bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysfunctional immunoregulation in human liver allograft rejection associated with compromised galectin-1/CD7 pathway function
Authors: Wei Sidong , Cao Ding , Liu Zuojin , Li Jinheng , Wu Hao , Gong Jianping , Liu Yiming , Wu Yakun
Published: February 2018

Regulatory T cells in rejected allograft patients display an inability to control responder T cells. Galectin-1 (Gal1) inhibits responder T cells through binding CD7. We investigated whether the dysfunctional immunoregulation in liver allograft rejection patients results from reduced regulatory T-cell Gal1 expression and/or responder T-cell CD7 expression. Circulating regulatory T cells and responder T cells were profiled from 31 acute rejection transplant patients, 85 transplant patients in remission, and 40 healthy controls. CD7+ and CD7− responder T cells were co-cultured with regulatory T cells to assess regulatory T-cell suppressor function. Gal1-small interfering RNA was used to silence regulatory T-cell Gal1. The CD7+ cell percentage was inversely correlated with AST, ALT, and GGT levels. The proportions of CD7+ responder T cells and Gal1+ regulatory T cells were higher in healthy controls than in transplant patients in remission and lowest in acute rejection transplant patients. Notably, CD7+ responder T-cell susceptibility to Gal1+ regulatory T-cell control was ranked in the same manner. Silencing Gal1 expression in regulatory T cells reduced their ability to suppress CD7+ (but not CD7−) responder T cells. Additionally, the proportions of CD43+ and CD45+ responder T cells were higher in healthy controls than in acute rejection transplant patients. CD43 co-expression (but not CD45 co-expression) on CD7+ responder T cells promoted their apoptosis in a Gal1-dependent manner. In sum, dysfunctional immunoregulation in liver allograft rejection patients can be partly attributed to reduced regulatory T-cell Gal1 expression and reduced responder T-cell CD7 expression. Responder T-cell CD43 downregulation in acute rejection patients may further contribute to reduced responder T-cell responsiveness to regulatory T-cell control.
GRK5 functions as an oncogenic factor in non-small-cell lung cancer
Authors: Jiang Li-Ping , Fan Song-Qing , Xiong Qiu-Xia , Zhou Yong-Chun , Yang Zuo-Zhang , Li Gao-Feng , Huang Yun-Chao , Wu Meng-Ge , Shen Qiu-Shuo , Liu Kun , Yang Cui-Ping , Chen Yong-Bin
Published: February 2018

Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small-cell lung cancer (NSCLC) accounts for about 80% of all cases, which is the major subgroup of lung cancer. G protein-coupled receptor kinase 5 (GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological conditions including cancer. Here, we found that GRK5 expression was significantly increased in 539 NSCLC cancerous tissues than that in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also showed intensive higher positive staining percentage in female and adenocarcinoma (ADC) NSCLC patients than that in male and squamous cell carcinoma (SCC) patients, respectively. In addition, GRK5 high expression NSCLC patients had a worse overall survival rate than the low expression patients. We provided evidence showing that both the mRNA and protein expression levels of GRK5 were increased in NSCLC cancerous cell lines (GLC-82, SPC-A-1, H520, H838, H358, A549, and H1299) comparing with that in normal human bronchial epithelium cell line (BEAS-2B), and identified many GRK5 mutations in NSCLC cancerous tissues. In addition, we found that depletion of GRK5 inhibited NSCLC cancerous cell proliferation, migration in vitro, and xenograft tumor formation in vivo. Furthermore, GRK5 knockdown promoted cell cycle arrest at G2/M phase and induced cellular apoptosis. In summary, our data reveal an oncogenic role of GRK5 in NSCLC progression, indicating that GRK5 could be used as a new therapeutic target in future.
Induction of ER and mitochondrial stress by the alkylphosphocholine erufosine in oral squamous cell carcinoma cells
Authors: Ansari Shariq S. , Sharma Ashwini K. , Soni Himanshu , Ali Doaa M. , Tews Björn , König Rainer , Eibl Hansjörg , Berger Martin R.
Published: February 2018

Endoplasmic reticulum (ER) plays an essential role in cell function and survival. Accumulation of unfolded or misfolded proteins in the lumen of the ER activates the unfolded protein response (UPR), resulting in ER stress and subsequent apoptosis. The alkylphosphocholine erufosine is a known Akt-mTOR inhibitor in oral squamous cell carcinoma (OSCC). In the present study, we evaluate erufosine’s role to induce ER and mitochondrial stress leading to autophagy, apoptosis, and ROS induction. The cellular toxicity of erufosine was determined in two OSCC cell lines and gene expression and enrichment analyses were performed. A positive enrichment of ER stress upon erufosine exposure was observed, which was verified at protein levels for the ER stress sensors and their downstream mediators. Knockdown and pharmacological inhibition of the ER stress sensors PERK and XBP1 revealed their involvement into erufosine’s cellular effects, including proliferation, apoptosis, and autophagy induction. Autophagy was confirmed by increased acidic vacuoles and LC3-B levels. Upon erufosine exposure, calcium influx into the cytoplasm of the two OSCC cell lines was seen. Apoptosis was confirmed by nuclear staining, Annexin-V, and immunoblotting of caspases. The induction of mitochondrial stress upon erufosine exposure was predicted by gene set enrichment analysis (GSEA) and shown by erufosine’s effect on mitochondrial membrane potential, ATP, and ROS production in OSCC cells. These data show that ER and mitochondrial targeting by erufosine represents a new facet of its mechanism of action as well as a promising new framework in the treatment of head and neck cancers.
Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation
Authors: Simões Ana P. , Silva Carla G. , Marques Joana M. , Pochmann Daniela , Porciúncula Lisiane O. , Ferreira Sofia , Oses Jean P. , Beleza Rui O. , Real Joana I. , Köfalvi Attila , Bahr Ben A. , Lerma Juan , Cunha Rodrigo A. , Rodrigues Ricardo J.
Published: February 2018

