bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiphospholipid antibodies enhance rat neonatal cardiomyocyte apoptosis in an in vitro hypoxia/reoxygenation injury model via p38 MAPK
Authors: Bourke Lauren T , McDonnell Thomas , McCormick James , Pericleous Charis , Ripoll Vera M , Giles Ian , Rahman Anisur , Stephanou Anastasis , Ioannou Yiannis
Published: January 2017

A significant amount of myocardial damage during a myocardial infarction (MI) occurs during the reperfusion stage, termed ischaemia/reperfusion (I/R) injury, and accounts for up to 50% of total infarcted tissue post-MI. During the reperfusion phase, a complex interplay of multiple pathways and mechanisms is activated, which ultimately leads to cell death, primarily through apoptosis. There is some evidence from a lupus mouse model that lupus IgG, specifically the antiphospholipid (aPL) antibody subset, is pathogenic in mesenteric I/R injury. Furthermore, it has previously been shown that the immunodominant epitope for the majority of circulating pathogenic aPLs resides in the N-terminal domain I (DI) of beta-2 glycoprotein I (β2GPI). This study describes the enhanced pathogenic effect of purified IgG derived from patients with lupus and/or the antiphospholipid syndrome in a cardiomyocyte H/R in vitro model. Furthermore, we have demonstrated a pathogenic role for aPL containing samples, mediated via aPL–β2GPI interactions, resulting in activation of the pro-apoptotic p38 MAPK pathway. This was shown to be inhibited using a recombinant human peptide of domain I of β2GPI in the fluid phase, suggesting that the pathogenic anti-β2GPI antibodies in this in vitro model target this domain.
Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism
Authors: Chen Tzu-Ling , Yang Hung-Chi , Hung Cheng-Yu , Ou Meng-Hsin , Pan Yi-Yun , Cheng Mei-Ling , Stern Arnold , Lo Szecheng J , Chiu Daniel Tsun-Yee
Published: January 2017

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.
HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity
Authors: Sami Saribas A , Cicalese Stephanie , Ahooyi Taha Mohseni , Khalili Kamel , Amini Shohreh , Sariyer Ilker Kudret
Published: January 2017

Human immunodeficiency virus-associated neurological disorders (HANDs) affect the majority of AIDS patients and are a significant problem among HIV-1-infected individuals who live longer because of combined anti-retroviral therapies. HIV-1 utilizes a number of viral proteins and subsequent cytokine inductions to unleash its toxicity on neurons. Among HIV-1 viral proteins, Nef is a small protein expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HAND. In order to explore its effect in the central nervous system, HIV-1 Nef was expressed in primary human fetal astrocytes (PHFAs) using an adenovirus. Our results revealed that HIV-1 Nef is released in extracellular vesicles (EVs) derived from PHFA cells expressing the protein. Interestingly, HIV-1 Nef release in EVs was enriched significantly when the cells were treated with autophagy activators perifosine, tomaxifen, MG-132, and autophagy inhibitors LY294002 and wortmannin suggesting a novel role of autophagy signaling in HIV-1 Nef release from astrocytes. Next, Nef-carrying EVs were purified from astrocyte cultures and neurotoxic effects on neurons were analyzed. We observed that HIV-1 Nef-containing EVs were readily taken up by neurons as demonstrated by immunocytochemistry and immunoblotting. Furthermore, treatment of neurons with Nef-carrying EVs induced oxidative stress as evidenced by a decrease in glutathione levels. To further investigate its neurotoxic effects, we expressed HIV-1 Nef in primary neurons by adenoviral transduction. Intracellular expression of HIV-1 Nef caused axonal and neurite degeneration of neurons. Furthermore, expression of HIV-1 Nef decreased the levels of phospho-tau while enhancing total tau in primary neurons. In addition, treatment of primary neurons with Nef-carrying EVs suppressed functional neuronal action potential assessed by multielectrode array studies. Collectively, these data suggested that HIV-1 Nef can be a formidable contributor to neurotoxicity along with other factors, which leads to HAND in HIV-1-infected AIDS patients.
HIF-2α and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts
Authors: Zhang Shaoheng , Zhao Lan , Wang Jiahong , Chen Nannan , Yan Jian , Pan Xin
Published: January 2017

