The Pandemic situation caused due to SARS-CoV-2 causing Coronavirus Disease (CoVID-19) around globe. Recent, COVID-19 main protease complex (M pro), highly modulating enzyme in SARS-CoV-2 was reported for viral replication and transcription. This multifunctionality of M pro attracts for identi cation of potential drug target. Considering impact, In silico analysis was performed for Palmatine alkaloid against M pro. Naturally, present in Tinospora cordifolia, found effective against Cancer, HIV, viral infections, diabetics. In methods, physico-chemical analysis by ProtParam tool and Structure of M pro was predicted by SWISS-MODEL Workspace homology modeling server. Superimposition Structure and signi cant equal QMQE, QSQE values were found for eight highly similar templates. Structural assessment validation by Ramachandran plot (97.67% favoured), Local Quality estimate ratio (>0.6) and higher QMEAN score (y-axis). Further, docking was performed with validated M pro model by SwissDock server. Interaction with-8.281919 ΔG indicates reliable Interaction. Also, comparative docking reveals, most favoured Palmatine interaction. Thus, an attempt was made to nd potent inhibitor for SARS-CoV-2, as there is no promising and speci c anti-viral drug or vaccine available for prevention and treatment of infections. However, In Vitro studies are required. Toxicity studies reported against Palmatine for acute effect (135 mg/kg body weight) on mouse model LD 50.
The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself1. However, little is known about what determines its evolution, as most studies of mutation rates have focused on single species with different methodologies2. Here we quantify germline mutation rates across vertebrates by sequencing and comparing the high-coverage genomes of 151 parent–offspring trios from 68 species of mammals, fishes, birds and reptiles. We show that the per-generation mutation rate varies among species by a factor of 40, with mutation rates being higher for males than for females in mammals and birds, but not in reptiles and fishes. The generation time, age at maturity and species-level fecundity are the key life-history traits affecting this variation among species. Furthermore, species with higher long-term effective population sizes tend to have lower mutation rates per generation, providing support for the drift barrier hypothesis3. The exceptionally high yearly mutation rates of domesticated animals, which have been continually selected on fecundity traits including shorter generation times, further support the importance of generation time in the evolution of mutation rates. Overall, our comparative analysis of pedigree-based mutation rates provides ecological insights on the mutation rate evolution in vertebrates.
In nature, the formation of spider silk fibers begins with dimerizing the pH‐sensitive N‐terminal domains of silk proteins (spidroins) upon lowering pH, and provides a natural masterpiece for programmable assembly. Inspired by the similarity of pH‐dependent dimerization behaviors, introduced here is an i‐motif‐guided model to mimic the initial step of spidroin assembly at the subcellular level. A framework nucleic acid (FNA) nanoplatform is designed using two tetrahedral DNA nanostructures (TDNs) with different branched vertexes carrying a bimolecular i‐motif and a split ATP aptamer. Once TDNs enter acidic lysosomes within living cells, they assemble into a heterodimeric architecture, thereby enabling the formation of a larger‐size framework and meanwhile subcellular imaging in response to endogenous ATP, which can be dynamically manipulated by adjusting intracellular pH and ATP levels with external drug stimuli.
The direct production of light α‐olefins (C2=‐C4=) from CO2 is of great importance as this process can convert the greenhouse gas into the desired chemicals. In this study, the crucial roles of Na and Mn promoter in CO2 hydrogenation to produce light α‐olefins via the Fischer‐Tropsch synthesis (FTS) over Fe3O4‐based catalysts are investigated. The results indicate that both Na and Mn promoter can enhance the reducibility of Fe3O4. In situ XPS and DFT calculations show that Na facilitates the reduction by electron donation from Na to Fe as the oxygen vacancy formation energy is reduced by Na. In contrast, Mn promotes the reduction by the presence of oxygen vacancy in MnO as the oxygen in Fe oxide can spillover to the vacancy in MnO spontaneously. For un‐promoted Fe3O4 catalysts, CO2 hydrogenation dominantly produces light n‐paraffins. The addition of Na remarkably shifts the selectivity to light α‐olefins with a sharp decline in the selectivity to light n‐paraffins, which is attributed to the electron donation from Na to Fe resulting in the promoted CO dissociation and the favorable β‐H abstraction of surface short alkyl‐metal intermediates. The addition of Mn into Na‐containing Fe3O4 catalysts can obviously further enhance the selectivity to light α‐olefins as the spatial hindrance of Mn suppresses the chain growth to increase the amount of surface short alkyl‐metal intermediates.
In the human fungal pathogen Cryptococcus neoformans, sex can benefit its pathogenicity through production of meiospores, which are believed to offer both physical and meiosis-created lineage advantages for its infections. Cryptococcus sporulation occurs following two parallel events, meiosis and differentiation of the basidium, the characteristic sexual structure of the basidiomycetes. However, the circuit integrating these events to ensure subsequent sporulation is unclear. Here, we show the spatiotemporal coordination of meiosis and basidial maturation by visualizing event-specific molecules in developing basidia defined by a quantitative approach. Monitoring of gene induction timing together with genetic analysis reveals co-regulation of the coordinated events by a shared regulatory program. Two RRM family regulators, Csa1 and Csa2, are crucial components that bridge meiosis and basidial maturation, further determining sporulation. We propose that the regulatory coordination of meiosis and basidial development serves as a determinant underlying the production of infectious meiospores in C. neoformans.
A composite Na/Fe and SiO2-coated HZSM-5 catalyst system has been developed for the highly selective production of aromatics (93–95%), especially para-xylene, in the liquid phase and light olefins in the gas phase from CO2.
Background Understanding the rate and pattern of germline mutations is of fundamental importance for understanding evolutionary processes. Results Here we analyzed 19 parent-offspring trios of rhesus macaques (Macaca mulatta) at high sequencing coverage of ∼76× per individual and estimated a mean rate of 0.77 × 10−8de novo mutations per site per generation (95% CI: 0.69 × 10−8 to 0.85 × 10−8). By phasing 50% of the mutations to parental origins, we found that the mutation rate is positively correlated with the paternal age. The paternal lineage contributed a mean of 81% of the de novo mutations, with a trend of an increasing male contribution for older fathers. Approximately 3.5% of de novo mutations were shared between siblings, with no parental bias, suggesting that they arose from early development (postzygotic) stages. Finally, the divergence times between closely related primates calculated on the basis of the yearly mutation rate of rhesus macaque generally reconcile with divergence estimated with molecular clock methods, except for the Cercopithecoidea/Hominoidea molecular divergence dated at 58 Mya using our new estimate of the yearly mutation rate. Conclusions When compared to the traditional molecular clock methods, new estimated rates from pedigree samples can provide insights into the evolution of well-studied groups such as primates.
Lions are one of the world’s most iconic megafauna, yet little is known about their temporal and spatial demographic history and population differentiation. We analyzed a genomic dataset of 20 specimens: two ca. 30,000-y-old cave lions (Panthera leo spelaea), 12 historic lions (Panthera leo leo/Panthera leo melanochaita) that lived between the 15th and 20th centuries outside the current geographic distribution of lions, and 6 present-day lions from Africa and India. We found that cave and modern lions shared an ancestor ca. 500,000 y ago and that the 2 lineages likely did not hybridize following their divergence. Within modern lions, we found 2 main lineages that diverged ca. 70,000 y ago, with clear evidence of subsequent gene flow. Our data also reveal a nearly complete absence of genetic diversity within Indian lions, probably due to well-documented extremely low effective population sizes in the recent past. Our results contribute toward the understanding of the evolutionary history of lions and complement conservation efforts to protect the diversity of this vulnerable species.
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