bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome
Authors: Barry Alexandra , McNulty Michelle T. , Jia Xiaoyuan , Gupta Yask , Debiec Hanna , Luo Yang , Nagano China , Horinouchi Tomoko , Jung Seulgi , Colucci Manuela , Ahram Dina F. , Mitrotti Adele , Sinha Aditi , Teeninga Nynke , Jin Gina , Shril Shirlee , Caridi Gianluca , Bodria Monica , Lim Tze Y. , Westland Rik , Zanoni Francesca , Marasa Maddalena , Turudic Daniel , Giordano Mario , Gesualdo Loreto , Magistroni Riccardo , Pisani Isabella , Fiaccadori Enrico , Reiterova Jana , Maringhini Silvio , Morello William , Montini Giovanni , Weng Patricia L. , Scolari Francesco , Saraga Marijan , Tasic Velibor , Santoro Domenica , van Wijk Joanna A. E. , Milošević Danko , Kawai Yosuke , Kiryluk Krzysztof , Pollak Martin R. , Gharavi Ali , Lin Fangmin , Simœs e Silva Ana Cristina , Loos Ruth J. F. , Kenny Eimear E. , Schreuder Michiel F. , Zurowska Aleksandra , Dossier Claire , Ariceta Gema , Drozynska-Duklas Magdalena , Hogan Julien , Jankauskiene Augustina , Hildebrandt Friedhelm , Prikhodina Larisa , Song Kyuyoung , Bagga Arvind , Cheong Hae , Ghiggeri Gian Marco , Vachvanichsanong Prayong , Nozu Kandai , Lee Dongwon , Vivarelli Marina , Raychaudhuri Soumya , Tokunaga Katsushi , Sanna-Cherchi Simone , Ronco Pierre , Iijima Kazumoto , Sampson Matthew G. 
Published: April 2023

AbstractPediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations—eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.
Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace
Authors: Qian Jingyang , Liao Jie , Liu Ziqi , Chi Ying , Fang Yin , Zheng Yanrong , Shao Xin , Liu Bingqi , Cui Yongjin , Guo Wenbo , Hu Yining , Bao Hudong , Yang Penghui , Chen Qian , Li Mingxiao , Zhang Bing , Fan Xiaohui 
Published: April 2023

AbstractTissues are highly complicated with spatial heterogeneity in gene expression. However, the cutting-edge single-cell RNA-seq technology eliminates the spatial information of individual cells, which contributes to the characterization of cell identities. Herein, we propose single-cell spatial position associated co-embeddings (scSpace), an integrative method to identify spatially variable cell subpopulations by reconstructing cells onto a pseudo-space with spatial transcriptome references (Visium, STARmap, Slide-seq, etc.). We benchmark scSpace with both simulated and biological datasets, and demonstrate that scSpace can accurately and robustly identify spatially variated cell subpopulations. When employed to reconstruct the spatial architectures of complex tissue such as the brain cortex, the small intestinal villus, the liver lobule, the kidney, the embryonic heart, and others, scSpace shows promising performance on revealing the pairwise cellular spatial association within single-cell data. The application of scSpace in melanoma and COVID-19 exhibits a broad prospect in the discovery of spatial therapeutic markers.
Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation
Authors: Li Ting , Jiang Shuhui , Zhang Ying , Luo Jie , Li Ming , Ke Hengte , Deng Yibin , Yang Tao , Sun Xiaohui , Chen Huabing 
Published: April 2023

AbstractThe survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor β (TGFβ) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.
A sensitive high repetition rate arrival time monitor for X-ray free electron lasers
Authors: Diez Michael , Kirchberg Henning , Galler Andreas , Schulz Sebastian , Biednov Mykola , Bömer Christina , Choi Tae-Kyu , Rodriguez-Fernandez Angel , Gawelda Wojciech , Khakhulin Dmitry , Kubicek Katharina , Lima Frederico , Otte Florian , Zalden Peter , Coffee Ryan , Thorwart Michael , Bressler Christian 
Published: April 2023

