bluuebunny/crossref_metadata_2025 huggingface dataset:
The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance
Authors: Gautheron Jérémie , Vucur Mihael , Schneider Anne T. , Severi Ilenia , Roderburg Christoph , Roy Sanchari , Bartneck Matthias , Schrammen Peter , Diaz Mauricio Berriel , Ehling Josef , Gremse Felix , Heymann Felix , Koppe Christiane , Lammers Twan , Kiessling Fabian , Van Best Niels , Pabst Oliver , Courtois Gilles , Linkermann Andreas , Krautwald Stefan , Neumann Ulf P. , Tacke Frank , Trautwein Christian , Green Douglas R. , Longerich Thomas , Frey Norbert , Luedde Mark , Bluher Matthias , Herzig Stephan , Heikenwalder Mathias , Luedde Tom
Published: June 2016

Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients.
Loss-tolerant state engineering for quantum-enhanced metrology via the reverse Hong–Ou–Mandel effect
Authors: Ulanov Alexander E. , Fedorov Ilya A. , Sychev Demid , Grangier Philippe , Lvovsky A. I.
Published: June 2016

Highly entangled quantum states, shared by remote parties, are vital for quantum communications and metrology. Particularly promising are the N00N states—entangled N-photon wavepackets delocalized between two different locations—which outperform coherent states in measurement sensitivity. However, these states are notoriously vulnerable to losses, making them difficult to both share them between remote locations and recombine in order to exploit interference effects. Here we address this challenge by utilizing the reverse Hong–Ou–Mandel effect to prepare a high-fidelity two-photon N00N state shared between two parties connected by a lossy optical medium. We measure the prepared state by two-mode homodyne tomography, thereby demonstrating that the enhanced phase sensitivity can be exploited without recombining the two parts of the N00N state. Finally, we demonstrate the application of our method to remotely prepare superpositions of coherent states, known as Schrödinger’s cat states.
Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies
Authors: Rennert Robert C. , Januszyk Michael , Sorkin Michael , Rodrigues Melanie , Maan Zeshaan N. , Duscher Dominik , Whittam Alexander J. , Kosaraju Revanth , Chung Michael T. , Paik Kevin , Li Alexander Y. , Findlay Michael , Glotzbach Jason P. , Butte Atul J. , Gurtner Geoffrey C.
Published: June 2016

Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles. We establish the usefulness of this platform in costly and highly morbid diabetic wounds by identifying a subpopulation of progenitor cells that is dysfunctional in the diabetic state, and normalizes diabetic wound healing rates following allogeneic application. We believe this work presents a logical framework for the development of targeted cell therapies that can be customized to any clinical application.
Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration
Authors: Brinkman C. Colin , Iwami Daiki , Hritzo Molly K. , Xiong Yanbao , Ahmad Sarwat , Simon Thomas , Hippen Keli L. , Blazar Bruce R. , Bromberg Jonathan S.
Published: June 2016

Regulatory T cells (Tregs) are essential to suppress unwanted immunity or inflammation. After islet allo-transplant Tregs must migrate from blood to allograft, then via afferent lymphatics to draining LN to protect allografts. Here we show that Tregs but not non-Treg T cells use lymphotoxin (LT) during migration from allograft to draining LN, and that LT deficiency or blockade prevents normal migration and allograft protection. Treg LTαβ rapidly modulates cytoskeletal and membrane structure of lymphatic endothelial cells; dependent on VCAM-1 and non-canonical NFκB signalling via LTβR. These results demonstrate a form of T-cell migration used only by Treg in tissues that serves an important role in their suppressive function and is a unique therapeutic focus for modulating suppression.
Correction: Corrigendum: Mechanical slowing-down of cytoplasmic diffusion allows in vivo counting of proteins in individual cells
Authors: Okumus Burak , Landgraf Dirk , Lai Ghee Chuan , Bakshi Somenath , Arias-Castro Juan Carlos , Yildiz Sadik , Huh Dann , Fernandez-Lopez Raul , Peterson Celeste N. , Toprak Erdal , El Karoui Meriem , Paulsson Johan
Published: June 2016

Nature Communications 7: Article number: 11641 (2016); Published: 18 May 2016; Updated: 24 June 2016. The original version of this Article contained an error in the spelling of the author Somenath Bakshi, which was incorrectly given as Somenath Bakhsi. This has now been corrected in both the PDF andHTML versions of the Article.
A foraminiferal δ18O record covering the last 2,200 years
Authors: Taricco Carla , Alessio Silvia , Rubinetti Sara , Vivaldo Gianna , Mancuso Salvatore
Published: June 2016

