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Book ; Thesis: Biosynthesis and heterologous production of myxobacterial secondary metabolites

Wenzel, Silke Christine

2006

Author's details	von Silke Christine Wenzel
Language	English
Size	Getr. Zählung, Ill., graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Techn. Univ., kumulative Diss.--Braunschweig, 2005
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article: Myxobacterial natural product assembly lines: fascinating examples of curious biochemistry.

Wenzel, Silke Christine / Müller, Rolf

Natural product reports

2007 Volume 24, Issue 6, Page(s) 1211–1224

Abstract: Over the last 20 years myxobacteria have made their way from highly exotic organisms to one of the major sources of microbial natural products with interesting biological activities. Recent progress towards achieving a better understanding of the ... ...

Abstract	Over the last 20 years myxobacteria have made their way from highly exotic organisms to one of the major sources of microbial natural products with interesting biological activities. Recent progress towards achieving a better understanding of the genetics and the biochemistry of myxobacterial secondary metabolism, revealed the involvement of numerous exceptional combinations of polyketide synthases and nonribosomal peptide synthetases operating far from textbook biosynthetic logic. In this Highlight, selected examples of recently described systems are discussed in comparison to all myxobacterial natural product assembly lines known to date.
MeSH term(s)	Biochemical Phenomena ; Biochemistry ; Biological Products/biosynthesis ; Biological Products/chemistry ; Biological Products/isolation & purification ; Models, Biological ; Molecular Structure ; Myxococcales/chemistry ; Myxococcales/genetics ; Myxococcales/metabolism ; Peptide Synthases/metabolism ; Polyketide Synthases/metabolism
Chemical Substances	Biological Products ; Polyketide Synthases (79956-01-7) ; Peptide Synthases (EC 6.3.2.-)
Language	English
Publishing date	2007-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2002546-4
ISSN	1460-4752 ; 0265-0568
ISSN (online)	1460-4752
ISSN	0265-0568
DOI	10.1039/b706416k
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Article: Myxobacterial natural product assembly lines: fascinating examples of curious biochemistry

Wenzel, Silke Christine / Müller, Rolf

Natural product reports. 2007 Nov. 21, v. 24, no. 6

2007

Abstract	Over the last 20 years myxobacteria have made their way from highly exotic organisms to one of the major sources of microbial natural products with interesting biological activities. Recent progress towards achieving a better understanding of the genetics and the biochemistry of myxobacterial secondary metabolism, revealed the involvement of numerous exceptional combinations of polyketide synthases and nonribosomal peptide synthetases operating far from textbook biosynthetic logic. In this Highlight, selected examples of recently described systems are discussed in comparison to all myxobacterial natural product assembly lines known to date.
Keywords	biosynthesis ; genetics ; ligases ; myxobacteria ; nonribosomal peptides ; polyketide synthases
Language	English
Dates of publication	2007-1121
Size	p. 1211-1224.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2002546-4
ISSN	1460-4752 ; 0265-0568
ISSN (online)	1460-4752
ISSN	0265-0568
DOI	10.1039/b706416k
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Cerebral small vessel disease burden and cognitive and functional outcomes after stroke: A multicenter prospective cohort study.

Georgakis, Marios K / Fang, Rong / Düring, Marco / Wollenweber, Frank A / Bode, Felix J / Stösser, Sebastian / Kindlein, Christine / Hermann, Peter / Liman, Thomas G / Nolte, Christian H / Kerti, Lucia / Ikenberg, Benno / Bernkopf, Kathleen / Poppert, Holger / Glanz, Wenzel / Perosa, Valentina / Janowitz, Daniel / Wagner, Michael / Neumann, Katja /

Speck, Oliver / Dobisch, Laura / Düzel, Emrah / Gesierich, Benno / Dewenter, Anna / Spottke, Annika / Waegemann, Karin / Görtler, Michael / Wunderlich, Silke / Endres, Matthias / Zerr, Inga / Petzold, Gabor / Dichgans, Martin

Alzheimer's & dementia : the journal of the Alzheimer's Association

2022 Volume 19, Issue 4, Page(s) 1152–1163

Abstract: Introduction: It remains unknown whether the global small vessel disease (SVD) burden predicts post-stroke outcomes.: Methods: In a prospective multicenter study of 666 ischemic and hemorrhagic stroke patients, we quantified magnetic resonance ... ...

