bluuebunny/crossref_metadata_2025_split huggingface dataset:
Planet‐Wide Ozone Destruction in the Middle Atmosphere on Mars During Global Dust Storm
Authors: Daerden F. , Neary L. , Wolff M. J. , Clancy R. T. , Lefèvre F. , Whiteway J. A. , Viscardy S. , Piccialli A. , Willame Y. , Depiesse C. , Aoki S. , Thomas I. R. , Ristic B. , Erwin J. , Gérard J.‐C. , Sandor B. J. , Khayat A. , Smith M. D. , Mason J. P. , Patel M. R. , Villanueva G. L. , Liuzzi G. , Bellucci G. , Lopez‐Moreno J.‐J. , Vandaele A. C. 
Published: May 2022

AbstractThe Nadir and Occultation for MArs Discovery (NOMAD)/UV‐visible (UVIS) spectrometer on the ExoMars Trace Gas Orbiter provided observations of ozone (O3) and water vapor in the global dust storm of 2018. Here we show in detail, using advanced data filtering and chemical modeling, how Martian O3 in the middle atmosphere was destroyed during the dust storm. In data taken exactly 1 year later when no dust storm occurred, the normal situation had been reestablished. The model simulates how water vapor is transported to high altitudes and latitudes in the storm, where it photolyzes to form odd hydrogen species that catalyze O3. O3 destruction is simulated at all latitudes and up to 100 km, except near the surface where it increases. The simulations also predict a strong increase in the photochemical production of atomic hydrogen in the middle atmosphere, consistent with the enhanced hydrogen escape observed in the upper atmosphere during global dust storms.
The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates
Authors: Chen Kuangqi , Li Yanqing , Zhang Xuhong , Ullah Rahim , Tong Jianping , Shen Ye 
Published: May 2022

AbstractPhosphatidylinositol 3 kinase (PI3K)/AKT (also called protein kinase B, PKB) signalling regulates various cellular processes, such as apoptosis, cell proliferation, the cell cycle, protein synthesis, glucose metabolism, and telomere activity. Corneal epithelial cells (CECs) are the outermost cells of the cornea; they maintain good optical performance and act as a physical and immune barrier. Various growth factors, including epidermal growth factor receptor (EGFR) ligands, insulin-like growth factor 1 (IGF1), neurokinin 1 (NK-1), and insulin activate the PI3K/AKT signalling pathway by binding their receptors and promote antiapoptotic, anti-inflammatory, proliferative, and migratory functions and wound healing in the corneal epithelium (CE). Reactive oxygen species (ROS) regulate apoptosis and inflammation in CECs in a concentration-dependent manner. Extreme environments induce excess ROS accumulation, inhibit PI3K/AKT, and cause apoptosis and inflammation in CECs. However, at low or moderate levels, ROS activate PI3K/AKT signalling, inhibiting apoptosis and stimulating proliferation of healthy CECs. Diabetes-associated hyperglycaemia directly inhibit PI3K/AKT signalling by increasing ROS and endoplasmic reticulum (ER) stress levels or suppressing the expression of growth factors receptors and cause diabetic keratopathy (DK) in CECs. Similarly, hyperosmolarity and ROS accumulation suppress PI3K/AKT signalling in dry eye disease (DED). However, significant overactivation of the PI3K/AKT signalling pathway, which mediates inflammation in CECs, is observed in both infectious and noninfectious keratitis. Overall, upon activation by growth factors and NK-1, PI3K/AKT signalling promotes the proliferation, migration, and anti-apoptosis of CECs, and these processes can be regulated by ROS in a concentration-dependent manner. Moreover, PI3K/AKT signalling pathway is inhibited in CECs from individuals with DK and DED, but is overactivated by keratitis.
Novel role for caspase 1 inhibitor VX765 in suppressing NLRP3 inflammasome assembly and atherosclerosis via promoting mitophagy and efferocytosis
Authors: Jin Ying , Liu Yao , Xu Lei , Xu Jie , Xiong Yulian , Peng Yazhi , Ding Ke , Zheng Shuang , Yang Nan , Zhang Zemei , Li Lin , Tan Liguo , Song HongXian , Fu Jian 
Published: May 2022

AbstractAtherosclerosis is a maladaptive chronic inflammatory disease, which remains the leading cause of death worldwide. The NLRP3 inflammasome constitutes a major driver of atherosclerosis, yet the mechanism of action is poorly understood. Mitochondrial dysfunction is essential for NLRP3 inflammasome activation. However, whether activated NLRP3 inflammasome exacerbates mitochondrial dysfunction remains to be further elucidated. Herein, we sought to address these issues applying VX765, a well-established inhibitor of caspase 1. VX765 robustly restrains caspase 1-mediated interleukin-1β production and gasdermin D processing. Our study assigned VX765 a novel role in antagonizing NLRP3 inflammasome assembly and activation. VX765 mitigates mitochondrial damage induced by activated NLRP3 inflammasome, as evidenced by decreased mitochondrial ROS production and cytosolic release of mitochondrial DNA. VX765 blunts caspase 1-dependent cleavage and promotes mitochondrial recruitment and phosphorylation of Parkin, a key mitophagy regulator. Functionally, VX765 facilitates mitophagy, efferocytosis and M2 polarization of macrophages. It also impedes foam cell formation, migration and pyroptosis of macrophages. VX765 boosts autophagy, promotes efferocytosis, and alleviates vascular inflammation and atherosclerosis in both ApoE−/− and Ldlr−/− mice. However, these effects of VX765 were abrogated upon ablation of Nlrp3 in ApoE−/− mice. This work provides mechanistic insights into NLRP3 inflammasome assembly and this inflammasome in dictating atherosclerosis. This study highlights that manipulation of caspase 1 paves a new avenue to treatment of atherosclerotic cardiovascular disease.
A topological fluctuation theorem
Authors: Mahault Benoît , Tang Evelyn , Golestanian Ramin 
Published: May 2022

AbstractFluctuation theorems specify the non-zero probability to observe negative entropy production, contrary to a naive expectation from the second law of thermodynamics. For closed particle trajectories in a fluid, Stokes theorem can be used to give a geometric characterization of the entropy production. Building on this picture, we formulate a topological fluctuation theorem that depends only by the winding number around each vortex core and is insensitive to other aspects of the force. The probability is robust to local deformations of the particle trajectory, reminiscent of topologically protected modes in various classical and quantum systems. We demonstrate that entropy production is quantized in these strongly fluctuating systems, and it is controlled by a topological invariant. We demonstrate that the theorem holds even when the probability distributions are non-Gaussian functions of the generated heat.
Mapping the cardiac vascular niche in heart failure
Authors: Peisker Fabian , Halder Maurice , Nagai James , Ziegler Susanne , Kaesler Nadine , Hoeft Konrad , Li Ronghui , Bindels Eric M. J. , Kuppe Christoph , Moellmann Julia , Lehrke Michael , Stoppe Christian , Schaub Michael T. , Schneider Rebekka K. , Costa Ivan , Kramann Rafael 
Published: May 2022

AbstractThe cardiac vascular and perivascular niche are of major importance in homeostasis and during disease, but we lack a complete understanding of its cellular heterogeneity and alteration in response to injury as a major driver of heart failure. Using combined genetic fate tracing with confocal imaging and single-cell RNA sequencing of this niche in homeostasis and during heart failure, we unravel cell type specific transcriptomic changes in fibroblast, endothelial, pericyte and vascular smooth muscle cell subtypes. We characterize a specific fibroblast subpopulation that exists during homeostasis, acquires Thbs4 expression and expands after injury driving cardiac fibrosis, and identify the transcription factor TEAD1 as a regulator of fibroblast activation. Endothelial cells display a proliferative response after injury, which is not sustained in later remodeling, together with transcriptional changes related to hypoxia, angiogenesis, and migration. Collectively, our data provides an extensive resource of transcriptomic changes in the vascular niche in hypertrophic cardiac remodeling.
A framework for reconstructing SARS-CoV-2 transmission dynamics using excess mortality data
Authors: Ghafari Mahan , Watson Oliver J. , Karlinsky Ariel , Ferretti Luca , Katzourakis Aris 
Published: May 2022