Poor cell survival and limited functional benefits have restricted mesenchymal stem cell (MSC) efficacy for treating myocardial infarction (MI), suggesting that a better understanding of stem cell biology is needed. The transcription factor HIF-2α is an essential regulator of the transcriptional response to hypoxia, which can interact with embryonic stem cells (ESCs) transcription factor Oct4 and modulate its signaling. Here, we obtained very small embryonic-like mesenchymal stem cells (vselMSCs) from MI patients, which possessed the very small embryonic-like stem cells’ (VSELs) morphology as well as ESCs’ pluripotency. Using microarray analysis, we compared HIF-2α-regulated gene profiles in vselMSCs with ESC profiles and determined that HIF-2α coexpressed Oct4 in vselMSCs similarly to ESCs. However, this coexpression was absent in unpurified MSCs (uMSCs). Under hypoxic condition, vselMSCs exhibited stronger survival, proliferation and differentiation than uMSCs. Transplantation of vselMSCs caused greater improvement in cardiac function and heart remodeling in the infarcted rats. We further demonstrated that HIF-2α and Oct4 jointly regulate their relative downstream gene expressions, including Bcl2 and Survivin; the important pluripotent markers Nanog, Klf4, and Sox2; and Ang-1, bFGF, and VEGF, promoting angiogenesis and engraftment. Importantly, these effects were generally magnified by upregulation of HIF-2α and Oct4 induced by HIF-2α or Oct4 overexpression, and the greatest improvements were elicited after co-overexpressing HIF-2α and Oct4; overexpressing one transcription factor while silencing the other canceled this increase, and HIF-2α or Oct4 silencing abolished these effects. Together, these findings demonstrated that HIF-2α in vselMSCs cooperated with Oct4 in survival and function. The identification of the cooperation between HIF-2α and Oct4 will lead to deeper characterization of the downstream targets of this interaction in vselMSCs and will have novel pathophysiological implications for the repair of infarcted myocardium.
Local dimensionality determines imaging speed in localization microscopy
Authors: Fox-Roberts Patrick , Marsh Richard , Pfisterer Karin , Jayo Asier , Parsons Maddy , Cox Susan
Published: January 2017

Localization microscopy allows biological samples to be imaged at a length scale of tens of nanometres. Live-cell super-resolution imaging is rare, as it is generally assumed to be too slow for dynamic samples. The speed of data acquisition can be optimized by tuning the density of activated fluorophores in each time frame. Here, we show that the maximum achievable imaging speed for a particular structure varies by orders of magnitude, depending on the sample dimensionality (that is, whether the sample is more like a point, a strand or an extended structure such as a focal adhesion). If too high an excitation density is used, we demonstrate that the analysis undergoes silent failure, resulting in reconstruction artefacts. We are releasing a tool to allow users to identify areas of the image in which the activation density was too high and correct for them, in both live- and fixed-cell experiments.
Does retinal configuration make the head and eyes of foveate birds move?
Authors: Moore Bret A. , Tyrrell Luke P. , Pita Diana , Bininda-Emonds Olaf R. P. , Fernández-Juricic Esteban
Published: January 2017

Animals move their heads and eyes to compensate for movements of the body and background, search, fixate, and track objects visually. Avian saccadic head/eye movements have been shown to vary considerably between species. We tested the hypothesis that the configuration of the retina (i.e., changes in retinal ganglion cell density from the retinal periphery to the center of acute vision-fovea) would account for the inter-specific variation in avian head/eye movement behavior. We characterized retinal configuration, head movement rate, and degree of eye movement of 29 bird species with a single fovea, controlling for the effects of phylogenetic relatedness. First, we found the avian fovea is off the retinal center towards the dorso-temporal region of the retina. Second, species with a more pronounced rate of change in ganglion cell density across the retina generally showed a higher degree of eye movement and higher head movement rate likely because a smaller retinal area with relatively high visual acuity leads to greater need to move the head/eye to align this area that contains the fovea with objects of interest. Our findings have implications for anti-predator behavior, as many predator-prey interaction models assume that the sensory system of prey (and hence their behavior) varies little between species.
Integrated crop management practices for maximizing grain yield of double-season rice crop
Authors: Wang Depeng , Huang Jianliang , Nie Lixiao , Wang Fei , Ling Xiaoxia , Cui Kehui , Li Yong , Peng Shaobing
Published: January 2017

Information on maximum grain yield and its attributes are limited for double-season rice crop grown under the subtropical environment. This study was conducted to examine key characteristics associated with high yielding double-season rice crop through a comparison between an integrated crop management (ICM) and farmers’ practice (FP). Field experiments were conducted in the early and late seasons in the subtropical environment of Wuxue County, Hubei Province, China in 2013 and 2014. On average, grain yield in ICM was 13.5% higher than that in FP. A maximum grain yield of 9.40 and 10.53 t ha−1 was achieved under ICM in the early- and late-season rice, respectively. Yield improvement of double-season rice with ICM was achieved with the combined effects of increased plant density and optimized nutrient management. Yield gain of ICM resulted from a combination of increases in sink size due to more panicle number per unit area and biomass production, further supported by the increased leaf area index, leaf area duration, radiation use efficiency, crop growth rate, and total nitrogen uptake compared with FP. Further enhancement in the yield potential of double-season rice should focus on increasing crop growth rate and biomass production through improved and integrated crop management practices.
High-field transport properties of a P-doped BaFe2As2 film on technical substrate
Authors: Iida Kazumasa , Sato Hikaru , Tarantini Chiara , Hänisch Jens , Jaroszynski Jan , Hiramatsu Hidenori , Holzapfel Bernhard , Hosono Hideo
Published: January 2017

