bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular serglycin upregulates the CD44 receptor in an autocrine manner to maintain self-renewal in nasopharyngeal carcinoma cells by reciprocally activating the MAPK/β-catenin axis
Authors: Chu Qiaoqiao , Huang Hongbing , Huang Tiejun , Cao Li , Peng Lixia , Shi Simei , Zheng Lisheng , Xu Liang , Zhang Shijun , Huang Jialing , Li Xinjian , Qian Chaonan , Huang Bijun
Published: November 2016

Serglycin is a proteoglycan that was first found to be secreted by hematopoietic cells. As an extracellular matrix (ECM) component, serglycin promotes nasopharyngeal carcinoma (NPC) metastasis and serves as an independent, unfavorable NPC prognostic indicator. The detailed mechanism underlying the roles of serglycin in cancer progression remains to be clarified. Here, we report that serglycin knockdown in NPC cells inhibited cell sphere formation and tumor seeding abilities. Serglycin downregulation enhanced high-metastasis NPC cell sensitivity to chemotherapy. It has been reported that serglycin is a novel ligand for the stem cell marker CD44. Interestingly, we found a positive correlation between serglycin expression and CD44 in nasopharyngeal tissues and NPC cell lines. Further study revealed that CD44 was an ERK-dependent downstream effector of serglycin signaling, and serglycin activated the MAPK/β-catenin axis to induce CD44 receptor expression in a positive feedback loop. Taken together, our novel findings suggest that ECM serglycin upregulated CD44 receptor expression to maintain NPC stemness by interacting with CD44 and activating the MAPK/β-catenin pathway, resulting in NPC cell chemoresistance. These findings suggest that the intervention of serglycin/CD44 axis and downstream signaling pathway is a rational strategy for targeting NPC cancer stem cell therapy.
The V-ATPase a2 isoform controls mammary gland development through Notch and TGF-β signaling
Authors: Pamarthy Sahithi , Mao Liquin , Katara Gajendra K , Fleetwood Sara , Kulshreshta Arpita , Gilman-Sachs Alice , Beaman Kenneth D
Published: November 2016

Among all tissues and organs, the mammary gland is unique because most of its development occurs in adulthood. Notch signaling has a major role in mammary gland development and has been implicated in breast cancer. The vacuolar-ATPase (V-ATPase) is a proton pump responsible for the regulation and control of pH in intracellular vesicles and the extracellular milieu. We have previously reported that a2V-ATPase (a2V), an isoform of ‘a’ subunit of V-ATPase, regulates processing of Notch receptor and alters Notch signaling in breast cancer. To study the role of a2V in mammary gland development, we generated an a2V-KO model (conditional mammary knockout a2V mouse strain). During normal mammary gland development, the basal level expression of a2V increased from puberty, virginity, and pregnancy through the lactation stage and then decreased during involution. Litters of a2V-KO mice weighed significantly less when compared with litters from wild-type mice and showed reduced expression of the lactation marker β-casein. Whole-mount analysis of mammary glands demonstrated impaired ductal elongation and bifurcation in a2V-KO mice. Consequently, we found disintegrated mammary epithelium as seen by basal and luminal epithelial staining, although the rate of proliferation remained unchanged. Delayed mammary morphogenesis in a2V-KO mice was associated with aberrant activation of Notch and TGF-β (transforming growth factor-β) pathways. Notably, Hey1 (hairy/enhancer-of-split related with YRPW motif) and Smad2, the key downstream mediators of Notch and TGF-β pathways, respectively, were upregulated in a2V-KO mice and also in human mammary epithelial cells treated with a2V siRNA. Taken together, our results show that a2V deficiency disrupts the endolysosomal route in Notch and TGF signaling, thereby impairing mammary gland development. Our findings have broader implications in developmental and oncogenic cellular environments where V-ATPase, Notch and TGF-β are crucial for cell survival.
Vascular endothelial growth factor promotes the activation of hepatic stellate cells in chronic schistosomiasis
Authors: Luo Jie , Liang Yuejin , Kong Fanping , Qiu Jingfan , Liu Xinjian , Chen Ailing , Luxon Bruce A , Wu Hannah W , Wang Yong
Published: November 2016

The activation of hepatic stellate cells (HSCs) is a key event in fibrotic pathogenesis. However, the mechanism involving activation of HSCs in chronic schistosomiasis is not entirely clear. Human HSC LX‐2 and human umbilical vein endothelial cells (ECs) were cultured with Schistosoma japonicum antigens (SA) in vitro. Fibrosis‐associated genes and cell proliferation were analyzed. HSCs were isolated from mice of chronic schistosomiasis with or without praziquantel (PZQ) treatment, followed by the microarray analysis for the liver fibrosis‐associated pathways. Although SA inhibited the activation and proliferation of HSCs, it induced the EC proliferation and vascular endothelial growth factor‐a (VEGF) production. VEGF significantly increased the proliferation of HSCs and upregulated the expression of collagen and α‐smooth muscle actin. For in vivo study, we found that several fibrosis‐associated pathways were involved in the HSCs during the reversal of liver fibrosis caused by schistosomiasis, including VEGF, platelet‐derived growth factor, tumor necrosis factor and endothelin‐1 pathways. The Ingenuity Pathway Analysis showed that VEGF directly regulated several pro‐fibrotic and immune cytokine genes in HSCs, including integrin, fibronectin, interferon‐γ, interleukin (IL)‐6 and IL‐10. Our data indicated the critical role of VEGF signaling in HSC activation in chronic schistosomiasis and highlighted several promising genes and pathways in HSCs as potential targets for therapeutic treatment of liver fibrosis.
Integration and segregation of large-scale brain networks during short-term task automatization
Authors: Mohr Holger , Wolfensteller Uta , Betzel Richard F. , Mišić Bratislav , Sporns Olaf , Richiardi Jonas , Ruge Hannes
Published: November 2016

