bluuebunny/crossref_metadata_2025_split huggingface dataset:
Di (2-ethylhexyl) phthalate exposure impairs meiotic progression and DNA damage repair in fetal mouse oocytes in vitro
Authors: Liu Jing-Cai , Lai Fang-Nong , Li Ling , Sun Xiao-Feng , Cheng Shun-Feng , Ge Wei , Wang Yu-Feng , Li Lan , Zhang Xi-Feng , De Felici Massimo , Dyce Paul W , Shen Wei 
Published: August 2017

AbstractDi (2-ethylhexyl) phthalate (DEHP), is the most common member of the class of phthalates that are used as plasticizers and have become common environmental contaminants. A number of studies have shown that DEHP exposure impacts reproductive health in both male and female mammals by acting as an estrogen analog. Here, we investigated the effects of DEHP on meiotic progression of fetal mouse oocytes by using an in vitro model of ovarian tissue culture. The results showed that 10 or 100 μM DEHP exposure inhibited the progression of oocytes throughout meiotic prophase I, specifically from the pachytene to diplotene stages. DEHP possibly impairs the ability to repair DNA double-strand breaks induced by meiotic recombination and as a consequence activates a pachytene check point. At later stages, such defects led to an increased number of oocytes showing apoptotic markers (TUNEL staining, expression of pro-apoptotic genes), resulting in reduced oocyte survival, gap junctions, and follicle assembly in the ovarian tissues. Microarray analysis of ovarian tissues exposed to DEHP showed altered expression of several genes including some involved in apoptosis and gonad development. The expression changes of some genes clustered in cell-cell communication and signal transduction, along with plasma membrane, extracellular matrix and ion channel function classes, were dependent on the DEHP concentration. Together, these results bring new support to the notion that exposure to DEHP during gestation might exert deleterious effects on ovary development, perturbing germ cell meiosis and the expression of genes involved in a wide range of biological processes including ovary development.
Pigment epithelium-derived factor promotes tumor metastasis through an interaction with laminin receptor in hepatocellular carcinomas
Authors: Hou Jianjing , Ge Chao , Cui Meiling , Liu Tengfei , Liu Xiaoqin , Tian Hua , Zhao Fangyu , Chen Taoyang , Cui Ying , Yao Ming , Li Jinjun , Li Hong 
Published: August 2017

AbstractPigment epithelium-derived factor (PEDF) has complex functions in tumor metastasis, but little is known about the roles of PEDF and its receptors in hepatocellular carcinoma (HCC). Here we found that high expression of PEDF is associated with shorter overall survival in HCC patients. Forced expression of PEDF enhanced HCC cell aggressive behavior in vitro and in vivo, whereas silencing PEDF expression reduced migration and invasion. Furthermore, PEDF expression led to changes in cell morphology and the expression of epithelial–mesenchymal transition (EMT)-related markers via ERK1/2 signaling pathway, including the upregulation of N-cadherin and slug, and the downregulation of E-cadherin in HCC cells. Our results further showed that PEDF could interact with laminin receptor (LR) and LR knockdown attenuated PEDF-induced migration, invasion and the change of EMT-related markers. More importantly, in clinical HCC specimens, we found that PEDF expression was correlated with subcellular localization of LR, and that high expression of PEDF and positive expression of LR predicted a poor prognosis. In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.
MicroRNA-519a-3p mediates apoptosis resistance in breast cancer cells and their escape from recognition by natural killer cells
Authors: Breunig Christian , Pahl Jens , Küblbeck Moritz , Miller Matthias , Antonelli Daniela , Erdem Nese , Wirth Cornelia , Will Rainer , Bott Alexander , Cerwenka Adelheid , Wiemann Stefan 
Published: August 2017

