bluuebunny/crossref_metadata_2025 huggingface dataset:
A Quantitative Approach to the Russian Past: A Comment on “European Statistics, Russian Numbers and Social Dynamics, 1861–1914” by Alessandro Stanziani
Authors: Markevich Andrei , Zhuravskaya Ekaterina
Published: May 2017

Alessandro Stanziani’s article re-launches the discussion about the quality of Russian imperial statistics and the relevance of quantitative analysis for historical research at an important moment for Russia’s economic history, when a lot of new data are being compiled and used by scholars. Similar productive discussions took place at other critical junctions for the fields of history, economics, political science, and other social sciences. For example, Robert Fogel’s and Stanley Engerman’s “Time on the Cross” (1974) triggered a profound discussion of potential benefits and limitations of quantitative approach to studying the history of the United States. The punch line of that discussion can be illustrated by the justification of the 1993 Nobel Prize in economics dedicated to Fogel “for having renewed research in economic history by applying economic theory and quantitative methods in order to explain economic and institutional change.” In the context of Russian history, similar discussions took place in the Soviet Union in the 1970s between Ivan Koval'chenko and Boris Litvak and then later in this journal in the 1990s.
Die Koronaranomalie – vom Zufallsbefund zum plötzlichen Herztod?
Authors: Benz Dominik C. , Kaufmann Philipp A.
Published: May 2017

Zusammenfassung. Koronaranomalien sind mit dem plötzlichen Herztod assoziiert. Manchmal ist er der erste und einzige Hinweis für eine Koronaranomalie. Aufgrund der potentiell letalen Folgen wird bei jungen Patienten mit typischen Thoraxschmerzen oder einer Synkope beim Sport versucht, eine Koronaranomalie mittels kardialer Bildgebung auszuschliessen. Viel häufiger ist die Koronaranomalie aber ein Zufallsbefund in der Abklärung von Patienten mit Verdacht auf eine koronare Herzkrankheit oder in der Vorbereitung von Patienten für eine Pulmonalvenenisolation mittels der Herz-CT-Untersuchung. Die Prävalenz der Koronaranomalie liegt an unserem Zentrum bei 2.6 %. Einige von ihnen – wie die Koronaranomalien, die dem gegenüberliegenden Sinus Valsalva entspringen (sogenannte ACAOS, anomalous coronary arteries originating from the opposite site of the sinus of Valsalva), Koronarfisteln oder das Bland-White-Garland Syndrom – gehen mit einem erhöhten kardiovaskulären Risiko einher. Eine weiterführende Abklärung der hämodynamischen Relevanz der Koronaranomalie ist in diesen Fällen empfohlen – unabhängig davon, ob es sich um die Verdachtsdiagnose oder einen Zufallsbefund handelt. Idealerweise wird eine Durchblutungsuntersuchung mittels der Single-Photon-Emissions-Computertomographie (SPECT) oder der Positronen-Emissions-Tomographie (PET) durchgeführt, die eine Fusion mit der Herz-CT-Untersuchung erlauben. In der Hybridbildgebung kann die Koronaranomalie dann einem minderdurchbluteten Areal zugeordnet werden und von einer allenfalls begleitenden koronaren Herzkrankheit abgegrenzt werden. Das Alter des Patienten, die klinische Präsentation und der Befund der Bildgebung sind entscheidend für das weitere therapeutische Vorgehen. Bei fehlenden prospektiv-randomisierten Studien sind die Therapie-Empfehlungen allerdings meist nur auf Expertenmeinungen gestützt und sollen im Einzelfall eingehend mit dem Patienten und in der kardiologisch-thoraxschirurgischen Konferenz besprochen werden.
Understanding Kamchatka’s Extraordinary Volcano Cluster
Authors: Shapiro Nikolai , Sens-Schönfelder Christoph , Lühr Birger , Weber Michael , Abkadyrov Ilyas , Gordeev Evegeny , Koulakov Ivan , Jakovlev Andrey , Kugaenko Yulia , Saltykov Vadim
Published: May 2017

An international seismological collaboration in Kamchatka, Russia, investigates the driving forces of one of the world’s largest, most active volcano clusters.
Denitrifying community in coastal sediments performs aerobic and anaerobic respiration simultaneously
Authors: Marchant Hannah K , Ahmerkamp Soeren , Lavik Gaute , Tegetmeyer Halina E , Graf Jon , Klatt Judith M , Holtappels Moritz , Walpersdorf Eva , Kuypers Marcel M M
Published: May 2017

Nitrogen (N) input to the coastal oceans has increased considerably because of anthropogenic activities, however, concurrent increases have not occurred in open oceans. It has been suggested that benthic denitrification in sandy coastal sediments is a sink for this N. Sandy sediments are dynamic permeable environments, where electron acceptor and donor concentrations fluctuate over short temporal and spatial scales. The response of denitrifiers to these fluctuations are largely unknown, although previous observations suggest they may denitrify under aerobic conditions. We examined the response of benthic denitrification to fluctuating oxygen concentrations, finding that denitrification not only occurred at high O2 concentrations but was stimulated by frequent switches between oxic and anoxic conditions. Throughout a tidal cycle, in situtranscription of genes for aerobic respiration and denitrification were positively correlated within diverse bacterial classes, regardless of O2 concentrations, indicating that denitrification gene transcription is not strongly regulated by O2 in sandy sediments. This allows microbes to respond rapidly to changing environmental conditions, but also means that denitrification is utilized as an auxiliary respiration under aerobic conditions when imbalances occur in electron donor and acceptor supply. Aerobic denitrification therefore contributes significantly to N-loss in permeable sediments making the process an important sink for anthropogenic N-inputs.
Mosaic evolution in an asymmetrically feathered troodontid dinosaur with transitional features
Authors: Xu Xing , Currie Philip , Pittman Michael , Xing Lida , Meng Qingjin , Lü Junchang , Hu Dongyu , Yu Congyu
Published: May 2017

Asymmetrical feathers have been associated with flight capability but are also found in species that do not fly, and their appearance was a major event in feather evolution. Among non-avialan theropods, they are only known in microraptorine dromaeosaurids. Here we report a new troodontid,Jianianhualong tengigen. et sp. nov., from the Lower Cretaceous Jehol Group of China, that has anatomical features that are transitional between long-armed basal troodontids and derived short-armed ones, shedding new light on troodontid character evolution. It indicates that troodontid feathering is similar toArchaeopteryxin having large arm and leg feathers as well as frond-like tail feathering, confirming that these feathering characteristics were widely present among basal paravians. Most significantly, the taxon has the earliest known asymmetrical troodontid feathers, suggesting that feather asymmetry was ancestral to Paraves. This taxon also displays a mosaic distribution of characters likeSinusonasus, another troodontid with transitional anatomical features.
Similarity in viral and host promoters couples viral reactivation with host cell migration
Authors: Bohn-Wippert Kathrin , Tevonian Erin N. , Megaridis Melina R. , Dar Roy D.
Published: May 2017

Viral–host interactomes map the complex architecture of an evolved arms race during host cell invasion. mRNA and protein interactomes reveal elaborate targeting schemes, yet evidence is lacking for genetic coupling that results in the co-regulation of promoters. Here we compare viral and human promoter sequences and expression to test whether genetic coupling exists and investigate its phenotypic consequences. We show that viral–host co-evolution is imprinted within promoter gene sequences before transcript or protein interactions. Co-regulation of human immunodeficiency virus (HIV) and human C-X-C chemokine receptor-4 (CXCR4) facilitates migration of infected cells. Upon infection, HIV can actively replicate or remain dormant. Migrating infected cells reactivate from dormancy more than non-migrating cells and exhibit differential migration–reactivation responses to drugs. Cells producing virus pose a risk for reinitiating infection within niches inaccessible to drugs, and tuning viral control of migration and reactivation improves strategies to eliminate latent HIV. Viral–host genetic coupling establishes a mechanism for synchronizing transcription and guiding potential therapies.
Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism
Authors: Hasel Philip , Dando Owen , Jiwaji Zoeb , Baxter Paul , Todd Alison C. , Heron Samuel , Márkus Nóra M. , McQueen Jamie , Hampton David W. , Torvell Megan , Tiwari Sachin S. , McKay Sean , Eraso-Pichot Abel , Zorzano Antonio , Masgrau Roser , Galea Elena , Chandran Siddharthan , Wyllie David J. A. , Simpson T. Ian , Hardingham Giles E.
Published: May 2017

The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte–neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte–neuron metabolic cooperation.
Ion-specific ice recrystallization provides a facile approach for the fabrication of porous materials
Authors: Wu Shuwang , Zhu Chongqin , He Zhiyuan , Xue Han , Fan Qingrui , Song Yanlin , Francisco Joseph S. , Zeng Xiao Cheng , Wang Jianjun
Published: May 2017

Ice recrystallization is of great importance to both fundamental research and practical applications, however understanding and controlling ice recrystallization processes remains challenging. Here, we report the discovery of an ion-specific effect on ice recrystallization. By simply changing the initial type and concentration of ions in an aqueous solution, the size of ice grains after recrystallization can be tuned from 27.4±4.1 to 277.5±30.9 μm. Molecular dynamics simulations show that the ability of the ion to be incorporated into the ice phase plays a key role in the ultimate size of the ice grains after recrystallization. Moreover, by using recrystallized ice crystals as templates, 2D and 3D porous networks with tuneable pore sizes could be prepared from various materials, for example, NaBr, collagen, quantum dots, silver and polystyrene colloids. These porous materials are suitable for a wide range of applications, for example, in organic electronics, catalysis and bioengineering.
Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice
Authors: Lucas Tina , Schäfer Florian , Müller Patricia , Eming Sabine A. , Heckel Alexander , Dimmeler Stefanie
Published: May 2017

