bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of dynamic eigenvalue in anticipating and distinguishing tipping points†
Authors: Kulkarni Kaustubh , Deb Smita , Dutta Partha Sharathi 
Published: January 2024

AbstractThe presence of tipping points in several natural systems necessitates having improved early warning indicators to provide accurate signals of an impending transition to a contrasting state while also detecting the type of transition. Various early warning signals (EWSs) have been devised to forecast the occurrence of tipping points, also called critical transitions. Dynamic eigenvalue (DEV) is a recently proposed EWS that can not only predict the occurrence of a transition but also certain types of accompanying bifurcations. Here, we study the effectiveness and limitations of DEV as an EWS for diverse kinds of critical phenomena. We demonstrate that DEV is a powerful EWS that shows promising results in anticipating catastrophic (first-order or discontinuous) and non-catastrophic (second-order or continuous) transitions in discrete and continuous dynamical systems. However, it falls short in the case of piecewise smooth systems. Further, the ability of DEV to forecast the type of transition is limited, as it cannot differentiate saddle-node bifurcation from transcritical and pitchfork bifurcations. Despite these limitations, we show that DEV can work as a robust indicator for varying rates at which the transition is approached and with systems involving colored noise.
Analysis of the Time-Dependent Behaviors of Atrial Fibrillation with Electrographic Flow Mapping
Authors: Haines David E. , Kong Melissa H. , Ruppersberg Peter , Castellano Steven , Spitzer Stefan G. , Noelker Georg , Rillig Andreas , Szili-Torok Tamas 
Published: January 2024

ABSTRACTBackgroundElectrographic flow (EGF) mapping algorithms employing Horn-Schunck flow estimations can create temporospatial visualizations of atrial electrical wavefront propagations during atrial fibrillation (AF). Reproducible patterns of centrifugal EGF activation from discrete sites may represent sites of AF origin or sources. Our objectives were to assess the patterns and prevalence of AF sources using EGF mapping.MethodsUnipolar electrograms were recorded for 1-minute with 64-pole basket catheters. Flow estimates were constructed by passing consecutive frames through an algorithm to learn and then compare typical wave direction patterns to describe flow-field evolution. During each 2-second segment, sites initiating centrifugal activation patterns were defined as AF sources. Maps of source location/activity duration were generated.ResultsThe EGF method was applied to 405 prospective and retrospective patients with persistent or long-standing persistent AF. Mean age 62.5 years; mean LA size 54 mm; mean AF duration 4.6 years. EGF mapping found 6.6 ± 2.4 AF sources/patient (range 1 to 17). Distribution was 55% LA and 45% RA. Dominant sources (prevalence ≥20%) were demonstrated in 185 (45.7%) patients, but only 10.7% of all sources were dominant. While AF cycle length (CL) was not affected by source prevalence, CL variance significantly decreased as source prevalence increased.ConclusionsComplex AF conduction patterns make ablation challenging, but EGF mapping enables detection and organization of time-dependent AF behaviors. Although many low prevalence sources are detected, they may not be clinically relevant, while higher prevalence sources seem to modulate AF. Recording durations of 1 minute facilitate source discrimination.
A cross-sectional questionnaire study: impaired awareness of hypoglycaemia remains prevalent in adults with type 1 diabetes and is associated with the risk of severe hypoglycaemia
Authors: Baxter F. , Baillie N. , Dover A. , Stimson R.H. , Gibb F. , Forbes S. 
Published: January 2024

AbstractObjectiveImpaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors.MethodsAdults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records.Results189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p=0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p=0.036). Socio-economic deprivation was associated with IAH (p=0.032) and SH (p=0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p=0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p=0.04).ConclusionIAH remains a risk factor for SH and is prevalent in females. Insulin pump and continuous glucose monitor use was comparable in IAH vs aware groups. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions.
Primary care access and feasibility of Spatial Accessibility Index (SAI) in assessing primary care in rural Sri Lanka
Authors: Abeyrathna Parami , Agampodi Suneth Buddhika , Weerasinghe Manjula , Samaranayake Shyamalee , Pushpakumara Pahala Hangidi Gedara Janaka 
Published: January 2024

