bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sweet and fatty symbionts: photosynthetic productivity and carbon storage boosted in microalgae within a host
Authors: Catacora-Grundy A. , Chevalier F. , Yee D. , LeKieffre C. , Schieber N. L. , Schwab Y. , Gallet B. , Jouneau P.H. , Curien G. , Decelle J. 
Published: December 2023

AbstractSymbiosis between a host and intracellular eukaryotic microalgae is a widespread life strategy in aquatic ecosystems. This partnership is considered to be mainly energized by the photosynthetically-derived carbon energy of microalgal symbionts. A major question is whether microalgae increase their photosynthetic production and decrease carbon storage in order to maximize carbon translocation to their host. By combining three-dimensional subcellular imaging and physiological analyses, we show that the photosynthetic machinery (chloroplast and CO2-fixing pyrenoid) of the symbiotic microalgaMicractinium conductrixsignificantly expands inside their host (the ciliateParamecium bursaria) compared to the free-living state. This is accompanied by a 13-fold higher quantity of Rubisco enzymes and 16-fold higher carbon fixation rate. Time-resolved subcellular imaging revealed that photosynthetically-derived carbon is first allocated to starch during the day, with five times higher production in symbiosis despite low growth. Nearly half of the carbon stored in starch is consumed overnight and some accumulates in lipid droplets, which are 20-fold more voluminous in symbiotic microalgae. We also show that carbon is transferred to the host and hypothesize that much of this is respired by the high density of surrounding host mitochondria. We provide evidence that the boosted photosynthetic production of symbiotic microalgae could be explained by the energetic demands of the host. Overall, this study provides an unprecedented view of the subcellular remodeling and dynamics of carbon metabolism of microalgae inside a host, highlighting the potentially key role of the source-sink relationship in aquatic photosymbiosis.Significance statementSymbiotic interactions between a heterotrophic host and intracellular microalgae are widespread in aquatic ecosystems and are considered to be energized by the photosynthetically-derived carbon energy. However, little is known on the impact of symbiosis on the algal bioenergetics (e.g. carbon production and storage). This study reveals the morphological and physiological changes of a microalga inside a host at the subcellular scale over the day. We show that the photosynthetic machinery expands and carbon fixation and storage are boosted in symbiotic microalgae beyond their growth needs. This high photosynthetic production is very likely enhanced by the host energetic demands. Our findings advance our basic understanding of photosymbiosis and open new perspectives on the mechanisms and drivers of metabolic exchange between partners.
Single-molecule imaging and molecular dynamics simulations reveal early activation of the MET receptorin situ
Authors: Li Yunqing , Arghittu Serena , Dietz Marina S. , Hella Gabriel J. , Haße Daniel , Ferraris Davide M. , Freund Petra , Barth Hans-Dieter , Niemann Hartmut H. , Covino Roberto , Heilemann Mike 
Published: December 2023

AbstractThe assembly of membrane receptors into signaling complexes is at the origin of key cellular events. Yet, we often lack detailed structural mechanistic understanding. Receptors are embedded into a complex cellular membrane, which defines their dynamics but also complicates their experimental characterizations significantly. Here, we showcase an integrative structural biology approach to investigate the activation mechanism of the human growth factor receptor MET. MET is a receptor tyrosine kinase involved in cell proliferation, migration, and survival. MET is also hijacked by the intracellular pathogenListeria monocytogenes. Its invasion protein, internalin B (InlB), binds to MET and promotes the formation of a signaling dimer that triggers the internalization of the pathogen. Crystallography had suggested two different 2:2 MET:InlB complexes. Here, we use a combination of structural biology, modeling, molecular dynamics simulations, andin situsingle-molecule Förster resonance energy transfer (smFRET) to elucidate the early events in MET activation. Simulations show that InlB binding stabilizes MET in a conformation that promotes dimer formation. smFRET identifies the organization of thein situsignaling dimer, which resembles one of the two crystal structures yet shows differences. Further MD simulations resulted in a refinement of the dimer model, which is in quantitative agreement with smFRET results. We accurately describe the structural dynamics underpinning an important cellular event and introduce a powerful methodological pipeline applicable to studying the activation of other plasma membrane receptorsin situ.
Integration of Multi-omics Data for the Classification of Glioma Types and Identification of Novel Biomarkers
Authors: Vieira Francisca G. , Bispo Regina , Lopes Marta B. 
Published: December 2023

