bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells
Authors: Khatri Bhuwan , Tessneer Kandice L. , Rasmussen Astrid , Aghakhanian Farhang , Reksten Tove Ragna , Adler Adam , Alevizos Ilias , Anaya Juan-Manuel , Aqrawi Lara A. , Baecklund Eva , Brun Johan G. , Bucher Sara Magnusson , Eloranta Maija-Leena , Engelke Fiona , Forsblad-d’Elia Helena , Glenn Stuart B. , Hammenfors Daniel , Imgenberg-Kreuz Juliana , Jensen Janicke Liaaen , Johnsen Svein Joar Auglænd , Jonsson Malin V. , Kvarnström Marika , Kelly Jennifer A. , Li He , Mandl Thomas , Martín Javier , Nocturne Gaétane , Norheim Katrine Brække , Palm Øyvind , Skarstein Kathrine , Stolarczyk Anna M. , Taylor Kimberly E. , Teruel Maria , Theander Elke , Venuturupalli Swamy , Wallace Daniel J. , Grundahl Kiely M. , Hefner Kimberly S. , Radfar Lida , Lewis David M. , Stone Donald U. , Kaufman C. Erick , Brennan Michael T. , Guthridge Joel M. , James Judith A. , Scofield R. Hal , Gaffney Patrick M. , Criswell Lindsey A. , Jonsson Roland , Eriksson Per , Bowman Simon J. , Omdal Roald , Rönnblom Lars , Warner Blake , Rischmueller Maureen , Witte Torsten , Farris A. Darise , Mariette Xavier , Alarcon-Riquelme Marta E. ,   PRECISESADS Clinical Consortium, Shiboski Caroline H. ,   Sjögren’s International Collaborative Clinical Alliance (SICCA), Wahren-Herlenius Marie , Ng Wan-Fai ,   UK Primary Sjögren’s Syndrome Registry, Sivils Kathy L. , Adrianto Indra , Nordmark Gunnel , Lessard Christopher J. 
Published: July 2022

AbstractSjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.
Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles
Authors: Tan Jian , Ni Duan , Taitz Jemma , Pinget Gabriela Veronica , Read Mark , Senior Alistair , Wali Jibran Abdul , Elnour Reem , Shanahan Erin , Wu Huiling , Chadban Steven J. , Nanan Ralph , King Nicholas Jonathan Cole , Grau Georges Emile , Simpson Stephen J. , Macia Laurence 
Published: July 2022

AbstractSecretory IgA is a key mucosal component ensuring host-microbiota mutualism. Here we use nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, and identify dietary protein as the major driver of secretory IgA production. Protein-driven secretory IgA induction is not mediated by T-cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high protein fed mice produces significantly higher quantities of extracellular vesicles, compared to those of mice fed high-carbohydrate or high-fat diets. These extracellular vesicles activate Toll-like receptor 4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We show that succinate, produced in high concentrations by microbiota of high protein fed animals, increases generation of reactive oxygen species by bacteria, which in turn promotes extracellular vesicles production. Here we establish a link between dietary macronutrient composition, gut microbial extracellular vesicles release and host secretory IgA response.
Large-area transfer of two-dimensional materials free of cracks, contamination and wrinkles via controllable conformal contact
Authors: Zhao Yixuan , Song Yuqing , Hu Zhaoning , Wang Wendong , Chang Zhenghua , Zhang Yan , Lu Qi , Wu Haotian , Liao Junhao , Zou Wentao , Gao Xin , Jia Kaicheng , Zhuo La , Hu Jingyi , Xie Qin , Zhang Rui , Wang Xiaorui , Sun Luzhao , Li Fangfang , Zheng Liming , Wang Ming , Yang Jiawei , Mao Boyang , Fang Tiantian , Wang Fuyi , Zhong Haotian , Liu Wenlin , Yan Rui , Yin Jianbo , Zhang Yanfeng , Wei Yujie , Peng Hailin , Lin Li , Liu Zhongfan 
Published: July 2022

