bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Metabolic Profiles Associate with Toxicity in SOD1G93A Astrocyte-Neuron Co-Cultures
Authors: Valbuena Gabriel N. , Tortarolo Massimo , Bendotti Caterina , Cantoni Lavinia , Keun Hector C. 
Published: February 2017

AbstractNon-cell autonomous processes involving astrocytes have been shown to contribute to motor neuron degeneration in amyotrophic lateral sclerosis. Mutant superoxide dismutase 1 (SOD1G93A) expression in astrocytes is selectively toxic to motor neurons in co-culture, even when mutant protein is expressed only in astrocytes and not in neurons. To examine metabolic changes in astrocyte-spinal neuron co-cultures, we carried out metabolomic analysis by 1H NMR spectroscopy of media from astrocyte-spinal neuron co-cultures and astrocyte-only cultures. We observed increased glucose uptake with SOD1G93A expression in all co-cultures, but while co-cultures with only SOD1G93A neurons had lower extracellular lactate, those with only SOD1G93A astrocytes exhibited the reverse. Reduced branched-chain amino acid uptake and increased accumulation of 3-methyl-2-oxovalerate were observed in co-culture with only SOD1G93A neurons while glutamate was reduced in all co-cultures expressing SOD1G93A. The shifts in these coupled processes suggest a potential block in glutamate processing that may impact motor neuron survival. We also observed metabolic alterations which may relate to oxidative stress responses. Overall, the different metabolite changes observed with the two SOD1G93A cell types highlight the role of the astrocyte-motor neuron interaction in the resulting metabolic phenotype, requiring further examination of altered met abolic pathways and their impact on motor neuron survival.
ZEB1 Regulates Multiple Oncogenic Components Involved in Uveal Melanoma Progression
Authors: Chen Yao , Lu Xiaoqin , Montoya-Durango Diego E. , Liu Yu-Hua , Dean Kevin C. , Darling Douglas S. , Kaplan Henry J. , Dean Douglas C. , Gao Ling , Liu Yongqing 
Published: February 2017

AbstractHuman uveal melanoma (UM) is a major ocular malignant tumor with high risk of metastasis and requires multiple oncogenic factors for progression. ZEB1 is a zinc finger E-box binding transcription factor known for participating epithelial-mesenchymal transition (EMT), a critical cellular event for metastasis of malignant tumors of epithelium origin. ZEB1 is also expressed in UM and high expression of ZEB1 correlates with UM advancement, but has little effect on cell morphology. We show that spindle UM cells can become epithelioid but not vice versa; and ZEB1 exerts its tumorigenic effects by promoting cell dedifferentiation, proliferation, invasiveness, and dissemination. We provide evidence that ZEB1 binds not only to repress critical genes involving in pigment synthesis, mitosis, adherent junctions, but also to transactivate genes involving in matrix degradation and cellular locomotion to propel UM progression towards metastasis. We conclude that ZEB1 is a major oncogenic factor required for UM progression and could be a potential therapeutic target for treating UM in the clinic.
An experimental investigation on the speed of sand flow through a fixed porous bed
Authors: Sui Wanghua , Liang Yankun , Zhang Xinjia , Jain Ravi , Zhu Tao 
Published: February 2017

AbstractIn this study, we document several experiments that investigate the speed of the flow of fine sand through a fixed porous bed of packed glass beads under various conditions, including the height of the sand column (H) and porous bed (h) and the diameter of the glass beads (D) and sand grains (d). The experiments are conducted with glass beads packed at a constant density and sand at a different dry bulk density. The results show that the height of the sand does not affect the speed of the sand flow. The speed of the sand flow (v) decreases with an increase in h until h approaches a certain value. An equation $${\boldsymbol{v}}={\boldsymbol{a}}\sqrt{{\bf{g}}{\boldsymbol{D}}}{\bf{l}}{\bf{n}}(\frac{{\boldsymbol{D}}}{{\boldsymbol{kd}}})$$
v
=
a

g
D

l
n

(

D

kd

)

is proposed, where a and k are the experimentally determined coefficients. Moreover, the flow of sand through a fixed porous bed could be regarded as parallel flow through multiple pipes, and therefore, the relationship between D and the number and diameter of pipes, N and Dp, are discussed. Further investigations are needed for the result that the flow of sand through a porous bed or multiple parallel pipes cannot be simplified to flow through one orifice with a certain diameter.
Relationship between somatic mosaicism of Pax6 mutation and variable developmental eye abnormalities—an analysis of CRISPR genome-edited mouse embryos
Authors: Yasue Akihiro , Kono Hitomi , Habuta Munenori , Bando Tetsuya , Sato Keita , Inoue Junji , Oyadomari Seiichi , Noji Sumihare , Tanaka Eiji , Ohuchi Hideyo 
Published: February 2017

