bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia
Authors: Charpignon Marie-Laure , Vakulenko-Lagun Bella , Zheng Bang , Magdamo Colin , Su Bowen , Evans Kyle , Rodriguez Steve , Sokolov Artem , Boswell Sarah , Sheu Yi-Han , Somai Melek , Middleton Lefkos , Hyman Bradley T. , Betensky Rebecca A. , Finkelstein Stan N. , Welsch Roy E. , Tzoulaki Ioanna , Blacker Deborah , Das Sudeshna , Albers Mark W. 
Published: December 2022

AbstractMetformin, a diabetes drug with anti-aging cellular responses, has complex actions that may alter dementia onset. Mixed results are emerging from prior observational studies. To address this complexity, we deploy a causal inference approach accounting for the competing risk of death in emulated clinical trials using two distinct electronic health record systems. In intention-to-treat analyses, metformin use associates with lower hazard of all-cause mortality and lower cause-specific hazard of dementia onset, after accounting for prolonged survival, relative to sulfonylureas. In parallel systems pharmacology studies, the expression of two AD-related proteins, APOE and SPP1, was suppressed by pharmacologic concentrations of metformin in differentiated human neural cells, relative to a sulfonylurea. Together, our findings suggest that metformin might reduce the risk of dementia in diabetes patients through mechanisms beyond glycemic control, and that SPP1 is a candidate biomarker for metformin’s action in the brain.
Cryo-electron tomography reveals structural insights into the membrane remodeling mode of dynamin-like EHD filaments
Authors: Melo Arthur A. , Sprink Thiemo , Noel Jeffrey K. , Vázquez-Sarandeses Elena , van Hoorn Chris , Mohd Saif , Loerke Justus , Spahn Christian M. T. , Daumke Oliver 
Published: December 2022

AbstractEps15-homology domain containing proteins (EHDs) are eukaryotic, dynamin-related ATPases involved in cellular membrane trafficking. They oligomerize on membranes into filaments that induce membrane tubulation. While EHD crystal structures in open and closed conformations were previously reported, little structural information is available for the membrane-bound oligomeric form. Consequently, mechanistic insights into the membrane remodeling mechanism have remained sparse. Here, by using cryo-electron tomography and subtomogram averaging, we determined structures of nucleotide-bound EHD4 filaments on membrane tubes of various diameters at an average resolution of 7.6 Å. Assembly of EHD4 is mediated via interfaces in the G-domain and the helical domain. The oligomerized EHD4 structure resembles the closed conformation, where the tips of the helical domains protrude into the membrane. The variation in filament geometry and tube radius suggests a spontaneous filament curvature of approximately 1/70 nm−1. Combining the available structural and functional data, we suggest a model for EHD-mediated membrane remodeling.
Ferromagnetic-antiferromagnetic coexisting ground state and exchange bias effects in MnBi4Te7 and MnBi6Te10
Authors: Xu Xiaolong , Yang Shiqi , Wang Huan , Guzman Roger , Gao Yuchen , Zhu Yaozheng , Peng Yuxuan , Zang Zhihao , Xi Ming , Tian Shangjie , Li Yanping , Lei Hechang , Luo Zhaochu , Yang Jinbo , Wang Yeliang , Xia Tianlong , Zhou Wu , Huang Yuan , Ye Yu 
Published: December 2022

AbstractNatural superlattice structures MnBi2Te4(Bi2Te3)n (n = 1, 2, ...), in which magnetic MnBi2Te4 layers are separated by nonmagnetic Bi2Te3 layers, hold band topology, magnetism and reduced interlayer coupling, providing a promising platform for the realization of exotic topological quantum states. However, their magnetism in the two-dimensional limit, which is crucial for further exploration of quantum phenomena, remains elusive. Here, complex ferromagnetic-antiferromagnetic coexisting ground states that persist down to the 2-septuple layers limit are observed and comprehensively investigated in MnBi4Te7 (n = 1) and MnBi6Te10 (n = 2). The ubiquitous Mn-Bi site mixing modifies or even changes the sign of the subtle interlayer magnetic interactions, yielding a spatially inhomogeneous interlayer coupling. Further, a tunable exchange bias effect, arising from the coupling between the ferromagnetic and antiferromagnetic components in the ground state, is observed in MnBi2Te4(Bi2Te3)n (n = 1, 2), which provides design principles and material platforms for future spintronic devices. Our work highlights a new approach toward the fine-tuning of magnetism and paves the way for further study of quantum phenomena in MnBi2Te4(Bi2Te3)n (n = 1, 2) as well as their magnetic applications.
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Authors: Zhang Haifeng , Li Busu , Huang Qunhua , López-Giráldez Francesc , Tanaka Yoshiaki , Lin Qun , Mehta Sameet , Wang Guilin , Graham Morven , Liu Xinran , Park In-Hyun , Eichmann Anne , Min Wang , Zhou Jenny Huanjiao 
Published: December 2022

