bluuebunny/crossref_metadata_2025 huggingface dataset:
The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma
Authors: Zhai Weiwei , Lim Tony Kiat-Hon , Zhang Tong , Phang Su-Ting , Tiang Zenia , Guan Peiyong , Ng Ming-Hwee , Lim Jia Qi , Yao Fei , Li Zheng , Ng Poh Yong , Yan Jie , Goh Brian K. , Chung Alexander Yaw-Fui , Choo Su-Pin , Khor Chiea Chuen , Soon Wendy Wei-Jia , Sung Ken Wing-Kin , Foo Roger Sik-Yin , Chow Pierce Kah-Hoe
Published: February 2017

Hepatocellular carcinoma (HCC) has one of the poorest survival rates among cancers. Using multi-regional sampling of nine resected HCC with different aetiologies, here we construct phylogenetic relationships of these sectors, showing diverse levels of genetic sharing, spanning early to late diversification. Unlike the variegated pattern found in colorectal cancers, a large proportion of HCC display a clear isolation-by-distance pattern where spatially closer sectors are genetically more similar. Two resected intra-hepatic metastases showed genetic divergence occurring before and after primary tumour diversification, respectively. Metastatic tumours had much higher variability than their primary tumours, suggesting that intra-hepatic metastasis is accompanied by rapid diversification at the distant location. The presence of co-existing mutations offers the possibility of drug repositioning for HCC treatment. Taken together, these insights into intra-tumour heterogeneity allow for a comprehensive understanding of the evolutionary trajectories of HCC and suggest novel avenues for personalized therapy.
A tailored double perovskite nanofiber catalyst enables ultrafast oxygen evolution
Authors: Zhao Bote , Zhang Lei , Zhen Dongxing , Yoo Seonyoung , Ding Yong , Chen Dongchang , Chen Yu , Zhang Qiaobao , Doyle Brian , Xiong Xunhui , Liu Meilin
Published: February 2017

Rechargeable metal–air batteries and water splitting are highly competitive options for a sustainable energy future, but their commercialization is hindered by the absence of cost-effective, highly efficient and stable catalysts for the oxygen evolution reaction. Here we report the rational design and synthesis of a double perovskite PrBa0.5Sr0.5Co1.5Fe0.5O5+δ nanofiber as a highly efficient and robust catalyst for the oxygen evolution reaction. Co-doping of strontium and iron into PrBaCo2O5+δ is found to be very effective in enhancing intrinsic activity (normalized by the geometrical surface area, ∼4.7 times), as validated by electrochemical measurements and first-principles calculations. Further, the nanofiber morphology enhances its mass activity remarkably (by ∼20 times) as the diameter is reduced to ∼20 nm, attributed to the increased surface area and an unexpected intrinsic activity enhancement due possibly to a favourable eg electron filling associated with partial surface reduction, as unravelled from chemical titration and electron energy-loss spectroscopy.
Correction: Corrigendum: Dynamic nuclear magnetic resonance field sensing with part-per-trillion resolution
Authors: Gross Simon , Barmet Christoph , Dietrich Benjamin E. , Brunner David O. , Schmid Thomas , Pruessmann Klaas P.
Published: February 2017

Nature Communications 7 Article number:13702 (2016); Published 2 December 2016; Updated 27 February 2017 The financial support for this Article was not fully acknowledged. The acknowledgements should have included the following: The authors acknowledge Nano-Tera.ch for financial support.
Pressure-induced superconductivity in the three-dimensional topological Dirac semimetal Cd3As2
Authors: He Lanpo , Jia Yating , Zhang Sijia , Hong Xiaochen , Jin Changqing , Li Shiyan
Published: February 2017

The recently discovered Dirac and Weyl semimetals are new members of topological materials. Starting from them, topological superconductivity may be achieved, e.g., by carrier doping or applying pressure. Here we report high-pressure resistance and X-ray diffraction study of the three-dimensional topological Dirac semimetal Cd3As2. Superconductivity with Tc≈2.0 K is observed at 8.5 GPa. The Tc keeps increasing to about 4.0 K at 21.3 GPa, then shows a nearly constant pressure dependence up to the highest pressure 50.9 GPa. The X-ray diffraction measurements reveal a structure phase transition around 3.5 GPa. Our observation of superconductivity in pressurised topological Dirac semimetal Cd3As2 provides a new candidate for topological superconductor, as argued in a recent point contact study and a theoretical work.
Biofilm disruption by an air bubble reveals heterogeneous age-dependent detachment patterns dictated by initial extracellular matrix distribution
Authors: Jang Hongchul , Rusconi Roberto , Stocker Roman
Published: February 2017

