bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization ofFLOWERING LOCUS Trelated genes and their putative gene regulatory network in semi-winterBrassica napuscultivar Zhongshaung11
Authors: Wang Juanjuan , Zhou Hao-Ran , Wang Jing , Turck Franziska 
Published: November 2024

SummaryFlowering time is a crucial phenological trait with a direct influence on biomass and seed yield of crop plants. In many plant species,FLOWERING LOCUS T(FT)-like genes promote transition to flowering by integrating environmental signals, in particular photoperiod, and internal cues.-Brassica napuscontains eightFT-like genes, of which four are orthologs ofFT, one functional and two pseudogenes belong to an Brassicacae linage II-specific and one gene to a Brassica C-genome-specific orthogroup.- All six extantFT-like genes induce early flowering inftmutant background if expressed at the shoot apex, but only three orthologs are fully functional as mobile florigens.- BnaFT.C6 was not fully functional al mobile florigen. A change of the last amino-acid from threonine to cysteine contributes to the reduced function and is private to a subset of semi-winter accessions- Both distal enhancers ofFTwere found at all four syntenic genes inB. napus; however, homeologsBnaFT.A7andBnaFT.C6showed rearrangements of DNA-motifs binding NF-Y/CO and NF-Y transcription activator complexes between the proximal promoter and the downstream enhancer Block E.- Homeologs with rearranged motifs could not be trans-activated byB. napusCO in transient reporter assays- AllFTorthologs were dependent on long day photoperiod and vernalization. Homeologs with rearranged and canonical motif arrangement showed higher transcript levels in vegetative and paraclade leaves, respectively- Diurnal transcriptome data of leaves fromB. napusplants grown in SD and LD photoperiod indicate that a large group of NF-Y encoding genes show a peak of expression in the critical phase between ZT12 and ZT16, exclusively in LD.In sum,B. napusphotoperiod dependent regulation ofFT-like genes is a case study for the consequence of gene duplications, indicating gene retraction through loss-of-function, homeolog retention partially explained by differences transcriptional regulation and possibly variation between cultivated varieties due to changes in protein function.
Interictal spikes during spatial working memory carry helpful or distracting representations of space and have opposing impacts on performance
Authors: Yi Justin D. , Pasdarnavab Maryam , Kueck Laura , Tarcsay Gergely , Ewell Laura A. 
Published: November 2024

SUMMARYIn temporal lobe epilepsy, interictal spikes (IS) – hypersynchronous bursts of network activity – occur at high rates in between seizures. We sought to understand the influence of IS on working memory by recording hippocampal local field potentials from epileptic mice while they performed a delayed alternation task. We found that IS disrupted performance when they were spatially non-restricted and occurred during running. In contrast, when IS were clustered at reward locations, animals performed well. A machine learning decoding approach revealed that IS at reward sites were larger than IS elsewhere on the maze, and could be classified as occurring at specific reward locations – suggesting they carry informative content for the memory task. Finally, a spiking model revealed that spatially clustered IS preserved hippocampal replay, while spatially dispersed IS disrupted replay by causing over-generalization. Together, these results show that IS can have opposing outcomes on memory.
Curcumin attenuates microglia-mediated chronic neuropathic pain through CDK5 /p35 signaling pathway
Authors: Tong Fei , Zhao li , Yang Yue , Zhang ZhuoYue , Liu Lu , Wu YaXuan , Di XuanYi , Zhang ZiWen , Xu XiaoXia , Zhang YuanLi , Shen Yue , Yu liang , Zhang lei , Yao YongXing , Zhang HongHai 
Published: November 2024

