bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth
Authors: Ku Zhiqiang , Xie Xuping , Lin Jianqing , Gao Peng , Wu Bin , El Sahili Abbas , Su Hang , Liu Yang , Ye Xiaohua , Tan Eddie Yongjun , Li Xin , Fan Xuejun , Goh Boon Chong , Xiong Wei , Boyd Hannah , Muruato Antonio E. , Deng Hui , Xia Hongjie , Zou Jing , Kalveram Birte K. , Menachery Vineet D. , Zhang Ningyan , Lescar Julien , Shi Pei-Yong , An Zhiqiang 
Published: September 2022

AbstractOne major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce emergence of antibody resistance. Here we engineer two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv)2 design (14-H-06) but not the CrossMAb design (14-crs-06) shows increased antigen-binding and virus-neutralizing activities against multiple SARS-CoV-2 variants as well as increased breadth of neutralizing activity compared to the cocktail. X-ray crystallography and cryo-EM reveal distinct binding models for individual cocktail antibodies, and computational simulations suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and multiple variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.
IL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis
Authors: Millet Nicolas , Solis Norma V. , Aguilar Diane , Lionakis Michail S. , Wheeler Robert T. , Jendzjowsky Nicholas , Swidergall Marc 
Published: September 2022

AbstractDuring infection the host relies on pattern-recognition receptors to sense invading fungal pathogens to launch immune defense mechanisms. While fungal recognition and immune effector responses are organ and cell type specific, during disseminated candidiasis myeloid cells exacerbate collateral tissue damage. The β-glucan receptor ephrin type-A 2 receptor (EphA2) is required to initiate mucosal inflammatory responses during oral Candida infection. Here we report that EphA2 promotes renal immunopathology during disseminated candidiasis. EphA2 deficiency leads to reduced renal inflammation and injury. Comprehensive analyses reveal that EphA2 restrains IL-23 secretion from and migration of dendritic cells. IL-23 signaling prevents ferroptotic host cell death during infection to limit inflammation and immunopathology. Further, host cell ferroptosis limits antifungal effector functions via releasing the lipid peroxidation product 4-hydroxynonenal to induce various forms of cell death. Thus, we identify ferroptotic cell death as a critical pathway of Candida-mediated renal immunopathology that opens a new avenue to tackle Candida infection and inflammation.
Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers
Authors: Feng Delong , Chen Yanhong , Dai Ranran , Bian Shasha , Xue Wei , Zhu Yongchang , Li Zhaoqiang , Yang Yiting , Zhang Yan , Zhang Jiarui , Bai Jie , Qin Litao , Kohwi Yoshinori , Shi Weili , Kohwi-Shigematsu Terumi , Ma Jing , Liao Shixiu , Hao Bingtao 
Published: September 2022

AbstractCD4+and CD8+double-positive (DP) thymocytes play a crucial role in T cell development in the thymus. DP cells rearrange the T cell receptor geneTcrato generate T cell receptors with TCRβ. DP cells differentiate into CD4 or CD8 single-positive (SP) thymocytes, regulatory T cells, or invariant nature kill T cells (iNKT) in response to TCR signaling. Chromatin organizer SATB1 is highly expressed in DP cells and is essential in regulatingTcrarearrangement and differentiation of DP cells. Here we explored the mechanism of SATB1 orchestrating gene expression in DP cells. Single-cell RNA sequencing shows thatSatb1deletion changes the cell identity of DP thymocytes and down-regulates genes specifically and highly expressed in DP cells. Super-enhancers regulate the expressions of DP-specific genes, and our Hi-C data show that SATB1 deficiency in thymocytes reduces super-enhancer activity by specifically decreasing interactions among super-enhancers and between super-enhancers and promoters. Our results reveal that SATB1 plays a critical role in thymocyte development to promote the establishment of DP cell identity by globally regulating super-enhancers of DP cells at the chromatin architectural level.
Scalable in situ single-cell profiling by electrophoretic capture of mRNA using EEL FISH
Authors: Borm Lars E. , Mossi Albiach Alejandro , Mannens Camiel C. A. , Janusauskas Jokubas , Özgün Ceren , Fernández-García David , Hodge Rebecca , Castillo Francisca , Hedin Charlotte R. H. , Villablanca Eduardo J. , Uhlén Per , Lein Ed S. , Codeluppi Simone , Linnarsson Sten 
Published: September 2022