Despite the characteristic etiologies and phenotypes, different brain disorders rely on common pathogenic events. Glutamate-induced neurotoxicity is a pathogenic event shared by different brain disorders. Another event occurring in different brain pathological conditions is the increase of the extracellular ATP levels, which is now recognized as a danger and harmful signal in the brain, as heralded by the ability of P2 receptors (P2Rs) to affect a wide range of brain disorders. Yet, how ATP and P2R contribute to neurodegeneration remains poorly defined. For that purpose, we now examined the contribution of extracellular ATP and P2Rs to glutamate-induced neurodegeneration. We found both in vitro and in vivo that ATP/ADP through the activation of P2Y1R contributes to glutamate-induced neuronal death in the rat hippocampus. We found in cultured rat hippocampal neurons that the exposure to glutamate (100 µM) for 30 min triggers a sustained increase of extracellular ATP levels, which contributes to NMDA receptor (NMDAR)-mediated hippocampal neuronal death through the activation of P2Y1R. We also determined that P2Y1R is involved in excitotoxicity in vivo as the blockade of P2Y1R significantly attenuated rat hippocampal neuronal death upon the systemic administration of kainic acid or upon the intrahippocampal injection of quinolinic acid. This contribution of P2Y1R fades with increasing intensity of excitotoxic conditions, which indicates that P2Y1R is not contributing directly to neurodegeneration, rather behaving as a catalyst decreasing the threshold from which glutamate becomes neurotoxic. Moreover, we unraveled that such excitotoxicity process began with an early synaptotoxicity that was also prevented/attenuated by the antagonism of P2Y1R, both in vitro and in vivo. This should rely on the observed glutamate-induced calpain-mediated axonal cytoskeleton damage, most likely favored by a P2Y1R-driven increase of NMDAR-mediated Ca2+ entry selectively in axons. This may constitute a degenerative mechanism shared by different brain diseases, particularly relevant at initial pathogenic stages.
ALCAM+ stromal cells: role in giant cell tumor of bone progression
Authors: Zhou Zhenhua , Li Yan , Wang Xudong , Hu Jingjing , Kuang Muyu , Wang Zhiwei , Li Song , Xu Weidong , Xiao Jianru
Published: February 2018

Giant cell tumor of bone(GCTB) is a special benign tumor with variable aggressiveness and recurrence rate. Increasing evidences suggest that a subset of cells called cancer stem cells (CSCs) are present as cancer-initiating cells in a range of malignant tumors. However, the role of CSCs in benign tumor such as GCTB remains unknown, and the connection between the presence of CSCs and biological characteristics of GCTB is unclear. To investigate this issue, we screened a panel of markers of normal stem cells and CSCs and found ALCAM+ stromal cells possessed characteristics of stem-like cells. Subsequently a series of experiments such cell proliferation, migration and invasion assays were performed to investigate the biological characteristics of ALCAM+ stromal cells in vivo and in vitro. The clinical significance of ALCAM expression were further evaluated using Kaplan-Meier analyses. The ALCAM+ GCTB cells showed the stem cell properties of self renewal and had the capacity to differentiate in vitro. The ALCAM+ GCTB cells showed increased resistance for chemotherapy- or radiation-induced cell death. ALCAM knockdown reduced stem/progenitor characteristics in GCTB Cells. Furthermore, ALCAM expression was associated with outcome in GCTB patients. Our work demonstrates for the first time ALCAM+ tumorigenic sub-population within stromal GCTB cells and may represent a potential therapeutic target in aggressive and recurrent GCTBs.
Contribution of TMEM16F to pyroptotic cell death
Authors: Ousingsawat Jiraporn , Wanitchakool Podchanart , Schreiber Rainer , Kunzelmann Karl
Published: February 2018

Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca2+ activated phospholipid scramblase and ion channel TMEM16F has been shown earlier to control cellular effects downstream of purinergic P2X7 receptors that ultimately lead to cell death. As pyroptotic cell death is accompanied by an increases in intracellular Ca2+, we asked whether TMEM16F is activated during pyroptosis. The N-terminal cleavage product of gasdermin D (GD-N) is an executioner of pyroptosis by forming large plasma membrane pores. Expression of GD-N enhanced basal Ca2+ levels and induced cell death. We observed that GD-N induced cell death in HEK293 and HAP1 cells, which was depending on expression of endogenous TMEM16F. GD-N activated large whole cell currents that were suppressed by knockdown or inhibition of TMEM16F. The results suggest that whole cell currents induced by the pore forming domain of gasdermin-D, are at least in part due to activation of TMEM16F. Knockdown of other TMEM16 paralogues expressed in HAP1 cells suggest TMEM16F as a crucial element during pyroptosis and excluded a role of other TMEM16 proteins. Thus TMEM16F supports pyroptosis and other forms of inflammatory cell death such as ferroptosis. Its potent inhibition by tannic acid may be part of the anti-inflammatory effects of flavonoids.
The genomic tool-kit of the truffle Tuber melanosporum programmed cell death
Authors: Zarivi Osvaldo , Cesare Patrizia , Poma Anna Maria , Colafarina Sabrina , Bonfigli Antonella , Kohler Annegret , Aimola Pierpaolo , Ragnelli Anna Maria , Pacioni Giovanni , Miranda Michele
Published: February 2018

A survey of the truffle Tuber melanosporum genome has shown the presence of 67 programmed cell death (PCD)-related genes. The 67 genes are all expressed during fruit body (FB) development of T. melanosporum development; their expression has been detected by DNA microarrays and qPCR. A set of 14 PCD-related genes have been chosen, those with the highest identities to the homologs of other species, for a deeper investigation. That PCD occurs during T. melanosporum development has been demonstrated by the TUNEL reaction and transmission electron microscopy. The findings of this work, in addition to the discovery of PCD-related genes in the T. melanosporum genome and their expression during the differentiation and development of the FB, would suggest that one of the PCD subroutines, maybe autophagy, is involved in the FB ripening, i.e., sporogenesis.
Lkb1 deficiency confers glutamine dependency in polycystic kidney disease
Authors: Flowers Ebony M. , Sudderth Jessica , Zacharias Lauren , Mernaugh Glenda , Zent Roy , DeBerardinis Ralph J. , Carroll Thomas J.
Published: February 2018

Polycystic kidney disease (PKD) is a common genetic disorder characterized by the growth of fluid-filled cysts in the kidneys. Several studies reported that the serine-threonine kinase Lkb1 is dysregulated in PKD. Here we show that genetic ablation of Lkb1 in the embryonic ureteric bud has no effects on tubule formation, maintenance, or growth. However, co-ablation of Lkb1 and Tsc1, an mTOR repressor, results in an early developing, aggressive form of PKD. We find that both loss of Lkb1 and loss of Pkd1 render cells dependent on glutamine for growth. Metabolomics analysis suggests that Lkb1 mutant kidneys require glutamine for non-essential amino acid and glutathione metabolism. Inhibition of glutamine metabolism in both Lkb1/Tsc1 and Pkd1 mutant mice significantly reduces cyst progression. Thus, we identify a role for Lkb1 in glutamine metabolism within the kidney epithelia and suggest that drugs targeting glutamine metabolism may help reduce cyst number and/or size in PKD.
Sodium enhances indium-gallium interdiffusion in copper indium gallium diselenide photovoltaic absorbers
Authors: Colombara Diego , Werner Florian , Schwarz Torsten , Cañero Infante Ingrid , Fleming Yves , Valle Nathalie , Spindler Conrad , Vacchieri Erica , Rey Germain , Guennou Mael , Bouttemy Muriel , Manjón Alba Garzón , Peral Alonso Inmaculada , Melchiorre Michele , El Adib Brahime , Gault Baptiste , Raabe Dierk , Dale Phillip J. , Siebentritt Susanne
Published: February 2018

Copper indium gallium diselenide-based technology provides the most efficient solar energy conversion among all thin-film photovoltaic devices. This is possible due to engineered gallium depth gradients and alkali extrinsic doping. Sodium is well known to impede interdiffusion of indium and gallium in polycrystalline Cu(In,Ga)Se2 films, thus influencing the gallium depth distribution. Here, however, sodium is shown to have the opposite effect in monocrystalline gallium-free CuInSe2 grown on GaAs substrates. Gallium in-diffusion from the substrates is enhanced when sodium is incorporated into the film, leading to Cu(In,Ga)Se2 and Cu(In,Ga)3Se5 phase formation. These results show that sodium does not decrease per se indium and gallium interdiffusion. Instead, it is suggested that sodium promotes indium and gallium intragrain diffusion, while it hinders intergrain diffusion by segregating at grain boundaries. The deeper understanding of dopant-mediated atomic diffusion mechanisms should lead to more effective chemical and electrical passivation strategies, and more efficient solar cells.
Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement
Authors: Shi Y. Z. , Xiong S. , Zhang Y. , Chin L. K. , Chen Y. –Y. , Zhang J. B. , Zhang T. H. , Ser W. , Larrson A. , Lim S. H. , Wu J. H. , Chen T. N. , Yang Z. C. , Hao Y. L. , Liedberg B. , Yap P. H. , Wang K. , Tsai D. P. , Qiu C.-W. , Liu A. Q.
Published: February 2018

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer’s theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
Authors: Hobor Fruzsina , Dallmann Andre , Ball Neil J. , Cicchini Carla , Battistelli Cecilia , Ogrodowicz Roksana W. , Christodoulou Evangelos , Martin Stephen R. , Castello Alfredo , Tripodi Marco , Taylor Ian A. , Ramos Andres
Published: February 2018

Exosomal miRNA transfer is a mechanism for cell–cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip’s amino-terminal domain, which was previously thought to mediate protein–protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip’s RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5′ to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences.
Marangoni-driven flower-like patterning of an evaporating drop spreading on a liquid substrate
Authors: Wodlei F. , Sebilleau J. , Magnaudet J. , Pimienta V.
Published: February 2018

Drop motility at liquid surfaces is attracting growing interest because of its potential applications in microfluidics and artificial cell design. Here we report the unique highly ordered pattern that sets in when a millimeter-size drop of dichloromethane spreads on an aqueous substrate under the influence of surface tension, both phases containing a surfactant. Evaporation induces a Marangoni flow that forces the development of a marked rim at the periphery of the spreading film. At some point this rim breaks up, giving rise to a ring of droplets, which modifies the aqueous phase properties in such a way that the film recoils. The process repeats itself, yielding regular large-amplitude pulsations. Wrinkles form at the film surface due to an evaporative instability. During the dewetting stage, they emit equally spaced radial strings of droplets which, combined with those previously expelled from the rim, make the top view of the system resemble a flower.
Convergent genomic signatures of domestication in sheep and goats
Authors: Alberto Florian J. , Boyer Frédéric , Orozco-terWengel Pablo , Streeter Ian , Servin Bertrand , de Villemereuil Pierre , Benjelloun Badr , Librado Pablo , Biscarini Filippo , Colli Licia , Barbato Mario , Zamani Wahid , Alberti Adriana , Engelen Stefan , Stella Alessandra , Joost Stéphane , Ajmone-Marsan Paolo , Negrini Riccardo , Orlando Ludovic , Rezaei Hamid Reza , Naderi Saeid , Clarke Laura , Flicek Paul , Wincker Patrick , Coissac Eric , Kijas James , Tosser-Klopp Gwenola , Chikhi Abdelkader , Bruford Michael W. , Taberlet Pierre , Pompanon François
Published: February 2018

The evolutionary basis of domestication has been a longstanding question and its genetic architecture is becoming more tractable as more domestic species become genome-enabled. Before becoming established worldwide, sheep and goats were domesticated in the fertile crescent 10,500 years before present (YBP) where their wild relatives remain. Here we sequence the genomes of wild Asiatic mouflon and Bezoar ibex in the sheep and goat domestication center and compare their genomes with that of domestics from local, traditional, and improved breeds. Among the genomic regions carrying selective sweeps differentiating domestic breeds from wild populations, which are associated among others to genes involved in nervous system, immunity and productivity traits, 20 are common toCapraandOvis. The patterns of selection vary between species, suggesting that while common targets of selection related to domestication and improvement exist, different solutions have arisen to achieve similar phenotypic end-points within these closely related livestock species.
A randomized and open-label phase II trial reports the efficacy of neoadjuvant lobaplatin in breast cancer
Authors: Wu Xiujuan , Tang Peng , Li Shifei , Wang Shushu , Liang Yueyang , Zhong Ling , Ren Lin , Zhang Ting , Zhang Yi
Published: February 2018

Currently, one sixth of triple-negative breast cancer (TNBC) patients who receive docetaxel (T) and epirubicin (E) as neoadjuvant chemotherapy achieve a pathologic complete response (pCR). This study evaluates the impact of adding lobaplatin (L) to the TE regimen. Here, we show data from 125 patients (63 TE and 62 TEL patients). Four patients did not complete all the cycles. Two-sided P values show that the addition of L (38.7% vs. 12.7%, P = 0.001) significantly increases the rate of pCR in the breast and the axilla (TpCR) and the overall response rate (ORR; 93.5% vs. 73.0%, P = 0.003). The occurrence of grade 3–4 anemia and thrombocytopenia is higher in the TEL group (52.5% vs. 10.0% and 34.4% vs. 1.7% respectively). These results demonstrate that the addition of L to the TE regimen as neoadjuvant chemotherapy improves the TpCR and the ORR rates of TNBC but with increased side effects.
Control over multiple molecular states with directional changes driven by molecular recognition
Authors: Hirao Takehiro , Kim Dong Sub , Chi Xiaodong , Lynch Vincent M. , Ohara Kazuaki , Park Jung Su , Yamaguchi Kentaro , Sessler Jonathan L.
Published: February 2018

Recently, ligand–metal coordination, stimuli-responsive covalent bonds, and mechanically interlinked molecular constructs have been used to create systems with a large number of accessible structural states. However, accessing a multiplicity of states in sequence from more than one direction and doing so without the need for external energetic inputs remain as unmet challenges, as does the use of relatively weak noncovalent interactions to stabilize the underlying forms. Here we report a system based on a bispyridine-substituted calix[4]pyrrole that allows access to six different discrete states with directional control via the combined use of metal-based self-assembly and molecular recognition. Switching can be induced by the selective addition or removal of appropriately chosen ionic guests. No light or redox changes are required. The tunable nature of the system has been established through a combination of spectroscopic techniques and single crystal X-ray diffraction analyses. The findings illustrate a new approach to creating information-rich functional materials.
The influence of the molecular packing on the room temperature phosphorescence of purely organic luminogens
Authors: Yang Jie , Zhen Xu , Wang Bin , Gao Xuming , Ren Zichun , Wang Jiaqiang , Xie Yujun , Li Jianrong , Peng Qian , Pu Kanyi , Li Zhen
Published: February 2018