Thanks to the precise core dating and the high sedimentation rate of the drilling site (Gallipoli Terrace, Ionian Sea) we were able to measure a foraminiferal δ18O series covering the last 2,200 years with a time resolution shorter than 4 years. In order to support the quality of this data-set we link the δ18O values measured in the foraminifera shells to temperature and salinity measurements available for the last thirty years covered by the core. Moreover, we describe in detail the dating procedures based on the presence of volcanic markers along the core and on the measurement of 210Pb and 137Cs activity in the most recent sediment layers. The high time resolution allows for detecting a δ18O decennial-scale oscillation, together with centennial and multicentennial components. Due to the dependence of foraminiferal δ18O on environmental conditions, these oscillations can provide information about temperature and salinity variations in past millennia. The strategic location of the drilling area makes this record a unique tool for climate and oceanographic studies of the Central Mediterranean.
The brain imaging data structure, a format for organizing and describing outputs of neuroimaging experiments
Authors: Gorgolewski Krzysztof J. , Auer Tibor , Calhoun Vince D. , Craddock R. Cameron , Das Samir , Duff Eugene P. , Flandin Guillaume , Ghosh Satrajit S. , Glatard Tristan , Halchenko Yaroslav O. , Handwerker Daniel A. , Hanke Michael , Keator David , Li Xiangrui , Michael Zachary , Maumet Camille , Nichols B. Nolan , Nichols Thomas E. , Pellman John , Poline Jean-Baptiste , Rokem Ariel , Schaefer Gunnar , Sochat Vanessa , Triplett William , Turner Jessica A. , Varoquaux Gaël , Poldrack Russell A.
Published: June 2016

The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this problem, we have developed the Brain Imaging Data Structure (BIDS), a standard for organizing and describing MRI datasets. The BIDS standard uses file formats compatible with existing software, unifies the majority of practices already common in the field, and captures the metadata necessary for most common data processing operations.
A collection of intrinsic disorder characterizations from eukaryotic proteomes
Authors: Vincent Michael , Schnell Santiago
Published: June 2016

Intrinsically disordered proteins and protein regions lack a stable three-dimensional structure under physiological conditions. Several proteomic investigations of intrinsic disorder have been performed to date and have found disorder to be prevalent in eukaryotic proteomes. Here we present descriptive statistics of intrinsic disorder features for ten model eukaryotic proteomes that have been calculated from computational disorder prediction algorithms. The data descriptor also provides consensus disorder annotations as well as additional physical parameters relevant to protein disorder, and further provides protein existence information for all proteins included in our analysis. The complete datasets can be downloaded freely, and it is envisaged that they will be updated periodically with new proteomes and protein disorder prediction algorithms. These datasets will be especially useful for assessing protein disorder, and conducting novel analyses that advance our understanding of intrinsic disorder and protein structure.
Experimental and Theoretical Investigation of Multispecies Oral Biofilm Resistance to Chlorhexidine Treatment
Authors: Shen Ya , Zhao Jia , de la Fuente-Núñez César , Wang Zhejun , Hancock Robert E. W. , Roberts Clive R. , Ma Jingzhi , Li Jun , Haapasalo Markus , Wang Qi
Published: June 2016

We investigate recovery of multispecies oral biofilms following chlorhexidine gluconate (CHX) and CHX with surface modifiers (CHX-Plus) treatment. Specifically, we examine the percentage of viable bacteria in the biofilms following their exposure to CHX and CHX-Plus for 1, 3 and 10 minutes, respectively. Before antimicrobial treatment, the biofilms are allowed to grow for three weeks. We find that (a). CHX-Plus kills bacteria in biofilms more effectively than the regular 2% CHX does, (b). cell continues to be killed for up to one week after exposure to the CHX solutions, (c). the biofilms start to recover after two weeks, the percentage of the viable bacteria recovers in the 1 and 3 minutes treatment groups but not in the 10 minutes treatment group after five weeks and the biofilms fully return to the pretreatment levels after eight weeks. To understand the mechanism, a mathematical model for multiple bacterial phenotypes is developed, adopting the notion that bacterial persisters exist in the biofilms together with regulatory quorum sensing molecules and growth factor proteins. The model reveals the crucial role played by the persisters, quorum sensing molecules and growth factors in biofilm recovery, accurately predicting the viable bacterial population after CHX treatment.
Comprehensive analysis of multi-tissue transcriptome data and the genome-wide investigation of GRAS family in Phyllostachys edulis
Authors: Zhao Hansheng , Dong Lili , Sun Huayu , Li Lichao , Lou Yongfeng , Wang Lili , Li Zuyao , Gao Zhimin
Published: June 2016

GRAS family is one of plant specific transcription factors and plays diverse roles in the regulation of plant growth and development as well as in the plant disease resistance and abiotic stress responses. However, the investigation of GRAS family and multi-tissue gene expression profiles still remains unavailable in bamboo (Phyllostachys edulis). Here, we applied RNA-Seq analysis to monitor global transcriptional changes and investigate expression patterns in the five tissues of Ph. edulis, and analyzed a large-scale transcriptional events and patterns. Moreover, the tissue-specific genes and DEGs in different tissues were detected. For example, DEGs in panicle and leaf tissues were abundant in photosynthesis, glutathione, porphyrin and chlorophyll metabolism, whereas those in shoot and rhizome were majority in glycerophospholipid metabolism. In the portion of Ph. edulis GRAS (PeGRAS) analyses, we performed the analysis of phylogenetic, gene structure, conserved motifs, and analyzed the expression profiles of PeGRASs in response to high light and made a co-expression analysis. Additionally, the expression profiles of PeGRASs were validated using quantitative real-time PCR. Thus, PeGRASs based on dynamics profiles of gene expression is helpful in uncovering the specific biological functions which might be of critical values for bioengineering to improve bamboo breeding in future.
An evolutionarily conserved SSNA1/DIP13 homologue is a component of both basal and apical complexes of Toxoplasma gondii
Authors: Lévêque Maude F. , Berry Laurence , Besteiro Sébastien
Published: June 2016