AbstractMethods to spatially profile the transcriptome are dominated by a trade-off between resolution and throughput. Here we develop a method named Enhanced ELectric Fluorescence in situ Hybridization (EEL FISH) that can rapidly process large tissue samples without compromising spatial resolution. By electrophoretically transferring RNA from a tissue section onto a capture surface, EEL speeds up data acquisition by reducing the amount of imaging needed, while ensuring that RNA molecules move straight down toward the surface, preserving single-cell resolution. We apply EEL on eight entire sagittal sections of the mouse brain and measure the expression patterns of up to 440 genes to reveal complex tissue organization. Moreover, EEL can be used to study challenging human samples by removing autofluorescent lipofuscin, enabling the spatial transcriptome of the human visual cortex to be visualized. We provide full hardware specifications, all protocols and complete software for instrument control, image processing, data analysis and visualization.
SAIGE-GENE+ improves the efficiency and accuracy of set-based rare variant association tests
Authors: Zhou Wei , Bi Wenjian , Zhao Zhangchen , Dey Kushal K. , Jagadeesh Karthik A. , Karczewski Konrad J. , Daly Mark J. , Neale Benjamin M. , Lee Seunggeun 
Published: September 2022

AbstractSeveral biobanks, including UK Biobank (UKBB), are generating large-scale sequencing data. An existing method, SAIGE-GENE, performs well when testing variants with minor allele frequency (MAF) ≤ 1%, but inflation is observed in variance component set-based tests when restricting to variants with MAF ≤ 0.1% or 0.01%. Here, we propose SAIGE-GENE+ with greatly improved type I error control and computational efficiency to facilitate rare variant tests in large-scale data. We further show that incorporating multiple MAF cutoffs and functional annotations can improve power and thus uncover new gene–phenotype associations. In the analysis of UKBB whole exome sequencing data for 30 quantitative and 141 binary traits, SAIGE-GENE+ identified 551 gene–phenotype associations.
Diversity and transmission of koala retrovirus: a case study in three captive koala populations
Authors: Joyce Briony A. , Blyton Michaela D. J. , Johnston Stephen D. , Meikle William D. , Vinette Herrin Kimberly , Madden Claire , Young Paul R. , Chappell Keith J. 
Published: September 2022

AbstractKoala retrovirus is a recently endogenized retrovirus associated with the onset of neoplasia and infectious disease in koalas. There are currently twelve described KoRV subtypes (KoRV-A to I, K–M), most of which were identified through recently implemented deep sequencing methods which reveal an animals’ overall KoRV profile. This approach has primarily been carried out on wild koala populations around Australia, with few investigations into the whole-population KoRV profile of captive koala colonies to date. This study conducted deep sequencing on 64 captive koalas of known pedigree, housed in three institutions from New South Wales and South-East Queensland, to provide a detailed analysis of KoRV genetic diversity and transmission. The final dataset included 93 unique KoRV sequences and the first detection of KoRV-E within Australian koala populations. Our analysis suggests that exogenous transmission of KoRV-A, B, D, I and K primarily occurs between dam and joey. Detection of KoRV-D in a neonate sample raises the possibility of this transmission occurring in utero. Overall, the prevalence and abundance of KoRV subtypes was found to vary considerably between captive populations, likely due to their different histories of animal acquisition. Together these findings highlight the importance of KoRV profiling for captive koalas, in particular females, who play a primary role in KoRV exogenous transmission.
Characteristics of children of the Microcephaly Epidemic Research Group Pediatric Cohort who developed postnatal microcephaly
Authors: Ramos Regina Coeli Ferreira , de Barros Miranda-Filho Demócrito , Martelli Celina Maria Turchi , de Araújo Thália Velho Barreto , Wanderley Rocha Maria Angela , van der Linden Vanessa , de Carvalho Maria Durce Costa Gomes , Rodrigues Laura Cunha , Montarroyos Ulisses Ramos , de Souza Wayner Vieira , de Albuquerque Maria de Fátima Pessoa Militão , Brickley Elizabeth B. , de Alencar Ximenes Ricardo Arraes 
Published: September 2022

