite-retrieved and reanalysis data were used to investigate the relationship between aerosols and precipitation in the Southeast Asia region from 2001 to 2015, with RH considered as a possible influencing factor. Different analyses in the study indicate that a positive correlation was present between Aerosol Optical Depth (AOD) and precipitation over northern Southeast Asia region during the autumn and the winter seasons, while a negative correlation was identified over the Maritime Continent during the autumn season. Subsequently, a partial correlation analysis revealed that while RH influences the long-term negative correlations between AOD and precipitation, it did not significantly affect the positive correlations seen in the winter season. The result of this study provides additional evidence with respect to the critical role of RH as an influencing factor in AOD-precipitation relationship over Southeast Asia.
Distorting temporal fine structure by phase shifting and its effects on speech intelligibility and neural phase locking
Authors: Xu Yingyue , Chen Maxin , LaFaire Petrina , Tan Xiaodong , Richter Claus-Peter
Published: October 2017

Envelope (E) and temporal fine structure (TFS) are important features of acoustic signals and their corresponding perceptual function has been investigated with various listening tasks. To further understand the underlying neural processing of TFS, experiments in humans and animals were conducted to demonstrate the effects of modifying the TFS in natural speech sentences on both speech recognition and neural coding. The TFS of natural speech sentences was modified by distorting the phase and maintaining the magnitude. Speech intelligibility was then tested for normal-hearing listeners using the intact and reconstructed sentences presented in quiet and against background noise. Sentences with modified TFS were then used to evoke neural activity in auditory neurons of the inferior colliculus in guinea pigs. Our study demonstrated that speech intelligibility in humans relied on the periodic cues of speech TFS in both quiet and noisy listening conditions. Furthermore, recordings of neural activity from the guinea pig inferior colliculus have shown that individual auditory neurons exhibit phase locking patterns to the periodic cues of speech TFS that disappear when reconstructed sounds do not show periodic patterns anymore. Thus, the periodic cues of TFS are essential for speech intelligibility and are encoded in auditory neurons by phase locking.
Switching behavior of droplets crossing nodes on a fiber network
Authors: Weyer F. , Duchesne A. , Vandewalle N.
Published: October 2017

Lately, curious structures have been erected in arid regions: they are large nets able to catch water from fog. Tiny droplets condense on the mesh and are collected on the bottom of it. This innovative technology is crucial to obtain drinkable water in these inhospitable areas. Many studies aim to understand the behavior of droplets trapped on this entanglement of fibers. However, the motion of a droplet sliding on a network of inclined fibers and encountering several crossings when going down remains an open question. Here, we look at the path chosen by such a drop and, especially, we analyze its behavior at the different nodes of the array. We show that droplets may change from one fiber to another one depending on the slope and the diameter of these fibers. We prove that we can force a droplet to follow a specific path simply by carefully designing the fiber mesh. These findings are expected to provide a very convenient way to manipulate small droplets in applications from microfluidics to fog harvesting.
Fan-out Estimation in Spin-based Quantum Computer Scale-up
Authors: Nguyen Thien , Hill Charles D. , Hollenberg Lloyd C. L. , James Matthew R.
Published: October 2017

Solid-state spin-based qubits offer good prospects for scaling based on their long coherence times and nexus to large-scale electronic scale-up technologies. However, high-threshold quantum error correction requires a two-dimensional qubit array operating in parallel, posing significant challenges in fabrication and control. While architectures incorporating distributed quantum control meet this challenge head-on, most designs rely on individual control and readout of all qubits with high gate densities. We analysed the fan-out routing overhead of a dedicated control line architecture, basing the analysis on a generalised solid-state spin qubit platform parameterised to encompass Coulomb confined (e.g. donor based spin qubits) or electrostatically confined (e.g. quantum dot based spin qubits) implementations. The spatial scalability under this model is estimated using standard electronic routing methods and present-day fabrication constraints. Based on reasonable assumptions for qubit control and readout we estimate 102–105 physical qubits, depending on the quantum interconnect implementation, can be integrated and fanned-out independently. Assuming relatively long control-free interconnects the scalability can be extended. Ultimately, the universal quantum computation may necessitate a much higher number of integrated qubits, indicating that higher dimensional electronics fabrication and/or multiplexed distributed control and readout schemes may be the preferredstrategy for large-scale implementation.
Compact-Morphology-based poly-metallic Nodule Delineation
Authors: Schoening Timm , Jones Daniel O. B. , Greinert Jens
Published: October 2017

