Biology subjects

Disney, M.

Publications and source records attributed to Disney, M..

11 recordsLinked to original sources

bioRxiv2026

Conformational dynamics at the pre-miR-377 Dicer site governs selective small-molecule recognition

Small molecules that target precursor microRNAs (pre-miRNAs) offer a strategy to modulate microRNA biogenesis, but rational design is limited by the intrinsic conformational dynamics of RNA. Here, we combine site-specific nuclear magnetic resonance (NMR) spectroscopy with enhanced-sampling molecular dynamics (MD) simulations to define the conformational ensemble of pre-miR-377 and its recognition by the small-molecule binder C1. Our data reveals that the Dicer cleavage site contains a dynamic adenosine bulge in which U25 shuffles between A3 and A4 with a [~]9:1 population ratio, generating two interconverting RNA triple structures. NMR-informed MD and binding simulations show that C1 engages this dynamic region through a pathway-dependent mechanism that favors minor-groove entry, stabilizes intermediate, partially reorganized Dicer-site conformations, and redistributes the conformational ensemble away from processing-competent states. A conformationally locked mutant abolishes binding, indicating that recognition depends on bulge-enabled RNA dynamics rather than a single static structure. These results define the structural and dynamic basis of small-molecule recognition at the pre-miR-377 Dicer site and highlight the importance of RNA conformational ensembles in RNA-targeted drug discovery.

biophysics↗

bioRxiv2024

Consistent and scalable monitoring of birds and habitats along a coffee production intensity gradient

Land use change associated with agricultural intensification is a leading driver of biodiversity loss in the tropics. To evaluate the habitat-biodiversity relationship in production systems of tropical agricultural commodities, which is critical for certifying and examining the success of biodiversity-friendly agricultural practices, birds are commonly used as indicators. However, consistently and reliably monitoring how bird communities are affected by land use change throughout the annual cycle in a way that can be scalable is challenging using traditional survey methods. In this study, we examined whether the automated analysis of audio data collected by passive acoustic monitoring, together with the analysis of remote sensing data, can be used to efficiently monitor avian biodiversity along the gradient of habitat degradation associated with the intensification of coffee production. Coffee is an important crop produced in tropical forested regions, whose production is expanding and intensifying, and coffee production systems form a gradient of ecological complexity ranging from forest-like shaded polyculture to dense sun-exposed monoculture. We used LiDAR technology to survey the habitat, in combination with autonomous recording units and a vocalisation classification algorithm to assess bird community composition in a coffee landscape comprising a shade-grown coffee farm, a sun coffee farm, and a forest remnant, located in southern Mexico. We found that combining LiDAR with the automated analysis of continuously collected bioacoustics data can capture the expected functional signatures of avian communities as a function of habitat quality in the coffee landscape. Thus, we show that this approach can be a robust way to monitor how biodiversity responds to land use intensification in the tropics. A major advantage of this approach is that it has the potential to be deployed cost-effectively at large scales to help design and certify biodiversity-friendly productive landscapes.

ecology↗

bioRxiv2024

Transcriptome-wide mapping of small-molecule RNA-binding sites in live cells

Small molecules targeting RNA can be valuable chemical probes and potential therapeutics. The interactions between small molecules, particularly fragments, and RNA, however, can be difficult to detect due to their modest affinities and short residence times. Here, we describe the procedures for mapping the molecular fingerprints of small molecules in vitro and throughout the human transcriptome in live cells, identifying both the targets bound by the small molecule and the sites of binding therein. For complete details on the use and execution of this protocol, please refer to 1.

biochemistry↗

bioRxiv2024

Tree Surface Area Allometry

Utilizing terrestrial laser scanning (TLS) and three-dimensional modeling, this study quantitatively assessed the woody surface areas of 2161 trees across ecosystems encompassing both tropical and temperate forests. TLS enables precise measurement of tree structures at unprecedented scales. This research builds on theoretical scaling relationships with empirical data, significantly refining our understanding of tree woody surface area. Key findings indicate that direct measurements diverge from theoretical predictions, particularly in the finer branch structures, suggesting modifications to existing allometric models might be necessary. This integration of direct measurements with TLS not only challenges established theories but also enhances our capability to accurately model tree surface area, which is key for understanding forest carbon dynamics and metabolic scaling in ecological systems.

