bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Simultaneous Measurement of Reversed Phase-Encoding EPI in a Single fMRI Session at 7T: Quantitative and Qualitative Evaluation of Geometric Distortion Correction in Submillimetre fMRI
Authors: Yun Seong Dae , Genc Erhan , Shah N. Jon 
Published: September 2024

AbstractMotivationCurrently, geometric distortions in EPI are generally corrected using a method that employs the reversed phase-encoding direction. This approach is usually implemented by applying an extra run of the same protocol, only with the phase-encoding direction changed, leading to a substantial increase in redundant acquisition time and specific absorption ratio. Furthermore, while the distortion correction method has been widely employed in numerous fMRI studies, its impact on submillimetre fMRI analysis has remained largely unexplored.MethodsThis work presents an EPI scheme that acquires both the original and reversed phase-encoding data in a single fMRI session. The feasibility of using the method for submillimetre EPI (0.73 × 0.73 mm2) was verified with visual fMRI at 7T. EPI distortions were corrected using the ANTs software, and its performance was evaluated using various criteria, including spatial resolution, functional mapping accuracy, and histogram distribution.ResultsThe presented scheme effectively reduced redundant acquisition time and therefore total radio-frequency energy. The distortion-corrected fMRI data demonstrated significant improvements in co-registration with anatomical scans and functional mapping accuracy. As a result, the ratio of grey-matter-activated voxels was substantially enhanced (on average, 88.58%). These improvements were achieved without significant degradation of spatial resolution or alternation of the functional activation distribution; a high degree of similarity between the original and distortion-corrected cases (ρ > 0.99) was observed in the t-value histograms.ConclusionsThis work presents a simultaneous acquisition scheme for reversed phase-encoding EPI, demonstrating its effectiveness and the benefits achieved through distortion correction in submillimetre fMRI at 7T.
Immortalization of human valve interstitial cells: anin vitrotool for studying fibro-calcific aortic valve degeneration
Authors: Moschetta Donato , Massaiu Ilaria , Bertolini Francesca , Valerio Vincenza , Rusconi Valentina , De Giorgi Donato , Myasoedova Veronika A. , Poggio Paolo 
Published: September 2024

ABSTRACTHuman primary valve interstitial cells (VIC) are essential for studying the detrimental fibrocalcification processes typical of aortic valve degeneration. However, their limited lifespan poses a significant challenge. To address this, we immortalized VICs to extend their lifespan and facilitate genetic manipulation, enabling the study of dysregulated molecular and cellular pathways in this pathology and the test of potential drugsin vitro. We achieved immortalization by transducing primary VICs with simian virus 40 gene and human telomerase large T gene. Post-immortalization, we conducted RNA sequencing on both primary and immortalized VICs to identify pathways regulation following infection. Additionally, we assessed whether immortalized VICs retained their mesenchymal markers and responded to the pro-osteogenic and pro-calcific stimuli similarly to primary VICs. Given the comparable data obtained from both cell types, we propose using immortalized VICs as a reliable tool forin vitrostudy of fibro-calcific aortic valve degeneration.
Cerebellar control of targeted tongue movements
Authors: Bina Lorenzo , Ciapponi Camilla , Yu Si-yang , Wang Xiang , Bosman Laurens W.J. , De Zeeuw Chris I. 
Published: September 2024

