bluuebunny/crossref_metadata_2025 huggingface dataset:
Small circular interfering RNAs (sciRNAs) as a potent therapeutic platform for gene-silencing
Authors: Jahns Hartmut , Degaonkar Rohan , Podbevsek Peter , Gupta Swati , Bisbe Anna , Aluri Krishna , Szeto John , Kumar Pawan , LeBlanc Sarah , Racie Tim , Brown Christopher R , Castoreno Adam , Guenther Dale C , Jadhav Vasant , Maier Martin A , Plavec Janez , Egli Martin , Manoharan Muthiah , Zlatev Ivan
Published: September 2021

In order to achieve efficient therapeutic post-transcriptional gene-silencing mediated by the RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) must be chemically modified. Several supra-RNA structures, with the potential to stabilize siRNAs metabolically have been evaluated for their ability to induce gene silencing, but all have limitations or have not been explored in therapeutically relevant contexts. Covalently closed circular RNA transcripts are prevalent in eukaryotes and have potential as biomarkers and disease targets, and circular RNA mimics are being explored for use as therapies. Here we report the synthesis and evaluation of small circular interfering RNAs (sciRNAs). To synthesize sciRNAs, a sense strand functionalized with the trivalent N-acetylgalactosamine (GalNAc) ligand and cyclized using ‘click’ chemistry was annealed to an antisense strand. This strategy was used for synthesis of small circles, but could also be used for synthesis of larger circular RNA mimics. We evaluated various sciRNA designs in vitro and in vivo. We observed improved metabolic stability of the sense strand upon circularization and off-target effects were eliminated. The 5′-(E)-vinylphosphonate modification of the antisense strand resulted in GalNAc-sciRNAs that are potent in vivo at therapeutically relevant doses. Physicochemical studies and NMR-based structural analysis, together with molecular modeling studies, shed light on the interactions of this novel class of siRNAs, which have a partial duplex character, with the RNAi machinery.
SPaRTAN, a computational framework for linking cell-surface receptors to transcriptional regulators
Authors: Ma Xiaojun , Somasundaram Ashwin , Qi Zengbiao , Hartman Douglas J , Singh Harinder , Osmanbeyoglu Hatice Ulku
Published: September 2021

The identity and functions of specialized cell types are dependent on the complex interplay between signaling and transcriptional networks. Recently single-cell technologies have been developed that enable simultaneous quantitative analysis of cell-surface receptor expression with transcriptional states. To date, these datasets have not been used to systematically develop cell-context-specific maps of the interface between signaling and transcriptional regulators orchestrating cellular identity and function. We present SPaRTAN (Single-cell Proteomic and RNA based Transcription factor Activity Network), a computational method to link cell-surface receptors to transcription factors (TFs) by exploiting cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) datasets with cis-regulatory information. SPaRTAN is applied to immune cell types in the blood to predict the coupling of signaling receptors with cell context-specific TFs. Selected predictions are validated by prior knowledge and flow cytometry analyses. SPaRTAN is then used to predict the signaling coupled TF states of tumor infiltrating CD8+ T cells in malignant peritoneal and pleural mesotheliomas. SPaRTAN enhances the utility of CITE-seq datasets to uncover TF and cell-surface receptor relationships in diverse cellular states.
ΩqPCR measures telomere length from single-cells in base pair units
Authors: Xiong Fusheng , Frasch Wayne D
Published: September 2021

ΩqPCR determines absolute telomere length in kb units from single cells. Accuracy and precision of ΩqPCR were assessed using 800 bp and 1600 bp synthetic telomeres inserted into plasmids, which were measured to be 819 ± 19.6 and 1590 ± 42.3 bp, respectively. This is the first telomere length measuring method verified in this way. The approach uses Ω-probes, a DNA strand containing sequence information that enables: (i) hybridization with the telomere via the 3′ and 5′ ends that become opposed; (ii) ligation of the hybridized probes to circularize the Ω-probes and (iii) circularized-dependent qPCR due to sequence information for a forward primer, and for a reverse primer binding site, and qPCR hydrolysis probe binding. Read through of the polymerase during qPCR occurs only in circularized Ω-probes, which quantifies their number that is directly proportional to telomere length. When used in concert with information about the cell cycle stage from a single-copy gene, and ploidy, the MTL of single cells measured by ΩqPCR was consistent with that obtained from large sample sizes by TRF.
Deciphering enhancer sequence using thermodynamics-based models and convolutional neural networks
Authors: Dibaeinia Payam , Sinha Saurabh
Published: September 2021

Deciphering the sequence-function relationship encoded in enhancers holds the key to interpreting non-coding variants and understanding mechanisms of transcriptomic variation. Several quantitative models exist for predicting enhancer function and underlying mechanisms; however, there has been no systematic comparison of these models characterizing their relative strengths and shortcomings. Here, we interrogated a rich data set of neuroectodermal enhancers in Drosophila, representing cis- and trans- sources of expression variation, with a suite of biophysical and machine learning models. We performed rigorous comparisons of thermodynamics-based models implementing different mechanisms of activation, repression and cooperativity. Moreover, we developed a convolutional neural network (CNN) model, called CoNSEPT, that learns enhancer ‘grammar’ in an unbiased manner. CoNSEPT is the first general-purpose CNN tool for predicting enhancer function in varying conditions, such as different cell types and experimental conditions, and we show that such complex models can suggest interpretable mechanisms. We found model-based evidence for mechanisms previously established for the studied system, including cooperative activation and short-range repression. The data also favored one hypothesized activation mechanism over another and suggested an intriguing role for a direct, distance-independent repression mechanism. Our modeling shows that while fundamentally different models can yield similar fits to data, they vary in their utility for mechanistic inference. CoNSEPT is freely available at: https://github.com/PayamDiba/CoNSEPT.
Fission yeast Stn1 maintains stability of repetitive DNA at subtelomere and ribosomal DNA regions
Authors: Yamamoto Io , Nakaoka Hidenori , Takikawa Masahiro , Tashiro Sanki , Kanoh Junko , Miyoshi Tomoichiro , Ishikawa Fuyuki
Published: September 2021

Telomere binding protein Stn1 forms the CST (Cdc13/CTC1-STN1-TEN1) complex in budding yeast and mammals. Likewise, fission yeast Stn1 and Ten1 form a complex indispensable for telomere protection. We have previously reported that stn1-1, a high-temperature sensitive mutant, rapidly loses telomere DNA at the restrictive temperature due to frequent failure of replication fork progression at telomeres and subtelomeres, both containing repetitive sequences. It is unclear, however, whether Stn1 is required for maintaining other repetitive DNAs such as ribosomal DNA. In this study, we have demonstrated that stn1-1 cells, even when grown at the permissive temperature, exhibited dynamic rearrangements in the telomere-proximal regions of subtelomere and ribosomal DNA repeats. Furthermore, Rad52 and γH2A accumulation was observed at ribosomal DNA repeats in the stn1-1 mutant. The phenotypes exhibited by the stn1-1 allele were largely suppressed in the absence of Reb1, a replication fork barrier-forming protein, suggesting that Stn1 is involved in the maintenance of the arrested replication forks. Collectively, we propose that Stn1 maintains the stability of repetitive DNAs at subtelomeres and rDNA regions.
scDeepSort: a pre-trained cell-type annotation method for single-cell transcriptomics using deep learning with a weighted graph neural network
Authors: Shao Xin , Yang Haihong , Zhuang Xiang , Liao Jie , Yang Penghui , Cheng Junyun , Lu Xiaoyan , Chen Huajun , Fan Xiaohui
Published: September 2021

Advances in single-cell RNA sequencing (scRNA-seq) have furthered the simultaneous classification of thousands of cells in a single assay based on transcriptome profiling. In most analysis protocols, single-cell type annotation relies on marker genes or RNA-seq profiles, resulting in poor extrapolation. Still, the accurate cell-type annotation for single-cell transcriptomic data remains a great challenge. Here, we introduce scDeepSort (https://github.com/ZJUFanLab/scDeepSort), a pre-trained cell-type annotation tool for single-cell transcriptomics that uses a deep learning model with a weighted graph neural network (GNN). Using human and mouse scRNA-seq data resources, we demonstrate the high performance and robustness of scDeepSort in labeling 764 741 cells involving 56 human and 32 mouse tissues. Significantly, scDeepSort outperformed other known methods in annotating 76 external test datasets, reaching an 83.79% accuracy across 265 489 cells in humans and mice. Moreover, we demonstrate the universality of scDeepSort using more challenging datasets and using references from different scRNA-seq technology. Above all, scDeepSort is the first attempt to annotate cell types of scRNA-seq data with a pre-trained GNN model, which can realize the accurate cell-type annotation without additional references, i.e. markers or RNA-seq profiles.
GTDB: an ongoing census of bacterial and archaeal diversity through a phylogenetically consistent, rank normalized and complete genome-based taxonomy
Authors: Parks Donovan H , Chuvochina Maria , Rinke Christian , Mussig Aaron J , Chaumeil Pierre-Alain , Hugenholtz Philip
Published: September 2021

The Genome Taxonomy Database (GTDB; https://gtdb.ecogenomic.org) provides a phylogenetically consistent and rank normalized genome-based taxonomy for prokaryotic genomes sourced from the NCBI Assembly database. GTDB R06-RS202 spans 254 090 bacterial and 4316 archaeal genomes, a 270% increase since the introduction of the GTDB in November, 2017. These genomes are organized into 45 555 bacterial and 2339 archaeal species clusters which is a 200% increase since the integration of species clusters into the GTDB in June, 2019. Here, we explore prokaryotic diversity from the perspective of the GTDB and highlight the importance of metagenome-assembled genomes in expanding available genomic representation. We also discuss improvements to the GTDB website which allow tracking of taxonomic changes, easy assessment of genome assembly quality, and identification of genomes assembled from type material or used as species representatives. Methodological updates and policy changes made since the inception of the GTDB are then described along with the procedure used to update species clusters in the GTDB. We conclude with a discussion on the use of average nucleotide identities as a pragmatic approach for delineating prokaryotic species.
A small regulatory RNA alters Staphylococcus aureus virulence by titrating RNAIII activity
Authors: Le Huyen Kim Boi , Gonzalez Cintia Daniela , Pascreau Gaëtan , Bordeau Valérie , Cattoir Vincent , Liu Wenfeng , Bouloc Philippe , Felden Brice , Chabelskaya Svetlana
Published: September 2021

Staphylococcus aureus is an opportunistic human and animal pathogen with an arsenal of virulence factors that are tightly regulated during bacterial infection. The latter is achieved through a sophisticated network of regulatory proteins and regulatory RNAs. Here, we describe the involvement of a novel prophage-carried small regulatory S. aureus RNA, SprY, in the control of virulence genes. An MS2-affinity purification assay reveals that SprY forms a complex in vivo with RNAIII, a major regulator of S. aureus virulence genes. SprY binds to the 13th stem-loop of RNAIII, a key functional region involved in the repression of multiple mRNA targets. mRNAs encoding the repressor of toxins Rot and the extracellular complement binding protein Ecb are among the targets whose expression is increased by SprY binding to RNAIII. Moreover, SprY decreases S. aureus hemolytic activity and virulence. Our results indicate that SprY titrates RNAIII activity by targeting a specific stem loop. Thus, we demonstrate that a prophage-encoded sRNA reduces the pathogenicity of S. aureus through RNA sponge activity.
gutMGene: a comprehensive database for target genes of gut microbes and microbial metabolites
Authors: Cheng Liang , Qi Changlu , Yang Haixiu , Lu Minke , Cai Yiting , Fu Tongze , Ren Jialiang , Jin Qu , Zhang Xue
Published: September 2021

gutMGene (http://bio-annotation.cn/gutmgene), a manually curated database, aims at providing a comprehensive resource of target genes of gut microbes and microbial metabolites in humans and mice. Metagenomic sequencing of fecal samples has identified 3.3 × 106 non-redundant microbial genes from up to 1500 different species. One of the contributions of gut microbiota to host biology is the circulating pool of bacterially derived small-molecule metabolites. It has been estimated that 10% of metabolites found in mammalian blood are derived from the gut microbiota, where they can produce systemic effects on the host through activating or inhibiting gene expression. The current version of gutMGene documents 1331 curated relationships between 332 gut microbes, 207 microbial metabolites and 223 genes in humans, and 2349 curated relationships between 209 gut microbes, 149 microbial metabolites and 544 genes in mice. Each entry in the gutMGene contains detailed information on a relationship between gut microbe, microbial metabolite and target gene, a brief description of the relationship, experiment technology and platform, literature reference and so on. gutMGene provides a user-friendly interface to browse and retrieve each entry using gut microbes, disorders and intervention measures. It also offers the option to download all the entries and submit new experimentally validated associations.
PlantGSAD: a comprehensive gene set annotation database for plant species
Authors: Ma Xuelian , Yan Hengyu , Yang Jiaotong , Liu Yue , Li Zhongqiu , Sheng Minghao , Cao Yaxin , Yu Xinyue , Yi Xin , Xu Wenying , Su Zhen
Published: September 2021

With the accumulation of massive data sets from high-throughput experiments and the rapid emergence of new types of omics data, gene sets have become more diverse and essential for the refinement of gene annotation at multidimensional levels. Accordingly, we collected and defined 236 007 gene sets across different categories for 44 plant species in the Plant Gene Set Annotation Database (PlantGSAD). These gene sets were divided into nine main categories covering many functional subcategories, such as trait ontology, co-expression modules, chromatin states, and liquid-liquid phase separation. The annotations from the collected gene sets covered all of the genes in the Brassicaceae species Arabidopsis and Poaceae species Oryza sativa. Several GSEA tools are implemented in PlantGSAD to improve the efficiency of the analysis, including custom SEA for a flexible strategy based on customized annotations, SEACOMPARE for the cross-comparison of SEA results, and integrated visualization features for ontological analysis that intuitively reflects their parent-child relationships. In summary, PlantGSAD provides numerous gene sets for multiple plant species and highly efficient analysis tools. We believe that PlantGSAD will become a multifunctional analysis platform that can be used to predict and elucidate the functions and mechanisms of genes of interest. PlantGSAD is publicly available at http://systemsbiology.cau.edu.cn/PlantGSEAv2/.
scAPAdb: a comprehensive database of alternative polyadenylation at single-cell resolution
Authors: Zhu Sheng , Lian Qiwei , Ye Wenbin , Qin Wei , Wu Zhe , Ji Guoli , Wu Xiaohui
Published: September 2021

Alternative polyadenylation (APA) is a widespread regulatory mechanism of transcript diversification in eukaryotes, which is increasingly recognized as an important layer for eukaryotic gene expression. Recent studies based on single-cell RNA-seq (scRNA-seq) have revealed cell-to-cell heterogeneity in APA usage and APA dynamics across different cell types in various tissues, biological processes and diseases. However, currently available APA databases were all collected from bulk 3′-seq and/or RNA-seq data, and no existing database has provided APA information at single-cell resolution. Here, we present a user-friendly database called scAPAdb (http://www.bmibig.cn/scAPAdb), which provides a comprehensive and manually curated atlas of poly(A) sites, APA events and poly(A) signals at the single-cell level. Currently, scAPAdb collects APA information from > 360 scRNA-seq experiments, covering six species including human, mouse and several other plant species. scAPAdb also provides batch download of data, and users can query the database through a variety of keywords such as gene identifier, gene function and accession number. scAPAdb would be a valuable and extendable resource for the study of cell-to-cell heterogeneity in APA isoform usages and APA-mediated gene regulation at the single-cell level under diverse cell types, tissues and species.
Dual targeting of higher-order DNA structures by azacryptands induces DNA junction-mediated DNA damage in cancer cells
Authors: Zell Joanna , Duskova Katerina , Chouh Leïla , Bossaert Madeleine , Chéron Nicolas , Granzhan Anton , Britton Sébastien , Monchaud David
Published: September 2021

