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Coronavirus disease-19 (COVID-19) is an acute resolved disease, with estimated 3.4% case fatality rate. Due to insufficient data and short onset time of the disease, researchers have to change the strategy against its associated virus, SARS-CoV-2. One of these strategies is the use of computational methods in the field of drug and vaccine design, which can greatly reduce the time and cost of the therapeutic or immunogenic development projects. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Their potential non-toxic and non-allergenic T- cell and B-cell binding and cytokine inducing epitopes were then identified through a priori immunoinformatic prediction. Selected epitopes were bonded to each other with appropriate links. A suitable adjuvant was added to the N-terminus of the vaccine polypeptide sequence to increase its immunogenicity. Molecular modelling of the 3D structure of the vaccine polypeptide, docking, molecular dynamics simulations and free energy calculations confirmed that the designed vaccine had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. Therefore, the designed polypeptide is promising for antigenicity and inducing an effective and safe immune response against SARS-CoV-2 inside the human body.

We report the detection of a Saturn-size exoplanet orbiting HD 332231 (TOI 1456) in light curves from the Transiting Exoplanet Survey Satellite (TESS). HD 332231, an F8 dwarf star with a V-band magnitude of 8.56, was observed by TESS in Sectors 14 and 15. We detect a single-transit event in the Sector 15 presearch data conditioning (PDC) light curve. We obtain spectroscopic follow-up observations of HD 332231 with the Automated Planet Finder, Keck I, and SONG telescopes. The orbital period we infer from the radial velocity (RV) observations leads to the discovery of another transit in Sector 14 that was masked by PDC due to scattered light contamination. A joint analysis of the transit and RV data confirms the planetary nature of HD 332231 b, a Saturn-size ($0.867^{+0.027}_{-0.025} \; R_{\rm J}$), sub-Saturn-mass ($0.244\pm0.021 \; M_{\rm J}$) exoplanet on a 18.71 day circular orbit. The low surface gravity of HD 332231 b and the relatively low stellar flux it receives make it a compelling target for transmission spectroscopy. Also, the stellar obliquity is likely measurable via the Rossiter-McLaughlin effect, an exciting prospect given the 0.14 au orbital separation of HD 332231 b. The spectroscopic observations do not provide substantial evidence for any additional planets in the HD 332231 system, but continued RV monitoring is needed to further characterize this system. We also predict that the frequency and duration of masked data in the PDC light curves for TESS Sectors 14-16 could hide transits of some exoplanets with orbital periods between 10.5 and 17.5 days., Comment: 17 pages, 9 figures, 4 tables. Published in the Astronomical Journal

We report the measurement of a spectroscopic transit of TOI-1726c, one of two planets transiting a G-type star with V = 6.9 in the Ursa Major Moving Group (∼400 Myr). With a precise age constraint from cluster membership, TOI-1726 provides a great opportunity to test various obliquity excitation scenarios that operate on different timescales. By modeling the Rossiter-McLaughlin (RM) effect, we derived a sky-projected obliquity of -1-+3235∘. This result rules out a polar/retrograde orbit and is consistent with an aligned orbit for planet c. Considering the previously reported, similarly prograde RM measurement of planet b and the transiting nature of both planets, TOI-1726 tentatively conforms to the overall picture that compact multitransiting planetary systems tend to have coplanar, likely aligned orbits. TOI-1726 is also a great atmospheric target for understanding differential atmospheric loss of sub-Neptune planets (planet b 2.2 R☉ and c 2.7 R☉ both likely underwent photoevaporation). The coplanar geometry points to a dynamically cold history of the system that simplifies any future modeling of atmospheric escape.

P7 is the only viral channel encoded by the Hepatitis C Virus (HCV) genome. It is a small, highly hydrophobic protein containing 63 amino acids. Structural studies have shown that p7 has two transmembrane (TM) α helices linked by a short dibasic cytoplasmic loop. P7, mostly placed in the endoplasmic reticulum (ER), is a membrane-associated protein. The results obtained from different studies revealed that p7 is a polytopic membrane protein that could oligomerize in membrane bilayer to create ion channels with cation selectivity. In addition, p7 is highly conserved and plays an important role in the assembly and release of mature viral particles. Thus, it can be considered as a potential target for anti-HCV drugs. It has been found that several compounds (amantadine, rimantadine, hexamethylene amiloride (HMA) and long-alkyl-chain iminosugar (IS) derivatives) inhibit p7 channel ability. Another new inhibitor identified as BIT225, a derivative of amiloride, also inhibits the viroporin function of HIV-1 Vpu and HCV p7. In the present study, molecular dynamics simulations were applied to get insights into molecular details of a BIT225 binding site. In addition, the g_mmpbsa approach was employed to calculate the binding free energy and free energy decomposition per residue. MD simulation results in the p7-BIT225 complex revealed that drug binding to hydrophobic pocket can allosterically inhibit ion conduction via the funnel tip by restricting significant intrinsic channel breath at the tip of the funnel. Based on the molecular dynamics simulation (MD) analysis and the energy profiles, the hydrophobic interactions were the main driving force for BIT225 binding.

