bluuebunny/crossref_metadata_2025_split huggingface dataset:
E4F1 COORDINATES PYRUVATE METABOLISM AND THE ACTIVITY OF THE ELONGATOR COMPLEX TO ENSURE TRANSLATION FIDELITY DURING BRAIN DEVELOPMENT
Authors: Michela Di Michele , Aurore Attina , Pierre-François Roux , Imène Tabet , Sophie Laguesse , Javier Florido , Morane Houdeville , Armelle Choquet , Betty Encislai , Giuseppe Arena , Carlo De Blasio , Olivia Wendling , Francois-Xavier Frenois , Laura Papon , Lucille Stuani , Maryse Fuentes , Céline Jahanault-Tagliani , Mélanie Rousseau , Justine Guégan , Yoan Buscail , Pierrick Dupré , Henri-Alexandre Michaud , Geneviève Rodier , Floriant Bellvert , Hanna Kulyk , Carole Ferraro Peyret , Hugo Mathieu , Pierre Close , Francesca Rapino , Cédric Chaveroux , Nelly Pirot , Lucie Rubio , Adeline Torro , Tania Sorg , Fabrice Ango , Christophe Hirtz , Vincent Compan , Elise Lebigot , Andrea Legati , Daniele Ghezzi , Laurent Nguyen , Alexandre David , Claude Sardet , Matthieu Lacroix , Laurent Le Cam 
Published: December 2022

SUMMARYPyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that is relevant to LS pathogenesis. We identified the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U34). E4F1-mediated direct transcriptional regulation ofDlatandElp3, two genes encoding key subunits of the PDC and of the Elongator complex, respectively, ensured proper translation fidelity and cell survival in the central nervous system (CNS) during mouse embryonic development. Furthermore, analysis of PDH-deficient cells highlighted a crosstalk linking the PDC to ELP3 expression that is perturbed in LS patients.
The K+exchange antiporter 3 senses the chloroplast energy status to synchronize photosynthesis
Authors: Uflewski Michal , Rindfleisch Tobias , Korkmaz Kübra , Tietz Enrico , Mielke Sarah , Galvis Viviana Correa , Dünschede Beatrix , Luzarowski Marcin , Skirycz Aleksandra , Schwarzländer Markus , Strand Deserah D. , Hertle Alexander P. , Schünemann Danja , Walther Dirk , Thalhammer Anja , Wolff Martin , Armbruster Ute 
Published: December 2022

AbstractPlant photosynthesis contains two functional modules, the light-driven reactions in the thylakoid membrane and the carbon-fixing reactions in the chloroplast stroma. In nature, light availability for photosynthesis often undergoes massive and rapid fluctuations. Efficient and productive use of such variable light supply requires an instant crosstalk and rapid synchronization of both functional modules. Here, we show that this communication involves the stromal exposed regulatory C-terminus (RCT) of the thylakoid K+-exchange antiporter KEA3. RCT-mediated control of KEA3 contributes to the balance between light capture and photoprotection. By combiningin silico, in vitro, andin vivoapproaches, we demonstrate that the RCT senses the energy state of the chloroplast in form of both, phosphorylation and redox potential, in a pH-dependent manner and regulates KEA3 activity in response. Together our data pinpoint a regulatory feedback loop by which the stromal energy state orchestrates light capture and photoprotection via KEA3.
Microbial diversity ensures the stability of carbon cycling processes under increasing temperature in model soils
Authors: Rohner Nadja , Lepori Selina , Loaiza Viviana , Sebag David , Verrechia Eric , Nelson Daniel B. , Kahmen Ansgar , Niklaus Pascal A. , Laine Anna-Liisa , Domeignoz-Horta Luiz A. 
Published: December 2022