AbstractThe transmission dynamics and burden of SARS-CoV-2 in many regions of the world is still largely unknown due to the scarcity of epidemiological analyses and lack of testing to assess the prevalence of disease. In this work, we develop a quantitative framework based on excess mortality data to reconstruct SARS-CoV-2 transmission dynamics and assess the level of underreporting in infections and deaths. Using weekly all-cause mortality data from Iran, we are able to show a strong agreement between our attack rate estimates and seroprevalence measurements in each province and find significant heterogeneity in the level of exposure across the country with 11 provinces reaching near 100% attack rates. Despite having a young population, our analysis reveals that incorporating limited access to medical services in our model, coupled with undercounting of COVID-19-related deaths, leads to estimates of infection fatality rate in most provinces of Iran that are comparable to high-income countries.
Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family
Authors: Nielsen Nadia Sukusu , Zarantonello Alessandra , Harwood Seandean Lykke , Jensen Kathrine Tejlgård , Kjøge Katarzyna , Thøgersen Ida B. , Schauser Leif , Karlsen Jesper Lykkegaard , Andersen Gregers R. , Enghild Jan J. 
Published: May 2022

AbstractA2ML1 is a monomeric protease inhibitor belonging to the A2M superfamily of protease inhibitors and complement factors. Here, we investigate the protease-inhibitory mechanism of human A2ML1 and determine the structures of its native and protease-cleaved conformations. The functional inhibitory unit of A2ML1 is a monomer that depends on covalent binding of the protease (mediated by A2ML1’s thioester) to achieve inhibition. In contrast to the A2M tetramer which traps proteases in two internal chambers formed by four subunits, in protease-cleaved monomeric A2ML1 disordered regions surround the trapped protease and may prevent substrate access. In native A2ML1, the bait region is threaded through a hydrophobic channel, suggesting that disruption of this arrangement by bait region cleavage triggers the extensive conformational changes that result in protease inhibition. Structural comparisons with complement C3/C4 suggest that the A2M superfamily of proteins share this mechanism for the triggering of conformational change occurring upon proteolytic activation.
Modular (de)construction of complex bacterial phenotypes by CRISPR/nCas9-assisted, multiplex cytidine base-editing
Authors: Volke Daniel C. , Martino Román A. , Kozaeva Ekaterina , Smania Andrea M. , Nikel Pablo I. 
Published: May 2022

AbstractCRISPR/Cas technologies constitute a powerful tool for genome engineering, yet their use in non-traditional bacteria depends on host factors or exogenous recombinases, which limits both efficiency and throughput. Here we mitigate these practical constraints by developing a widely-applicable genome engineering toolset for Gram-negative bacteria. The challenge is addressed by tailoring a CRISPR base editor that enables single-nucleotide resolution manipulations (C·G → T·A) with >90% efficiency. Furthermore, incorporating Cas6-mediated processing of guide RNAs in a streamlined protocol for plasmid assembly supports multiplex base editing with >85% efficiency. The toolset is adopted to construct and deconstruct complex phenotypes in the soil bacterium Pseudomonas putida. Single-step engineering of an aromatic-compound production phenotype and multi-step deconstruction of the intricate redox metabolism illustrate the versatility of multiplex base editing afforded by our toolbox. Hence, this approach overcomes typical limitations of previous technologies and empowers engineering programs in Gram-negative bacteria that were out of reach thus far.
BRD4 promotes resection and homology-directed repair of DNA double-strand breaks
Authors: Barrows John K. , Lin Baicheng , Quaas Colleen E. , Fullbright George , Wallace Elizabeth N. , Long David T. 
Published: May 2022

AbstractDouble-strand breaks (DSBs) are one of the most toxic forms of DNA damage and represent a major source of genomic instability. Members of the bromodomain and extra-terminal (BET) protein family are characterized as epigenetic readers that regulate gene expression. However, evidence suggests that BET proteins also play a more direct role in DNA repair. Here, we establish a cell-free system using Xenopus egg extracts to elucidate the gene expression-independent functions of BET proteins in DSB repair. We identify the BET protein BRD4 as a critical regulator of homologous recombination and describe its role in stimulating DNA processing through interactions with the SWI/SNF chromatin remodeling complex and resection machinery. These results establish BRD4 as a multifunctional regulator of chromatin binding that links transcriptional activity and homology-directed repair.
Efficacy, T cell activation and antibody responses in accelerated Plasmodium falciparum sporozoite chemoprophylaxis vaccine regimens
Authors: Ibanez Javier , Fendel Rolf , Lorenz Freia-Raphaella , Granados-Bayon Patricia , Brückner Sina , Esen Meral , Sulyok Mihály , Sulyok Zita , Borrmann Steffen , Bacher Petra , Scheffold Alexander , Hoffman Stephen L. , Kremsner Peter G. , Mordmüller Benjamin 
Published: May 2022