AbstractCurcumin is a phenolic compound derived from turmeric, one of the main ingredients of curry powder, which is widely used for its antioxidant, anti-inflammatory and immunomodulatory effects. Curcumin has been reported to help relieve pain, such as neuropathic pain caused by injury or disease, but the specific mechanism of its antinociceptive effect on pathological pain is unclear. Cyclin-dependent kinase 5 (Cdk5) is a key control point for the release of neurotransmitters from presynaptic vesicles. Cdk5 and its activator p35 couple to regulate key signaling cascades, thereby participating in the pain process. In this study, we established a NP model by chronic constriction injury (CCI) of the bilateral sciatic nerve in rats and evaluated behavioral hyperalgesia using mechanical and hot and cold tests. Protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that Iba-1 and Cdk5/p35 were co-localized in the dorsal horn and dorsal root ganglia, respectively. After CCI, the expression of Cdk5 and p35 was upregulated in the dorsal horn and dorsal root ganglia, while intraperitoneal injection of curcumin significantly reversed the activation of Cdk5/p35 protein and alleviated the hyperalgesia in rats. In addition, the injection of curcumin reduced the co-localization expression of Iba-1 and Cdk5/p35, indicating that curcumin inhibited the activation of Cdk5/p35 protein in the dorsal horn and dorsal root ganglia, thereby affecting the activation of microglia, thereby having a destructive effect on the neuronal cell plasticity and synaptic structure remodeling in the development of NP. Our study provides new evidence that Cdk5/p35 in the dorsal horn and dorsal root ganglia is related to the occurrence of NP, introduces microglia as the basis for the long-term maintenance of NP, and provides insights into the molecular mechanisms involved in the analgesic effect of curcumin.Graphical Abstract
Pathological microcircuits initiate epileptiform events in patient hippocampal slices
Authors: Elliott Matthew A.T. , Andrews John P. , van der Molen Tjitse , Geng Jinghui , Spaeth Alex , Voituik Kateryna , Core Cordero , Gillespie Thomas , Sinervo Ari , Parks David F. , Robbins Ash , Solís Daniel , Chang Edward F. , Nowakowski Tomasz Jan , Teodorescu Mircea , Haussler David , Sharf Tal 
Published: November 2024

AbstractHow seizures begin at the level of microscopic neural circuits remains unknown. High-density CMOS microelectrode arrays provide a new avenue for investigating neuronal network activity, with unprecedented spatial and temporal resolution. We use high-density CMOS-based microelectrode arrays to probe the network activity of human hippocampal brain slices from six patients with mesial temporal lobe epilepsy in the presence of hyperactivity promoting media. Two slices from the dentate gyrus exhibited epileptiform activity in the presence of low magnesium media with kainic acid. Both slices displayed an electrophysiological phenotype consistent with a reciprocally connected circuit, suggesting a recurrent feedback loop is a key driver of epileptiform onset. Larger prospective studies are needed, but these findings have the potential to elucidate the network signals underlying the initiation of seizure behavior.
Evolutionary consequences of domestication on the selective effects of new amino acid changing mutations in canids
Authors: Amorim Carlos Eduardo G. , Di Chenlu , Lin Meixi , Marsden Clare , Del Carpio Christina A. , Mah Jonathan C. , Robinson Jacqueline , Kim Bernard Y. , Mooney Jazlyn A. , Cornejo Omar E. , Lohmueller Kirk E. 
Published: November 2024