AbstractAggressive breast cancer is associated with poor patient outcome and characterized by the development of tumor cell variants that are able to escape from control of the immune system or are resistant to targeted therapies. The complex molecular mechanisms leading to immune escape and therapy resistance are incompletely understood. We have previously shown that high miR-519a-3p levels are associated with poor survival in breast cancer. Here, we demonstrate that miR-519a-3p confers resistance to apoptosis induced by TRAIL, FasL and granzyme B/perforin by interfering with apoptosis signaling in breast cancer cells. MiR-519a-3p diminished the expression of its direct target genes for TRAIL-R2 (TNFRSF10B) and for caspase-8 (CASP8) and its indirect target gene for caspase-7 (CASP7), resulting in reduced sensitivity and tumor cell apoptosis in response to apoptotic stimuli. Furthermore, miR-519a-3p impaired tumor cell killing by natural killer (NK) cells via downregulation of the NKG2D ligands ULBP2 and MICA on the surface of tumor cells that are crucial for the recognition of these tumor cells by NK cells. We determined that miR-519a-3p was overexpressed in more aggressive mutant TP53 breast cancer that was associated with poor survival. Furthermore, low levels of TRAIL-R2, caspase-7 and caspase-8 correlated with poor survival, suggesting that the inhibitory effect of miR-519a-3p on TRAIL-R2 and caspases may have direct clinical relevance in lowering patient’s prognosis. In conclusion, we demonstrate that miR-519a-3p is a critical factor in mediating resistance toward cancer cell apoptosis and impairing tumor cell recognition by NK cells. This joint regulation of apoptosis and immune cell recognition through miR-519a-3p supports the hypothesis that miRNAs are key regulators of cancer cell fate, facilitating cancer progression and evasion from immunosurveillance at multiple and interconnected levels.
Autophagy couteracts weight gain, lipotoxicity and pancreatic β-cell death upon hypercaloric pro-diabetic regimens
Authors: Fernández Álvaro F , Bárcena Clea , Martínez-García Gemma G , Tamargo-Gómez Isaac , Suárez María F , Pietrocola Federico , Castoldi Francesca , Esteban Lorena , Sierra-Filardi Elena , Boya Patricia , López-Otín Carlos , Kroemer Guido , Mariño Guillermo 
Published: August 2017

AbstractIn the last years, autophagy has been revealed as an essential pathway for multiple biological processes and physiological functions. As a catabolic route, autophagy regulation by nutrient availability has been evolutionarily conserved from yeast to mammals. On one hand, autophagy induction by starvation is associated with a significant loss in body weight in mice. Here, we demonstrate that both genetic and pharmacological inhibition of the autophagy process compromise weight loss induced by starvation. Moreover, autophagic potential also impacts on weight gain induced by distinct hypercaloric regimens. Atg4b-deficient mice, which show limited autophagic competence, exhibit a major increase in body weight in response to distinct obesity-associated metabolic challenges. This response is characterized by the presence of larger adipocytes in visceral fat tissue, increased hepatic steatosis, as well as reduced glucose tolerance and attenuated insulin responses. Similarly, autophagy-deficient mice are more vulnerable to experimentally induced type-I diabetes, showing an increased susceptibility to acute streptozotocin administration. Notably, pharmacological stimulation of autophagy in wild-type mice by spermidine reduced both weight gain and obesity-associated alterations upon hypercaloric regimens. Altogether, these results indicate that systemic autophagic activity influences the resilience of the organism to weight gain induced by high-calorie diets, as well as to the obesity-associated features of both type-1 and type-2 diabetes.
Identification and characterization of a novel botulinum neurotoxin
Authors: Zhang Sicai , Masuyer Geoffrey , Zhang Jie , Shen Yi , Lundin Daniel , Henriksson Linda , Miyashita Shin-Ichiro , Martínez-Carranza Markel , Dong Min , Stenmark Pål 
Published: August 2017

AbstractBotulinum neurotoxins are known to have seven serotypes (BoNT/A–G). Here we report a new BoNT serotype, tentatively named BoNT/X, which has the lowest sequence identity with other BoNTs and is not recognized by antisera against known BoNTs. Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). Remarkably, BoNT/X is the only toxin that also cleaves non-canonical substrates VAMP4, VAMP5 and Ykt6. To validate its activity, a small amount of full-length BoNT/X was assembled by linking two non-toxic fragments using a transpeptidase (sortase). Assembled BoNT/X cleaves VAMP2 and VAMP4 in cultured neurons and causes flaccid paralysis in mice. Thus, BoNT/X is a novel BoNT with a unique substrate profile. Its discovery posts a challenge to develop effective countermeasures, provides a novel tool for studying intracellular membrane trafficking, and presents a new potential therapeutic toxin for modulating secretions in cells.
Autonomous model protocell division driven by molecular replication
Authors: Taylor J. W. , Eghtesadi S. A. , Points L. J. , Liu T. , Cronin L. 
Published: August 2017

