bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial ischemia-reperfusion injury upregulates nucleostemin expression via HIF-1α and c-Jun pathways and alleviates apoptosis by promoting autophagy
Authors: Han Xiao , Jiang Zhicheng , Hou Yufeng , Zhou Xiaorong , Hu Baoying 
Published: October 2024

AbstractMyocardial ischemia-reperfusion (I/R) injury, often arising from interventional therapy for acute myocardial infarction, leads to irreversible myocardial cell death. While previous studies indicate that nucleostemin (NS) is induced by myocardial I/R injury and mitigates myocardial cell apoptosis, the underlying mechanisms are poorly understood. Here, our study reveals that NS upregulation is critical for preventing cardiomyocyte death following myocardial I/R injury. Elevated NS protein levels were observed in myocardial I/R injury mouse and rat models, as well as Hypoxia/reoxygenation (H/R) cardiac cell lines (H9C2 cells). We identified binding sites for c-Jun and HIF-1α in the NS promoter region. Inhibition of JNK and HIF-1α led to a significant decrease in NS transcription and protein expression. Furthermore, inhibition of autophagy and NS expression promoted myocardial cell apoptosis in H/R. Notably, the cell model showed reduced LC3I transformation to LC3II, downregulated Beclin1, upregulated p62, and altered expression of autophagy-related proteins upon NS interference in H/R cells. These findings suggest that NS expression, driven by c-Jun and HIF-1α pathways, facilitates autophagy, providing protection against both myocardial I/R injury and H/R-induced cardiomyocyte apoptosis.
Unraveling the landscape of m6A RNA methylation in wound healing and scars
Authors: Zhang Qi , Dong Liming , Gong Song , Wang Ting 
Published: October 2024

AbstractWound healing is a complex process involving sequential stages of hemostasis, inflammation, proliferation, and remodeling. Multiple cell types and factors, including underlying conditions like diabetes and bacterial colonization, can influence healing outcomes and scar formation. N6-methyladenosine (m6A), a predominant RNA modification, plays crucial roles in gene expression regulation, impacting various biological processes and diseases. m6A regulates embryonic skin morphogenesis, wound repair, and pathophysiological processes like inflammation and angiogenesis. Recent studies have highlighted the role of m6A in wound healing, scar formation, and tissue remodeling. Additionally, m6A presents a unique expression pattern in pathological wounds and scars, potentially influencing wound healing and scar formation through modulating gene expression and cellular signaling, thereby serving as potential biomarkers or therapeutic targets. Targeting m6A modifications are potential strategies to enhance wound healing and reduce scar formation. This review aims to explore the roles and mechanisms of m6A RNA methylation in wound healing and scars, and discuss current challenges and perspectives. Continued research in this field will provide significant value for optimal wound repair and scar treatment.
Physiological and pathogenic T cell autoreactivity converge in type 1 diabetes
Authors: Eugster Anne , Lorenc Anna , Kotrulev Martin , Kamra Yogesh , Goel Manisha , Steinberg-Bains Katja , Sabbah Shereen , Dietz Sevina , Bonifacio Ezio , Peakman Mark , Gomez-Tourino Iria 
Published: October 2024

AbstractAutoimmune diseases result from autoantigen-mediated activation of adaptive immunity; intriguingly, autoantigen-specific T cells are also present in healthy donors. An assessment of dynamic changes of this autoreactive repertoire in both health and disease is thus warranted. Here we investigate the physiological versus pathogenic autoreactive processes in the context of Type 1 diabetes (T1D) and one of its landmark autoantigens, glutamic acid decarboxylase 65 (GAD65). Using single cell gene expression profiling and tandem T cell receptor (TCR) sequencing, we find that GAD65-specific true naïve cells are present in both health and disease, with GAD65-specific effector and memory responses showing similar ratios in healthy donors and patients. Deeper assessment of phenotype and TCR repertoire uncover differential features in GAD65-specific TCRs, including lower clonal sizes of healthy donor-derived clonotypes in patients. We thus propose a model whereby physiological autoimmunity against GAD65 is needed during early life, and that alterations of these physiological autoimmune processes in predisposed individuals trigger overt Type 1 diabetes.
A temperature-sensitive metabolic valve and a transcriptional feedback loop drive rapid homeoviscous adaptation in Escherichia coli
Authors: Hoogerland Loles , van den Berg Stefan Pieter Hendrik , Suo Yixing , Moriuchi Yuta W. , Zoumaro-Djayoon Adja , Geurken Esther , Yang Flora , Bruggeman Frank , Burkart Michael D. , Bokinsky Gregory 
Published: October 2024

AbstractAll free-living microorganisms homeostatically maintain the fluidity of their membranes by adapting lipid composition to environmental temperatures. Here, we quantify enzymes and metabolic intermediates of the Escherichia coli fatty acid and phospholipid synthesis pathways, to describe how this organism measures temperature and restores optimal membrane fluidity within a single generation after a temperature shock. A first element of this regulatory system is a temperature-sensitive metabolic valve that allocates flux between the saturated and unsaturated fatty acid synthesis pathways via the branchpoint enzymes FabI and FabB. A second element is a transcription-based negative feedback loop that counteracts the temperature-sensitive valve. The combination of these elements accelerates membrane adaptation by causing a transient overshoot in the synthesis of saturated or unsaturated fatty acids following temperature shocks. This strategy is comparable to increasing the temperature of a water bath by adding water that is excessively hot rather than adding water at the desired temperature. These properties are captured in a mathematical model, which we use to show how hard-wired parameters calibrate the system to generate membrane compositions that maintain constant fluidity across temperatures. We hypothesize that core features of the E. coli system will prove to be ubiquitous features of homeoviscous adaptation systems.
Structure of the turnover-ready state of an ancestral respiratory complex I
Authors: Ivanov Bozhidar S. , Bridges Hannah R. , Jarman Owen D. , Hirst Judy 
Published: October 2024

AbstractRespiratory complex I is pivotal for cellular energy conversion, harnessing energy from NADH:ubiquinone oxidoreduction to drive protons across energy-transducing membranes for ATP synthesis. Despite detailed structural information on complex I, its mechanism of catalysis remains elusive due to lack of accompanying functional data for comprehensive structure-function analyses. Here, we present the 2.3-Å resolution structure of complex I from the α-proteobacterium Paracoccus denitrificans, a close relative of the mitochondrial progenitor, in phospholipid-bilayer nanodiscs. Three eukaryotic-type supernumerary subunits (NDUFS4, NDUFS6 and NDUFA12) plus a novel L-isoaspartyl-O-methyltransferase are bound to the core complex. Importantly, the enzyme is in a single, homogeneous resting state that matches the closed, turnover-ready (active) state of mammalian complex I. Our structure reveals the elements that stabilise the closed state and completes P. denitrificans complex I as a unified platform for combining structure, function and genetics in mechanistic studies.
Innate immune control of influenza virus interspecies adaptation via IFITM3
Authors: Denz Parker J. , Speaks Samuel , Kenney Adam D. , Eddy Adrian C. , Papa Jonathan L. , Roettger Jack , Scace Sydney C. , Rubrum Adam , Hemann Emily A. , Forero Adriana , Webby Richard J. , Bowman Andrew S. , Yount Jacob S. 
Published: October 2024

AbstractInfluenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigate whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in interspecies virus infection and adaptation. We find that IFITM3-deficient mice and human cells can be infected with low doses of avian influenza viruses that fail to infect WT counterparts, identifying a new role for IFITM3 in controlling the minimum infectious virus dose threshold. Remarkably, influenza viruses passaged through Ifitm3−/− mice exhibit enhanced host adaptation, a result that is distinct from viruses passaged in mice deficient for interferon signaling, which exhibit attenuation. Our data demonstrate that IFITM3 deficiency uniquely facilitates potentially zoonotic influenza virus infections and subsequent adaptation, implicating IFITM3 deficiencies in the human population as a vulnerability for emergence of new pandemic viruses.
Resolving optimal ionomer interaction in fuel cell electrodes via operando X-ray absorption spectroscopy
Authors: Wang Mengnan , Zhang Jiaguang , Favero Silvia , Higgins Luke J. R. , Luo Hui , Stephens Ifan E. L. , Titirici Maria-Magdalena 
Published: October 2024

