bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solar Hysteresis Pattern and Spectral Components in TEC Time Series (GPS and TIE‐GCM) of the Quadrilaterally Coupled Geomagnetic Conjugate Low‐Latitude Stations
Authors: Rao S. S. , Chakrabarty D. , Srivastava Nandita 
Published: April 2023

AbstractThe current study is a first‐of‐its‐kind in that it compares the Total Electron Content (TEC) of the solar cycle from the Global Positioning System (GPS) and Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model (TIE‐GCM) over the geomagnetically conjugate low‐latitude stations with the particular scenario of lower atmospheric conditions over land‐ and sea‐locked locations. For this, TEC data for the period 2009–2017 is used from northern hemispheric stations Varanasi (25.31°N; 82.97°E) and LHAZ (29.65°N; 91.10°E) and southern hemispheric stations DGAR (7.27°S; 72.37°E) and COCO Island (12.18°S; 96.83°E). The solar cycle variation in TEC is identified by two distinct maxima and hysteresis between the ascending and descending phases. The solar cycle trends are modulated by the equatorial ionization anomaly as well as longitudinal biases. The Lomb‐Scargle periodogram shows that the improved TIE‐GCM version 2.0, which incorporates variable eddy diffusion to provide an accurate simulation of seasonal variability, is largely successful in simulating semi‐annual and annual oscillations but still needs to resolve the seasonal anomaly feature, particularly in the case of southern low latitude stations. Terannual (120‐day) and 1.4‐year (500‐day) periodicities in the TEC time series are observed only at EIA region stations, not at off‐crest location LHAZ, and are most likely caused by E x B drift. The wavelet coherence analysis reveals that the Quasi Biannual Oscillations (QBO) in the TEC time series (597‐, 773‐, and 930‐day) have a strong physical affinity with the QBO oscillation of F10.7 flux. Results indicate that both solar activity and equatorial electrodynamics significantly influence the QBO oscillation in the TEC.
The EGR3 regulome of infant KMT2A-r acute lymphoblastic leukemia identifies differential expression of B-lineage genes predictive for outcome
Authors: Külp Marius , Larghero Patrizia , Alten Julia , Cario Gunnar , Eckert Cornelia , Caye-Eude Aurélie , Cavé Hélène , Schmachtel Tessa , Bardini Michela , Cazzaniga Giovanni , De Lorenzo Paola , Valsecchi Maria Grazia , Bonig Halvard , Meyer Claus , Rieger Michael A. , Marschalek Rolf 
Published: April 2023

AbstractKMT2A-rearranged acute lymphoblastic infant leukemia (KMT2A-r iALL) is associated with outsize risk of relapse and relapse mortality. We previously reported strong upregulation of the immediate early gene EGR3 in KMT2A::AFF1 iALL at relapse; now we provide analyses of the EGR3 regulome, which we assessed through binding and expression target analysis of an EGR3-overexpressing t(4;11) cell culture model. Our data identify EGR3 as a regulator of early B-lineage commitment. Principal component analysis of 50 KMT2A-r iALL patients at diagnosis and 18 at relapse provided strictly dichotomous separation of patients based on the expression of four B-lineage genes. Absence of B-lineage gene expression translates to more than two-fold poorer long-term event-free survival. In conclusion, our study presents four B-lineage genes with prognostic significance, suitable for gene expression-based risk stratification of KMT2A-r iALL patients.
Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex
Authors: Cai Sihui , Zhang Chenqiu , Zhuang Zhen , Zhang Shengnan , Ma Ling , Yang Shuai , Zhou Tao , Wang Zheyu , Xie Weihong , Jin Shouheng , Zhao Jincun , Guan Xiangdong , Wu Jianfeng , Cui Jun , Wu Yaoxing 
Published: April 2023

