bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models
Authors: Costa-Machado Luis Filipe , Garcia-Dominguez Esther , McIntyre Rebecca L. , Lopez-Aceituno Jose Luis , Ballesteros-Gonzalez Álvaro , Tapia-Gonzalez Andrea , Fabregat-Safont David , Eisenberg Tobias , Gomez Jesús , Plaza Adrian , Sierra-Ramirez Aranzazu , Perez Manuel , Villanueva-Bermejo David , Fornari Tiziana , Loza María Isabel , Herradon Gonzalo , Hofer Sebastian J. , Magnes Christoph , Madeo Frank , Duerr Janet S. , Pozo Oscar J. , Galindo Maximo-Ibo , del Pino Isabel , Houtkooper Riekelt H. , Megias Diego , Viña Jose , Gomez-Cabrera Mari Carmen , Fernandez-Marcos Pablo J. 
Published: May 2023

AbstractReversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood–brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.
Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis
Authors: Conroy Lindsey R. , Clarke Harrison A. , Allison Derek B. , Valenca Samuel Santos , Sun Qi , Hawkinson Tara R. , Young Lyndsay E. A. , Ferreira Juanita E. , Hammonds Autumn V. , Dunne Jaclyn B. , McDonald Robert J. , Absher Kimberly J. , Dong Brittany E. , Bruntz Ronald C. , Markussen Kia H. , Juras Jelena A. , Alilain Warren J. , Liu Jinze , Gentry Matthew S. , Angel Peggi M. , Waters Christopher M. , Sun Ramon C. 
Published: May 2023

AbstractMatrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.
Microbiota-assisted iron uptake promotes immune tolerance in the intestine
Authors: Zhu Lizhen , Li Geng , Liang Zhixin , Qi Tuan , Deng Kui , Yu Jiancheng , Peng Yue , Zheng Jusheng , Song Yan , Chang Xing 
Published: May 2023

AbstractIron deficiencies are the most common nonenteric syndromes observed in patients with inflammatory bowel disease, but little is known about their impacts on immune tolerance. Here we show that homeostasis of regulatory T cells in the intestine was dependent on high cellular iron levels, which were fostered by pentanoate, a short-chain fatty acid produced by intestinal microbiota. Iron deficiencies in Treg caused by the depletion of Transferrin receptor 1, a major iron transporter, result in the abrogation of Treg in the intestine and lethal autoimmune disease. Transferrin receptor 1 is required for differentiation of c-Maf+ Treg, major constituents of intestinal Treg. Mechanistically, iron enhances the translation of HIF-2α mRNA, and HIF-2α in turn induces c-Maf expression. Importantly, microbiota-produced pentanoate promotes iron uptake and Treg differentiation in the intestine. This subsequently restores immune tolerance and ameliorated iron deficiencies in mice with colitis. Our results thus reveal an association between nutrient uptake and immune tolerance in the intestine.
Complex phase transitions and phase engineering in the aqueous solution of an isopolyoxometalate cluster
Authors: Wang Zhi-Da , Liang Song , Yang Yuqing , Liu Zhen-Ning , Duan Xiao-Zheng , Li Xinpei , Liu Tianbo , Zang Hong-Ying 
Published: May 2023

AbstractInorganic salts usually demonstrate simple phasal behaviors in dilute aqueous solution mainly involving soluble (homogeneous) and insoluble (macrophase separation) scenarios. Herein, we report the discovery of complex phase behavior involving multiple phase transitions of clear solution – macrophase separation – gelation – solution – macrophase separation in the dilute aqueous solutions of a structurally well-defined molecular cluster [Mo7O24]6− macroanions with the continuous addition of Fe3+. No chemical reaction was involved. The transitions are closely related to the strong electrostatic interaction between [Mo7O24]6− and their Fe3+ counterions, the counterion-mediated attraction and the consequent charge inversion, leading to the formation of linear/branched supramolecular structures, as confirmed by experimental results and molecular dynamics simulations. The rich phase behavior demonstrated by the inorganic cluster [Mo7O24]6− expands our understanding of nanoscale ions in solution.
Glutamatergic cerebellar neurons differentially contribute to the acquisition of motor and social behaviors
Authors: van der Heijden Meike E. , Rey Hipolito Alejandro G. , Kim Linda H. , Kizek Dominic J. , Perez Ross M. , Lin Tao , Sillitoe Roy V. 
Published: May 2023

