bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight
Authors: Wu Fei , Du Huixun , Overbey Eliah , Kim JangKeun , Makhijani Priya , Martin Nicolas , Lerner Chad A. , Nguyen Khiem , Baechle Jordan , Valentino Taylor R. , Fuentealba Matias , Bartleson Juliet M. , Halaweh Heather , Winer Shawn , Meydan Cem , Garrett-Bakelman Francine , Sayed Nazish , Melov Simon , Muratani Masafumi , Gerencser Akos A. , Kasler Herbert G. , Beheshti Afshin , Mason Christopher E. , Furman David , Winer Daniel A.
Published: June 2024

Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station. Overall, microgravity alters specific pathways for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, innate inflammation (e.g., Coronavirus pathogenesis pathway and IL-6 signaling), nuclear receptors, and sirtuin signaling. Microgravity directs monocyte inflammatory parameters, and impairs T cell and NK cell functionality. Using machine learning, we identify numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results define immune cell alterations in microgravity, and provide opportunities for countermeasures to maintain normal immunity in space.
Ethical considerations for the age of non-governmental space exploration
Authors: Seylani Allen , Galsinh Aman Singh , Tasoula Alexia , I Anu R , Camera Andrea , Calleja-Agius Jean , Borg Joseph , Goel Chirag , Kim JangKeun , Clark Kevin B. , Das Saswati , Arif Shehbeel , Boerrigter Michael , Coffey Caroline , Szewczyk Nathaniel , Mason Christopher E. , Manoli Maria , Karouia Fathi , Schwertz Hansjörg , Beheshti Afshin , Tulodziecki Dana
Published: June 2024

Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.
Transcranial focused ultrasound to V5 enhances human visual motion brain-computer interface by modulating feature-based attention
Authors: Kosnoff Joshua , Yu Kai , Liu Chang , He Bin
Published: June 2024

A brain-computer interface (BCI) enables users to control devices with their minds. Despite advancements, non-invasive BCIs still exhibit high error rates, prompting investigation into the potential reduction through concurrent targeted neuromodulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive neuromodulation technology with high spatiotemporal precision. This study examines whether tFUS neuromodulation can improve BCI outcomes, and explores the underlying mechanism of action using high-density electroencephalography (EEG) source imaging (ESI). As a result, V5-targeted tFUS significantly reduced the error in a BCI speller task. Source analyses revealed a significantly increase in theta and alpha activities in the tFUS condition at both V5 and downstream in the dorsal visual processing pathway. Correlation analysis indicated that the connection within the dorsal processing pathway was preserved during tFUS stimulation, while the ventral connection was weakened. These findings suggest that V5-targeted tFUS enhances feature-based attention to visual motion.
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

More 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

High-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

As 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

The 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

RNF214 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

Twisted 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

Quantum 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

Rheumatoid 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

Molecular 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

Metabolic 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

Focal 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

C − 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

It 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

Organic-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

Optical 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.
iPS cell generation-associated point mutations include many C > T substitutions via different cytosine modification mechanisms
Authors: Araki Ryoko , Suga Tomo , Hoki Yuko , Imadome Kaori , Sunayama Misato , Kamimura Satoshi , Fujita Mayumi , Abe Masumi
Published: June 2024

Genomic aberrations are a critical impediment for the safe medical use of iPSCs and their origin and developmental mechanisms remain unknown. Here we find through WGS analysis of human and mouse iPSC lines that genomic mutations are de novo events and that, in addition to unmodified cytosine base prone to deamination, the DNA methylation sequence CpG represents a significant mutation-prone site. CGI and TSS regions show increased mutations in iPSCs and elevated mutations are observed in retrotransposons, especially in the AluY subfamily. Furthermore, increased cytosine to thymine mutations are observed in differentially methylated regions. These results indicate that in addition to deamination of cytosine, demethylation of methylated cytosine, which plays a central role in genome reprogramming, may act mutagenically during iPSC generation.
Non-viral DNA delivery and TALEN editing correct the sickle cell mutation in hematopoietic stem cells
Authors: Moiani Arianna , Letort Gil , Lizot Sabrina , Chalumeau Anne , Foray Chloe , Felix Tristan , Le Clerre Diane , Temburni-Blake Sonal , Hong Patrick , Leduc Sophie , Pinard Noemie , Marechal Alan , Seclen Eduardo , Boyne Alex , Mayer Louisa , Hong Robert , Pulicani Sylvain , Galetto Roman , Gouble Agnès , Cavazzana Marina , Juillerat Alexandre , Miccio Annarita , Duclert Aymeric , Duchateau Philippe , Valton Julien
Published: June 2024

