bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective subviral particles modify ecological equilibria and enhance viral coexistence
Authors: Lucía-Sanz Adriana , Aguirre Jacobo , Fraile Aurora , García-Arenal Fernando , Manrubia Susanna 
Published: May 2022

ABSTRACTCooperation is a main driver of biological complexity at all levels. In the viral world, gene sharing among viral genomes, complementation between genomes or interactions within quasispecies are frequently observed. In this contribution, we explore the advantages that flexible associations between fully fledged viruses and subviral entities, such as virus satellites, might yield. We devise a mathematical model to compare different situations of competition between two viruses and to quantify how the association with a satellite qualitatively modifies dynamical equilibria. The relevant parameter is the invasion fitness of each virus or of the virus-satellite tandem, which in the model depends on the transmission rate of viruses and on their effect on host survival. While in a virus-virus competition one of the viruses becomes eventually extinct, an association with a satellite might change the outcome of the competition to favor the less competitive virus (regardless of whether it is the helper virus or not) or to allow for the stable coexistence of the two viruses and the satellite. We hypothesize that the latter scenario, in particular, constitutes a parsimonious evolutionary pathway towards more stable cooperative associations, such as bipartite viral forms.
Multifaceted role of RIMBP2 in promoting hearing in murine cochlear hair cells
Authors: Liao Menghui , Chen Xin , Lu Ling , Guo Rongrong , Zhang Panpan , Li Yige , Zhang Yuhua , Fang Qiaojun , Hu Yangnan , Cai Jiaying , Chen Xiaoyan , Tang Mingliang , Gao Xia , He Shuijin , Li Huawei , Li Geng-Lin , Chai Renjie 
Published: May 2022

AbstractIn peripheral, the mammalian cochlea is a remarkable sensory apparatus, owning to its outer and inner hair cells (OHCs and IHCs) that amplify and transmit auditory signals to the brain, respectively. Rab3-interacting molecular (RIM) binding protein 2 (RIMBP2) is widely expressed in receptor cells and neurons, specifically in the active zones for exocytosis of synaptic vesicles (SVs), but its exact functions in the cochlea are not very well understood. We therefore generated a Rimbp2 knockout mouse model (Rimbp2-/-), which exhibited severely impaired hearing with not only elevated hearing thresholds but also increased latencies and reduced amplitudes in the Wave I of their auditory brainstem responses (ABRs). Consistent with the threshold elevation, we found significant loss of OHCs, likely through apoptosis, in the Rimbp2-/- cochlea. Consistent with changes observed in the ABR Wave I, we found greatly reduced exocytosis, both spontaneously and upon stimulation, in Rimbp2-/- IHCs. Specifically, our patch-clamp analysis on IHCs and postsynaptic spiral ganglion neurons (SGNs) revealed not only reduced readily releasable pool (RRP) of SVs but also reduced sustained release rate, along with complete blockade of fast endocytosis, in Rimbp2-/- IHCs. Lastly, with immunostaining of whole-mounted cochleae, we found that while the number of ribbon synapses in Rimbp2-/- IHCs was unchanged, their localization moved subtly but significantly towards the basal pole of IHCs. Taken together, we uncovered an unexpected role of RIMBP2 for OHC survival and a more extensive role in promoting IHC exocytosis than previously believed.
Gene expression analysis of the Xenopus laevis early limb bud proximodistal axis
Authors: Hudson D.T. , Bromell J. S. , Day R.C. , McInnes T , Ward J.M. , Beck C.W. 
Published: May 2022

AbstractBackgroundLimb buds develop as bilateral outgrowths of the lateral plate mesoderm and are patterned along three axes. Current models of proximal to distal patterning of early amniote limb buds suggest that two signals, a distal organising signal from the apical epithelial ridge (AER, Fgfs) and an opposing proximal (retinoic acid) act early on pattern this axis.ResultsTranscriptional analysis of stage 51 Xenopus laevis hindlimb buds sectioned along the proximal-distal axis, showed that the distal region is distinct from the rest of the limb. Expression of capn8.3, a novel calpain, was located in cells immediately flanking the AER. The Wnt antagonist Dkk1 was AER-specific in Xenopus limbs. Two transcription factors, sall1 and zic5, were expressed in distal mesenchyme. Zic5 has no described association with limb development. We also describe expression of two proximal genes, gata5 and tnn, not previously associated with limb development. Differentially expressed genes were associated with Fgf, Wnt and retinoic acid (RA) signalling as well as differential cell adhesion and proliferation.ConclusionsWe identify new candidate genes for early proximodistal limb patterning. Our analysis of RA-regulated genes supports a role for transient RA gradients in early limb bud in proximal-to-distal patterning in this anamniote model organism.
Hippocampal subfields and their neocortical interactions during autobiographical memory
Authors: Leelaarporn Pitshaporn , Dalton Marshall A. , Stirnberg Rüdiger , Stöcker Tony , Spottke Annika , Schneider Anja , McCormick Cornelia 
Published: May 2022

AbstractAdvances in ultra-high field 7 Tesla functional magnetic resonance imaging (7T fMRI) have provided unprecedented opportunities to gain insights into the neural underpinnings supporting human memory. The hippocampus, a heterogeneous brain structure comprising several subfields plays a central role during vivid re-experiencing of autobiographical memories (AM). However, due to technical limitations, how hippocampal subfields differentially support AM, whether this contribution is specific to one portion along the hippocampal long-axis, and how subfields are functionally connected with other brain regions typically associated with AM retrieval remains elusive. Here, we leveraged technical advances of parallel imaging and employed a submillimeter Echo Planar Imaging sequence over the whole brain while participants re-experienced vivid, detail-rich AM. We found that all hippocampal subfields along the long-axis were engaged during AM retrieval. Nonetheless, only the pre/parasubiculum within the anterior body of the hippocampus, contributed over and above to AM retrieval. Moreover, whole-brain functional connectivity analyses of the same data revealed that this part of the hippocampus was the only one that was strongly connected to other brain regions typically associated with AM, such as the ventromedial prefrontal cortex (vmPFC) and medial/lateral parietal regions. In the context of the broader literature, our results support recent proposals that the anterior body of the pre/parasubiculum may play an essential role in scene-based cognition, such as the re-experience of personal past events.HighlightsAll hippocampal subfields differentiate AM retrieval from mental arithmetic problem solvingThe anterior body of the pre/parasubiculum engages in AM more than other subfieldsThe anterior body of the pre/parasubiculum is strongly connected to the AM networkThe pre/parasubiculum may be preferentially involved in scene-based cognition
Introducing the Dendrify framework for incorporating dendrites to spiking neural networks
Authors: Pagkalos Michalis , Chavlis Spyridon , Poirazi Panayiota 
Published: May 2022

AbstractComputational modeling has been indispensable for understanding how subcellular neuronal features influence circuit processing. However, the role of dendritic computations in network-level operations remains largely unexplored. This is partly because existing tools do not allow the development of realistic and efficient network models that account for dendrites. Current spiking neural networks, although efficient, are usually quite simplistic, overlooking essential dendritic properties. Conversely, circuit models with morphologically detailed neuron models are computationally costly, thus impractical for large-network simulations. To bridge the gap between these two extremes and facilitate the adoption of dendritic features in spiking neural networks, we introduce Dendrify, an open-source Python package based on Brian 2. Dendrify, through simple commands, automatically generates reduced compartmental neuron models with simplified yet biologically relevant dendritic and synaptic integrative properties. Such models strike a good balance between flexibility, performance, and biological accuracy, allowing us to explore dendritic contributions to network-level functions while paving the way for developing more powerful neuromorphic systems.
Modeling Reactive Species Metabolism in Colorectal Cancer for Identifying Metabolic Targets and Devising Therapeutics
Authors: Bhalla Prerna , Sridhar Subasree , Kullu Justin , Veerapaneni Sriya , Sahoo Swagatika , Bhatt Nirav , Suraishkumar GK 
Published: May 2022

