Background: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated ...discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). Methods: Transmission electron microscopy was used to analyze mitochondria within 0–3.5 μm and 3.5–7 μm of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm2 and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. Results: AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well. Conclusion: Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions.
Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in ...modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.
To accelerate the cardiac drug discovery pipeline, we set out to develop a platform that would be capable of quantifying tissue-level functions such as contractile force and be amenable to standard ...multiwell-plate manipulations. We report a 96-well-based array of 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues - termed Cardiac MicroRings (CaMiRi) - in custom 3D-print-molded multiwell plates capable of contractile force measurement. Within each well, two elastomeric microcantilevers are situated above a circumferential ramp. The wells are seeded with cell-laden collagen, which, in response to the gradual slope of the circumferential ramp, self-organizes around tip-gated microcantilevers to form contracting CaMiRi. The contractile force exerted by the CaMiRi is measured and calculated using the deflection of the cantilevers. Platform responses were robust and comparable across wells, and we used it to determine an optimal tissue formulation. We validated the contractile force response of CaMiRi using selected cardiotropic compounds with known effects. Additionally, we developed automated protocols for CaMiRi seeding, image acquisition, and analysis to enable the measurement of contractile force with increased throughput. The unique tissue fabrication properties of the platform, and the consequent effects on tissue function, were demonstrated upon adding hPSC-derived epicardial cells to the system. This platform represents an open-source contractile force screening system useful for drug screening and tissue engineering applications.
ABSTRACT
Between 2014 December 31 and 2015 March 17, the OSIRIS cameras on Rosetta documented the growth of a $140\, \mathrm{\hbox{-}m}$ wide and $0.5\, \mathrm{\hbox{-}m}$ deep depression in the ...Hapi region on Comet 67P/Churyumov–Gerasimenko. This shallow pit is one of several that later formed elsewhere on the comet, all in smooth terrain that primarily is the result of airfall of coma particles. We have compiled observations of this region in Hapi by the microwave instrument MIRO on Rosetta, acquired during October and November 2014. We use thermophysical and radiative transfer models in order to reproduce the MIRO observations. This allows us to place constraints on the thermal inertia, diffusivity, chemical composition, stratification, extinction coefficients, and scattering properties of the surface material, and how they evolved during the months prior to pit formation. The results are placed in context through long-term comet nucleus evolution modelling. We propose that (1) MIRO observes signatures that are consistent with a solid-state greenhouse effect in airfall material; (2) CO2 ice is sufficiently close to the surface to have a measurable effect on MIRO antenna temperatures, and likely is responsible for the pit formation in Hapi observed by OSIRIS; (3) the pressure at the CO2 sublimation front is sufficiently strong to expel dust and water ice outwards, and to compress comet material inwards, thereby causing the near-surface compaction observed by CONSERT, SESAME, and groundbased radar, manifested as the ‘consolidated terrain’ texture observed by OSIRIS.
Maltose, the major product of starch breakdown in Arabidopsis (Arabidopsis thaliana) leaves, exits the chloroplast via the maltose exporter1 MEX1. Consequently, mex1 loss-of-function plants exhibit ...substantial maltose accumulation, a starch-excess phenotype and a specific chlorotic phenotype during leaf development. Here, we investigated whether the introduction of an alternative metabolic route could suppress the marked developmental defects typical for mex1 loss-of-function mutants. To this end, we ectopically expressed in mex1 chloroplasts a functional maltase (MAL) from baker's yeast (Saccharomyces cerevisiae, chloroplastidial MAL cpMAL mutants). Remarkably, the stromal MAL activity substantially alleviates most phenotypic peculiarities typical for mex1 plants. However, the cpMAL lines contained only slightly less maltose than parental mex1 plants and their starch levels were, surprisingly, even higher. These findings point to a threshold level of maltose responsible for the marked developmental defects in mex1. While growth and flowering time were only slightly retarded, cpMAL lines exhibited a substantially improved frost tolerance, when compared to wild-types. In summary, these results demonstrate the possibility to bypass the MEX1 transporter, allow us to differentiate between possible starch-excess and maltose-excess responses, and demonstrate that stromal maltose accumulation prevents frost defects. The latter insight may be instrumental for the development of crop plants with improved frost tolerance.
The objective of the Phoenix mission is to determine if Mars' polar region can support life. Since liquid water is a basic ingredient for life, as we know it, an important goal of the mission is to ...determine if liquid water exists at the landing site. It is believed that a layer of Martian soil preserves ice by forming a barrier against high temperatures and sublimation, but that exposed ice sublimates without the formation of the liquid phase. Here we show possible independent physical and thermodynamical evidence that besides ice, liquid saline water exists in areas disturbed by the Phoenix Lander. Moreover, we show that the thermodynamics of freeze‐thaw cycles can lead to the formation of saline solutions with freezing temperatures lower than current summer ground temperatures on the Phoenix landing site on Mars' Arctic. Thus, we hypothesize that liquid saline water might occur where ground ice exists near the Martian surface. The ideas and results presented in this article provide significant new insights into the behavior of water on Mars.
A comparison of pneumonias due to SARS-CoV-2 and influenza, in terms of clinical course and predictors of outcomes, might inform prognosis and resource management. We aimed to compare clinical course ...and outcome predictors in SARS-CoV-2 and influenza pneumonia using multi-state modelling and supervised machine learning on clinical data among hospitalised patients.
This multicenter retrospective cohort study of patients hospitalised with SARS-CoV-2 (March-December 2020) or influenza (Jan 2015-March 2020) pneumonia had the composite of hospital mortality and hospice discharge as the primary outcome. Multi-state models compared differences in oxygenation/ventilatory utilisation between pneumonias longitudinally throughout hospitalisation. Differences in predictors of outcome were modelled using supervised machine learning classifiers.
Among 2,529 hospitalisations with SARS-CoV-2 and 2,256 with influenza pneumonia, the primary outcome occurred in 21% and 9%, respectively. Multi-state models differentiated oxygen requirement progression between viruses, with SARS-CoV-2 manifesting rapidly-escalating early hypoxemia. Highly contributory classifier variables for the primary outcome differed substantially between viruses.
SARS-CoV-2 and influenza pneumonia differ in presentation, hospital course, and outcome predictors. These pathogen-specific differential responses in viral pneumonias suggest distinct management approaches should be investigated.
This project was supported by NIH/NCATS UL1 TR002345, NIH/NCATS KL2 TR002346 (PGL), the Doris Duke Charitable Foundation grant 2015215 (PGL), NIH/NHLBI R35 HL140026 (CSC), and a Big Ideas Award from the BJC HealthCare and Washington University School of Medicine Healthcare Innovation Lab and NIH/NIGMS R35 GM142992 (PS).
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