bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial Association of HDL Cholesterol With Reperfusion Injury And Functional Outcome After Thrombectomy For Stroke
Authors: Sedghi Annahita , Schreckenbauer Sonja , Kaiser Daniel P. O. , Cuberi Ani , Polanski Witold H. , Arndt Martin , Barlinn Kristian , Puetz Volker , Siepmann Timo 
Published: October 2024

AbstractBackgroundAnimal studies suggest that high-density lipoprotein cholesterol (HDL-C) protects against reperfusion injury. We hypothesised that higher serum HDL-C levels would have a protective effect against cerebral reperfusion injury in human stroke survivors treated with thrombectomy.MethodsWe included consecutive patients from our prospective anterior circulation large-vessel occlusion (acLVO) registry who underwent thrombectomy between January 2017 and January 2023 at a tertiary stroke centre in Germany in a propensity score-matched analysis. We assessed the association between serum HDL-C levels and imaging indices of post-interventional reperfusion injury according to the Heidelberg Bleeding Classification as well as 90-day functional outcome quantified by the modified Rankin Scale (mRS). We performed sensitivity analyses using multivariable lasso logistic and linear regression adjusted for demographic, clinical and imaging characteristics.ResultsOut of 1702 patients assessed for eligibility, 807 acLVO patients treated with thrombectomy (420 females, median age 77 years [66-84, IQR]) were included. Reperfusion injury reduced the probability of a favourable functional outcome (90-day mRS 0-2) by 14.8% (ß=0.15; 95% CI [0.06;0.24];p=0.001. A serum HDL-C level above the median (1.15 mmol/L) decreased the probability of reperfusion injury by 13.6% (ß=-0.14; 95CI% [−0.22; −0.05];p=0.002) and increased the probability of favourable functional outcome by 13.2% (ß=-0.13; 95CI% [-0.22;-0.05];p=0.003). In sensitivity analyses, higher HDL-C levels were associated with lower odds of reperfusion injury (adjusted OR 0.62; 95% CI [0.43;0.88];p=0.008) and emerged as a predictor of a favourable functional outcome (adjusted OR 0.60; 95% CI [0.40; 0.90];p=0.015).ConclusionsIn patients undergoing thrombectomy for acLVO, higher serum levels of HDL-C were associated with a reduced probability of reperfusion injury and favourable functional outcome at 90 days.
GCS-H2 is essential for growth as it acts as the main relay for mitochondrial lipoylation in heterotrophic tissues ofArabidopsis thaliana
Authors: Przybyla-Toscano Jonathan , Boussardon Clément , Juvany Marta , Alseekh Saleh , Modde Katharina , Valentin Aurélien , Stenlund Hans , Bauwe Hermann , Fernie Alisdair R , Keech Olivier 
Published: October 2024

ABSTRACTH-protein is part of the multi-protein glycine cleavage system found in both prokaryotes and eukaryotes. TheArabidopsis thalianagenome contains three loci for genes encoding H-protein. We show that in land plants, there are two clades of mitochondrial H-proteins; one that clusters with H1 and H3, and another that clusters with H2, an isoform mostly expressed in heterotrophic tissue and for which a null mutation results in a >99% impeded growth. After showing that all three isoforms fulfill the same metabolic function, we evidenced that the impaired root growth inh2results from an altered cell cycle progression concomitant to a lower Target Of Rapamycin kinase activity. Subsequent metabolomic approaches revealed an accumulation of storage sugars and a significant decrease of the TCA intermediates and several vitamins in theh2root cells as compared to the wild-type ones.Additional investigations evidenced that H2 acts as the main relay for lipoylation in root mitochondria, which diverges from the current lipoylation model proposed for photosynthetic tissues. Together, this work provides new insight on the control of the cell cycle by mitochondrial metabolism, and also challenges the current dogma for lipoylation in mitochondria of plant cells.Once sentence summaryThe absence of GCS-H2, an isoform of H-protein found in heterotrophic tissue, impedes the cell cycle, and drastically affects plant growth as it acts as the main relay for mitochondrial lipoylation.
Charting the molecular landscape of neuronal organisation within the hippocampus using cryo electron tomography
Authors: Glynn Calina , Smith Jake L.R. , Case Matthew , Csöndör Rebecca , Katsini Ana , Sanita Maria E. , Glen Thomas S. , Pennington Avery , Grange Michael 
Published: October 2024