AbstractCurrently, the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide. COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon (IFN-I) signal, along with limited activation of antiviral immune responses as well as enhanced viral infectivity. Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways. However, it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection. In the current study, we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA (mtDNA), which in turn triggers cGAS to activate IFN-I signaling. As countermeasures, SARS-CoV-2 nucleocapsid (N) protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling. Mechanically, N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation (LLPS), subsequently impairs the double-strand DNA (dsDNA) detection ability of cGAS. Taken together, our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation.
Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis
Authors: Wu Yutong , Ai Hongbo , Xi Yuhang , Yin Pengbin , Qu Ying , Xu Jianzhong , Dou Ce , Luo Fei 
Published: April 2023

AbstractOsteoporosis is associated with excessive activity of osteoclasts. In bone turn over, most osteoclasts undergo apoptosis after bone resorption and produce a large number of apoptotic bodies (ABs). However, the biological function of osteoclast-derived apoptotic bodies (OC-ABs) in the progression of osteoporosis is still unknow. In our study, we identified a reduction of OC-AB quantity in the bone marrow cavity during the progression of osteoporosis, an apoptotic body-deficient MRL/lpr mice were used to study the pro-osteogenic ability of OC-ABs. Mechanistically, OC-ABs promote osteogenesis of bone mesenchymal stem cells (BMSCs) by activating the downstream mTOR pathway via RANKL-mediated reverse signaling. Moreover, systemic infusion of exogenous OC-ABs effectively delayed the bone loss in ovariectomized (OVX) mice, validated the role of OC-ABs as bone protective factor in the pathogenesis of osteoporosis. Taken together, our study elucidates the biological function of OC-ABs in the pathological progression of osteoporotic bone loss and suggests a potential therapeutic strategy to delay bone loss.
Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM
Authors: Saotome Kei , Dudgeon Drew , Colotti Kiersten , Moore Michael J. , Jones Jennifer , Zhou Yi , Rafique Ashique , Yancopoulos George D. , Murphy Andrew J. , Lin John C. , Olson William C. , Franklin Matthew C. 
Published: April 2023

AbstractThe recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230–239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230–239) peptide and the closely related MAGEA8 (232–241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions.
Sequence-structure-function relationships in the microbial protein universe
Authors: Koehler Leman Julia , Szczerbiak Pawel , Renfrew P. Douglas , Gligorijevic Vladimir , Berenberg Daniel , Vatanen Tommi , Taylor Bryn C. , Chandler Chris , Janssen Stefan , Pataki Andras , Carriero Nick , Fisk Ian , Xavier Ramnik J. , Knight Rob , Bonneau Richard , Kosciolek Tomasz 
Published: April 2023

AbstractFor the past half-century, structural biologists relied on the notion that similar protein sequences give rise to similar structures and functions. While this assumption has driven research to explore certain parts of the protein universe, it disregards spaces that don’t rely on this assumption. Here we explore areas of the protein universe where similar protein functions can be achieved by different sequences and different structures. We predict ~200,000 structures for diverse protein sequences from 1,003 representative genomes across the microbial tree of life and annotate them functionally on a per-residue basis. Structure prediction is accomplished using the World Community Grid, a large-scale citizen science initiative. The resulting database of structural models is complementary to the AlphaFold database, with regards to domains of life as well as sequence diversity and sequence length. We identify 148 novel folds and describe examples where we map specific functions to structural motifs. We also show that the structural space is continuous and largely saturated, highlighting the need for a shift in focus across all branches of biology, from obtaining structures to putting them into context and from sequence-based to sequence-structure-function based meta-omics analyses.
Cell surface-localized CsgF condensate is a gatekeeper in bacterial curli subunit secretion
Authors: Swasthi Hema M. , Basalla Joseph L. , Dudley Claire E. , Vecchiarelli Anthony G. , Chapman Matthew R. 
Published: April 2023

