bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical autism subscales have common genetic liabilities that are heritable, pleiotropic, and generalizable to the general population
Authors: Thomas Taylor R. , Koomar Tanner , Casten Lucas G. , Tener Ashton J. , Bahl Ethan , Michaelson Jacob J. 
Published: June 2022

AbstractThe complexity of autism’s phenotypic spectra is well-known, yet most genetic research uses case-control status as the target trait. It is undetermined if autistic symptom domain severity underlying this heterogeneity is heritable and pleiotropic with other psychiatric and behavior traits in the same manner as autism case-control status. InN = 6064 autistic children in the SPARK cohort, we investigated the common genetic properties of twelve subscales from three clinical autism instruments measuring autistic traits: the Social Communication Questionnaire (SCQ), the Repetitive Behavior Scale-Revised (RBS-R), and the Developmental Coordination Disorder Questionnaire (DCDQ). Educational attainment polygenic scores (PGS) were significantly negatively correlated with eleven subscales, while ADHD and major depression PGS were positively correlated with ten and eight of the autism subscales, respectively. Loneliness and neuroticism PGS were also positively correlated with many subscales. Significant PGS by sex interactions were found—surprisingly, the autism case-control PGS was negatively correlated in females and had no strong correlation in males. SNP-heritability of the DCDQ subscales ranged from 0.04 to 0.08, RBS-R subscales ranged from 0.09 to 0.24, and SCQ subscales ranged from 0 to 0.12. GWAS in SPARK followed by estimation of polygenic scores (PGS) in the typically-developing ABCD cohort (N = 5285), revealed significant associations of RBS-R subscale PGS with autism-related behavioral traits, with several subscale PGS more strongly correlated than the autism case-control PGS. Overall, our analyses suggest that the clinical autism subscale traits show variability in SNP-heritability, PGS associations, and significant PGS by sex interactions, underscoring the heterogeneity in autistic traits at a genetic level. Furthermore, of the three instruments investigated, the RBS-R shows the greatest evidence of genetic signal in both (1) autistic samples (greater heritability) and (2) general population samples (strongest PGS associations).
Prevalence of Molar-incisor hypomineralization in Iranian children – A systematic review and narrative synthesis
Authors: Afshari Elham , Dehghan Farzaneh , Vakili Mohammad Ali , Abbasi Marzieh 
Published: June 2022

AbstractIntroductionMolar-incisor hypomineralization is a developmental defect of enamel with clinical features vary from demarcated opacities to severe tissue breakdown which calls for considerable preventive and interceptive measures. The aim of this article was to systematically review the literature on the prevalence of MIH in Iran and highlight the condition in Iranian children.Materials and MethodsA systematic search of literature was conducted in Scopus, Pubmed, Ovid, Embase, Web of Science, and Google-Scholar as well as national Iranian database and digital archives of dental schools from the beginning of 2000 to the end of 2021 for published and unpublished studies. Data from cross-sectional, cohort, and case-control studies on prevalence of molar-incisor hypomineralization among 6–13-year-old children was gathered, using the following MeSH terms and keywords and their Persian equivalents: Prevalence, Hypomineralisation, Hypomineralization, MIH, “molar incisor”, “molar-incisor”, “cheese molars”, “Hypomineralised first permanent molars”, “Hypomineralized first permanent molars”, “developmental defects of enamel”, “enamel developmental defects”, Iran*. Methodological quality and the risk of bias of quantitative studies was assessed using a modified version of Newcastle-Ottawa Scale. Due to the considerable clinical and statistical heterogeneity of the included studies, pooling of data through meta-analysis was not possible. Therefore, a descriptive synthesis of data was performed.ResultsFifteen cross-sectional studies with a total number of 12011 participants were included in the systematic review. The prevalence of MIH ranged from 5.1% to 25.6%. All of the included studies were at a moderate risk of bias (NOS of 4-6). The lowest prevalence of MIH was reported in Kerman (5.14%) and the highest in Tehran (25.6%). Substantial methodological, clinical and statistical heterogeneity was observed.ConclusionThis is the first study to systematically review the available literature on MIH prevalence in Iran. However, the present review has some limitations such as limited number of included studies, large heterogeneity of the research, and moderate quality of included studies. Further high-quality research is warranted.
Histone H3K36me2 demethylase KDM2A promotes bladder cancer progression through epigenetically silencing RARRES3
Authors: Lu Bing , Wei Jiatian , Zhou Houhong , Chen Jie , Li Yuqing , Ye Liefu , Zhao Wei , Wu Song 
Published: June 2022

