bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel variant of the ciliopathic gene FUZZY associated with craniosynostosis
Authors: Barrell William B. , Adel Al-Lami Hadeel , Goos Jacqueline A. C. , Swagemakers Sigrid M. A. , van Dooren Marieke , Torban Elena , van der Spek Peter J. , Mathijssen Irene M. J. , Liu Karen J. 
Published: November 2021

AbstractCraniosynostosis is a birth defect occurring in approximately one in 2000 live births, where premature fusion of the cranial bones inhibits growth of the skull during critical periods of brain development. The resulting changes in skull shape can lead to compression of the brain, causing severe complications. While we have some understanding of the molecular pathology of craniosynostosis, a large proportion of cases are of unknown genetic aetiology. Based on studies in mouse, we previously proposed that the ciliopathy geneFuzshould be considered a candidate craniosynostosis gene. Here, we report a novel variant ofFUZ(c.851 G > C, p.(Arg284Pro)) found in monozygotic twins presenting with craniosynostosis. To investigate whetherFuzhas a direct role in regulating osteogenic fate and mineralisation, we cultured primary osteoblasts and mouse embryonic fibroblasts (MEFs) fromFuzmutant mice. Loss ofFuzresulted in increased osteoblastic mineralisation. This suggests that FUZ protein normally acts as a negative regulator of osteogenesis. We then usedFuzmutant MEFs, which lose functional primary cilia, to test whether the FUZ p.(Arg284Pro) variant could restore FUZ function during ciliogenesis. We found that expression of the FUZ p.(Arg284Pro) variant was sufficient to partially restore cilia numbers, but did not mediate a comparable response to Hedgehog pathway activation. Together, this suggests the osteogenic effects of FUZ p.(Arg284Pro) do not depend upon initiation of ciliogenesis.
N-glucosyltransferase GbNGT1 from ginkgo complements the auxin metabolic pathway
Authors: Yin Qinggang , Zhang Jing , Wang Shuhui , Cheng Jintang , Gao Han , Guo Cong , Ma Lianbao , Sun Limin , Han Xiaoyan , Chen Shilin , Liu An 
Published: November 2021

AbstractAs auxins are among the most important phytohormones, the regulation of auxin homeostasis is complex. Generally, auxin conjugates, especially IAA glucosides, are predominant at high auxin levels. Previous research on terminal glucosylation focused mainly on the O-position, while IAA-N-glucoside and IAA-Asp-N-glucoside have been neglected since their discovery in 2001. In our study, IAA-Asp-N-glucoside was found to be specifically abundant (as high as 4.13 mg/g) in the seeds of 58 ginkgo cultivars. Furthermore, a novel N-glucosyltransferase, termed GbNGT1, was identified via differential transcriptome analysis and in vitro enzymatic testing. It was found that GbNGT1 could catalyze IAA-Asp and IAA to form their corresponding N-glucosides. The enzyme was demonstrated to possess a specific catalytic capacity toward the N-position of the IAA-amino acid or IAA from 52 substrates. Docking and site-directed mutagenesis of this enzyme confirmed that the E15G mutant could almost completely abolish its N-glucosylation ability toward IAA-Asp and IAA in vitro and in vivo. The IAA modification of GbNGT1 and GbGH3.5 was verified by transient expression assay in Nicotiana benthamiana. The effect of GbNGT1 on IAA distribution promotes root growth in Arabidopsis thaliana.
Integrating full-length transcriptomics and metabolomics reveals the regulatory mechanisms underlying yellow pigmentation in tree peony (Paeonia suffruticosa Andr.) flowers
Authors: Luo Xiaoning , Sun Daoyang , Wang Shu , Luo Sha , Fu Yaqi , Niu Lixin , Shi Qianqian , Zhang Yanlong 
Published: November 2021

