scholarly journals Physical and geometric determinants of transport in fetoplacental microvascular networks

2019 ◽  
Vol 5 (4) ◽  
pp. eaav6326 ◽  
Author(s):  
Alexander Erlich ◽  
Philip Pearce ◽  
Romina Plitman Mayo ◽  
Oliver E. Jensen ◽  
Igor L. Chernyavsky
Keyword(s):  
Mammalian Species ◽  
Blood Rheology ◽  
Maternal Blood ◽  
Exchange Capacity ◽  
Microvascular Networks ◽  
Terminal Villi ◽  
Function Relationship ◽  
And Function ◽  
Disordered Networks ◽  
Relationship Of

Across mammalian species, solute exchange takes place in complex microvascular networks. In the human placenta, the primary exchange units are terminal villi that contain disordered networks of fetal capillaries and are surrounded externally by maternal blood. We show how the irregular internal structure of a terminal villus determines its exchange capacity for diverse solutes. Distilling geometric features into three parameters, obtained from image analysis and computational fluid dynamics, we capture archetypal features of the structure-function relationship of terminal villi using a simple algebraic approximation, revealing transitions between flow- and diffusion-limited transport at vessel and network levels. Our theory accommodates countercurrent effects, incorporates nonlinear blood rheology, and offers an efficient method for testing network robustness. Our results show how physical estimates of solute transport, based on carefully defined geometrical statistics, provide a viable method for linking placental structure and function and offer a framework for assessing transport in other microvascular systems.

Structure and Function Relationship of Murine Insulin-like Peptide 5 (INSL5): Free C-Terminus Is Essential for RXFP4 Receptor Binding and Activation

Biochemistry ◽  
2011 ◽  
Vol 50 (39) ◽  
pp. 8352-8361 ◽  
Author(s):  
Alessia Belgi ◽  
Mohammed A. Hossain ◽  
Fazel Shabanpoor ◽  
Linda Chan ◽  
Suode Zhang ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structure And Function ◽  
C Terminus ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of

scholarly journals Structure-function studies of CrmK, an oxidase involved in Caerulomycin A biosynthesis

2014 ◽  
Vol 70 (a1) ◽  
pp. C1669-C1669
Author(s):  
Marie-Ève Picard ◽  
Julie Barma ◽  
Yiguang Zhu ◽  
Xavier Murphy Després ◽  
Jean-Baptiste Duvignaud ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Pocket ◽  
Antimicrobial Activities ◽  
Active Site Residues ◽  
Covalent Bonds ◽  
Protein Residues ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of

Caerulomycin A (CRM A) is an immunosupressive agent that has a unique 2,2'-bipyridine core structure. Isolated from a marine-derived Actinoalloteichus cyanogriseus, this natural product exhibits antifungal, anti-amoebic, antitumor, and antimicrobial activities. Its biosynthetic pathway consists of more than 20 enzymes, at least seven of which are putatively involved in post-PKS/NRPS modifications of the scaffold. Among these, CrmK is a flavin-dependent oxidase. We have determined the crystal structure of CrmK bound to its flavin adenin dinucleotide (FAD) cofactor at 1.9 Å resolution. FAD linkage to CrmK is observed via two covalent bonds with protein residues His64 and Cys124. This crystal structure, combined with the activity analysis of both wild-type CrmK and a series of mutants, has revealed the role of active site residues lining the substrate and FAD binding pocket. Our studies add additional molecular insights into the structure and function relationship of the bicovalently flavinylated oxidases.

scholarly journals Natural Mutations Affect Structure and Function of gC1q Domain of Otolin-1

2021 ◽  
Vol 22 (16) ◽  
pp. 9085
Author(s):  
Rafał Hołubowicz ◽  
Andrzej Ożyhar ◽  
Piotr Dobryszycki
Keyword(s):  
Wild Type ◽  
Positional Vertigo ◽  
Natural Variants ◽  
Self Association ◽  
Function Relationship ◽  
The Stability ◽  
And Function ◽  
Relationship Of ◽  
Wild Type Form ◽  
Paroxysmal Positional Vertigo

Otolin-1 is a scaffold protein of otoliths and otoconia, calcium carbonate biominerals from the inner ear. It contains a gC1q domain responsible for trimerization and binding of Ca2+. Knowledge of a structure–function relationship of gC1q domain of otolin-1 is crucial for understanding the biology of balance sensing. Here, we show how natural variants alter the structure of gC1q otolin-1 and how Ca2+ are able to revert some effects of the mutations. We discovered that natural substitutions: R339S, R342W and R402P negatively affect the stability of apo-gC1q otolin-1, and that Q426R has a stabilizing effect. In the presence of Ca2+, R342W and Q426R were stabilized at higher Ca2+ concentrations than the wild-type form, and R402P was completely insensitive to Ca2+. The mutations affected the self-association of gC1q otolin-1 by inducing detrimental aggregation (R342W) or disabling the trimerization (R402P) of the protein. Our results indicate that the natural variants of gC1q otolin-1 may have a potential to cause pathological changes in otoconia and otoconial membrane, which could affect sensing of balance and increase the probability of occurrence of benign paroxysmal positional vertigo (BPPV).

scholarly journals Assessment of cerebrovascular responses to physiological stimuli in identical twins using multimodal imaging and computational fluid dynamics

2020 ◽  
Vol 129 (5) ◽  
pp. 1024-1032
Author(s):  
Hannah J. Thomas ◽  
Usaid Rana ◽  
Channa E. Marsh ◽  
Harrison T. Caddy ◽  
Lachlan J. Kelsey ◽  
...  
Keyword(s):  
Multimodal Imaging ◽  
Fluid Dynamic ◽  
Monozygotic Twins ◽  
Structure And Function ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Genetically Determined ◽  
Relationship Of ◽  
Computational Fluid Dynamic Modeling

There is acknowledged variability in the Circle of Willis in the general population, yet the structure and function relationship of the cerebrovasculature is poorly understood. Using a combination of magnetic resonance imaging, high-resolution Doppler ultrasound, and computational fluid dynamic modeling, we show that monozygotic twins exhibit differences in cerebrovascular structure and function when exposed to physiological stimuli. These data suggest that the morphology, function, and health of cerebrovascular arteries are not primarily genetically determined.

Abstract 127: Structure and Function Relationship of Phospholipid Transfer Protein in Lipid Transfer Activity Revealed by Electron Microscopy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Meng Zhang
Keyword(s):  
Electron Microscopy ◽  
High Density Lipoproteins ◽  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Function Relationship ◽  
Structure And Function Relationship ◽  
And Function ◽  
Relationship Of

Human phospholipid transfer protein (PLTP) mediates the transfer of lipids among atheroprotective high-density lipoproteins (HDL) and atherogenic low-density lipoproteins (LDL) by an unknown mechanism. Delineating this mechanism would be an important step toward the understanding and regulation of PLTP for treating cardiovascular diseases, hypoalphalipoproteinemia and hyperalphalipoproteinemia. Using electron microscopy, negative-staining, and single-particle image processing, we discovered that PLTP penetrates each class of HDL, LDL and liposome independently, and also bridges a ternary complex with one of its distal end-domains penetrating into HDL and another distal domain interacting with LDL. These new insights into PLTP interaction with lipoproteins and liposomes provide a molecular basis for analyzing PLTP-dependent lipid transfer between lipoprotein particles.

Sign in / Sign up

Export Citation Format

Share Document