AbstractEpigenetic dysregulation contributes to bladder cancer tumorigenesis. H3K36me2 demethylase KDM2A functions as an important epigenetic regulator of cell fate in many types of tumors. However, its role in bladder cancer remains unknown. Here, we revealed a positive correlation between KDM2A gene copy number gain and upregulation of KDM2A mRNA expression in bladder cancer. Moreover, a super-enhancer (SE) driving KDM2A transcription was found in high-grade bladder cancer, resulting in a significantly higher expression of KDM2A mRNA compared to that in low-grade bladder tumors. KDM2A knockdown (KD) decreased the proliferation, invasion, and spheroid formation of high-grade bladder cancer cells and inhibited tumor growth in mouse xenograft models. Furthermore, we identified RARRES3 as a key KDM2A target gene. KDM2A suppresses RARRES3 expression via demethylation of H3K36me2 in the RARRES3 promoter. Intriguingly, RARRES3 KD attenuated the inhibitory effects of KDM2A depletion on the malignant phenotypes of high-grade bladder cancer cells. The combination of the KDM2A inhibitor IOX1 and the RARRES3 agonist all-trans retinoic acid (ATRA) synergistically inhibited the proliferation of high-grade bladder cancer cells, suggesting that the KDM2A/RARRES3 axis may be a promising therapeutic target for the treatment of high-grade bladder cancer.
Asgard archaea shed light on the evolutionary origins of the eukaryotic ubiquitin-ESCRT machinery
Authors: Hatano Tomoyuki , Palani Saravanan , Papatziamou Dimitra , Salzer Ralf , Souza Diorge P. , Tamarit Daniel , Makwana Mehul , Potter Antonia , Haig Alexandra , Xu Wenjue , Townsend David , Rochester David , Bellini Dom , Hussain Hamdi M. A. , Ettema Thijs J. G. , Löwe Jan , Baum Buzz , Robinson Nicholas P. , Balasubramanian Mohan 
Published: June 2022

AbstractThe ESCRT machinery, comprising of multiple proteins and subcomplexes, is crucial for membrane remodelling in eukaryotic cells, in processes that include ubiquitin-mediated multivesicular body formation, membrane repair, cytokinetic abscission, and virus exit from host cells. This ESCRT system appears to have simpler, ancient origins, since many archaeal species possess homologues of ESCRT-III and Vps4, the components that execute the final membrane scission reaction, where they have been shown to play roles in cytokinesis, extracellular vesicle formation and viral egress. Remarkably, metagenome assemblies of Asgard archaea, the closest known living relatives of eukaryotes, were recently shown to encode homologues of the entire cascade involved in ubiquitin-mediated membrane remodelling, including ubiquitin itself, components of the ESCRT-I and ESCRT-II subcomplexes, and ESCRT-III and Vps4. Here, we explore the phylogeny, structure, and biochemistry of Asgard homologues of the ESCRT machinery and the associated ubiquitylation system. We provide evidence for the ESCRT-I and ESCRT-II subcomplexes being involved in ubiquitin-directed recruitment of ESCRT-III, as it is in eukaryotes. Taken together, our analyses suggest a pre-eukaryotic origin for the ubiquitin-coupled ESCRT system and a likely path of ESCRT evolution via a series of gene duplication and diversification events.
Plasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa
Authors: Silva Joana C. , Dwivedi Ankit , Moser Kara A. , Sissoko Mahamadou S. , Epstein Judith E. , Healy Sara A. , Lyke Kirsten E. , Mordmüller Benjamin , Kremsner Peter G. , Duffy Patrick E. , Murshedkar Tooba , Sim B. Kim Lee , Richie Thomas L. , Hoffman Stephen L. 
Published: June 2022

AbstractControlled human malaria infection (CHMI) has supported Plasmodium falciparum (Pf) malaria vaccine development by providing preliminary estimates of vaccine efficacy (VE). Because CHMIs generally use Pf strains similar to vaccine strains, VE against antigenically heterogeneous Pf in the field has been required to establish VE. We increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African parasite (PfNF54) in our PfSPZ vaccines. Using two regimens to identically immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than VE against CHMI at 24 weeks in the US. To explain this finding, here we quantify differences in the genome, proteome, and predicted CD8 T cell epitopes of PfNF54 relative to 704 Pf isolates from Africa and Pf7G8. We show that Pf7G8 is more distant from PfNF54 than any African isolates tested. We propose VE against Pf7G8 CHMI for providing pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from the Pf vaccine strain makes it a stringent surrogate for Pf parasites in Africa.
High throughput, label-free isolation of circulating tumor cell clusters in meshed microwells
Authors: Boya Mert , Ozkaya-Ahmadov Tevhide , Swain Brandi E. , Chu Chia-Heng , Asmare Norh , Civelekoglu Ozgun , Liu Ruxiu , Lee Dohwan , Tobia Sherry , Biliya Shweta , McDonald L. DeEtte , Nazha Bassel , Kucuk Omer , Sanda Martin G. , Benigno Benedict B. , Moreno Carlos S. , Bilen Mehmet A. , McDonald John F. , Sarioglu A. Fatih 
Published: June 2022

AbstractExtremely rare circulating tumor cell (CTC) clusters are both increasingly appreciated as highly metastatic precursors and virtually unexplored. Technologies are primarily designed to detect single CTCs and often fail to account for the fragility of clusters or to leverage cluster-specific markers for higher sensitivity. Meanwhile, the few technologies targeting CTC clusters lack scalability. Here, we introduce the Cluster-Wells, which combines the speed and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips. The >100,000 microwells in the Cluster-Wells physically arrest CTC clusters in unprocessed whole blood, gently isolating virtually all clusters at a throughput of >25 mL/h, and allow viable clusters to be retrieved from the device. Using the Cluster-Wells, we isolated CTC clusters ranging from 2 to 100+ cells from prostate and ovarian cancer patients and analyzed a subset using RNA sequencing. Routine isolation of CTC clusters will democratize research on their utility in managing cancer.
Cellulose photonic pigments
Authors: Parker Richard M. , Zhao Tianheng H. , Frka-Petesic Bruno , Vignolini Silvia 
Published: June 2022

AbstractWhen pursuing sustainable approaches to fabricate photonic structures, nature can be used as a source of inspiration for both the nanoarchitecture and the constituent materials. Although several biomaterials have been promised as suitable candidates for photonic materials and pigments, their fabrication processes have been limited to the small to medium-scale production of films. Here, by employing a substrate-free process, structurally coloured microparticles are produced via the confined self-assembly of a cholesteric cellulose nanocrystal (CNC) suspension within emulsified microdroplets. Upon drying, the droplets undergo multiple buckling events, which allow for greater contraction of the nanostructure than predicted for a spherical geometry. This buckling, combined with a solvent or thermal post-treatment, enables the production of dispersions of vibrant red, green, and blue cellulose photonic pigments. The hierarchical structure of these pigments enables the deposition of coatings with angular independent colour, offering a consistent visual appearance across a wide range of viewing angles.
A proteogenomic signature of age-related macular degeneration in blood
Authors: Emilsson Valur , Gudmundsson Elias F. , Jonmundsson Thorarinn , Jonsson Brynjolfur G. , Twarog Michael , Gudmundsdottir Valborg , Li Zhiguang , Finkel Nancy , Poor Stephen , Liu Xin , Esterberg Robert , Zhang Yiyun , Jose Sandra , Huang Chia-Ling , Liao Sha-Mei , Loureiro Joseph , Zhang Qin , Grosskreutz Cynthia L. , Nguyen Andrew A. , Huang Qian , Leehy Barrett , Pitts Rebecca , Aspelund Thor , Lamb John R. , Jonasson Fridbert , Launer Lenore J. , Cotch Mary Frances , Jennings Lori L. , Gudnason Vilmundur , Walshe Tony E. 
Published: June 2022

