bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary convergence in experimental Pseudomonas populations
Authors: Lind Peter A , Farr Andrew D , Rainey Paul B 
Published: December 2016

Abstract
Model microbial systems provide opportunity to understand the genetic bases of ecological traits, their evolution, regulation and fitness contributions. Experimental populations of Pseudomonas fluorescens rapidly diverge in spatially structured microcosms producing a range of surface-colonising forms. Despite divergent molecular routes, wrinkly spreader (WS) niche specialist types overproduce a cellulosic polymer allowing mat formation at the air–liquid interface and access to oxygen. Given the range of ways by which cells can form mats, such phenotypic parallelism is unexpected. We deleted the cellulose-encoding genes from the ancestral genotype and asked whether this mutant could converge on an alternate phenotypic solution. Two new traits were discovered. The first involved an exopolysaccharide encoded by pgaABCD that functions as cell–cell glue similar to cellulose. The second involved an activator of an amidase (nlpD) that when defective causes cell chaining. Both types form mats, but were less fit in competition with cellulose-based WS types. Surprisingly, diguanylate cyclases linked to cellulose overexpression underpinned evolution of poly-beta-1,6-N-acetyl-d-glucosamine (PGA)-based mats. This prompted genetic analyses of the relationships between the diguanylate cyclases WspR, AwsR and MwsR, and both cellulose and PGA. Our results suggest that c-di-GMP regulatory networks may have been shaped by evolution to accommodate loss and gain of exopolysaccharide modules facilitating adaptation to new environments.
Functional optoacoustic neuro-tomography for scalable whole-brain monitoring of calcium indicators
Authors: Deán-Ben X Luís , Sela Gali , Lauri Antonella , Kneipp Moritz , Ntziachristos Vasilis , Westmeyer Gil G , Shoham Shy , Razansky Daniel 
Published: December 2016

AbstractNon-invasive observation of spatiotemporal activity of large neural populations distributed over entire brains is a longstanding goal of neuroscience. We developed a volumetric multispectral optoacoustic tomography platform for imaging neural activation deep in scattering brains. It can record 100 volumetric frames per second across scalable fields of view ranging between 50 and 1000 mm3 with respective spatial resolution of 35–200 μm. Experiments performed in immobilized and freely swimming larvae and in adult zebrafish brains expressing the genetically encoded calcium indicator GCaMP5G demonstrate, for the first time, the fundamental ability to directly track neural dynamics using optoacoustics while overcoming the longstanding penetration barrier of optical imaging in scattering brains. The newly developed platform thus offers unprecedented capabilities for functional whole-brain observations of fast calcium dynamics; in combination with optoacoustics' well-established capacity for resolving vascular hemodynamics, it could open new vistas in the study of neural activity and neurovascular coupling in health and disease.
L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling
Authors: Jacquemet Guillaume , Baghirov Habib , Georgiadou Maria , Sihto Harri , Peuhu Emilia , Cettour-Janet Pierre , He Tao , Perälä Merja , Kronqvist Pauliina , Joensuu Heikki , Ivaska Johanna 
Published: December 2016

AbstractMounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src. Moreover, L-type calcium channels promote filopodia stability and maturation into talin-rich adhesions through the spatially restricted regulation of calcium entry and subsequent activation of the protease calpain-1. Altogether we uncover a novel and clinically relevant signalling pathway that regulates filopodia formation in cancer cells and propose that cycles of filopodia stabilization, followed by maturation into focal adhesions, directs cancer cell migration and invasion.
A grand unified model for liganded gold clusters
Authors: Xu Wen Wu , Zhu Beien , Zeng Xiao Cheng , Gao Yi 
Published: December 2016

AbstractA grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three ‘flavours’ (namely, bottom, middle and top) to represent three possible valence states. The ‘composite particles’ in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design.
Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses
Authors: Wang Wenshuai , Sun Xiaoyu , Li Yanbing , Su Jinpeng , Ling Zhiyang , Zhang Tianlong , Wang Fang , Zhang Hong , Chen Hualan , Ding Jianping , Sun Bing 
Published: December 2016

AbstractAs influenza A viruses remain a major threat to human health worldwide, the discovery of broadly neutralizing monoclonal antibodies that recognize conserved epitopes would facilitate the development of antibody-based therapeutic strategies. Here we report that a VH4-4-encoded human mAb named 3E1 could neutralize H1 and H5 subtype viruses in vitro and protect mice against the H1N1 and H5N6 viruses by inhibiting the low pH-induced conformational rearrangement of haemagglutinin (HA), hence blocking membrane fusion. The crystal structures of 3E1 Fab in complex with HA of two H1N1 strains reveal that 3E1, with both heavy and light chains, binds to a conserved epitope of the HA stem region, comprising parts of the fusion peptide, the F subdomain and the outermost β-strand preceding helix A. Altogether, these data suggest the potential of 3E1 as a therapeutic drug against H1 and H5 subtype viruses.
Ecological networking of cystic fibrosis lung infections
Authors: Quinn Robert A , Whiteson Katrine , Lim Yan Wei , Zhao Jiangchao , Conrad Douglas , LiPuma John J , Rohwer Forest , Widder Stefanie 
Published: December 2016