Microtubule-based cytoskeletal structures have fundamental roles in several essential eukaryotic processes, including transport of intracellular constituents as well as ciliary and flagellar mobility. Temporal and spatial organisation of microtubules is determined by microtubule organising centers and a number of appendages and accessory proteins. Members of the SSNA1/DIP13 family are coiled coil proteins that are known to localise to microtubular structures like centrosomes and flagella, but are otherwise poorly characterised. We have identified a homologue of SSNA1/DIP13 in the parasitic protist Toxoplasma gondii and found it localises to parasite-specific cytoskeletal structures: the conoid in the apical complex of mature and dividing cells and the basal complex in elongating daughter cells during cell division. This protein is dispensable for parasite growth in vitro. However, quite remarkably, this coiled coil protein is able to self-associate into higher order structures both in vitro and in vivo and its overexpression is impairing parasite division.
Metal organic frameworks as sorption media for volatile and semi-volatile organic compounds at ambient conditions
Authors: Vellingiri Kowsalya , Szulejko Jan E. , Kumar Pawan , Kwon Eilhann E. , Kim Ki-Hyun , Deep Akash , Boukhvalov Danil W. , Brown Richard J. C.
Published: June 2016

In this research, we investigated the sorptive behavior of a mixture of 14 volatile and semi-volatile organic compounds (four aromatic hydrocarbons (benzene, toluene, p-xylene, and styrene), six C2-C5 volatile fatty acids (VFAs), two phenols, and two indoles) against three metal-organic frameworks (MOFs), i.e., MOF-5, Eu-MOF, and MOF-199 at 5 to 10 mPa VOC partial pressures (25 °C). The selected MOFs exhibited the strongest affinity for semi-volatile (polar) VOC molecules (skatole), whereas the weakest affinity toward was volatile (non-polar) VOC molecules (i.e., benzene). Our experimental results were also supported through simulation analysis in which polar molecules were bound most strongly to MOF-199, reflecting the presence of strong interactions of Cu2+ with polar VOCs. In addition, the performance of selected MOFs was compared to three well-known commercial sorbents (Tenax TA, Carbopack X, and Carboxen 1000) under the same conditions. The estimated equilibrium adsorption capacity (mg.g−1) for the all target VOCs was in the order of; MOF-199 (71.7) >Carboxen-1000 (68.4) >Eu-MOF (27.9) >Carbopack X (24.3) >MOF-5 (12.7) >Tenax TA (10.6). Hopefully, outcome of this study are expected to open a new corridor to expand the practical application of MOFs for the treatment diverse VOC mixtures.
Long-range wetting transparency on top of layered metal-dielectric substrates
Authors: Noginov M. A. , Barnakov Yuri A. , Liberman Vladimir , Prayakarao Srujana , Bonner Carl E. , Narimanov Evgenii E.
Published: June 2016

It has been recently shown that scores of physical and chemical phenomena (including spontaneous emission, scattering and Förster energy transfer) can be controlled by nonlocal dielectric environments provided by metamaterials with hyperbolic dispersion and simpler metal/dielectric structures. At this time, we have researched van der Waals interactions and experimentally studied wetting of several metallic, dielectric and composite multilayered substrates. We have found that the wetting angle of water on top of MgF2 is highly sensitive to the thickness of the MgF2 layer and the nature of the underlying substrate that could be positioned as far as ~100 nm beneath the water/MgF2 interface. We refer to this phenomenon as long range wetting transparency. The latter effect cannot be described in terms of the most basic model of dispersion van der Waals-London forces based on pair-wise summation of dipole-dipole interactions across an interface or a gap separating the two media. We infer that the experimentally observed gradual change of the wetting angle with increase of the thickness of the MgF2 layer can possibly be explained by the distance dependence of the Hamaker function (describing the strength of interaction), which originates from retardation of electromagnetic waves at the distances comparable to a wavelength.
Circulating follicular T helper cells and cytokine profile in humans following vaccination with the rVSV-ZEBOV Ebola vaccine
Authors: Farooq Fouzia , Beck Kevin , Paolino Kristopher M. , Phillips Revell , Waters Norman C. , Regules Jason A. , Bergmann-Leitner Elke S.
Published: June 2016

The most recent Zaire Ebolavirus (ZEBOV) outbreak was the largest and most widespread in recorded history, emphasizing the need for an effective vaccine. Here, we analyzed human cellular immune responses induced by a single dose of the rVSV-ZEBOV vaccine candidate, which showed significant protective efficacy in endemic populations in Guinea. This is the first in-depth characterization of ZEBOV-GP specific, circulating follicular T cells (cTfh). Since antibody titers correlated with protection in preclinical models of ZEBOV infection, Tfh were predicted to correlate with protection. Indeed, the ZEBOV-specific cTfh data correlated with antibody titers in human vaccines and unexpectedly with the Tfh17 subset. The combination of two cutting edge technologies allowed the immuno-profiling of rare cell populations and may help elucidate correlates of protection for a variety of vaccines.
Body surface area formulae: an alarming ambiguity
Authors: Redlarski Grzegorz , Palkowski Aleksander , Krawczuk Marek
Published: June 2016