The human brain is organized into large-scale functional networks that can flexibly reconfigure their connectivity patterns, supporting both rapid adaptive control and long-term learning processes. However, it has remained unclear how short-term network dynamics support the rapid transformation of instructions into fluent behaviour. Comparing fMRI data of a learning sample (N=70) with a control sample (N=67), we find that increasingly efficient task processing during short-term practice is associated with a reorganization of large-scale network interactions. Practice-related efficiency gains are facilitated by enhanced coupling between the cingulo-opercular network and the dorsal attention network. Simultaneously, short-term task automatization is accompanied by decreasing activation of the fronto-parietal network, indicating a release of high-level cognitive control, and a segregation of the default mode network from task-related networks. These findings suggest that short-term task automatization is enabled by the brain’s ability to rapidly reconfigure its large-scale network organization involving complementary integration and segregation processes.
Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death
Authors: Thurston Teresa L. M. , Matthews Sophie A. , Jennings Elliott , Alix Eric , Shao Feng , Shenoy Avinash R. , Birrell Mark A. , Holden David W.
Published: November 2016

Sensing bacterial products in the cytosol of mammalian cells by NOD-like receptors leads to the activation of caspase-1 inflammasomes, and the production of the pro-inflammatory cytokines interleukin (IL)-18 and IL-1β. In addition, mouse caspase-11 (represented in humans by its orthologs, caspase-4 and caspase-5) detects cytosolic bacterial LPS directly. Activation of caspase-1 and caspase-11 initiates pyroptotic host cell death that releases potentially harmful bacteria from the nutrient-rich host cell cytosol into the extracellular environment. Here we use single cell analysis and time-lapse microscopy to identify a subpopulation of host cells, in which growth of cytosolic Salmonella Typhimurium is inhibited independently or prior to the onset of cell death. The enzymatic activities of caspase-1 and caspase-11 are required for growth inhibition in different cell types. Our results reveal that these proteases have important functions beyond the direct induction of pyroptosis and proinflammatory cytokine secretion in the control of growth and elimination of cytosolic bacteria.
DNA looping mediates nucleosome transfer
Authors: Brennan Lucy D. , Forties Robert A. , Patel Smita S. , Wang Michelle D.
Published: November 2016

Proper cell function requires preservation of the spatial organization of chromatin modifications. Maintenance of this epigenetic landscape necessitates the transfer of parental nucleosomes to newly replicated DNA, a process that is stringently regulated and intrinsically linked to replication fork dynamics. This creates a formidable setting from which to isolate the central mechanism of transfer. Here we utilized a minimal experimental system to track the fate of a single nucleosome following its displacement, and examined whether DNA mechanics itself, in the absence of any chaperones or assembly factors, may serve as a platform for the transfer process. We found that the nucleosome is passively transferred to available dsDNA as predicted by a simple physical model of DNA loop formation. These results demonstrate a fundamental role for DNA mechanics in mediating nucleosome transfer and preserving epigenetic integrity during replication.
Erratum: Comparative genomics reveals adaptive evolution of Asian tapeworm in switching to a new intermediate host
Authors: Wang Shuai , Wang Sen , Luo Yingfeng , Xiao Lihua , Luo Xuenong , Gao Shenghan , Dou Yongxi , Zhang Huangkai , Guo Aijiang , Meng Qingshu , Hou Junling , Zhang Bing , Zhang Shaohua , Yang Meng , Meng Xuelian , Mei Hailiang , Li Hui , He Zilong , Zhu Xueliang , Tan Xinyu , Zhu Xing-quan , Yu Jun , Cai Jianping , Zhu Guan , Hu Songnian , Cai Xuepeng
Published: November 2016

Nature Communications 7:: Article number: 12485 (2016); Published: 22 September 2016; Updated: 3 November 2016 This Article contains errors in Fig. 3. In panel b, the axes are displaced relative to the data, and in panel c, the label ‘Species-specific GD’ in red should read ‘Species-specific GD (tandem)’.
First maintenance therapy for COPD in the UK between 2009 and 2012: a retrospective database analysis
Authors: Price David , Miravitlles Marc , Pavord Ian , Thomas Mike , Wedzicha Jadwiga , Haughney John , Bichel Katsiaryna , West Daniel
Published: November 2016