AbstractDespite decades of global health efforts and policies, inequitable access to primary care in low and middle-income countries remains an ongoing challenge. This study assessed accessibility to curative sector-primary healthcare services in the Anuradhapura district of Sri Lanka in 2020 and 2021. In this study, we included both private and state-owned primary care facilities (PCF) and their corresponding primary care doctors (PCD), covering both allopathic and complementary and alternative medicine (CAM) practices. Spatial locations of private sector PCF of the entire district were collected by conducting a comprehensive road-based survey and documenting information from publicly displayed boards. Data on state PCF were collected from provincial health departments (allopathic and Ayurveda). The Spatial Accessibility Index (SAI) of 657 GND (Grama Niladhari Division: the smallest administrative division) was calculated in ARC-GIS using the 2-Steps-Floating-Catchment-Area method in 5 km and 10 km spatial-distances from a GND. The majority of the PCF were allopathic (n=318, 78%) and belonged to the private sector (n=317, 79%) whereas CAM PCD represented one-fifth of the primary care workforce. Average SAI of 4.50X 10-4and 4.67X 10-4were reported for both 5 km and 10 km spatial-distance. A statistically significant difference in mean SAI was measured between urban and rural populations. The highest SAI were observed from urban populations and it gradually declined towards the rural remotes. The national primary care coverage target of 1 allopathic PCD per 5000 population was achieved only in 64% of the population in a 5 km spatial-distance and it further depleted to 25% with only of state allopathic PCD. SAI was negatively associated with the poverty headcount indices and distance to main roads and the main town (Anuradhapura). While the private allopathic sector is the main primary care provider in this study setting, a significant proportion of the population reported limited primary care access dueto their geographic and economic status. Health policymakers need to address primary care workforce shortages in rural for the planning of human and physical resources. SAI can be recommended as a feasible method for healthcare planning and assessing service coverage in low-facility settings.
Complete absence of GLUT1 does not impair human terminal erythroid differentiation
Authors: Freire CM , King NR , Dzieciatkowska M , Stephenson D , Moura PL , Dobbe J.G.G , Streekstra GJ , D’Alessandro A , Toye AM , Satchwell TJ 
Published: January 2024

AbstractThe Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR-mediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signalling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 deficiency syndrome.Key PointsGLUT1 knockout does not affect erythroid differentiation and minimally impacts reticulocyte membrane compositionMetabolic adaptation facilitates reticulocyte tolerance of GLUT1 absence
Cell-cycle dependence of bursty gene expression: insights from fitting mechanistic models to single-cell RNA-seq data
Authors: Sukys Augustinas , Grima Ramon 
Published: January 2024

AbstractBursty gene expression is characterised by two intuitive parameters, burst frequency and burst size, the cell-cycle dependence of which has not been extensively profiled at the transcriptome level. In this study, we estimate the burst parameters per allele in the G1 and G2/M cell-cycle phases for thousands of mouse genes by fitting mechanistic models of gene expression to mRNA count data, obtained by sequencing of single cells whose cell-cycle position has been inferred using a deep-learning method. We find that upon DNA replication, the median burst frequency approximately halves, while the burst size remains mostly unchanged. Genome-wide distributions of the burst parameter ratios between the G2/M and G1 phases are wide, indicating substantial heterogeneity in transcriptional regulation patterns. We also observe a significant negative correlation between the burst frequency and size ratios, suggesting that regulatory processes do not independently control the burst parameters. Finally, we argue that to accurately estimate the burst parameter ratios, mechanistic models must explicitly account for gene copy number variation and extrinsic noise due to the coupling of transcription to cell age within the cell cycle, but corrections for technical noise due to imperfect capture of RNA molecules in sequencing experiments are less critical.
The triose phosphate/phosphate translocator exports photosynthetic glyceraldehyde 3-phosphate from chloroplasts to trigger antimicrobial immunity in plants
Authors: Zuo Deng-Pan , Wang Bin , Liu Yu-Zi , Chen Zheng-Song , Hu Ru-Jian , He Meng-Jun , Zhang Zong-Ying , Wang Ying , Han Cheng-Gui 
Published: January 2024

AbstractChloroplasts play a crucial role in plant immunity against invading microbes. However, it remains poorly understood whether photosynthetic metabolites from chloroplasts participate directly in host defenses. Here, we uncoveredArabidopsis thalinanatriose phosphate/phosphate translocator (AtTPT), a known translocator for chloroplast inner membrane, plays an indispensable role in suppressing virus infection and evoking defense responses. Interestingly, overexpression of AtTPT impairs virus accumulation in plants, while loss-of-function tpt3 mutants exhibit an increased viral load. The antiviral activity of AtTPT requires its phosphate transport capacity, implying that it actually functions through its metabolite(s). To this end, we found that glyceraldehyde 3-phosphate (GAP), one of AtTPT’s translocated metabolites, can drastically enhance expression of defense-related genes and prominently induce defense signaling pathways. More excitingly, AtTPT or GAP robustly restricts the proliferation of multiple types of phytopathogens. Collectively, we propose that AtTPT exports GAP to mediate broad-spectrum resistance to pathogens, which provides new insights into the mechanism underlying the chloroplast-mediated immunity by a photosynthetic metabolite.
Hebbian activity only temporarily stabilizes synaptic transmission at CA3-CA1 synapses in the developing hippocampus
Authors: Strandberg Joakim , Gustafsson Bengt 
Published: January 2024

ABSTRACTProlonged low frequency (0.05-1 Hz) stimulation of previously non-stimulated (naive) CA3-CA1 synapses in the developing hippocampus results in a profound synaptic depression explained by a postsynaptic AMPA silencing. It has been proposed that Hebbian activity can stabilize the synapses by preventing such depression. Using field recordings, we have examined to which extent strong repeated high frequency tetanization simulating Hebbian activity results in such prevention. The tetanization resulted within minutes in a field EPSP potentiation to 150-170% of the naive field EPSP level which remained unaltered if stimulation was suspended. If test pulse stimulation (0.2 Hz) was allowed to continue after the tetanization the field EPSP continuously decreased and was after 2700 stimuli depressed by 75% from the potentiated level. This depression did not differ in relative terms from that induced in naive synapses (by 82% from the naive level). The long-lasting component of this depression revealed by a subsequent 30 min stimulus interruption (by 59% from the potentiated level) did not differ from that of naive synapses (by 66% from the naive level). This equal relative degree of depression of tetanized and naive synapses was also observed following 2700 stimuli at 1 Hz. On the other hand, when examined at earlier time points during the test pulse stimulation (e.g. after 400-900 stimuli) tetanized synapses were less depressed than naive synapses, and the long-lasting depression after 900 stimuli at 1 Hz was only half that observed in naive synapses. This effect of tetanization was observed independently of whether the 1 Hz stimulation was commenced 15 min or 2 hours after the tetanization. In conclusion, while a strong preceding tetanization results in a partial stabilization of transmission at CA3-CA1 synapses in the developing hippocampus, this effect appears only temporary. This temporary effect is not linked to time after tetanization but to the number of low frequency stimuli given.
Emotional prosody modulates visual mental imagery
Authors: Huang Weifang , Zhang Fengxiang , Zhang Chenghui , Wang Can , Zhang Shiyu , Pu Yi , Kong Xiang-Zhen 
Published: January 2024

AbstractPerceptual stimuli’s emotional properties are vital for human evolution and adaptation. While visual imagery is predominantly regarded as a weak form of perception, the influence of cross-modal emotional features on imagery is still unknown. The present study aims to investigate how emotional prosody modulates imagery quality (i.e., accuracy and clarity) and neural mechanisms using a combination of behavioral tasks and functional magnetic resonance imaging (fMRI). At the behavioral level, our results showed that frustrated conditions induced significant prosody effects on visual mental imagery quality measures, and the effects were particularly pronounced in individuals with lower imagery use tendency. At the neural level, compared with the neutral condition, the emotional prosody conditions (both happy and frustrated) showed stronger activation in various regions including the middle occipital gyrus, supporting the critical role of primary visual system in imagery. Moreover, compared to the frustrated prosody condition, the happy prosody showed stronger activation in the precuneus and anterior cingulate cortex, which are core components of the default mode network. A machine learning prediction analysis with a random forest model identified a significant brain-behavioral correlation between prosody-linked neural activity and individual imagery use tendency. A subsequent Shapley Additive exPlanations (SHAP) analysis further highlighted the primary visual and default mode regions as top contributors to this prediction. Taken together, these results provide new insights for the understanding of how emotional prosody modulates visual mental imagery, considering individual differences, and provide compelling evidence for incorporating emotion as important shaping factor in more general model for imagery.
Photoswitchable endocytosis of biomolecular condensates in giant vesicles
Authors: Mangiarotti Agustín , Aleksanyan Mina , Siri Macarena , Lipowsky Reinhard , Dimova Rumiana 
Published: January 2024