Organic luminogens with persistent room temperature phosphorescence (RTP) have attracted great attention for their wide applications in optoelectronic devices and bioimaging. However, these materials are still very scarce, partially due to the unclear mechanism and lack of designing guidelines. Herein we develop seven 10-phenyl-10H-phenothiazine-5,5-dioxide-based derivatives, reveal their different RTP properties and underlying mechanism, and exploit their potential imaging applications. Coupled with the preliminary theoretical calculations, it is found that strong π–π interactions in solid state can promote the persistent RTP. Particularly, CS-CF3 shows the unique photo-induced phosphorescence in response to the changes in molecular packing, further confirming the key influence of the molecular packing on the RTP property. Furthermore, CS-F with its long RTP lifetime could be utilized for real-time excitation-free phosphorescent imaging in living mice. Thus, our study paves the way for the development of persistent RTP materials, in both the practical applications and the inherent mechanism.
MSD1 regulates pedicellate spikelet fertility in sorghum through the jasmonic acid pathway
Authors: Jiao Yinping , Lee Young Koung , Gladman Nicholas , Chopra Ratan , Christensen Shawn A. , Regulski Michael , Burow Gloria , Hayes Chad , Burke John , Ware Doreen , Xin Zhanguo
Published: February 2018

Grain number per panicle (GNP) is a major determinant of grain yield in cereals. However, the mechanisms that regulate GNP remain unclear. To address this issue, we isolate a series of sorghum [Sorghum bicolor (L.) Moench] multiseeded (msd) mutants that can double GNP by increasing panicle size and altering floral development so that all spikelets are fertile and set grain. Through bulk segregant analysis by next-generation sequencing, we identify MSD1 as a TCP (Teosinte branched/Cycloidea/PCF) transcription factor. Whole-genome expression profiling reveals that jasmonic acid (JA) biosynthetic enzymes are transiently activated in pedicellate spikelets. Young msd1 panicles have 50% less JA than wild-type (WT) panicles, and application of exogenous JA can rescue the msd1 phenotype. Our results reveal a new mechanism for increasing GNP, with the potential to boost grain yield, and provide insight into the regulation of plant inflorescence architecture and development.
Encapsulation of catalyst in block copolymer micelles for the polymerization of ethylene in aqueous medium
Authors: Boucher-Jacobs Camille , Rabnawaz Muhammad , Katz Joshua S. , Even Ralph , Guironnet Damien
Published: February 2018

The catalytic emulsion polymerization of ethylene has been a long-lasting technical challenge as current techniques still suffer some limitations. Here we report an alternative strategy for the production of semi-crystalline polyethylene latex. Our methodology consists of encapsulating a catalyst precursor within micelles composed of an amphiphilic block copolymer. These micelles act as nanoreactors for the polymerization of ethylene in water. Phosphinosulfonate palladium complexes were used to demonstrate the success of our approach as they were found to be active for hours when encapsulated in micelles. Despite this long stability, the activity of the catalysts in micelles remains significantly lower than in organic solvent, suggesting some catalyst inhibition. The inhibition strength of the different chemicals present in the micelle were determined and compared. The combination of the small volume of the micelles, and the coordination of PEG appear to be the culprits for the low activity observed in micelles.
Self-interaction of NPM1 modulates multiple mechanisms of liquid–liquid phase separation
Authors: Mitrea Diana M. , Cika Jaclyn A. , Stanley Christopher B. , Nourse Amanda , Onuchic Paulo L. , Banerjee Priya R. , Phillips Aaron H. , Park Cheon-Gil , Deniz Ashok A. , Kriwacki Richard W.
Published: February 2018

Nucleophosmin (NPM1) is an abundant, oligomeric protein in the granular component of the nucleolus with roles in ribosome biogenesis. Pentameric NPM1 undergoes liquid–liquid phase separation (LLPS) via heterotypic interactions with nucleolar components, including ribosomal RNA (rRNA) and proteins which display multivalent arginine-rich linear motifs (R-motifs), and is integral to the liquid-like nucleolar matrix. Here we show that NPM1 can also undergo LLPS via homotypic interactions between its polyampholytic intrinsically disordered regions, a mechanism that opposes LLPS via heterotypic interactions. Using a combination of biophysical techniques, including confocal microscopy, SAXS, analytical ultracentrifugation, and single-molecule fluorescence, we describe how conformational changes within NPM1 control valency and switching between the different LLPS mechanisms. We propose that this newly discovered interplay between multiple LLPS mechanisms may influence the direction of vectorial pre-ribosomal particle assembly within, and exit from the nucleolus as part of the ribosome biogenesis process.
Widespread erosion on high plateaus during recent glaciations in Scandinavia
Authors: Andersen Jane L. , Egholm David L. , Knudsen Mads F. , Linge Henriette , Jansen John D. , Pedersen Vivi K. , Nielsen Søren B. , Tikhomirov Dmitry , Olsen Jesper , Fabel Derek , Xu Sheng
Published: February 2018

