bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteolysis regulates cardiomyocyte maturation and tissue integration
Authors: Fukuda Ryuichi , Gunawan Felix , Beisaw Arica , Jimenez-Amilburu Vanesa , Maischein Hans-Martin , Kostin Sawa , Kawakami Koichi , Stainier Didier Y. R.
Published: February 2017

Tissue integrity is critical for organ formation and function. During heart development, cardiomyocytes differentiate and integrate to form a coherent tissue that contracts synchronously. However, the molecular mechanisms regulating cardiac tissue integrity are poorly understood. Here we show that proteolysis, via the E3 ubiquitin ligase ASB2, regulates cardiomyocyte maturation and tissue integrity. Cardiomyocytes in asb2b zebrafish mutants fail to terminally differentiate, resulting in reduced cardiac contractility and output. Mosaic analyses reveal a cell-autonomous requirement for Asb2b in cardiomyocytes for their integration as asb2b mutant cardiomyocytes are unable to meld into wild-type myocardial tissue. In vitro and in vivo data indicate that ASB2 negatively regulates TCF3, a bHLH transcription factor. TCF3 must be degraded for cardiomyocyte maturation, as TCF3 gain-of-function causes a number of phenotypes associated with cardiomyocyte dedifferentiation. Overall, our results show that proteolysis has an important role in cardiomyocyte maturation and the formation of a coherent myocardial tissue.
Ecological and genetic basis of metapopulation persistence of the Glanville fritillary butterfly in fragmented landscapes
Authors: Hanski Ilkka , Schulz Torsti , Wong Swee Chong , Ahola Virpi , Ruokolainen Annukka , Ojanen Sami P.
Published: February 2017

Ecologists are challenged to construct models of the biological consequences of habitat loss and fragmentation. Here, we use a metapopulation model to predict the distribution of the Glanville fritillary butterfly during 22 years across a large heterogeneous landscape with 4,415 small dry meadows. The majority (74%) of the 125 networks into which the meadows were clustered are below the extinction threshold for long-term persistence. Among the 33 networks above the threshold, spatial configuration and habitat quality rather than the pooled habitat area predict metapopulation size and persistence, but additionally allelic variation in a SNP in the gene Phosphoglucose isomerase (Pgi) explains 30% of variation in metapopulation size. ThePgigenotypes are associated with dispersal rate and hence with colonizations and extinctions. Associations betweenPgigenotypes, population turnover and metapopulation size reflect eco-evolutionary dynamics, which may be a common feature in species inhabiting patch networks with unstable local dynamics.
Mechanisms driving variability in the ocean forcing of Pine Island Glacier
Authors: Webber Benjamin G. M. , Heywood Karen J. , Stevens David P. , Dutrieux Pierre , Abrahamsen E. Povl , Jenkins Adrian , Jacobs Stanley S. , Ha Ho Kyung , Lee Sang Hoon , Kim Tae Wan
Published: February 2017

Pine Island Glacier (PIG) terminates in a rapidly melting ice shelf, and ocean circulation and temperature are implicated in the retreat and growing contribution to sea level rise of PIG and nearby glaciers. However, the variability of the ocean forcing of PIG has been poorly constrained due to a lack of multi-year observations. Here we show, using a unique record close to the Pine Island Ice Shelf (PIIS), that there is considerable oceanic variability at seasonal and interannual timescales, including a pronounced cold period from October 2011 to May 2013. This variability can be largely explained by two processes: cumulative ocean surface heat fluxes and sea ice formation close to PIIS; and interannual reversals in ocean currents and associated heat transport within Pine Island Bay, driven by a combination of local and remote forcing. Local atmospheric forcing therefore plays an important role in driving oceanic variability close to PIIS.
Displacement efficiency of alternative energy and trans-provincial imported electricity in China
Authors: Hu Yuanan , Cheng Hefa
Published: February 2017

China has invested heavily on alternative energy, but the effectiveness of such energy sources at substituting the dominant coal-fired generation remains unknown. Here we analyse the displacement of fossil-fuel-generated electricity by alternative energy, primarily hydropower, and by trans-provincial imported electricity in China between 1995 and 2014 using two-way fixed-effects panel regression models. Nationwide, each unit of alternative energy displaces nearly one-quarter of a unit of fossil-fuel-generated electricity, while each unit of imported electricity (regardless of the generation source) displaces ∼0.3 unit of fossil-fuel electricity generated locally. Results from the six regional grids indicate that significant displacement of fossil-fuel-generated electricity occurs once the share of alternative energy in the electricity supply mix exceeds ∼10%, which is accompanied by 10–50% rebound in the consumption of fossil-fuel-generated electricity. These findings indicate the need for a policy that integrates carbon taxation, alternative energy and energy efficiency to facilitate China’s transition towards a low-carbon economy.
Architecture, component, and microbiome of biofilm involved in the fouling of membrane bioreactors
Authors: Inaba Tomohiro , Hori Tomoyuki , Aizawa Hidenobu , Ogata Atsushi , Habe Hiroshi
Published: February 2017