AbstractGlioma is currently one of the most prevalent types of primary brain cancer. Given its high level of heterogeneity along with the complex biological molecular markers, many efforts have been made to accurately classify the type of glioma in each patient, which, in turn, is critical to improve early diagnosis and increase survival. Nonetheless, as a result of the fast-growing technological advances in high throughput sequencing and evolving molecular understanding of glioma biology, its classification has been recently subject to significant alterations. In this study, we integrate multiple glioma omics modalities (including mRNA, DNA methylation, and miRNA) from The Cancer Genome Atlas (TCGA), while using the revised glioma reclassified labels, with a supervised method based on sparse canonical correlation analysis (DIABLO) to discriminate between glioma types. We were able to find a set of highly correlated features distinguishing glioblastoma from lower-grade gliomas (LGG) that were mainly associated with the disruption of receptor tyrosine kinases signaling pathways and extracellular matrix organization and remodeling. On the other hand, the discrimination of the LGG types was characterized primarily by features involved in ubiquitination and DNA transcription processes. Furthermore, we could identify several novel glioma biomarkers likely helpful in both diagnosis and prognosis of the patients, including the genesPPP1R8, GPBP1L1, KIAA1614, C14orf23, CCDC77, BVES, EXD3, CD300AandHEPN1. Overall, this classification method allowed to discriminate the different TCGA glioma patients with very high performance, while seeking for common information across multiple data types, ultimately enabling the understanding of essential mechanisms driving glioma heterogeneity and unveiling potential therapeutic targets.
Bidirectional relationship between attentional deficits and escalation of nicotine intake
Authors: Vouillac-Mendoza Caroline , Ahmed Serge H. , Guillem Karine 
Published: December 2023

AbstractSmoking addicts have deficits in cognition, in particular deficits in attention, even long after smoking cessation. It is not clear however, whether deficits are a cause or a consequence, or both, of chronic nicotine use. Here we set out a series of experiments in rats to address this question and, more specifically, to assess the long-term effects of exposure to and withdrawal from chronic nicotine self-administration on attentional performance. Animals were trained in a 5-choice serial reaction time task to probe individual attentional performance and, then, were given access to a fixed versus increasing dose of intravenous nicotine for self-administration, a differential dose procedure known to induce two between-session patterns of nicotine intake: a stable versus escalation pattern. Attentional performance was measured daily before, during and also 24-h after chronic access to the differential dose procedure of nicotine self-administration. We found that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake. Moreover, while chronic nicotine self-administration increases attention, withdrawal from nicotine intake escalation induces attentional deficits, a withdrawal effect that is dose-dependently reversed by acute nicotine. Together, these results suggest that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake, and that part of the motivation for using nicotine during escalation might be to alleviate withdrawal-induced attentional deficits.
Dual carbon sequestration with photosynthetic living materials
Authors: Dranseike Dalia , Cui Yifan , Ling Andrea S. , Donat Felix , Bernhard Stéphane , Bernero Margherita , Areeckal Akhil , Qin Xiao-Hua , Oakey John S. , Dillenburger Benjamin , Studart André R. , Tibbitt Mark W. 
Published: December 2023

AbstractNatural ecosystems offer efficient pathways for carbon sequestration, serving as a resilient approach to remove CO2from the atmosphere with minimal environmental impact. However, the control of living systems outside of their native environments is often challenging. Here, we engineered a photosynthetic living material for dual CO2sequestration by immobilizing photosynthetic microorganisms within a printable polymeric network. The carbon concentrating mechanism of the cyanobacteria enabled accumulation of CO2within the cell, resulting in biomass production. Additionally, the metabolic production of OH-ions in the surrounding medium created an environment for the formation of insoluble carbonates via microbially-induced calcium carbonate precipitation (MICP). Digital design and fabrication of the living material ensured sufficient access to light and nutrient transport of the encapsulated cyanobacteria, which were essential for long-term viability (more than one year) as well as efficient photosynthesis and carbon sequestration. The photosynthetic living materials sequestered approximately 2.5 mg of CO2per gram of hydrogel material over 30 days via dual carbon sequestration, with 2.2 ± 0.9 mg stored as insoluble carbonates. Over an extended incubation period of 400 days, the living materials sequestered 26 ± 7 mg of CO2per gram of hydrogel material in the form of stable minerals. These findings highlight the potential of photosynthetic living materials for scalable carbon sequestration, carbon-neutral infrastructure, and green building materials. The simplicity of maintenance, coupled with its scalability nature, suggests broad applications of photosynthetic living materials as a complementary strategy to mitigate CO2emissions.
Brg1 regulates fibroblast-myofibroblast transition to promote renal fibrosis
Authors: Wu Xiaoyan , Luo Yajun , Kang Aoqi , Ni Jiayao , Kong Ming , Zhang Tao 
Published: December 2023

