bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza‐induced lung Trm: not all memories last forever
Authors: Van Braeckel‐Budimir Natalija , Harty John T
Published: April 2017

In the light of new findings that lung tissue resident memory CD8+ T cells (Trm) represent major mediators of heterosubtypic immunity against influenza virus, it is of utmost importance to understand the basic biological mechanisms behind induction, formation and maintenance of this cell population. Addressing these important knowledge gaps will potentially inform development of superior, broadly protective influenza vaccines and new immunization strategies.
Cell-matrix adhesion and cell-cell adhesion differentially control basal myosin oscillation and Drosophila egg chamber elongation
Authors: Qin Xiang , Park Byung Ouk , Liu Jiaying , Chen Bing , Choesmel-Cadamuro Valerie , Belguise Karine , Heo Won Do , Wang Xiaobo
Published: April 2017

Pulsatile actomyosin contractility, important in tissue morphogenesis, has been studied mainly in apical but less in basal domains. Basal myosin oscillation underlying egg chamber elongation is regulated by both cell–matrix and cell–cell adhesions. However, the mechanism by which these two adhesions govern basal myosin oscillation and tissue elongation is unknown. Here we demonstrate that cell–matrix adhesion positively regulates basal junctional Rho1 activity and medio-basal ROCK and myosin activities, thus strongly controlling tissue elongation. Differently, cell–cell adhesion governs basal myosin oscillation through controlling medio-basal distributions of both ROCK and myosin signals, which are related to the spatial limitations of cell–matrix adhesion and stress fibres. Contrary to cell–matrix adhesion, cell–cell adhesion weakly affects tissue elongation. In vivo optogenetic protein inhibition spatiotemporally confirms the different effects of these two adhesions on basal myosin oscillation. This study highlights the activity and distribution controls of basal myosin contractility mediated by cell–matrix and cell–cell adhesions, respectively, during tissue morphogenesis.
Pathways for balancing CO2 emissions and sinks
Authors: Walsh Brian , Ciais Philippe , Janssens Ivan A. , Peñuelas Josep , Riahi Keywan , Rydzak Felicjan , van Vuuren Detlef P. , Obersteiner Michael
Published: April 2017

In December 2015 in Paris, leaders committed to achieve global, net decarbonization of human activities before 2100. This achievement would halt and even reverse anthropogenic climate change through the net removal of carbon from the atmosphere. However, the Paris documents contain few specific prescriptions for emissions mitigation, leaving various countries to pursue their own agendas. In this analysis, we project energy and land-use emissions mitigation pathways through 2100, subject to best-available parameterization of carbon-climate feedbacks and interdependencies. We find that, barring unforeseen and transformative technological advancement, anthropogenic emissions need to peak within the next 10 years, to maintain realistic pathways to meeting the COP21 emissions and warming targets. Fossil fuel consumption will probably need to be reduced below a quarter of primary energy supply by 2100 and the allowable consumption rate drops even further if negative emissions technologies remain technologically or economically unfeasible at the global scale.
Rapid population decline in migratory shorebirds relying on Yellow Sea tidal mudflats as stopover sites
Authors: Studds Colin E. , Kendall Bruce E. , Murray Nicholas J. , Wilson Howard B. , Rogers Danny I. , Clemens Robert S. , Gosbell Ken , Hassell Chris J. , Jessop Rosalind , Melville David S. , Milton David A. , Minton Clive D. T. , Possingham Hugh P. , Riegen Adrian C. , Straw Phil , Woehler Eric J. , Fuller Richard A.
Published: April 2017

Migratory animals are threatened by human-induced global change. However, little is known about how stopover habitat, essential for refuelling during migration, affects the population dynamics of migratory species. Using 20 years of continent-wide citizen science data, we assess population trends of ten shorebird taxa that refuel on Yellow Sea tidal mudflats, a threatened ecosystem that has shrunk by >65% in recent decades. Seven of the taxa declined at rates of up to 8% per year. Taxa with the greatest reliance on the Yellow Sea as a stopover site showed the greatest declines, whereas those that stop primarily in other regions had slowly declining or stable populations. Decline rate was unaffected by shared evolutionary history among taxa and was not predicted by migration distance, breeding range size, non-breeding location, generation time or body size. These results suggest that changes in stopover habitat can severely limit migratory populations.
Organic light emitting board for dynamic interactive display
Authors: Kim Eui Hyuk , Cho Sung Hwan , Lee Ju Han , Jeong Beomjin , Kim Richard Hahnkee , Yu Seunggun , Lee Tae-Woo , Shim Wooyoung , Park Cheolmin
Published: April 2017

Interactive displays involve the interfacing of a stimuli-responsive sensor with a visual human-readable response. Here, we describe a polymeric electroluminescence-based stimuli-responsive display method that simultaneously detects external stimuli and visualizes the stimulant object. This organic light-emitting board is capable of both sensing and direct visualization of a variety of conductive information. Simultaneous sensing and visualization of the conductive substance is achieved when the conductive object is coupled with the light emissive material layer on application of alternating current. A variety of conductive materials can be detected regardless of their work functions, and thus information written by a conductive pen is clearly visualized, as is a human fingerprint with natural conductivity. Furthermore, we demonstrate that integration of the organic light-emitting board with a fluidic channel readily allows for dynamic monitoring of metallic liquid flow through the channel, which may be suitable for biological detection and imaging applications.
Tunable transmission of quantum Hall edge channels with full degeneracy lifting in split-gated graphene devices
Authors: Zimmermann Katrin , Jordan Anna , Gay Frédéric , Watanabe Kenji , Taniguchi Takashi , Han Zheng , Bouchiat Vincent , Sellier Hermann , Sacépé Benjamin
Published: April 2017