AbstractIn the context of a polymicrobial infection, treating a specific pathogen poses challenges because of unknown consequences on other members of the community. The presence of ecological interactions between microbes can change their physiology and response to treatment. For example, in the cystic fibrosis lung polymicrobial infection, antimicrobial susceptibility testing on clinical isolates is often not predictive of antibiotic efficacy. Novel approaches are needed to identify the interrelationships within the microbial community to better predict treatment outcomes. Here we used an ecological networking approach on the cystic fibrosis lung microbiome characterized using 16S rRNA gene sequencing and metagenomics. This analysis showed that the community is separated into three interaction groups: Gram-positive anaerobes,Pseudomonas aeruginosa,andStaphylococcus aureus. TheP. aeruginosaandS. aureusgroups both anti-correlate with the anaerobic group, indicating a functional antagonism. When patients are clinically stable, these major groupings were also stable, however, during exacerbation, these communities fragment. Co-occurrence networking of functional modules annotated from metagenomics data supports that the underlying taxonomic structure is driven by differences in the core metabolism of the groups. Topological analysis of the functional network identified the non-mevalonate pathway of isoprenoid biosynthesis as a keystone for the microbial community, which can be targeted with the antibiotic fosmidomycin. This study uses ecological theory to identify novel treatment approaches against a polymicrobial disease with more predictable outcomes.
Glyoxalase 1-knockdown in human aortic endothelial cells – effect on the proteome and endothelial function estimates
Authors: Stratmann Bernd , Engelbrecht Britta , Espelage Britta C. , Klusmeier Nadine , Tiemann Janina , Gawlowski Thomas , Mattern Yvonne , Eisenacher Martin , Meyer Helmut E. , Rabbani Naila , Thornalley Paul J. , Tschoepe Diethelm , Poschmann Gereon , Stühler Kai 
Published: November 2016

AbstractMethylglyoxal (MG), an arginine-directed glycating agent, is implicated in diabetic late complications. MG is detoxified by glyoxalase 1 (GLO1) of the cytosolic glyoxalase system. The aim was to investigate the effects of MG accumulation by GLO1-knockdown under hyperglycaemic conditions in human aortic endothelial cells (HAECs) hypothesizing that the accumulation of MG accounts for the deleterious effects on vascular function. SiRNA-mediated knockdown of GLO1 was performed and MG concentrations were determined. The impact of MG on the cell proteome and targets of MG glycation was analysed, and confirmed by Western blotting. Markers of endothelial function and apoptosis were assessed. Collagen content was assayed in cell culture supernatant. GLO1-knockdown increased MG concentration in cells and culture medium. This was associated with a differential abundance of cytoskeleton stabilisation proteins, intermediate filaments and proteins involved in posttranslational modification of collagen. An increase in fibrillar collagens 1 and 5 was detected. The extracellular concentration of endothelin-1 was increased following GLO1-knockdown, whereas the phosphorylation and amount of eNOS was not influenced by GLO1-knockdown. The expression of ICAM-1, VCAM-1 and of MCP-1 was elevated and apoptosis was increased. MG accumulation by GLO1-knockdown provoked collagen expression, endothelial inflammation and dysfunction and apoptosis which might contribute to vascular damage.
Effects of annual influenza vaccination on morbidity and mortality in patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study
Authors: Chang Chi-Ching , Chang Yu-Sheng , Chen Wei-Sheng , Chen Yi-Hsuan , Chen Jin-Hua 
Published: December 2016

AbstractStudies on the clinical efficacy of influenza vaccination on patients with systemic lupus erythematosus (SLE) are scant. The present study compared the incidence of hospitalization, morbidity, and mortality in patients with SLE between cohorts with and without influenza vaccination. We used the Taiwan’s insurance claims data between 2001 and 2012 for identifying annual adult patients with SLE with (N = 1765) and without (N = 8360) influenza vaccination. The incidence rate ratio and hazard ratio (HR) for morbidities and mortality were measured for the vaccine and nonvaccine cohorts. The vaccine cohort had a lower hospitalization rate than did the nonvaccine cohort, with an adjusted HR of 0.82 (95% CI 0.73–0.92). Furthermore, the vaccine cohort was less likely to be admitted to the intensive care unit [adjusted HR 0.55 (95% CI 0.39–0.79)], to be hospitalized for septicemia, bacteremia, or viremia [adjusted HR 0.48 (95% CI 0.32–0.73)], to undergo in-hospital dialysis [adjusted HR 0.40 (95% CI 0.20–0.81)], and were less predisposed to death [adjusted HR 0.41 (95% CI 0.27–0.61)]. In conclusion, influenza vaccination in patients with SLE is associated with a reduced risk of morbidity and mortality.
Long intergenic non-coding RNA expression signature in human breast cancer
Authors: Zhang Yanfeng , Wagner Erin K. , Guo Xingyi , May Isaac , Cai Qiuyin , Zheng Wei , He Chunyan , Long Jirong 
Published: November 2016