High temperature (high-Tc) superconductors like cuprates have superior critical current properties in magnetic fields over other superconductors. However, superconducting wires for high-field-magnet applications are still dominated by low-Tc Nb3Sn due probably to cost and processing issues. The recent discovery of a second class of high-Tc materials, Fe-based superconductors, may provide another option for high-field-magnet wires. In particular, AEFe2As2 (AE: Alkali earth elements, AE-122) is one of the best candidates for high-field-magnet applications because of its high upper critical field, Hc2, moderate Hc2 anisotropy, and intermediate Tc. Here we report on in-field transport properties of P-doped BaFe2As2 (Ba-122) thin films grown on technical substrates by pulsed laser deposition. The P-doped Ba-122 coated conductor exceeds a transport Jc of 105 A/cm2 at 15 T for main crystallographic directions of the applied field, which is favourable for practical applications. Our P-doped Ba-122 coated conductors show a superior in-field Jc over MgB2 and NbTi, and a comparable level to Nb3Sn above 20 T. By analysing the E − J curves for determining Jc, a non-Ohmic linear differential signature is observed at low field due to flux flow along the grain boundaries. However, grain boundaries work as flux pinning centres as demonstrated by the pinning force analysis.
Local geology controlled the feasibility of vitrifying Iron Age buildings
Authors: Wadsworth Fabian B. , Heap Michael J. , Damby David E. , Hess Kai-Uwe , Najorka Jens , Vasseur Jérémie , Fahrner Dominik , Dingwell Donald B.
Published: January 2017

During European prehistory, hilltop enclosures made from polydisperse particle-and-block stone walling were exposed to temperatures sufficient to partially melt the constituent stonework, leading to the preservation of glassy walls called ‘vitrified forts’. During vitrification, the granular wall rocks partially melt, sinter viscously and densify, reducing inter-particle porosity. This process is strongly dependent on the solidus temperature, the particle sizes, the temperature-dependence of the viscosity of the evolving liquid phase, as well as the distribution and longevity of heat. Examination of the sintering behaviour of 45 European examples reveals that it is the raw building material that governs the vitrification efficiency. As Iron Age forts were commonly constructed from local stone, we conclude that local geology directly influenced the degree to which buildings were vitrified in the Iron Age. Additionally, we find that vitrification is accompanied by a bulk material strengthening of the aggregates of small sizes, and a partial weakening of larger blocks. We discuss these findings in the context of the debate surrounding the motive of the wall-builders. We conclude that if wall stability by bulk strengthening was the desired effect, then vitrification represents an Iron Age technology that failed to be effective in regions of refractory local geology.
Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China
Authors: Pei Junrui , Li Bingyun , Liu Yang , Liu Xiaona , Li Mang , Chu Yanru , Yang Qing , Jiang Wei , Chen Fuxun , Darko Gottfried M. , Yang Yanmei , Gao Yanhui
Published: January 2017

Brick tea skeletal fluorosis is still a public health issue in the north-western area of China. However its pathogenesis remains unknown. Our previous study reveals that the severity of skeletal fluorosis in Tibetans is more serious than that in Kazaks, although they have similar fluoride exposure, suggesting the onset of brick tea type skeletal fluorosis might be genetically influenced. Here we show that MMP-2 rs2287074 SNP (G/A), but not rs243865, was associated with Brick tea type fluorosis in Tibetans and Kazaks, China. The trend test reveals a decline in probability for skeletal fluorosis with increasing number of A alleles in Tibetans. After controlling potential confounders, AA genotype had about 80 percent lower probability of developing skeletal fluorosis than GG genotype in Tibetans (odds ratio = 0.174, 95% CI: 0.053, 0.575), and approximately 53 percent lower probability in Kazaks (odds ratio = 0.462, 95% CI: 0.214, 0.996). A meta-analysis shows that the AA genotype had approximately 63 percent lower odds (odds ratio = 0.373, 95% CI: 0.202, 0.689) compared with GG genotype within the two ethnicities. A significant correlation was also found between the genotype of MMP2 rs2287074 and skeletal fluorosis severity. Therefore, the A allele of MMP2 rs2287074 could be a protective factor for brick tea skeletal fluorosis.
Blood Occludin Level as a Potential Biomarker for Early Blood Brain Barrier Damage Following Ischemic Stroke
Authors: Pan Rong , Yu Kewei , Weatherwax Theodore , Zheng Handong , Liu Wenlan , Liu Ke Jian
Published: January 2017

Concern about intracerebral hemorrhage (ICH) is the primary reason for withholding tPA therapy from patients with ischemic stroke. Early blood brain barrier (BBB) damage is the major risk factor for fatal post-thrombolysis ICH, but rapidly assessing BBB damage before tPA administration is highly challenging. We recently reported that ischemia induced rapid degradation of tight junction protein occludin in cerebromicrovessels. The present study investigates whether the cleaved occludin is released into the blood stream and how blood occludin levels correlate to the extent of BBB damage using a rat model of ischemic stroke. Cerebral ischemia induced a time-dependent increase of blood occludin with a sharp increase at 4.5-hour post-ischemia onset, which concurrently occurred with the loss of occludin from ischemic cerebral microvessels and a massive BBB leakage at 4.5-hour post-ischemia. Two major occludin fragments were identified in the blood during cerebral ischemia. Furthermore, blood occludin levels remained significantly higher than its basal level within the first 24 hours after ischemia onset. Our findings demonstrate that blood occludin levels correlate well with the extent of BBB damage and thus may serve as a clinically relevant biomarker for evaluating the risk of ICH before tPA administration.
Enhanced Radiation-tolerant Oxide Dispersion Strengthened Steel and its Microstructure Evolution under Helium-implantation and Heavy-ion Irradiation
Authors: Lu Chenyang , Lu Zheng , Wang Xu , Xie Rui , Li Zhengyuan , Higgins Michael , Liu Chunming , Gao Fei , Wang Lumin
Published: January 2017

