Silence of the mutations Mahadevan, S
Journal of biosciences,
12/2022, Letnik:
47, Številka:
4
Journal Article
Recenzirano
A major presumption of the neutral theory of evolution proposed by Kimura in the late 1960s is that synonymous mutations (mutations that do not alter the primary sequence of a protein due to the ...redundancy of the genetic code) are supposed to be selectively neutral or nearly neutral (Kimura 1968). However, Shen et al. (2022) have recently demonstrated that 75.9% of synonymous mutations in genes involved in important cellular functions in the haploid yeast
show reduced fitness in different environments examined. Based on their analyses of fitness effects in different growth conditions, the authors argue that non-synonymous mutants show a more significant fitness variation across growth environments compared with synonymous mutants, although the two mutant classes have similar patterns of fitness susceptibility in the same environment. They propose that a larger proportion of synonymous mutants reach fixation compared with their non-synonymous counterparts because more of them survive environmental challenges. In this Clipboard article, I examine the evidence provided by the authors to evaluate whether their evidence is sufficient to substantiate this claim and explore possible consequences of these observations.
This paper proposes a computational methodology to quantify the individual contributions of variability and distribution parameter uncertainty to the overall uncertainty in a random variable. Even if ...the distribution type is assumed to be known, sparse or imprecise data leads to uncertainty about the distribution parameters. If uncertain distribution parameters are represented using probability distributions, then the random variable can be represented using a family of probability distributions. The family of distributions concept has been used to obtain qualitative, graphical inference of the contributions of natural variability and distribution parameter uncertainty. The proposed methodology provides quantitative estimates of the contributions of the two types of uncertainty. Using variance-based global sensitivity analysis, the contributions of variability and distribution parameter uncertainty to the overall uncertainty are computed. The proposed method is developed at two different levels; first, at the level of a variable whose distribution parameters are uncertain, and second, at the level of a model output whose inputs have uncertain distribution parameters.
Long‐term chemical durability of borosilicate glasses that makes them a widely accepted form of nuclear waste disposal is achieved through the formation of a porous aluminosilicate gel layer that ...provides passivity and limits the transport of water to the reaction front. Detailed understanding of the porous silicate gel layer is thus critical in elucidating the corrosion mechanism of these glasses and to design of new glass composition for waste immobilization and other applications. In this paper, we use the diffuse charge reactive potential to generate porous aluminosilicate glass structures with compositions equivalent to the gel layers formed at the glass‐water interface with an aim to understand the processing condition on the microstructure and atomic structure of these systems. We demonstrate the use of the charge scaling techniques is an effective approach to generate these porous structures with controllable pore mophologies. After initial validation of the potentials and calcium aluminosilicate glass structures using neutron diffraction, we created gel structures with compositions similar to well‐known model nuclear waste borosilicate glasses. The porosities and the pore size distribution bear a strong correlation to the processing temperature, as well as to the local atomic structure. Thus, by controlling the processing parameters, the generated porous structures can be customized to closely resemble gel structures due to borosilicate glass corrosion. These results provide insights of the micro‐ and atomic structure features of the porous aluminosilicate glasses and on the optimal procedure to generate porous structures that can be comparable to experimentally observed gel layer structures thus to elaborate on the correlations between the structure and phenomena in glass‐water interactions.
Understanding the interactions between amorphous silica surfaces and water provides insight into material degradation of silicate glasses and minerals in aqueous environment. Molecular dynamics (MD) ...simulations of water and nanometer sized silica structures were used in this work to evaluate the reactivity of flat silica surface and surfaces with curvature. We compared two dissociable water/silica potentials, namely the Reactive Force Field (ReaxFF) and the Mahadevan–Garofalini water/silica force field (MGFF) that have been in development over the past decade, to study their performance in simulating bulk water as well as silica–water interactions. Significant differences in the properties of bulk water as well as surface interactions were observed between the two types of potentials, as well in the same potential type with two parametrizations for ReaxFF, suggesting a need for improvement of the existing water/silica ReaxFF potentials. Our simulation results show that a majority of the silanols were formed by reactions between water and strained siloxane bonds that mainly exist on the surface of amorphous silica, within a few nanoseconds of the simulation time scale, in agreement with previous studies. Effect of surface curvature on the reactivity with water was investigated. Our results indicate that defect concentration at the surface bears a strong correlation to the concentration of silanols (Si–OH) that eventually form. We observe undercoordinated Si’s at the surface that are attacked by water before the hydrolysis reaction of the siloxane bonds and demonstrate possible mechanisms of water reacting with these undercoordinated Si’s. We also find that the method of generating surfaces in simulation determines the defect concentration and hence influences the reactivity of the amorphous silica surface.
