A framework for exploration and cleaning of environmental data : Tehran air quality data experience

Management and cleaning of large environmental monitored data sets is a specific challenge. In this article, the authors present a novel framework for exploring and cleaning large datasets. As a case study, we applied the method on air quality data of Tehran, Iran from 1996 to 2013. ; The framework consists of data acquisition [here, data of particulate matter with aerodynamic diameter ≤10 µm (PM10)], development of databases, initial descriptive analyses, removing inconsistent data with plausibility range, and detection of missing pattern. Additionally, we developed a novel tool entitled spatiotemporal screening tool (SST), which considers both spatial and temporal nature of data in process of outlier detection. We also evaluated the effect of dust storm in outlier detection phase.; The raw mean concentration of PM10 before implementation of algorithms was 88.96 µg/m3 for 1996-2013 in Tehran. After implementing the algorithms, in total, 5.7% of data points were recognized as unacceptable outliers, from which 69% data points were detected by SST and 1% data points were detected via dust storm algorithm. In addition, 29% of unacceptable outlier values were not in the PR.  The mean concentration of PM10 after implementation of algorithms was 88.41 µg/m3. However, the standard deviation was significantly decreased from 90.86 µg/m3 to 61.64 µg/m3 after implementation of the algorithms. There was no distinguishable significant pattern according to hour, day, month, and year in missing data.; We developed a novel framework for cleaning of large environmental monitored data, which can identify hidden patterns. We also presented a complete picture of PM10 from 1996 to 2013 in Tehran. Finally, we propose implementation of our framework on large spatiotemporal databases, especially in developing countries

Comparative Structural and Computational Analysis Supports Eighteen Cellulose Synthases in the Plant Cellulose Synthesis Complex

A six-lobed membrane spanning cellulose synthesis complex (CSC) containing multiple cellulose synthase (CESA) glycosyltransferases mediates cellulose microfibril formation. The number of CESAs in the CSC has been debated for decades in light of changing estimates of the diameter of the smallest microfibril formed from the β-1,4 glucan chains synthesized by one CSC. We obtained more direct evidence through generating improved transmission electron microscopy (TEM) images and image averages of the rosette-type CSC, revealing the frequent triangularity and average cross-sectional area in the plasma membrane of its individual lobes. Trimeric oligomers of two alternative CESA computational models corresponded well with individual lobe geometry. A six-fold assembly of the trimeric computational oligomer had the lowest potential energy per monomer and was consistent with rosette CSC morphology. Negative stain TEM and image averaging showed the triangularity of a recombinant CESA cytosolic domain, consistent with previous modeling of its trimeric nature from small angle scattering (SAXS) data. Six trimeric SAXS models nearly filled the space below an average FF-TEM image of the rosette CSC. In summary, the multifaceted data support a rosette CSC with 18 CESAs that mediates the synthesis of a fundamental microfibril composed of 18 glucan chains

Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice

The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vaccines against the Merbecovirus and Sarbecovirus betacoronavirus subgenera. While SARS-CoV-2 vaccines protect against severe COVID-19, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor-binding domains (RBDs), which elicited live-virus neutralizing antibody responses. The trivalent RBD scNP elicited serum neutralizing antibodies against bat zoonotic Wuhan Institute of Virology-1 (WIV-1)-CoV, SARS-CoV, SARS-CoV-2 BA.1, SARS-CoV-2 XBB.1.5, and MERS-CoV live viruses. The monovalent SARS-CoV-2 RBD scNP vaccine only protected against Sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both Merbecovirus and Sarbecovirus challenge in highly pathogenic and lethal mouse models. This study demonstrates proof of concept for a single pan-sarbecovirus/pan-merbecovirus vaccine that protects against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera

A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice

Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly effective countermeasures against them, which could be key in the prevention and mitigation of current and future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat coronaviruses WIV-1, RsSHC014, and SARS-CoV-2 variants D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, B.1.617.1, and B.1.617.2 by a receptor-binding domain (RBD)-specific human antibody, DH1047. Prophylactic and therapeutic treatment with DH1047 was protective against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B.1.351 infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among sarbecoviruses. Thus, DH1047 is a broadly protective antibody that can prevent infection and mitigate outbreaks caused by SARS-related strains and SARS-CoV-2 variants. Our results also suggest that the conserved RBD epitope bound by DH1047 is a rational target for a universal sarbecovirus vaccin

