bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensification and Poleward Shift of Compound Wind and Precipitation Extremes in a Warmer Climate
Authors: Li Delei , Zscheischler Jakob , Chen Yang , Yin Baoshu , Feng Jianlong , Freund Mandy , Qi Jifeng , Zhu Yuchao , Bevacqua Emanuele 
Published: June 2024

AbstractCompound wind and precipitation extremes (CWPEs) can severely impact natural and socioeconomic systems. However, our understanding of CWPE future changes, drivers, and uncertainties under a warmer climate is limited. Here, by analyzing the event both on oceans and landmasses via state‐of‐the‐art climate model simulations, we reveal a poleward shift of CWPE occurrences by the late 21st century, with notable increases at latitudes exceeding 50° in both hemispheres and decreases in the subtropics around 25°. CWPE intensification occurs across approximately 90% of global landmasses, and is most pronounced under a high‐emission scenario. Most changes in CWPE frequency and intensity (about 70% and 80%, respectively) stem from changes in precipitation extremes. We further identify large uncertainties in CWPE changes, which can be understood at the regional level by considering climate model differences in trends of CWPE drivers. These results provide insights into understanding CWPE changes under a warmer climate, aiding robust regional adaptation strategy development.
Neuron type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct
Authors: Kim Ra Gyung , Cho Jongwook , Park Ji-Young , Kim Young Ro , Lee Min-Cheol , Kim Hyoung-Ihl 
Published: June 2024

AbstractCortical neuromodulation (CNM) is widely used to promote recovery after stroke. Despite the beneficial results of CNM, the roles played by different neuron types in the effects of current CNM techniques are unable to be differentiated. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to poststroke recovery. We transduced the sensory-parietal cortex (SPC) of rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons resulted in significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed a significant reduction in cortical diaschisis and activation of the corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in the stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that the plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could improve poststroke outcomes.
O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts
Authors: Very Ninon , Boulet Clémence , Gheeraert Céline , Berthier Alexandre , Johanns Manuel , Bou Saleh Mohamed , Guille Loïc , Bray Fabrice , Strub Jean-Marc , Bobowski-Gerard Marie , Zummo Francesco P. , Vallez Emmanuelle , Molendi-Coste Olivier , Woitrain Eloise , Cianférani Sarah , Montaigne David , Ntandja-Wandji Line Carolle , Dubuquoy Laurent , Dubois-Chevalier Julie , Staels Bart , Lefebvre Philippe , Eeckhoute Jérôme 
Published: June 2024

AbstractTissue injury causes activation of mesenchymal lineage cells into wound-repairing myofibroblasts (MFs), whose uncontrolled activity ultimately leads to fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, we report that the metabolic sensor post-translational modification O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) is increased and required for myofibroblastic activation. Inhibition of protein O-GlcNAcylation impairs archetypal myofibloblast cellular activities including extracellular matrix gene expression and collagen secretion/deposition as defined in vitro and using ex vivo and in vivo murine liver injury models. Mechanistically, a multi-omics approach combining proteomic, epigenomic, and transcriptomic data mining revealed that O-GlcNAcylation controls the MF transcriptional program by targeting the transcription factors Basonuclin 2 (BNC2) and TEA domain transcription factor 4 (TEAD4) together with the Yes-associated protein 1 (YAP1) co-activator. Indeed, inhibition of protein O-GlcNAcylation impedes their stability leading to decreased functionality of the BNC2/TEAD4/YAP1 complex towards promoting activation of the MF transcriptional regulatory landscape. We found that this involves O-GlcNAcylation of BNC2 at Thr455 and Ser490 and of TEAD4 at Ser69 and Ser99. Altogether, this study unravels protein O-GlcNAcylation as a key determinant of myofibroblastic activation and identifies its inhibition as an avenue to intervene with fibrogenic processes.
Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila
Authors: Pilesi Eleonora , Tesoriere Giulia , Ferriero Angelo , Mascolo Elisa , Liguori Francesco , Argirò Luca , Angioli Chiara , Tramonti Angela , Contestabile Roberto , Volontè Cinzia , Vernì Fiammetta 
Published: June 2024

AbstractVitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5’-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign RasV12 tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgllPNPO gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating RasV12 and downregulating Discs-large (Dlg) gene. Moreover, we found that RasV12 eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding RasV12 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in RasV12DlgRNAi 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.
Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency
Authors: Goehring Liana , Keegan Sarah , Lahiri Sudipta , Xia Wenxin , Kong Michael , Jimenez-Sainz Judit , Gupta Dipika , Drapkin Ronny , Jensen Ryan B. , Smith Duncan J. , Rothenberg Eli , Fenyö David , Huang Tony T. 
Published: June 2024

AbstractBRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of head-on transcription-replication conflicts (HO-TRCs). Using Okazaki-fragment sequencing (Ok-seq) and computational analysis, we identified origins (dormant origins) that are activated near the transcription termination sites (TTS) of highly expressed, long genes in response to replication stress. Dormant origins are a source for HO-TRCs, and drug treatments that inhibit dormant origin firing led to a reduction in HO-TRCs, R-loop formation, and DNA damage. Using super-resolution microscopy, we showed that HO-TRC events track with elongating RNA polymerase II, but not with transcription initiation. Importantly, RNase H2 is recruited to sites of HO-TRCs in a BRCA2-dependent manner to help alleviate toxic R-loops associated with HO-TRCs. Collectively, our results provide a mechanistic basis for how BRCA2 shields against genomic instability by preventing HO-TRCs through both direct and indirect means occurring at predetermined genomic sites based on the pre-cancer transcriptome.
Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status
Authors: Wearn Alfie , Tremblay Stéfanie A. , Tardif Christine L. , Leppert Ilana R. , Gauthier Claudine J. , Baracchini Giulia , Hughes Colleen , Hewan Patrick , Tremblay-Mercier Jennifer , Rosa-Neto Pedro , Poirier Judes , Villeneuve Sylvia , Schmitz Taylor W. , Turner Gary R. , Spreng R. Nathan ,   PREVENT-AD Research Group
Published: June 2024

AbstractThe neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer’s disease (AD). They project broadly throughout the brain’s white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.
IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice
Authors: Muckenhuber Moritz , Mengrelis Konstantinos , Weijler Anna Marianne , Steiner Romy , Kainz Verena , Buresch Marlena , Regele Heinz , Derdak Sophia , Kubetz Anna , Wekerle Thomas 
Published: June 2024

AbstractThe efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with ATG allowed CTLA4-Ig therapy to achieve long-term, rejection-free heart allograft survival. This beneficial effect was abolished upon Treg depletion. Combining ATG with IL-6 blockade prevents costimulation blockade-resistant rejection, thereby eliminating a major impediment to clinical use of costimulation blockers in transplantation.
Recovery of europium from E-waste using redox active tetrathiotungstate ligands
Authors: Perrin Marie A. , Dutheil Paul , Wörle Michael , Mougel Victor 
Published: June 2024

AbstractRare-earth elements (REEs) are critical to our modern economy, yet their mining from natural ores bears a profound environmental impact. Traditional separation techniques are chemical and energy-intensive because their chemical similarities make REEs very challenging to purify, requiring multiple extraction steps to achieve high purity products. This emphasizes the need for sustainable and straightforward separation methods. Here we introduce a strategy for the direct separation of europium (Eu) from complex mixtures under ambient conditions, leveraging on the redox non innocence of purely inorganic tungsten tetrathiolate (WS42−) ligands. The recovery of Eu is achieved upon reduction of Eu(III) to a Eu(II) coordination polymer, driven by an induced internal electron transfer from the tetrathiotungstate ligand. Applying this strategy to unconventional feedstock such as spent energy-saving lamps allows selective europium recovery with separation factors over 1000 and recovery efficiency as high as 99% without pre-treatment of the waste.
Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
Authors: Salihovic Samira , Nyström Niklas , Mathisen Charlotte Bache-Wiig , Kruse Robert , Olbjørn Christine , Andersen Svend , Noble Alexandra J. , Dorn-Rasmussen Maria , Bazov Igor , Perminow Gøri , Opheim Randi , Detlie Trond Espen , Huppertz-Hauss Gert , Hedin Charlotte R. H. , Carlson Marie , Öhman Lena , Magnusson Maria K. , Keita Åsa V. , Söderholm Johan D. , D’Amato Mauro , Orešič Matej , Wewer Vibeke , Satsangi Jack , Lindqvist Carl Mårten , Burisch Johan , Uhlig Holm H. , Repsilber Dirk , Hyötyläinen Tuulia , Høivik Marte Lie , Halfvarson Jonas 
Published: June 2024

AbstractImproved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.
Observation of nonlinear response and Onsager regression in a photon Bose-Einstein condensate
Authors: Sazhin Alexander , Gladilin Vladimir N. , Erglis Andris , Hellmann Göran , Vewinger Frank , Weitz Martin , Wouters Michiel , Schmitt Julian 
Published: June 2024