AbstractThe coupling of compartmentalisation with molecular replication is thought to be crucial for the emergence of the first evolvable chemical systems. Minimal artificial replicators have been designed based on molecular recognition, inspired by the template copying of DNA, but none yet have been coupled to compartmentalisation. Here, we present an oil-in-water droplet system comprising an amphiphilic imine dissolved in chloroform that catalyses its own formation by bringing together a hydrophilic and a hydrophobic precursor, which leads to repeated droplet division. We demonstrate that the presence of the amphiphilic replicator, by lowering the interfacial tension between droplets of the reaction mixture and the aqueous phase, causes them to divide. Periodic sampling by a droplet-robot demonstrates that the extent of fission is increased as the reaction progresses, producing more compartments with increased self-replication. This bridges a divide, showing how replication at the molecular level can be used to drive macroscale droplet fission.
Non-uniform self-assembly: On the anisotropic architecture of α-synuclein supra-fibrillar aggregates
Authors: Semerdzhiev Slav A. , Shvadchak Volodymyr V. , Subramaniam Vinod , Claessens Mireille M. A. E. 
Published: August 2017

AbstractAlthough the function of biopolymer hydrogels in nature depends on structural anisotropy at mesoscopic length scales, the self-assembly of such anisotropic structures in vitro is challenging. Here we show that fibrils of the protein α-synuclein spontaneously self-assemble into structurally anisotropic hydrogel particles. While the fibrils in the interior of these supra-fibrillar aggregates (SFAs) are randomly oriented, the fibrils in the periphery prefer to cross neighboring fibrils at high angles. This difference in organization coincides with a significant difference in polarity of the environment in the central and peripheral parts of the SFA. We rationalize the structural anisotropy of SFAs in the light of the observation that αS fibrils bind a substantial amount of counterions. We propose that, with the progress of protein polymerization into fibrils, this binding of counterions changes the ionic environment which triggers a change in fibril organization resulting in anisotropy in the architecture of hydrogel particles.
Genome-wide dissection of heterosis for yield traits in two-line hybrid rice populations
Authors: Zhen Gang , Qin Peng , Liu Kai Yu , Nie Dong Yang , Yang Yuan Zhu , Deng Xing Wang , He Hang 
Published: August 2017

AbstractHeterosis has been widely utilized in agriculture and is important for world food safety. Many genetic models have been proposed as mechanisms underlying heterosis during the past century, yet more evidence is needed to support such models. To investigate heterosis in two-line hybrid rice, we generated a partial diallel crossing scheme, which consisted of approximately 500 F1 hybrids derived from 14 male sterile lines and 39 restorer lines. In this population, increased panicle number played the most important role in yield heterosis of hybrid rice. Genome-wide association studies identified many QTLs related to the yield traits of F1 hybrids, better paternal heterosis and special combining ability. Relevant genes, includingHd3a,qGL3,OsmiR156h, andLAX2, were identified as candidates within these QTLs. Nearly forty percent of the QTLs had only two genotypes in the F1 hybrids, mainly because the maternal lines were under intense selective pressure. Further analysis found male sterile lines and restorer lines made different superior allele contributions to F1 hybrids, and their contributions varied among different traits. These results extend our understanding of the molecular basis of heterosis in two-line hybrid rice.
Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition
Authors: Ribeiro Tatiane Aparecida , Tófolo Laize Peron , Martins Isabela Peixoto , Pavanello Audrei , de Oliveira Júlio Cezar , Prates Kelly Valério , Miranda Rosiane Aparecida , da Silva Franco Claudinéia Conationi , Gomes Rodrigo Mello , Francisco Flávio Andrade , Alves Vander Silva , de Almeida Douglas Lopes , Moreira Veridiana Mota , Palma-Rigo Kesia , Vieira Elaine , Fabricio Gabriel Sergio , da Silva Rodrigues Marcos Ricardo , Rinaldi Wilson , Malta Ananda , de Freitas Mathias Paulo Cezar 
Published: August 2017

