bluuebunny/crossref_metadata_2025_split huggingface dataset:
MorphoGraphX 2.0: Providing context for biological image analysis with positional information
Authors: Strauss Soeren , Runions Adam , Lane Brendan , Eschweiler Dennis , Bajpai Namrata , Trozzi Nicola , Routier-Kierzkowska Anne-Lise , Yoshida Saiko , Rodrigues da Silveira Sylvia , Vijayan Athul , Tofanelli Rachele , Majda Mateusz , Echevin Emillie , Le Gloanec Constance , Bertrand-Rakusova Hana , Adibi Milad , Schneitz Kay , Bassel George , Kierzkowski Daniel , Stegmaier Johannes , Tsiantis Miltos , Smith Richard S. 
Published: August 2021

AbstractPositional information is a central concept in developmental biology. In developing organs, positional information can be idealized as a local coordinate system that arises from morphogen gradients controlled by organizers at key locations. This offers a plausible mechanism for the integration of the molecular networks operating in individual cells into the spatially-coordinated multicellular responses necessary for the organization of emergent forms. Understanding how positional cues guide morphogenesis requires the quantification of gene expression and growth dynamics in the context of their underlying coordinate systems. Here we present recent advances in the MorphoGraphX software (Barbier de Reuille et al. eLife 2015;4:e05864) that implement a generalized framework to annotate developing organs with local coordinate systems. These coordinate systems introduce an organ-centric spatial context to microscopy data, allowing gene expression and growth to be quantified and compared in the context of the positional information thought to control them.
Bending-torsional elasticity and energetics of the plus-end microtubule tip
Authors: Igaev Maxim , Grubmüller Helmut 
Published: August 2021

AbstractMicrotubules (MTs), mesoscopic cellular filaments, grow primarily by the addition of GTP-bound tubulin dimers at their dynamic flaring plus-end tips. They operate as chemomechanical energy transducers with stochastic transitions to an astounding shortening motion upon hydrolyzing GTP to GDP. Time-resolved dynamics of the MT tip – a key determinant of this behavior – as a function of nucleotide state, internal lattice strain, and stabilizing lateral interactions have not been fully understood. Here, we use atomistic simulations to study the spontaneous relaxation of complete GTP-MT and GDP-MT tip models from unfavorable straight to relaxed splayed conformations and to comprehensively characterize the elasticity of MT tips. Our simulations reveal the dominance of viscoelastic dynamics of MT protofilaments during the relaxation process, driven by the stored bending-torsional strain and counterbalanced by the inter-protofilament interactions. We show that the post-hydrolysis MT tip is exposed to higher activation energy barriers for straight lattice formation, which translates into its inability to elongate. Our study provides an ‘information ratchet’ mechanism for the elastic energy conversion and release by MT tips and offers new insights into the mechanoenzymatics of MTs.
MetaProFi: A protein-based Bloom filter for storing and querying sequence data for accurate identification of functionally relevant genetic variants
Authors: Srikakulam Sanjay K. , Keller Sebastian , Dabbaghie Fawaz , Bals Robert , Kalinina Olga V. 
Published: August 2021

AbstractTechnological advances of next-generation sequencing present new computational challenges to develop methods to store and query these data in time- and memory-efficient ways. We present MetaProFi (https://github.com/kalininalab/metaprofi), a Bloom filter-based tool that, in addition to supporting nucleotide sequences, can for the first time directly store and query amino acid sequences and translated nucleotide sequences, thus bringing sequence comparison to a more biologically relevant protein level. Owing to the properties of Bloom filters, it has a zero false-negative rate, allows for exact and inexact searches, and leverages disk storage and Zstandard compression to achieve high time and space efficiency. We demonstrate the utility of MetaProFi by indexing UniProtKB datasets at organism- and at sequence-level in addition to the indexing of Tara Oceans dataset and the 2585 human RNA-seq experiments, showing that MetaProFi consumes far less disk space than state-of-the-art-tools while also improving performance.
Binding specificity of ASHH2 CW-domain towards H3K4me1 ligand is coupled to its structural stability through its α1-helix
Authors: Bril’kov Maxim S. , Dobrovolska Olena , Ødegård-Fougner Øyvind , Strømland Øyvind , Aasland Rein , Halskau Øyvind 
Published: August 2021