Transforming growth factor-β (TGF-β)-induced Epithelial-to-mesenchymal transition (EMT) process is a fundamental target for preventing cervical cancer cells' progression and invasion. Green tea and its principal active substance, Epigallocatechin-3-gallate (EGCG), demonstrate anti-tumor activities in various tumor cells.The cell viability of two cervical cancer cell lines, Hela and SiHa, in the experimental groups was examined employing the MTT method, and ROS generation was probed applying 2',7'-dichlorofluorescein diacetate-based assay. The Smad signaling and EMT process was evaluated utilizing western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Chromatin immunoprecipitation (ChIP) and Smad binding element (SBE)-luciferase assays were employed to measure Smad-DNA interaction and Smad transcriptional activity, respectively.EGCG (0-100 μmol/L) and green tea extract (0-250 μg/ml) suppressed the viability of cancer cells in a dose-dependent manner (p 0.01). Our conclusions affirmed that pre-incubation with green tea extract (80 μg/ml) and EGCG (60 μmol/L) significantly reversed the impacts of TGF-β in Hela and SiHa cells by decreasing Vimentin, ZEB, Slug, Snail, and Twist and increasing E-cadherin expression. The molecular mechanism of green tea extract and EGCG for TGF-β-induced EMT inhibition interfered with ROS generation and Smad signaling. Green tea extract and EGCG could significantly decrease ROS levels, the phosphorylation of Smad2/3, the translocation, DNA binding, and activity of Smads in cervical cancer cell lines treated with TGF-β1 (p 0.01).EGCG and green tea extract suppressed TGF-β-induced EMT in Hela and SiHa cells, and the underlying molecular mechanism may be related to the ROS generation and Smad signaling pathway.

Background Green tea is a natural compound with anti-neoplastic properties. Paclitaxel (PTX) is a natural anti-tumor medication used to manage patients with advanced ovarian cancer. This manuscript evaluated the cytotoxic effects of green tea extract combined with PTX drug in two human ovarian cancer cell lines (p53-negative cell line, SKOV-3; and mutant type p53 cell line, OVCAR-3) and underlying mechanisms. Methods The human ovarian cancer cell lines were treated with green tea extract, PTX, and green tea plus PTX for 24 h, and cell viability was assessed using the MTT method. Flow cytometric analyses were carried out to detect apoptosis. For the apoptotic process, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were applied to study pAkt, Bax, Bcl-2, Cytochrome C (Cyt-C), cleaved-caspase-3, and cleaved-caspase-9 levels after drug treatments. Results Our results pointed out that various green tea (25 and 50 µg/ml) concentrations combined with PTX (20 and 40 µg/ml) synergistically inhibited cell viability of cancer cells more than green tea or PTX alone after 24 h of treatment. Also, green tea and PTX combination induced apoptosis in ovarian cancer cells by blocking the phosphorylation of Akt and the expression of Bcl-2 while inducing Bax, Cyt-C, cleaved-caspase 3, and cleaved-caspase 9. Conclusion Our results showed that the combination of green tea and PTX could be more potent than the individual drug to induce cytotoxicity and apoptosis in ovarian cancer cells.

Water-quality monitoring networks (WQMNs) are principal to planning and management of water resources. However, constructing and maintaining monitoring stations as well as analyzing the acquired data are costly processes. A well-designed network is one that provides the greatest possible amount of data from the fewest number of stations, so that the overall cost of monitoring is reduced. In this study, WQMN sampling locations of the Karun River, in south-western Iran were evaluated by simultaneously applying two geostatistical methods: ordinary kriging (OK) and sequential Gaussian simulation (SGS). In the evaluation, kriging estimations, and their variances and realizations of the concentrations of two main water-quality variables [electrical conductivity (EC) and dissolved oxygen (DO)] were considered. The results showed that the system of sampling locations should be modified to reach an optimized network. It is necessary to set up stations or increase sampling frequency in some existing stations when adjacent ones are far away or when some polluters exist nearby. The combining of the two techniques (OK and SGS) applied simultaneously was evaluated in this study to evaluate the existing WQMN. The results showed that this process applies to evaluating and optimizing other WQMNs as well.

