Epithelial antimicrobial peptides in host defense against infection

One component of host defense at mucosal surfaces seems to be epithelium-derived antimicrobial peptides. Antimicrobial peptides are classified on the basis of their structure and amino acid motifs. Peptides of the defensin, cathelicidin, and histatin classes are found in humans. In the airways, α-defensins and the cathelicidin LL-37/hCAP-18 originate from neutrophils. β-Defensins and LL-37/hCAP-18 are produced by the respiratory epithelium and the alveolar macrophage and secreted into the airway surface fluid. Beside their direct antimicrobial function, antimicrobial peptides have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing such diverse processes as proliferation, immune induction, wound healing, cytokine release, chemotaxis, protease-antiprotease balance, and redox homeostasis. Further, antimicrobial peptides qualify as prototypes of innovative drugs that might be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation

HATS-47b, HATS-48Ab, HATS-49b and HATS-72b: Four Warm Giant Planets Transiting K Dwarfs

We report the discovery of four transiting giant planets around K dwarfs. The planets HATS-47b, HATS-48Ab, HATS49b, and HATS-72b have masses of 0.369+ 0.0210.031MJ, 0.243+ 0.0300.022 MJ, 0.353+ 0.0270.038 MJ, and 0.1254. 0.0039 MJ, respectively, and radii of 1.117. 0.014 RJ, 0.800. 0.015 RJ, 0.765. 0.013 RJ, and 0.7224. 0.0032 RJ, respectively. The planets orbit close to their host stars with orbital periods of 3.9228 days, 3.1317 days, 4.1480 days, and 7.3279 days, respectively. The hosts are main-sequence K dwarfs with masses of 0.674+ 0.0120.016.M, 0.7279. 0.0066.M, 0.7133. 0.0075.M, and 0.7311. 0.0028, and with V-band magnitudes of V = 14.829. 0.010, 14.35. 0.11, 14.998. 0.040 and 12.469. 0.010. The super-Neptune HATS-72b (a.k.a. WASP-191b and TOI 294.01) was independently identified as a transiting planet candidate by the HATSouth, WASP, and TESS surveys, and we present a combined analysis of all of the data gathered by each of these projects (and their follow-up programs). An exceptionally precise mass is measured for HATS-72b thanks to high-precision radial velocity (RV) measurements obtained with VLT/ESPRESSO, FEROS, HARPS, and Magellan/PFS. We also incorporate TESS observations of the warm Saturn-hosting systems HATS-47 (a.k.a. TOI.1073.01), HATS-48A, and HATS-49. HATS-47 was independently identified as a candidate by the TESS team, while the other two systems were not previously identified from the TESS data. The RV orbital variations are measured for these systems using Magellan/PFS. HATS-48A has a resolved 5.. 4 neighbor in Gaia.DR2, which is a common-proper-motion binary star companion to HATS-48A with a mass of 0.22.M and a current projected physical separation of similar to 1400 au

Mechanistic model of natural killer cell proliferative response to IL-15 receptor stimulation

Natural killer (NK) cells are innate lymphocytes that provide early host defense against intracellular pathogens, such as viruses. Although NK cell development, homeostasis, and proliferation are regulated by IL-15, the influence of IL-15 receptor (IL-15R)-mediated signaling at the cellular level has not been quantitatively characterized. We developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Our computational results demonstrated that IL-15/IL-15R complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. Ligand binding and receptor internalization modulated IL-15R occupancy. Our work supports the hypothesis that the total number and duration of IL-15/IL-15R complexes on the cell surface crosses a quantitative threshold prior to the initiation of NK cell division. Furthermore, our model predicted that the upregulation of IL-15Rα on NK cells substantially increased IL-15R complex formation and accelerated the expansion of dividing NK cells with the greatest impact at low IL-15 concentrations. Model predictions of the threshold requirement for NK cell recruitment to the cell cycle and the subsequent exponential proliferation correlated well with experimental data. In summary, our modeling analysis provides quantitative insight into the regulation of NK cell proliferation at the receptor level and provides a framework for the development of IL-15 based immunotherapies to modulate NK cell proliferation

The Antimicrobial Peptide Histatin-5 Causes a Spatially Restricted Disruption on the Candida albicans Surface, Allowing Rapid Entry of the Peptide into the Cytoplasm

Antimicrobial peptides play an important role in host defense against microbial pathogens. Their high cationic charge and strong amphipathic structure allow them to bind to the anionic microbial cell membrane and disrupt the membrane bilayer by forming pores or channels. In contrast to the classical pore-forming peptides, studies on histatin-5 (Hst-5) have suggested that the peptide is transported into the cytoplasm of Candida albicans in a non-lytic manner, and cytoplasmic Hst-5 exerts its candicidal activities on various intracellular targets, consistent with its weak amphipathic structure. To understand how Hst-5 is internalized, we investigated the localization of FITC-conjugated Hst-5. We find that Hst-5 is internalized into the vacuole through receptor-mediated endocytosis at low extracellular Hst-5 concentrations, whereas under higher physiological concentrations, Hst-5 is translocated into the cytoplasm through a mechanism that requires a high cationic charge on Hst-5. At intermediate concentrations, two cell populations with distinct Hst-5 localizations were observed. By cell sorting, we show that cells with vacuolar localization of Hst-5 survived, while none of the cells with cytoplasmic Hst-5 formed colonies. Surprisingly, extracellular Hst-5, upon cell surface binding, induces a perturbation on the cell surface, as visualized by an immediate and rapid internalization of Hst-5 and propidium iodide or rhodamine B into the cytoplasm from the site using time-lapse microscopy, and a concurrent rapid expansion of the vacuole. Thus, the formation of a spatially restricted site in the plasma membrane causes the initial injury to C. albicans and offers a mechanism for its internalization into the cytoplasm. Our study suggests that, unlike classical channel-forming antimicrobial peptides, action of Hst-5 requires an energized membrane and causes localized disruptions on the plasma membrane of the yeast. This mechanism of cell membrane disruption may provide species-specific killing with minimal damage to microflora and the host and may be used by many other antimicrobial peptides

The Multiplanet System TOI-421*: A Warm Neptune and a Super Puffy Mini-Neptune Transiting a G9 V Star in a Visual Binary*

We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations—comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echellé Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution Échelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements—and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of Pb = 5.19672 ± 0.00049 days, a mass of Mb = 7.17 ± 0.66 M⊕, and a radius of Rb = ${2.68}_{-0.18}^{+0.19}$ R⊕, whereas the outer warm Neptune, TOI-421 c, has a period of Pc = 16.06819 ± 0.00035 days, a mass of Mc = ${16.42}_{-1.04}^{+1.06}$ M⊕, a radius of Rc = ${5.09}_{-0.15}^{+0.16}$ R⊕, and a density of ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3. With its characteristics, the outer planet (ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Lyα transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed

Absence of a thick atmosphere on the terrestrial exoplanet LHS 3844b

Most known terrestrial planets orbit small stars with radii less than 60 per cent of that of the Sun. Theoretical models predict that these planets are more vulnerable to atmospheric loss than their counterparts orbiting Sun-like stars. To determine whether a thick atmosphere has survived on a small planet, one approach is to search for signatures of atmospheric heat redistribution in its thermal phase curve. Previous phase curve observations of the super-Earth 55 Cancri e (1.9 Earth radii) showed that its peak brightness is offset from the substellar point (latitude and longitude of 0 degrees)—possibly indicative of atmospheric circulation. Here we report a phase curve measurement for the smaller, cooler exoplanet LHS 3844b, a 1.3-Earth-radii world in an 11-hour orbit around the small nearby star LHS 3844. The observed phase variation is symmetric and has a large amplitude, implying a dayside brightness temperature of 1,040 ± 40 kelvin and a nightside temperature consistent with zero kelvin (at one standard deviation). Thick atmospheres with surface pressures above 10 bar are ruled out by the data (at three standard deviations), and less-massive atmospheres are susceptible to erosion by stellar wind. The data are well fitted by a bare-rock model with a low Bond albedo (lower than 0.2 at two standard deviations). These results support theoretical predictions that hot terrestrial planets orbiting small stars may not retain substantial atmospheres

HD 183579b: a warm sub-Neptune transiting a solar twin detected by TESS

We report the discovery and characterization of a transiting warm sub-Neptune planet around the nearby bright (V = 8.75 mag, K = 7.15 mag) solar twin HD 183579, delivered by the Transiting Exoplanet Survey Satellite (TESS). The host star is located 56.8 ± 0.1 pc away with a radius of R* = 0.97 ± 0.02 R⊙ and a mass of M* = 1.03 ± 0.05 M⊙. We confirm the planetary nature by combining space and ground-based photometry, spectroscopy, and imaging. We find that HD 183579b (TOI-1055b) has a radius of Rp = 3.53 ± 0.13 R⊕ on a 17.47 d orbit with a mass of Mp = 11.2 ± 5.4 M⊕ (3σ mass upper limit of 27.4 M⊕). HD 183579b is the fifth brightest known sub-Neptune planet system in the sky, making it an excellent target for future studies of the interior structure and atmospheric properties. By performing a line-by-line differential analysis using the high-resolution and signal-to-noise ratio HARPS spectra, we find that HD 183579 joins the typical solar twin sample, without a statistically significant refractory element depletion

TESS Hunt for Young and Maturing Exoplanets (THYME). IV. Three Small Planets Orbiting a 120 Myr Old Star in the Pisces-Eridanus Stream

Young exoplanets can offer insight into the evolution of planetary atmospheres, compositions, and architectures. We present the discovery of the young planetary system TOI 451 (TIC 257605131, Gaia DR2 4844691297067063424). TOI 451 is a member of the 120 Myr old Pisces–Eridanus stream (Psc–Eri). We confirm membership in the stream with its kinematics, its lithium abundance, and the rotation and UV excesses of both TOI 451 and its wide-binary companion, TOI 451 B (itself likely an M-dwarf binary). We identified three candidate planets transiting in the Transiting Exoplanet Survey Satellite data and followed up the signals with photometry from Spitzer and ground-based telescopes. The system comprises three validated planets at periods of 1.9, 9.2, and 16 days, with radii of 1.9, 3.1, and 4.1 R ⨂, respectively. The host star is near-solar mass with V = 11.0 and H = 9.3 and displays an infrared excess indicative of a debris disk. The planets offer excellent prospects for transmission spectroscopy with the Hubble Space Telescope and the James Webb Space Telescope, providing the opportunity to study planetary atmospheres that may still be in the process of evolving