AbstractAlthough mitochondrial activity is critical for angiogenesis, its mechanism is not entirely clear. Here we show that mice with endothelial deficiency of any one of the three nuclear genes encoding for mitochondrial proteins, transcriptional factor (TFAM), respiratory complex IV component (COX10), or redox protein thioredoxin 2 (TRX2), exhibit retarded retinal vessel growth and arteriovenous malformations (AVM). Single-cell RNA-seq analyses indicate that retinal ECs from the three mutant mice have increased TGFβ signaling and altered gene expressions associated with vascular maturation and extracellular matrix, correlating with vascular malformation and increased basement membrane thickening in microvesels of mutant retinas. Mechanistic studies suggest that mitochondrial dysfunction from Tfam, Cox10, or Trx2 depletion induces a mitochondrial localization and MAPKs-mediated phosphorylation of SMAD2, leading to enhanced ALK5-SMAD2 signaling. Importantly, pharmacological blockade of ALK5 signaling or genetic deficiency of SMAD2 prevented retinal vessel growth retardation and AVM in all three mutant mice. Our studies uncover a novel mechanism whereby mitochondrial dysfunction via the ALK5-SMAD2 signaling induces retinal vascular malformations, and have therapeutic values for the alleviation of angiogenesis-associated human retinal diseases.
Unlocking the hidden chemical space in cubic-phase garnet solid electrolyte for efficient quasi-all-solid-state lithium batteries
Authors: Jung Sung-Kyun , Gwon Hyeokjo , Kim Hyungsub , Yoon Gabin , Shin Dongki , Hong Jihyun , Jung Changhoon , Kim Ju-Sik 
Published: December 2022

AbstractGarnet-type Li7La3Zr2O12 (LLZO) solid electrolytes (SE) demonstrates appealing ionic conductivity properties for all-solid-state lithium metal battery applications. However, LLZO (electro)chemical stability in contact with the lithium metal electrode is not satisfactory for developing practical batteries. To circumvent this issue, we report the preparation of various doped cubic-phase LLZO SEs without vacancy formation (i.e., Li = 7.0 such as Li7La3Zr0.5Hf0.5Sc0.5Nb0.5O12 and Li7La3Zr0.4Hf0.4Sn0.4Sc0.4Ta0.4O12). The entropy-driven synthetic approach allows access to hidden chemical space in cubic-phase garnet and enables lower solid-state synthesis temperature as the cubic-phase nucleation decreases from 750 to 400 °C. We demonstrate that the SEs with Li = 7.0 show better reduction stability against lithium metal compared to SE with low lithium contents and identical atomic species (i.e., Li = 6.6 such as Li6.6La3Zr0.4Hf0.4Sn0.4Sc0.2Ta0.6O12). Moreover, when a Li7La3Zr0.4Hf0.4Sn0.4Sc0.4Ta0.4O12 pellet is tested at 60 °C in coin cell configuration with a Li metal negative electrode, a LiNi1/3Co1/3Mn1/3O2-based positive electrode and an ionic liquid-based electrolyte at the cathode|SE interface, discharge capacity retention of about 92% is delivered after 700 cycles at 0.8 mA/cm2 and 60 °C.
Spatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding
Authors: Shen Rongbo , Liu Lin , Wu Zihan , Zhang Ying , Yuan Zhiyuan , Guo Junfu , Yang Fan , Zhang Chao , Chen Bichao , Feng Wanwan , Liu Chao , Guo Jing , Fan Guozhen , Zhang Yong , Li Yuxiang , Xu Xun , Yao Jianhua 
Published: December 2022