AbstractCurli are functional amyloids present on the outer membrane of E. coli. CsgF is required for the proper assembly of curli. Here, we found that the CsgF phase separates in vitro and that the ability of CsgF variants to phase-separate is tightly correlated with CsgF function during curli biogenesis. Substitution of phenylalanine residues in the CsgF N-terminus both reduced the propensity of CsgF to phase-separate and impaired curli assembly. Exogenous addition of purified CsgF complemented csgF − cells. This exogenous addition assay was used to assess the ability of CsgF variants to complement csgF ‒ cells. CsgF on the cell surface modulated the secretion of CsgA, the curli major subunit, to the cell surface. We also found that the CsgB nucleator protein can form SDS-insoluble aggregates within the dynamic CsgF condensate. We propose that these multicomponent CsgF-B condensates form a nucleation-competent complex that templates CsgA amyloid formation on the cell surface.
Designing tailored combinations of structural units in polymer dielectrics for high-temperature capacitive energy storage
Authors: Wang Rui , Zhu Yujie , Fu Jing , Yang Mingcong , Ran Zhaoyu , Li Junluo , Li Manxi , Hu Jun , He Jinliang , Li Qi 
Published: April 2023

AbstractMany mainstream dielectric energy storage technologies in the emergent applications, such as renewable energy, electrified transportations and advanced propulsion systems, are usually required to operate under harsh-temperature conditions. However, excellent capacitive performance and thermal stability tend to be mutually exclusive in the current polymer dielectric materials and applications. Here, we report a strategy to tailor structural units for the design of high-temperature polymer dielectrics. A library of polyimide-derived polymers from diverse combinations of structural units are predicted, and 12 representative polymers are synthesized for direct experimental investigation. This study provides important insights into decisive structural factors necessary to achieve robust and stable dielectrics with high energy storage capabilities at elevated temperature. We also find that the high-temperature insulation performance would experience diminishing marginal utility as the bandgap increases beyond a critical point, which is strongly correlated to the dihedral angle between neighboring planes of conjugation in these polymers. By experimentally testing the optimized and predicted structures, an increased energy storage at temperatures up to 250 °C is observed. We discuss the possibility for this strategy to be generally applied to other polymer dielectrics to achieve further performance enhancement.
Importance of incorporating spatial and temporal variability of biomass yield and quality in bioenergy supply chain
Authors: Roni Mohammad S. , Lin Yingqian , Hartley Damon S. , Thompson David N. , Hoover Amber N. , Emerson Rachel M. 
Published: April 2023

AbstractBiofuels made from biomass and waste residues will largely contribute to United States’ 2050 decarbonization goal in the aviation sector. While cellulosic biofuels have the potential fuel performance equivalent to petroleum-based jet fuel, the biofuel industry needs to overcome the supply chain barrier caused by temporal and spatial variability of biomass yield and quality. This study highlights the importance of incorporating spatial and temporal variability during biomass supply chain planning via optimization modeling that incorporates 10 years of drought index data, a primary factor contributing to yield and quality variability. The results imply that the cost of delivering biomass to biorefinery may be significantly underestimated if the multi-year temporal and spatial variation in biomass yield and quality is not captured. For long term sustainable biorefinery operations, the industry should optimize supply chain strategy by studying the variability of yield and quality of biomass in their supply sheds.
Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients
Authors: Klussmann Jens Peter , Grosheva Maria , Meiser Peter , Lehmann Clara , Nagy Eszter , Szijártó Valéria , Nagy Gábor , Konrat Robert , Flegel Michael , Holzer Frank , Groß Dorothea , Steinmetz Charlotte , Scherer Barbara , Gruell Henning , Schlotz Maike , Klein Florian , de Aragão Paula Aguiar , Morr Henning , Al Saleh Helal , Bilstein Andreas , Russo Belisa , Müller-Scholtz Susanne , Acikel Cengizhan , Sahin Hacer , Werkhäuser Nina , Allekotte Silke , Mösges Ralph 
Published: April 2023

AbstractWith the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. The current study was a randomized, parallel, double-blind, placebo-controlled trial. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11 days, during which viral loads were assessed by quantitative PCR. Investigators assessed patients’ status throughout the trial including safety follow-ups (days 16 and 60). Symptoms were documented in patient diaries. Initial viral loads were log10 6.85 ± 1.31 (mean ± SD) copies/mL (ORF 1a/b gene). After treatment, virus load was reduced in all groups (p < 0.0001) but was greater in the 0.1% group compared to placebo (p = 0.007). In a subset of patients (initial Ct < 25) viral load was strongly reduced on day 4 in the 0.1% group compared to placebo (p = 0.005). Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. Comparable numbers of adverse events occurred in all treatment groups with no safety concerns. The shown effects of azelastine nasal spray may thus be suggestive of azelastine’s potential as an antiviral treatment.Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). EudraCT number: 2020-005544-34.
Never in mitosis gene A-related kinase-8 promotes proliferation, migration, invasion, and stemness of breast cancer cells via β-catenin signalling activation
Authors: Kang Eunji , Kim Hong-Kyu , Lee Han-Byoel , Han Wonshik 
Published: April 2023