AbstractThe availability of graphene and other two-dimensional (2D) materials on a wide range of substrates forms the basis for large-area applications, such as graphene integration with silicon-based technologies, which requires graphene on silicon with outperforming carrier mobilities. However, 2D materials were only produced on limited archetypal substrates by chemical vapor deposition approaches. Reliable after-growth transfer techniques, that do not produce cracks, contamination, and wrinkles, are critical for layering 2D materials onto arbitrary substrates. Here we show that, by incorporating oxhydryl groups-containing volatile molecules, the supporting films can be deformed under heat to achieve a controllable conformal contact, enabling the large-area transfer of 2D films without cracks, contamination, and wrinkles. The resulting conformity with enhanced adhesion facilitates the direct delamination of supporting films from graphene, providing ultraclean surfaces and carrier mobilities up to 1,420,000 cm2 V−1 s−1 at 4 K.
Divergent synthesis of benzazepines and bridged polycycloalkanones via dearomative rearrangement
Authors: Shi Qiu , Liao Zhehui , Liu Zhili , Wen Jiajia , Li Chenguang , He Jiamin , Deng Jiazhen , Cen Shan , Cao Tongxiang , Zhou Jinming , Zhu Shifa 
Published: July 2022

AbstractThe dearomative functionalization of aromatic compounds represents a fascinating but challenging transformation, as it typically needs to overcome a great kinetic barrier. Here, a catalyst-free dearomative rearrangement of o-nitrophenyl alkyne is successfully established by leveraging the remote oxygen transposition and a weak N-O bond acceleration. This reaction features high atom-, step- and redox-economy, which provides a divergent entry to a series of biologically important benzazepines and bridged polycycloalkanones. The reaction is proposed to proceed through a tandem oxygen transfer cyclization/(3 + 2) cycloaddition/(homo-)hetero-Claisen rearrangement reaction. The resulting polycyclic system is richly decorated with transformable functionalities, such as carbonyl, imine and diene, which enables diversity-oriented synthesis of alkaloid-like polycyclic framework.
Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET
Authors: Peter Martin F. , Gebhardt Christian , Mächtel Rebecca , Muñoz Gabriel G. Moya , Glaenzer Janin , Narducci Alessandra , Thomas Gavin H. , Cordes Thorben , Hagelueken Gregor 
Published: July 2022

AbstractPulsed electron-electron double resonance spectroscopy (PELDOR/DEER) and single-molecule Förster resonance energy transfer spectroscopy (smFRET) are frequently used to determine conformational changes, structural heterogeneity, and inter probe distances in biological macromolecules. They provide qualitative information that facilitates mechanistic understanding of biochemical processes and quantitative data for structural modelling. To provide a comprehensive comparison of the accuracy of PELDOR/DEER and smFRET, we use a library of double cysteine variants of four proteins that undergo large-scale conformational changes upon ligand binding. With either method, we use established standard experimental protocols and data analysis routines to determine inter-probe distances in the presence and absence of ligands. The results are compared to distance predictions from structural models. Despite an overall satisfying and similar distance accuracy, some inconsistencies are identified, which we attribute to the use of cryoprotectants for PELDOR/DEER and label-protein interactions for smFRET. This large-scale cross-validation of PELDOR/DEER and smFRET highlights the strengths, weaknesses, and synergies of these two important and complementary tools in integrative structural biology.
Defunctionalizing intracellular organelles such as mitochondria and peroxisomes with engineered phospholipase A/acyltransferases
Authors: Watanabe Satoshi , Nihongaki Yuta , Itoh Kie , Uyama Toru , Toda Satoshi , Watanabe Shigeki , Inoue Takanari 
Published: July 2022