AbstractLow intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively. Exercised mothers showed low mesenteric fat pad stores and fasting glucose and improved glucose-insulin tolerance, VO2max during lactation and sympathetic activity. Moreover, the breast milk contained elevated levels of insulin. In addition, SL of sedentary mothers presented metabolic dysfunction and glucose and insulin intolerance and were hyperglycemic and hyperinsulinemic in adulthood. SL of exercised mothers showed lower fat tissue accretion and improvements in glucose tolerance, insulin sensitivity, insulinemia and glycemia. The results suggest that maternal exercise during the perinatal period can have a possible reprogramming effect to prevent metabolic dysfunction in adult rat offspring exposed to early overnutrition, which may be associated with the improvement in maternal health caused by exercise.
Dynamic Mechano-Regulation of Myoblast Cells on Supramolecular Hydrogels Cross-Linked by Reversible Host-Guest Interactions
Authors: Hörning Marcel , Nakahata Masaki , Linke Philipp , Yamamoto Akihisa , Veschgini Mariam , Kaufmann Stefan , Takashima Yoshinori , Harada Akira , Tanaka Motomu 
Published: August 2017

AbstractA new class of supramolecular hydrogels, cross-linked by host-guest interactions between β-cyclodextrin (βCD) and adamantane, were designed for the dynamic regulation of cell-substrate interactions. The initial substrate elasticity can be optimized by selecting the molar fraction of host- and guest monomers for the target cells. Moreover, owing to the reversible nature of host-guest interactions, the magnitude of softening and stiffening of the substrate can be modulated by varying the concentrations of free, competing host molecules (βCD) in solutions. By changing the substrate elasticity at a desired time point, it is possible to switch the micromechanical environments of cells. We demonstrated that the Young’s modulus of our “host-guest gels”, 4–11 kPa, lies in an optimal range not only for static (ex situ) but also for dynamic (in situ) regulation of cell morphology and cytoskeletal ordering of myoblasts. Compared to other stimulus-responsive materials that can either change the elasticity only in one direction or rely on less biocompatible stimuli such as UV light and temperature change, our supramolecular hydrogel enables to reversibly apply mechanical cues to various cell types in vitro without interfering cell viability.
Complete mitochondrial genomes of Anopheles stephensi and An. dirus and comparative evolutionary mitochondriomics of 50 mosquitoes
Authors: Hao You-Jin , Zou Yi-Lin , Ding Yi-Ran , Xu Wen-Yue , Yan Zhen-Tian , Li Xu-Dong , Fu Wen-Bo , Li Ting-Jing , Chen Bin 
Published: August 2017

AbstractTo better understand the phylogeny and evolution of mosquitoes, the complete mitochondrial genome (mitogenome) ofAnopheles stephensiandAn. diruswere sequenced and annotated, and a total of 50 mosquito mitogenomes were comparatively analyzed. The complete mitogenome ofAn. stephensiandAn. dirusis 1,5371 bp and 1,5406 bp long, respectively. The main features of the 50 mosquito mitogenomes are conservative: 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 transfer RNA genes, positive AT-skew and negative GC-skew. The gene ordertrnA-trnRin ancestral insects is rearranged. All tRNA genes have the typical clover leaf secondary structure buttRNASer. The control regions are highly variable in size. PCGs show signals of purifying selection, but evidence for positive selection inND2,ND4andND6is found. Bayesian and Maximum Likelihood phylogenetic analyses based on all PCG nucleotides produce an identical tree topology and strongly support the monophyly of subgeneraCellia,Anopheles,KetersziaandNyssorhynchus, the sister relationship of the subgeneraNyssorhynchusandKeterszia, andCelliaandAnopheles. The most recent ancestor of the genusAnophelesand Culicini + Aedini exited ~145 Mya ago. This is the first comprehensive study of mosquito mitogenomes, which are effective for mosquito phylogeny at various taxonomic levels.
The Female Perspective of Personality in a Wild Songbird: Repeatable Aggressiveness Relates to Exploration Behaviour
Authors: Thys Bert , Pinxten Rianne , Raap Thomas , De Meester Gilles , Rivera-Gutierrez Hector F. , Eens Marcel 
Published: August 2017