AbstractThe CW-domain binds to histone-tail modifications found in different protein families involved in epigenetic regulation and chromatin remodelling. CW-domains recognize the methylation state of the fourth lysine on histone 3, and could therefore be viewed as a reader of epigentic information. The specificity towards different methylation states such as me1, me2 or me3 depends on the particular CW subtype. For example, the CW domain of ASHH2-methyltransferase binds preferentially to H3K4me1, MORC3 binds to both H3K4me2 and me3 modifications, while ZCWPW1 is more specific to H3K4me3. The structural basis for these preferential bindings are not well understood, and recent research suggests that a more complete picture will emerge if dynamical and energetic assessments are included in the analysis of interactions. This study uses fold assessment by NMR in combination with mutagenesis, ITC affinity measurements and thermal denaturation studies to investigate possible couplings between ASHH2 CW selectivity towards H3K4me1 and the stabilization of the domain and loops implicated in binding. Key elements of the binding site – the two tryptophans and the α1-helix form and maintain the binding pocket were perturbed by mutagenesis and investigated. Results show that α1-helix maintains the overall stability of the fold via the I915 and L919 residues, and that correct binding consolidates the loops designated η1, η3, as well as the C-terminal. This consolidation is incomplete for H3K4me3 binding to CW, which experiences a decrease in overall thermal stability upon binding. Moreover, loop-mutations not directly involved in the binding site nonetheless affect the equillibrium positions of key residues.
Subtle alterations in neonatal neurodevelopment following early or late exposure to prenatal maternal immune activation
Authors: Guma Elisa , Snook Emily , Spring Shoshana , Lerch Jason P. , Nieman Brian J. , Devenyi Gabriel A. , Chakravarty M. Mallar 
Published: August 2021

AbstractPrenatal exposure to maternal immune activation (MIA) is a risk factor for a variety of neurodevelopmental and psychiatric disorders. The timing of MIA-exposure has been shown to affect adolescent and adult offspring neurodevelopment, however, less is known about these effects in the neonatal period. To better understand the impact of MIA-exposure on neonatal brain development, we first assess neonate communicative abilities with the ultrasonic vocalization task, followed by high-resolution ex vivo magnetic resonance imaging (MRI) on the neonatal (postnatal day 8) brain. Early exposed offspring displayed decreased communicative ability, while brain anatomy appeared largely unaffected, apart from some subtle alterations. By integrating MRI and behavioural assays to investigate the effects of MIA-expsoure on neonatal neurodevelopment we show that offspring neuroanatomy and behaviour are only subtly affected by both early and late exposure. This suggests that the deficits often observed in later stages of life may be dormant, not yet developed in the neonatal period, or not as easily detectable using a cross-sectional approach.
Phylogenetic, ecological and intraindividual variability patterns in grass phytolith shape
Authors: Hošková Kristýna , Neustupa Jiří , Pokorný Petr , Pokorná Adéla 
Published: August 2021

SummaryGrass silica short cell (GSSC) phytoliths appear to be the most reliable source of fossil evidence for tracking the evolutionary history and paleoecology of grasses. In recent years, modern techniques have been used to quantitatively assess phytolith shape variation. This progress has widened opportunities with respect to the classification of grass fossil phytoliths. However, phylogenetic, ecological and intraindividual variability patterns in phytolith shape remain largely unexplored.The full range of intraindividual phytolith shape variation (3650 2D outlines) from 73 extant grass species, 48 genera, 18 tribes, and 8 subfamilies (with special attention paid to Pooideae) was analysed using the geometric morphometric analysis based on the semilandmarks spanning phytolith outlines.Although we showed that 2D phytolith shape is mainly driven by deep-time diversification of grass subfamilies, a closer look uncovered distinct phytolith shape variation in early-diverging lineages of Pooideae.The phylogenetic pattern in phytolith shape was successfully revealed by applying geometric morphometrics to 2D phytolith shape outlines. This finding strengthens the potential of phytoliths to track the evolutionary history and paleoecology of grasses. Moreover, geometric morphometrics of 2D phytolith shape proved to be an excellent tool for analysis requiring large sums of phytolith outlines, making it useful for quantitative palaeoecological reconstruction.
Microbial colonization of tannin-rich tropical plants: interplay between degradability, methane production and tannin disappearance in the rumen
Authors: Rira Moufida , Morgavi Diego P. , Popova Milka , Maxin Gaёlle , Doreau Michel 
Published: August 2021

AbstractCondensed tannins in plants are found free and attached to protein and fibre but it is not known whether these fractions influence rumen degradation and microbial colonization. This study explored the rumen degradation of tropical tannins-rich plants and the relationship between condensed tannins fractions’ disappearance and microbial communities colonising plant particles. Leaves from Calliandra calothyrsus, Gliricidia sepium, and Leucaena leucocephala, pods from Acacia nilotica and the leaves of two agricultural by-products: Manihot esculenta and Musa spp. were incubated in situ in the rumen of dairy cows. An in vitro approach was also used to assess the effects of these plants on rumen fermentation parameters. All plants contained more than 100 g/kg of condensed tannins with a large proportion (32 to 61%) bound to proteins. Calliandra calothyrsus had the highest concentration of condensed tannins at 361 g/kg, whereas Acacia nilotica was particularly rich in hydrolysable tannins (350 g/kg). Hydrolysable and free condensed tannins from all plants completely disappeared after 24 h incubation in the rumen. Disappearance of protein-bound condensed tannins was variable with values ranging from 93% for Gliricidia sepium to 21% for Acacia nilotica. In contrast, fibre-bound condensed tannins disappearance averaged ~82% and did not vary between plants. Disappearance of bound fractions of condensed tannins was not associated with degradability of plant fractions. The presence of tannins interfered with the microbial colonisation of plants. Each plant had distinct bacterial and archaeal communities after 3 and 12 h of incubation in the rumen and distinct protozoal communities at 3 h. Adherent communities in tannin-rich plants had a lower relative abundance of fibrolytic microbes, notably Fibrobacter spp. Whereas, archaea diversity was reduced in high tannin-containing Calliandra calothyrsus and Acacia nilotica at 12 h of incubation. Concurrently, in vitro methane production was lower for Calliandra calothyrsus, Acacia nilotica and Leucaena leucocephala although for the latter total volatile fatty acids production was not affected and was similar to control. Here we show that the total amount of hydrolysable and condensed tannins contained in a plant govern the interaction with rumen microbes affecting degradability and fermentation. The effect of protein- and fibre-bound condensed tannins on degradability is less important.
Ecdysone exerts biphasic control of regenerative signaling, coordinating the completion of regeneration with developmental progression
Authors: Karanja Faith , Sahu Subhshri , Weintraub Sara , Bhandari Rajan , Jaszczak Rebecca , Sitt Jason , Halme Adrian 
Published: August 2021

AbstractIn Drosophila melanogaster, loss of regenerative capacity in wing imaginal discs coincides with an increase in systemic levels of the steroid hormone ecdysone, a key coordinator of their developmental progression. Regenerating discs release the relaxin hormone Dilp8, which limits ecdysone synthesis and extends the regenerative period. Here, we describe how regenerating tissues produce a biphasic response to ecdysone levels: lower concentrations of ecdysone promote local and systemic regenerative signaling, whereas higher concentrations suppress regeneration through the expression of broad splice isoforms. Ecdysone also promotes the expression of wingless during both regeneration and normal development through a distinct regulatory pathway. This dual role for ecdysone explains how regeneration can still be completed successfully in dilp8- mutant larvae: higher ecdysone levels increase the regenerative activity of tissues, allowing regeneration to reach completion in a shorter time. From these observations, we propose that ecdysone hormone signaling functions to coordinate regeneration with developmental progression.Summary StatementEcdysone coordinates regenerative activity with developmental progression through the biphasic, concentration-dependent activation, and suppression of regenerative signaling.
Gut bacteria regulate the pathogenesis of Huntington’s disease in Drosophila model
Authors: Chongtham Anjalika , Yoo Jung Hyun , Chin Theodore M. , Akingbesote Ngozi D. , Huda Ainul , Khoshnan Ali 
Published: August 2021

AbstractChanges in the composition of gut microbiota are implicated in the pathogenesis of several neurodegenerative disorders. Here, we investigated whether gut bacteria affect the progression of Huntington’s disease (HD) in transgenic Drosophila melanogaster (fruit fly) models expressing human full-length or N-terminal fragments of mutant huntingtin (HTT) protein, here referred to as HD flies. We find that elimination of commensal gut bacteria by antibiotics reduces the aggregation of amyloidogenic N-terminal fragments of HTT and delays the development of motor defects. Conversely, colonization of HD flies with Escherichia coli (E. coli), a known pathobiont of human gut with links to neurodegeneration, accelerates HTT aggregation, aggravates immobility and shortens lifespan. Similar to antibiotics, treatment of HD flies with small compounds such as luteolin, a flavone, or crocin a beta-carotenoid, ameliorates disease phenotypes and promotes survival. Crocin prevents colonization of E. coli in the gut and alters the abundance of commensal bacteria, which may be linked to its protective effects. The opposing effects of E. coli and crocin on HTT aggregation, motor defects and survival in transgenic Drosophila models support the involvement of gut-brain networks in the pathogenesis of HD.
The Molecular Subtyping Resource (MouSR): a user-friendly tool for rapid biological discovery from human or mouse transcriptional data
Authors: Ahmaderaghi Baharak , Amirkhah Raheleh , Jackson James , Lannagan Tamsin RM , Gilroy Kathryn , Malla Sudhir B , Redmond Keara L ,   ACRCelerate Consortium, Maughan Tim , Leedham Simon , Campbell Andrew S , Sansom Owen J , Lawler Mark , Dunne Philip D 
Published: August 2021

ABSTRACTGeneration of transcriptional data has dramatically increased in the last decade, driving the development of analytical algorithms that enable interrogation of the biology underpinning the profiled samples. However, these resources require users to have expertise in data wrangling and analytics, reducing opportunities for biological discovery by “wet-lab” users with a limited programming skillset. Although commercial solutions exist, costs for software access can be prohibitive for academic research groups.To address these challenges, we have developed an open source and user-friendly data analysis platform for on-the-fly bioinformatic interrogation of transcriptional data derived from human or mouse tissue, called “MouSR”. This internet-accessible analytical tool, https://mousr.qub.ac.uk/, enables users to easily interrogate their data using an intuitive “point and click” interface, which includes a suite of molecular characterisation options including QC, differential gene expression, gene set enrichment and microenvironmental cell population analyses from RNA-Seq. Users are provided with adjustable options for analysis parameters to generate results that can be saved as publication-quality images. To highlight its ability to perform high quality data analysis, we utilise the MouSR tool to interrogate our recently published tumour dataset, derived from genetically engineered mouse models and matched organoids, where we rapidly reproduced the key transcriptional findings.The MouSR online tool provides a unique freely-available option for users to perform rapid transcriptomic analyses and comprehensive interrogation of the signalling underpinning transcriptional datasets, which alleviates a major bottleneck for biological discovery.
De novo chromosome-length assembly of the mule deer (Odocoileus hemionus) genome
Authors: Lamb Sydney , Taylor Adam M. , Hughes Tabitha A. , McMillan Brock R. , Larsen Randy T. , Khan Ruqayya , Weisz David , Dudchenko Olga , Aiden Erez Lieberman , Frandsen Paul B. 
Published: August 2021

ABSTRACTThe mule deer (Odocoileus hemionus) is an ungulate species that ranges from western Canada to central Mexico. Mule deer are an essential source of food for many predators, are relatively abundant, and commonly make broad migration movements. A clearer understanding of the mule deer genome can help facilitate knowledge of its population genetics, movements, and demographic history, aiding in conservation efforts. While mule deer are excellent candidates for population genomic studies because of their large population size, continuous distribution, and diversity of habitat, few genomic resources are currently available for this species. Here, we sequence and assemble the mule deer genome into a highly contiguous chromosome-length assembly for use in future research using long-read sequencing and Hi-C. We also provide a genome annotation and compare demographic histories of the mule deer and white-tail deer using PSMC. We expect this assembly to be a valuable resource in the continued study and conservation of mule deer.
The impact of evolutionary processes in shaping the genetics of complex traits in East Asia and Europe: a specific contribution from Denisovan and Neanderthal introgression
Authors: Koller Dora , Wendt Frank R , Pathak Gita A , De Lillo Antonella , De Angelis Flavio , Cabrera-Mendoza Brenda , Tucci Serena , Polimanti Renato 
Published: August 2021

AbstractEvidence of how human evolution shaped the polygenicity of human traits and diseases has been extensively studied in populations of European descent. However, limited information is currently available about its impact on other ancestry groups. Here, we investigated how different evolutionary processes affected the common variant heritability of traits and diseases in East Asians. Leveraging genome-wide association statistics from the Biobank Japan (up to 158,284 participants), we assessed natural selection (negative and positive), archaic introgression from Neanderthal and Denisova, and several genomic functional categories with respect to the heritability of physiological and pathological conditions. Similar to reports in European descent populations, the heritability estimates for East Asian traits were ubiquitously enriched for negative selection annotations (false discovery rate, FDR q<0.05). Enrichment of Denisovan introgression was identified in coronary artery disease (1.69-fold enrichment, p=0.003). We followed up these enrichments by conducting a phenome-wide association study (PheWAS) of Denisovan and Neanderthal alleles in participants of six ancestral backgrounds from the UK Biobank. In East Asians, Denisovan-inherited alleles were associated with 22 phenotypes, including metabolic, immunological, cardiovascular, endocrine, and dermatological traits. The strongest association was observed for the Denisovan-inherited locus rs59185462 with rheumatoid arthritis (beta=0.82, p=1.91×10−105). In summary, our study provides the first evidence regarding the impact of evolutionary processes on the genetics of complex traits in worldwide populations, highlighting the specific contribution of Denisovan introgression in East Asian populations.
Motor learning without movement
Authors: Kim Olivia A. , Forrence Alexander D. , McDougle Samuel D. 
Published: August 2021

ABSTRACTPrediction errors guide many forms of learning, providing teaching signals that help us improve our performance. Implicit motor adaptation, for instance, is driven by sensory prediction errors (SPEs), which occur when the expected and observed consequences of a movement differ. Traditionally, SPE computation is thought to require movement execution. However, recent work suggesting that the brain generates and accounts for sensory predictions based on motor imagery or planning alone calls this assumption into question. Here, by measuring implicit adaptation during a visuomotor task, we tested whether motor planning and well-timed sensory feedback are sufficient for SPE computation. Human participants were cued to reach to a target and were, on a subset of trials, rapidly cued to withhold these movements. Errors displayed both on trials with and without movements induced single-trial implicit learning. Learning following trials without movements persisted even when movement trials had never been paired with errors, and when the direction of movement and sensory feedback trajectories were decoupled. These observations demonstrate that the brain can compute SPEs without generating overt movements, leading to the adaptation of planned movements even when they are not performed.SIGNIFICANCE STATEMENTWe are always learning from our mistakes, because the brain is constantly generating predictions and monitoring the world for any surprises, which are also referred to as “prediction errors.” Whenever a prediction error occurs, the brain learns to update future predictions and be more accurate. Here, we demonstrate that the brain predicts the consequences of movements, computes prediction errors, and updates future movements, even if we subsequently decide to withhold the movement. Thus, the brain can learn to update movements that are not performed, representing a mechanism for learning based only on movement planning and sensory expectation. These findings also provide further support for the role of prediction in motor control.SIGNIFICANCE STATEMENTOur brains control aspects of our movement without our conscious awareness – allowing many of us to effortlessly pick up a glass of water or wave “hello.” Here, we demonstrate that this implicit motor system can learn to refine movements that we plan but ultimately decide not to perform. Participants planned to reach to a target, and they sometimes withheld these reaches. When reaches were withheld, an animation simulating a reach that missed the target played. Afterwards, participants reached opposite the direction of the mistake without awareness of this change in their movements, indicating that the implicit motor system had learned from the animated mistake. These findings indicate that movement is not strictly necessary for motor adaptation, and that we can learn to update our actions based only on movement planning and observation of related events in the world.