AbstractThe clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system is a rapid gene-targeting technology that does not require embryonic stem cells. To demonstrate dosage effects of the Pax6 gene on eye formation, we generated Pax6-deficient mice with the CRISPR/Cas system. Eyes of founder embryos at embryonic day (E) 16.5 were examined and categorized according to macroscopic phenotype as class 1 (small eye with distinct pigmentation), class 2 (pigmentation without eye globes), or class 3 (no pigmentation and no eyes). Histologically, class 1 eyes were abnormally small in size with lens still attached to the cornea at E16.5. Class 2 eyes had no lens and distorted convoluted retinas. Class 3 eyes had only rudimentary optic vesicle-like tissues or histological anophthalmia. Genotyping of neck tissue cells from the founder embryos revealed somatic mosaicism and allelic complexity for Pax6. Relationships between eye phenotype and genotype were developed. The present results demonstrated that development of the lens from the surface ectoderm requires a higher gene dose of Pax6 than development of the retina from the optic vesicle. We further anticipate that mice with somatic mosaicism in a targeted gene generated by CRISPR/Cas-mediated genome editing will give some insights for understanding the complexity in human congenital diseases that occur in mosaic form.
Functional Characterization of Populus PsnSHN2 in Coordinated Regulation of Secondary Wall Components in Tobacco
Authors: Liu Yingying , Wei Minjing , Hou Cong , Lu Tingting , Liu Lulu , Wei Hairong , Cheng Yuxiang , Wei Zhigang 
Published: February 2017

AbstractWood formation is a biological process during which the most abundant lignocellulosic biomass on earth is produced. Although a number of transcription factors have been linked to the regulation of wood formation process, none of them has been demonstrated to be a higher hierarchical regulator that coordinately regulates secondary wall biosynthesis genes. Here, we identified a Populus gene, PsnSHN2, a counterpart of the Arabidopsis AP2/ERF type transcription factor, SHINE2. PsnSHN2 is predominantly expressed in xylem tissues and acted evidently as a high hierarchical transcriptional activator. Overexpression of PsnSHN2 in tobacco significantly altered the expression of both transcription factors and biosynthesis genes involved in secondary wall formation, leading to the thickened secondary walls and the changed cell wall composition. The most significant changes occurred in the contents of cellulose and hemicellulose that increased 37% and 28%, respectively, whereas the content of lignin that decreased 34%. Furthermore, PsnSHN2 activated or repressed the promoter activities of transcription factors involved in secondary wall biosynthesis and bound to five cis-acting elements enriched in the promoter regions of these transcription factors. Taken together, our results suggest PsnSHN2 coordinately regulate secondary wall formation through selective up/down-regulation of its downstream transcription factors that control secondary wall formation.
Grape seed proanthocyanidins prevent irradiation-induced differentiation of human lung fibroblasts by ameliorating mitochondrial dysfunction
Authors: Yang XiaoHong , Liu Tao , Chen Bo , Wang Fangqin , Yang Qunfang , Chen XiaoHong 
Published: February 2017

AbstractRadiation-induced lung fibrosis (RILF) is a long-term adverse effect of curative radiotherapy. The accumulation of myofibroblasts in fibroblastic foci is a pivotal feature of RILF. In the study, we found the inhibitory effect of grape seed proanthocyanidins (GSPs) on irradiation-induced differentiation of human fetal lung fibroblasts (HFL1). To explore the mechanism by which GSPs inhibit fibroblast differentiation, we measured the reactive oxygen species (ROS) levels, mitochondrial function, mitochondrial dynamics, glycolysis and the signaling molecules involved in fibroblast transdifferentiation. GSPs significantly reduced the production of cellular and mitochondrial ROS after radiation. The increases in mitochondrial respiration, proton leak, mitochondrial ATP production, lactate release and glucose consumption that occurred in response to irradiation were ameliorated by GSPs. Furthermore, GSPs increased the activity of complex I and improved the mitochondrial dynamics, which were disturbed by irradiation. In addition, the elevation of phosphorylation of p38MAPK and Akt, and Nox4 expression induced by irradiation were attenuated by GSPs. Blocking Nox4 attenuated irradiation-mediated fibroblast differentiation. Taken together, these results indicate that GSPs have the ability to inhibit irradiation-induced fibroblast-to-myofibroblast differentiation by ameliorating mitochondrial dynamics and mitochondrial complex I activity, regulating mitochondrial ROS production, ATP production, lactate release, glucose consumption and thereby inhibiting p38MAPK-Akt-Nox4 pathway.
Vigour in active avoidance
Authors: Nord Camilla L , Prabhu Gita , Nolte Tobias , Fonagy Peter , Dolan Ray , Moutoussis Michael 
Published: February 2017

