44,106 research outputs found
Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions
No full text""The rate-limiting step of cholesterol biosynthetic. pathway is catalyzed by 3-hydroxy-3-methylglutaryl. coenzyme reductase (HGMR), whose inhibitors,. the statins, widely used in clinical practice to treat. hypercholesterolemia, often cause myopathy, and. rarely rhabdomyolysis. All studies to date are limited to. the definition of statin-induced myotoxicity omitting to. investigate whether and how HMGR inhibition influences. muscle functions. To this end, 3-mo-old male rats. (Rattus norvegicus) were treated for 3 wk with a daily. intraperitoneal injection of simvastatin (1.5 mg\\\/kg\\\/d),. and biochemical, morphological, mechanical, and functional. analysis were performed on extensor digitorum. longus (EDL) muscle. Our results show that EDL. muscles from simvastatin-treated rats exhibited reduced. HMGR activity; a 15% shift from the fastest. myosin heavy-chain (MHC) isoform IIb to the slower. IIa\\\/x; and reduced power output and unloaded shortening. velocity, by 41 and 23%, respectively, without any. change in isometric force and endurance. Moreover,. simvastatin-treated rats showed a decrease of maximum. speed reached and the latency to fall off the rotaroad. (30%). These results indicate that the molecular. mechanism of the impaired muscle function following. statin treatment could be related to the plasticity of fast. MHC isoform expression.—Trapani, L., Melli, L., Segatto,. M., Trezza, V., Campolongo, P., Jozwiak, A.,. Swiezewska, E., Pucillo, L.P., Moreno, S., Fanelli, F.,. Linari, M., Pallottini, V. Effects of myosin heavy chain. (MHC) plasticity induced by HMGCoA-reductase inhibition. on skeletal muscle functions."
The Metabolic Regimes at the Scale of an Entire Stream Network Unveiled Through Sensor Data and Machine Learning
No full textStreams and rivers form dense networks that drain the terrestrial landscape and are relevant for biodiversity dynamics, ecosystem functioning, and transport and transformation of carbon. Yet, resolving in both space and time gross primary production (GPP), ecosystem respiration (ER) and net ecosystem production (NEP) at the scale of entire stream networks has been elusive so far. Here, combining Random Forest (RF) with time series of sensor data in 12 reach sites, we predicted annual regimes of GPP, ER, and NEP in 292 individual stream reaches and disclosed properties emerging from the network they form. We further predicted available light and thermal regimes for the entire network and expanded the library of stream metabolism predictors. We found that the annual network-scale metabolism was heterotrophic yet with a clear peak of autotrophy in spring. In agreement with the River Continuum Concept, small headwaters and larger downstream reaches contributed 16% and 60%, respectively, to the annual network-scale GPP. Our results suggest that ER rather than GPP drives the metabolic stability at the network scale, which is likely attributable to the buffering function of the streambed for ER, while GPP is more susceptible to flow-induced disturbance and fluctuations in light availability. Furthermore, we found large terrestrial subsidies fueling ER, pointing to an unexpectedly high network-scale level of heterotrophy, otherwise masked by simply considering reach-scale NEP estimations. Our machine learning approach sheds new light on the spatiotemporal dynamics of ecosystem metabolism at the network scale, which is a prerequisite to integrate aquatic and terrestrial carbon cycling at relevant scales
Modeling the coupled dynamics of stream metabolism and microbial biomass
No full textEstimating and interpreting ecosystem metabolism remains an important challenge in stream ecology. Here, we propose a novel approach to model, estimate, and predict multiseasonal patterns of stream metabolism (gross primary production [GPP] and ecosystem respiration [ER]) at the reach scale leveraging on increasingly available long-term, high-frequency measurements of dissolved oxygen (DO). The model uses DO measurements to estimate the parameters of a simple ecosystem model describing the underlying dynamics of stream autotrophic and heterotrophic microbial biomass. The model has been applied to four reaches within the Ybbs river network, Austria. Even if microbial biomasses are not observed, that is, they are treated as latent variables, results show that by accounting for the temporal dynamics of biomass, the model reproduces variability in metabolic fluxes that is not explained by fluctuations of light, temperature, and resources. The model is particularly data-demanding: to estimate the 11 parameters used in this formulation, it requires sufficiently long, for example, annual, time series, and significant scouring events. On the other hand, the approach has the potential to separate ER into its autotrophic and heterotrophic components, estimate a richer set of ecosystem carbon fluxes (i.e., carbon uptake, loss, and scouring), extrapolate metabolism estimates for periods when DO measurements are unavailable, and predict how ecosystem metabolism would respond to variations of the driving forces. The model is seen as a building block to develop tools to fully appreciate multiseasonal patterns of metabolic activity in river networks and to provide reliable estimations of carbon fluxes from land to ocean