MicroRNAs (miRs) are small non-coding RNAs that post-transcriptionally control gene expression. Inhibition of miRs by antisense RNAs (antimiRs) might be a therapeutic option for many diseases, but systemic inhibition can have adverse effects. Here we show that light-activatable antimiRs efficiently and locally restricted target miR activity in vivo. We use an antimiR-92a and establish a therapeutic benefit in diabetic wound healing. AntimiR-92a is modified with photolabile protecting groups, so called ‘cages’. Irradiation activates intradermally injected caged antimiR-92a without substantially affecting miR-92a expression in other organs. Light activation of caged antimiR-92a improves healing in diabetic mice to a similar extent as conventional antimiRs and derepresses the miR-92a targets Itga5 and Sirt1, thereby regulating wound cell proliferation and angiogenesis. These data show that light can be used to locally activate therapeutically active antimiRs in vivo.
Directly converting CO2 into a gasoline fuel
Authors: Wei Jian , Ge Qingjie , Yao Ruwei , Wen Zhiyong , Fang Chuanyan , Guo Lisheng , Xu Hengyong , Sun Jian
Published: May 2017

The direct production of liquid fuels from CO2 hydrogenation has attracted enormous interest for its significant roles in mitigating CO2 emissions and reducing dependence on petrochemicals. Here we report a highly efficient, stable and multifunctional Na–Fe3O4/HZSM-5 catalyst, which can directly convert CO2 to gasoline-range (C5–C11) hydrocarbons with selectivity up to 78% of all hydrocarbons while only 4% methane at a CO2 conversion of 22% under industrial relevant conditions. It is achieved by a multifunctional catalyst providing three types of active sites (Fe3O4, Fe5C2 and acid sites), which cooperatively catalyse a tandem reaction. More significantly, the appropriate proximity of three types of active sites plays a crucial role in the successive and synergetic catalytic conversion of CO2 to gasoline. The multifunctional catalyst, exhibiting a remarkable stability for 1,000 h on stream, definitely has the potential to be a promising industrial catalyst for CO2 utilization to liquid fuels.
Membraneless water filtration using CO2
Authors: Shin Sangwoo , Shardt Orest , Warren Patrick B. , Stone Howard A.
Published: May 2017

Water purification technologies such as microfiltration/ultrafiltration and reverse osmosis utilize porous membranes to remove suspended particles and solutes. These membranes, however, cause many drawbacks such as a high pumping cost and a need for periodic replacement due to fouling. Here we show an alternative membraneless method for separating suspended particles by exposing the colloidal suspension to CO2. Dissolution of CO2 into the suspension creates solute gradients that drive phoretic motion of particles. Due to the large diffusion potential generated by the dissociation of carbonic acid, colloidal particles move either away from or towards the gas–liquid interface depending on their surface charge. Using the directed motion of particles induced by exposure to CO2, we demonstrate a scalable, continuous flow, membraneless particle filtration process that exhibits low energy consumption, three orders of magnitude lower than conventional microfiltration/ultrafiltration processes, and is essentially free from fouling.
Benchmarking of RNA-sequencing analysis workflows using whole-transcriptome RT-qPCR expression data
Authors: Everaert Celine , Luypaert Manuel , Maag Jesper L. V. , Cheng Quek Xiu , Dinger Marcel E. , Hellemans Jan , Mestdagh Pieter
Published: May 2017

RNA-sequencing has become the gold standard for whole-transcriptome gene expression quantification. Multiple algorithms have been developed to derive gene counts from sequencing reads. While a number of benchmarking studies have been conducted, the question remains how individual methods perform at accurately quantifying gene expression levels from RNA-sequencing reads. We performed an independent benchmarking study using RNA-sequencing data from the well established MAQCA and MAQCB reference samples. RNA-sequencing reads were processed using five workflows (Tophat-HTSeq, Tophat-Cufflinks, STAR-HTSeq, Kallisto and Salmon) and resulting gene expression measurements were compared to expression data generated by wet-lab validated qPCR assays for all protein coding genes. All methods showed high gene expression correlations with qPCR data. When comparing gene expression fold changes between MAQCA and MAQCB samples, about 85% of the genes showed consistent results between RNA-sequencing and qPCR data. Of note, each method revealed a small but specific gene set with inconsistent expression measurements. A significant proportion of these method-specific inconsistent genes were reproducibly identified in independent datasets. These genes were typically smaller, had fewer exons, and were lower expressed compared to genes with consistent expression measurements. We propose that careful validation is warranted when evaluating RNA-seq based expression profiles for this specific gene set.
The first two complete mitochondrial genomes for the family Triglidae and implications for the higher phylogeny of Scorpaeniformes
Authors: Cui Lei , Dong Yuelei , Liu Fenghua , Gao Xingchen , Zhang Hua , Li Li , Cen Jingyi , Lu Songhui
Published: May 2017

The mitochondrial genome (mitogenome) can provide useful information for analyzing phylogeny and molecular evolution. Scorpaeniformes is one of the most diverse teleostean orders and has great commercial importance. To develop mitogenome data for this important group, we determined the complete mitogenomes of two gurnards Chelidonichthys kumu and Lepidotrigla microptera of Triglidae within Scorpaeniformes for the first time. The mitogenomes are 16,495 bp long in C. kumu and 16,610 bp long in L. microptera. Both the mitogenomes contain 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and two non-coding regions. All PCGs are initiated by ATG codons, except for the cytochrome coxidase subunit 1 (cox1) gene. All of the tRNA genes could be folded into typical cloverleaf secondary structures, with the exception of tRNASer(AGN) lacks a dihydrouracil (DHU) stem. The control regions are both 838 bp and contain several features common to Scorpaeniformes. The phylogenetic relationships of 33 fish mitogenomes using Bayesian Inference (BI) and Maximum Likelihood (ML) based on nucleotide and amino acid sequences of 13 PCGs indicated that the mitogenome sequences could be useful in resolving higher-level relationship of Scorpaeniformes. The results may provide more insight into the mitogenome evolution of teleostean species.
Exact firing time statistics of neurons driven by discrete inhibitory noise
Authors: Olmi Simona , Angulo-Garcia David , Imparato Alberto , Torcini Alessandro
Published: May 2017