AbstractCellular cryo-electron tomography (cryoET) enables the capture of detailed structural information within a biologically relevant environment. However, information in more complex samples, such as tissues, is lacking. Importantly, these observations need to be set in context of populations; imaging on the molecular scale to-date is limited to few observationsin-situthat struggle to be generalised. This is due to limitations in throughput and versatility employed by current instrumentation. Here, we utilise plasma focused ion beam milling to examine the molecular landscape of mouse hippocampus by cryoET in targeted regions across multiple individuals revealing the complex organisation of macromolecules from the CA1 strata pyramidale (sp) to radiatum (sr). Our data represent a molecular atlas, producing snapshots of hippocampal architecture in adult mouse. The combination of instrumentation and application of technical advancements provides a framework to explore specific structural questions within native tissues in a targeted manner.
Deficient Memory, Long-Term Potentiation and Hippocampal Synaptic Plasticity in Galectin-4-KO Mice
Authors: Brocca María Elvira , Mora-Rubio Arancha , Alonso-Calviño Elena , Fernández-López Elena , Díez-Revuelta Natalia , Guirado Juan C. , Álvarez-Vélez Rebeca , Dopazo Ana , López-Merino Esperanza , Martos-Puñal David , Esteban José A. , Aguilar Juan , Higuero Alonso M. , Abad-Rodríguez José 
Published: October 2024

AbstractIntestinal infections trigger inflammation and can contribute to degenerative and cognitive brain pathologies through the microbiota-gut-brain axis. Galectin-4 is an intestinal lectin key in the control of pathogenic bacterial infections. Here we report that galectin-4 deficient mice (Lgals4-KO) show an altered intestinal commensal microbiota in the absence of pathogens, defining a new role of galectin-4 in the modulation of commensal bacteria. Strikingly, Lgals4-KO mice present a deficient memory formation, and impaired hippocampal long-term potentiation (LTP)in vivoandex vivo. Furthermore, Lgals4-KO neurons show a reduced activation of the AMPA receptor and of the CaMKII upon chemically induced LTPin vitro. These mice also display significantly lower dendritic spine density and shorter spine length in hippocampal dendrites, as well as an increased area of the postsynaptic densities, all coherent with an alteration of the synaptic function. In all, our results demonstrate that the absence of galectin-4 induces synaptic dysfunctions and memory impairment, along with changes in gut microbial composition, suggesting that variations in endogenous intestinal microbiota may cause or contribute to such neurological pathologies.
Cardiolipin Inhibits the Noncanonical Inflammasome by Preventing LPS Binding to Caspase 4/11 to Mitigate Endotoxemia in Vivo
Authors: Pizzuto Malvina , Monteleone Mercedes , Burgener Sabrina Sofia , Began Jakub , Kurera Melan , Chia Jing Rong , Frampton Emmanuelle , Crawford Joanna , Oliveira Monalisa , Kenney Kirsten M. , Coombs Jared R. , Yamamoto Masahiro , Man Si Ming , Broz Petr , Pelegrin Pablo , Schroder Kate 
Published: October 2024

AbstractIn Gram-negative bacterial sepsis, excessive caspase 4/11 activation in response to circulating bacterial lipid LPS (endotoxemia) can cause organ damage and mortality. Current inhibitors of caspase 4/11 also block caspase 1 activity and are therefore not appealing clinical candidates for treating Gram-negative sepsis. Here, we identify double-unsaturated 18:2 cardiolipin as a selective inhibitor of caspase 4/11-dependent inflammatory cytokine secretion and pyroptosis, without affecting caspase-1 responses. Cardiolipin targets the CARD domain of caspase 4/11, impeding its interaction with LPS to restrain caspase 4/11 activation, thereby suppressing endotoxemia-induced systemic inflammationin vivo. Thus, we present cardiolipin as a promising candidate for preventing endotoxemia- induced sequelae in sepsis while preserving caspase-1-driven anti-microbial immune responses. By identifying cardiolipin as a specific caspase 4/11 inhibitor, we provide an urgently-needed tool for studying caspase 4/11 functions in inflammatory pathways, and open the way to studies of noncanonical inflammasome regulation by endogenous cardiolipin.
Annual Variability in Diffuse Ratio and Spectral Characteristics of Solar Radiation: Cloud Effects in a Temperate Monsoon Region
Authors: Siriwardana Amila Nuwan , Kume Atsushi 
Published: October 2024

AbstractSolar radiation (SR) dynamics have a profound effect on plant growth, development, and ecosystems, and they act as a primary energy source and important environmental signal that plants perceive through their photoreceptors, which primarily sense critical wavelength ratios (CWRs). The diffuse fraction of solar radiation (DF) is a key factor affecting the quality and distribution of light within the plant canopy. We analyzed one year of SR spectral observations measured by a ground-based rotating shadow-band spectroradiometer to evaluate the potential effects of DF and CWRs on plants in an outdoor environment in Fukuoka, Japan. The daily mean DF and all considered CWRs showed significant seasonal variations regardless of the solar meridian altitude. Cloudy or partly cloudy skies were prevalent throughout the year. The ratios of ultraviolet-A (UV-A)/UV-B, red (R)/blue (B), and R/green (G) increased during winter and decreased during summer. Conversely, the ratios of photosynthetically active radiation (PAR)/global solar radiation (GSI), UV/GSI, UV/PAR, B/G, R/far-red (FR), and UV-B/B increased during summer and decreased during winter. Specific CWRs correlated with air mass (AM) and vapor pressure (VP), and most of the CWR correlated with DF. AM, VP, and DF were also found to have a combined effect on specific CWRs that are important for plant light signals. This highlights the potential influence of AM, VP, and DF on plant light signals, thereby opening avenues for the development of innovative models of plant growth and ecological responses that incorporate plant photoreception.
Generalizability of Normative Models of Brain Morphometry Across Distinct Ethnoracial Groups
Authors: Ge Ruiyang , Yu Yuetong , New Faye , Haas Shalaila S , Sanford Nicole , Yu Kevin , Leon Julian Camillo Becerra , Yang Guoyuan , Gao Jia-Hong , Nemoto Kiyotaka , Fukunaga Masaki , Matsumoto Junya , Hashimoto Ryota , Jahanshad Neda , Thompson Paul M , Frangou Sophia 
Published: October 2024

ABSTRACTNormative modeling of brain morphometric data can inform about the clinical significance of deviations from typical patterns in brain structure. Their usefulness, however, is dependent on their applicability to diverse ethnoracial groups. With this in mind, we developed age- and sex-specific normative models for cortical thickness, surface area, and subcortical volumes using brain scans from 37,407 healthy individuals from a diverse international sample. Here we demonstrate the validity of these models in diverse and distinct populations. Specifically, we tested these pre-trained models on independent samples of healthy individuals that either self-identified as Black, South Asian, East Asian Chinese, East Asian Japanese, or we categorized as African, Admixed American, East Asian, and European based on their genetic ancestry. Regardless of ethnoracial definition, the performance of the pretrained models in these samples was exceptionally high; the relative mean absolute error for each regional brain morphometry measure was less than 10% across all the distinct ethnoracial groups. These findings affirm the broad applicability of our models, ensuring that brain morphometry assessments using these models are accurate and reliable for individuals regardless of background. This broad applicability has significant implications for advancing personalized medicine and improving health outcomes in diverse populations.
Effects of a transmissible cancer on life-history traits in Tasmanian devils
Authors: Strickland Kasha , Jones Menna , Lachish Shelly , Comte Sebastien , Hamede Rodrigo , Hohenlohe Paul , McCallum Hamish , Storfer Andrew , Kruuk Loeske 
Published: October 2024

AbstractShifts in life history traits, such as timing of reproduction, can help mediate population declines following perturbations, and early reproduction should be favoured when adult survival is impacted more than juvenile survival. In Tasmanian devils, following the emergence of a fatal transmissible cancer, females started to breed precocially (i.e., at age one instead of typically age two) and the same time as populations started to decline following disease emergence. Here, we focus on a diseased site (Freycinet Peninsula, Tasmania, Australia) with 18 years of continuous mark-recapture data to test: (1) whether rates of precocial breeding in females continued to increase after the initial rise after the emergence of the disease, (2) whether there was a relationship between body size and breeding success for either one-year-olds or adult females (i.e., at least two-years-old), and (3) whether there was inbreeding depression in breeding success for either age category. We show that rates of precocial breeding did not continue to rise, and that the proportion of precocially breeding females has plateaued at around 50%. We also show that there was no effect of body size on the probability of breeding for either one-year-old or for adult females. Finally, we show that there was no evidence for inbreeding depression in breeding success for either age class. We discuss possible constraints that may have inhibited further rise in rates of precocial breeding in the context of limitations to growth in the offspring of precocially breeding (and therefore smaller) females.
Origin of plant trait data matters: Shared species of Northwestern Europe and the Pannonian Ecoregion have different trait values in the two regions
Authors: Sonkoly Judit , Török Péter 
Published: October 2024

AbstractTrait-based ecology considerably increased our comprehension of various fields related to ecology and evolution. As measuring traits can be time-consuming and costly, analyses regularly gather trait data from databases instead of carrying out new measurements. However, intraspecific trait variability can cause considerable differences between the trait values of different population and regions. Here we evaluated whether intraspecific trait variability causes considerable differences in trait values measured in two different regions of Europe. We tested whether regionally measured trait data from the Pannonian Ecoregion differ from trait data of the same species originating from Northwestern Europe, by comparing data from the Pannonian Database of Plant Traits (PADAPT) and the LEDA Traitbase. We evaluated six traits of the same set of species: thousand-seed mass (TSM), seed bank persistence index (SBPI), leaf area (LA), leaf dry matter content (LDMC), specific leaf area (SLA), and leaf dry mass. We found that trait data from the two databases significantly differed for TSM, SBPI, SLA, and LDMC. Our results indicate that the markedly different climate of the two regions can cause substantial intraspecific trait variation, therefore, the geographical origin of trait data matters in trait-based analyses. The findings corroborate the assumption that regionally measured trait data and building regional databases are essential for reliable regional-scale trait-based studies. We conclude that for studies analysing traits in the Pannonian Ecoregion (and possibly in Easter and Central Europe in general), it is advisable to use PADAPT instead of databases compiling data from regions with markedly different climatic conditions.
Mechanistic Insights into Alcohol-Induced DNA Crosslink Repair by the Fanconi Anemia Nuclease Slx4-Xpf-Ercc1
Authors: Havlikova Jana , Dejmek Milan , Huskova Andrea , Allan Anthony , Boura Evzen , Nencka Radim , Silhan Jan 
Published: October 2024

AbstractDuring cell division, DNA replication stalls upon alcohol-derived interstrand crosslink, employing DNA repair pathways. Acetaldehyde, a toxic metabolite of alcohol, can induce DNA crosslinks between complementary DNA strands, causing significant genomic instability. The repair of acetaldehyde DNA crosslinks (AA-ICLs) is vital for maintaining genome integrity and preventing mutagenic events. The Fanconi anemia (FA) repair pathway’s involvement in fixing the AA-ICLs is crucial, ensuring cellular homeostasis and safeguarding genomic stability. Dysregulation of the FA pathway has been linked to Fanconi anemia, a rare genetic disorder characterized by hypersensitivity to DNA-damaging agents, including acetaldehyde. However, the precise mechanism of the repair and incision of AA-ICLs is unknown. Here, we demonstrate the role of the FA pathway nuclease SLX4-XPF-ERCC1 (SXE) in the repair of AA-ICL. We have generated site-specific AA-ICL within the replication fork, and we found SXE to excise the crosslink from the replication fork, bringing evidence of its role in the repair of alcohol-induced DNA lesions. This nuclease complex performs two precise incisions around the lesion. We also demonstrate that the SXE nuclease excises an abasic site interstrand crosslink in a similar manner. Given the evidence in conjunction with previous repair studies that have been conducted, our work suggests that SXE is a versatile nuclease complex.
Human Brain-Wide Activation of Sleep Rhythms
Authors: Wang Haiteng , Zou Qihong , Zhang Jinbo , Gao Jia-Hong , Liu Yunzhe 
Published: October 2024