The world eagerly needs cleanly-generated electricity in the future. Fusion reactor is one of the most ideal energy resources to defeat the environmental degradation caused by the consumption of traditional fossil energy. To meet the design requirements of fusion reactor, the development of the structural materials which can sustain the elevated temperature, high helium concentration and extreme radiation environments is the biggest challenge for the entire material society. Oxide dispersion strengthened steel is one of the most popular candidate materials for the first wall/blanket applications in fusion reactor. In this paper, we evaluate the radiation tolerance of a 9Cr ODS steel developed in China. Compared with Ferritic/Martensitic steel, this ODS steel demonstrated a significantly higher swelling resistance under ion irradiation at 460 °C to 188 displacements per atom. The role of oxides and grain boundaries on void swelling has been explored. The results indicated that the distribution of higher density and finer size of nano oxides will lead a better swelling resistance for ODS alloy. The original pyrochlore-structured Y2Ti2O7 particles dissolved gradually while fine Y-Ti-O nano clusters reprecipitated in the matrix during irradiation. The enhanced radiation tolerance is attributed to the reduced oxide size and the increased oxide density.
Development of a 690 K SNP array in catfish and its application for genetic mapping and validation of the reference genome sequence
Authors: Zeng Qifan , Fu Qiang , Li Yun , Waldbieser Geoff , Bosworth Brian , Liu Shikai , Yang Yujia , Bao Lisui , Yuan Zihao , Li Ning , Liu Zhanjiang
Published: January 2017

Single nucleotide polymorphisms (SNPs) are capable of providing the highest level of genome coverage for genomic and genetic analysis because of their abundance and relatively even distribution in the genome. Such a capacity, however, cannot be achieved without an efficient genotyping platform such as SNP arrays. In this work, we developed a high-density SNP array with 690,662 unique SNPs (herein 690 K array) that were relatively evenly distributed across the entire genome, and covered 98.6% of the reference genome sequence. Here we also report linkage mapping using the 690 K array, which allowed mapping of over 250,000 SNPs on the linkage map, the highest marker density among all the constructed linkage maps. These markers were mapped to 29 linkage groups (LGs) with 30,591 unique marker positions. This linkage map anchored 1,602 scaffolds of the reference genome sequence to LGs, accounting for over 97% of the total genome assembly. A total of 1,007 previously unmapped scaffolds were placed to LGs, allowing validation and in few instances correction of the reference genome sequence assembly. This linkage map should serve as a valuable resource for various genetic and genomic analyses, especially for GWAS and QTL mapping for genes associated with economically important traits.
Subwavelength grating as both emission mirror and electrical contact for VCSELs in any material system
Authors: Czyszanowski Tomasz , Gebski Marcin , Dems Maciej , Wasiak Michał , Sarzała Robert , Panajotov Krassimir
Published: January 2017

Semiconductor-metal subwavelength grating (SMSG) can serve a dual purpose in vertical-cavity surface-emitting lasers (VCSELs), as both optical coupler and current injector. SMSGs provide optical as well as lateral current confinement, eliminating the need for ring contacts and lateral build-in optical and current confinement, allowing their implementation on arbitrarily large surfaces. Using an SMSG as the top mirror enables fabrication of monolithic VCSELs from any type of semiconductor crystal. The construction of VCSELs with SMSGs requires significantly less p-type material, in comparison to conventional VCSELs. In this paper, using a three-dimensional, fully vectorial optical model, we analyse the properties of the stand-alone SMSG in a number of semiconductor materials for a broad range of wavelengths. Integrating the optical model with thermal and electrical numerical models, we then simulate the threshold operation of an exemplary SMSG VCSEL.
Environmental DNA metabarcoding reveals local fish communities in a species-rich coastal sea
Authors: Yamamoto Satoshi , Masuda Reiji , Sato Yukuto , Sado Tetsuya , Araki Hitoshi , Kondoh Michio , Minamoto Toshifumi , Miya Masaki
Published: January 2017

Environmental DNA (eDNA) metabarcoding has emerged as a potentially powerful tool to assess aquatic community structures. However, the method has hitherto lacked field tests that evaluate its effectiveness and practical properties as a biodiversity monitoring tool. Here, we evaluated the ability of eDNA metabarcoding to reveal fish community structures in species-rich coastal waters. High-performance fish-universal primers and systematic spatial water sampling at 47 stations covering ~11 km2 revealed the fish community structure at a species resolution. The eDNA metabarcoding based on a 6-h collection of water samples detected 128 fish species, of which 62.5% (40 species) were also observed by underwater visual censuses conducted over a 14-year period. This method also detected other local fishes (≥23 species) that were not observed by the visual censuses. These eDNA metabarcoding features will enhance marine ecosystem-related research, and the method will potentially become a standard tool for surveying fish communities.
Parallel-META 3: Comprehensive taxonomical and functional analysis platform for efficient comparison of microbial communities
Authors: Jing Gongchao , Sun Zheng , Wang Honglei , Gong Yanhai , Huang Shi , Ning Kang , Xu Jian , Su Xiaoquan
Published: January 2017