DNA is intrinsically dynamic and folds transiently into alternative higher-order structures such as G-quadruplexes (G4s) and three-way DNA junctions (TWJs). G4s and TWJs can be stabilised by small molecules (ligands) that have high chemotherapeutic potential, either as standalone DNA damaging agents or combined in synthetic lethality strategies. While previous approaches have claimed to use ligands that specifically target either G4s or TWJs, we report here on a new approach in which ligands targeting both TWJs and G4s in vitro demonstrate cellular effects distinct from that of G4 ligands, and attributable to TWJ targeting. The DNA binding modes of these new, dual TWJ-/G4-ligands were studied by a panel of in vitro methods and theoretical simulations, and their cellular properties by extensive cell-based assays. We show here that cytotoxic activity of TWJ-/G4-ligands is mitigated by the DNA damage response (DDR) and DNA topoisomerase 2 (TOP2), making them different from typical G4-ligands, and implying a pivotal role of TWJs in cells. We designed and used a clickable ligand, TrisNP-α, to provide unique insights into the TWJ landscape in cells and its modulation upon co-treatments. This wealth of data was exploited to design an efficient synthetic lethality strategy combining dual ligands with clinically relevant DDR inhibitors.
Nano-sandwich composite by kinetic trapping assembly from protein and nucleic acid
Authors: Chen Shi , Xing Li , Zhang Douglas , Monferrer Alba , Hermann Thomas
Published: September 2021

Design and preparation of layered composite materials alternating between nucleic acids and proteins has been elusive due to limitations in occurrence and geometry of interaction sites in natural biomolecules. We report the design and kinetically controlled stepwise synthesis of a nano-sandwich composite by programmed noncovalent association of protein, DNA and RNA modules. A homo-tetramer protein core was introduced to control the self-assembly and precise positioning of two RNA–DNA hybrid nanotriangles in a co-parallel sandwich arrangement. Kinetically favored self-assembly of the circularly closed nanostructures at the protein was driven by the intrinsic fast folding ability of RNA corner modules which were added to precursor complex of DNA bound to the protein. The 3D architecture of this first synthetic protein–RNA–DNA complex was confirmed by fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures from protein, DNA and RNA components, which expand the design repertoire for bottom-up preparation of layered biomaterials.
Frequency and patterns of ribonucleotide incorporation around autonomously replicating sequences in yeast reveal the division of labor of replicative DNA polymerases
Authors: Xu Penghao , Storici Francesca
Published: September 2021

Ribonucleoside triphosphate (rNTP) incorporation in DNA by DNA polymerases is a frequent phenomenon that results in DNA structural change and genome instability. However, it is unclear whether the rNTP incorporation into DNA follows any specific sequence patterns. We analyzed multiple datasets of ribonucleoside monophosphates (rNMPs) embedded in DNA, generated from three rNMP-sequencing techniques. These rNMP libraries were obtained from Saccharomyces cerevisiae cells expressing wild-type or mutant replicative DNA polymerase and ribonuclease H2 genes. We performed computational analyses of rNMP sites around early and late-firing autonomously replicating sequences (ARSs) of the yeast genome, where leading and lagging DNA synthesis starts bidirectionally. We found the preference of rNTP incorporation on the leading strand in wild-type DNA polymerase yeast cells. The leading/lagging-strand ratio of rNTP incorporation changes dramatically within the first 1,000 nucleotides from ARSs, highlighting the Pol δ - Pol ϵ handoff during early leading-strand synthesis. Furthermore, the pattern of rNTP incorporation is markedly distinct between the leading and lagging strands not only in mutant but also in wild-type polymerase cells. Such specific signatures of Pol δ and Pol ϵ provide a new approach to track the labor of these polymerases.
circMine: a comprehensive database to integrate, analyze and visualize human disease–related circRNA transcriptome
Authors: Zhang Wenliang , Liu Yang , Min Zhuochao , Liang Guodong , Mo Jing , Ju Zhen , Zeng Binghui , Guan Wen , Zhang Yan , Chen Jianliang , Zhang Qianshen , Li Hanguang , Zeng Chunxia , Wei Yanjie , Chan Godfrey Chi-Fung
Published: September 2021

Many circRNA transcriptome data were deposited in public resources, but these data show great heterogeneity. Researchers without bioinformatics skills have difficulty in investigating these invaluable data or their own data. Here, we specifically designed circMine (http://hpcc.siat.ac.cn/circmine and http://www.biomedical-web.com/circmine/) that provides 1 821 448 entries formed by 136 871 circRNAs, 87 diseases and 120 circRNA transcriptome datasets of 1107 samples across 31 human body sites. circMine further provides 13 online analytical functions to comprehensively investigate these datasets to evaluate the clinical and biological significance of circRNA. To improve the data applicability, each dataset was standardized and annotated with relevant clinical information. All of the 13 analytic functions allow users to group samples based on their clinical data and assign different parameters for different analyses, and enable them to perform these analyses using their own circRNA transcriptomes. Moreover, three additional tools were developed in circMine to systematically discover the circRNA–miRNA interaction and circRNA translatability. For example, we systematically discovered five potential translatable circRNAs associated with prostate cancer progression using circMine. In summary, circMine provides user-friendly web interfaces to browse, search, analyze and download data freely, and submit new data for further integration, and it can be an important resource to discover significant circRNA in different diseases.
PncsHub: a platform for annotating and analyzing non-classically secreted proteins in Gram-positive bacteria
Authors: Dai Wei , Li Jiahui , Li Qi , Cai Jiasheng , Su Jianzhong , Stubenrauch Christopher , Wang Jiawei
Published: September 2021