AbstractThe quantum regression theorem states that the correlations of a system at two different times are governed by the same equations of motion as the single-time averages. This provides a powerful framework for the investigation of the intrinsic microscopic behaviour of physical systems by studying their macroscopic response to a controlled external perturbation. Here we experimentally demonstrate that the two-time particle number correlations in a photon Bose-Einstein condensate inside a dye-filled microcavity exhibit the same dynamics as the response of the condensate to a sudden perturbation of the dye molecule bath. This confirms the regression theorem for a quantum gas, and, moreover, demonstrates it in an unconventional form where the perturbation acts on the bath and only the condensate response is monitored. For strong perturbations, we observe nonlinear relaxation dynamics which our microscopic theory relates to the equilibrium fluctuations, thereby extending the regression theorem beyond the regime of linear response.
Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice
Authors: Mao Xiaotian , Larsen Sabina Birgitte , Zachariassen Line Sidsel Fisker , Brunse Anders , Adamberg Signe , Mejia Josue Leonardo Castro , Larsen Frej , Adamberg Kaarel , Nielsen Dennis Sandris , Hansen Axel Kornerup , Hansen Camilla Hartmann Friis , Rasmussen Torben Sølbeck 
Published: June 2024

AbstractMetabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.
Novel temperatures are already widespread beneath the world’s tropical forest canopies
Authors: Trew Brittany T. , Edwards David P. , Lees Alexander C. , Klinges David H. , Early Regan , Svátek Martin , Plichta Roman , Matula Radim , Okello Joseph , Niessner Armin , Barthel Matti , Six Johan , Maeda Eduardo E. , Barlow Jos , do Nascimento Rodrigo Oliveria , Berenguer Erika , Ferreira Joice , Sallo-Bravo Jhonatan , Maclean Ilya M. D. 
Published: June 2024

AbstractTropical forest biodiversity is potentially at high risk from climate change, but most species reside within or below the canopy, where they are buffered from extreme temperatures. Here, by modelling the hourly below-canopy climate conditions of 300,000 tropical forest locations globally between 1990 and 2019, we show that recent small increases in below-canopy temperature (<1 °C) have led to highly novel temperature regimes across most of the tropics. This is the case even within contiguous forest, suggesting that tropical forests are sensitive to climate change. However, across the globe, some forest areas have experienced relatively non-novel temperature regimes and thus serve as important climate refugia that require urgent protection and restoration. This pantropical analysis of changes in below-canopy climatic conditions challenges the prevailing notion that tropical forest canopies reduce the severity of climate change impacts.
Fractional dynamics study: analytical solutions of modified Kordeweg-de Vries equation and coupled Burger’s equations using Aboodh transform
Authors: Iqbal Naveed , Hussain Shah , Hamza Amjad E. , Abdullah Ali , Mohammed Wael W. , Yar Mohammad 
Published: June 2024

AbstractThe study examines the using of Aboodh residual power series method and the Aboodh transform iteration method (ATIM) to analyze modified Korteweg-de Vries equation (mKdV) beside coupled Burger’s equations in the framework of the Caputo operator. These sets of equations represent the non-linear wave description for various physical systems. Through APM and ATIM, the solution for the coupled Burger’s equations and the mKdV equation get accurate dynamics information that will reveal the nature of their interactions. Using mathematically proven techniques and computational simulations, the developed methods’ efficiency and reliability are illustrated in the complex behaviors of these nonlinear wave equations, so that we can gain deeper insights into their complex dynamics. The research is aimed at an increase of the knowledge about the fractional calculus utilization for nonlinear wave motion and it also provides analytical tools for an analysis of wave acting in different scientific and engineering areas.
Effects of bone surface topography and chemistry on macrophage polarization
Authors: Özcolak Birgün , Erenay Berkay , Odabaş Sedat , Jandt Klaus D. , Garipcan Bora 
Published: June 2024

AbstractSurface structure plays a crucial role in determining cell behavior on biomaterials, influencing cell adhesion, proliferation, differentiation, as well as immune cells and macrophage polarization. While grooves and ridges stimulate M2 polarization and pits and bumps promote M1 polarization, these structures do not accurately mimic the real bone surface. Consequently, the impact of mimicking bone surface topography on macrophage polarization remains unknown. Understanding the synergistic sequential roles of M1 and M2 macrophages in osteoimmunomodulation is crucial for effective bone tissue engineering. Thus, exploring the impact of bone surface microstructure mimicking biomaterials on macrophage polarization is critical. In this study, we aimed to sequentially activate M1 and M2 macrophages using Poly-l-Lactic acid (PLA) membranes with bone surface topographical features mimicked through the soft lithography technique. To mimic the bone surface topography, a bovine femur was used as a model surface, and the membranes were further modified with collagen type-I and hydroxyapatite to mimic the bone surface microenvironment. To determine the effect of these biomaterials on macrophage polarization, we conducted experimental analysis that contained estimating cytokine release profiles and characterizing cell morphology. Our results demonstrated the potential of the hydroxyapatite-deposited bone surface-mimicked PLA membranes to trigger sequential and synergistic M1 and M2 macrophage polarizations, suggesting their ability to achieve osteoimmunomodulatory macrophage polarization for bone tissue engineering applications. Although further experimental studies are required to completely investigate the osteoimmunomodulatory effects of these biomaterials, our results provide valuable insights into the potential advantages of biomaterials that mimic the complex microenvironment of bone surfaces.