Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

The GRAVITY young stellar object survey: VIII. Gas and dust faint inner rings in the hybrid disk of HD141569

Stars and planetary system

Unveiling the β Pictoris system, coupling high contrast imaging, interferometric, and radial velocity data

Context. The nearby and young β Pictoris system hosts a well resolved disk, a directly imaged massive giant planet orbiting at ≃9 au, as well as an inner planet orbiting at ≃2.7 au, which was recently detected through radial velocity (RV). As such, it offers several unique opportunities for detailed studies of planetary system formation and early evolution. Aims: We aim to further constrain the orbital and physical properties of β Pictoris b and c using a combination of high contrast imaging, long base-line interferometry, and RV data. We also predict the closest approaches or the transit times of both planets, and we constrain the presence of additional planets in the system. Methods: We obtained six additional epochs of SPHERE data, six additional epochs of GRAVITY data, and five additional epochs of RV data. We combined these various types of data in a single Markov-chain Monte Carlo analysis to constrain the orbital parameters and masses of the two planets simultaneously. The analysis takes into account the gravitational influence of both planets on the star and hence their relative astrometry. Secondly, we used the RV and high contrast imaging data to derive the probabilities of presence of additional planets throughout the disk, and we tested the impact of absolute astrometry. Results: The orbital properties of both planets are constrained with a semi-major axis of 9.8 ± 0.4 au and 2.7 ± 0.02 au for b and c, respectively, and eccentricities of 0.09 ± 0.1 and 0.27 ± 0.07, assuming the HIPPARCOS distance. We note that despite these low fitting error bars, the eccentricity of β Pictoris c might still be over-estimated. If no prior is provided on the mass of β Pictoris b, we obtain a very low value that is inconsistent with what is derived from brightness-mass models. When we set an evolutionary model motivated prior to the mass of β Pictoris b, we find a solution in the 10-11 M[SUB]Jup[/SUB] range. Conversely, β Pictoris c's mass is well constrained, at 7.8 ± 0.4 M[SUB]Jup[/SUB], assuming both planets are on coplanar orbits. These values depend on the assumptions on the distance of the β Pictoris system. The absolute astrometry HIPPARCOS-Gaia data are consistent with the solutions presented here at the 2σ level, but these solutions are fully driven by the relative astrometry plus RV data. Finally, we derive unprecedented limits on the presence of additional planets in the disk. We can now exclude the presence of planets that are more massive than about 2.5 M[SUB]Jup[/SUB] closer than 3 au, and more massive than 3.5 M[SUB]Jup[/SUB] between 3 and 7.5 au. Beyond 7.5 au, we exclude the presence of planets that are more massive than 1-2 M[SUB]Jup[/SUB]. Conclusions: Combining relative astrometry and RVs allows one to precisely constrain the orbital parameters of both planets and to give lower limits to potential additional planets throughout the disk. The mass of β Pictoris c is also well constrained, while additional RV data with appropriate observing strategies are required to properly constrain the mass of β Pictoris b.Peer reviewe

Risk of Food Insecurity in the U.S. Military: Definitions, Distributions, and Solutions

Prepared for: OPNAV Nl7 - Navy Culture and Force Resilience Office. This research is supported by funding from the Naval Postgraduate School, Naval Research Program (PE 0605853N/2098). NRP Project TD: NRP-23-N095-A.We use data from the Current Population Survey to identify factors associated with food insecurity in the civilian setting, then use a machine learning model to predict rates of food insecurity using the same characteristics based on administrative pay and personnel records from the Department of Defense. We next wargame potential policy solutions, including the new Basic Needs Allowance (BNA) to assess how various policies might change the risk of food insecurity. Policies in the prediction wargame change the threshold for eligibility for the BNA, add additional income based on number of dependents, increase spouse employment, and change SNAP eligibility. There are 6 major takeaways from this research: Takeaway 1: Having a larger family size and if the head of house is a woman, divorced, Black, or Hispanic are associated with a higher probability of being food insecure (risk factors). Takeaway 2: Being from a military family, being married, having more education, and more income are associated with a lower probability of being food insecure (protective factors). Takeaway 3: Few service members have income levels at or below BNA eligibility criteria. Takeaway 4: The FY2023 NDAA's method of eligibility for the BNA will not significantly reduce military food insecurity. Takeaway 5: We estimate that 6.9% of the military is likely to be food insecure. Takeaway 6: Moderate increases in benefits or income will not eliminate food insecurity. We take our results as an indication that food insecurity is a multi-faceted issue that will not be solved with money alone. Military members-and their families-should not face food insecurity. The current BNA will not change much about current rates of food insecurity. Indeed, moderate tweaks to pay are unlikely to have a meaningful effect on rates of food insecurity. Instead, a more comprehensive approach to food insecurity is needed.Approved for public release; distribution is unlimited.Naval Postgraduate School, Naval Research Program (PE 0605853N/2098).OPNAV N17 - Navy Culture and Force Resilience Offic

The Navy Needs A Fully Baked Plan for Cannabis Legalization

Popular support for federal legalization of cannabis use is growing in the United States. Eleven states and the District of Columbia have legalized the consumption and production of cannabis, 13 states have decriminalized its use or dramatically reduced enforcement, and 44 states allow medical marijuana use.1 Like the nation's recent experience with gay marriage, radical shifts in public opinion affect the law in dynamic and surprising ways. Thus, it is likely only a matter of time before cannabis is legal at the federal level. The Navy must prepare for the challenges and opportunities of this new environment. Specifically, upon federal legalization of cannabis use, the Department of the Navy should be prepared to remove marijuana from the its zero-tolerance drug policy. Liberalizing the policy to allow cannabis use is not unambiguously positive, but the likely benefits of so doing convincingly exceed the costs

Strategies to improve the explanatory power of a dynamic slope stability model by enhancing land cover parameterisation and model complexity

Despite the importance of land cover on landscape hydrology and slope stability, the representation of land cover dynamics in physically based models and their associated ecohydrological effects on slope stability is rather scarce. In this study, we assess the impact of different levels of complexity in land cover parameterisation on the explanatory power of a dynamic and process-based spatial slope stability model. Firstly, we present available and collected data sets and account for the stepwise parameterisation of the model. Secondly, we present approaches to simulate land cover: 1) a grassland landscape without forest coverage; 2) spatially static forest conditions, in which we assume limited knowledge about forest composition; 3) more detailed information of forested areas based on the computation of leaf area development and the implementation of vegetation-related processes; 4) similar to the third approach but with the additional consideration of the spatial expansion and vertical growth of vegetation. Lastly, the model is calibrated based on meteorological data sets and groundwater measurements. The model results are quantitatively validated for two landslide-triggering events that occurred in Western Austria. Predictive performances are estimated using the Area Under the receiver operating characteristic Curve (AUC). Our findings indicate that the performance of the slope stability model was strongly determined by model complexity and land cover parameterisation. The implementation of leaf area development and land cover dynamics further yield an acceptable predictive performance (AUC ~0.71-0.75) and a better conservativeness of the predicted unstable areas (FoC ~0.71). The consideration of dynamic land cover expansion provided better performances than the solely consideration of leaf area development. The results of this study highlight that an increase of effort in the land cover parameterisation of a dynamic slope stability model can increase the explanatory power of the model.Water Resource