AbstractDuring sleep, our brain undergoes highly synchronized activity, orchestrated by distinct neural rhythms. Little is known about the associated brain activation during these sleep rhythms, and even less about their functional implications. In this study, we investigated the brain-wide activation underlying human sleep rhythms by employing simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in 107 participants during nocturnal nap (first half of the night). We identified robust coupling between slow oscillations (SOs) and fast spindles during deep non-rapid eye movement (NREM) sleep (N2/3 stages), with spindle peaks consistently occurring just before the SO UP-state. This SO-spindle coupling was linked to elevated activation in both the thalamus and hippocampus, alongside increased functional connectivity from the hippocampus to the thalamus and from the thalamus to the medial prefrontal cortex (mPFC). An open-ended cognitive state decoding analysis suggested that these activations may relate to episodic memory processes, yet were distinct from task-related networks. Together, these findings highlight the thalamus as a key coordinator of hippocampal-cortical communication during sleep and provide new insights into the mechanisms by which synchronized sleep rhythms may support memory consolidation.
Synaptic targets and cellular sources of CB1 cannabinoid receptor and vesicular glutamate transporter-3 expressing nerve terminals in relation to GABAergic neurons in the human cerebral cortex
Authors: Somogyi Peter , Horie Sawa , Lukacs Istvan , Hunter Emily , Sarkany Barbara , Viney Tim James , Livermore James , Plaha Puneet , Stacey Richard , Ansorge Olaf , El Mestikawy Salah , Zhao Qianru 
Published: October 2024

AbstractCannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunorective axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3. Of the CB1-immunopositive GABAergic terminals, 25% were vesicular-glutamate-transporter-3 (VGLUT3)-immunoreactive, suggesting GABAergic/glutamatergic co-transmission on dendritic shafts.In vitrorecorded and labelled VGLUT3 or CB1-positive GABAergic interneurons expressed cholecystokinin, vasoactive-intestinal-polypeptide and calretinin, had diverse firing, axons and dendrites, and included rosehip, neurogliaform and basket cells, but not double bouquet or axo-axonic cells. CB1-positive interneurons innervated pyramidal cells and GABAergic interneurons. Most glutamatergic synaptic terminals formed type-1 synapses and some were positive for CB1 receptor concentrated in the presynaptic active zone, unlike in GABAergic terminals. From the sampled VGLUT3-positive terminals, 60% formed type-1 synapses with dendritic spines (80%) or shafts (20%) and 52% were also positive for VGLUT1, suggesting intracortical origin. Some VGLUT3-positive terminals were immunopositive for vesicular-monoamine-transporter-2, suggesting 5-HT/glutamate co-transmission. Overall, the results show that CB1 regulates GABA release mainly to dendritic shafts of both pyramidal cells and interneurons, and predict CB1-regulated co-release of GABA and glutamate from single cortical interneurons. We also demonstrate the co-existence of multiple vesicular glutamate transporters in a select population of terminals probably originating from cortical neurons and innervating dendritic spines in the human cerebral cortex.
Lowering the switching cost related to the activation of burdensome gene circuits promotes cell population homogeneity and productivity
Authors: Henrion Lucas , Vandenbroucke Vincent , Martinez Juan Andres , Kopp Julian , Telek Samuel , Zicler Andrew , Delvigne Frank 
Published: October 2024

AbstractThe activation of gene circuits can impose a significant burden on cells, leading to heterogeneous expression and reduced productivity. In this work, we focused on the T7 production system inE. coliBL21, a prime example of a burdensome gene circuit, to investigate the main cause for this gene expression heterogeneity and methods to mitigate it. Based on continuous cultivation analyzed and control by automated flow cytometry, we quantified the trade-off between cellular growth and gene expression and tracked the cell-to-cell heterogeneity in gene expression (measured as entropy). We concluded that the growth reduction associated to the activation of the burdensome gene circuit, i.e., the switching cost, is at the origin of the population heterogeneity. The loss of growth rate imposed by the burdensome activation of the gene is compensated at the population level by the overgrowth of less induced cells that safeguard the population by generating entropy. We tried to homogenize the population by pulsing the inducer with increasing frequency but found that the population escapes control through promoter mutation, leading to a genotype exhibiting reduced gene expression, but also, reduced entropy. To engineer a more homogeneous population without sacrificing gene expression, we decreased the switching cost associated to the induction by lowering the quality of the main carbon source. This strategy successfully led to a more homogeneous and productive population. Our approach allows for a precise quantification of the trade-off between growth and gene expression in cell population cultivated under dynamic conditions and highlights the importance of the switching cost for designing efficient approaches of cell population control.