The article is dedicated to analysis of the existing calculation methods of thermalphysic characteristics of steel of different chemical composition depending on temperature and development of new ...methods for determination of actual heat capacity of the carbon types of steel.
A common feature of neurodegenerative disorders, in particular Alzheimer's disease (AD), is a chronic neuroinflammation associated with aberrant neuroplasticity. Development of neuroinflammation ...affects efficacy of stem and progenitor cells proliferation, differentiation, migration, and integration of newborn cells into neural circuitry. However, precise mechanisms of neurogenesis alterations in neuroinflammation are not clear yet. It is well established that expression of NLRP3 inflammasomes in glial cells marks neuroinflammatory events, but less is known about contribution of NLRP3 to deregulation of neurogenesis within neurogenic niches and whether neural stem cells (NSCs), neural progenitor cells (NPCs) or immature neuroblasts may express inflammasomes in (patho)physiological conditions. Thus, we studied alterations of neurogenesis in rats with the AD model (intra-hippocampal injection of Aβ1-42). We found that in Aβ-affected brain, number of CD133+ cells was elevated after spatial training in the Morris water maze. The number of PSA-NCAM+ neuroblasts diminished by Aβ injection was completely restored by subsequent spatial learning. Spatial training leads to elevated expression of NLRP3 inflammasomes in the SGZ (subgranular zones): CD133+ and PSA-NCAM+ cells started to express NLRP3 in sham-operated, but not AD rats. Taken together, our data suggest that expression of NLRP3 inflammasomes in CD133+ and PSA-NCAM+ cells may contribute to stimulation of adult neurogenesis in physiological conditions, whereas Alzheimer’s type neurodegeneration abolishes stimuli-induced overexpression of NLRP3 within the SGZ neurogenic niche.
Blood-brain barrier (BBB) modeling
is a huge area of research covering study of intercellular communications and development of BBB, establishment of specific properties that provide controlled ...permeability of the barrier. Current approaches in designing new BBB models include development of new (bio) scaffolds supporting barriergenesis/angiogenesis and BBB integrity; use of methods enabling modulation of BBB permeability; application of modern analytical techniques for screening the transfer of metabolites, bio-macromolecules, selected drug candidates and drug delivery systems; establishment of 3D models; application of microfluidic technologies; reconstruction of microphysiological systems with the barrier constituents. Acceptance of idea that BBB
models should resemble real functional activity of the barrier in different periods of ontogenesis and in different (patho) physiological conditions leads to proposal that establishment of BBB
model with alterations specific for aging brain is one of current challenges in neurosciences and bioengineering. Vascular dysfunction in the aging brain often associates with leaky BBB, alterations in perivascular microenvironment, neuroinflammation, perturbed neuronal and astroglial activity within the neurovascular unit, impairments in neurogenic niches where microvascular scaffold plays a key regulatory role. The review article is focused on aging-related alterations in BBB and current approaches to development of "aging" BBB models
.
Members of the Bcl-2 family of proteins regulate apoptosis, with some of their physiological effects mediated by their modulation of endoplasmic reticulum (ER) Ca²⁺ homeostasis. Antiapoptotic Bcl-xL ...binds to the inositol trisphosphate receptor (InsP₃R) Ca²⁺ release channel to enhance Ca²⁺- and InsP₃-dependent regulation of channel gating, resulting in reduced ER Ca²⁺, increased oscillations of cytoplasmic Ca²⁺ concentration (Ca²⁺i), and apoptosis resistance. However, it is controversial which InsP₃R isoforms mediate these effects and whether reduced ER Ca²⁺ or enhanced Ca²⁺i signaling is most relevant for apoptosis protection. DT40 cell lines engineered to express each of the three mammalian InsP₃R isoforms individually displayed enhanced apoptosis sensitivity compared with cells lacking InsP₃R. In contrast, coexpression of each isoform with Bcl-xL conferred enhanced apoptosis resistance. In single-channel recordings of channel gating in native ER membranes, Bcl-xL increased the apparent sensitivity of all three InsP₃R isoforms to subsaturating levels of InsP₃. Expression of Bcl-xL reduced ER Ca²⁺ in type 3 but not type 1 or 2 InsP₃R-expressing cells. In contrast, Bcl-xL enhanced spontaneous Ca²⁺i signaling in all three InsP₃R isoform-expressing cell lines. These results demonstrate a redundancy among InsP₃R isoforms in their ability to sensitize cells to apoptotic insults and to interact with Bcl-xL to modulate their activities that result in enhanced apoptosis resistance. Furthermore, these data suggest that modulation of ER Ca²⁺ is not a specific requirement for ER-dependent antiapoptotic effects of Bcl-xL. Rather, apoptosis protection is conferred by enhanced spontaneous Ca²⁺i signaling by Bcl-xL interaction with all isoforms of the InsP₃R.
