Browse Articles

Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines

Abstract Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900’s, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future.

A novel approach for target deconvolution from phenotype-based screening using knowledge graph

SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs

Automated system for calving time prediction and cattle classification utilizing trajectory data and movement features

Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS

Abstract Sevenless, the Drosophila homologue of ROS1 (University of Rochester Sarcoma) (herein, dROS1) is a receptor tyrosine kinase (RTK) essential for the differentiation of Drosophila R7 photoreceptor cells. Activation of dROS1 is mediated by binding to the extracellular region (ECR) of the GPCR (G protein coupled receptor) BOSS (Bride Of Sevenless) on adjacent cells. Activation of dROS1 by BOSS leads to subsequent downstream signaling pathways including SOS (Son of Sevenless). However, the physical basis for how dROS1 interacts with BOSS has long remained unknown. Here we provide a cryo-EM structure of dROS1’s extracellular region, which mediates ligand binding. We show that the extracellular region of dROS1 adopts a folded-over conformation stabilized by an N-terminal domain comprised of two disulfide stapled helical hairpins. We further narrowed down the interacting binding epitopes on both dROS1 and BOSS using hydrogen-deuterium exchange mass spectrometry (HDX-MS). This includes beta-strands in dROS1’s third Fibronectin type III (FNIII) domain and a C-terminal peptide in BOSS’ ECR. Our mutagenesis studies, coupled with AlphaFold complex predictions, support a binding interaction mediated by a hydrophobic interaction and beta-strand augmentation between these regions. Our findings provide a fundamental understanding of the regulatory function of dROS1 and further provide mechanistic insight into the human ortholog and oncogene ROS1.

Identification of MORF4L1 as an endogenous substrate of CRBN and its potential role as a therapeutic target in cancer

A data-driven latent variable approach to validating the research domain criteria framework

Spatiotemporal evolution of landscape ecological risk and its driving factors of the Beijing–Tianjin–Hebei major mineral belt, 1985–2022

Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data

Abstract As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples. We find that these methods are important for obtaining accurate results in low biomass samples (e.g., tissue, skin). Overall, we demonstrate that rigorous host filtration is a key component of privacy-minded analyses of patient microbiomes and provide computationally efficient pipelines for accomplishing this task on large-scale datasets.

First record of microplastic contamination in adult endemic amazonian anuran species

Abstract The microplastics (MPs), due to their high dispersion and bioaccumulation rates, have been identified in various animal groups, such as anuran amphibians during both larval and adult stages. However, current studies on adult anuran amphibians focus on assessing only one exposure route, the digestive system, while other routes remain underestimated. Therefore, this present study aimed to evaluate the degree of contamination in the digestive, respiratory, and integumentary systems, in situ, of two endemic Amazonian adult anuran species (Physalaemus ephippifer and Boana multifasciata). From this, we identified and characterized microplastic particles for each exposure route, assessed the effects of morphometric measures on the total MP contamination level and in the gastrointestinal tract (GIT). Additionally, we determined different contamination indices and how they vary according to species and systems. Based on our data, the digestive and integumentary exposure routes showed the highest contamination levels for both species. Additionally, variations in MP contamination levels indicated that P. ephippifer had a higher level of MP contamination. Thus, this study provides the first evidence of microplastic exposure through respiratory and integumentary routes in adult anurans in situ, and it is the first to identify MP contamination in terrestrial biomonitors in the Amazon.

Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs

Advancements in Frank’s sign Identification using deep learning on 3D brain MRI

Incremental accumulation of linguistic context in artificial and biological neural networks

Evaluating the effectiveness of handheld ultrasound in primary blast lung injury: a comprehensive study

Numerous rRNA molecules form the apicomplexan mitoribosome via repurposed protein and RNA elements

Abstract Mitochondrial ribosomes (mitoribosomes) are essential, and their function of synthesising mitochondrial proteins is universal. The core of almost all mitoribosomes is formed from a small number of long and self-folding rRNA molecules. In contrast, the mitoribosome of the apicomplexan parasite Toxoplasma gondii assembles from over 50 extremely short rRNA molecules. Here, we use cryo-EM to discover the features that enable this unusual mitoribosome to perform its function. We reveal that poly-A tails added to rRNA molecules are integrated into the ribosome, and we demonstrate their essentiality for mitoribosome formation and for parasite survival. This is a distinct function for poly-A tails, which are otherwise known primarily as stabilisers of messenger RNAs. Furthermore, while ribosomes typically consist of unique rRNA sequences, here nine sequences are used twice, each copy integrated in a different mitoribosome domain, revealing one of the mechanisms enabling the extreme mitochondrial genome reduction characteristic to Apicomplexa and to a large group of related microbial eukaryotes. Finally, several transcription factor-like proteins are repurposed to compensate for reduced or lost critical ribosomal domains, including members of the ApiAP2 family thus far considered to be DNA-binding transcription factors.

