bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging
Authors: van Rhijn Norman , Zhao Can , Al-Furaiji Narjes , Storer Isabelle S. R. , Valero Clara , Gago Sara , Chown Harry , Baldin Clara , Grant Rachael-Fortune , Bin Shuraym Hajer , Ivanova Lia , Kniemeyer Olaf , Krüger Thomas , Bignell Elaine , Goldman Gustavo H. , Amich Jorge , Delneri Daniela , Bowyer Paul , Brakhage Axel A. , Haas Hubertus , Bromley Michael J. 
Published: June 2024

AbstractMore than 10 million people suffer from lung diseases caused by the pathogenic fungus Aspergillus fumigatus. Azole antifungals represent first-line therapeutics for most of these infections but resistance is rising, therefore the identification of antifungal targets whose inhibition synergises with the azoles could improve therapeutic outcomes. Here, we generate a library of 111 genetically barcoded null mutants of Aspergillus fumigatus in genes encoding protein kinases, and show that loss of function of kinase YakA results in hypersensitivity to the azoles and reduced pathogenicity. YakA is an orthologue of Candida albicans Yak1, a TOR signalling pathway kinase involved in modulation of stress responsive transcriptional regulators. We show that YakA has been repurposed in A. fumigatus to regulate blocking of the septal pore upon exposure to stress. Loss of YakA function reduces the ability of A. fumigatus to penetrate solid media and to grow in mouse lung tissue. We also show that 1-ethoxycarbonyl-beta-carboline (1-ECBC), a compound previously shown to inhibit C. albicans Yak1, prevents stress-mediated septal spore blocking and synergises with the azoles to inhibit A. fumigatus growth.
Using scalable computer vision to automate high-throughput semiconductor characterization
Authors: Siemenn Alexander E. , Aissi Eunice , Sheng Fang , Tiihonen Armi , Kavak Hamide , Das Basita , Buonassisi Tonio 
Published: June 2024

AbstractHigh-throughput materials synthesis methods, crucial for discovering novel functional materials, face a bottleneck in property characterization. These high-throughput synthesis tools produce 104 samples per hour using ink-based deposition while most characterization methods are either slow (conventional rates of 101 samples per hour) or rigid (e.g., designed for standard thin films), resulting in a bottleneck. To address this, we propose automated characterization (autocharacterization) tools that leverage adaptive computer vision for an 85x faster throughput compared to non-automated workflows. Our tools include a generalizable composition mapping tool and two scalable autocharacterization algorithms that: (1) autonomously compute the band gaps of 200 compositions in 6 minutes, and (2) autonomously compute the environmental stability of 200 compositions in 20 minutes, achieving 98.5% and 96.9% accuracy, respectively, when benchmarked against domain expert manual evaluation. These tools, demonstrated on the formamidinium (FA) and methylammonium (MA) mixed-cation perovskite system FA1−xMAxPbI3, 0 ≤ x ≤ 1, significantly accelerate the characterization process, synchronizing it closer to the rate of high-throughput synthesis.
Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight
Authors: Houerbi Nadia , Kim JangKeun , Overbey Eliah G. , Batra Richa , Schweickart Annalise , Patras Laura , Lucotti Serena , Ryon Krista A. , Najjar Deena , Meydan Cem , Damle Namita , Chin Christopher , Narayanan S. Anand , Guarnieri Joseph W. , Widjaja Gabrielle , Beheshti Afshin , Tobias Gabriel , Vatter Fanny , Hirschberg Jeremy Wain , Kleinman Ashley , Afshin Evan E. , MacKay Matthew , Chen Qiuying , Miller Dawson , Gajadhar Aaron S. , Williamson Lucy , Tandel Purvi , Yang Qiu , Chu Jessica , Benz Ryan , Siddiqui Asim , Hornburg Daniel , Gross Steven , Shirah Bader , Krumsiek Jan , Mateus Jaime , Mao Xiao , Matei Irina , Mason Christopher E. 
Published: June 2024

AbstractAs spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated “spaceflight secretome profiles,” which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.
Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses
Authors: Grigorev Kirill , Nelson Theodore M. , Overbey Eliah G. , Houerbi Nadia , Kim JangKeun , Najjar Deena , Damle Namita , Afshin Evan E. , Ryon Krista A. , Thierry-Mieg Jean , Thierry-Mieg Danielle , Melnick Ari M. , Mateus Jaime , Mason Christopher E. 
Published: June 2024

AbstractThe advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery. We report key genetic pathways, including changes in erythrocyte regulation, stress induction, and immune changes affected by spaceflight. We also present the first m6A methylation profiles for a human space mission, suggesting a significant spike in m6A levels immediately post-flight. These data and results represent the first longitudinal long-read RNA profiles and RNA modification maps for each gene for astronauts, improving our understanding of the human transcriptome’s dynamic response to spaceflight.
The RNF214-TEAD-YAP signaling axis promotes hepatocellular carcinoma progression via TEAD ubiquitylation
Authors: Lin Mengjia , Zheng Xiaoyun , Yan Jianing , Huang Fei , Chen Yilin , Ding Ran , Wan Jinkai , Zhang Lei , Wang Chenliang , Pan Jinchang , Cao Xiaolei , Fu Kaiyi , Lou Yan , Feng Xin-Hua , Ji Junfang , Zhao Bin , Lan Fei , Shen Li , He Xianglei , Qiu Yunqing , Jin Jianping 
Published: June 2024

AbstractRNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling. Moreover, YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, RNF214 is overexpressed in hepatocellular carcinoma (HCC) and inversely correlates with differentiation status and patient survival. Consistently, RNF214 promotes tumor cell proliferation, migration, and invasion, and HCC tumorigenesis in mice. Collectively, our data reveal RNF214 as a critical component in the Hippo pathway by forming a signaling axis of RNF214-TEAD-YAP and suggest that RNF214 is an oncogene of HCC and could be a potential drug target of HCC therapy.
Molecular mechanism of BMP signal control by Twisted gastrulation
Authors: Malinauskas Tomas , Moore Gareth , Rudolf Amalie F. , Eggington Holly , Belnoue-Davis Hayley L. , El Omari Kamel , Griffiths Samuel C. , Woolley Rachel E. , Duman Ramona , Wagner Armin , Leedham Simon J. , Baldock Clair , Ashe Hilary L. , Siebold Christian 
Published: June 2024

AbstractTwisted gastrulation (TWSG1) is an evolutionarily conserved secreted glycoprotein which controls signaling by Bone Morphogenetic Proteins (BMPs). TWSG1 binds BMPs and their antagonist Chordin to control BMP signaling during embryonic development, kidney regeneration and cancer. We report crystal structures of TWSG1 alone and in complex with a BMP ligand, Growth Differentiation Factor 5. TWSG1 is composed of two distinct, disulfide-rich domains. The TWSG1 N-terminal domain occupies the BMP type 1 receptor binding site on BMPs, whereas the C-terminal domain binds to a Chordin family member. We show that TWSG1 inhibits BMP function in cellular signaling assays and mouse colon organoids. This inhibitory function is abolished in a TWSG1 mutant that cannot bind BMPs. The same mutation in the Drosophila TWSG1 ortholog Tsg fails to mediate BMP gradient formation required for dorsal-ventral axis patterning of the early embryo. Our studies reveal the evolutionarily conserved mechanism of BMP signaling inhibition by TWSG1.
The SpinBus architecture for scaling spin qubits with electron shuttling
Authors: Künne Matthias , Willmes Alexander , Oberländer Max , Gorjaew Christian , Teske Julian D. , Bhardwaj Harsh , Beer Max , Kammerloher Eugen , Otten René , Seidler Inga , Xue Ran , Schreiber Lars R. , Bluhm Hendrik 
Published: June 2024