The cerebellum is critical for coordinating movements related to eating, drinking and swallowing. Cerebellar Purkinje cell activity has been shown to encode ongoing tongue movements, but it is unclear how this activity can alter the trajectory of the tongue. To elucidate the impact of Purkinje cells on goal-directed tongue movements, we recorded their activity in the vermis and hemispheres during spontaneous licking from a stationary or moving water spout. Some Purkinje cells encode rhythmic tongue movements with their complex spikes, others with their simple spikes or a combination of both. Complex spikes predominantly marked the start and end of a licking bout, and thus encoded behavioural state changes, while simple spike firing was more related to individual licks. In addition, complex spikes reported unexpected changes in the position of the water spout and subsequent modulation of simple spike firing caused bending of the tongue, reaching out for the new target position. Using machine learning, we demonstrated that it is possible to predict licking activity based on the spiking patterns of individual Purkinje cells. Using optogenetic stimulation of Purkinje cells, we could experimentally replicate the impact of modulated simple spike firing, suggesting that increased simple spike activity indeed causes ipsilateral bending of the tongue during goal-directed movements. Our data highlight that directional control of movements is paramount in cerebellar function and that complex spike and simple spike modulation complement each other during sensorimotor coordination. These results bring us closer to understanding clinical implications of cerebellar disorders during eating, drinking and swallowing.Key pointsWhen drinking, mice make rhythmic tongue movements directed towards the water source.Cerebellar Purkinje cells can fire rhythmically in tune with the tongue movements.Purkinje cells encode changes in the position of the water source with complex spikes.Purkinje cell simple spike firing affects the direction of tongue movements.Purkinje cells that report changes in the position of the target can also adjust movements in the right direction.
Brain-derived neurotrophic factor and adenosine A2A receptor interaction modulates oligodendrogenesis derived from postnatal SVZ neural stem cells
Authors: Mateus J.M. , Barateiro A. , Santos B. , Moreira J.B. , Plachtij N. , Sebastião A.M. , Fernandes A. , Xapelli S. 
Published: September 2024

AbstractOligodendrocytes (OLs) are vital for myelin formation in the Central Nervous System. OLs can be produced by the maturation of oligodendrocyte precursor cells (OPCs) present throughout the brain parenchyma or from the differentiation of subventricular zone-derived neural stem cells (SVZ-NSCs). Importantly, efficient differentiation from SVZ-NSCs remains a significant area of research due to its potential for remyelination in demyelinating disorders. In this work, we studied the role of brain-derived neurotrophic factor (BDNF) and adenosine A2A receptors (A2ARs), as well as the putative crosstalk between these two modulatory mechanisms, in regulating oligodendrogenesis from SVZ-NSCs. Using a neurosphere culture system, we observed that BDNF significantly increased the mRNA expression levels of OPC cell markers after 2 days in vitro (DIV), an effect blocked by the A2AR antagonist ZM 241385. This early transcriptional regulation by BDNF was followed by changes in the percentage of both OPCs and mature OLs in culture at DIV 7 and 14. Interestingly, blocking A2ARs prevented the potentiating effect of BDNF on the percentage of OLs at DIV 14. Concerning the morphology of mature OLs, BDNF influenced their maturation by reducing branching near the soma at DIV 7, an effect that was not observed at 14 DIV, when all treatments resulted in similar OL morphology. Overall, our results establish BDNF as a regulator of OL formation from SVZ-NSCs, with A2AR-BDNF interaction modulating the differentiation process.
Comparative transcriptomic rhythms in the mouse and human prefrontal cortex
Authors: Burns Jennifer N. , Jenkins Aaron K. , Xue Xiangning , Petersen Kaitlyn A. , Ketchesin Kyle D. , Perez Megan S. , Vadnie Chelsea A. , Scott Madeline R. , Seney Marianne L. , Tseng George C. , McClung Colleen A. 
Published: September 2024

AbstractAlterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents. Here, we use RNA sequencing to lay the groundwork for translational studies of molecular rhythms through a sex-specific, cross species comparison of transcriptomic rhythms between the mouse medial PFC (mPFC) and two subregions of the human PFC, the anterior cingulate cortex (ACC) and the dorsolateral PFC (DLPFC). We find that while circadian rhythm signaling is conserved across species and subregions, there is a phase shift in the expression of core clock genes between the mouse mPFC and human PFC subregions that differs by sex. Furthermore, we find that the identity of rhythmic transcripts is largely unique between the mouse mPFC and human PFC subregions, with the most overlap (20%, 236 transcripts) between the mouse mPFC and the human ACC in females. Nevertheless, we find that basic biological processes are enriched for rhythmic transcripts across species, with key differences between regions and sexes. Together, this work highlights both the evolutionary conservation of transcriptomic rhythms and the advancement of the human PFC, underscoring the importance of considering cross-species differences when using animal models.
Weak, specific chemical interactions dictate barnase stability in diverse cellular environments
Authors: Tahir Ume , Davis Caitlin M. 
Published: September 2024