Bacteria often adhere to surfaces, where they form communities known as biofilms. Recently, it has been shown that biofilm formation initiates with the microscopically heterogeneous deposition of a skeleton of extracellular polymeric substances (EPS) by individual cells crawling on the surface, followed by growth of the biofilm into a surface-covering continuum. Here we report microfluidic experiments with Pseudomonas aeruginosa biofilms showing that their “hidden” heterogeneity can affect the later dynamics of their disruption. Using controlled air bubbles as a model for mechanical insult, we demonstrate that biofilm disruption is strongly dependent on biofilm age, and that disruption to early-stage biofilms can take the shape of a semi-regular pattern of ~15 µm diameter holes from which bacteria have been removed. We explain hole formation in terms of the rupture and retreat of the thin liquid layer created by the long bubble, which scrapes bacteria off the surface and rearranges their distribution. We find that the resulting pattern correlates with the spatial distribution of EPS: holes form where there is less EPS, whereas regions with more EPS act as strongholds against the scraping liquid front. These results show that heterogeneity in the microscale EPS skeleton of biofilms has profound consequences for later dynamics, including disruption. Because few attached cells suffice to regrow a biofilm, these results point to the importance of considering microscale heterogeneity when designing and assessing the effectiveness of biofilm removal strategies by mechanical forces.
The protein tyrosine phosphatase 1B inhibitor MSI-1436 stimulates regeneration of heart and multiple other tissues
Authors: Smith Ashley M. , Maguire-Nguyen Katie K. , Rando Thomas A. , Zasloff Michael A. , Strange Kevin B. , Yin Viravuth P.
Published: February 2017

Regenerative medicine holds substantial promise for repairing or replacing tissues and organs damaged by disease, injury, and degeneration. Much of the field has focused on development of cell-based therapeutics, gene-based therapeutics, and tissue engineering-based therapeutics. In contrast, development of small molecule regenerative medicine therapies is an emerging area. Using the adult zebrafish as a novel screening platform, we identified MSI-1436 as a first-in-class regenerative medicine drug candidate. MSI-1436 is a naturally occurring aminosterol that inhibits protein tyrosine phosphatase 1B. Treatment of adult zebrafish by intraperitoneal injection of MSI-1436 increased the rate of regeneration of the amputated caudal fin, which is comprised of bone, connective, skin, vascular and nervous tissues and also increased the rate of adult zebrafish heart regeneration. Intraperitoneal administration of MSI-1436 to adult mice for 4 weeks after induction of myocardial infarction increased survival, improved heart function, reduced infarct size, reduced ventricular wall thinning and increased cardiomyocyte proliferation. Satellite cell activation in injured mouse skeletal muscle was stimulated by MSI-1436. MSI-1436 was well tolerated by patients in Phase 1 and 1b obesity and type 2 diabetes clinical trials. Doses effective at stimulating regeneration are 5–50-times lower than the maximum well tolerated human dose. The demonstrated safety and well established pharmacological properties of MSI-1436 underscore the potential of this molecule as a novel treatment for heart attack and multiple other degenerative diseases.
On the performance of de novo pathway enrichment
Authors: Batra Richa , Alcaraz Nicolas , Gitzhofer Kevin , Pauling Josch , Ditzel Henrik J. , Hellmuth Marc , Baumbach Jan , List Markus
Published: February 2017

De novo pathway enrichment is a powerful approach to discover previously uncharacterized molecular mechanisms in addition to already known pathways. To achieve this, condition-specific functional modules are extracted from large interaction networks. Here, we give an overview of the state of the art and present the first framework for assessing the performance of existing methods. We identified 19 tools and selected seven representative candidates for a comparative analysis with more than 12,000 runs, spanning different biological networks, molecular profiles, and parameters. Our results show that none of the methods consistently outperforms the others. To mitigate this issue for biomedical researchers, we provide guidelines to choose the appropriate tool for a given dataset. Moreover, our framework is the first attempt for a quantitative evaluation of de novo methods, which will allow the bioinformatics community to objectively compare future tools against the state of the art.
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

Non-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

Human 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

In 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

The 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

Wood 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

Radiation-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

It 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

The 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

It 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

The 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

Two 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.
Erratum: Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia
Authors: Stuchlý Jan , Kanderová Veronika , Vlková Marcela , Heřmanová Ivana , Slámová Lucie , Pelák Ondřej , Taraldsrud Eli , Jílek Dalibor , Králíčková Pavlína , Fevang Børre , Trková Marie , Hrušák Ondřej , Froňková Eva , Šedivá Anna , Litzman Jiří , Kalina Tomáš
Published: February 2017

