bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantify the Information Contributions of External Drivers to Global Ionospheric TEC
Authors: Wang Sicheng , Huang Sixun 
Published: September 2023

AbstractThe ionospheric variabilities are influenced by various drivers, and quantifying their relative contributions is beneficial to ionospheric modeling and ionospheric forecasting, but this is still a significant challenge in the ionospheric community. In present paper, the global ionosphere maps, solar indices, solar wind and interplanetary parameters, geomagnetic indices, and lower atmospheric parameters from 2001 to 2021 are collected, and the Liang‐Kleeman information flow is used to measure the amount of information exchanges from external drivers to ionospheric TEC at different geographical regions, and the normalized Liang‐Kleeman information flow is adopted to quantify their relative information contributions. The results show that the geographical distribution of information flow has prominent hemispheric asymmetry, and overall, the information flows from solar indices (solar wind and interplanetary parameters, geomagnetic indices) to ionospheric TEC in the northern hemisphere are larger than those in the southern hemisphere. Ionospheric self‐influence (i.e., internal processes of the ionosphere) has the largest information contribution to ionospheric TEC, accounting for about 46.78%. Solar activity manifested as P index has the second largest contribution (nearly 35.29%). Solar wind and interplanetary activity represented as IMF magnitude contributes around 2.94%, geomagnetic activity characterized as ASYH index accounts for about 1.52%, lower atmospheric forcing contributes nearly 7.75%, and noise accounts for approximately 5.73%. What's more, the performances of the IRI‐2020 model are evaluated from the perspective of information flow.
Bidirectional genetic overlap between autism spectrum disorder and cognitive traits
Authors: Hope Sigrun , Shadrin Alexey A. , Lin Aihua , Bahrami Shahram , Rødevand Linn , Frei Oleksandr , Hübenette Saira J. , Cheng Weiqiu , Hindley Guy , Nag Heidi , Ulstein Line , Efrim-Budisteanu Magdalena , O’Connell Kevin , Dale Anders M. , Djurovic Srdjan , Nærland Terje , Andreassen Ole A. 
Published: September 2023

AbstractAutism spectrum disorder (ASD) is a highly heritable condition with a large variation in cognitive function. Here we investigated the shared genetic architecture between cognitive traits (intelligence (INT) and educational attainment (EDU)), and risk loci jointly associated with ASD and the cognitive traits. We analyzed data from genome-wide association studies (GWAS) of INT (n = 269,867), EDU (n = 766,345) and ASD (cases n = 18,381, controls n = 27,969). We used the bivariate causal mixture model (MiXeR) to estimate the total number of shared genetic variants, local analysis of co-variant annotation (LAVA) to estimate local genetic correlations, conditional false discovery rate (cond/conjFDR) to identify specific overlapping loci. The MiXeR analyses showed that 12.7k genetic variants are associated with ASD, of which 12.0k variants are shared with EDU, and 11.1k are shared with INT with both positive and negative relationships within overlapping variants. The majority (59–68%) of estimated shared loci have concordant effect directions, with a positive, albeit modest, genetic correlation between ASD and EDU (rg = 0.21, p = 2e−13) and INT (rg = 0.22, p = 4e−12). We discovered 43 loci jointly associated with ASD and cognitive traits (conjFDR<0.05), of which 27 were novel for ASD. Functional analysis revealed significant differential expression of candidate genes in the cerebellum and frontal cortex. To conclude, we quantified the genetic architecture shared between ASD and cognitive traits, demonstrated mixed effect directions, and identified the associated genetic loci and molecular pathways. The findings suggest that common genetic risk factors for ASD can underlie both better and worse cognitive functioning across the ASD spectrum, with different underlying biology.
Börjeson–Forssman–Lehmann syndrome: delineating the clinical and allelic spectrum in 14 new families
Authors: Jain Vani , Foo Seow Hoong , Chooi Stephen , Moss Celia , Goodwin Richard , Berland Siren , Clarke Angus J. , Davies Sally J. , Corrin Sian , Murch Oliver , Doyle Samantha , Graham Gail E. , Greenhalgh Lynn , Holder Susan E. , Johnson Diana , Kumar Ajith , Ladda Roger L. , Sell Susan , Begtrup Amber , Lynch Sally A. , McCann Emma , Østern Rune , Pottinger Caroline , Splitt Miranda , Fry Andrew E. 
Published: September 2023

AbstractBörjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported. Six variants were novel. We analysed the clinical and genetic findings in our series and compared them with reported BFLS patients. Affected males had classic features of BFLS including intellectual disability, distinctive facies, large ears, gynaecomastia, hypogonadism and truncal obesity. Carrier female relatives of affected males were unaffected or had only mild symptoms. The phenotype of affected females with de novo variants overlapped with the males but included linear skin hyperpigmentation and a higher frequency of dental, retinal and cortical brain anomalies. Complications observed in our series included keloid scarring, digital fibromas, absent vaginal orifice, neuropathy, umbilical hernias, and talipes. Our analysis highlighted sex-specific differences in PHF6 variant types and locations. Affected males often have missense variants or small in-frame deletions while affected females tend to have truncating variants or large deletions/duplications. Missense variants were found in a minority of affected females and clustered in the highly constrained PHD2 domain of PHF6. We propose recommendations for the evaluation and management of BFLS patients. These results further delineate and extend the genetic and phenotypic spectrum of BFLS.
Pro-phagocytic function and structural basis of GPR84 signaling
Authors: Zhang Xuan , Wang Yujing , Supekar Shreyas , Cao Xu , Zhou Jingkai , Dang Jessica , Chen Siqi , Jenkins Laura , Marsango Sara , Li Xiu , Liu Guibing , Milligan Graeme , Feng Mingye , Fan Hao , Gong Weimin , Zhang Cheng 
Published: September 2023

AbstractGPR84 is a unique orphan G protein-coupled receptor (GPCR) that can be activated by endogenous medium-chain fatty acids (MCFAs). The signaling of GPR84 is largely pro-inflammatory, which can augment inflammatory response, and GPR84 also functions as a pro-phagocytic receptor to enhance phagocytic activities of macrophages. In this study, we show that the activation of GPR84 by the synthetic agonist 6-OAU can synergize with the blockade of CD47 on cancer cells to induce phagocytosis of cancer cells by macrophages. We also determine a high-resolution structure of the GPR84-Gi signaling complex with 6-OAU. This structure reveals an occluded binding pocket for 6-OAU, the molecular basis of receptor activation involving non-conserved structural motifs of GPR84, and an unusual Gi-coupling interface. Together with computational docking and simulations studies, this structure also suggests a mechanism for the high selectivity of GPR84 for MCFAs and a potential routes of ligand binding and dissociation. These results provide a framework for understanding GPR84 signaling and developing new drugs targeting GPR84.
Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification
Authors: Vijayakumar Sivakamasundari , Sala Roberta , Kang Gugene , Chen Angela , Pablo Michelle Ann , Adebayo Abidemi Ismail , Cipriano Andrea , Fowler Jonas L. , Gomes Danielle L. , Ang Lay Teng , Loh Kyle M. , Sebastiano Vittorio 
Published: September 2023

AbstractGenerating primordial germ cell-like cells (PGCLCs) from human pluripotent stem cells (hPSCs) advances studies of human reproduction and development of infertility treatments, but often entails complex 3D aggregates. Here we develop a simplified, monolayer method to differentiate hPSCs into PGCs within 3.5 days. We use our simplified differentiation platform and single-cell RNA-sequencing to achieve further insights into PGCLC specification. Transient WNT activation for 12 h followed by WNT inhibition specified PGCLCs; by contrast, sustained WNT induced primitive streak. Thus, somatic cells (primitive streak) and PGCLCs are related—yet distinct—lineages segregated by temporally-dynamic signaling. Pluripotency factors including NANOG are continuously expressed during the transition from pluripotency to posterior epiblast to PGCs, thus bridging pluripotent and germline states. Finally, hPSC-derived PGCLCs can be easily purified by virtue of their CXCR4+PDGFRA-GARP- surface-marker profile and single-cell RNA-sequencing reveals that they harbor transcriptional similarities with fetal PGCs.
Germinal center output is sustained by HELLS-dependent DNA-methylation-maintenance in B cells
Authors: Cousu Clara , Mulot Eléonore , De Smet Annie , Formichetti Sara , Lecoeuche Damiana , Ren Jianke , Muegge Kathrin , Boulard Matthieu , Weill Jean-Claude , Reynaud Claude-Agnès , Storck Sébastien 
Published: September 2023

AbstractHELLS/LSH (Helicase, Lymphoid Specific) is a SNF2-like chromatin remodelling protein involved in DNA methylation. Its loss-of-function in humans causes humoral immunodeficiency, called ICF4 syndrome (Immunodeficiency, Centromeric Instability, Facial anomalies). Here we show by our newly generated B-cell-specificHellsconditional knockout mouse model that HELLS plays a pivotal role in T-dependent B-cell responses. HELLS deficiency induces accelerated decay of germinal center (GC) B cells and impairs the generation of high affinity memory B cells and circulating antibodies. Mutant GC B cells undergo dramatic DNA hypomethylation and massive de-repression of evolutionary recent retrotransposons, which surprisingly does not directly affect their survival. Instead, they prematurely upregulate either memory B cell markers or the transcription factor ATF4, which is driving an mTORC1-dependent metabolic program typical of plasma cells. Treatment of wild type mice with a DNMT1-specific inhibitor phenocopies the accelerated kinetics, thus pointing towards DNA-methylation maintenance by HELLS being a crucial mechanism to fine-tune the GC transcriptional program and enable long-lasting humoral immunity.
Multistage coupling water-enabled electric generator with customizable energy output
Authors: Li Puying , Hu Yajie , He Wenya , Lu Bing , Wang Haiyan , Cheng Huhu , Qu Liangti 
Published: September 2023

AbstractConstant water circulation between land, ocean and atmosphere contains great and sustainable energy, which has been successfully employed to generate electricity by the burgeoning water-enabled electric generator. However, water in various forms (e.g. liquid, moisture) is inevitably discharged after one-time use in current single-stage water-enabled electric generators, resulting in the huge waste of inherent energy within water circulation. Herein, a multistage coupling water-enabled electric generator is proposed, which utilizes the internal liquid flow and subsequently generated moisture to produce electricity synchronously, achieving a maximum output power density of ~92 mW m−2 (~11 W m−3). Furthermore, a distributary design for internal water in different forms enables the integration of water-flow-enabled and moisture-diffusion-enabled electricity generation layers into mc-WEG by a “flexible building blocks” strategy. Through a three-stage adjustment process encompassing size control, space optimization, and large-scale integration, the multistage coupling water-enabled electric generator realizes the customized electricity output for diverse electronics. Twenty-two units connected in series can deliver ~10 V and ~280 μA, which can directly lighten a table lamp for 30 min without aforehand capacitor charging. In addition, multistage coupling water-enabled electric generators exhibit excellent flexibility and environmental adaptability, providing a way for the development of water-enabled electric generators.
Neurofunctional underpinnings of individual differences in visual episodic memory performance
Authors: Geissmann Léonie , Coynel David , Papassotiropoulos Andreas , de Quervain Dominique J. F. 
Published: September 2023

AbstractEpisodic memory, the ability to consciously recollect information and its context, varies substantially among individuals. While prior fMRI studies have identified certain brain regions linked to successful memory encoding at a group level, their role in explaining individual memory differences remains largely unexplored. Here, we analyze fMRI data of 1,498 adults participating in a picture encoding task in a single MRI scanner. We find that individual differences in responsivity of the hippocampus, orbitofrontal cortex, and posterior cingulate cortex account for individual variability in episodic memory performance. While these regions also emerge in our group-level analysis, other regions, predominantly within the lateral occipital cortex, are related to successful memory encoding but not to individual memory variation. Furthermore, our network-based approach reveals a link between the responsivity of nine functional connectivity networks and individual memory variability. Our work provides insights into the neurofunctional correlates of individual differences in visual episodic memory performance.
Molecular basis of TASL recruitment by the peptide/histidine transporter 1, PHT1
Authors: Custódio Tânia F. , Killer Maxime , Yu Dingquan , Puente Virginia , Teufel Daniel P. , Pautsch Alexander , Schnapp Gisela , Grundl Marc , Kosinski Jan , Löw Christian 
Published: September 2023

