Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.

Collagen IV, an essential and evolutionarily conserved component of basement membranes, is one of the most extensively post-translationally modified proteins. Despite substantial research on fibrillar collagen biosynthesis, our understanding of collagen IV biosynthesis, including its post-translational modifications (PTMs), remains limited. Most PTMs occur intracellularly, primarily within the endoplasmic reticulum (ER).

Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1.

During collagen biosynthesis, lysine residues undergo extensive post-translational modifications through the alternate action of two distinct metal ion-dependent enzyme families (i.e., LH/PLODs and GLT25D/COLGALT), ultimately producing the highly conserved α-(1,2)-glucosyl-β-(1,O)-galactosyl-5-hydroxylysine pattern.

Effect of Spiroplasma infection on the mating behavior of Glossina fuscipes fuscipes.

Tsetse flies are insects of significant public health and zoonotic importance as they are the main vectors of African trypanosomes. To date, an effective vaccine is unavailable and efforts to limit the spread of the disease primarily rely on controlling the tsetse populations. The discovery of Spiroplasma (class Mollicutes) in Glossina fuscipes fuscipes (Gff) (palpalis subgroup), offers promising insights into its potential use as a biological control agent to hinder trypanosomes infection in tsetse flies.

On the tracks of an uninvited guest, the Asian tiger mosquito, Aedes albopictus in Cyprus.

Background: Aedes albopictus, the Asian tiger mosquito, which is listed among the world's 100 most dangerous invasive species, is the main vector of chikungunya, dengue and Zika viruses. This mosquito species has rapidly dispersed and invaded much of the globe assisted by its life history traits and high propagule pressure driven by human activities. Aedes albopictus is currently widespread across mainland Europe and the Mediterranean region, including the islands.

Corrigendum: Bi-specific autoantigen-T cell engagers as targeted immunotherapy for autoreactive B cell depletion in autoimmune diseases.

[This corrects the article DOI: 10.3389/fimmu.2024.

Bi-specific autoantigen-T cell engagers as targeted immunotherapy for autoreactive B cell depletion in autoimmune diseases.

Introduction: In autoimmune diseases, autoreactive B cells comprise only the 0.1-0.5% of total circulating B cells.

Efficient SARS-CoV-2 infection antagonization by rhACE2 ectodomain multimerized onto the Avidin-Nucleic-Acid-NanoASsembly.

Nanodecoy systems based on analogues of viral cellular receptors assembled onto fluid lipid-based membranes of nano/extravescicles are potential new tools to complement classic therapeutic or preventive antiviral approaches. The need for lipid-based membranes for transmembrane receptor anchorage may pose technical challenges along industrial translation, calling for alternative geometries for receptor multimerization. Here we developed a semisynthetic self-assembling SARS-CoV-2 nanodecoy by multimerizing the biotin labelled virus cell receptor -ACE2- ectodomain onto a poly-avidin nanoparticle (NP) based on the Avidin-Nucleic-Acid-NanoASsembly-ANANAS.

IgE response to Aed al 13 and Aed al 14 recombinant allergens from saliva in humans.

Background: Mosquito bite is normally associated with mild allergic responses, but severe localized or systemic reactions are also possible. Reliable tools for the diagnosis of mosquito allergy are still unavailable. Here, we investigated the IgE response to 3 potential salivary allergens identified in the saliva of the tiger mosquito .

Identification of Regulatory Molecular "Hot Spots" for LH/PLOD Collagen Glycosyltransferase Activity.

Hydroxylysine glycosylations are post-translational modifications (PTMs) essential for the maturation and homeostasis of fibrillar and non-fibrillar collagen molecules. The multifunctional collagen lysyl hydroxylase 3 (LH3/PLOD3) and the collagen galactosyltransferase GLT25D1 are the human enzymes that have been identified as being responsible for the glycosylation of collagen lysines, although a precise description of the contribution of each enzyme to these essential PTMs has not yet been provided in the literature. LH3/PLOD3 is thought to be capable of performing two chemically distinct collagen glycosyltransferase reactions using the same catalytic site: an inverting beta-1,O-galactosylation of hydroxylysines (Gal-T) and a retaining alpha-1,2-glucosylation of galactosyl hydroxylysines (Glc-T).

Modeling of Protein Complexes.

The recent advances in structural biology, combined with continuously increasing computational capabilities and development of advanced softwares, have drastically simplified the workflow for protein homology modeling. Modeling of individual proteins is nowadays quick and straightforward for a large variety of protein targets, thanks to guided pipelines relying on advanced computational tools and user-friendly interfaces, which have extended and promoted the use of modeling also to scientists not focusing on molecular structures of proteins. Nevertheless, construction of models of multi-protein complexes remains quite challenging for the non-experts, often due to the usage of specific procedures depending on the system under investigation and the need for experimental validation approaches to strengthen the generated output.

Selection of a PD-1 blocking antibody from a novel fully human phage display library.

Programmed cell death protein 1 (PD-1) is an immunoregulatory target which is recognized by different monoclonal antibodies, approved for the therapy of multiple types of cancer. Different anti-PD-1 antibodies display different therapeutic properties and there is a pharmaceutical interest to generate and characterize novel anti-PD-1 antibodies. We screened multiple human antibody phage display libraries to target novel epitopes on the PD-1 surface and we discovered a unique and previously undescribed binding specificity (termed D12) from a new antibody library (termed AMG).

