Biology subjects

Miele, A. E.

Publications and source records attributed to Miele, A. E..

4 recordsLinked to original sources

bioRxiv2026

Biophysical characterization of novel biomarkers and bioaffinity reagents (NanoMIPs): on the road for a low-cost diagnostic test for intestinal schistosomiasis

Schistosoma mansoni is a vector-borne intestinal parasite, endemic in [~]70 tropical countries. Most of the World Health Organization interventions are based on mass drug administration (MDA) and sanitation. Since the parasite does not induce permanent immunity, reinfection rate is high, inducing scheduling of several MDA campaigns. To follow up after treatment and avoid blind MDA, providing a new rapid and cheap diagnostic test is needed, since the most used method is fifty years-old, lacks sensitivity and efficiency. Venom Allergen-Like proteins (SmVALs) have been previously identified as secreted/excreted proteins and potential biomarkers. Here we present the biophysical characterization of SmVAL11 and SmVAL13, their recognition by both specific antibodies and molecularly imprinted polymers (nanoMIPs), an easy-to-standardize alternative. The specific antibodies showed no cross-reactivity, while initial characterization of the nanoMIPs indicates a promising level of selectivity, establishing them as a reliable, cost-effective alternative. Therefore, our results are promising for the future development of a new cheap diagnostic test of intestinal schistosomiasis.

biophysics↗

bioRxiv2023

Revisiting annotation of Schistosoma mansoni Micro-Exon Gene (MEG) family

Genome sequencing of the human parasite Schistosoma mansoni revealed an interesting gene superfamily called micro-exon gene (MEG) that encodes MEG secreted proteins. The genes are composed of short exons (3-81 base pairs) with symmetrically inserted long introns (up to 5 kbp). This article recollects 35 S. mansoni specific meg genes that are distributed over 7 autosomes and one pair of sex chromosomes and that code for at least 87 verified MEG proteins. We used various bioinformatics tools to produce an optimal alignment, propose a phylogenetic analysis and highlight intriguing conserved patterns/motifs in the sequences of these MEG proteins. Based on the analyses, we were able to classify the MEG proteins into two subfamilies and to hypothesize their duplication and colonization of all the chromosomes. Together with motif identification, we also proposed to revisit MEGs common names and annotation in order to avoid duplication, to help reproducibility of research results and to avoid possible misunderstandings. Author AbstractSchistosoma mansoni is a parasitic worm, the etiological agent of schistosomiasis or bilharzia, a chronic tropical disease. It is a vector-borne parasite with a complex life cycle and an equally complex genome, assembled in 7 autosomes and a pair of sexual chromosomes. Within the gene products, one superfamily is particularly interesting, since it is specific to Schistosomatidae, highly variable and redundant: the micro-exon gene (MEG) family. As the name implies, these genes are made by short coding exons (3 to 81 base pairs), symmetrically interspersed by long introns (from 0.2 to 5 kbp). There are 35 megs allover the chromosomes, which code for at least 87 MEG proteins. We have aligned all of them, constructed a phylogenetic tree and proposed a theory for their duplication and genome colonization. Based on that, we propose a rational nomenclature to help the community to study MEGs elusive role. We also propose to help WormBaseParaSite to adopt this new nomenclature to avoid giving the same acronym to different protein sequences.

bioinformatics↗

bioRxiv2022

Cellular redox metabolism is modulated by the distinct localization of cyclic nucleotide phosphodiesterase 5A isoforms

3-5 cyclic nucleotide phosphodiesterases (PDEs) are a family of evolutionary conserved cAMP and/or cGMP hydrolysing enzymes, components of transduction pathways regulating crucial aspects of cell life. Among them, cGMP-specific PDE5, being a regulator of vascular smooth muscle contraction, is the molecular target of several drugs used to treat erectile dysfunction and pulmonary hypertension. Production of full-length murine PDE5A isoforms in the milk-yeast Kluyveromyces lactis showed that the quaternary assembly of MmPDE5A1 is a mixture of dimers and tetramers, while MmPDE5A2 and MmPDE5A3 only assembled as dimers. We showed that the N-terminal peptide is responsible for the tetramer assembly of MmPDE5A1, while that of MmPDE5A2 for its mitochondrial localization. Overexpression of the three isoforms alters at different levels the cAMP/cGMP equilibrium as well as the NAD(P)+/NAD(P)H balance and induces a metabolic switch from oxidative to fermentative. In particular, the mitochondrial localization of MmPDE5A2 unveiled the existence of a cAMP-cGMP signaling cascade in this organelle, for which we propose a metabolic model that could explain the role of PDE5 in some cardiomyopathies and some of the side effects of its inhibitors.

cell biology↗

bioRxiv2021

The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding.

Recent evidence indicated that HIV-1 Integrase (IN) binds genomic viral RNA (gRNA) playing a critical role in viral particle morphogenesis and gRNA stability in host cells. Combining biophysical and biochemical approaches we show that the C-terminal flexible 18-residues tail of IN acts as a sensor of the peculiar apical structure of trans-activation response element RNA (TAR), directly interacting with its hexaloop. We highlighted how the whole IN C-terminal domain, once bound to TAR, can change its structure assisting the binding of Tat, the HIV trans-activator protein, which finally displaces IN from TAR. Our results are consistent with the emerging role of IN in early stage of proviral transcription and suggest new steps of HIV-1 life cycle that can be considered as therapeutic targets.

biochemistry↗