AbstractBiodiversity loss and climate change are two of the most alarming threats to ecosystem functioning and stability. These factors are, however, typically investigated separately, overlooking potential interactions between species extinctions and climate change on ecosystems. Here, we evaluated how different temperature regimes impact the relationship between microbial diversity and ecosystem functioning, in terms of temperature sensitivity of carbon (C) cycling functions. We hypothesized that more diverse soil communities promote the stability of C cycling functions under both temperature regimes. We did not observe a ubiquitous response of all C-cycling processes to temperature increases within the distinct community diversities. While growth was stable with increasing temperatures among the diversity levels, respiration rates increased more strongly at low diversity levels than high diversity levels at higher temperatures. Carbon use efficiency, which integrates both growth and respiration, tended to decrease with temperature at lower levels of diversity. Jointly, these results demonstrate the importance of belowground soil community diversity for maintaining C-cycling thermal response under changing climate.
Unveiling the intertwined roles of the spatial-temporal environment and behavioural modes in animal movement
Authors: Linssen Hans , de Knegt Henrik J. , Eikelboom Jasper A.J. 
Published: December 2022

AbstractAnimal movement arises from complex interactions between animals and their heterogeneous environment, making it challenging to capture the movement process in a single analysis. This has lead to a bias towards lower-dimensional representations of the process in such analyses. In order to better understand animal movement, its multiple components should be included and addressed simultaneously.We present an analytic framework that integrates thebehavioural,spatial, andtemporalcomponents of the movement process and their interactions, and allows for assessing the relative importance of these components. We propose adaily cyclic covariateto represent temporally cyclic movement patterns, for example diel variation in activity, and combine the three components in multi-modal Hidden Markov Models. We compare the statistical fits of models that include or exclude any of the behavioural, spatial and temporal components, and perform variance partitioning on the model that included all components to assess their relative importance to the movement process, both in isolation and in interaction.We apply our framework to a case study on the movements of zebra, wildebeest and eland antelope in a South African reserve. Behavioural modes impacted movement the most, followed by diel rhythms and then the spatial environment (i.e. tree cover and terrain slope). Interactions between the components often explained more of the movement variation than the marginal effect of the spatial environment did on its own. Omitting components from the analysis led either to failure to detect relationships between input and response variables, resulting in overgeneralisations when drawing conclusions about the movement process, or to erroneously detecting spurious relationships, resulting in factually incorrect conclusions.Our analytic framework can be used to study animal movement by integrating the different components of the movement process, thereby preventing incomplete or overly generic ecological interpretations. We demonstrate that understanding the drivers of animal movement, and ultimately the ecological phenomena that emerge from it, critically depends on considering the various components of the movement process, and especially the interactions between them.Data/code for peer review statement: the data and code needed to reproduce the study and results are uploaded as a file with the initial submission.
Age-dependent structural reorganization of utricular ribbon synapses
Authors: Michanski Susann , Henneck Timo , Mukhopadhyay Mohona , Steyer Anna M. , Gonzalez Paola Agüi , Grewe Katharina , Ilgen Peter , Gültas Mehmet , Fornasiero Eugenio F. , Jakobs Stefan , Möbius Wiebke , Vogl Christian , Pangršič Tina , Rizzoli Silvio O. , Wichmann Carolin 
Published: December 2022

AbstractIn mammals, spatial orientation is synaptically-encoded by sensory hair cells of the vestibular labyrinth. Vestibular hair cells (VHCs) harbor synaptic ribbons at their presynaptic active zones (AZs), which play a critical role in molecular scaffolding and facilitate synaptic release and vesicular replenishment. With advancing age, the prevalence of vestibular deficits increases; yet, a direct link to the functional decline of VHC ribbon synapses remains to be demonstrated. To address this issue, we investigated the effects of aging on the ultrastructure of the ribbon-type AZs in murine utricles using various electron microscopic techniques and combined them with confocal and super-resolution light microscopy as well as metabolic imaging up to one year of age. In older animals, we detected predominantly in type I VHCs the formation of floating ribbon clusters. Our findings suggest that VHC ribbon-type AZs undergo dramatic structural alterations upon aging.
Structural characterizations of a unusual peptide CORO1C-47aa encoded by circRNA hsa-circ-0000437 associated with endometrial cancer
Authors: Biswas Sima , Bhagat Gaurav Kumar , Bagchi Angshuman 
Published: December 2022

AbstractCircular RNAs, which have covalently closed ends, is a special type of non-coding RNAs. Recent studies reveal that they are associated with various biochemical pathways. One such involvements of circular RNAs is in the onset of different types of cancers. Though the circular RNAs are known as non-coding RNAs, however, some of them are found to possess the capacities to code for proteins. One such circular RNA is hsa-circ-0000437 which is known to code for a short peptide referred to as CORO1C-47aa. The peptide has anti-angiogenic activity and are associated with the prevention of endometrial cancer. However, till date only the amino acid sequence of the peptide is known and no structural details of the peptide are available. Therefore, in this work, our aim was to predict how the peptide would fold and what could be its possible ligand binding sites. We used computational tools to determine the structure of the peptide. The structure was refined by molecular dynamics simulations. The possible binding sites and the binding partners of the peptide were also predicted. From this structure function analysis study, we tried to elucidate the possible mechanism of the involvements of the peptide in the onset of endometrial cancer. This is the first report on the structural characterization of the peptide. This study may therefore be useful in determining the structures of new drug candidates for the treatment of endometrial cancer.
Intermittent cocaine self-administration has sex-specific effects on addiction-like behaviors in rats
Authors: Bender Brooke N. , Torregrossa Mary M. 
Published: December 2022

AbstractIntermittent access (IntA) models of cocaine self-administration were developed to better model in rodents how cocaine is used by human drug users. Compared to traditional continuous access (ContA) models, IntA has been shown to enhance several pharmacological and behavioral effects of cocaine, but few studies have examined sex differences in IntA. Moreover, no one has examined the efficacy of cue extinction to reduce cocaine seeking in the IntA model, which has previously shown to be ineffective in other models that promote habit-like cocaine seeking. Therefore, rats were implanted with jugular vein catheters and dorsolateral striatum (DLS) cannulae and trained to self-administer cocaine paired with an audiovisual cue with ContA or IntA. In subsets of rats, we evaluated: the ability of Pavlovian cue extinction to reduce cue-induced drug seeking; motivation for cocaine using a progressive ratio procedure; compulsive cocaine taking by pairing cocaine infusions with footshocks; and dependence of drug-seeking on DLS dopamine (a measure of habit-like behavior) with the dopamine antagonistcis-flupenthixol. Overall, cue extinction reduced cue-induced drug seeking after ContA or IntA. Compared to ContA, IntA resulted in increased motivation for cocaine exclusively in females, but IntA facilitated more compulsive cocaine taking exclusively in males. After 10 days of IntA training, but not fewer, drug-seeking was dependent on DLS dopamine most notably in males. Our results suggest that IntA may be valuable for identifying sex differences in the early stages of drug use and provide a foundation for the investigation of the mechanisms involved.Highlights- IntA promotes increased motivation for cocaine in females- IntA augments compulsive cocaine self-administration in males- IntA promotes DLS dopamine-dependent cocaine seeking, most notably in males- Cue extinction overall reduces cue-induced drug seeking after ContA or IntA- Under IntA, females self-administer more cocaine when in estrous
The cortico-thalamic loop attunes competitive lateral interactions across retinotopic and orientation preference maps
Authors: Guarino Domenico G. , Davison Andrew P. , Frégnac Yves , Antolík Ján 
Published: December 2022