AbstractBreast cancer is a complex disease, characterized by gene deregulation. There is less systematic investigation of the capacity of long intergenic non-coding RNAs (lincRNAs) as biomarkers associated with breast cancer pathogenesis or several clinicopathological variables including receptor status and patient survival. We designed a two-stage study, including 1,000 breast tumor RNA-seq data from The Cancer Genome Atlas (TCGA) as the discovery stage, and RNA-seq data of matched tumor and adjacent normal tissue from 50 breast cancer patients as well as 23 normal breast tissue from healthy women as the replication stage. We identified 83 lincRNAs showing the significant expression changes in breast tumors with a false discovery rate (FDR) < 1% in the discovery dataset. Thirty-seven out of the 83 were validated in the replication dataset. Integrative genomic analyses suggested that the aberrant expression of these 37 lincRNAs was probably related with the expression alteration of several transcription factors (TFs). We observed a differential co-expression pattern between lincRNAs and their neighboring genes. We found that the expression levels of one lincRNA (RP5-1198O20 with Ensembl ID ENSG00000230615) were associated with breast cancer survival with P < 0.05. Our study identifies a set of aberrantly expressed lincRNAs in breast cancer.
Super-Resolution Imaging at Mid-Infrared Waveband in Graphene-nanocavity formed on meta-surface
Authors: Yang Jingzhong , Wang Taisheng , Chen Zuolong , Hu Bingliang , Yu Weixing 
Published: November 2016

AbstractPlasmonic structured illumination microscopy (PSIM) is one of the promising wide filed optical imaging methods, which takes advantage of the surface plasmons to break the optical diffraction limit and thus to achieve a super-resolution optical image. To further improve the imaging resolution of PSIM, we propose in this work a so called graphene nanocavity on meta-surface structure (GNMS) to excite graphene surface plasmons with a deep sub-wavelength at mid-infrared waveband. It is found that surface plasmonic interference pattern with a period of around 52 nm can be achieved in graphene nanocavity formed on structured meta-surface for a 7 μm wavelength incident light. Moreover, the periodic plasmonic interference pattern can be tuned by simply changing the nanostructures fabricated on meta-surface for different application purposes. At last, the proposed GNMS structure is applied for super-resolution imaging in PSIM and it is found that an imaging resolution of 26 nm can be achieved, which is nearly 100 folds higher than that can be achieved by conventional epi-fluorescence microscopy. In comparison with visible waveband, mid-infrared is more gently and safe to biological cells and thus this work opens the new possibility for optical super-resolution imaging at mid-infrared waveband for biological research field.
Global gene regulation during activation of immunoglobulin class switching in human B cells
Authors: Zhang Youming , Fear David J. , Willis-Owen Saffron A. G. , Cookson William O. , Moffatt Miriam F. 
Published: November 2016

AbstractImmunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed. CCL22 and CCL17 were dramatically induced but followed a temporal trajectory distinct from classical mediators of isotype switching. AICDA, NFIL3, IRF4, XBP1 and BATF3 shared a profile with several genes involved in innate immunity, but with no recognised role in CSR. A transcription factor BHLHE40 was identified at the core of this profile. B-cell activation was also accompanied by variation in exon retention affecting >200 genes including CCL17. The data indicate a circadian component and central roles for the Th2 chemokines CCL22 and CCL17 in the activation of CSR.
Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase
Authors: Li Quanjie , Fan Shuai , Li Xiaoyu , Jin Yuanyuan , He Weiqing , Zhou Jinming , Cen Shan , Yang ZhaoYong 
Published: December 2016

AbstractHuman ubiquitous mitochondrial creatine kinase (uMtCK) is responsible for the regulation of cellular energy metabolism. To investigate the phosphoryl-transfer mechanism catalyzed by human uMtCK, in this work, molecular dynamic simulations of uMtCK∙ATP-Mg2+∙creatine complex and quantum mechanism calculations were performed to make clear the puzzle. The theoretical studies hereof revealed that human uMtCK utilizes a two-step dissociative mechanism, in which the E227 residue of uMtCK acts as the catalytic base to accept the creatine guanidinium proton. This catalytic role of E227 was further confirmed by our assay on the phosphatase activity. Moreover, the roles of active site residues in phosphoryl transfer reaction were also identified by site directed mutagenesis. This study reveals the structural basis of biochemical activity of uMtCK and gets insights into its phosphoryl transfer mechanism.
Hydrogen sulfide (H2S) emission control by aerobic sulfate reduction in landfill
Authors: Long Yuyang , Fang Yuan , Shen Dongsheng , Feng Huajun , Chen Ting 
Published: December 2016

