bluuebunny/crossref_metadata_2025_split huggingface dataset:
LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models
Authors: Szabó Áron , Vincze Virág , Chhatre Aishwarya Sanjay , Jipa András , Bognár Sarolta , Varga Katalin Eszter , Banik Poulami , Harmatos-Ürmösi Adél , Neukomm Lukas J. , Juhász Gábor 
Published: May 2023

AbstractGlial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms governing the efficiency of debris degradation in glia have remained largely unexplored. Here we show that LC3-associated phagocytosis (LAP), an engulfment pathway assisted by certain autophagy factors, promotes glial phagosome maturation in theDrosophilawing nerve. A LAP-specific subset of autophagy-related genes is required in glia for axon debris clearance, encoding members of the Atg8a (LC3) conjugation system and the Vps34 lipid kinase complex including UVRAG and Rubicon. Phagosomal Rubicon and Atg16 WD40 domain-dependent conjugation of Atg8a mediate proper breakdown of internalized axon fragments, and Rubicon overexpression in glia accelerates debris elimination. Finally, LAP promotes survival following traumatic brain injury. Our results reveal a role of glial LAP in the clearance of neuronal debris in vivo, with potential implications for the recovery of the injured nervous system.
Direct haplotype-resolved 5-base HiFi sequencing for genome-wide profiling of hypermethylation outliers in a rare disease cohort
Authors: Cheung Warren A. , Johnson Adam F. , Rowell William J. , Farrow Emily , Hall Richard , Cohen Ana S. A. , Means John C. , Zion Tricia N. , Portik Daniel M. , Saunders Christopher T. , Koseva Boryana , Bi Chengpeng , Truong Tina K. , Schwendinger-Schreck Carl , Yoo Byunggil , Johnston Jeffrey J. , Gibson Margaret , Evrony Gilad , Rizzo William B. , Thiffault Isabelle , Younger Scott T. , Curran Tom , Wenger Aaron M. , Grundberg Elin , Pastinen Tomi 
Published: May 2023

AbstractLong-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and large hypermethylation events (>1 kb), respectively. We identify repeat expansions in proximal promoters predicting allelic gene silencing via hypermethylation and demonstrate allelic transcriptional events downstream. On average 30–40 rare hypermethylation tiles overlap rare disease genes per patient, providing indications for variation prioritization including a previously undiagnosed pathogenic allele in DIP2B causing global developmental delay. We propose that use of HiFi genome sequencing in unsolved rare disease cases will allow detection of unconventional diseases alleles due to loss of regulatory element activity.
An E2-E3 pair contributes to seed size control in grain crops
Authors: Tang Sha , Zhao Zhiying , Liu Xiaotong , Sui Yi , Zhang Dandan , Zhi Hui , Gao Yuanzhu , Zhang Hui , Zhang Linlin , Wang Yannan , Zhao Meicheng , Li Dongdong , Wang Ke , He Qiang , Zhang Renliang , Zhang Wei , Jia Guanqing , Tang Wenqiang , Ye Xingguo , Wu Chuanyin , Diao Xianmin 
Published: May 2023

AbstractUnderstanding the molecular mechanisms that regulate grain yield is important for improving agricultural productivity. Protein ubiquitination controls various aspects of plant growth but lacks understanding on how E2-E3 enzyme pairs impact grain yield in major crops. Here, we identified a RING-type E3 ligase SGD1 and its E2 partner SiUBC32 responsible for grain yield control in Setaria italica. The conserved role of SGD1 was observed in wheat, maize, and rice. Furthermore, SGD1 ubiquitinates the brassinosteroid receptor BRI1, stabilizing it and promoting plant growth. Overexpression of an elite SGD1 haplotype improved grain yield by about 12.8% per plant, and promote complex biological processes such as protein processing in endoplasmic reticulum, stress responses, photosystem stabilization, and nitrogen metabolism. Our research not only identifies the SiUBC32-SGD1-BRI1 genetic module that contributes to grain yield improvement but also provides a strategy for exploring key genes controlling important traits in Poaceae crops using the Setaria model system.
Photonic crystals with rainbow colors by centrifugation-assisted assembly of colloidal lignin nanoparticles
Authors: Liu Jinrong , Nero Mathias , Jansson Kjell , Willhammar Tom , Sipponen Mika H. 
Published: May 2023

