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Berlin Brandenburg

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  • Wiley Online Library  (12)
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  • 1
    In: Molecular Microbiology, April 2010, Vol.76(2), pp.409-427
    Description: attachment is mediated by the holdfast, a complex of polysaccharide anchored to the cell by HfaA, HfaB and HfaD. We show that all three proteins are surface exposed outer membrane (OM) proteins. HfaA is similar to fimbrial proteins and assembles into a high molecular weight (HMW) form requiring HfaD, but not holdfast polysaccharide. The HfaD HMW form is dependent on HfaA but not on holdfast polysaccharide. We show that HfaA and HfaD form homomultimers and that they require HfaB for stability and OM translocation. All three proteins localize to the late pre‐divisional flagellar pole, remain at this pole in swarmer cells, and localize at the stalk tip after the stalk is synthesized at the same pole. Hfa protein localization requires the holdfast polysaccharide secretion proteins and the polar localization factor PodJ. An mutant is much more severely deficient in adherence and holdfast attachment than and mutants. An , double mutant phenocopies either single mutant, suggesting that HfaB is involved in holdfast attachment beyond secretion of HfaA and HfaD. We hypothesize that HfaB secretes HfaA and HfaD across the outer membrane, and the three proteins form a complex anchoring the holdfast to the stalk.
    Keywords: Proteins ; Polysaccharides;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 2
    In: Evolution & Development, July 2013, Vol.15(4), pp.243-256
    Description: Byline: Elizabeth C. Raff, Mary E. Andrews, F. Rudolf Turner, Evelyn Toh, David E. Nelson, Rudolf A. Raff SUMMARY Fossils of soft tissues provide important records of early animals and embryos, and there is substantial evidence for a role for microbes in soft tissue fossilization. We are investigating the initial events in interactions of bacteria with freshly dead tissue, using marine embryos as a model system. We previously found that microbial invasion can stabilize embryo tissue that would otherwise disintegrate in hours or days by generating a bacterial pseudomorph, a three-dimensional biofilm that both replaces the tissue and replicates its morphology. In this study, we sampled seawater at different times and places near Sydney, Australia, and determined the range and frequency of different taphonomic outcomes. Although destruction was most common, bacteria in 35% of seawater samples yielded morphology-preserving biofilms. We could replicate the taphonomic pathways seen with seawater bacterial communities using single cultured strains of marine gammaproteobacteria. Each given species reproducibly generated a consistent taphonomic outcome and we identified species that yielded each of the distinct pathways produced by seawater bacterial communities. Once formed, bacterial pseudomorphs are stable for over a year and resist attack by other bacteria and destruction by proteases and other lytic enzymes. Competition studies showed that the initial action of a pseudomorphing strain can be blocked by a strain that destroys tissues. Thus embryo preservation in nature may depend on contingent interactions among bacterial species that determine if pseudomorphing occurs. We used Artemia nauplius larvae to show that bacterial biofilm replacement of tissue is not restricted to embryos, but is relevant for preservation of small multicellular organisms. We present a model for bacterial self-assembly of large-scale three-dimensional tissue pseudomorphs, based on small-scale interactions among individual bacterial cells to form local biofilms at structural boundaries within the tissue. Local biofilms then conjoin to generate the pseudomorph. Author Affiliation:
    Keywords: Seawater -- Protection And Preservation ; Seawater -- Analysis ; Fossilization -- Protection And Preservation ; Fossilization -- Analysis ; Bacteria -- Protection And Preservation ; Bacteria -- Analysis ; Pseudomorphs -- Protection And Preservation ; Pseudomorphs -- Analysis ; Embryonic Development -- Protection And Preservation ; Embryonic Development -- Analysis;
    ISSN: 1520-541X
    E-ISSN: 1525-142X
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  • 3
    In: Molecular Microbiology, September 2003, Vol.49(6), pp.1671-1683
    Description: The differentiating bacterium produces two different cell types at each cell division, a motile swarmer cell and an adhesive stalked cell. The stalked cell harbours a stalk, a thin cylindrical extension of the cell surface. The tip of the stalk is decorated with a holdfast, an adhesive organelle composed at least in part of polysaccharides. The synthesis of the stalk and holdfast occur at the same pole during swarmer cell differentiation. Mutations in the gene cluster had been shown to disrupt the attachment of the holdfast to the tip of the stalk, but the role of individual genes was unknown. We used fusions of various DNA fragments from the region to show that these genes form an operon. In order to analyse the relative contribution of the different genes to holdfast attachment, mutations were constructed for each gene. was not required for holdfast attachment or binding to surfaces. The and mutants shed some holdfast material into the surrounding medium and were partially deficient in binding to surfaces. Unlike and mutants, mutants were still able to form rosettes efficiently. Cells with insertions in were unable to bind to surfaces, and lectin binding studies indicated that the mutants had the strongest holdfast shedding phenotype. We determined that HfaB and HfaD are membrane‐associated proteins and that HfaB is a lipoprotein. Purification of stalks and cell bodies indicated that both HfaB and HfaD are enriched in the stalk as compared to the cell body. These results suggest that HfaB and HfaD, and probably HfaA, serve to anchor the holdfast to the tip of the stalk.