Hepatitis C virus can cause inflammation in human liver cells, leading to liver cirrhosis and liver cancer. Based on the World Health Organization reports, about 228 million people in the world have hepatitis C. To date, some inhibitory medicines against the hepatitis C virus nonstructural 3/4A protease, such as boceprevir, have entered clinical trial phases. However, several hepatitis C virus nonstructural 3/4A protease mutations have been recognized to decrease susceptibility of boceprevir to hepatitis C virus. The molecular details behind inhibitor resistance of these single-point mutations are not still understood. Thus, in this research, computational strategies were applied to clarify the inhibitor resistance mechanism. From umbrella sampling simulation and energy profiles, the polar interactions are the main driving force for boceprevir binding. Based on the analyzed R155T mutant, the main reason for the occurrence of boceprevir resistance is the conformation alterations of S4 and extended S2 binding pockets. These changes, lead to decreased binding ability of the key residues to P2 and P4 moieties of boceprevir. Moreover, structural results show that the disappearance of important salt bridges can bring about the great conformation changes of the binding pockets in R155T.Communicated by Ramaswamy H. Sarma.

The advent of large-scale spectroscopic surveys underscores the need to develop robust techniques for determining stellar properties ("labels", i.e., physical parameters and elemental abundances). However, traditional spectroscopic methods that utilize stellar models struggle to reproduce cool ($, Comment: 9 pages, 7 figures. Accepted for publication in The Astrophysical Journal

Small hydrocarbons are an important organic reservoir in protostellar and protoplanetary environments. Constraints on desorption temperatures and binding energies of such hydrocarbons are needed for accurate predictions of where these molecules exist in the ice vs. gas-phase during the different stages of star and planet formation. Through a series of temperature programmed desorption (TPD) experiments, we constrain the binding energies of 2 and 3-carbon hydrocarbons (C$_{2}$H$_{2}$ - acetylene, C$_{2}$H$_{4}$ - ethylene, C$_{2}$H$_{6}$ - ethane, C$_{3}$H$_{4}$ - propyne, C$_{3}$H$_{6}$ - propene, and C$_{3}$H$_{8}$ - propane) to 2200-4200 K in the case of pure amorphous ices, to 2400-4400 K on compact amorphous H$_{2}$O, and to 2800-4700 K on porous amorphous H$_{2}$O. The 3-carbon hydrocarbon binding energies are always larger than the 2-carbon hydrocarbon binding energies. Within the 2- and 3-carbon hydrocarbon families, the alkynes (i.e., least-saturated) hydrocarbons exhibit the largest binding energies, while the alkane and alkene binding energies are comparable. Binding energies are $\sim$5-20% higher on water ice substrates compared to pure ices, which is a small increase compared to what has been measured for other volatile molecules such as CO and N$_{2}$. Thus in the case of hydrocarbons, H$_{2}$O has a less pronounced effect on sublimation front locations (i.e., snowlines) in protoplanetary disks., 12 pages, 15 figures. Accepted for publication in The Astrophysical Journal

International audience; The small size of the SETI workforce is a major problem for NASA and the search for life elsewhere in the universe. The Astro2020 Decadal should address this issue by making nurturing the field an explicit priority for the next decade.

We report detection of quasi-periodic (1.5 day) dimming of HD 240779, the solar-mass primary in a 5" visual binary (also TIC 284730577), by the Transiting Exoplanet Survey Satellite. This dimming, as has been shown for other "dipper" stars, is likely due to occultation by circumstellar dust. The barycentric space motion, lithium abundance, rotation, and chromospheric emission of the stars in this system point to an age of ~125 Myr, and possible membership in the AB Doradus moving group. As such it occupies an important but poorly explored intermediate regime of stars with transient dimming between young stellar objects in star forming regions and main sequence stars, and between UX Orionis-type Ae/Be stars and M-type "dippers". HD 240779, but not its companion BD+10714B, has WISE-detected excess infrared emission at 12 and 22 microns indicative of circumstellar dust. We propose that infrared emission is produced by collisions of planetesimals during clearing of a residual disk at the end of rocky planet formation, and that quasi-periodic dimming is produced by the rapid disintegration of a 100 km planetesimal near the silicate evaporation radius. Further studies of this and similar systems will illuminate a poorly understood final phase of rocky planet formation like that which produced the inner Solar System., Comment: to appear in MNRAS

Streamflow forecasting is a crucial task for hydropower operations, flood forecasting and water resource use optimization. Ensemble Streamflow Prediction (ESP) is commonly used in the case of long-term lead times (a few months or seasons ahead). ESP covers the use of historical meteorological scenarios in driving a hydrological model to generate an ensemble of possible future streamflow. Many studies have evaluated methods for selecting optimal subsets of scenarios to improve forecasting skill, and indeed, this is still an ongoing area of research. In this study, we propose a procedure that calculates the maximum potential skill of a classic ESP forecast. A genetic algorithm (GA) is used to determine the best possible set of climatological scenarios given any ensemble size. Along with providing a direct estimate of the ESP forecasting potential in hindcast experiments, the method can be used as a reference for comparing other methods to ESP. The procedure is also used to compare classical ESP, a well-established forecasting method, with two new methods, namely, the Analogue method and the Contingency Table (CT) approach. A discriminant analysis is finally implemented to attempt to identify key features of ESP members that performed well as compared to their counterparts using historic climatology and climate indices. It is shown while there exists a potential for improvement, a lot of research must still be realized to exploit this potential. The procedure was tested over two basins in Canada. In general, results showed that for any forecast date, decreasing the ensemble size led to a higher potential for better forecasting skills. However, the method does not yet allow identifying the subset of the entire climatology to be used to maximize the ESP forecast performance.

HD 106315 and GJ 9827 are two bright, nearby stars that host multiple super-Earths and sub-Neptunes discovered by K2 that are well suited for atmospheric characterization. We refined the planets’ ephemerides through Spitzer transits, enabling accurate transit prediction required for future atmospheric characterization through transmission spectroscopy. Through a multiyear high-cadence observing campaign with Keck/High Resolution Echelle Spectrometer and Magellan/Planet Finder Spectrograph, we improved the planets’ mass measurements in anticipation of Hubble Space Telescope transmission spectroscopy. For GJ 9827, we modeled activity-induced radial velocity signals with a Gaussian process informed by the Calcium II H&K lines in order to more accurately model the effect of stellar noise on our data. We measured planet masses of M b = 4.87 ± 0.37 M ⊕, M c = 1.92 ± 0.49 M ⊕, and M d = 3.42 ± 0.62 M ⊕. For HD 106315, we found that such activity radial velocity decorrelation was not effective due to the reduced presence of spots and speculate that this may extend to other hot stars as well (T eff > 6200 K). We measured planet masses of M b = 10.5 ± 3.1 M ⊕ and M c = 12.0 ± 3.8 M ⊕. We investigated all of the planets’ compositions through comparison of their masses and radii to a range of interior models. GJ 9827 b and GJ 9827 c are both consistent with a 50/50 rock-iron composition, GJ 9827 d and HD 106315 b both require additional volatiles and are consistent with moderate amounts of water or hydrogen/helium, and HD 106315 c is consistent with a ∼10% hydrogen/helium envelope surrounding an Earth-like rock and iron core.

Viral miniproteins possess common properties such as a small length of sequence, hydrophobicity because of the presence of at least one hydrophobic domain which contributes to the forming of an amp...

Small planets on close-in orbits tend to exhibit envelope mass fractions of either effectively zero or up to a few percent depending on their size and orbital period. Models of thermally-driven atmospheric mass loss and of terrestrial planet formation in a gas-poor environment make distinct predictions regarding the location of this rocky/non-rocky transition in period-radius space. Here we present the confirmation of TOI-1235 b ($P=3.44$ days, $r_p=1.738^{+0.087}_{-0.076}$ R$_{\oplus}$), a planet whose size and period are intermediate between the competing model predictions thus making the system an important test case for emergence models of the rocky/non-rocky transition around early M dwarfs ($R_s=0.630\pm 0.015$ R$_{\odot}$, $M_s=0.640\pm 0.016$ M$_{\odot}$). We confirm the TESS planet discovery using reconnaissance spectroscopy, ground-based photometry, high-resolution imaging, and a set of 38 precise radial-velocities from HARPS-N and HIRES. We measure a planet mass of $6.91^{+0.75}_{-0.85}$ M$_{\oplus}$, which implies an iron core mass fraction of $20^{+15}_{-12}$% in the absence of a gaseous envelope. The bulk composition of TOI-1235 b is therefore consistent with being Earth-like and we constrain a H/He envelope mass fraction to be $, Accepted to The Astronomical Journal. 8 figures & 5 tables. Table 2 is provided in the arXiv source code