AbstractMales often express traits that improve competitive ability, such as aggressiveness. Females also express such traits but our understanding about why is limited. Intraspecific aggression between females might be used to gain access to reproductive resources but simultaneously incurs costs in terms of energy and time available for reproductive activities, resulting in a trade-off. Although consistent individual differences in female behaviour (i.e. personality) like aggressiveness are likely to influence these reproductive trade-offs, little is known about the consistency of aggressiveness in females. To quantify aggression we presented a female decoy to free-living female great tits (Parus major) during the egg-laying period, and assessed whether they were consistent in their response towards this decoy. Moreover, we assessed whether female aggression related to consistent individual differences in exploration behaviour in a novel environment. We found that females consistently differed in aggressiveness, although first-year females were on average more aggressive than older females. Moreover, conform life history theory predictions, ‘fast’ exploring females were more aggressive towards the decoy than ‘slow’ exploring females. Given that personality traits are often heritable, and correlations between behaviours can constrain short term adaptive evolution, our findings highlight the importance of studying female aggression within a multivariate behavioural framework.
A controlled ac Stark echo for quantum memories
Authors: Ham Byoung S. 
Published: August 2017

AbstractA quantum memory protocol of controlled ac Stark echoes (CASE) based on a double rephasing photon echo scheme via controlled Rabi flopping is proposed. The double rephasing scheme of photon echoes inherently satisfies the no-population inversion requirement for quantum memories, but the resultant absorptive echo remains a fundamental problem. Herein, it is reported that the first echo in the double rephasing scheme can be dynamically controlled so that it does not affect the second echo, which is accomplished by using unbalanced ac Stark shifts. Then, the second echo is coherently controlled to be emissive via controlled coherence conversion. Finally a near perfect ultralong CASE is presented using a backward echo scheme. Compared with other methods such as dc Stark echoes, the present protocol is all-optical with advantages of wavelength-selective dynamic control of quantum processing for erasing, buffering, and channel multiplexing.
Traveling Theta Waves and the Hippocampal Phase Code
Authors: Leibold Christian , Monsalve-Mercado Mauro M. 
Published: August 2017

AbstractHippocampal place fields form a neuronal map of the spatial environment. In addition, the distance between two place field centers is proportional to the firing phase difference of two place cells with respect to the local theta rhythm. This consistency between spatial distance and theta phase is generally assumed to result from hippocampal phase precession: The firing phase of a place cell decreases with distance traveled in the place field. The rate of phase precession depends on place field width such that the phase range covered in a traversal of a place field is independent of field width. Width-dependent precession rates, however, generally disrupt the consistency between distance and phase differences. In this paper we provide a mathematical theory suggesting that this consistency can only be secured for different place field widths if phase precession starts at a width-dependent phase offset. These offsets are in accordance with the experimentally observed theta wave traveling from the dorsal to the ventral pole of the hippocampus. Furthermore the theory predicts that sequences of place cells with different widths should be ordered according to the end of the place field. The results also hold for considerably nonlinear phase precession profiles.
Tunable High-Pressure Field Operating on a Cationic Biphenyl Derivative Intercalated in Clay Minerals
Authors: Tominaga Makoto , Nishioka Yukihiro , Tani Seiji , Suzuki Yasutaka , Kawamata Jun 
Published: August 2017

AbstractWe propose a methodology for applying a pseudo uniaxial pressure to an organic molecule under ordinary temperature and pressure, namely by intercalation into smectites. The pseudo pressure on a biphenyl derivative (BP) was estimated from the averaged dihedral angle around the central bond of BP. In a high hydrostatic pressure field, biphenyl takes a planar conformation. In the interlayer space of synthetic saponite (SSA), the averaged dihedral angle of BP at a loading level of 27% versus the cation exchange capacity was ~26.3°, which indicates that the pseudo pressure applied to BP in the SSA interlayer space corresponds to 0.99 GPa. The high pseudo-pressure field in the interlayer space of SSA was also confirmed by absorption measurements. The dihedral angle around the central bond of the biphenyl moiety decreased to enhance the planarity of the molecule, mainly in response to the electrostatic force that operates between the negatively charged SSA layer and the interlayer cation. The pseudo pressure operating on BP in the smectite interlayer space could be controlled by varying the smectite layer charge density and/or the BP loading level. By using this methodology, controllable pseudo high-pressure properties of organic molecules can be obtained at ordinary temperatures and pressures.