AbstractExcessive fibrogenesis serves to disrupt the anatomical and functional integrity of the kidneys contributing to renal failure. Renal fibroblast is the major precursor to myofibroblast, the effector cell type of renal fibrosis. How fibroblast-myofibroblast transition (FMyT) is regulated in the kidneys remains incompletely understood. In the present study we investigated the role of Brahma related gene 1 (Brg1), a chromatin remodeling protein, in renal fibrosis focusing on mechanistic insights and translational potential. We report that Brg1 was up-regulated during FMyT bothin vitroandin vivo. Brg1 deletion in fibroblasts partially blocked TGF-β induced FMyTin vitroand attenuated renal fibrosis in three different animal models. Importantly, conditional Brg1 knockout inPostn+mature myofibroblasts mitigated renal fibrosis induced by unilateral ureteral obstruction (UUO) or ischemia-reperfusion (IR) in mice. Transcriptomic analysis uncovered Prune2 as a potential target for Brg1. Brg1 interacted with E2F1 to activate Prune2 transcription during FMyT. Concordantly, Prune2 knockdown suppressed TGF-β induced FMyTin vitroand dampened renal fibrosis in mice. Mechanistically, Prune2 likely contributed to FMyT by augmenting phosphorylation and activity of the pro-fibrogenic transcription factor PU.1. Finally, small-molecule Brg1 inhibitor PFI-3 exhibited strong antifibrotic potency in established models of renal fibrosis. In conclusion, our data provide compelling evidence that BRG1 is a pivotal regulator of as well as a promising therapeutic target for renal fibrosis.
Optimization of neuromuscular blockade protocols in cynomolgus macaques: monitoring, doses and antagonism
Authors: Letscher Hélène , Lemaitre Julien , Burban Emma , Grand Roger Le , Bruhns Pierre , Relouzat Francis , Gouel-Chéron Aurélie 
Published: December 2023

ABSTRACTBackgroundNeuromuscular blocking agents (NMBAs) are a crucial component of anaesthesia and intensive care. NMBAs are a family of molecules defined by their ability to compete with acetylcholine for binding to the acetylcholine receptor at the neuromuscular junction. This functional homology relies on the presence of ammonium groups in all NMBAs that, however, display vastly different chemical structures. Among animal models, non-human primates (NHP) are an essential model for a great diversity of human disease models but remain poorly characterized for the effectiveness of the diverse NMBAs.MethodsSeven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anaesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anaesthesia was maintained with isofluorane. Either rocuronium bromine or atracurium besylate was evaluated, with reversal with sugammadex. Monitoring was performed with two devices, TOF-Watch® and ToFscan®, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann-Whitney statistical analyses were done when indicated.ResultsNMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrodes placement, to be efficient and valid in Cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro-muscular blockade at equivalent doses to clinical doses in humans. Rocuronium-induced profound neuromuscular blockade could be reverted using the cyclodextrin sugammadex’s reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count.ConclusionThese results support the use of non-human primate models for neuromuscular blockade monitoring and testing novel NMBA or their reversal agents.
Phase coding in phoneme processing slows with age
Authors: Dapper Konrad , Schirmer Jakob , Rüttiger Lukas , Gaudrain Etienne , Başkent Deniz , Verhulst Sarah , Braun Christoph , Dalhoff Ernst , Wolpert Stehpan M. , Knipper Marlies , Munk Matthias H. J. 
Published: December 2023

AbstractThe comprehension of phonemes is a fundamental component of speech processing which relies on both, temporal fine structure (TFS) and temporal envelope (TE) coding. EEG amplitude in response to phonemes has been identified as indicator of speech performance in hearing aid users. Presbyacusis may also alter neuro-electric responses to phonemes, even with minimally or unaffected hearing thresholds. Elevated speech reception thresholds (SRT) in absence of pure-tone threshold (PTT) elevation suggest central processing deficits. We therefore collected audiometric data (PTT, SRT) and EEG during passive listening in 80 subjects, ranging in age from 18 to 76 years. We confirm phoneme-evoked EEG response amplitude (PEA) as indicator of speech comprehension. Specifically, PEA decreased with elevated SRT, PTT and increased age. As novel observation, we report the temporal delay of phoneme-evoked EEG responses (PED) to increase with age and PTT. The absolute duration of PED, its age-correlation, and the lack of PEA-lateralization combined with the frequency of phoneme stimuli used here suggest a predominantly thalamic generator of phoneme-evoked EEG responses. Hearing loss in extended high-frequencies affects PED more than PEA. In our sample, neural compensation for increased PTT came at the cost of decreased temporal processing speed. Most importantly, PED correlates with SRT and explains SRT-variance in quiet and in ipsilateral noise that PTT cannot. PED was a better predictor of TFS coding in quiet and of TE coding in ipsilateral noise. As PED reflects both TFS and TE coding, thalamic activity may provide integrated information at the gate of neocortex.Significance StatementIntact speech comprehension is essential for social participation which protects against depression and dementia. Age-related hearing loss is a growing problem in aging societies, as hearing deficits constitute the third most important modifiable risk factor for cognitive decline. This work uses electrical brain responses to phonemes in a cohort covering age 18 to 76 years. As the temporal delay of phoneme responses showed the most significant correlations with age and high-frequency thresholds, we demonstrated that speed of neural processing seems essential for speech comprehension. The observed neural signals likely originate from thalamus which receives feedback from neocortex and is embedded in cognitive processing. Developing objective markers for speech processing is key for ensuring cognitive fitness in aging.
An exploratory computational analysis in mice brain networks of widespread epileptic seizure onset locations along with potential strategies for effective intervention and propagation control
Authors: Courson Juliette , Quoy Mathias , Timofeeva Yulia , Manos Thanos 
Published: December 2023

