scholarly journals Metabolic regulation of species-specific developmental rates

2021 ◽  
Author(s):  
Margarete Diaz-Cuadros ◽  
Teemu P Miettinen ◽  
Dylan Sheedy ◽  
Carlos Manlio Diaz-Garcia ◽  
Svetlana Gapon ◽  
...  

Animals display significant inter-specific variation in the rate of embryonic development despite broad conservation of the overall sequence of developmental events. Differences in biochemical reaction speeds, including the rates of protein production and degradation, are thought to be responsible for distinct species-specific rates of development. However, the cause of differential biochemical reaction speeds between species remains unknown. Using pluripotent stem cells, we have established an in vitro system that recapitulates the two-fold difference in developmental rate between early mouse and human embryos. This system provides a quantitative measure of developmental speed as revealed by the period of the segmentation clock, a molecular oscillator associated with the rhythmic production of vertebral precursors. Using this system, we showed that mass-specific metabolic rates scale with developmental rate and are therefore elevated in mouse cells compared to human cells. We further showed that reducing these metabolic rates by pharmacologically inhibiting the electron transport chain slows down the segmentation clock. The effect of the electron transport chain on the segmentation clock is mediated by the cellular NAD+/NADH redox balance independent of ATP production and, further downstream, by the global rate of protein synthesis. These findings represent a starting point for the manipulation of developmental rate, which would find multiple translational applications including the acceleration of human pluripotent stem cell differentiation for disease modeling and cell-based therapies.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1318.2-1318
Author(s):  
H. R. Lee ◽  
S. J. Yoo ◽  
J. Kim ◽  
I. S. Yoo ◽  
C. K. Park ◽  
...  

Background:Reactive oxygen species (ROS) and T helper 17 (TH17) cells have been known to play an important role in the pathogenesis of rheumatoid arthritis (RA). However, the interrelationship between ROS and TH17 remains unclear in RAObjectives:To explore whether ROS affect TH17 cells in peripheral blood mononuclear cells (PBMC) of RA patients, we analyzed ROS expressions among T cell subsets following treatment with mitochondrial electron transport chain complex inhibitors.Methods:Blood samples were collected from 40 RA patients and 10 healthy adult volunteers. RA activity was divided according to clinical parameter DAS28. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. Following PBMC was stained with Live/Dead stain dye, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. After fixation and permeabilization, samples were stained with antibodies for FoxP3 and IL-17A. MitoSox were used for mitochondrial specific staining.Results:The frequency of TH17 cells was increased by 4.83 folds in moderate disease activity group (5.1>DAS28≥3.2) of RA patients compared to healthy control. Moderate RA activity patients also showed higher ratio of TH17/Treg than healthy control (3.57 folds). All RA patients had elevated expression of mitochondrial specific ROS than healthy control. When PBMC cells were treated with 2.5uM of antimycin A (mitochondrial electron transport chain complex III inhibitor) for 16 h, the frequency of TH17 cells was significantly decreased.Conclusion:The mitochondrial electron transport chain complex III inhibitor markedly downregulated the frequency of TH17 cells in moderate disease activity patients with RA. These findings provide a novel approach to regulate TH17 function in RA through mitochondrial metabolism related ROS production.References:[1]Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p. 13-9.[2]Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p. 44-8.Disclosure of Interests:None declared


Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 276
Author(s):  
Wanying Chen ◽  
Bo Jia ◽  
Junyu Chen ◽  
Yujiao Feng ◽  
Yue Li ◽  
...  

The mutual shading among individual field-grown maize plants resulting from high planting density inevitably reduces leaf photosynthesis, while regulating the photosynthetic transport chain has a strong impact on photosynthesis. However, the effect of high planting density on the photosynthetic electron transport chain in maize currently remains unclear. In this study, we simultaneously measured prompt chlorophyll a fluorescence (PF), modulated 820 nm reflection (MR) and delayed chlorophyll a fluorescence (DF) in order to investigate the effect of high planting density on the photosynthetic electron transport chain in two maize hybrids widely grown in China. PF transients demonstrated a gradual reduction in their signal amplitude with increasing planting density. In addition, high planting density induced positive J-step and G-bands of the PF transients, reduced the values of PF parameters PIABS, RC/CSO, TRO/ABS, ETO/TRO and REO/ETO, and enhanced ABS/RC and N. MR kinetics showed an increase of their lowest point with increasing high planting density, and thus the values of MR parameters VPSI and VPSII-PSI were reduced. The shapes of DF induction and decay curves were changed by high planting density. In addition, high planting density reduced the values of DF parameters I1, I2, L1 and L2, and enhanced I2/I1. These results suggested that high planting density caused harm on multiple components of maize photosynthetic electron transport chain, including an inactivation of PSII RCs, a blocked electron transfer between QA and QB, a reduction in PSI oxidation and re-reduction activities, and an impaired PSI acceptor side. Moreover, a comparison between PSII and PSI activities demonstrated the greater effect of plant density on the former.


2021 ◽  
Author(s):  
Jong Hyun Kim ◽  
Samuel Ofori ◽  
Sean Parkin ◽  
Hemendra Vekaria ◽  
Patrick G. Sullivan ◽  
...  

Expanding the chemical diversity of metal complexes provides a robust platform to generate functional bioactive reagents.


2021 ◽  
pp. 0271678X2110041
Author(s):  
Jesse A Stokum ◽  
Bosung Shim ◽  
Weiliang Huang ◽  
Maureen Kane ◽  
Jesse A Smith ◽  
...  

The perivascular astrocyte endfoot is a specialized and diffusion-limited subcellular compartment that fully ensheathes the cerebral vasculature. Despite their ubiquitous presence, a detailed understanding of endfoot physiology remains elusive, in part due to a limited understanding of the proteins that distinguish the endfoot from the greater astrocyte body. Here, we developed a technique to isolate astrocyte endfeet from brain tissue, which was used to study the endfoot proteome in comparison to the astrocyte somata. In our approach, brain microvessels, which retain their endfoot processes, were isolated from mouse brain and dissociated, whereupon endfeet were recovered using an antibody-based column astrocyte isolation kit. Our findings expand the known set of proteins enriched at the endfoot from 10 to 516, which comprised more than 1/5th of the entire detected astrocyte proteome. Numerous critical electron transport chain proteins were expressed only at the endfeet, while enzymes involved in glycogen storage were distributed to the somata, indicating subcellular metabolic compartmentalization. The endfoot proteome also included numerous proteins that, while known to have important contributions to blood-brain barrier function, were not previously known to localize to the endfoot. Our findings highlight the importance of the endfoot and suggest new routes of investigation into endfoot function.


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