The number of metagenomes is increasing rapidly. However, current methods for metagenomic analysis are limited by their capability for in-depth data mining among a large number of microbiome each of which carries a complex community structure. Moreover, the complexity of configuring and operating computational pipeline also hinders efficient data processing for the end users. In this work we introduce Parallel-META 3, a comprehensive and fully automatic computational toolkit for rapid data mining among metagenomic datasets, with advanced features including 16S rRNA extraction for shotgun sequences, 16S rRNA copy number calibration, 16S rRNA based functional prediction, diversity statistics, bio-marker selection, interaction network construction, vector-graph-based visualization and parallel computing. Application of Parallel-META 3 on 5,337 samples with 1,117,555,208 sequences from diverse studies and platforms showed it could produce similar results as QIIME and PICRUSt with much faster speed and lower memory usage, which demonstrates its ability to unravel the taxonomical and functional dynamics patterns across large datasets and elucidate ecological links between microbiome and the environment. Parallel-META 3 is implemented in C/C++ and R, and integrated into an executive package for rapid installation and easy access under Linux and Mac OS X. Both binary and source code packages are available at http://bioinfo.single-cell.cn/parallel-meta.html.
The prognostic role of EGFR-TKIs for patients with advanced non-small cell lung cancer
Authors: Zhao Dan , Chen Xuejing , Qin Na , Su Dan , Zhou Lijuan , Zhang Quan , Li Xi , Zhang Xinyong , Jin Mulan , Wang Jinghui
Published: January 2017

Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11.7 months. Cox analysis showed that PS 0–1, recurrent disease, EGFR mutations, or EGFR-TKI treatment were associated with improved OS. In patients with EGFR-activating mutations, Cox analysis showed that patients with adenocarcinoma, recurrent disease, or EGFR-TKI treatment had significantly longer survival. Patients with EGFR-activating mutations who received EGFR-TKI therapy had a median OS of 24.3 months, which was significantly longer than those who had not received EGFR-TKI therapy (10.8 months). Patients with wild-type EGFR had a median OS of 9.7 months and Cox analysis showed that PS score and disease type were independent predictors. EGFR-TKI therapy is an independently prognostic factor for NSCLC with mutated EGFR. A more effective therapy is needed for patients with wild-type EGFR.
Methionine residues around phosphorylation sites are preferentially oxidized in vivo under stress conditions
Authors: Veredas Francisco J. , Cantón Francisco R. , Aledo J. Carlos
Published: January 2017

Protein phosphorylation is one of the most prevalent and well-understood protein modifications. Oxidation of protein-bound methionine, which has been traditionally perceived as an inevitable damage derived from oxidative stress, is now emerging as another modification capable of regulating protein activity during stress conditions. However, the mechanism coupling oxidative signals to changes in protein function remains unknown. An appealing hypothesis is that methionine oxidation might serve as a rheostat to control phosphorylation. To investigate this potential crosstalk between phosphorylation and methionine oxidation, we have addressed the co-occurrence of these two types of modifications within the human proteome. Here, we show that nearly all (98%) proteins containing oxidized methionine were also phosphoproteins. Furthermore, phosphorylation sites were much closer to oxidized methionines when compared to non-oxidized methionines. This proximity between modification sites cannot be accounted for by their co-localization within unstructured clusters because it was faithfully reproduced in a smaller sample of structured proteins. We also provide evidence that the oxidation of methionine located within phosphorylation motifs is a highly selective process among stress-related proteins, which supports the hypothesis of crosstalk between methionine oxidation and phosphorylation as part of the cellular defence against oxidative stress.
Comfortable, high-efficiency heat pump with desiccant-coated, water-sorbing heat exchangers
Authors: Tu Y. D. , Wang R. Z. , Ge T. S. , Zheng X.
Published: January 2017

Comfortable, efficient, and affordable heating, ventilation, and air conditioning systems in buildings are highly desirable due to the demands of energy efficiency and environmental friendliness. Traditional vapor-compression air conditioners exhibit a lower coefficient of performance (COP) (typically 2.8–3.8) owing to the cooling-based dehumidification methods that handle both sensible and latent loads together. Temperature- and humidity-independent control or desiccant systems have been proposed to overcome these challenges; however, the COP of current desiccant systems is quite small and additional heat sources are usually needed. Here, we report on a desiccant-enhanced, direct expansion heat pump based on a water-sorbing heat exchanger with a desiccant coating that exhibits an ultrahigh COP value of more than 7 without sacrificing any comfort or compactness. The pump’s efficiency is doubled compared to that of pumps currently used in conventional room air conditioners, which is a revolutionary HVAC breakthrough. Our proposed water-sorbing heat exchanger can independently handle sensible and latent loads at the same time. The desiccants adsorb moisture almost isothermally and can be regenerated by condensation heat. This new approach opens up the possibility of achieving ultrahigh efficiency for a broad range of temperature- and humidity-control applications.
Growth and Morbidity of Gambian Infants are Influenced by Maternal Milk Oligosaccharides and Infant Gut Microbiota
Authors: Davis Jasmine C. C. , Lewis Zachery T. , Krishnan Sridevi , Bernstein Robin M. , Moore Sophie E. , Prentice Andrew M. , Mills David A. , Lebrilla Carlito B. , Zivkovic Angela M.
Published: January 2017

Human milk oligosaccharides (HMOs) play an important role in the health of an infant as substrate for beneficial gut bacteria. Little is known about the effects of HMO composition and its changes on the morbidity and growth outcomes of infants living in areas with high infection rates. Mother’s HMO composition and infant gut microbiota from 33 Gambian mother/infant pairs at 4, 16, and 20 weeks postpartum were analyzed for relationships between HMOs, microbiota, and infant morbidity and growth. The data indicate that lacto-N-fucopentaose I was associated with decreased infant morbidity, and 3′-sialyllactose was found to be a good indicator of infant weight-for-age. Because HMOs, gut microbiota, and infant health are interrelated, the relationship between infant health and their microbiome were analyzed. While bifidobacteria were the dominant genus in the infant gut overall, Dialister and Prevotella were negatively correlated with morbidity, and Bacteroides was increased in infants with abnormal calprotectin. Mothers nursing in the wet season (July to October) produced significantly less oligosaccharides compared to those nursing in the dry season (November to June). These results suggest that specific types and structures of HMOs are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota.
The Herbivore-Induced Plant Volatiles Methyl Salicylate and Menthol Positively affect Growth and Pathogenicity of Entomopathogenic Fungi
Authors: Lin Yongwen , Qasim Muhammad , Hussain Mubasher , Akutse Komivi Senyo , Avery Pasco Bruce , Dash Chandra Kanta , Wang Liande
Published: January 2017

Some herbivore-induced-plant volatiles (HIPVs) compounds are vital for the functioning of an ecosystem, by triggering multi-trophic interactions for natural enemies, plants and herbivores. However, the effect of these chemicals, which play a crucial role in regulating the multi-trophic interactions between plant-herbivore-entomopathogenic fungi, is still unknown. To fill this scientific gap, we therefore investigated how these chemicals influence the entomopathogenic fungi growth and efficacy. In this study, Lipaphis erysimi induced Arabidopsis thaliana HIPVs were collected using headspace system and detected with GC-MS, and then analyzed the effects of these HIPVs chemicals on Lecanicillium lecanii strain V3450. We found that the HIPVs menthol and methyl salicylate at 1 and 10 nmol·ml−1 improved many performance aspects of the fungus, such as germination, sporulation, appressorial formation as well as its pathogenicity and virulence. These findings are not only important for understanding the multi-trophic interactions in an ecosystem, but also would contribute for developing new and easier procedures for conidial mass production as well as improve the pathogenicity and virulence of entomopathogenic fungi in biological pest management strategies.
Modulation of snow reflectance and snowmelt from Central Asian glaciers by anthropogenic black carbon
Authors: Schmale Julia , Flanner Mark , Kang Shichang , Sprenger Michael , Zhang Qianggong , Guo Junming , Li Yang , Schwikowski Margit , Farinotti Daniel
Published: January 2017

Deposited mineral dust and black carbon are known to reduce the albedo of snow and enhance melt. Here we estimate the contribution of anthropogenic black carbon (BC) to snowmelt in glacier accumulation zones of Central Asia based on in-situ measurements and modelling. Source apportionment suggests that more than 94% of the BC is emitted from mostly regional anthropogenic sources while the remaining contribution comes from natural biomass burning. Even though the annual deposition flux of mineral dust can be up to 20 times higher than that of BC, we find that anthropogenic BC causes the majority (60% on average) of snow darkening. This leads to summer snowmelt rate increases of up to 6.3% (7 cm a−1) on glaciers in three different mountain environments in Kyrgyzstan, based on albedo reduction and snowmelt models.
Feeling Touched: Emotional Modulation of Somatosensory Potentials to Interpersonal Touch
Authors: Ravaja N. , Harjunen V. , Ahmed I. , Jacucci G. , Spapé M. M.
Published: January 2017

Although the previous studies have shown that an emotional context may alter touch processing, it is not clear how visual contextual information modulates the sensory signals, and at what levels does this modulation take place. Therefore, we investigated how a toucher’s emotional expressions (anger, happiness, fear, and sadness) modulate touchee’s somatosensory-evoked potentials (SEPs) in different temporal ranges. Participants were presented with tactile stimulation appearing to originate from expressive characters in virtual reality. Touch processing was indexed using SEPs, and self-reports of touch experience were collected. Early potentials were found to be amplified after angry, happy and sad facial expressions, while late potentials were amplified after anger but attenuated after happiness. These effects were related to two stages of emotional modulation of tactile perception: anticipation and interpretation. The findings show that not only does touch affect emotion, but also emotional expressions affect touch perception. The affective modulation of touch was initially obtained as early as 25 ms after the touch onset suggesting that emotional context is integrated to the tactile sensation at a very early stage.
Tempo of magma degassing and the genesis of porphyry copper deposits
Authors: Chelle-Michou Cyril , Rottier Bertrand , Caricchi Luca , Simpson Guy
Published: January 2017

