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A multichannel seismic reflection profile acquired during the SISMAORE cruise (2021) provides the first in-depth image of the submarine volcanic edifice, named Fani Maore, that formed 50 km east of Mayotte Island (Comoros Archipelago) in 2018–2019. This new edifice sits on a ${\sim }$140 m thick sedimentary layer, which is above a major, volcanic layer up to ${\sim }$1 km thick and extends over 120 km along the profile. This volcanic unit is made of several distinct seismic facies that indicate successive volcanic phases. We interpret this volcanic layer as witnessing the main phase of construction of the Mayotte Island volcanic edifice. A ${\sim }$2.2–2.5 km thick sedimentary unit is present between this volcanic layer and the top of the crust. A complex magmatic feeder system is observed within this unit, composed of saucer-shape sills and seal bypass systems. The deepest tip of this volcanic layer lies below the top-Oligocene seismic horizon, indicating that the volcanism of Mayotte Island likely began around 26.5 Ma, earlier than previously assumed.

Geophysical and geological data from the North Mozambique Channel acquired during the 2020–2021 SISMAORE oceanographic cruise reveal a corridor of recent volcanic and tectonic features 200 km wide and 600 km long within and north of Comoros Archipelago. Here we identify and describe two major submarine tectono-volcanic fields: the N’Droundé province oriented N160°E north of Grande-Comore Island, and the Mwezi province oriented N130°E north of Anjouan and Mayotte Islands. The presence of popping basaltic rocks sampled in the Mwezi province suggests post-Pleistocene volcanic activity. The geometry and distribution of recent structures observed on the seafloor are consistent with a current regional dextral transtensional context. Their orientations change progressively from west to east (${\sim }$N160°E, ${\sim }$N130°E, ${\sim }$EW). The volcanism in the western part appears to be influenced by the pre-existing structural fabric of the Mesozoic crust. The 200 km-wide and 600 km-long tectono-volcanic corridor underlines the incipient Somalia–Lwandle dextral lithospheric plate boundary between the East-African Rift System and Madagascar.

We investigate, using observations from seismic reflection data, the lateral variability in breakup extrusive magmatic addition along the strike of the Pelotas segment of the austral South Atlantic rifted margin and its control on post-rift accommodation space and sediment deposition. Our analysis of regional seismic reflection profiles shows that magmatic addition on the Pelotas margin varies substantially along strike from extremely magma-rich to magma-normal within a distance of ∼300 km. Using 2D flexural back-stripping, we determine the post-rift accommodation space above top volcanics. In the north, where volcanic seaward-dipping reflectors (SDRs) are thickest, the Torres High shows SDRs up to ∼20 km thick, and post-breakup water-loaded accommodation space is much less than in the south, where magmatic addition is normal and SDRs are thinner. We show that post-breakup accommodation space correlates inversely with SDR thickness, being less for magma-rich margins and more for magma-normal/intermediate margins. The Rio Grande Cone, with large sediment thickness, is underlain by small SDR thicknesses allowing large post-breakup accommodation space. A relationship is observed between the amount of volcanic material and the two-way travel time (TWTT) of first volcanics: first volcanics are observed between 1.2 and 2.2 s TWTT for the highly magmatic Torres High profile, while, in contrast, for the normally magmatic profiles in the south, first volcanics are observed between 4.2 and 6.5 s TWTT. The observed inverse relationship between post-breakup accommodation space and SDR thickness is consistent with predictions by a simple isostatic model of continental lithosphere thinning and magmatic addition melting during breakup. The methodology that we use in this paper provides a new approach for investigating the complex magmatic and sedimentary evolution of rifted continental margins. [ABSTRACT FROM AUTHOR]

Many COVID‐19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function is thought to play a key role in Long COVID. Despite its importance, the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco‐2 cells, mucus‐secreting HT29 cells and Raji cells. This gut epithelial model allows efficient differentiation of Caco‐2 cells into microfold‐like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS‐CoV‐2 infection. Early strains of SARS‐CoV‐2 and the Delta variant replicated with high efficiency, severely disrupted barrier function, and depleted tight junction proteins, such as claudin‐1, occludin, and ZO‐1. In comparison, Omicron subvariants also depleted ZO‐1 from tight junctions but had fewer damaging effects on mucosal integrity and barrier function. Remdesivir, the fusion inhibitor EK1 and the transmembrane serine protease 2 inhibitor Camostat inhibited SARS‐CoV‐2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS‐CoV‐2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains. [ABSTRACT FROM AUTHOR]

The design of a novel anamorphic optofluidic imaging system based on a pair of liquid lenses whose toroidal surfaces create different optical powers in the symmetry-axes is presented. Using electrowetting-ondieletrics for actuation, a cylindrical fluidic system is actuated by 32 azimuthally-distributed electrodes allowing the definition of non-rotationally-symmetric surface shapes. We present the design and simulation of this optical system and show that an anamorphic ratio of 1.43 at a maximum field of view of 6:82° is attainable.