AbstractTo bridge the gap between oxygen reduction electrocatalysts development and their implementation in real proton exchange membrane fuel cell electrodes, an important aspect to be understood is the interaction between the carbon support, the active sites, and the proton conductive ionomer as it greatly affects the local transportations to the catalyst surface. Here we show that three Pt/C catalysts, synthesized using the polyol method with different carbon supports (low surface area Vulcan, high surface area Ketjenblack, and biomass-derived highly ordered mesoporous carbon), revealed significant variations in ionomer-catalyst interactions. The Pt/C catalysts supported on ordered mesoporous carbon derived from biomass showed the best performance under the gas diffusion electrode configuration. Through a unique approach of operando X-ray Absorption Spectroscopy combined with gas sorption analysis, we were able to demonstrate the beneficial effect of mesopore presence for optimal ionomer-catalyst interaction at both molecular and structural level.
Imprinted atomic displacements drive spin–orbital order in a vanadate perovskite
Authors: Radhakrishnan Padma , Rabinovich Ksenia S. , Boris Alexander V. , Fürsich Katrin , Minola Matteo , Christiani Georg , Logvenov Gennady , Keimer Bernhard , Benckiser Eva 
Published: October 2024

Abstract
Perovskites with the generic composition ABO3 exhibit an enormous variety of quantum states, such as orbital order, magnetism and superconductivity. Their flexible and comparatively simple structure allows for straightforward chemical substitution and cube-on-cube combination of different compounds in atomically sharp epitaxial heterostructures. Many of the diverse physical properties of perovskites are determined by small deviations from the ideal cubic perovskite structure, which are challenging to control. Here we show that directional imprinting of atomic displacements in the antiferromagnetic Mott insulator YVO3 can be achieved by depositing epitaxial films on different facets of the same isostructural substrate. These facets were chosen such that other well-known control parameters, including lattice and polarity mismatch with the overlayer, remain nearly unchanged. We observe signatures of staggered orbital and magnetic order and demonstrate distinct spin–orbital ordering patterns on different facets. We attribute these results to the influence of specific octahedral rotation and cation displacement patterns, which are imprinted by the substrate facet, on the covalency of the bonds and the superexchange interactions in YVO3. Our results show that substrate-induced templating of lattice distortion patterns constitutes a pathway for materials design beyond established strain-engineering strategies.
Universality of ecological memory for local and global net ecosystem exchange, atmospheric CO2, and sea surface temperature
Authors: Elnar Allan Roy B. , Bernido Christopher C. 
Published: October 2024

AbstractModeling global net ecosystem exchange is essential to understanding and quantifying the complex interactions between the Earth’s terrestrial ecosystems and the atmosphere. Emphasizing the inter-relatedness between the global net ecosystem exchange, global sea surface temperature, and atmospheric $${\text {CO}}_{2}$$

CO
2

levels, intuitively suggests that all three systems may exhibit collective environmental memory. Motivated by this, we explicitly identified a collective memory function and showed a similar non-Markovian stochastic behavior for these systems exhibiting superdiffusive behavior in short time intervals. We obtained the values of the memory parameter, $$\mu$$
μ
, and the characteristic frequencies, $$\nu$$
ν
, for global net ecosystem exchange (GNEE) ($$\mu = 0.94\pm 0.03, \nu = 0.67\pm 0.08/mo.$$

μ
=
0.94
±
0.03
,
ν
=
0.67
±
0.08
/
m
o
.

), global sea surface temperature (GSST) ($$\mu = 0.68\pm 0.11, \nu = 0.30\pm 0.18/mo.$$

μ
=
0.68
±
0.11
,
ν
=
0.30
±
0.18
/
m
o
.

), and atmospheric $${\text {CO}}_{2}$$

CO
2

($$\mu = 0.78\pm 0.08, \nu =0.66\pm 0.13/wk.$$

μ
=
0.78
±
0.08
,
ν
=
0.66
±
0.13
/
w
k
.

