Exogenous, but not Endogenous Nitric Oxide Inhibits Adhesion Molecule Expression in Human Endothelial Cells

Nitric oxide (NO) has many beneficial actions on the vascular wall including suppression of inflammation. The mechanism(s) by which NO antagonizes cytokine signaling are poorly understood, but are thought to involve inhibition of the pro-inflammatory transcription factor, NF-κB. NO represses nuclear translocation of NF-κB via the S-nitrosylation of its subunits which decreases the expression of target genes including adhesion molecules. In previous studies, we have shown that the intracellular location of endothelial nitric oxide synthase (eNOS) can influence the amount of NO produced and that NO levels are paramount in regulating the S-nitrosylation of target proteins. The purpose of the current study was to investigate the significance of subcellular eNOS to NF-κB signaling induced by pro-inflammatory cytokines in human aortic endothelial cells (HAECs). We found that in HAECs stimulated with TNFα, L-NAME did not influence the expression of intercellular adhesion molecule 1 (ICAM-1) or vascular cell adhesion molecular 1 (VCAM-1). In eNOS “knock down” HAECs reconstituted with either plasma membrane or Golgi restricted forms of eNOS, there was no significant effect on the activation of the NF-κB pathway over different times and concentrations of TNFα. Similarly, the endogenous production of NO did not influence the phosphorylation of IκBα. In contrast, higher concentrations of NO derived from the use of the exogenous NO donor, DETA NONOate, effectively suppressed the expression of ICAM-1/VCAM-1 in response to TNFα and induced greater S-nitrosylation of IKKβ and p65. Collectively these results suggest that neither endogenous eNOS nor eNOS location is an important influence on inflammatory signaling via the NF-κB pathway and that higher NO concentrations are required to suppress NF-κB in HAECs

Empty pews take a financial toll on many US congregations

Most Christian churches were relying heavily on 'collection plates' to pay their bills before the pandemic struck. And less than half were doing any online fundraising as of 2018.Lilly Endowment Inc

TESS Delivers Its First Earth-sized Planet and a Warm Sub-Neptune

The future of exoplanet science is bright, as Transiting Exoplanet Survey Satellite (TESS) once again demonstrates with the discovery of its longest-period confirmed planet to date. We hereby present HD 21749b (TOI 186.01), a sub-Neptune in a 36 day orbit around a bright (V = 8.1) nearby (16 pc) K4.5 dwarf. TESS measures HD 21749b to be 2.61^(+0.17)_(-0.16) R⊕, and combined archival and follow-up precision radial velocity data put the mass of the planet at 22.7^(+2.2)_(-1.9) M⊕. HD 21749b contributes to the TESS Level 1 Science Requirement of providing 50 transiting planets smaller than 4 R⊕ with measured masses. Furthermore, we report the discovery of HD 21749c (TOI 186.02), the first Earth-sized (R_p = 0.892^(+0.064)_(-0.058)R⊕) planet from TESS. The HD 21749 system is a prime target for comparative studies of planetary composition and architecture in multi-planet systems

KELT-22Ab: A Massive, Short-Period 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∼11.1) Sun-like G2V star TYC 7518-468-1. The planet has an orbital period of P = 1.3866529±0.0000027 days, a radius of R_P = 1.285^(+0.12)_(−0.071) R_J, and a relatively large mass of M_P = 3.47^(+0.15)_(−0.14) M_J. The star has R⋆ = 1.099^(+0.079)_(−0.046) R⊙, M⋆ = 1.092^(+0.045)_(−0.041) M⊙, T_(eff) = 5767^(+50)_(−49) K, log g⋆ = 4.393^(+0.039)_(−0.060) (cgs), and [m/H] = +0.259^(+0.085)_(−0.083), 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” (∼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⋆ = 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

KELT-23Ab: A Hot Jupiter Transiting a Near-solar Twin Close to the TESS and JWST Continuous Viewing Zones

We announce the discovery of KELT-23Ab, a hot Jupiter transiting the relatively bright (V = 10.3) star BD+66 911 (TYC 4187-996-1), and characterize the system using follow-up photometry and spectroscopy. A global fit to the system yields host-star properties of T_(eff)=5900±49K, M∗=0.945^(+0.060)_(−0.054)M⊙, R∗=0.995±0.015R⊙, L∗=1.082^(+0.051)_(−0.048)L⊙, logg∗=4.418^(+0.026)_(−0.025) (cgs), and [Fe/H]=−0.105±0.077. KELT-23Ab is a hot Jupiter with a mass of MP=0.938^(+0.045)_(−0.042)M_J, radius of R_P=1.322±0.025RJ, and density of ρ_P=0.504^(+0.038)_(−0.035) g cm^(−3). Intense insolation flux from the star has likely caused KELT-23Ab to become inflated. The time of inferior conjunction is T_0=2458149.40776±0.00091 BJD_(TDB) and the orbital period is P=2.255353^(+0.000031)_(−0.00003) days. There is strong evidence that KELT-23A is a member of a long-period binary star system with a less luminous companion, and due to tidal interactions, the planet is likely to spiral into its host within roughly a gigayear. This system has one of the highest positive ecliptic latitudes of all transiting planet hosts known to date, placing it near the Transiting Planet Survey Satellite and James Webb Space Telescope continuous viewing zones. Thus we expect it to be an excellent candidate for long-term monitoring and follow up with these facilities

Global ecological success of Thalassoma fishes in extreme coral reef habitats

Phenotypic adaptations can allow organisms to relax abiotic selection and facilitate their ecological success in challenging habitats, yet we have relatively little data for the prevalence of this phenomenon at macroecological scales. Using data on the relative abundance of coral reef wrasses and parrotfishes (f. Labridae) spread across three ocean basins and the Red Sea, we reveal the consistent global dominance of extreme wave-swept habitats by fishes in the genus Thalassoma, with abundances up to 15 times higher than any other labrid. A key locomotor modification-a winged pectoral fin that facilitates efficient underwater flight in high-flow environments-is likely to have underpinned this global success, as numerical dominance by Thalassoma was contingent upon the presence of high-intensity wave energy. The ecological success of the most abundant species also varied with species richness and the presence of congeneric competitors. While several fish taxa have independently evolved winged pectoral fins, Thalassoma appears to have combined efficient high-speed swimming (to relax abiotic selection) with trophic versatility (to maximize exploitation of rich resources) to exploit and dominate extreme coral reef habitats around the world

Haem oxygenase in GtoPdb v.2023.1

Haem oxygenase (heme,hydrogen-donor:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)), E.C. 1.14.99.3, converts heme into biliverdin and carbon monoxide, utilizing NADPH as cofactor

Haem oxygenase (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Haem oxygenase (heme,hydrogen-donor:oxygen oxidoreductase (α-methene-oxidizing, hydroxylating)), E.C. 1.14.99.3, converts heme into biliverdin and carbon monoxide, utilizing NADPH as cofactor

Hydrogen sulphide synthesis (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Hydrogen sulfide is a gasotransmitter, with similarities to nitric oxide and carbon monoxide. Although the enzymes indicated below have multiple enzymatic activities, the focus here is the generation of hydrogen sulphide (H2S) and the enzymatic characteristics are described accordingly. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are pyridoxal phosphate (PLP)-dependent enzymes. 3-mercaptopyruvate sulfurtransferase (3-MPST) functions to generate H2S; only CAT is PLP-dependent, while 3-MPST is not. Thus, this third pathway is sometimes referred to as PLP-independent. CBS and CSE are predominantly cytosolic enzymes, while 3-MPST is found both in the cytosol and the mitochondria. For an authoritative review on the pharmacological modulation of H2S levels, see Szabo and Papapetropoulos, 2017 [4]

Hydrogen sulphide synthesis in GtoPdb v.2023.1

Hydrogen sulfide is a gasotransmitter, with similarities to nitric oxide and carbon monoxide. Although the enzymes indicated below have multiple enzymatic activities, the focus here is the generation of hydrogen sulphide (H2S) and the enzymatic characteristics are described accordingly. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are pyridoxal phosphate (PLP)-dependent enzymes. 3-mercaptopyruvate sulfurtransferase (3-MPST) functions to generate H2S; only CAT is PLP-dependent, while 3-MPST is not. Thus, this third pathway is sometimes referred to as PLP-independent. CBS and CSE are predominantly cytosolic enzymes, while 3-MPST is found both in the cytosol and the mitochondria. For an authoritative review on the pharmacological modulation of H2S levels, see Szabo and Papapetropoulos, 2017 [8]