AbstractRepeated direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ) together with antimalarial chemoprophylaxis (PfSPZ–CVac) is the most potent way to induce sterile immunity against P. falciparum infection in malaria-naive volunteers. However, established schedules are complex and long. Here, we tested two accelerated three-dose schedules (28- and 10-day regimen) assessing efficacy by controlled human malaria infection (CHMI) against placebo, comparing vaccine-specific T cell and antibody responses by antigen-reactive T cell enrichment (ARTE) and protein microarray, respectively. Both regimens were similarly efficacious (67 and 63% vaccine efficacy) but different in the induction of vaccine-specific T cells and antibodies. The 10-day regimen resulted in higher numbers of antigen-specific CD4+ effector memory pro-inflammatory T cells and a broader antibody response compared with the 28-day regimen. Usually in nature, P. falciparum liver stage lasts about 6.5 days. The short vaccination-interval of the 10-day regimen prolongs the time of continuous exposure to liver-stage parasites, which may explain the stronger response. Besides dose and number of vaccinations, duration of liver-stage exposure is a factor to optimize PfSPZ–CVac immunogenicity.
A benchmark study on economic impact of Neem Coated Urea on Indian agriculture
Authors: Ramappa K. B. , Jadhav Vilas , Manjunatha A. V. 
Published: May 2022

AbstractThe policy of mandatory production and distribution of Neem Coated Urea (NCU) was implemented by the Government of India since 2015. In this article, authors have made an attempt to explore the benefits of NCU recognized by the producers of six major crops such as paddy, maize, sugarcane, tur, jute and soybean across six major states viz., Karnataka, Maharashtra, Madhya Pradesh, Bihar, Punjab and Assam. The results reveal that NCU use has contributed positively in terms of increasing the yield levels of main product and by-products, as well as net returns with regard to almost all reference crops however; the extent varies from crop to crop. Moreover, NCU has helped reduce the cost of production by minimizing the cost of urea as well as other fertilizers and pesticides usage. Interestingly, the diversion of urea has stopped completely, post the production and distribution of NCU. Hence, it is concluded that the application of NCU has a positive impact on Indian agriculture, by way of increasing yield levels & returns for the farming community. These results are in line with the PM's vision of doubling farmers’ income by 2022 and Sustainable Development Goals of the Country.
Optogenetic modulation of electroacupuncture analgesia in a mouse inflammatory pain model
Authors: Hsiao I-Han , Liao Hsien-Yin , Lin Yi‑Wen 
Published: May 2022

AbstractPeripheral tissue damage and associated inflammation can trigger neuroplastic changes in somatic pain pathways, such as reduced neuronal firing thresholds and synaptic potentiation, that ultimately lead to peripheral sensitization and chronic pain. Electroacupuncture (EA) can relieve chronic inflammatory pain, but the underlying mechanisms are unknown, including the contributions of higher pain centers such as somatosensory cortex (SSC). We investigated these mechanisms using optogenetic modulation of SSC activity in a mouse inflammatory pain model. Injection of Complete Freund's Adjuvant into the hind paw reliably induced inflammation accompanied by reduced mechanical and thermal pain thresholds (hyperalgesia) within three days (mechanical: 1.54 ± 0.13 g; thermal: 3.94 ± 0.43 s). Application of EA produced significant thermal and mechanical analgesia, but these responses were reversed by optogenetic activation of SSC neurons, suggesting that EA-induced analgesia involves modulation of central pain pathways. Western blot and immunostaining revealed that EA also attenuated CaMKIIα signaling in the dorsal root ganglion, central spinal cord, SSC, and anterior cingulate cortex (ACC). In contrast, optogenetic activation of the SSC induced CaMKIIα signaling in SSC and ACC. These findings suggest that AE can relieve inflammatory pain by suppressing CaMKIIα-dependent plasticity in cortical pain pathways. The SSC and ACC CaMKIIα signaling pathways may be valuable therapeutic targets for chronic inflammatory pain treatment.
Scale, context, and heterogeneity: the complexity of the social space
Authors: Balsa-Barreiro José , Menendez Mónica , Morales Alfredo J. 
Published: May 2022

