bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble P-selectin promotes retinal ganglion cell survival through activation of Nrf2 signaling after ischemia injury
Authors: Kapupara Kishan , Wen Yao-Tseng , Tsai Rong-Kung , Huang Shun-Ping 
Published: November 2017

AbstractRetinal ischemic injuries play an important role in the pathogenesis of several eye disorders. Inflammation and oxidative stress are key players in ischemic injuries. Following retinal ischemia, vascular endothelial cells and leukocytes express several inflammatory adhesion receptors, such as selectins and cell adhesion molecules. P-selectin stimulates leukocyte recruitment to platelet aggregates and has an important role in vascular homeostasis and inflammatory leukocyte extravasation. Soluble P-selectin can be neuroprotective through competitive binding to the receptors of endogenous P-selectin molecules. Here, we demonstrate the neuroprotective effect of a recombinant P-selectin immunoglobin G (P-sel-IgG) chimeric fusion protein in a rat anterior ischemic optic neuropathy (rAION) model. rAION was induced by photodynamic therapy. P-sel-IgG treatment reduced optic nerve edema and stabilized the blood–optic nerve barrier (BONB) in the acute phase of rAION. Further, P-sel-IgG increased the retinal ganglion cell (RGC) survival rate, reduced RGC apoptosis, preserved visual function, maintained retinal nerve fiber layer thickness, and reduced macrophage infiltration in optic nerve tissue in the chronic phase (day 28). Increased NAD(P)H quinone dehydrogenase 1 (NQO1) and heme oxygenase 1(HO-1) expression levels, along with increased transcription factor Nrf2, suggesting an antioxidant role of P-sel-IgG via the Nrf2 signaling pathway. In conclusion, this study is the first to demonstrate that P-sel-IgG treatment promotes RGC survival by stabilizing the BONB and activating the Nrf2 signaling pathway in a rAION model.
The role of Atlantic overturning circulation in the recent decline of Atlantic major hurricane frequency
Authors: Yan Xiaoqin , Zhang Rong , Knutson Thomas R. 
Published: November 2017

AbstractObserved Atlantic major hurricane frequency has exhibited pronounced multidecadal variability since the 1940s. However, the cause of this variability is debated. Using observations and a coupled earth system model (GFDL-ESM2G), here we show that the decline of the Atlantic major hurricane frequency during 2005–2015 is associated with a weakening of the Atlantic Meridional Overturning Circulation (AMOC) inferred from ocean observations. Directly observed North Atlantic sulfate aerosol optical depth has not increased (but shows a modest decline) over this period, suggesting the decline of the Atlantic major hurricane frequency during 2005–2015 is not likely due to recent changes in anthropogenic sulfate aerosols. Instead, we find coherent multidecadal variations involving the inferred AMOC and Atlantic major hurricane frequency, along with indices of Atlantic Multidecadal Variability and inverted vertical wind shear. Our results provide evidence for an important role of the AMOC in the recent decline of Atlantic major hurricane frequency.
Exocytosis-coordinated mechanisms for tip growth underlie pollen tube growth guidance
Authors: Luo Nan , Yan An , Liu Gang , Guo Jingzhe , Rong Duoyan , Kanaoka Masahiro M. , Xiao Zhen , Xu Guanshui , Higashiyama Tetsuya , Cui Xinping , Yang Zhenbiao 
Published: November 2017

AbstractMany tip-growing cells are capable of responding to guidance cues, during which cells precisely steer their growth toward the source of guidance signals. Though several players in signal perception have been identified, little is known about the downstream signaling that controls growth direction during guidance. Here, using combined modeling and experimental studies, we demonstrate that the growth guidance of Arabidopsis pollen tubes is regulated by the signaling network that controls tip growth. Tip-localized exocytosis plays a key role in this network by integrating guidance signals with the ROP1 Rho GTPase signaling and coordinating intracellular signaling with cell wall mechanics. This model reproduces the high robustness and responsiveness of pollen tube guidance and explains the connection between guidance efficiency and the parameters of the tip growth system. Hence, our findings establish an exocytosis-coordinated mechanism underlying the cellular pathfinding guided by signal gradients and the mechanistic linkage between tip growth and guidance.
Balancing a genetic toggle switch by real-time feedback control and periodic forcing
Authors: Lugagne Jean-Baptiste , Sosa Carrillo Sebastián , Kirch Melanie , Köhler Agnes , Batt Gregory , Hersen Pascal 
Published: November 2017