Poly-metallic nodules are a marine resource considered for deep sea mining. Assessing nodule abundance is of interest for mining companies and to monitor potential environmental impact. Optical seafloor imaging allows quantifying poly-metallic nodule abundance at spatial scales from centimetres to square kilometres. Towed cameras and diving robots acquire high-resolution imagery that allow detecting individual nodules and measure their sizes. Spatial abundance statistics can be computed from these size measurements, providing e.g. seafloor coverage in percent and the nodule size distribution. Detecting nodules requires segmentation of nodule pixels from pixels showing sediment background. Semi-supervised pattern recognition has been proposed to automate this task. Existing nodule segmentation algorithms employ machine learning that trains a classifier to segment the nodules in a high-dimensional feature space. Here, a rapid nodule segmentation algorithm is presented. It omits computation-intense feature-based classification and employs image processing only. It exploits a nodule compactness heuristic to delineate individual nodules. Complex machine learning methods are avoided to keep the algorithm simple and fast. The algorithm has successfully been applied to different image datasets. These data sets were acquired by different cameras, camera platforms and in varying illumination conditions. Their successful analysis shows the broad applicability of the proposed method.
Reduced nitric oxide levels during drought stress promote drought tolerance in barley and is associated with elevated polyamine biosynthesis
Authors: Montilla-Bascón Gracia , Rubiales Diego , Hebelstrup Kim H. , Mandon Julien , Harren Frans J. M. , Cristescu Simona M. , Mur Luis A. J. , Prats Elena
Published: October 2017

Nitric oxide (NO) is a key messenger in plant stress responses but its exact role in drought response remains unclear. To investigate the role of NO in drought response we employed transgenic barley plants (UHb) overexpressing the barley non-symbiotic hemoglobin gene HvHb1 that oxidizes NO to NO3−. Reduced NO production under drought conditions in UHb plants was associated with increased drought tolerance. Since NO biosynthesis has been related to polyamine metabolism, we investigated whether the observed drought-related NO changes could involve polyamine pathway. UHb plants showed increases in total polyamines and in particular polyamines such as spermidine. These increases correlated with the accumulation of the amino acid precursors of polyamines and with the expression of specific polyamine biosynthesis genes. This suggests a potential interplay between NO and polyamine biosynthesis during drought response. Since ethylene has been linked to NO signaling and it is also related to polyamine metabolism, we explored this connection. In vivo ethylene measurement showed that UHb plants significantly decrease ethylene production and expression of aminocyclopropane-1-carboxylic acid synthase gene, the first committed step in ethylene biosynthesis compared with wild type. These data suggest a NO-ethylene influenced regulatory node in polyamine biosynthesis linked to drought tolerance/susceptibility in barley.
A Novel Technique for Accelerated Culture of Murine Mesenchymal Stem Cells that Allows for Sustained Multipotency
Authors: Caroti Courtney M. , Ahn Hyunhee , Salazar Hector F. , Joseph Giji , Sankar Sitara B. , Willett Nick J. , Wood Levi B. , Taylor W. Robert , Lyle Alicia N.
Published: October 2017

Bone marrow derived mesenchymal stem cells (MSCs) are regularly utilized for translational therapeutic strategies including cell therapy, tissue engineering, and regenerative medicine and are frequently used in preclinical mouse models for both mechanistic studies and screening of new cell based therapies. Current methods to culture murine MSCs (mMSCs) select for rapidly dividing colonies and require long-term expansion. These methods thus require months of culture to generate sufficient cell numbers for feasibility studies in a lab setting and the cell populations often have reduced proliferation and differentiation potential, or have become immortalized cells. Here we describe a simple and reproducible method to generate mMSCs by utilizing hypoxia and basic fibroblast growth factor supplementation. Cells produced using these conditions were generated 2.8 times faster than under traditional methods and the mMSCs showed decreased senescence and maintained their multipotency and differentiation potential until passage 11 and beyond. Our method for mMSC isolation and expansion will significantly improve the utility of this critical cell source in pre-clinical studies for the investigation of MSC mechanisms, therapies, and cell manufacturing strategies.
Controlling sound radiation through an opening with secondary loudspeakers along its boundaries
Authors: Wang Shuping , Tao Jiancheng , Qiu Xiaojun
Published: October 2017