From industry to food to health, bacteria play an important role in all facets of life. Some of the most important bacteria have been purposely engineered to produce commercial quantities of antibiotics and therapeutics, and non-classical secretion systems are at the forefront of these technologies. Unlike the classical Sec or Tat pathways, non-classically secreted proteins share few common characteristics and use much more diverse secretion pathways for protein transport. Systematically categorizing and investigating the non-classically secreted proteins will enable a deeper understanding of their associated secretion mechanisms and provide a landscape of the Gram-positive secretion pathway distribution. We therefore developed PncsHub (https://pncshub.erc.monash.edu/), the first universal platform for comprehensively annotating and analyzing Gram-positive bacterial non-classically secreted proteins. PncsHub catalogs 4,914 non-classically secreted proteins, which are delicately categorized into 8 subtypes (including the ‘unknown’ subtype) and annotated with data compiled from up to 26 resources and visualisation tools. It incorporates state-of-the-art predictors to identify new and homologous non-classically secreted proteins and includes three analytical modules to visualise the relationships between known and putative non-classically secreted proteins. As such, PncsHub aims to provide integrated services for investigating, predicting and identifying non-classically secreted proteins to promote hypothesis-driven laboratory-based experiments.
The function of twister ribozyme variants in non-LTR retrotransposition in Schistosoma mansoni
Authors: Liu Getong , Jiang Hengyi , Sun Wenxia , Zhang Jun , Chen Dongrong , Murchie Alastair I H
Published: September 2021

The twister ribozyme is widely distributed over numerous organisms and is especially abundant in Schistosoma mansoni, but has no confirmed biological function. Of the 17 non-LTR retrotransposons known in S. mansoni, none have thus far been associated with ribozymes. Here we report the identification of novel twister variant (T-variant) ribozymes and their function in S. mansoni non-LTR retrotransposition. We show that T-variant ribozymes are located at the 5′ end of Perere-3 non-LTR retrotransposons in the S. mansoni genome. T-variant ribozymes were demonstrated to be catalytically active in vitro. In reporter constructs, T-variants were shown to cleave in vivo, and cleavage of T-variants was sufficient for the translation of downstream reporter genes. Our analysis shows that the T-variants and Perere-3 are transcribed together. Target site duplications (TSDs); markers of target-primed reverse transcription (TPRT) and footmarks of retrotransposition, are located adjacent to the T-variant cleavage site and suggest that T-variant cleavage has taken place inS. mansoni. Sequence heterogeneity in the TSDs indicates that Perere-3 retrotransposition is not site-specific. The TSD sequences contribute to the 5′ end of the terminal ribozyme helix (P1 stem). Based on these results we conclude that T-variants have a functional role in Perere-3 retrotransposition.
Genomic impact of stress-induced transposable element mobility in Arabidopsis
Authors: Roquis David , Robertson Marta , Yu Liang , Thieme Michael , Julkowska Magdalena , Bucher Etienne
Published: September 2021

Transposable elements (TEs) have long been known to be major contributors to plant evolution, adaptation and crop domestication. Stress-induced TE mobilization is of particular interest because it may result in novel gene regulatory pathways responding to stresses and thereby contribute to stress adaptation. Here, we investigated the genomic impacts of stress induced TE mobilization in wild type Arabidopsis plants. We find that the heat-stress responsive ONSEN TE displays an insertion site preference that is associated with specific chromatin states, especially those rich in H2A.Z histone variant and H3K27me3 histone mark. In order to better understand how novel ONSEN insertions affect the plant's response to heat stress, we carried out an in-depth transcriptomic analysis. We find that in addition to simple gene knockouts, ONSEN can produce a plethora of gene expression changes such as: constitutive activation of gene expression, alternative splicing, acquisition of heat-responsiveness, exonisation and genesis of novel non-coding and antisense RNAs. This report shows how the mobilization of a single TE-family can lead to a rapid rise of its copy number increasing the host's genome size and contribute to a broad range of transcriptomic novelty on which natural selection can then act.
Operative Treatment of Severe Scoliosis in Symptomatic Adults: Multicenter Assessment of Outcomes and Complications With Minimum 2-Year Follow-up
Authors: Buell Thomas J , Smith Justin S , Shaffrey Christopher I , Kim Han Jo , Klineberg Eric O , Lafage Virginie , Lafage Renaud , Protopsaltis Themistocles S , Passias Peter G , Mundis Gregory M , Eastlack Robert K , Deviren Vedat , Kelly Michael P , Daniels Alan H , Gum Jeff L , Soroceanu Alex , Hamilton D Kojo , Gupta Munish C , Burton Douglas C , Hostin Richard A , Kebaish Khaled M , Hart Robert A , Schwab Frank J , Bess Shay , Ames Christopher P ,   on behalf of The International Spine Study Group (ISSG)
Published: September 2021

BACKGROUND

Few reports focus on adults with severe scoliosis.

OBJECTIVE

To report surgical outcomes and complications for adults with severe scoliosis.

METHODS

A multicenter, retrospective review was performed on operatively treated adults with severe scoliosis (minimum coronal Cobb: thoracic [TH] ≥ 75°, thoracolumbar [TL] ≥ 50°, lumbar [L] ≥ 50°).