AbstractCybergenetics is a novel field of research aiming at remotely pilot cellular processes in real-time with to leverage the biotechnological potential of synthetic biology. Yet, the control of only a small number of genetic circuits has been tested so far. Here we investigate the control of multistable gene regulatory networks, which are ubiquitously found in nature and play critical roles in cell differentiation and decision-making. Using an in silico feedback control loop, we demonstrate that a bistable genetic toggle switch can be dynamically maintained near its unstable equilibrium position for extended periods of time. Importantly, we show that a direct method based on dual periodic forcing is sufficient to simultaneously maintain many cells in this undecided state. These findings pave the way for the control of more complex cell decision-making systems at both the single cell and the population levels, with vast fundamental and biotechnological applications.
Persistence and reversal of plasmid-mediated antibiotic resistance
Authors: Lopatkin Allison J. , Meredith Hannah R. , Srimani Jaydeep K. , Pfeiffer Connor , Durrett Rick , You Lingchong 
Published: November 2017

AbstractIn the absence of antibiotic-mediated selection, sensitive bacteria are expected to displace their resistant counterparts if resistance genes are costly. However, many resistance genes persist for long periods in the absence of antibiotics. Horizontal gene transfer (primarily conjugation) could explain this persistence, but it has been suggested that very high conjugation rates would be required. Here, we show that common conjugal plasmids, even when costly, are indeed transferred at sufficiently high rates to be maintained in the absence of antibiotics in Escherichia coli. The notion is applicable to nine plasmids from six major incompatibility groups and mixed populations carrying multiple plasmids. These results suggest that reducing antibiotic use alone is likely insufficient for reversing resistance. Therefore, combining conjugation inhibition and promoting plasmid loss would be an effective strategy to limit conjugation-assisted persistence of antibiotic resistance.
Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes
Authors: Ait-Bouziad Nadine , Lv Guohua , Mahul-Mellier Anne-Laure , Xiao Shifeng , Zorludemir Gizem , Eliezer David , Walz Thomas , Lashuel Hilal A. 
Published: November 2017

AbstractThe microtubule-associated protein Tau plays a central role in the pathogenesis of Alzheimer’s disease. Although Tau interaction with membranes is thought to affect some of its physiological functions and its aggregation properties, the sequence determinants and the structural and functional consequences of such interactions remain poorly understood. Here, we report that the interaction of Tau with vesicles results in the formation of highly stable protein/phospholipid complexes. These complexes are toxic to primary hippocampal cultures and are detected by MC-1, an antibody recognizing pathological Tau conformations. The core of these complexes is comprised of the PHF6* and PHF6 hexapeptide motifs, the latter in a β-strand conformation. Studies using Tau-derived peptides enabled the design of mutants that disrupt Tau interactions with phospholipids without interfering with its ability to form fibrils, thus providing powerful tools for uncoupling these processes and investigating the role of membrane interactions in regulating Tau function, aggregation and toxicity.
Non-universal transmission phase behaviour of a large quantum dot
Authors: Edlbauer Hermann , Takada Shintaro , Roussely Grégoire , Yamamoto Michihisa , Tarucha Seigo , Ludwig Arne , Wieck Andreas D. , Meunier Tristan , Bäuerle Christopher 
Published: November 2017

AbstractThe electron wave function experiences a phase modification at coherent transmission through a quantum dot. This transmission phase undergoes a characteristic shift of π when scanning through a Coulomb blockade resonance. Between successive resonances either a transmission phase lapse of π or a phase plateau is theoretically expected to occur depending on the parity of quantum dot states. Despite considerable experimental effort, this transmission phase behaviour has remained elusive for a large quantum dot. Here we report on transmission phase measurements across such a large quantum dot hosting hundreds of electrons. Scanning the transmission phase along 14 successive resonances with an original two-path interferometer, we observe both phase lapses and plateaus. We demonstrate that quantum dot deformation alters the sequence of phase lapses and plateaus via parity modifications of the involved quantum dot states. Our findings set a milestone towards an comprehensive understanding of the transmission phase of quantum dots.
Evolution of tribo-induced interfacial nanostructures governing superlubricity in a-C:H and a-C:H:Si films
Authors: Chen Xinchun , Zhang Chenhui , Kato Takahisa , Yang Xin-an , Wu Sudong , Wang Rong , Nosaka Masataka , Luo Jianbin 
Published: November 2017