Body surface area (BSA) plays a key role in several medical fields, including cancer chemotherapy, transplantology, burn treatment and toxicology. BSA is often a major factor in the determination of the course of treatment and drug dosage. A series of formulae to simplify the process have been developed. Because easy-to-identify, yet general, body coefficient results of those formulae vary considerably, the question arises as to whether the choice of a particular formula is valid and safe for patients. Here we show that discrepancies between most of the known BSA formulae can reach 0.5 m2 for the standard adult physique. Although many previous studies have demonstrated that certain BSA formulae provide an almost exact fit with the patients examined, all of these studies have been performed on a limited and isolated group of people. Our analysis presents a broader perspective, considering 25 BSA formulae. The analysis revealed that the choice of a particular formula is a difficult task. Differences among calculations made by the formulae are so great that, in certain cases, they may considerably affect patients’ mortality, especially for people with an abnormal physique or for children.
Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea
Authors: Barberán Sara , Martín-Durán José M. , Cebrià Francesc
Published: June 2016

The EGFR pathway is an essential signaling system in animals, whose core components are the epidermal growth factors (EGF ligands) and their trans-membrane tyrosine kinase receptors (EGFRs). Despite extensive knowledge in classical model organisms, little is known of the composition and function of the EGFR pathway in most animal lineages. Here, we have performed an extensive search for the presence of EGFRs and EGF ligands in representative species of most major animal clades, with special focus on the planarian Schmidtea mediterranea. With the exception of placozoans and cnidarians, we found that the EGFR pathway is potentially present in all other analyzed animal groups and has experienced frequent independent expansions. We further characterized the expression domains of the EGFR/EGF identified in S. mediterranea, revealing a wide variety of patterns and localization in almost all planarian tissues. Finally, functional experiments suggest an interaction between one of the previously described receptors, Smed-egfr-5 and the newly found ligand Smed-egf-6. Our findings provide the most comprehensive overview to date of the EGFR pathway and indicate that the last common metazoan ancestor had an initial complement of one EGFR and one putative EGF ligand, which was often expanded or lost during animal evolution.
Differential effect of HLA class-I versus class-II transgenes on human T and B cell reconstitution and function in NRG mice
Authors: Majji Sai , Wijayalath Wathsala , Shashikumar Soumya , Pow-Sang Luis , Villasante Eileen , Brumeanu Teodor D. , Casares Sofia
Published: June 2016

Humanized mice expressing Human Leukocyte Antigen (HLA) class I or II transgenes have been generated, but the role of class I vs class II on human T and B cell reconstitution and function has not been investigated in detail. Herein we show that NRG (NOD.RagKO.IL2RγcKO) mice expressing HLA-DR4 molecules (DRAG mice) and those co-expressing HLA-DR4 and HLA-A2 molecules (DRAGA mice) did not differ in their ability to develop human T and B cells, to reconstitute cytokine-secreting CD4 T and CD8 T cells, or to undergo immunoglobulin class switching. In contrast, NRG mice expressing only HLA-A2 molecules (A2 mice) reconstituted lower numbers of CD4 T cells but similar numbers of CD8 T cells. The T cells from A2 mice were deficient at secreting cytokines, and their B cells could not undergo immunoglobulin class switching. The inability of A2 mice to undergo immunoglobulin class switching is due to deficient CD4 helper T cell function. Upon immunization, the frequency and cytotoxicity of antigen-specific CD8 T cells in DRAGA mice was significantly higher than in A2 mice. The results indicated a multifactorial effect of the HLA-DR4 transgene on development and function of human CD4 T cells, antigen-specific human CD8 T cells, and immunoglobulin class switching.
Rapid and High-Efficiency Laser-Alloying Formation of ZnMgO Nanocrystals
Authors: Liu Peisheng , Wang Hao , Chen Jun , Li Xiaoming , Zeng Haibo
Published: June 2016

Applications of ZnMgO nanocrystals (NCs), especially in photoelectric detectors, have significant limitations because of the unresolved phase separation in the synthesis process. Here, we propose a rapid and highly efficient ZnMgO NC alloying method based on pulsed laser ablation in liquid. The limit value of homogeneous magnesium (Mg) is pushed from 37% to 62% and the optical band gap is increased to 3.7 eV with high doping efficiency (>100%). Further investigations on the lattice geometry of ZnMgO NCs indicate that all ZnMgO NCs are hexagonal wurtzite structures and the (002) and (100) peaks shift to higher diffraction angles with the increase in Mg doping content. The calculated results of the lattice constants a and c slightly decrease based on Bragg’s law and lattice geometry equations. Furthermore, the relationship between annealing temperature and the limit value of homogeneous Mg is examined and the results reveal that the latter decreases with the former because of the phase separation of MgO. A probable mechanism of zinc magnesium alloy is introduced to expound on the details of the laser-alloying process.
A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans
Authors: Bhomia Manish , Balakathiresan Nagaraja S. , Wang Kevin K. , Papa Linda , Maheshwari Radha K.
Published: June 2016

