Emergence of tip singularities in dissolution patterns.

Chemical erosion, one of the two major erosion processes along with mechanical erosion, occurs when a soluble rock-like salt, gypsum, or limestone is dissolved in contact with a water flow. The coupling between the geometry of the rocks, the mass transfer, and the flow leads to the formation of remarkable patterns, like scallop patterns in caves. We emphasize the common presence of very sharp shapes and spikes, despite the diversity of hydrodynamic conditions and the nature of the soluble materials. We explain the generic emergence of such spikes in dissolution processes by a geometrical approach. Singularities at the interface emerge as a consequence of the erosion directed in the normal direction, when the surface displays curvature variations, like those associated with a dissolution pattern. First, we demonstrate the presence of singular structures in natural interfaces shaped by dissolution. Then, we propose simple surface evolution models of increasing complexity demonstrating the emergence of spikes and allowing us to explain at long term by coarsening the formation of cellular structures. Finally, we perform a dissolution pattern experiment driven by solutal convection, and we report the emergence of a cellular pattern following well the model predictions. Although the precise prediction of dissolution shapes necessitates performing a complete hydrodynamic study, we show that the characteristic spikes which are reported ultimately for dissolution shapes are explained generically by geometrical arguments due to the surface evolution. These findings can be applied to other ablation patterns, reported for example in melting ice.

Harnessing the Vnn1 pantetheinase pathway boosts short chain fatty acids production and mucosal protection in colitis.

OBJECTIVE: In the management of patients with IBD, there is a need to identify prognostic markers and druggable biological pathways to improve mucosal repair and probe the efficacy of tumour necrosis factor alpha biologics. Vnn1 is a pantetheinase that degrades pantetheine to pantothenate (vitamin B5, a precursor of coenzyme A (CoA) biosynthesis) and cysteamine. Vnn1 is overexpressed by inflamed colonocytes. We investigated its contribution to the tolerance of the intestinal mucosa to colitis-induced injury. DESIGN: We performed an RNA sequencing study on colon biopsy samples from patients with IBD stratified according to clinical severity and modalities of treatment. We generated the VIVA mouse transgenic model, which specifically overexpresses Vnn1 on intestinal epithelial cells and explored its susceptibility to colitis. We developed a pharmacological mimicry of Vnn1 overexpression by administration of Vnn1 derivatives. RESULTS: VNN1 overexpression on colonocytes correlates with IBD severity. VIVA mice are resistant to experimentally induced colitis. The pantetheinase activity of Vnn1 is cytoprotective in colon: it enhances CoA regeneration and metabolic adaptation of colonocytes; it favours microbiota-dependent production of short chain fatty acids and mostly butyrate, shown to regulate mucosal energetics and to be reduced in patients with IBD. This prohealing phenotype is recapitulated by treating control mice with the substrate (pantethine) or the products of pantetheinase activity prior to induction of colitis. In severe IBD, the protection conferred by the high induction of VNN1 might be compromised because its enzymatic activity may be limited by lack of available substrates. In addition, we identify the elevation of indoxyl sulfate in urine as a biomarker of Vnn1 overexpression, also detected in patients with IBD. CONCLUSION: The induction of Vnn1/VNN1 during colitis in mouse and human is a compensatory mechanism to reinforce the mucosal barrier. Therefore, enhancement of vitamin B5-driven metabolism should improve mucosal healing and might increase the efficacy of anti-inflammatory therapy.

Impact of intertendinous connections between the flexor digitorum brevis and longus on percutaneous tenotomy for the treatment of claw toes: an anatomic and ultrasound study.

PURPOSE: Selective percutaneous tenotomy of the flexor digitorum longus (FDL) is a treatment for claw toes that gives astonishingly good functional results despite tendon sacrifice. However, the involution of the FDL tendon stump after tenotomy is unknown. The aim of our study was to assess the involution of the tendon stump after selective percutaneous tenotomy of the FDL. METHODS: The study included two parts. In the clinical part, an ultrasound analysis of 15 FDL tenotomies in 7 patients was carried out 3 months post-surgery. In the anatomic part, the feet of 10 bodies donated to science were dissected and examined anatomically. RESULTS: The proximal stump of the FDL was located near the base of the proximal phalanx and moved synchronously with the flexor digitorum brevis (FDB).Separating the FDB and FDL revealed a large tissue connection between the plantar surface of the tendinous chiasm of the FDB and the dorsal part of the FDL. These connections had significant resistance ranging from 2 to 9 Newtons depending on the toe. Tenotomy of the FDL followed by proximal traction of it led to retraction of the stump up to the base of the proximal phalanx and transfer of its action to the FDB by tensioning the intertendinous structure. Histologically, these structures were mostly comprised of tendon connective tissue. Their vascular component was small. CONCLUSION: The presence of this intertendinous connection leads, in the case of isolated tenotomy of the FDL, to equivalent transfer of the latter to the FDB.