Scientific Reports 7: Article number: 39710; published online: 05 January 2017; updated: 27 February 2017. The original version of this Article contained errors in the Abstract. “The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, naïve CD4+ and CD27− CD28+ over three years.
Correction: Corrigendum: Residue Geometry Networks: A Rigidity-Based Approach to the Amino Acid Network and Evolutionary Rate Analysis
Authors: Fokas Alexander S. , Cole Daniel J. , Ahnert Sebastian E. , Chin Alex W.
Published: February 2017

Scientific Reports 6: Article number: 33213; published online: 14 September 2016; updated: 27 February 2017. In this Article, the legend of Figure 6 is incorrect: A portion of the RGN of GGPPS is shown, displaying interactions made by coloured nodes. It can be seen that G157 interacts with only two residues (low degree).
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

Casein 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

Understanding 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

To 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

Remnants 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.
Nonsteroidal anti-inflammatory drugs modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways
Authors: Mozolewski Paweł , Moskot Marta , Jakóbkiewicz-Banecka Joanna , Węgrzyn Grzegorz , Bocheńska Katarzyna , Banecki Bogdan , Gabig-Cimińska Magdalena
Published: February 2017

In this report, selected non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin and nimesulide, and analgesics acetaminophen, alone, as well as in combination with isoflavone genistein as potential glycosaminoglycan (GAG) metabolism modulators were considered for the treatment of mucopolysaccharidoses (MPSs) with neurological symptoms due to the effective blood-brain barrier (BBB) penetration properties of these compounds. We found that indomethacin and nimesulide, but not acetaminophen, inhibited GAG synthesis in fibroblasts significantly, while the most pronounced impairment of glycosaminoglycan production was observed after exposure to the mixture of nimesulide and genistein. Phosphorylation of the EGF receptor (EGFR) was inhibited even more effective in the presence of indomethacin and nimesulide than in the presence of genistein. When examined the activity of phosphatidylinositol-3-kinase (PI3K) production, we observed its most significant decrease in the case of fibroblast exposition to nimesulide, and afterwards to indomethacin and genistein mix, rather than indomethacin used alone. Some effects on expression of individual GAG metabolism-related and lysosomal function genes, and significant activity modulation of a number of genes involved in intracellular signal transduction pathways and metabolism of DNA and proteins were detected. This study documents that NSAIDs, and their mixtures with genistein modulate cellular glycosaminoglycan synthesis by affecting EGFR and PI3K signaling pathways.
miR-21 deficiency inhibits osteoclast function and prevents bone loss in mice
Authors: Hu Cheng-Hu , Sui Bing-Dong , Du Fang-Ying , Shuai Yi , Zheng Chen-Xi , Zhao Pan , Yu Xiao-Rui , Jin Yan
Published: February 2017

MicroRNAs emerge as critical post-transcriptional regulators in bone metabolism. We have previously reported in vitro that miR-21 promotes osteogenesis, while studies have also revealed miR-21 as a regulator of osteoclastogenesis and a promoter of osteoclast differentiation in vitro. However, in vivo data are still lacking in identifying skeletal function of miR-21, particularly its effects on osteoporosis. Here, using miR-21 knockout (miR-21−/−) mice, we investigated effects of miR-21 on bone development, bone remodeling and bone loss. Unexpectedly, miR-21−/− mice demonstrated normal skeletal phenotype in development and maintained osteoblastogenesis in vivo. Besides, miR-21−/− mice showed increased receptor activator of nuclear factor κB ligand (RANKL) and decreased osteoprotegerin (OPG) through miR-21 targeting Sprouty 1 (Spry1). Nevertheless, interestingly, miR-21 deficiency promoted trabecular bone mass accrual physiologically. Furthermore, in pathological states, the protection of bone mass was prominent in miR-21−/− mice. These skeletal effects were attributed to inhibition of bone resorption and osteoclast function by miR-21 deficiency through miR-21 targeting programmed cell death 4 (PDCD4), despite the existence of RANKL. As far as we know, this is the first in vivo evidence of a pro-osteoclastic microRNA. Together, these findings clarified function of miR-21 in bone metabolism, particularly uncovering osteo-protective potential of miR-21 inactivation in osteoporosis.
Mammalian TRAPPIII Complex positively modulates the recruitment of Sec13/31 onto COPII vesicles
Authors: Zhao Shan , Li Chun Man , Luo Xiao Min , Siu Gavin Ka Yu , Gan Wen Jia , Zhang Lin , Wu William K. K. , Chan Hsiao Chang , Yu Sidney
Published: February 2017