Charge carriers in the quantum Hall regime propagate via one-dimensional conducting channels that form along the edges of a two-dimensional electron gas. Controlling their transmission through a gate-tunable constriction, also called quantum point contact, is fundamental for many coherent transport experiments. However, in graphene, tailoring a constriction with electrostatic gates remains challenging due to the formation of p–n junctions below gate electrodes along which electron and hole edge channels co-propagate and mix, short circuiting the constriction. Here we show that this electron–hole mixing is drastically reduced in high-mobility graphene van der Waals heterostructures thanks to the full degeneracy lifting of the Landau levels, enabling quantum point contact operation with full channel pinch-off. We demonstrate gate-tunable selective transmission of integer and fractional quantum Hall edge channels through the quantum point contact. This gate control of edge channels opens the door to quantum Hall interferometry and electron quantum optics experiments in the integer and fractional quantum Hall regimes of graphene.
Nanoscale interface confinement of ultrafast spin transfer torque driving non-uniform spin dynamics
Authors: Razdolski Ilya , Alekhin Alexandr , Ilin Nikita , Meyburg Jan P. , Roddatis Vladimir , Diesing Detlef , Bovensiepen Uwe , Melnikov Alexey
Published: April 2017

Spintronics had a widespread impact over the past decades due to transferring information by spin rather than electric currents. Its further development requires miniaturization and reduction of characteristic timescales of spin dynamics combining the sub-nanometre spatial and femtosecond temporal ranges. These demands shift the focus of interest towards the fundamental open question of the interaction of femtosecond spin current (SC) pulses with a ferromagnet (FM). The spatio-temporal properties of the impulsive spin transfer torque exerted by ultrashort SC pulses on the FM open the time domain for probing non-uniform magnetization dynamics. Here we employ laser-generated ultrashort SC pulses for driving ultrafast spin dynamics in FM and analysing its transient local source. Transverse spins injected into FM excite inhomogeneous high-frequency spin dynamics up to 0.6 THz, indicating that the perturbation of the FM magnetization is confined to 2 nm.
Single-molecule electrical contacts on silicon electrodes under ambient conditions
Authors: Aragonès Albert C. , Darwish Nadim , Ciampi Simone , Sanz Fausto , Gooding J. Justin , Díez-Pérez Ismael
Published: April 2017

The ultimate goal in molecular electronics is to use individual molecules as the active electronic component of a real-world sturdy device. For this concept to become reality, it will require the field of single-molecule electronics to shift towards the semiconducting platform of the current microelectronics industry. Here, we report silicon-based single-molecule contacts that are mechanically and electrically stable under ambient conditions. The single-molecule contacts are prepared on silicon electrodes using the scanning tunnelling microscopy break-junction approach using a top metallic probe. The molecular wires show remarkable current–voltage reproducibility, as compared to an open silicon/nano-gap/metal junction, with current rectification ratios exceeding 4,000 when a low-doped silicon is used. The extension of the single-molecule junction approach to a silicon substrate contributes to the next level of miniaturization of electronic components and it is anticipated it will pave the way to a new class of robust single-molecule circuits.
Correction: Corrigendum: DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs
Authors: Rossiello Francesca , Aguado Julio , Sepe Sara , Iannelli Fabio , Nguyen Quan , Pitchiaya Sethuramasundaram , Carninci Piero , d’Adda di Fagagna Fabrizio
Published: April 2017

Nature Communications 8: Article number: 13980 (2017); Published: 27 February 2017; Updated: 13 April 2017 In Supplementary Fig. 3d, the two columns of DAPI images associated with pATM and pS/TQ images were inadvertently swapped. The correct version of this figure appears below.
The microbiome of glaciers and ice sheets
Authors: Anesio Alexandre M. , Lutz Stefanie , Chrismas Nathan A. M. , Benning Liane G.
Published: April 2017

Glaciers and ice sheets, like other biomes, occupy a significant area of the planet and harbour biological communities with distinct interactions and feedbacks with their physical and chemical environment. In the case of the glacial biome, the biological processes are dominated almost exclusively by microbial communities. Habitats on glaciers and ice sheets with enough liquid water to sustain microbial activity include snow, surface ice, cryoconite holes, englacial systems and the interface between ice and overridden rock/soil. There is a remarkable similarity between the different specific glacial habitats across glaciers and ice sheets worldwide, particularly regarding their main primary producers and ecosystem engineers. At the surface, cyanobacteria dominate the carbon production in aquatic/sediment systems such as cryoconite holes, while eukaryotic Zygnematales and Chlamydomonadales dominate ice surfaces and snow dynamics, respectively. Microbially driven chemolithotrophic processes associated with sulphur and iron cycle and C transformations in subglacial ecosystems provide the basis for chemical transformations at the rock interface under the ice that underpin an important mechanism for the delivery of nutrients to downstream ecosystems. In this review, we focus on the main ecosystem engineers of glaciers and ice sheets and how they interact with their chemical and physical environment. We then discuss the implications of this microbial activity on the icy microbiome to the biogeochemistry of downstream ecosystems.
Mycobacterium tuberculosis Lineage Distribution in Xinjiang and Gansu Provinces, China
Authors: Chen Haixia , He Li , Huang Hairong , Shi Chengmin , Ni Xumin , Dai Guangming , Ma Liang , Li Weimin
Published: April 2017