AbstractTree peony (Paeonia suffruticosa Andr.) is a popular ornamental plant in China due to its showy and colorful flowers. However, yellow-colored flowers are rare in both wild species and domesticated cultivars. The molecular mechanisms underlying yellow pigmentation remain poorly understood. Here, petal tissues of two tree peony cultivars, “High Noon” (yellow flowers) and “Roufurong” (purple–red flowers), were sampled at five developmental stages (S1–S5) from early flower buds to full blooms. Five petal color indices (brightness, redness, yellowness, chroma, and hue angle) and the contents of ten different flavonoids were determined. Compared to “Roufurong,” which accumulated abundant anthocyanins at S3–S5, the yellow-colored “High Noon” displayed relatively higher contents of tetrahydroxychalcone (THC), flavones, and flavonols but no anthocyanin production. The contents of THC, flavones, and flavonols in “High Noon” peaked at S3 and dropped gradually as the flower bloomed, consistent with the color index patterns. Furthermore, RNA-seq analyses at S3 showed that structural genes such as PsC4Hs, PsDFRs, and PsUFGTs in the flavonoid biosynthesis pathway were downregulated in “High Noon,” whereas most PsFLSs, PsF3Hs, and PsF3’Hs were upregulated. Five transcription factor (TF) genes related to flavonoid biosynthesis were also upregulated in “High Noon.” One of these TFs, PsMYB111, was overexpressed in tobacco, which led to increased flavonols but decreased anthocyanins. Dual-luciferase assays further confirmed that PsMYB111 upregulated PsFLS. These results improve our understanding of yellow pigmentation in tree peony and provide a guide for future molecular-assisted breeding experiments in tree peony with novel flower colors.
Direct copolymerization of ethylene with protic comonomers enabled by multinuclear Ni catalysts
Authors: Ji Gang , Chen Zhou , Wang Xiao-Yan , Ning Xiao-Shan , Xu Chong-Jie , Zhang Xing-Min , Tao Wen-Jie , Li Jun-Fang , Gao Yanshan , Shen Qi , Sun Xiu-Li , Wang Hao-Yang , Zhao Jun-Bo , Zhang Bo , Guo Yin-Long , Zhao Yanan , Sun Jiajie , Luo Yi , Tang Yong 
Published: November 2021

AbstractEthylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.
Atomic scale crystal field mapping of polar vortices in oxide superlattices
Authors: Susarla Sandhya , García-Fernández Pablo , Ophus Colin , Das Sujit , Aguado-Puente Pablo , McCarter Margaret , Ercius Peter , Martin Lane W. , Ramesh Ramamoorthy , Junquera Javier 
Published: November 2021

AbstractPolar vortices in oxide superlattices exhibit complex polarization topologies. Using a combination of electron energy loss near-edge structure analysis, crystal field multiplet theory, and first-principles calculations, we probe the electronic structure within such polar vortices in [(PbTiO3)16/(SrTiO3)16] superlattices at the atomic scale. The peaks in Ti $$L$$
L
-edge spectra shift systematically depending on the position of the Ti4+ cations within the vortices i.e., the direction and magnitude of the local dipole. First-principles computation of the local projected density of states on the Ti $$3d$$
3
d
orbitals, together with the simulated crystal field multiplet spectra derived from first principles are in good agreement with the experiments.
Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes
Authors: Lehmann Brian D. , Colaprico Antonio , Silva Tiago C. , Chen Jianjiao , An Hanbing , Ban Yuguang , Huang Hanchen , Wang Lily , James Jamaal L. , Balko Justin M. , Gonzalez-Ericsson Paula I. , Sanders Melinda E. , Zhang Bing , Pietenpol Jennifer A. , Chen X. Steven 
Published: November 2021

