Biology subjects

Martino, F.

Publications and source records attributed to Martino, F..

7 recordsLinked to original sources

bioRxiv2026

Assembly of minimally fragmented metagenomic pangenome graphs

Pangenome variation graphs are a powerful tool for representing genetic diversity within and across populations. For comparative and evolutionary genomic analyses leveraging these graph-based structures, it is important that graph topology reflects the underlying phylogenetic and genetic similarities of the genomes embedded within the graph. However, in metagenomic settings these approaches often produce highly fragmented multi-component graphs, hindering comparisons of genomes embedded across different components. This challenge is particularly pronounced for hypervariable viral families like Anelloviridae, whose short circular genomes frustrate existing variation graph construction methods. We present PANIMaSTA (Progressive Average Nucleotide Identity and Maximum Spanning Tree-Based Assembly), a workflow to construct minimally fragmented metagenomic pangenome sequence variation graphs through progressive assembly. The order in which the genomes are incorporated into the graph is informed by a maximum spanning tree (MST) inferred from an all-to-all genome similarity matrix comprised of pairwise Anelloviridae average nucleotide identities (ANI). Applied to over 5,200 diverse Anelloviridae genomes, we construct a sequence variation graph whose graph topology reflects the global genome similarities observed across the ANI matrix. PANIMaSTA constructs minimally fragmented metagenomic pangenome sequence variation graphs that are not achievable with existing methods suitable for similarity-aware sequence-to-graph mapping and downstream genetic analyses across highly diverse genomes.

bioinformatics↗

bioRxiv2025

eDNA on the go: a direct comparison of fixed and vehicle mounted airborne eDNA sampling methods for terrestrial vertebrate species detection at large spatial scales

Air is receiving increasing recognition as a biologically rich source of taxonomically diverse environmental DNA (eDNA). Multiple proof-of-concept studies have explored air as a medium for the detection of single terrestrial species, and even entire terrestrial communities, including mammals, non-anemophilous plants and insects. Airborne eDNA has been sampled using various stationary devices but if we can access it using mobile collection methods, we can rapidly assess biodiversity at large spatial scales. We therefore compared passive eDNA filters deployed for short (30 mins) and long periods (24 hrs) with filters attached to cars that sampled transects through natural and human-modified environments. Our metabarcoding procedure detected 49 vertebrate taxa (33 birds, 15 mammals and 1 amphibian) from all three eDNA air sampling approaches combined, with 29 of these taxa detected in samples collected using the mobile method. The total number of taxa, or proportions of unique taxa detected, did not differ by sampling method, land use or day. Community composition was not significantly impacted by sampling method or sampling day but differed significantly between land uses. We propose that our car-mounted air eDNA sampler could be a game changer for large scale, rapid biomonitoring efforts.

ecology↗

bioRxiv2024

Unwrapping the ciliary coat: high-resolution structure and function of the ciliary glycocalyx

The glycocalyx, a highly heterogeneous glycoprotein layer of cilia regulates adhesion and force transduction, and is involved in signalling. The high-resolution molecular architecture of this layer is currently not understood. We describe the structure of the ciliary coat in the green alga Chlamydomonas reinhardtii by cryo-electron tomography and proteomic approaches and present the high-resolution cryoEM structure of the main component, FMG1B. We describe FMG1B as a mucin orthologue which lacks the major O-glycosylation of mammalian mucins, but is N-glycosylated. FMG1A, a previously undescribed isoform of FMG1B is expressed in C. reinhardtii. By microflow-based adhesion assays we observe increased surface adhesion in the glycocalyx deficient double-mutant fmg1a-fmg1b. We find this mutant to be capable of surface-gliding, with neither isoform required for extracellular force transduction by intraflagellar transport. Our results find FMG1 to form a protective layer with adhesion-regulative instead of adhesion-conferring properties and an example of an undescribed class of mucins.

cell biology↗

bioRxiv2024

YAP1 Contributes to The Development of Contractile Force and Sarcomere Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes

BackgroundPerspective regenerative therapies for injured myocardium focus on reactivating developmental processes to regenerate damaged contractile tissue. In animal models, the Hippo pathway was shown to improve heart regeneration after myocardial infarction, possibly by expanding the pool of cardiomyocytes. We hypothesized that activating the Hippo pathways downstream effector, Yes Associated Protein (YAP1), may have effects beyond promoting proliferation in human cardiomyocytes. We have therefore investigated how YAP1 influences human cardiomyocyte maturation, sarcomere structure, electrophysiological properties, their response to mechanical stimuli, intracellular Ca2+'' dynamics and force development using models of cardiomyocytes derived from pluripotent stem cells. MethodsWe employed genetic models of YAP1 deficient human embryonic and induced pluripotent stem cells, cardiomyocyte differentiation, compliant cultivation substrates, mechanical actuation, ECM deposition, super resolution microscopy, electrophysiological measurements and engineered heart tissues (EHTs) to characterize the effects of YAP1 deficiency on cardiomyocytes during maturation. We also used full length YAP1 re- expression to rescue the effects of YAP1 deficiency in contracting cardiomyocytes. ResultsYAP1 contributes to cardiomyocyte maturation, participates in the formation and alignment of myofibrils, as well as in the maturation of electrophysiological properties. The net effect of YAP1 deficiency in cardiomyocytes is the inability to respond to physiological stimuli by compensatory growth resulting in reduced force development. Additionally, YAP1 reactivation in contracting cardiomyocytes leads to rescue of myofibril maturation. ConclusionsThis research demonstrates that YAP1 activity is essential to promote cardiomyocyte maturation, contractility, and response to regeneration inducing stimuli.

cell biology↗

bioRxiv2023

The Tubulin Nano-Code: a protofilament-specific pattern of tubulin post-translational modifications regulates ciliary beating mechanics

Control of ciliary beating is crucial for motility and signaling in eukaryotic cells and requires spatially restricted interactions between axonemal proteins and specific protofilaments within the ciliary microtubules. How these interactions are regulated remains poorly understood, but increasing evidence indicates that tubulin post-translational modifications (tPTMs) are required for proper ciliary motility. The Tubulin Code refers to the concept that tPTMs can modulate the function of individual microtubules in cells. Here we use a combination of immuno-cryo-electron tomography, expansion microscopy and mutant analysis to show that, in motile cilia, tubulin glycylation and polyglutamylation form mutually exclusive protofilament-specific nano-patterns at sub-microtubular scale. We show that these two nano-patterns are consistent with the distributions of axonemal dyneins and nexin-dynein regulatory complexes, respectively, and are required for their regulation during ciliary beating. Our discovery of a tubulin nano-code in cilia highlights the need of higher-resolution studies also in other cellular compartments to understand the molecular role of tPTMs. One-Sentence SummaryTubulin post-translational modifications form nanopatterns at sub-microtubular scale that enable individual protofilaments to perform specific functions Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/546853v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@253704org.highwire.dtl.DTLVardef@13f0a8forg.highwire.dtl.DTLVardef@1ce673dorg.highwire.dtl.DTLVardef@1dc04e1_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

The mechanical regulation of RNA binding protein hnRNPC in the failing heart

Cardiac pathologies are characterized by intense remodeling of the extracellular matrix (ECM) that eventually leads to heart failure. Cardiomyocytes respond to the ensuing biomechanical stress by re-expressing fetal contractile proteins via transcriptional and post-transcriptional processes, like alternative splicing (AS). Here, we demonstrate that the heterogeneous nuclear ribonucleoprotein C (hnRNPC) is upregulated and relocates to the sarcomeric Z-disk upon ECM pathological remodeling. We show that this is an active site of localized translation, where the ribonucleoprotein associates to the translation machinery. Alterations in hnRNPC expression and localization can be mechanically determined and affect the AS of numerous mRNAs involved in mechanotransduction and cardiovascular diseases, like Hippo pathway effector YAP1. We propose that cardiac ECM remodeling serves as a switch in RNA metabolism by impacting an associated regulatory protein of the spliceosome apparatus. These findings offer new insights on the mechanism of mRNAs homeostasis mechanoregulation in pathological conditions.

pathology↗

bioRxiv2019

Microtubule Nucleation by Single Human γTuRC in a Partly Open Asymmetric Conformation

The {gamma}-tubulin ring complex ({gamma}TuRC) is the major microtubule nucleator in cells. However, the mechanism of its regulation is not understood. Here, we purified human {gamma}TuRC and quantitatively characterized its nucleation properties in a TIRF microscopy-based real-time nucleation assay. We find that microtubule nucleation by {gamma}TuRC is kinetically inhibited compared to microtubule elongation. Determining the cryo-EM structure of {gamma}TuRC at 4 [A] resolution reveals an asymmetric conformation with only part of the complex in a closed conformation matching the microtubule geometry. Several factors stabilise the closed conformation. One is actin in the core of the complex and others, likely MZT1 or MZT2, line the outer perimeter of the closed part of {gamma}TuRC. The opposed side of {gamma}TuRC is in an open, nucleation-incompetent conformation, leading to a structural asymmetry, explaining the kinetic inhibition of nucleation by human {gamma}TuRC. Our data suggest possible regulatory mechanisms for microtubule nucleation by {gamma}TuRC closure.

biochemistry↗