ABSTRACTMean-field models have been developed to replicate key features of epileptic seizure dynamics. However, the precise mechanisms and the role of the brain area responsible for seizure onset and propagation remain incompletely understood. In this study, we employ computational methods within The Virtual Brain framework and the Epileptor model to explore how the location and connectivity of an Epileptogenic Zone (EZ) in a mouse brain are related to focal seizures (seizures that start in one brain area and may or may not remain localized), with a specific focus on the hippocampal region known for its association with epileptic seizures. We then devise computational strategies to confine seizures (prevent widespread propagation), simulating medical-like treatments such as tissue resection and the application of an anti-seizure drugs or neurostimulation to suppress hyperexcitability. Through selectively removing (blocking) specific connections informed by the structural connectome and graph network measurements or by locally reducing outgoing connection weights of EZ areas, we demonstrate that seizures can be kept constrained around the EZ region. We successfully identified the minimal connections necessary to prevent widespread seizures, with a particular focus on minimizing surgical or medical intervention while simultaneously preserving the original structural connectivity and maximizing brain functionality.
Nutritional characterisation and seasonal variation of goat forages in Central Malawi
Authors: Cooke A. S. , Mvula W. , Nalivata P. , Ventura-Cordero J. , Gwiriri L.C. , Takahashi T. , Morgan E. R. , Lee M. R. F. , Safalaoh A. 
Published: December 2023

AbstractGoat ownership is prevalent across rural Malawi and provides a vital source of income, nutrition, and food security. However, goat performance is poor, and this presents a risk to individuals and communities who depend on them. Whilst mitigating this through supplementation of persevered forages may be possible, this is a challenge due to limitations of resources and the fact that goats typically free-roam during the dry season. Nutrition is fundamental to health and productivity of any livestock enterprise, it is required to be able to deal with stresses, such as disease, and to enable growth and production. The aim of this study was to characterise the nutritional profile of naturally available forages in Malawi, including the seasonal variation in nutrition. Samples of herbaceous forages and browse were collected over a 17-month period, across four villages (30 farms/smallholders) in Central Malawi. Forages underwent nutritional analysis for crude protein, fibre fractions, and ash/organic matter and NDVI obtained from satellite imagery was used as a measure of forage availability. Forage nutrition and availability were most adequate in the wet season, with higher concentrations of crude protein and a greater availability of herbaceous plants. There were significant differences in low-digestibility fibre fractions between locations, likely due to local factors such as soil and hydrology. The fall in crude protein concentrations from the wet season to the dry season represent a seasonal nutrition-gap which may result in risks to goat health and productivity.
Decoding Pain: Uncovering the Factors that Affect Performance of Neuroimaging-Based Pain Models
Authors: Lee Dong Hee , Lee Sungwoo , Woo Choong-Wan 
Published: December 2023

AbstractNeuroimaging-based pain biomarkers, when combined with machine learning techniques, have demonstrated potential in decoding pain intensity and diagnosing clinical pain conditions. However, a systematic evaluation of how different modeling options affect model performance remains unexplored. This study presents results from a comprehensive literature survey and benchmarking analysis. We conducted a survey of 57 previously published articles that included neuroimaging-based predictive modeling of pain, comparing classification and prediction performance based on the following modeling variables—the levels of data, spatial scales, idiographic vs. population models, and sample sizes. The findings revealed a preference for population-level modeling with brain-wide features, aligning with the goal of clinical translation of neuroimaging biomarkers. However, a systematic evaluation of the influence of different modeling options was hindered by a limited number of independent test results. This prompted us to conduct benchmarking analyses using a locally collected functional Magnetic Resonance Imaging (fMRI) dataset (N= 124) involving an experimental thermal pain task. The results clearly demonstrated that data levels, spatial scales, and sample sizes significantly impact model performance. Specifically, incorporating more pain-related brain regions, increasing sample sizes, and using less data averaging in training while increasing it in testing enhanced performance. These findings provide a useful reference for decision-making in the development of neuroimaging-based biomarkers, highlighting the importance of the careful selection of modeling strategies and options to build better-performing neuroimaging pain biomarkers. These findings offer useful guidance for developing neuroimaging-based biomarkers, underscoring the importance of strategic selection of modeling approaches to build better-performing neuroimaging pain biomarkers.