Biofilm formation on the filtration membrane and the subsequent clogging of membrane pores (called biofouling) is one of the most persistent problems in membrane bioreactors for wastewater treatment and reclamation. Here, we investigated the structure and microbiome of fouling-related biofilms in the membrane bioreactor using non-destructive confocal reflection microscopy and high-throughput Illumina sequencing of 16S rRNA genes. Direct confocal reflection microscopy indicated that the thin biofilms were formed and maintained regardless of the increasing transmembrane pressure, which is a common indicator of membrane fouling, at low organic-loading rates. Their solid components were primarily extracellular polysaccharides and microbial cells. In contrast, high organic-loading rates resulted in a rapid increase in the transmembrane pressure and the development of the thick biofilms mainly composed of extracellular lipids. High-throughput sequencing revealed that the biofilm microbiomes, including major and minor microorganisms, substantially changed in response to the organic-loading rates and biofilm development. These results demonstrated for the first time that the architectures, chemical components, and microbiomes of the biofilms on fouled membranes were tightly associated with one another and differed considerably depending on the organic-loading conditions in the membrane bioreactor, emphasizing the significance of alternative indicators other than the transmembrane pressure for membrane biofouling.
Molecular genetic and clinical evaluation of three Chinese families with X-linked ocular albinism
Authors: Zou Xuan , Li Hui , Yang Lizhu , Sun Zixi , Yuan Zhisheng , Li Huajin , Sui Ruifang
Published: February 2017

X-linked ocular albinism (OA1) is an X-linked inherited disease characterized by hypopigmentation of the fundus and nystagmus. Our study performed mutation analysis of the G protein-coupled receptor 143 gene (GPR143) and assessed the clinical characteristics of OA1 in three Chinese families. Three novel mutations, c.333_360+14del42insCTT, c.276G>A (p.W92X), and c.793C>T (p.R265X), were identified in GPR143 by PCR followed by Sanger sequencing in these families. All affected individuals presented with nystagmus, photophobia, poor visual acuity, foveal hypoplasia and varying degrees of hypopigmentation of the fundus. The fundus of female carriers showed pigmented streaks alternating with hypopigmented streaks. These results allowed us to expand the spectrum of mutations in GPR143 and phenotypes associated with ocular albinism.
Soil aggregate mediates the impacts of land uses on organic carbon, total nitrogen, and microbial activity in a Karst ecosystem
Authors: Xiao Shuangshuang , Zhang Wei , Ye Yingying , Zhao Jie , Wang Kelin
Published: February 2017

Understanding the effect of land use on soil carbon, nitrogen, and microbial activity associated with aggregates is critical for thorough comprehension of the C and N dynamics of karst landscapes/ecosystems. We monitored soil organic carbon (SOC), total nitrogen (TN), microbial biomass carbon (MBC), and Cmic: Corg ratio in large macro- (>2 mm), small macro- (0.25–2 mm), and micro- (0.053–0.25 mm) aggregates to determine the changes in soil properties under different land uses in the karst area of Southwest China. Five common land-use types—enclosure land (natural system, control), prescribed-burning land, fuel-wood shrubland, pasture and maize fields—were selected. Results showed that pasture and maize fields remarkably decreased the SOC and TN concentrations in aggregates. Conversion of natural system to other land uses decreased MBC (except for prescribed-burning) and increased Cmic: Corg ratios in aggregates. The extent of the response to land uses of SOC and TN concentrations was similar whereas that of MBC and Cmic: Corg ratios differed across the three aggregate sizes. Further, the SOC concentrations were significantly higher in macro-aggregates than micro-aggregates; the MBC and Cmic: Corg ratios were highest in small macro-aggregates. Therefore, small macro-aggregates might have more active C dynamics.
Video monitoring of brown planthopper predation in rice shows flaws of sentinel methods
Authors: Zou Yi , de Kraker Joop , Bianchi Felix J. J. A. , van Telgen Mario D. , Xiao Haijun , van der Werf Wopke
Published: February 2017

Immobilized preys are routinely used in agro-ecological exposure studies to quantify predation of pests under field conditions, but this method has not been validated. Our purpose was to determine the validity of using immobilized adults of the major rice pest Nilaparvata lugens, brown plant hopper (BPH), as sentinels. We used direct observation by video recording to determine the causal agents of removal of field exposed BPH sentinels with two experiments: 1) we recorded removal events of dead, immobilized BPH; and 2) we compared removal of (i) dead, immobilized BPH, (ii) live, immobilized BPH, and (iii) live, mobile BPH. Long-horned grasshoppers were responsible for most removals of dead, immobilized BPH, in both experiments. Predatory ground beetles removed most of the live, immobilized BPH, whereas frogs were the major predators of live, mobile BPH. Overall, we showed that removal of immobilized sentinel prey is not representative for predation of live, mobile prey, stressing the need for a critical assessment of commonly used sentinel methods. In addition, we found that frogs played the major role in predation of BPH in rice. As current strategies to enhance biocontrol of planthoppers in rice focus on arthropod natural enemies, this finding could have major implications.
Decreasing trend in severe weather occurrence over China during the past 50 years
Authors: Zhang Qinghong , Ni Xiang , Zhang Fuqing
Published: February 2017