AbstractIn the early visual system, corticothalamic feedback projections greatly outnumber thalamocortical feedforward projections. Extensive experimental and modeling work has been devoted to the functional impact of the feedforward pathway, but the role of its denser feedback counterpart remains elusive. Here, we propose a novel unifying framework where thalamic recurrent interactions and corticothalamic feedback act in a closed-loop fashion to attune multiple stimulus representations. At each position of the visual field, the loop puts into competition local representations of the stimulus in thalamus and cortex through direct excitation of narrow topologically-aligned portions of the thalamus, accompanied with peri-geniculate nucleus mediated broad inhibition suppressing the topological surround. We built a detailed conductance-based spiking model incorporating retinal input, lateral geniculate nucleus, peri-geniculate nucleus, primary visual cortex, and all the relevant intra-areal and feedback pathways. For the first time we perform comparative analyses between model configurations with completely or locally inactivated cortico-thalamic feedback, as in the experimental preparations. The model mechanistically explains (i) the existence of intra-thalamic surround suppression, (ii) the sensitivity of thalamic neurons to orientation tuning, (iii) the cortex-dependent center-surround opponency in thalamic cells, (iv) the cortical increase of size and orientation selectivity, (v) the cortically enhanced competition between cross-oriented domains within the hypercolumn, and (vi) the selective suppression of cortical functional connectivity. Our results integrate decades of experimental and theoretical research, supporting the hypothesis that cortico-thalamic loop exerts competitive influence between neighboring regions in the thalamus and cortex, complementing the lateral intra-V1 interactions in center-surround contextual modulation.
Off the shelf: Investigating transfer of learning using commercially available virtual reality equipment
Authors: Markwell Logan Taylor , Cochran Koleton , Porter Jared M. 
Published: December 2022

AbstractThe evolution of virtual reality (VR) has created the opportunity for a relatively low-cost and accessible method to practice motor skills. Previous studies have demonstrated how motor skill practice in non-immersive virtual environments transfers to physical environments. Though minimal research has investigated motor learning and transfer within immersive VR, multiple experiments provide empirical evidence of positive transfer effects. To enhance the similarities between virtual and physical environments, most studies have used software engines and modified hardware. However, many learners and practitioners are currently using commercially available VR with the goal of enhancing real-world performance, though there is very little evidence to support the notion of positive transfer for these systems. Therefore, the purpose of this experiment was to investigate how motor skill practice using a commercially available VR system improved real-world performance and how that compared to physical practice. Participants (n = 68) were randomly selected into one of two groups: virtual reality (VR) practice (n = 33) or real-world (RW) practice (n = 35). The experiment took place over two consecutive days with a pretest, posttest, and practice phase occurring on both days. The pre- and post-testing phases were identical for both groups and consisted of putting a golf ball 10 times on a carpeted surface towards the center of a target. The practice phases consisted of 60 total putts per day in the respective environment (VR or RW). Participants continuously alternated golf putting holes from three different distances until they accrued 60 total putts. Participants in the RW group performed golf putts to three targets. Participants in the VR group also performed golf putts on three different miniature golf putting holes, using the commercially available Oculus Rift and the Cloudlands VR Minigolf game. The VR putting targets were designed to replicate the putting holes in the physical environment. Separate 2 (condition) x 4 (test phase) repeated measures ANOVAs were used to assess accuracy and club head kinematics. The results revealed a significant main effect for test phase, but not for condition. Post hoc analyses revealed both groups significantly improved their putting accuracy and club head kinematics at similar rates. The results from this study indicate that the transfer of learning that occurred from the commercially available VR practice was equally effective when compared to RW practice.
Cold and warmth intensify pain-linked sodium channel gating effects and persistent currents
Authors: Kriegeskorte Sophia , Bott Raya , Hampl Martin , Korngreen Alon , Hausmann Ralf , Lampert Angelika 
Published: December 2022

AbstractVoltage-gated sodium channels (Nav) are key players in excitable tissues with the capability to generate and propagate action potentials. Mutations in the genes encoding Navs can lead to severe inherited diseases, and some of these so-called channelopathies are showing temperature sensitive phenotypes, for example paramyotonia congenita, Brugada-syndrome, febrile seizure syndromes and inherited pain syndromes like erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). Nevertheless, most investigations of mutation-induced gating effects were conducted at room temperature and thus the role of cooling or warming in channelopathies remains poorly understood. Here, we investigated the temperature sensitivity of four Navsubtypes: Nav1.3, Nav1.5, Nav1.6, and Nav1.7 and two mutations in Nav1.7 causing IEM (Nav1.7/L823R) and PEPD (Nav1.7/I1461T), using an automated patch clamp system. Our experiments at 15 °C, 25 °C and 35 °C revealed a shift of the voltage dependence of activation to more hyperpolarized potentials with increasing temperature for all investigated subtypes. Nav1.3 exhibited strongly slowed inactivation kinetics compared to the other subtypes that resulted in enhanced persistent current especially at 15 °C, indicating a possible role in cold induced hyperexcitability. Impaired fast inactivation of Nav1.7/I1461T was significantly enhanced by cooling temperature to 15 °C. The subtype specific modulation as well as the intensified mutation induced gating changes stress the importance to consider temperature as regulator for channel gating and its impact on cellular excitability as well as disease phenotypes.SummaryActivation of the sodium channel subtypes Nav1.3, Nav1.5, Nav1.6, and Nav1.7 and two pain linked mutations is alleviated by warmth. Cooler temperatures, on the other hand, strongly enhance persistent currents of Nav1.3. The impaired fast inactivation of the pain-linked Nav1.7/I1461T mutation is further impaired by cooling, mimicking clinical findings.
Profiling intra- and inter-individual differences in brain development across early adolescence
Authors: Bottenhorn Katherine L. , Cardenas-Iniguez Carlos , Mills Kathryn L. , Laird Angela R. , Herting Megan M. 
Published: December 2022

AbstractAs we move toward population-level developmental neuroscience, understanding intra- and inter-individual variability in brain maturation and sources of neurodevelopmental heterogeneity becomes paramount. Large-scale, longitudinal neuroimaging studies have uncovered group-level neurodevelopmental trajectories, and while recent work has begun to untangle intra- and inter-individual differences, they remain largely unclear. Here, we aim to quantify both intra- and inter-individual variability across facets of neurodevelopment across early adolescence (ages 8.92 to 13.83 years) in the Adolescent Brain Cognitive Development (ABCD) Study and examine inter-individual variability as a function of age, sex, and puberty. Our results provide novel insight into differences in annualized percent change in macrostructure, microstructure, and functional brain development from ages 9-13 years old. These findings reveal moderate age-related intra-individual change, but age-related differences in inter-individual variability only in a few measures of cortical macro- and microstructure development. Greater inter-individual variability in brain development were seen in mid-pubertal individuals, except for a few aspects of white matter development that were more variable between prepubertal individuals in some tracts. Although both sexes contributed to inter-individual differences in macrostructure and functional development in a few regions of the brain, we found limited support for hypotheses regarding greater male-than-female variability. This work highlights pockets of individual variability across facets of early adolescent brain development, while also highlighting regional differences in heterogeneity to facilitate future investigations in quantifying and probing nuances in normative development, and deviations therefrom.
Genes and genome-resolved metagenomics reveal the microbial functional make up of Amazon peatlands under geochemical gradients
Authors: Pavia Michael J. , Finn Damien , Macedo-Tafur Franco , Tello-Espinoza Rodil , Penaccio Christa , Bouskill Nicholas , Cadillo-Quiroz Hinsby 
Published: December 2022

AbstractThe Pastaza-Marañón Foreland Basin (PMFB) holds the most extensive tropical peatland area in South America. PMFB peatlands store 7.07 Gt of organic carbon interacting with multiple microbial heterotrophic, methanogenic, and other oxic/anoxic respirations. Little is understood about the contribution of distinct microbial community members inhabiting tropical peatlands. Here, we studied the metagenomes of three geochemically distinct peatlands spanning minerotrophic, mixed, and ombrotrophic conditions. Using gene- and genome-centric approaches, we evaluate the functional potential of the underlying microbial communities. Abundance analyses shows significant differences in C, N, P, and S acquisition genes. Further, community interactions mediated by Toxin-antitoxin and CRISPR-Cas systems were enriched in oligotrophic soils, suggesting that non-metabolic interactions may exert additional controls in low nutrient environments. Similarly, we reconstructed 519 metagenome-assembled genomes spanning 28 phyla. Our analyses detail key differences across the nutrient gradient in the predicted microbial populations involved in degradation of organic matter, and the cycling of N and S. Notably, we observed differences in the nitrogen oxide (NO) reduction strategies between sites with high and low N2O fluxes and found phyla putatively capable of both NO and sulfate reduction. Our findings detail how gene abundances and microbial populations are influenced by geochemical differences in tropical peatlands.