AbstractPhotonic crystals are optical materials that are often fabricated by assembly of particles into periodically arranged structures. However, assembly of lignin nanoparticles has been limited due to lacking methods and incomplete understanding of the interparticle forces and packing mechanisms. Here we show a centrifugation-assisted fabrication of photonic crystals with rainbow structural colors emitted from the structure covering the entire visible spectrum. Our results show that centrifugation is crucial for the formation of lignin photonic crystals, because assembly of lignin nanoparticles without centrifugation assistance leads to the formation of stripe patterns rather than photonic crystals. We further prove that the functions of centrifugation are to classify lignin nanoparticles according to their particle size and produce monodispersed particle layers that display gradient colors from red to violet. The different layers of lignin nanoparticles were assembled in a way that created semi-closed packing structures, which gave rise to coherent scattering. The diameter of the lignin nanoparticles in each color layer is smaller than that predicted by a modified Bragg’s equation. In situ optical microscope images provided additional evidence on the importance of dynamic rearrangement of lignin nanoparticles during their assembly into semi-closed packing structures. The preparation of lignin nanoparticles combined with the methodology for their classification and assembly pave the way for sustainable photonic crystals.
Magnetic control of self-assembly and disassembly in organic materials
Authors: Jung You-jin , Kim Hyoseok , Cheong Hae-Kap , Lim Yong-beom 
Published: May 2023

AbstractBecause organic molecules and materials are generally insensitive or weakly sensitive to magnetic fields, a certain means to enhance their magnetic responsiveness needs to be exploited. Here we show a strategy to amplify the magnetic responsiveness of self-assembled peptide nanostructures by synergistically combining the concepts of perfect α-helix and rod-coil supramolecular building blocks. Firstly, we develop a monomeric, nonpolar, and perfect α-helix (MNP-helix). Then, we employ the MNP-helix as the rod block of rod-coil amphiphiles (rod-coils) because rod-coils are well-suited for fabricating responsive assemblies. We show that the self-assembly processes of the designed rod-coils and disassembly of rod-coil/DNA complexes can be controlled in a magnetically responsive manner using the relatively weak magnetic field provided by the ordinary neodymium magnet [0.07 ~ 0.25 Tesla (T)]. These results demonstrate that magnetically responsive organic assemblies usable under practical conditions can be realized by using rod-coil supramolecular building blocks containing constructively organized diamagnetic moieties.
Retention time prediction for chromatographic enantioseparation by quantile geometry-enhanced graph neural network
Authors: Xu Hao , Lin Jinglong , Zhang Dongxiao , Mo Fanyang 
Published: May 2023

AbstractThe enantioseparation of chiral molecules is a crucial and challenging task in the field of experimental chemistry, often requiring extensive trial and error with different experimental settings. To overcome this challenge, here we show a research framework that employs machine learning techniques to predict retention times of enantiomers and facilitate chromatographic enantioseparation. A documentary dataset of chiral molecular retention times in high-performance liquid chromatography (CMRT dataset) is established to handle the challenge of data acquisition. A quantile geometry-enhanced graph neural network is proposed to learn the molecular structure-retention time relationship, which shows a satisfactory predictive ability for enantiomers. The domain knowledge of chromatography is incorporated into the machine learning model to achieve multi-column prediction, which paves the way for chromatographic enantioseparation prediction by calculating the separation probability. The proposed research framework works well in retention time prediction and chromatographic enantioseparation facilitation, which sheds light on the application of machine learning techniques to the experimental scene and improves the efficiency of experimenters to speed up scientific discovery.
Highly lethal genotype I and II recombinant African swine fever viruses detected in pigs
Authors: Zhao Dongming , Sun Encheng , Huang Lianyu , Ding Leilei , Zhu Yuanmao , Zhang Jiwen , Shen Dongdong , Zhang Xianfeng , Zhang Zhenjiang , Ren Tao , Wang Wan , Li Fang , He Xijun , Bu Zhigao 
Published: May 2023