Understanding the trend of localized severe weather under the changing climate is of great significance but remains challenging which is at least partially due to the lack of persistent and homogeneous severe weather observations at climate scales while the detailed physical processes of severe weather cannot be resolved in global climate models. Based on continuous and coherent severe weather reports from over 500 manned stations, for the first time, this study shows a significant decreasing trend in severe weather occurrence across China during the past five decades. The total number of severe weather days that have either thunderstorm, hail and/or damaging wind decrease about 50% from 1961 to 2010. It is further shown that the reduction in severe weather occurrences correlates strongly with the weakening of East Asian summer monsoon which is the primary source of moisture and dynamic forcing conducive for warm-season severe weather over China.
Leading modes of tropical Pacific subsurface ocean temperature and associations with two types of El Niño
Authors: Zhang Zhiyuan , Ren Baohua , Zheng Jianqiu
Published: February 2017

Using empirical orthogonal function (EOF) analysis of the monthly tropical Pacific subsurface ocean temperature anomalies (SOTA) from 1979 to 2014, we detected three leading modes in the tropical Pacific subsurface temperature. The first mode has a dipole pattern, with warming in the eastern Pacific and cooling in the western Pacific, and is closely related to traditional El Niño. The second mode has a monopole pattern, with only warming in the central Pacific subsurface. The third mode has a zonal tripole pattern, with warming in the off-equatorial central Pacific and cooling in the far eastern Pacific and western Pacific. The second and third modes are both related to El Niño Modoki. Mode 1 is linked with a Kelvin wave that propagates from the central to the eastern Pacific and is induced by the anomalous westerlies that propagate from the western to the central Pacific. Mode 2 is also linked with a Kelvin wave that propagates from the western to the central Pacific induced by the enhancement of westerlies over the western Pacific. Mode 3 is linked with a Rossby wave that propagates from the central to the western Pacific driven by the anomalous easterlies over the eastern Pacific.
Dissection of genomic features and variations of three pathotypes of Puccinia striiformis through whole genome sequencing
Authors: Kiran Kanti , Rawal Hukam C. , Dubey Himanshu , Jaswal R. , Bhardwaj Subhash C. , Prasad P. , Pal Dharam , Devanna B. N. , Sharma Tilak R.
Published: February 2017

Stripe rust of wheat, caused by Puccinia striiformis f. sp. tritici, is one of the important diseases of wheat. We used NGS technologies to generate a draft genome sequence of two highly virulent (46S 119 and 31) and a least virulent (K) pathotypes of P. striiformis from the Indian subcontinent. We generated ~24,000–32,000 sequence contigs (N50;7.4–9.2 kb), which accounted for ~86X–105X sequence depth coverage with an estimated genome size of these pathotypes ranging from 66.2–70.2 Mb. A genome-wide analysis revealed that pathotype 46S 119 might be highly evolved among the three pathotypes in terms of year of detection and prevalence. SNP analysis revealed that ~47% of the gene sets are affected by nonsynonymous mutations. The extracellular secreted (ES) proteins presumably are well conserved among the three pathotypes, and perhaps purifying selection has an important role in differentiating pathotype 46S 119 from pathotypes K and 31. In the present study, we decoded the genomes of three pathotypes, with 81% of the total annotated genes being successfully assigned functional roles. Besides the identification of secretory genes, genes essential for pathogen-host interactions shall prove this study as a huge genomic resource for the management of this disease using host resistance.
Voltage-induced magnetization dynamics in CoFeB/MgO/CoFeB magnetic tunnel junctions
Authors: Miura Katsuya , Yabuuchi Shin , Yamada Masaki , Ichimura Masahiko , Rana Bivas , Ogawa Susumu , Takahashi Hiromasa , Fukuma Yasuhiro , Otani Yoshichika
Published: February 2017

Recent progress in magnetic tunnel junctions (MTJs) with a perpendicular easy axis consisting of CoFeB and MgO stacking structures has shown that magnetization dynamics are induced due to voltage-controlled magnetic anisotropy (VCMA), which will potentially lead to future low-power-consumption information technology. For manipulating magnetizations in MTJs by applying voltage, it is necessary to understand the coupled magnetization motion of two magnetic (recording and reference) layers. In this report, we focus on the magnetization motion of two magnetic layers in MTJs consisting of top layers with an in-plane easy axis and bottom layers with a perpendicular easy axis, both having perpendicular magnetic anisotropy. According to rectified voltage (Vrec) measurements, the amplitude of the magnetization motion depends on the initial angles of the magnetizations with respect to the VCMA direction. Our numerical simulations involving the micromagnetic method based on the Landau-Lifshitz-Gilbert equation of motion indicate that the magnetization motion in both layers is induced by a combination of VCMA and transferred angular momentum, even though the magnetic easy axes of the two layers are different. Our study will lead to the development of voltage-controlled MTJs having perpendicular magnetic anisotropy by controlling the initial angle between magnetizations and VCMA directions.
Pnc1 piggy-back import into peroxisomes relies on Gpd1 homodimerisation
Authors: Saryi Nadal A. Al , Hutchinson John D. , Al-hejjaj Murtakab Y. , Sedelnikova Svetlana , Baker Patrick , Hettema Ewald H.
Published: February 2017

