Listeria monocytogenes exploits host caveolin for cell-to-cell spreading

Listeria monocytogenes moves from one cell to another using actin-rich membrane protrusions that propel the bacterium toward neighboring cells. Despite cholesterol being required for this transfer process, the precise host internalization mechanism remains elusive. Here, we show that caveolin endocytosis is key to this event as bacterial cell-to-cell transfer is severely impaired when cells are depleted of caveolin-1. Only a subset of additional caveolar components (cavin-2 and EHD2) are present at sites of bacterial transfer, and although clathrin and the clathrin-associated proteins Eps15 and AP2 are absent from the bacterial invaginations, efficient L. monocytogenes spreading requires the clathrin-interacting protein epsin-1. We also directly demonstrated that isolated L. monocytogenes membrane protrusions can trigger the recruitment of caveolar proteins in a neighboring cell. The engulfment of these bacterial and cytoskeletal structures through a caveolin-based mechanism demonstrates that the classical nanometer-scale theoretical size limit for this internalization pathway is exceeded by these bacterial pathogens. IMPORTANCE Listeria monocytogenes moves from one cell to another as it disseminates within tissues. This bacterial transfer process depends on the host actin cytoskeleton as the bacterium forms motile actin-rich membranous protrusions that propel the bacteria into neighboring cells, thus forming corresponding membrane invaginations. Here, we examine these membrane invaginations and demonstrate that caveolin-1–based endocytosis is crucial for efficient bacterial cell-to-cell spreading. We show that only a subset of caveolin-associated proteins (cavin-2 and EHD2) are involved in this process. Despite the absence of clathrin at the invaginations, the classical clathrin-associated protein epsin-1 is also required for efficient bacterial spreading. Using isolated L. monocytogenes protrusions added onto naive host cells, we demonstrate that actin-based propulsion is dispensable for caveolin-1 endocytosis as the presence of the protrusion/invagi-nation interaction alone triggers caveolin-1 recruitment in the recipient cells. Finally, we provide a model of how this caveolin-1–based internalization event can exceed the theoretical size limit for this endocytic pathway

Very high-energy gamma-ray detection and long-term multiwavelength view of the flaring blazar B2 1811+31

Abstract Context: Among the blazars whose emission has been detected up to very high-energy (VHE; 100 GeV < E < 100 TeV) γ rays, intermediate synchrotron-peaked BL Lacs (IBLs) are quite rare. The IBL B2 1811+31 (z = 0.117) exhibited intense flaring activity in 2020. Detailed characterization of the source emission from radio to γ-ray energies was achieved with quasi-simultaneous observations, which led to the first-time detection of VHE γ-ray emission from the source with the MAGIC telescopes. Aims: In this work, we present a comprehensive multiwavelength (MWL) view of B2 1811+31, with a specific focus on the 2020 VHE flare, employing data from MAGIC, Fermi-LAT, Swift-XRT, Swift-UVOT, and several optical and radio ground-based telescopes. Methods: Long-term MWL data were employed to contextualize the high-state episode within the source emissions over 18 years. We investigated the variability, cross-correlations, and classification of the source emissions during low and high states. We propose an interpretative leptonic model for the observed radiative high state. Results: During the 2020 flaring state, the synchrotron peak frequency shifted to higher values and reached the limit of the IBL classification. Variability in timescales of a few hours in the high-energy (HE; 100 MeV < E < 100 GeV) γ-ray band poses an upper limit of 6×1014 δD cm on the size of the emission region responsible for the γ-ray flare, with δD being the relativistic Doppler factor of the region. During the 2020 high state, the average spectrum became harder in the HE γ-ray band compared to the low states. A similar behavior has been observed in X-rays. Conversely, during different activity periods, we find harder-when-brighter trends in X-rays and a hint of softer-when-brighter trends at HE γ rays. A long-term HE γ-ray and optical correlation indicates that the same emission regions dominate the radiative output in both ranges, whereas the evolution at 15 GHz shows no correlation with the fluxes at higher frequencies. We test one-zone and two-zone synchrotron-self-Compton models for describing the broadband spectral energy distribution during the 2020 flaring state and investigate the self-consistency of the proposed scenario.Abstract Context: Among the blazars whose emission has been detected up to very high-energy (VHE; 100 GeV < E < 100 TeV) γ rays, intermediate synchrotron-peaked BL Lacs (IBLs) are quite rare. The IBL B2 1811+31 (z = 0.117) exhibited intense flaring activity in 2020. Detailed characterization of the source emission from radio to γ-ray energies was achieved with quasi-simultaneous observations, which led to the first-time detection of VHE γ-ray emission from the source with the MAGIC telescopes. Aims: In this work, we present a comprehensive multiwavelength (MWL) view of B2 1811+31, with a specific focus on the 2020 VHE flare, employing data from MAGIC, Fermi-LAT, Swift-XRT, Swift-UVOT, and several optical and radio ground-based telescopes. Methods: Long-term MWL data were employed to contextualize the high-state episode within the source emissions over 18 years. We investigated the variability, cross-correlations, and classification of the source emissions during low and high states. We propose an interpretative leptonic model for the observed radiative high state. Results: During the 2020 flaring state, the synchrotron peak frequency shifted to higher values and reached the limit of the IBL classification. Variability in timescales of a few hours in the high-energy (HE; 100 MeV < E < 100 GeV) γ-ray band poses an upper limit of 6×1014 δD cm on the size of the emission region responsible for the γ-ray flare, with δD being the relativistic Doppler factor of the region. During the 2020 high state, the average spectrum became harder in the HE γ-ray band compared to the low states. A similar behavior has been observed in X-rays. Conversely, during different activity periods, we find harder-when-brighter trends in X-rays and a hint of softer-when-brighter trends at HE γ rays. A long-term HE γ-ray and optical correlation indicates that the same emission regions dominate the radiative output in both ranges, whereas the evolution at 15 GHz shows no correlation with the fluxes at higher frequencies. We test one-zone and two-zone synchrotron-self-Compton models for describing the broadband spectral energy distribution during the 2020 flaring state and investigate the self-consistency of the proposed scenario