AbstractOrganelles vitally achieve multifaceted functions to maintain cellular homeostasis. Genetic and pharmacological approaches to manipulate individual organelles are powerful in probing their physiological roles. However, many of them are either slow in action, limited to certain organelles, or rely on toxic agents. Here, we design a generalizable molecular tool utilizing phospholipase A/acyltransferases (PLAATs) for rapid defunctionalization of organelles via remodeling of the membrane phospholipids. In particular, we identify catalytically active PLAAT truncates with minimal unfavorable characteristics. Chemically-induced translocation of the optimized PLAAT to the mitochondria surface results in their rapid deformation in a phospholipase activity dependent manner, followed by loss of luminal proteins as well as dissipated membrane potential, thus invalidating the functionality. To demonstrate wide applicability, we then adapt the molecular tool in peroxisomes, and observe leakage of matrix-resident functional proteins. The technique is compatible with optogenetic control, viral delivery and operation in primary neuronal cultures. Due to such versatility, the PLAAT strategy should prove useful in studying organelle biology of diverse contexts.
Transcription factor network analysis identifies REST/NRSF as an intrinsic regulator of CNS regeneration in mice
Authors: Cheng Yuyan , Yin Yuqin , Zhang Alice , Bernstein Alexander M. , Kawaguchi Riki , Gao Kun , Potter Kyra , Gilbert Hui-Ya , Ao Yan , Ou Jing , Fricano-Kugler Catherine J. , Goldberg Jeffrey L. , He Zhigang , Woolf Clifford J. , Sofroniew Michael V. , Benowitz Larry I. , Geschwind Daniel H. 
Published: July 2022

AbstractThe inability of neurons to regenerate long axons within the CNS is a major impediment to improving outcome after spinal cord injury, stroke, and other CNS insults. Recent advances have uncovered an intrinsic program that involves coordinate regulation by multiple transcription factors that can be manipulated to enhance growth in the peripheral nervous system. Here, we use a systems genomics approach to characterize regulatory relationships of regeneration-associated transcription factors, identifying RE1-Silencing Transcription Factor (REST; Neuron-Restrictive Silencer Factor, NRSF) as a predicted upstream suppressor of a pro-regenerative gene program associated with axon regeneration in the CNS. We validate our predictions using multiple paradigms, showing that mature mice bearing cell type-specific deletions of REST or expressing dominant-negative mutant REST show improved regeneration of the corticospinal tract and optic nerve after spinal cord injury and optic nerve crush, which is accompanied by upregulation of regeneration-associated genes in cortical motor neurons and retinal ganglion cells, respectively. These analyses identify a role for REST as an upstream suppressor of the intrinsic regenerative program in the CNS and demonstrate the utility of a systems biology approach involving integrative genomics and bio-informatics to prioritize hypotheses relevant to CNS repair.
SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model
Authors: Lieber Carolin M. , Cox Robert M. , Sourimant Julien , Wolf Josef D. , Juergens Kate , Phung Quynh , Saindane Manohar T. , Smith Meghan K. , Sticher Zachary M. , Kalykhalov Alexander A. , Natchus Michael G. , Painter George R. , Sakamoto Kaori , Greninger Alexander L. , Plemper Richard K. 
Published: July 2022

AbstractSARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency against omicron is unknown. This study evaluates molnupiravir against VOC in human airway epithelium organoids, ferrets, and a lethal Roborovski dwarf hamster model of severe COVID-19-like lung injury. VOC were equally inhibited by molnupiravir in cells and organoids. Treatment reduced shedding in ferrets and prevented transmission. Pathogenicity in dwarf hamsters was VOC-dependent and highest for delta, gamma, and omicron. All molnupiravir-treated dwarf hamsters survived, showing reduction in lung virus load from one (delta) to four (gamma) orders of magnitude. Treatment effect size varied in individual dwarf hamsters infected with omicron and was significant in males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir in human trials and alerts that benefit must be reassessed in vivo as VOC evolve.
Three-dimensional printing of photonic colloidal glasses into objects with isotropic structural color
Authors: Demirörs Ahmet F. , Poloni Erik , Chiesa Maddalena , Bargardi Fabio L. , Binelli Marco R. , Woigk Wilhelm , de Castro Lucas D. C. , Kleger Nicole , Coulter Fergal B. , Sicher Alba , Galinski Henning , Scheffold Frank , Studart André R. 
Published: July 2022