Peroxisomes are eukaryotic organelles that posttranslationally import proteins via one of two conserved peroxisomal targeting signal (PTS1 or 2) mediated pathways. Oligomeric proteins can be imported via these pathways but evidence is accumulating that at least some PTS1-containing monomers enter peroxisomes before they assemble into oligomers. Some proteins lacking a PTS are imported by piggy-backing onto PTS-containing proteins. One of these proteins is the nicotinamidase Pnc1, that is co-imported with the PTS2-containing enzyme Glycerol-3-phosphate dehydrogenase 1, Gpd1. Here we show that Pnc1 co-import requires Gpd1 to form homodimers. A mutation that interferes with Gpd1 homodimerisation does not prevent Gpd1 import but prevents Pnc1 co-import. A suppressor mutation that restores Gpd1 homodimerisation also restores Pnc1 co-import. In line with this, Pnc1 interacts with Gpd1 in vivo only when Gpd1 can form dimers. Redirection of Gpd1 from the PTS2 import pathway to the PTS1 import pathway supports Gpd1 monomer import but not Gpd1 homodimer import and Pnc1 co-import. Our results support a model whereby Gpd1 may be imported as a monomer or a dimer but only the Gpd1 dimer facilitates co-transport of Pnc1 into peroxisomes.
Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in nasopharyngeal carcinoma patients with cervical nodal necrosis
Authors: Lan Mei , Chen Chunyan , Huang Ying , Tian Li , Duan Zhijun , Han Fei , Liao Junfang , Deng Meiling , Sio Terence T. , Prayongrat Anussara , Zheng Lie , Wu Shaoxiong , Lu Taixiang
Published: February 2017

The effectiveness of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared with CCRT alone in nasopharyngeal carcinoma (NPC) patients who presented with cervical nodal necrosis (CNN) is unknown. A total of 792 patients with stage T1-4N1-3M0 NPC and presented with CNN based on magnetic resonance imaging were retrospectively reviewed. Propensity score matching method was used to balance treatment arms for baseline characteristics. Eventually, 508 patients were propensity-matched on a 1:1 basis to create two groups (NACT + CCRT and CCRT groups). Survival rates were calculated by Kaplan–Meier method and differences were compared by using the log-rank test. The 5-year disease specific survival, disease-free survival and distant metastasis-free survival were significantly higher in NACT + CCRT group relative to the matched CCRT group (82.1% vs. 72.5%, P = 0.021; 70.3% vs. 54.1%, P < 0.001; 81.9% vs. 67.3%, P < 0.001, respectively). Although the rates of grade 3–4 leucopenia and mucositis were higher in NACT + CCRT group than CCRT group, compliance with the combined treatment was good and no significant difference was observed between two groups. NACT followed by CCRT was relatively safe and could achieve better survival than CCRT alone in NPC patients with CNN by reducing the risk of death, tumor progression and distant metastasis.
Optimization of the production of knock-in alleles by CRISPR/Cas9 microinjection into the mouse zygote
Authors: Raveux Aurélien , Vandormael-Pournin Sandrine , Cohen-Tannoudji Michel
Published: February 2017

Microinjection of the CRISPR/Cas9 system in zygotes is an efficient and comparatively fast method to generate genetically modified mice. So far, only few knock-in mice have been generated using this approach, and because no systematic study has been performed, parameters controlling the efficacy of CRISPR/Cas9-mediated targeted insertion are not fully established. Here, we evaluated the effect of several parameters on knock-in efficiency changing only one variable at a time. We found that knock-in efficiency was dependent on injected Cas9 mRNA and single-guide RNA concentrations and that cytoplasmic injection resulted in more genotypic complexity compared to pronuclear injection. Our results also indicated that injection into the pronucleus compared to the cytoplasm is preferable to generate knock-in alleles with an oligonucleotide or a circular plasmid. Finally, we showed that Cas9D10A nickase variant was less efficient than wild-type Cas9 for generating knock-in alleles and caused a higher rate of mosaicism. Thus, our study provides valuable information that will help to improve the future production of precise genetic modifications in mice.
Molecular Interplay between the Dimer Interface and the Substrate-Binding Site of Human Peptidylarginine Deiminase 4
Authors: Lee Chien-Yun , Lin Chu-Cheng , Liu Yi-Liang , Liu Guang-Yaw , Liu Jyung-Hurng , Hung Hui-Chih
Published: February 2017

Our previous studies suggest that the fully active form of Peptidylarginine deiminase 4 (PAD4) should be a dimer and not a monomer. This paper provides a plausible mechanism for the control of PAD4 catalysis by molecular interplay between its dimer-interface loop (I-loop) and its substrate-binding loop (S-loop). Mutagenesis studies revealed that two hydrophobic residues, W347 and V469, are critical for substrate binding at the active site; mutating these two residues led to a severe reduction in the catalytic activity. We also identified several hydrophobic amino acid residues (L6, L279 and V283) at the dimer interface. Ultracentrifugation analysis revealed that interruption of the hydrophobicity of this region decreases dimer formation and, consequently, enzyme activity. Molecular dynamic simulations and mutagenesis studies suggested that the dimer interface and the substrate-binding site of PAD4, which consist of the I-loop and the S-loop, respectively, are responsible for substrate binding and dimer stabilization. We identified five residues with crucial roles in PAD4 catalysis and dimerization: Y435 and R441 in the I-loop, D465 and V469 in the S-loop, and W548, which stabilizes the I-loop via van der Waals interactions with C434 and Y435. The molecular interplay between the S-loop and the I-loop is crucial for PAD4 catalysis.
Structural basis for fragmenting the exopolysaccharide of Acinetobacter baumannii by bacteriophage ΦAB6 tailspike protein
Authors: Lee I-Ming , Tu I-Fan , Yang Feng-Ling , Ko Tzu-Ping , Liao Jiahn-Haur , Lin Nien-Tsung , Wu Chung-Yi , Ren Chien-Tai , Wang Andrew H.-J. , Chang Ching-Ming , Huang Kai-Fa , Wu Shih-Hsiung
Published: February 2017