Sickle cell disease is a devastating blood disorder that originates from a single point mutation in the HBB gene coding for hemoglobin. Here, we develop a GMP-compatible TALEN-mediated gene editing process enabling efficient HBB correction via a DNA repair template while minimizing risks associated with HBB inactivation. Comparing viral versus non-viral DNA repair template delivery in hematopoietic stem and progenitor cells in vitro, both strategies achieve comparable HBB correction and result in over 50% expression of normal adult hemoglobin in red blood cells without inducing β-thalassemic phenotype. In an immunodeficient female mouse model, transplanted cells edited with the non-viral strategy exhibit higher engraftment and gene correction levels compared to those edited with the viral strategy. Transcriptomic analysis reveals that non-viral DNA repair template delivery mitigates P53-mediated toxicity and preserves high levels of long-term hematopoietic stem cells. This work paves the way for TALEN-based autologous gene therapy for sickle cell disease.
Acetylation of histones and non-histone proteins is not a mere consequence of ongoing transcription
Authors: Liebner Tim , Kilic Sinan , Walter Jonas , Aibara Hitoshi , Narita Takeo , Choudhary Chunaram
Published: June 2024

In all eukaryotes, acetylation of histone lysine residues correlates with transcription activation. Whether histone acetylation is a cause or consequence of transcription is debated. One model suggests that transcription promotes the recruitment and/or activation of acetyltransferases, and histone acetylation occurs as a consequence of ongoing transcription. However, the extent to which transcription shapes the global protein acetylation landscapes is not known. Here, we show that global protein acetylation remains virtually unaltered after acute transcription inhibition. Transcription inhibition ablates the co-transcriptionally occurring ubiquitylation of H2BK120 but does not reduce histone acetylation. The combined inhibition of transcription and CBP/p300 further demonstrates that acetyltransferases remain active and continue to acetylate histones independently of transcription. Together, these results show that histone acetylation is not a mere consequence of transcription; acetyltransferase recruitment and activation are uncoupled from the act of transcription, and histone and non-histone protein acetylation are sustained in the absence of ongoing transcription.
t-SMILES: a fragment-based molecular representation framework for de novo ligand design
Authors: Wu Juan-Ni , Wang Tong , Chen Yue , Tang Li-Juan , Wu Hai-Long , Yu Ru-Qin
Published: June 2024

Effective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with shared atom), TSDY (t-SMILES with dummy atom but without ID) and TSID (t-SMILES with ID and dummy atom). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility of constructing a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. In addition, it can avoid overfitting and achieve higher novelty scores while maintaining reasonable similarity on labeled low-resource datasets, regardless of whether the model is original, data-augmented, or pre-trained then fine-tuned. Furthermore, it significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. And it surpasses state-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9.
Growth of electroautotrophic microorganisms using hydrovoltaic energy through natural water evaporation
Authors: Ren Guoping , Ye Jie , Hu Qichang , Zhang Dong , Yuan Yong , Zhou Shungui
Published: June 2024

It has been previously shown that devices based on microbial biofilms can generate hydrovoltaic energy from water evaporation. However, the potential of hydrovoltaic energy as an energy source for microbial growth has remained unexplored. Here, we show that the electroautotrophic bacterium Rhodopseudomonas palustris can directly utilize evaporation-induced hydrovoltaic electrons for growth within biofilms through extracellular electron uptake, with a strong reliance on carbon fixation coupled with nitrate reduction. We obtained similar results with two other electroautotrophic bacterial species. Although the energy conversion efficiency for microbial growth based on hydrovoltaic energy is low compared to other processes such as photosynthesis, we hypothesize that hydrovoltaic energy may potentially contribute to microbial survival and growth in energy-limited environments, given the ubiquity of microbial biofilms and water evaporation conditions.
Dispersive Fourier transform based dual-comb ranging
Authors: Chang Bing , Tan Teng , Du Junting , He Xinyue , Liang Yupei , Liu Zihan , Wang Chun , Xia Handing , Wu Zhaohui , Wang Jindong , Wong Kenneth K. Y. , Zhu Tao , Kong Lingjiang , Li Bowen , Rao Yunjiang , Yao Baicheng
Published: June 2024