AbstractHydrogenated amorphous carbon (a-C:H) is capable of providing a near-frictionless lubrication state when rubbed in dry sliding contacts. Nevertheless, the mechanisms governing superlubricity in a-C:H are still not well comprehended, mainly due to the lack of spatially resolved structural information of the buried contact surface. Here, we present structural analysis of the carbonaceous sliding interfaces at the atomic scale in two superlubricious solid lubricants, a-C:H and Si-doped a-C:H (a-C:H:Si), by probing the contact area using state-of-the-art scanning electron transmission microscopy and electron energy-loss spectroscopy. The results emphasize the diversity of superlubricity mechanisms in a-C:Hs. They suggest that the occurrence of a superlubricious state is generally dependent on the formation of interfacial nanostructures, mainly a tribolayer, by different carbon rehybridization pathways. The evolution of such anti-friction nanostructures highly depends on the contact mechanics and the counterpart material. These findings enable a more effective manipulation of superlubricity and developments of new carbon lubricants with robust lubrication properties.
Structural insights into substrate and inhibitor binding sites in human indoleamine 2,3-dioxygenase 1
Authors: Lewis-Ballester Ariel , Pham Khoa N. , Batabyal Dipanwita , Karkashon Shay , Bonanno Jeffrey B. , Poulos Thomas L. , Yeh Syun-Ru 
Published: November 2017

AbstractHuman indoleamine 2,3-dioxygenase 1 (hIDO1) is an attractive cancer immunotherapeutic target owing to its role in promoting tumoral immune escape. However, drug development has been hindered by limited structural information. Here, we report the crystal structures of hIDO1 in complex with its substrate, Trp, an inhibitor, epacadostat, and/or an effector, indole ethanol (IDE). The data reveal structural features of the active site (Sa) critical for substrate activation; in addition, they disclose a new inhibitor-binding mode and a distinct small molecule binding site (Si). Structure-guided mutation of a critical residue, F270, to glycine perturbs the Si site, allowing structural determination of an inhibitory complex, where both the Sa and Si sites are occupied by Trp. The Si site offers a novel target site for allosteric inhibitors and a molecular explanation for the previously baffling substrate-inhibition behavior of the enzyme. Taken together, the data open exciting new avenues for structure-based drug design.
Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes
Authors: Santos Ruda de Luna Almeida , Bai Lin , Singh Pradeep K. , Murakami Naoka , Fan Hao , Zhan Wenhu , Zhu Yingrong , Jiang Xiuju , Zhang Kaiming , Assker Jean Pierre , Nathan Carl F. , Li Huilin , Azzi Jamil , Lin Gang 
Published: November 2017

AbstractProteasome inhibitors benefit patients with multiple myeloma and B cell-dependent autoimmune disorders but exert toxicity from inhibition of proteasomes in other cells. Toxicity should be minimized by reversible inhibition of the immunoproteasome β5i subunit while sparing the constitutive β5c subunit. Here we report β5i-selective inhibition by asparagine-ethylenediamine (AsnEDA)-based compounds and present the high-resolution cryo-EM structural analysis of the human immunoproteasome. Despite inhibiting noncompetitively, an AsnEDA inhibitor binds the active site. Hydrophobic interactions are accompanied by hydrogen bonding with β5i and β6 subunits. The inhibitors are far more cytotoxic for myeloma and lymphoma cell lines than for hepatocarcinoma or non-activated lymphocytes. They block human B-cell proliferation and promote apoptotic cell death selectively in antibody-secreting B cells, and to a lesser extent in activated human T cells. Reversible, β5i-selective inhibitors may be useful for treatment of diseases involving activated or neoplastic B cells or activated T cells.
Widespread theta synchrony and high-frequency desynchronization underlies enhanced cognition
Authors: Solomon E. A. , Kragel J. E. , Sperling M. R. , Sharan A. , Worrell G. , Kucewicz M. , Inman C. S. , Lega B. , Davis K. A. , Stein J. M. , Jobst B. C. , Zaghloul K. A. , Sheth S. A. , Rizzuto D. S. , Kahana M. J. 
Published: November 2017

