Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing

X-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratory μCT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment

Oligodendrocyte–axon metabolic coupling is mediated by extracellular K+ and maintains axonal health

Abstract The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and how rapid axon–OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca 2+ ) and metabolite fluxes in the mouse optic nerve. We show that fast axonal spiking triggers Ca 2+ signaling and glycolysis in OLs. OLs detect axonal activity through increases in extracellular potassium (K + ) concentrations and activation of Kir4.1 channels, thereby regulating metabolite supply to axons. Both pharmacological inhibition and OL-specific inactivation of Kir4.1 reduce the activity-induced axonal lactate surge. Mice lacking oligodendroglial Kir4.1 exhibit lower resting lactate levels and altered glucose metabolism in axons. These early deficits in axonal energy metabolism are associated with late-onset axonopathy. Our findings reveal that OLs detect fast axonal spiking through K + signaling, making acute metabolic coupling possible and adjusting the axon–OL metabolic unit to promote axonal health

Vesicle condensation induced by synapsin: condensate size, geometry, and vesicle shape deformations

We study the formation of vesicle condensates induced by the protein synapsin, as a cell-free model system mimicking vesicle pool formation in the synapse. The system can be considered as an example of liquid-liquid phase separation (LLPS) in biomolecular fluids, where one phase is a complex fluid itself consisting of vesicles and a protein network. We address the pertinent question why the LLPS is self-limiting and stops at a certain size, i.e., why macroscopic phase separation is prevented. Using fluorescence light microscopy, we observe different morphologies of the condensates (aggregates) depending on the protein-to-lipid ratio. Cryogenic electron microscopy then allows us to resolve individual vesicle positions and shapes in a condensate and notably the size and geometry of adhesion zones between vesicles. We hypothesize that the membrane tension induced by already formed adhesion zones then in turn limits the capability of vesicles to bind additional vesicles, resulting in a finite condensate size. In a simple numerical toy model we show that this effect can be accounted for by redistribution of effective binding particles on the vesicle surface, accounting for the synapsin-induced adhesion zone

A minimal physical model for curvotaxis driven by curved protein complexes at the cell’s leading edge

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed “curvotaxis.” The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a “minimal cell” model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.Agence Nationale de la Recherche 501100001665Israel Research FoundationSlovenian Research Agency 501100004329Marie Curie Individual FellowshipInitiatives d'exellenceEC | European Research Council 501100000781Agence Nationale de la Recherche 501100001665Agence Nationale de la Recherche 501100001665Deutsche Forschungsgemeinschaft 501100001659FEDER prostem researchFRS-FNRS EpiforceFRS-FNRS cellsqueezerFRS-FNRS optopatter

Community diversity and composition affect ecosystem multifunctionality across environmental gradients in boreal and temperate forests

http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100012166 National Key Research and Development Program of Chin

Fabrication of fluidic submicron-channels by pulsed laser-induced buckling of SiOx films on fused silica

Recently, considerable attention has been drawn to the field of micro/nanofluidic channels. However, current methods for fabricating micro/nanochannels are complex, costly, and time-intensive. In the present work, we successfully fabricated transparent submicron-channels on fused silica substrates (SiO 2 ) using a straightforward laser process. To achieve this, a single-pulse excimer laser irradiation in a rear side configuration was employed to treat a thin film of UV-absorbing silicon suboxide (SiO x ) through the transparent SiO 2 substrate. A polydimethylsiloxane (PDMS) superstrate (coating layer) was applied over the SiO x film before laser exposure, serving as a confinement for controlled structure formation induced by the laser. Under optimal laser fluence, the thin SiO x film buckled, leading to the formation of channels with a width ranging from 10 to 20 µm and a height of 800 to 1200 nm, exhibiting a bell-like cross-sections following the so-called Euler buckling mode. Wider channels displayed morphologies resembling varicose or telephone cord modes. Subsequent high-temperature annealing led to the oxidation of SiO x , resulting transparent SiO 2 channels on the fused silica substrate. The manufactured nanochannels exhibited promising potential for effectively transporting fluids of diverse viscosities. Various fluids were conveyed through these nanochannels via capillary action and in accordance with the Lucas-Washburn equation

Ideal Structure of Nica-Toeplitz Algebras

Abstract We study the gauge-invariant ideal structure of the Nica-Toeplitz algebra $\mathcal {N}\mathcal {T}(X)$ N T ( X ) of a product system ( A ,  X ) over $\mathbb {N}^n$ N n . We obtain a clear description of X -invariant ideals in A , that is, restrictions of gauge-invariant ideals in $\mathcal {N\hspace{-1.111pt}T}(X)$ N T ( X ) to A . The main result is a classification of gauge-invariant ideals in $\mathcal {N\hspace{-1.111pt}T}(X)$ N T ( X ) for a proper product system in terms of families of ideals in A . We also apply our results to higher-rank graphs

Interviewer biases in medical survey data: The example of blood pressure measurements

Abstract Health agencies rely upon survey-based physical measures to estimate the prevalence of key global health indicators such as hypertension. Such measures are usually collected by nonhealthcare worker personnel and are potentially subject to measurement error due to variations in interviewer technique and setting, termed “interviewer effects.” In the context of physical measurements, particularly in low- and middle-income countries, interviewer-induced biases have not yet been examined. Using blood pressure as a case study, we aimed to determine the relative contribution of interviewer effects on the total variance of blood pressure measurements in three large nationally representative health surveys from the Global South. We utilized 169,681 observations between 2008 and 2019 from three health surveys (Indonesia Family Life Survey, National Income Dynamics Study of South Africa, and Longitudinal Aging Study in India). In a linear mixed model, we modeled systolic blood pressure as a continuous dependent variable and interviewer effects as random effects alongside individual factors as covariates. To quantify the interviewer effect-induced uncertainty in hypertension prevalence, we utilized a bootstrap approach comparing subsamples of observed blood pressure measurements to their adjusted counterparts. Our analysis revealed that the proportion of variation contributed by interviewers to blood pressure measurements was statistically significant but small: ∼0.24−−2.2% depending on the cohort. Thus, hypertension prevalence estimates were not substantially impacted at national scales. However, individual extreme interviewers could account for measurement divergences as high as 12%. Thus, highly biased interviewers could have important impacts on hypertension estimates at the subdistrict level

Offshoring and job polarisation between firms

http://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschaf