Epiisopilosine alkaloid has activity against schistosoma mansoni in mice without acute toxicity

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSchistosomiasis is a disease caused by parasites of the genus Schistosoma, currently affecting more than 200 million people. Among the various species of this parasite that infect humans, S. mansoni is the most common. Pharmacological treatment is limited135119CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP404134/2012-22014/02282-76, 2016/18023-5, 2016/22488-3The authors are grateful to Phytobios Pesquisa Desenvolvimento e Inovação LTDA.,company of the Centroflora Group, for its support during the realization of this research. SMA is grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico

HD 213885b: a transiting 1-d-period super-Earth with an Earth-like composition around a bright (V = 7.9) star unveiled by TESS

We report the discovery of the 1.008-d, ultrashort period (USP) super-Earth HD 213885b (TOI-141b) orbiting the bright (V = 7.9) star HD 213885 (TOI-141, TIC 403224672), detected using photometry from the recently launched TESS mission. Using FEROS, HARPS, and CORALIE radial velocities, we measure a precise mass of 8.8 ± 0.6 M⊕ for this 1.74 ± 0.05 R⊕ exoplanet, which provides enough information to constrain its bulk composition – similar to Earth’s but enriched in iron. The radius, mass, and stellar irradiation of HD 213885b are, given our data, very similar to 55 Cancri e, making this exoplanet a good target to perform comparative exoplanetology of short period, highly irradiated super-Earths. Our precise radial velocities reveal an additional 4.78-d signal which we interpret as arising from a second, non-transiting planet in the system, HD 213885c, whose minimum mass of 19.9 ± 1.4 M⊕ makes it consistent with being a Neptune-mass exoplanet. The HD 213885 system is very interesting from the perspective of future atmospheric characterization, being the second brightest star to host an USP transiting super-Earth (with the brightest star being, in fact, 55 Cancri). Prospects for characterization with present and future observatories are discussed

Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD

Epiisopilosine alkaloid has activity against Schistosoma mansoni in mice without acute toxicity

Schistosomiasis is a disease caused by parasites of the genus Schistosoma, currently affecting more than 200 million people. Among the various species of this parasite that infect humans, S. mansoni is the most common. Pharmacological treatment is limited to the use of a single drug, praziquantel (PZQ), despite reports of parasite resistance and low efficacy. It is therefore necessary to investigate new potential schistosomicidal compounds. In this study, we tested the efficacy of epiisopilosine (EPIIS) in a murine model of schistosomiasis. A single dose of EPIIS (100 or 400 mg/kg) administered orally to mice infected with adult S. mansoni resulted in reduced worm burden and egg production. The treatment with the lower dose of EPIIS (100 mg/kg) significantly reduced total worm burden by 60.61% (P < 0.001), as well as decreasing hepatosplenomegaly and egg excretion. Scanning electron microscopy revealed morphological changes in the worm tegument after treatment. Despite good activity of EPIIS in adult S. mansoni, oral treatment with single dose of EPIIS 100 mg/kg had only moderate effects in mice infected with juvenile S. mansoni. In addition, we performed cytotoxicity and toxicological studies with EPIIS and found no in vitro cytotoxicity (in HaCaT, and NIH-3T3 cells) at a concentration of 512 μg/mL. We also performed in silico analysis of toxicological properties and showed that EPIIS had low predicted toxicity. To confirm this, we investigated systemic acute toxicity in vivo by orally administering a 2000 mg/kg dose to Swiss mice. Treated mice showed no significant changes in hematological, biochemical, or histological parameters compared to non-treated animals. Epiisopilosine showed potential as a schistosomicidal drug: it did not cause acute toxicity and it displayed an acceptable safety profile in the animal model

A long-period transiting substellar companion in the super-Jupiters to brown dwarfs mass regime and a prototypical warm-Jupiter detected by TESS

We report on the confirmation and follow-up characterization of two long-period transiting substellar companions on low-eccentricity orbits around TIC 4672985 and TOI-2529, whose transit events were detected by the TESS space mission. Ground-based photometric and spectroscopic follow up from different facilities, confirmed the substellar nature of TIC 4672985 b, a massive gas giant, in the transition between the super-Jupiters and brown-dwarfs mass regime. From the joint analysis we derived the following orbital parameters: P = 69.0480+0.0004−0.0005 d, Mp = 12.74+1.01−1.01 MJ, Rp =1.026+0.065−0.067 RJ and e = 0.018+0.004−0.004 . In addition, the RV time series revealed a significant trend at the ∼ 350 m s−1 yr−1level, which is indicative of the presence of a massive outer companion in the system. TIC 4672985 b is a unique example of a transiting substellar companion with a mass above the deuterium-burning limit, located beyond 0.1 AU and in a nearly circular orbit. These planetary properties are difficult to reproduce from canonical planet formation and evolution models. For TOI-2529 b, we obtained the following orbital parameters: P = 64.5949+0.0003−0.0003 d, Mp =2.340+0.197−0.195 MJ, Rp = 1.030+0.050−0.050 RJ and e = 0.021+0.024−0.015 , making this object a new example of a growing population of transiting warm giant planets

An Eccentric Massive Jupiter Orbiting a Subgiant on a 9.5-day Period Discovered in the <i>Transiting Exoplanet Survey Satellite</i> Full Frame Images

We report the discovery of TOI-172 b from the Transiting Exoplanet Survey Satellite (TESS) mission, a massive hot Jupiter transiting a slightly evolved G star with a 9.48-day orbital period. This is the first planet to be confirmed from analysis of only the TESS full frame images, because the host star was not chosen as a two-minute cadence target. From a global analysis of the TESS photometry and follow-up observations carried out by the TESS Follow-up Observing Program Working Group, TOI-172 (TIC 29857954) is a slightly evolved star with an effective temperature of T eff = 5645 ± 50 K, a mass of M ⋆ = {1.128}-0.061+0.065 M ⊙, radius of R ⋆ = {1.777}-0.044+0.047 R ⊙, a surface gravity of log g ⋆ = {3.993}-0.028+0.027, and an age of {7.4}-1.5+1.6 {Gyr}. Its planetary companion (TOI-172 b) has a radius of R P = {0.965}-0.029+0.032 R J, a mass of M P = {5.42}-0.20+0.22 M J, and is on an eccentric orbit (e={0.3806}-0.0090+0.0093). TOI-172 b is one of the few known massive giant planets on a highly eccentric short-period orbit. Future study of the atmosphere of this planet and its system architecture offer opportunities to understand the formation and evolution of similar systems