The present paper describes the generation of derivatives from the hybrid peptide called Ent35-MccV, active against Gram-positive and Gram-negative bacteria. This peptide has a triple glycine hinge ...region between enterocin CRL35 and microcin V. In order to obtain variants of Ent35-MccV with greater biotechnological potential, a saturation mutagenesis was carried out in the hinge region. As a result, we obtained a bank of
E. coli
strains expressing different mutated hybrid bacteriocins in the central position of the hinge region. From all these variants, we found that the one bearing a tyrosine in the central region of the hinge (Ent35-GYG-MccV) is 2-fold more active against
E. coli
and 4-fold more active against
Listeria
than the original peptide Ent35-MccV. This derivative was purified and characterized. The development and evaluation of alternative hinges for Ent35-MccV represents a step forward in the bioengineering of antimicrobial peptides. This approach fosters the rational design of peptides with enhanced antimicrobial activity.
Context.
High-precision planetary densities are key pieces of information necessary to derive robust atmospheric properties for extrasolar planets. Measuring precise masses is the most challenging ...part of this task, especially in multi-planetary systems. The ESO-K2 collaboration focuses on the follow-up of a selection of multi-planetary systems detected by the K2 mission using the HARPS instrument with this goal in mind.
Aims.
In this work, we measure the masses and densities of two multi-planetary systems: a four-planet near resonant chain system (K2-32) and a young (~400 Myr old) planetary system consisting of three close-in small planets (K2-233).
Methods.
We obtained 199 new HARPS observations for K2-32 and 124 for K2-233 covering a long baseline of more than three years. We performed a joint analysis of the radial velocities and K2 photometry with
PASTIS
to precisely measure and constrained the properties of these planets, focusing on their masses and orbital properties.
Results.
We find that K2-32 is a compact scaled-down version of the Solar System’s architecture, with a small rocky inner planet (
M
e
= 2.1
−1.1
+1.3
M
⊕
,
P
e
~ 4.35 days) followed by an inflated Neptune-mass planet (
M
b
= 15.0
−1.7
+1.8
M
⊕
,
P
b
~ 8.99 days) and two external sub-Neptunes (
M
c
= 8.1 ± 2.4
M
⊕
,
P
c
~ 20.66 days;
M
d
= 6.7 ± 2.5
M
⊕
,
P
d
~ 31.72 days). K2-32 becomes one of the few multi-planetary systems with four or more planets known where all have measured masses and radii. Additionally, we constrain the masses of the three planets in the K2-233 system through marginal detection of their induced radial velocity variations. For the two inner Earth-size planets we constrain their masses at a 95% confidence level to be smaller than
M
b
< 11.3
M
⊕
(
P
b
~ 2.47 days),
M
c
< 12.8
M
⊕
(
P
c
~ 7.06 days). The outer planet is a sub-Neptune size planet with an inferred mass of
M
d
= 8.3
−4.7
+5.2
M
⊕
(
M
d
< 21.1
M
⊕
,
P
d
~ 24.36 days).
Conclusions.
Our observations of these two planetary systems confirm for the first time the rocky nature of two planets orbiting a young star, with relatively short orbital periods (<7 days). They provide key information for planet formation and evolution models of telluric planets. Additionally, the Neptune-like derived masses of the three planets, K2-32 b, c, d, puts them in a relatively unexplored regime of incident flux and planet mass, which is key for transmission spectroscopy studies in the near future.
Pesticides are used to control and combat insects and pests in the agricultural sector, households, and public health programs. The frequent and disorderly use of these pesticides may lead to variety ...of undesired effects. Therefore, natural products have many advantages over to synthetic compounds to be used as insecticides. The goal of this study was to find natural products with insecticidal potential against Musca domestica and Mythimna separata. To achieve this goal, we developed predictive QSAR models using MuDRA, PLS, and RF approaches and performed virtual screening of 117 natural products. As a result of QSAR modeling, we formulated the recommendations regarding physico-chemical characteristics for promising compounds active against Musca domestica and Mythimna separata. Homology models were successfully built for both species and molecular docking of QSAR hits vs known insecticides allowed us to prioritize twenty-two compounds against Musca domestica and six against Mythimna separata. Our results suggest that pimarane diterpenes, abietanes diterpenes, dimeric diterpenes and scopadulane diterpenes obtained from aerial parts of species of the genus Calceolaria (Calceolariaceae: Scrophulariaceae) can be considered as potential insecticidal.
•Promising compounds active against Musca domestica and Mythimna separata.•MuDRA, PLS, RF QSAR models using Volsurf descriptors and structure-based studies.•Inhibitory activity against acetylcholinesterase and chitinase.•Diterpenes from aerial parts of the Calceolaria as a potential insecticidal.
Polygonatum sibiricum Redouté (PS, also called Huangjing in traditional Chinese medicine), is a perennial herb as homology of medicine and food. According to the traditional Chinese medicine theory ...“Special Records of Famous Doctors”, its functions include invigorating qi and nourishing yin, tonifying spleen and kidney. Traditionally, qi and blood therapy has been believed as most applicable to the treatment of uterine disease. The current research has focused on the effect and mechanism of dioscin, the main active component of PS, on Endometrial carcinoma (EC).
To study the efficacy of dioscin on proliferation and migration of Endometrial carcinoma cell line, we conducted experiments by using xenograft model and Ishikawa cells, and explored the potential molecular mechanism.
mRNA and miRNA omics techniques were employed to investigate the regulatory mechanism of dioscin on EC Ishikawa cells. Based on in vivo and in vitro experiments, cell clone formation, cell scratching, Transwell, H&E staining, immunohistochemistry, q-PCR, and Western blot techniques were used to determine the molecular effects and mechanisms of dioscin on cell migration.
