bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanotransductive cascade of Myo-II-dependent mesoderm and endoderm invaginations in embryo gastrulation
Authors: Mitrossilis Démosthène , Röper Jens-Christian , Le Roy Damien , Driquez Benjamin , Michel Aude , Ménager Christine , Shaw Gorky , Le Denmat Simon , Ranno Laurent , Dumas-Bouchiat Frédéric , Dempsey Nora M. , Farge Emmanuel 
Published: January 2017

AbstractAnimal development consists of a cascade of tissue differentiation and shape change. Associated mechanical signals regulate tissue differentiation. Here we demonstrate that endogenous mechanical cues also trigger biochemical pathways, generating the active morphogenetic movements shaping animal development through a mechanotransductive cascade of Myo-II medio-apical stabilization. To mimic physiological tissue deformation with a cell scale resolution, liposomes containing magnetic nanoparticles are injected into embryonic epithelia and submitted to time-variable forces generated by a linear array of micrometric soft magnets. Periodic magnetically induced deformations quantitatively phenocopy the soft mechanical endogenous snail-dependent apex pulsations, rescue the medio-apical accumulation of Rok, Myo-II and subsequent mesoderm invagination lacking in sna mutants, in a Fog-dependent mechanotransductive process. Mesoderm invagination then activates Myo-II apical accumulation, in a similar Fog-dependent mechanotransductive process, which in turn initiates endoderm invagination. This reveals the existence of a highly dynamic self-inductive cascade of mesoderm and endoderm invaginations, regulated by mechano-induced medio-apical stabilization of Myo-II.
Transformable topological mechanical metamaterials
Authors: Rocklin D. Zeb , Zhou Shangnan , Sun Kai , Mao Xiaoming 
Published: January 2017

AbstractMechanical metamaterials are engineered materials whose structures give them novel mechanical properties, including negative Poisson’s ratios, negative compressibilities and phononic bandgaps. Of particular interest are systems near the point of mechanical instability, which recently have been shown to distribute force and motion in robust ways determined by a nontrivial topological state. Here we discuss the classification of and propose a design principle for mechanical metamaterials that can be easily and reversibly transformed between states with dramatically different mechanical and acoustic properties via a soft strain. Remarkably, despite the low energetic cost of this transition, quantities such as the edge stiffness and speed of sound can change by orders of magnitude. We show that the existence and form of a soft deformation directly determines floppy edge modes and phonon dispersion. Finally, we generalize the soft strain to generate domain structures that allow further tuning of the material.
Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer
Authors: Ding J , Xie M , Lian Y , Zhu Y , Peng P , Wang J , Wang L , Wang K 
Published: January 2017

AbstractLong noncoding RNAs (lncRNAs) have received increased attention as a new class of functional regulators involved in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2) is a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes in the HOXA cluster that regulates gene expression at a transcription level. HOXA-AS2 is previously found to be overexpressed in gastric cancer (GC) and promotes GC cells proliferation. However, its potential role and molecular mechanism in colorectal cancer (CRC) are not known. Here, we identified that HOXA-AS2 is significantly upregulated in CRC tissue. In addition, increased HOXA-AS2 expression is associated with a larger tumor size and an advanced pathological stage in CRC patients. HOXA-AS2 knockdown significantly suppressed proliferation by blocking the G1/S transition and caused apoptosis of CRC cells in vitro and in vivo. The mechanistic investigations showed that HOXA-AS2 could interact with EZH2 (enhancer of zeste homolog 2), LSD1 (lysine specific demethylase 1) and recruit them to p21 (CDKN1A), KLF2 promoter regions to repress their transcription. Furthermore, the rescue experiments demonstrated that HOXA-AS2 oncogenic function is partly through regulating p21. In conclusion, our data suggest that HOXA-AS2 may function as an oncogene by modulating the multiple genes expression involved in CRC proliferation, and also provides a potential target for CRC therapy.
The role of the cancer stem cell marker CD271 in DNA damage response and drug resistance of melanoma cells
Authors: Redmer T , Walz I , Klinger B , Khouja S , Welte Y , Schäfer R , Regenbrecht C 
Published: January 2017

AbstractSeveral lines of evidence have suggested that stemness and acquired resistance to targeted inhibitors or chemotherapeutics are mechanistically linked. Here we observed high cell surface and total levels of nerve growth factor receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of chemoresistant cell lines. CD271 expression was increased in drug-sensitive cells but not resistant cells in response to DNA-damaging chemotherapeutics etoposide, fotemustine and cisplatin. Comparative analysis of melanoma cells engineered to stably express CD271 or a targeting short hairpin RNA by expression profiling provided numerous genes regulated in a CD271-dependent manner. In-depth analysis of CD271-responsive genes uncovered the association of CD271 with regulation of DNA repair components. In addition, gene set enrichment analysis revealed enrichment of CD271-responsive genes in drug-resistant cells, among them DNA repair components. Moreover, our comparative screen identified the fibroblast growth factor 13 (FGF13) as a target of CD271, highly expressed in chemoresistant cells. Further we show that levels of CD271 determine drug response. Knock-down of CD271 in fotemustine-resistant cells decreased expression of FGF13 and at least partly restored sensitivity to fotemustine. Together, we demonstrate that expression of CD271 is responsible for genes associated with DNA repair and drug response. Further, we identified 110 CD271-responsive genes predominantly expressed in melanoma metastases, among them were NEK2, TOP2A and RAD51AP1 as potential drivers of melanoma metastasis. In addition, we provide mechanistic insight in the regulation of CD271 in response to drugs. We found that CD271 is potentially regulated by p53 and in turn is needed for a proper p53-dependent response to DNA-damaging drugs. In summary, we provide for the first time insight in a CD271-associated signaling network connecting CD271 with DNA repair, drug response and metastasis.
Evolutionary adaptations of biofilms infecting cystic fibrosis lungs promote mechanical toughness by adjusting polysaccharide production
Authors: Kovach Kristin , Davis-Fields Megan , Irie Yasuhiko , Jain Kanishk , Doorwar Shashvat , Vuong Katherine , Dhamani Numa , Mohanty Kishore , Touhami Ahmed , Gordon Vernita D 
Published: January 2017

AbstractBiofilms are communities of microbes embedded in a matrix of extracellular polymeric substances, largely polysaccharides. Multiple types of extracellular polymeric substances can be produced by a single bacterial strain. The distinct polymer components of biofilms are known to provide chemical protection, but little is known about how distinct extracellular polysaccharides may also protect biofilms against mechanical stresses such as shear or phagocytic engulfment. Decades-long infections of Pseudomonas. aeruginosa biofilms in the lungs of cystic fibrosis patients are natural models for studies of biofilm fitness under pressure from antibiotics and the immune system. In cystic fibrosis infections, production of the extracellular polysaccharide alginate has long been known to increase with time and to chemically protect biofilms. More recently, it is being recognized that chronic cystic fibrosis infections also evolve to increase production of another extracellular polysaccharide, Psl; much less is known about Psl’s protective benefits to biofilms. We use oscillatory bulk rheology, on biofilms grown from longitudinal clinical isolates and from genetically-manipulated lab strains, to show that increased Psl stiffens biofilms and increases biofilm toughness, which is the energy cost to cause the biofilm to yield mechanically. Further, atomic force microscopy measurements reveal greater intercellular cohesion for higher Psl expression. Of the three types of extracellular polysaccharides produced by P. aeruginosa, only Psl increases the stiffness. Stiffening by Psl requires CdrA, a protein that binds to mannose groups on Psl and is a likely cross-linker for the Psl components of the biofilm matrix. We compare the elastic moduli of biofilms to the estimated stresses exerted by neutrophils during phagocytosis, and infer that increased Psl could confer a mechanical protection against phagocytic clearance.
DNA methylation in schizophrenia in different patient-derived cell types
Authors: Vitale Alejandra M. , Matigian Nicholas A. , Cristino Alexandre S. , Nones Katia , Ravishankar Sugandha , Bellette Bernadette , Fan Yongjun , Wood Stephen A. , Wolvetang Ernst , Mackay-Sim Alan 
Published: January 2017

AbstractDNA methylation of gene promoter regions represses transcription and is a mechanism via which environmental risk factors could affect cells during development in individuals at risk for schizophrenia. We investigated DNA methylation in patient-derived cells that might shed light on early development in schizophrenia. Induced pluripotent stem cells may reflect a “ground state” upon which developmental and environmental influences would be minimal. Olfactory neurosphere-derived cells are an adult-derived neuro-ectodermal stem cell modified by developmental and environmental influences. Fibroblasts provide a non-neural control for life-long developmental and environmental influences. Genome-wide profiling of DNA methylation and gene expression was done in these three cell types from the same individuals. All cell types had distinct, statistically significant schizophrenia-associated differences in DNA methylation and linked gene expression, with Gene Ontology analysis showing that the differentially affected genes clustered in networks associated with cell growth, proliferation, and movement, functions known to be affected in schizophrenia patient-derived cells. Only five gene loci were differentially methylated in all three cell types. Understanding the role of epigenetics in cell function in the brain in schizophrenia is likely to be complicated by similar cell type differences in intrinsic and environmentally induced epigenetic regulation.
Resource footprints and their ecosystem consequences
Authors: Verones Francesca , Moran Daniel , Stadler Konstantin , Kanemoto Keiichiro , Wood Richard 
Published: January 2017

AbstractA meaningful environmental impact analysis should go beyond the accounting of pressures from resource use and actually assess how resource demand affects ecosystems. The various currently available footprints of nations report the environmental pressures e.g. water use or pollutant emissions, driven by consumption. However, there have been limited attempts to assess the environmental consequences of these pressures. Ultimately, consequences, not pressures, should guide environmental policymaking. The newly released LC-Impact method demonstrates progress on the path to providing this missing link. Here we present “ecosystem impact footprints” in terms of the consequences for biodiversity and assess the differences in impact footprint results from MRIO-based pressure footprints. The new perspective reveals major changes in the relative contribution of nations to global footprints. Wealthy countries have high pressure footprints in lower-income countries but their impact footprints often have their origin in higher-income countries. This shift in perspective provides a different insight on where to focus policy responses to preserve biodiversity.
Zika virus disrupts molecular fingerprinting of human neurospheres
Authors: Garcez Patricia P. , Nascimento Juliana Minardi , de Vasconcelos Janaina Mota , Madeiro da Costa Rodrigo , Delvecchio Rodrigo , Trindade Pablo , Loiola Erick Correia , Higa Luiza M. , Cassoli Juliana S. , Vitória Gabriela , Sequeira Patricia C. , Sochacki Jaroslaw , Aguiar Renato S. , Fuzii Hellen Thais , de Filippis Ana M. Bispo , da Silva Gonçalves Vianez Júnior João Lídio , Tanuri Amilcar , Martins-de-Souza Daniel , Rehen Stevens K. 
Published: January 2017

AbstractZika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.
Genome and transcriptome analysis of surfactin biosynthesis in Bacillus amyloliquefaciens MT45
Authors: Zhi Yan , Wu Qun , Xu Yan 
Published: January 2017