AbstractThe idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30–100 Hz) and slow theta (3–8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, gamma power rises as that region desynchronizes with gamma activity elsewhere in the brain, establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon of theta synchrony is positively correlated with a brain region’s gamma power, suggesting a predominant low-frequency mechanism for inter-regional communication.
Organic carbon burial in global lakes and reservoirs
Authors: Mendonça Raquel , Müller Roger A. , Clow David , Verpoorter Charles , Raymond Peter , Tranvik Lars J. , Sobek Sebastian 
Published: November 2017

AbstractBurial in sediments removes organic carbon (OC) from the short-term biosphere-atmosphere carbon (C) cycle, and therefore prevents greenhouse gas production in natural systems. Although OC burial in lakes and reservoirs is faster than in the ocean, the magnitude of inland water OC burial is not well constrained. Here we generate the first global-scale and regionally resolved estimate of modern OC burial in lakes and reservoirs, deriving from a comprehensive compilation of literature data. We coupled statistical models to inland water area inventories to estimate a yearly OC burial of 0.15 (range, 0.06–0.25) Pg C, of which ~40% is stored in reservoirs. Relatively higher OC burial rates are predicted for warm and dry regions. While we report lower burial than previously estimated, lake and reservoir OC burial corresponded to ~20% of their C emissions, making them an important C sink that is likely to increase with eutrophication and river damming.
Coupling of Polo kinase activation to nuclear localization by a bifunctional NLS is required during mitotic entry
Authors: Kachaner David , Garrido Damien , Mehsen Haytham , Normandin Karine , Lavoie Hugo , Archambault Vincent 
Published: November 2017

AbstractThe Polo kinase is a master regulator of mitosis and cytokinesis conserved from yeasts to humans. Polo is composed of an N-term kinase domain (KD) and a C-term polo-box domain (PBD), which regulates its subcellular localizations. The PBD and KD can interact and inhibit each other, and this reciprocal inhibition is relieved when Polo is phosphorylated at its activation loop. How Polo activation and localization are coupled during mitotic entry is unknown. Here we report that PBD binding to the KD masks a nuclear localization signal (NLS). Activating phosphorylation of the KD leads to exposure of the NLS and entry of Polo into the nucleus before nuclear envelope breakdown. Failures of this mechanism result in misregulation of the Cdk1-activating Cdc25 phosphatase and lead to mitotic and developmental defects in Drosophila. These results uncover spatiotemporal mechanisms linking master regulatory enzymes during mitotic entry.
The roles of photo-carrier doping and driving wavelength in high harmonic generation from a semiconductor
Authors: Wang Zhou , Park Hyunwook , Lai Yu Hang , Xu Junliang , Blaga Cosmin I. , Yang Fengyuan , Agostini Pierre , DiMauro Louis F. 
Published: November 2017

AbstractHigh-harmonic generation from gases produces attosecond bursts and enables high-harmonic spectroscopy to explore electron dynamics in atoms and molecules. Recently, high-harmonic generation from solids has been reported, resulting in novel phenomena and unique control of the emission, absent in gas-phase media. Here we investigate high harmonics from semiconductors with controllable induced photo-carrier densities, as well as the driving wavelengths. We demonstrate that the dominant generation mechanism can be identified by monitoring the variation of the harmonic spectra with the carrier density. Moreover, the harmonic spectral dependence on the driving wavelength is reported and a different dependence from the well-known one in gas-phase media is observed. Our study provides distinct control of the harmonic process from semiconductors, sheds light on the underlying mechanism and helps optimize the harmonic properties for future solid-state attosecond light sources.
Widely tunable black phosphorus mid-infrared photodetector
Authors: Chen Xiaolong , Lu Xiaobo , Deng Bingchen , Sinai Ofer , Shao Yuchuan , Li Cheng , Yuan Shaofan , Tran Vy , Watanabe Kenji , Taniguchi Takashi , Naveh Doron , Yang Li , Xia Fengnian 
Published: November 2017