AbstractQuantum processor architectures must enable scaling to large qubit numbers while providing two-dimensional qubit connectivity and exquisite operation fidelities. For microwave-controlled semiconductor spin qubits, dense arrays have made considerable progress, but are still limited in size by wiring fan-out and exhibit significant crosstalk between qubits. To overcome these limitations, we introduce the SpinBus architecture, which uses electron shuttling to connect qubits and features low operating frequencies and enhanced qubit coherence. Device simulations for all relevant operations in the Si/SiGe platform validate the feasibility with established semiconductor patterning technology and operation fidelities exceeding 99.9%. Control using room temperature instruments can plausibly support at least 144 qubits, but much larger numbers are conceivable with cryogenic control circuits. Building on the theoretical feasibility of high-fidelity spin-coherent electron shuttling as key enabling factor, the SpinBus architecture may be the basis for a spin-based quantum processor that meets the scalability requirements for practical quantum computing.
Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium
Authors: Dunlap Garrett , Wagner Aaron , Meednu Nida , Wang Ruoqiao , Zhang Fan , Ekabe Jabea Cyril , Jonsson Anna Helena , Wei Kevin , Sakaue Saori , Nathan Aparna ,   Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Albrecht Jennifer , Apruzzese William , Barnas Jennifer L. , Bathon Joan M. , Ben-Artzi Ami , Boyce Brendan F. , Bridges S. Louis , Campbell Debbie , Carr Hayley L. , Ceponis Arnold , Chicoine Adam , Cordle Andrew , Curtis Michelle , Deane Kevin D. , DiCarlo Edward , Dunn Patrick , Forbess Lindsy , Geraldino-Pardilla Laura , Gravallese Ellen M. , Gregersen Peter K. , Guthridge Joel M. , Horowitz Diane , Hughes Laura B. , Ishigaki Kazuyoshi , Ivashkiv Lionel B. , James Judith A. , Kang Joyce B. , Keras Gregory , Korsunsky Ilya , Lakhanpal Amit , Lederer James A. , Li Yuhong , Li Zhihan J. , Liao Katherine P. , Maecker Holden , Mandelin Arthur M. , Mantel Ian , Maybury Mark , McGeachy Mandy J. , Mears Joseph , Nerviani Alessandra , Orange Dana E. , Perlman Harris , Rangel-Moreno Javier , Raza Karim , Reshef Yakir , Ritchlin Christopher , Rivellese Felice , Robinson William H. , Rumker Laurie , Sahbudin Ilfita , Salomon-Escoto Karen , Scheel-Toellner Dagmar , Seifert Jennifer A. , Singaraju Anvita , Smith Melanie H. , Utz Paul J. , Weinand Kathryn , Weisenfeld Dana , Weisman Michael H. , Xiao Qian , Zhu Zhu , Bykerk Vivian P. , Donlin Laura T. , Goodman Susan M. , Firestein Gary S. , Boyle David L. , Holers V. Michael , Moreland Larry W. , Tabechian Darren , Pitzalis Costantino , Filer Andrew , Raychaudhuri Soumya , Brenner Michael B. , Thakar Juilee , McDavid Andrew , Rao Deepak A. , Anolik Jennifer H. 
Published: June 2024

AbstractRheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
Counterion docking: a general approach to reducing energetic disorder in doped polymeric semiconductors
Authors: Xiong Miao , Deng Xin-Yu , Tian Shuang-Yan , Liu Kai-Kai , Fang Yu-Hui , Wang Juan-Rong , Wang Yunfei , Liu Guangchao , Chen Jupeng , Villalva Diego Rosas , Baran Derya , Gu Xiaodan , Lei Ting 
Published: June 2024

AbstractMolecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm−1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.
MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration
Authors: Chen Jianxiong , Duan Shiyu , Wang Yulu , Ling Yuping , Hou Xiaotao , Zhang Sijing , Liu Xunhua , Long Xiaoli , Lan Jiawen , Zhou Miao , Xu Huimeng , Zheng Haoxuan , Zhou Jun 
Published: June 2024

AbstractMetabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3′−5′ RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.
Membrane-induced 2D phase separation of the focal adhesion protein talin
Authors: Litschel Thomas , Kelley Charlotte F. , Cheng Xiaohang , Babl Leon , Mizuno Naoko , Case Lindsay B. , Schwille Petra 
Published: June 2024

AbstractFocal adhesions form liquid-like assemblies around activated integrin receptors at the plasma membrane. How they achieve their flexible properties is not well understood. Here, we use recombinant focal adhesion proteins to reconstitute the core structural machinery in vitro. We observe liquid-liquid phase separation of the core focal adhesion proteins talin and vinculin for a spectrum of conditions and interaction partners. Intriguingly, we show that binding to PI(4,5)P2-containing membranes triggers phase separation of these proteins on the membrane surface, which in turn induces the enrichment of integrin in the clusters. We suggest a mechanism by which 2-dimensional biomolecular condensates assemble on membranes from soluble proteins in the cytoplasm: lipid-binding triggers protein activation and thus, liquid-liquid phase separation of these membrane-bound proteins. This could explain how early focal adhesions maintain a structured and force-resistant organization into the cytoplasm, while still being highly dynamic and able to quickly assemble and disassemble.
Zinc-indium-sulfide favors efficient C − H bond activation by concerted proton-coupled electron transfer
Authors: Wu Xuejiao , Fan Xueting , Xie Shunji , Scodeller Ivan , Wen Xiaojian , Vangestel Dario , Cheng Jun , Sels Bert 
Published: June 2024