Consensus Report : 2nd European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals

Tobacco use has been identified as a major risk factor for oral disorders such as cancer and periodontal disease. Tobacco use cessation (TUC) is associated with the potential for reversal of precancer, enhanced outcomes following periodontal treatment, and better periodontal status compared to patients who continue to smoke. Consequently, helping tobacco users to quit has become a part of both the responsibility of oral health professionals and the general practice of dentistry. TUC should consist of behavioural support, and if accompanied by pharmacotherapy, is more likely to be successful. It is widely accepted that appropriate compensation of TUC counselling would give oral health professionals greater incentives to provide these measures. Therefore, TUC-related compensation should be made accessible to all dental professionals and be in appropriate relation to other therapeutic interventions. International and national associations for oral health professionals are urged to act as advocates to promote population, community and individual initiatives in support of tobacco use prevention and cessation (TUPAC) counselling, including integration in undergraduate and graduate dental curricula. In order to facilitate the adoption of TUPAC strategies by oral health professionals, we propose a level of care model which includes 1) basic care: brief interventions for all patients in the dental practice to identify tobacco users, assess readiness to quit, and request permission to re-address at a subsequent visit, 2) intermediate care: interventions consisting of (brief) motivational interviewing sessions to build on readiness to quit, enlist resources to support change, and to include cessation medications, and 3) advanced care: intensive interventions to develop a detailed quit plan including the use of suitable pharmacotherapy. To ensure that the delivery of effective TUC becomes part of standard care, continuing education courses and updates should be implemented and offered to all oral health professionals on a regular basis

Do mucositis lesions around implants differ from gingivitis lesions around teeth?

The purpose of this review was to compare peri-implant mucositis and gingivitis with respect to the pathogenesis aspects

First-week Postoperative Flow Measurements are Highly Predictive of Primary Patency of Radiocephalic Arteriovenous Fistulas

Purpose This study was conducted to determine whether volume flow rate at the first postoperative visit could predict early failure of radiocephalic arteriovenous fistulas (RCAVFs). Methods We retrospectively studied the records of 264 patients who received a RCAVF between 2007 and 2013 at our centers. Data collected included patient demographics, medical history, arterial and venous mapping, and volume flow rate intraoperatively after fistula creation but before closing the surgical incision. An intraoperative flow rate &gt;100 mL/minute was targeted. We measured volume flow at the first postoperative visit 1 week after surgery and thereafter as needed. Results Intraoperative flow was not a significant predictor of primary patency (p = 0.44) but flow at the first postoperative visit was a statistically significant predictor of fistula primary patency (p = 0.002). No fistula with a blood flow &lt;200 mL/minute at the 1-week postoperative visit reached maturity without receiving a maturation procedure. The hazard ratio for the first follow-up flow (mL/min) was 0.9973 (95% CI 0.9956, 0.9989), indicating that for every 100 mL increase in blood flow the primary patency increases by 10%. Conclusions Flow rate at the 1-week postoperative visit was the most important predictor of RCAVF patency. Thus, it should be possible to identify patients who would benefit from early intervention or closer follow-up as soon as the first postoperative visit. This should help reduce the use of bridging hemodialysis catheters and minimize the risks of catheter dependency. </jats:sec

Mechanisms in Experimental Venous Valve Failure and their Modification by Daflon© 500 mg

ObjectivesTo characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon® 500), on this response.Material and methodsA femoral arteriovenous fistula was created in Wistar rats (n=48). A cohort of 24 rats received oral treatment with MPFF (100mg/kg/day body weight), 24 rats underwent the arteriovenous fistula procedure and received no treatment. At days 1, 7 and 21 the animals (n=8 at each time point) were killed. Experimental parameters measured included limb circumference, blood flow at the sapheno-femoral junction, leukocyte infiltration and gelatinase activity (matrix metalloproteinase, MMP).ResultsThe acute rise in venous hypertension was accompanied by limb edema and venous reflux together with an eventual loss of valve leaflets in the saphenous vein. There was an increase in granulocyte and macrophage infiltration into the venous wall and the surrounding tissue, and a lesser increase in T- and B-lymphocyte infiltration. These changes were accompanied by a local increase in the proteolytic enzymes, MMP-2 and MMP-9. Administration of MPFF reduced the edema and lessened the venous reflux produced by the acute arteriovenous fistula. Decreased levels of granulocyte and macrophage infiltration into the valves were also observed compared with untreated animals.ConclusionsVenous hypertension caused by an arteriovenous fistula resulted in the development of venous reflux and an inflammatory reaction in venous valves culminating in their destruction. MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension