LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L

The linear ubiquitin chain assembly complex (LUBAC), composed of HOIP, HOIL-1 and SHARPIN, is required for optimal TNF-mediated gene activation and to prevent cell death induced by TNF. Here, we demonstrate that keratinocyte-specific deletion of HOIP or HOIL-1 (E-KO) results in severe dermatitis causing postnatal lethality. We provide genetic and pharmacological evidence that the postnatal lethal dermatitis in HoipE-KO and Hoil-1E-KO mice is caused by TNFR1-induced, caspase-8-mediated apoptosis that occurs independently of the kinase activity of RIPK1. In the absence of TNFR1, however, dermatitis develops in adulthood, triggered by RIPK1-kinase-activity-dependent apoptosis and necroptosis. Strikingly, TRAIL or CD95L can redundantly induce this disease-causing cell death, as combined loss of their respective receptors is required to prevent TNFR1-independent dermatitis. These findings may have implications for the treatment of patients with mutations that perturb linear ubiquitination and potentially also for patients with inflammation-associated disorders that are refractory to inhibition of TNF alone

Mapping the Risk of Soil-Transmitted Helminthic Infections in the Philippines

The authors thank the regional coordinators, regional directors, provincial health officers, provincial health team leaders, municipal health officers, medical technologists, midwives, and barangay health workers for their commitment, which was key to completing all the phases of the national prevalence survey. We would like to thank Prof. May Lebanan for assisting us in the preparation of the data set.Author Summary Soil-transmitted helminth (STH) infections with A. lumbricoides, T. trichiura and hookworms are endemic in all 80 provinces of the Philippines, but the spatial variation in the prevalence of these infections has not been previously described. This analysis revealed that while A. lumbricoides and T. trichiura infections were widespread and highly endemic, hookworm infections were more circumscribed to smaller foci in the Visayas and Mindanao. The results also suggest that it may be necessary to place greater emphasis on improving the provision of water, sanitation and the promotion of behavioral change for improved hygiene for the control and prevention of STH infections, particularly for hookworm.Yeshttp://www.plosntds.org/static/editorial#pee

Matriptase: Potent Proteolysis on the Cell Surface

Matriptase is a type II transmembrane serine protease expressed in most human epithelia, where it is coexpressed with its cognate transmembrane inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. Activation of the matriptase zymogen requires sequential N-terminal cleavage, activation site autocleavage, and transient association with HAI-1. Matriptase has an essential physiological role in profilaggrin processing, corneocyte maturation, and lipid matrix formation associated with terminal differentiation of the oral epithelium and the epidermis, and is also critical for hair follicle growth. Matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression that is unopposed by HAI-1 potently promotes carcinogenesis and metastatic dissemination in animal models

WASP-167b/KELT-13b: joint discovery of a hot Jupiter transiting a rapidly-rotating F1V star

We report the joint WASP/KELT discovery of WASP-167b/KELT-13b, a transiting hot Jupiter with a 2.02-d orbit around a V = 10.5, F1V star with [Fe/H] = 0.1 ± 0.1. The 1.5 RJup planet was confirmed by Doppler tomography of the stellar line profiles during transit. We place a limit of < 8 MJup on its mass. The planet is in a retrograde orbit with a sky-projected spin-orbit angle of λ = −165° ± 5° This is in agreement with the known tendency for orbits around hotter stars to be more likely to be misaligned. WASP-167/KELT-13 is one of the few systems where the stellar rotation period is less than the planetary orbital period. We find evidence of non-radial stellar pulsations in the host star, making it a δ-Scuti or γ-Dor variable. The similarity to WASP-33, a previously known hot-Jupiter host with pulsations, adds to the suggestion that close-in planets might be able to excite stellar pulsations

KELT-22Ab: A Massive Hot Jupiter Transiting a Near Solar Twin

We present the discovery of KELT-22Ab, a hot Jupiter from the KELT-South survey. KELT-22Ab transits the moderately bright ($V\sim 11.1$) Sun-like G2V star TYC 7518-468-1. The planet has an orbital period of $P = 1.3866529 \pm 0.0000027$ days, a radius of $R_{P} = 1.285_{-0.071}^{+0.12}~R_{J}$, and a relatively large mass of $M_{P} = 3.47_{-0.14}^{+0.15}~ M_{J}$. The star has $R_{\star} = 1.099_{-0.046}^{+0.079}~ R_{\odot}$, $M_{\star} = 1.092_{-0.041}^{+0.045}~ M_{\odot}$, ${T_{\rm eff}\,} = 5767_{-49}^{+50}~$ K, ${\log{g_\star}} = 4.393_{-0.060}^{+0.039}~$ (cgs), and [m/H] = $+0.259_{-0.083}^{+0.085}~$, and thus, other than its slightly super-solar metallicity, appears to be a near solar twin. Surprisingly, KELT-22A exhibits kinematics and a Galactic orbit that are somewhat atypical for thin disk stars. Nevertheless, the star is rotating quite rapidly for its estimated age, shows evidence of chromospheric activity, and is somewhat metal rich. Imaging reveals a slightly fainter companion to KELT-22A that is likely bound, with a projected separation of 6\arcsec ($\sim$1400 AU). In addition to the orbital motion caused by the transiting planet, we detect a possible linear trend in the radial velocity of KELT-22A suggesting the presence of another relatively nearby body that is perhaps non-stellar. KELT-22Ab is highly irradiated (as a consequence of the small semi-major axis of $a/R_{\star} = 4.97$), and is mildly inflated. At such small separations, tidal forces become significant. The configuration of this system is optimal for measuring the rate of tidal dissipation within the host star. Our models predict that, due to tidal forces, the semi-major axis of KELT-22Ab is decreasing rapidly, and is thus predicted to spiral into the star within the next Gyr