AbstractH2S emissions from landfill sites resulting from sulfate reduction has become a serious human health and ecological safety issue. This study investigated H2S emission behavior and sulfate metabolism occurring in simulated landfills under different operating conditions. Under aerobic conditions, great attenuation of the original sulfate content (from around 6000 mg kg−1 dropped to below 800 mg kg−1) with corresponding accumulation of sulfides and elemental sulfur were observed, indicating that sulfate reduction processes were intense under such conditions. Analysis of the bacterial community in these landfills showed great abundance (1.10%) and diversity of sulfur reducing types, confirming their active involvement in this process. In particular, the total abundance of sulfate-reducing bacteria increased nearly 30 times under aerobic conditions, leading to the transformation of sulfate to sulfide and other reduced sulfur species. Although exposure to air promoted the accumulation of sulfide, it did not lead to an increase in H2S release in these landfills.
Undiluted Serum Eye Drops for the Treatment of Persistent Corneal Epitheilal Defects
Authors: Lekhanont Kaevalin , Jongkhajornpong Passara , Anothaisintawee Thunyarat , Chuckpaiwong Varintorn 
Published: December 2016

AbstractSeveral studies found that 50–100% serum eye drops provided greater benefits without inducing detrimental effects on the corneal epithelial healing. This study assessed the efficacy of undiluted serum eye drops for the treatment of persistent corneal epithelial defects (PED). A total of 109 eyes received 100% serum eye drops for PED were recruited into this study. The data were compared with an historical control group of 79 eyes with PED who received conventional treatments from 2006–2011 at the same institution. Main outcome measures were complete healing of PED and incidence of adverse events. No significant difference in demographics between the 2 groups was noted. The success rate of the treatment and control groups were 87.16% (95% CI 0.79–0.93) and 69.62% (95% CI 0.59–0.80) (P = 0.001), respectively. The median time to complete epithelialization was 14 days (95% CI 12–21) in the treatment group and 28 days (95% CI 21–59) in the control group (P = 0.001). Serum treatment, primary diagnosis of non-limbal stem cell deficiency etiology, and prior contact lens wear significantly correlated with the corneal re-epithelialization. There were no serious side effects encountered during the study period. In conclusion, undiluted serum therapy is effective and safe for treating PED.
Nanoscale self-templating for oxide epitaxy with large symmetry mismatch
Authors: Gao Xiang , Lee Shinbuhm , Nichols John , Meyer Tricia L. , Ward Thomas Z. , Chisholm Matthew F. , Lee Ho Nyung 
Published: December 2016

AbstractDirect observations using scanning transmission electron microscopy unveil an intriguing interfacial bi-layer that enables epitaxial growth of a strain-free, monoclinic, bronze-phase VO2(B) thin film on a perovskite SrTiO3 (STO) substrate. We observe an ultrathin (2–3 unit cells) interlayer best described as highly strained VO2(B) nanodomains combined with an extra (Ti,V)O2 layer on the TiO2 terminated STO (001) surface. By forming a fully coherent interface with the STO substrate and a semi-coherent interface with the strain-free epitaxial VO2(B) film above, the interfacial bi-layer enables the epitaxial connection of the two materials despite their large symmetry and lattice mismatch.
Paper-based CRP Monitoring Devices
Authors: Lin Shang-Chi , Tseng Chung-Yuh , Lai Po-Liang , Hsu Min-Yen , Chu Shueh-Yao , Tseng Fan-Gang , Cheng Chao-Min 
Published: December 2016

AbstractHere, we discuss the development of a paper-based diagnostic device that is inexpensive, portable, easy-to-use, robust, and capable of running simultaneous tests to monitor a relevant inflammatory protein for clinical diagnoses i.e. C-reactive protein (CRP). In this study, we first attempted to make a paper-based diagnostic device via the wax printing method, a process that was used in previous studies. This device has two distinct advantages: 1) reduced manufacturing and assay costs and operation duration via using wax printing method to define hydrophobic boundaries (for fluidic devices or general POC devices); and, 2) the hydrophilicity of filter paper, which is used to purify and chromatographically correct interference caused by whole blood components with a tiny amount of blood sample (only 5 μL). Diagnosis was based on serum stain length retained inside the paper channels of our device. This is a balanced function between surface tension and chromatographic force following immune reactions (CRP assays) with a paper-embedded biomarker.