Abstract	Introduction: It remains unknown whether the global small vessel disease (SVD) burden predicts post-stroke outcomes. Methods: In a prospective multicenter study of 666 ischemic and hemorrhagic stroke patients, we quantified magnetic resonance imaging (MRI)-based SVD markers (lacunes, white matter hyperintensities, microbleeds, perivascular spaces) and explored associations with 6- and 12-month cognitive (battery of 15 neuropsychological tests) and functional (modified Rankin scale) outcomes. Results: A global SVD score (range 0-4) was associated with cognitive impairment; worse performance in executive function, attention, language, and visuospatial ability; and worse functional outcome across a 12-month follow-up. Although the global SVD score did not improve prediction, individual SVD markers, assessed across their severity range, improved the calibration, discrimination, and reclassification of predictive models including demographic, clinical, and other imaging factors. Discussion: SVD presence and severity are associated with worse cognitive and functional outcomes 12 months after stroke. Assessing SVD severity may aid prognostication for stroke patients. Highlights: In a multi-center cohort, we explored associations of small vessel disease (SVD) burden with stroke outcomes. SVD burden associates with post-stroke cognitive and functional outcomes. A currently used score of SVD burden does not improve the prediction of poor outcomes. Assessing the severity of SVD lesions adds predictive value beyond known predictors. To add predictive value in assessing SVD in stroke patients, SVD burden scores should integrate lesion severity.
MeSH term(s)	Humans ; Prospective Studies ; Stroke/complications ; Stroke/pathology ; Cerebral Small Vessel Diseases/pathology ; Cognitive Dysfunction/complications ; Magnetic Resonance Imaging ; Cognition
Language	English
Publishing date	2022-07-25
Publishing country	United States
Document type	Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12744
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Article ; Online: Lung area estimation using functional tidal electrical impedance variation images and active contouring.

Borgmann, Silke / Linz, Kim / Braun, Christian / Dzierzawski, Patryk / Spassov, Sashko / Wenzel, Christin / Schumann, Stefan

Physiological measurement

2022 Volume 43, Issue 7

Abstract: Objective. ...

Abstract	Objective.
MeSH term(s)	Electric Impedance ; Lung/diagnostic imaging ; Positive-Pressure Respiration/methods ; Tidal Volume ; Tomography/methods ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2022-07-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1149545-5
ISSN	1361-6579 ; 0967-3334
ISSN (online)	1361-6579
ISSN	0967-3334
DOI	10.1088/1361-6579/ac7cc3
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Article ; Online: Antibiotics. Targeting DnaN for tuberculosis therapy using novel griselimycins.

Kling, Angela / Lukat, Peer / Almeida, Deepak V / Bauer, Armin / Fontaine, Evelyne / Sordello, Sylvie / Zaburannyi, Nestor / Herrmann, Jennifer / Wenzel, Silke C / König, Claudia / Ammerman, Nicole C / Barrio, María Belén / Borchers, Kai / Bordon-Pallier, Florence / Brönstrup, Mark / Courtemanche, Gilles / Gerlitz, Martin / Geslin, Michel / Hammann, Peter /

Heinz, Dirk W / Hoffmann, Holger / Klieber, Sylvie / Kohlmann, Markus / Kurz, Michael / Lair, Christine / Matter, Hans / Nuermberger, Eric / Tyagi, Sandeep / Fraisse, Laurent / Grosset, Jacques H / Lagrange, Sophie / Müller, Rolf

Science (New York, N.Y.)

2015 Volume 348, Issue 6239, Page(s) 1106–1112

Abstract: The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant ... ...