AbstractPHT1 is a histidine /oligopeptide transporter with an essential role in Toll-like receptor innate immune responses. It can act as a receptor by recruiting the adaptor protein TASL which leads to type I interferon production via IRF5. Persistent stimulation of this signalling pathway is known to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Understanding how PHT1 recruits TASL at the molecular level, is therefore clinically important for the development of therapeutics against SLE and other autoimmune diseases. Here we present the Cryo-EM structure of PHT1 stabilized in the outward-open conformation. By combining biochemical and structural modeling techniques we propose a model of the PHT1-TASL complex, in which the first 16 N-terminal TASL residues fold into a helical structure that bind in the central cavity of the inward-open conformation of PHT1. This work provides critical insights into the molecular basis of PHT1/TASL mediated type I interferon production.
Polyamine detergents tailored for native mass spectrometry studies of membrane proteins
Authors: Zhu Yun , Peng Bo-Ji , Kumar Smriti , Stover Lauren , Chang Jing-Yuan , Lyu Jixing , Zhang Tianqi , Schrecke Samantha , Azizov Djavdat , Russell David H. , Fang Lei , Laganowsky Arthur 
Published: September 2023

AbstractNative mass spectrometry (MS) is a powerful technique for interrogating membrane protein complexes and their interactions with other molecules. A key aspect of the technique is the ability to preserve native-like structures and noncovalent interactions, which can be challenging depending on the choice of detergent. Different strategies have been employed to reduce charge on protein complexes to minimize activation and preserve non-covalent interactions. Here, we report the synthesis of a class of polyamine detergents tailored for native MS studies of membrane proteins. These detergents, a series of spermine covalently attached to various alkyl tails, are exceptional charge-reducing molecules, exhibiting a ten-fold enhanced potency over spermine. Addition of polyamine detergents to proteins solubilized in maltoside detergents results in improved, charge-reduced native mass spectra and reduced dissociation of subunits. Polyamine detergents open new opportunities to investigate membrane proteins in different detergent environments that have thwarted previous native MS studies.
Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent
Authors: Kumar Brijesh , Khatpe Aditi S. , Guanglong Jiang , Batic Katie , Bhat-Nakshatri Poornima , Granatir Maggie M. , Addison Rebekah Joann , Szymanski Megan , Baldridge Lee Ann , Temm Constance J. , Sandusky George , Althouse Sandra K. , Cote Michele L. , Miller Kathy D. , Storniolo Anna Maria , Nakshatri Harikrishna 
Published: September 2023

AbstractThe biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.
Activator-blocker model of transcriptional regulation by pioneer-like factors
Authors: Riesle Aileen Julia , Gao Meijiang , Rosenblatt Marcus , Hermes Jacques , Hass Helge , Gebhard Anna , Veil Marina , Grüning Björn , Timmer Jens , Onichtchouk Daria 
Published: September 2023

AbstractZygotic genome activation (ZGA) in the development of flies, fish, frogs and mammals depends on pioneer-like transcription factors (TFs). Those TFs create open chromatin regions, promote histone acetylation on enhancers, and activate transcription. Here, we use the panel of single, double and triple mutants for zebrafish genome activators Pou5f3, Sox19b and Nanog, multi-omics and mathematical modeling to investigate the combinatorial mechanisms of genome activation. We show that Pou5f3 and Nanog act differently on synergistic and antagonistic enhancer types. Pou5f3 and Nanog both bind as pioneer-like TFs on synergistic enhancers, promote histone acetylation and activate transcription. Antagonistic enhancers are activated by binding of one of these factors. The other TF binds as non-pioneer-like TF, competes with the activator and blocks all its effects, partially or completely. This activator-blocker mechanism mutually restricts widespread transcriptional activation by Pou5f3 and Nanog and prevents premature expression of late developmental regulators in the early embryo.
Assembling membraneless organelles from de novo designed proteins
Authors: Hilditch Alexander T. , Romanyuk Andrey , Cross Stephen J. , Obexer Richard , McManus Jennifer J. , Woolfson Derek N. 
Published: September 2023