With an increase in antibiotic-resistant strains, the nosocomial pathogen Acinetobacter baumannii has become a serious threat to global health. Glycoconjugate vaccines containing fragments of bacterial exopolysaccharide (EPS) are an emerging therapeutic to combat bacterial infection. Herein, we characterize the bacteriophage ΦAB6 tailspike protein (TSP), which specifically hydrolyzed the EPS of A. baumannii strain 54149 (Ab-54149). Ab-54149 EPS exhibited the same chemical structure as two antibiotic-resistant A. baumannii strains. The ΦAB6 TSP-digested products comprised oligosaccharides of two repeat units, typically with stoichiometric pseudaminic acid (Pse). The 1.48-1.89-Å resolution crystal structures of an N-terminally-truncated ΦAB6 TSP and its complexes with the semi-hydrolyzed products revealed a trimeric β-helix architecture that bears intersubunit carbohydrate-binding grooves, with some features unusual to the TSP family. The structures suggest that Pse in the substrate is an important recognition site for ΦAB6 TSP. A region in the carbohydrate-binding groove is identified as the determinant of product specificity. The structures also elucidated a retaining mechanism, for which the catalytic residues were verified by site-directed mutagenesis. Our findings provide a structural basis for engineering the enzyme to produce desired oligosaccharides, which is useful for the development of glycoconjugate vaccines against A. baumannii infection.
Visualization of Au Nanoparticles Buried in a Polymer Matrix by Scanning Thermal Noise Microscopy
Authors: Yao Atsushi , Kobayashi Kei , Nosaka Shunta , Kimura Kuniko , Yamada Hirofumi
Published: February 2017

Several researchers have recently demonstrated visualization of subsurface features with a nanometer-scale resolution using various imaging schemes based on atomic force microscopy. Since all these subsurface imaging techniques require excitation of the oscillation of the cantilever and/or sample surface, it has been difficult to identify a key imaging mechanism. Here we demonstrate visualization of Au nanoparticles buried 300 nm into a polymer matrix by measurement of the thermal noise spectrum of a microcantilever with a tip in contact to the polymer surface. We show that the subsurface Au nanoparticles are detected as the variation in the contact stiffness and damping reflecting the viscoelastic properties of the polymer surface. The variation in the contact stiffness well agrees with the effective stiffness of a simple one-dimensional model, which is consistent with the fact that the maximum depth range of the technique is far beyond the extent of the contact stress field.
Reversal of the Apoptotic Resistance of Non-Small-Cell Lung Carcinoma towards TRAIL by Natural Product Toosendanin
Authors: Li Xin , You Ming , Liu Yong-jian , Ma Lin , Jin Pei-pei , Zhou Ri , Zhang Zhao-Xin , Hua Baojin , Ji Xiao-jun , Cheng Xiao-ying , Yin Fangzhou , Chen Yan , Yin Wu
Published: February 2017

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues. The underlying apoptotic mechanisms involved upregulation of death receptor 5 (DR5) and CCAAT/enhancer binding protein homologous protein, which is related to the endoplasmic reticulum stress response, and is further associated with reactive oxygen species generation and Ca2+ accumulation. Surprisingly, TSN also induced autophagy in NSCLC cells, which recruited membrane DR5, and subsequently antagonized the apoptosis-sensitizing effect of TSN. Taken together, TSN can be used to sensitize tumors and the combination of TRAIL and TSN may represent a useful strategy for NSCLC therapy; moreover, autophagy serves as an important drug resistance mechanism for TSN.
Antisense miR-132 blockade via the AChE-R splice variant mitigates cortical inflammation
Authors: Mishra Nibha , Friedson Lyndon , Hanin Geula , Bekenstein Uriya , Volovich Meshi , Bennett Estelle R. , Greenberg David S. , Soreq Hermona
Published: February 2017

MicroRNA (miR)-132 brain-to-body messages suppress inflammation by targeting acetylcholinesterase (AChE), but the target specificity of 3’-AChE splice variants and the signaling pathways involved remain unknown. Using surface plasmon resonance (SPR), we identified preferential miR-132 targeting of soluble AChE-R over synaptic-bound AChE-S, potentiating miR-132-mediated brain and body cholinergic suppression of pro-inflammatory cytokines. Inversely, bacterial lipopolysaccharide (LPS) reduced multiple miR-132 targets, suppressed AChE-S more than AChE-R and elevated inflammatory hallmarks. Furthermore, blockade of peripheral miR-132 by chemically protected AM132 antisense oligonucleotide elevated muscle AChE-R 10-fold over AChE-S, and cortical miRNA-sequencing demonstrated inverse brain changes by AM132 and LPS in immune-related miRs and neurotransmission and cholinergic signaling pathways. In neuromuscular junctions, AM132 co-elevated the nicotinic acetylcholine receptor and AChE, re-balancing neurotransmission and reaching mild muscle incoordination. Our findings demonstrate preferential miR-132-induced modulation of AChE-R which ignites bidirectional brain and body anti-inflammatory regulation, underscoring splice-variant miR-132 specificity as a new complexity level in inflammatory surveillance.
Expression profiling of TRIM protein family in THP1-derived macrophages following TLR stimulation
Authors: Jiang Mei-Xiu , Hong Xuan , Liao Bin-Bin , Shi Shui-Zhen , Lai Xiao-Fang , Zheng Huai-Yu , Xie Lin , Wang Yuan , Wang Xiao-Lei , Xin Hong-Bo , Fu Mingui , Deng Ke-Yu
Published: February 2017

Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup. Besides TRIM21, TRIM22 and TRIM38 were shown to be upregulated by TLR3 and TLR4 ligands as previous reported, we identified a novel group of TRIM genes (TRIM14, 15, 31, 34, 43, 48, 49, 51 and 61) that were significantly up-regulated by TLR3 and TLR4 ligands. In contrast, the expression of TRIM59 was down-regulated by TLR3 and TLR4 ligands in both human and mouse macrophages. The alternations of the TRIM proteins were confirmed by Western blot. Finally, overexpression of TRIM59 significantly suppressed LPS-induced macrophage activation, whereas siRNA-mediated knockdown of TRIM59 enhanced LPS-induced macrophage activation. Taken together, the study provided an insight into the TLR ligands-induced expressions of TRIM family in macrophages.
Multiple crossovers between positive and negative magnetoresistance versus field due to fragile spin structure in metallic GdPd3
Authors: Pandey Abhishek , Mazumdar Chandan , Ranganathan R. , Johnston D. C.
Published: February 2017

Studies on the phenomenon of magnetoresistance (MR) have produced intriguing and application-oriented outcomes for decades–colossal MR, giant MR and recently discovered extremely large MR of millions of percents in semimetals can be taken as examples. We report here the discovery of novel multiple sign changes versus applied magnetic field of the MR in the cubic intermetallic compound GdPd3. Our study shows that a very strong correlation between magnetic, electrical and magnetotransport properties is present in this compound. The magnetic structure in GdPd3 is highly fragile since applied magnetic fields of moderate strength significantly alter the spin arrangement within the system–a behavior that manifests itself in the oscillating MR. Intriguing magnetotransport characteristics of GdPd3 are appealing for field-sensitive device applications, especially if the MR oscillation could materialize at higher temperature by manipulating the magnetic interaction through perturbations caused by chemical substitutions.
Regulation of mRNA splicing by MeCP2 via epigenetic modifications in the brain
Authors: Cheng Tian-Lin , Chen Jingqi , Wan Huida , Tang Bin , Tian Weidong , Liao Lujian , Qiu Zilong
Published: February 2017

Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines. We further showed that Mecp2 knockdown in cultured cortical neurons led to widespread alternations of mRNA alternative splicing. Analysis of ChIP-seq datasets indicated that MeCP2-regulated exons display specific epigenetic signatures, with DNA modification 5-hydroxymethylcytosine (5hmC) and histone modification H3K4me3 are enriched in down-regulated exons, while the H3K36me3 signature is enriched in exons up-regulated in Mecp2-knockdown neurons comparing to un-affected neurons. Functional analysis reveals that genes containing MeCP2-regulated exons are mainly involved in synaptic functions and mRNA splicing. These results suggested that MeCP2 regulated mRNA splicing through interacting with 5hmC and epigenetic changes in histone markers, and provide functional insights of MeCP2-mediated mRNA splicing in the nervous system.
Focus on PNA Flexibility and RNA Binding using Molecular Dynamics and Metadynamics
Authors: Verona Massimiliano Donato , Verdolino Vincenzo , Palazzesi Ferruccio , Corradini Roberto
Published: February 2017

Peptide Nucleic Acids (PNAs) can efficiently target DNA or RNA acting as chemical tools for gene regulation. Their backbone modification and functionalization is often used to increase the affinity for a particular sequence improving selectivity. The understanding of the trading forces that lead the single strand PNA to bind the DNA or RNA sequence is preparatory for any further rational design, but a clear and unique description of this process is still not complete. In this paper we report further insights into this subject, by a computational investigation aiming at the characterization of the conformations of a single strand PNA and how these can be correlated to its capability in binding DNA/RNA. Employing Metadynamics we were able to better define conformational pre-organizations of the single strand PNA and γ-modified PNA otherwise unrevealed through classical molecular dynamics. Our simulations driven on backbone modified PNAs lead to the conclusion that this γ-functionalization affects the single strand preorganization and targeting properties to the DNA/RNA, in agreement with circular dichroism (CD) spectra obtained for this class of compounds. MD simulations on PNA:RNA dissociation and association mechanisms allowed to reveal the critical role of central bases and preorganization in the binding process.
25-Hydroxyvitamin D3 induces osteogenic differentiation of human mesenchymal stem cells
Authors: Lou Yan-Ru , Toh Tai Chong , Tee Yee Han , Yu Hanry
Published: February 2017