AbstractIt is well-established that in vitro measurements do not reflect protein behaviors in-cell, where macromolecular crowding and chemical interactions modulate protein stability and kinetics. Recent work suggests that peptides and small proteins experience the cellular environment differently from larger proteins, as their small sizes leave them primarily susceptible to chemical interactions. Here, we investigate this principle in diverse cellular environments, different intracellular compartments and host organisms. Our small protein folding model is barnase, a bacterial ribonuclease that has been extensively characterized in vitro. Using fast relaxation imaging, we find that FRET-labeled barnase is stabilized in the cytoplasm and destabilized in the nucleus of U2-OS cells. These trends could not be reproduced in vitro by Ficoll and M-PERTM, which mimic macromolecular crowding and non-specific chemical interactions, respectively. Instead, in-cell trends were best replicated by cytoplasmic and nuclear lysates, indicating that weak specific interactions with proteins in either compartment are responsible for the in-cell observations. Interestingly, in the cytoplasm barnase’s unfolded state is unstable and prone to aggregation, while in the nucleus a stable unfolded state exists prior to aggregation. In the more biologically relevant environment of bacterial cells, barnase folding resembled that in the nucleus, but with no aggregation at higher temperatures. These findings show that protein interactions are evolved for their native environment, which highlights the importance of studying and designing proteins in situ.
TRiC/CCT Chaperonin Governs RNA Polymerase II Activity in the Nucleus to Support RNA Homeostasis
Authors: Gvozdenov Zlata , Peng Audrey Yi Tyan , Biswas Anusmita , Barcutean Zeno , Gestaut Daniel , Frydman Judith , Struhl Kevin , Freeman Brian C. 
Published: September 2024

ABSTRACTThe chaperonin TRiC/CCT is a large hetero-oligomeric ringed-structure that is essential in eukaryotes. While present in the nucleus, TRiC/CCT is typically considered to function in the cytosol where it mediates nascent polypeptide folding and the assembly/disassembly of protein complexes. Here, we investigated the nuclear role of TRiC/CCT. Inactivation of TRiC/CCT resulted in a significant increase in the production of nascent RNA leading to the accumulation of noncoding transcripts. The influence on transcription was not due to cytoplasmic TRiC/CCT-activities or other nuclear proteins as the effect was observed when TRiC/CCT was evicted from the nucleus and restricted to the cytoplasm. Rather, our data support a direct role of TRiC/CCT in regulating RNA polymerase II activity, as the chaperonin modulated nascent RNA production both in vivo and in vitro. Overall, our studies reveal a new avenue by which TRiC/CCT contributes to cell homeostasis by regulating the activity of nuclear RNA polymerase II.
Collaborative role of two distinct cilium-specific cytoskeletal systems in driving Hedgehog-responsive transcription factor trafficking
Authors: Ku Pei-I , Sreeja Jamuna S , Chadha Abhishek , Williams David S , Engelke Martin F , Subramanian Radhika 
Published: September 2024

ABSTRACTCalibrated transcriptional outputs in cellular signaling require fine regulation of transcription factor activity. In vertebrate Hedgehog (Hh) signaling, the precise output of the final effectors, the GLI (Glioma-associated-oncogene) transcription factors, depends on the primary cilium. In particular, the formation of the activator form of GLI upon pathway initiation requires its concentration at the distal cilium tip. However, the mechanisms underlying this critical step in Hh signaling are unclear. We developed a real-time imaging assay to visualize GLI2, the primary GLI activator isoform, at single particle resolution within the cilium. We observed that GLI2 is a cargo of Intraflagellar Transport (IFT) machinery and is transported with anterograde bias during a restricted time window following pathway activation. Our findings position IFT as a crucial mediator of transcription factor transport within the cilium for vertebrate Hh signaling, in addition to IFT’s well-established role in ciliogenesis. Surprisingly, a conserved Hh pathway regulator, the atypical non-motile kinesin KIF7, is critical for the temporal control of GLI2 transport by IFT and the spatial control of GLI2 localization at the cilium tip. This discovery underscores the collaborative role of a motile and a non-motile cilium-specific cytoskeletal system in determining the transcriptional output during Hh signaling.
Phospholipase D3 regulates TFEB/TFE3 metabolism to maintain lysosomal homeostasis
Authors: Wang Yongchao , Rieschick Paige , Romero-Fernandez Wilber , Appelbaum Nathan , Carvajal-Tapia Cristian , Shostak Alena , Schrag Matthew 
Published: September 2024