RESULTS

Of 178 consecutive patients, 146 (82%; TH = 8, TL = 88, L = 50) achieved minimum 2-yr follow-up (mean age = 53.9 ± 13.2 yr, 92% women). Operative details included posterior-only (58%), 3-column osteotomy (14%), iliac fixation (72%), and mean posterior fusion = 13.2 ± 3.7 levels. Global coronal alignment (3.8 to 2.8 cm, P = .001) and maximum coronal Cobb improved significantly (P ≤.020): TH (84º to 57º; correction = 32%), TL (67º to 35º; correction = 48%), L (61º to 29º; correction = 53%). Sagittal alignment improved significantly (P < .001), most notably for L: C7-sagittal vertical axis 6.7 to 2.5 cm, pelvic incidence-lumbar lordosis mismatch 18º to 3º. Health-related quality-of-life (HRQL) improved significantly (P < .001), most notably for L: Oswestry Disability Index (44.4 ± 20.5 to 26.1 ± 18.3), Short Form-36 Physical Component Summary (30.2 ± 10.8 to 39.9 ± 9.8), and Scoliosis Research Society-22r Total (2.9 ± 0.7 to 3.8 ± 0.7). Minimal clinically important difference and substantial clinical benefit thresholds were achieved in 36% to 75% and 29% to 51%, respectively. Ninety-four (64%) patients had ≥1 complication (total = 191, 92 minor/99 major, most common = rod fracture [13.0%]). Fifty-seven reoperations were performed in 37 (25.3%) patients, with most common indications deep wound infection (11) and rod fracture (10).

CONCLUSION

Although results demonstrated high rates of complications, operative treatment of adults with severe scoliosis was associated with significant improvements in mean HRQL outcome measures for the study cohort at minimum 2-yr follow-up.
Formation, Growth, or Rupture of De Novo Intracranial Aneurysms: Long-Term Follow-up Study of Subarachnoid Hemorrhage Survivors
Authors: Han Hyun Jin , Lee Woosung , Kim Junhyung , Park Keun Young , Park Sang Kyu , Chung Joonho , Kim Yong Bae
Published: September 2021

BACKGROUND

The survival rate of aneurysmal subarachnoid hemorrhage (aSAH) has gradually increased, leading to more clinical cases of de novo intracranial aneurysms (DNIAs).

OBJECTIVE

To identify the characteristics of patients with DNIA growth or rupture.

METHODS

We included 1601 patients with aSAH treated by clipping from January 1993 to May 2010. According to the inclusion and exclusion criteria, 233 patients had no DNIAs, and 63 patients had 77 DNIAs. We assessed the incidence rate of DNIAs and risk factors for DNIA formation. After dichotomizing the DNIA group into the heed (patients with DNIA rupture or growth) and stable groups (patients without DNIA growth), we assessed the risk factors for DNIA growth or rupture.

RESULTS

The total follow-up period was 4427.9 patient-years. The incidence rate per patient-year was 1.42%. Age ≤50 yr, family history of aneurysm, and multiplicity at initial aSAH were significant risk factors for DNIA formation. Multivariate regression analysis revealed that female sex (odds ratio [OR], 5.566; 95% confidence interval [CI], 1.241-24.952), duration from initial aSAH to DNIA detection <120 mo (OR, 5.043; 95% CI, 1.362-18.668), multiplicity at initial aSAH (OR, 4.859; 95% CI, 1.207-19.563), and maximum DNIA diameter ≥4 mm (OR, 11.104; 95% CI, 2.337-52.772) were significant risk factors for DNIA growth or rupture.

CONCLUSION

DNIAs had a higher incidence rate than expected. Taking into account the presented incidence rate and risk factors, long-term surveillance in aSAH survivors for more than a decade may be worth considering, at least on a case-by-case basis.
Thrombus Histology as It Relates to Mechanical Thrombectomy: A Meta-Analysis and Systematic Review
Authors: Bhambri Ankur , Adapa Arjun Rohit , Liu Yang , Boeckh-Behrens Tobias , Procházka Václav , Hernández-Fernández Francisco , Barbella-Aponte Rosa Angélica , Hashimoto Tetsuya , Savastano Luis E , Gemmete Joseph J , Chaudhary Neeraj , Shih Albert J , Pandey Aditya S
Published: September 2021

BACKGROUND

Appropriate thrombus-device interaction is critical for recanalization. Histology can serve as a proxy for mechanical properties, and thus inform technique selection.

OBJECTIVE

To investigate the value of histologic characterization, we conducted a systematic review and meta-analysis on the relationship between thrombus histology and recanalization, technique, etiology, procedural efficiency, and imaging findings.

METHODS

In this meta-analysis, we identified studies published between March 2010 and March 2020 reporting findings related to the histologic composition of thrombi in large vessel occlusion stroke. Studies with at least 10 patients who underwent mechanical thrombectomy using stent retriever or aspiration were considered. Only studies in which retrieved thrombi were histologically processed were included. Patient-level data were requested when data could not be directly extracted. The primary outcome assessed was the relationship between thrombus histology and angiographic outcome.

RESULTS

A total of 22 studies encompassing 1623 patients met inclusion criteria. Clots associated with good angiographic outcome had higher red blood cell (RBC) content (mean difference [MD] 9.60%, 95% CI 3.85-15.34,P = .008). Thrombi retrieved by aspiration had less fibrin (MD −11.39, 95% CI −22.50 to −0.27,P = .046) than stent-retrieved thrombi. Fibrin/platelet-rich clots were associated with longer procedure times (MD 13.20, 95% CI 1.30-25.10,P = .037). Hyperdense artery sign was associated with higher RBC content (MD 14.17%, 95% CI 3.07-25.27,P = .027). No relationship was found between composition and etiology.

CONCLUSION

RBC-rich thrombi were associated with better recanalization outcomes and shorter procedure times, suggesting that preinterventional compositional characterization may yield important prognostic and therapeutic guidance.
Broadband impedance modulation via non-local acoustic metamaterials
Authors: Zhou Zhiling , Huang Sibo , Li Dongting , Zhu Jie , Li Yong
Published: September 2021

Causality of linear time-invariant systems inherently defines the wave-matter interaction process in wave physics. This principle imposes strict constraints on the interfacial response of materials on various physical platforms. A typical consequence is that a delicate balance has to be struck between the conflicting bandwidth and geometric thickness when constructing a medium with desired impedance, which makes it challenging to realize broadband impedance modulation with compact structures. In pursuit of improvement, the over-damped recipe and the reduced excessive response recipe are creatively presented in this work. As a proof-of-concept demonstration, we construct a metamaterial with intensive mode density that supports strong non-locality over a frequency band from 320 Hz to 6400 Hz. Under the guidelines of the over-damped recipe and the reduced excessive response recipe, the metamaterial realizes impedance matching to air and exhibits broadband near-perfect absorption without evident impedance oscillation and absorption dips in the working frequency band. We further present a dual-functional design capable of frequency-selective absorption and reflection by concentrating the resonance modes in three frequency bands. Our research reveals the significance of over-damped recipe and the strong non-local effect in broadband impedance modulation, which may open up avenues for constructing efficient artificial impedance boundaries for energy absorption and other wave manipulation.
Updated Health and Cost Impacts of Electronic Nicotine Delivery Systems, Using Recent Estimates of Relative Harm for Vaping Compared to Smoking
Authors: Summers Jennifer A , Ait Ouakrim Driss , Wilson Nick , Blakely Tony
Published: September 2021

Background

Measuring population health and costs effects of liberalizing access to electronic nicotine delivery systems (ENDS) is an evolving field with high persisting uncertainty. A critical area of uncertainty for policy-makers are estimates of net harms from ENDS relative to cigarettes, therefore, we model these harms using updated estimates incorporating disease specificity.

Methods

We use updated estimates of relative harm of vaping vs smoking, based upon relevant biomarker studies to model the impact of liberalizing access to ENDS in New Zealand (NZ), relative to a ban (where ENDS are not legally available), in an existing proportional multi-state life-table model of 16 tobacco-related diseases.

Results

This modeling suggests that ENDS liberalization results in an expected gain of 195 000 quality-adjusted life-years (QALYs) over the remainder of the NZ population’s lifespan. There was wide uncertainty in QALYs gained (95% uncertainty interval [UI] = −8000 to 406 000) with a 3.2% probability of net health loss (based upon the number of simulation runs returning positive QALY gains). The average per capita health gain was 0.044 QALYs (equivalent to an extra 16 days of healthy life). Health system cost-savings were expected to be NZ$2.8 billion (US$2.1 billion in 2020 US$; 95%UI: −0.3 to 6.2 billion [2011 NZ$]), with an estimated 3% chance of a net increase in per capita cost.

Conclusions

This updated modeling around liberalizing ENDs in NZ, still suggests likely net health and cost-saving benefits—but of lesser magnitude than previous work and with a small possibility of net harm to population health.

Implications

This study found evidence using updated biomarker studies that ENDS liberalization could result in QALY gains across the New Zealand population lifespan that are also cost-saving to the health system. Governments should include the information from these types of modeling studies in their decision-making around potentially improving access to ENDS for existing smokers, while at the same further reducing access to tobacco.
Fish intake, n-3 fatty acid body status, and risk of cognitive decline: a systematic review and a dose–response meta-analysis of observational and experimental studies
Authors: Kosti Rena I , Kasdagli Maria I , Kyrozis Andreas , Orsini Nicola , Lagiou Pagona , Taiganidou Fani , Naska Androniki
Published: September 2021

Context

Randomized controlled trials (RCTs) testing supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have failed to provide evidence supporting a suggested inverse association between fish intake and dementia risk.

Objective

Dose–response analyses were conducted to evaluate associations between fish intake, all-cause dementia or Alzheimer’s Disease (AD), and the effect of EPA/DHA supplementation on cognitive performance.

Data Sources

PubMed, Scopus and Web of Science databases were searched for original research evaluating either associations between fish intake and dementia or AD, or the impact of EPA and/or DHA supplementation on the risk of cognitive decline.

Data Extraction

Data were collected on study characteristics and methods; number of cases/deaths (for observational studies); categories of exposure; model covariates; risk estimates from the most-adjusted model; type and dosage of supplementation (from RCTs); fatty acid levels in blood; and differences in cognition test results before and after supplementation. Risk of bias was assessed through the ROBINS-E and RoB2.0 tools for observational and experimental studies, respectively.

Data Analysis

Weighted mixed-effects models were applied, allowing for the inclusion of studies with 2 levels of exposure. Based on findings with low/moderate risk of bias, fish intake of up to 2 portions (250 g) per week was associated with a 10% reduction (95% confidence interval [CI]: 0.79, 1.02, Ν = 5) in all-cause dementia and a 30% reduction (95% CI: 0.54, 0.89, Ν = 3) in AD risk. Changes in EPA and DHA body status had a positive impact on participants’ executive functions, but not on their overall cognitive performance.

