Hydrodynamics of spike proteins dictate a transport-affinity competition for SARS-CoV-2 and other enveloped viruses

Many viruses, such as SARS-CoV-2 or Influenza, possess spike-decorated envelopes. Depending on the virus type, a large variability is present in spikes number, morphology and reactivity, which remains generally unexplained. Since viruses' transmissibility depend on features beyond their genetic sequence, new tools are required to discern the effects of spikes functionality, interaction, and morphology. Here, we postulate the relevance of hydrodynamic interactions in the viral infectivity of enveloped viruses and propose micro-rheological characterization as a platform for viruses differentiation. To understand how the spikes affect virion mobility and infectivity, we investigate the diffusivity of spike-decorate structures using mesoscopic-hydrodynamic simulations. Furthermore, we explored the interplay between affinity and passive viral transport. Our results revealed that the diffusional mechanism of SARS-CoV-2 is strongly influenced by the size and distribution of its spikes. We propose and validate a universal mechanism to explain the link between optimal virion structure and maximal infectivity for many virus families.

Energy Bilocalization Effect and the Emergence of Molecular Functions in Proteins

Proteins are among the most complex molecular structures, which have evolved to develop broad functions, such as energy conversion and transport, information storage and processing, communication, and regulation of chemical reactions. However, the mechanisms by which these dynamical entities coordinate themselves to perform biological tasks remain hotly debated. Here, a physical theory is presented to explain how functional dynamical behavior possibly emerge in complex/macro molecules, thanks to the effect that we term bilocalization of thermal vibrations. More specifically, our approach allows us to understand how structural irregularities lead to a partitioning of the energy of the vibrations into two distinct sets of molecular domains, corresponding to slow and fast motions. This shape-encoded spectral allocation, associated to the genetic sequence, provides a close access to a wide reservoir of dynamical patterns, and eventually allows the emergence of biological functions by natural selection. To illustrate our approach, the SPIKE protein structure of SARS-COV2 is considered.

Genetic sequence analysis of Arthrobotrys thaumasia DS01 (Monacrosporium thaumasium): A new report from North Sumatra, Indonesia

Exploration of nematode-trapping fungi (NTF) has been conducted previously in urban area, the Medan city, North Sumatra, Indonesia. The survey reported a number of NTF species inhabiting soil samples of organic wastes and decaying litter. Upon finding a suitable NTF isolate as nematode biocontrol agent, species identification is currently carried out based on molecular evidences. One morphotype named isolate DS01 is suspected as member of Arthrobotrys based on morphological characteristics. Molecular sequencing on rDNA or ITS-DNA region has successfully been performed. The genetic sequence was analyzed with database retrieved in NCBI, revealing the identity of A. thaumasia/M. thamasium. Based on recent findings, this is the first report on indigenous strain of A. thaumasia from Indonesia.

Revision of the West Palaearctic Euura bergmanni and oligospila groups (Hymenoptera, Tenthredinidae)