AbstractThe domestication of wild canids led to dogs no longer living in the wild but instead residing alongside humans. Extreme changes in behavior and diet associated with domestication may have led to the relaxation of the selective pressure on traits that may be less important in the domesticated context. Thus, here we hypothesize that strongly deleterious mutations may have become less deleterious in domesticated populations. We test this hypothesis by estimating the distribution of fitness effects (DFE) for new amino acid changing mutations using whole-genome sequence data from 24 gray wolves and 61 breed dogs. We find that the DFE is strikingly similar across canids, with 26-28% of new amino acid changing mutations being neutral/nearly neutral (|s|< 1e-5), and 41-48% under strong purifying selection (|s|> 1e-2). Our results are robust to different model assumptions suggesting that the DFE is stable across short evolutionary timescales, even in the face of putative drastic changes in the selective pressure caused by artificial selection during domestication and breed formation. On par with previous works describing DFE evolution, our data indicate that the DFE of amino acid changing mutations depends more strongly on genome structure and organismal characteristics, and less so on shifting selective pressures or environmental factors. Given the constant DFE and previous data showing that genetic variants that differentiate wolf and dog populations are enriched in regulatory elements, we speculate that domestication may have had a larger impact on regulatory variation than on amino acid changing mutations.Significance StatementDomestication of dogs to live alongside humans resulted in a dramatic shift in the pressures of natural selection. Thus, comparing dogs and wolves offers a unique opportunity to assess how these shifts in selective pressures have impacted the fitness effects of individual mutations. In this project, we use patterns of genetic variation in dogs and wolves to estimate the distribution of fitness effects (DFE), or the proportions of amino acid changing mutations with varying fitness effects throughout the genome. Overall, we find that the DFE for amino acid changing mutations is similar between dogs and wolves. Even genes thought to be most affected by domestication show a similar DFE, suggesting that the DFE has remained stable over evolutionary time.
Peripheral CGRP engages brain-wide electrical network activity of migraine
Authors: Johnson Micah , Eberle Maureen , Hultman Ian , Zhang Xinyu , Filali Yassine , Hing Benjamin , Jimenez Alli , Matkovich Molly , Mitchell Sara , Adegboyo Anjayooluwa , Velamuri Radha , Miller Julia , Chan Kung-Sik , Srivastava Sanvesh , Hultman Rainbo 
Published: November 2024

SummaryMigraine is a disorder consisting of severe, recurrent headaches and debilitating sensory symptoms which often include affective symptoms or comorbidities such as depression, anxiety, and irritability. As such, migraine is a complex nervous system disorder that involves integration of many modalities across the brain. This makes migraine a complex systems neuroscience problem represented by the confluence of sensory, pain, cognitive, autonomic, and affect-related circuits. Thus, it is essential to understand how neuronal activity across various brain regions implicated in migraine is coordinated during migraine pathophysiology. Using a calcitonin gene-related peptide (CGRP) mouse model of migraine, we probed neural oscillatory activity in the anterior cingulate cortex, amygdala (BLA and CeA), thalamus (Po, VPM, and MDthal), and parabrachial nucleus following peripheral administration of CGRP. We identified three frequency bands in which directional signals occur in this network and found that power in these frequencies across the network was lower than vehicle within 10 minutes of peripheral CGRP exposure, which was sustained for (∼40-50 min). Coherence, on the other hand, was mostly disrupted in CeA brain region pairings, and took on a shorter timecourse. Sumatriptan partially blunted or reversed these CGRP-induced network responses, especially with regard to amygdala power and coherence pairings. Early life stress, which has been shown to increase the likelihood of migraine in adulthood in humans, exacerbated CGRP-induced migraine-related behavioral phenotypes and induced corresponding network changes in LFP power in the CeA and Po and coherence in Po-related pairings. Clustering based on a changepoint analysis of coherence identified individual mice hypersusceptible to migraine. Overall, our findings demonstrate coordinated brain-wide network activity by which migraine is mediated in the brain in response to peripheral CGRP.
High plasticity increases phenotype-environment mismatch leading to sub-optimal performance in underutilized crop species
Authors: Alagarasan Ganesh , Arnold Pieter A. , Ramireddy Eswarayya 
Published: November 2024

AbstractAs climate change threatens agricultural yields, crop diversification, including the reintroduction of underutilized species, has emerged as a proposed solution for resilience. But what determines the extent of environmental change that underutilized crop species can cope with upon their reintroduction? One critical factor is maladaptive plasticity, a theoretical concept suggesting that populations may respond negatively to rapid environmental shifts, at least in the short term. To test this empirically, we conducted a repeated-measures study using historically underutilizedAmaranthusspecies as a model. Upon reintroduction, we observed higher plasticity in vegetative and reproductive traits than in life-history traits. This suggests that while these species adapt to immediate environmental changes through adjustments in growth and reproduction, limited plasticity in life-history traits may constrain long-term adaptation. Our study aimed to (1) identify the environmental factors driving these plastic responses, (2) determine whether these responses are maladaptive, and (3) assess if maladaptive plasticity also occurs within native environments. Using machine learning models, we found that temperature was a primary driver of plastic responses. Generalized Additive Model (GAM) reaction norm analysis further revealed these temperature-induced responses to be maladaptive, suggesting a mismatch betweenAmaranthus’ traits and the new environment. Applying transfer learning to predict responses in native settings, we found similar maladaptive responses to temperature, indicating that maladaptive plasticity may not be limited to non-native environments, thereby complicating climate adaptation efforts. This study underscore the need for detailed trait plasticity assessments before crop reintroduction for agricultural resilience.
Ribosome abundance, not paralogue composition, is essential for germline development
Authors: Grobicki Katarina Z A , Gebert Daniel , Sun Carol , Teixeira Felipe Karam 
Published: November 2024