AbstractNaturalBacillusisolates generate limited amounts of surfactin (<10% of their biomass), which functions as an antibiotic or signalling molecule in inter-/intra-specific interactions. However, overproduction of surfactin inBacillus amyloliquefaciensMT45 was observed at a titre of 2.93 g/l, which is equivalent to half of the maximum biomass. To systemically unravel this efficient biosynthetic process, the genome and transcriptome of this bacterium were compared with those ofB. amyloliquefacienstype strain DSM7T. MT45 possesses a smaller genome while containing more unique transporters and resistance-associated genes. Comparative transcriptome analysis revealed notable enrichment of the surfactin synthesis pathway in MT45, including central carbon metabolism and fatty acid biosynthesis to provide sufficient quantities of building precursors. Most importantly, the modular surfactin synthase overexpressed (9 to 49-fold) in MT45 compared to DSM7Tsuggested efficient surfactin assembly and resulted in the overproduction of surfactin. Furthermore, based on the expression trends observed in the transcriptome, there are multiple potential regulatory genes mediating the expression of surfactin synthase. Thus, the results of the present study provide new insights regarding the synthesis and regulation of surfactin in high-producing strain and enrich the genomic and transcriptomic resources available forB. amyloliquefaciens.
Predictive value of serum cystatin C for acute kidney injury in adults: a meta-analysis of prospective cohort trials
Authors: Yong Zhenzhu , Pei Xiaohua , Zhu Bei , Yuan Haichuan , Zhao Weihong 
Published: January 2017

AbstractThe role of serum cystatin C (Scys) for the detection of acute kidney injury (AKI) has not been fully discussed. This meta-analysis was aimed to investigate the overall diagnostic accuracy of Scys for AKI in adults, and further identify factors affecting its performance. Studies before Sept. 2016 were retrieved from PubMed, Embase, Web of Science and the Cochrane Library. A total of 30 prospective cohort studies (involving 4247 adults from 15 countries, 982 patients occurring AKI) were included. The revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools demonstrated no significant bias had influenced the methodological quality of the included studies. Scys showed a high predictive power for all-cause AKI, that the area under the receiver operating characteristic curve was 0.89. The detailed assessment parameters, such as sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for Scys were 0.82, 0.82, 4.6, 0.22 and 21, respectively. Although Scys could be slightly influenced by the following factors: settings, AKI diagnostic criteria, ethnicity, determination method, age and gender, these factors above did not reach statistically significance. In conclusion, Scys could be a vital promising marker to screen out AKI.
Impact of Social Reward on the Evolution of the Cooperation Behavior in Complex Networks
Authors: Wu Yu’e , Chang Shuhua , Zhang Zhipeng , Deng Zhenghong 
Published: January 2017

AbstractSocial reward, as a significant mechanism explaining the evolution of cooperation, has attracted great attention both theoretically and experimentally. In this paper, we study the evolution of cooperation by proposing a reward model in network population, where a third strategy, reward, as an independent yet particular type of cooperation is introduced in 2-person evolutionary games. Specifically, a new kind of role corresponding to reward strategy, reward agents, is defined, which is aimed at increasing the income of cooperators by applying to them a social reward. Results from numerical simulations show that consideration of social reward greatly promotes the evolution of cooperation, which is confirmed for different network topologies and two evolutionary games. Moreover, we explore the microscopic mechanisms for the promotion of cooperation in the three-strategy model. As expected, the reward agents play a vital role in the formation of cooperative clusters, thus resisting the aggression of defectors. Our research might provide valuable insights into further exploring the nature of cooperation in the real world.
Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K/AKT/mTOR and AMPK/SIRT1/FOXO3 pathways
Authors: Zhang Chao , Li Chuwen , Chen Shenghui , Li Zhiping , Ma Lijuan , Jia Xuejing , Wang Kai , Bao Jiaolin , Liang Yeer , Chen Meiwan , Li Peng , Su Huanxing , Lee Simon Ming Yuen , Liu Kechun , Wan Jian-Bo , He Chengwei 
Published: January 2017

