bluuebunny/crossref_metadata_2025 huggingface dataset:
PSI-A-10 Correlations of NR3C1 Gene Expression with Pork Quality and Carcass Characteristics
Authors: Schmidt Grace E , Luttman Andrea M , Steibel Juan P , Raney Nancy E , Ernst Catherine W
Published: October 2023

Genetic control of carcass and meat quality traits is of great interest to the pork industry, and Hypothalamic-Pituitary-Adrenal (HPA) activation has been reported to have an inverse relationship with lean carcass growth traits in swine. The objective of this study was to determine if transcript abundance of the glucocorticoid receptor (NR3C1) in liver is associated with carcass trait variation. The liver is a key player in energy partitioning towards muscle or adipose accretion, and hepatic glucocorticoid receptors that bind cortisol are known to play a role in glucose metabolism. We hypothesized that NR3C1 expression levels are associated with differences in pork quality and carcass traits. We collected liver tissue from 18 gilts at slaughter (avg. BW =127 kg, age at slaughter = 164 d). Additionally, we collected measurements of carcass traits including dressing percentage, loin muscle area, 10th-rib backfat depth, subjective color and marbling scores, Minolta Colorimeter measures of L*, a*, b*, 45-min and ultimate pH, and driploss (Table 1). We extracted RNA from liver samples using a Qiagen miRNeasy kit and performed qRT-PCR using a TaqMan assay to quantify NR3C1 transcript abundance, with ACTB and HPRT1 as reference genes. Pearson correlation analysis was conducted between the carcass traits and NR3C1 expression. While liver NR3C1 transcript abundance was not significantly correlated with a majority of these traits, it was found to have a significant positive correlation with dressing percentage (r = 0.606, t = 3.05, P = 0.008). In conclusion, transcript abundance of NR3C1 in liver does not appear have a relationship with carcass merit and meat quality, but does have a positive relationship with dressing percentage. Further investigation into tissue-specific expression of NR3C1 may reveal the molecular mechanisms underlying the reported associations between HPA activation and differences in pork quality and carcass traits.
The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm
Authors: Hamdorf Matthias , Imhof Thomas , Bailey-Elkin Ben , Betz Janina , Theobald Sebastian J , Simonis Alexander , Di Cristanziano Veronica , Gieselmann Lutz , Dewald Felix , Lehmann Clara , Augustin Max , Klein Florian , Alejandre Alcazar Miguel A , Rongisch Robert , Fabri Mario , Rybniker Jan , Goebel Heike , Stetefeld Jörg , Brachvogel Bent , Cursiefen Claus , Koch Manuel , Bock Felix
Published: October 2023

The novel coronavirus pandemic, first reported in December 2019, was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells, which can elicit acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread inflammation, the so-called cytokine storm. In response to viral infections, monocytes are recruited into the lung and subsequently differentiate into dendritic cells (DCs). DCs are critical players in the development of acute lung inflammation that causes ARDS. Here, we focus on the interaction of a specific SARS-CoV-2 open reading frame protein, ORF8, with DCs. We show that ORF8 binds to DCs, causes pre-maturation of differentiating DCs, and induces the secretion of multiple proinflammatory cytokines by these cells. In addition, we identified DC-SIGN as a possible interaction partner of ORF8 on DCs. Blockade of ORF8 leads to reduced production of IL-1β, IL-6, IL-12p70, TNF-α, MCP-1 (also named CCL2), and IL-10 by DCs. Therefore, a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.
Feeding and reproductive parameters of adult female Ixodes scapularis (Acari: Ixodidae) and Amblyomma americanum parasitizing white-tailed deer (Odocoileus virginianus)
Authors: Baker Alec S , Persinger Kelly A , Olafson Pia U , Mulenga Albert O , Johnson Tammi L
Published: October 2023

White-tailed deer Odocoileus virginianus (Zimmermann) (Artiodactyla: Cervidae) are the main host for adult Ixodes scapularis Say (Acari: Ixodidae) (blacklegged tick) and all stages of Amblyomma americanum Linnaeus (Acari: Ixodidae) (lone star tick). However, literature describing the feeding and reproductive parameters of these tick species when feeding on this host is limited. We experimentally infested white-tailed deer with adult pairs of either I. scapularis or A. americanum to improve our understanding of these tick–host relationships. Our study used tick-naïve white-tailed deer and restricted host grooming throughout the infestation. For I. scapularis, the days to repletion (mean ± SE, 6.04 ± 0.07), engorgement weight of replete females (0.20 ± 0.0032 g), duration of oviposition (32 ± 0.45 d), egg mass weight (0.10 ± 0.0027 g), and number of eggs laid per tick (1,803.00 ± 49.00) were recorded. Data from A. americanum were also recorded, including days to repletion (11.00 ± 0.063), engorgement weight of replete females (0.63 ± 0.025 g), duration of oviposition (37.00 ± 1.30 d), egg mass weight (0.34 ± 0.017 g), and number of eggs laid per tick (5,873.00 ± 291.00). These biological parameter data could be used as variables in models (e.g., LYMESIM 2.0) to determine how white-tailed deer influence I. scapularis and A. americanum populations in nature, and to evaluate the protective efficacy of tick-antigen-based antitick vaccines.
A numerical investigation of microtube length effect on convective boiling
Authors: Hsu Hua-Yi , Lin Yu-Chen , Chen Zong-You , Wang Ying , Li Cheng-En , Pai Shong-Han , Lin Chia-Wei
Published: October 2023