Neurons in the intact brain receive a continuous and irregular synaptic bombardment from excitatory and inhibitory pre- synaptic neurons, which determines the firing activity of the stimulated neuron. In order to investigate the influence of inhibitory stimulation on the firing time statistics, we consider Leaky Integrate-and-Fire neurons subject to inhibitory instantaneous post- synaptic potentials. In particular, we report exact results for the firing rate, the coefficient of variation and the spike train spectrum for various synaptic weight distributions. Our results are not limited to stimulations of infinitesimal amplitude, but they apply as well to finite amplitude post-synaptic potentials, thus being able to capture the effect of rare and large spikes. The developed methods are able to reproduce also the average firing properties of heterogeneous neuronal populations.
Synergic bactericidal effects of reduced graphene oxide and silver nanoparticles against Gram-positive and Gram-negative bacteria
Authors: Prasad Karthika , Lekshmi G. S. , Ostrikov Kola , Lussini Vanessa , Blinco James , Mohandas Mandhakini , Vasilev Krasimir , Bottle Steven , Bazaka Kateryna , Ostrikov Kostya
Published: May 2017

Reduced graphene oxide (rGO) is a promising antibacterial material, the efficacy of which can be further enhanced by the addition of silver nanoparticles (nAg). In this study, the mechanisms of antibacterial activity of rGO–nAg nanocomposite against several important human pathogenic multi-drug resistant bacteria, namely Gram-positive coccal Staphylococcus aureus and Gram-negative rod-shaped Escherichia coli and Proteus mirabilis are investigated. At the same concentration (100 µg/ml), rGO–nAg nanocomposite was significantly more effective against all three pathogens than either rGO or nAg. The nanocomposite was equally active against P. mirabilis and S. aureus as systemic antibiotic nitrofurantoin, and significantly more effective against E. coli. Importantly, the inhibition was much faster in the case of rGO–nAg nanocomposite compared to nitrofurantoin, attributed to the synergistic effects of rGO–nAg mediated contact killing and oxidative stress. This study may provide new insights for the better understanding of antibacterial actions of rGO–nAg nanocomposite and for the better designing of graphene-based antibiotics or other biomedical applications.
An all-in-one, Tet-On 3G inducible PiggyBac system for human pluripotent stem cells and derivatives
Authors: Randolph Lauren N. , Bao Xiaoping , Zhou Chikai , Lian Xiaojun
Published: May 2017

Human pluripotent stem cells (hPSCs) offer tremendous promise in tissue engineering and cell-based therapies due to their unique combination of two properties: pluripotency and unlimited proliferative capacity. However, directed differentiation of hPSCs to clinically relevant cell lineages is needed to achieve the goal of hPSC-based therapies. This requires a deep understanding of how cell signaling pathways converge on the nucleus to control differentiation and the ability to dissect gene function in a temporal manner. Here, we report the use of the PiggyBac transposon and a Tet-On 3G drug-inducible gene expression system to achieve versatile inducible gene expression in hPSC lines. Our new system, XLone, offers improvement over previous Tet-On systems with significantly reduced background expression and increased sensitivity to doxycycline. Transgene expression in hPSCs is tightly regulated in response to doxycycline treatment. In addition, the PiggyBac elements in our XLone construct provide a rapid and efficient strategy for generating stable transgenic hPSCs. Our inducible gene expression PiggyBac transposon system should facilitate the study of gene function and directed differentiation in human stem cells.
The antifungal effects and mechanical properties of silver bromide/cationic polymer nano-composite-modified Poly-methyl methacrylate-based dental resin
Authors: Zhang Yu , Chen Yin-yan , Huang Li , Chai Zhi-guo , Shen Li-juan , Xiao Yu-hong
Published: May 2017

Poly-methyl methacrylate (PMMA)-based dental resins with strong and long-lasting antifungal properties are critical for the prevention of denture stomatitis. This study evaluated the antifungal effects on Candida albicans ATCC90028, the cytotoxicity toward human dental pulp cells (HDPCs), and the mechanical properties of a silver bromide/cationic polymer nano-composite (AgBr/NPVP)-modified PMMA-based dental resin. AgBr/NPVP was added to the PMMA resin at 0.1, 0.2, and 0.3 wt%, and PMMA resin without AgBr/NPVP served as the control. Fungal growth was inhibited on the AgBr/NPVP-modified PMMA resin compared to the control (P < 0.05), and the antifungal activity increased as the incorporation of the AgBr/NPVP antimicrobial composite increased. Confocal laser scanning microscopy (CLSM) showed that the number of fungal cells attached to the modified PMMA resin was considerably lower than in the control. The relative growth rate of HDPCs of modified groups were higher than 75%. The flexural strength (FS) and flexural modulus (FM) were not significantly different (P > 0.05) between the experimental and control groups. These data indicate that the incorporation of AgBr/NPVP conferred strong and long-lasting antifungal effects against Candida albicans to the PMMA resin, and it has low toxicity toward HDPCs, and its mechanical properties were not significantly affected.
Inhibition of Sp1 prevents ER homeostasis and causes cell death by lysosomal membrane permeabilization in pancreatic cancer
Authors: Dauer Patricia , Gupta Vineet K. , McGinn Olivia , Nomura Alice , Sharma Nikita S. , Arora Nivedita , Giri Bhuwan , Dudeja Vikas , Saluja Ashok K. , Banerjee Sulagna
Published: May 2017