AbstractAfrican swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF_505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry.
Mechanism of action for small-molecule inhibitors of triacylglycerol synthesis
Authors: Sui Xuewu , Wang Kun , Song Kangkang , Xu Chen , Song Jiunn , Lee Chia-Wei , Liao Maofu , Farese Robert V. , Walther Tobias C. 
Published: May 2023

AbstractInhibitors of triacylglycerol (TG) synthesis have been developed to treat metabolism-related diseases, but we know little about their mechanisms of action. Here, we report cryo-EM structures of the TG-synthesis enzyme acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a membrane bound O-acyltransferase (MBOAT), in complex with two different inhibitors, T863 and DGAT1IN1. Each inhibitor binds DGAT1’s fatty acyl-CoA substrate binding tunnel that opens to the cytoplasmic side of the ER. T863 blocks access to the tunnel entrance, whereas DGAT1IN1 extends further into the enzyme, with an amide group interacting with more deeply buried catalytic residues. A survey of DGAT1 inhibitors revealed that this amide group may serve as a common pharmacophore for inhibition of MBOATs. The inhibitors were minimally active against the related MBOAT acyl-CoA:cholesterol acyltransferase 1 (ACAT1), yet a single-residue mutation sensitized ACAT1 for inhibition. Collectively, our studies provide a structural foundation for developing DGAT1 and other MBOAT inhibitors.
Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines
Authors: Yadav Shambhu , Waldeck-Weiermair Markus , Spyropoulos Fotios , Bronson Roderick , Pandey Arvind K. , Das Apabrita Ayan , Sisti Alexander C. , Covington Taylor A. , Thulabandu Venkata , Caplan Shari , Chutkow William , Steinhorn Benjamin , Michel Thomas 
Published: May 2023

AbstractOxidative stress is associated with cardiovascular and neurodegenerative diseases. Here we report studies of neurovascular oxidative stress in chemogenetic transgenic mouse lines expressing yeast D-amino acid oxidase (DAAO) in neurons and vascular endothelium. When these transgenic mice are fed D-amino acids, DAAO generates hydrogen peroxide in target tissues. DAAO-TGCdh5 transgenic mice express DAAO under control of the putatively endothelial-specific Cdh5 promoter. When we provide these mice with D-alanine, they rapidly develop sensory ataxia caused by oxidative stress and mitochondrial dysfunction in neurons within dorsal root ganglia and nodose ganglia innervating the heart. DAAO-TGCdh5 mice also develop cardiac hypertrophy after chronic chemogenetic oxidative stress. This combination of ataxia, mitochondrial dysfunction, and cardiac hypertrophy is similar to findings in patients with Friedreich’s ataxia. Our observations indicate that neurovascular oxidative stress is sufficient to cause sensory ataxia and cardiac hypertrophy. Studies of DAAO-TGCdh5 mice could provide mechanistic insights into Friedreich’s ataxia.
Computational discovery of ultra-strong, stable, and lightweight refractory multi-principal element alloys. Part I: design principles and rapid down-selection
Authors: Elder Kate L. M. , Berry Joel , Bocklund Brandon , McCall Scott K. , Perron Aurélien , McKeown Joseph T. 
Published: May 2023