AbstractInsults to the developing cerebellum can cause motor, language, and social deficits. Here, we investigate whether developmental insults to different cerebellar neurons constrain the ability to acquire cerebellar-dependent behaviors. We perturb cerebellar cortical or nuclei neuron function by eliminating glutamatergic neurotransmission during development, and then we measure motor and social behaviors in early postnatal and adult mice. Altering cortical and nuclei neurons impacts postnatal motor control and social vocalizations. Normalizing neurotransmission in cortical neurons but not nuclei neurons restores social behaviors while the motor deficits remain impaired in adults. In contrast, manipulating only a subset of nuclei neurons leaves social behaviors intact but leads to early motor deficits that are restored by adulthood. Our data uncover that glutamatergic neurotransmission from cerebellar cortical and nuclei neurons differentially control the acquisition of motor and social behaviors, and that the brain can compensate for some but not all perturbations to the developing cerebellum.
Machine learning-guided discovery of ionic polymer electrolytes for lithium metal batteries
Authors: Li Kai , Wang Jifeng , Song Yuanyuan , Wang Ying 
Published: May 2023

AbstractAs essential components of ionic polymer electrolytes (IPEs), ionic liquids (ILs) with high ionic conductivity and wide electrochemical window are promising candidates to enable safe and high-energy-density lithium metal batteries (LMBs). Here, we describe a machine learning workflow embedded with quantum calculation and graph convolutional neural network to discover potential ILs for IPEs. By selecting subsets of the recommended ILs, combining with a rigid-rod polyelectrolyte and a lithium salt, we develop a series of thin (~50 μm) and robust (>200 MPa) IPE membranes. The Li|IPEs|Li cells exhibit ultrahigh critical-current-density (6 mA cm−2) at 80 °C. The Li|IPEs|LiFePO4 (10.3 mg cm−2) cells deliver outstanding capacity retention in 350 cycles (>96% at 0.5C; >80% at 2C), fast charge/discharge capability (146 mAh g−1 at 3C) and excellent efficiency (>99.92%). This performance is rarely reported by other single-layer polymer electrolytes without any flammable organics for LMBs.
Structure and sucrose binding mechanism of the plant SUC1 sucrose transporter
Authors: Bavnhøj Laust , Driller Jan Heiner , Zuzic Lorena , Stange Amanda Dyrholm , Schiøtt Birgit , Pedersen Bjørn Panyella 
Published: May 2023

AbstractSucrose import from photosynthetic tissues into the phloem is mediated by transporters from the low-affinity sucrose transporter family (SUC/SUT family). Furthermore, sucrose redistribution to other tissues is driven by phloem sap movement, the product of high turgor pressure created by this import activity. Additionally, sink organs such as fruits, cereals and seeds that accumulate high concentrations of sugar also depend on this active transport of sucrose. Here we present the structure of the sucrose–proton symporter, Arabidopsis thaliana SUC1, in an outward open conformation at 2.7 Å resolution, together with molecular dynamics simulations and biochemical characterization. We identify the key acidic residue required for proton-driven sucrose uptake and describe how protonation and sucrose binding are strongly coupled. Sucrose binding is a two-step process, with initial recognition mediated by the glucosyl moiety binding directly to the key acidic residue in a stringent pH-dependent manner. Our results explain how low-affinity sucrose transport is achieved in plants, and pinpoint a range of SUC binders that help define selectivity. Our data demonstrate a new mode for proton-driven symport with links to cation-driven symport and provide a broad model for general low-affinity transport in highly enriched substrate environments.
Ocular conditions and injuries, detection and management in spaceflight
Authors: Meer Elana , Grob Seanna , Antonsen Erik L. , Sawyer Aenor 
Published: May 2023

AbstractOcular trauma or other ocular conditions can be significantly debilitating in space. A literature review of over 100 articles and NASA evidence books, queried for eye related trauma, conditions, and exposures was conducted. Ocular trauma and conditions during NASA space missions during the Space Shuttle Program and ISS through Expedition 13 in 2006 were reviewed. There were 70 corneal abrasions, 4 dry eyes, 4 eye debris, 5 complaints of ocular irritation, 6 chemical burns, and 5 ocular infections noted. Unique exposures on spaceflight, such as foreign bodies, including celestial dust, which may infiltrate the habitat and contact the ocular surface, as well as chemical and thermal injuries due to prolonged CO2 and heat exposure were reported. Diagnostic modalities used to evaluate the above conditions in space flight include vision questionnaires, visual acuity and Amsler grid testing, fundoscopy, orbital ultrasound, and ocular coherence tomography. Several types of ocular injuries and conditions, mostly affecting the anterior segment, are reported. Further research is necessary to understand the greatest ocular risks that astronauts face and how better we can prevent, but also diagnose and treat these conditions in space.
Global economic burden per episode for multiple diseases caused by group A Streptococcus
Authors: Lee Jung-Seok , Kim Sol , Excler Jean-Louis , Kim Jerome H. , Mogasale Vittal 
Published: May 2023

AbstractConsidering the lack of existing evidence on economic burden for diseases caused by group A Streptococcus, we estimated the economic burden per episode for selected diseases. Each cost component of direct medical costs (DMCs), direct non-medical costs (DNMCs), and indirect costs (ICs) was separately extrapolated and aggregated to estimate the economic burden per episode by income group as classified by the World Bank. Adjustment factors for DMC and DNMC were generated to overcome related data insufficiencies. To address uncertainty surrounding input parameters, a probabilistic multivariate sensitivity was carried out. The average economic burden per episode ranged from $22 to $392 for pharyngitis, $25 to $2,903 for impetigo, $47 to $2,725 for cellulitis, $662 to $34,330 for invasive and toxin-mediated infections, $231 to $6,332 for acute rheumatic fever (ARF), $449 to $11,717 for rheumatic heart disease (RHD), and $949 to $39,560 for severe RHD across income groups. The economic burden for multiple Group A Streptococcus diseases underscores an urgent need to develop effective prevention strategies including vaccines.
Sympathetic modulation of hindlimb muscle contractility is altered in aged rats
Authors: Hotta Harumi , Iimura Kaori , Watanabe Nobuhiro , Suzuki Harue , Sugie Masamitsu , Shigemoto Kazuhiro 
Published: May 2023

AbstractIt has recently been demonstrated that reflex excitation of muscle sympathetic nerves triggered by muscle contraction contributes to the maintenance of tetanic force (TF) in rat hindlimb muscles. We hypothesized that this feedback mechanism between the contraction of hindlimb muscles and the lumbar sympathetic nerves declines during aging. In this study, we examined the contribution of sympathetic nerves on skeletal muscle contractility in young adult (4–9 months old, n = 11) and aged (32–36 months old, n = 11) male and female rats. The tibial nerve was electrically stimulated to measure the TF of the triceps surae muscles resulting from motor nerve activation before and after cutting or stimulating (at 5–20 Hz) the lumbar sympathetic trunk (LST). The TF amplitude decreased by cutting the LST in the young and aged groups; however, the magnitude of the decrease in TF following transection of the LST in the aged rats (6.2%) was significantly (P = 0.02) smaller compared with that in the young rats (12.9%). The TF amplitude was increased by LST stimulation at ≥ 5 Hz in the young and ≥ 10 Hz in the aged groups. The overall TF response to LST stimulation was not significantly different between the two groups; however, an increase in muscle tonus resulting from LST stimulation, independent of motor nerve stimulation, was significantly (P = 0.03) greater in aged compared with young rats. The sympathetic contribution to support motor nerve-induced muscle contraction declined, whereas sympathetic-mediated muscle tonus, independent of motor nerve activity, was augmented in aged rats. These changes in sympathetic modulation of hindlimb muscle contractility may underlie the reduction of skeletal muscle strength during voluntary contraction and rigidity of motion during senescence.
Spatial and seasonal distribution of human schistosomiasis intermediate host snails and their interactions with other freshwater snails in 7 districts of KwaZulu-Natal province, South Africa
Authors: Nwoko Onyekachi Esther , Manyangadze Tawanda , Chimbari Moses John 
Published: May 2023

AbstractThe spatial and seasonal distribution, abundance, and infection rates of human schistosomiasis intermediate host snails and interactions with other freshwater snails, water physicochemical parameters, and climatic factors was determined in this study. A longitudinal malacology survey was conducted at seventy-nine sites in seven districts in KwaZulu-Natal province between September 2020 and August 2021. Snail sampling was done simultaneously by two trained personnel for fifteen minutes, once in three months. A total of 15,756 snails were collected during the study period. Eight freshwater snails were found: Bulinus globosus (n = 1396), Biomphalaria pfeifferi (n = 1130), Lymnaea natalensis (n = 1195), Bulinus tropicus (n = 1722), Bulinus forskalii (n = 195), Tarebia granifera (n = 8078), Physa acuta (n = 1579), and Bivalves (n = 461). The infection rates of B. globosus and B. pfeifferi are 3.5% and 0.9%, respectively. In our study, rainfall, pH, type of habitats, other freshwater snails and seasons influenced the distribution, abundance, and infection rates of human schistosomiasis intermediate host snails (p-value < 0.05). Our findings provide useful information which can be adopted in designing and implementing snail control strategies as part of schistosomiasis control in the study area.
Modeling of H2S solubility in ionic liquids: comparison of white-box machine learning, deep learning and ensemble learning approaches
Authors: Mousavi Seyed-Pezhman , Nakhaei-Kohani Reza , Atashrouz Saeid , Hadavimoghaddam Fahimeh , Abedi Ali , Hemmati-Sarapardeh Abdolhossein , Mohaddespour Ahmad 
Published: May 2023