Interferome v2.0: an updated database of annotated interferon-regulated genes.

Interferome v2.0 (http://interferome.its.monash.edu.au/interferome/) is an update of an earlier version of the Interferome DB published in the 2009 NAR database edition. Vastly improved computational infrastructure now enables more complex and faster queries, and supports more data sets from types I, II and III interferon (IFN)-treated cells, mice or humans. Quantitative, MIAME compliant data are collected, subjected to thorough, standardized, quantitative and statistical analyses and then significant changes in gene expression are uploaded. Comprehensive manual collection of metadata in v2.0 allows flexible, detailed search capacity including the parameters: range of -fold change, IFN type, concentration and time, and cell/tissue type. There is no limit to the number of genes that can be used to search the database in a single query. Secondary analysis such as gene ontology, regulatory factors, chromosomal location or tissue expression plots of IFN-regulated genes (IRGs) can be performed in Interferome v2.0, or data can be downloaded in convenient text formats compatible with common secondary analysis programs. Given the importance of IFN to innate immune responses in infectious, inflammatory diseases and cancer, this upgrade of the Interferome to version 2.0 will facilitate the identification of gene signatures of importance in the pathogenesis of these diseases.

Assessment of the Efficiency of Measuring Foot and Ankle Edema with a 3D Portable Scanner.

Background: To prospectively evaluate the reliability of a portable optical scanner compared to the water displacement technique for volumetric measurements of the foot and ankle and to compare the acquisition time associated with these two methods. Methods: Foot volume was measured in 29 healthy volunteers (58 feet, 24 females and 5 males) by a 3D scanner (UPOD-S 3D Laser Full-Foot Scanner®) and by water displacement volumetry. Measurements were performed on both feet, up to a height of 10 cm above the ground. The acquisition time for each method was evaluated. The Kolmogorov-Smirnov test, Lin's Concordance Correlation Coefficient, and a Student's t-test were performed. Results: Mean foot volume was 869.7 +/- 165.1 cm3 (3D scanner) versus 867.9 +/- 155.4 cm3 (water-displacement volumetry) (p < 10-5). The concordance of measurements was 0.93, indicative of a high correlation between the two techniques. Volumes were 47.8 cm3 lower when using the 3D scanner versus water volumetry. After statistically correcting this underestimation, the concordance was improved (0.98, residual bias = -0.03 +/- 35.1 cm3). The mean examination time was 4.2 +/- 1.7 min (3D optical scanner) versus 11.1 +/- 2.9 min (water volumeter) (p < 10-4). Conclusions: Ankle/foot volumetric measurements performed using this portable 3D scanner are reliable and fast and can be used in clinical practice and research.

Natural killer cells and dendritic epidermal γδ T cells orchestrate type 1 conventional DC spatiotemporal repositioning toward CD8+ T cells.

Successful immune responses rely on a regulated delivery of the right signals to the right cells at the right time. Here we show that natural killer (NK) and dendritic epidermal γδ T cells (DETCs) use similar mechanisms to spatiotemporally orchestrate conventional type 1 dendritic cell (cDC1) functions in the spleen, skin, and its draining lymph nodes (dLNs). Upon MCMV infection in the spleen, cDC1 clusterize with activated NK cells in marginal zones. This XCR1-dependent repositioning of cDC1 toward NK cells allows contact delivery of IL-12 and IL-15/IL-15Rα by cDC1, which is critical for NK cell responses. NK cells deliver granulocyte-macrophage colony-stimulating factor (GM-CSF) to cDC1, guiding their CCR7-dependent relocalization into the T cell zone. In MCMV-infected skin, XCL1-secreting DETCs promote cDC1 migration from the skin to the dLNs. This XCR1-dependent licensing of cDC1 both in the spleen and skin accelerates antiviral CD8+ T cell responses, revealing an additional mechanism through which cDC1 bridge innate and adaptive immunity.

Fatty muscle infiltration of the hip lateral rotator muscles following direct anterior minimally invasive total hip arthroplasty.