Laser-based light detection and ranging (LIDAR) offers a powerful tool to real-timely map spatial information with exceptional accuracy and owns various applications ranging from industrial manufacturing, and remote sensing, to airborne and in-vehicle missions. Over the past two decades, the rapid advancements of optical frequency combs have ushered in a new era for LIDAR, promoting measurement precision to quantum noise limited level. For comb LIDAR systems, to further improve the comprehensive performances and reconcile inherent conflicts between speed, accuracy, and ambiguity range, innovative demodulation strategies become crucial. Here we report a dispersive Fourier transform (DFT) based LIDAR method utilizing phase-locked Vernier dual soliton laser combs. We demonstrate that after in-line pulse stretching, the delay of the flying pulses can be identified via the DFT-based spectral interferometry instead of temporal interferometry or pulse reconstruction. This enables absolute distance measurements with precision starting from 262 nm in single shot, to 2.8 nm after averaging 1.5 ms, in a non-ambiguity range over 1.7 km. Furthermore, our DFT-based LIDAR method distinctly demonstrates an ability to completely eliminate dead zones. Such an integration of frequency-resolved ultrafast analysis and dual-comb ranging technology may pave a way for the design of future LIDAR systems.
Viviparity imparts a macroevolutionary signature of ecological opportunity in the body size of female Liolaemus lizards
Authors: Domínguez-Guerrero Saúl F. , Esquerré Damien , Burress Edward D. , Maciel-Mata Carlos A. , Alencar Laura R. V. , Muñoz Martha M.
Published: June 2024

Viviparity evolved ~115 times across squamate reptiles, facilitating the colonization of cold habitats, where oviparous species are scarce or absent. Whether the ecological opportunity furnished by such colonization reconfigures phenotypic diversity and accelerates evolution is unclear. We investigated the association between viviparity and patterns and rates of body size evolution in female Liolaemus lizards, the most species-rich tetrapod genus from temperate regions. Here, we discover that viviparous species evolve ~20% larger optimal body sizes than their oviparous relatives, but exhibit similar rates of body size evolution. Through a causal modeling approach, we find that viviparity indirectly influences body size evolution through shifts in thermal environment. Accordingly, the colonization of cold habitats favors larger body sizes in viviparous species, reconfiguring body size diversity in Liolaemus. The catalyzing influence of viviparity on phenotypic evolution arises because it unlocks access to otherwise inaccessible sources of ecological opportunity, an outcome potentially repeated across the tree of life.
Bioreactor development for skeletal muscle hypertrophy and atrophy by manipulating uniaxial cyclic strain: proof of concept
Authors: Kamal Khaled Y. , Othman Mariam Atef , Kim Joo-Hyun , Lawler John M.
Published: June 2024

Skeletal muscles overcome terrestrial, gravitational loading by producing tensile forces that produce movement through joint rotation. Conversely, the microgravity of spaceflight reduces tensile loads in working skeletal muscles, causing an adaptive muscle atrophy. Unfortunately, the design of stable, physiological bioreactors to model skeletal muscle tensile loading during spaceflight experiments remains challenging. Here, we tested a bioreactor that uses initiation and cessation of cyclic, tensile strain to induce hypertrophy and atrophy, respectively, in murine lineage (C2C12) skeletal muscle myotubes. Uniaxial cyclic stretch of myotubes was conducted using a StrexCell® (STB-1400) stepper motor system (0.75 Hz, 12% strain, 60 min day^-1). Myotube groups were assigned as follows: (a) quiescent over 2- or (b) 5-day (no stretch), (c) experienced 2-days (2dHY) or (d) 5-days (5dHY) of cyclic stretch, or (e) 2-days of cyclic stretch followed by a 3-day cessation of stretch (3dAT). Using ß-sarcoglycan as a sarcolemmal marker, mean myotube diameter increased significantly following 2dAT (51%) and 5dAT (94%) vs. matched controls. The hypertrophic, anabolic markers talin and Akt phosphorylation (Thr308) were elevated with 2dHY but not in 3dAT myotubes. Inflammatory, catabolic markers IL-1ß, IL6, and NF-kappaB p65 subunit were significantly higher in the 3dAT group vs. all other groups. The ratio of phosphorylated FoxO3a/total FoxO3a was significantly lower in 3dAT than in the 2dHY group, consistent with elevated catabolic signaling during unloading. In summary, we demonstrated proof-of-concept for a spaceflight research bioreactor, using uniaxial cyclic stretch to produce myotube hypertrophy with increased tensile loading, and myotube atrophy with subsequent cessation of stretch.
Sequential closed-loop Bayesian optimization as a guide for organic molecular metallophotocatalyst formulation discovery
Authors: Li Xiaobo , Che Yu , Chen Linjiang , Liu Tao , Wang Kewei , Liu Lunjie , Yang Haofan , Pyzer-Knapp Edward O. , Cooper Andrew I.
Published: June 2024