Mycobacterium tuberculosis (M. tuberculosis) genotyping has dramatically improved the understanding of the epidemiology of tuberculosis (TB). In this study, 187 M. tuberculosis isolates from Xinjiang Uygur Autonomous Region (Xinjiang) and Gansu province in China were genotyped using large sequence polymorphisms (LSPs) and variable number tandem repeats (VNTR). Ten isolates, which represent major nodes of VNTR-based minimum spanning tree, were selected and subsequently subjected to multi-locus sequence analyses (MLSA) that include 82 genes. Based on a robust lineage assignment, we tested the association between lineages and clinical characteristics by logistic regression. There are three major lineages of M. tuberculosis prevalent in Xinjiang, viz. the East Asian Lineage 2 (42.1%; 56/133), the Euro-American Lineage 4 (33.1%; 44/133), and the Indian and East African Lineage 3 (24.8%; 33/133); two lineages prevalent in Gansu province, which are the Lineage 2 (87%; 47/54) and the Lineage 4 (13%; 7/54). The topological structures of the MLSA-based phylogeny support the LSP-based identification of M. tuberculosis lineages. The statistical results suggest an association between the Lineage 2 and the hemoptysis/bloody sputum symptom, fever in Uygur patients. The pathogenicity of the Lineage 2 remains to be further investigated.
Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines
Authors: Ahmed Mohaned , Basheer Haneen A. , Ayuso Jose M. , Ahmet Djevdet , Mazzini Marco , Patel Roshan , Shnyder Steven D. , Vinader Victoria , Afarinkia Kamyar
Published: April 2017

We describe a novel protocol to quantitatively and simultaneously compare the chemotactic responses of cells towards different chemokines. In this protocol, droplets of agarose gel containing different chemokines are applied onto the surface of a Petri dish, and then immersed under culture medium in which cells are suspended. As chemokine molecules diffuse away from the spot, a transient chemoattractant gradient is established across the spots. Cells expressing the corresponding cognate chemokine receptors migrate against this gradient by crawling under the agarose spots towards their centre. We show that this migration is chemokine-specific; meaning that only cells that express the cognate chemokine cell surface receptor, migrate under the spot containing its corresponding chemokine ligand. Furthermore, we show that migration under the agarose spot can be modulated by selective small molecule antagonists present in the cell culture medium.
Identification and Characterization of Differentially-Regulated Type IVb Pilin Genes Necessary for Predation in Obligate Bacterial Predators
Authors: Avidan Ofir , Petrenko Margarita , Becker René , Beck Sebastian , Linscheid Michael , Pietrokovski Shmuel , Jurkevitch Edouard
Published: April 2017

Bdellovibrio bacteriovorus is an obligate predator of bacteria that grows and divides within the periplasm of its prey. Functions involved in the early steps of predation have been identified and characterized, but mediators of prey invasion are still poorly detailed. By combining omics data available for Bdellovibrio and like organisms (BALO’s), we identified 43 genes expressed in B. bacteriovorus during the early interaction with prey. These included genes in a tight adherence (TAD) operon encoding for two type IVb fimbriae-like pilin proteins (flp1 and flp2), and their processing and export machinery. Two additional flp genes (flp3 and flp4) were computationally identified at other locations along the chromosome, defining the largest and most diverse type IVb complement known in bacteria to date. Only flp1, flp2 and flp4 were expressed; their respective gene knock-outs resulted in a complete loss of the predatory ability without losing the ability to adhere to prey cells. Additionally, we further demonstrate differential regulation of the flp genes as the TAD operon of BALOs with different predatory strategies is controlled by a flagellar sigma factor FliA, while flp4 is not. Finally, we show that FliA, a known flagellar transcriptional regulator in other bacteria, is an essential Bdellovibrio gene.
Disease biomarker identification from gene network modules for metastasized breast cancer
Authors: Sharma Pooja , Bhattacharyya Dhruba K. , Kalita Jugal
Published: April 2017

Advancement in science has tended to improve treatment of fatal diseases such as cancer. A major concern in the area is the spread of cancerous cells, technically refered to as metastasis into other organs beyond the primary organ. Treatment in such a stage of cancer is extremely difficult and usually palliative only. In this study, we focus on finding gene-gene network modules which are functionally similar in nature in the case of breast cancer. These modules extracted during the disease progression stages are analyzed using p-value and their associated pathways. We also explore interesting patterns associated with the causal genes, viz., SCGB1D2, MET, CYP1B1 and MMP9 in terms of expression similarity and pathway contexts. We analyze the genes involved in both the stages– non metastasis and metastatsis and change in their expression values, their associated pathways and roles as the disease progresses from one stage to another. We discover three additional pathways viz., Glycerophospholipid metablism, h-Efp pathway and CARM1 and Regulation of Estrogen Receptor, which can be related to the metastasis phase of breast cancer. These new pathways can be further explored to identify their relevance during the progression of the disease.
Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
Authors: Tokumoto Yasuhito , Tamaki Shinpei , Kabe Yasuaki , Takubo Keiyo , Suematsu Makoto
Published: April 2017