Endoplasmic reticulum (ER) stress initiates an important mechanism for cell adaptation and survival, named the unfolded protein response (UPR). Severe or chronic/prolonged UPR can breach the threshold for survival and lead to cell death. There is a fundamental gap in knowledge on the molecular mechanism of how chronic ER stress is stimulated and leads to cell death in pancreatic ductal adenocarcinoma (PDAC). Our study shows that downregulating specificity protein 1 (Sp1), a transcription factor that is overexpressed in pancreatic cancer, activates UPR and results in chronic ER stress. In addition, downregulation of Sp1 results in its decreased binding to the ER stress response element present in the promoter region of Grp78, the master regulator of ER stress, thereby preventing homeostasis. We further show that inhibition of Sp1, as well as induction of ER stress, leads to lysosomal membrane permeabilization (LMP), a sustained accumulation of cytosolic calcium, and eventually cell death in pancreatic cancer.
Effect of Canal Anastomosis on Periapical Fluid Pressure Build-up during Needle Irrigation in Single Roots with Double Canals using a Polycarbonate Model
Authors: Huang Qi , Barnes Jonathan B. , Schoeffel G. John , Fan Bing , Tay Candice , Bergeron Brian E. , Susin Lisiane F. , Ling Jun-qi , Niu Li-na , Tay Franklin R.
Published: May 2017

Sodium hypochlorite is an effective irrigant for chemical debridement of root canals. However, increasing the intracanal pressure during irrigant delivery may result in irrigant extrusion into the bone and soft tissues surrounding the tooth. Because clinicians often encounter teeth with intracanal communications, the objective of the present study was to examine the effects of canal anastomosis on the generation of periapical fluid pressure at different fluid flow rates and insertion depths. Two similar polycarbonate models were used to simulate a single root with double canals, one containing, and the other without communicating channels between the canals. For both models, periapical pressure increased with increasing irrigant flow rates and insertion depths of a 30-gauge side-venting needle. In the presence of communicating channels, the magnitude of pressure build-up decreased by almost 90% irrespective of the fluid flow rate or needle insertion depth. Pressure reduction in anastomoses-containing roots provides an explanation why pressure generation in single roots is considerably higher. Nevertheless, it is still possible in teeth with canal anastomoses for pressure exceeding the intraosseous pressure to be generated when the fluid flow rate is sufficiently high and when the needle tip is close to the apical terminus.
Multimodality analysis of Hyper-reflective Foci and Hard Exudates in Patients with Diabetic Retinopathy
Authors: Niu Sijie , Yu Chenchen , Chen Qiang , Yuan Songtao , Lin Jiang , Fan Wen , Liu Qinghuai
Published: May 2017

To investigate the correlations between hyper-reflective foci and hard exudates in patients with non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) by spectral-domain optical coherence tomography (SD OCT) images. Hyper-reflective foci in retinal SD OCT images were automatically detected by the developed algorithm. Then, the cropped CFP images generated by the semi-automatic registration method were automatically segmented for the hard exudates and corrected by the experienced clinical ophthalmologist. Finally, a set of 5 quantitative imaging features were automatically extracted from SD OCT images, which were used for investigating the correlations of hyper-reflective foci and hard exudates and predicting the severity of diabetic retinopathy. Experimental results demonstrated the positive correlations in area and amount between hard exudates and hyper-reflective foci at different stages of diabetic retinopathy, with statistical significance (all p < 0.05). In addition, the area and amount can be taken as potential discriminant indicators of the severity of diabetic retinopathy.
Genomic evidence for local adaptation in the ovoviviparous marine fish Sebastiscus marmoratus with a background of population homogeneity
Authors: Xu Shengyong , Song Na , Zhao Linlin , Cai Shanshan , Han Zhiqiang , Gao Tianxiang
Published: May 2017

Advances in next-generation sequencing techniques have allowed for the generation of genome-wide sequence data, to gain insight into the dynamics influencing genetic structure and the local adaptation of marine fish. Here, using genotyping-by-sequencing (GBS) technique, we identified 31,119 single nucleotide polymorphisms (SNPs) for Sebastiscus marmoratus in 59 individuals from three populations in Chinese coastal waters. Based on all SNPs, there was little evidence of genetic differentiation among populations. However, outlier tests revealed 329 SNPs putatively under divergent selection across populations. Structural and phylogenetic topology analyses based on the outliers showed clear genetic differentiation among populations. Gene Ontology (GO) annotation results revealed that most of these outliers are known or hypothesized to be involved in metabolic process. Together with previous work using mitochondrial cytochrome b sequences, the present results further suggest that the population structure is strongly influenced by locally adaptive pressure. Overall, adaptive evolution in a heterogeneous environment plays an important role in inducing genetic differentiation among local populations. This study increases understanding of the factors (including gene flow and local adaptation) promoting and constraining population genetic differentiation in marine organisms.
Length effects on the dynamic process of cellular uptake and exocytosis of single-walled carbon nanotubes in murine macrophage cells
Authors: Cui Xuejing , Wan Bin , Yang Yu , Ren Xiaomin , Guo Liang-Hong
Published: May 2017