Glaciers create some of Earth’s steepest topography; yet, many areas that were repeatedly overridden by ice sheets in the last few million years include extensive plateaus. The distinct geomorphic contrast between plateaus and the glacial troughs that dissect them has sustained two long-held hypotheses: first, that ice sheets perform insignificant erosion beyond glacial troughs, and, second, that the plateaus represent ancient pre-glacial landforms bearing information of tectonic and geomorphic history prior to Pliocene–Pleistocene global cooling (~3.5 Myr ago). Here we show that the Fennoscandian ice sheets drove widespread erosion across plateaus far beyond glacial troughs. We apply inverse modelling to 118 new cosmogenic 10Be and 26Al measurements to quantify ice sheet erosion on the plateaus fringing the Sognefjorden glacial trough in western Norway. Our findings demonstrate substantial modification of the pre-glacial landscape during the Quaternary, and that glacial erosion of plateaus is important when estimating the global sediment flux to the oceans.
Non-catalytic hydrogenation of VO2 in acid solution
Authors: Chen Yuliang , Wang Zhaowu , Chen Shi , Ren Hui , Wang Liangxin , Zhang Guobin , Lu Yalin , Jiang Jun , Zou Chongwen , Luo Yi
Published: February 2018

Hydrogenation is an effective way to tune the property of metal oxides. It can conventionally be performed by doping hydrogen into solid materials with noble-metal catalysis, high-temperature/pressure annealing treatment, or high-energy proton implantation in vacuum condition. Acid solution naturally provides a rich proton source, but it should cause corrosion rather than hydrogenation to metal oxides. Here we report a facile approach to hydrogenate monoclinic vanadium dioxide (VO2) in acid solution at ambient condition by placing a small piece of low workfunction metal (Al, Cu, Ag, Zn, or Fe) on VO2 surface. It is found that the attachment of a tiny metal particle (~1.0 mm) can lead to the complete hydrogenation of an entire wafer-size VO2 (>2 inch). Moreover, with the right choice of the metal a two-step insulator–metal–insulator phase modulation can even be achieved. An electron–proton co-doping mechanism has been proposed and verified by the first-principles calculations.
ThMn12-type phases for magnets with low rare-earth content: Crystal-field analysis of the full magnetization process
Authors: Tereshina I. S. , Kostyuchenko N. V. , Tereshina-Chitrova E. A. , Skourski Y. , Doerr M. , Pelevin I. A. , Zvezdin A. K. , Paukov M. , Havela L. , Drulis H.
Published: February 2018

Rare-earth (R)-iron alloys are a backbone of permanent magnets. Recent increase in price of rare earths has pushed the industry to seek ways to reduce the R-content in the hard magnetic materials. For this reason strong magnets with the ThMn12 type of structure came into focus. Functional properties of R(Fe,T)12 (T-element stabilizes the structure) compounds or their interstitially modified derivatives, R(Fe,T)12-X (X is an atom of hydrogen or nitrogen) are determined by the crystal-electric-field (CEF) and exchange interaction (EI) parameters. We have calculated the parameters using high-field magnetization data. We choose the ferrimagnetic Tm-containing compounds, which are most sensitive to magnetic field and demonstrate that TmFe11Ti-H reaches the ferromagnetic state in the magnetic field of 52 T. Knowledge of exact CEF and EI parameters and their variation in the compounds modified by the interstitial atoms is a cornerstone of the quest for hard magnetic materials with low rare-earth content.
Population-specific expression of antimicrobial peptides conferring pathogen resistance in the invasive ladybird Harmonia axyridis
Authors: Gegner Tobias , Schmidtberg Henrike , Vogel Heiko , Vilcinskas Andreas
Published: February 2018

The harlequin ladybird Harmonia axyridis has emerged as a model species in the context of invasion biology and possesses an expanded repertoire of antimicrobial peptides (AMPs). Here we measured the expression of 22 AMP genes in adult beetles from native and introduced populations, and from a biocontrol population, allowing us to compare populations differing in terms of invasive performance. Strikingly, we observed population-specific expression profiles for particular AMPs. Following an immune challenge, the genes for Coleoptericin1 (Col1), Coleoptericin-likeB and Defensin1 were induced up to several thousand times more strongly in the invasive populations compared to the native and biocontrol populations. To determine the role of Col1 in pathogen resistance, the corresponding gene was silenced by RNA interference (RNAi), causing higher mortality in beetles subsequently infected with the entomopathogen Pseudomonas entomophila. The RNAi-triggered susceptibility to this pathogen was reversed by the injection of a synthetic Col1 peptide. We show that a native population is more susceptible to P. entomomophila infection than an invasive population. This is the first study demonstrating population-specific differences in the immune system of an invasive species and suggests that rapid gene expression changes and a highly adaptive immune system could promote pathogen resistance and thereby invasive performance.
Somatic Mitochondrial DNA Mutations in Diffuse Large B-Cell Lymphoma
Authors: Zeng Andy G. X. , Leung Andy C. Y. , Brooks-Wilson Angela R.
Published: February 2018