AbstractX-ray free-electron laser sources enable time-resolved X-ray studies with unmatched temporal resolution. To fully exploit ultrashort X-ray pulses, timing tools are essential. However, new high repetition rate X-ray facilities present challenges for currently used timing tool schemes. Here we address this issue by demonstrating a sensitive timing tool scheme to enhance experimental time resolution in pump-probe experiments at very high pulse repetition rates. Our method employs a self-referenced detection scheme using a time-sheared chirped optical pulse traversing an X-ray stimulated diamond plate. By formulating an effective medium theory, we confirm subtle refractive index changes, induced by sub-milli-Joule intense X-ray pulses, that are measured in our experiment. The system utilizes a Common-Path-Interferometer to detect X-ray-induced phase shifts of the optical probe pulse transmitted through the diamond sample. Owing to the thermal stability of diamond, our approach is well-suited for MHz pulse repetition rates in superconducting linear accelerator-based free-electron lasers.
Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis
Authors: Tan Huanhuan , Wang Weixu , Zhou Congjin , Wang Yanfeng , Zhang Shu , Yang Pinglan , Guo Rui , Chen Wei , Zhang Jinwen , Ye Lan , Cui Yiqiang , Ni Ting , Zheng Ke 
Published: April 2023

AbstractMammalian spermatogenesis shows prominent chromatin and transcriptomic switches in germ cells, but it is unclear how such dynamics are controlled. Here we identify RNA helicase DDX43 as an essential regulator of the chromatin remodeling process during spermiogenesis. Testis-specificDdx43knockout mice show male infertility with defective histone-to-protamine replacement and post-meiotic chromatin condensation defects. The loss of its ATP hydrolysis activity by a missense mutation replicates the infertility phenotype in globalDdx43knockout mice. Single-cell RNA sequencing analyses of germ cells depleted ofDdx43or expressing theDdx43ATPase-dead mutant reveals that DDX43 regulates dynamic RNA regulatory processes that underlie spermatid chromatin remodeling and differentiation. Transcriptomic profiling focusing on early-stage spermatids combined with enhanced crosslinking immunoprecipitation and sequencing further identifiesElfn2as DDX43-targeted hub gene. These findings illustrate an essential role for DDX43 in spermiogenesis and highlight the single-cell-based strategy to dissect cell-state-specific regulation of male germline development.
Virus diversity, wildlife-domestic animal circulation and potential zoonotic viruses of small mammals, pangolins and zoo animals
Authors: Cui Xinyuan , Fan Kewei , Liang Xianghui , Gong Wenjie , Chen Wu , He Biao , Chen Xiaoyuan , Wang Hai , Wang Xiao , Zhang Ping , Lu Xingbang , Chen Rujian , Lin Kaixiong , Liu Jiameng , Zhai Junqiong , Liu Ding Xiang , Shan Fen , Li Yuqi , Chen Rui Ai , Meng Huifang , Li Xiaobing , Mi Shijiang , Jiang Jianfeng , Zhou Niu , Chen Zujin , Zou Jie-Jian , Ge Deyan , Yang Qisen , He Kai , Chen Tengteng , Wu Ya-Jiang , Lu Haoran , Irwin David M. , Shen Xuejuan , Hu Yuanjia , Lu Xiaoman , Ding Chan , Guan Yi , Tu Changchun , Shen Yongyi 
Published: April 2023

AbstractWildlife is reservoir of emerging viruses. Here we identified 27 families of mammalian viruses from 1981 wild animals and 194 zoo animals collected from south China between 2015 and 2022, isolated and characterized the pathogenicity of eight viruses. Bats harbor high diversity of coronaviruses, picornaviruses and astroviruses, and a potentially novel genus of Bornaviridae. In addition to the reported SARSr-CoV-2 and HKU4-CoV-like viruses, picornavirus and respiroviruses also likely circulate between bats and pangolins. Pikas harbor a new clade of Embecovirus and a new genus of arenaviruses. Further, the potential cross-species transmission of RNA viruses (paramyxovirus and astrovirus) and DNA viruses (pseudorabies virus, porcine circovirus 2, porcine circovirus 3 and parvovirus) between wildlife and domestic animals was identified, complicating wildlife protection and the prevention and control of these diseases in domestic animals. This study provides a nuanced view of the frequency of host-jumping events, as well as assessments of zoonotic risk.
The origin of magnetization-caused increment in water oxidation
Authors: Ren Xiao , Wu Tianze , Gong Zizhao , Pan Lulu , Meng Jianling , Yang Haitao , Dagbjartsdottir Freyja Bjork , Fisher Adrian , Gao Hong-Jun , Xu Zhichuan J. 
Published: April 2023