Cellular uptake and exocytosis of SWCNTs are fundamental processes determining their intracellular concentration and effects. Despite the great potential of acid-oxidized SWCNTs in biomedical field, understanding of the influencing factors on these processes needs to be deepened. Here, we quantitatively investigated uptake and exocytosis of SWCNTs in three lengths-630 (±171) nm (L-SWCNTs), 390 (±50) nm (M-SWCNTs), and 195 (±63) nm (S-MWCNTs) in macrophages. The results showed that the cellular accumulation of SWCNTs was a length-independent process and non-monotonic in time, with the most SWCNTs (3950 fg/cell) accumulated at 8 h and then intracellular SWCNTs dropped obviously with time. The uptake rate of SWCNTs decreased with increasing concentration, suggesting that intracellular SWCNTs accumulation is a saturable process. After refreshing culture medium, we found increasing SWCNTs in supernatant and decreasing intracellular SWCNTs over time, confirming the exocytosis occurred. Selective inhibition of endocytosis pathways showed that the internalization of SWCNTs involves several pathways, in the order of macropinocytosis> caveolae-mediated endocytosis> clathrin-dependent endocytosis. Intriguingly, clathrin-mediated endocytosis is relatively important for internalizing shorter SWCNTs. The dynamic processes of SWCNTs uptake and exocytosis and the mechanisms revealed by this study may render a better understanding on SWCNT toxicity and facilitate the design of CNT products with mitigated toxicity and desired functions.
Biological early diagenesis and insolation-paced paleoproductivity signified in deep core sediment organic matter
Authors: Chen Meilian , Kim Ji-Hoon , Choi Jiyoung , Lee Yun Kyung , Hur Jin
Published: May 2017

The dynamics of a large stock of organic matter contained in deep sediments of marginal seas plays pivotal role in global carbon cycle, yet it is poorly constrained. Here, dissolved organic matter (DOM) in sediments was investigated for core sediment up to ~240 meters deep in the East/Japan Sea. The upper downcore profile (≤118 mbsf, or meters below seafloor) at a non-chimney site (U1) featured the exponential production of dissolved organic carbon (DOC) and optically active DOM with time in the pore water above sulfate-methane-transition-zone (SMTZ), concurrent with the increases of nutrients and alkalinity, and the reduction of sulfate. Such depth profiles signify a biological pathway of the DOM production during the early diagenesis of particulate organic matter presumably dominated by sulfate reduction. Below the SMTZ, an insolation-paced oscillation of DOM in a ~405-Kyr cycle of orbital eccentricity was observed at site U1, implying astronomically paced paleoproductivity stimulated by light availability. Furthermore, DOM dynamics of the deep sediments were likely governed by intensive humification as revealed by the less pronounced protein-like fluorescence and the lower H/C and O/C ratios below SMTZ among 15,281 formulas identified. Our findings here provide novel insights into organic matter dynamics in deep sediments.
Inflammatory state exists in familial amyloid polyneuropathy that may be triggered by mutated transthyretin
Authors: Suenaga Genki , Ikeda Tokunori , Masuda Teruaki , Motokawa Hiroaki , Yamashita Taro , Takamatsu Kotaro , Misumi Yohei , Ueda Mitsuharu , Matsui Hirotaka , Senju Satoru , Ando Yukio
Published: May 2017

The relationship between familial amyloid polyneuropathy (FAP), which is caused by mutated transthyretin (TTR), and inflammation has only recently been noted. To determine whether inflammation is present in FAP carriers and patients, serum interleukin (IL)−6 concentration in 57 healthy donors (HD), 21 FAP carriers, and 66 FAP patients was examined, with the relationship between IL-6 and TTR assessed in each group by multiple regression analysis and structural equation models (SEM). Compared with HD, IL-6 concentration was elevated in FAP carriers (p = 0.001, 95% CI 0.398–1.571) and patients (p = 0.002, 95% CI 0.362–1.521). Further, SEM indicated a positive relationship between IL-6 and TTR in FAP carriers (p = 0.010, 95% CI 0.019–0.140), but not in HD and FAP patients. In addition, we determined whether TTR induces production of pro-inflammatory cytokines ex vivo. HD-derived CD14 + monocytes and induced pluripotent stem cell-derived myeloid lineage cells from a HD and FAP patient dose-dependently produced IL-6 under mutated and aggregated TTR conditions, compared with wild-type TTR. In conclusion, FAP carriers and patients are in an inflammatory state, with the presence of mutated TTR being a trigger of inflammation, especially in FAP carriers.
A novel non genomic glucocorticoid signaling mediated by a membrane palmitoylated glucocorticoid receptor cross talks with GnRH in gonadotrope cells
Authors: Ayrout Mohsen , Simon Violaine , Bernard Valérie , Binart Nadine , Cohen-Tannoudji Joëlle , Lombès Marc , Chauvin Stéphanie
Published: May 2017