AbstractIt would be maladaptive to learn about catastrophes by trial and error alone. Investment in planning and effort are necessary. Devoting too many resources to averting disaster, however, can impair quality of life, as in anxiety and paranoia. Here, we developed a novel task to explore how people adjust effort expenditure (vigor) so as to avoid negative consequences. Our novel paradigm is immersive, enabling us to measure vigor in the context of (simulated) disaster. We found that participants (N = 118) exerted effort to avoid disaster-associated states, adjusting their effort expenditure according to the baseline probability of catastrophe, in agreement with theoretical predictions. Furthermore, negative subjective emotional states were associated both with threat level and with increasing vigor in the face of disaster. We describe for the first time effort expenditure in the context of irreversible losses, with important implications for disorders marked by excessive avoidance.
Creation of mutant mice with megabase-sized deletions containing custom-designed breakpoints by means of the CRISPR/Cas9 system
Authors: Kato Tomoko , Hara Satoshi , Goto Yuji , Ogawa Yuya , Okayasu Haruka , Kubota Souichirou , Tamano Moe , Terao Miho , Takada Shuji 
Published: February 2017

AbstractThe clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a useful tool for creation of mutant mice with mutations mirroring those in human patients. Various methods have been developed for this purpose, including deletions, inversions, and translocations. So far, mutant mice with deletions of up to 1.2 megabases (Mb) have been generated by microinjection of the CRISPR/Cas9 system into fertilized eggs; however, a method for generation of mutant mice with a deletion of more than several Mb size is necessary because such deletions have often been identified as possible causes of human diseases. With an aim to enable the generation of disease models carrying large deletions with a breakpoint in custom-designed sequences, we developed a method for induction of an Mb-sized deletion by microinjection of a pair of sgRNAs, Cas9, and a donor plasmid into fertilized eggs. Using this method, we efficiently and rapidly generated mutant mice carrying deletions up to 5 Mb.
AMD3100 inhibits the migration and differentiation of neural stem cells after spinal cord injury
Authors: Liu Jia-Ming , Zhao Kai , Du Liu-Xue , Zhou Yang , Long Xin-Hua , Chen Xuan-Yin , Liu Zhi-Li 
Published: February 2017

AbstractIt was reported that CXCR4 signaling played an important role in the migration and differentiation of endogenous neural stem cells after spinal cord injury (SCI). However, the molecular mechanism of it is still unclear. Here, we established a model of SCI in rats and AMD3100 was used to treat them. The rats were then sacrificed and the injured spinal cord specimens were harvested. Additionally, the neural stem cells (NSCs) line was culture and treated with AMD3100 in vitro. Results showed the locomotor function of SCI rats was worse after treated with AMD3100. And the expression levels of Nestion in neural stem cells and β-tubulin in neuron cells were significantly increased in the injured spinal cord, which can be inhibited by the CXCR4 antagonist of AMD3100. Additionally, the expression of β-catenin and phosphorylase β-catenin protein was significantly down regulated by AMD3100. In vitro, the NSCs proliferation ability was inhibited and the migration was decreased after treated with AMD3100. Also, the expression of Nestion, β-tubulin, β-catenin and phosphorylase β-catenin protein was significantly decreased in AMD3100 group comparing with untreated group. Taken together, this study suggested that AMD3100 could inhibit the migration and differentiation of endogenous neural stem cells in rats with SCI. The mechanism of it maybe that AMD3100 could down regulate of SDF-1/CXCR4 by targeting β-catenin signaling pathway.
PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3
Authors: Zhang Huizhi , Kozlov Guennadi , Li Xinlu , Wu Howie , Gulerez Irina , Gehring Kalle 
Published: February 2017