MicroRNAs (MiRNAs) are small endogenous RNA molecules and have emerged as novel serum diagnostic biomarkers for several diseases due to their stability and detection at minute quantities. In this study, we have identified a serum miRNA signature in human serum samples of mild to severe TBI, which can be used for diagnosis of mild and moderate TBI (MMTBI). Human serum samples of MMTBI, severe TBI (STBI), orthopedic injury and healthy controls were used and miRNA profiling was done using taqman real time PCR. The real time PCR data for the MMTBI, STBI and orthopedic injury was normalized to the control samples which showed upregulation of 39, 37 and 33 miRNAs in MMTBI, STBI and orthopedic injury groups respectively. TBI groups were compared to orthopedic injury group and an up-regulation of 18 and 20 miRNAs in MMTBI and STBI groups was observed. Among these, a signature of 10 miRNAs was found to be present in both MMTBI and STBI groups. These 10 miRNAs were validated in cerebrospinal fluid (CSF) from STBI and four miRNAs were found to be upregulated in CSF. In conclusion, we identified a subset of 10 unique miRNAs which can be used for diagnosis of MMTBI and STBI.
Time-varying land subsidence detected by radar altimetry: California, Taiwan and north China
Authors: Hwang Cheinway , Yang Yuande , Kao Ricky , Han Jiancheng , Shum C. K. , Galloway Devin L. , Sneed Michelle , Hung Wei-Chia , Cheng Yung-Sheng , Li Fei
Published: June 2016

Contemporary applications of radar altimetry include sea-level rise, ocean circulation, marine gravity and icesheet elevation change. Unlike InSAR and GNSS, which are widely used to map surface deformation, altimetry is neither reliant on highly temporally-correlated ground features nor as limited by the available spatial coverage and can provide long-term temporal subsidence monitoring capability. Here we use multi-mission radar altimetry with an approximately 23 year data-span to quantify land subsidence in cropland areas. Subsidence rates from TOPEX/POSEIDON, JASON-1, ENVISAT and JASON-2 during 1992–2015 show time-varying trends with respect to displacement over time in California’s San Joaquin Valley and central Taiwan, possibly related to changes in land use, climatic conditions (drought) and regulatory measures affecting groundwater use. Near Hanford, California, subsidence rates reach 18 cm yr−1 with a cumulative subsidence of 206 cm, which potentially could adversely affect operations of the planned California High-Speed Rail. The maximum subsidence rate in central Taiwan is 8 cm yr−1. Radar altimetry also reveals time-varying subsidence in the North China Plain consistent with the declines of groundwater storage and existing water infrastructure detected by the Gravity Recovery And Climate Experiment (GRACE) satellites, with rates reaching 20 cm yr−1 and cumulative subsidence as much as 155 cm.
Phase Modulation of Photonic Band Gap Signal
Authors: Wang Zhiguo , Gao Mengqin , Mahesar Abdul Rasheed , Zhang Yanpeng
Published: June 2016

We first investigate the probe transmission signal (PTS) and the four wave mixing band gap signal (FWM BGS) modulated simultaneously by the relative phase and the nonlinear phase shift in the photonic band gap (PBG) structure. The switch between the absorption enhancement of PTS and the transmission enhancement of PTS with the help of changing the relative phase and the nonlinear phase shift is obtained in inverted Y-type four level atomic system experimentally and theoretically. The corresponding switch in PTS can be used to realize all optical switches. On other hand, the relative phase and the nonlinear phase shift also play the vital role to modulate the intensity of FWM BGS reflected from the PBG structure. And it can be potentially used to realize the optical amplifier.
Screening for protein-protein interactions using Förster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM)
Authors: Margineanu Anca , Chan Jia Jia , Kelly Douglas J. , Warren Sean C. , Flatters Delphine , Kumar Sunil , Katan Matilda , Dunsby Christopher W. , French Paul M. W.
Published: June 2016

We present a high content multiwell plate cell-based assay approach to quantify protein interactions directly in cells using Förster resonance energy transfer (FRET) read out by automated fluorescence lifetime imaging (FLIM). Automated FLIM is implemented using wide-field time-gated detection, typically requiring only 10 s per field of view (FOV). Averaging over biological, thermal and shot noise with 100’s to 1000’s of FOV enables unbiased quantitative analysis with high statistical power. Plotting average donor lifetime vs. acceptor/donor intensity ratio clearly identifies protein interactions and fitting to double exponential donor decay models provides estimates of interacting population fractions that, with calibrated donor and acceptor fluorescence intensities, can yield dissociation constants. We demonstrate the application to identify binding partners of MST1 kinase and estimate interaction strength among the members of the RASSF protein family, which have important roles in apoptosis via the Hippo signalling pathway. KD values broadly agree with published biochemical measurements.
Anti-obesity effect of intranasal administration of galanin-like peptide (GALP) in obese mice
Authors: Kageyama Haruaki , Shiba Kanako , Hirako Satoshi , Wada Nobuhiro , Yamanaka Satoru , Nogi Yukinori , Takenoya Fumiko , Nonaka Naoko , Hirano Tsutomu , Inoue Shuji , Shioda Seiji
Published: June 2016