Porphyry deposits are copper-rich orebodies formed by precipitation of metal sulphides from hydrothermal fluids released from magmatic intrusions that cooled at depth within the Earth’s crust. Finding new porphyry deposits is essential because they are our largest source of copper and they also contain other strategic metals including gold and molybdenum. However, the discovery of giant porphyry deposits is hindered by a lack of understanding of the factors governing their size. Here, we use thermal modelling and statistical simulations to quantify the tempo and the chemistry of fluids released from cooling magmatic systems. We confirm that typical arc magmas produce fluids similar in composition to those that form porphyry deposits and conclude that the volume and duration of magmatic activity exert a first order control on the endowment (total mass of deposited copper) of economic porphyry copper deposits. Therefore, initial magma enrichment in copper and sulphur, although adding to the metallogenic potential, is not necessary to form a giant deposit. Our results link the respective durations of magmatic and hydrothermal activity from well-known large to supergiant deposits to their metal endowment. This novel approach can readily be implemented as an additional exploration tool that can help assess the economic potential of magmatic-hydrothermal systems.
Dietary phytochemical PEITC restricts tumor development via modulation of epigenetic writers and erasers
Authors: Park Jung Eun , Sun Yang , Lim Sai Kiang , Tam James P. , Dekker Matthijs , Chen Hong , Sze Siu Kwan
Published: January 2017

Dietary intake of bioactive phytochemicals including the cruciferous vegetable derivative phenethyl isothiocyanate (PEITC) can reduce risk of human cancers, but possible epigenetic mechanisms of these effects are yet unknown. We therefore sought to identify the molecular basis of PEITC-mediated epigenetic tumor restriction. Colon cancer cells treated with low-dose PEITC for >1 month exhibited stable alterations in expression profile of epigenetic writers/erasers and chromatin-binding of histone deacetylases (HDACs) and Polycomb-group (PcG) proteins. Sustained PEITC exposure not only blocked HDAC binding to euchromatin but was also associated with hypomethylation of PcG target genes that are typically hypermethylated in cancer. Furthermore, PEITC treatment induced expression of pro-apoptotic genes in tumor cells, which was partially reversed by overexpression of PcG member BMI-1, suggesting opposing roles for PEITC and PcG proteins in control of tumor progression. These data demonstrate that PEITC regulates chromatin binding of key epigenetic writers/erasers and PcG complexes to restrict tumor development.
Oxytocin biases men but not women to restore social connections with individuals who socially exclude them
Authors: Xu Xiaolei , Yao Shuxia , Xu Lei , Geng Yayuan , Zhao Weihua , Ma Xiaole , Kou Juan , Luo Ruixue , Kendrick Keith M.
Published: January 2017

We normally react to individuals who exclude us socially by either avoiding them or increasing our attempts to interact with them. The neuropeptide oxytocin can promote social bonds and reduce social conflict and we therefore investigated whether it facilitates more positive social responses towards individuals who exclude or include us. In a double-blind, placebo-controlled, between-subject design 77 healthy Chinese male and female participants received intranasal oxytocin (40 IU) or placebo before playing a modified virtual ball-tossing game with three fictitious partners who either showed exclusion, inclusion or neutral behavioral interactions with them. Results showed that both male and female subjects threw the ball more often to individuals who excluded rather than included them, although oxytocin did not alter this or awareness/feelings of exclusion or inclusion. However, when subjects returned a week later males, but not females, in the oxytocin group exhibited an increased liking for, and preference for playing again with, players who had previously excluded them. This oxytocin effect was positively associated with independent traits. Our findings suggest that in a collectivist culture oxytocin may promote the desire of males, but not females, with a stronger independent orientation to rebuild social connections with individuals who have previously excluded them.
Spatiotemporal Pattern of PM2.5 Concentrations in Mainland China and Analysis of Its Influencing Factors using Geographically Weighted Regression
Authors: Luo Jieqiong , Du Peijun , Samat Alim , Xia Junshi , Che Meiqin , Xue Zhaohui
Published: January 2017

Based on annual average PM2.5 gridded dataset, this study first analyzed the spatiotemporal pattern of PM2.5 across Mainland China during 1998–2012. Then facilitated with meteorological site data, land cover data, population and Gross Domestic Product (GDP) data, etc., the contributions of latent geographic factors, including socioeconomic factors (e.g., road, agriculture, population, industry) and natural geographical factors (e.g., topography, climate, vegetation) to PM2.5 were explored through Geographically Weighted Regression (GWR) model. The results revealed that PM2.5 concentrations increased while the spatial pattern remained stable, and the proportion of areas with PM2.5 concentrations greater than 35 μg/m3 significantly increased from 23.08% to 29.89%. Moreover, road, agriculture, population and vegetation showed the most significant impacts on PM2.5. Additionally, the Moran’s I for the residuals of GWR was 0.025 (not significant at a 0.01 level), indicating that the GWR model was properly specified. The local coefficient estimates of GDP in some cities were negative, suggesting the existence of the inverted-U shaped Environmental Kuznets Curve (EKC) for PM2.5 in Mainland China. The effects of each latent factor on PM2.5 in various regions were different. Therefore, regional measures and strategies for controlling PM2.5 should be formulated in terms of the local impacts of specific factors.
Proteome Response of Chicken Embryo Fibroblast Cells to Recombinant H5N1 Avian Influenza Viruses with Different Neuraminidase Stalk Lengths
Authors: Li Yongtao , Ming Fan , Huang Huimin , Guo Kelei , Chen Huanchun , Jin Meilin , Zhou Hongbo
Published: January 2017