Clinical guidelines recommend long-acting bronchodilators as first maintenance therapy for chronic obstructive pulmonary disease (COPD), with inhaled corticosteroids (ICS) reserved for patients with more severe disease and exacerbations. The aim of this analysis was to examine real-life prescribing of first maintenance therapy for COPD in the UK. Data were extracted from the UK Optimum Patient Care Research Database for patients with a first prescription for COPD maintenance therapy between 2009 and 2012 and a diagnosis of COPD at or before the date of the first prescription for COPD maintenance therapy. Routine clinical data including demographics, disease history and symptoms, comorbidities, therapy, hospitalisation rate and exacerbation rate were collected and used to characterise patients stratified by disease severity and Global Initiative for Chronic Obstructive Lung Disease (GOLD) group (A–D). The analysis population included 2,217 individuals (55.4% male, 45.2% smokers). Long-acting muscarinic antagonists (LAMA) as monotherapy were prescribed as first maintenance therapy for 40.2% of patients. ICS were prescribed as ICS/long-acting beta-agonists combination for 29.1% of patients or as monotherapy for 15.5%. ICS (alone or in combination) were prescribed to >40% of patients in each GOLD group. ICS-containing regimens were prescribed to patients with a history of pneumonia and comorbid conditions for whom the risks of ICS therapy may outweigh the benefits. The clinical reality of prescribing indicates that ICS are often prescribed outside current guideline recommendations for many patients newly diagnosed with COPD in the UK. Encouragingly, LAMAs are increasingly being prescribed as first maintenance therapy for these patients.
The formation of the ocean’s anthropogenic carbon reservoir
Authors: Iudicone Daniele , Rodgers Keith B. , Plancherel Yves , Aumont Olivier , Ito Takamitsu , Key Robert M. , Madec Gurvan , Ishii Masao
Published: November 2016

The shallow overturning circulation of the oceans transports heat from the tropics to the mid-latitudes. This overturning also influences the uptake and storage of anthropogenic carbon (Cant). We demonstrate this by quantifying the relative importance of ocean thermodynamics, circulation and biogeochemistry in a global biochemistry and circulation model. Almost 2/3 of the Cant ocean uptake enters via gas exchange in waters that are lighter than the base of the ventilated thermocline. However, almost 2/3 of the excess Cant is stored below the thermocline. Our analysis shows that subtropical waters are a dominant component in the formation of subpolar waters and that these water masses essentially form a common Cant reservoir. This new method developed and presented here is intrinsically Lagrangian, as it by construction only considers the velocity or transport of waters across isopycnals. More generally, our approach provides an integral framework for linking ocean thermodynamics with biogeochemistry.
Molecular Characterization of A Novel Effector Expansin-like Protein from Heterodera avenae that Induces Cell Death in Nicotiana benthamiana
Authors: Liu Jing , Peng Huan , Cui Jiangkuan , Huang Wenkun , Kong Lingan , Clarke Jihong Liu , Jian Heng , Wang Guo Liang , Peng Deliang
Published: November 2016

Cereal cyst nematodes are sedentary biotrophic endoparasites that maintain a complex interaction with their host plants. Nematode effector proteins are synthesized in the oesophageal glands and are secreted into plant tissues through the stylet. To understand the function of nematode effectors in parasitic plants, we cloned predicted effectors genes from Heterodera avenae and transiently expressed them in Nicotiana benthamiana. Infiltration assays showed that HaEXPB2, a predicted expansin-like protein, caused cell death in N. benthamiana. In situ hybridization showed that HaEXPB2 transcripts were localised within the subventral gland cells of the pre-parasitic second-stage nematode. HaEXPB2 had the highest expression levels in parasitic second-stage juveniles. Subcellular localization assays revealed that HaEXPB2 could be localized in the plant cell wall after H. avenae infection.This The cell wall localization was likely affected by its N-terminal and C-terminal regions. In addition, we found that HaEXPB2 bound to cellulose and its carbohydrate-binding domain was required for this binding. The infectivity of H. avenae was significantly reduced when HaEXPB2 was knocked down by RNA interference in vitro. This study indicates that HaEXPB2 may play an important role in the parasitism of H. avenae through targeting the host cell wall.
Future C loss in mid-latitude mineral soils: climate change exceeds land use mitigation potential in France
Authors: Meersmans Jeroen , Arrouays Dominique , Van Rompaey Anton J. J. , Pagé Christian , De Baets Sarah , Quine Timothy A.
Published: November 2016

Many studies have highlighted significant interactions between soil C reservoir dynamics and global climate and environmental change. However, in order to estimate the future soil organic carbon sequestration potential and related ecosystem services well, more spatially detailed predictions are needed. The present study made detailed predictions of future spatial evolution (at 250 m resolution) of topsoil SOC driven by climate change and land use change for France up to the year 2100 by taking interactions between climate, land use and soil type into account. We conclude that climate change will have a much bigger influence on future SOC losses in mid-latitude mineral soils than land use change dynamics. Hence, reducing CO2 emissions will be crucial to prevent further loss of carbon from our soils.
An improved d-band model of the catalytic activity of magnetic transition metal surfaces
Authors: Bhattacharjee Satadeep , Waghmare Umesh V. , Lee Seung-Cheol
Published: November 2016

The d-band center model of Hammer and Nørskov is widely used in understanding and predicting catalytic activity on transition metal (TM) surfaces. Here, we demonstrate that this model is inadequate for capturing the complete catalytic activity of the magnetically polarized TM surfaces and propose its generalization. We validate the generalized model through comparison of adsorption energies of the NH3 molecule on the surfaces of 3d TMs (V, Cr, Mn, Fe, Co, Ni, Cu and Zn) determined with spin-polarized density functional theory (DFT)-based methods with the predictions of our model. Compared to the conventional d-band model, where the nature of the metal-adsorbate interaction is entirely determined through the energy and the occupation of the d-band center, we emphasize that for the surfaces with high spin polarization, the metal-adsorbate system can be stabilized through a competition of the spin-dependent metal-adsorbate interactions.
Analysis of codon usage patterns in Ginkgo biloba reveals codon usage tendency from A/U-ending to G/C-ending
Authors: He Bing , Dong Hui , Jiang Cong , Cao Fuliang , Tao Shentong , Xu Li-an
Published: November 2016