We propose a virtual sound barrier system that blocks sound transmission through openings without affecting access, light and air circulation. The proposed system applies active control technique to cancel sound transmission with a double layered loudspeaker array at the edge of the opening. Unlike traditional transparent glass windows, recently invented double-glazed ventilation windows and planar active sound barriers or any other metamaterials designed to reduce sound transmission, secondary loudspeakers are put only along the boundaries of the opening, which provides the possibility to make it invisible. Simulation and experimental results demonstrate its feasibility for broadband sound control, especially for low frequency sound which is usually hard to attenuate with existing methods.
Unravelling the Chemical Influence of Water on the PMMA/Aluminum Oxide Hybrid Interface In Situ
Authors: Pletincx Sven , Marcoen Kristof , Trotochaud Lena , Fockaert Laura-Lynn , Mol Johannes M. C. , Head Ashley R. , Karslioğlu Osman , Bluhm Hendrik , Terryn Herman , Hauffman Tom
Published: October 2017

Understanding the stability of chemical interactions at the polymer/metal oxide interface under humid conditions is vital to understand the long-term durability of hybrid systems. Therefore, the interface of ultrathin PMMA films on native aluminum oxide, deposited by reactive adsorption, was studied. The characterization of the interface of the coated substrates was performed using ambient pressure X-ray photoelectron spectroscopy (APXPS), Fourier transform infrared spectroscopy in the Kretschmann geometry (ATR-FTIR Kretschmann) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The formation of hydrogen bonds and carboxylate ionic bonds at the interface are observed. The formed ionic bond is stable up to 5 Torr water vapour pressure as shown by APXPS. However, when the coated samples are exposed to an excess of aqueous electrolyte, an increase in the amount of carboxylate bonds at the interface, as a result of hydrolysis of the methoxy group, is observed by ATR-FTIR Kretschmann. These observations, supported by ToF-SIMS spectra, lead to the proposal of an adsorption mechanism of PMMA on aluminum oxide, which shows the formation of methanol at the interface and the effect of water molecules on the different interfacial interactions.
Lipid polymorphism in chloroplast thylakoid membranes – as revealed by 31P-NMR and time-resolved merocyanine fluorescence spectroscopy
Authors: Garab Győző , Ughy Bettina , Waard Pieter de , Akhtar Parveen , Javornik Uroš , Kotakis Christos , Šket Primož , Karlický Václav , Materová Zuzana , Špunda Vladimír , Plavec Janez , van Amerongen Herbert , Vígh László , As Henk Van , Lambrev Petar H.
Published: October 2017

Chloroplast thylakoid membranes contain virtually all components of the energy-converting photosynthetic machinery. Their energized state, driving ATP synthesis, is enabled by the bilayer organization of the membrane. However, their most abundant lipid species is a non-bilayer-forming lipid, monogalactosyl-diacylglycerol; the role of lipid polymorphism in these membranes is poorly understood. Earlier 31P-NMR experiments revealed the coexistence of a bilayer and a non-bilayer, isotropic lipid phase in spinach thylakoids. Packing of lipid molecules, tested by fluorescence spectroscopy of the lipophilic dye, merocyanine-540 (MC540), also displayed heterogeneity. Now, our 31P-NMR experiments on spinach thylakoids uncover the presence of a bilayer and three non-bilayer lipid phases; time-resolved fluorescence spectroscopy of MC540 also reveals the presence of multiple lipidic environments. It is also shown by 31P-NMR that: (i) some lipid phases are sensitive to the osmolarity and ionic strength of the medium, (ii) a lipid phase can be modulated by catalytic hydrogenation of fatty acids and (iii) a marked increase of one of the non-bilayer phases upon lowering the pH of the medium is observed. These data provide additional experimental evidence for the polymorphism of lipid phases in thylakoids and suggest that non-bilayer phases play an active role in the structural dynamics of thylakoid membranes.
Serum SAA1 and APOE are novel indicators for human cytomegalovirus infection
Authors: Xie Ni , Li Zhonghang , Zuo Ran , Qi Suwen , Zhu Ting , Liu Litao , Wan Lili , Yuan Jianhui
Published: October 2017