INTRODUCTION: There is no consensus as to the best surgical approach to use when doing total hip arthroplasty (THA). There has been renewed interest in recent years in so-called anatomic minimally invasive direct anterior approaches (DAA). However, their reduced impact has not been confirmed with imaging data. This led us to carry out a prospective study to 1) evaluate fatty infiltration (FI) of muscles around the hip joint and 2) analyze how this FI changes over time. HYPOTHESIS: THA done by the DAA induces FI of the anterolateral muscles around the hip adjacent to the approach. MATERIAL AND METHODS: A continuous case series of THA by DAA using a traction table was done by a single experienced surgeon. MRI images (GE Optima* MR360 1.5T) were taken preoperatively, then at 3 months and 1 year after the THA surgery. Muscle FI was classified as described by Goutallier by an independent radiologist on all the muscles around the hip joint. A Wilcoxon test was used to compare the preoperative MRI data to the data at 3 months and 1 year postoperative. RESULTS: Sixty-nine MRI examinations were done in 23 patients. Two were not interpretable because the patient moved during the preoperative acquisition. No intraoperative or postoperative complications were reported. None of the patients had hip pain or limped at 1 year postoperative. The FI was significantly worse from the preoperative MRI to the 3-month postoperative MRI (p=0.02) and 1-year MRI (p=0.0007) in the internal obturator muscle and at 1 year in the piriformis muscle (p=0.04). There was no significant difference for the other muscles. The rectus femoris, superior and inferior gemellus muscles and the quadratus femoris could not be analyzed. DISCUSSION: Our hypothesis was not confirmed, although we had a paradoxical finding of muscle FI in the posterior lateral rotator muscles not the anterolateral muscles after THA by DAA. These lesions may be secondary to detachment or denervation of these muscles when elevating the femur to prepare the femoral canal or insert the stem. LEVEL OF EVIDENCE: IV; Prospective case series.

Fluvial Regimes, Morphometry, and Age of Jezero Crater Paleolake Inlet Valleys and Their Exobiological Significance for the 2020 Rover Mission Landing Site.

Jezero crater has been selected as the landing site for the Mars 2020 Perseverance rover, because it contains a paleolake with two fan-deltas, inlet and outlet valleys. Using the data from the High Resolution Stereo Camera (HRSC) and the High Resolution Imaging Science Experiment (HiRISE), we conducted a quantitative geomorphological study of the inlet valleys of the Jezero paleolake. Results show that the strongest erosion is related to a network of deep valleys that cut into the highland bedrock well upstream of the Jezero crater and likely formed before the formation of the regional olivine-rich unit. In contrast, the lower sections of valleys display poor bedrock erosion and a lack of tributaries but are characterized by the presence of pristine landforms interpreted as fluvial bars from preserved channels, the discharge rates of which have been estimated at 103-104 m3s-1. The valleys' lower sections postdate the olivine-rich unit, are linked directly to the fan-deltas, and are thus formed in an energetic, late stage of activity. Although a Late Noachian age for the fan-deltas' formation is not excluded based on crosscutting relationships and crater counts, this indicates evidence of a Hesperian age with significant implications for exobiology.

Differentiation Paths of Peyer's Patch LysoDCs Are Linked to Sampling Site Positioning, Migration, and T Cell Priming.

The monocyte-derived phagocytes termed LysoDCs are hallmarks of Peyer's patches, where their main function is to sample intestinal microorganisms. Here, we study their differentiation pathways in relation with their sampling, migratory, and T cell-priming abilities. Among four identified LysoDC differentiation stages displaying similar phagocytic activity, one is located in follicles, and the others reside in subepithelial domes (SED), where they proliferate and mature as they get closer to the epithelium. Mature LysoDCs but not macrophages express a gene set in common with conventional dendritic cells and prime naive helper T cells in vitro. At steady state, they do not migrate into naive T cell-enriched interfollicular regions (IFRs), but upon stimulation, they express the chemokine receptor CCR7 and migrate from SED to the IFR periphery, where they strongly interact with proliferative immune cells. Finally, we show that LysoDCs populate human Peyer's patches, strengthening their interest as targets for modulating intestinal immunity.

Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression.

Macrophages possess intrinsic tumoricidal activity, yet tumor-associated macrophages (TAMs) rapidly adopt an alternative phenotype within the tumor microenvironment that is marked by tumor-promoting immunosuppressive and trophic functions. The mechanisms that promote such TAM polarization remain poorly understood, but once identified, they may represent important therapeutic targets to block the tumor-promoting functions of TAMs and restore their anti-tumor potential. Here, we have characterized TAMs in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted IL-4-mediated reprogramming, including inhibition of IFNγ-induced gene expression. Genetic deletion of ABC transporters, which mediate cholesterol efflux, reverts the tumor-promoting functions of TAMs and reduces tumor progression. These studies reveal an unexpected role for membrane-cholesterol efflux in driving TAM-mediated tumor progression while pointing to a potentially novel anti-tumor therapeutic strategy.

Gene expression profiling of the Peyer's patch mononuclear phagocyte system.

Peyer's patches (PPs) are primary inductive sites of mucosal immunity. The PP mononuclear phagocyte system, which encompasses both dendritic cells (DCs) and macrophages, is essential for the initiation of the mucosal immune response. We recently developed a method to isolate each mononuclear phagocyte subset of PP (Bonnardel et al., 2015). We performed a transcriptional analysis of three of these subsets: the CD11b(+) conventional DC, the lysozyme-expressing monocyte-derived DC termed LysoDC and the CD11c(hi) lysozyme-expressing macrophages. Here, we provide details of the gating strategy we used to isolate each phagocyte subset and show the quality controls and analysis associated with our gene array data deposited into Gene Expression Omnibus (GEO) under GSE65514.