As one of the most ancient tree species, the codon usage pattern analysis of Ginkgo biloba is a useful way to understand its evolutionary and genetic mechanisms. Several studies have been conducted on angiosperms, but seldom on gymnosperms. Based on RNA-Seq data of the G. biloba transcriptome, amount to 17,579 unigenes longer than 300 bp were selected and analyzed from 68,547 candidates. The codon usage pattern tended towards more frequently use of A/U-ending codons, which showed an obvious gradient progressing from gymnosperms to dicots to monocots. Meanwhile, analysis of high/low-expression unigenes revealed that high-expression unigenes tended to use G/C-ending codons together with more codon usage bias. Variation of unigenes with different functions suggested that unigenes involving in environment adaptation use G/C-ending codons more frequently with more usage bias, and these results were consistent with the conclusion that the formation of G. biloba codon usage bias was dominated by natural selection.
β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces
Authors: Brown James W. P. , Buell Alexander K. , Michaels Thomas C. T. , Meisl Georg , Carozza Jacqueline , Flagmeier Patrick , Vendruscolo Michele , Knowles Tuomas P. J. , Dobson Christopher M. , Galvagnion Céline
Published: November 2016

α-Synuclein is an intrinsically disordered protein that is associated with the pathogenesis of Parkinson’s disease through the processes involved in the formation of amyloid fibrils. α and β-synuclein are homologous proteins found at comparable levels in presynaptic terminals but β-synuclein has a greatly reduced propensity to aggregate and indeed has been found to inhibit α-synuclein aggregation. In this paper, we describe how sequence differences between α- and β-synuclein affect individual microscopic processes in amyloid formation. In particular, we show that β-synuclein strongly suppresses both lipid-induced aggregation and secondary nucleation of α-synuclein by competing for binding sites at the surfaces of lipid vesicles and fibrils, respectively. These results suggest that β-synuclein can act as a natural inhibitor of α-synuclein aggregation by reducing both the initiation of its self-assembly and the proliferation of its aggregates.
C2-domain mediated nano-cluster formation increases calcium signaling efficiency
Authors: Bonny Mike , Hui Xin , Schweizer Julia , Kaestner Lars , Zeug André , Kruse Karsten , Lipp Peter
Published: November 2016

Conventional protein kinase Cs (cPKCs) are key signaling proteins for transducing intracellular Ca2+ signals into downstream phosphorylation events. However, the lifetime of individual membrane-bound activated cPKCs is an order of magnitude shorter than the average time needed for target-protein phosphorylation. Here, we employed intermolecular Förster resonance energy transfer (FRET) in living cells combined with computational analysis to study the spatial organization of cPKCs bound to the plasma membrane. We discovered Ca2+-dependent cPKC nano-clusters that significantly extend cPKC’s plasma-membrane residence time. These protein patterns resulted from self-assembly mediated by Ca2+-binding C2-domains, which are widely used for membrane-targeting of Ca2+-sensing proteins. We also established clustering of other unrelated C2-domain containing proteins, suggesting that nano-cluster formation is a key step for efficient cellular Ca2+-signaling.
Human vision is determined based on information theory
Authors: Delgado-Bonal Alfonso , Martín-Torres Javier
Published: November 2016

It is commonly accepted that the evolution of the human eye has been driven by the maximum intensity of the radiation emitted by the Sun. However, the interpretation of the surrounding environment is constrained not only by the amount of energy received but also by the information content of the radiation. Information is related to entropy rather than energy. The human brain follows Bayesian statistical inference for the interpretation of visual space. The maximization of information occurs in the process of maximizing the entropy. Here, we show that the photopic and scotopic vision absorption peaks in humans are determined not only by the intensity but also by the entropy of radiation. We suggest that through the course of evolution, the human eye has not adapted only to the maximum intensity or to the maximum information but to the optimal wavelength for obtaining information. On Earth, the optimal wavelengths for photopic and scotopic vision are 555 nm and 508 nm, respectively, as inferred experimentally. These optimal wavelengths are determined by the temperature of the star (in this case, the Sun) and by the atmospheric composition.
Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions
Authors: Hebecker Betty , Vlaic Sebastian , Conrad Theresia , Bauer Michael , Brunke Sascha , Kapitan Mario , Linde Jörg , Hube Bernhard , Jacobsen Ilse D.
Published: November 2016

Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses.
Think global, act local: Preserving the global commons
Authors: Hauser Oliver P. , Hendriks Achim , Rand David G. , Nowak Martin A.
Published: November 2016