Abstract	The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification.
MeSH term(s)	Animals ; Antitubercular Agents/chemistry ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Bacterial Proteins/antagonists & inhibitors ; Cell Line, Tumor ; Crystallography, X-Ray ; DNA-Directed DNA Polymerase ; Disease Models, Animal ; Drug Design ; Humans ; Mice ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Molecular Targeted Therapy ; Mycobacterium smegmatis/drug effects ; Mycobacterium smegmatis/enzymology ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/enzymology ; Peptides, Cyclic/chemistry ; Peptides, Cyclic/pharmacology ; Peptides, Cyclic/therapeutic use ; Protein Structure, Secondary ; Streptomyces/chemistry ; Streptomyces/drug effects ; Streptomyces/metabolism ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/microbiology
Chemical Substances	Antitubercular Agents ; Bacterial Proteins ; Peptides, Cyclic ; cyclohexylgriselimycin ; griselimycin ; methylgriselimycin ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; dnaN protein, Bacteria (EC 2.7.7.7)
Language	English
Publishing date	2015-06-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aaa4690
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Zs.MG 77: Show issues

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Article ; Online: Glottic visibility for laryngeal surgery: Tritube vs. microlaryngeal tube: A randomised controlled trial.

Schmidt, Johannes / Günther, Franziska / Weber, Jonas / Kehm, Vadim / Pfeiffer, Jens / Becker, Christoph / Wenzel, Christin / Borgmann, Silke / Wirth, Steffen / Schumann, Stefan

European journal of anaesthesiology

2019 Volume 36, Issue 12, Page(s) 963–971

Abstract: Background: Good visibility is essential for successful laryngeal surgery. A Tritube with outer diameter 4.4 mm, combined with flow-controlled ventilation (FCV), enables ventilation by active expiration with a sealed trachea and may improve laryngeal ... ...

Abstract	Background: Good visibility is essential for successful laryngeal surgery. A Tritube with outer diameter 4.4 mm, combined with flow-controlled ventilation (FCV), enables ventilation by active expiration with a sealed trachea and may improve laryngeal visibility. Objectives: We hypothesised that a Tritube with FCV would provide better laryngeal visibility and surgical conditions for laryngeal surgery than a conventional microlaryngeal tube (MLT) with volume-controlled ventilation (VCV). Design: Randomised, controlled trial. Setting: University Medical Centre. Patients: A total of 55 consecutive patients (>18 years) undergoing elective laryngeal surgery were assessed for participation, providing 40 evaluable data sets with 20 per group. Interventions: Random allocation to intubation with Tritube and ventilation with FCV (Tritube-FCV group) or intubation with MLT 6.0 and ventilation with VCV (MLT-VCV) as control. Tidal volumes of 7 ml kg predicted body weight, and positive end-expiratory pressure of 7 cmH2O were standardised between groups. Main outcome measures: Primary endpoint was the tube-related concealment of laryngeal structures, measured on videolaryngoscopic photographs by appropriate software. Secondary endpoints were surgical conditions (categorical four-point rating scale), respiratory variables and change of end-expiratory lung volume from atmospheric airway pressure to ventilation with positive end-expiratory pressure. Data are presented as median [IQR]. Results: There was less concealment of laryngeal structures with the Tritube than with the MLT; 7 [6 to 9] vs. 22 [18 to 27] %, (P < 0.001). Surgical conditions were rated comparably (P = 0.06). A subgroup of residents in training perceived surgical conditions to be better with the Tritube compared with the MLT (P = 0.006). Respiratory system compliance with the Tritube was higher at 61 [52 to 71] vs. 46 [41 to 51] ml cmH2O (P < 0.001), plateau pressure was lower at 14 [13 to 15] vs. 17 [16 to 18] cmH2O (P < 0.001), and change of end-expiratory lung volume was higher at 681 [463 to 849] vs. 414 [194 to 604] ml, (P = 0.023) for Tritube-FCV compared with MLT-VCV. Conclusion: During laryngeal surgery a Tritube improves visibility of the surgical site but not surgical conditions when compared with a MLT 6.0. FCV improves lung aeration and respiratory system compliance compared with VCV. Trial registry number: DRKS00013097.
MeSH term(s)	Aged ; Anesthesia, General ; Anesthesia, Intravenous ; Elective Surgical Procedures/instrumentation ; Female ; Glottis/diagnostic imaging ; Glottis/surgery ; Humans ; Laryngeal Diseases/surgery ; Laryngeal Masks ; Male ; Middle Aged ; Positive-Pressure Respiration/instrumentation ; Tidal Volume ; Treatment Outcome
Language	English
Publishing date	2019-10-23
Publishing country	England
Document type	Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605770-6
ISSN	1365-2346 ; 0265-0215
ISSN (online)	1365-2346
ISSN	0265-0215
DOI	10.1097/EJA.0000000000001110
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Article ; Online: Track J. Clinical Engineering and Hospital Technology.