AbstractSpatially resolved transcriptomics provides the opportunity to investigate the gene expression profiles and the spatial context of cells in naive state, but at low transcript detection sensitivity or with limited gene throughput. Comprehensive annotating of cell types in spatially resolved transcriptomics to understand biological processes at the single cell level remains challenging. Here we propose Spatial-ID, a supervision-based cell typing method, that combines the existing knowledge of reference single-cell RNA-seq data and the spatial information of spatially resolved transcriptomics data. We present a series of benchmarking analyses on publicly available spatially resolved transcriptomics datasets, that demonstrate the superiority of Spatial-ID compared with state-of-the-art methods. Besides, we apply Spatial-ID on a self-collected mouse brain hemisphere dataset measured by Stereo-seq, that shows the scalability of Spatial-ID to three-dimensional large field tissues with subcellular spatial resolution.
Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity
Authors: McEvoy Caitriona M. , Murphy Julia M. , Zhang Lin , Clotet-Freixas Sergi , Mathews Jessica A. , An James , Karimzadeh Mehran , Pouyabahar Delaram , Su Shenghui , Zaslaver Olga , Röst Hannes , Arambewela Rangi , Liu Lewis Y. , Zhang Sally , Lawson Keith A. , Finelli Antonio , Wang Bo , MacParland Sonya A. , Bader Gary D. , Konvalinka Ana , Crome Sarah Q. 
Published: December 2022

AbstractKnowledge of the transcriptional programs underpinning the functions of human kidney cell populations at homeostasis is limited. We present a single-cell perspective of healthy human kidney from 19 living donors, with equal contribution from males and females, profiling the transcriptome of 27677 cells to map human kidney at high resolution. Sex-based differences in gene expression within proximal tubular cells were observed, specifically, increased anti-oxidant metallothionein genes in females and aerobic metabolism-related genes in males. Functional differences in metabolism were confirmed in proximal tubular cells, with male cells exhibiting higher oxidative phosphorylation and higher levels of energy precursor metabolites. We identified kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions. Significant heterogeneity in myeloid cells was observed, with a MRC1+LYVE1+FOLR2+C1QC+ population representing a predominant population in healthy kidney. This study provides a detailed cellular map of healthy human kidney, and explores the complexity of parenchymal and kidney-resident immune cells.
Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction
Authors: Klapproth Erik , Witt Anke , Klose Pauline , Wiedemann Johanna , Vavilthota Nikitha , Künzel Stephan R. , Kämmerer Susanne , Günscht Mario , Sprott David , Lesche Mathias , Rost Fabian , Dahl Andreas , Rauch Erik , Kattner Lars , Weber Silvio , Mirtschink Peter , Kopaliani Irakli , Guan Kaomei , Lorenz Kristina , Saftig Paul , Wagner Michael , El-Armouche Ali 
Published: December 2022

AbstractAfter myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Here, we address the value of targeting a previously unknown a disintegrin and metalloprotease 10 (ADAM10)/CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in myocardial biopsies from patients with ischemia-driven cardiomyopathy. Intriguingly, upon MI in mice, pharmacological ADAM10 inhibition as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, abolished ADAM10-mediated CX3CL1 ectodomain shedding leads to diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.
An HSV-1-H129 amplicon tracer system for rapid and efficient monosynaptic anterograde neural circuit tracing
Authors: Xiong Feng , Yang Hong , Song Yi-Ge , Qin Hai-Bin , Zhang Qing-Yang , Huang Xian , Jing Wei , Deng Manfei , Liu Yang , Liu Zhixiang , Shen Yin , Han Yunyun , Lu Youming , Xu Xiangmin , Holmes Todd C. , Luo Minmin , Zhao Fei , Luo Min-Hua , Zeng Wen-Bo 
Published: December 2022

AbstractMonosynaptic viral tracers are essential tools for dissecting neuronal connectomes and for targeted delivery of molecular sensors and effectors. Viral toxicity and complex multi-injection protocols are major limiting application barriers. To overcome these barriers, we developed an anterograde monosynaptic H129Amp tracer system based on HSV-1 strain H129. The H129Amp tracer system consists of two components: an H129-dTK-T2-pacFlox helper which assists H129Amp tracer’s propagation and transneuronal monosynaptic transmission. The shared viral features of tracer/helper allow for simultaneous single-injection and subsequent high expression efficiency from multiple-copy of expression cassettes in H129Amp tracer. These improvements of H129Amp tracer system shorten experiment duration from 28-day to 5-day for fast-bright monosynaptic tracing. The lack of toxic viral genes in the H129Amp tracer minimizes toxicity in postsynaptic neurons, thus offering the potential for functional anterograde mapping and long-term tracer delivery of genetic payloads. The H129Amp tracer system is a powerful tracing tool for revealing neuronal connectomes.
The B-type response regulator GmRR11d mediates systemic inhibition of symbiotic nodulation
Authors: Chen Jiahuan , Wang Zhijuan , Wang Lixiang , Hu Yangyang , Yan Qiqi , Lu Jingjing , Ren Ziyin , Hong Yujie , Ji Hongtao , Wang Hui , Wu Xinying , Lin Yanru , Su Chao , Ott Thomas , Li Xia 
Published: December 2022