Objective
This study questions whether increased dopamine (DA) turnover in nigral neurons leads to formation of Lewy bodies (LBs), the characteristic α‐synuclein–containing cytoplasmic inclusion of ...Parkinson disease (PD).
Methods
Mice with targeted deletion of the dopamine D2 receptor gene (D2R−/−) have higher striatal and nigral dopamine turnover and elevated oxidative stress. These mice were examined for evidence of histological, biochemical, and gene expression changes consistent with a synucleinopathy.
Results
LB‐like cytoplasmic inclusions containing α‐synuclein and ubiquitin were present in substantia nigra pars compacta (SNpc) neurons of older D2R(−/−) mice, and were also occasionally seen in aged wild‐type mice. These inclusions displaced the nucleus of affected cells and were eosinophilic. Diffuse cytosolic α‐synuclein immunoreactivity in SNpc neurons increased with age in both wild‐type and D2R(−/−) mice, most likely because of redistribution of α‐synuclein from striatal terminals to SNpc cell bodies. Gene and protein expression studies indicated endoplasmic reticulum (ER) stress and changes in trafficking and autophagic pathways in D2R(−/−) SNpc. These changes were accompanied by a loss of DA terminals in the dorsal striatum, although there was no evidence of progressive cell death in the SNpc.
Interpretation
Increased sprouting and DA turnover, as observed in PD and D2R(−/−) mice, augments LB‐like inclusions and axonal degeneration of dopaminergic neurons. These changes are associated with ER stress and autophagy. Ann Neurol 2009;66:472–484
Extreme Light Diagnostics Vais, O. E.; Ivanov, K. A.; Tsymbalov, I. N. ...
Bulletin of the Lebedev Physics Institute,
10/2023, Volume:
50, Issue:
Suppl 8
Journal Article
Peer reviewed
The generation of high-power short laser pulses of ultrarelativistic intensity (over 10
20
W/cm
2
) using the XCELS 1 infrastructure and their application to solve problems of laser-plasma ...interaction and acceleration of charged particles, as well as problems of quantum electrodynamics, require correct diagnostics of the laser pulse parameters in the interaction region upon sharp focusing. An approach is proposed for measuring the key parameters of the XCELS beam, such as its size in the caustic and the peak laser intensity. The proposed method is based on using the process of vacuum acceleration of charged particles—electrons and protons—from the focal volume. When using the distribution of the laser pulse fields near the focus using the Stratton-Chu diffraction integrals and the test particle method, the characteristics of accelerated electrons and ions (for example, the energies of accelerated particles and their emission angles) can be accurately quantified. The latter allows us to offer a practically accessible experimental method for diagnosing radiation in a single laser shot and the design of the XCELS experiment.
In this paper, we demonstrate III-V HBTs fabricated on GaAs/InGaP layers realized by merging the nano-ridges to create a bulk-like stack on a 300 mm Si substrate. The emitter-base and base-collector ...diodes show an ideality factor of ∼1.2 and ∼2.0, respectively. A maximum DC current gain of ∼120 and breakdown voltage, BVCBO, of 10 V is achieved at Ft ∼17GHz. A direct correlation between threading dislocation density (TDD) and various device metrics is shown using DC, RF and reliability measurements. Furthermore, 3D Monte Carlo simulations were done to model and understand the impact of different types of merged structures on the thermal performance of the device. With this work, we show the potential of merged nano-ridges, in enabling an efficient hybrid III-V/CMOS technology for mm-wave applications, as a material-independent tool to understand the impact of defects on the performance of III-V devices.