AbstractLately rediscovered orthorhombic black phosphorus (BP) exhibits promising properties for near- and mid-infrared optoelectronics. Although recent electrical measurements indicate that a vertical electric field can effectively reduce its transport bandgap, the impact of the electric field on light-matter interaction remains unclear. Here we show that a vertical electric field can dynamically extend the photoresponse in a 5 nm-thick BP photodetector from 3.7 to beyond 7.7 μm, leveraging the Stark effect. We further demonstrate that such a widely tunable BP photodetector exhibits a peak extrinsic photo-responsivity of 518, 30, and 2.2 mA W−1 at 3.4, 5, and 7.7 μm, respectively, at 77 K. Furthermore, the extracted photo-carrier lifetime indicates a potential operational speed of 1.3 GHz. Our work not only demonstrates the potential of BP as an alternative mid-infrared material with broad optical tunability but also may enable the compact, integrated on-chip high-speed mid-infrared photodetectors, modulators, and spectrometers.
Overweight in patients with chronic obstructive pulmonary disease needs more attention: a cross-sectional study in general practice
Authors: Verberne Lisa D. M. , Leemrijse Chantal J. , Swinkels Ilse C. S. , van Dijk Christel E. , de Bakker Dinny H. , Nielen Mark M. J. 
Published: November 2017

AbstractGuidelines for management of chronic obstructive pulmonary disease (COPD) primarily focus on the prevention of weight loss, while overweight and obesity are highly prevalent in patients with milder stages of COPD. This cross-sectional study examines the association of overweight and obesity with the prevalence of comorbid disorders and prescribed medication for obstructive airway disease, in patients with mild to moderate COPD. Data were used from electronic health records of 380 Dutch general practices in 2014. In total, we identified 4938 patients with mild or moderate COPD based on spirometry data, and a recorded body mass index (BMI) of ≥21 kg/m2. Outcomes in overweight (BMI ≥ 25 and <30 kg/m2) and obese (BMI ≥30 kg/m2) patients with COPD were compared to those with a normal weight (BMI ≥ 21 and <25 kg/m2), by logistic multilevel analyses. Compared to COPD patients with a normal weight, positive associations were found for diabetes, osteoarthritis, and hypertension, for both overweight (OR: 1.4–1.7) and obese (OR: 2.4–3.8) patients, and for heart failure in obese patients (OR: 2.3). Osteoporosis was less prevalent in overweight (OR: 0.7) and obese (OR: 0.5) patients, and anxiety disorders in obese patients (OR: 0.5). No associations were found for coronary heart disease, stroke, sleep disturbance, depression, and pneumonia. Furthermore, obese patients were in general more often prescribed medication for obstructive airway disease compared to patients with a normal weight. The findings of this study underline the need to increase awareness in general practitioners for excess weight in patients with mild to moderate COPD.
Correlation between tunability and anisotropy in magnetoelectric voltage tunable inductor (VTI)
Authors: Yan Yongke , Geng Liwei D. , Zhang Lujie , Gao Xiangyu , Gollapudi Sreenivasulu , Song Hyun-Cheol , Dong Shuxiang , Sanghadasa Mohan , Ngo Khai , Wang Yu U. , Priya Shashank 
Published: November 2017

AbstractElectric field modulation of magnetic properties via magnetoelectric coupling in composite materials is of fundamental and technological importance for realizing tunable energy efficient electronics. Here we provide foundational analysis on magnetoelectric voltage tunable inductor (VTI) that exhibits extremely large inductance tunability of up to 1150% under moderate electric fields. This field dependence of inductance arises from the change of permeability, which correlates with the stress dependence of magnetic anisotropy. Through combination of analytical models that were validated by experimental results, comprehensive understanding of various anisotropies on the tunability of VTI is provided. Results indicate that inclusion of magnetic materials with low magnetocrystalline anisotropy is one of the most effective ways to achieve high VTI tunability. This study opens pathway towards design of tunable circuit components that exhibit field-dependent electronic behavior.