Eight Western Palaearctic Euura species are here assigned to the bergmanni group (bergmanni, brevivalvis, dispar, glutinosae, leptocephalus, respondens, sylvestris, and viridis) and two species to the oligospila group (frenalis and oligospila). Euura pallens (Konow, 1903) (bergmanni group) is removed from the list of West Palaearctic taxa. Euura pyramidalis (Hellén, 1948) is treated as incertae sedis within the bergmanni group. Definitions of the bergmanni and oligospila groups are primarily based on genetic sequence data (mitochondrial COI and nuclear NaK and POL2). We report likely occurrence of heteroplasmy and amplification of NUMTs among some of the treated species, complicating the use of DNA barcoding in species discrimination. Based on morphological and genetic evidence, we establish that the correct name for the invasive willow sawfly in the southern hemisphere (South America, southern Africa, Australia, New Zealand), known there only in the female sex, is Euura respondens (Förster, 1854). The species is probably native to the Palaearctic (or even Holarctic) where males are common: possibly as common as females (examined from Europe and Central Asia). The name Euura oligospila (Förster, 1854) has been incorrectly used for the species in the southern hemisphere. The examination of type material and reliable association of males and females based on genetics revealed that females of E. oligospila are morphologically extremely similar to E. respondens (and to some other E. bergmanni group species), but male penis valves and genetics enable reliable separation of these species. Morphological separation of females of E. oligospila and E. respondens is possible, but challenging. Identification keys for males and females of the bergmanni and oligospila groups are provided. The following 15 new synonymies are proposed: Nematus validicornis Förster, 1854, syn. nov. with Euura bergmanni (Dahlbom, 1835); Pteronidea woollatti Lindqvist, 1971, syn. nov. and Nematus turgaiensis Safjanov, 1977, syn. nov. with Euura brevivalvis (Thomson, 1871); Pteronidea pseudodispar Lindqvist, 1969, syn. nov. with Euura dispar (Zaddach, 1876); Nematus (Pteronidea) fastosus var. ponojense Hellén, 1948, syn. nov. and N. (P.) fastosus var. punctiscuta Hellén, 1948, syn. nov. with Euura frenalis (Thomson, 1888); Nematus declaratus Muche, 1974, syn. nov. and N. desantisi D.R. Smith, 1983, syn. nov. with Euura respondens (Förster, 1854); Pteronidea straminea Lindqvist, 1958, syn. nov., P. angustiserra Lindqvist, 1969, syn. nov., and P. disparoides Lindqvist, 1969, syn. nov. with Euura sylvestris (Cameron, 1884); Pteronidea breviseta Lindqvist, 1946, syn. nov., P. breviseta Lindqvist, 1949, syn. nov., P. abscondita Lindqvist, 1949, syn. nov., and P. lauroi Lindqvist, 1960, syn. nov. with Euura viridis (Stephens, 1835). Lectotypes are designated for 18 nominal taxa: Amauronematus longicornis Konow, 1897; A. spurcus Konow, 1904; Nematus bergmanni Dahlbom, 1835; N. brevivalvis Thomson, 1871; N. curtispina Thomson, 1871; N. (Pteronidea) fastosus var. ponojense Hellén, 1948; N. (P.) fastosus var. punctiscuta Hellén, 1948; N. glutinosae Cameron, 1882; N. microcercus Thomson, 1871; N. polyspilus Förster, 1854; N. prasinus Hartig, 1837; N. respondens Förster, 1854; N. salicivorus Cameron, 1882; N. validicornis Förster, 1854; N. virescens Hartig, 1837; Pteronidea curtispina var. luctuosa Enslin, 1916; Pteronus fastosus Konow, 1904; and P. pallens Konow, 1903.

A new lithostratigraphic framework for portions of the Pongola Supergroup within the Nkandla sub-basin, southern Kaapvaal Craton, South Africa; insights into Mozaan Group stratigraphy

A revised lithostratigraphic framework for Mozaan Group-equivalent strata within the Nkandla sub-basin is presented based on new field data, remote sensing and genetic sequence stratigraphic interpretations. Although previous literature has suggested that no Mozaan Group lithologies were deposited within the sub-basin, reinterpretations presented here indicate that 90% of the lithostratigraphy developed within the main basin occurs within the Nkandla and Mhlatuze inliers. Mozaan Group units previously defined as the Vutshini and Ekombe formations are correlated with stratigraphy from the lowermost Sinqeni Formation to the Gabela Formation. Although thinner than units within the type area in the main basin, thicknesses of the Sinqeni Formation are comparable to those observed within the White Mfolozi Inlier. A ~1 000 m composite reference profile is measured within the Mdlelanga Syncline of the Nkandla Inlier. Further profiles were measured for sequences in the Gem-Vuleka Syncline of the Nkandla Inlier, as well as within the Mhlatuze Inlier. These latter profiles, however, host only lower Mozaan Group strata. In all sections the basal portion of the sequence comprises two quartz arenite units, separated by a ferruginous shale, which hosts minor iron formation interbeds. This predominantly coarse-grained lower sequence is overlain by a shale-dominated succession with multiple sandstone interbeds. A prominent coarse-grained quartz arenite unit forms a distinct marker in the middle portion of the sequence. This is overlain by a sequence of shales and sandstones with two prominent igneous units present. Genetic sequence stratigraphic interpretations indicate cyclical deposition of dominantly shallow marine sediments with condensed sections, marked by iron formations or ferruginous shales, denoting periods of marine highstand along the southeastern margin of the Kaapvaal Craton. The evidence of Mozaan Group stratigraphy within the Nkandla sub-basin supports a passive margin tectonic model whereby deposition occurred in an arcuate shallow continental margin which opened to the southeast. The extension of Mozaan Group strata into the Nkandla sub-basin suggests that the Mozaan Basin likely formed a single depository rather than separate sub-basins as previously proposed.

Recombination patterns in coronaviruses

As shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from different hosts can be described by a branching phylogenetic tree. Recombination breaks this assumption. This makes it problematic to apply phylogenetic methods to study recombining pathogens, including, for example, coronaviruses. Here, we introduce a Markov chain Monte Carlo approach that allows inference of recombination networks from genetic sequence data under a template switching model of recombination. Using this method, we first show that recombination is extremely common in the evolutionary history of SARS-like coronaviruses. We then show how recombination rates across the genome of the human seasonal coronaviruses 229E, OC43 and NL63 vary with rates of adaptation. This suggests that recombination could be beneficial to fitness of human seasonal coronaviruses. Additionally, this work sets the stage for Bayesian phylogenetic tracking of the spread and evolution of SARS-CoV-2 in the future, even as recombinant viruses become prevalent.