    Keywords: Bacterial Adhesion ; Bacterial Proteins -- Metabolism ; Caulobacter Crescentus -- Cytology ; Membrane Proteins -- Metabolism;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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  • 4
    Language: English
    In: Chemistry – A European Journal, 13 June 2016, Vol.22(25), pp.8404-8430
    Description: Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti‐biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications. : This review provides a comprehensive summary of advances in enzyme mimics research, covering supramolecular, dendrimeric, polymeric, nanoparticulate and proteinic enzyme mimics. The accessibility and tunability of different scaffolds allow enzyme mimics to have a wide variety of applications, which have been categorised herein as biological reactions, biosensors, medical uses, production of fuels, green chemistry and anti‐biofouling.
    Keywords: Catalysis ; Enzymes ; Host–Guest Systems ; Macrocycles ; Supramolecular Chemistry
    ISSN: 0947-6539
    E-ISSN: 1521-3765
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  • 5
    Language: English
    In: Cancer, 15 January 2013, Vol.119(2), pp.380-387
    Description: BACKGROUND: The efficacy and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single-arm, open-label, multicenter trial.METHODS: Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.25 mg/kg,. The primary endpoint was the progression-free rate at 16 weeks. Tumor response was assessed every 8 weeks. Secondary endpoints included the time to disease progression, overall survival, and objective response rate. Safety was also assessed.RESULTS: Of the 44 patients enrolled, the majority were Asian (89%), had received no prior systemic therapy (82%), had Child-Pugh class A hepatic function (86%), and had hepatitis B virus infection (61%). The estimated progression-free rate at 16 weeks was 31.8% (34.2% for patients with Child-Pugh class A hepatic function), the estimated objective response rate was 9.1% (10.5% for patients with Child-Pugh class A hepatic function), the median time to disease progression was 3.7 months (3.7 months for patients with Child-Pugh class A hepatic function), and the median overall survival was 9.7 months (10.4 months for patients with Child-Pugh class A hepatic function). The most common linifanib-related adverse events were diarrhea (55%) and fatigue (52%). The most common linifanib-related grade 3/4 adverse events were hypertension (25%) and fatigue (14%). Serum levels of biomarkers cancer antigen (CA) 125, cytokeratin fragment (CYFRA)21.1, and protein induced by vitamin K absence or antagonist II (PIVKA) demonstrated potential as prognostic indicators of patient response or outcome.CONCLUSIONS: Single-agent linifanib was found to be clinically active in patients with advanced hepatocellular carcinoma, with an acceptable safety profile.
    Keywords: Angiogenesis ; Hepatocellular Carcinoma Hcc ; Platelet‐Derived Growth Factor Receptor Pdgfr ; Sorafenib ; Vascular Endothelial Growth Factor Receptor Vegfr ; Linifanib
    ISSN: 0008-543X
    E-ISSN: 1097-0142
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  • 6
    Language: English
    In: ChemInform, August 2016, Vol.47(35), pp.no-no
    Description: Review: 301 refs.