AbstractThe phosphatases of regenerating liver (PRLs) are involved in tumorigenesis and metastatic cancer yet their cellular function remains unclear. Recent reports have shown PRL phosphatases bind tightly to the CNNM family of membrane proteins to regulate magnesium efflux. Here, we characterize the interactions between the CBS-pair (Bateman) domain of CNNM3 and either PRL2 or PRL3 using X-ray crystallography, isothermal titration calorimetry, and activity assays. We report four new crystal structures of PRL proteins bound to the CNNM3 CBS-pair domain that reveal the effects of cysteine disulphide formation and nucleotide binding on complex formation. We use comprehensive mutagenesis of the PRL3 catalytic site to quantify the importance of different PRL amino acids, including cysteine 104, leucine 108, and arginine 110, for CNNM binding and phosphatase activity. We show the PRL3 R138E mutant is selectively deficient in CNNM3 binding with the potential to distinguish between the downstream effects of phosphatase and CNNM-binding activities in vivo. Through a novel activity assay, we show that PRL3 has magnesium-sensitive phosphatase activity with ATP and other nucleotides. Our results identify a strong correlation between phosphatase activity and CNNM binding and support the contention that PRL function as pseudophosphatases regulated by chemical modifications of their catalytic cysteine.
Somatic Embryogenesis of Immature Cunninghamia lanceolata (Lamb.) Hook Zygotic Embryos
Authors: Hu Ruiyang , Sun Yuhan , Wu Bo , Duan Hongjing , Zheng Huiquan , Hu Dehuo , Lin Huazhong , Tong Zaikang , Xu Jinliang , Li Yun 
Published: February 2017

AbstractTwo efficient somatic embryogenesis systems were developed in Chinese fir, the most important conifer for industrial wood production in China. Three development stages (cleavage polyembryony, dominant embryo, and precotyledon) of immature embryos derived from 25 genotypes of open-pollinated mother trees were used as initial explants. Cleavage polyembryony-stage embryos with a 12.44% induction rate was the most embryogenic response stage. The highest frequency of embryogenic callus (13.86%) induction was obtained from DCR medium supplemented with 1.5 mg L−1 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.3 mg L−1 kinetin (KN). An average of 53.33 early somatic embryos were produced from approximately 0.2 g (fresh weight) embryogenic callus after 2 weeks of incubation on medium supplemented with 50 μmol L−1 abscisic acid (ABA) and 100 g L−1 polyethylene glycol (PEG) 6000. About 53% dominant embryos have an embryogenic response after a 6-week cultivation on medium supplemented with 1.0–2.0 mg L−1 benzyladenine (BA), 0.2 mg L−1 naphthylacetic acid (NAA) or 2,4-D, and 0.004 mg L−1 thidiazuron (TDZ). After three successive transfer cultures on medium supplemented with 1.5 mg L−1 BA, 0.2 mg L−1 NAA, and 0.004 mg L−1 TDZ, 4.49–16.51% of the embryos developed into somatic embryos.
Proteomic analysis and cross species comparison of casein fractions from the milk of dairy animals
Authors: Wang Xiaxia , Zhao Xiaowei , Huang Dongwei , Pan Xiaocheng , Qi Yunxia , Yang Yongxin , Zhao Huiling , Cheng Guanglong 
Published: February 2017

AbstractCasein micelles contribute to the physicochemical properties of milk and may also influence its functionality. At present, however, there is an incomplete understanding of the casein micelle associated proteins and its diversity among the milk obtained from different species. Therefore, milk samples were collected from seven dairy animals groups, casein fractions were prepared by ultracentrifugation and their constituent proteins were identified by liquid chromatography tandem mass spectrometry. A total of 193 distinct proteins were identified among all the casein micelle preparations. Protein interaction analysis indicated that caseins could interact with major whey proteins, including β-lactoglobulin, α-lactalbumin, lactoferrin, and serum albumin, and then whey proteins interacted with other proteins. Pathway analysis found that the peroxisome proliferator-activated receptor signaling pathway is shared among the studied animals. Additionally, galactose metabolism pathway is also found to be commonly involved for proteins derived from camel and horse milk. According to the similarity of casein micelle proteomes, two major sample clusters were classified into ruminant animals (Holstein and Jersey cows, buffaloes, yaks, and goats) and non-ruminants (camels and horses). Our results provide new insights into the protein profile associated with casein micelles and the functionality of the casein micelle from the studied animals.
The microscopic origin of the extreme glass-forming ability of Albite and B2O3
Authors: Zanotto Edgar D. , Cassar Daniel R. 
Published: February 2017