AbstractInteractions between membranes and biomolecular condensates can give rise to complex phenomena such as wetting transitions, mutual remodeling, and endocytosis. In this study, we demonstrate a light-triggered manipulation of condensate engulfment using giant vesicles containing photoswitchable lipids. UV irradiation increases the membrane area, facilitating a rapid condensate endocytosis, which can be reverted by blue light. The affinity of the protein-rich condensates to the membrane and the reversibility of the engulfment processes is quantified from confocal microscopy images. The degree of engulfment, whether partial or complete, depends on the initial membrane excess area and the relative sizes of vesicles and condensates. Theoretical estimates suggest that utilizing the light-induced excess area to increase the vesicles-condensate adhesion interface is energetically more favorable than the energy gain from folding the membrane into invaginations and tubes. Our overall findings demonstrate that membrane-condensate interactions can be easily and quickly modulated via light, providing a versatile system for building platforms to control cellular events and design intelligent drug delivery systems for cell repair.
Starvation resistant cavefish reveal conserved mechanisms of starvation-induced hepatic lipotoxicity
Authors: Pozo-Morales Macarena , Cobham Ansa E , Centola Cielo , McKinney Mary Cathleen , Liu Peiduo , Perazzolo Camille , Lefort Anne , Libert Frédérick , Bai Hua , Rohner Nicolas , Singh Sumeet Pal 
Published: January 2024

AbstractStarvation causes the accumulation of lipid droplets in the liver, a somewhat counterintuitive phenomenon that is nevertheless conserved from flies to humans. Much like fatty liver resulting from overfeeding, hepatic lipid accumulation (steatosis) during undernourishment can lead to lipotoxicity and atrophy of the liver. Here, we found that while surface populations of Astyanax mexicanus undergo this evolutionarily conserved response to starvation, the starvation-resistant cavefish larvae of the same species do not display an accumulation of lipid droplets upon starvation. Moreover, cavefish are resistant to liver atrophy during starvation, providing a unique system to explore strategies for liver protection. Using comparative transcriptomics between zebrafish, surface fish, and cavefish, we identified the fatty acid transporter slc27a2a/fatp2 to be correlated with the development of fatty liver. Pharmacological inhibition of slc27a2a in zebrafish rescues steatosis and atrophy of the liver upon starvation. Further, down-regulation of FATP2 in drosophila larvae inhibits the development of starvation-induced steatosis, suggesting the evolutionary conserved importance of the gene in regulating fatty liver upon nutrition deprivation. Overall, our study identifies a conserved, druggable target to protect the liver from atrophy during starvation.One-Sentence SummaryCavefish evolved protection from starvation-induced liver damage through reduction of fatty acid uptake regulated byFATP2, a mechanism conserved through 400 million years of animal evolution.
Genetic legacies of mega-landslides: cycles of isolation and contact across flank collapses in an oceanic island
Authors: Noguerales Víctor , Arjona Yurena , García-Olivares Víctor , Machado Antonio , López Heriberto , Patiño Jairo , Emerson Brent C. 
Published: January 2024

AbstractCatastrophic flank collapses are recognised as important drivers of insular biodiversity dynamics, through the disruption of species ranges and subsequent allopatric divergence. However, little empirical data supports this conjecture, with their evolutionary consequences remaining poorly understood. Using genome-wide data within a population genomics and phylogenomics framework, we evaluate how mega-landslides have impacted evolutionary and demographic history within a species complex of weevils (Curculionidae) within the Canary island of Tenerife. We reveal a complex genomic landscape, within which individuals of single ancestry were sampled in areas characterised by long-term geological stability, relative to the timing of flank collapses. In contrast, individuals of admixed ancestry were almost exclusively sampled within the boundaries of flank collapses. Estimated divergence times among ancestral populations aligned with the timings of mega-landslide events. Our results provide first evidence for a cyclical dynamic of range fragmentation and secondary contact across flank collapse landscapes, with support for a model where this dynamic is mediated by Quaternary climate oscillations. The context within which we reveal climate and topography to interact cyclically through time to shape the geographic structure of genetic variation, together with related recent work, highlights the importance of topoclimatic phenomena as an agent of diversification within insular invertebrates.