AbstractRefractory metal-based multi-principal element alloys (MPEAs) are compelling materials for high-temperature (1000–2000 K) structural applications. However, only a minuscule fraction of their vast and heterogeneous compositional design space has been explored, leaving many potentially interesting alloys undiscovered. In this two-part work, a large region of the 11-element Al-Cr-Fe-Hf-Mo-Nb-Ta-Ti-V-W-Zr design space is computationally explored to identify refractory MPEAs with simultaneously high yield strength or specific yield strength and body-centered cubic (BCC) solid solution stability. In Part I, two case studies illuminate key factors and considerations in the yield strength versus phase stability tradeoff, provide guidelines for narrowing the expansive design space, and identify many candidates predicted to be stronger than refractory MPEAs reported to date, with BCC phase stability. Our findings indicate that medium entropy ternary alloys can outperform alloys with more elements and highlight the importance of exploring regions away from the equiatomic center of composition space.
Linear Jacobi-Legendre expansion of the charge density for machine learning-accelerated electronic structure calculations
Authors: Focassio Bruno , Domina Michelangelo , Patil Urvesh , Fazzio Adalberto , Sanvito Stefano 
Published: May 2023

AbstractKohn–Sham density functional theory (KS-DFT) is a powerful method to obtain key materials’ properties, but the iterative solution of the KS equations is a numerically intensive task, which limits its application to complex systems. To address this issue, machine learning (ML) models can be used as surrogates to find the ground-state charge density and reduce the computational overheads. We develop a grid-centred structural representation, based on Jacobi and Legendre polynomials combined with a linear regression, to accurately learn the converged DFT charge density. This integrates into a ML pipeline that can return any density-dependent observable, including energy and forces, at the quality of a converged DFT calculation, but at a fraction of the computational cost. Fast scanning of energy landscapes and producing starting densities for the DFT self-consistent cycle are among the applications of our scheme.
Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
Authors: Adlam David , Berrandou Takiy-Eddine , Georges Adrien , Nelson Christopher P. , Giannoulatou Eleni , Henry Joséphine , Ma Lijiang , Blencowe Montgomery , Turley Tamiel N. , Yang Min-Lee , Chopade Sandesh , Finan Chris , Braund Peter S. , Sadeg-Sayoud Ines , Iismaa Siiri E. , Kosel Matthew L. , Zhou Xiang , Hamby Stephen E. , Cheng Jenny , Liu Lu , Tarr Ingrid , Muller David W. M. , d’Escamard Valentina , King Annette , Brunham Liam R. , Baranowska-Clarke Ania A. , Debette Stéphanie , Amouyel Philippe , Olin Jeffrey W. , Patil Snehal , Hesselson Stephanie E. , Junday Keerat , Kanoni Stavroula , Aragam Krishna G. , Butterworth Adam S. ,   CARDIoGRAMPlusC4D,   MEGASTROKE,   International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, Bakker Mark K. , Ruigrok Ynte M. , Tweet Marysia S. , Gulati Rajiv , Combaret Nicolas ,   DISCO register, Kadian-Dodov Daniella , Kalman Jonathan M. , Fatkin Diane , Hingorani Aroon D. , Saw Jacqueline , Webb Tom R. , Hayes Sharonne N. , Yang Xia , Ganesh Santhi K. , Olson Timothy M. , Kovacic Jason C. , Graham Robert M. , Samani Nilesh J. , Bouatia-Naji Nabila 
Published: May 2023

AbstractSpontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.
Spontaneously established syntrophic yeast communities improve bioproduction
Authors: Aulakh Simran Kaur , Sellés Vidal Lara , South Eric J. , Peng Huadong , Varma Sreejith Jayasree , Herrera-Dominguez Lucia , Ralser Markus , Ledesma-Amaro Rodrigo 
Published: May 2023