AbstractNever in mitosis gene A (NIMA)-related kinase-8 (NEK8) is involved in cell cycle progression, cytoskeleton development, and DNA damage repair. However, its role in breast cancer has not yet been explored. To investigate this, NEK8 was knocked down in MDA-MB-231, BT549, and HCC38 breast cancer cell lines. We observed a decrease in cell proliferation and colony formation owing to regulation of the G1/S and G2/M transitions. Furthermore, the expression of several cell cycle regulatory proteins was altered, including that of cyclin D1, cyclin B1, CDK4, CDK2, and surviving. NEK8 knockdown impaired cell migration and invasion as well as reduced the expression of epithelial-mesenchymal transition markers. Regarding stem-cell characteristics, NEK8 knockdown decreased the tumour sphere formation, aldehyde dehydrogenase activity, and stem-cell marker expression, including that of CD44, Sox2, Oct4a, and Nanog. Further analysis revealed that NEK8 interacts with β-catenin. Also, NEK8 knockdown promoted β-catenin degradation. NEK8-silenced MDA-MB-231 cells inhibited xenograft tumour growth, metastasis, and tumour initiation in vivo. Using the Oncomine and TNMplot public databases, we found a significant correlation between NEK8 overexpression and poor clinical outcomes in breast cancer patients. Thus, NEK8 may be a crucial regulator of breast cancer progression and a potential therapeutic target.
Prevalence and incidence of stroke in Latin America and the Caribbean: a systematic review and meta-analysis
Authors: Cagna-Castillo Diego , Salcedo-Carrillo A. Lucia , Carrillo-Larco Rodrigo M. , Bernabé-Ortiz Antonio 
Published: April 2023

AbstractStroke is a recurrent and well-known cardiovascular event and a leading cause of death worldwide. We identified reliable epidemiological evidence of stroke in Latin America and the Caribbean (LAC) and estimated the prevalence and incidence of stroke, overall and by sex, in that region. A systematic search in OVID (Medline, Embase and Global Health) and in the Latin America and Caribbean Health Sciences Literature (LILACS) until the end of 2020 was made for all cross-sectional or longitudinal studies estimating (or allowing the estimation of) the prevalence or incidence of stroke among individuals of the general population ≥ 18 years from LAC countries. No language restriction was applied. Studies were assessed for methodological quality and risk of bias. Pooled estimates were calculated using random effect meta-analysis as high heterogeneity was expected. A total of 31 papers for prevalence and 11 papers for incidence were included in the review for analysis. The overall pooled stroke prevalence was 32 (95% CI 26–38) per 1000 subjects and were similar among men (21; 95% CI 17–25) and women (20; 95% CI 16–23) per 1000 subjects. The overall pooled stroke incidence was 255 (95% CI 217–293) per 100 000 person-years, being higher in men (261; 95% CI 221–301) compared to women (217; 95% CI 184–250) per 100 000 person-years. Our results highlight the relevance of the prevalence and incidence of stroke in the LAC region. The estimates were similar in stroke prevalence by sex, but with higher incidence rates among males than females. Subgroup analyses highlight the need for standardized methodologies to obtain appropriate prevalence and incidence estimates at the population level in a region with a great burden of cardiovascular events.
Evidence for unconventional superconductivity and nontrivial topology in PdTe
Authors: Chapai Ramakanta , Reddy P. V. Sreenivasa , Xing Lingyi , Graf David E. , Karki Amar B. , Chang Tay-Rong , Jin Rongying 
Published: April 2023