The variation on neuraminidase (NA) stalk region of highly pathogenic avian influenza H5N1 virus results in virulence change in animals. In our previous studies, the special NA stalk-motif of H5N1 viruses has been demonstrated to play a significant role in the high virulence and pathogenicity in chickens. However, the molecular mechanisms underlying the pathogenicity of viruses with different NA stalk remain poorly understood. This study presents a comprehensive characterization of the proteome response of chicken cells to recombinant H5N1 virus with stalk-short NA (rNA-wt) and the stalkless NA mutant virus (rSD20). 208 proteins with differential abundance profiles were identified differentially expressed (DE), and these proteins were mainly related to stress response, transcription regulation, transport, metabolic process, cellular component and cytoskeleton. Through Ingenuity Pathways Analysis (IPA), the significant biological functions of DE proteins represented included Post-Translational Modification, Protein Folding, DNA Replication, Recombination and Repair. It was interesting to find that most DE proteins were involved in the TGF-β mediated functional network. Moreover, the specific DE proteins may play important roles in the innate immune responses and H5N1 virus replication. Our data provide important information regarding the comparable host response to H5N1 influenza virus infection with different NA stalk lengths.
Oriented and Ordered Biomimetic Remineralization of the Surface of Demineralized Dental Enamel Using HAP@ACP Nanoparticles Guided by Glycine
Authors: Wang Haorong , Xiao Zuohui , Yang Jie , Lu Danyang , Kishen Anil , Li Yanqiu , Chen Zhen , Que Kehua , Zhang Qian , Deng Xuliang , Yang Xiaoping , Cai Qing , Chen Ning , Cong Changhong , Guan Binbin , Li Ting , Zhang Xu
Published: January 2017

Achieving oriented and ordered remineralization on the surface of demineralized dental enamel, thereby restoring the satisfactory mechanical properties approaching those of sound enamel, is still a challenge for dentists. To mimic the natural biomineralization approach for enamel remineralization, the biological process of enamel development proteins, such as amelogenin, was simulated in this study. In this work, carboxymethyl chitosan (CMC) conjugated with alendronate (ALN) was applied to stabilize amorphous calcium phosphate (ACP) to form CMC/ACP nanoparticles. Sodium hypochlorite (NaClO) functioned as the protease which decompose amelogenin in vivo to degrade the CMC-ALN matrix and generate HAP@ACP core-shell nanoparticles. Finally, when guided by 10 mM glycine (Gly), HAP@ACP nanoparticles can arrange orderly and subsequently transform from an amorphous phase to well-ordered rod-like apatite crystals to achieve oriented and ordered biomimetic remineralization on acid-etched enamel surfaces. This biomimetic remineralization process is achieved through the oriented attachment (OA) of nanoparticles based on non-classical crystallization theory. These results indicate that finding and developing analogues of natural proteins such as amelogenin involved in the biomineralization by natural macromolecular polymers and imitating the process of biomineralization would be an effective strategy for enamel remineralization. Furthermore, this method represents a promising method for the management of early caries in minimal invasive dentistry (MID).
Interstitial atoms enable joint twinning and transformation induced plasticity in strong and ductile high-entropy alloys
Authors: Li Zhiming , Tasan Cemal Cem , Springer Hauke , Gault Baptiste , Raabe Dierk
Published: January 2017

High-entropy alloys (HEAs) consisting of multiple principle elements provide an avenue for realizing exceptional mechanical, physical and chemical properties. We report a novel strategy for designing a new class of HEAs incorporating the additional interstitial element carbon. This results in joint activation of twinning- and transformation-induced plasticity (TWIP and TRIP) by tuning the matrix phase’s instability in a metastable TRIP-assisted dual-phase HEA. Besides TWIP and TRIP, such alloys benefit from massive substitutional and interstitial solid solution strengthening as well as from the composite effect associated with its dual-phase structure. Nanosize particle formation and grain size reduction are also utilized. The new interstitial TWIP-TRIP-HEA thus unifies all metallic strengthening mechanisms in one material, leading to twice the tensile strength compared to a single-phase HEA with similar composition, yet, at identical ductility.
Profiling, characterization, and analysis of natural and synthetic acylsugars (sugar esters)
Authors: Ghosh Banibrata , Jones A. Daniel
Published: January 2017

Acylsugars are an underappreciated group of specialized metabolites and synthetic products comprised of a sugar core esterified to one or more carboxylic acids at specific positions on the ring.