Glucocorticoid hormones (GC) are the main stress mediators associated with reproductive disorders. GC exert their effects through activation of the glucocorticoid receptor (GR) principally acting as a transcription factor. Beside well-established GR-mediated genomic actions, several lines of evidence suggest a role for rapid membrane-initiated GC signaling in gonadotrope cells triggered by a membrane-associated GR. Herein, we demonstrate the existence of a specific membrane-initiated GC signaling in LβT2 gonadotrope cells involving two related phosphoproteins: Ca2+/Calmodulin-dependent protein kinase II (CaMKII) and synapsin-I. Within 5 min, LβT2 cells treated with stress range of 10−7 M Corticosterone or a membrane impermeable-GC, BSA-conjugated corticosterone, exhibited a 2-fold increase in levels of phospho-CaMKII and phospho-synapsin-I. Biochemical approaches revealed that this rapid signaling is promoted by a palmitoylated GR. Importantly, GC significantly alter GnRH-induced CaMKII phosphorylation, consistent with a novel cross-talk between the GnRH receptor and GC. This negative effect of GC on GnRH signaling was further observed on LH release by mouse pituitary explants. Altogether, our work provides new findings in GC field by bringing novel understanding on how GR integrates plasma membrane, allowing GC membrane-initiated signaling that differs in presence of GnRH to disrupt GnRH-dependent signaling and LH secretion.
No protection of permafrost due to desertification on the Qinghai–Tibet Plateau
Authors: Wu Qingbai , Yu Wenbing , Jin Huijun
Published: May 2017

Desertification of tundra regions may form an escalating cycle with permafrost degradation where more permafrost thaw leads to continued desertification. This traditional viewpoint has been challenged in recent reports that state desertification protects the underlying permafrost. However, our measurements of soil temperature from nine sites in the Honglianghe River Basin, interior Qinghai-Tibet Plateau, show that desertification can degrade permafrost. If one compares the permafrost temperatures at sites with thin sand covers (e.g. site Yu-7, permafrost temperature of −0.64 °C; site Yu-6, permafrost temperature of −1.15 °C) with that of site Xie-1 (−0.65 °C, with a 120-cm-thick sand cover), the permafrost temperature is not significantly different. It is clear that a thick sand cover does not influence the underlying permafrost temperature. Our observations support traditional geocryological knowledge which states that, under most circumstances, desertification does not protect, but rather degrades, permafrost.
FRET-based Visualization of PDGF Receptor Activation at Membrane Microdomains
Authors: Seong Jihye , Huang Min , Sim Kyoung Mi , Kim Hyunbin , Wang Yingxiao
Published: May 2017

Platelet-derived growth factor receptor (PDGFR) senses extracellular growth factors and transfer the signals inside the cells regulating cell proliferation, migration and survival. It has been controversial at which membrane microdomains PDGFRs reside and how they control such diverse intracellular signaling pathways. Here, we developed a novel PDGFR biosensor based on fluorescence resonance energy transfer (FRET), which can detect the real-time PDGFR activity in live cells with high spatiotemporal resolutions. To study subcellular PDGFR activity at membrane microdomains, this PDGFR biosensor was further targeted in or outside lipid rafts via different lipid modification signals. The results suggest that, in response to PDGF stimulation, PDGFR activity is evenly distributed at different membrane microdomains, while integrin-mediated signaling events have inhibitory effects on the activation of PDGFR specifically located in lipid rafts but not outside rafts, implying the role of lipid microdomains as segregated signaling platforms.
Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin
Authors: Chelakkot Chaithanya , Ghim Jaewang , Rajasekaran Nirmal , Choi Jong-Sun , Kim Jung-Hwan , Jang Myoung Ho , Shin Young Kee , Suh Pann-Ghill , Ryu Sung Ho
Published: May 2017

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal-specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis.
Tumor protein 53 mutations are enriched in diffuse large B-cell lymphoma with irregular CD19 marker expression
Authors: Kazantseva Marina , Hung Noelyn A. , Mehta Sunali , Roth Imogen , Eiholzer Ramona , Rich Alison M. , Seo Benedict , Baird Margaret A. , Braithwaite Antony W. , Slatter Tania L.
Published: May 2017

Accumulating evidence suggests tumor protein 53 (p53) promotes correct cellular differentiation. Thus, mutant TP53 may be more frequent in tumors with irregular differentiation. This study investigated whether TP53 mutations were more frequent in diffuse large B cell lymphoma (DLBCL) that lacked the B cell lineage marker CD19. Sixteen CD19 negative and 78 CD19 positive DLBCL were sequenced for TP53 mutations. Twenty nine tumors had TP53 mutations and were associated with poorer survival. Mutant TP53 was more frequent in CD19 negative lymphomas (81% versus 21%, p < 0.0001). Analysis of other B cell markers revealed a lack of paired box 5 (PAX5) in CD19 positive lymphomas with mutant TP53 (50%), which was more frequent compared to tumors with wild-type TP53 (15%, p = 0.002). In summary, DLBCL lacking CD19 or PAX5 expression were more likely to have mutant TP53, suggesting irregular B cell marker phenotypes are associated with TP53 mutation.
Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis
Authors: Abadpour Shadab , Göpel Sven O. , Schive Simen W. , Korsgren Olle , Foss Aksel , Scholz Hanne
Published: May 2017