25-Hydroxyvitamin D3 [25(OH)D3] has recently been found to be an active hormone. Its biological actions are demonstrated in various cell types. 25(OH)D3 deficiency results in failure in bone formation and skeletal deformation. Here, we investigated the effect of 25(OH)D3 on osteogenic differentiation of human mesenchymal stem cells (hMSCs). We also studied the effect of 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2D3], a metabolite of 25(OH)D3. One of the vitamin D responsive genes, 25(OH)D3-24-hydroxylase (cytochrome P450 family 24 subfamily A member 1) mRNA expression is up-regulated by 25(OH)D3 at 250–500 nM and by 1α,25-(OH)2D3 at 1–10 nM. 25(OH)D3 and 1α,25-(OH)2D3 at a time-dependent manner alter cell morphology towards osteoblast-associated characteristics. The osteogenic markers, alkaline phosphatase, secreted phosphoprotein 1 (osteopontin), and bone gamma-carboxyglutamate protein (osteocalcin) are increased by 25(OH)D3 and 1α,25-(OH)2D3 in a dose-dependent manner. Finally, mineralisation is significantly increased by 25(OH)D3 but not by 1α,25-(OH)2D3. Moreover, we found that hMSCs express very low level of 25(OH)D3-1α-hydroxylase (cytochrome P450 family 27 subfamily B member 1), and there is no detectable 1α,25-(OH)2D3 product. Taken together, our findings provide evidence that 25(OH)D3 at 250–500 nM can induce osteogenic differentiation and that 25(OH)D3 has great potential for cell-based bone tissue engineering.
Structure and polymorphisms of the major histocompatibility complex in the Oriental stork, Ciconia boyciana
Authors: Tsuji Hiroki , Taniguchi Yukio , Ishizuka Shintaro , Matsuda Hirokazu , Yamada Takahisa , Naito Kazuaki , Iwaisaki Hiroaki
Published: February 2017

The major histocompatibility complex (MHC) is highly polymorphic and plays a central role in the vertebrate immune system. Despite its functional consistency, the MHC genomic structure differs substantially among organisms. In birds, the MHCs of Galliformes and the Japanese crested ibis (Pelecaniformes) are well-characterized, but information about other avian MHCs remains scarce. The Oriental stork (Ciconia boyciana, order Ciconiiformes) is a large endangered migrant. The current Japanese population of this bird originates from a few founders; thus, understanding the genetic diversity among them is critical for effective population management. We report the structure and polymorphisms in C. boyciana MHC. One contig (approximately 128 kb) was assembled by screening of lambda phage genomic library and its complete sequence was determined, revealing a gene order of COL11A2, two copies of MHC-IIA/IIB pairs, BRD2, DMA/B1/B2, MHC-I, TAP1/2, and two copies each of pseudo MHC-I and TNXB. This structure was highly similar to that of the Japanese crested ibis, but largely different from that of Galliformes, at both the terminal regions. Genotyping of the MHC-II region detected 10 haplotypes among the six founders. These results provide valuable insights for future studies on the evolution of the avian MHCs and for conservation of C. boyciana.
Colonisation in social species: the importance of breeding experience for dispersal in overcoming information barriers
Authors: Payo-Payo A. , Genovart M. , Sanz-Aguilar A. , Greño J. L. , García-Tarrasón M. , Bertolero A. , Piccardo J. , Oro D.
Published: February 2017

Studying colonisation is crucial to understand metapopulations, evolutionary ecology and species resilience to global change. Unfortunately, few empirical data are available because field monitoring that includes empty patches at large spatiotemporal scales is required. We examine the colonisation dynamics of a long-lived seabird over 34 years in the western Mediterranean by comparing population and individual data from both source colony and the newly-formed colonies. Since social information is not available, we hypothesize that colonisation should follow particular dispersal dynamics and personal information must be crucial in decision making. We test if adverse breeding conditions trigger colonisation events, if personal information plays a role in colonisation and if colonisers experience greater fitness. Our results show a temporal mismatch between colonisation events and both density-dependence and perturbations at the source colony, probably because colonisers needed a longer prospecting period to compensate for the lack of public information. Colonisers were mostly experienced individuals gaining higher breeding success in the new colony. Our results highlight the demographic value that experienced individuals can have on metapopulation dynamics of social long-lived organisms.
Long-lasting solid lubrication by CNT-coated patterned surfaces
Authors: Reinert L. , Lasserre F. , Gachot C. , Grützmacher P. , MacLucas T. , Souza N. , Mücklich F. , Suarez S.
Published: February 2017

The use of lubricants (solid or liquid) is a well-known and suitable approach to reduce friction and wear of moving machine components. Another possibility to influence the tribological behaviour is the formation of well-defined surface topographies such as dimples, bumps or lattice-like pattern geometries by laser surface texturing. However, both methods are limited in their effect: surface textures may be gradually destroyed by plastic deformation and lubricants may be removed from the contact area, therefore no longer properly protecting the contacting surfaces. The present study focuses on the combination of both methods as an integral solution, overcoming individual limitations of each method. Multiwall carbon nanotubes (MWCNT), a known solid lubricant, are deposited onto laser surface textured samples by electrophoretic deposition. The frictional behaviour is recorded by a tribometer and resulting wear tracks are analysed by scanning electron microscopy and Raman spectroscopy in order to reveal the acting tribological mechanisms. The combined approach shows an extended, minimum fivefold longevity of the lubrication and a significantly reduced degradation of the laser textures. Raman spectroscopy proves decelerated MWCNT degradation and oxide formation in the contact. Finally, a lubricant entrapping model based on surface texturing is proposed and demonstrated.
Soil wettability can be explained by the chemical composition of particle interfaces - An XPS study
Authors: Woche Susanne K. , Goebel Marc-O. , Mikutta Robert , Schurig Christian , Kaestner Matthias , Guggenberger Georg , Bachmann Jörg
Published: February 2017

Soil wettability (quantified in terms of contact angle, CA) is crucial for physical, chemical, and biological soil functioning. As the CA is determined by components present within the outmost nanometer of particles, this study applied X-ray photoelectron spectroscopy (XPS) with a maximum analysis depth of 10 nm to test the relationship between CA and surface elemental composition, using soil samples from a chronosequence where CA increased from 0° (0 yrs) to about 98° (120 yrs). Concurrently, as seen by XPS, C and N content increased and the content of O and the mineral-derived cations (Si, Al, K, Na, Ca, Mg, Fe) decreased. The C content was positively correlated with CA and least squares fitting indicated increasing amounts of non-polar C species with soil age. The contents of O and the mineral-derived cations were negatively correlated with CA, suggesting an increasing organic coating of the minerals that progressively masked the underlying mineral phase. The atomic O/C ratio was found to show a close negative relationship with CA, which applied as well to further sample sets of different texture and origin. This suggests the surface O/C ratio to be a general parameter linking surface wettability and surface elemental composition.
Characterization of biocarbon-source recovery and microbial community shifts from waste activated sludge by conditioning with cornstover: Assessment of cellulosic compositions
Authors: Wen Kaili , Zhou Aijuan , Zhang Jiaguang , Liu Zhihong , Wang Guoying , Liu Wenzong , Wang Aijie , Yue Xiuping
Published: February 2017

Most studies on the production of volatile fatty acids (VFAs) from waste activated sludge (WAS) digestion have focused on operating conditions, pretreatments and characteristic adjustments. Conditioning by extra carbon sources (ECS), normally added in a solid form, has been reported to be an efficient approach. However, this has caused considerable waste of monomeric sugars in the hydrolysate. In this study, the effects of two added forms (pretreated straw (S) and hydrolyzed liquid (L)) of cornstover (CS) on WAS acidification were investigated. To obtain different cellulosic compositions of CS, low-thermal or autoclaved assisted alkaline (TA or AA) pretreatments were conducted. The results showed that AA-L test achieved the highest VFAs value (653 mg COD/g VSS), followed by AA-S (613 mg COD/g VSS). These values were 12% and 28% higher, respectively, than that obtained in the TA-L and TA-S tests. Meanwhile, higher percentages of acetic acid were observed after AA pretreatment (~62% versus ~53% in TA). The added forms of CS played an important role in structuring the innate microbial community in the WAS, as shown by high-throughput sequencing and canonical correspondence analysis. The findings obtained in this work may provide a scientific basis for the potential implementation of co-digesting WAS with ECS simultaneously obtaining energy and high value-added products.
Depth-specific fluctuations of gene expression and protein abundance modulate the photophysiology in the seagrass Posidonia oceanica
Authors: Procaccini Gabriele , Ruocco Miriam , Marín-Guirao Lázaro , Dattolo Emanuela , Brunet Christophe , D’Esposito Daniela , Lauritano Chiara , Mazzuca Silvia , Serra Ilia Anna , Bernardo Letizia , Piro Amalia , Beer Sven , Björk Mats , Gullström Martin , Buapet Pimchanok , Rasmusson Lina M. , Felisberto Paulo , Gobert Sylvie , Runcie John W. , Silva João , Olivé Irene , Costa Monya M. , Barrote Isabel , Santos Rui
Published: February 2017

Here we present the results of a multiple organizational level analysis conceived to identify acclimative/adaptive strategies exhibited by the seagrass Posidonia oceanica to the daily fluctuations in the light environment, at contrasting depths. We assessed changes in photophysiological parameters, leaf respiration, pigments, and protein and mRNA expression levels. The results show that the diel oscillations of P. oceanica photophysiological and respiratory responses were related to transcripts and proteins expression of the genes involved in those processes and that there was a response asynchrony between shallow and deep plants probably caused by the strong differences in the light environment. The photochemical pathway of energy use was more effective in shallow plants due to higher light availability, but these plants needed more investment in photoprotection and photorepair, requiring higher translation and protein synthesis than deep plants. The genetic differentiation between deep and shallow stands suggests the existence of locally adapted genotypes to contrasting light environments. The depth-specific diel rhythms of photosynthetic and respiratory processes, from molecular to physiological levels, must be considered in the management and conservation of these key coastal ecosystems.
Differential Effects of Hormones on Cellular Metabolism in Keratoconus In Vitro
Authors: McKay Tina B. , Hjortdal Jesper , Sejersen Henrik , Karamichos Dimitrios
Published: February 2017

Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3Din vitromodel to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs). Our data showed that exogenous DHEA significantly downregulated IGF-1 and its receptor in both HCFs and HKCs with HKCs showing consistently lower basal pentose phosphate flux. Prolactin caused no significant change in IGF-1 levels and an increase in IGF-2 in HKCs correlating with an increase in ATP and NADH levels. 17β-estradiol led to a significant upregulation in pentose phosphate flux and glycolytic intermediates in HCFs. Our results identified hormone-specific responses regulated in HKCs compared to HCFs revealing a novel role for hormones on bioenergetics in KC.