). The values of the memory parameter are within the range, $$0< \mu < 1$$

0
<
μ
<
1

, and thus all three systems are in the superdiffusive regime. We emphasize, further, that these results were consistent with our previous analyses at the ecosystem level (i.e. Great Barrier Reef) suggesting scale invariance for these phenomena. Thus, the observed superdiffusive behavior operating at different scales suggests universality of the collective memory function for these systems.
Rapid increase of MFGE8 secretion from endometrial epithelial cells is an indicator of extracellular vesicle mediated embryo maternal dialogue
Authors: Muhandiram Subhashini , Kodithuwakku Suranga , Godakumara Kasun , Fazeli Alireza 
Published: October 2024

AbstractSuccessful embryo implantation relies on synchronized dialog between the embryo and endometrium, and the role of extracellular vesicles (EVs) in facilitating this cross-talk has been recently established. In our previous study, milk fat globule-EGF factor 8 protein (MFGE8) was identified as increasing in receptive endometrial epithelial cells (EECs) in response to trophoblastic EVs. However, the dynamics of MFGE8 protein in this context are not completely understood. Therefore, we examined its expression and secretion in EECs exposed to estrogen, progesterone, and trophoblastic EVs to gain deeper insights into its potential as an indicator of EV-mediated embryo-maternal dialogue. Our findings revealed that MFGE8 secretion is sensitive to estrogen and progesterone, and that trophoblastic EVs stimulate their release in both receptive and non-receptive EECs. Furthermore, trophoblast EV function was dose and time-dependent. Notably, the secretion of MFGE8 increased within a short timeframe of 30 min after addition of EVs, suggesting the possibility of rapid processes such as binding, fusion or internalization of trophoblastic EVs within EECs. Interestingly, MFGE8 released from EECs was associated with EVs, suggesting increased EV secretion from EECs in response to embryonic signals. In conclusion, increased MFGE8 secretion in this embryo implantation model can serve as an indicator of EV-mediated embryo-maternal dialogue.
Biofilms in modern CaCO3-supersaturated freshwater environments reveal viral proxies
Authors: Słowakiewicz Mirosław , Borkowski Andrzej , Perri Edoardo , Działak Paweł , Tagliasacchi Ezher , Gradziński Michał , Kele Sándor , Reuning Lars , Kibblewhite Tom , Whitaker Fiona , Reid R. Pamela , Tucker Maurice E. 
Published: October 2024

AbstractBiofilms are mucilaginous-organic layers produced by microbial activity including viruses. Growing biofilms form microbial mats which enhance sediment stability by binding particles with extracellular polymeric substances and promoting growth through nutrient cycling and organic matter accumulation. They preferentially develop at the sediment-water interface of both marine and non-marine environments, and upon the growing surfaces of modern tufa and travertine. In this context, however, little is known about the factors, environmental or anthropogenic, which affect viral communities in freshwater spring settings. To explore this issue, geochemical and metagenomic data were subjected to multidimensional analyses (Principal Component Analysis, Classical Multidimensional Scaling, Partial Least Squares analysis and cluster analysis based on beta-diversity), and these show that viral composition is specific and dependent on environment. Indeed, waters precipitating tufa and travertine do vary in their geochemistry with their viruses showing distinct variability between sites. These differences between virus groups allow the formulation of a viral proxy, based on the Caudoviricetes/Megaviricetes ratio established on the most abundant groups of viruses. This ratio may be potentially used in analysing ancient DNA preserved in carbonate formations as an additional source of information on the microbiological community during sedimentation.
Gastrointestinal and respiratory morbidity when introducing eggs as complementary food: a randomised controlled trial in South African infants
Authors: Nakiranda Regina , Malan Linda , Ricci Hannah , Kruger Herculina S. , Nienaber Arista , Visser Marina , Ricci Cristian , Faber Mieke , Smuts Cornelius M. 
Published: October 2024

AbstractWe investigated the incidence and duration of morbidity symptoms among infants aged 6 to 9 months from a low socioeconomic community receiving one egg daily for 6 months. This was a secondary outcome of a randomised controlled trial (RCT) of 500 infants conducted in Jouberton, South Africa. The primary outcome was linear growth. Morbidity data were collected weekly using a symptoms diary and qualitative data with focus group discussions at the endpoint. Ethical approval was obtained from the North-West University Health Research Ethics Committee. The intervention group had a ~ 5% higher incidence of gastrointestinal morbidity (17.0%) compared to the control group (11.9%). Gastrointestinal morbidity without fever tended to be 1.4 times higher in the intervention group (OR: 1.43, 95% CI: 1.03, 1.93; P = 0.058) and tended to be 4 times higher with fever (OR: 4.07, 95% CI: 0.86, 19.23; P = 0.077). The duration of total gastrointestinal and respiratory morbidity was 1.5 days longer in the intervention group (β: 1.491; 95% CI 0.064, 2.918; P = 0.041). Complementary feeding with eggs may have contributed towards an increased risk for gastrointestinal morbidity.
The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells
Authors: Fernández Laura , Kong Chow-Seng , Alkhoury Majd , Tryfonos Maria , Brighton Paul J. , Rawlings Thomas M. , Muter Joanne , Gori Maria Soledad , Leirós Claudia Pérez , Lucas Emma S. , Brosens Jan J. , Ramhorst Rosanna 
Published: October 2024

AbstractDecidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulator of cell fate divergence of decidualizing EnSC into anti-inflammatory DC and pro-inflammatory senescent decidual cells (snDC). Knockdown of HSPA5 in primary EnSC resulted both in decreased expression of DC marker genes and attenuated induction of senescence associated β-galactosidase activity, a marker of snDC. Stalling of the decidual reaction upon HSPA5 knockdown was apparent at 8 days of differentiation and was preceded by the upregulation of ER stress associated proteins IRE1α and PERK. Further, HSPA5 knockdown impaired colony-forming unit activity of primary EnSC, indicative of loss of cellular plasticity. Together, our results point to a key role for HSPA5/BiP in decidual transformation of EnSCs and highlight the importance of constraining ER stress levels during this process.
Humans versus models: a comparative assessment of ecosystem services models and stakeholders’ perceptions
Authors: David João , Cabral Pedro , Campos Felipe S. 
Published: October 2024

AbstractMapping the production of Ecosystem Services (ES) is imperative for sustainable ecosystem management. Likewise, incorporating expert knowledge enhances ES research. Here, we calculate eight multi-temporal ES indicators for mainland Portugal using a spatial modelling approach. These indicators are then integrated into the novel ASEBIO index—Assessment of Ecosystem Services and Biodiversity—which depicts a combined ES potential based on CORINE Land Cover, using a multi-criteria evaluation method with weights defined by stakeholders through an Analytical Hierarchy Process (AHP). Outputs from the modelling show how ES have changed in Portugal in relation to land use changes, including trade-offs between 1990 and 2018. The composed ASEBIO index is compared against the stakeholders’ valuation of ES potential for the year 2018. The results reveal a significant mismatch between the ES potential perceived by stakeholders and the models, with stakeholder estimates being 32.8% higher on average. All the selected ES were overestimated by the stakeholders. Drought regulation and erosion prevention have the highest contrasts, while water purification, food production and recreation are the most closely aligned among both approaches. Providing the first national overview about the status of multiple ES over a 28 year-period, our findings highlight potential disparities between data-driven and stakeholder-based evaluations. Therefore, we suggest the need for integrative strategies that consider scientific models with expert knowledge for more effective ES assessments and land-use planning. This approach could help bridge the gap between data-driven models and human perspectives, resulting in more balanced and inclusive decision-making.
Data-driven modeling of subharmonic forced response due to nonlinear resonance
Authors: Axås Joar , Bäuerlein Bastian , Avila Kerstin , Haller George 
Published: October 2024

AbstractComplex behavior in nonlinear dynamical systems often arises from resonances, which enable intricate energy transfer mechanisms among modes that otherwise would not interact. Theoretical, numerical and experimental methods are available to study such behavior when the resonance arises among modes of the linearized system. Much less understood are, however, resonances arising from nonlinear modal interactions, which cannot be detected from a classical linear analysis. Academic examples of such phenomena have been known, but no systematic method has been developed to detect and model nonlinear resonant interactions purely from numerical or experimental data. Here, we develop such a data-driven methodology that identifies nonlinear resonant response on low-dimensional spectral submanifolds (SSMs) of the dynamical system. Our approach is generally applicable to nonlinear resonances, but we specifically focus here on one particular behavior: subharmonic response in forced nonlinear systems without any resonance among the linearized frequencies of the unforced system. We first illustrate analytically how such a response is born out of a nonlinear resonance hidden in the conservative limit of the system. We then show how this effect can be identified and modeled purely from data. As our main example, we isolate and model previously unexplained response patterns in fluid sloshing experiments.