Preserving global public goods, such as the planet’s ecosystem, depends on large-scale cooperation, which is difficult to achieve because the standard reciprocity mechanisms weaken in large groups. Here we demonstrate a method by which reciprocity can maintain cooperation in a large-scale public goods game (PGG). In a first experiment, participants in groups of on average 39 people play one round of a Prisoner’s Dilemma (PD) with their two nearest neighbours on a cyclic network after each PGG round. We observe that people engage in “local-to-global” reciprocity, leveraging local interactions to enforce global cooperation: Participants reduce PD cooperation with neighbours who contribute little in the PGG. In response, low PGG contributors increase their contributions if both neighbours defect in the PD. In a control condition, participants do not know their neighbours’ PGG contribution and thus cannot link play in the PD to the PGG. In the control we observe a sharp decline of cooperation in the PGG, while in the treatment condition global cooperation is maintained. In a second experiment, we demonstrate the scalability of this effect: in a 1,000-person PGG, participants in the treatment condition successfully sustain public contributions. Our findings suggest that this simple “local-to-global” intervention facilitates large-scale cooperation.
Mitochondrial genomes and comparative genomics of Aphanomyces astaci and Aphanomyces invadans
Authors: Makkonen Jenny , Vesterbacka Arto , Martin Frank , Jussila Japo , Diéguez-Uribeondo Javier , Kortet Raine , Kokko Harri
Published: November 2016

The genus Aphanomyces (Saprolegniales, Oomycetes) includes species with a variety of ecologies from saprotrophs to plant and animal parasites. Two important species in this genus are A. astaci, the cause of crayfish plague and its close relative, A. invadans, which causes the epizootic ulcerative syndrome on fish. In this study, we have assembled and annotated the mitochondrial (mt) genomes of A. astaci and A. invadans from the whole genome shotgun sequence reads (PRJNA187372; PRJNA258292, respectively). The assembly was generated from A. astaci Pc-genotype strain APO3 and A. invadans strain NJM9701. The sizes of the mtDNAs were 49,489 bp and 49,061 bp for A. astaci and A. invadans, respectively. The species shared similar genetic content and organization encoding 35 proteins, two ribosomal RNAs, three putative open reading frames and 33 transfer RNAs of 19 amino acids for peptide synthesis. Both species also had a large inverted repeat region (LIR) of approximately 12 kb, the LIR contained large and small ribosomal RNAs and eight protein coding genes. These annotated mt genomes serve as a valuable genetic backbone for further development of diagnostic methods and phylogenetic and migration studies of the animal parasitic species of Aphanomyces.
Characterization of the starch-acting MaAmyB enzyme from Microbacterium aurum B8.A representing the novel subfamily GH13_42 with an unusual, multi-domain organization
Authors: Valk Vincent , van der Kaaij Rachel M. , Dijkhuizen Lubbert
Published: November 2016

The bacterium Microbacterium aurum strain B8.A degrades granular starches, using the multi-domain MaAmyA α-amylase to initiate granule degradation through pore formation. This paper reports the characterization of the M. aurum B8.A MaAmyB enzyme, a second starch-acting enzyme with multiple FNIII and CBM25 domains. MaAmyB was characterized as an α-glucan 1,4-α-maltohexaosidase with the ability to subsequently hydrolyze maltohexaose to maltose through the release of glucose. MaAmyB also displays exo-activity with a double blocked PNPG7 substrate, releasing PNP. In M. aurum B8.A, MaAmyB may contribute to degradation of starch granules by rapidly hydrolyzing the helical and linear starch chains that become exposed after pore formation by MaAmyA. Bioinformatics analysis showed that MaAmyB represents a novel GH13 subfamily, designated GH13_42, currently with 165 members, all in Gram-positive soil dwelling bacteria, mostly Streptomyces. All members have an unusually large catalytic domain (AB-regions), due to three insertions compared to established α-amylases, and an aberrant C-region, which has only 30% identity to established GH13 C-regions. Most GH13_42 members have three N-terminal domains (2 CBM25 and 1 FNIII). This is unusual as starch binding domains are commonly found at the C-termini of α-amylases. The evolution of the multi-domain M. aurum B8.A MaAmyA and MaAmyB enzymes is discussed.
Origin of multiple band gap values in single width nanoribbons
Authors: Deepika  , Kumar Shailesh , Shukla Alok , Kumar Rakesh
Published: November 2016

Deterministic band gap in quasi-one-dimensional nanoribbons is prerequisite for their integrated functionalities in high performance molecular-electronics based devices. However, multiple band gaps commonly observed in graphene nanoribbons of the same width, fabricated in same slot of experiments, remain unresolved, and raise a critical concern over scalable production of pristine and/or hetero-structure nanoribbons with deterministic properties and functionalities for plethora of applications. Here, we show that a modification in the depth of potential wells in the periodic direction of a supercell on relative shifting of passivating atoms at the edges is the origin of multiple band gap values in nanoribbons of the same width in a crystallographic orientation, although they carry practically the same ground state energy. The results are similar when calculations are extended from planar graphene to buckled silicene nanoribbons. Thus, the findings facilitate tuning of the electronic properties of quasi-one-dimensional materials such as bio-molecular chains, organic and inorganic nanoribbons by performing edge engineering.
Periodic protein adsorption at the gold/biotin aqueous solution interface: evidence of kinetics with time delay
Authors: Neff H. , Laborde H. M. , Lima A. M. N.
Published: November 2016