Guanylate binding proteins (GBPs) are an evolutionarily ancient family of proteins that are widely distributed among eukaryotes. They belong to the dynamin superfamily of GTPases, and their expression can be partially induced by interferons (IFNs). GBPs are involved in the cell-autonomous innate immune response against bacterial, parasitic and viral infections. Evolutionary studies have shown that GBPs exhibit a pattern of gene gain and loss events, indicative for the birth-and-death model of evolution. Most species harbor large GBP gene clusters that encode multiple paralogs. Previous functional and in-depth evolutionary studies have mainly focused on murine and human GBPs. Since rabbits are another important model system for studying human diseases, we focus here on lagomorphs to broaden our understanding of the multifunctional GBP protein family by conducting evolutionary analyses and performing a molecular and functional characterization of rabbit GBPs. We observed that lagomorphs lack GBP3, 6 and 7. Furthermore, Leporidae experienced a loss of GBP2, a unique duplication of GBP5 and a massive expansion of GBP4. Gene expression analysis by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and transcriptome data revealed that leporid GBP expression varied across tissues. Overexpressed rabbit GBPs localized either uniformly and/or discretely to the cytoplasm and/or to the nucleus. Oryctolagus cuniculus (oc)GBP5L1 and rarely ocGBP5L2 were an exception, colocalizing with the trans-Golgi network (TGN). In addition, four ocGBPs were IFN-inducible and only ocGBP5L2 inhibited furin activity. In conclusion, from an evolutionary perspective, lagomorph GBPs experienced multiple gain and loss events, and the molecular and functional characteristics of ocGBP suggest a role in innate immunity. [ABSTRACT FROM AUTHOR]

Due to an insufficient amount of image annotation, artificial intelligence in computational histopathology usually relies on fine-tuning pre-trained neural networks. While vanilla fine-tuning has shown to be effective, research on computer vision has recently proposed improved algorithms, promising better accuracy. While initial studies have demonstrated the benefits of these algorithms for medical AI, in particular for radiology, there is no empirical evidence for improved accuracy in histopathology. Therefore, based on the ConvNeXt architecture, our study performs a systematic comparison of nine task adaptation techniques, namely, DELTA, L2-SP, MARS-PGM, Bi-Tuning, BSS, MultiTune, SpotTune, Co-Tuning, and vanilla fine-tuning, on five histopathological classification tasks using eight datasets. The results are based on external testing and statistical validation and reveal a multifaceted picture: some techniques are better suited for histopathology than others, but depending on the classification task, a significant relative improvement in accuracy was observed for five advanced task adaptation techniques over the control method, i.e., vanilla fine-tuning (e.g., Co-Tuning: P(≫) = 0.942, d = 2.623). Furthermore, we studied the classification accuracy for three of the nine methods with respect to the training set size (e.g., Co-Tuning: P(≫) = 0.951, γ = 0.748). Overall, our results show that the performance of advanced task adaptation techniques in histopathology is affected by influencing factors such as the specific classification task or the size of the training dataset. [ABSTRACT FROM AUTHOR]

Most SARS‐CoV‐2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41‐amino‐acid peptide. Here, we show that ORF3c is expressed in SARS‐CoV‐2‐infected cells and suppresses RIG‐I‐ and MDA5‐mediated IFN‐β induction. ORF3c interacts with the signaling adaptor MAVS, induces its C‐terminal cleavage, and inhibits the interaction of RIG‐I with MAVS. The immunosuppressive activity of ORF3c is conserved among members of the subgenus sarbecovirus, including SARS‐CoV and coronaviruses isolated from bats. Notably, however, the SARS‐CoV‐2 delta and kappa variants harbor premature stop codons in ORF3c, demonstrating that this reading frame is not essential for efficient viral replication in vivo and is likely compensated by other viral proteins. In agreement with this, disruption of ORF3c does not significantly affect SARS‐CoV‐2 replication in CaCo‐2, CaLu‐3, or Rhinolophus alcyone cells. In summary, we here identify ORF3c as an immune evasion factor of SARS‐CoV‐2 that suppresses innate sensing in infected cells. Synopsis: SARS‐CoV‐2‐encoded ORF3c is expressed in infected cells. This small viral protein is conserved among sarbecoviruses and suppresses the induction of IFN‐β by targeting the signaling adaptor protein MAVS.SARS‐CoV‐2 ORF3c is expressed in infected cells and suppresses IFN‐β induction.SARS‐CoV‐2 ORF3c interacts with the signaling adaptor MAVS.SARS‐CoV‐2 ORF3c induces C‐terminal cleavage of MAVS and inhibits its interaction with RIG‐I.The immunosuppressive activity of ORF3c is conserved among sarbecoviruses. [ABSTRACT FROM AUTHOR]

Coronavirus infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S), inducing lysosomal degradation of Tetherin, and ORF7a, altering its glycosylation. Similarly, SARS-CoV-2 has also been shown to use ORF7a and Spike to enhance virion release in the presence of Tetherin. Here, we directly compare the abilities and mechanisms of these two viral proteins to counteract Tetherin. Therefore, cell surface and total Tetherin levels upon ORF7a or S expression were investigated using flow cytometry and Western blot analysis. SARS-CoV and SARS-CoV-2 S only marginally reduced Tetherin cell surface levels in a cell type-dependent manner. In HEK293T cells, under conditions of high exogenous Tetherin expression, SARS-CoV-2 S and ORF7a reduced total cellular Tetherin levels much more efficiently than the respective counterparts derived from SARS-CoV. Nevertheless, ORF7a from both species was able to alter Tetherin glycosylation. The ability to decrease total protein levels of Tetherin was conserved among S proteins from different SARS-CoV-2 variants (α, γ, δ, ο). While SARS-CoV-2 S and ORF7a both colocalized with Tetherin, only ORF7a directly interacted with the restriction factor in a two-hybrid assay. Despite the presence of multiple Tetherin antagonists, SARS-CoV-2 replication in Caco-2 cells was further enhanced upon Tetherin knockout. Altogether, our data show that endogenous Tetherin restricts SARS-CoV-2 replication and that the antiviral activity of Tetherin is only partially counteracted by viral antagonists with differential and complementary modes of action. [ABSTRACT FROM AUTHOR]

Author(s): David Palesch [1]; Steven E. Bosinger [1, 2]; Gregory K. Tharp [1]; Thomas H. Vanderford [1]; Mirko Paiardini [1, 2]; Ann Chahroudi [1, 3]; Zachary P. Johnson [1]; Frank [...]