AbstractMagnetization promoted activity of magnetic catalysts towards the oxygen evolution reaction (OER) has attracted great attention, but remains a puzzle where the increment comes from. Magnetization of a ferromagnetic material only changes its magnetic domain structure. It does not directly change the spin orientation of unpaired electrons in the material. The confusion is that each magnetic domain is a small magnet and theoretically the spin-polarization promoted OER already occurs on these magnetic domains, and thus the enhancement should have been achieved without magnetization. Here, we demonstrate that the enhancement comes from the disappeared domain wall upon magnetization. Magnetization leads to the evolution of the magnetic domain structure, from a multi-domain one to a single domain one, in which the domain wall disappears. The surface occupied by the domain wall is reformatted into one by a single domain, on which the OER follows the spin-facilitated pathways and thus the overall increment on the electrode occurs. This study fills the missing gap for understanding the spin-polarized OER and it further explains the type of ferromagnetic catalysts which can give increment by magnetization.
The diffuse gamma-ray flux from clusters of galaxies
Authors: Hussain Saqib , Alves Batista Rafael , de Gouveia Dal Pino Elisabete M. , Dolag Klaus 
Published: April 2023

AbstractThe origin of the diffuse gamma-ray background (DGRB), the one that remains after subtracting all individual sources from observed gamma-ray sky, is unknown. The DGRB possibly encompasses contributions from different source populations such as star-forming galaxies, starburst galaxies, active galactic nuclei, gamma-ray bursts, or galaxy clusters. Here, we combine cosmological magnetohydrodynamical simulations of clusters of galaxies with the propagation of cosmic rays (CRs) using Monte Carlo simulations, in the redshift range z ≤ 5.0, and show that the integrated gamma-ray flux from clusters can contribute up to 100% of the DGRB flux observed by Fermi-LAT above 100 GeV, for CRs spectral indices α = 1.5 − 2.5 and energy cutoffs $${E}_{\max }=1{0}^{16}-1{0}^{17}$$

E

max

=
1

0

16

−
1

0

17

eV. The flux is dominated by clusters with masses 1013 ≲ M/M⊙ ≲ 1015 and redshift z ≲ 0.3. Our results also predict the potential observation of high-energy gamma rays from clusters by experiments like the High Altitude Water Cherenkov (HAWC), the Large High Altitude Air Shower Observatory (LHAASO), and potentially the upcoming Cherenkov Telescope Array (CTA).
Nucleotide exchange is sufficient for Hsp90 functions in vivo
Authors: Reidy Michael , Garzillo Kevin , Masison Daniel C. 
Published: April 2023

AbstractHsp90 is an essential eukaryotic chaperone that regulates the activity of many client proteins. Current models of Hsp90 function, which include many conformational rearrangements, specify a requirement of ATP hydrolysis. Here we confirm earlier findings that the Hsp82-E33A mutant, which binds ATP but does not hydrolyze it, supports viability ofS. cerevisiae, although it displays conditional phenotypes. We find binding of ATP to Hsp82-E33A induces the conformational dynamics needed for Hsp90 function. Hsp90 orthologs with the analogous EA mutation from several eukaryotic species, including humans and disease organisms, support viability of bothS. cerevisiaeandSz. pombe. We identify second-site suppressors of EA that rescue its conditional defects and allow EA versions of all Hsp90 orthologs tested to support nearly normal growth of both organisms, without restoring ATP hydrolysis. Thus, the requirement of ATP for Hsp90 to maintain viability of evolutionarily distant eukaryotic organisms does not appear to depend on energy from ATP hydrolysis. Our findings support earlier suggestions that exchange of ATP for ADP is critical for Hsp90 function. ATP hydrolysis is not necessary for this exchange but provides an important control point in the cycle responsive to regulation by co-chaperones.
PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis
Authors: Bertschi Nicole L. , Steck Oliver , Luther Fabian , Bazzini Cecilia , von Meyenn Leonhard , Schärli Stefanie , Vallone Angela , Felser Andrea , Keller Irene , Friedli Olivier , Freigang Stefan , Begré Nadja , Radonjic-Hoesli Susanne , Lamos Cristina , Gabutti Max Philip , Benzaquen Michael , Laimer Markus , Simon Dagmar , Nuoffer Jean-Marc , Schlapbach Christoph 
Published: April 2023

