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2021 ◽  
Author(s):  
Joonhyuk Choi ◽  
Shuhao Wang ◽  
Yang Li ◽  
Nan Hao ◽  
Brian M Zid

Aging is an irreversible process characterized by a progressive loss of homeostasis in cells, which often manifests as protein aggregates. Recently, it has been speculated that aggregates of RNA-binding proteins (RBPs) may go through pathological transitions during aging and drive the progression of age-associated neurodegenerative diseases. Using Saccharomyces cerevisiae as a model system of aging, we find that P-bodies - an RBP granule that is formed and can be beneficial for cell growth during stress conditions - naturally form during aging without any external stresses and an increase in P-body intensity is negatively correlated with the future lifespan of yeast cells. When mother cells transfer age-induced P-bodies to daughter cells, the mother cells extend lifespan, while the daughter cells grow poorly, suggesting that these age-induced P-bodies may be directly pathological. Furthermore, we find that suppressing acidification of the cytosol during aging slows down the increase in the intensity of P-body foci and extends lifespan. Our data suggest that acidification of the cytosol may facilitate the pathological transition of RBP granules during aging.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhaolin Xue ◽  
Weizhen Wang ◽  
Jinghuan Shen ◽  
Jinhui Zhang ◽  
Xitao Zhang ◽  
...  

Patched (Ptc) and Patched-related (Ptr) proteins containing sterol-sensing domains (SSD) and Patched domains are highly conserved in eukaryotes for lipid transport and metabolism. Four proteins containing predicted SSD and Patched domains were simultaneously found by searching the Phytophthora sojae genome database, and one of them was identified as a Patched-like (PTL) protein. Here, we investigated the biological function of PsPTL. The expression level of PsPTL was higher during mycelial and sporulation stages, compared to zoospore (ZO), cyst, and germinated-cyst stages, without significant change during infection. However, deletion of PsPTL using CRISPR/Cas9 had no significant effect on the growth, development, or virulence of P. sojae. Further investigations showed that PsPTL is not essential for P. sojae to cope with external stresses such as temperature, pH, oxidative and osmotic pressure. In addition, this gene did not appear to play an essential role in P. sojae’s response to exogenous sterols. The transcript levels of the other three proteins containing predicted SSD and Patched domains were also not significantly upregulated in PsPTL deletion transformants. Our studies demonstrated that PsPTL is not an essential protein for P. sojae under the tested conditions, and more in-depth research is required for revealing the potential functions of PsPTL under special conditions or in other signaling pathways.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shahaf Armon ◽  
Matthew S. Bull ◽  
Avraham Moriel ◽  
Hillel Aharoni ◽  
Manu Prakash

AbstractConfluent epithelial tissues can be viewed as soft active solids, as their individual cells contract in response to local conditions. Little is known about the emergent properties of such materials. Empirical observations have shown contraction waves propagation in various epithelia, yet the governing mechanism, as well as its physiological function, is still unclear. Here we propose an experiment-inspired model for such dynamic epithelia. We show how the widespread cellular response of contraction-under-tension is sufficient to give rise to propagating contraction pulses, by mapping numerically and theoretically the consequences of such a cellular response. The model explains observed phenomena but also predicts enhanced rip-resistance as an emergent property of such cellular sheets. Unlike healing post-rupture, these sheets avoid it by actively re-distributing external stresses across their surface. The mechanism is relevant to a broad class of tissues, especially such under challenging mechanical conditions, and may inspire engineering of synthetic materials.


2021 ◽  
Author(s):  
Stefan Schulze ◽  
Heather Schiller ◽  
Jordan Solomonic ◽  
Orkan Telhan ◽  
Kyle Costa ◽  
...  

AbstractMost microorganisms exist in biofilms, which comprise aggregates of cells surrounded by an extracellular matrix that provides protection from external stresses. Based on the conditions under which they form, biofilm structures vary in significant ways. For instance, biofilms that develop when microbes are incubated under static conditions differ from those formed when microbes encounter the shear forces of a flowing liquid. Moreover, biofilms develop dynamically over time. Here, we describe a cost-effective, 3D-printed coverslip holder that facilitates surface adhesion assays under a broad range of standing and shaking culture conditions. This multi-panel adhesion (mPAD) mount further allows cultures to be sampled at multiple time points, ensuring consistency and comparability between samples and enabling analyses of the dynamics of biofilm formation. As a proof of principle, using the mPAD mount for shaking, oxic cultures, we confirm previous flow chamber experiments showing that Pseudomonas aeruginosa wild type and a phenazine deletion mutant (Δphz) form similar biofilms. Extending this analysis to anoxic conditions, we reveal that microcolony and biofilm formation can only be observed under shaking conditions and are decreased in the Δphz mutant compared to wild-type cultures, indicating that phenazines are crucial for the formation of biofilms if oxygen as an electron acceptor is not available. Furthermore, while the model archaeon Haloferax volcanii does not require archaella for attachment to surfaces under static conditions, we demonstrate that H. volcanii mutants that lack archaella are negatively affected in their early stages of biofilm formation under shaking conditions.ImportanceDue to the versatility of the mPAD mount, we anticipate that it will aid the analysis of biofilm formation in a broad range of bacteria and archaea. Thereby, it contributes to answering critical biological questions about the regulatory and structural components of biofilm formation and understanding this process in a wide array of environmental, biotechnological, and medical contexts.


Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5409 ◽  
Author(s):  
Ji Yeon Choi ◽  
Ji-Eun Bae ◽  
Joon Bum Kim ◽  
Doo Sin Jo ◽  
Na Yeon Park ◽  
...  

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.


Horticulturae ◽  
2021 ◽  
Vol 7 (8) ◽  
pp. 204
Author(s):  
Yongzan Wei ◽  
Huayuan Mu ◽  
Guangzhao Xu ◽  
Yi Wang ◽  
Yang Li ◽  
...  

Grape (Vitis vinifera) produces a variety of secondary metabolites, which can enhance nutrients and flavor in fruit and wine. Uridine diphosphate-glycosyltransferases (UGTs) are primarily responsible for the availability of secondary metabolites by glycosylation modification. Here, a total of 228 putative UGTs were identified in V. vinifera, and VvUGTs were clustered into 15 groups (A to O) and unevenly distributed on 18 chromosomes. Diverse VvUGT members from 12 groups were transcribed, and they responded to different external stresses. More than 72% of VvUGT members were expressed at one or more stages of grape fruit development, and the expression levels of 34 VvUGT members increased gradually with fruit ripening. The VvUGT members of different groups may be involved in the synthesis and accumulation of flavonoid glycosides, glycosidically bound volatiles, and stilbenes. These results will provide guidance for further research on the functions and regulating mechanisms of UGT genes.


Metals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1142
Author(s):  
S. V. Sajadifar ◽  
P. Krooß ◽  
H. Fröck ◽  
B. Milkereit ◽  
O. Kessler ◽  
...  

In the present study, microstructural and mechanical properties of EN AW 7075 following stress-aging were assessed. For this purpose, properties of stress-aged samples were compared with values obtained for conventionally aged counterparts. It is revealed that the strength and hardness of EN AW 7075 can be increased by the presence of external stresses during aging. Precipitation kinetics were found to be accelerated. The effects of conventional and stress-aging on the microstructure were analyzed using synergetic techniques: the differently aged samples were probed by differential scanning calorimetry (DSC) in order to characterize the precipitation processes. DSC was found to be an excellent screening tool for the analysis of precipitation processes during aging of this alloy with and without the presence of external stresses. Furthermore, using electron microscopy it was revealed that an improvement in mechanical properties can be correlated to changes in the morphologies and sizes of precipitates formed.


Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1408
Author(s):  
Adrianna Wiktoria Bara ◽  
Agnieszka Braszewska ◽  
Jolanta Kwasniewska

The chromatin structure is significantly influenced by some epigenetic modifications including DNA methylation. The nuclear organization plays an essential role in the cell response to external stresses including mutagens. We present an analysis of the correlation between epigenetic modifications and the instability of the Brachypodium distachyon genome, which are observed as micronuclei, following maleic hydrazide (MH) and nitroso-N-methylurea (MNU) treatments. We compared the level of DNA methylation in the control (untreated) and mutagen-treated B. distachyon nuclei. An immunostaining method using specific antibodies against modified DNA anti-5-methylcytosine was used for the evaluation of DNA methylation in a single nucleus and micronucleus. Interestingly, we showed an alteration of DNA methylation in cells after mutagenic treatments. The results indicate that DNA methylation might be involved in the response of the B. distachyon genome to mutagenic treatments. This demonstrates that analyses of the epigenetic modifications should be integrated into current plant genetic toxicology in order to explain the mechanisms of DNA damage and repair in plants.


2021 ◽  
Author(s):  
Li Ren ◽  
Yi-Ping Hou ◽  
Yuanye Zhu ◽  
Fei-Fei Zhao ◽  
Yabing Duan ◽  
...  

Trehalase is considered the main target of the biological fungicide validamycin A, and toxicology mechanism of validamycin A is unknown. 14-3-3 proteins, highly conserved proteins, participate in diverse cellular processes, including enzyme activation, protein localization and molecular chaperone. In Saccharomyces cerevisiae, the 14-3-3 protein Bmh1could interact with Nth1 to respond specific external stimuli. Here, we characterized FgNth, FgBmh1, and FgBmh2 in Fusarium graminearum. ΔFgNth, ΔFgBmh1, and ΔFgBmh2 displayed great growth defects when compared to wild-type PH-1. When exposed to validamycin A, high osmotic and high temperature stresses, ΔFgNth, ΔFgBmh1, and ΔFgBmh2 showed more tolerance than WT. Both ΔFgNth and ΔFgBmh1 displayed reduced deoxynivalenol (DON) production but opposite for ΔFgBmh2, and all three deletion mutants showed reduced virulence on wheat coleoptiles. In addition, Co-immunoprecipitation (Co-IP) experiments suggested that FgBmh1 and FgBmh2 both interact with FgNth, but no interaction was detected between FgBmh1 and FgBmh2 in our experiments. Further, validamycin A enhances the interaction between FgBmh1 and FgNth in a positive correlation under concentrations of 1-100μg/mL. Besides, both high osmotic and high temperature stresses promote the interaction between FgBmh1 and FgNth. Co-IP assay also showed that neither FgBmh1 nor FgBmh2 could interact with FgPbs2, a MAPKK kinase in the high-osmolarity glycerol (HOG) pathway. However, FgBmh2 but not FgBmh1 binds to the heat shock protein FgHsp70 in F. graminearum. Taken together, our results demonstrate that FgNth and FgBmhs are involved in growth, responces to external stresses and virulence, and validamycin A enhanced the interaction between FgNth and FgBmh1in F. graminearum.


2021 ◽  
Vol 2 (3) ◽  
pp. 27-33
Author(s):  
Nina VRYNCHANU ◽  
Yurii KOROTKIJ ◽  
Nataliia HRYNCHUK ◽  
Irina BOIKO ◽  
Elena SMERTENKO ◽  
...  

Introduction. The microbial biofilm-forming ability is one of the major aspects of the emerging issue of antibiotic resistance, which makes them tolerant to antibiotics and host defense systems and other external stresses, thus contributing to persistent chronic infections. A series of relevant studies confirmed the high efficiency of aminopropanol derivatives as potential antibacterial and antifungal agents. This present study was aimed to evaluate the antimicrobial activity of new 1-[(2,4-(di-tert-butylphenoxy))-3-dialkylamino-2-propanol] derivatives on the planktonic bacterial/fungal cells and biofilms. Material and methods. The minimum inhibitory concentrations (MIC) of the new compounds were determined by a standard method, along with their effects on biofilms estimated via the gentian violet adsorption-desorption assay.Results. The КVM-219 compound showed the most pronounced effect on planktonic bacterial and fungal cells. The MIC values ranged between 0.78 μg/mL to 12.5 μg/mL, depending on the microbial strain. The KVM-316 compound exhibited the strongest inhibitory effect on biofilms, thus preventing their formation by S. aureus (96.1%), E. coli (57.2%), and P. aeruginosa (96.1%). Conclusions. The 15 newly synthesized 1-[(2,4-(di-tert-butylphenoxy))-3-dialkylamino-2-propanol] derivatives revealed marked antibacterial and antifungal effects on planktonic microorganisms. Most of these compounds showed a strain-specific inhibition of biofilm formation by at least 50% for S. aureus 222, E. coli 311, P. aeruginosa 449 and C. glabrata 404 strains.


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