AbstractStructural color is frequently exploited by living organisms for biological functions and has also been translated into synthetic materials as a more durable and less hazardous alternative to conventional pigments. Additive manufacturing approaches were recently exploited for the fabrication of exquisite photonic objects, but the angle-dependence observed limits a broader application of structural color in synthetic systems. Here, we propose a manufacturing platform for the 3D printing of complex-shaped objects that display isotropic structural color generated from photonic colloidal glasses. Structurally colored objects are printed from aqueous colloidal inks containing monodisperse silica particles, carbon black, and a gel-forming copolymer. Rheology and Small-Angle-X-Ray-Scattering measurements are performed to identify the processing conditions leading to printed objects with tunable structural colors. Multimaterial printing is eventually used to create complex-shaped objects with multiple structural colors using silica and carbon as abundant and sustainable building blocks.
Thermal control of the topological edge flow in nonlinear photonic lattices
Authors: Jung Pawel S. , Pyrialakos Georgios G. , Wu Fan O. , Parto Midya , Khajavikhan Mercedeh , Krolikowski Wieslaw , Christodoulides Demetrios N. 
Published: July 2022

AbstractThe chaotic evolution resulting from the interplay between topology and nonlinearity in photonic systems generally forbids the sustainability of optical currents. Here, we systematically explore the nonlinear evolution dynamics in topological photonic lattices within the framework of optical thermodynamics. By considering an archetypical two-dimensional Haldane photonic lattice, we discover several prethermal states beyond the topological phase transition point and a stable global equilibrium response, associated with a specific optical temperature and chemical potential. Along these lines, we provide a consistent thermodynamic methodology for both controlling and maximizing the unidirectional power flow in the topological edge states. This can be achieved by either employing cross-phase interactions between two subsystems or by exploiting self-heating effects in disordered or Floquet topological lattices. Our results indicate that photonic topological systems can in fact support robust photon transport processes even under the extreme complexity introduced by nonlinearity, an important feature for contemporary topological applications in photonics.
Real-time precision opto-control of chemical processes in live cells
Authors: Clark Matthew G. , Gonzalez Gil A. , Luo Yiyang , Aldana-Mendoza Jesus A. , Carlsen Mark S. , Eakins Gregory , Dai Mingji , Zhang Chi 
Published: July 2022

AbstractPrecision control of molecular activities and chemical reactions in live cells is a long-sought capability by life scientists. No existing technology can probe molecular targets in cells and simultaneously control the activities of only these targets at high spatial precision. We develop a real-time precision opto-control (RPOC) technology that detects a chemical-specific optical response from molecular targets during laser scanning and uses the optical signal to couple a separate laser to only interact with these molecules without affecting other sample locations. We demonstrate precision control of molecular states of a photochromic molecule in different regions of the cells. We also synthesize a photoswitchable compound and use it with RPOC to achieve site-specific inhibition of microtubule polymerization and control of organelle dynamics in live cells. RPOC can automatically detect and control biomolecular activities and chemical processes in dynamic living samples with submicron spatial accuracy, fast response time, and high chemical specificity.
Gata6+ resident peritoneal macrophages promote the growth of liver metastasis
Authors: Hossain Mokarram , Shim Raymond , Lee Woo-Yong , Sharpe Arlene H. , Kubes Paul 
Published: July 2022

AbstractEmerging evidence suggests that resident macrophages within tissues are enablers of tumor growth. However, a second population of resident macrophages surrounds all visceral organs within the cavities and nothing is known about these GATA6+ large peritoneal macrophages (GLPMs) despite their ability to invade injured visceral organs by sensing danger signals. Here, we show that GLPMs invade growing metastases that breach the visceral mesothelium of the liver via the “find me signal”, ATP. Depleting GLPMs either by pharmacological or genetic tools, reduces metastases growth. Apoptotic bodies from tumor cells induces programmed cell death ligand 1 (PD-L1) upregulation on GLPMs which block CD8+ T cell function. Direct targeting of GLPMs by intraperitoneal but not intravenous administration of anti-PD-L1 reduces tumor growth. Thermal ablation of liver metastases recruits huge numbers of GLPMs and enables rapid regrowth of tumors. GLPMs contribute to metastatic growth and tumor recurrence.
CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors
Authors: Lloyd Sarah M. , Leon Daniel B. , Brady Mari O. , Rodriguez Deborah , McReynolds Madison P. , Kweon Junghun , Neely Amy E. , Blumensaadt Laura A. , Ho Patric J. , Bao Xiaomin 
Published: July 2022