Integrated miRNA and mRNA omics data showed that 513 significantly different genes marked enrichment in MAPK signaling pathway. The in vivo data showed that dioscin (24 mg/kg) significantly inhibited tumor growth. The in vitro proliferation and invasiveness of dioscin on Ishikawa cells showed that dioscin could significantly decrease the colony numbers, and suppress the Ishikawa cell wound healing, migration and invasion. Molecular data revealed that dioscin decreased the MMP2 and MMP9 expression in vitro and in vivo. The p-MEK, p-ERK, and p-JNK expression levels were also confirmed to be significantly reduced. Key regulators in the MAPK signaling pathway were further validated in xenograft tumors.
Our data indicated that dioscin inhibited Ishikawa cell migration and invasion mediated through MEK/ERK and JNK signaling. More importantly, screened hub miRNAs and genes can be regarded as potential molecular targets for future EC treatment.
Display omitted
•Dioscin suppressed human endometrial carcinoma migration and invasion in Ishikawa cells.•The significantly different expressed genes were marked enrichment in MAPK signaling pathway.•The anti-metastatic mechanisms of dioscin were mainly through MEK/ERK and JNK pathways.•miR-940, miR-9933_L-4, MAP3K1, CACNA1D, ILRAP and JUN were identified as hub miRNAs and genes.
Four xanthones, α-mangostin (
), β-mangostin (
), mangostenol (
), mangaxanthone B (
), three benzophenones, mangaphenone (
), benthamianone (
), congestiflorone (
) and one sterol, stigmasterol (
) ...were isolated from the stem barks of
L. and
(Planch. & Triana) Pipoly. Compounds
,
,
and
exhibited significant cytotoxicity through MTT assay towards MCF-7 and MDA-MB-231 cells with the IC
values range from 4.4 to 12.0 µM. Remarkably, mangaphenone (
showed non-cytotoxicity against normal Vero cells, revealing its potential as lead compound for anti-breast cancer drug. Structure-activity relationship postulated that the prenyl and hydroxyl groups present in xanthones are important in promoting anti-proliferative effects. Molecular docking simulation study of
,
,
and
with 2OCF and 4PIV implied that the induction of apoptosis for both cancer cells involve ER and FAS signaling pathways. Future study on the lead optimization of
is highly recommended.
Cyclopeptide alkaloids with different biological activities are present in plants of the family Rhamnaceae. Plants of this family grow in a symbiotic relationship with aerobic Gram‐positive ...actinomycetes belonging to the genus Frankia. This goal of this research was a study of the comparative profile of alkaloids present in Discaria chacaye and to establish a connection between the presence or absence of Frankia sp. and the alkaloids. In addition, insecticidal activities of the alkaloidal extract were examined. A total of 24 alkaloids were identified, of which 12 have a benzylisoquinoline skeleton, 9 were cyclopeptides, 2 isoquinolines, and 1 aporphine. The presence of cyclopeptide alkaloids is associated with Frankia nodules in the plant root. The alkaloid extracts showed insecticidal activity with mortality dose‐dependence and LD50 values between 44 to 71 μg/mL.
Context
. The stellar activity of M dwarfs is the main limiting factor in the discovery and characterization of the exoplanets orbiting them, because it induces quasi-periodic radial velocity (RV) ...variations.
Aims
. We aim to characterize the magnetic field and stellar activity of the early, moderately active M dwarf Gl 205 in the optical and near-infrared (NIR) domains.
Methods
. We obtained high-precision quasi-simultaneous spectra in the optical and NIR with the SOPHIE spectrograph and SPIRou spectropolarimeter between 2019 and 2022. We computed the RVs from both instruments and the SPIRou Stokes
V
profiles. We used Zeeman–Doppler imaging (ZDI) to map the large-scale magnetic field over the time span of the observations. We studied the temporal behavior of optical and NIR RVs and activity indicators with the Lomb-Scargle periodogram and a quasi-periodic Gaussian process regression (GPR). In the NIR, we studied the equivalent width of Al I, Ti I, K I, Fe I, and He I. We modeled the activity-induced RV jitter using a multi-dimensional GPR with activity indicators as ancillary time series.
Results
. The optical and NIR RVs show similar scatter but NIR shows a more complex temporal evolution. We observe an evolution of the magnetic field topology from a poloidal dipolar field in 2019 to a dominantly toroidal field in 2022. We measured a stellar rotation period of
P
rot
= 34.4 ± 0.5 days in the longitudinal magnetic field. Using ZDI, we measure the amount of latitudinal differential rotation (DR) shearing the stellar surface, yielding rotation periods of
P
eq
= 32.0 ± 1.8 days at the stellar equator and
P
pol
= 45.5 ± 0.3 days at the poles. We observed inconsistencies in the periodicities of the activity indicators that could be explained by these DR values. The multi-dimensional GP modeling yields an RMS of the RV residuals down to the noise level of 3 m s
−1
for both instruments while using
Hα
and the BIS in the optical and the full width at half maximum (FWHM) in the NIR as ancillary time series.
Conclusions
. The RV variations observed in Gl 205 are due to stellar activity, with a complex evolution and different expressions in the optical and NIR revealed thanks to an extensive follow-up. Spectropolarimetry remains the best technique to constrain the stellar rotation period over standard activity indicators, particularly for moderately active M dwarfs.
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