Expression of TLR7 in the murine eye during the embryonic period and in the adult animal

In the present study, we evaluated Toll-like receptor 7 (TLR7) expression at different stages of the murine eye development and in the adult organ. In mammals, TLRs are best known for their immunitary function, however data from the literature are demonstrating that in analogy to their Drosophila homologue Toll, they also participate in developmental mechanisms (Okun, Griffioen and Mattson 2011, Shechter et al. 2008). Immunohistochemistry for TLR7 and double immunofluorescence for TLR7/PCNA were performed on E12, E14 and E16 formalin-fixed paraffin-embedded mouse heads and on eyes enucleated from 3 months adult mice Results of experiments indicate that TLR7 expression is present in different compartments of the mouse eye (cornea, pigmented epithelium, neural retina, and lens) during gestation both in proliferating and differentiating cells and that such expression persists also in the adult organ. These observations indicate that besides being involved in protective mechanisms in the adult eye, TLR7 is also likely involved in the morphogenetic processes of this complex organ to which cells and tissues of different embryological origin contribute

Expression of Toll-like receptors 4 and 7 in the embryonic and adult pancreas, liver and adrenal gland of the mouse

The role of Toll protein in development and immunity is very well understood in Drosophila melanogaster (Anderson et al.,1985). Conversely, the contribution of Tolllike receptors (TLRs) in mammalian development is just beginning to be revealed. In this study, we evaluated the expression of TLR4 and TLR7 by immunohistochemistry on paraffin-embedded tissue in the adrenal gland, liver and pancreas of mouse embryos from stages E12, E14 and E16 and in the adult organs. Results show that TLR4 and TLR7 start to be detectable during embryonic development already at the first stage examined (E12). This expression follows the maturation of the organs and is still present in the adult with a different distribution pattern. Before this study no data in the literature were present on TLR4 and 7 expression in mammalian splanchnic organs development and in the adult no localization studies were available for TLR7. A possible interpretation of the results suggests that, besides their immunitary function, TLRs might be involved in a shared mechanism that regulates proliferation and differentiation both in embryonic organs and adult organs (Sato et al., 2009). These results also suggest that the contribution of TLRs in the context of carcinogenesis should be investigated not only in relation to chronic inflammation and tissue damage but also in relation to their contribution to the process of organogenesis

The Large ARtery Intracranial Occlusion Stroke Scale: A New Tool With High Accuracy in Predicting Large Vessel Occlusion

Objectives: The combination of systemic thrombolysis and mechanical thrombectomy is indicated in patients with ischemic stroke due to a large vessel occlusion (LVO) and these treatments are time-dependent. Rapid identification of patients with suspected LVO also in a prehospital setting could influence the choice of the destination hospital. Aim of this pilot study was to evaluate the predictive role of a new stroke scale for LVO, comparing it to other scores.Patients and Methods: All consecutive patients admitted to our comprehensive stroke center with suspected ischemic stroke were studied with a CT angiography and 5 different stroke scales were applied. The Large ARtery Occlusion (LARIO) stroke scale consists of 5 items including the assessment of facial palsy, language alteration, grip and arm weakness, and the presence of neglect. A Receiving Operating Characteristic curve was evaluated for each stroke scale to explore the level of accuracy in LVO prediction.Results: A total of 145 patients were included in the analysis. LVO was detected in 37.2% of patients. The Area Under Curve of the LARIO score was 0.951 (95%CI: 0.902–0.980), similar to NIHSS and higher than other scales. The cut-off score for best performance of the LARIO stroke scale was higher than 3 (positive predictive value: 77% and negative predictive value: 100%).Conclusion: The LARIO stroke scale is a simple tool, showing high accuracy in detecting LVO, even if with some limitations due to some false positive cases. Its efficacy has to be confirmed in a pre-hospital setting and other centers

ANTONIO: Towards a Systematic Method of Generating NLP Benchmarks for Verification

Verification of machine learning models used in Natural Language Processing (NLP) is known to be a hard problem. In particular, many known neural network verification methods that work for computer vision and other numeric datasets do not work for NLP. Here, we study technical reasons that underlie this problem. Based on this analysis, we propose practical methods and heuristics for preparing NLP datasets and models in a way that renders them amenable to known verification methods based on abstract interpretation. We implement these methods as a Python library called ANTONIO that links to the neural network verifiers ERAN and Marabou. We perform evaluation of the tool using an NLP dataset R-U-A-Robot suggested as a benchmark for verifying legally critical NLP applications. We hope that, thanks to its general applicability, this work will open novel possibilities for including NLP verification problems into neural network verification competitions, and will popularise NLP problems within this community.Comment: To appear in proceedings of 6th Workshop on Formal Methods for ML-Enabled Autonomous Systems (Affiliated with CAV 2023

Activation of Enteroendocrine Cells via TLRs Induces Hormone, Chemokine, and Defensin Secretion