AbstractNutritional codependence (syntrophy) has underexplored potential to improve biotechnological processes by using cooperating cell types. So far, design of yeast syntrophic communities has required extensive genetic manipulation, as the co-inoculation of most eukaryotic microbial auxotrophs does not result in cooperative growth. Here we employ high-throughput phenotypic screening to systematically test pairwise combinations of auxotrophic Saccharomyces cerevisiae deletion mutants. Although most coculture pairs do not enter syntrophic growth, we identify 49 pairs that spontaneously form syntrophic, synergistic communities. We characterized the stability and growth dynamics of nine cocultures and demonstrated that a pair of tryptophan auxotrophs grow by exchanging a pathway intermediate rather than end products. We then introduced a malonic semialdehyde biosynthesis pathway split between different pairs of auxotrophs, which resulted in increased production. Our results report the spontaneous formation of stable syntrophy in S. cerevisiae auxotrophs and illustrate the biotechnological potential of dividing labor in a cooperating intraspecies community.
Propagative α-synuclein seeds as serum biomarkers for synucleinopathies
Authors: Okuzumi Ayami , Hatano Taku , Matsumoto Gen , Nojiri Shuko , Ueno Shin-ichi , Imamichi-Tatano Yoko , Kimura Haruka , Kakuta Soichiro , Kondo Akihide , Fukuhara Takeshi , Li Yuanzhe , Funayama Manabu , Saiki Shinji , Taniguchi Daisuke , Tsunemi Taiji , McIntyre Deborah , Gérardy Jean-Jacques , Mittelbronn Michel , Kruger Rejko , Uchiyama Yasuo , Nukina Nobuyuki , Hattori Nobutaka 
Published: May 2023

Abstract
Abnormal α-synuclein aggregation is a key pathological feature of a group of neurodegenerative diseases known as synucleinopathies, which include Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA). The pathogenic β-sheet seed conformation of α-synuclein is found in various tissues, suggesting potential as a biomarker, but few studies have been able to reliably detect these seeds in serum samples. In this study, we developed a modified assay system, called immunoprecipitation-based real-time quaking-induced conversion (IP/RT-QuIC), which enables the detection of pathogenic α-synuclein seeds in the serum of individuals with synucleinopathies. In our internal first and second cohorts, IP/RT-QuIC showed high diagnostic performance for differentiating PD versus controls (area under the curve (AUC): 0.96 (95% confidence interval (CI) 0.95–0.99)/AUC: 0.93 (95% CI 0.84–1.00)) and MSA versus controls (AUC: 0.64 (95% CI 0.49–0.79)/AUC: 0.73 (95% CI 0.49–0.98)). IP/RT-QuIC also showed high diagnostic performance in differentiating individuals with PD (AUC: 0.86 (95% CI 0.74–0.99)) and MSA (AUC: 0.80 (95% CI 0.65–0.97)) from controls in a blinded external cohort. Notably, amplified seeds maintained disease-specific properties, allowing the differentiation of samples from individuals with PD versus MSA. In summary, here we present a novel platform that may allow the detection of individuals with synucleinopathies using serum samples.
Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage
Authors: Kumar Senthil T. , Nazarov Sergey , Porta Sílvia , Maharjan Niran , Cendrowska Urszula , Kabani Malek , Finamore Francesco , Xu Yan , Lee Virginia M.-Y. , Lashuel Hilal A. 
Published: May 2023

AbstractDespite the strong evidence linking the transactive response DNA-binding protein 43 (TDP-43) aggregation to the pathogenesis of frontotemporal lobar degeneration with TDP-43, amyotrophic lateral sclerosis and several neurodegenerative diseases, our knowledge of the sequence and structural determinants of its aggregation and neurotoxicity remains incomplete. Herein, we present a new method for producing recombinant full-length TDP-43 filaments that exhibit sequence and morphological features similar to those of brain-derived TDP-43 filaments. We show that TDP-43 filaments contain a β-sheet-rich helical amyloid core that is fully buried by the flanking structured domains of the protein. We demonstrate that the proteolytic cleavage of TDP-43 filaments and exposure of this amyloid core are necessary for propagating TDP-43 pathology and enhancing the seeding of brain-derived TDP-43 aggregates. Only TDP-43 filaments with exposed amyloid core efficiently seeded the aggregation of endogenous TDP-43 in cells. These findings suggest that inhibiting the enzymes mediating cleavage of TDP-43 aggregates represents a viable disease-modifying strategy to slow the progression of amyotrophic lateral sclerosis and other TDP-43 proteinopathies.