AbstractKey to the success of legumes is the ability to form and maintain optimal symbiotic nodules that enable them to balance the trade-off between symbiosis and plant growth. Cytokinin is essential for homeostatic regulation of nodulation, but the mechanism remains incompletely understood. Here, we show that a B-type response regulator GmRR11d mediates systemic inhibition of nodulation.GmRR11dis induced by rhizobia and low level cytokinin, and GmRR11d can suppress the transcriptional activity of GmNSP1 onGmNIN1ato inhibit soybean nodulation. GmRR11d positively regulates cytokinin response and its binding on theGmNIN1apromoter is enhanced by cytokinin. Intriguingly, rhizobial induction ofGmRR11dand its function are dependent upon GmNARK that is a CLV1-like receptor kinase and inhibits nodule number in shoots. Thus, GmRR11d governs a transcriptional program associated with nodulation attenuation and cytokinin response activation essential for systemic regulation of nodulation.
Chemoselective carbene insertion into the N−H bonds of NH3·H2O
Authors: Liu Zhaohong , Yang Yong , Song Qingmin , Li Linxuan , Zanoni Giuseppe , Liu Shaopeng , Xiang Meng , Anderson Edward A. , Bi Xihe 
Published: December 2022

AbstractThe conversion of inexpensive aqueous ammonia (NH3·H2O) into value-added primary amines by N−H insertion persists as a longstanding challenge in chemistry because of the tendency of Lewis basic ammonia (NH3) to bind and inhibit metal catalysts. Herein, we report a chemoselective carbene N−H insertion of NH3·H2O using a TpBr3Ag-catalyzed two-phase system. Coordination by a homoscorpionate TpBr3 ligand renders silver compatible with NH3 and H2O and enables the generation of electrophilic silver carbene. Water promotes subsequent [1,2]-proton shift to generate N−H insertion products with high chemoselectivity. The result of the reaction is the coupling of an inorganic nitrogen source with either diazo compounds or N-triftosylhydrazones to produce useful primary amines. Further investigations elucidate the reaction mechanism and the origin of chemoselectivity.
Recent global decline in rainfall interception loss due to altered rainfall regimes
Authors: Lian Xu , Zhao Wenli , Gentine Pierre 
Published: December 2022

AbstractEvaporative loss of interception (Ei) is the first process occurring during rainfall, yet its role in large-scale surface water balance has been largely underexplored. Here we show thatEican be inferred from flux tower evapotranspiration measurements using physics-informed hybrid machine learning models built under wet versus dry conditions. Forced by satellite and reanalysis data, this framework provides an observationally constrained estimate ofEi, which is on average 84.1 ± 1.8 mm per year and accounts for 8.6 ± 0.2% of total rainfall globally during 2000–2020. Rainfall frequency regulates long-term averageEichanges, and rainfall intensity, rather than vegetation attributes, determines the fraction ofEiin gross precipitation (Ei/P). Rain events have become less frequent and more intense since 2000, driving a global decline inEi(andEi/P) by 4.9% (6.7%). This suggests that ongoing rainfall changes favor a partitioning towards more soil moisture and runoff, benefiting ecosystem functions but simultaneously increasing flood risks.
A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling
Authors: Perry Sarah , Han Yifu , Qiu Chengjie , Chien Chun , Goel Pragya , Nishimura Samantha , Sajnani Manisha , Schmid Andreas , Sigrist Stephan J. , Dickman Dion 
Published: December 2022