AbstractTriple-negative breast cancer (TNBC) is a collection of biologically diverse cancers characterized by distinct transcriptional patterns, biology, and immune composition. TNBCs subtypes include two basal-like (BL1, BL2), a mesenchymal (M) and a luminal androgen receptor (LAR) subtype. Through a comprehensive analysis of mutation, copy number, transcriptomic, epigenetic, proteomic, and phospho-proteomic patterns we describe the genomic landscape of TNBC subtypes. Mesenchymal subtype tumors display high mutation loads, genomic instability, absence of immune cells, low PD-L1 expression, decreased global DNA methylation, and transcriptional repression of antigen presentation genes. We demonstrate that major histocompatibility complex I (MHC-I) is transcriptionally suppressed by H3K27me3 modifications by the polycomb repressor complex 2 (PRC2). Pharmacological inhibition of PRC2 subunits EZH2 or EED restores MHC-I expression and enhances chemotherapy efficacy in murine tumor models, providing a rationale for using PRC2 inhibitors in PD-L1 negative mesenchymal tumors. Subtype-specific differences in immune cell composition and differential genetic/pharmacological vulnerabilities suggest additional treatment strategies for TNBC.
A live measles-vectored COVID-19 vaccine induces strong immunity and protection from SARS-CoV-2 challenge in mice and hamsters
Authors: Frantz Phanramphoei N. , Barinov Aleksandr , Ruffié Claude , Combredet Chantal , Najburg Valérie , de Melo Guilherme Dias , Larrous Florence , Kergoat Lauriane , Teeravechyan Samaporn , Jongkaewwattana Anan , Billon-Denis Emmanuelle , Tournier Jean-Nicolas , Prot Matthieu , Levillayer Laurine , Conquet Laurine , Montagutelli Xavier , Tichit Magali , Hardy David , Fernandes Priyanka , Strick-Marchand Hélène , Di Santo James , Simon-Lorière Etienne , Bourhy Hervé , Tangy Frédéric 
Published: November 2021

AbstractSeveral COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.
Long-term priors influence visual perception through recruitment of long-range feedback
Authors: Hardstone Richard , Zhu Michael , Flinker Adeen , Melloni Lucia , Devore Sasha , Friedman Daniel , Dugan Patricia , Doyle Werner K. , Devinsky Orrin , He Biyu J. 
Published: November 2021

AbstractPerception results from the interplay of sensory input and prior knowledge. Despite behavioral evidence that long-term priors powerfully shape perception, the neural mechanisms underlying these interactions remain poorly understood. We obtained direct cortical recordings in neurosurgical patients as they viewed ambiguous images that elicit constant perceptual switching. We observe top-down influences from the temporal to occipital cortex, during the preferred percept that is congruent with the long-term prior. By contrast, stronger feedforward drive is observed during the non-preferred percept, consistent with a prediction error signal. A computational model based on hierarchical predictive coding and attractor networks reproduces all key experimental findings. These results suggest a pattern of large-scale information flow change underlying long-term priors’ influence on perception and provide constraints on theories about long-term priors’ influence on perception.
A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii
Authors: Bateman Thomas J. , Shah Megha , Ho Timothy Pham , Shin Hyejin Esther , Pan Chuxi , Harris Greg , Fegan Jamie E. , Islam Epshita A. , Ahn Sang Kyun , Hooda Yogesh , Gray-Owen Scott D. , Chen Wangxue , Moraes Trevor F. 
Published: November 2021

AbstractNutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs.
A deep learning approach for complex microstructure inference
Authors: Durmaz Ali Riza , Müller Martin , Lei Bo , Thomas Akhil , Britz Dominik , Holm Elizabeth A. , Eberl Chris , Mücklich Frank , Gumbsch Peter 
Published: November 2021