Galanin-like peptide (GALP) has an anti-obesity effect in rats and mice. It has been reported that the uptake of GALP by the brain is higher after intranasal administration than with intravenous injection. This study therefore aimed to clarify the effect of intranasal administration of GALP on the feeding behavior of lean and obese mice. Autoradiography revealed the presence of 125I-GALP in the olfactory bulb and the brain microcirculation. The body weights of ob/ob mice gradually increased during vehicle treatment, but remained unchanged in response to repeated intranasal administration of GALP, with both ob/ob and diet-induced obese mice displaying significantly decreased food intake, water intake and locomotor activity when treated with GALP. These results suggest that intranasal administration is an effective route whereby GALP can exert its effect as an anti-obesity drug.
Heart rhythm complexity impairment in patients undergoing peritoneal dialysis
Authors: Lin Yen-Hung , Lin Chen , Ho Yi-Heng , Wu Vin-Cent , Lo Men-Tzung , Hung Kuan-Yu , Liu Li-Yu Daisy , Lin Lian-Yu , Huang Jenq-Wen , Peng Chung-Kang
Published: June 2016

Cardiovascular disease is one of the leading causes of death in patients with advanced renal disease. The objective of this study was to investigate impairments in heart rhythm complexity in patients with end-stage renal disease. We prospectively analyzed 65 patients undergoing peritoneal dialysis (PD) without prior cardiovascular disease and 72 individuals with normal renal function as the control group. Heart rhythm analysis including complexity analysis by including detrended fractal analysis (DFA) and multiscale entropy (MSE) were performed. In linear analysis, the PD patients had a significantly lower standard deviation of normal RR intervals (SDRR) and percentage of absolute differences in normal RR intervals greater than 20 ms (pNN20). Of the nonlinear analysis indicators, scale 5, area under the MSE curve for scale 1 to 5 (area 1–5) and 6 to 20 (area 6–20) were significantly lower than those in the control group. In DFA anaylsis, both DFA α1 and DFA α2 were comparable in both groups. In receiver operating characteristic curve analysis, scale 5 had the greatest discriminatory power for two groups. In both net reclassification improvement model and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of SDRR, pNN20, and pNN50. In conclusion, PD patients had worse cardiac complexity parameters. MSE parameters are useful to discriminate PD patients from patients with normal renal function.
Prognostic value of decreased expression of RBM4 in human gastric cancer
Authors: Yong Hongmei , Zhu Huijun , Zhang Shu , Zhao Wei , Wang Wei , Chen Chen , Ding Guipeng , Zhu Lun , Zhu Ziyuan , Liu Huaidong , Zhang Yongjie , Wen Jinbo , Kang Xing , Zhu Jin , Feng Zhenqing , Liu Baorui
Published: June 2016

RNA-binding motif 4 (RBM4) is a multifunctional protein that participates in regulating alternative splicing and mRNA translation. Its reduced expression has been associated with poor overall survival in lung cancer, breast cancer and ovarian cancer. We assessed RBM4 protein expression levels with immunohistochemistry in tissue microarrays containing malignant gastric cancer tissues and benign tissues from 813 patients. We also examined the expression levels of RBM4 mRNA in twenty-five paired gastric cancer samples and adjacent noncancerous tissues. Both RBM4 protein and mRNA expression levels were significantly lower in gastric cancer tissues compared with the adjacent noncancerous tissues. There was a significant association between reduced RBM4 protein expression and differentiation (P < 0.001), lymph node metastasis (P = 0.026), TNM state (P = 0.014) and distant metastasis (P = 0.036).Patients with reduced RBM4 expression (P < 0.001, CI = 0.315–0.710) and TNM stage III and IV (P < 0.001, CI = 4.757–11.166) had a poor overall survival. These findings suggest that RBM4 is a new biomarker in gastric cancer, as the reduced expression of this protein is correlated with poor differentiation, lymph node status and distant metastasis. Further, lower RBM4 expression is an independent prognostic marker for gastric cancer.
A series of compact rejection filters based on the interaction between spoof SPPs and CSRRs
Authors: Zhang Qian , Zhang Hao Chi , Yin Jia Yuan , Pan Bai Cao , Cui Tie Jun
Published: June 2016

We propose a method to synthesize several band-rejection filters by etching split-ring resonators (SRRs) on the transmission line for spoof surface plasmon polaritons (SPPs), which is made of double-side or single-side corrugated metal strips. From dispersion relations, the corrugated strips can support spoof SPP modes when the operating frequency is less than the cutoff frequency. The electric field component perpendicular to the strip surface of the SPP modes can excite the complementary SRRs (CSRRs), leading to resonant modes preventing the SPP propagation near the resonant frequencies. Using this principle, single-frequency rejection filters, double-frequency rejection filters and broad band-stop filters with bandwidth of 1.5 GHz have been designed and fabricated using the single- and/or double-side corrugated strips. Both measured results and numerical simulations demonstrate the excellent filtering characteristics of all design, which are in good agreements. The isolation of all filters can be less than −20 dB and even reach to −38 dB at rejection frequencies. The proposed rejection and stop-band filters give important potentials to develop integrated plasmonic functional devices and circuits at microwave and terahertz frequencies.
Brain phosphorylation of MeCP2 at serine 164 is developmentally regulated and globally alters its chromatin association
Authors: Stefanelli Gilda , Gandaglia Anna , Costa Mario , Cheema Manjinder S. , Di Marino Daniele , Barbiero Isabella , Kilstrup-Nielsen Charlotte , Ausió Juan , Landsberger Nicoletta
Published: June 2016