AbstractProgenitors in epithelial tissues, such as human skin epidermis, continuously make fate decisions between self-renewal and differentiation. Here we show that the Super Elongation Complex (SEC) controls progenitor fate decisions by directly suppressing a group of “rapid response” genes, which feature high enrichment of paused Pol II in the progenitor state and robust Pol II elongation in differentiation. SEC’s repressive role is dependent on the AFF1 scaffold, but not AFF4. In the progenitor state, AFF1-SEC associates with the HEXIM1-containing inactive CDK9 to suppress these rapid-response genes. A key rapid-response SEC target is ATF3, which promotes the upregulation of differentiation-activating transcription factors (GRHL3, OVOL1, PRDM1, ZNF750) to advance terminal differentiation. SEC peptidomimetic inhibitors or PKC signaling activates CDK9 and rapidly induces these transcription factors within hours in keratinocytes. Thus, our data suggest that the activity switch of SEC-associated CDK9 underlies the initial processes bifurcating progenitor fates between self-renewal and differentiation.
Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling
Authors: Feng Shouya , Enosi Tuipulotu Daniel , Pandey Abhimanu , Jing Weidong , Shen Cheng , Ngo Chinh , Tessema Melkamu B. , Li Fei-Ju , Fox Daniel , Mathur Anukriti , Zhao Anyang , Wang Runli , Pfeffer Klaus , Degrandi Daniel , Yamamoto Masahiro , Reading Patrick C. , Burgio Gaetan , Man Si Ming 
Published: July 2022

AbstractInflammasomes are cytosolic signaling complexes capable of sensing microbial ligands to trigger inflammation and cell death responses. Here, we show that guanylate-binding proteins (GBPs) mediate pathogen-selective inflammasome activation. We show that mouse GBP1 and GBP3 are specifically required for inflammasome activation during infection with the cytosolic bacterium Francisella novicida. We show that the selectivity of mouse GBP1 and GBP3 derives from a region within the N-terminal domain containing charged and hydrophobic amino acids, which binds to and facilitates direct killing of F. novicida and Neisseria meningitidis, but not other bacteria or mammalian cells. This pathogen-selective recognition by this region of mouse GBP1 and GBP3 leads to pathogen membrane rupture and release of intracellular content for inflammasome sensing. Our results imply that GBPs discriminate between pathogens, confer activation of innate immunity, and provide a host-inspired roadmap for the design of synthetic antimicrobial peptides that may be of use against emerging and re-emerging pathogens.
Pyro-catalysis for tooth whitening via oral temperature fluctuation
Authors: Wang Yang , Wang Shuhao , Meng Yanze , Liu Zhen , Li Dijie , Bai Yunyang , Yuan Guoliang , Wang Yaojin , Zhang Xuehui , Li Xiaoguang , Deng Xuliang 
Published: July 2022

AbstractTooth whitening has recently become one of the most popular aesthetic dentistry procedures. Beyond classic hydrogen peroxide-based whitening agents, photo-catalysts and piezo-catalysts have been demonstrated for non-destructive on-demand tooth whitening. However, their usage has been challenged due to the relatively limited physical stimuli of light irradiation and ultrasonic mechanical vibration. To address this challenge, we report here a non-destructive and convenient tooth whitening strategy based on the pyro-catalysis effect, realized via ubiquitous oral motion-induced temperature fluctuations. Degradation of organic dyes via pyro-catalysis is performed under cooling/heating cycling to simulate natural temperature fluctuations associated with intake and speech. Teeth stained by habitual beverages and flavorings can be whitened by the pyroelectric particles-embedded hydrogel under a small surrounding temperature fluctuation. Furthermore, the pyro-catalysis-based tooth whitening procedure exhibits a therapeutic biosafety and sustainability. In view of the exemplary demonstration, the most prevalent oral temperature fluctuation will enable the pyro-catalysis-based tooth whitening strategy to have tremendous potential for practical applications.