An oscillatory molecular adsorption pattern of the protein neutravidin from aqueous solution onto gold, in presence of a pre-deposited self assembled mono-molecular biotin film, is reported. Real time surface Plasmon resonance sensing was utilized for evaluation of the adsorption kinetics. Two different fractions were identified: in the initial phase, protein molecules attach irreversibly onto the Biotin ligands beneath towards the jamming limit, forming a neutravidin-biotin fraction. Afterwards, the growth rate exhibits distinct, albeit damped adsorption-desorption oscillations over an extended time span, assigned to a quasi reversibly bound fraction. These findings agree with, and firstly confirm a previously published model, proposing macro-molecular adsorption with time delay. The non-linear dynamic model is applicable to and also resembles non-damped oscillatory binding features of the hetero-catalytic oxidation of carbon monoxide molecules on platinum in the gas phase. An associated surface residence time can be linked to the dynamics and time scale required for self-organization.
Multi-phasic bi-directional chemotactic responses of the growth cone
Authors: Naoki Honda , Nishiyama Makoto , Togashi Kazunobu , Igarashi Yasunobu , Hong Kyonsoo , Ishii Shin
Published: November 2016

The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue. With biologically realistic sigmoidal dose-responses, our model predicted tri-phasic turning response depending on intracellular Ca2+ level, which was then experimentally confirmed by growth cone turning assays and Ca2+ imaging. Furthermore, we took a reverse-engineering analysis to identify balanced regulation between CaMKII (activator) and PP1 (inhibitor) and then the model performance was validated by reproducing turning assays with inhibitions of CaMKII and PP1. Thus, our study implies that the balance between activator and inhibitor underlies the multi-phasic bi-directional turning response of the growth cone.
Functional variants of the 5-methyltetrahydrofolate-homocysteine methyltransferase gene significantly increase susceptibility to prostate cancer: Results from an ethnic Han Chinese population
Authors: Qu Yuan-Yuan , Zhou Shu-Xian , Zhang Xuan , Zhao Rui , Gu Cheng-Yuan , Chang Kun , Yang Xiao-Qun , Gan Hua-Lei , Dai Bo , Zhang Hai-Liang , Shi Guo-Hai , Zhu Yao , Ye Ding-Wei , Zhao Jian-Yuan
Published: November 2016

Aberrant DNA methylation has been implicated in prostate carcinogenesis. The one-carbon metabolism pathway and related metabolites determine cellular DNA methylation and thus is thought to play a pivotal role in PCa occurrence. This study aimed to investigate the contribution of genetic variants in one-carbon metabolism genes to prostate cancer (PCa) risk and the underlying biological mechanisms. In this hospital-based case-control study of 1817 PCa cases and 2026 cancer-free controls, we genotyped six polymorphisms in three one-carbon metabolism genes and assessed their association with the risk of PCa. We found two noncoding MTR variants, rs28372871 T > G and rs1131450 G > A, were independently associated with a significantly increased risk of PCa. The rs28372871 GG genotype (adjusted OR = 1.40, P = 0.004) and rs1131450 AA genotype (adjusted OR = 1.64, P = 0.007) exhibited 1.40-fold and 1.64-fold higher risk of PCa, respectively, compared with their respective homozygous wild-type genotypes. Further functional analyses revealed these two variants contribute to reducing MTR expression, elevating homocysteine and SAH levels, reducing methionine and SAM levels, increasing SAH/SAM ratio, and promoting the invasion of PCa cells in vitro. Collectively, our data suggest regulatory variants of the MTR gene significantly increase the PCa risk via decreasing methylation potential. These findings provide a novel molecular mechanism for the prostate carcinogenesis.
Faster poleward range shifts in moths with more variable colour patterns
Authors: Forsman Anders , Betzholtz Per-Eric , Franzén Markus
Published: November 2016

Range shifts have been documented in many organisms, and climate change has been implicated as a contributing driver of latitudinal and altitudinal range modifications. However, little is known about what species trait(s) allow for faster environmental tracking and improved capacity for distribution expansions. We used data for 416 species of moths, and show that range limits in Sweden have shifted to the north by on average 52.4 km per decade between 1973 and 2014. When also including non-expanding species, average expansion rate was 23.2 km per decade. The rate of boundary shifts increased with increasing levels of inter-individual variation in colour patterns and decreased with increasing latitude. The association with colour patterns indicate that variation in this functionally important trait enables species to cope with novel and changing conditions. Northern range limits also increased with average abundance and decreased with increasing year-to-year abundance fluctuations, implicating production of dispersers as a driver of range dynamics. Studies of terrestrial animals show that rates of poleward shifts differ between taxonomic groups, increase over time, and depend on study duration and latitude. Knowledge of how distribution shifts change with time, location, and species characteristics may improve projections of responses to climate change and aid the protection of biodiversity.
Decoding of top-down cognitive processing for SSVEP-controlled BMI
Authors: Min Byoung-Kyong , Dähne Sven , Ahn Min-Hee , Noh Yung-Kyun , Müller Klaus-Robert
Published: November 2016