MeCP2 is a transcriptional regulator whose functional alterations are responsible for several autism spectrum and mental disorders. Post-translational modifications (PTMs) and particularly differential phosphorylation, modulate MeCP2 function in response to diverse stimuli. Understanding the detailed role of MeCP2 phosphorylation is thus instrumental to ascertain how MeCP2 integrates the environmental signals and directs its adaptive transcriptional responses. The evolutionarily conserved serine 164 (S164) was found phosphorylated in rodent brain but its functional role has remained uncharacterized. We show here that phosphorylation of S164 in brain is dynamically regulated during neuronal maturation. S164 phosphorylation highly impairs MeCP2 binding to DNA in vitro and largely affects its nucleosome binding and chromatin affinity in vivo. Strikingly, the chromatin-binding properties of the global MeCP2 appear also extensively altered during the course of brain maturation. Functional assays reveal that proper temporal regulation of S164 phosphorylation controls the ability of MeCP2 to regulate neuronal morphology. Altogether, our results support the hypothesis of a complex PTM-mediated functional regulation of MeCP2 potentially involving a still poorly characterized epigenetic code. Furthermore, they demonstrate the relevance of the Intervening Domain of MeCP2 for binding to DNA.
Horizontally assembled green InGaN nanorod LEDs: scalable polarized surface emitting LEDs using electric-field assisted assembly
Authors: Park Hoo Keun , Yoon Seong Woong , Eo Yun Jae , Chung Won Woo , Yoo Gang Yeol , Oh Ji Hye , Lee Keyong Nam , Kim Woong , Do Young Rag
Published: June 2016

In this study, we report the concerted fabrication process, which is easy to transform the size of active emitting area and produce polarized surface light, using the electric-field-assisted assembly for horizontally assembled many tiny nanorod LEDs between two metal electrodes. We fabricate the millions of individually separated 1D nanorod LEDs from 2D nanorod arrays using nanosphere lithography, etching and cutting process of InGaN/GaN LED structure on a flat sapphire substrate. The horizontally assembled InGaN-based nanorods LED device shows bright (~2,130 cd/m2) and uniform polarized (polarization ratio, ρ = ~0.61) green emissions from large area (0.7 cm × 0.6 cm) planar surface. The realization of a horizontally assembled nanorod LED device can prove the concept of an innovative idea to fabricate formable and scalable polarized surface LED lighting.
Doses Lactobacillus reuteri depend on adhesive ability to modulate the intestinal immune response and metabolism in mice challenged with lipopolysaccharide
Authors: Gao Kan , Liu Li , Dou Xiaoxiao , Wang Chong , Liu Jianxin , Zhang Wenming , Wang Haifeng
Published: June 2016

The objective of this study was to evaluate the modulatory effects of Lactobacillus reuteri ZJ617 and ZJ615, which have high and low adhesive abilities, respectively, and Lactobacillus rhamnosus GG (LGG) on immune responses and metabolism in mice stimulated with lipopolysaccharide (LPS). Six C57BL/6 mice per group were orally inoculated with ZJ617, ZJ615 or LGG for one week (1 × 108 CFU/mouse) and i.p. injected with LPS (10 mg/kg) for 24 h. Compared with the LPS stimulation group, ZJ615, ZJ617 and LGG significantly decreased TNF-α levels in the sera of mice stimulated by LPS. ZJ615 and LGG significantly down-regulated mRNA levels of cytokines and Toll-like receptors, and suppressed activation of MAPK and NF-κB signaling, while ZJ617 up-regulated anti-inflammatory cytokine IL-10 mRNA levels in the ilea of mice stimulated by LPS. Correlation analysis confirmed that adhesive ability is relative with the immunomodulation in the ilea of mice. There were 24, 7 and 10 metabolites and 10, 9 and 8 major metabolic pathways with significant differences (VIP > 1, P < 0.05) between the LPS and ZJ617 + LPS groups, the LPS and ZJ615 + LPS groups, and the ZJ617 + LPS and ZJ615 + LPS groups, respectively. The results indicated that both ZJ617 and ZJ615 could modulate the intestinal immune responses and metabolism in LPS-stimulated mice.
Elimination of a ligand gating site generates a supersensitive olfactory receptor
Authors: Sharma Kanika , Ahuja Gaurav , Hussain Ashiq , Balfanz Sabine , Baumann Arnd , Korsching Sigrun I.
Published: June 2016

Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors.
Developmental and stress regulation on expression of a novel miRNA, Fan-miR73 and its target ABI5 in strawberry
Authors: Li Dongdong , Mou Wangshu , Luo Zisheng , Li Li , Limwachiranon Jarukitt , Mao Linchun , Ying Tiejin
Published: June 2016