AbstractThe number of studies published on postnatal microcephaly in children with Congenital Zika Syndrome is small, clinical presentations vary and aspects of the evolution of these children remain unclarified. The present case series examined clinical characteristics and assessed the growth velocity of the head circumference, weight and height Z-scores in 23 children who developed postnatal microcephaly during follow-up in the Microcephaly Epidemic Research Group Pediatric Cohort. To estimate the change in the head circumference, weight and height Z-scores over time and compare the mean difference between sexes, we used multilevel mixed-effects linear regressions with child-specific random effects. Among these children, 60.9% (n = 14/23) presented with craniofacial disproportion, 60.9% (n = 14/23) with strabismus, 47.8% (n = 11/23) with early onset seizures, 47.8% (n = 11/23) with dysphagia and 43.5% (n = 10/23) with arthrogryposis. Of the 82.7% (n = 19/23) children who underwent neuroimaging, 78.9% (n = 15/19) presented with alterations in the central nervous system. Monthly growth velocity, expressed in Z-scores, of the head circumference was − 0.098 (95% CI % − 0.117 to − 0.080), of weight was: − 0.010 (95%-CI − 0.033 to 0.014) and of height was: − 0.023 (95%-CI − 0.046 to 0.0001). Postnatal microcephaly occurred mainly in children who had already presented with signs of severe brain damage at birth; there was variability in weight and height development, with no set pattern.
Correlating gut microbial membership to brown bear health metrics
Authors: Trujillo Sarah M. , McKenney Erin A. , Hilderbrand Grant V. , Mangipane Lindsey S. , Rogers Matthew C. , Joly Kyle , Gustine David D. , Erlenbach Joy A. , Mangipane Buck A. , Lafferty Diana J. R. 
Published: September 2022

AbstractThe internal mechanisms responsible for modulating physiological condition, particularly those performed by the gut microbiome (GMB), remain under-explored in wildlife. However, as latitudinal and seasonal shifts in resource availability occur, the myriad micro-ecosystem services facilitated by the GMB may be especially important to wildlife health and resilience. Here, we use brown bears (Ursus arctos) as an ecological model to quantify the relationship between wildlife body condition metrics that are commonly used to assess individual and population-level health and GMB community composition and structure. To achieve these aims, we subsampled brown bear fecal samples collected during United States National Park Service research activities at three National Parks and Preserves (Katmai, Lake Clark, and Gates of the Arctic) and extracted microbial DNA for 16S rRNA amplicon sequencing and microbial taxonomic classification. We analyzed GMB communities using alpha diversity indices, subsequently using Spearman’s correlation analysis to examine relationships between alpha diversity and brown bear health metrics. We found no differences in GMB composition among bears with differing body conditions, nor any correlations between alpha diversity and body condition. Our results indicate that GMB composition reflects diverse foraging strategies while allowing brown bears to achieve similar body condition outcomes.
Hereditary E200K mutation within the prion protein gene alters human iPSC derived cardiomyocyte function
Authors: Wood Aleksandar R. , Foliaki Simote T. , Groveman Bradley R. , Walters Ryan O. , Williams Katie , Yuan Jue , Zou Wen-Quan , Haigh Cathryn L. 
Published: September 2022

AbstractCardiomyopathy is a co-morbidity of some prion diseases including genetic disease caused by mutations within the PrP gene (PRNP). Although the cellular prion protein (PrP) has been shown to protect against cardiotoxicity caused by oxidative stress, it is unclear if the cardiomyopathy is directly linked to PrP dysfunction. We differentiated cardiomyocyte cultures from donor human induced pluripotent stem cells and found a direct influence of the PRNP E200K mutation on cellular function. The PRNP E200K cardiomyocytes showed abnormal function evident in the irregularity of the rapid repolarization; a phenotype comparable with the dysfunction reported in Down Syndrome cardiomyocytes. PRNP E200K cardiomyocyte cultures also showed increased mitochondrial superoxide accompanied by increased mitochondrial membrane potential and dysfunction. To confirm that the changes were due to the E200K mutation, CRISPR-Cas9 engineering was used to correct the E200K carrier cells and insert the E200K mutation into control cells. The isotype matched cardiomyocytes showed that the lysine expressing allele does directly influence electrophysiology and mitochondrial function but some differences in severity were apparent between donor lines. Our results demonstrate that cardiomyopathy in hereditary prion disease may be directly linked to PrP dysfunction.
Massive annotation of bacterial l-asparaginases reveals their puzzling distribution and frequent gene transfer events
Authors: Zielezinski Andrzej , Loch Joanna I. , Karlowski Wojciech M. , Jaskolski Mariusz 
Published: September 2022