AbstractRecent advances in de novo protein design have delivered a diversity of discrete de novo protein structures and complexes. A new challenge for the field is to use these designs directly in cells to intervene in biological processes and augment natural systems. The bottom-up design of self-assembled objects such as microcompartments and membraneless organelles is one such challenge. Here we describe the design of genetically encoded polypeptides that form membraneless organelles in Escherichia coli. To do this, we combine de novo α-helical sequences, intrinsically disordered linkers and client proteins in single-polypeptide constructs. We tailor the properties of the helical regions to shift protein assembly from arrested assemblies to dynamic condensates. The designs are characterized in cells and in vitro using biophysical methods and soft-matter physics. Finally, we use the designed polypeptide to co-compartmentalize a functional enzyme pair in E. coli, improving product formation close to the theoretical limit.
Distinct monkeypox virus lineages co-circulating in humans before 2022
Authors: Ndodo Nnaemeka , Ashcroft Jonathan , Lewandowski Kuiama , Yinka-Ogunleye Adesola , Chukwu Chimaobi , Ahmad Adama , King David , Akinpelu Afolabi , Maluquer de Motes Carlos , Ribeca Paolo , Sumner Rebecca P. , Rambaut Andrew , Chester Michael , Maishman Tom , Bamidele Oluwafemi , Mba Nwando , Babatunde Olajumoke , Aruna Olusola , Pullan Steven T. , Gannon Benedict , Brown Colin S. , Ihekweazu Chikwe , Adetifa Ifedayo , Ulaeto David O. 
Published: September 2023

AbstractThe 2022 global mpox outbreak raises questions about how this zoonotic disease established effective human-to-human transmission and its potential for further adaptation. The 2022 outbreak virus is related to an ongoing outbreak in Nigeria originally reported in 2017, but the evolutionary path linking the two remains unclear due to a lack of genomic data between 2018, when virus exportations from Nigeria were first recorded, and 2022, when the global mpox outbreak began. Here, 18 viral genomes obtained from patients across southern Nigeria in 2019–2020 reveal multiple lineages of monkeypox virus (MPXV) co-circulated in humans for several years before 2022, with progressive accumulation of mutations consistent with APOBEC3 activity over time. We identify Nigerian A.2 lineage isolates, confirming the lineage that has been multiply exported to North America independently of the 2022 outbreak originated in Nigeria, and that it has persisted by human-to-human transmission in Nigeria for more than 2 years before its latest exportation. Finally, we identify a lineage-defining APOBEC3-style mutation in all A.2 isolates that disrupts gene A46R, encoding a viral innate immune modulator. Collectively, our data demonstrate MPXV capacity for sustained diversification within humans, including mutations that may be consistent with established mechanisms of poxvirus adaptation.
Conformational coupling of redox-driven Na+-translocation in Vibrio cholerae NADH:quinone oxidoreductase
Authors: Hau Jann-Louis , Kaltwasser Susann , Muras Valentin , Casutt Marco S. , Vohl Georg , Claußen Björn , Steffen Wojtek , Leitner Alexander , Bill Eckhard , Cutsail George E. , DeBeer Serena , Vonck Janet , Steuber Julia , Fritz Günter 
Published: September 2023

AbstractIn the respiratory chain, NADH oxidation is coupled to ion translocation across the membrane to build up an electrochemical gradient. In the human pathogen Vibrio cholerae, the sodium-pumping NADH:quinone oxidoreductase (Na+-NQR) generates a sodium gradient by a so far unknown mechanism. Here we show that ion pumping in Na+-NQR is driven by large conformational changes coupling electron transfer to ion translocation. We have determined a series of cryo-EM and X-ray structures of the Na+-NQR that represent snapshots of the catalytic cycle. The six subunits NqrA, B, C, D, E, and F of Na+-NQR harbor a unique set of cofactors that shuttle the electrons from NADH twice across the membrane to quinone. The redox state of a unique intramembranous [2Fe-2S] cluster orchestrates the movements of subunit NqrC, which acts as an electron transfer switch. We propose that this switching movement controls the release of Na+ from a binding site localized in subunit NqrB.