AbstractPresynaptic homeostatic plasticity (PHP) adaptively enhances neurotransmitter release following diminished postsynaptic glutamate receptor (GluR) functionality to maintain synaptic strength. While much is known about PHP expression mechanisms, postsynaptic induction remains enigmatic. For over 20 years, diminished postsynaptic Ca2+ influx was hypothesized to reduce CaMKII activity and enable retrograde PHP signaling at the Drosophila neuromuscular junction. Here, we have interrogated inductive signaling and find that active CaMKII colocalizes with and requires the GluRIIA receptor subunit. Next, we generated Ca2+-impermeable GluRs to reveal that both CaMKII activity and PHP induction are Ca2+-insensitive. Rather, a GluRIIA C-tail domain is necessary and sufficient to recruit active CaMKII. Finally, chimeric receptors demonstrate that the GluRIIA tail constitutively occludes retrograde homeostatic signaling by stabilizing active CaMKII. Thus, the physical loss of the GluRIIA tail is sensed, rather than reduced Ca2+, to enable retrograde PHP signaling, highlighting a unique, Ca2+-independent control mechanism for CaMKII in gating homeostatic plasticity.
Core–shell dry adhesives for rough surfaces via electrically responsive self-growing strategy
Authors: Tian Hongmiao , Wang Duorui , Zhang Yahui , Jiang Yuanze , Liu Tianci , Li Xiangming , Wang Chunhui , Chen Xiaoliang , Shao Jinyou 
Published: December 2022

AbstractBioinspired dry adhesives have an extraordinary impact in the field of robotic manipulation and locomotion. However, there is a considerable difference between artificial structures and biological ones regarding surface adaptability, especially for rough surfaces. This can be attributed to their distinct structural configuration and forming mechanism. Here, we propose a core–shell adhesive structure that is obtained through a growth strategy, i.e., an electrically responsive self-growing core–shell structure. This growth strategy results in a specific mushroom-shaped structure with a rigid core and a soft shell, which exhibits excellent adhesion on typical target surfaces with roughness ranging from the nanoscale to the microscale up to dozens of micrometers. The proposed adhesion strategy extends dry adhesives from smooth surfaces to rough ones, especially for rough surfaces with roughness up to dozens or hundreds of micrometers, opening an avenue for the development of dry adhesive-based devices and systems.
Nomenclature of cell-cultivated meat & seafood products
Authors: Malerich Marlana , Bryant Christopher 
Published: December 2022

AbstractCell-cultivated meat and seafood is getting closer to a reality for consumers in the US and around the world. However, regulators are still largely lagging behind on regulating production and labelling of these products. In a large experimental study using a representative US sample (N = 2653), we tested 9 different names for 3 different types of meat and seafood products in terms of their clarity, consumer appeal, and communication of safety and allergenicity. We found that terms proposed by the conventional meat and seafood industry including ‘artificial’ and ‘lab-grown’ tended to score low in terms of consumer appeal, purchase intent, and perceived safety, while ‘artificial’ also had the lowest score on clarity and communicating allergenicity. On the other hand, terms proposed by the cell-cultivated industry including ‘Novari’ scored high in terms of appeal and purchase intent but scored low in terms of clarity. The terms ‘cell-cultured’ and ‘cell-cultivated’ were the best all round labels in terms of clarity, appeal, and communicating safety and allergenicity – in particular, the addition of the prefix ‘cell-’ increased understanding compared to ‘cultured’ or ‘cultivated’ labels. The most-understood label was a short descriptive phrase (‘grown from [animal] cells, not farmed [or fished]’), suggesting that additional wording on packaging could aid consumer understanding in this early stage. A high proportion of consumers were uncertain about the allergen status of cell-cultivated products under all names, suggesting that cell-cultivated products should be labelled as the type of meat they are, and carry applicable allergen information.
Extensive proteome and functional genomic profiling of variability between genetically identical human B-lymphoblastoid cells
Authors: Laczik Miklós , Erdős Edina , Ozgyin Lilla , Hevessy Zsuzsanna , Csősz Éva , Kalló Gergő , Nagy Tibor , Barta Endre , Póliska Szilárd , Szatmári István , Bálint Bálint László 
Published: December 2022

AbstractIn life-science research isogenic B-lymphoblastoid cell lines (LCLs) are widely known and preferred for their genetic stability – they are often used for studying mutations for example, where genetic stability is crucial. We have shown previously that phenotypic variability can be observed in isogenic B-lymphoblastoid cell lines. Isogenic LCLs present well-defined phenotypic differences on various levels, for example on the gene expression level or the chromatin level. Based on our investigations, the phenotypic variability of the isogenic LCLs is accompanied by certain genetic variation too. We have developed a compendium of LCL datasets that present the phenotypic and genetic variability of five isogenic LCLs from a multiomic perspective. In this paper, we present additional datasets generated with Next Generation Sequencing techniques to provide genomic and transcriptomic profiles (WGS, RNA-seq, single cell RNA-seq), protein-DNA interactions (ChIP-seq), together with mass spectrometry and flow cytometry datasets to monitor the changes in the proteome. We are sharing these datasets with the scientific community according to the FAIR principles for further investigations.