Members of the Bcl-2 family of proteins regulate apoptosis, with some of their physiological effects mediated by their modulation of endoplasmic reticulum (ER) Ca(2+) homeostasis. Antiapoptotic ...Bcl-x(L) binds to the inositol trisphosphate receptor (InsP(3)R) Ca(2+) release channel to enhance Ca(2+)- and InsP(3)-dependent regulation of channel gating, resulting in reduced ER Ca(2+), increased oscillations of cytoplasmic Ca(2+) concentration (Ca(2+)(i)), and apoptosis resistance. However, it is controversial which InsP(3)R isoforms mediate these effects and whether reduced ER Ca(2+) or enhanced Ca(2+)(i) signaling is most relevant for apoptosis protection. DT40 cell lines engineered to express each of the three mammalian InsP(3)R isoforms individually displayed enhanced apoptosis sensitivity compared with cells lacking InsP(3)R. In contrast, coexpression of each isoform with Bcl-x(L) conferred enhanced apoptosis resistance. In single-channel recordings of channel gating in native ER membranes, Bcl-x(L) increased the apparent sensitivity of all three InsP(3)R isoforms to subsaturating levels of InsP(3). Expression of Bcl-x(L) reduced ER Ca(2+) in type 3 but not type 1 or 2 InsP(3)R-expressing cells. In contrast, Bcl-x(L) enhanced spontaneous Ca(2+)(i) signaling in all three InsP(3)R isoform-expressing cell lines. These results demonstrate a redundancy among InsP(3)R isoforms in their ability to sensitize cells to apoptotic insults and to interact with Bcl-x(L) to modulate their activities that result in enhanced apoptosis resistance. Furthermore, these data suggest that modulation of ER Ca(2+) is not a specific requirement for ER-dependent antiapoptotic effects of Bcl-x(L). Rather, apoptosis protection is conferred by enhanced spontaneous Ca(2+)(i) signaling by Bcl-x(L) interaction with all isoforms of the InsP(3)R.
Mutations in the DIIS4–S5 linker and DIIS5 have identified hotspots of pyrethroid and DDT interaction with the Drosophila
para sodium channel. Wild-type and mutant channels were expressed in
Xenopus ...oocytes and subjected to voltage-clamp analysis. Substitutions L914I, M918T, L925I, T929I and C933A decreased deltamethrin potency, M918T, L925I and T929I decreased permethrin potency and T929I, L925I and I936V decreased fenfluthrin potency. DDT potency was unaffected by M918T, but abolished by T929I and reduced by L925I, L932F and I936V, suggesting that DIIS5 contains at least part of the DDT binding domain. The data support a computer model of pyrethroid and DDT binding.
P-selectin glycoprotein ligand-1 (PSGL-1), a glycoprotein expressed on the cell surface of leukocytes, binds to selectins and mediates leukocyte rolling on the vascular endothelium. Here we report ...that PSGL-1 binds to the C-terminal (G3 domain) of the extracellular proteoglycan PG-M/versican. Cells transfected with PSGL-1 or a shorter form containing the binding site, or cells expressing endogenous PSGL-1 aggregate in the presence of versican or G3 product. The aggregation appears to be induced by G3 multimers that bind to PSGL-1 and form a network. Endogenous versican and/or G3-containing fragments also bind to PSGL-1 in human plasma. Removal of the endogenous G3-containing fragments reduces the effect of plasma on leukocyte aggregation. Finally, the roles of G3-containing fragments in leukocyte aggregation were confirmed in a mouse model. Taken together, our results strongly support a physiologically relevant role for PSGL-1/versican binding and may have implications in the immunoresponse.
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