SummaryRibosomes catalyse all protein synthesis, and mutations altering their levels and function underlie many developmental diseases and cancer. Historically considered to be invariant machines, ribosomes differ in composition between tissues and developmental stages, incorporating a diversity of ribosomal proteins (RP) encoded by duplicated paralogous genes. Here, we useDrosophilato systematically investigate the origins and functions of non-canonical RP paralogues. We show that new paralogues mainly originated through retroposition, and that only a few new copies retain coding capacity over time. Although transcriptionally active non-canonical RP paralogues often present tissue-specific expression, we show that the majority of those are not required for either viability or fertility inDrosophila melanogaster. The only exception, RpS5b, which is required for oogenesis, is functionally interchangeable with its canonical paralogue, indicating that theRpS5b-/-phenotype results from insufficient ribosomes rather than the absence of an RpS5b-specific, functionally-specialised ribosome. Altogether our results provide evidence that, instead of new functions, RP gene duplications provide a means to regulate ribosome levels during development.
A multi-tissue developmental gene expression atlas towards understanding the biological basis of phenotypes in sheep
Authors: Zhao Bingru , Luo Hanpeng , Fu Xuefeng , Zhang Guoming , Clark Emily L. , Wang Feng , Dalrymple Brian Paul , Oddy V. Hutton , Vercoe Philip E. , Wu Cuiling , Liu George E. , Li Cong-jun , Xiang Ruidong , Tian Kechuan , Zhang Yanli , Fang Lingzhao 
Published: November 2024

AbstractSheep (Ovis aries) represents one of the most important livestock species for animal protein and wool production worldwide. However, little is known about the genetic and biological basis of ovine phenotypes, particularly for those of high economic value and environmental impact. Here, by generating and integrating 1,413 RNA-seq samples from 51 distinct tissues across 14 developmental time points, representing early prenatal, late prenatal, neonate, lamb, juvenile, adult, and elderly stages, we built a high-resolution developmental Gene Expression Atlas (dGEA) in sheep. We observed dynamic patterns of gene expression and regulatory networks across tissues and developmental stages. When harnessing this resource for interpreting genomic associations of 48 monogenetic and 12 complex traits in sheep, we found that genes upregulated at prenatal developmental stages played more important roles in shaping these phenotypes than those upregulated at postnatal stages. For instance, genetic associations of crimp number, mean staple length (MSL), and individual birth weight were significantly enriched in the prenatal rather than postnatal skin and immune tissues. By comprehensively integrating fine-mapping results and the sheep dGEA, we identified several key genes associated with complex traits in sheep, such as SOX9 (associated with MSL), GNRHR (associated with litter size at birth), and PRKDC (associated with live weight). These results provide novel insights into the gene regulatory and developmental architecture underlying ovine phenotypes. The dGEA (https://sheepdgea.njau.edu.cn/) will serve as an invaluable resource for sheep developmental biology, genetics, genomics, and selective breeding.
Biofilm Formation and Niche Adaptation Play Fundamental Role in Shaping Long-Distance Transported Dust Microbial Community
Authors: Lang-Yona Naama , Levy Barazany Hilit , Salti Talal , Ben Navi Rahamim , Rahamin Ben-Navi Liat , Kolodkin-Gal Ilana 
Published: November 2024

AbstractThe long-distance transport of microorganisms via dust events is expected to become more prominent and intensified. At the same time, the survival mechanisms of air/dust-borne bacteria and their possible contribution to global processes remain poorly understood. In this study, we characterizedBacillusspecies from transitional season dust storms, previously identified as a significant component of the bioactive community of the dust microbiome. Our results demonstrated substantial growth and biofilm formation diversification, potentially linked to niche adaptation and surface-associated biofilm formation within heterogeneous dust particles. Most dust isolates form biofilms while exhibiting different preferences for media composition. Sterile dust induced biofilm formation, growth, matrix gene expression ofB. subtilis, and robust biofilms in key related dust isolates. Overall, our results highlight the significance of biofilm formation as an adaptive mechanism in the distinct habitat of dust storms, with niche adaptation potentially playing a role in microenvironments within the dust particle. These results hold significant potential for implications on terrestrial and aquatic ecology and health, suggesting a pivotal process by which bacteria survive and evolve in this understudied habitat.
Recurrent Inhibitory Dynamics in the Entorhinal Cortex Support Pattern Separation
Authors: Zheng Yicong , Antony James , Ranganath Charan , O’Reilly Randall C. 
Published: November 2024

AbstractThe entorhinal cortex (EC) provides the major input to the hippocampus (HPC). Numerous computational models on the EC propose that its grid cells serve as a spatial metric, supporting path integration and efficient generalization. However, little is known about how these cells could contribute to episodic memory, which emphasizes episode-specific representations that align with pattern separation. Taking into consideration anatomical specifications of EC inputs to the HPC and computational principles underlying the EC-HPC memory system, we argue that EC layer IIa (EC2a) supports pattern separation and EC layer IIb/III (EC2b/3) supports generalization. Utilizing recurrent inhibition and the nature of single EC2a neurons binding converging inputs from the neocortex (i.e., conjunctive coding), we built a biologically-based neural network model of the EC-HPC system for episodic memory. By examining how EC2a transformed its cortical inputs and output them to the trisynaptic pathway (EC2a - Dentate Gyrus - CA3 - CA1), we found that instead of systematically generalizing across similar inputs, recurrent inhibition and conjunctive coding in EC2a neurons support strong pattern separation and increase mnemonic discrimination. Furthermore, lesioning EC2a neurons in the model resembled memory impairments found in people with Alzheimer’s Disease, suggesting an intertwined relationship between memory and the majority of pure grid cells in the EC. On the other hand, the topographically organized monosynaptic pathway (EC2b/3 - CA1) is computationally more suitable for efficient factorization and generalization. This model provides novel anatomically-based predictions regarding the computational roles of EC cells in pattern separation and generalization, which together form a critical computational framework for both episodic memory and spatial navigation.
Modeling of blood flow dynamics in the rat somatosensory cortex
Authors: Battini Stéphanie , Cantarutti Nicola , Kotsalos Christos , Roussel Yann , Cattabiani Alessandro , Arnaudon Alexis , Favreau Cyrille , Antonel Stefano , Markram Henry , Keller Daniel 
Published: November 2024

AbstractThe cerebral microvasculature forms a dense network of interconnected blood vessels where flow is modulated partly by astrocytes. Increased neuronal activity stimulates astrocytes to release vasoactive substances at the endfeet, altering the diameters of connected vessels. Our study simulated the coupling between blood flow variations and vessel diameter changes driven by astrocytic activity in the rat somatosensory cortex. We developed a framework with three key components: coupling between vasculature and synthesized astrocytic morphologies, a fluid dynamics model to compute flow in each vascular segment, and a stochastic process replicating the effect of astrocytic endfeet on vessel radii. The model was validated against experimental flow values from literature across cortical depths. We found that local vasodilation from astrocyte activity increased blood flow, especially in capillaries, exhibiting a layer-specific response in deeper cortical layers. Additionally, the highest blood flow variability occurred in capillaries, emphasizing their role in cerebral perfusion regulation. We discovered that astrocytic activity impacts blood flow dynamics in a localized, clustered manner, with most vascular segments influenced by two to three neighboring endfeet. These insights enhance our understanding of neurovascular coupling and guide future research on blood flow-related diseases.