The emergence of antibiotic resistance has attracted the attention of scientists and scientific circles over the decades. β-Lactam antibiotics resistance is a worldwide therapeutic challenge in bacterial infections, mediated through several mechanisms of which mutations in Penicillin Binding Proteins (PBPs) are an important issue, making critical therapeutic problems in the human population. Accordingly, investigating the dynamic structures of mutant variants could result in a profound understanding of such a specific resistance. Therefore, this work investigated structural properties sampled by all-atom molecular dynamics (MD) simulations, umbrella sampling, and binding free energy calculations for both a wild-type and a cefotaxime-resistant T to S mutant of PBP1A. The T to S mutation significantly reduces the binding affinity of cefotaxime (a frequently clinically-administrated β-lactam antibiotic) as the PBP1A inhibitor. In the conventional MD simulations presented here, more fluctuations of the mutant's active site cleft margins were detected. The cleft of the mutant protein also opened remarkably more than the wild-type's cleft and displayed more flexibility. Thus, our findings have shown that flexibility of cleft margins of the active site in the mutant PBP1A immediately results in the catalytic cleft opening. In addition, binding free energy calculation suggests that reducing hydrophobic contacts and increasing the polar contribution in the binding energy may play an important role in cefotaxime resistance.

Metatranscriptomics has recently been applied to investigate the active biogeochemical processes and elemental cycles, and in situ responses of microbiomes to environmental stimuli and stress factors. De novo assembly of RNA-Sequencing (RNA-Seq) data can reveal a more detailed description of the metabolic interactions amongst the active microbial communities. However, the quality of the assemblies and the depiction of the metabolic network provided by various de novo assemblers have not yet been thoroughly assessed. In this study, we compared 15 de novo metatranscriptomic assemblies for a fracture fluid sample collected from a borehole located at 1.34 km below land surface in a South African gold mine. These assemblies were constructed from total, non-coding, and coding reads using five de novo transcriptomic assemblers (Trans-ABySS, Trinity, Oases, IDBA-tran, and Rockhopper). They were evaluated based on the number of transcripts, transcript length, range of transcript coverage, continuity, percentage of transcripts with confident annotation assignments, as well as taxonomic and functional diversity patterns. The results showed that these parameters varied considerably among the assemblies, with Trans-ABySS and Trinity generating the best assemblies for non-coding and coding RNA reads, respectively, because the high number of transcripts assembled covered a wide expression range, and captured extensively the taxonomic and metabolic gene diversity, respectively. We concluded that the choice of de novo transcriptomic assemblers impacts substantially the taxonomic and functional compositions. Care should be taken to obtain high-quality assemblies for informing the in situ metabolic landscape.

Antibiotic resistance is a threatening challenge for global health, as the expansion of resistance to current antibiotics has made serious therapeutic problems. Genome mutations are key evolutionary mechanisms conferring antibiotic resistance in bacterial pathogens. For example, penicillin and cephalosporins resistance is mostly mediated by mutations in penicillin binding proteins to change the affinity of the drug. Accordingly, threonine point mutations were reported to develop antibiotic resistance in various bacterial infections including pneumococcal infections. In this study, conventional molecular dynamics simulations, umbrella sampling simulations and MM/GBSA free energy calculations were applied to figure out how the Threonine to Alanine mutation (T to A) at STMK motif affects the binding of cefotaxime to Penicillin Binding Protein 1a and to reveal the resistance mechanism induced by the T to A mutation. The results obtained from the computational methods demonstrate that the T to A mutation increases the flexibility of the binding pocket and changes its conformation, which leads to increased conformational entropy change (−TΔS) and attenuates the bonds between the ligand and the receptor. In brief, our findings indicate that both of the alterations of the conformational enthalpy and entropy contribute to the T to A-induced resistance in the binding of cefotaxime into penicillin binding protein 1a.