The new age of nutraceuticals is now embracing the centuries old herbal extract of Ginkgo biloba (Mantissa Plantarum Altera, 1771, Ginkgoceae). The standardized preparation of the Ginkgo leaf extract ...(EGb 761) contained 2 main bioactive constituents, flavonoid glycosides (24%) and terpene lactones (6%), along with less than 5 ppm of the allergenic component, ginkgolic acid. The Ginkgo leaf extract has been reported to have neuroprotective, anticancer, cardioprotective, stress alleviating, and memory enhancing effects and possible effects on tinnitus, geriatric complaints, and psychiatric disorders. The therapeutic mechanisms of action of the Ginkgo leaf extract are suggested to be through its antioxidant, antiplatelet, antihypoxic, antiedemic, hemorrheologic, and microcirculatory actions, where the flavonoid and the terpenoid constituents may act in a complementary manner. Toxicity studies show that the Ginkgo leaf extract is relatively safe for consumption, although a few side effects have been reported, that is, intracerbral hemorrhage, gastrointestinal disturbances, headaches, dizziness, and allergic skin reactions. The use of Ginkgo leaf extract may be promising for treatment of certain conditions, although its long-term use still needs to be evaluated.
Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD), with most cases occurring in patients with congenital cardiac shunts. In patients with an uncorrected ...left-to-right shunt, increased pulmonary pressure leads to vascular remodelling and dysfunction, resulting in a progressive rise in pulmonary vascular resistance and increased pressures in the right heart. Eventually, reversal of the shunt may arise, with the development of Eisenmenger's syndrome, the most advanced form of PAH-CHD. The prevalence of PAH-CHD has fallen in developed countries over recent years and the number of patients surviving into adulthood has increased markedly. Today, the majority of PAH-CHD patients seen in clinical practice are adults, and many of these individuals have complex disease or received a late diagnosis of their defect. While there have been advances in the management and therapy in recent years, PAH-CHD is a heterogeneous condition and some subgroups, such as those with Down's syndrome, present particular challenges. This article gives an overview of the demographics, pathophysiology and treatment of PAH-CHD and focuses on individuals with Down's syndrome as an important and challenging patient group.
Simeprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, displays nonlinear pharmacokinetics (PK) at therapeutic doses. Using physiologically based PK modeling, various drug‐drug interactions ...were simulated with simeprevir as victim drug to identify whether saturation of the predominant metabolic enzyme (CYP3A4) or the active hepatic transporters (organic anion‐transporting polypeptide (OATP)1B1/3) could account for the nonlinear PK. Interactions with ritonavir, a strong CYP3A4 inhibitor that does not affect OATP (at 100 mg dose), erythromycin, a moderate CYP3A4 inhibitor, and efavirenz, a moderate CYP3A inducer that does not affect OATP, demonstrated the involvement of CYP3A4. Interaction studies with low‐dose cyclosporine confirmed the role of OATP. The interplay between hepatic uptake and CYP3A4 metabolism was verified by simulations with rifampicin, a potent CYP3A4 inducer and OATP1B1/3 inhibitor, and maintenance doses of cyclosporine. Saturation of gut and liver metabolism by CYP3A4, and saturation of hepatic uptake by OATP1B1/3, seem to account for the observed nonlinear PK of simeprevir.
In the recent decades, nanotechnology has become an important research field of modern material science. Green synthesized nanoparticles have garnered wide interest due to its inherent features like ...rapidity, eco-friendly and cost-effectiveness. For the first time, Zinc Oxide nanoparticles were successfully synthesized using Atalantia monophylla leaf extract in the present's investigation. The biosynthesized Zinc Oxide nanoparticles were characterized by UV- Vis spectrophotometer, Fluorescence spectrometer (PL) and their peaks were identified to be at 352 and 410 nm respectively. The morphology of the Zinc Oxide nanoparticles was characterized by TEM with EDAX. The X- ray diffraction (XRD) studies showed the crystalline nature and revealed the purity of Zinc Oxide nanoparticles. FTIR spectroscopy was used to analyze the specific functional groups responsible for reduction, stabilization and capping agents present in the nanoparticles. The success-ability of bacteria and fungi with Synthesized ZnO nanoparticles tested using agar well diffusion method were discussed. The bacterial and fungal destruction was better for ZnO nanoparticles than reported for plant extracts and standard drugs. Thus this study proves that Zinc Oxide nanoparticles would contain natural anti-microbial agents through green synthesis which may serve for the production of drugs for antimicrobial therapeutics.
ABSTRACT Given the potential of ensemble asteroseismology for understanding fundamental properties of large numbers of stars, it is critical to determine the accuracy of the scaling relations on ...which these measurements are based. From several powerful validation techniques, all indications so far show that stellar radius estimates from the asteroseismic scaling relations are accurate to within a few percent. Eclipsing binary systems hosting at least one star with detectable solar-like oscillations constitute the ideal test objects for validating asteroseismic radius and mass inferences. By combining radial velocity (RV) measurements and photometric time series of eclipses, it is possible to determine the masses and radii of each component of a double-lined spectroscopic binary. We report the results of a four-year RV survey performed with the échelle spectrometer of the Astrophysical Research Consortium's 3.5 m telescope and the APOGEE spectrometer at Apache Point Observatory. We compare the masses and radii of 10 red giants (RGs) obtained by combining radial velocities and eclipse photometry with the estimates from the asteroseismic scaling relations. We find that the asteroseismic scaling relations overestimate RG radii by about 5% on average and masses by about 15% for stars at various stages of RG evolution. Systematic overestimation of mass leads to underestimation of stellar age, which can have important implications for ensemble asteroseismology used for Galactic studies. As part of a second objective, where asteroseismology is used for understanding binary systems, we confirm that oscillations of RGs in close binaries can be suppressed enough to be undetectable, a hypothesis that was proposed in a previous work.
Biosynthesized nanoparticles have an incredible application in biomedicine owing to its simplicity, eco-friendly properties and low cost. The present study aims to determine the green synthesized ...zinc oxide nanoparticles from methanolic leaf extract of Glycosmis pentaphylla. The synthesized nanoparticles were characterized using UV-VIS Spectroscopy, Fluorescence spectrometer, FT-IR, XRD, SEM with EDAX and TEM. The confirmations of synthesized nanoparticles were characterized by peak at 351 and 410 nm in the UV-VIS spectrum and photoluminescence spectrum respectively. FT-IR studies revealed the functional group of the nanoparticles. The XRD data showed the crystalline nature of the nanoparticles and EDAX measurements indicated the 20.70% of highly pure zinc oxide metal. The morphological characterization of synthesized zinc oxide nanoparticles was analyzed by SEM and TEM and size of the particles were ranging from 32 to 36 nm. The synthesized zinc oxide nanoparticles exhibited interesting antimicrobial activity against pathogenic organisms. In addition, this is the first report on leaf mediated synthesis of zinc oxide (ZnO) nanoparticles from Glycosmis pentaphylla.
•Bio-synthesize of ZnO nanoparticles is using Glycosmis pentaphylla for the first time.•XRD pattern confirmed ZnO hexagonal phase (wurtzite structure).•The synthesized ZnO nanoparticles have shown excellent antimicrobial activity against pathogenic microorganisms.
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