AbstractC − H bond activation is a ubiquitous reaction that remains a major challenge in chemistry. Although semiconductor-based photocatalysis is promising, the C − H bond activation mechanism remains elusive. Herein, we report value-added coupling products from a wide variety of biomass and fossil-derived reagents, formed via C − H bond activation over zinc-indium-sulfides (Zn-In-S). Contrary to the commonly accepted stepwise electron-proton transfer pathway (PE-ET) for semiconductors, our experimental and theoretical studies evidence a concerted proton-coupled electron transfer (CPET) pathway. A pioneering microkinetic study, considering the relevant elementary steps of the surface chemistry, reveals a faster C − H activation with Zn-In-S because of circumventing formation of a charged radical, as it happens in PE-ET where it retards the catalysis due to strong site adsorption. For CPET over Zn-In-S, H abstraction, forming a neutral radical, is rate-limiting, but having lower energy barriers than that of PE-ET. The rate expressions derived from the microkinetics provide guidelines to rationally design semiconductor catalysis, e.g., for C − H activation, that is based on the CPET mechanism.
Spatiotemporal expression and control of haemoglobin in space
Authors: Borg Josef , Loy Conor , Kim JangKeun , Buhagiar Alfred , Chin Christopher , Damle Namita , De Vlaminck Iwijn , Felice Alex , Liu Tammy , Matei Irina , Meydan Cem , Muratani Masafumi , Mzava Omary , Overbey Eliah , Ryon Krista A. , Smith Scott M. , Tierney Braden T. , Trudel Guy , Zwart Sara R. , Beheshti Afshin , Mason Christopher E. , Borg Joseph 
Published: June 2024

AbstractIt is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.
Microdroplets initiate organic-inorganic interactions and mass transfer in thermal hydrous geosystems
Authors: Yuan Guanghui , Jin Zihao , Cao Yingchang , Schulz Hans-Martin , Gluyas Jon , Liu Keyu , He Xingliang , Wang Yanzhong 
Published: June 2024

AbstractOrganic-inorganic interactions regulate the dynamics of hydrocarbons, water, minerals, CO2, and H2 in thermal rocks, yet their initiation remains debated. To address this, we conducted isotope-tagged and in-situ visual thermal experiments. Isotope-tagged studies revealed extensive H/O transfers in hydrous n-C20H42-H2O-feldspar systems. Visual experiments observed water microdroplets forming at 150–165 °C in oil phases near the water-oil interface without surfactants, persisting until complete miscibility above 350 °C. Electron paramagnetic resonance (EPR) detected hydroxyl free radicals concurrent with microdroplet formation. Here we propose a two-fold mechanism: water-derived and n-C20H42-derived free radicals drive interactions with organic species, while water-derived and mineral-derived ions trigger mineral interactions. These processes, facilitated by microdroplets and bulk water, blur boundaries between organic and inorganic species, enabling extensive interactions and mass transfer. Our findings redefine microscopic interplays between organic and inorganic components, offering insights into diagenetic and hydrous-metamorphic processes, and mass transfer cycles in deep basins and subduction zones.
All-optical phase conjugation using diffractive wavefront processing
Authors: Shen Che-Yung , Li Jingxi , Gan Tianyi , Li Yuhang , Jarrahi Mona , Ozcan Aydogan 
Published: June 2024

AbstractOptical phase conjugation (OPC) is a nonlinear technique used for counteracting wavefront distortions, with applications ranging from imaging to beam focusing. Here, we present a diffractive wavefront processor to approximate all-optical phase conjugation. Leveraging deep learning, a set of diffractive layers was optimized to all-optically process an arbitrary phase-aberrated input field, producing an output field with a phase distribution that is the conjugate of the input wave. We experimentally validated this wavefront processor by 3D-fabricating diffractive layers and performing OPC on phase distortions never seen during training. Employing terahertz radiation, our diffractive processor successfully performed OPC through a shallow volume that axially spans tens of wavelengths. We also created a diffractive phase-conjugate mirror by combining deep learning-optimized diffractive layers with a standard mirror. Given its compact, passive and multi-wavelength nature, this diffractive wavefront processor can be used for various applications, e.g., turbidity suppression and aberration correction across different spectral bands.