bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Ameliorative Effect of Chronic Oral Nicotine on Olfactory Dysfunction in Young Adult Presenilin-1/2 Double Knockout Mice of a Dementia Model
Authors: Si Youwen , Qiu Shuai , Jia Jingyan , Duan Jiale , Feng Wenbo , Meng Bo , Qi Feiyan 
Published: November 2024

AbstractOlfactory dysfunction is a prevalent and early feature of neurodegenerative diseases including Alzheimer’s disease while the features and underlying mechanisms remain inadequately understood. This investigation aimed to elucidate the olfactory function characteristics of presenilin-1/2 double knockout (DKO) mice, an established mouse model of dementia. Through a series of behavioral tests on DKO and wildtype (WT) mice at 2 and 6 months of age, we assessed their abilities in odor detection, discrimination, and olfactory memory. The findings revealed a substantial deficit in odor detection in 2-month-old DKO mice compared to WT mice, with a noteworthy age-related deterioration observed from 2 to 6 months. Although DKO mice exhibited normal odor discrimination and olfactory memory capabilities at 2 months, these functions declined with age, falling significantly lower levels than observed in WT mice by the age of 6 months. Subsequently, 2-month-old DKO and WT mice underwent a 4-month chronic nicotine treatment through drinking water. This intervention failed to ameliorate olfactory dysfunctions in DKO mice and exhibited no significant impact on WT mice, despite a discernible trend of a potential negative effect. In summary, this behavioral study elucidates that Presenilin-1/2 double knockout impairs odor detection in young adult mice and accelerates declines of olfactory discrimination and memory. The chronic administration of nicotine did not effectively mitigate olfactory function deficiencies in young adult DKO mice, and the results also highlight age as an important contributing factor.
The glycosomal ATP-dependent phosphofructokinase ofTrypanosoma bruceioperates in the gluconeogenic directionin cellulounderin vivo-like conditions
Authors: Plazolles Nicolas , Kulyk Hanna , Cahoreau Edern , Biran Marc , Wargnies Marion , Pineda Erika , Kadri Mohammad El , Rimoldi Aline , Hervé Perrine , Asencio Corinne , Rivière Loïc , Michels Paul , Inaoka Daniel , Tétaud Emmanuel , Portais Jean-Charles , Bringaud Frédéric 
Published: November 2024

AbstractIn the glucose-free environment of the midgut of the tsetse fly vector, the procyclic forms ofTrypanosoma bruceiprimarily consume proline to feed its central carbon and energy metabolism. In this context, the parasite produces through gluconeogenesis glucose 6- phosphate (G6P), the precursor of essential metabolic pathways, from proline catabolism. We showed here that the parasite uses three different enzymes to perform the key gluconeogenic reaction producing fructose 6-phosphate (F6P) from fructose 1,6-bisphosphate, (i) fructose-1,6- bisphosphatase (FBPase), the canonical enzyme performing this reaction, (ii) sedoheptulose- 1,7-bisphosphatase (SBPase) and (iii) more surprisingly ATP-dependent phosphofructokinase (PFK), an enzyme considered to irreversibly catalyse the opposite reaction involved in glycolysis. These three enzymes, as well as six other glycolytic/gluconeogenic enzymes, are located in peroxisome-related organelles, named glycosomes. Incorporation of13C-enriched glycerol (a more effective alternative to proline for monitoring gluconeogenic activity) into F6P and G6P was more affected in the PFK null mutant than in the FBPase null mutant, suggesting the PFK contributes at least as much as FBPase to gluconeogenesis. We also showed that glucose deprivation did not affect the quantities of PFK substrates and products, whereas a 500-fold increase in the substrate/product ratio was expected for PFK to carry out the gluconeogenic reaction. In conclusion, we showed for the first time that ATP-dependent PFK can functionin vivoin the gluconeogenic direction, even in the presence of FBPase activity. This particular feature, which precludes loss of ATP through a futile cycle involving PFK and FBPase working simultaneously in the glycolytic and gluconeogenic directions, respectively, is probably due to the supramolecular organisation of the metabolic pathway within glycosomes to overcome thermodynamic barriers through metabolic channelling.
CPSM: R-package of an Automated Machine Learning Pipeline for Predicting the Survival Probability of Single Cancer Patient
Authors: Kaur Harpreet , Das Pijush , Camphausen Kevin , Shankavaram Uma 
Published: November 2024