Abstract Enteroendocrine cells are known primarily for their production of hormones that affect digestion, but they might also be implicated in sensing and neutralizing or expelling pathogens. We evaluate the expression of TLRs and the response to specific agonists in terms of cytokines, defensins, and hormones in enteroendocrine cells. The mouse enteroendocrine cell line STC-1 and C57BL/6 mice are used for in vitro and in vivo studies, respectively. The presence of TLR4, 5, and 9 is investigated by RT-PCR, Western blot, and immunofluorescence analyses. Activation of these receptors is studied evaluating keratinocyte-derived chemokine, defensins, and cholecystokinin production in response to their specific agonists. In this study, we show that the intestinal enteroendocrine cell line STC-1 expresses TLR4, 5, and 9 and releases cholecystokinin upon stimulation with the respective receptor agonists LPS, flagellin, and CpG-containing oligodeoxynucleotides. Release of keratinocyte-derived chemokine and β-defensin 2 was also observed after stimulation of STC-1 cells with the three TLR agonists, but not with fatty acids. Consistent with these in vitro data, mice showed increased serum cholecystokinin levels after oral challenge with LPS, flagellin, or CpG oligodeoxynucleotides. In addition to their response to food stimuli, enteroendocrine cells sense the presence of bacterial Ags through TLRs and are involved in neutralizing intestinal bacteria by releasing chemokines and defensins, and maybe in removing them by releasing hormones such as cholecystokinin, which induces contraction of the muscular tunica, favoring the emptying of the distal small intestine

Skin morphology in double apoA-I/apoE knock-out mice: a structural and ultrastructural study

Apolipoprotein(apo)A-I, the main protein component of high density lipoproteins (HDLs), plays a major role in cholesterol removal from peripheral tissues and increasing evidence supports its function as an important regulator of the immune response (Annema et al., 2013). The aim of the study was to evaluate the effect of apoA-I deficiency in dyslipidemic mice, when fed a low-fat/low-cholesterol diet. Three lines of male mice were considered: wild-type mice as controls, apoE-KO mice as dyslipidemic model (Zhang et al.,1992) and apoA-I/apoE double KO mice (DKO mice). Whereas in wild-type mice cholesterol circulates almost exclusively in HDLs, apoE-KO mice are hypercholesterolemic and cholesterol mostly circulates in low-density lipoproteins. In DKO mice, cholesterol levels are comparable to wild-type mice, but HDLs are almost absent and cholesterol entirely accumulates in low-density lipoproteins. In the present study, all animals were maintained on a low-fat/low-cholesterol diet up to 30 weeks of age. At sacrifice, skin biopsies from two different anatomical areas (thoracic and abdominal regions) were harvested from each animal and processed for both light (LM) and transmission electron microscopy (TEM). Whereas the skin of apoE-KO mice was comparable to that of control mice, LM analysis in DKO mice revealed an increase in dermal thickness and a massive presence of foam cells and lymphocytes. TEM analysis showed the presence of cholesterol clefts in the papillary dermis and inside foam cells in the reticular dermis. In conclusion, our results demonstrate that in DKO mice fed a low-fat/low-cholesterol diet, the lack of apoA-I is responsible for an aberrant skin morphology, with an exacerbated inflammatory response, possibly caused by a local cholesterol accumulation

Ultra diffuse galaxies in the Hydra I cluster from the LEWIS Project: Phase-Space distribution and globular cluster richness

Although ultra diffuse galaxies (UDGs) are found in large numbers in clusters of galaxies, the role of the cluster environment in shaping their low surface brightness and large sizes is still uncertain. Here we examine a sample of UDGs in the Hydra I cluster (D = 51 Mpc) with new radial velocities obtained as part of the LEWIS (Looking into the faintest with MUSE) project using VLT/MUSE data. Using a phase-space, or infall diagnostic, diagram we compare the UDGs to other known galaxies in the Hydra I cluster and to UDGs in other clusters. The UDGs, along with the bulk of regular Hydra I galaxies, have low relative velocities and are located near the cluster core, and thus consistent with very early infall into the cluster. Combining with literature data, we do not find the expected trend of GC-rich UDGs associated with earlier infall times. This result suggests that quenching mechanisms other than cluster infall should be further considered, e.g. quenching by strong feedback or in cosmic sheets and filaments. Tidal stripping of GCs in the cluster environment also warrants further modelling.Comment: 6 pages, 2 figures, MNRAS, 525, 9

The VMC survey - XI : Radial Stellar Population Gradients in the Galactic Globular Cluster 47 Tucanae

Copyright American Astronomical SocietyWe present a deep near-infrared color-magnitude diagram of the Galactic globular cluster 47 Tucanae, obtained with the Visible and Infrared Survey Telescope for Astronomy (VISTA) as part of the VISTA near-infrared Y, J, Ks survey of the Magellanic System (VMC). The cluster stars comprising both the subgiant and red giant branches exhibit apparent, continuous variations in color-magnitude space as a function of radius. Subgiant branch stars at larger radii are systematically brighter than their counterparts closer to the cluster core; similarly, red-giant-branch stars in the cluster's periphery are bluer than their more centrally located cousins. The observations can very well be described by adopting an age spread of ~0.5 Gyr as well as radial gradients in both the cluster's helium abundance (Y) and metallicity (Z), which change gradually from (Y = 0.28, Z = 0.005) in the cluster core to (Y = 0.25, Z = 0.003) in its periphery. We conclude that the cluster's inner regions host a significant fraction of second-generation stars, which decreases with increasing radius; the stellar population in the 47 Tuc periphery is well approximated by a simple stellar population.Peer reviewe