bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal ganglia output coding - entopeduncular nucleus - of contextual kinematics and reward in the freely moving mouse
Authors: Verma-Rodríguez Anil K , Ramírez-Jarquín Josué O , Rossi-Pool Román , Tecuapetla Fatuel 
Published: March 2024

AbstractThe entopeduncular nucleus (EPN) is often termed as one of the output nuclei of the basal ganglia owing to their highly convergent anatomy. The rodent EPN has been implicated in reward and value coding whereas the primate analogue internal Globus Pallidus has been found to be modulated by some movements and in some circumstances. In this study we sought to understand how the rodent EPN might be coding kinematic, reward, and difficulty parameters, particularly during locomotion. Furthermore, we aimed to understand the level of movement representation: whole-body or specific body parts. To this end, mice were trained in a freely moving two-alternative forced choice task with two periods of displacement (return and go trajectories) and performed electrophysiological recordings together with video-based tracking. We found 1) robust reward coding but not difficulty. 2) Spatio-temporal variables better explain EPN activity during movement compared to kinematic variables, while both types of variables were more robustly represented in reward-related movement. 3) Reward sensitive units encode kinematics similarly to reward insensitive ones. 4) Population dynamics that best account for differences between these two periods of movement can be explained by allocentric references like distance to reward port. 5) The representation of paw and licks is not mutually exclusive, discarding a somatotopic muscle-level representation of movement in the EPN. Our data suggest that EPN activity represents movements and reward in a complex way: highly multiplexed, influenced by the objective of the displacement, where trajectories that lead to reward better represent spatial and kinematic variables. Interestingly, there are intertwining representations of whole-body movement kinematics with single paw and licking variables. Further, reward sensitive units encode kinematics similarly to reward insensitive ones, challenging the notion of distinct pathways for reward and movement processing.Significance StatementThe entopeduncular nucleus is one of the main outputs of the basal ganglia whose activity has been hypothesized to be inversely correlated with movement. This study examines motor and reward coding simultaneously, finding that besides the great level of multiplexing of these variables, spatio-temporal coding is better represented than kinematic coding. The level of movement representation seems to be greatly influenced by the goal of a movement, with spatially biased variables influencing the population dynamics of this nucleus. Further, we uncover the coexistence of EPN modulation by movement at different timescales and body parts. The simple overall activity of this output nucleus cannot explain kinematic coding, challenging leading theories of basal ganglia function.
Palmitoylation regulates norepinephrine transporter trafficking and expression and is potentially involved in the pathogenesis of postural orthostatic tachycardia syndrome
Authors: Brown Christopher R. , Foster James D. 
Published: March 2024

ABSTRACTPostural orthostatic tachycardia syndrome (POTS) is an adrenergic signaling disorder characterized by excessive plasma norepinephrine, postural tachycardia, and syncope. The norepinephrine transporter (NET) modulates adrenergic homeostasisviareuptake of extracellular catecholamines and is implicated in the pathogenesis of adrenergic and neurological disorders. Previous research has outlined that NET activity and trafficking is modulatedviareversible post-translational modifications like phosphorylation and ubiquitylation. S-palmitoylation, or the addition of a 16-carbon saturated fatty acid, is another post-translational modification responsible for numerous biological mechanisms. In this study, we reveal that NET is dynamically palmitoylated and inhibition of this modification with the palmitoyl acyltransferase (DHHC) inhibitor, 2-bromopalmitate (2BP), results in decreased NET palmitoylation within 90 min of treatment. This result was followed closely with a reduction in transport capacity, cell surface, and total cellular NET expression after 120 min of treatment. Increasing 2BP concentrations and treatment time revealed a nearly complete loss of total NET protein. Co-expression with individual DHHCs revealed a single DHHC enzyme, DHHC1, promoted WT hNET palmitoylation and elevated NET protein levels. The POTS associated NET mutant, A457P, exhibits dramatically decreased transport capacity and cell surface levels which we have confirmed in the current study. In an attempt to recover A457P NET expression we co-expressed the A457P variant with DHHC1 to drive expression as seen with the WT protein but instead saw an increase in NET N-terminal immuno-detectable fragments. Further investigation of A457P NET palmitoylation and surface expression is necessary, but our preliminary novel findings reveal palmitoylation as a mechanism of NET regulation and suggest that dysregulation of this process may contribute to the pathogenesis of POTS.
Unveiling the double-edged sword: SOD1 trimers possess tissue-selective toxicity and bind septin-7 in motor neuron-like cells
Authors: Choi Esther Sue , Hnath Brianna Leigh , Sha Congzhou Mike , Dokholyan Nikolay V 
Published: March 2024

