bluuebunny/crossref_metadata_2025_split huggingface dataset:
A microtubule stability switch alters isolated vascular smooth muscle calcium flux in response to matrix rigidity
Authors: Johnson Robert , Wostear Finn , Solanki Reesha , Steward Oliver , Morris Christopher , Bidula Stefan , Warren Derek T 
Published: November 2022

AbstractDuring ageing, the extracellular matrix of the aortic wall becomes more rigid. In response, VSMCs generate enhanced contractile forces. Our previous findings demonstrate that VSMC volume is enhanced in response to increased matrix rigidity, but our understanding of mechanisms regulating this process remain incomplete. In this current study, we show that microtubule stability in VSMCs is reduced in response to enhanced matrix rigidity via piezo1-mediated Ca2+influx. Moreover, VSMC volume and Ca2+flux was regulated by microtubule dynamics; microtubule stabilising agents reduced both VSMC volume and Ca2+flux on rigid hydrogels, whereas microtubule destabilising agents increased VSMC volume and Ca2+flux on pliable hydrogels. Finally, we show that disruption of the microtubule deacetylase HDAC6 uncoupled these processes and increased K40 alpha tubulin acetylation, VSMC volume and Ca2+flux on pliable hydrogels, but did not alter VSMC microtubule stability. These findings uncover a microtubule stability switch that controls VSMC volume by regulating Ca2+flux. Together, these data demonstrate that manipulation of microtubule stability can modify VSMC matrix rigidity response.
Miniature spatial transcriptomics for studying parasite-endosymbiont relationships at the micro scale
Authors: Sounart Hailey , Voronin Denis , Masarapu Yuvarani , Chung Matthew , Saarenpää Sami , Ghedin Elodie , Giacomello Stefania 
Published: November 2022

AbstractSeveral important human infectious diseases are caused by microscale-sized parasitic nematodes like filarial worms. Filarial worms have their own spatial tissue organization and to uncover this tissue structure, we need methods that can spatially resolve these miniature specimens. Most filarial worms evolved a mutualistic association with endosymbiotic bacteriaWolbachia, however, the mechanisms underlying the dependency of filarial worms on the fitness of these bacteria remain unknown. AsWolbachiais essential for the development, reproduction, and survival of filarial worms, we focused on studying a posterior region containing reproductive tissue and developing embryos of adult femaleBrugia malayiworms. To spatially explore howWolbachiainteracts with the worm’s reproductive system, we performed a spatial characterization using Spatial Transcriptomics (ST) across our region of interest. We provide a proof-of-concept for miniature-ST to explore spatial gene expression patterns in small sample types, demonstrating the method’s ability to uncover nuanced tissue region expression patterns, observe the spatial localization of keyB. malayi-Wolbachiapathway genes, and co-localize theB. malayispatial transcriptome inWolbachiatissue regions. We envision our approach to open up new scenarios for the study of infectious diseases caused by micro-scale parasitic worms.
Temporal characteristics of gamma rhythm constrain properties of noise in an inhibition-stabilized network model
Authors: Krishnakumaran R , Ray Supratim 
Published: November 2022

AbstractGamma rhythm refers to oscillatory neural activity between 30-80 Hz, often induced in visual cortex by presentation of stimuli such as iso-luminant hues or gratings. Further, the power and peak frequency of gamma depend on the properties of the stimulus such as size and contrast. Gamma also has a typical arch shape, with a narrow trough and a broad peak, which can be replicated by a self-oscillating Wilson-Cowan (WC) model operating in an appropriate regime. However, oscillations in this model are infinitely long, unlike physiological gamma that occurs in short bursts. Further, unlike the model, gamma is faster after stimulus onset and slows down over time. Here, we first characterized gamma burst duration in LFP data recorded from two monkeys while they viewed full screen iso-luminant hues. We then added different types of noise in the inputs to the WC model and tested how that affected duration and temporal dynamics of gamma. While the model failed with the often-used Poisson noise, Ornstein-Uhlenbeck (OU) noise applied to both the excitatory and inhibitory populations in the WC model replicated the duration and slowing of gamma, and also replicated the shape and stimulus dependencies. Therefore, temporal dynamics of gamma oscillations put constraints on the type and properties of underlying neural noise.
Poly ADP-Ribose Signaling is Dysregulated in Huntington Disease
Authors: Maiuri Tamara , Bazan Carlos Barba , Harding Rachel J. , Begeja Nola , Kam Tae-In , Byrne Lauren M. , Rodrigues Filipe B. , Warner Monica M. , Neuman Kaitlyn , Mansoor Muqtasid , Badiee Mohsen , Dasovich Morgan , Wang Keona , Thompson Leslie M , Leung Anthony K. L. , Andres Sara N. , Wild Edward J. , Dawson Ted M. , Dawson Valina L. , Arrowsmith Cheryl H. , Truant Ray 
Published: November 2022

AbstractHuntington disease (HD) is a genetic neurodegenerative disease caused by CAG expansion in theHuntingtin (HTT)gene, translating to an expanded polyglutamine tract in the huntingtin (HTT) protein. Age at disease onset correlates to CAG repeat length but varies by decades between individuals with identical repeat lengths. Genome-wide association studies link HD modification to DNA repair and mitochondrial health pathways. Clinical studies show elevated DNA damage in HD, even at the premanifest stage. A major DNA repair node influencing neurodegenerative disease is the PARP pathway. Accumulation of poly ADP-ribose (PAR) has been implicated in Alzheimer and Parkinson diseases, as well as cerebellar ataxia. We report that HD mutation carriers have lower cerebrospinal fluid PAR levels than healthy controls, starting at the premanifest stage. Human HD iPSC-derived neurons and patient- derived fibroblasts have diminished PAR response in the context of elevated DNA damage. We have defined a PAR-binding motif in huntingtin, detected huntingtin complexed with PARylated proteins in human cells during stress, and localized huntingtin to mitotic chromosomes upon inhibition of PAR degradation. Direct huntingtin PAR binding was measured by fluorescence polarization and visualized by atomic force microscopy at the single molecule level. While wild type and mutant huntingtin did not differ in their PAR binding ability, purified wild type huntingtin protein increasedin vitroPARP1 activity while mutant huntingtin did not. These results provide insight into an early molecular mechanism of HD, suggesting possible targets for the design of early preventive therapies.Significance statementA consensus on dysfunctional DNA repair has emerged in neurodegenerative disease research, with elevated poly ADP-ribose (PAR) signaling more recently implicated. In contrast, we have identified a deficient PAR response in Huntington’s disease (HD) patient spinal fluid samples and cells. This may be explained by the inability of huntingtin protein bearing the HD-causing mutation to stimulate production of PAR the way the wild type protein does. Since drugs that target PAR production and degradation have already been developed, these findings present an exciting avenue for therapeutic intervention for HD.
Fast imaging of millimeter-scale areas with beam deflection transmission electron microscopy
Authors: Zheng Zhihao , Own Christopher S. , Wanner Adrian A. , Koene Randal A. , Hammerschmith Eric W. , Silversmith William M. , Kemnitz Nico , Lu Ran , Tank David W. , Seung H. Sebastian 
Published: November 2022

AbstractSerial section transmission electron microscopy (TEM) has proven to be one of the leading methods for millimeter-scale 3D imaging of brain tissues at nanoscale resolution. It is important to further improve imaging efficiency to acquire larger and more brain volumes. We report here a three fold increase in the speed of TEM by using a beam deflecting mechanism to enable highly efficient acquisition of multiple image tiles (nine) for each motion of the mechanical stage. For millimeter-scale areas, the duty cycle of imaging doubles to more than 30%, yielding a net average imaging rate of 0.3 gigapixels per second. If fully utilized, an array of beam deflection TEMs should be capable of imaging a dataset of cubic millimeter scale in several weeks.
Spatial variation in relative abundances of two butterfly species sharing both host plant and natural enemies
Authors: Colom P. , Traveset A. , Shaw M. R. , Stefanescu C. 
Published: November 2022

ABSTRACTThe decline of insect populations is of great concern because they play an essential part in several services that are key for ecosystem functioning and human well-being. Therefore, full understanding of the processes and factors shaping spatial variation in insects is required for their effective conservation. Here, we study a system comprising two congeneric butterfly species (BrimstoneGonepteryx rhamniand CleopatraG. cleopatra) that share both host plants and natural enemies and analyse whether biotic and/or abiotic factors explain their relative abundances. The two species coexist in continental Spain but not on a nearby archipelago, where only the Cleopatra occurs. The hypotheses tested were based on (H1) dispersal behaviour; (H2) apparent competition mediated via shared parasitoids; and (H3) environmental conditions (overwintering habitat availability, abundance of host plants and temperature). H1 explained differences in Brimstone abundance between climate regions on the mainland since in warmer summers populations increased in cooler areas but decreased in warmer areas. Cleopatra did not show the same pattern but was found to have twice the number of summer adults on one island than on the mainland. It is unlikely that H2 can explain this result because, although richer parasitoid communities were found on the mainland, larval mortality rates were similar. H3 was important in explaining variation in abundances between sites within each climate region even though similar environmental conditions were found on the mainland and on the islands. Our study demonstrates the complexity of any attempt to understand insect population dynamics in space due to the number of factors that are potentially involved. We argue thus that a more comprehensive approach taking into account landscape topography and resource connectivity on a broader scale is required to unravel the factors shaping the relative abundance of insects in island systems.
The role of the thalamus in human reinforcement learning
Authors: Collomb-Clerc Antoine , Gueguen Maëlle C. M. , Lorella Minotti , Philippe Kahane , Vincent Navarro , Fabrice Bartolomei , Romain Carron , Jean Regis , Stephan Chabardès , Palminteri Stefano , Bastin Julien 
Published: November 2022

AbstractAlthough the thalamus is supposed to be involved in reinforcement-based decision-making, there is no direct evidence regarding the involvement of this subcortical structure in humans. To fill this gap, we leveraged rare intra-thalamic electrophysiological recordings in patients and found that temporally structured thalamic oscillations encode key learning signals. Our findings also provide neural insight into the computational mechanisms of action inhibition in punishment avoidance learning.
Re-implementation of an algorithm to integrate transcriptome and ChIP-seq data
Authors: Ahmed Mahmoud , Kim Deok Ryong 
Published: November 2022

AbstractTranscription factor binding to a gene regulatory region induces or represses its expression. Binding and expression target analysis (BETA) integrates the binding and gene expression data to predict this function. First, the regulatory potential of the factor is modeled based on the distance of its binding sites from the transcription start sites in a decay function. Then the differential expression statistics from an experiment where this factor was perturbed represent the binding effect. The rank product of the two values is employed to order in importance. This algorithm was originally implemented in Python. We reimplemented the algorithm in R to take advantage of existing data structures and other tools for downstream analyses. Here, we attempted to replicate the findings in the original BETA paper. We applied the new implementation to the same datasets using default and varying inputs and cutoffs. We successfully replicated the original results. Moreover, we showed that the method was appropriately influenced by varying the input and was robust to choices of cutoffs in statistical testing.
Anin vivomassively parallel platform for deciphering tissue-specific regulatory function
Authors: Brown Ashley R. , Fox Grant A. , Kaplow Irene M. , Lawler Alyssa J. , Phan BaDoi N. , Wirthlin Morgan E. , Ramamurthy Easwaran , May Gemma E. , Chen Ziheng , Su Qiao , McManus C. Joel , Pfenning Andreas R. 
Published: November 2022

AbstractGenetic studies are rapidly identifying non-protein-coding human disease-associated loci. Understanding the regulatory mechanisms underlying these loci remains a challenge because the causal variants and the tissues in which they act are often unclear. Massively parallel reporter assays (MPRAs) have the potential to link differences in genome sequence, including genetic variants, to tissue-specific regulatory function. Although MPRA and similar technologies have been widely adopted in cell culture, there have been several barriers to widespread use in animals. We overcome these challenges with a new whole-animal MPRA (WhAMPRA), where systemic intravenous AAV effectively transduces the plasmid MPRA library to mouse tissues. Our WhAMPRA approach revealed models of tissue-specific regulation that generally match machine learning model predictions. In addition, we measured the regulatory effects of disrupting MEF2C transcription factor binding sites and impacts of late onset Alzheimer’s disease-associated genetic variations. Overall, our WhAMPRA technology simultaneously determines the transcriptional functions of hundreds of enhancersin vivoacross multiple tissues.
TDCS MODULATES WORKING MEMORY MAINTENANCE PROCESSES IN HEALTHY INDIVIDUALS
Authors: Nikolin Stevan , Martin Donel , Loo Colleen K. , Boonstra Tjeerd W. 
Published: November 2022