AbstractAccurate survival prediction is vital for optimizing treatment strategies in clinical practice. The advent of high-throughput multi-omics data and computational methods has enabled machine learning (ML) models for survival analysis. However, handling high-dimensional omics data remains challenging.This study introduces the Cancer Patient Survival Model (CPSM), an R package developed to provide individualized survival predictions through a fully integrated and reproducible computational pipeline. The CPSM package encompasses nine modules that streamline the survival modeling workflow, organized into four key stages: (1) Data Preprocessing and Normalization, (2) Feature Selection, (3) Survival Prediction Model Development, and (4) Visualization. The visual tools facilitate the interpretation of survival predictions, enhancing clinical decision-making. By providing an end-to-end solution for multi-omics data integration and analysis, CPSM not only enhances the precision of survival predictions but also aids in discovering clinically relevant biomarkers.Availability and ImplementationThe CPSM Package is freely available at the GitHub URL:https://github.com/hks5august/CPSM
Nuclear DNA replication inLeishmania majorrelies on a single constitutive origin per chromosome supplemented by thousands of stochastic initiation events
Authors: Damasceno Jeziel D. , Silva Gabriel L. A. , Marques Catarina A. , Krasilnikova Marija , Lapsley Craig , Beraldi Dario , McCulloch Richard 
Published: November 2024

AbstractUnderstanding genome duplication requires characterisation of the locations where DNA replication initiates, termed origins. Genome-wide mapping of DNA replication origins has mainly been derived from population-based techniques, with only a few studies examining origin location and usage at the single-cell or single-molecule level.Leishmaniaare protozoan parasites where the first attempt to map DNA replication suggested the unprecedented use, for a eukaryote, of just a single origin per chromosome, while a subsequent approach suggested around 200-fold more origins. To reconcile these data and understand DNA replication dynamics inLeishmania major, we have applied DNAscent, a deep learning assay that uses long-read Nanopore sequencing to detect patterns of BrdU incorporation in individual DNA molecules, allowing the description of DNA replication fork movement and prediction of initiation and termination sites across the parasite genome. Our findings confirm the pre-eminence of a single locus of DNA replication initiation in each chromosome and reveal that this locus alone is constitutively activated in S-phase, with bidirectional forks emerging from discrete sites at the ends of multigene transcription units. DNAscent also reveals a much larger number of DNA replication initiation events that have not been detected in any previous mapping and are used stochastically, but whose abundance is greater as chromosome size increases. We show that each of these stochastic initiation sites localise to regions with high AT content, increased G-quadruplex levels and lower chromatin occupancy. In addition, we find markedly increased stochastic DNA replication initiation at sites with lower levels of nascent RNA transcripts. Finally, we show that all DNA replication initiation events result in mutagenesis. This work reveals a novel, bimodal strategy for DNA replication programming inLeishmaniathat drives genome transmission, replication timing and variation.
Single-cell transcriptomic analysis of macaque LGN neurons reveals novel subpopulations
Authors: Sun Shi Hai , Renshaw Kai , Pezaris John S. 
Published: November 2024

AbstractNeurons in the lateral geniculate nucleus (LGN) provide a pivotal role in the visual system by modulating and relaying signals from the retina to the visual cortex. Although the primate LGN, with its distinct divisions (magnocellular, M; parvocellular, P; and koniocellular, K), has been extensively characterized, the intrinsic heterogeneity of LGN neurons has remained unexplained. With the development of high-throughput single-cell transcriptomics, researchers can rapidly isolate and profile large sets of neuronal nuclei, revealing a surprising diversity of genetic expression within the nervous systems. Here, we analyzed the transcriptomes of individual cells belonging to macaque LGN using raw data from a public database to explore the heterogeneity of LGN neurons. Using statistical analyses, we found additional subpopulations within the LGN transcriptomic population, whose gene expressions imply functional differences. Our results suggest the existence of a more nuanced complexity in LGN processing beyond the classic view of the three cell types and highlight a need to combine transcriptomic and functional assessments. A complete account of the cell type diversity of the primate LGN is critical to understanding how vision works.
Calcium-based input timing learning
Authors: Shafiee Shirin , Schmitt Sebastian , Tetzlaff Christian 
Published: November 2024