AbstractHormesis is an adaptive response of living organisms to a moderate stress. However, its biomedical implication and molecular mechanisms remain to be intensively investigated. Panaxatriol saponins (PTS) is the major bioactive components extracted fromPanax notoginseng, a widely used herbal medicine for cerebrovascular diseases. This study aims to examine the hormetic and neuroprotective effects of PTS in PC12 cells and zebrafish Parkinson’s disease (PD) models. Our results demonstrated that PTS stimulated PC12 cell growth by about 30% at low doses, while PTS at high doses inhibited cell growth, which is a typical hormetic effect. Moreover, we found that low dose PTS pretreatment significantly attenuated 6-OHDA-induced cytotoxicity and up-regulated PI3K/AKT/mTOR cell proliferation pathway and AMPK/SIRT1/FOXO3 cell survival pathway in PC12 cells. These results strongly suggested that neuroprotective effects of PTS may be attributable to the hormetic effect induced by PTS through activating adaptive response-related signaling pathways. Notably, low dose PTS could significantly prevent the 6-OHDA-induced dopaminergic neuron loss and improve the behavior movement deficiency in zebrafish, whereas relative high dose PTS exhibited neural toxicity, further supporting the hormetic and neuroprotective effects of PTS. This study indicates that PTS may have the potential in the development of future therapeutic medicines for PD.
Mincle activation enhances neutrophil migration and resistance to polymicrobial septic peritonitis
Authors: Lee Wook-Bin , Yan Ji-Jing , Kang Ji-Seon , Zhang Quanri , Choi Won Young , Kim Lark Kyun , Kim Young-Joon 
Published: January 2017

AbstractSepsis is a systemic inflammatory response to bacterial infection. The therapeutic options for treating sepsis are limited. Impaired neutrophil recruitment into the infection site is directly associated with severe sepsis, but the precise mechanism is unclear. Here, we show that Mincle plays a key role in neutrophil migration and resistance during polymicrobial sepsis. Mincle-deficient mice exhibited lower survival rates in experimental sepsis from cecal ligation and puncture and Escherichia coli–induced peritonitis. Mincle deficiency led to higher serum inflammatory cytokine levels and reduced bacterial clearance and neutrophil recruitment. Transcriptome analyses revealed that trehalose dimycolate, a Mincle ligand, reduced the expression of G protein–coupled receptor kinase 2 (GRK2) in neutrophils. Indeed, GRK2 expression was upregulated, but surface expression of the chemokine receptor CXCR2 was downregulated in blood neutrophils from Mincle-deficient mice with septic injury. Moreover, CXCL2-mediated adhesion, chemotactic responses, and F-actin polymerization were reduced in Mincle-deficient neutrophils. Finally, we found that fewer Mincle-deficient neutrophils infiltrated from the blood circulation into the peritoneal fluid in bacterial septic peritonitis compared with wild-type cells. Thus, our results indicate that Mincle plays an important role in neutrophil infiltration and suggest that Mincle signaling may provide a therapeutic target for treating sepsis.
Color-coded visualization of magnetic resonance imaging multiparametric maps
Authors: Kather Jakob Nikolas , Weidner Anja , Attenberger Ulrike , Bukschat Yannick , Weis Cleo-Aron , Weis Meike , Schad Lothar R. , Zöllner Frank Gerrit 
Published: January 2017

AbstractMultiparametric magnetic resonance imaging (mpMRI) data are emergingly used in the clinic e.g. for the diagnosis of prostate cancer. In contrast to conventional MR imaging data, multiparametric data typically include functional measurements such as diffusion and perfusion imaging sequences. Conventionally, these measurements are visualized with a one-dimensional color scale, allowing only for one-dimensional information to be encoded. Yet, human perception places visual information in a three-dimensional color space. In theory, each dimension of this space can be utilized to encode visual information. We addressed this issue and developed a new method for tri-variate color-coded visualization of mpMRI data sets. We showed the usefulness of our method in a preclinical and in a clinical setting: In imaging data of a rat model of acute kidney injury, the method yielded characteristic visual patterns. In a clinical data set of N = 13 prostate cancer mpMRI data, we assessed diagnostic performance in a blinded study with N = 5 observers. Compared to conventional radiological evaluation, color-coded visualization was comparable in terms of positive and negative predictive values. Thus, we showed that human observers can successfully make use of the novel method. This method can be broadly applied to visualize different types of multivariate MRI data.