AbstractIn the context of gas processing and carbon sequestration, an adequate understanding of the solubility of acid gases in ionic liquids (ILs) under various thermodynamic circumstances is crucial. A poisonous, combustible, and acidic gas that can cause environmental damage is hydrogen sulfide (H2S). ILs are good choices for appropriate solvents in gas separation procedures. In this work, a variety of machine learning techniques, such as white-box machine learning, deep learning, and ensemble learning, were established to determine the solubility of H2S in ILs. The white-box models are group method of data handling (GMDH) and genetic programming (GP), the deep learning approach is deep belief network (DBN) and extreme gradient boosting (XGBoost) was selected as an ensemble approach. The models were established utilizing an extensive database with 1516 data points on the H2S solubility in 37 ILs throughout an extensive pressure and temperature range. Seven input variables, including temperature (T), pressure (P), two critical variables such as temperature (Tc) and pressure (Pc), acentric factor (ω), boiling temperature (Tb), and molecular weight (Mw), were used in these models; the output was the solubility of H2S. The findings show that the XGBoost model, with statistical parameters such as an average absolute percent relative error (AAPRE) of 1.14%, root mean square error (RMSE) of 0.002, standard deviation (SD) of 0.01, and a determination coefficient (R2) of 0.99, provides more precise calculations for H2S solubility in ILs. The sensitivity assessment demonstrated that temperature and pressure had the highest negative and highest positive affect on the H2S solubility in ILs, respectively. The Taylor diagram, cumulative frequency plot, cross-plot, and error bar all demonstrated the high effectiveness, accuracy, and reality of the XGBoost approach for predicting the H2S solubility in various ILs. The leverage analysis shows that the majority of the data points are experimentally reliable and just a small number of data points are found beyond the application domain of the XGBoost paradigm. Beyond these statistical results, some chemical structure effects were evaluated. First, it was shown that the lengthening of the cation alkyl chain enhances the H2S solubility in ILs. As another chemical structure effect, it was shown that higher fluorine content in anion leads to higher solubility in ILs. These phenomena were confirmed by experimental data and the model results. Connecting solubility data to the chemical structure of ILs, the results of this study can further assist to find appropriate ILs for specialized processes (based on the process conditions) as solvents for H2S.
SOC stocks prediction on the basis of spatial and temporal variation in soil properties by using partial least square regression
Authors: Usman Jawaria , Begum Shaheen 
Published: May 2023

AbstractGlobal warming is a wide-scale problem and soil carbon sequestration is its local scale, natural solution. Role of soil as carbon sink has been researched extensively but the knowledge regarding the role of soil variables in predicting soil carbon uptake and its retention is scarce. The current study predicts SOC stocks in the topsoil of Islamabad-Rawalpindi region keeping the soil properties as explanatory variables and applying the partial least square regression model on two different seasons’ datasets. Samples collected from the twin cities of Islamabad and Rawalpindi were tested for soil color, texture, moisture-content, SOM, bulk density, soil pH, EC, SOC, sulphates, nitrates, phosphates, fluorides, calcium, magnesium, sodium, potassium, and heavy metals (nickel, chromium, cadmium, copper and manganese) by applying standard protocols. Afterwards, PLSR was applied to predict the SOC-stocks. Although, current SOC stocks, ranged from 2.4 to 42.5 Mg/hectare, but the outcomes of PLSR projected that if soil variables remain unaltered, the SOC stocks would be likely to get concentrated around 10 Mg/hectare in the region. The study also identified variable importance for both seasons’ datasets so that noisy variables in the datasets could be ruled out in future researches and precise and accurate estimations could be made.
Constraining the tectonic evolution of rifted continental margins by U–Pb calcite dating
Authors: Hestnes Åse , Drost Kerstin , Sømme Tor O. , Gasser Deta , Scheiber Thomas , Linge Henriette , Chew David , Jacobs Joachim 
Published: May 2023

AbstractWe employ U–Pb calcite dating of structurally-controlled fracture fills within crystalline Caledonian basement in western Norway to reveal subtle large-scale tectonic events that affected this rifted continental margin. The ages (15 in total) fall into four distinct groups with ages mainly ranging from latest Cretaceous to Pleistocene. (1) The three oldest (Triassic-Jurassic) ages refine the complex faulting history of a reactivated fault strand originated from the Caledonian collapse and broadly correlate with known rifting events offshore. (2) Two ages of ca. 90–80 Ma relate to lithospheric stretching and normal fault reactivation of a major ENE-WSW trending late Caledonian shear zone. (3) We correlate five ages between ca. 70 and 60 Ma with far-field effects and dynamic uplift related to the proto-Iceland mantle plume, the effect and extent of which is highly debated. (4) The five youngest ages (< 50 Ma) from distinct NE–SW trending faults are interpreted to represent several episodes of post-breakup fracture dilation, indicating a long-lived Cenozoic deformation history. Our new U–Pb data combined with structural and isotopic data show that much larger tracts of the uplifted continental margin of western Norway have been affected by far-field tectonic stresses than previously anticipated, with deformation continuing into the late Cenozoic.