ABSTRACTStimulus-triggered synaptic long-term plasticity is the foundation of learning and other cognitive abilities of the brain. In general, long-term synaptic plasticity is subdivided into two different forms: homosynaptic plasticity describes synaptic changes at stimulated synapses, while heterosynaptic plasticity summarizes synaptic changes at non-stimulated synapses. For homosy-naptic plasticity, the Ca2+-hypothesis pinpoints the calcium concentration within a stimulated dendritic spine as key mediator or controller of underlying biochemical and -physical processes. On the other hand, for heterosynaptic plasticity, although the-oretical studies attribute important functional roles to it, such as synaptic competition and cooperation, experimental results remain ambiguous regarding its manifestation and biological basis. By integrating insights from Ca2+-dependent homosynaptic plasticity with experimental data of dendritic Ca2+-dynamics, we developed a mathematical model that describes the complex temporal and spatial dynamics of calcium in the dendritic shaft and respective dendritic spines. We show that the increased influx of calcium into a stimulated spine can lead to its diffusion through the shaft to neighboring spines, triggering heterosy-naptic effects such as synaptic competition or cooperation. By considering different input strengths, our model explains the ambiguity of reported experimental results of heterosynaptic plasticity, suggesting that the Ca2+-hypothesis of homosynaptic plasticity can be extended to also model heterosynaptic plasticity. Furthermore, our model predicts that, via diffusion of calcium, a synapse can modulate the expression of homosynaptic plasticity at a neighboring synapse in an input-timing-dependent manner, without the need of postsynaptic spiking. The resulting sensitivity of synaptic plasticity on input-spike-timing can be influenced by the distance between involved spines as well as the local diffusion properties of the connecting dendritic shaft, providing a new way of dendritic computation.
Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation
Authors: Kawanabe-Kobayashi Riku , Uchiyama Sawako , Yoshihara Kohei , Kojima Daiki , McHugh Thomas , Hatada Izuho , Matsui Ko , Tanaka Kenji F. , Tsuda Makoto 
Published: November 2024

AbstractIt is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC→SDH-NA neurons), that is activated by acute exposure to restraint stress and is required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, the primary target of spinal NA released from descending LC→SDH-NAergic terminals causing the stress-induced pain hypersensitivity was α1A-adrenaline receptors (α1ARs) in Hes5-positive (Hes5+) astrocytes located in the SDH, an astrocyte subset that has an ability to induce pain sensitization. Furthermore, activation of Hes5+astrocytes reduced activity of SDH-inhibitory neurons (SDH-INs) that have an inhibitory role in pain processing. This astrocytic reduction of IN activity was canceled by an A1-adenosine receptor (A1R)-knockdown in SDH-INs, and the A1R-knockdown suppressed pain hypersensitivity caused by acute restraint stress. Therefore, our findings suggest that LC→SDH-NA neuronal signaling to Hes5+SDH astrocytes and subsequent astrocytic reduction of SDH-IN activity are essential for pain facilitation caused by stress.
Humans anticipate the consequences of motor control demands when making perceptual decisions between actions
Authors: Leroy Élise , Koun Éric , Thura David 
Published: November 2024

ABSTRACTAnimals, including humans, are often faced with situations where they must decide between potential actions to perform based on various sources of information, including movement parameters that incur time and energy costs. Consistent with this fact, many behavioral studies indicate that decisions and actions show a high level of integration during goal-directed behavior. In particular, motor costs very often bias the choice process of human and non-human subjects facing successive decisions between actions. However, it appears as well that depending on the design in which the experiment occurs, the effect of motor costs on decisions can vary or even vanish. This suggests a contextual dependence of the influence of motor costs on decision-making. Moreover, it is not currently known whether or not the impact of motor costs on perceptual decisions depend on the difficulty of the decision. We addressed these two important issues by studying the behavior of healthy human subjects engaged in a new perceptual decision-making paradigm in which the constraint level associated with the movement executed to report a choice was volitionally chosen by the participants, and in which the difficulty of the perceptual decision to make continuously evolved depending on their motor performance. The results indicate that the level of constraint associated with a movement executed to express a perceptual decision strongly impacts the duration of these decisions, with a shortening of decisions when these are expressed by demanding movements. This influence appears most important when the decisions are difficult, but it is also present for easy decisions. We interpret this strategy as an adaptive way to optimize the participants’ overall rate of success at the session level.
Nrf2 controls homeostatic transcriptional signatures and inflammatory responses in a cell-type specific manner in the adult mouse brain
Authors: He Xin , Dando Owen , Qiu Jing 
Published: November 2024

AbstractNrf2 is an attractive potential therapeutic target for various neurological disorders including neurodegenerative diseases. The mechanisms behind Nrf2-mediated cytoprotection are incompletely understood, however, an anti-inflammatory effect is a popular hypothesis, based primarily on studies where the prior pharmacological activation of Nrf2 has suppressed subsequent responses to inflammatory insults. In the adult brain, Nrf2 is highly expressed in microglia, astrocytes and brain endothelial cells, with minimal expression in neurons. As yet, the brain cell type-specific role of Nrf2 in regulating the basal transcriptome and controlling neuroinflammation is unknown. To address this, we employed three inducible conditional Nrf2 knockout mice in which Nrf2 is deleted in microglia, astrocytes, and brain endothelial cells respectively in a tamoxifen-inducible manner. We discovered that in the healthy brain Nrf2 controls distinct transcriptional signatures in the three brain cell types under study. Surprisingly, following a systemic inflammatory challenge, we found that Nrf2-deficient microglia and astrocytes (but not endothelial cells) both mount a suppressed inflammatory response compared to wild type cells. Moreover, comparison of Nrf2-deficient with wild-type microglia revealed that even in the absence of any insult, microglial Nrf2 supports basal activity of inflammation response genes. Thus, our study uncovers a novel cell type-specific role for endogenous Nrf2 activity in supporting inflammatory responses in the brain.
Categorical and semantic perception of the meaning of call-types in zebra finches
Authors: Elie Julie E. , de Witasse-Thézy Aude , Thomas Logan , Malit Ben , Theunissen Frédéric E. 
Published: November 2024

AbstractVocal communication in social animals involves the production and perception of various calls that ethologists categorize into call-types, based on their acoustical structure and the behavioral context of production. Whether animals perceive these categories and associate distinct meanings to them remains unknown. The zebra finch, a gregarious songbird, uses approximately 11 call-types to communicate hunger, danger, social conflict, and establish social contact and bonding. Using auditory discrimination tasks, we show that the birds discriminate and categorize all the call-types in their vocal repertoire. In addition, systematic errors were more frequent between call-types used in similar behavioral contexts than could be expected from their acoustic similarity. Thus, zebra finches organize their calls into categories and create a mental representation of the meaning of these sounds.
Filling-in of the Blindspot is Multisensory
Authors: Chan Ailene Y. C. , Stiles Noelle R. B. , Levitan Carmel A. , Tanguay Armand R. , Shimojo Shinsuke 
Published: November 2024

AbstractThe blind spot is an area on the retina that lacks photoreceptors, thus no visual information is encoded. Yet, we can maintain the sense of a seamless visual field owing to perceptual filling-in. Traditionally viewed as a surface interpolation mechanism, filling-in has been studied predominantly under unimodal conditions. However, there are limits to this process; the brain cannot always reconstruct all surfaces. Multi-sensory processing may bolster the process of perceptual filling-in to occur even with complex and dynamic perceptual stimuli. In this study, we employed the Audiovisual (AV) Rabbit Illusion to investigate how auditory stimuli influence visual filling-in at the blind spot. Our findings confirmed that auditory cues can induce the perception of an illusory flash within the blind spot, indicating that the brain leverages multimodal information to enrich visual scenes. This suggests that perceptual filling-in is not merely unimodal surface interpolation but a cross-modally integrated spatial representation and therefore more similar to other visual field locations than previously hypothesized. Furthermore, for blind spot filling-in to occur, visual stimuli do not need to be spatially contiguous, they simply need to be crossmodally associated (or grouped), which supports a higher-level sensory processing in filling-in than previously understood.
Insects evolved a monomeric histone-fold domain in the CENP-T protein family
Authors: Sankaranarayanan Sundar Ram , Ulmer Jonathan , Mørch Anna , Ali-Ahmad Ahmad , Sekulić Nikolina , Drinnenberg Ines Anna 
Published: November 2024

AbstractThe histone fold domain (HFD) is a conserved protein interaction module that requires stabilization through a handshake interaction with an HFD partner. All HFD proteins known to date form obligate dimers to shield the extensive hydrophobic residues along the HFD. Here, we find that the lepidopteran kinetochore protein CENP-T is soluble as a monomer. We attribute this stability to a structural rearrangement, which leads to the repositioning of the HFD helix α3. This brings a conserved two-helical extension closer to the histone fold, where it takes over the position and function of the CENP-T partner CENP-W. This change has no effect on the DNA binding ability of the lepidopteran CENP-T. Our analysis suggests that the monomeric HFD originated in the last common ancestor of insects, with a possible second independent origin in acariformes, both of which lack CENP-W. Our study highlights an unexpected structural variation in a protein module as conserved and optimized as the HFD providing a unique perspective on the evolution of protein structure and the forces driving it.
Examining the nexus between carbon dioxide emissions, economic growth, fossil fuel energy use, urbanization and renewable energy towards achieving environmental sustainability in India
Authors: Kumari Diksha , Shashwat Srijan , Verma Prashant Kumar , Giri Arun Kumar 
Published: November 2024

Purpose
Global urbanization has accelerated due to the persistent trend of rural-to-urban migration in search of better prospects and livelihoods, which has had serious negative effects on the environment, especially in rapidly developing economies. Hence, the purpose of the study is to analyse the relationship between urbanization, economic growth, consumption of renewable energy and carbon emissions with careful examination, particularly in the context of India, where urban population growth has skyrocketed.

Design/methodology/approach
This study uses econometric methods like Granger causality analysis and the ARDL bound tests, to analyse the intricate relationships between the selected time series variables for India from 1970 to 2022.

Findings
This research highlights the difficult task of striking a balance between economic development and environmental preservation by emphasizing the crucial role that urbanization and economic expansion play in causing carbon emissions. India’s urbanization trajectory presents a significant policy problem that calls for a move towards renewable energy sources to successfully decrease carbon emissions. Moreover, this research indicates a two-way causal relationship between economic growth, urbanization and carbon emissions, pointing to the intricate interactions between these variables during the developmental stage.

Research limitations/implications
Despite India’s per capita emissions remaining below the global average, this study highlights the mounting policy challenge of balancing economic development with environmental sustainability as urbanization persists. The paper emphasizes the need for India to invest in renewable energy capacity to replace non-renewable sources and mitigate the carbon footprint of its growing energy demands. Collaborative efforts between India and the developed world to facilitate access to clean energy technologies are crucial for India to achieve sustainable growth in the long run.

Originality/value
To the best of the authors’ knowledge, existing literature predominantly focuses on investigating the relationship between renewable energy and economic growth, with only a limited number of studies exploring the impact on sustainable development to attain carbon neutrality. Furthermore, these studies have not considered the role of urbanization and non-renewable energy in addressing the challenge of sustainability issues in an emerging country like India. Hence, this study is a comprehensive study that addresses the research gap in these directions.