Biology subjects

Carlesso, A.

Publications and source records attributed to Carlesso, A..

3 recordsLinked to original sources

bioRxiv2026

Moisture structures litter faunal communities through productivity and trait filtering effects

Litter invertebrates mediate a substantial proportion of decomposition and nutrient cycling in terrestrial ecosystems, yet how moisture availability structures their communities remains poorly understood. We propose that moisture availability could shape litter faunal communities through two alternate pathways: (1) a productivity effect: greater productivity and detrital inputs in wetter forests should increase litter-faunal abundance, (2) a trait effect: phylogenetic differences in water balance should filter communities according to taxon-specific moisture tolerances. We tested these expectations across 100 forest sites spanning a moisture gradient in south-eastern Australia, from dry sclerophyll forest to cool temperate rainforest. Measuring 11 focal invertebrate taxa, total litter-faunal abundance increased threefold across the moisture gradient, from 400,000 individuals per hectare of dry forest to 1.2 million individuals per hectare of rainforest - consistent with greater resource availability in wetter and more productive habitats. However, this overall abundance trend masked pronounced variation in community composition across habitat types. While moisture-sensitive crustaceans and myriapods (particularly Isopoda and Chilopoda) were concentrated in rainforest litter, two groups of hexapods (Blattodea and Embioptera) were most abundant in dry forest litter and declined sharply toward rainforest habitat. These contrasting responses indicate that dry forests do not simply represent depauperate versions of wet-forest communities but harbour their own distinct and abundant litter invertebrate assemblages. Thus, moisture structures litter faunal communities via both proposed mechanisms: (1) a productivity effect and (2) a trait filtering effect. Given that moisture fundamentally structures litter faunal communities, shifts in forest moisture regimes under climate change may substantially alter detritivore communities, with consequences for decomposition processes and nutrient cycling globally.

ecology↗

bioRxiv2024

Mechanistic Insights into ASO-RNA Complexation: Advancing Antisense Oligonucleotide Design Strategies.

Oligonucleotide drugs, an emerging modulator class, hold promise for targeting previously undruggable biomacromolecules. To date, only 18 oligonucleotide drugs, including sought-after antisense oligonucleotides (ASO) and splice-switching oligonucleotides (SSO), have FDA approval. These agents effectively bind mRNA, inducing degradation or modulating splicing. Current oligonucleotide drug design strategies prioritize full Watson-Crick base pair complementarity, overlooking mRNA target 3D shapes. Given that mRNA conformational diversity can impact hybridization, incorporating mRNA key-structural properties into the design may expedite ASO lead discovery. Using atomistic molecular dynamics simulations inspired by experimental data, we demonstrate the advantages of incorporating common triple base pairs into the design of antisense oligonucleotides (ASOs) targeting RNA hairpin motifs, which are highly accessible regions for interactions. By employing an RNA pseudoknot modified into an ASO-hairpin complex, we investigate the effects of ASO length and hairpin loop mutations. Our findings suggest that ASO-mRNA complex stability is influenced by ASO length, number of common triple base pairs, and the dynamic accessibility of bases in the hairpin loop. Our study offers new mechanistic insights into ASO-mRNA complexation and underscores the value of pseudoknots in constructing training datasets for machine learning models aimed at designing novel ASO leads.

biophysics↗

bioRxiv2019

Structural distortions induced by Kinase Inhibiting RNase Attenuator (KIRA) compounds prevent the formation of face-to-face dimers of Inositol Requiring Enzyme 1α

Inositol-Requiring Enzyme 1 (IRE1) is a transmembrane dual kinase/ribonuclease protein involved in propagation of the unfolded protein response (UPR). IRE1 is currently explored as a potential drug target due to growing evidence of its role in variety of disease conditions. Upon activation, IRE1 cleaves X-box Binding Protein 1 (XBP1) mRNA through its RNase domain. Small molecules targeting the kinase site are known to either increase or decrease RNase activity, but the allosteric relationship between the kinase and RNase domains of IRE1 is poorly understood. Subsets of IRE1 kinase inhibitors (known as \"KIRA\" compounds) bind to the ATP-binding site and allosterically impede the RNase activity. KIRA compounds are able to regulate the RNase activity by stabilizing monomeric form of IRE1.\n\nIn the present work, computational analysis, protein-protein and protein-ligand docking studies, and molecular dynamics simulations were applied to different IRE1 dimer systems to provide structural insights into the perturbation of IRE1 dimers by small molecules kinase inhibitors that regulate the RNase activity. By analyzing structural deviations, energetic components and number of hydrogen bonds in the interface region, we propose that the KIRA inhibitors act at an early stage of IRE1 activation by interfering with IRE1 face-to-face dimer formation, thus disabling the activation of the RNase domain. The work sheds light on the mechanism of action of KIRA compounds and may assist in development of further compounds in e.g. cancer therapeutics. The work also provides information on the sequence of events and protein-protein interactions initiating the unfolded protein response.\n\nNon-technical SummaryThe unfolded protein response is a protective feedback mechanism whereby cells regulate high levels of misfolded proteins in the endoplasmic reticulum. Due to its significance in cell survival, the UPR has become an interesting target in cancer therapy. A key pathway of the UPR is initiated by the activation of inositol requiring enzyme 1 (IRE1), which must first dimerise in order to mediate the stress signal. Different inhibitors have been proposed in order to block the UPR at the level of IRE1. We here unveil, through detailed computational studies, the mode of action of a set of IRE1 inhibitors targeting the kinase domain, which in turn helps us to further understand the mechanism of activation and progression of the UPR.

biochemistry↗