AbstractThe social space refers to physical or virtual places where people interact with one another. It decisively influences the emergence of human behaviors. However, little is known about the nature and complexity of the social space, nor its relationship to context and spatial scale. Recently, the science of complex systems has bridged between fields of knowledge to provide quantitative responses to fundamental sociological questions. In this paper, we analyze the shifting behavior of social space in terms of human interactions and wealth distribution across multiple scales using fine-grained data collected from both official (US Census Bureau) and unofficial data sources (social media). We use these data to unveil how patterns strongly depend upon the observation scale. Therefore, it is crucial for any analysis to be framed within the appropriate context to avoid biased results and/or misleading conclusions. Biased data analysis may lead to the adoption of fragile and poor decisions. Including context and a proper understanding of the spatial scale are essential nowadays, especially with the pervasive role of data-driven tools in decision-making processes.
Necrolytic migratory erythema is an important visual cutaneous clue of glucagonoma
Authors: Li Wei , Yang Xue , Deng Yuan , Jiang Yina , Xu Guiping , Li Enxiao , Wu Yinying , Ren Juan , Ma Zhenhua , Dong Shunbin , Han Liang , Ma Qingyong , Wu Zheng , Wang Zheng 
Published: May 2022

AbstractGlucagonoma is an extremely rare neuroendocrine tumor that arises from pancreatic islet alpha cells. Although glucagonoma is usually accompanied by a variety of characteristic clinical symptoms, early diagnosis is still difficult due to the scarcity of the disease. In this study, we present the cumulative experiences, clinical characteristics and treatments of seven patients diagnosed with glucagonoma during the past 10 years at the First Affiliated Hospital of Xi’an Jiaotong University. The seven patients in our cohort consisted of six females and one male with an average diagnosis age of 40.1 years (range 23–51). The average time from onset of symptoms to diagnosis of glucagonoma was 14 months (range 2–36 months). All the patients visited dermatology first for necrolytic migratory erythema (NME) 7/7 (100%), and other presenting symptoms included diabetes mellitus (DM) 4/7 (57%), stomatitis 2/7 (28%), weight loss 4/7 (57%), anemia 4/7 (57%), diarrhea 1/7 (14%), and DVT1/7 (14%). Plasma glucagon levels were increased in all patients (range 216.92–3155 pg/mL) and declined after surgery. Imaging studies revealed that four of seven patients had liver metastasis. Six of seven patients received surgical resection, and all of them received somatostatin analog therapy. Symptoms improved significantly in 6 out of 7 patients. Three of seven patients died of this disease by the time of follow-up. Our data suggest that if persistent NME is associated with DM and high glucagon levels, timely abdominal imaging should be performed to confirm glucagonoma. Once diagnosed, surgery and somatostatin analogs are effective for symptom relief and tumor control.
Nanofibrous materials affect the reaction of cytotoxicity assays
Authors: Podgórski Rafał , Wojasiński Michał , Ciach Tomasz 
Published: May 2022

AbstractNanofibrous materials are widely investigated as a replacement for the extracellular matrix, the 3D foundation for cells in all tissues. However, as with every medical material, nanofibers too must pass all safety evaluations like in vitro cytotoxicity assays or in vivo animal tests. Our literature research showed that differences in results of widely used cytotoxicity assays applied to evaluate nanofibrous materials are poorly understood. To better explore this issue, we prepared three nanofibrous materials with similar physical properties made of poly-L-lactic acid, polyurethane, and polycaprolactone. We tested five metabolic cytotoxicity assays (MTT, XTT, CCK-8, alamarBlue, PrestoBlue) and obtained different viability results for the same nanofibrous materials. Further, the study revealed that nanofibrous materials affect the reaction of cytotoxicity assays. Considering the results of both described experiments, it is evident that validating all available cytotoxicity assays for nanofibrous materials and possibly other highly porous materials should be carefully planned and verified using an additional analytical tool, like scanning electron microscopy or, more preferably, confocal microscopy.
Development of gut microbiota during the first 2 years of life
Authors: Wernroth Mona-Lisa , Peura Sari , Hedman Anna M. , Hetty Susanne , Vicenzi Silvia , Kennedy Beatrice , Fall Katja , Svennblad Bodil , Andolf Ellika , Pershagen Göran , Theorell-Haglöw Jenny , Nguyen Diem , Sayols-Baixeras Sergi , Dekkers Koen F. , Bertilsson Stefan , Almqvist Catarina , Dicksved Johan , Fall Tove 
Published: May 2022

AbstractAlthough development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.