AbstractAutomated, reliable, and objective microstructure inference from micrographs is essential for a comprehensive understanding of process-microstructure-property relations and tailored materials development. However, such inference, with the increasing complexity of microstructures, requires advanced segmentation methodologies. While deep learning offers new opportunities, an intuition about the required data quality/quantity and a methodological guideline for microstructure quantification is still missing. This, along with deep learning’s seemingly intransparent decision-making process, hampers its breakthrough in this field. We apply a multidisciplinary deep learning approach, devoting equal attention to specimen preparation and imaging, and train distinct U-Net architectures with 30–50 micrographs of different imaging modalities and electron backscatter diffraction-informed annotations. On the challenging task of lath-bainite segmentation in complex-phase steel, we achieve accuracies of 90% rivaling expert segmentations. Further, we discuss the impact of image context, pre-training with domain-extrinsic data, and data augmentation. Network visualization techniques demonstrate plausible model decisions based on grain boundary morphology.
Post-translational insertion of boron in proteins to probe and modulate function
Authors: Mollner Tim A. , Isenegger Patrick G. , Josephson Brian , Buchanan Charles , Lercher Lukas , Oehlrich Daniel , Hansen D. Flemming , Mohammed Shabaz , Baldwin Andrew J. , Gouverneur Véronique , Davis Benjamin G. 
Published: November 2021

AbstractBoron is absent in proteins, yet is a micronutrient. It possesses unique bonding that could expand biological function including modes of Lewis acidity not available to typical elements of life. Here we show that post-translational Cβ–Bγ bond formation provides mild, direct, site-selective access to the minimally sized residue boronoalanine (Bal) in proteins. Precise anchoring of boron within complex biomolecular systems allows dative bond-mediated, site-dependent protein Lewis acid–base-pairing (LABP) by Bal. Dynamic protein-LABP creates tunable inter- and intramolecular ligand–host interactions, while reactive protein-LABP reveals reactively accessible sites through migratory boron-to-oxygen Cβ–Oγ covalent bond formation. These modes of dative bonding can also generate de novo function, such as control of thermo- and proteolytic stability in a target protein, or observation of transient structural features via chemical exchange. These results indicate that controlled insertion of boron facilitates stability modulation, structure determination, de novo binding activities and redox-responsive ‘mutation’.
Metabolomic profiling of Burkholderia cenocepacia in synthetic cystic fibrosis sputum medium reveals nutrient environment-specific production of virulence factors
Authors: Jaiyesimi Olakunle A. , McAvoy Andrew C. , Fogg David N. , Garg Neha 
Published: November 2021

AbstractInfections by Burkholderia cenocepacia lead to life-threatening disease in immunocompromised individuals, including those living with cystic fibrosis (CF). While genetic variation in various B. cenocepacia strains has been reported, it remains unclear how the chemical environment of CF lung influences the production of small molecule virulence factors by these strains. Here we compare metabolomes of three clinical B. cenocepacia strains in synthetic CF sputum medium (SCFM2) and in a routine laboratory medium (LB), in the presence and absence of the antibiotic trimethoprim. Using a mass spectrometry-based untargeted metabolomics approach, we identify several compound classes which are differentially produced in SCFM2 compared to LB media, including siderophores, antimicrobials, quorum sensing signals, and various lipids. Furthermore, we describe that specific metabolites are induced in the presence of the antibiotic trimethoprim only in SCFM2 when compared to LB. Herein, C13-acyl-homoserine lactone, a quorum sensing signal previously not known to be produced by B. cenocepacia as well as pyochelin-type siderophores were exclusively detected during growth in SCFM2 in the presence of trimethoprim. The comparative metabolomics approach described in this study provides insight into environment-dependent production of secondary metabolites by B. cenocepacia strains and suggests future work which could identify personalized strain-specific regulatory mechanisms involved in production of secondary metabolites. Investigations into whether antibiotics with different mechanisms of action induce similar metabolic alterations will inform development of combination treatments aimed at effective clearance of Burkholderia spp. pathogens.
Redesigning an antibody H3 loop by virtual screening of a small library of human germline-derived sequences
Authors: Corbeil Christopher R. , Manenda Mahder Seifu , Sulea Traian , Baardsnes Jason , Picard Marie-Ève , Hogues Hervé , Gaudreault Francis , Deprez Christophe , Shi Rong , Purisima Enrico O. 
Published: November 2021