Human cytomegalovirus (HCMV) infection is a global concern and highly infectious. HCMV-infected individuals are often carriers with damaged immunity. However few diagnostic indicators block HMCV control and prevention. Thus, we measured 21 serum proteins related to HCMV infection using iTRAQ-labeling based quantitative proteomic approaches and SAA1 and APOE were confirmed as candidate serum indicators for identification of HMCV infection according to ROC curve analysis and that co-occurrence of SAA1 and APOE are better markers than individual proteins.
Immunoproteasome subunit ß5i/LMP7-deficiency in atherosclerosis
Authors: Hewing Bernd , Ludwig Antje , Dan Cristian , Pötzsch Max , Hannemann Carmen , Petry Andreas , Lauer Dilyara , Görlach Agnes , Kaschina Elena , Müller Dominik N. , Baumann Gert , Stangl Verena , Stangl Karl , Wilck Nicola
Published: October 2017

Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR−/−LMP7−/− and LDLR−/− mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively. Lesion burden was similar between genotypes in both stages. Macrophage content and abundance of polyubiquitin conjugates in aortic root plaques were unaltered by β5i/LMP7-deficiency. In vitro experiments using bone marrow-derived macrophages (BMDM) showed that β5i/LMP7-deficiency did not influence macrophage polarization or accumulation of polyubiquitinated proteins and cell survival upon hydrogen peroxide and interferon-γ treatment. Analyses of proteasome core particle composition by Western blot revealed incorporation of standard proteasome subunits in β5i/LMP7-deficient BMDM and spleen. Chymotrypsin-, trypsin- and caspase-like activities assessed by using short fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes. Taken together, deficiency of IP subunit β5i/LMP7 does not disturb protein homeostasis and does not aggravate atherogenesis in LDLR−/− mice.
Equation of state and self-bound droplet in Rabi-coupled Bose mixtures
Authors: Cappellaro Alberto , Macrì Tommaso , Bertacco Giovanni F. , Salasnich Luca
Published: October 2017

Laser induced transitions between internal states of atoms have been playing a fundamental role to manipulate atomic clouds for many decades. In absence of interactions each atom behaves independently and their coherent quantum dynamics is described by the Rabi model. Since the experimental observation of Bose condensation in dilute gases, static and dynamical properties of multicomponent quantum gases have been extensively investigated. Moreover, at very low temperatures quantum fluctuations crucially affect the equation of state of many-body systems. Here we study the effects of quantum fluctuations on a Rabi-coupled two-component Bose gas of interacting alkali atoms. The divergent zero-point energy of gapless and gapped elementary excitations of the uniform system is properly regularized obtaining a meaningful analytical expression for the beyond-mean-field equation of state. In the case of attractive inter-particle interaction we show that the quantum pressure arising from Gaussian fluctuations can prevent the collapse of the mixture with the creation of a self-bound droplet. We characterize the droplet phase and discover an energetic instability above a critical Rabi frequency provoking the evaporation of the droplet. Finally, we suggest an experiment to observe such quantum droplets using Rabi-coupled internal states of K39 atoms.
Remarkably enhanced current-driven 360° domain wall motion in nanostripe by tuning in-plane biaxial anisotropy
Authors: Su Yuanchang , Weng Lianghao , Dong Wenjun , Xi Bin , Xiong Rui , Hu Jingguo
Published: October 2017