AbstractMisfolded soluble trimeric species of superoxide dismutase 1 (SOD1) are associated with increased death in neuron-like cell models and greater disease severity in amyotrophic lateral sclerosis (ALS) patients compared to insoluble protein aggregates. The mechanism by which structurally independent SOD1 trimers cause cellular toxicity is unknown but may be a driver of disease pathology. Here, we uncovered the SOD1 trimer interactome – a map of potential tissue-selective protein binding partners in the brain, spinal cord, and skeletal muscle. We identified binding partners and key pathways associated with SOD1 trimers, comparing them to those of wild-type SOD1 dimers. We found that trimers may affect normal cellular functions such as dendritic spine morphogenesis and synaptic function in the central nervous system and cellular metabolism in skeletal muscle. We also identified key pathways using transcriptomic data from motor neuron-like cells (NSC-34s) expressing SOD1 trimers. We discovered differential gene expression in cells that express SOD1 trimers with selective enrichment of genes responsible for protein localization to membranes and a global upregulation of cellular senescence pathways. We performed detailed computational and biochemical characterization of protein binding for septin-7, an SOD1 trimer binding partner. We found that septin-7 preferentially binds SOD1 trimers and co-localizes in neuron-like cells. We explore a double-edged sword theory regarding the toxicity of SOD1 trimers. These trimers are implicated in causing dysfunction not only in the central nervous system but also in muscle tissues. Our investigation highlights key protein factors and pathways within each system, revealing a plausible intersection of genetic and pathophysiological mechanisms in ALS through interactions involving SOD1 trimers.SummaryIn amyotrophic lateral sclerosis (ALS), misfolded soluble species of superoxide dismutase 1 (SOD1) are associated with disease severity and, specifically, trimeric forms of SOD1 are toxic in neuron-like cells compared to insoluble aggregates. The role of toxic SOD1 trimers in cells is unknown. Using molecular engineering and pull-down experiments, we found that SOD1 trimers have tissue-selective protein interactions that affect pathways such as dendritic spine morphogenesis and synaptic function in the nerves, energy, and amino acid metabolism in skeletal muscle. We investigated the SOD1 trimer transcriptome to reveal a global upregulation of genes associated with cellular senescence compared to SOD1 dimers. We further validated septin-7, a shared brain and spinal cord protein binding hit, using integrative computational and biochemical approaches, and confirmed that septin-7 binds SOD1 trimers and not native dimers. Taken together, we show evidence that SOD1 trimers play a central role in the convergence of ALS pathophysiology.Graphical abstract
Efficient differentiation of human retinal pigment epithelium cells from chemically induced pluripotent stem cells
Authors: Zhang Ke , Wang Yanqiu , An Qi , Ji Hengjing , Wu Defu , Li Xuri , Dong Xuran , Zhang Chun 
Published: March 2024