AbstractUnderstanding the conditions that favour crystallisation and vitrification has been a longstanding scientific endeavour. Here we demonstrate that the extremely high glass-forming ability of unseeded supercooled Na2O·Al2O3·6SiO2 (Albite) and B2O3—known for decades as “crystallisation anomaly”—is caused by insufficient crystal nucleation. The predicted temperatures of the maximum homogeneous nucleation rates are located well below their glass transition temperatures (Tg), in a region of very high viscosity, which leads to extremely long nucleation time-lags and low nucleation rates. This behaviour is due to the remarkably small supercoolings where the glass transition occurs for these liquids, which correspond to a very small driving force for crystallisation at and above the Tg, where crystallisation is normally observed. This meagre nucleation ability is caused by the significant difference in the structures of the supercooled liquids and their isochemical crystals. These findings elucidate the cause behind the crystallisation anomaly, and could be used for the design of other oxide glasses that are extremely stable against crystallisation.
Hierarchical Cobalt Hydroxide and B/N Co-Doped Graphene Nanohybrids Derived from Metal-Organic Frameworks for High Energy Density Asymmetric Supercapacitors
Authors: Tabassum Hassina , Mahmood Asif , Wang Qingfei , Xia Wei , Liang Zibin , Qiu Bin , zhao Ruo , Zou Ruqiang 
Published: February 2017

AbstractTo cater for the demands of electrochemical energy storage system, the development of cost effective, durable and highly efficient electrode materials is desired. Here, a novel electrode material based on redox active β-Co(OH)2 and B, N co-doped graphene nanohybrid is presented for electrochemical supercapacitor by employing a facile metal-organic frameworks (MOFs) route through pyrolysis and hydrothermal treatment. The Co(OH)2 could be firmly stabilized by dual protection of N-doped carbon polyhedron (CP) and B/N co-doped graphene (BCN) nanosheets. Interestingly, the porous carbon and BCN nanosheets greatly improve the charge storage, wettability, and redox activity of electrodes. Thus the hybrid delivers specific capacitance of 1263 F g−1 at a current density of 1A g−1 with 90% capacitance retention over 5000 cycles. Furthermore, the new aqueous asymmetric supercapacitor (ASC) was also designed by using Co(OH)2@CP@BCN nanohybrid and BCN nanosheets as positive and negative electrodes respectively, which leads to high energy density of 20.25 Whkg−1. This device also exhibits excellent rate capability with energy density of 15.55 Whkg−1 at power density of 9331 Wkg−1 coupled long termed stability up to 6000 cycles.
The world’s earliest Aral-Sea type disaster: the decline of the Loulan Kingdom in the Tarim Basin
Authors: Mischke Steffen , Liu Chenglin , Zhang Jiafu , Zhang Chengjun , Zhang Hua , Jiao Pengcheng , Plessen Birgit 
Published: February 2017

AbstractRemnants of cities and farmlands in China’s hyperarid Tarim Basin indicate that environmental conditions were significantly wetter two millennia ago in a region which is barren desert today. Historical documents and age data of organic remains show that the Loulan Kingdom flourished during the Han Dynasty (206 BCE–220 CE) but was abandoned between its end and 645 CE. Previous archaeological, geomorphological and geological studies suggest that deteriorating climate conditions led to the abandonment of the ancient desert cities. Based on analyses of lake sediments from Lop Nur in the eastern Tarim Basin and a review of published records, we show that the Loulan Kingdom decline resulted from a man-made environmental disaster comparable to the recent Aral Sea crisis rather than from changing climate. Lop Nur and other lakes within the Han Dynasty realm experienced rapidly declining water levels or even desiccation whilst lakes in adjacent regions recorded rising levels and relatively wet conditions during the time of the Loulan Kingdom decline. Water withdrawal for irrigation farming in the middle reaches of rivers likely caused water shortage downstream and eventually the widespread deterioration of desert oases a long time before man initiated the Aral Sea disaster in the 1960s.