ecology↗

bioRxiv2022

Tree segmentation in airborne laser scanning data is only accurate for canopy trees

Individual tree segmentation from airborne laser scanning data is a longstanding and important challenge in forest remote sensing. There are a number of segmentation algorithms but robust intercomparison studies are rare due to the difficulty of obtaining reliable reference data. Here we provide a benchmark data set for temperate and tropical broadleaf forests generated from labelled terrestrial laser scanning data. We compare the performance of four widely used tree segmentation algorithms against this benchmark data set. All algorithms achieved reasonable accuracy for the canopy trees, but very low accuracy for the understory trees. The point cloud based algorithm AMS3D (Adaptive Mean Shift 3D) had the highest overall accuracy, closely followed by the 2D raster based region growing algorithm Dalponte2016+. This result was consistent across both forest types. This study emphasises the need to assess tree segmentation algorithms directly using benchmark data. We provide the first openly available benchmark data set for tropical forests and we hope future studies will extend this work to other regions.

ecology↗

bioRxiv2022

Gaining insight into the allometric scaling of trees by utilizing 3d reconstructed tree models - a SimpleForest study

Forestry utilizes volume predictor functions utilizing as input the diameter at breast height. Some of those functions take the power form Y = a * Xb. In fact this function is fundamental for the biology field of allometric scaling theories founded round about a century ago. The theory describes the relationships between organs/body parts and the complete body of organisms. With digital methods we can generate 3d forest point clouds non destructively in short time frames. SimpleForest is one free available tool which generates fully automated ground and tree models from high resoluted forest plots. Generated topological ordered cylinder models are called commonly QSMs. We use SimpleForest QSMs an build a function which estimates the total supported wood volume at any given point of the tree. As input we use the supported soft wood volume for those query points. Instead of measuring directly the soft wood volume we use as a proxy the number of supported twigs. We argue with the pipe model theory for the correctness of the proxy. We can use the named relationship to also filter our QSMs made of an open data set of tree clouds. The filter corrects overestimated radii. And we compare the corrected QSM volume against the harvested reference data for 66 felled trees. We also found QSM data of TreeQSM, a competitive and broadly accepted QSM modeling tool. Our RMSE was less than 40% of the tree QSM RMSE. And for other error measures, the r2adj. and the CCC, the relative improvement looked even better with 27% and 21% respectively. We consider this manuscript as highly impactful because of the magnitude of quality improvement we do. The relation between soft volume and total volume distributions seems to be really strong and tree data can easily also be used as example data for the generic field of allometric scaling.

bioinformatics↗

bioRxiv2021

SimpleForest - a comprehensive tool for 3d reconstruction of trees from forest plot point clouds

The here-on presented SimpleForest is written in C++ and published under GPL v3. As input data SimpleForest utilizes forestry scenes recorded as terrestrial laser scan clouds. SimpleForest provides a fully automated pipeline to model the ground as a digital terrain model, then segment the vegetation and finally build quantitative structure models of trees (QSMs) consisting of up to thousands of topologically ordered cylinders. These QSMs allow us to calculate traditional forestry metrics such as diameter at breast height, but also volume and other structural metrics that are hard to measure in the field. Our volume evaluation on three data sets with destructive volumes show high prediction qualities with concordance correlation coefficient CCC [Formula] of 0.91 (0.87), 0.94 (0.92) and 0.97 (0.93) for each data set respectively. We combine two common assumptions in plant modeling "The sum of cross sectional areas after a branch junction equals the one before the branch junction" (Pipe Model Theory) and "Twigs are self-similar" (West, Brown and Enquist model). As even sized twigs correspond to even sized cross sectional areas for twigs we define the Reverse Pipe Radius Branchorder (RPRB) as the square root of the number of supported twigs. The prediction model radius = B0 * RPRB relies only on correct topological information and can be used to detect and correct overestimated cylinders. In QSM building the necessity to handle overestimated cylinders is well known. The RPRB correction performs better with a CCC [Formula] of 0.97 (0.93) than former published ones 0.80 (0.88) and 0.86 (0.85) in our validation. We encourage forest ecologists to analyze output parameters such as the GrowthVolume published in earlier works, but also other parameters such as the GrowthLength, VesselVolume and RPRB which we define in this manuscript. Upload statementSelf-uploaded pre-print for peer-review submitted manuscript. The manuscript was submitted on 26th of July 2021 to Plos Computational Biology: I, Jan Hackenberg uploaded this manuscript because the automated journal upload was rejected for the following reason: Thank you for considering posting your manuscript "SimpleForest - a comprehensive tool for 3d reconstruction of tree from forest plot point clouds." as a preprint. Your manuscript does not meet bioRxivs criteria and therefore we will not be sending it for posting as a preprint. For more information about our checks, see link. We have noted that it contains material that is potentially subject to copyright. In particular, screenshot in Figure 1. Preprints posted to bioRxiv following submission to PLOS journals are done so under the CC BY license. To avoid a potential breach of the copyright that applies to the material listed above, we are unable to make the manuscript publicly available. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/454344v1_fig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@1094b17org.highwire.dtl.DTLVardef@120d7a3org.highwire.dtl.DTLVardef@12d2fbcorg.highwire.dtl.DTLVardef@1990a4d_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFig 1.C_FLOATNO Submission system screenshot. C_FIG Please note that this decision does not affect the editorial process at PLOS Computational Biology. Your manuscript is being separately assessed with regards to sending for peer review. From section Abstract on, the pdf you see is same as submitted one.

plant biology↗

bioRxiv2020

New insights into large tropical tree mass and structure from direct harvest and terrestrial lidar

A large portion of the terrestrial vegetation carbon stock is stored in the above-ground biomass (AGB) of tropical forests, but the exact amount remains uncertain, partly due to the lack of measurements. To date, accessible peer-reviewed data are available for just 10 large tropical trees in the Amazon that have been harvested and directly measured entirely via weighing. Here, we harvested four large tropical rainforest trees (stem diameter: 0.6-1.2m, height: 30-46m, AGB: 3960-18 584 kg) in intact old-growth forest in East Amazonia, and measured above-ground green mass, moisture content and woody tissue density. We first present rare ecological insights provided by these data, including unsystematic intra-tree variations in density, with both height and radius. We also found the majority of AGB was usually found in the crown, but varied from 42-62%. We then compare non-destructive approaches for estimating the AGB of these trees, using both classical allometry, and new lidar-based methods. Terrestrial lidar point clouds were collected pre-harvest, on which we fitted cylinders to model woody structure, enabling retrieval of volume-derived AGB. Estimates from this approach were more accurate than allometric counterparts (mean tree-scale relative error: 3% vs. 15%), and error decreased when up-scaling to the cumulative AGB of the four trees (1% vs. 15%). Further, whilst allometric error increased four-fold with tree size over the diameter range, lidar error remained constant. This suggests error in these lidar-derived estimates is random and additive. Were these results transferable across forest scenes, terrestrial lidar methods would reduce uncertainty in stand-scale AGB estimates, and therefore advance our understanding of the role of tropical forests in the global carbon cycle.

ecology↗

bioRxiv2019

A Toxic RNA Catalyzes the Cellular Synthesis of Its Own Inhibitor, Shunting It to Endogenous Decay Pathways