Diffuse Large B-Cell Lymphoma (DLBCL) is an aggressive hematological cancer for which mitochondrial metabolism may play an important role. Mitochondrial DNA (mtDNA) encodes crucial mitochondrial proteins, yet the relationship between mtDNA and DLBCL remains unclear. We analyzed the functional consequences and mutational spectra of mtDNA somatic mutations and private constitutional variants in 40 DLBCL tumour-normal pairs. While private constitutional variants occurred frequently in the D-Loop, somatic mutations were randomly distributed across the mitochondrial genome. Heteroplasmic constitutional variants showed a trend towards loss of heteroplasmy in the corresponding tumour regardless of whether the reference or variant allele was being lost, suggesting that these variants are selectively neutral. The mtDNA mutational spectrum showed minimal support for ROS damage and revealed strand asymmetry with increased C > T and A > G transitions on the heavy strand, consistent with a replication-associated mode of mutagenesis. These heavy strand transitions carried higher proportions of amino acid changes – which were also more pathogenic – than equivalent substitutions on the light strand. Taken together, endogenous replication-associated events underlie mtDNA mutagenesis in DLBCL and preferentially generate functionally consequential mutations. Yet mtDNA somatic mutations remain selectively neutral, suggesting that mtDNA-encoded mitochondrial functions may not play an important role in DLBCL.
Correlation between the timing of autonomous selfing and floral traits: a comparative study from three selfing Gentianopsis species (Gentianaceae)
Authors: Yang Ji-Qin , Fan Yong-Li , Jiang Xian-Feng , Li Qing-Jun , Zhu Xing-Fu
Published: February 2018

About 20% of angiosperms employ self-fertilization as their main mating strategy. In this study, we aimed to examine how the selfing timing correlated with floral traits in threeGentianopsisspecies in which autonomous selfing is achieved through filament elongation. Although the threeGentianopsisspecies exhibit no significant variation in their capacity for autonomous selfing, flowers ofG.grandislast longer, are larger and have a higher corolla biomass, P/O ratios and male biomass allocation than those ofG.paludosa, and especially those ofG.contorta. Autonomous selfing occurs in the early floral life ofG.paludosaandG.contortaand in the later floral life ofG.grandis. Seed production mainly results from autonomous selfing inG.paludosaandG.contorta; however,G.grandiscould be more described as having a mixed mating system. We suggest that autonomous selfing in later floral life increases the chance of cross-pollination prior to this, while autonomous selfing in early floral life offers a selective advantage to plants by reducing the resource investment in traits that may increase pollinator attraction and visitation.
Phosphorus speciation in a prairie soil amended with MBM and DDG ash: Sequential chemical extraction and synchrotron-based XANES spectroscopy investigations
Authors: Alotaibi Khaled D. , Schoenau Jeff. J. , Kar Gourango , Peak Derek , Fonstad Terry
Published: February 2018

Sequential chemical extraction and synchrotron-based XANES spectroscopy techniques were used to identify P species in two ashes before and after addition to a prairie soil. The used ashes were: meat and bone meal ash (MBMA) and dried distillers grains ash (DDGA) plus mineral P fertilizer (MP) for comparison. Soil treated with MP contained higher content of resin-Pi and NaHCO3-Pi followed by DDGA and MBMA. The MBMA amended soil had the highest (47%) proportion of the soil P contained in recalcitrant HCl extractable fraction, reflecting more Ca-bound P present and being formed in soil after application. Analysis of both ashes with XANES spectroscopy before application to soil revealed that MBMA had strong spectral features consistent with hydroxyapatite (Ca5(PO4)3(OH)). DDGA exhibited spectral features consistent with a mixture of several Mg and K phosphate salts rather than a single mineral species. The distinctive features in the XANES spectra of both ashes largely disappeared after amendment to the soil, suggesting transformation to different P forms in the soil after application. It is also possible that the added amount of P to the studied soil via DDGS or MBMA was small enough so that P speciation is not different from the background P level.
Network Motifs Capable of Decoding Transcription Factor Dynamics
Authors: Gao Zongmao , Chen Siheng , Qin Shanshan , Tang Chao
Published: February 2018

Transcription factors (TFs) can encode the information of upstream signal in terms of its temporal activation dynamics. However, it remains unclear how different types of TF dynamics are decoded by downstream signalling networks. In this work, we studied all three-node transcriptional networks for their ability to distinguish two types of TF dynamics: amplitude modulation (AM), where the TF is activated with a constant amplitude, and frequency modulation (FM), where the TF activity displays an oscillatory behavior. We found two sets of network topologies: one set can differentially respond to AM TF signal but not to FM; the other set to FM signal but not to AM. Interestingly, there is little overlap between the two sets. We identified the prevalent topological features in each set and gave a mechanistic explanation as to why they can differentially respond to only one type of TF signal. We also found that some network topologies have a weak (not robust) ability to differentially respond to both AM and FM input signals by using different values of parameters for AM and FM cases. Our results provide a novel network mechanism for decoding different TF dynamics.
Bumetanide for autism: more eye contact, less amygdala activation
Authors: Hadjikhani Nouchine , Åsberg Johnels Jakob , Lassalle Amandine , Zürcher Nicole R. , Hippolyte Loyse , Gillberg Christopher , Lemonnier Eric , Ben-Ari Yehezkel
Published: February 2018