Evaluation of the corrosion resistance of bronze patina or/and protective coating on the surface of the archaeological coins

Abstract Archaeological coins are considered essential sources of historical documentation. Over time, they are subjected to corrosion processes that gradually alter their appearance, shape, and composition. This study aims to evaluate the effects of the patina and/or protective coating on the corrosion process. Protection of the original coin surface was crucial following the completion of the cleaning protocol. Various finishes of coin fragments (uncoated, aged, and freshly coated) were investigated to determine their chemical composition, nature of the patina, and corrosion products on their surface using stereo microscopy(SM), X-ray diffraction (XRD), and scanning electron microscopy (SEM) equipped with energy dispersive X-ray spectroscopy (EDX). The analysis revealed that the coins were composed of a Cu–Sn- and Pb bronze alloy. Furthermore, the efficiency of the patina and/or protective coatings on the coin fragments was evaluated using potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV) techniques. The highest protection was achieved for patinated-freshly protective coated fragments, while the most corrosive fragments were those affected by bronze diseases.

Liquid-infused nanostructured composite as a high-performance thermal interface material for effective cooling

Novel adaptive immune systems in pristine Antarctic soils

Abstract Antarctic environments are dominated by microorganisms, which are vulnerable to viral infection. Although several studies have investigated the phylogenetic repertoire of bacteria and viruses in these poly-extreme environments with freezing temperatures, high ultra violet irradiation levels, low moisture availability and hyper-oligotrophy, the evolutionary mechanisms governing microbial immunity remain poorly understood. Using genome-resolved metagenomics, we test the hypothesis that Antarctic poly-extreme high-latitude microbiomes harbour diverse adaptive immune systems. Our analysis reveals the prevalence of prophages in bacterial genomes (Bacteroidota and Verrucomicrobiota), suggesting the significance of lysogenic infection strategies in Antarctic soils. Furthermore, we demonstrate the presence of diverse CRISPR-Cas arrays, including Class 1 arrays (Types I-B, I-C, and I-E), alongside systems exhibiting novel gene architecture among their effector cas genes. Notably, a Class 2 system featuring type V variants lacks CRISPR arrays, encodes Cas1 and Cas2 adaptation module genes. Phylogenetic analysis of Cas12 effector proteins hints at divergent evolutionary histories compared to classified type V effectors and indicates that TnpB is likely the ancestor of Cas12 nucleases. Our findings suggest substantial novelty in Antarctic cas sequences, likely driven by strong selective pressures. These results underscore the role of viral infection as a key evolutionary driver shaping polar microbiomes.

A metal-trap tests and refines blueprints to engineer cellular protein metalation with different elements

Abstract It has been challenging to test how proteins acquire specific metals in cells. The speciation of metalation is thought to depend on the preferences of proteins for different metals competing at intracellular metal-availabilities. This implies mis-metalation may occur if proteins become mis-matched to metal-availabilities in heterologous cells. Here we use a cyanobacterial Mn II -cupin (MncA) as a metal trap, to test predictions of metalation. By re-folding MncA in buffered competing metals, metal-preferences are determined. Relating metal-preferences to metal-availabilities estimated using cellular metal sensors, predicts mis-metalation of MncA with Fe II in E. coli . After expression in E. coli , predominantly Fe II -bound MncA is isolated experimentally. It is predicted that in metal-supplemented viable cells metal-MncA speciation should switch. Mn II -, Co II -, or Ni II -MncA are recovered from the respective metal-supplemented cells. Differences between observed and predicted metal-MncA speciation are used to refine estimated metal availabilities. Values are provided as blueprints to guide engineering biological protein metalation.

Development and assessment of a mortality risk prediction nomogram model for pneumocystis disease in ICU within 28 days