AbstractAge-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.
Defect engineering of layered double hydroxide nanosheets as inorganic photosensitizers for NIR-III photodynamic cancer therapy
Authors: Shen Weicheng , Hu Tingting , Liu Xueyan , Zha Jiajia , Meng Fanqi , Wu Zhikang , Cui Zhuolin , Yang Yu , Li Hai , Zhang Qinghua , Gu Lin , Liang Ruizheng , Tan Chaoliang 
Published: June 2022

AbstractAlthough two-dimensional (2D) layered double hydroxides (LDHs) have been widely used as efficient nanoagents for biological diagnosis and treatment, they have been found to be inert as photosensitizers (PSs) for photodynamic therapy (PDT). Herein, we report the defect engineering of ultrathin 2D CoMo-LDH and NiMo-LDH nanosheets as highly active inorganic PSs for PDT in the third near-infrared (NIR-III) window. Hydrothermal-synthesized 2D CoMo-LDH and NiMo-LDH nanosheets are etched via a simple acid treatment to obtain defect-rich CoMo-LDH and NiMo-LDH nanosheets. Importantly, the defect-rich CoMo-LDH nanosheets exhibit much higher activity (~97 times) for generation of reactive oxygen species than that of the pristine CoMo-LDH nanosheets under a NIR-III 1567 nm laser irradiation. Therefore, after modification with polyethylene glycol, the defect-rich CoMo-LDH nanosheets can be used as an efficient inorganic PS for PDT to efficiently induce cancer cells apoptosis in vitro and eradicate tumors in vivo under 1567 nm laser irradiation.
Compact IF2 allows initiator tRNA accommodation into the P site and gates the ribosome to elongation
Authors: Basu Ritwika S. , Sherman Michael B. , Gagnon Matthieu G. 
Published: June 2022

AbstractDuring translation initiation, initiation factor 2 (IF2) holds initiator transfer RNA (fMet-tRNAifMet) in a specific orientation in the peptidyl (P) site of the ribosome. Upon subunit joining IF2 hydrolyzes GTP and, concomitant with inorganic phosphate (Pi) release, changes conformation facilitating fMet-tRNAifMet accommodation into the P site and transition of the 70 S ribosome initiation complex (70S-IC) to an elongation-competent ribosome. The mechanism by which IF2 separates from initiator tRNA at the end of translation initiation remains elusive. Here, we report cryo-electron microscopy (cryo-EM) structures of the 70S-IC from Pseudomonas aeruginosa bound to compact IF2-GDP and initiator tRNA. Relative to GTP-bound IF2, rotation of the switch 2 α-helix in the G-domain bound to GDP unlocks a cascade of large-domain movements in IF2 that propagate to the distal tRNA-binding domain C2. The C2-domain relocates 35 angstroms away from tRNA, explaining how IF2 makes way for fMet-tRNAifMet accommodation into the P site. Our findings provide the basis by which IF2 gates the ribosome to the elongation phase.
Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction
Authors: Zijlmans Dick W. , Talon Irene , Verhelst Sigrid , Bendall Adam , Van Nerum Karlien , Javali Alok , Malcolm Andrew A. , van Knippenberg Sam S. F. A. , Biggins Laura , To San Kit , Janiszewski Adrian , Admiraal Danielle , Knops Ruth , Corthout Nikky , Balaton Bradley P. , Georgolopoulos Grigorios , Panda Amitesh , Bhanu Natarajan V. , Collier Amanda J. , Fabian Charlene , Allsop Ryan N. , Chappell Joel , Pham Thi Xuan Ai , Oberhuemer Michael , Ertekin Cankat , Vanheer Lotte , Athanasouli Paraskevi , Lluis Frederic , Deforce Dieter , Jansen Joop H. , Garcia Benjamin A. , Vermeulen Michiel , Rivron Nicolas , Dhaenens Maarten , Marks Hendrik , Rugg-Gunn Peter J. , Pasque Vincent 
Published: June 2022

AbstractHuman naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stem cells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition of PRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
Lower oceanic crust formed by in situ melt crystallization revealed by seismic layering
Authors: Guo Peng , Singh Satish C. , Vaddineni Venkata A. , Grevemeyer Ingo , Saygin Erdinc 
Published: June 2022