By micromagnetic simulations, we study the current-driven 360° domain wall (360DW) motion in ferromagnetic nanostripe with an in-plane biaxial anisotropy. We observe the critical annihilation current of 360° domain wall can be enhanced through such a type of anisotropy, the reason of which is the suppression of out-of-plane magnetic moments generated simultaneously with domain-wall motion. In details, We have found that the domain-wall width is only related to K
y
 − K
x
, with K
x(y) the anisotropy constant in x(y) direction. Taking domain-wall width into consideration, a prior choice is to keep K
y
 ≈ K
x
with large enough K. The mode of domain-wall motion has been investigated as well. The traveling-wave-motion region increases with K, while the average DW velocity is almost unchanged. Another noteworthy feature is that a Walker-breakdown-like motion exists before annihilation. In this region, though domain wall moves with an oscillating behavior, the average velocity does not reduce dramatically, but even rise again for a large K.
A DNA Contact Map for the Mouse Runx1 Gene Identifies Novel Haematopoietic Enhancers
Authors: Marsman Judith , Thomas Amarni , Osato Motomi , O’Sullivan Justin M. , Horsfield Julia A.
Published: October 2017

The transcription factor Runx1 is essential for definitive haematopoiesis, and the RUNX1 gene is frequently translocated or mutated in leukaemia. Runx1 is transcribed from two promoters, P1 and P2, to give rise to different protein isoforms. Although the expression of Runx1 must be tightly regulated for normal blood development, the mechanisms that regulate Runx1 isoform expression during haematopoiesis remain poorly understood. Gene regulatory elements located in non-coding DNA are likely to be important for Runx1 transcription. Here we use circular chromosome conformation capture sequencing to identify DNA interactions with the P1 and P2 promoters of Runx1, and the previously identified +24 enhancer, in the mouse multipotent haematopoietic progenitor cell line HPC-7. The active promoter, P1, interacts with nine non-coding regions that are occupied by transcription factors within a 1 Mb topologically associated domain. Eight of nine regions function as blood-specific enhancers in zebrafish, of which two were previously shown to harbour blood-specific enhancer activity in mice. Interestingly, the +24 enhancer interacted with multiple distant regions on chromosome 16, suggesting it may regulate the expression of additional genes. The Runx1 DNA contact map identifies connections with multiple novel and known haematopoietic enhancers that are likely to be involved in regulating Runx1 expression in haematopoietic progenitor cells.
Effects of intranasal insulin application on the hypothalamic BOLD response to glucose ingestion
Authors: Opstal Anna M. van , Akintola Abimbola A. , Elst Marjan van der , Westendorp Rudi G. , Pijl Hanno , Heemst Diana van , Grond Jeroen van der
Published: October 2017

The hypothalamus is a crucial structure in the brain that responds to metabolic cues and regulates energy homeostasis. Patients with type 2 diabetes demonstrate a lack of hypothalamic neuronal response after glucose ingestion, which is suggested to be an underlying cause of the disease. In this study, we assessed whether intranasal insulin can be used to enhance neuronal hypothalamic responses to glucose ingestion. In a randomized, double-blinded, placebo-controlled 4-double cross-over experiment, hypothalamic activation was measured in young non- diabetic subjects by determining blood-oxygen-level dependent MRI signals over 30 minutes before and after ingestion of 75 g glucose dissolved in 300 ml water, under intranasal insulin or placebo condition. Glucose ingestion under placebo condition lead to an average 1.4% hypothalamic BOLD decrease, under insulin condition the average response to glucose was a 2.2% decrease. Administration of water did not affect the hypothalamic BOLD responses. Intranasal insulin did not change circulating glucose and insulin levels. Still, circulating glucose levels showed a significant dampening effect on the BOLD response and insulin levels a significant strengthening effect. Our data provide proof of concept for future experiments testing the potential of intranasal application of insulin to ameliorate defective homeostatic control in patients with type 2 diabetes.
A generalized simulation development approach for predicting refugee destinations
Authors: Suleimenova Diana , Bell David , Groen Derek
Published: October 2017