AbstractHuman induced pluripotent stem cells (hiPSCs) hold considerable promise for autologous cellular therapies, particularly in ocular disease treatment, because of the low numbers of cells required for transplantation and the non-invasive nature of graft monitoring. However, the use of hiPSCs in ocular disease treatment faces challenges because the production of clinical-grade autologous hiPSCs via genetic techniques remains expensive, time-consuming, and subject to safety concerns. Here, we utilize a recently reported chemical method to derive human chemically induced pluripotent stem cells (hCiPSCs), demonstrating that hiPSC lines can be generated using small molecules in a simple and robust manner. Moreover, we show that these cell lines can be efficiently differentiated into retinal pigment epithelium (RPE) cells, which may aid in the treatment of age-related macular degeneration (AMD). Our study provides a foundation for cost-effective, fast, and safe methods that enable efficient production of autologous retinal cell types for ocular disease treatment.
TAK1-mediated phosphorylation of PLCE1 represses PIP2 hydrolysis to impede esophageal squamous cancer metastasis
Authors: Ju Qianqian , Sheng Wenjing , Zhang Meichen , Chen Jing , Wu Liucheng , Liu Xiaoyu , Fang Wentao , Shi Hui , Sun Cheng 
Published: March 2024

AbstractTAK1 is a serine/threonine protein kinase that is a key regulator in a wide variety of cellular processes. However, the functions and mechanisms involved in cancer metastasis are still not well understood. Here, we found that TAK1 knockdown promoted esophageal squamous cancer cell (ESCC) migration and invasion, whereas TAK1 overexpression resulted in the opposite outcome. Thesein vitrofindings were recapitulatedin vivoin a xenograft metastatic mouse model. Mechanistically, co-immunoprecipitation and mass spectrometry demonstrated that TAK1 interacted with phospholipase C epsilon 1 (PLCE1), and phosphorylated PLCE1 at serine 1060 (S1060). Functional studies revealed that phosphorylation at S1060 in PLCE1 resulted in decreased enzyme activity, leading to the repression of PIP2 hydrolysis. As a result, the degradation products of PIP2 including diacylglycerol (DAG) and inositol IP3 were reduced, which thereby suppressed signal transduction in the axis of PKC/GSK-3β/β-Catenin. Consequently, expression of cancer metastasis-related genes was impeded by TAK1. Overall, our data indicate that TAK1 plays a negative role in ESCC metastasis, which depends on the TAK1 induced phosphorylation of PLCE1 at S1060.
From presence/absence to reliable prey proportions: A field test of dietary DNA for characterizing seabird diets
Authors: Clucas Gemma V , Stillman Andrew , Craig Elizabeth C 
Published: March 2024

AbstractClimate change and human impacts are causing rapid shifts in species’ distributions and abundance, potentially disrupting predator-prey relationships. Monitoring animal diets can elucidate these relationships and potentially provide a mechanistic understanding of population declines, but efficient methods to monitor diets are needed. Dietary DNA can be used to gather data on species’ diets with high-taxonomic resolution, but the question of whether it can provide quantitative information on animal diets has so far limited its applications. Here we show that dietary DNA can efficiently provide quantitative information on the relative proportions of fish in the diets of piscivorous seabirds. Over three breeding seasons, we observed common tern chick feeding events and collected fecal samples from chicks. We compared the frequency of occurrence (FOO) and relative read abundance (RRA) of fish prey in the fecal samples to the relative biomass recorded through visual observations and found a high correlation (R = 0.94) between RRA and relative biomass at the colony level. We also found that RRA outperformed FOO in capturing interannual changes in relative prey biomass, and that FOO systematically over-estimated the relative importance across all prey categories. The high taxonomic resolution provided by dietary DNA and the high correlation between RRA and relative biomass we found here suggest that dietary DNA can be used as a quantitative metric to monitor seabird diets. This has important applications for studying the impact of changing forage fish availability on seabird populations, but also for harnessing seabirds as sentinels of ecosystem health. Since quantitative diet data can be collected highly efficiently using dietary DNA, this method could provide key information about food web dynamics and forage fish availability as we move towards ecosystem-based fisheries management.
Effect of temperature on circadian clock functioning of trees in the context of global warming
Authors: Estravis-Barcala Maximiliano , Gaischuk Sofía , Gonzalez-Polo Marina , Martínez-Meier Alejandro , Gutiérrez Rodrigo A. , Yanovsky Marcelo , Bellora Nicolás , Arana María Verónica 
Published: March 2024

