bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons
Authors: Li Chun Hei , Kersten Noortje , Özkan Nazmiye , Koppers Max , Post Harm , Altelaar Maarten , Farias Ginny G. 
Published: May 2024

AbstractLysosomes are membrane-bound organelles critical for maintaining cellular homeostasis. Delivery of biosynthetic lysosomal proteins to lysosomes is crucial to orchestrate proper lysosomal function. However, it remains unknown how the delivery of biosynthetic lysosomal proteins to lysosomes is ensured in neurons, which are highly polarized cells. Here, we developed Protein Origin, Trafficking And Targeting to Organelle Mapping (POTATOMap), by combining trafficking synchronization and proximity-labelling based proteomics, to unravel the trafficking routes and interactome of the biosynthetic lysosomal membrane protein LAMP1 at specified time points. This approach, combined with advanced microscopy, enabled us to identify the neuronal domain-specific trafficking machineries of biosynthetic LAMP1. We revealed a role in replenishing axonal lysosomes, in delivery of newly synthesized axonal synaptic proteins, and interactions with RNA granules to facilitate hitchhiking in the axon. POTATOMap offers a robust approach to map out dynamic biosynthetic protein trafficking and interactome from their origin to destination.
An in vivo CRISPR screen in chick embryos reveals a role for MLLT3 in specification of neural cells from the caudal epiblast
Authors: Libby Ashley RG , Rito Tiago , Radley Arthur , Briscoe James 
Published: May 2024

ABSTRACTTissue development relies on the coordinated differentiation of stem cells in dynamically changing environments. The formation of the vertebrate neural tube from stem cells in the caudal lateral epiblast (CLE) is a well characterized example. Despite an understanding of the signalling pathways involved, the gene regulatory mechanisms remain poorly defined. To address this, we developed a multiplexed in vivo CRISPR screening approach in chick embryos targeting genes expressed in the caudal epiblast and neural tube. This revealed a role forMLLT3, a component of the super elongation complex, in the specification of neural fate. Perturbation ofMLLT3disrupted neural tube morphology and reduced neural fate acquisition. Mutant forms of Retinoic Acid Receptor A lacking theMLLT3binding domain similarly reduced neural fate acquisition. Together, these findings validate an in vivo CRISPR screen strategy in chick embryos and identify a previously unreported role forMLLT3in caudal neural tissue specification.
Impaired sleep-dependent memory consolidation predicted by reduced sleep spindles in Rolandic epilepsy
Authors: Kwon Hunki , Chinappen Dhinakaran M. , Kinard Elizabeth A. , Goodman Skyler K. , Huang Jonathan F. , Berja Erin D. , Walsh Katherine G. , Shi Wen , Manoach Dara S. , Kramer Mark A. , Chu Catherine J. 
Published: May 2024

AbstractBackground and ObjectivesSleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in Rolandic epilepsy and related sleep-activated epileptic encephalopathies. We investigate the relationship between sleep spindle deficits and deficient sleep dependent memory consolidation in children with Rolandic epilepsy.MethodsIn this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using a validated automated detector.ResultsTwenty-three children with Rolandic epilepsy (14 with resolved disease), and 19 age- and sex-matched controls were enrolled. Children with active Rolandic epilepsy had decreased memory consolidation compared to control children (p=0.001, mean percentage reduction: 25.7%, 95% CI [10.3, 41.2]%) and compared to children with resolved Rolandic epilepsy (p=0.007, mean percentage reduction: 21.9%, 95% CI [6.2, 37.6]%). Children with active Rolandic epilepsy had decreased sleep spindle rates in the centrotemporal region compared to controls (p=0.008, mean decrease 2.5 spindles/min, 95% CI [0.7, 4.4] spindles/min). Spindle rate positively predicted sleep-dependent memory consolidation (p=0.004, mean MST improvement of 3.9%, 95% CI [1.3, 6.4]%, for each unit increase in spindles per minute).DiscussionChildren with Rolandic epilepsy have a sleep spindle deficit during the active period of disease which predicts deficits in sleep dependent memory consolidation. This finding provides a mechanism and noninvasive biomarker to aid diagnosis and therapeutic discovery for cognitive dysfunction in Rolandic epilepsy and related sleep activated epilepsy syndromes.
High delay discounting relates to core symptoms and to pulvinar atrophy in frontotemporal dementia
Authors: Godefroy Valérie , Durand Anaïs , Levy Richard , Batrancourt Bénédicte , Schmidt Liane , Koban Leonie , Plassmann Hilke 
Published: May 2024

AbstractBehavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by behavioural changes and atrophy in brain regions important for decision-making. Computations such as trading off between larger later (LL) and smaller sooner (SS) rewards — called delay discounting in behavioural economics — might be heavily impaired by bvFTD. In this cross-sectional study, our objectives were to investigate (1) whether bvFTD patients show higher delay discounting than healthy controls, (2) whether this maladaptive discounting correlates with impulsivity-related bvFTD symptoms, and (3) in which brain regions atrophy is related to bvFTD’s steeper discounting. BvFTD patients (N=24) and matched controls (N=18) performed two delay discounting tasks: one with monetary rewards and one with food rewards. We compared discount rates (log(k)) in bvFTD patients and controls and tested their correlations with symptoms. We used participants’ structural MRI data and applied whole-brain mediation analyses to investigate brain structures mediating the effect of bvFTD on delay discounting. For both monetary and food rewards, delay discounting was significantly higher in bvFTD patients than in healthy controls. BvFTD patients’ higher discounting of both money and food was associated with their greater disinhibition and eating behaviour changes. Whole-brain mediation analyses revealed that (1) several brain regions (left thalamic pulvinar, left parahippocampal cortex, right temporal lobe) were predictive of steeper discounting of both money and food and (2) grey matter density in these brain regions, including most prominently the medial pulvinar, mediated the effect of bvFTD on discounting. The impulsive preference for sooner rewards captured by delay discounting might constitute a common mechanism of the behavioural symptoms of inhibition deficit and eating behaviour changes in bvFTD. Future studies could further investigate the potential role of medial pulvinar structural modifications as a transdiagnostic marker and a therapeutic target of impulsivity troubles.
Balancing postural control and motor inhibition during gait initiation
Authors: Fiori Lorenzo , Ramawat Surabhi , Marc Isabel Beatrice , Giuffrida Valentina , Ranavolo Alberto , Draicchio Francesco , Pani Pierpaolo , Ferraina Stefano , Brunamonti Emiliano 
Published: May 2024

SummaryThis study examines the relationship between stopping a planned gait initiation due to sudden environmental changes and maintaining body stability. Using a gait initiation version of the Stop Signal Task (SST), we studied changes in anticipatory postural adjustments (APA) during gait initiation and suppression. We found that trial-level variables, such as the time to start or stop stepping, interacted with biomechanical factors like the center of mass displacement relative to the base of support, affecting performance. A critical biomechanical threshold was identified, beyond which stopping movement was unlikely. These findings highlight the strong link between limb action control and body equilibrium, offering a framework within a motor control paradigm. By integrating biomechanical elements, the model effectively simulates real-life scenarios, identifying key variables for studying neural correlations between action and postural control, and aiding in the development of injury prevention and rehabilitation tools for individuals with movement and posture impairments.
Genomic and Transcriptomic Analysis of Ninein Alternative Splicing Between C57BL/6J and DBA/2J Mice
Authors: Gnatowski ER , Jurmain JL , Dozmorov M , Wolstenholme JT , Miles MF 
Published: May 2024