AbstractBackgroundThe effects of tDCS at the prefrontal cortex are often investigated using cognitive paradigms, particularly working memory tasks. However, the neural basis for the neuromodulatory cognitive effects of tDCS, including which subprocesses are affected by stimulation, is not completely understood.AimsWe investigated the effects of tDCS on working memory task-related spectral activity during and after tDCS to gain better insights into the neurophysiological changes associated with stimulation.MethodsWe reanalysed data from 100 healthy participants grouped by allocation to receive either Sham (0 mA, 0.016 mA, and 0.034 mA) or Active (1 mA or 2 mA) stimulation during a 3-back task. Electroencephalography (EEG) data was used to analyse event-related spectral power in frequency bands associated with working memory performance.ResultsFrontal theta event-related synchronisation (ERS) was significantly reduced post-tDCS in the active group. Participants receiving active tDCS had slower response times following tDCS compared to Sham, suggesting interference with practice effects associated with task repetition. Theta ERS was not significantly correlated with response times or accuracy.ConclusionstDCS reduced frontal theta ERS post-stimulation, suggesting a selective disruption to working memory cognitive control and maintenance processes. These findings suggest that tDCS selectively affects specific subprocesses during working memory, which may explain heterogenous behavioural effects.
Spatial scale influences taxon conservation in the eukaryotic virome of a mosquito
Authors: Gil Patricia , Exbrayat Antoni , Loire Etienne , Rakotoarivony Ignace , Charriat Florian , Baldet Thierry , Boisseau Michel , Marie Albane , Frances Benoît , L’Ambert Gregory , Bessat Mohamed , Otify Yehia , Goffredo Maria , Mancini Giuseppe , Busquets-Martí Núria , Birnberg Lotty , Talavera Sandra , Aranda Carlos , Ayari Emna , Mejri Selma , Sghaier Soufien , Bennouna Amal , El Rhaffouli Hicham , Balenghien Thomas , Chlyeh Ghita , Fihri Ouafaa Fassi , Reveillaud Julie , Simonin Yannick , Eloit Marc , Gutierrez Serafin 
Published: November 2022

AbstractOur knowledge on the diversity of eukaryotic viruses has recently undergone a massive expansion. This diversity could influence host physiology through yet unknown phenomena of potential interest to the fields of health and food production. However, the assembly processes in eukaryotic viromes of terrestrial animals remain elusive. This situation hinders hypothesis-driven tests of virome influence on host physiology. Here, we explore virome assembly at different spatial scales in the eukaryotic virome of the mosquitoCulex pipiens. This mosquito is a vector of human pathogens worldwide. Several new aspects of virome assembly were unveiled through a sampling involving five countries in Africa and Europe and large sample sizes. A group of viruses was conserved inC. pipienspopulations in all countries. This core group represented a relatively large and diverse fraction of the virome. However, core viruses were not shared by all host individuals in a given country, and their infection rates fluctuated between countries and years. Moreover, the distribution of co-infections in individual mosquitoes suggested random co-occurrence of certain core viruses. We also observed differences in the virome depending on geography, with viromes tending to cluster depending on the continent. Thus, our results unveil that taxon conservation in a eukaryotic virome changes with spatial scale. Thus, predictions on virome assembly seem possible at a large geographical scale inC. pipiens.IMPORTANCEThe study of the eukaryotic virome of mosquitoes is an emerging research field. Beyond its fundamental interest, this field could lead to the development of control tools against the transmission of mosquito-borne human pathogens. However, we yet know little on the assembly patterns in the eukaryotic viromes of mosquitoes, as well as of terrestrial animals in general. This situation hampers the design of hypothesis-driven studies on the influence of the virome on pathogen transmission. Here, we have analyzed virome assembly in the mosquito vectorCulex pipienswithin and between countries in Africa and Europe. Our results show that integrating contrasted spatial scales allows to identify deterministic patterns in virome assembly. Such patterns can guide future studies of virome influence on mosquito physiology.
3D volumetric muscle reconstruction of theAustralopithecus afarensispelvis and limb, with estimations of limb leverage
Authors: Wiseman Ashleigh L. A. 
Published: November 2022