AbstractPlant survival in a warmer world requires the timely adjustment of biological processes to cyclical changes in the new environment. Circadian oscillators have been proposed to contribute to thermal adaptation and plasticity in plants, due to their ability to maintain periodicity in biological rhythms over a wide temperature range, promoting fitness. However, the influence of temperature and circadian clock performance on plant behaviour in natural ecosystems is not well understood. Here we used two co-occurringNothofagustree species from the Patagonian forests that are adapted to contrasting thermal environments derived from their different altitudinal profiles. We revealed that the upper thermal limits for accurate clock function are linked to the species’ thermal niches and contribute to seedling plasticity in natural environments. We computationally identified 24 circadian clock-related genes, which showed a high degree of structural conservation with clock genes from both annual and perennial species, and very similar patterns of gene expression to those ofArabidopsis thaliana. Warm temperatures produced a strong transcriptomic rearrangement, which affected the expression of clock-related genes and direct clock targets, evidencing the extent of clock functioning disruption by temperature.N. pumilio, the species from colder environments, showed reduced ability to keep rhythmicity at high temperatures compared toN. obliqua, which inhabits warmer zones. Accordingly,N. pumilio, but notN. obliqua, showed a limited oscillator function in warmer zones of the forest, reduced survival, and growth. Together, our results highlight the potential role of a resonating oscillator in ecological adaptation to a warming environment.
Functional characterization of Lipid storage droplets 1 (LSD1) in growth and lipolysis ofHermetia illucens
Authors: Jiang Yuguo , Kou Zongqing , Chen Bihui , Xingyu Luo , Huang Yongping 
Published: March 2024

AbstractAs intracellular organelles in adipose tissue, lipids droplets manage the balance between triglyceride accumulation and energy consumption in animals. Perilipin family members, associated with surface of lipid droplets, participate the regulation of lipid metabolism. Lipid storage droplet-1 (LSD1)/Perilipin-1 acts as a gatekeeper for adipose lipid storage in animals. Despite extensive studies in fruit fly, the function ofLSD1in insect larval stage remain indistinct. In this study, we characterized the function ofLSD1in black soldier flyHermetia illucens, a nova resource insect to recycle organic wastes. We found thatLSD1was broadly present in dipteran species and evolved with divergence between mosquitos and flies. We further constructedin vivomutagenesis mediated by CRISPR/Cas9 and found that mutations inLSD1increased the larval weight and did not bring any defects in development. Raw fat content was also not significantly influenced in late larval stage and new-emerged adults. Our results not only extend our knowledge ofLSD1in insects, but also help for better understanding of the lipid homeostasis in BSF.
Exploiting De Novo Serine Synthesis as a Metabolic Vulnerability to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma
Authors: Teisseire Manon , Sahu Umakant , Parola Julien , Tsai Meng-Chen , Vial Valérie , Durivault Jérôme , Grépin Renaud , Cormerais Yann , Pagès Gilles , Ben-Sahra Issam , Giuliano Sandy 
Published: March 2024

SummarySunitinib, an oral tyrosine kinase inhibitor used in advanced renal cell carcinoma (RCC), exhibits significant efficacy but faces resistance in 30% of patients. Yet, the molecular mechanisms underlying this therapy resistance remain elusive. Here, we show that sunitinib induces a metabolic shift leading to increased serine synthesis in RCC cells. The activation of the GCN2-ATF4 stress response pathway is identified as the mechanistic link between sunitinib treatment and elevated serine production. Inhibiting key enzymes in the serine synthesis pathway, such as PHGDH and PSAT1, enhances the sensitivity of resistant cells to sunitinib. The study underscores the role of serine biosynthesis in nucleotide synthesis, influencing cell proliferation, migration, and invasion. Beyond RCC, similar activation of serine synthesis occurs in other cancer types, suggesting a shared adaptive response to sunitinib therapy. This research identifies serine synthesis as a potential target to overcome sunitinib resistance, offering insights into therapeutic strategies applicable across diverse cancer contexts.Graphical abstractHighlightsSunitinib induces an increase in endogenous serine production in metastatic ccRCC.The heightened serine biosynthesis promoted by sunitinib facilitates nucleotide synthesis, thereby sustaining tumor cell proliferation.Sunitinib-induced enhancement of serine biosynthesis enables cell migration and invasion.The stimulation in serine synthesis is also observed in other cancer models treated with sunitinib.
The FAIR-Device - a non-lethal and generalist semi-automatic Malaise trap for insect biodiversity monitoring: Proof of concept
Authors: Chiavassa Juan A. , Kraft Martin , Noack Patrick , Walther Simon , Kirse Ameli , Scherber Christoph 
Published: March 2024

AbstractField monitoring plays a crucial role in understanding insect dynamics within ecosystems. It facilitates pest distribution assessment, control measure evaluation, and prediction of pest outbreaks. Additionally, it provides important information on bioindicators with which the state of biodiversity and ecological integrity in specific habitats and ecosystems can be accurately assessed. However, traditional monitoring systems can present various difficulties, leading to a limited temporal and spatial resolution of the obtained information. Despite recent advancements in automatic insect monitoring traps, also called e-traps, most of these systems focus exclusively on studying agricultural pests, rendering them unsuitable for monitoring diverse insect populations. To address this issue, we introduce the Field Automatic Insect Recognition (FAIR)-Device, a novel non-lethal field tool that relies on semi-automatic image capture and species identification using artificial intelligence via the iNaturalist platform. Our objective was to develop an automatic, cost-effective, and non-specific monitoring solution capable of providing high-resolution data for assessing insect diversity. During a 26-day proof-of-concept evaluation, the FAIR-Device recorded 24.8 GB of video, identifying 431 individuals from 9 orders, 50 families, and 69 genera. While improvements are possible, our device demonstrated potential as a cost-effective, non-lethal tool for monitoring insect biodiversity. Looking ahead, we envision new monitoring systems such as e-traps as valuable tools for real-time insect monitoring, offering unprecedented insights for ecological research and agricultural practices.
Cerebrovascular reactivity mapping using breath-hold BOLD-fMRI: comparison of signal models combined with voxelwise lag optimization
Authors: Domingos Catarina , Esteves Inês , Fouto Ana R. , Ruiz-Tagle Amparo , Caetano Gina , Figueiredo Patrícia 
Published: March 2024

ABSTRACTCerebrovascular reactivity (CVR) can be mapped noninvasively using blood oxygenation level dependent (BOLD) fMRI during a breath-hold (BH) task. Previous studies showed that the BH BOLD response is best modeled as the convolution of the partial pressure of end-tidal CO2 (PetCO2) with a canonical hemodynamic response function (HRF). However, previous model comparisons employed a global bulk time lag, which is now well accepted to provide only a rough approximation of the heterogeneous distribution of response latencies across the brain. Here, we investigate the best modeling approach for mapping CVR based on BH BOLD-fMRI data, when using a lagged general linear model approach combined with voxelwise lag optimization. In a group of fourteen healthy participants, we compared models considering: two types of regressors (PetCO2 and Block), three convolution models (no convolution; convolution with a single gamma HRF; and convolution with a double gamma HRF), and a variable HRF delay (3-11s). We found no significant improvements in model fit with other delays, and hence selected the canonical delay of 6s. Although the two regressor types yielded similar model fits, PetCO2 produced significantly greater CVR values than Block models. Interestingly, a single gamma HRF yielded the greatest CVR values in PetCO2 models, while block models benefited from convolution with a double gamma HRF. In conclusion, when modeling BH BOLD-fMRI signals with voxelwise lag optimization, PetCO2 regressors convolved with a single gamma HRF should be preferentially used. In case good quality PetCO2 recordings are unavailable, a block-based model convolved with the canonical HRF may be a good alternative. In conclusion, our manuscript reports the first systematic signal model comparison, providing evidence to support the use of specific modeling approaches for CVR mapping based on BH BOLD-fMRI.