    Keywords: Biochemistry ; Review ; Enzymes
    ISSN: 0931-7597
    E-ISSN: 1522-2667
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  • 7
    Language: English
    In: Biotechnology and Bioengineering, May 2019, Vol.116(5), pp.1164-1175
    Description: Human pluripotent stem cell‐derived endothelial cells (hPSC‐ECs) present an attractive alternative to primary EC sources for vascular grafting. However, there is a need to mature them towards either an arterial or venous subtype. A vital environmental factor involved in the arteriovenous specification of ECs during early embryonic development is fluid shear stress; therefore, there have been attempts to employ adult arterial shear stress conditions to mature hPSC‐ECs. However, hPSC‐ECs are naïve to fluid shear stress, and their shear responses are still not well understood. Here, we used a multiplex microfluidic platform to systematically investigate the dose‐time shear responses on hPSC‐EC morphology and arterial‐venous phenotypes over a range of magnitudes coincidental with physiological levels of embryonic and adult vasculatures. The device comprised of six parallel cell culture chambers that were individually linked to flow‐setting resistance channels, allowing us to simultaneously apply shear stress ranging from 0.4 to 15 dyne/cm . We found that hPSC‐ECs required up to 40 hr of shear exposure to elicit a stable phenotypic change. Cell alignment was visible at shear stress 〈1 dyne/cm , which was independent of shear stress magnitude and duration of exposure. We discovered that the arterial markers NOTCH1 and EphrinB2 exhibited a dose‐dependent increase in a similar manner beyond a threshold level of 3.8 dyne/cm , whereas the venous markers COUP‐TFII and EphB4 expression remained relatively constant across different magnitudes. These findings indicated that hPSC‐ECs were sensitive to relatively low magnitudes of shear stress, and a critical level of ~4 dyne/cm was sufficient to preferentially enhance their maturation into an arterial phenotype for future vascular tissue engineering applications. A multiplex microfluidic platform was employed to systematically investigate the dose‐time shear responses on human pluripotent stem cell derived endothelial cell (hPSC‐EC) over a range of magnitudes coincidental with physiological levels of embryonic and adult vasculatures. The arterial markers NOTCH1 and EphrinB2 exhibited a dose‐dependent increase at 40 h beyond a threshold level of 3.8 dyne/cm2, which has been determined as a critical shear stress to preferentially enhance hPSC‐ECs maturation into an arterial phenotype.
    Keywords: Arterial‐Venous Specification ; Biophysical Cues ; Functional Maturation ; Human Pluripotent Stem Cell‐Derived Endothelial Cells ; Microfluidics ; Shear Stress
    ISSN: 0006-3592
    E-ISSN: 1097-0290
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  • 8
    In: Liver International, April 2013, Vol.33(4), pp.642-646
    Description: Keywords: drug resistance; hepatitis B Abstract Aim Few cases of primary entecavir resistance in chronic hepatitis B patients have been reported to date. The serial profiling of the HBV polymerase gene mutations from a treatment-naive patient who developed drug resistance after 32 months of entecavir therapy is presented here. Design Serum samples were collected at multiple time points from before the start of therapy to virological and biochemical breakthrough. The evolution of the hepatitis B virus polymerase gene mutations was analysed with commercial line probe assay and pyrosequencing. Results Drug resistance mutation analysis by pyrosequencing revealed a two-step process in the selection of drug resistance. The patient had a good initial response to entecavir 0.5 mg/day. A partially resistant HBV strain first emerged as the predominant species from as early as 2 weeks. After a period of non-compliance to therapy, there was virological breakthrough, which resolved on restarting entecavir. Shortly after, there was secondary failure of entecavir therapy, caused by a new resistant strain carrying all three mutations required. Conclusion In this patient, pre-existence of minor population of partially resistant viral strains and treatment non-compliance probably contributed to his development of primary entecavir resistance. Author Affiliation:
    Keywords: Drug Resistance ; Hepatitis B
    ISSN: 1478-3223
    E-ISSN: 1478-3231
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  • 9
    In: Pediatric Allergy and Immunology, August 2017, Vol.28(5), pp.490-495
    Description: Byline: Evelyn Xiu Ling Loo, Jordan Zheng Ting Sim, Jia Ying Toh, Anne Goh, Oon Hoe Teoh, Yiong Huak Chan, Seang Mei Saw, Kenneth Kwek, Kok Hian Tan, Peter D. Gluckman, Keith M. Godfrey, Hugo Van Bever, Bee Wah Lee, Yap Seng Chong, Mary Foong-Fong Chong, Lynette Pei-chi Shek ***** No abstract is available for this article. ***** Article Note: Chong and Shek contributed equally to the work. CAPTION(S):
    Keywords: Food Habits;
    ISSN: 0905-6157
    E-ISSN: 1399-3038
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  • 10
    In: Internal Medicine Journal, September 2016, Vol.46, pp.11-12
    Description: Byline: Elizabeth Huiwen Tham, Toh Jia Ying, Evelyn Xiu Ling Loo, Anne Goh, Oon Hoe Teoh, Yap Seng Chong, Seang Mei Saw, Kenneth Kwek, Peter D Gluckman, Keith M Godfrey, Hugo Van Bever, Lynette Pei-chi Shek, Chong Mary F, Bee Wah Lee ***** No abstract is available for this article. *****
    Keywords: Food Hypersensitivity;
    ISSN: 1444-0903
    E-ISSN: 1445-5994
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