Schmidt, Johannes / Wenzel, Christin / Mahn, Marlene / Spassov, Sashko / Cristina-Schmitz, Heidi / Borgmann, Silke / Haberstroh, Jörg / Meckel, Stephan / Wirth, Steffen / Schumann, Stefan

Biomedizinische Technik. Biomedical engineering

2016 Volume 61, Issue s1, Page(s) 90–95

Language	English
Publishing date	2016-09-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	120817-2
ISSN	1862-278X ; 0013-5585
ISSN (online)	1862-278X
ISSN	0013-5585
DOI	10.1515/bmt-2016-5008
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Article ; Online: Flow-Controlled Ventilation Attenuates Lung Injury in a Porcine Model of Acute Respiratory Distress Syndrome: A Preclinical Randomized Controlled Study.

Schmidt, Johannes / Wenzel, Christin / Spassov, Sashko / Borgmann, Silke / Lin, Ziwei / Wollborn, Jakob / Weber, Jonas / Haberstroh, Jörg / Meckel, Stephan / Eiden, Sebastian / Wirth, Steffen / Schumann, Stefan

Critical care medicine

2019 Volume 48, Issue 3, Page(s) e241–e248

Abstract: Objectives: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. "Flow-controlled ventilation", ... ...

Abstract	Objectives: Lung-protective ventilation for acute respiratory distress syndrome aims for providing sufficient oxygenation and carbon dioxide clearance, while limiting the harmful effects of mechanical ventilation. "Flow-controlled ventilation", providing a constant expiratory flow, has been suggested as a new lung-protective ventilation strategy. The aim of this study was to test whether flow-controlled ventilation attenuates lung injury in an animal model of acute respiratory distress syndrome. Design: Preclinical, randomized controlled animal study. Setting: Animal research facility. Subjects: Nineteen German landrace hybrid pigs. Intervention: Flow-controlled ventilation (intervention group) or volume-controlled ventilation (control group) with identical tidal volume (7 mL/kg) and positive end-expiratory pressure (9 cm H2O) after inducing acute respiratory distress syndrome with oleic acid. Measurements and main results: PaO2 and PaCO2, minute volume, tracheal pressure, lung aeration measured via CT, alveolar wall thickness, cell infiltration, and surfactant protein A concentration in bronchoalveolar lavage fluid. Five pigs were excluded leaving n equals to 7 for each group. Compared with control, flow-controlled ventilation elevated PaO2 (154 ± 21 vs 105 ± 9 torr; 20.5 ± 2.8 vs 14.0 ± 1.2 kPa; p = 0.035) and achieved comparable PaCO2 (57 ± 3 vs 54 ± 1 torr; 7.6 ± 0.4 vs 7.1 ± 0.1 kPa; p = 0.37) with a lower minute volume (6.4 ± 0.5 vs 8.7 ± 0.4 L/min; p < 0.001). Inspiratory plateau pressure was comparable in both groups (31 ± 2 vs 34 ± 2 cm H2O; p = 0.16). Flow-controlled ventilation increased normally aerated (24% ± 4% vs 10% ± 2%; p = 0.004) and decreased nonaerated lung volume (23% ± 6% vs 38% ± 5%; p = 0.033) in the dependent lung region. Alveolar walls were thinner (5.5 ± 0.1 vs 7.8 ± 0.2 µm; p < 0.0001), cell infiltration was lower (20 ± 2 vs 32 ± 2 n/field; p < 0.0001), and normalized surfactant protein A concentration was higher with flow-controlled ventilation (1.1 ± 0.04 vs 1.0 ± 0.03; p = 0.039). Conclusions: Flow-controlled ventilation enhances lung aeration in the dependent lung region and consequently improves gas exchange and attenuates lung injury. Control of the expiratory flow may provide a novel option for lung-protective ventilation.
MeSH term(s)	Animals ; Disease Models, Animal ; Random Allocation ; Respiration, Artificial/methods ; Respiratory Distress Syndrome/therapy ; Swine ; Ventilator-Induced Lung Injury/prevention & control
Language	English
Publishing date	2019-10-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000004209
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Article ; Online: Improved lung recruitment and oxygenation during mandatory ventilation with a new expiratory ventilation assistance device: A controlled interventional trial in healthy pigs.

Schmidt, Johannes / Wenzel, Christin / Mahn, Marlene / Spassov, Sashko / Cristina Schmitz, Heidi / Borgmann, Silke / Lin, Ziwei / Haberstroh, Jörg / Meckel, Stephan / Eiden, Sebastian / Wirth, Steffen / Buerkle, Hartmut / Schumann, Stefan

European journal of anaesthesiology

2018 Volume 35, Issue 10, Page(s) 736–744

Abstract: Background: In contrast to conventional mandatory ventilation, a new ventilation mode, expiratory ventilation assistance (EVA), linearises the expiratory tracheal pressure decline.: Objective: We hypothesised that due to a recruiting effect, ... ...

Abstract	Background: In contrast to conventional mandatory ventilation, a new ventilation mode, expiratory ventilation assistance (EVA), linearises the expiratory tracheal pressure decline. Objective: We hypothesised that due to a recruiting effect, linearised expiration oxygenates better than volume controlled ventilation (VCV). We compared the EVA with VCV mode with regard to gas exchange, ventilation volumes and pressures and lung aeration in a model of peri-operative mandatory ventilation in healthy pigs. Design: Controlled interventional trial. Setting: Animal operating facility at a university medical centre. Animals: A total of 16 German Landrace hybrid pigs. Intervention: The lungs of anaesthetised pigs were ventilated with the EVA mode (n=9) or VCV (control, n=7) for 5 h with positive end-expiratory pressure of 5 cmH2O and tidal volume of 8 ml kg. The respiratory rate was adjusted for a target end-tidal CO2 of 4.7 to 6 kPa. Main outcome measures: Tracheal pressure, minute volume and arterial blood gases were recorded repeatedly. Computed thoracic tomography was performed to quantify the percentages of normally and poorly aerated lung tissue. Results: Two animals in the EVA group were excluded due to unstable ventilation (n=1) or unstable FiO2 delivery (n=1). Mean tracheal pressure and PaO2 were higher in the EVA group compared with control (mean tracheal pressure: 11.6 ± 0.4 versus 9.0 ± 0.3 cmH2O, P < 0.001 and PaO2: 19.2 ± 0.7 versus 17.5 ± 0.4 kPa, P = 0.002) with comparable peak inspiratory tracheal pressure (18.3 ± 0.9 versus 18.0 ± 1.2 cmH2O, P > 0.99). Minute volume was lower in the EVA group compared with control (5.5 ± 0.2 versus 7.0 ± 1.0 l min, P = 0.02) with normoventilation in both groups (PaCO2 5.4 ± 0.3 versus 5.5 ± 0.3 kPa, P > 0.99). In the EVA group, the percentage of normally aerated lung tissue was higher (81.0 ± 3.6 versus 75.8 ± 3.0%, P = 0.017) and of poorly aerated lung tissue lower (9.5 ± 3.3 versus 15.7 ± 3.5%, P = 0.002) compared with control. Conclusion: EVA ventilation improves lung aeration via elevated mean tracheal pressure and consequently improves arterial oxygenation at unaltered positive end-expiratory pressure (PEEP) and peak inspiratory pressure (PIP). These findings suggest the EVA mode is a new approach for protective lung ventilation.
MeSH term(s)	Animals ; Exhalation/physiology ; Lung/physiology ; Positive-Pressure Respiration/instrumentation ; Positive-Pressure Respiration/trends ; Respiratory Mechanics/physiology ; Swine ; Ventilators, Mechanical/trends
Language	English
Publishing date	2018-05-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605770-6
ISSN	1365-2346 ; 0265-0215
ISSN (online)	1365-2346
ISSN	0265-0215
DOI	10.1097/EJA.0000000000000819
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