The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal. While adult OPCs develop from rapidly dividing perinatal OPCs, the mechanisms underlying their quiescence remain unknown. Here, we show that perinatal rodent OPCs cultured with thyroid hormone (TH) under hypoxia become quiescent and acquire adult OPCs-like characteristics. The cyclin-dependent kinase inhibitor p15/INK4b plays crucial roles in the TH-dependent cell cycle deceleration in OPCs under hypoxia. Klf9 is a direct target of TH-dependent signaling. Under hypoxic conditions, hypoxia-inducible factors mediates runt-related transcription factor 1 activity to induce G1 arrest in OPCs through enhancing TH-dependent p15/INK4b expression. As adult OPCs display phenotypes of adult somatic stem cells in the CNS, the current results shed light on environmental requirements for the quiescence of adult somatic stem cells during their development from actively proliferating stem/progenitor cells.
Psiguajadials A–K: Unusual Psidium Meroterpenoids as Phosphodiesterase-4 Inhibitors from the Leaves of Psidium guajava
Authors: Tang Gui-Hua , Dong Zhen , Guo Yan-Qiong , Cheng Zhong-Bin , Zhou Chu-Jun , Yin Sheng
Published: April 2017

Bioassay-guided fractionation of the ethanolic extract of the leaves of Psidium guajava led to the isolation of 11 new Psidium meroterpenoids, psiguajadials A–K (1–11), along with 17 known ones (12–28). Their structures and absolute configurations were elucidated by spectroscopic methods and comparison of experimental and calculated ECD. Compounds 1 and 2 represent two unprecedented skeletons of 3,5-diformyl-benzyl phloroglucinol-coupled sesquiterpenoid, while 3 is the first example of Psidium meroterpenoids coupling via an oxepane ring. Putative biosynthetic pathways towards 1 and 2 are proposed. Compounds 1–13 and 16–26 exhibited moderate inhibitory activities against phosphodiesterase-4 (PDE4), a drug target for asthma and chronic obstructive pulmonary disease, with IC50 values in the range of 1.34–7.26 μM.
Structural and functional analysis of lysozyme after treatment with dielectric barrier discharge plasma and atmospheric pressure plasma jet
Authors: Choi Sooho , Attri Pankaj , Lee Inhwan , Oh Jeongmin , Yun Ji-Hye , Park Ji Hoon , Choi Eun Ha , Lee Weontae
Published: April 2017

The variation in the biological function of proteins plays an important role in plasma medicine and sterilization. Several non-thermal plasma sources with different feeding gases are used worldwide for plasma treatment, including dielectric barrier discharge (DBD) and atmospheric-pressure plasma jet (APPJ) as the most commonly used sources. Therefore, in the present work, we used both DBD and APPJ plasma sources with N2 and air as feeding gases to evaluate the effects on the structural, thermodynamic, and activity changes of enzymes. In the current work, we used lysozyme as a model enzyme and verified the structural changes using circular dichroism (CD), fluorescence, and X-ray crystallography. In addition, we investigated the lysozyme thermodynamics using CD thermal analysis and changes in the B-factor from X-ray crystallography. The results showed that lysozyme activity decreased after the plasma treatment. From these analyses, we concluded that N2-feeding gas plasma disturbs the structure and activity of lysozyme more than Air feeding gas plasma in our experimental studies. This study provides novel fundamental information on the changes to enzymes upon plasma treatment, which has been absent from the literature until now.
Refractive index tomograms and dynamic membrane fluctuations of red blood cells from patients with diabetes mellitus
Authors: Lee SangYun , Park HyunJoo , Kim Kyoohyun , Sohn YongHak , Jang Seongsoo , Park YongKeun
Published: April 2017

In this paper, we present the optical characterisations of diabetic red blood cells (RBCs) in a non-invasive manner employing three-dimensional (3-D) quantitative phase imaging. By measuring 3-D refractive index tomograms and 2-D time-series phase images, the morphological (volume, surface area and sphericity), biochemical (haemoglobin concentration and content) and mechanical (membrane fluctuation) parameters were quantitatively retrieved at the individual cell level. With simultaneous measurements of individual cell properties, systematic correlative analyses on retrieved RBC parameters were also performed. Our measurements show there exist no statistically significant alterations in morphological and biochemical parameters of diabetic RBCs, compared to those of healthy (non-diabetic) RBCs. In contrast, membrane deformability of diabetic RBCs is significantly lower than that of healthy, non-diabetic RBCs. Interestingly, non-diabetic RBCs exhibit strong correlations between the elevated glycated haemoglobin in RBC cytoplasm and decreased cell deformability, whereas diabetic RBCs do not show correlations. Our observations strongly support the idea that slow and irreversible glycation of haemoglobin and membrane proteins of RBCs by hyperglycaemia significantly compromises RBC deformability in diabetic patients.
Chemical and Electrochemical Synthesis of Platinum Black
Authors: Stanca S. E. , Hänschke F. , Ihring A. , Zieger G. , Dellith J. , Kessler E. , Meyer H.-G.
Published: April 2017