One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin:insulin ratio in nutrient deprived human islets. Furthermore, GDNF alleviated thapsigargin-induced ER stress evidenced by reduced expressions of IRE1α and BiP and consequently apoptosis. Importantly, this was associated with an increase in phosphorylation of PI3K/AKT and GSK3B signaling pathway. Transplantation of ER stressed human islets pre-treated with GDNF under kidney capsule of diabetic mice resulted in reduced expressions of IRE1α and BiP in human islet grafts with improved grafts function shown by higher levels of human C-peptide post-transplantation. We suggest that GDNF has protective and anti-apoptotic effects on nutrient deprived and ER stress activated human islets and could play a significant role in rescuing human islets from stress responses.
Multi-Colored Light-Emitting Electrochemical Cells Based on Thermal Activated Delayed Fluorescence Host
Authors: Liu Jiang , Oliva Jorge , Tong Kwing , Zhao Fangchao , Chen Dustin , Pei Qibing
Published: May 2017

Light-emitting electrochemical cells (LECs) with the thermally activated delayed fluorescence(TADF) host and phosphorescent guests were fabricated using solution process. It is demonstrated for the first time that TADF, a well-known phenomenon that helps to increase electroluminescence efficiency by harvesting excitons from triplet states, is used as a host in LECs. Devices with green, yellow, red and warm white emissions were fabricated, with the best devices showing more than 7000 cd/m2 stable emission and a peak efficiency over 7 cd/A. Under high voltage stress, a burst of extremely high luminance of over 30,000 cd/m2 was observed. All these LEC devices are extremely simple with only one active layer. Thus, our results could pave way to produce low- cost light source with high luminance, using TADF molecules.
Human ancestry correlates with language and reveals that race is not an objective genomic classifier
Authors: Baker Jennifer L. , Rotimi Charles N. , Shriner Daniel
Published: May 2017

Genetic and archaeological studies have established a sub-Saharan African origin for anatomically modern humans with subsequent migrations out of Africa. Using the largest multi-locus data set known to date, we investigated genetic differentiation of early modern humans, human admixture and migration events, and relationships among ancestries and language groups. We compiled publicly available genome-wide genotype data on 5,966 individuals from 282 global samples, representing 30 primary language families. The best evidence supports 21 ancestries that delineate genetic structure of present-day human populations. Independent of self-identified ethno-linguistic labels, the vast majority (97.3%) of individuals have mixed ancestry, with evidence of multiple ancestries in 96.8% of samples and on all continents. The data indicate that continents, ethno-linguistic groups, races, ethnicities, and individuals all show substantial ancestral heterogeneity. We estimated correlation coefficients ranging from 0.522 to 0.962 between ancestries and language families or branches. Ancestry data support the grouping of Kwadi-Khoe, Kx’a, and Tuu languages, support the exclusion of Omotic languages from the Afroasiatic language family, and do not support the proposed Dené-Yeniseian language family as a genetically valid grouping. Ancestry data yield insight into a deeper past than linguistic data can, while linguistic data provide clarity to ancestry data.
HIV-1 CRF01_AE strain is associated with faster HIV/AIDS progression in Jiangsu Province, China
Authors: Chu Minjie , Zhang Wuhong , Zhang Xuan , Jiang Wenjie , Huan Xiping , Meng Xiaojun , Zhu Bowen , Yang Yue , Tao Yusha , Tian Tian , Lu Yihua , Jiang Liying , Zhang Lei , Zhuang Xun
Published: May 2017

The goal of this study was to assess risk factors associated with HIV/AIDS progression. Between May 2007 and December 2014, 114 subjects were enrolled in Wuxi City and examined every 6 months. The pol gene sequence was amplified to ascertain the HIV-1 subtype. A Cox proportional hazards regression model was used to estimate the factors associated with HIV/AIDS progression. The median follow-up time for all 114 subjects was 26.70 months (IQR: 18.50–41.47), while the median progression time of the 38 progressed subjects was 24.80 months (IQR: 14.13–34.38). Overall, the CRF01_AE subtype was correlated with a significant risk of accelerated progression compared to non-CRF01_AE subtypes (HR = 3.14, 95%CI: 1.39–7.08, P = 0.006). In addition, a lower CD4 count (350–499) at baseline was associated with a risk of accelerated HIV/AIDS progression compared to higher CD4 count (≥500) (HR = 4.38, 95%CI: 1.95–9.82, P < 0.001). Furthermore, interaction analyses showed that HIV-1 subtypes interacted multiplicatively with transmission routes or CD4 count at baseline to contribute to HIV/AIDS progression (P = 0.023 and P < 0.001, respectively). In conclusion, the CRF01_AE subtype and a lower CD4 count at baseline tend to be associated with the faster progression of HIV/AIDS. Understanding the factors affecting HIV/AIDS progression is crucial for developing personalized management and clinical counselling strategies.