Transcription and Cancer in Eukaryotes

Organisms demand pinpoint and correlated gene expression controls for growth, advancement, and operation. This control is also known as transcriptional regulation. It is a complicated process especially in eukaryotes since it is responsible for all biological processes. Transcription control and its concept were brought up about half a century ago1. These concepts gave a basic understanding on DNA binding transcription factors (trans-factors) which inhabit specific DNA sequences at control elements (cis-elements). They regulate transcription apparatus2. Mis-regulation of transcription may cause failure of gene expression that is responsible for cell division, through disproportionate activation of once positively acting transcriptional factors and nuclear oncogenes3. Epigenetic is learning heritable alterations in gene expression that do not occur and involve in DNA sequence. These changes can be established all the time almost randomly, and alternations are passed and inherited through cell division and replication, allowing cells to have different identities while having the same genetic sequence. Due to loss of epigenetic control and failure of keeping proper epigenetic marks, which result in inappropriate activation and will lead to disease state including cancer4. This review focuses on transcriptions, epigenetics, cancers, and potential therapies to regulate and control cancer cells.

Machine Learning Prediction and Experimental Validation of Antigenic Drift in H3 Influenza A Viruses in Swine

ABSTRACT The antigenic diversity of influenza A viruses (IAV) circulating in swine challenges the development of effective vaccines, increasing zoonotic threat and pandemic potential. High-throughput sequencing technologies can quantify IAV genetic diversity, but there are no accurate approaches to adequately describe antigenic phenotypes. This study evaluated an ensemble of nonlinear regression models to estimate virus phenotype from genotype. Regression models were trained with a phenotypic data set of pairwise hemagglutination inhibition (HI) assays, using genetic sequence identity and pairwise amino acid mutations as predictor features. The model identified amino acid identity, ranked the relative importance of mutations in the hemagglutinin (HA) protein, and demonstrated good prediction accuracy. Four previously untested IAV strains were selected to experimentally validate model predictions by HI assays. Errors between predicted and measured distances of uncharacterized strains were 0.35, 0.61, 1.69, and 0.13 antigenic units. These empirically trained regression models can be used to estimate antigenic distances between different strains of IAV in swine by using sequence data. By ranking the importance of mutations in the HA, we provide criteria for identifying antigenically advanced IAV strains that may not be controlled by existing vaccines and can inform strain updates to vaccines to better control this pathogen. IMPORTANCE Influenza A viruses (IAV) in swine constitute a major economic burden to an important global agricultural sector, impact food security, and are a public health threat. Despite significant improvement in surveillance for IAV in swine over the past 10 years, sequence data have not been integrated into a systematic vaccine strain selection process for predicting antigenic phenotype and identifying determinants of antigenic drift. To overcome this, we developed nonlinear regression models that predict antigenic phenotype from genetic sequence data by training the model on hemagglutination inhibition assay results. We used these models to predict antigenic phenotype for previously uncharacterized IAV, ranked the importance of genetic features for antigenic phenotype, and experimentally validated our predictions. Our model predicted virus antigenic characteristics from genetic sequence data and provides a rapid and accurate method linking genetic sequence data to antigenic characteristics. This approach also provides support for public health by identifying viruses that are antigenically advanced from strains used as pandemic preparedness candidate vaccine viruses.

Efficacy and Safety of AZD1222, BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2

SARS-CoV-2, the beta coronavirus causing COVID-19, was isolated and categorizes as a novel one on January 7th, 2020 in China.[1] To date, official reports depict that SARS-CoV-2 has already infected 88.828.387 persons and caused 1.926.625 deaths worldwide.[2] On January 12th, 2020, China officials made public its genetic sequence, thus paving the way towards the research and development of diagnostic tests and vaccines. With regard to vaccination, e large number of clinical trials were designed and are currently undergoing, of which 189 are listed in ClinicalTrials.gov. [3] However, up to date, only three vaccines have published their respective phase III clinical trial results in peer-reviewed medical journals. [4-6] Vaccines are needed to reduce the morbidity and mortality associated with Covid-19, and multiple vaccine platforms as AZD1222 (AstraZeneca) [4], BNT162b2 (Pfizer/BioNTech) [5] and mRNA-1273 (Moderna) have been involved in the rapid development of vaccine candidates. Methodology: In this review, PubMed, Embase, Web of Science, Scopus, medRxiv, and bioRxiv were systematically scrutinized for peer-reviewed and preprint articles on phase III clinical trials of vaccines against SARS-CoV-2. In total, only three peer-reviewed papers fulfilling the search criteria were identified. Conclusions; All vaccine candidates should publish in peer-reviewed journals their efficacy and safety well before requesting approval to the national or international authorities…