Myotonic dystrophy type 2 (DM2) is a genetically defined muscular dystrophy caused by a toxic expanded repeat of r(CCUG) [heretofore (CCUG)exp], harbored in intron 1 of CHC-Type Zinc Finger Nucleic Acid Binding Protein (CNBP) pre-mRNA. This r(CCUG)exp causes DM2 via a gain-of-function mechanism that results in three hallmarks of its pathology: (i) binding to RNA-binding proteins (RBPs) that aggregate into nuclear foci; (ii) sequestration of muscleblind-like-1 (MBNL1) protein, a regulator of alternative pre-mRNA splicing, leading to splicing defects; and (iii) retention of intron 1 in the CNBP mRNA. Here, we find that CNBP intron retention is caused by the r(CCUG)exp-MBNL1 complex and can be rescued by small molecules. We studied two types of small molecules with different modes of action, ones that simply bind and ones that can be synthesized by a r(CCUG)exp-templated reaction in cells, that is the RNA synthesizes its own drug. Indeed, our studies completed in DM2 patient-derived fibroblasts show that the compounds disrupt the r(CCUG)exp-MBNL1 complex, reduce intron retention, subjecting the liberated intronic r(CCUG)exp to native decay pathways, and rescue other DM2-associated cellular defects. Collectively, this study shows that small molecules can affect RNA biology by shunting toxic transcripts towards native decay pathways.\n\nHIGHLIGHTSO_LIIntron retention in RNA repeat expansions can be due to repeats binding to proteins\nC_LIO_LISmall molecules that bind RNA repeats and inhibit protein binding can trigger decay\nC_LIO_LIA toxic RNA repeat can catalyze the synthesis of its own inhibitor on-site\nC_LIO_LIOn-site drug synthesis most potently affects disease biology\nC_LI\n\neTOC BLURBThe most common way to target RNA is to use antisense oligonucleotides to target unstructured RNAs for destruction. Here, we show for the first time that small molecules targeting structured, disease-causing RNAs can shunt them towards native decay pathways by affecting their processing.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC=\"FIGDIR/small/741926v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (21K):\norg.highwire.dtl.DTLVardef@1ff5d1forg.highwire.dtl.DTLVardef@3adccborg.highwire.dtl.DTLVardef@75caf0org.highwire.dtl.DTLVardef@15e58f4_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

The mechanical stability of the worlds tallest broadleaf trees

The factors that limit the maximum height of trees, whether ecophysiological or mechanical, are the subject of longstanding debate. Here we examine the role of mechanical stability in limiting tree height and focus on trees from the tallest tropical forests on Earth, in Sabah, Malaysian Borneo, including the recently discovered tallest tropical tree, a 100.8 m Shorea faguetiana. We use terrestrial laser scans, in situ strain gauge data and finite-element simulations to map the architecture of tall broadleaf trees and monitor their response to wind loading. We demonstrate that a trees risk of breaking due to gravity or self-weight decreases with tree height and is much more strongly affected by tree architecture than by material properties. In contrast, wind damage risk increases with tree height despite the larger diameters of tall trees, resulting in a U-shaped curve of mechanical risk with tree height. The relative rarity of extreme wind speeds in north Borneo may be the reason it is home to the tallest trees in the tropics.

ecology↗

bioRxiv2019

Scans of the MYC mRNA reveal multiple stable secondary structures—including a 3′ UTR motif, conserved across vertebrates, that can affect gene expression.

The MYC gene encodes a human transcription factor and proto-oncogene that is dysregulated in over half of all known cancers. To better understand potential post-transcriptional regulatory features affecting MYC expression, we analyzed secondary structure in the MYC mRNA using a program that is optimized for finding small locally-folded motifs with a high propensity for function. This was accomplished by calculating folding metrics across the MYC sequence using a sliding analysis window and generating unique consensus base pairing models weighted by their lower-than-random predicted folding energy. A series of 30 motifs were identified, primarily in the 5 and 3 untranslated regions, which show evidence of structural conservation and compensating mutations across vertebrate MYC homologs. This analysis was able to recapitulate known elements found within an internal ribosomal entry site, as well as discover a novel element in the 3 UTR that is unusually stable and conserved. This novel motif was shown to affect MYC expression: likely via modulation of miRNA target accessibility. In addition to providing basic insights into mechanisms that regulate MYC expression, this study provides numerous, potentially druggable RNA targets for the MYC gene, which is considered "undruggable" at the protein level.

bioinformatics↗