AbstractEthanol’s anxiolytic actions contribute to increased consumption and the development of Alcohol Use Disorder (AUD). Our laboratory previously identified genetic loci contributing to the anxiolytic-like properties of ethanol in BXD recombinant inbred mice, derived from C57BL/6J (B6) and DBA/2J (D2) progenitor strains. That work identified Ninein (Nin) as a candidate gene underlying ethanol’s acute anxiolytic-like properties in BXD mice.Ninhas a complex exonic content with known alternative splicing events that alter cellular distribution of the NIN protein.Wehypothesize that strain-specific differences inNinalternative splicing contribute to changes inNingene expression and B6/D2 strain differences in ethanol anxiolysis. Using quantitative reverse-transcriptase PCR to targetNinalternative splicing, we identified isoform-specific exon expression differences between B6 and D2 mice in prefrontal cortex, nucleus accumbens and amygdala. We extended this analysis using deep RNA sequencing in B6 and D2 nucleus accumbens samples and thatNinexpression was significantly higher in D2 mice. Furthermore, exon utilization and alternative splicing analyses identified 8 differentially utilized exons and significant exon-skipping events between the strains, including 3 novel splicing events in the 3’ end of theNingene that were specific to the D2 strain. Our studies provide the first in-depth analysis ofNinalternative splicing in brain and identify a potential genetic mechanism alteringNinexpression between B6 and D2 mice, thus contributing to differences in the anxiolytic-like properties of ethanol between these strains. This work contributes to our understanding of genetic differences modulating ethanol actions on anxiety that may contribute to the risk for alcohol use disorder.
Asymmetric stem cell division maintains genetic heterogeneity of tissue cells
Authors: Bener Muhammed Burak , Slepchenko Boris M. , Inaba Mayu 
Published: May 2024

ABSTRACTWithin a given tissue, the stem cell niche provides the microenvironment for stem cells suitable for their self-renewal. Conceptually, the niche space constrains the size of a stem-cell pool, as the cells sharing the niche compete for its space. It has been suggested that either neutral-or non-neutral-competition of stem cells changes the clone dynamics of stem cells. Theoretically, if the rate of asymmetric division is high, the stem cell competition is limited, thus suppressing clonal expansion. However, the effects of asymmetric division on clone dynamics have never been experimentally tested. Here, using theDrosophilagermline stem cell (GSC) system, as a simple model of the in-vivo niche, we examine the effect of division modes (asymmetric or symmetric) on clonal dynamics by combining experimental approaches with mathematical modeling. Our results suggest that the rate of asymmetric division positively correlates with the time a stem cell clone takes to expand. Taken together, our data suggests that asymmetric division is essential for maintaining the genetic variation of stem cells and thus serves as a critical mechanism for safeguarding fertility over the animal age or preventing multiple disorders caused by the clonal expansion of stem cells.
Nucleoporin NUP210L and BAF-paralogue BAF-L together ensure microtubule organization and nuclear integrity in spermatids
Authors: Al Dala Ali Maha , Longepied Guy , Lévy Nicolas , Metzler-Guillemain Catherine , Mitchell Michael J 
Published: May 2024

AbstractDuring spermiogenesis, haploid round spermatids differentiate into spermatozoa. This involves nuclear elongation, chromatin compaction, cytoplasm reduction, and formation of the acrosome and the flagellum. These events are orchestrated by cytoskeletal elements - acroplaxome and manchette - that attach to the nuclear envelope (NE) except at the caudal pole where the nuclear pore complexes (NPCs) shift to form a dense array. Here, we use a genetic dissection approach to reveal function at the caudal NE, through the study of two spermatid-specific proteins, whose human orthologues persist there as spermatids elongate: NUP210L, a transmembrane nucleoporin and BAF-L, paralogue and interactor of chromatin protein BAF. In mice, inactivation of either BAF-L or NUP210L has no impact on fertility. However, we show here that in mice lacking NUP210L, two copies of BAF-L become essential for fertility; inNup210l−/−,Banf2+/−orNup210l−/−,Banf2−/−mice, most spermatids arrest during nuclear elongation (step 10-11) with mislocalized NPCs and disorganized manchette microtubules that frequently invaginate the nucleus from the caudal pole. Our results suggest that the NPC array, and BAF-L/BAF, ensure nuclear integrity at the caudal pole during spermatid remodeling.Summary:Nucleoporin NUP210L and BAF-paralogue BAF-L function redundantly during mouse spermatid nuclear remodeling to concentrate nuclear pores to the flagellar pole, organize the manchette cytoskeleton and prevent nuclear invagination by microtubules.
Psilocybin increases optimistic engagement over time: computational modelling of behavior in rats
Authors: Fisher Elizabeth L. , Smith Ryan , Corcoran Andrew W. , Milton Laura K. , Conn Kyna , Hohwy Jakob , Foldi Claire J. 
Published: May 2024

AbstractPsilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit computational models of underlying decision-making mechanisms to behaviour in rats. The model revealed that rats treated with psilocybin achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.
Impact of deprivation and preferential usage on functional connectivity between early visual cortex and category selective visual regions
Authors: Fleming Leland L. , Defenderfer Matthew , Demirayak Pinar , Stewart Paul , Decarlo Dawn K. , Visscher Kristina M. 
Published: May 2024

AbstractHuman behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how the removal of input changes brain function. However, an important question has yet to be answered: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details. However, when central vision is lost in conditions like macular degeneration, peripheral vision must be relied upon for those everyday tasks, with certain portions receiving “preferential” usage over others. Using resting-state fMRI collected during total darkness, we examined how deprivation and preferential usage influence the intrinsic functional connectivity of sensory cortex by studying individuals with selective vision loss due to late stages of macular degeneration. We found that cortical regions representing spared portions of the peripheral retina, regardless of whether they are preferentially used, exhibit plasticity of intrinsic functional connectivity in macular degeneration. Cortical representations of spared peripheral retinal locations showed stronger connectivity to MT, a region involved in processing motion. These results suggest that long-term loss of central vision can produce widespread effects throughout spared representations in early visual cortex, regardless of whether those representations are preferentially used. These findings support the idea that connections to visual cortex maintain the capacity for change well after critical periods of visual development.HighlightsPortions of early visual cortex representing central vs. peripheral vision exhibit different patterns of connectivity to category-selective visual regions.When central vision is lost, cortical representations of peripheral vision display stronger functional connections to MT than central representations.When central vision is lost, connectivity to regions selective for tasks that involve central vision (FFA and PHA) are not significantly altered.These effects do not depend on which locations of peripheral vision are used more.
The differential effect of optogenetic serotonergic manipulation on sustained motor actions and stationary waiting for future rewards in mice
Authors: Taira Masakazu , Miyazaki Kayoko W. , Miyazaki Katsuhiko , Chen Jianning , Okitsu-Sakurayama Shiho , Chaudhary Anupama , Nishio Mika , Miyake Tsukasa , Yamanaka Akihiro , Tanaka Kenji F. , Doya Kenji 
Published: May 2024

AbstractSerotonin is an essential neuromodulator that affects behavioral and cognitive functions. Previous studies have shown that activation of serotonergic neurons in the dorsal raphe nucleus (DRN) promotes patience to wait for future rewards. However, it is still unclear whether serotonergic neurons also regulate persistence to act for future rewards. Here we used optogenetic activation and inhibition of DRN serotonergic neurons to examine their effects on sustained motor actions for future rewards. We trained mice to perform stationary waiting and repeated lever-pressing tasks with variable reward delays and tested effects of optogenetic activation and inhibition of DRN serotonergic neurons on task performance. Interestingly, in the lever-pressing task, mice tolerated longer delays as they repeatedly pressed a lever than in the stationary waiting task, suggesting that lever-pressing actions may not simply be costly, but may also be subjectively rewarding. Optogenetic activation of DRN serotonergic neurons prolonged waiting in the stationary waiting task, consistent with previous studies, but it did not affect lever pressing time or numbers. While optogenetic inhibition decreased waiting, it did not affect lever pressing time or numbers. In generalized linear model analysis that incorporated the time during each session and the number of sessions, however, optogenetic activation negatively affected the number and the speed of lever pressing. These results revealed that the necessity of motor actions may increase motivation for delayed rewards and that DRN serotonergic neurons more significantly promote stationary waiting rather than persistent motor actions for future rewards.
Electrophysiological correlates of visual memory search
Authors: Williams Lauren H. , Wiegand Iris , Lavelle Mark , Wolfe Jeremy M. , Fukuda Keisuke , Peelen Marius V. , Drew Trafton 
Published: May 2024