Conjugated organic photoredox catalysts (OPCs) can promote a wide range of chemical transformations. It is challenging to predict the catalytic activities of OPCs from first principles, either by expert knowledge or by using a priori calculations, as catalyst activity depends on a complex range of interrelated properties. Organic photocatalysts and other catalyst systems have often been discovered by a mixture of design and trial and error. Here we report a two-step data-driven approach to the targeted synthesis of OPCs and the subsequent reaction optimization for metallophotocatalysis, demonstrated for decarboxylative sp3–sp2 cross-coupling of amino acids with aryl halides. Our approach uses a Bayesian optimization strategy coupled with encoding of key physical properties using molecular descriptors to identify promising OPCs from a virtual library of 560 candidate molecules. This led to OPC formulations that are competitive with iridium catalysts by exploring just 2.4% of the available catalyst formulation space (107 of 4,500 possible reaction conditions).
A decrease in radiative forcing and equivalent effective chlorine from hydrochlorofluorocarbons
Authors: Western Luke M. , Daniel John S. , Vollmer Martin K. , Clingan Scott , Crotwell Molly , Fraser Paul J. , Ganesan Anita L. , Hall Brad , Harth Christina M. , Krummel Paul B. , Mühle Jens , O’Doherty Simon , Salameh Peter K. , Stanley Kieran M. , Reimann Stefan , Vimont Isaac , Young Dickon , Rigby Matt , Weiss Ray F. , Prinn Ronald G. , Montzka Stephen A.
Published: June 2024

The Montreal Protocol and its successive amendments have been successful in curbing emissions of ozone-depleting substances and potent greenhouse gases via production/consumption controls. Here we show that the radiative forcing and equivalent effective chlorine from hydrochlorofluorocarbons has decreased from 61.75 mW m−2 and 321.69 ppt, respectively, since 2021, 5 years before the most recent projected decrease. This important milestone demonstrates the benefits of the Protocol for mitigating climate change and stratospheric ozone layer loss.
Decision uncertainty as a context for motor memory
Authors: Ogasa Kisho , Yokoi Atsushi , Okazawa Gouki , Nishigaki Morimichi , Hirashima Masaya , Hagura Nobuhiro
Published: June 2024

The current view of perceptual decision-making suggests that once a decision is made, only a single motor programme associated with the decision is carried out, irrespective of the uncertainty involved in decision making. In contrast, we show that multiple motor programmes can be acquired on the basis of the preceding uncertainty of the decision, indicating that decision uncertainty functions as a contextual cue for motor memory. The actions learned after making certain (uncertain) decisions are only partially transferred to uncertain (certain) decisions. Participants were able to form distinct motor memories for the same movement on the basis of the preceding decision uncertainty. Crucially, this contextual effect generalizes to novel stimuli with matched uncertainty levels, demonstrating that decision uncertainty is itself a contextual cue. These findings broaden the understanding of contextual inference in motor memory, emphasizing that it extends beyond direct motor control cues to encompass the decision-making process.
An immune-related eleven-RNA signature-drived risk score model for prognosis of osteosarcoma metastasis
Authors: Teng Jia-Song , Wang Yang
Published: June 2024

This study aimed to determine an immune-related RNA signature as a prognostic marker, in this study, we developed a risk score model for predicting the prognosis of osteosarcoma metastasis. We first downloaded the clinical information and expression data of osteosarcoma samples from the UCSC Xena and GEO databases, of which the former was the training set and the latter was the validation set. Immune infiltration was assessed using the ssGSEA and ESTIMATE algorithms, and the osteosarcoma samples were divided into the Immunity_L and Immunity_H groups. Then, eleven RNAs were identified as the optimal prognostic RNA signatures using LASSO Cox regression analysis for establishing a risk score (RS) model. Kaplan–Meier approach indicated the high-risk group exhibited a shorter survival. Furthermore, we analyzed the tumor metastasis, age, and RS model status were determined to be independent clinical prognostic factors using Cox regression analysis. Decision curve analysis (DCA) indicated that the prognostic factor + RS model had the best net benefit. Finally, nine tumor-infiltrating immune cells (TIICs) showed significant differences in abundance between high- and low-risk groups via CIBERSORT deconvolution algorithm. In conclusion, the immune-related eleven-RNA signature be could served as a potential prognostic biomarker for osteosarcoma metastasis.
Aging and putative frailty biomarkers are altered by spaceflight
Authors: Camera Andrea , Tabetah Marshall , Castañeda Veronica , Kim JangKeun , Galsinh Aman Singh , Haro-Vinueza Alissen , Salinas Ivonne , Seylani Allen , Arif Shehbeel , Das Saswati , Mori Marcelo A. , Carano Anthony , de Oliveira Lorraine Christine , Muratani Masafumi , Barker Richard , Zaksas Victoria , Goel Chirag , Dimokidis Eleni , Taylor Deanne M. , Jeong Jisu , Overbey Eliah , Meydan Cem , Porterfield D. Marshall , Díaz Juan Esteban , Caicedo Andrés , Schisler Jonathan C. , Laiakis Evagelia C. , Mason Christopher E. , Kim Man S. , Karouia Fathi , Szewczyk Nathaniel J. , Beheshti Afshin
Published: June 2024

Human space exploration poses inherent risks to astronauts’ health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA’s GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.