We present a fast and accurate non-invasive brain-machine interface (BMI) based on demodulating steady-state visual evoked potentials (SSVEPs) in electroencephalography (EEG). Our study reports an SSVEP-BMI that, for the first time, decodes primarily based ontop-downand notbottom-upvisual information processing. The experimental setup presents a grid-shaped flickering line array that the participants observe while intentionally attending to a subset of flickering lines representing the shape of a letter. While the flickering pixels stimulate the participant’s visual cortex uniformly with equal probability, the participant’s intention groups the strokes and thus perceives a ‘letter Gestalt’. We observed decoding accuracy of 35.81% (up to 65.83%) with a regularized linear discriminant analysis; on average 2.05-fold, and up to 3.77-fold greater than chance levels in multi-class classification. Compared to the EEG signals, an electrooculogram (EOG) did not significantly contribute to decoding accuracies. Further analysis reveals that the top-down SSVEP paradigm shows the most focalised activation pattern around occipital visual areas; Granger causality analysis consistently revealed prefrontal top-down control over early visual processing. Taken together, the present paradigm provides the first neurophysiological evidence for the top-down SSVEP BMI paradigm, which potentially enables multi-class intentional control of EEG-BMIs without using gaze-shifting.
Assessing the effectiveness of problem-based learning in physical diagnostics education in China: a meta-analysis
Authors: Wang Jianmiao , Xu Yongjian , Liu Xiansheng , Xiong Weining , Xie Jungang , Zhao Jianping
Published: November 2016

Problem-based learning (PBL) has been extensively applied as an experimental educational method in Chinese medical schools over the past decade. A meta-analysis was performed to assess the effectiveness of PBL on students’ learning outcomes in physical diagnostics education. Related databases were searched for eligible studies evaluating the effects of PBL compared to traditional teaching on students’ knowledge and/or skill scores of physical diagnostics. Standardized mean difference (SMD) with 95% confidence interval (CI) was estimated. Thirteen studies with a total of 2086 medical students were included in this meta-analysis. All of these studies provided usable data on knowledge scores, and the pooled analysis showed a significant difference in favor of PBL compared to the traditional teaching (SMD = 0.76, 95%CI = 0.33–1.19). Ten studies provided usable data on skill scores, and a significant difference in favor of PBL was also observed (SMD = 1.46, 95%CI = 0.89–2.02). Statistically similar results were obtained in the sensitivity analysis, and there was no significant evidence of publication bias. These results suggested that PBL in physical diagnostics education in China appeared to be more effective than traditional teaching method in improving knowledge and skills.
Past climate changes facilitated homoploid speciation in three mountain spiny fescues (Festuca, Poaceae)
Authors: Marques I. , Draper D. , López-Herranz M. L. , Garnatje T. , Segarra-Moragues J. G. , Catalán P.
Published: November 2016

Apart from the overwhelming cases of allopolyploidization, the impact of speciation through homoploid hybridization is becoming more relevant than previously thought. Much less is known, however, about the impact of climate changes as a driven factor of speciation. To investigate these issues, we selected Festuca picoeuropeana, an hypothetical natural hybrid between the diploid species F. eskia and F. gautieri that occurs in two different mountain ranges (Cantabrian Mountains and Pyrenees) separated by more than 400 km. To unravel the outcomes of this mode of speciation and the impact of climate during speciation we used a multidisciplinary approach combining genome size and chromosome counts, data from an extensive nuclear genotypic analysis, plastid sequences and ecological niche models (ENM). Our results show that the same homoploid hybrid was originated independently in the two mountain ranges, being currently isolated from both parents and producing viable seeds. Parental species had the opportunity to contact as early as 21000 years ago although niche divergence occurs nowadays as result of a climate-driven shift. A high degree of niche divergence was observed between the hybrid and its parents and no recent introgression or backcrossed hybrids were detected, supporting the current presence of reproductive isolation barriers between these species.
Nanostructured MoS2/BiVO4 Composites for Energy Storage Applications
Authors: Arora Yukti , Shah Amit P. , Battu Shateesh , Maliakkal Carina B. , Haram Santosh , Bhattacharya Arnab , Khushalani Deepa
Published: November 2016

We report the optimized synthesis and electrochemical characterization of a composite of few-layered nanostructured MoS2 along with an electroactive metal oxide BiVO4. In comparison to pristine BiVO4, and a composite of graphene/BiVO4, the MoS2/BiVO4 nanocomposite provides impressive values of charge storage with longer discharge times and improved cycling stability. Specific capacitance values of 610 Fg−1 (170 mAhg−1) at 1 Ag−1 and 166 Fg−1 (46 mAhg−1) at 10 Ag−1 were obtained for just 2.5 wt% MoS2 loaded BiVO4. The results suggest that the explicitly synthesized small lateral-dimensioned MoS2 particles provide a notable capacitive component that helps augment the specific capacitance. We discuss the optimized synthesis of monoclinic BiVO4, and few-layered nanostructured MoS2. We report the discharge capacities and cycling performance of the MoS2/BiVO4 nanocomposite using an aqueous electrolyte. The data obtained shows the MoS2/BiVO4 nanocomposite to be a promising candidate for supercapacitor energy storage applications.
Giant Gyroid and Templates from High-Molecular-Weight Block Copolymer Self-assembly
Authors: Park Sungmin , Kim Yeongsik , Ahn Hyungju , Kim Jong Hak , Yoo Pil J. , Ryu Du Yeol
Published: November 2016