AbstractOceanic crust forms at mid-ocean spreading centres through a combination of magmatic and tectonic processes, with the magmatic processes creating two distinct layers: the upper and the lower crust. While the upper crust is known to form from lava flows and basaltic dykes based on geophysical and drilling results, the formation of the gabbroic lower crust is still debated. Here we perform a full waveform inversion of wide-angle seismic data from relatively young (7–12-Myr-old) crust formed at the slow-spreading Mid-Atlantic Ridge. The seismic velocity model reveals alternating, 400–500 m thick, high- and low-velocity layers with ±200 m s−1 velocity variations, below ~2 km from the oceanic basement. The uppermost low-velocity layer is consistent with hydrothermal alteration, defining the base of extensive hydrothermal circulation near the ridge axis. The underlying layering supports that the lower crust is formed through the intrusion of melt as sills at different depths, which cool and crystallize in situ. The layering extends up to 5–15 km distance along the seismic profile, covering 300,000–800,000 years, suggesting that this form of lower crustal accretion is a stable process.
A database of anti-coronavirus peptides
Authors: Zhang Qianyue , Chen Xue , Li Bowen , Lu Chunying , Yang Shanshan , Long Jinjin , Chen Heng , Huang Jian , He Bifang 
Published: June 2022

AbstractSince 2019, the novel coronavirus (SARS-COV-2) disease (COVID-19) has caused a worldwide epidemic. Anti-coronavirus peptides (ACovPs), a type of antimicrobial peptides (AMPs), have demonstrated excellent inhibitory effects on coronaviruses. However, state-of-the-art AMP databases contain only a small number of ACovPs. Additionally, the fields of these databases are not uniform, and the units or evaluation standards of the same field are inconsistent. Most of these databases have not included the target domains of ACovPs and description of in vitro and in vivo assays to measure the inhibitory effects of ACovPs. Here, we present a database focused on ACovPs (ACovPepDB), which contains comprehensive and precise ACovPs information of 518 entries with 214 unique ACovPs manually collected from public databases and published peer-reviewed articles. We believe that ACovPepDB is of great significance for facilitating the development of new peptides and improving treatment for coronavirus infection. The database will become a portal for ACovPs and guide and help researchers perform further studies. The ACovPepDB is available at http://i.uestc.edu.cn/ACovPepDB/.
A digital assay for programmed death-ligand 1 (22C3) quantification combined with immune cell recognition algorithms in non-small cell lung cancer
Authors: Paces Will , Ergon Elliott , Bueche Elizabeth , Young G. Dave , Adisetiyo Vitria , Luengo Cris , James Meredith , Caldwell Charles , Miller Dannah , Wambaugh Morgan , Metcalf Geoffrey , Gianani Roberto 
Published: June 2022

AbstractPD-L1 (22C3) checkpoint inhibitor therapy represents a mainstay of modern cancer immunotherapy for non-small cell lung cancer (NSCLC). In vitro diagnostic (IVD) PD-L1 antibody staining is widely used to predict clinical intervention efficacy. However, pathologist interpretation of this assay is cumbersome and variable, resulting in poor positive predictive value concerning patient therapy response. To address this, we developed a digital assay (DA) termed Tissue Insight (TI) 22C3 NSCLC, for the quantification of PD-L1 in NSCLC tissues, including digital recognition of macrophages and lymphocytes. We completed clinical validation of this digital image analysis solution in 66 NSCLC patient samples, followed by concordance studies (comparison of PD-L1 manual and digital scores) in an additional 99 patient samples. We then combined this DA with three distinct immune cell recognition algorithms for detecting tissue macrophages, alveolar macrophages, and lymphocytes to aid in sample interpretation. Our PD-L1 (22C3) DA was successfully validated and had a scoring agreement (digital to manual) higher than the inter-pathologist scoring. Furthermore, the number of algorithm-identified immune cells showed significant correlation when compared with those identified by immunohistochemistry in serial sections stained by double immunofluorescence. Here, we demonstrated that TI 22C3 NSCLC DA yields comparable results to pathologist interpretation while eliminating the intra- and inter-pathologist variability associated with manual scoring while providing characterization of the immune microenvironment, which can aid in clinical treatment decisions.