AbstractPdTe is a superconductor with Tc ~ 4.25 K. Recently, evidence for bulk-nodal and surface-nodeless gap features has been reported in PdTe. Here, we investigate the physical properties of PdTe in both the normal and superconducting states via specific heat and magnetic torque measurements and first-principles calculations. Below Tc, the electronic specific heat initially decreases in T3 behavior (1.5 K < T < Tc) then exponentially decays. Using the two-band model, the superconducting specific heat can be well described with two energy gaps: one is 0.372 meV and another 1.93 meV. The calculated bulk band structure consists of two electron bands (α and β) and two hole bands (γ and η) at the Fermi level. Experimental detection of the de Haas-van Alphen (dHvA) oscillations allows us to identify four frequencies (Fα = 65 T, Fβ = 658 T, Fγ = 1154 T, and Fη = 1867 T for H // a), consistent with theoretical predictions. Nontrivial α and β bands are further identified via both calculations and the angle dependence of the dHvA oscillations. Our results suggest that PdTe is a candidate for unconventional superconductivity.
Adsorption of radon on silver exchanged zeolites at ambient temperatures
Authors: Heinitz Stephan , Mermans Jasper , Maertens Dominic , Skliarova Hanna , Aerts Alexander , Cardinaels Thomas , Gueibe Christophe , Rutten Jos , Ireland Natalie , Kuznicki Daniel , Kuznicki Steven 
Published: April 2023

AbstractSince more than 100 years, the adsorption of the radioactive noble gas radon (222Rn) is performed on activated charcoal at cryogenic temperatures. There is little—if any—progress in the field of radon adsorption at ambient conditions to facilitate the development of simple and compact radon adsorption systems. We report here on the truly remarkable property of the synthetic silver-exchanged zeolites Ag-ETS-10 and Ag-ZSM-5 to strongly adsorb radon gas at room temperature. 222Rn breakthrough experiments in nitrogen carrier gas have shown that these materials exhibit radon adsorption coefficients exceeding 3000 m3/kg at 293 K, more than two orders of magnitude larger than any noble gas adsorbent known to date. Water vapor and carrier gas type were found to strongly influence radon adsorption, practically qualifying these silver exchanged materials as a new class of radon adsorbents. Our results demonstrate that Ag-ETS-10 and Ag-ZSM-5 are materials that show high affinity towards radon gas at ambient temperatures making them candidate materials for environmental and industrial 222Rn mitigation applications. Adsorption systems based on silver loaded zeolites have the potential to replace activated charcoal as material of choice in many radon related research areas by avoiding the necessity of cryogenic cooling.
The aorta in humans and African great apes, and cardiac output and metabolic levels in human evolution
Authors: Ríos Luis , Sleeper Meg M. , Danforth Marietta D. , Murphy Hayley Weston , Kutinsky Ilana , Rosas Antonio , Bastir Markus , Gómez-Cambronero José , Sanjurjo Ricardo , Campens Laurence , Rider Oliver , Pastor Francisco 
Published: April 2023

AbstractHumans have a larger energy budget than great apes, allowing the combination of the metabolically expensive traits that define our life history. This budget is ultimately related to the cardiac output, the product of the blood pumped from the ventricle and the number of heart beats per minute, a measure of the blood available for the whole organism physiological activity. To show the relationship between cardiac output and energy expenditure in hominid evolution, we study a surrogate measure of cardiac output, the aortic root diameter, in humans and great apes. When compared to gorillas and chimpanzees, humans present an increased body mass adjusted aortic root diameter. We also use data from the literature to show that over the human lifespan, cardiac output and total energy expenditure follow almost identical trajectories, with a marked increase during the period of brain growth, and a plateau during most of the adult life. The limited variation of adjusted cardiac output with sex, age and physical activity supports the compensation model of energy expenditure in humans. Finally, we present a first study of cardiac output in the skeleton through the study of the aortic impression in the vertebral bodies of the spine. It is absent in great apes, and present in humans and Neanderthals, large-brained hominins with an extended life cycle. An increased adjusted cardiac output, underlying higher total energy expenditure, would have been a key process in human evolution.