AbstractThe design of superior biologic therapeutics, including antibodies and engineered proteins, involves optimizing their specific ability to bind to disease-related molecular targets. Previously, we developed and applied the Assisted Design of Antibody and Protein Therapeutics (ADAPT) platform for virtual affinity maturation of antibodies (Vivcharuk et al. in PLoS One 12(7):e0181490,https://doi.org/10.1371/journal.pone.0181490, 2017). However, ADAPT is limited to point mutations of hot-spot residues in existing CDR loops. In this study, we explore the possibility of wholesale replacement of the entire H3 loop with no restriction to maintain the parental loop length. This complements other currently published studies that sample replacements for the CDR loops L1, L2, L3, H1 and H2. Given the immense sequence space theoretically available to H3, we focused on the virtual grafting of over 5000 human germline-derived H3 sequences from the IGMT/LIGM database increasing the diversity of the sequence space when compared to using crystalized H3 loop sequences. H3 loop conformations are generated and scored to identify optimized H3 sequences. Experimental testing of high-ranking H3 sequences grafted into the framework of the bH1 antibody against human VEGF-A led to the discovery of multiple hits, some of which had similar or better affinities relative to the parental antibody. In over 75% of the tested designs, the re-designed H3 loop contributed favorably to overall binding affinity. The hits also demonstrated good developability attributes such as high thermal stability and no aggregation. Crystal structures of select re-designed H3 variants were solved and indicated that although some deviations from predicted structures were seen in the more solvent accessible regions of the H3 loop, they did not significantly affect predicted affinity scores.
Local adaptations of Mediterranean sheep and goats through an integrative approach
Authors: Serranito Bruno , Cavalazzi Marco , Vidal Pablo , Taurisson-Mouret Dominique , Ciani Elena , Bal Marie , Rouvellac Eric , Servin Bertrand , Moreno-Romieux Carole , Tosser-Klopp Gwenola , Hall Stephen J. G. , Lenstra Johannes A. , Pompanon François , Benjelloun Badr , Da Silva Anne 
Published: November 2021

AbstractSmall ruminants are suited to a wide variety of habitats and thus represent promising study models for identifying genes underlying adaptations. Here, we considered local Mediterranean breeds of goats (n = 17) and sheep (n = 25) from Italy, France and Spain. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original cradle (i.e., the geographical area in which the breed has emerged), including transhumant pastoral areas. We then used the programs PCAdapt and LFMM to identify signatures of artificial and environmental selection. Considering cradles instead of current GPS coordinates resulted in a greater number of signatures identified by the LFMM analysis. The results, combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles in relation to the gradient of aridity and altitude. Some of these genes have been previously implicated in lipid metabolism (SUCLG2, BMP2), hypoxia stress/lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). Selection signatures involving the PCDH9 and KLH1 genes, as well as NBEA/NBEAL1, were identified in both species and thus could play an important adaptive role.
Motion and Sash Height (MASH) alarms for efficient fume hood use
Authors: Kongoletos Johnathan , Munden Ethan , Ballew Jennifer , Preston Daniel J. 
Published: November 2021

AbstractVentilation, including fume hoods, consumes 40–70% of the total energy used by modern laboratories. Energy-conscious fume hood usage—for example, closing the sash when a hood is unused—can significantly reduce energy expenditures due to ventilation. Prior approaches to promote such behaviors among lab users have primarily relied on passive feedback methods. In this work, we developed a low-cost fume hood monitoring device with active feedback to alert lab users when a fume hood is left open and unused. Using data collected by the building management system, we observed a 75.6% decrease in the average sash height after installation of these “Motion and Sash Height” (MASH) alarms, which would result in a reduction roughly equal to 43% of the annual carbon emissions of a typical American vehicle, for each fume hood. The MASH alarm presented here reduced energy costs by approximately $1,159 per year, per hood, at MIT.