Abstractl-Asparaginases, which convert l-asparagine to l-aspartate and ammonia, come in five types, AI-AV. Some bacterial type AII enzymes are a key element in the treatment of acute lymphoblastic leukemia in children, but new l-asparaginases with better therapeutic properties are urgently needed. Here, we search publicly available bacterial genomes to annotate l-asparaginase proteins belonging to the five known types. We characterize taxonomic, phylogenetic, and genomic patterns of l-asparaginase occurrences pointing to frequent horizontal gene transfer (HGT) events, also occurring multiple times in the same recipient species. We show that the reference AV gene, encoding a protein originally found and structurally studied in Rhizobium etli, was acquired via HGT from Burkholderia. We also describe the sequence variability of the five l-asparaginase types and map the conservation levels on the experimental or predicted structures of the reference enzymes, finding the most conserved residues in the protein core near the active site, and the most variable ones on the protein surface. Additionally, we highlight the most common sequence features of bacterial AII proteins that may aid in selecting therapeutic l-asparaginases. Finally, we point to taxonomic units of bacteria that do not contain recognizable sequences of any of the known l-asparaginase types, implying that those microorganisms most likely contain new, as yet unknown types of l-asparaginases. Such novel enzymes, when properly identified and characterized, could hold promise as antileukemic drugs.
Plastomes of limestone karst gesneriad genera Petrocodon and Primulina, and the comparative plastid phylogenomics of Gesneriaceae
Authors: Hsieh Chia-Lun , Xu Wei-Bin , Chung Kuo-Fang 
Published: September 2022

AbstractPetrocodon and Primulina are two characteristic genera of Gesneriaceae that exhibit remarkable species and floral diversity, and high endemism across the Sino-Vietnamese Limestone Karsts. To better understand the evolution of limestone gesneriad plastomes, we report nine complete plastomes of seven Primulina and two Petrocodon which have never been assembled before. The newly generated plastomes range from 152,323 to 153,786 bp in size and display a typical quadripartite structure. To further explore the plastome evolution across Gesneriaceae, we assembled five additional plastomes from public reads data and incorporated 38 complete Gesneriaceae plastomes available online into comparative and phylogenomic analyses. The comparison of 52 Gesneriaceae plastomes reveals that not only Primulina and Petrocodon but all gesneriad genera analyzed are highly conserved in genome size, genome structure, gene contents, IR boundary configurations, and codon usage bias. Additionally, sliding window analyses were implemented across alignments of Primulina and Petrocodon for identifying highly variable regions, providing informative markers for future studies. Meanwhile, the SSRs and long repeats of Gesneriaceae plastomes were characterized, serving as useful data in studying population and repetitive sequence evolutions. The results of plastome phylogenetics represent a preliminary but highly resolved maternal backbone genealogy of Primulina and the Old World subtribes of Gesneriaceae.
Bending analysis of sandwich panel composite with a re-entrant lattice core using zig-zag theory
Authors: Khoshgoftar M. J. , Barkhordari A. , Limuti M. , Buccino F. , Vergani L. , Mirzaali M. J. 
Published: September 2022

AbstractThe sandwich panel structures have been widely used in many industrial applications because of their high mechanical properties. The middle layer of these structures is very important factor in controlling and enhancing their mechanical performance under various loading scenarios. The re-entrant lattice configurations, are prominent candidates that can be used as the middle layer in such sandwich structures because of several reasons namely the simplicity in tuning their elastic (e.g., values of Poisson’s ratio and elastic stiffness) and plastic (e.g., high strength-to-weight ratio) properties by only adjusting the geometrical features of the constituting unit cells. Here, we investigated the response of a three-layered sandwich plate with a re-entrant core lattice under flexural bending using analytical (i.e., zig-zag theory), computational (i.e., finite element) and experimental tests. We also analyzed the effects of different geometrical parameters (e.g., angle, thicknesses, and length to the height ratio of unit cells) of re-entrant lattice structures on the overall mechanical behavior of sandwich structures. We found that the core structures with auxetic behavior (i.e., negative Poisson’s ratio) resulted in a higher bending strength and a minimum out-of-plane shear stress as compared to those with conventional lattices. Our results can pave way in designing advanced engineered sandwich structures with architected core lattices for aerospace and biomedical applications.
Drosophila suzukii preferentially lays eggs on spherical surfaces with a smaller radius
Authors: Akutsu Junichi , Matsuo Takashi 
Published: September 2022

AbstractDrosophila suzukii is an agricultural pest that predominantly harms small fruits, having a serrated ovipositor that is able to pierce the skin of ripening fruits. Its oviposition preference has been studied from various aspects including chemical and physical properties of oviposition substrates. However, its preference for certain shapes or sizes of substrates has not been explored. In this study, we tested the oviposition preference of D. suzukii for artificial oviposition substrates with different surface curvatures using 27 strains recently established from wild populations collected in Japan. We found that D. suzukii laid more eggs on a surface with smaller radii (4.8 and 5.7 mm) compared with larger radii (7.7 and 9.6 mm). We also found that the most preferred radius differed among strains. Notably, the preference was independent of the volume of substrates, suggesting that D. suzukii uses the surface curvature as a cue for its oviposition site selection. These results provide an additional explanation for why D. suzukii preferentially uses small fruits as its oviposition sites.
Carbon clusters on substrate surface for graphene growth- theoretical and experimental approach
Authors: Kaneko Satoru , Tokumasu Takashi , Yasui Manabu , Kurouchi Masahito , Tanaka Satomi , Kato Chihiro , Yasuhara Shigeo , Endo Tamio , Matsuda Akifumi , Yoshimoto Mamoru , Can Musa , Sahoo Sumanta Kumar , Sardar Kripasindhu , Ting Jyh-Ming , Yoshimura Masahiro 
Published: September 2022

AbstractGrowth morphology of carbon clusters deposited on different substrates were investigated by theoretical and experimental approach. For theoretical approach, molecular dynamics was employed to evaluate an adsorptive stability of different size of carbon clusters placed on different substrates. The adsorptive stability was estimated by the difference of total energy of supercell designed as carbon cluster placed on a certain crystal plane of substrate. Among the simulations of this study, carbon cluster flatly settled down on the surface of SrTiO$$_{3}$$

3

(001). The result was experimentally verified with layer by layer growth of graphene by pulsed laser deposition in carbon dioxide atmosphere. The absorptive stability can be useful reference for screening substrate for any target material other than graphene.
Analyzing integrated network of methylation and gene expression profiles in lung squamous cell carcinoma
Authors: Heryanto Yusri Dwi , Katayama Kotoe , Imoto Seiya 
Published: September 2022

AbstractGene expression, DNA methylation, and their organizational relationships are commonly altered in lung squamous cell carcinoma (LUSC). To elucidate these complex interactions, we reconstructed a differentially expressed gene network and a differentially methylated cytosine (DMC) network by partial information decomposition and an inverse correlation algorithm, respectively. Then, we performed graph union to integrate the networks. Community detection and enrichment analysis of the integrated network revealed close interactions between the cell cycle, keratinization, immune system, and xenobiotic metabolism gene sets in LUSC. DMC analysis showed that hypomethylation targeted the gene sets responsible for cell cycle, keratinization, and NRF2 pathways. On the other hand, hypermethylated genes affected circulatory system development, the immune system, extracellular matrix organization, and cilium organization. By centrality measurement, we identified NCAPG2, PSMG3, and FADD as hub genes that were highly connected to other nodes and might play important roles in LUSC gene dysregulation. We also found that the genes with high betweenness centrality are more likely to affect patients’ survival than those with low betweenness centrality. These results showed that the integrated network analysis enabled us to obtain a global view of the interactions and regulations in LUSC.