In recent years, global forced displacement has reached record levels, with 22.5 million refugees worldwide. Forecasting refugee movements is important, as accurate predictions can help save refugee lives by allowing governments and NGOs to conduct a better informed allocation of humanitarian resources. Here, we propose a generalized simulation development approach to predict the destinations of refugee movements in conflict regions. In this approach, we synthesize data from UNHCR, ACLED and Bing Maps to construct agent-based simulations of refugee movements. We apply our approach to develop, run and validate refugee movement simulations set in three major African conflicts, estimating the distribution of incoming refugees across destination camps, given the expected total number of refugees in the conflict. Our simulations consistently predict more than 75% of the refugee destinations correctly after the first 12 days, and consistently outperform alternative naive forecasting techniques. Using our approach, we are also able to reproduce key trends in refugee arrival rates found in the UNHCR data.
Signalling mechanisms in PAF-induced intestinal failure
Authors: Lautenschläger Ingmar , Wong Yuk Lung , Sarau Jürgen , Goldmann Torsten , Zitta Karina , Albrecht Martin , Frerichs Inéz , Weiler Norbert , Uhlig Stefan
Published: October 2017

Capillary leakage syndrome, vasomotor disturbances and gut atony are common clinical problems in intensive care medicine. Various inflammatory mediators and signalling pathways are involved in these pathophysiological alterations among them platelet-activating factor (PAF). The related signalling mechanisms of the PAF-induced dysfunctions are only poorly understood. Here we used the model of the isolated perfused rat small intestine to analyse the role of calcium (using calcium deprivation, IP-receptor blockade (2-APB)), cAMP (PDE-inhibition plus AC activator), myosin light chain kinase (inhibitor ML-7) and Rho-kinase (inhibitor Y27632) in the following PAF-induced malfunctions: vasoconstriction, capillary and mucosal leakage, oedema formation, malabsorption and atony. Among these, the PAF-induced vasoconstriction and hyperpermeability appear to be governed by similar mechanisms that involve IP3 receptors, extracellular calcium and the Rho-kinase. Our findings further suggest that cAMP-elevating treatments – while effective against hypertension and oedema – bear the risk of dysmotility and reduced nutrient uptake. Agents such as 2-APB or Y27632, on the other hand, showed no negative side effects and improved most of the PAF-induced malfunctions suggesting that their therapeutic usefulness should be explored.
Hormone Signaling Regulates Nymphal Diapause in Laodelphax striatellus (Hemiptera: Delphacidae)
Authors: Zhai Yifan , Zhang Zhiming , Gao Huanhuan , Chen Hao , Sun Meng , Zhang Wenqing , Yu Yi , Zheng Li
Published: October 2017

Diapause is a physiological adaptation that allows an organism to survive adverse environmental conditions. Diapause occurs at a specific developmental stage in each species. There are few reports regarding the molecular regulatory mechanism of nymphal diapause in Laodelphax striatellus, which is an important graminaceous crop pest. Our previous studies identified the conditions for nymphal diapause in this species. Here, we combined RNA sequencing transcriptomics and quantitative proteomic analyses to identify nymphal diapause-related genes and proteins. The analysis of differentially regulated genes identified four gene/protein pairs that were synchronously up-regulated, and six gene/protein pairs that were synchronously down-regulated, suggesting that these genes may regulate nymphal diapause. The up-regulated gene juvenile hormone acid methyl transferase (JHAMT) and the down-regulated gene cytochrome P450 monooxygenase (CYP314A1, Shd) were chosen for further functional studies. After knocking-down of LsJHAMT and LsShd in vivo by RNA interference, the titer of JH III and 20E decreased significantly, and the duration of the nymphal development period was severely altered. Thus LsJHAMT and LsShd regulated JH III and 20E titers in the hemolymph to control the nymphal diapause status. This study may lead to new information on the regulation nymphal diapause of this important agricultural insect pest.
Abnormal M1/M2 macrophage phenotype profiles in the small airway wall and lumen in smokers and chronic obstructive pulmonary disease (COPD)
Authors: Eapen Mathew Suji , Hansbro Philip M. , McAlinden Kielan , Kim Richard Y. , Ward Chris , Hackett Tillie-Louise , Walters Eugene H. , Sohal Sukhwinder Singh
Published: October 2017

We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD. We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects. Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages. Multiplex ELISA measured BAL cytokines. Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles. We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups. However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects. BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs. The mouse-model of COPD showed similar increase in mRNA for M2 markers. Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance. There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD.