cell compartments
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2022 ◽  
Vol 119 (3) ◽  
pp. e2108540119
Author(s):  
Abdouramane Camara ◽  
Alice C. Lavanant ◽  
Jun Abe ◽  
Henri Lee Desforges ◽  
Yannick O. Alexandre ◽  
...  

CD169+ macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169+ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTβ) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTβR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTβR revealed that both receptors contribute equally to LN CD169+ macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8+ T cells. Taken together, the data provide evidence that CD169+ macrophage differentiation in LN and spleen requires dual signals from LTβR and RANK with implications for the immune response.


2022 ◽  
Author(s):  
Vadim Warshavsky ◽  
Marcelo Marucho

The ability of actins and tubulins to change dynamically from alterations in the number density of actins/tubulin, number density and type of binding agents, and electrolyte concentration is crucial for eukaryotic cells to regulate their cytoskeleton conformations in different cellular compartments. Conventional approaches on biopolymers solution break down for cytoskeleton filaments because they entail several approximations to treat their polyelectrolyte and mechanical properties. In this article, we introduce a novel density functional theory for polydisperse, semiflexible cytoskeleton filaments. The approach accounts for the equilibrium polymerization kinetics, length, and orientation filament distributions, as well as the electrostatic interaction between filaments and the electrolyte. This is essential for cytoskeleton polymerization in different cell compartments generating filaments of different lengths, sometimes long enough to become semiflexible. We characterized the thermodynamics properties of actin filaments in electrolyte aqueous solutions. We calculated the free energy, pressure, chemical potential, and second virial coefficient for each filament conformation. We also calculated the phase diagram of actin filaments solution and compared it with available experimental data.


2022 ◽  
Author(s):  
Ling Liu ◽  
Matthew T Buckley ◽  
Jaime M Reyes ◽  
Soochi Kim ◽  
Lei Tian ◽  
...  

Exercise has the ability to rejuvenate stem cells and improve tissue homeostasis and regeneration in aging animals. However, the cellular and molecular changes elicited by exercise have not been systematically studied across a broad range of cell types in stem cell compartments. To gain better insight into the mechanisms by which exercise affects niche and stem cell function, we subjected young and old mice to aerobic exercise and generated a single cell transcriptomic atlas of muscle, neural and hematopoietic stem cells with their niche cells and progeny. Complementarily, we also performed whole transcriptome analysis of single myofibers from these animals. We identified common and unique pathways that are compromised across these tissues and cell types in aged animals. We found that exercise has a rejuvenating effect on subsets of stem cells, and a profound impact in the composition and transcriptomic landscape of both circulating and tissue resident immune cells. Exercise ameliorated the upregulation of a number of inflammatory pathways as well as restored aspects of cell-cell communication within these stem cell compartments. Our study provides a comprehensive view of the coordinated responses of multiple aged stem cells and niche cells to exercise at the transcriptomic level.


immuneACCESS ◽  
2022 ◽  
Author(s):  
N Zeng ◽  
C Capelle ◽  
A Baron ◽  
T Kobayashi ◽  
S Cire ◽  
...  
Keyword(s):  
T Cell ◽  

Author(s):  
Carlos Enrich ◽  
Albert Lu ◽  
Francesc Tebar ◽  
Carles Rentero ◽  
Thomas Grewal

Membrane contact sites (MCS) are specialized small areas of close apposition between two different organelles that have led researchers to reconsider the dogma of intercellular communication via vesicular trafficking. The latter is now being challenged by the discovery of lipid and ion transfer across MCS connecting adjacent organelles. These findings gave rise to a new concept that implicates cell compartments not to function as individual and isolated entities, but as a dynamic and regulated ensemble facilitating the trafficking of lipids, including cholesterol, and ions. Hence, MCS are now envisaged as metabolic platforms, crucial for cellular homeostasis. In this context, well-known as well as novel proteins were ascribed functions such as tethers, transporters, and scaffolds in MCS, or transient MCS companions with yet unknown functions. Intriguingly, we and others uncovered metabolic alterations in cell-based disease models that perturbed MCS size and numbers between coupled organelles such as endolysosomes, the endoplasmic reticulum, mitochondria, or lipid droplets. On the other hand, overexpression or deficiency of certain proteins in this narrow 10–30 nm membrane contact zone can enable MCS formation to either rescue compromised MCS function, or in certain disease settings trigger undesired metabolite transport. In this “Mini Review” we summarize recent findings regarding a subset of annexins and discuss their multiple roles to regulate MCS dynamics and functioning. Their contribution to novel pathways related to MCS biology will provide new insights relevant for a number of human diseases and offer opportunities to design innovative treatments in the future.


2022 ◽  
Author(s):  
Cory A Perugino ◽  
Hang Liu ◽  
Jared Feldman ◽  
Blake M Hauser ◽  
Catherine Jacob-Dolan ◽  
...  

In previously unvaccinated and uninfected individuals, non-RBD SARS-CoV-2 spike specific B cells were prominent in two distinct, durable, resting, cross-reactive, preexisting switched memory B cell compartments. While pre-existing RBD-specific B cells were extremely rare in uninfected and unvaccinated individuals, these two preexisting switched memory B cell compartments were molded by vaccination and infection to become the primary source of RBD-specific B cells that are triggered by vaccine boosting. The frequency of wild-type RBD-binding memory B cells that cross-react with the Omicron variant RBD did not alter with boosting. In contrast, after a boost, B cells recognizing the full-length Omicron variant spike protein expanded, with pre-existing resting memory B cells differentiating almost quantitatively into effector B cell populations. B cells derived from ancient pre-existing memory cells and that recognize the full-length wild-type spike with the highest avidity after boosting are the B cells that also bind the Omicron variant spike protein.


Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1331
Author(s):  
Ana Bura ◽  
Antonija Jurak Begonja

Phosphoinositides (PIs) are phosphorylated membrane lipids that have a plethora of roles in the cell, including vesicle trafficking, signaling, and actin reorganization. The most abundant PIs in the cell are phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol-4-monophosphate (PI4P). The localization and roles of both PI(4,5)P2 and PI4P are well established, is the broadly accepted methodological approach for their immunocytochemical visualization in different cell compartments in several cell lines. However, not much is known about these PIs in platelets (PLTs), the smallest blood cells that detect vessel wall injury, activate, and stop the bleeding. Therefore, we sought to investigate the localization of PI(4,5)P2 and PI4P in resting and activated PLTs by antibody staining. Here, we show that the intracellular pools of PI(4,5)P2 and PI4P can be detected by the established staining protocol, and these pools can be modulated by inhibitors of OCRL phosphatase and PI4KIIIα kinase. However, although resting PLTs readily stain for the plasma membrane (PM) pools of PI(4,5)P2 and PI4P, just a few activated cells were stained with the established protocol. We show that optimized protocol allows for the visualization of PI(4,5)P2 and PI4P at PM in activated PLTs, which could also be modulated by OCRL and PI4KIIIα inhibitors. We conclude that PI(4,5)P2 and PI4P are more sensitive to lipid extraction by permeabilizing agents in activated than in resting human PLTs, which suggests their different roles during PLT activation.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2292
Author(s):  
Elizabeth R. Duke ◽  
Florencia A. T. Boshier ◽  
Michael Boeckh ◽  
Joshua T. Schiffer ◽  
E. Fabian Cardozo-Ojeda

Cytomegalovirus (CMV) causes significant morbidity and mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Whereas insights gained from mathematical modeling of other chronic viral infections such as HIV, hepatitis C, and herpes simplex virus-2 have aided in optimizing therapy, previous CMV modeling has been hindered by a lack of comprehensive quantitative PCR viral load data from untreated episodes of viremia in HCT recipients. We performed quantitative CMV DNA PCR on stored, frozen serum samples from the placebo group of participants in a historic randomized controlled trial of ganciclovir for the early treatment of CMV infection in bone marrow transplant recipients. We developed four main ordinary differential Equation mathematical models and used model selection theory to choose between 38 competing versions of these models. Models were fit using a population, nonlinear, mixed-effects approach. We found that CMV kinetics from untreated HCT recipients are highly variable. The models that recapitulated the observed patterns most parsimoniously included explicit, dynamic immune cell compartments and did not include dynamic target cell compartments, consistent with the large number of tissue and cell types that CMV infects. In addition, in our best-fitting models, viral clearance was extremely slow, suggesting severe impairment of the immune response after HCT. Parameters from our best model correlated well with participants’ clinical risk factors and outcomes from the trial, further validating our model. Our models suggest that CMV dynamics in HCT recipients are determined by host immune response rather than target cell limitation in the absence of antiviral treatment.


2021 ◽  
Author(s):  
◽  
Edward Kazimierz Mroczek

<p>A high temperature hydrogen electrode concentration cell based on a design published by Macdonald, Butler and Owen1, was constructed and used to study the following protolytic equilibria. Thermodynamic equilibrium constants were derived by the usual method of extrapolation to zero ionic strength. 1. The ionization of water at temperatures from 75 to 225 degrees C in 0.1, 0.3, 0.5 and 1.0 mol kg-1 KCl solution. pK degrees w = 7229.701 /T + 30.285logT - 85.007 2. The pH calibration of 0.01 and 0.05 mol kg-1 sodium tetraborate at temperatures from 75 to 250 degrees C in O.1, 0.3 and 0.5 mol kg-1 NaCl solution. 0.0l mol kg-1 Sodium Tetraborate Solution pH = -0.4830t1 + 5.5692t2 + 7.7167t3 + 8.6983 0.05 mol kg-1 Sodium Tetraborate Solution pH = -0.0455tl + 8.3987t2 + O.2123t3 8.8156 3. The second dissociation of sulphuric acid at temperatures from 75 to 225 degree C in 0.1, 0.3 and 0.5 mol kg-l KCl solution. pK degrees 2 = 5.3353t1 - 15.9518t2 - 111.4929t3 + 3.8458 pK degrees 2 = 6.1815t*1 + 12.7301t*2. + 3.0660 (up to 150 degrees C) Where the t1 to t3= and t*1 and t*2 are the Clark-Glew temperature variable terms at reference temperatures of 423.15 and 373.15 K respectively2. 4. The acid hydrolysis of K-feldspar to K-mica and quartz at a temperature of 225 degrees C. The determination of the hydrolysis equilibrium constant was limited to one temperature because of the very slow reaction rate at temperatures less than 300 degrees C. log(mK+/mH+) = 4.2 (at 225 degrees C) Where a comparison could be made, the results of this study agreed well with previously published work, with the exception of the second dissociation constant of sulphuric acid at temperatures above 150 degrees C. Accurate values for the molal dissociation constant of the KSO-4 ion pair are required at elevated temperatures before the pK degrees 2 results can be fully evaluated. This research was severely restricted by the unpredictable loss of electrical continuity between the two cell compartments at temperatures above 150 degrees C. The problem appeared to be associated with the non-wettability of the porous Teflon plug which formed the liquid junction.</p>


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