AbstractT helper 9 (TH9) cells promote allergic tissue inflammation and express the type 2 cytokines, IL-9 and IL-13, as well as the transcription factor, PPAR-γ. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments show that the PPAR-γ-mTORC1-IL-9 pathway is active in TH9 cells in human skin inflammation. Additionally, we find dynamic regulation of tissue glucose levels in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological functions in vivo. Furthermore, paracrine IL-9 induces expression of the lactate transporter, MCT1, in TH cells and promotes their aerobic glycolysis and proliferative capacity. Altogether, our findings uncover a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and pathogenic effector functions in human TH9 cells.
Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis
Authors: Obeidat Alia M. , Wood Matthew J. , Adamczyk Natalie S. , Ishihara Shingo , Li Jun , Wang Lai , Ren Dongjun , Bennett David A. , Miller Richard J. , Malfait Anne-Marie , Miller Rachel E. 
Published: April 2023

AbstractNon-opioid targets are needed for addressing osteoarthritis pain, which is mechanical in nature and associated with daily activities such as walking and climbing stairs. Piezo2 has been implicated in the development of mechanical pain, but the mechanisms by which this occurs remain poorly understood, including the role of nociceptors. Here we show that nociceptor-specific Piezo2 conditional knock-out mice were protected from mechanical sensitization associated with inflammatory joint pain in female mice, joint pain associated with osteoarthritis in male mice, as well as both knee swelling and joint pain associated with repeated intra-articular injection of nerve growth factor in male mice. Single cell RNA sequencing of mouse lumbar dorsal root ganglia and in situ hybridization of mouse and human lumbar dorsal root ganglia revealed that a subset of nociceptors co-express Piezo2 and Ntrk1 (the gene that encodes the nerve growth factor receptor TrkA). These results suggest that nerve growth factor-mediated sensitization of joint nociceptors, which is critical for osteoarthritic pain, is also dependent on Piezo2, and targeting Piezo2 may represent a therapeutic option for osteoarthritis pain control.
Clustering of charged colloidal particles in the microgravity environment of space
Authors: Miki Hiroyuki , Ishigami Teruyoshi , Yamanaka Junpei , Okuzono Tohru , Toyotama Akiko , Mata Jitendra , Komazawa Honoka , Takeda Yushi , Minami Madoka , Fujita Minori , Doi Maho , Higuchi Tsunehiko , Takase Hiroshi , Adachi Satoshi , Sakashita Tetsuya , Shimaoka Taro , Nagai Masae , Watanabe Yuki , Fukuyama Seijiro 
Published: April 2023

AbstractWe conducted a charge–charge clustering experiment of positively and negatively charged colloidal particles in aqueous media under a microgravity environment at the International Space Station. A special setup was used to mix the colloid particles in microgravity and then these structures were immobilized in gel cured using ultraviolet (UV) light. The samples returned to the ground were observed by optical microscopy. The space sample of polystyrene particles with a specific gravity ρ (=1.05) close to the medium had an average association number of ~50% larger than the ground control and better structural symmetry. The effect of electrostatic interactions on the clustering was also confirmed for titania particles (ρ ~ 3), whose association structures were only possible in the microgravity environment without any sedimentation they generally suffer on the ground. This study suggests that even slight sedimentation and convection on the ground significantly affect the structure formation of colloids. Knowledge from this study will help us to develop a model which will be used to design photonic materials and better drugs.
Cortical thinning in relation to impaired insight into illness in patients with treatment resistant schizophrenia
Authors: Kim Julia , Song Jianmeng , Kambari Yasaman , Plitman Eric , Shah Parita , Iwata Yusuke , Caravaggio Fernando , Brown Eric E. , Nakajima Shinichiro , Chakravarty M. Mallar , De Luca Vincenzo , Remington Gary , Graff-Guerrero Ariel , Gerretsen Philip 
Published: April 2023