The L-p-to-L-q boundedness of commutators with applications to the Jacobian operator
No full textSupplying the missing necessary conditions, we complete the characterisation of the L-p -> L-q boundedness of commutators [b, T] of pointwise multiplication and Calderon-Zygmund operators, for arbitrary pairs of 1 q, our results are new even for special classical operators with smooth kernels. As an application, we show that every f is an element of L-p(R-d) can be represented as a convergent series of normalised Jacobians J(u) = det del uof u is an element of (over dot(W))(1,dp)(R-d)(d). This extends, from p = 1 to p > 1, a result of Coifman, Lions, Meyer and Semmes about J:. (over dot(W))(1,d)(R-d)(d) -> H-1(R-d), and supports a conjecture of Iwaniec about the solvability of the equation Ju = f is an element of L-p(R-d). (C) 2021 The Author(s). Published by Elsevier Masson SAS.Peer reviewe
Molecular effects of diphenyl diselenide on cholesterol and glucose cell metabolism
No full text""This study was designed to investigate the molecular effects of diphenyl diselenide ((PhSe)2) on cholesterol metabolism in HepG2 cell line in a dose-dependent manner. The protein levels of both total and phosphorylated 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR and P-HMGR), low-density lipoprotein receptors (LDLr) and the proteins involved in their regulatory network were analyzed by Western blotting, and the effect of (PhSe)2 on HMGR activity was measured. Additionally, we also evaluated the effects of this compound on glucose transporter type 4 (GLUT4) translocation using fluorescence microscopy in L6 skeletal muscle cell line. Results demonstrated that (PhSe)2 increased P-HMGR, HMGR, and LDLr protein levels as well as simvastatin treatment, which was used as positive control, without directly affecting HMGR activity. We observed that both long- and short-term HMGR regulation mechanisms are involved in the effects of (PhSe)2, as this compound was able to augment Sterol regulatory element binding proteins (SREBP)-1 and Insulin induced gene (Insig)1 protein levels, and to increase AMP activated kinase (AMPK) activation state. We also found that, in L6 skeletal myotubes, 10 μ M (PhSe)2 increases GLUT4 translocation through AMPK activation Taken together, these findings suggest that (PhSe)2 can modulate the expression of some proteins involved in cholesterol and glucose cell metabolism.. . "
De Maiestate / Praeside M. Jacobo Thomasio, Moralis Philosoph. P. P., publice disputabit Johannes Dunte, R. L. Author & Respon: ad diem 9. Septembr. H L. Q. C.
No full textDE MAIESTATE / PRAESIDE M. JACOBO THOMASIO, MORALIS PHILOSOPH. P. P., PUBLICE DISPUTABIT JOHANNES DUNTE, R. L. AUTHOR & RESPON: AD DIEM 9. SEPTEMBR. H L. Q. C.
De Maiestate / Praeside M. Jacobo Thomasio, Moralis Philosoph. P. P., publice disputabit Johannes Dunte, R. L. Author & Respon: ad diem 9. Septembr. H L. Q. C. (1)
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Beiträge (21
3-Hydroxy 3-methylglutaryl Coenzyme A reductase inhibition impairs muscle regeneration
No full text""Skeletal muscle has the ability to regenerate new muscle fibers after injury. The process of new muscle formation requires that quiescent. mononuclear muscle precursor cells (myoblasts) become activated, proliferate, differentiate, and fuse into multinucleated myotubes which, in. turn, undergo further differentiation and mature to form functional muscle fibers. Previous data demonstrated the crucial role played by. 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthetic pathway, in fetal rat. myoblast (L6) differentiation. This finding, along with epidemiological studies assessing the myotoxic effect of statins, HMGR inhibitors,. allowed us to speculate that HMGR could be strongly involved in skeletal muscle repair. Thus, our research was aimed at evaluating such. involvement: in vitro and in vivo experiments were performed on both mouse adult satellite cell derived myoblasts (SCDM) and mouse. muscles injured with cardiotoxin. Results demonstrate that HMGR inhibition by the statin Simvastatin reduces SCDM fusion index, fast MHC. protein levels by 60% and slow MHC by 40%. Most importantly, HMGR inhibition delays skeletal muscle regeneration in vivo. Thus, besides. complaining of myopathies, patients given Simvastatin could also undergo an impairment in muscle repair."
Identification and biochemical characterization of novel putative substrates for the epidermal growth factor receptor kinase
No full textTo gain insight into the mechanisms which control the mitogenic response to epidermal growth factor (EGF), we have partially purified and characterized several intracellular proteins which are phosphorylated on tyrosine residues following activation of the epidermal growth factor receptor (EGFR). Partial purification was achieved by immunoaffinity chromatography using immobilized anti-phosphotyrosine antibodies. Antisera generated against the partially purified proteins were used to identify at least five novel EGFR putative substrates, designated, on the basis of their apparent molecular weight, p97, p68, p61, p56, and p23. All of these proteins became specifically phosphorylated on tyrosine after EGF treatment of intact cells, as assessed by phosphoamino acid analysis, and none of them represented an EGFR degradation product. The phosphorylation of these proteins appeared to be relatively specific for the EGFR. In particular, an EGFR-related kinase, erbB-2 was much less efficient than EGFR at phosphorylating p97, p56, and p23 and incapable of phosphorylating p68. The identification of these novel EGFR putative substrates should lead to a better understanding of the mechanisms controlling the specificity of EGFR- mediated mitogenic signaling
Predicting perceived stress related to the covid-19 outbreak through stable psychological traits and machine learning models
No full textThe global SARS-CoV-2 outbreak and subsequent lockdown had a significant impact on people’s daily lives, with strong implications for stress levels due to the threat of contagion and restrictions to freedom. Given the link between high stress levels and adverse physical and mental consequences, the COVID-19 pandemic is certainly a global public health issue. In the present study, we assessed the effect of the pandemic on stress levels in N = 2053 Italian adults, and characterized more vulnerable individuals on the basis of sociodemographic features and stable psychological traits. A set of 18 psycho-social variables, generalized regressions, and predictive machine learning approaches were leveraged. We identified higher levels of perceived stress in the study sample relative to Italian normative values. Higher levels of distress were found in women, participants with lower income, and participants living with others. Higher rates of emotional stability and self-control, as well as a positive coping style and internal locus of control, emerged as protective factors. Predictive learning models identified participants with high perceived stress, with a sensitivity greater than 76%. The results suggest a characterization of people who are more vulnerable to experiencing high levels of stress during the COVID-19 pandemic. This characterization may contribute to early and targeted intervention strategies
Molecular effects of diphenyl diselenide on cholesterol and glucose cell metabolism
No full textThis study was designed to investigate the molecular effects of diphenyl diselenide ((PhSe)2) on cholesterol metabolism in HepG2 cell line in a dose-dependent manner. The protein levels of both total and phosphorylated 3- hydroxy-3-methylglutaryl coenzyme A reductase (HMGR and P-HMGR), low-density lipoprotein receptors (LDLr) and the proteins involved in their regulatory network were analyzed by Western blotting, and the effect of (PhSe)2 on HMGR activity was measured. Additionally, we also evaluated the effects of this compound on glucose transporter type 4 (GLUT4) translocation using fluorescence microscopy in L6 skeletal muscle cell line. Results demonstrated that (PhSe)2 increased P-HMGR, HMGR, and LDLr protein levels as well as simvastatin treatment, which was used as positive control, without directly affecting HMGR activity. We observed that both long- and short-term HMGR regulation mechanisms are involved in the effects of (PhSe)2, as this compound was able to augment Sterol regulatory element binding proteins (SREBP)-1 and Insulin induced gene (Insig)1 protein levels, and to increase AMP activated kinase (AMPK) activation state. We also found that, in L6 skeletal myotubes, 10 μM (PhSe)2 increases GLUT4 translocation through AMPK activation. Taken together, these findings suggest that (PhSe)2 can modulate the expression of some proteins involved in cholesterol and glucose cell metabolism
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