We present a feasible approach to the direct development of three-dimensionally (3D) bicontinuous gyroid (GYR) nanostructure in high-molecular-weight, composition-controlled polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) films. The use of a neutral solvent vapor to elaborately control the swelling of block copolymer (BCP) films is essential to generate a direct pathway to GYR (or giant GYR) structure through a hexagonal (HEX) cylindrical morphology in the same material, because the thermal ordering of highly entangled BCP imposes the limit on the chain mobility. Along with the improved mechanical strength arising from the high molecular weight property of the polymers, the structural integrity and overall excellence of a large-scale GYR morphology were confirmed by the results of membrane performance, which showed greater permeability through the nanoporous GYR structure up to by a factor of three than that through the HEX structure. Moreover, a 3D nanoporous GYR template was applied to an affordable material to reproduce an inverse skeletal replica of the GYR structure with its structure being uniformly interconnected. This simple approach to the GYR template, owing to its structural tunability in a controlled composition of BCP, is anticipated to be applicable to a wide range of materialization for practical systems.
α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses
Authors: Sugeno Naoto , Jäckel Sandra , Voigt Aaron , Wassouf Zinah , Schulze-Hentrich Julia , Kahle Philipp J.
Published: November 2016

α-Synuclein (αS) is a protein linked to Parkinson’s disease (PD) and related neurodegenerative disorders. It is mostly localized within synapses, but αS has also been suggested to play a role in the nucleus. We used transgenicDrosophilaand inducible SH-SY5Y neuroblastoma cells to investigate the effects of αS on chromatin with a particular focus on histone modifications. Overexpression of αS in male flies as well as in retinoic acid pre-treated neuroblastoma cells led to an elevation of histone H3K9 methylations, mostly mono- (H3K9me1) and di- (H3K9me2). The transient increase of H3K9 methylation in αS-induced SH-SY5Y cells was preceded by mRNA induction of the euchromatic histone lysineN-methyltransferase 2 (EHMT2). EHMT2 and H3K9me2 can function within the REST complex. Chromatin immunoprecipitation (ChIP) analyses of selected candidate, REST regulated genes showed significantly increased H3K9me2 promoter occupancy of genes encoding the L1CAM cell adhesion molecule and the synaptosomal-associated protein SNAP25, whose reduced expression levels were confirmed by RT-qPCR in αS induced cells. Treatment with EHMT inhibitor UNC0638 restored the mRNA levels ofL1CAMandSNAP25. Thus, αS overexpression enhances H3K9 methylations via ΕΗΜΤ2 resulting in elevated H3K9me2 at theSNAP25promoter, possibly affecting SNARE complex assembly and hence synaptic vesicle fusion events regulated by αS.
Physical interactions between DNA and sepiolite nanofibers, and potential application for DNA transfer into mammalian cells
Authors: Castro-Smirnov Fidel Antonio , Piétrement Olivier , Aranda Pilar , Bertrand Jean-Rémi , Ayache Jeanne , Le Cam Eric , Ruiz-Hitzky Eduardo , Lopez Bernard S.
Published: November 2016

Nanofibers of sepiolite, a natural silicate belonging to the clay minerals family, might constitute a potential promising nanocarrier for the non-viral transfer of bio-molecules. We show here that sepiolite nanofibers efficiently bind different types of DNA molecules through electrostatic interactions, hydrogen bonding, cation bridges, and van der Waals forces. Moreover, Fourier-transform infrared spectroscopy identified the external silanol groups as the main sites of interaction with the DNA. Furthermore, as a proof of concept, we show that sepiolite is able to stably transfer plasmid DNA into mammalian cells and that the efficiency can be optimized. Indeed, sonication of sepiolite 100-fold stimulated DNA transfection efficiency. These results open the way to the use of sepiolite-based biohybrids as a novel class of nanoplatform for gene transfer with potential clinical applications.
Origin and Quenching of Novel ultraviolet and blue emission in NdGaO3: Concept of Super-Hydrogenic Dopants
Authors: Ghosh Siddhartha , Saha Surajit , Liu Zhiqi , Motapothula M. , Patra Abhijeet , Yakovlev Nikolai , Cai Yao , Prakash Saurav , Huang Xiao Hu , Tay Chuan Beng , Cong Chun Xiao , Bhatt Thirumaleshwara , Dolmanan Surani B. , Chen Jianqiang , Lü Weiming , Huang Zhen , Tripathy Sudhiranjan , Chua Soo Jin , Yu Ting , Asta Mark , Ariando A. , Venkatesan T.
Published: November 2016

In this study we report the existence of novel ultraviolet (UV) and blue emission in rare-earth based perovskite NdGaO3 (NGO) and the systematic quench of the NGO photoluminescence (PL) by Ce doping. Study of room temperature PL was performed in both single-crystal and polycrystalline NGO (substrates and pellets) respectively. Several NGO pellets were prepared with varying Ce concentration and their room temperature PL was studied using 325 nm laser. It was found that the PL intensity shows a systematic quench with increasing Ce concentration. XPS measurements indicated that nearly 50% of Ce atoms are in the 4+ state. The PL quench was attributed to the novel concept of super hydrogenic dopant (SHD)”, where each Ce4+ ion contributes an electron which forms a super hydrogenic atom with an enhanced Bohr radius, due to the large dielectric constant of the host. Based on the critical Ce concentration for complete quenching this SHD radius was estimated to be within a range of 0.85 nm and 1.15 nm whereas the predicted theoretical value of SHD radius for NdGaO3 is ~1.01 nm.