We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli. In keeping with clinical trials, our data support the Excitatory/Inhibitory dysfunction hypothesis in autism, and indicate that bumetanide may improve specific aspects of social processing in autism. Future double-blind placebo controlled studies with larger cohorts of participants will help clarify the mechanisms of bumetanide action in autism.
Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats
Authors: Zhai Rujun , Wang Yongchun , Qi Le , Williams George Melville , Gao Bin , Song Guang , Burdick James F. , Sun Zhaoli
Published: February 2018

Rapid regeneration of the remnant liver is critical for preventing liver failure and promoting recovery after extensive liver resection. Numerous studies have demonstrated the involvement of bone marrow-derived stem cells in liver regeneration and the potential benefits of bone marrow stem cell therapy. To avoid the preparation of stem cells, we proposed in this study to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (A), an antagonist of CXCR4 and low-dose FK506 (F). Here we show that AF combination therapy significantly increased lineage negative (Lin-) CD34+ and Lin-CD133+ stem cells in peripheral blood and enhanced recruitment of CD133+ cells into the remnant liver in a rat model of 85% partial hepatectomy. Recruiting CD133+ stem cells in the remnant liver was associated with increased proliferation of hepatic oval cells and paralleled the increased SDF-1, CXCR4 and HGF expression. Importantly, AF combination therapy increased the number of Ki67 positive hepatocytes and BrdU incorporation in the remnant liver and improved serum levels of albumin. Our results demonstrate that pharmacological mobilization of endogenous bone marrow stem cells with AF combination therapy can enhance endogenous stem cell mobilization to promote liver regeneration and improve liver function after extensive hepatectomy.
Spider dragline silk composite films doped with linear and telechelic polyalanine: Effect of polyalanine on the structure and mechanical properties
Authors: Tsuchiya Kousuke , Ishii Takaoki , Masunaga Hiroyasu , Numata Keiji
Published: February 2018

Spider dragline silks have attracted intensive attention as eco-friendly tough materials because of their excellent mechanical property and biomass-based origin. Composite films based on a recombinant spider dragline silk protein (ADF3) from Araneus diadematus were prepared by doping with linear or telechelic poly(l-alanine) (L- or T-polyA, respectively) as a reinforcing agent. Higher tensile strength and toughness of the composite films were achieved with the addition of polyA compared with the tensile strength and toughness of the silk-only film. The difference in the reinforcing behavior between L- and T-polyA was associated with their primary structures, which were revealed by wide angle X-ray diffraction analysis. L-polyA showed a tendency to aggregate in the composite films and induce crystallization of the inherent silk β-sheet to afford rigid but brittle films. By contrast, T-polyA dispersion in the composite films led to the formation of β-sheet crystal of both T-polyA and the inherent silk, which imparted high strength and toughness to the silk films.
Lightning initiation: Strong pulses of VHF radiation accompany preliminary breakdown
Authors: Kolmašová Ivana , Santolík Ondřej , Defer Eric , Rison William , Coquillat Sylvain , Pedeboy Stéphane , Lán Radek , Uhlíř Luděk , Lambert Dominique , Pinty Jean-Pierre , Prieur Serge , Pont Véronique
Published: February 2018

We analyze lightning initiation process using magnetic field waveforms of preliminary breakdown (PB) pulses observed at time scales of a few tens of microseconds by a broad-band receiver. We compare these pulses with sources of narrow-band very high frequency (VHF) radiation at 60–66 MHz recorded by two separate Lightning Mapping Arrays (LMAs). We find that almost none of the observed PB pulses correspond to geo-located VHF radiation sources, in agreement with previous results and with the hypothesis that processes generating VHF radiation and PB pulses are only weakly related. However, our detailed analysis discovers that individual peaks of strong VHF radiation seen by separate LMA stations correspond surprisingly well to the PB pulses. This result shows that electromagnetic radiation generated during fast stepwise extension of developing lightning channels is spread over a large interval of frequencies. We also show that intense VHF radiation abruptly starts with the first PB pulse and that it is then continuously present during the entire PB phase of developing discharges.
Social status and parasitism in male and female vertebrates: a meta-analysis
Authors: Habig Bobby , Doellman Meredith M. , Woods Kourtney , Olansen Jonathan , Archie Elizabeth A.
Published: February 2018

Social status is an important predictor of parasite risk in vertebrates. To date, general frameworks to explain status-related variation in parasitism have remained elusive. In this meta-analysis, we evaluated five hypotheses proposed to explain status-related variation in parasitism in male and female vertebrates by leveraging variation in hierarchy type, mating system, parasite transmission mode, and allostatic load to test associated predictions. Our meta-analyses span 66 analyses (26 studies) of male vertebrates (two orders and five classes), and 62 analyses (13 studies) of female vertebrates (four vertebrate orders). Contrary to the prevailing paradigm that low status is linked to poor health, we found that dominant animals typically faced higher parasite risk than subordinates. This pattern was especially well-supported in analyses of males versus females, in linear versus egalitarian hierarchies, in mating systems where dominance rank predicts mating effort, and for contact- and environmentally-transmitted parasites rather than vector-borne parasites. These findings supported the priority-of-access and tradeoffs hypotheses suggesting that variation in parasitism is driven by rank-associated differences in exposure to parasites and mating effort. Together, these results suggest that high parasite risk might sometimes be an unappreciated cost of high rank, and conversely, reduced parasite risk might be a benefit of social subordination.