Phospholipase C Gamma 2 Is Critical for Development of a Murine Model of Inflammatory Arthritis by Affecting Actin Dynamics in Dendritic Cells

BACKGROUND:Dendritic cells (DCs) are highly specialized cells, which capture antigen in peripheral tissues and migrate to lymph nodes, where they dynamically interact with and activate T cells. Both migration and formation of DC-T cell contacts depend on cytoskeleton plasticity. However, the molecular bases governing these events have not been completely defined. METHODOLOGY/PRINCIPAL FINDINGS:Utilizing a T cell-dependent model of arthritis, we find that PLCgamma2-/- mice are protected from local inflammation and bone erosion. PLCgamma2 controls actin remodeling in dendritic cells, thereby affecting their capacity to prime T cells. DCs from PLCgamma2-/- mice mature normally, however they lack podosomes, typical actin structures of motile cells. Absence of PLCgamma2 impacts both DC trafficking to the lymph nodes and migration towards CCL21. The interaction with T cells is also affected by PLCgamma2 deficiency. Mechanistically, PLCgamma2 is activated by CCL21 and modulates Rac activation. Rac1/2-/- DCs also lack podosomes and do not respond to CCL21. Finally, antigen pulsed PLCgamma2-/- DCs fail to promote T cell activation and induce inflammation in vivo when injected into WT mice. Conversely, injection of WT DCs into PLCgamma2-/- mice rescues the inflammatory response but not focal osteolysis, confirming the importance of PLCgamma2 both in immune and bone systems. CONCLUSIONS/SIGNIFICANCE:This study demonstrates a critical role for PLCgamma2 in eliciting inflammatory responses by regulating actin dynamics in DCs and positions the PLCgamma2 pathway as a common orchestrator of bone and immune cell functions during arthritis

Testing accuracy and repeatability of UAV blocks oriented with gnss-supported aerial triangulation

UAV Photogrammetry today already enjoys a largely automated and efficient data processing pipeline. However, the goal of dispensing with Ground Control Points looks closer, as dual-frequency GNSS receivers are put on board. This paper reports on the accuracy in object space obtained by GNSS-supported orientation of four photogrammetric blocks, acquired by a senseFly eBee RTK and all flown according to the same flight plan at 80 m above ground over a test field. Differential corrections were sent to the eBee from a nearby ground station. Block orientation has been performed with three software packages: PhotoScan, Pix4D and MicMac. The influence on the checkpoint errors of the precision given to the projection centers has been studied: in most cases, values in Z are critical. Without GCP, the RTK solution consistently achieves a RMSE of about 2-3 cm on the horizontal coordinates of checkpoints. In elevation, the RMSE varies from flight to flight, from 2 to 10 cm. Using at least one GCP, with all packages and all test flights, the geocoding accuracy of GNSS-supported orientation is almost as good as that of a traditional GCP orientation in XY and only slightly worse in Z

Inhibition of Listeria monocytogenes by a formulation of selected dairy starter cultures and probiotics in an in vitro model

Three strains of lactic acid bacteria (LAB) and a commercial probiotic were selected to evaluate their in vitro activity towards Listeria monocytogenes. The strains Lactococcus lactis ssp. lactis, strain 340, L. lactis ssp. lactis, strain 16; Lactobacillus casei ssp. casei, strain 208 and Enterococcus faecium UBEF-41 were inoculated into skim milk and brain heart infusion broth (BHI) to get an initial Lactococcus: Lactobacillus: E. faecium UBEF-41 ratio of 2:1:1 and a concentration of approximately 7 log cfu mL−1 until challenge vs. pathogen. L. monocytogenes ATCC 7644 was also inoculated in same media to get approximately 4 log cfu mL−1. Growth curves in skim milk and BHI at 4, 10 and 30 °C, respectively were studied for: (i) LAB formulation; (ii) L. monocytogenes and (iii) LAB vs. L. monocytogenes. When challenged with LAB, at 30 °C in milk, L. monocytogenes was not detectable after day-3 and in BHI it decreased below log cfu mL−1 after day-5. At 10 and 4 °C, in both media, L. monocytogenes counts were always significantly lower (p < .001) than the counts of L. monocytogenes alone from day-2 for milk at 4 °C and BHI at 10 °C and from day-7 for BHI at 4 °C and milk at 10 °C. In conclusion, the proposed formulation was able to limit L. monocytogenes in vitro growth, even at refrigeration temperature

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Estimating the Rates of Acquisition and loss of Resistance of Enterobacteriaceae to Antimicrobial Drugs in Pre-Weaned Dairy Calves.

The objective of this study was to investigate the effect of the antimicrobial drugs (AMD) on the shedding of resistant Enterobacteriaceae in feces of pre-weaned dairy calves. The AMD considered were ceftiofur, administered parenterally, and neomycin sulfate added in milk replacer and fed to calves during the first 20 days of life. Fifty-five calves, aged one to three days, were enrolled and followed to 64 days. Fecal samples were collected three times/week and treatments recorded daily. Enterobacteriaceae were quantified for a subset of 33 calves using spiral plating on plain, ceftiofur supplemented, and neomycin supplemented MacConkey agar. Negative binomial models were used to predict the association between treatment with AMD and the gain and loss of Enterobacteriaceae resistance over time. Acquisition of resistance by the Enterobacteriaceae occurred during treatment and peaked between days three to four post-treatment before decreasing to below treatment levels at days seven to eight post-treatment. Acquisition of neomycin resistance was observed on the first sampling day (day four from the start of feeding medicated milk replacer) to day eight, followed by cyclical peaks until day 29, when the Enterobacteriaceae counts decreased below pre-treatment. Enterobacteriaceae resistance against both AMD increased after AMD administration and didn’t return to pre-therapeutic status until seven or more days after therapy had been discontinued. The study findings provide valuable insights into the dynamics of Enterobacteriaceae under routine AMD use in calves