The Transport protein particle (TRAPP) complex is a tethering factor for COPII vesicle. Of three forms of TRAPP (TRAPPI, II and III) complexes identified so far, TRAPPIII has been largely considered to play a role in autophagy. While depletion of TRAPPIII specific subunits caused defects in the early secretory pathway and TRAPPIII might interact with components of the COPII vesicle coat, its exact role remains to be determined. In this study, we studied the function of TRAPPIII in early secretory pathway using a TRAPPIII-specific subunit, TRAPPC12, as starting point. We found that TRAPPC12 was localized to the ER exit sites and ERGIC. In cells deleted with TRAPPC12, ERGIC and to a lesser extent, the Golgi became dispersed. ER-to-Golgi transport was also delayed. TRAPPC12, but not TRAPPC8, bound to Sec13/Sec31A tetramer but each Sec protein alone could not interact with TRAPPC12. TRAPPIII positively modulated the assembly of COPII outer layer during COPII vesicle formation. These results identified a novel function of TRAPPIII as a positive modulator of the outer layer of the COPII coat.
Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models
Authors: Lee Peter , Calvo Conrado J. , Alfonso-Almazán José M. , Quintanilla Jorge G. , Chorro Francisco J. , Yan Ping , Loew Leslie M. , Filgueiras-Rama David , Millet José
Published: February 2017

Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost optical mapping systems for panoramic imaging using Langendorff-perfused pig hearts, a clinically-relevant model in basic research and bioengineering. By significantly lowering financial thresholds, this powerful cardiac electrophysiology imaging modality may gain wider use in research and, even, teaching laboratories, which we substantiated using the lower-cost Langendorff-perfused rabbit heart model.
Coherent activity between brain regions that code for value is linked to the malleability of human behavior
Authors: Cooper Nicole , Bassett Danielle S. , Falk Emily B.
Published: February 2017

Brain activity in medial prefrontal cortex (MPFC) during exposure to persuasive messages can predict health behavior change. This brain-behavior relationship has been linked to areas of MPFC previously associated with self-related processing; however, the mechanism underlying this relationship is unclear. We explore two components of self-related processing – self-reflection and subjective valuation – and examine coherent activity between relevant networks of brain regions during exposure to health messages encouraging exercise and discouraging sedentary behaviors. We find that objectively logged reductions in sedentary behavior in the following month are linked to functional connectivity within brain regions associated with positive valuation, but not within regions associated with self-reflection on personality traits. Furthermore, functional connectivity between valuation regions contributes additional information compared to average brain activation within single brain regions. These data support an account in which MPFC integrates the value of messages to the self during persuasive health messaging and speak to broader questions of how humans make decisions about how to behave.
Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy
Authors: Leal-Campanario Rocio , Alarcon-Martinez Luis , Rieiro Hector , Martinez-Conde Susana , Alarcon-Martinez Tugba , Zhao Xiuli , LaMee Jonathan , Popp Pamela J. Osborn , Calhoun Michael E. , Arribas Juan I. , Schlegel Alexander A. , Stasi Leandro L. Di , Rho Jong M. , Inge Landon , Otero-Millan Jorge , Treiman David M. , Macknik Stephen L.
Published: February 2017

Seizure-driven brain damage in epilepsy accumulates over time, especially in the hippocampus, which can lead to sclerosis, cognitive decline, and death. Excitotoxicity is the prevalent model to explain ictal neurodegeneration. Current labeling technologies cannot distinguish between excitotoxicity and hypoxia, however, because they share common molecular mechanisms. This leaves open the possibility that undetected ischemic hypoxia, due to ictal blood flow restriction, could contribute to neurodegeneration previously ascribed to excitotoxicity. We tested this possibility with Confocal Laser Endomicroscopy (CLE) and novel stereological analyses in several models of epileptic mice. We found a higher number and magnitude of NG2+ mural-cell mediated capillary constrictions in the hippocampus of epileptic mice than in that of normal mice, in addition to spatial coupling between capillary constrictions and oxidative stressed neurons and neurodegeneration. These results reveal a role for hypoxia driven by capillary blood flow restriction in ictal neurodegeneration.
Measuring speaker–listener neural coupling with functional near infrared spectroscopy
Authors: Liu Yichuan , Piazza Elise A. , Simony Erez , Shewokis Patricia A. , Onaral Banu , Hasson Uri , Ayaz Hasan
Published: February 2017

The present study investigates brain-to-brain coupling, defined as inter-subject correlations in the hemodynamic response, during natural verbal communication. We used functional near-infrared spectroscopy (fNIRS) to record brain activity of 3 speakers telling stories and 15 listeners comprehending audio recordings of these stories. Listeners’ brain activity was significantly correlated with speakers’ with a delay. This between-brain correlation disappeared when verbal communication failed. We further compared the fNIRS and functional Magnetic Resonance Imaging (fMRI) recordings of listeners comprehending the same story and found a significant relationship between the fNIRS oxygenated-hemoglobin concentration changes and the fMRI BOLD in brain areas associated with speech comprehension. This correlation between fNIRS and fMRI was only present when data from the same story were compared between the two modalities and vanished when data from different stories were compared; this cross-modality consistency further highlights the reliability of the spatiotemporal brain activation pattern as a measure of story comprehension. Our findings suggest that fNIRS can be used for investigating brain-to-brain coupling during verbal communication in natural settings.
Characterization of photocatalytic TiO2 powder under varied environments using near ambient pressure X-ray photoelectron spectroscopy
Authors: Krishnan Padmaja , Liu Minghui , Itty Pierre A. , Liu Zhi , Rheinheimer Vanessa , Zhang Min-Hong , Monteiro Paulo J. M. , Yu Liya E.
Published: February 2017

Consecutive eight study phases under the successive presence and absence of UV irradiation, water vapor, and oxygen were conducted to characterize surface changes in the photocatalytic TiO2 powder using near-ambient-pressure X-ray photoelectron spectroscopy (XPS). Both Ti 2p and O 1s spectra show hysteresis through the experimental course. Under all the study environments, the bridging hydroxyl (OHbr) and terminal hydroxyl (OHt) are identified at 1.1–1.3 eV and 2.1–2.3 eV above lattice oxygen, respectively. This enables novel and complementary approach to characterize reactivity of TiO2 powder. The dynamic behavior of surface-bound water molecules under each study environment is identified, while maintaining a constant distance of 1.3 eV from the position of water vapor. In the dark, the continual supply of both water vapor and oxygen is the key factor retaining the activated state of the TiO2 powder for a time period. Two new surface peaks at 1.7–1.8 and 4.0–4.2 eV above lattice oxygen are designated as peroxides (OOH/H2O2) and H2O2 dissolved in water, respectively. The persistent peroxides on the powder further explain previously observed prolonged oxidation capability of TiO2 powder without light irradiation.
A Fast and Efficient Algorithm for Mining Top-k Nodes in Complex Networks
Authors: Liu Dong , Jing Yun , Zhao Jing , Wang Wenjun , Song Guojie
Published: February 2017

One of the key problems in social network analysis is influence maximization, which has great significance both in theory and practical applications. Given a complex network and a positive integer k, and asks the k nodes to trigger the largest expected number of the remaining nodes. Many mature algorithms are mainly divided into propagation-based algorithms and topology- based algorithms. The propagation-based algorithms are based on optimization of influence spread process, so the influence spread of them significantly outperforms the topology-based algorithms. But these algorithms still takes days to complete on large networks. Contrary to propagation based algorithms, the topology-based algorithms are based on intuitive parameter statistics and static topology structure properties. Their running time are extremely short but the results of influence spread are unstable. In this paper, we propose a novel topology-based algorithm based on local index rank (LIR). The influence spread of our algorithm is close to the propagation-based algorithm and sometimes over them. Moreover, the running time of our algorithm is millions of times shorter than that of propagation-based algorithms. Our experimental results show that our algorithm has a good and stable performance in IC and LT model.
The enhanced photo absorption and carrier transportation of InGaN/GaN Quantum Wells for photodiode detector applications
Authors: Yang Haojun , Ma Ziguang , Jiang Yang , Wu Haiyan , Zuo Peng , Zhao Bin , Jia Haiqiang , Chen Hong
Published: February 2017

We have conducted a series of measurements of resonantly excited photoluminescence, photocurrent and photovoltage on InGaN/GaN quantum wells with and without a p-n junction under reverse bias condition. The results indicate that most of the resonantly excited photo-generated carriers are extracted from the quantum wells when a p-n junction exists, and the photon absorption of quantum wells is enhanced by the p-n junction. Additionally, the carrier extraction becomes more distinct under a reverse bias. Our finding brings better understanding of the physical characteristics of quantum wells with p-n junction, which also suggests that the quantum well is suitable for photodiode detectors applications when a p-n junction is used.