We present electrochemical and chemical synthesis of platinum black at room temperature in aqueous and non-aqueous media. X-ray analysis established the purity and crystalline nature. The electron micrographs indicate that the nanostructures consist of platinum crystals that interconnect to form porous assemblies. Additionally, the electron micrographs of the platinum black thin layer, which was electrochemically deposited on different metallic and semiconductive substrates (aluminium, platinum, silver, gold, tin-cooper alloy, indium-tin-oxide, stainless steel, and copper), indicate that the substrate influences its porous features but not its absorbance characteristics. The platinum black exhibited a broad absorbance and low reflectance in the ultraviolet, visible, and infrared regions. These characteristics make this material suitable for use as a high-temperature resistant absorber layer for the fabrication of microelectronics.
Crispr/Cas9 Mediated Inactivation of Argonaute 2 Reveals its Differential Involvement in Antiviral Responses
Authors: Ludman Márta , Burgyán József , Fátyol Károly
Published: April 2017

RNA silencing constitutes an important antiviral mechanism in plants. Small RNA guided Argonaute proteins fulfill essential role in this process by acting as executors of viral restriction. Plants encode multiple Argonaute proteins of which several exhibit antiviral activities. A recent addition to this group is AGO2. Its involvement in antiviral responses is established predominantly by studies employing mutants of Arabidopsis thaliana. In the virological model plant, Nicotiana benthamiana, the contribution of AGO2 to antiviral immunity is much less certain due to the lack of appropriate genetic mutants. Previous studies employed various RNAi based tools to down-regulate AGO2 expression. However, these techniques have several disadvantages, especially in the context of antiviral RNA silencing. Here, we have utilized the CRISPR/Cas9 technology to inactivate the AGO2 gene of N. benthamiana. The ago2 plants exhibit differential sensitivities towards various viruses. AGO2 is a critical component of the plants’ immune responses against PVX, TuMV and TCV. In contrast, AGO2 deficiency does not significantly influence the progression of tombusvirus and CMV infections. In summary, our work provides unequivocal proof for the virus-specific antiviral role of AGO2 in a plant species other than A. thaliana for the first time.
Nontrivial nonradiating all-dielectric anapole
Authors: Nemkov Nikita A. , Stenishchev Ivan V. , Basharin Alexey A.
Published: April 2017

Dynamic anapole is a promising element for future nonradiating devices, such as cloaked sources and sensors, quantum emitters, and especially the sources for observing dynamic Aharonov-Bohm effect. However, the anapole response can be damped by the Joule losses. In this paper we theoretically propose and experimentally demonstrate a novel type of active all-dielectric source, which is in some sense, realizes the elementary anapole of Afanasiev, and study its radiative/nonradiative regimes in the microwave range.
Optimization of amino acid replacement costs by mutational pressure in bacterial genomes
Authors: Błażej Paweł , Mackiewicz Dorota , Grabińska Małgorzata , Wnętrzak Małgorzata , Mackiewicz Paweł
Published: April 2017

Mutations are considered a spontaneous and random process, which is important component of evolution because it generates genetic variation. On the other hand, mutations are deleterious leading to non-functional genes and energetically costly repairs. Therefore, one can expect that the mutational pressure is optimized to simultaneously generate genetic diversity and preserve genetic information. To check if empirical mutational pressures are optimized in these ways, we compared matrices of nucleotide mutation rates derived from bacterial genomes with their best possible alternatives that minimized or maximized costs of amino acid replacements associated with differences in their physicochemical properties (e.g. hydropathy and polarity). It should be noted that the studied empirical nucleotide substitution matrices and the costs of amino acid replacements are independent because these matrices were derived from sites free of selection on amino acid properties and the amino acid costs assumed only amino acid physicochemical properties without any information about mutation at the nucleotide level. Obtained results indicate that the empirical mutational matrices show a tendency to minimize costs of amino acid replacements. It implies that bacterial mutational pressures can evolve to decrease consequences of amino acid substitutions. However, the optimization is not full, which enables generation of some genetic variability.
Role of the Ion Channel Extracellular Collar in AMPA Receptor Gating
Authors: Yelshanskaya Maria V. , Mesbahi-Vasey Samaneh , Kurnikova Maria G. , Sobolevsky Alexander I.
Published: April 2017

AMPA subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission and are implicated in numerous neurological diseases. Ionic currents through AMPA receptor channels can be allosterically regulated via different sites on the receptor protein. We used site-directed mutagenesis and patch-clamp recordings to probe the ion channel extracellular collar, the binding region for noncompetitive allosteric inhibitors. We found position and substitution-dependent effects for introduced mutations at this region on AMPA receptor gating. The results of mutagenesis suggested that the transmembrane domains M1, M3 and M4, which contribute to the ion channel extracellular collar, undergo significant relative displacement during gating. We used molecular dynamics simulations to predict an AMPA receptor open state structure and rationalize the results of mutagenesis. We conclude that the ion channel extracellular collar plays a distinct role in gating and represents a hub for powerful allosteric modulation of AMPA receptor function that can be used for developing novel therapeutics.
Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction
Authors: Giorgi-Coll Susan , Amaral Ana I. , Hutchinson Peter J. A. , Kotter Mark R. , Carpenter Keri L. H.
Published: April 2017