AbstractA coding variant in Phospholipase D3 (PLD3) increases the risk of Alzheimer’s disease (AD). PLD3 is a lysosomal protein, and endosomal and lysosomal abnormalities are linked to AD; however, the role of PLD3 in lysosomal homeostasis and its implications in AD remain poorly understood. To address this knowledge gap, we conducted comprehensive studies integrating transcriptomics, proteomics, and cell biology approaches. We observed significant enlargement of lysosomes in neurons lacking PLD3, accompanied by increased endocytosis and autophagy, but a decline in lysosomal proteolytic activity. Lysosomes of PLD3-deficient cells underwent proteome remodeling, manifested by an enrichment of proteins involved in lysosomal biogenesis, endocytosis and calcium signaling. Mechanistically, we discovered that PLD3 mediates TFEB/TFE3 degradation through the proteasome, and as a result, PLD3 deficiency leads to increased TFEB/TFE3 levels, nuclear translocation, and transcriptional activities. Notably, variants in PLD3, e.g., V232M or K486R, do not alter its impact on TFEB/TFE3 metabolism. Transcriptomic profiling further confirmed the enrichment of transcripts involved in lysosomal biogenesis, endocytosis, autophagy, mTOR signaling and AD in response to PLD3 loss. Additionally, PLD3 ablation has synergistic effects with β-amyloid in causing lysosomal abnormalities and modifying TFEB/TFE3 signaling. In conclusion, our findings demonstrate that PLD3 is involved in regulating lysosomal biogenesis via TFEB/TFE3 signaling, and lysosomal abnormalities resulting from PLD3 deficiency are potentially a risk factor for AD.
Conserved role for spliceosomal component PRPF40A in microexon splicing
Authors: Choudhary Bikash , Norris Adam 
Published: September 2024

ABSTRACTMicroexons (exons ≤30 nts) are important features of neuronal transcriptomes, but pose mechanistic challenges to the splicing machinery. We previously showed that PRP-40, a component of the U1 spliceosome, is globally required for microexon splicing inC. elegans. Here we show that the homologous PRPF40A is also globally required for microexon splicing in mouse neuroblastoma cells. We find that PRPF40A co-regulates microexons along with SRRM4, a neuron-specific regulator of microexon splicing. The relationship between exon size and dependence on PRPF40A/SRRM4 is distinct, with SRRM4-dependence exhibiting a size threshold (∼30 nts) and PRPF40A-dependence exhibiting a graded decrease as exon size increases. Finally, we show that PRPF40A knockdown causes an increase in productive splicing of its spliceosomal binding partnerLuc7lby skipping of a small “poison exon.” Similar homeostatic cross-regulation is often observed across paralogous RNA binding proteins. Here we find this concept likewise applies across evolutionarily unrelated but functionally and physically coupled spliceosomal components.
HuBMAPR: an R Client for the HuBMAP Data Portal
Authors: Hou Christine , Ghazanfar Shila , Marini Federico , Morgan Martin , Hicks Stephanie C. 
Published: September 2024

AbstractSummaryThe Human BioMolecular Atlas Program (HuBMAP) constructs the worldwide available platform to research the human body at the cellular level. The HuBMAP Data Portal encompasses a wide range of data resources measured on emerging experimental technologies at a spatial resolution. To broaden access to the HuBMAP Data Portal, we introduce an R client calledHuBMAPRavailable on Bioconductor. This gives an efficient and programmatic interface, enabling researchers to discover and retrieve HuBMAP data easier and faster.AvailabilityThis package is available on GitHub (https://github.com/christinehou11/HuBMAPR) and has been submitted to Bioconductor.
Dysregulation of the fluid homeostasis system by aging
Authors: Jang Heeun , Sharma Alexis B. , Dan Usan , Wong Jasmine H. , Knight Zachary A. , Garrison Jennifer L. 
Published: September 2024

SUMMARYChronic dehydration is a leading cause of morbidity for the elderly, but how aging alters the fluid homeostasis system is not well understood. Here, we used a combination of physiologic, behavioral and circuit analyses to characterize how fluid balance is affected by aging in mice. We found that old mice have a primary defect in sensing and producing the anti-diuretic hormone vasopressin, which results in chronic dehydration. Recordings and manipulations of the thirst circuitry revealed that old mice retain the ability to sense systemic cues of dehydration but are impaired in detecting presystemic, likely oropharyngeal, cues generated during eating and drinking, resulting in disorganized drinking behavior on short timescales. Surprisingly, old mice had increased drinking and motivation after 24-hour water deprivation, indicating that aging does not result in a general impairment in the thirst circuit. These findings reveal how a homeostatic system undergoes coordinated changes during aging.
Adaptation of retinal discriminability to natural scenes
Authors: Ding Xuehao , Lee Dongsoo , Melander Joshua B. , Ganguli Surya , Baccus Stephen A. 
Published: September 2024

AbstractSensory systems discriminate between stimuli to direct behavioral choices, a process governed by two distinct properties - neural sensitivity to specific stimuli, and neural variability that importantly includes correlations between neurons. Two questions that have received extensive investigation and debate are whether visual systems are optimized for natural scenes, and whether correlated neural variability contributes to this optimization. However, the lack of sufficient computational models has made these questions inaccessible in the context of the normal function of the visual system, which is to discriminate between natural stimuli. Here we take a direct approach to analyze discriminability under natural scenes for a population of salamander retinal ganglion cells using a model of the retinal neural code that captures both sensitivity and variability. Using methods of information geometry and generative machine learning, we analyzed the manifolds of natural stimuli and neural responses, finding that discriminability in the ganglion cell population adapts to enhance information transmission about natural scenes, in particular about localized motion. Contrary to previous proposals, correlated noise reduces information transmission and arises simply as a natural consequence of the shared circuitry that generates changing spatiotemporal visual sensitivity. These results address a long-standing debate as to the role of retinal correlations in the encoding of natural stimuli and reveal how the highly nonlinear receptive fields of the retina adapt dynamically to increase information transmission under natural scenes by performing the important ethological function of local motion discrimination.
Seed2LP: seed inference in metabolic networks for reverse ecology applications
Authors: Ghassemi Nedjad Chabname , Bolteau Mathieu , Bourneuf Lucas , Paulevé Loïc , Frioux Clémence 
Published: September 2024

AbstractA challenging problem in microbiology is to determine nutritional requirements of microorganisms and culture them, especially for the microbial dark matter detected solely with culture-independent methods. The latter foster an increasing amount of genomic sequences that can be explored with reverse ecology approaches to raise hypotheses on the corresponding populations. Building upon genome scale metabolic networks (GSMNs) obtained from genome annotations, metabolic models predict contextualised phenotypes using nutrient information. We developed the toolSeed2LP, addressing the inverse problem of predicting source nutrients, orseeds, from a GSMN and a metabolic objective. The originality of Seed2LP is its hybrid model, combining a scalable and discrete Boolean approximation of metabolic activity, with the numerically accurate flux balance analysis (FBA). Seed inference is highly customisable, with multiple search and solving modes, exploring the search space of external and internal metabolites combinations. Application to a benchmark of 107 curated GSMNs highlights the usefulness of a logic modelling method over a graph-based approach to predict seeds, and the relevance of hybrid solving to satisfy FBA constraints. Focusing on the dependency between metabolism and environment, Seed2LP is a computational support contributing to address the multifactorial challenge of culturing possibly uncultured microorganisms. Seed2LP is available onhttps://github.com/bioasp/seed2lp.