A network model to investigate structural and electrical properties of proteins

One of the main trend in to date research and development is the miniaturization of electronic devices. In this perspective, integrated nanodevices based on proteins or biomolecules are attracting a major interest. In fact, it has been shown that proteins like bacteriorhodopsin and azurin, manifest electrical properties which are promising for the development of active components in the field of molecular electronics. Here we focus on two relevant kinds of proteins: The bovine rhodopsin, prototype of GPCR protein, and the enzyme acetylcholinesterase (AChE), whose inhibition is one of the most qualified treatments of Alzheimer disease. Both these proteins exert their functioning starting with a conformational change of their native structure. Our guess is that such a change should be accompanied with a detectable variation of their electrical properties. To investigate this conjecture, we present an impedance network model of proteins, able to estimate the different electrical response associated with the different configurations. The model resolution of the electrical response is found able to monitor the structure and the conformational change of the given protein. In this respect, rhodopsin exhibits a better differential response than AChE. This result gives room to different interpretations of the degree of conformational change and in particular supports a recent hypothesis on the existence of a mixed state already in the native configuration of the protein.Comment: 25 pages, 12 figure

Diversity of respiratory parameters and metabolic adaptation to low oxygen tension in mesenchymal stromal cells

Objective Cell metabolism has been shown to play an active role in regulation of stemness and fate decision. In order to identify favorable culture conditions for mesenchymal stromal cells (MSCs) prior to transplantation, this study aimed to characterize the metabolic function of MSCs from different developmental stages in response to different oxygen tension during expansion. Materials and methods We cultured human fetal cardiac MSCs and human adult bone-marrow MSCs for a week under hypoxia (3% O2) and normoxia (20% O2). We performed mitochondrial characterization and assessed oxygen consumption- and extracellular acidification-rates (OCR and ECAR) in addition to oxygen-sensitive respiration and mitochondrial complex activities, using both the Seahorse and Oroboros systems. Results Adult and fetal MSCs displayed similar basal respiration and mitochondrial amount, however fetal MSCs had lower spare respiratory capacity and apparent coupling efficiency. Fetal MSCs expanded in either hypoxia or normoxia demonstrated similar acidification rates, while adult MSCs downregulated their aerobic glycolysis in normoxia. Acute decrease in oxygen tension caused a higher respiratory inhibition in adult compared to fetal MSCs. In both sources of MSCs, minor changes in complex activities in normoxic and hypoxic cultures were found. Conclusions In contrast to adult MSCs, fetal MSCs displayed similar respiration and aerobic glycolysis at different O2 culture concentrations during expansion. Adult MSCs adjusted their respiration to glycolytic activities, depending on the culture conditions thus displaying a more mature metabolic function. These findings are relevant for establishing optimal in vitro culturing conditions, with the aim to maximize engraftment and therapeutic outcome.CC BY-NC-ND 4.0Corresponding author: Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden. E-mail address: [email protected] (K.-H. Grinnemo).Available online 3 February 2022, Version of Record 5 February 2022The project was funded by Karolinska Institute-Mayo Clinic Collaborative Grant 2013; The Swedish Research Council young investigator: 2013–3590; Stockholm county; The Swedish Research Council; The Family Erling-Persson Foundation; ERC-2018-AdG (834860 EYELETS); Uppsala county; Uppsala County Association against Heart and Lung Diseases; and Higher Education of the Russian Federation (agreement no. 075-15-2020-899).</p

Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

Streptococcus pneumoniae is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogenously produced hydrogen peroxide (H2O2) and from the host through the oxidative burst. How S. pneumoniae, an aerotolerant anaerobic bacterium that lacks catalase, protects itself against hydrogen peroxide stress is still unclear. Bioinformatic analysis of its genome identified a hypothetical open reading frame belonging to the thiol-specific antioxidant (TlpA/TSA) family, located in an operon consisting of three open reading frames. For all four strains tested, deletion of the gene resulted in an approximately 10-fold reduction in survival when strains were exposed to external peroxide stress. However, no role for this gene in survival of internal superoxide stress was observed. Mutagenesis and complementation analysis demonstrated that all three genes are necessary and sufficient for protection against oxidative stress. Interestingly, in a competitive index mouse pneumonia model, deletion of the operon had no impact shortly after infection but was detrimental during the later stages of disease. Thus, we have identified a gene complex involved in the protection of S. pneumoniae against external oxidative stress, which plays an important role during invasive disease.

Fe2O3 supported on hollow micro/mesospheres silica for the catalytic partial oxidation of H2S to sulfur

[EN] A family of Fe-based catalysts supported hollow silica mesospheres has been synthesized and tested in the catalytic partial oxidation of H2S to elemental sulfur at 170.180 degrees C, atmospheric pressure and under 300 min of time-on-stream. The characterization of the synthesized catalysts by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), diffuse reflectance UV-vis spectra (DRS), H-2-termoprogrammed reduction (H-2-TPR), N-2 adsorption-desorption at -196 degrees C and X-ray photoelectron spectroscopy (XPS) reveals the formation of a catalytic system with high micro- and mesoporosity with high dispersion of the Fe2O3 species. The catalytic results reported high activity in the selective oxidation of H2S, reaching a highest conversion value close to 94% with a selectivity towards elemental sulfur of 98% after 300 min of time on stream (TOS) at 180 degrees C for the HMS-10Fe catalyst. The comparison of Fe-containing HMS (10 wt% of iron loading) with other SiO2-based supports, as a fumed silica (Cab-osil) or a mesoporous silica (SBA-15), presents different H2S conversion values, following the next trend: HMS-10Fe > SBA-10Fe > Cab-10Fe. These results suggest that the use of a support with a narrow pore tend to facilitate the iron dispersion favoring higher conversion rates.The authors wish to acknowledge the financial support provided by the Ministry of Economy and Competitiveness (Spain) (MINECO) CTQ2015-68951-C1-3R y CTQ2015-68951-C3-3R, Junta de Andalucia (Spain) P12-RNM 1565 and FEDER funds. In addition, the authors also thank Fundacao Cearense de Apoio ao Desenvolvimento Cientifico e Tecnologico (FUNCAP) by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) - Processo: PDSE 99999.002602/2014-08.Cecilia, J.; Soriano Rodríguez, MD.; Marques Correia, L.; Rodríguez-Castellón, E.; López Nieto, JM.; Silveira Vieira, R. (2020). Fe2O3 supported on hollow micro/mesospheres silica for the catalytic partial oxidation of H2S to sulfur. Microporous and Mesoporous Materials. 294:1-10. https://doi.org/10.1016/j.micromeso.2019.109875S11029

D-meson decay constants and a check of factorization in non-leptonic B-decays

We compute the vector meson decay constants fD*, fDs* from the simulation of twisted mass QCD on the lattice with Nf = 2 dynamical quarks. When combining their values with the pseudoscalar D(s)-meson decay constants, we were able (i) to show that the heavy quark spin symmetry breaking effects with the charm quark are large, fDs*/fDs = 1.26(3), and (ii) to check the factorization approximation in a few specific B-meson non-leptonic decay modes. Besides our main results, fD* = 278 \pm 13 \pm 10 MeV, and fDs* = 311 \pm 9 MeV, other phenomenologically interesting results of this paper are: fDs*/fD* = 1.16 \pm 0.02 \pm 0.06, fDs*/fD = 1.46 \pm 0.05 \pm 0.06, and fDs/fD* = 0.89 \pm 0.02 \pm 0.03. Finally, we correct the value for B(B0 \rightarrow D+ pi-) quoted by PDG, and find B(B0 \rightarrow D+ pi-) = (7.8 \pm 1.4) \times 10-7. Alternatively, by using the ratios discussed in this paper, we obtain B(B0 \rightarrow D+ pi-) = (8.3 \pm 1.0 \pm 0.8)\times10-7.Comment: 16 pages, 4 eps figure

The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity