AlphaFold changed the field of structural biology by achieving three-dimensional (3D) structure prediction from protein sequence at experimental quality. The astounding success even led to claims ...that the protein folding problem is "solved". However, protein folding problem is more than just structure prediction from sequence. Presently, it is unknown if the AlphaFold-triggered revolution could help to solve other problems related to protein folding. Here we assay the ability of AlphaFold to predict the impact of single mutations on protein stability (ΔΔG) and function. To study the question we extracted the pLDDT and metrics from AlphaFold predictions before and after single mutation in a protein and correlated the predicted change with the experimentally known ΔΔG values. Additionally, we correlated the same AlphaFold pLDDT metrics with the impact of a single mutation on structure using a large scale dataset of single mutations in GFP with the experimentally assayed levels of fluorescence. We found a very weak or no correlation between AlphaFold output metrics and change of protein stability or fluorescence. Our results imply that AlphaFold may not be immediately applied to other problems or applications in protein folding.
ABSTRACT
We present the public data release of the AbacusSummit cosmological N-body simulation suite, produced with the Abacus N-body code on the Summit supercomputer of the Oak Ridge Leadership ...Computing Facility. Abacus achieves $\mathcal {O}(10^{-5})$ median fractional force error at superlative speeds, calculating 70M particle updates per second per node at early times, and 45M particle updates per second per node at late times. The simulation suite totals roughly 60 trillion particles, the core of which is a set of 139 simulations with particle mass $2\times 10^{9}\, h^{-1}\, \mathrm{M}_\odot$ in box size $2\, h^{-1}\, \mathrm{Gpc}$. The suite spans 97 cosmological models, including Planck 2018, previous flagship simulation cosmologies, and a linear derivative and cosmic emulator grid. A subsuite of 1883 boxes of size $500\, h^{-1}\, \mathrm{Mpc}$ is available for covariance estimation. AbacusSummit data products span 33 epochs from z = 8 to 0.1 and include light cones, full particle snapshots, halo catalogues, and particle subsets sampled consistently across redshift. AbacusSummit is the largest high-accuracy cosmological N-body data set produced to date.
The abacus cosmological N-body code Garrison, Lehman H; Eisenstein, Daniel J; Ferrer, Douglas ...
Monthly Notices of the Royal Astronomical Society,
11/2021, Letnik:
508, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
We present abacus, a fast and accurate cosmological N-body code based on a new method for calculating the gravitational potential from a static multipole mesh. The method analytically ...separates the near- and far-field forces, reducing the former to direct 1/r2 summation and the latter to a discrete convolution over multipoles. The method achieves 70 million particle updates per second per node of the Summit supercomputer, while maintaining a median fractional force error of 10−5. We express the simulation time-step as an event-driven ‘pipeline’, incorporating asynchronous events such as completion of co-processor work, input/output, and network communication. abacus has been used to produce the largest suite of N-body simulations to date, the abacussummit suite of 60 trillion particles, incorporating on-the-fly halo finding. abacus enables the production of mock catalogues of the volume and resolution required by the coming generation of cosmological surveys.
The association of latent toxoplasmosis with mental disorders in general and with schizophrenia in particular was noticed in the mid-1950s. In subsequent years, the role of Toxoplasma gondii was ...established based on its ability to survive for long periods of time in the nerve cells of the brain. The acute manifestations of the infection include psychopathic symptoms resembling those of schizophrenia. In the former USSR, and in other parts of the world, a number of studies were performed with respect to the association of latent toxoplasmosis and schizophrenia. However, with the dissolution of the USSR at the beginning of the 1990s, studies on the subject were halted due to financial problems and have resumed only recently. The reasons for the resumption of such studies in contemporary Russia are related to the progressively increasing incidence of schizophrenia over the last 25-30 years in the country. According to official data, approximately 550 000 persons reported suffering from the disease in 2014. There are reasons to believe that this is only a fraction of the real burden of the disease. Economically, it cost the state no less than approximately US $10 billion. The purpose of the study was to identify the level of toxoplasmosis seroprevalence in patients with verified diagnoses of schizophrenia in comparison to healthy people in Moscow City and in the Moscow region. A total of 155 persons constituted the patients group and 152 healthy people were in the control group. An integrated approach to the diagnosis and comparison of data from the entire spectrum of serological markers of infection was used, including the detection of specific IgM and the determination of IgG concentrations. It was found that among persons with neuropsychiatric disorders, the incidence of cases with latent toxoplasmosis was higher than in the control group. The effect of toxoplasmosis was significant and similar for men and women. Further statistical analyses revealed that among patients with a diagnosis of schizophrenia, the incidence of latent toxoplasmosis was significantly higher than in the control group. These data are in agreement with the results of similar studies in other countries.
The ability of model animal species, such as Drosophila melanogaster, to adapt quickly to various adverse conditions has been shown in many experimental evolution studies. It is usually assumed by ...default that such adaptation is due to changes in the gene pool of the studied population of macroorganisms. At the same time, it is known that microbiome can influence biological processes in macroorganisms. In order to assess the possible impact of microbiome on adaptation, we performed an evolutionary experiment in which some D. melanogaster lines were reared on a food substrate with high NaCl concentration while the others were reared on the standard (favourable) substrate. We evaluated the reproductive efficiency of experimental lines on the high salt substrate three years after the experiment started. Our tests confirmed that the lines reared on the salty substrate became more tolerant to high NaCl concentration. Moreover, we found that pre-inoculation of the high salt medium with homogenized salt-tolerant flies tended to improve reproductive efficiency of naïve flies on this medium (compared to pre-inoculation with homogenized control flies). The analysis of yeast microbiome in fly homogenates revealed significant differences in number and species richness of yeasts between salt-tolerant and control lines. We also found that some individual yeast lines extracted from the salt-tolerant flies improved reproductive efficiency of naïve flies on salty substrate (compared to baker's yeast and no yeast controls), whereas the effect of the yeast lines extracted from the control flies tended to be smaller. The yeast Starmerella bacillaris extracted from the salt-tolerant flies showed the strongest positive effect. This yeast is abundant in all salt-tolerant lines, and very rare or absent in all control lines. The results are consistent with the hypothesis that some components of the yeast microbiome of D. melanogaster contribute to to flies' tolerance to food substrate with high NaCl concentration.
The review summarizes and analyzes information regarding the effect of nanoparticles (NPs) of metals, metal oxides and carbon on the biofilm formation and mature biofilms of microorganisms. The ...viability of individual microbial cells, including direct disruption of cell surface structures and oxidative stress associated with the formation of reactive oxygen species (ROS), as well as the effect on the production of the exopolymer matrix and the quorum sensing system are considered as the mechanisms of NPs action on biofilms. The effects of silver NPs, gold NPs, some metal oxides, and carbon nanomaterials on microbial biofilms have been described in more detail. The effects of metal and carbon NPs on microbial biofilms are compared. Both antibiofilm and probiofilm effects of NPs are noted, depending on their nature, and the prospect of their use as antimicrobial agents and carriers for the production of microbial biofilms of biotechnological significance are considered.
Mounting evidence from genomic and transcriptomic studies suggests that most genetic networks regulating the morphogenesis of land plant sporophytes were co-opted and modified from those already ...present in streptophyte algae and gametophytes of bryophytes
. However, thus far, no candidate genes have been identified that could be responsible for "planation", a conversion from a three-dimensional to a two-dimensional growth pattern. According to the telome theory, "planation" was required for the genesis of the leaf blade in the course of leaf evolution. The key transcription factors responsible for leaf blade development in angiosperms are YABBY proteins, which until recently were thought to be unique for seed plants. Yet, identification of a YABBY homologue in a green alga and the recent findings of YABBY homologues in lycophytes and hornworts suggest that YABBY proteins were already present in the last common ancestor of land plants. Thus, these transcriptional factors could have been involved in "planation", which fosters our understanding of the origin of leaves. Here, we summarise the current data on functions of YABBY proteins in the vegetative and reproductive development of diverse angiosperms and gymnosperms as well as in the development of lycophytes. Furthermore, we discuss a putative role of YABBY proteins in the genesis of multicellular shoot apical meristems and in the evolution of leaves in early divergent terrestrial plants.
The meter-scale variations of material properties of the 20-m sized Chelyabinsk meteoroid are critical for understanding why the meteoroid fragmented the way it did and caused the devastating ...airburst that sent over 1600 people to the hospital for treatment of glass cuts and minor injuries on February 15, 2013. From a range of differently looking unweathered meteorite fragments that were recovered shortly after the event, these material differences were probed by means of optical and scanning electron microscopy, X-ray diffraction (XRD), and the high velocity resolution Mössbauer spectroscopy. All main and some minor iron-bearing phases were identified on the basis of XRD data and Mössbauer spectra. The Fe2+ partitioning between the M1 and M2 sites in silicate phases was determined independently using XRD and Mössbauer data. Different meteorite fragments show a range of 570–1180 K in the temperature of the Fe2+ and Mg2+ equilibrium distribution between the M1 and M2 sites in olivine, while that in orthopyroxene falls in the range 870–1180 K (these ranges were estimated using both techniques). This fact points out a slightly different thermal history of these minerals before they accumulated in different parts of the Chelyabinsk meteoroid. The Chelyabinsk meteoroid is a fragmental breccia from materials formed at different depths in their parent body, or from materials that experienced different annealing temperatures in impacts. In addition, the fusion crust from two fragments, studied by XRD and Mössbauer spectroscopy, experienced a different thermal history during entry, suggesting that the fragment with mixed light and dark lithologies was located deeper inside the initial meteoroid than the fragment with only light lithology, or fragmented less readily.
Mössbauer spectrum of Chelyabinsk LL5 fragment No 2 (left) and differences in the total relative areas for the Mössbauer spectral components corresponding to iron-bearing minerals (variations in the relative iron content in these minerals) for different fragments of Chelyabinsk LL5 meteorite: No 1 and No 1a with light lithology, No 2 and No 2a with mixed light and dark lithologies and No 3 with black lithology: Ol – olivine, OPy – orthopyroxene, CPy – clinopyroxene, Tr – troilite, Chr – chromite, Her – hercynite, Ilm – ilmenite, M – metallic iron alloy (right). Display omitted
•The internal differences on a meter-size scale in the 20-m sized Chelyabinsk meteoroid•Physical properties of different Chelyabinsk meteoroid fragments•Different thermal histories of silicates in different parts of the Chelyabinsk meteoroid
Ordinary chondrites from H, L and LL groups were studied using Mössbauer spectroscopy with a high velocity resolution. Mössbauer parameters of spectral components were obtained using new fitting ...model excluding the effect of previous misfits of troilite component. Obtained parameters were related to corresponding iron-bearing minerals in ordinary chondrites. The differences of these minerals content as well as small differences in the hyperfine parameters of the same iron-bearing minerals were revealed for different meteorites. The temperatures of equilibrium cations distribution in silicates were estimated and suitable parameters for classification of H, L and LL chondrites were supposed using Mössbauer parameters.
Display omitted
•Mössbauer spectra of H, L and LL ordinary chondrites with a high velocity resolution•New fitting model for Mössbauer spectra of ordinary chondrites•Comparison of Mössbauer parameters for iron-bearing minerals in ordinary chondrites•Classification of H, L and LL chondrites using Mössbauer parameters
PDF