Deconstruction of Neurotrypsin Reveals a Multi-factorially Regulated Activity Affecting Myotube Formation and Neuronal Excitability.

Neurotrypsin (NT) is a highly specific nervous system multi-domain serine protease best known for its selective processing of the potent synaptic organizer agrin. Its enzymatic activity is thought to influence processes of synaptic plasticity, with its deregulation causing accelerated neuromuscular junction (NMJ) degeneration or contributing to forms of mental retardation. These biological effects are likely to stem from NT-based regulation of agrin signaling.

Memory CD8 T cell diversity and B cell responses correlate with protection against SARS-CoV-2 following mRNA vaccination.

Understanding immune responses to SARS-CoV-2 messenger RNA (mRNA) vaccines is of great interest, principally because of the poor knowledge about the mechanisms of protection. In the present study, we analyzed longitudinally B cell and T cell memory programs against the spike (S) protein derived from ancestral SARS-CoV-2 (Wuhan-1), B.1.

A Fe-dependent self-inhibited state influences the druggability of human collagen lysyl hydroxylase (LH/PLOD) enzymes.

Multifunctional human collagen lysyl hydroxylase (LH/PLOD) enzymes catalyze post-translational hydroxylation and subsequent glycosylation of collagens, enabling their maturation and supramolecular organization in the extracellular matrix (ECM). Recently, the overexpression of LH/PLODs in the tumor microenvironment results in abnormal accumulation of these collagen post-translational modifications, which has been correlated with increased metastatic progression of a wide variety of solid tumors. These observations make LH/PLODs excellent candidates for prospective treatment of aggressive cancers.

Dimerization of kringle 1 domain from hepatocyte growth factor/scatter factor provides a potent MET receptor agonist.

Hepatocyte growth factor/scatter factor (HGF/SF) and its cognate receptor MET play several essential roles in embryogenesis and regeneration in postnatal life of epithelial organs such as the liver, kidney, lung, and pancreas, prompting a strong interest in harnessing HGF/SF-MET signalling for regeneration of epithelial organs after acute or chronic damage. The limited stability and tissue diffusion of native HGF/SF, however, which reflect the tightly controlled, local mechanism of action of the morphogen, have led to a major search of HGF/SF mimics for therapy. In this work, we describe the rational design, production, and characterization of K1K1, a novel minimal MET agonist consisting of two copies of the kringle 1 domain of HGF/SF in tandem orientation.

A salivary factor binds a cuticular protein and modulates biting by inducing morphological changes in the mosquito labrum.

The mosquito proboscis is an efficient microelectromechanical system, which allows the insect to feed on vertebrate blood quickly and painlessly. Its efficiency is further enhanced by the insect saliva, although through unclear mechanisms. Here, we describe the initial trigger of an unprecedented feedback signaling pathway in Aedes mosquitoes affecting feeding behavior.

Crystal structure of the kringle domain of human receptor tyrosine kinase-like orphan receptor 1 (hROR1).

Receptor tyrosine kinase-like orphan receptors (RORs) are monotopic membrane proteins belonging to the receptor tyrosine kinase (RTK) family. RTKs play a role in the control of most basic cellular processes, including cell proliferation, differentiation, migration and metabolism. New emerging roles for RORs in cancer progression have recently been proposed: RORs have been shown to be overexpressed in various malignancies but not in normal tissues, and moreover an abnormal expression level of RORs on the cellular surface is correlated with high levels of cytotoxicity in primary cancer cells.

Epidemic Preparedness- as an Easy-to-Handle Tool to Produce Antigens for Viral Diagnosis: Application to COVID-19.

To detect and prevent emerging epidemics, discovery platforms are urgently needed, for the rapid development of diagnostic assays. Molecular diagnostic tests for COVID-19 were developed shortly after the isolation of SARS-CoV-2. However, serological tests based on antiviral antibody detection, revealing previous exposure to the virus, required longer testing phases, due to the need to obtain correctly folded and glycosylated antigens.

New mechanistic insights to PLOD1-mediated human vascular disease.

Heritable thoracic aortic disease and familial thoracic aortic aneurysm/dissection are important causes of human morbidity/mortality, most without identifiable genetic cause. In a family with familial thoracic aortic aneurysm/dissection, we identified a missense p. (Ser178Arg) variant in PLOD1 segregating with disease, and evaluated PLOD1 enzymatic activity, collagen characteristics and in human aortic vascular smooth muscle cells, studied the effect on function.

A ligand-insensitive UNC5B splicing isoform regulates angiogenesis by promoting apoptosis.

The Netrin-1 receptor UNC5B is an axon guidance regulator that is also expressed in endothelial cells (ECs), where it finely controls developmental and tumor angiogenesis. In the absence of Netrin-1, UNC5B induces apoptosis that is blocked upon Netrin-1 binding. Here, we identify an UNC5B splicing isoform (called UNC5B-Δ8) expressed exclusively by ECs and generated through exon skipping by NOVA2, an alternative splicing factor regulating vascular development.

A Pilot Study on Covid and Autism: Prevalence, Clinical Presentation and Vaccine Side Effects.

: Several neurobiological mechanisms have been proposed to support the hypothesis of a higher COVID-19 risk in individuals with autism spectrum disorder (ASD). However, no real-world data are available on this population. : We compared the period prevalence (March-May 2020) and symptom presentation of COVID-19 infections between a sample of individuals with severe ASD ( = 36) and the staff personnel ( = 35) of two specialized centers.