AbstractTo understand how an extinct species may have moved, we first need to reconstruct the missing soft tissues of the skeleton which rarely preserve, with an understanding of segmental volume and the muscular composition within the body. TheAustralopithecus afarensisspecimen AL 288-1 is one of the most complete hominin skeletons. Whilst it is generally accepted that this species walked with an erect limb, the frequency and efficiency of such movement is still debated. Here, 36 muscles of the pelvis and lower limb were reconstructed in the specimen AL 288-1 using 3D polygonal modelling which was guided by imaging scan data and muscle scarring. Reconstructed muscle masses and configurations guided biomechanical modelling of the lower limb in comparison to a modern human. Muscle moment arms were calculated and summed per muscle group. Simulated error margins were computed using Monte Carlo analyses. Results show that the moment arms of both species were comparable, hinting towards similar limb functionality. Moving forward, the polygonal muscle modelling approach has demonstrated promise for reconstructing the soft tissues of hominins and providing information on muscle configuration and space filling. This approach is recommended for future studies aiming to model musculature in extinct taxa.
Genomics of Preaxostyla Flagellates Illuminates the Path Towards the Loss of Mitochondria
Authors: Novák Lukáš V. F. , Treitli Sebastian C. , Pyrih Jan , Hałakuc Paweł , Pipaliya Shweta V. , Vacek Vojtěch , Brzoň Ondřej , Soukal Petr , Eme Laura , Dacks Joel B. , Karnkowska Anna , Eliáš Marek , Hampl Vladimír 
Published: November 2022

AbstractThe notion that mitochondria cannot be lost was shattered with the report of an oxymonadMonocercomonoides exilis, the first eukaryote arguably without any mitochondrion. Yet, questions remain about whether this extends beyond the single species and how this transition took place. The Oxymonadida is a group of gut endobionts taxonomically housed in the Preaxostyla which also contains free-living flagellates of the generaTrimastixandParatrimastix. The latter two taxa harbour conspicuous mitochondrion-related organelles (MROs). Here we report high-quality genome and transcriptome assemblies of two Preaxostyla representatives, the free-livingParatrimastix pyriformisand the oxymonadBlattamonas nauphoetae. We performed thorough comparisons among all available genomic and transcriptomic data of Preaxostyla to further decipher the evolutionary changes towards amitochondriality, endobiosis, and unstacked Golgi. Our results provide insights into the metabolic and endomembrane evolution, but most strikingly the data confirm the complete loss of mitochondria for all three oxymonad species investigated (M. exilis,B. nauphoetae, andStreblomastix strix), suggesting the amitochondriate status is common to a large part if not whole group of Oxymonadida. This observation moves this unique loss to 100 MYA when oxymonad lineage diversified.Author summaryMitochondria are nearly ubiquitous components of eukaryotic cells that constitute bodies of animals, fungi, plants, algae, and a broad diversity of single-celled eukaryotes,akaprotists. Many groups of protists have substantially reduced the complexity of their mitochondria because they live in oxygen-poor environments, so they are unable to utilize the most salient feature of mitochondria – their ATP-producing oxidative phosphorylation metabolism. However, for a long time, scientists thought that it is impossible to completely lose a mitochondrion because this organelle provides other essential services to the cell, e.g. synthesis of protein cofactors called iron-sulfur clusters. Detailed investigation of chinchilla symbiont M.exilisdocumented the first case of an organism without mitochondrion, and it also provided a scenario explaining how this unique evolutionary experiment might have happened. In this work, we expand on this discovery by exploring genomes of multiple relatives ofM. exilis. We show that the loss of the mitochondrion is not limited to a single species but possibly extends to its entire group, the oxymonads. We also compare the predicted metabolic capabilities of oxymonads to their closest known mitochondrion-containing relatives and map out various changes that occurred during the transition to amitochondriality.