AbstractImpaired insight into illness is a common element of schizophrenia that contributes to treatment nonadherence and negative clinical outcomes. Previous studies suggest that impaired insight may arise from brain abnormalities. However, interpretations of these findings are limited due to small sample sizes and inclusion of patients with a narrow range of illness severity and insight deficits. In a large sample of patients with schizophrenia, the majority of which were designated as treatment-resistant, we investigated the associations between impaired insight and cortical thickness and subcortical volumes. A total of 94 adult participants with a schizophrenia spectrum disorder were included. Fifty-six patients (60%) had treatment-resistant schizophrenia. The core domains of insight were assessed with the VAGUS insight into psychosis scale. We obtained 3T MRI T1-weighted images, which were analysed using CIVET and MAGeT-Brain. Whole-brain vertex-wise analyses revealed impaired insight, as measured by VAGUS average scores, was related to cortical thinning in left frontotemporoparietal regions. The same analysis in treatment-resistant patients showed thinning in the same regions, even after controlling for age, sex, illness severity, and chlorpromazine antipsychotic dose equivalents. No association was found in non-treatment-resistant patients. Region-of-interest analyses revealed impaired general illness awareness was associated with cortical thinning in the left supramarginal gyrus when controlling for covariates. Reduced right and left thalamic volumes were associated with VAGUS symptom attribution and awareness of negative consequences subscale scores, respectively, but not after correction for multiple testing. Our results suggest impaired insight into illness is related to cortical thinning in left frontotemporoparietal regions in patients with schizophrenia, particularly those with treatment resistance where insight deficits may be more chronic.
An intuitionistic approach for the predictability of anti-angiogenic inhibitors in cancer diagnosis
Authors: Ansar Syed Anas , Aggarwal Shruti , Arya Swati , Haq Mohd. Anul , Mittal Vikas , Gared Fikreselam 
Published: April 2023

AbstractMalignant cancer angiogenesis has historically attracted enormous scientific attention. Although angiogenesis is requisite for a child’s development and conducive to tissue homeostasis, it is deleterious when cancer lurks. Today, anti-angiogenic biomolecular receptor tyrosine kinase inhibitors (RTKIs) to target angiogenesis have been prolific in treating various carcinomas. Angiogenesis is a pivotal component in malignant transformation, oncogenesis, and metastasis that can be activated by a multiplicity of factors (e.g., VEGF (Vascular endothelial growth factor), (FGF) Fibroblast growth factor, (PDGF) Platelet-derived growth factor and others). The advent of RTKIs, which primarily target members of the VEGFR (VEGF Receptor) family of angiogenic receptors has greatly ameliorated the outlook for some cancer forms, including hepatocellular carcinoma, malignant tumors, and gastrointestinal carcinoma. Cancer therapeutics have evolved steadily with active metabolites and strong multi-targeted RTK inhibitors such as E7080, CHIR-258, SU 5402, etc. This research intends to determine the efficacious anti-angiogenesis inhibitors and rank them by using the Preference Ranking Organization Method for Enrichment Evaluation (PROMETHEE- II) decision-making algorithm. The PROMETHEE-II approach assesses the influence of growth factors (GFs) in relation to the anti-angiogenesis inhibitors. Due to their capacity to cope with the frequently present vagueness while ranking alternatives, fuzzy models constitute the most suitable tools for producing results for analyzing qualitative information. This research’s quantitative methodology focuses on ranking the inhibitors according to their significance concerning criteria. The evaluation findings indicate the most efficacious and idle alternative for inhibiting angiogenesis in cancer.