AbstractIn everyday life, we frequently engage in ‘hybrid’ search, where we look for multiple items stored in memory (e.g., a mental shopping list) in our visual environment. Across three experiments, we used event-related potentials to better understand the contributions of visual working memory (VWM) and long-term memory (LTM) during the memory search component of hybrid search. Experiments 1 and 2 demonstrated that the FN400 – an index of LTM recognition – and the CDA – an index of VWM – increased with memory set size (target load), suggesting that both VWM and LTM are involved in memory search, even when memory load exceeds capacity limitations of VWM. In Experiment 3, we used these electrophysiological indices to test how categorical similarity of targets and distractors affects memory search. The CDA and FN400 were modulated by memory set size only if items resembled targets. This suggests that dissimilar distractor items can be rejected before eliciting a memory search. Together, our findings demonstrate the interplay of VWM and LTM processes during memory search for multiple targets.
Optokinetic response inD. Melanogasterreveals the nature of common repellent odorants
Authors: Menti Giulio Maria , Bruzzone Matteo , Zordan Mauro Agostino , Visentin Patrizia , Drago Andrea , Dal Maschio Marco , Megighian Aram 
Published: May 2024

AbstractAnimals’ ability to orient and navigate relies on selecting an appropriate motor response based on the perception and integration of the environmental information. This is the case, for instance, of the optokinetic response (OKR) inDrosophila melanogaster, where optic flow visual stimulation modulates the walking or flying patterns. Despite a large body of literature on the OKR, there’s still a limited understanding of the impact on OKR of concomitant, potentially conflicting, inputs. To evaluate the impact of this multimodal integration, we combined inD. melanogaster, while flying in a tethered condition, the optic flow stimulation leading to OKR with the simultaneous presentation of olfactory cues, based on repellent or masking compounds typically used against noxious insect species.First, this approach al lowed us to directly quantify the effect of several substances and their concentration, on the dynamics of the flies’ OKR in response to moving gratings by evaluating the number of saccades and the velocity of its slow phase. Subsequently, this analysis was capable of easily revealing the actual effect, i.e. masking vs repellent, of the compound tested. In conclusion, we show thatD. melanogaster, a cost-affordable species, represents a viable option for studying the effects of several compounds on the navigational abilities of insects.
Saccades Influence Functional Modularity in the Human Cortical Vision Network
Authors: Tomou G. , Baltaretu B. , Ghaderi A. , Crawford J. D. 
Published: May 2024

ABSTRACTVisual cortex is thought to show both dorsoventral and hemispheric modularity, but it is not known if the same functional modules emerge spontaneously from an unsupervised network analysis, or how they interact when saccades necessitate increased sharing of spatial information. Here, we address these issues by applying graph theory analysis to fMRI data obtained while human participants decided whether an object’s shape or orientation changed, with or without an intervening saccade across the object. BOLD activation from 50 vision-related cortical nodes was used to identify local and global network properties. Modularity analysis revealed three sub-networks during fixation: a bilateral parietofrontal network linking areas implicated in visuospatial processing and two lateralized occipitotemporal networks linking areas implicated in object feature processing. When horizontal saccades required visual comparisons between visual hemifields, functional interconnectivity and information transfer increased, and the two lateralized ventral modules became functionally integrated into a single bilateral sub-network. This network included ‘between module’ connectivity hubs in lateral intraparietal cortex and dorsomedial occipital areas previously implicated in transsaccadic integration. These results provide support for functional modularity in the visual system and show that the hemispheric sub-networks are modified and functionally integrated during saccades.