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies

SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-g (FcgR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcgR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques

Comparative ultrastructure of apical cells and derivatives in bryophytes, with special reference to plasmodesmata

This study focused on the primary cell wall constituents and plasmodesmata (PD) density in three mosses and four liverwort apical cells (AC) and immediate derivatives. The three mosses have tetrahedral apical cells and the liverworts possess tetrahedral, hemidiscoid and lenticular AC geometries. The primary cell wall in the studied taxa is comprised of two layers. A fibrillar layer, which is the outer wall layer, contains compacted cellulosic fibrils, and represents the two adjacent primary walls and middle lamella, the latter of which is rarely discernible. An electron-lucent inner wall layer abuts the plasma membrane. This layer has faint fibrous materials that extend from the plasma membrane to the fibrillar layer. Generally, as the cell wall ages it thickens, the fibrillar layer increases in width while the electron-lucent wall stays more or less consistent in width. In the four liverworts, the most recent wall of the AC has the highest PD density in the apical region regardless of AC geometry. As the walls elongate, primary wall is laid down between PD, separating them and resulting in lower densities and wider PD diameters in older walls. The season of fixation and whether plants were studied from nature or culture have an influence on AC ultrastructure. A developmental study of Physcomitrella patents gametophores in four stages, bud, 2-leaved, 7-8-leaved and ∼20-leaved, reveals that the primary cell wall constituents change slightly during development. Specifically, LM5 a RG-I pectin antibody against the galactan branch epitope is only localized in the fibrillar layer of young water-conducting cells in the 7-8-leaved and 20-leaved gametophores. LM20, an antibody against HG esterified pectins, does not localize in any of the cell walls during development. The distribution patterns for AGPs (JIM13 and LM2) are consistent during gametophore development and predominantly localize on the electron-lucent layer and wall/plasma membrane interface. However, LM2 is mainly localized on the fibrillar layer in 7-8-leaved cell walls. AGPs also localize on element of the cytoplasm. LM6, an antibody against an RG-I pectin with arabinan branch epitopes, also localizes AGPs and because it expressed similar distribution patterns as JIM13 and LM2 on the cell wall, it likely localizes AGP in Physcomitrella. In addition, LM6 localizes pectins on the fibrillar layer similar to LM5 and LM19 for HG unesterified pectins. Callose predominantly localizes at the PD neck region. This study provides the first documentation of changes in size and shape of AC with age in Physcomitrella patens gametophores. The PD densities of gametophytes examined in this study fall into the lineage-specific network of PD (LPD) group designated for sporophytes of monilophytes and Selaginella (heterosporous lycophyte) with single ACs. Takakia lepidozioides leafy shoot has a tetrahedral AC with a highly curved free surface. This peculiar moss has mucilage hair (MH) associated with axil of phyllids. Mucilage hair in both species are 3-celled with a forth epidermal cell as the base. However, occasional 2-celled MH is seen in T. ceratophylla . The ultrastructure of MH has similarities with other mosses and liverworts

Network analysis uncovers the communication structure of SARS-CoV-2 spike protein identifying sites for immunogen design

Summary: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has triggered myriad efforts to understand the structure and dynamics of this complex pathogen. The spike glycoprotein of SARS-CoV-2 is a significant target for immunogens as it is the means by which the virus enters human cells, while simultaneously sporting mutations responsible for immune escape. These functional and escape processes are regulated by complex molecular-level interactions. Our study presents quantitative insights on domain and residue contributions to allosteric communication, immune evasion, and local- and global-level control of functions through the derivation of a weighted graph representation from all-atom MD simulations. Focusing on the ancestral form and the D614G-variant, we provide evidence of the utility of our approach by guiding the selection of a mutation that alters the spike’s stability. Taken together, the network approach serves as a valuable tool to evaluate communication “hot-spots” in proteins to guide design of stable immunogens

Engineered immunogens to elicit antibodies against conserved coronavirus epitopes

Abstract Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine