scholarly journals A Genome-Scale Insight into the Effect of Shear Stress During the Fed-Batch Production of Clavulanic Acid by Streptomyces Clavuligerus

2020 ◽  
Vol 8 (9) ◽  
pp. 1255
Author(s):  
David Gómez-Ríos ◽  
Victor A. López-Agudelo ◽  
Howard Ramírez-Malule ◽  
Peter Neubauer ◽  
Stefan Junne ◽  
...  
Keyword(s):  
Shear Stress ◽  
Clavulanic Acid ◽  
Streptomyces Clavuligerus ◽  
Oxygen Availability ◽  
Stress Conditions ◽  
Phosphate Limitation ◽  
A Genome ◽  
Low Shear Stress ◽  
Genome Scale ◽  
Low Shear

Streptomyces clavuligerus is a filamentous Gram-positive bacterial producer of the β-lactamase inhibitor clavulanic acid. Antibiotics biosynthesis in the Streptomyces genus is usually triggered by nutritional and environmental perturbations. In this work, a new genome scale metabolic network of Streptomyces clavuligerus was reconstructed and used to study the experimentally observed effect of oxygen and phosphate concentrations on clavulanic acid biosynthesis under high and low shear stress. A flux balance analysis based on experimental evidence revealed that clavulanic acid biosynthetic reaction fluxes are favored in conditions of phosphate limitation, and this is correlated with enhanced activity of central and amino acid metabolism, as well as with enhanced oxygen uptake. In silico and experimental results show a possible slowing down of tricarboxylic acid (TCA) due to reduced oxygen availability in low shear stress conditions. In contrast, high shear stress conditions are connected with high intracellular oxygen availability favoring TCA activity, precursors availability and clavulanic acid (CA) production.

scholarly journals Nucleolin mediates the binding of cancer cells to L-selectin under conditions of lymphodynamic shear stress

2020 ◽  
Vol 318 (1) ◽  
pp. C83-C93 ◽  
Author(s):  
Tovë M. Goldson ◽  
Kevin L. Turner ◽  
Yinan Huang ◽  
Grady E. Carlson ◽  
Emily G. Caggiano ◽  
...  
Keyword(s):  
Shear Stress ◽  
Affinity Purification ◽  
Stress Conditions ◽  
Dependent Manner ◽  
Force Microscopy ◽  
Selectin Ligands ◽  
Ligand Interactions ◽  
Low Shear Stress ◽  
Selectin Ligand ◽  
Low Shear

Head and neck squamous cell carcinoma (HNSCC) cells bind to lymphocytes via L-selectin in a shear-dependent manner. This interaction takes place exclusively under low-shear stress conditions, such as those found within the lymph node parenchyma. This represents a novel functional role for L-selectin-selectin ligand interactions. Our previous work has characterized as-of-yet unidentified L-selectin ligands expressed by HNSCC cells that are specifically active under conditions of low shear stress consistent with lymph flow. Using an affinity purification approach, we now show that nucleolin expressed on the surface of HNSCC cells is an active ligand for L-selectin. Parallel plate chamber flow-based experiments and atomic force microscopy (AFM) experiments show that nucleolin is the main functional ligand under these low-force conditions. Furthermore, AFM shows a clear relationship between work of deadhesion and physiological loading rates. Our results reveal nucleolin as the first major ligand reported for L-selectin that operates under low-shear stress conditions.

scholarly journals Characterization of the Metabolic Response of Streptomyces clavuligerus to Shear Stress in Stirred Tanks and Single-Use 2D Rocking Motion Bioreactors for Clavulanic Acid Production

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 168 ◽  
Author(s):  
David Gómez-Ríos ◽  
Stefan Junne ◽  
Peter Neubauer ◽  
Silvia Ochoa ◽  
Rigoberto Ríos-Estepa ◽  
...  
Keyword(s):  
Shear Stress ◽  
Clavulanic Acid ◽  
Metabolic Response ◽  
Streptomyces Clavuligerus ◽  
High Shear ◽  
Shear Forces ◽  
Rocking Motion ◽  
Single Use ◽  
The Impact ◽  
Low Shear

Streptomyces clavuligerus is a gram-positive filamentous bacterium notable for producing clavulanic acid (CA), an inhibitor of β-lactamase enzymes, which confers resistance to bacteria against several antibiotics. Here we present a comparative analysis of the morphological and metabolic response of S. clavuligerus linked to the CA production under low and high shear stress conditions in a 2D rocking-motion single-use bioreactor (CELL-tainer ®) and stirred tank bioreactor (STR), respectively. The CELL-tainer® guarantees high turbulence and enhanced volumetric mass transfer at low shear stress, which (in contrast to bubble columns) allows the investigation of the impact of shear stress without oxygen limitation. The results indicate that high shear forces do not compromise the viability of S. clavuligerus cells; even higher specific growth rate, biomass, and specific CA production rate were observed in the STR. Under low shear forces in the CELL-tainer® the mycelial diameter increased considerably (average diameter 2.27 in CELL-tainer® vs. 1.44 µm in STR). This suggests that CA production may be affected by a lower surface-to-volume ratio which would lead to lower diffusion and transport of nutrients, oxygen, and product. The present study shows that there is a strong correlation between macromorphology and CA production, which should be an important aspect to consider in industrial production of CA.

scholarly journals Restoring vascular endothelial autophagic flux reduces atherosclerotic lesions

2021 ◽  
Author(s):  
Shruti Chatterjee ◽  
Marouane Kheloufi ◽  
Stephane M.I Mazlan ◽  
Xavier Loyer ◽  
Timothy A. McKinsey ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Stress Conditions ◽  
Intercellular Adhesion Molecule ◽  
Autophagic Flux ◽  
Histone Deacetylase 6 ◽  
Tubulin Acetylation ◽  
Atherosclerotic Lesions ◽  
Low Shear Stress ◽  
Low Shear

Atherosclerotic lesions preferentially develop in arterial areas exposed to low shear stress, where endothelial cells express a pro-inflammatory, apoptotic, and senescent phenotype. Autophagy is a lysosomal mechanism that recycles damaged organelles and protein aggregates to maintain cellular homeostasis. Stimulation of autophagy in high shear stress conditions is an atheroprotective process. Conversely, endothelial cells exposed to atheroprone low shear stress present a defective autophagic flux, which favors a pro-inflammatory phenotype and the formation of atherosclerotic lesions. Since an efficient autophagic flux is dependent on α-tubulin acetylation, which is reduced under low shear stress, we hypothesized that increasing α-tubulin acetylation could restore adequate levels of autophagy in endothelial cells exposed to low shear stress. We found that blocking Histone Deacetylase 6 (HDAC6) activity, either by pharmacological inhibition (Tubastatin-A) or genetic approaches (shHDAC6), raised levels of acetylated α-tubulin, as well as LC3-II/I ratio, LC3 punctae area and autophagic flux in cultured endothelial cells exposed to low shear stress. This effect was associated with a reduced expression of inflammatory markers (Intercellular adhesion molecule-1 (ICAM-1), Vascular cell Adhesion Protein-1 (VCAM-1) and Monocyte Chemoattractant Protein-1 (MCP-1)) in Tumor Necrosis Factor-alpha (TNF-α)-stimulated cells. We observed increased endothelial autophagic flux in the aortic arch of the HDAC6-/-/ApoE-/- mice. Subsequently, atherosclerotic plaque size was significantly reduced in the atheroprone areas of chimeric HDAC6-/-/ApoE-/- mice, transplanted with HDAC6+/+/ApoE-/- bone marrow, when compared to HDAC6+/+/ApoE-/- littermate controls. Taken together, these results indicate that targeting α-tubulin acetylation, via HDAC6-inhibition, may be an interesting strategy to restore endothelial autophagic flux and to promote an atheroprotective endothelial phenotype despite unfavorable shear stress conditions.

Low shear stress-induced endothelial mesenchymal transformation via the down-regulation of TET2

2021 ◽  
Vol 545 ◽  
pp. 20-26
Author(s):  
AFang Li ◽  
LiLan Tan ◽  
ShuLei Zhang ◽  
Jun Tao ◽  
Zuo Wang ◽  
...  
Keyword(s):  
Shear Stress ◽  
Down Regulation ◽  
Low Shear Stress ◽  
Mesenchymal Transformation ◽  
Low Shear

Plaque and Shear Stress Distribution in Human Coronary Bifurcations: a Multi-Slice Computed Tomography Study

2007 ◽  
Author(s):  
Alina G. van der Giessen ◽  
Jolanda J. Wentzel ◽  
Frans N. van de Vosse ◽  
Antonius F. van der Steen ◽  
Pim J. de Feyter ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Shear Stress ◽  
Outer Wall ◽  
Atherosclerotic Plaques ◽  
Advanced Stage ◽  
Flow Divider ◽  
Low Shear Stress ◽  
Curved Vessels ◽  
Early Atherosclerosis ◽  
Low Shear

It is generally accepted that early atherosclerosis develops in low shear-stress (SS) regions such as the outer wall of arterial bifurcations and the inner bend of curved vessels (1). However, in clinical practice, it is common to observe atherosclerotic plaques at the flow-divider, or carina, of coronary bifurcations (2). Plaques at the carina are more frequently found in symptomatic patients, and may represent a more advanced stage of atherosclerosis. The carina is located in a region which is exposed to high SS. We hypothesize that if plaques are located in atheroprotective high SS regions, they have grown circumferentially from the atherogenic low SS regions.

CXCR4 expression in atherosclerotic lesions induced by low shear stress

2008 ◽  
Vol 32 (3) ◽  
pp. S18-S19
Author(s):  
Dang Heng Wei ◽  
Gui Xue Wang ◽  
Yi Ping Xia ◽  
Jian Jun Lei ◽  
Lu Shang Liu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cxcr4 Expression ◽  
Atherosclerotic Lesions ◽  
Low Shear Stress ◽  
Low Shear

scholarly journals Low Shear Stress Induced HMGB1 Translocation and Release via PECAM-1/PARP-1 Pathway to Induce Inflammation Response

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120586 ◽  
Author(s):  
Wei-dong Qin ◽  
Shao-hua Mi ◽  
Chen Li ◽  
Gui-xia Wang ◽  
Jian-ning Zhang ◽  
...  
Keyword(s):  
Shear Stress ◽  
Inflammation Response ◽  
Low Shear Stress ◽  
Parp 1 ◽  
Low Shear
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