Conclusion

The protection offered by fish intake against cognitive decline levels off at intakes higher than 2 portions/week and likely relates to the impact of EPA and DHA on the individual’s executive functions, although there remain questions about the mechanisms linking the short- and long-term effects.

Systematic Review Registration

PROSPERO registration no. CRD42019139528.
Dairy matrix: is the whole greater than the sum of the parts?
Authors: Weaver Connie M
Published: September 2021

Dairy foods are a heterogeneous group of products that vary in physical state and structure; profile and amounts of essential nutrients, bioactive ingredients, and other constituents; the extent of alteration of these constituents by processing, whether they are fermented or aged; and addition of constituents during manufacture. The complexity of the dairy matrix is associated with a heterogeneous impact on health outcomes from increased, decreased, or neutral effects for specific dairy products and specific health outcomes. Researchers must become more nuanced and systematic in their study of the role of dairy products in health to develop meaningful dietary recommendations. This review of the evidence for the dairy matrix and health points out the dearth of randomized controlled trials and of mechanistic insights. The variable effects of dairy-product consumption on health suggest possibilities for personalized nutrition advice.
The impact of collagen protein ingestion on musculoskeletal connective tissue remodeling: a narrative review
Authors: Holwerda Andrew M , van Loon Luc J C
Published: September 2021

Collagen is the central structural component of extracellular connective tissue, which provides elastic qualities to tissues. For skeletal muscle, extracellular connective tissue transmits contractile force to the tendons and bones. Connective tissue proteins are in a constant state of remodeling and have been shown to express a high level of plasticity. Dietary-protein ingestion increases muscle protein synthesis rates. High-quality, rapidly digestible proteins are generally considered the preferred protein source to maximally stimulate myofibrillar (contractile) protein synthesis rates. In contrast, recent evidence demonstrates that protein ingestion does not increase muscle connective tissue protein synthesis. The absence of an increase in muscle connective tissue protein synthesis after protein ingestion may be explained by insufficient provision of glycine and/or proline. Dietary collagen contains large amounts of glycine and proline and, therefore, has been proposed to provide the precursors required to facilitate connective tissue protein synthesis. This literature review provides a comprehensive evaluation of the current knowledge on the proposed benefits of dietary collagen consumption to stimulate connective tissue remodeling to improve health and functional performance.
Shrinking capitalism: components of a new political economy paradigm
Authors: Bowles Samuel , Carlin Wendy
Published: September 2021

The climate emergency, rising inequality, and pandemic diffusion have raised the question: for what purpose is capitalism fit? Implementing new policies and institutions to meet these challenges will require a realignment of political forces on a scale similar to that achieved by neoliberal policies and ideas over the past four decades. We suggest that a successful new paradigm must provide the basis of a dynamic and sustainable economy and be constituted by a synergistic set of ethical commitments, economic models, emblematic policies, and a new vernacular economics by which people understand and seek to improve their livelihoods and futures. We illustrate these four components by reference to the classical liberal, Keynesian-social democratic, and neoliberal paradigms. Using an expanded space for policies and institutions that integrates markets, states, and civil society, we propose elements of a new paradigm, including diminished space for capitalism and greater equality not only of economic endowments but also of dignity and voice.
Non-Partisan Advisors in the Minister’s Office—Ghosts in the Core Executive Machine?
Authors: Cole Rose
Published: September 2021

The ‘core executive’ is conceived of as the collection of organisations and procedures that coordinate executive government. Two approaches to core executive studies are: the resource dependency approach, which focusses on how roles interact and resources are utilised; and the functional approach, which focusses on how roles change over time. Both approaches are applied to non-partisan advisors (private secretaries) in ministerial office settings, actors which to date core executive studies have ignored. It reveals the resources that non-partisan advisors apply to contribute to policy coordination and maintain political neutrality; and that their role has changed since the increased presence of partisan advisors in ministers’ offices in the past 20 years. Six distinct roles describe how non-partisan advisors respond to and meet the needs of both minister and public service in the core executive. When compared with political advisory roles, five of the roles appear strongly aligned in function.
Analyses of a datable solar eclipse record in Maya Classic period monumental inscriptions
Authors: Hayakawa Hisashi , Sôma Misturu , Kinsman J Hutch
Published: September 2021

Historical records of total solar eclipses provide vital information for computing the rotation of the Earth and understanding its long-term variations in the time before modern measurements. While eclipses recorded around Eurasia and North Africa for millennia have been subjected to consideration in this context, eclipse records in the American continents have received little attention. In this study, we analysed the solitary observational record for a solar eclipse conducted by the ancient Maya on 790 July 16 in the Julian calendar, recorded on the Stela 3 of Santa Elena Poco Uinic (N16°35′, W91°44′). This stela has an eclipse glyph and is associated with a total solar eclipse. Taking the up-to-date Earth rotation (ΔT) rate into account, our calculations locate this site slightly out of the totality path. The visibility of the total solar eclipse from Santa Elena Poco Uinic would require ΔT to be 4074 s < ΔT < 4873 s. In comparison with the contemporary eclipse records, this yields a short-term increase in ΔT ≥ 800 s between 761 and 790 and a decrease in ΔT ≥ 580 s between 790 and 873. Therefore, the total solar eclipse on 790 July 16 cannot be expected to have been visible from Santa Elena Poco Uinic, unlike what has been previously considered. We conclude that this stela probably records a partial solar eclipse of great magnitude (≈0.946) visible under favourable meteorological conditions or is based on hearsay from the southern coastal area.