Mitochondrial dysfunction, the inability to efficiently utilise metabolic fuels and oxygen, contributes to pathological changes following traumatic spinal cord or traumatic brain injury (TBI). In the present study, we tested the hypothesis that succinate supplementation can improve cellular energy state under metabolically stressed conditions in a robust, reductionist in vitro model of mitochondrial dysfunction in which primary mixed glial cultures (astrocytes, microglia and oligodendrocytes) were exposed to the mitochondrial complex I inhibitor rotenone. Cellular response was determined by measuring intracellular ATP, extracellular metabolites (glucose, lactate, pyruvate), and oxygen consumption rate (OCR). Rotenone produced no significant changes in glial ATP levels. However, it induced metabolic deficits as evidenced by lactate/pyruvate ratio (LPR) elevation (a clinically-established biomarker for poor outcome in TBI) and decrease in OCR. Succinate addition partially ameliorated these metabolic deficits. We conclude that succinate can improve glial oxidative metabolism, consistent our previous findings in TBI patients’ brains. The mixed glial cellular model may be useful in developing therapeutic strategies for conditions involving mitochondrial dysfunction, such as TBI.
How visual experience impacts the internal and external spatial mapping of sensorimotor functions
Authors: Crollen Virginie , Albouy Geneviève , Lepore Franco , Collignon Olivier
Published: April 2017

Tactile perception and motor production share the use of internally- and externally-defined coordinates. In order to examine how visual experience affects the internal/external coding of space for touch and movement, early blind (EB) and sighted controls (SC) took part in two experiments. In experiment 1, participants were required to perform a Temporal Order Judgment task (TOJ), either with their hands in parallel or crossed over the body midline. Confirming previous demonstration, crossing the hands led to a significant decrement in performance in SC but did not affect EB. In experiment 2, participants were trained to perform a sequence of five-finger movements. They were tested on their ability to produce, with the same hand but with the keypad turned upside down, the learned (internal) or the mirror (external) sequence. We observed significant transfer of motor sequence knowledge in both EB and SC irrespective of whether the representation of the sequence was internal or external. Together, these results demonstrate that visual experience differentially impacts the automatic weight attributed to internal versus external coordinates depending on task-specific spatial requirements.
Efficacy of alprostadil for preventing of contrast-induced nephropathy: A meta-analysis
Authors: Zhang Jing-Zhan , Kang Xiao-Jing , Gao Ying , Zheng Ying-Ying , Wu Ting-Ting , Li Long , Liu Fen , Yang Yi-Ning , Li Xiao-Mei , Ma Yi-Tong , Xie Xiang
Published: April 2017

Contrast-induced nephropathy (CIN) has become the third-leading cause of hospital-acquired acute renal injury. Although alprostadil has been proposed as an effective preventative measure, this conclusion remains inconsistent. Thus, we performed a meta-analysis of the published studies on this topic to evaluate the preventative effect of alprostadil on CIN. Databases, including PubMed, the Web of Science, Cochrane Library, Wanfang, the China Biological Medicine Database (SinoMed) and the China National Knowledge Infrastructure (CNKI) were systematically searched. Nineteen clinical trials involving 2267 individuals were identified. We utilized a random or a fixed effect model to calculate the pooled odd ratios (ORs) and the standardized mean differences (SMD), respectively. Compared to the control group, the CIN risk decreased significantly in the alprostadil group (P < 0.00001, OR = 0.29, 95% CI = 0.21–0.39). In the subgroup of coronary angiography patients, the use of alprostadil also decreased the risk of CIN (P < 0.00001, OR = 0.27, 95% CI: 0.19–0.39). In conclusion, Alprostadil might be associated with a significant reduction in postcontrast Scr, BUN and CysC level and decrease the incidence of CIN.
Regulation of viral gene expression by duck enteritis virus UL54
Authors: Liu Chaoyue , Cheng Anchun , Wang Mingshu , Chen Shun , Jia Renyong , Zhu Dekang , Liu Mafeng , Sun Kunfeng , Yang Qiao , Wu Ying , Zhao Xinxin , Chen Xiaoyue
Published: April 2017

Duck enteritis virus (DEV) UL54 is a homologue of human herpes simplex virus-1 (HSV-1) ICP27, which plays essential regulatory roles during infection. Our previous studies indicated that DEV UL54 is an immediate-early protein that can shuttle between the nucleus and the cytoplasm. In the present study, we found that UL54-deleted DEV (DEV-ΔUL54) exhibits growth kinetics, a plaque size and a viral DNA copy number that are significantly different from those of its parent wild-type virus (DEV-LoxP) and the revertant (DEV-ΔUL54 (Revertant)). Relative viral mRNA levels, reflecting gene expression, the transcription phase and the translation stage, are also significantly different between DEV-ΔUL54-infected cells and DEV-LoxP/DEV-ΔUL54 (Revertant)-infected cells. However, the localization pattern of UL30 mRNA is obviously changed in DEV-ΔUL54-infected cells. These findings suggest that DEV UL54 is important for virus growth and may regulate viral gene expression during transcription, mRNA export and translation.
Differential sensitivity to infections and antimicrobial peptide-mediated immune response in four silkworm strains with different geographical origin
Authors: Romoli Ottavia , Saviane Alessio , Bozzato Andrea , D’Antona Paola , Tettamanti Gianluca , Squartini Andrea , Cappellozza Silvia , Sandrelli Federica
Published: April 2017