Abscisic acid (ABA) is a critical plant hormone for fruit ripening and adaptive stress responses in strawberry. Previous high-throughput sequencing results indicated that ABA-insensitive (ABI)5, an important transcription factor in the ABA signaling pathway, was a target for a novel microRNA (miRNA), Fan-miR73. In the present study, exogenous ABA treatment was found to accelerate fruit ripening through differentially regulating the transcripts of ABA metabolism and signal transduction related genes, including NCED1, PYR1, ABI1 and SnRK2.2. Expression of Fan-miR73 was down-regulated in response to exogenous ABA treatment in a dosage-dependent manner, which resulted in an accumulation of ABI5 transcripts in the ripening-accelerated fruits. In addition, both UV-B radiation and salinity stress reduced the transcript levels of Fan-miR73, whereas promoted ABI5 expression. Furthermore, high negative correlations between the transcriptional abundance of Fan-miR73 and ABI5 were observed during ripening and in response to stress stimuli. These results enriched the possible regulatory role of miRNA involved in the post-transcriptional modification of ABI5 during strawberry ripening, as well as responses to environmental stresses.
Precision Modulation of Neurodegenerative Disease-Related Gene Expression in Human iPSC-Derived Neurons
Authors: Heman-Ackah Sabrina Mahalia , Bassett Andrew Roger , Wood Matthew John Andrew
Published: June 2016

The ability to reprogram adult somatic cells into induced pluripotent stem cells (iPSCs) and the subsequent development of protocols for their differentiation into disease-relevant cell types have enabled in-depth molecular analyses of multiple disease states as hitherto impossible. Neurons differentiated from patient-specific iPSCs provide a means to recapitulate molecular phenotypes of neurodegenerative diseases in vitro. However, it remains challenging to conduct precise manipulations of gene expression in iPSC-derived neurons towards modeling complex human neurological diseases. The application of CRISPR/Cas9 to mammalian systems is revolutionizing the utilization of genome editing technologies in the study of molecular contributors to the pathogenesis of numerous diseases. Here, we demonstrate that CRISPRa and CRISPRi can be used to exert precise modulations of endogenous gene expression in fate-committed iPSC-derived neurons. This highlights CRISPRa/i as a major technical advancement in accessible tools for evaluating the specific contributions of critical neurodegenerative disease-related genes to neuropathogenesis.
Transcriptional repression of SIRT1 by protein inhibitor of activated STAT 4 (PIAS4) in hepatic stellate cells contributes to liver fibrosis
Authors: Sun Lina , Fan Zhiwen , Chen Junliang , Tian Wenfang , Li Min , Xu Huihui , Wu Xiaoyan , Shao Jing , Bian Yaoyao , Fang Mingming , Xu Yong
Published: June 2016

Interstitial fibrosis represents a key pathological process in non-alcoholic steatohepatitis (NASH). In the liver, fibrogenesis is primarily mediated by activated hepatic stellate cells (HSCs) transitioning from a quiescent state in response to a host of stimuli. The molecular mechanism underlying HSC activation is not completely understood. Here we report that there was a simultaneous up-regulation of PIAS4 expression and down-regulation of SIRT1 expression accompanying increased hepatic fibrogenesis in an MCD-diet induced mouse model of NASH. In cultured primary mouse HSCs, stimulation with high glucose activated PIAS4 while at the same time repressed SIRT1. Over-expression of PIAS4 directly repressed SIRT1 promoter activity. In contrast, depletion of PIAS4 restored SIRT1 expression in HSCs treated with high glucose. Estrogen, a known NASH-protective hormone, antagonized HSC activation by targeting PIAS4. Lentivirus-mediated delivery of short hairpin RNA (shRNA) targeting PIAS4 in mice ameliorated MCD diet induced liver fibrosis by normalizing SIRT1 expression in vivo. PIAS4 promoted HSC activation in a SIRT1-dependent manner in vitro. Mechanistically, PIAS4 mediated SIRT1 repression led to SMAD3 hyperacetylation and enhanced SMAD3 binding to fibrogenic gene promoters. Taken together, our data suggest SIRT1 trans-repression by PIAS4 plays an important role in HSC activation and liver fibrosis.
Quantum spin Hall insulator in halogenated arsenene films with sizable energy gaps
Authors: Wang Dongchao , Chen Li , Shi Changmin , Wang Xiaoli , Cui Guangliang , Zhang Pinhua , Chen Yeqing
Published: June 2016

Based on first-principles calculations, the electronic and topological properties of halogenated (F-, Cl-, Br- and I-) arsenene are investigated in detail. It is found that the halogenated arsenene sheets show Dirac type characteristic in the absence of spin-orbital coupling (SOC), whereas energy gap will be induced by SOC with the values ranging from 0.194 eV for F-arsenene to 0.255 eV for I-arsenene. Noticeably, these four newly proposed two-dimensional (2D) systems are verified to be quantum spin Hall (QSH) insulators by calculating the edge states with obvious linear cross inside bulk energy gap. It should be pointed out that the large energy gap in these 2D materials consisted of commonly used element is quite promising for practical applications of QSH insulators at room temperature.