AbstractReactive species (RS) are known to play significant roles in cancer development as well as in treating or managing cancer. On the other hand, genome scale metabolic models are being used to understand cell metabolism in disease contexts including cancer, and also in planning strategies to handle diseases. Despite their crucial roles in cancers, the reactive species have not been adequately modeled in the genome scale metabolic models (GSMMs) when probing disease models for their metabolism or detection of drug targets. In this work, we have developed a module of reactive species reactions, which is scalable - it can be integrated with any human metabolic model as it is, or with any metabolic model with fine-tuning. When integrated with a cancer (colorectal cancer in this case) metabolic model, the RS module highlighted the deregulation occurring in important CRC pathways such as fatty acid metabolism, cholesterol metabolism, arachidonic acid and eicosanoid metabolism. We show that the RS module helps in better deciphering crucial metabolic targets for devising better therapeutics such as FDFT1, FADS2 and GUK1 by taking into account the effects mediated by reactive species during colorectal cancer progression. The results from this reactive species integrated CRC metabolic model reinforces ferroptosis as a potential target for colorectal cancer therapy.
Digital holography-based 3D particle localisation for single molecule tweezer techniques
Authors: Flewellen James L. , Minoughan Sophie , Garcia Isabel Llorente , Tolar Pavel 
Published: May 2022

ABSTRACTWe present a three-dimensional imaging technique for fast tracking of microscopic objects in a fluid environment. Our technique couples digital holographic microscopy with three-dimensional localisation via parabolic masking. Compared with existing approaches, our method reconstructs 3D volumes from single-plane images, which greatly simplifies image acquisition, reduces the demand on microscope hardware, and facilitates tracking higher densities of microscopic particles while maintaining similar levels of precision. We demonstrate utility of this method in magnetic tweezer experiments, opening their use to multiplexed single-molecule force spectroscopy assays. We propose that our technique will also be useful in other applications that involve the tracking of microscopic objects in three dimensions.SIGNIFICANCETracking objects in 3D is a common task in biology, but typically requires the acquisition of image stacks, which is limited by speed, the depth of field of microscope objectives and by the presence of other objects that obscure the illumination. Here we develop HoloMiP (Holographic Microscopy with Parabolic masking), which uses digital holography to reconstruct the three-dimensional images from a single plane allowing tracking of light-scattering objects in 3D. HoloMiP outperforms existing methods in precision, speed, simplicity and tolerance to crowding. We show that it is particularly suitable for fast, multiplexed magnetic tweezer experiments, opening new avenues to high-throughput force spectroscopy.
Brain Structure and Episodic Learning Rate in Cognitively Healthy Ageing
Authors: Frank Darya , Garo-Pascual Marta , Reyes Velasquez Pablo Alejandro , Frades Belén , Peled Noam , Zhang Linda , Strange Bryan A. 
Published: May 2022

AbstractMemory normally declines with ageing and these age-related cognitive changes are associated with changes in brain structure. Episodic memory retrieval has been widely studied during ageing, whereas learning has received less attention. Here we examined the neural correlates of episodic learning rate in ageing. Our study sample consisted of 982 cognitively healthy female and male older participants from the Vallecas Project cohort, without a clinical diagnosis of mild cognitive impairment or dementia. The learning rate across the three consecutive recall trials of the verbal memory task (Free and Cued Selective Reminding Test) recall trials was used as a predictor of grey matter (GM) using voxel-based morphometry, and WM microstructure using tract-based spatial statistics on fractional anisotropy (FA) and mean diffusivity (MD) measures. Immediate Recall improved by 1.4 items per trial on average, and this episodic learning rate was faster in women and negatively associated with age. Structurally, hippocampal and anterior thalamic GM volume correlated positively with learning rate. Learning also correlated with the integrity of WM microstructure (high FA and low MD) in an extensive network of tracts including bilateral anterior thalamic radiation, fornix, and long-range tracts. These results suggest that episodic learning rate is associated with key anatomical structures for memory functioning, motivating further exploration of the differential diagnostic properties between episodic learning rate and retrieval in ageing.
A molecular plugin rescues GroEL/ES substrates from pre-folding oxidation
Authors: Dupuy Emile , Van der Verren Sander E. , Lin Jiusheng , Wilson Mark A. , Dachsbeck Alix , Viela Felipe , Latour Emmanuelle , Gennaris Alexandra , Vertommen Didier , Dufrêne Yves F. , Iorga Bogdan I. , Goemans Camille V. , Remaut Han , Collet Jean-François 
Published: May 2022

SUMMARYHsp60 chaperonins and their Hsp10 cofactors assist protein folding in all living cells, constituting the paradigmatic example of molecular chaperones. Despite extensive investigations of their structure and mechanism, crucial questions regarding how these chaperonins promote folding remain unsolved. Here, we report that the bacterial Hsp60 chaperonin GroEL forms a stable, functionally relevant complex with the chaperedoxin CnoX, a protein combining a chaperone and a redox function. Binding of GroES (Hsp10) to GroEL induces CnoX release. Cryo-electron microscopy provided crucial structural information on the GroEL-CnoX complex, showing that CnoX binds GroEL outside the substrate-binding site via a highly conserved C-terminal α-helix. Furthermore, the identification of complexes in which CnoX, bound to GroEL, forms mixed-disulfides with GroEL substrates indicates that CnoX likely functions as a redox quality-control plugin for GroEL. Proteins sharing structural features with CnoX exist in eukaryotes, which suggests that Hsp60 molecular plugins have been conserved through evolution.
Mixtures of large-scale dynamic functional brain network modes
Authors: Gohil Chetan , Roberts Evan , Timms Ryan , Skates Alex , Higgins Cameron , Quinn Andrew , Pervaiz Usama , van Amersfoort Joost , Notin Pascal , Gal Yarin , Adaszewski Stanislaw , Woolrich Mark 
Published: May 2022

AbstractAccurate temporal modelling of functional brain networks is essential in the quest for understanding how such networks facilitate cognition. Researchers are beginning to adopt time-varying analyses for electrophysiological data that capture highly dynamic processes on the order of milliseconds. Typically, these approaches, such as clustering of functional connectivity profiles and Hidden Markov Modelling (HMM), assume mutual exclusivity of networks over time. Whilst a powerful constraint, this assumption may be compromising the ability of these approaches to describe the data effectively. Here, we propose a new generative model for functional connectivity as a time-varying linear mixture of spatially distributed statistical “modes”. The temporal evolution of this mixture is governed by a recurrent neural network, which enables the model to generate data with a rich temporal structure. We use a Bayesian framework known as amortised variational inference to learn model parameters from observed data. We call the approach DyNeMo (for Dynamic Network Modes), and show using simulations it outperforms the HMM when the assumption of mutual exclusivity is violated. In resting-state MEG, DyNeMo reveals a mixture of modes that activate on fast time scales of 100-150 ms, which is similar to state lifetimes found using an HMM. In task MEG data, DyNeMo finds modes with plausible, task-dependent evoked responses without any knowledge of the task timings. Overall, DyNeMo provides decompositions that are an approximate remapping of the HMM’s while showing improvements in overall explanatory power. However, the magnitude of the improvements suggests that the HMM’s assumption of mutual exclusivity can be reasonable in practice. Nonetheless, DyNeMo provides a flexible framework for implementing and assessing future modelling developments.
Using Shape Fluctuations to Probe the Mechanics of Stress Granules
Authors: Law Jack O. , Jones Carl M. , Stevenson Thomas , Turner Matthew S. , Kusumaatmaja Halim , Grellscheid Sushma N. 
Published: May 2022

AbstractSurface tension plays a significant role in many functions of biomolecular condensates, from governing the dynamics of droplet coalescence to determining how condensates interact with and deform lipid membranes and biological filaments. To date, however, there is a lack of accurate methods to measure the surface tension of condensates in living cells. Here, we present a high-throughput flicker spectroscopy technique that is able to analyse the thermal fluctuations of the surfaces of tens of thousands of condensates to extract the distribution of surface tensions. Demonstrating this approach on stress granules, we show for the first time that the measured fluctuation spectra cannot be explained by surface tension alone. It is necessary to include an additional energy contribution, which we attribute to an elastic bending rigidity and suggests the presence of structure at the granule-cytoplasm interface. Our data also show that stress granules do not have a spherical base-shape, but fluctuate around a more irregular geometry. Taken together, these results demonstrate quantitatively that the mechanics of stress granules clearly deviate from those expected for simple liquid droplets.
Transient dynamics in plant-pollinator networks: Fewer but higher quality of pollinator visits determines plant invasion success
Authors: Valdovinos Fernanda , Dritz Sabine , Marsland Robert 
Published: May 2022

AbstractInvasive plants often use mutualisms to establish in their new habitats and tend to be visited by resident pollinators similarly or more frequently than native plants. The quality and resulting reproductive success of those visits, however, have rarely been studied in a network context. Here, we use a dynamic model to evaluate the invasion success and impacts on natives of various types of non-native plant species introduced into thousands of plant-pollinator networks of varying structure. We found that network structure properties did not predict invasion success, but non-native traits and interactions did. Specifically, non-native plants producing high amounts of floral rewards but visited by few pollinators at the moment of their introduction were the only plant species able to invade the networks. This result is determined by the transient dynamics occurring right after the plant introduction. Successful invasions increased the abundance of pollinators that visited the invader, but the reallocation of the pollinators’ foraging effort from native plants to the invader reduced the quantity and quality of visits received by native plants and made the networks slightly more modular and nested. The positive and negative effects of the invader on pollinator and plant abundance, respectively, were buffered by plant richness. Our results call for evaluating the impact of invasive plants not only on visitation rates and network structure, but also on processes beyond pollination including seed production and recruitment of native plants.
Endogenous sterol synthesis is dispensable for Trypanosoma cruzi epimastigote growth but not stress tolerance
Authors: Dumoulin Peter C. , Vollrath Joshua , Won Madalyn , Wang Jennifer X. , Burleigh Barbara A. 
Published: May 2022

AbstractIn addition to scavenging exogenous cholesterol, the parasitic kinetoplastid Trypanosoma cruzi can endogenously synthesize sterols. Similar to fungal species, T. cruzi synthesizes ergostane type sterols and is sensitive to a class of azole inhibitors of ergosterol biosynthesis that target the enzyme lanosterol 14α-demethylase (CYP51). In the related kinetoplastid parasite Leishmania donovani, CYP51 is essential, yet in Leishmania major, the cognate enzyme is dispensable for growth; but not heat resistance. The essentiality of CYP51 and the specific role of ergostane-type sterol products in T. cruzi has not been established. To better understand the importance of this pathway, we have disrupted the CYP51 gene in T. cruzi epimastigotes (ΔCYP51). Disruption of CYP51 leads to accumulation of 14-methylated sterols and a concurrent absence of the final sterol product ergosterol. While ΔCYP51 epimastigotes have slowed proliferation compared to wild type parasites, the enzyme is not required for growth; however, ΔCYP51 epimastigotes exhibit sensitivity to elevated temperature, an elevated mitochondrial membrane potential and fail to establish growth as intracellular amastigotes in vitro. Further genetic disruption of squalene epoxidase (ΔSQLE) results in the absence of all endogenous sterols and sterol auxotrophy, yet failed to rescue tolerance to stress in ΔCYP51 parasites, suggesting the loss of ergosterol and not accumulation of 14-methylated sterols modulates stress tolerance.