The domesticated silkworm Bombyx mori has an innate immune system, whose main effectors are the antimicrobial peptides (AMPs). Silkworm strains are commonly grouped into four geographical types (Japanese, Chinese, European and Tropical) and are generally characterised by a variable susceptibility to infections. To clarify the genetic and molecular mechanisms on which the different responses to infections are based, we exposed one silkworm strain for each geographical area to oral infections with the silkworm pathogens Enterococcus mundtii or Serratia marcescens. We detected a differential susceptibility to both bacteria, with the European strain displaying the lowest sensitivity to E. mundtii and the Indian one to S. marcescens. We found that all the strains were able to activate the AMP response against E. mundtii. However, the highest tolerance of the European strain appeared to be related to the specific composition of its AMP cocktail, containing more effective variants such as a peculiar Cecropin B6 isoform. The resistance of the Indian strain to S. marcescens seemed to be associated with its prompt capability to activate the systemic transcription of AMPs. These data suggest that B. mori strains with distinct genetic backgrounds employ different strategies to counteract bacterial infections, whose efficacy appears to be pathogen-dependent.
Low-cost, Low-bias and Low-input RNA-seq with High Experimental Verifiability based on Semiconductor Sequencing
Authors: Mai Zhibiao , Xiao Chuanle , Jin Jingjie , Zhang Gong
Published: April 2017

Low-input RNA-seq is powerful to represent the gene expression profiles with limited number of cells, especially when single-cell variations are not the aim. However, pre-amplification-based and molecule index-based library construction methods boost bias or require higher throughput. Here we demonstrate a simple, low-cost, low-bias and low-input RNA-seq with ion torrent semiconductor sequencing (LIEA RNA-seq). We also developed highly accurate and error-tolerant spliced mapping algorithm FANSe2splice to accurately map the single-ended reads to the reference genome with better experimental verifiability than the previous spliced mappers. Combining the experimental and computational advancements, our solution is comparable with the bulk mRNA-seq in quantification, reliably detects splice junctions and minimizes the bias with much less mappable reads.
COX-1/PGE2/EP4 alleviates mucosal injury by upregulating β-arr1-mediated Akt signaling in colitis
Authors: Peng Xiaojie , Li Jianzhong , Tan Siwei , Xu Minyi , Tao Jin , Jiang Jie , Liu Huiling , Wu Bin
Published: April 2017

COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). β-arrestin1 (β-arr1), which acts as a scaffold protein, is involved in PGE2-mediated signaling pathways. However, the interaction between PGE2 and β-arr1 in maintaining mucosal barrier integrity remains unexplored. In this study, we demonstrated that COX-1 and PGE2 were significantly decreased, and EP4 mRNA was downregulated in both UC patients and mice during the injury phase. PGE2 treatment was found to alleviate mucosal injury and induce EP4 expression during dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) mice. Following DSS-induced injury, β-arr1 deficient mice showed increased signs of colitis compared to β-arr1 WT mice, and the expression of PI3K and p-Akt were remarkably downregulated in β-arr1 deficient mice. In parallel, HCT116 cells transfected with β-arr1 siRNA were examined in the presence or absence of PGE2in vitro. PGE2 treatment in the β-arr1 WT/KO DSS model and β-arr1 siRNA transfection of HCT116 cells confirmed that PGE2 upregulated β-arr1 in vivo and in vitro. Collectively, our results indicate that COX-1/PGE2/EP4 upregulates the β-arr1 mediated Akt signaling pathway to provide mucosal protection in colitis. Thus, these findings provide support for the future development and clinical application of COX-1/PGE2 in UC.
Enhancing the throughput and multiplexing capabilities of next generation sequencing for efficient implementation of pooled shRNA and CRISPR screens
Authors: Islam Md. Fahmid , Watanabe Atsushi , Wong Lai , Lazarou Conor , Vizeacoumar Frederick S. , Abuhussein Omar , Hill Wayne , Uppalapati Maruti , Geyer C. Ronald , Vizeacoumar Franco J.
Published: April 2017

Next generation sequencing is becoming the method of choice for functional genomic studies that use pooled shRNA or CRISPR libraries. A key challenge in sequencing these mixed-oligo libraries is that they are highly susceptible to hairpin and/or heteroduplex formation. This results in polyclonal, low quality, and incomplete reads and reduces sequencing throughput. Unfortunately, this challenge is significantly magnified in low-to-medium throughput bench-top sequencers as failed reads significantly perturb the maximization of sequence coverage and multiplexing capabilities. Here, we report a methodology that can be adapted to maximize the coverage on a bench-top, Ion PGM System for smaller shRNA libraries with high efficiency. This ligation-based, half-shRNA sequencing strategy minimizes failed sequences and is also equally amenable to high-throughput sequencers for increased multiplexing. Towards this, we also demonstrate that our strategy to reduce heteroduplex formation improves multiplexing capabilities of pooled CRISPR screens using Illumina NextSeq 500. Overall, our method will facilitate sequencing of pooled shRNA or CRISPR libraries from genomic DNA and maximize sequence coverage.
A novel mechanism linking memory stem cells with innate immunity in protection against HIV-1 infection
Authors: Wang Yufei , Whittall Trevor , Neil Stuart , Britton Gary , Mistry Mukesh , Rerks-Ngarm Supachai , Pitisuttithum Punnee , Kaewkungwal Jaranit , Nitayaphan Sorachai , Yu Xuesong , Sato Alicia , O’Connell Robert J. , Michael Nelson L. , Robb Merlin L. , Kim Jerome H. , Lehner Thomas
Published: April 2017

HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4+ T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated. In contrast, CD4+ TSCM cells expressing CCR5 co-receptors and α4β7 mucosal homing integrins were decreased. A parallel increase in CD4+ T cells was recorded with IL-15 receptors, APOBEC3G and CC chemokines, the latter downmodulating CCR5 molecules. We suggest a novel mechanism of dual memory stem cells; the established sequential memory pathway, TSCM →Central →Effector memory CD4+ T cells and the innate pathway consisting of the 4 subsets of TSCM. Both pathways are likely to be activated by endogenous HSP70. The TSCM memory stem cell and innate immunity pathways have to be optimised to boost the efficacy and immune memory of protection against HIV-1 in the clinical trial.
Formation of CuO nano-flowered surfaces via submerged photo-synthesis of crystallites and their antimicrobial activity
Authors: Nishino Fumika , Jeem Melbert , Zhang Lihua , Okamoto Kazumasa , Okabe Satoshi , Watanabe Seiichi
Published: April 2017

We report the fabrication of flower-like CuO nanostructured surfaces via submerged photo-synthesis of crystallites (SPSC), which requires only UV illumination in neutral water. In this paper, we discuss the reaction mechanism of the photochemical formation of the SPSC-fabricated CuO nanostructures in detail based on surface microstructural analyses and a radiation-chemical consideration with additional gamma-ray irradiation. Since the SPSC method for surface nanostructural fabrication can work at low temperatures at atmospheric pressure without using harmful substances, it is a potential fabrication method for green nanotechnology applications. In this vein, the antibacterial activity of the nano-flowered CuO surfaces was tested against Gram-positive (Staphylococcus aureus) bacteria and Gram-negative (Escherichia coli K12) bacteria, and the results demonstrate that the nano-flowered CuO nanostructures act as an effective antimicrobial agent.
Simple Rectangular Gratings as a Near-Field “Anti-Reflection” Pattern for GaSb TPV Cells
Authors: Yu Haitong , Liu Dong , Yang Zhen , Duan Yuanyuan
Published: April 2017

We show theoretically that 2D rectangular gratings on the surface of GaSb can serve as an “anti-reflection” pattern for nano-gap thermophotovoltaic (TPV) devices, which significantly enhances near-field radiative flux from the emitter to a GaSb cell, thus improving output power and conversion efficiency. The system in this study is a 200-nm gap TPV power generation system with a planar infrared plasmonic emitter and GaSb cell. Rigorous coupled-wave analysis is used to calculate the spectral near-field radiative flux involving periodic structures. The simulation shows that when coupled with a near-infrared plasmonic bulk emitter, adding gratings on the GaSb cell surface results in strong spectral enhancement above the cell’s bandgap and suppression for low-energy photon transmission, an effect that cannot be fully predicted by the effective medium theory. The resultant peak spectral heat flux is 2.8 times as high as the case without surface structures and the radiative transfer efficiency increased to 24.8% from the original 14.5% with the emitter temperature at 1800 K. The influence of the grating’s geometry parameters on the enhancement and peak frequency is further discussed with rigorous calculation of the spatial distribution of thermal radiative transfer that provided insight into the physical mechanism.
Functionally interchangeable cis-acting RNA elements in both genome segments of a picorna-like plant virus
Authors: Guo Jiangbo , Han Junping , Lin Junyan , Finer John , Dorrance Anne , Qu Feng
Published: April 2017

Cis-acting RNA structures in the genomes of RNA viruses play critical roles in viral infection, yet their importance in the bipartite genomes of the picorna-like, plant-infecting comoviruses has not been carefully investigated. We previously characterized SLC, a stem-loop structure in the 5′ untranslated region (UTR) of the bean pod mottle comovirus (BPMV) RNA2, and found it to be essential for RNA2 accumulation in infected cells. Here we report the identification of SL1, a similar cis-acting element in the other BPMV genome segment - RNA1. SL1 encompasses a portion of RNA1 5′ UTR but extends into the coding sequence for nine nucleotides, thus was missed in the previous study. While the stems of SL1 and SLC share little sequence similarity, their end loops are of the same size and identical for 11 of 15 nucleotides. Importantly, SL1 and SLC are functionally interchangeable, and separate exchanges of the stem and loop portions were likewise well tolerated. By contrast, the conserved loop sequence tolerated minimal perturbations. Finally, stem-loop structures with similar configurations were identified in two other comoviruses. Therefore, SL1 and SLC are likely essential comoviral RNA structures that play a conserved function in viral infection cycles.