The microtube length significantly influences the convective boiling process and associated heat transfer characteristics. Other than high heat transfer, low pressure drop is also desired to improve the energy efficiency of the pumping system. This work numerically investigates the microtube length effect on heat transfer and pressure drops of convective boiling with the volume of fluid (VOF) method. The simulation results of vapor formation, heat transfer coefficient, and pressure drop are shown with different microtube lengths L = 2–20 mm. The onset of boiling is around 2 mm away from the mass flux inlet. The subcooled boiling regime can be observed between 2 and 10 mm. Three distinct regimes, liquid single-phase flow, bubbly flow, and plug flow, are shown in the longer microtubes (L = 15 mm and 20 mm). It is found that shorter microtubes can lead to less bubble formation with higher heat transfer and lower pressure drop. The average heat transfer coefficient can achieve 2432 W/(m2K) with a lower quasi-steady total pressure drop Δp|total of 32.8 Pa inside a 2-mm-long microtube. This work offers a detailed study of the impact of microtube length on convective boiling, along with pertinent physical insights. It may serve as an indicator for future microscale heat transfer application designs.
Homeostatic evidence of management-induced phosphorus decoupling from soil microbial carbon and nitrogen metabolism
Authors: Zhang Lihua , Jia Lizhi , He Liyuan , Lipson David A , Wang Yihui , Wang Shunzhong , Xu Xiaofeng
Published: October 2023

The theory of microbial stoichiometry can predict the proportional coupling of microbial assimilation of carbon (C), nitrogen (N), and phosphorus (P). The proportional coupling is quantified by the homeostasis value (H). Covariation of H values for C, N, and P indicates that microbial C, N, and P assimilation are coupled. Here, we used a global dataset to investigate the spatiotemporal dynamics of H values of microbial C, N, and P across biomes. We found that land use and management led to the decoupling of P from C and N metabolism over time and across space. Results from structural equation modeling revealed that edaphic factors dominate the microbial homeostasis of P, while soil elemental concentrations dominate the homeostasis of C and N. This result was further confirmed using the contrasting factors on microbial P vs. microbial C and N derived from a machine-learning algorithm. Overall, our study highlights the impacts of management on shifting microbial roles in nutrient cycling.
Styrax (Liquidambar orientalis Mill.) promotes mitochondrial function and reduces cardiac damage following myocardial ischemic injury: the role of the AMPK-PGC1α signaling pathway
Authors: Mu Fei , Zhao Jiaxin , Zhao Meina , Lin Rui , Liu Kedi , Zhao Shi , Tao Xingru , Li Weihong , Dai Qi , Xi Miaomiao , Tang Haifeng , Wang Jingwen
Published: October 2023

Objectives

To explore the effect of extract of Styrax (ES) on myocardial ischemic injury and its molecular mechanism, indirectly providing a theoretical basis for the development of ES.

Methods

In order to assess the impact of ES treatment on ischemic heart disease, both a left anterior descending ligation-induced myocardial infarction (MI) model and an ischemia/hypoxia (I/H)-induced H9c2 cell injury model have been constructed. Specifically, Sprague–Dawley rats were randomly assigned to the following groups (n = 8) and administered intragastrically once a day for seven consecutive days: Sham group, MI group, ES-L (0.2 g/kg) group, ES-M (0.4 g/kg) group, ES-H (0.8 g/kg) group, and trimetazidine (TMZ, 0.02 g/kg) group. The cardiac functions and biochemical assessment of rats were detected. Then, we validated experimentally the targets and mechanism of ES on these pathological processes in I/H-induced H9c2 cell injury model.

Key findings

These results showed that different doses of ES (0.2 g/kg, 0.4 g/kg, 0.8 g/kg, intragastric) significantly improved myocardial structure and function when compared to the MI group. The results of 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin-eosin, and masson staining indicated that ES could significantly reduce infarct size, inhibit myocardium apoptosis, and decrease myocardial fibrosis. Moreover, ES distinctly suppressed the serum levels of lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and creatine kinase-MB (CK-MB), alleviated myocardial mitochondrial morphology, and stimulated adenosine triphosphate (ATP) production, increased the level of succinate dehydrogenase (SDH), complex I and complex V activity. Different doses of ES (5 μg/ml, 10 μg/ml, 20 μg/ml) also improved cardiomyocyte morphology and decreased the apoptosis rate in H9c2 cells that had been exposed to I/H. Furthermore, the results of western blotting and qRT-PCR indicated that ES promoted the expression of proteins and mRNA related to energy metabolism, including phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), peroxisome proliferator activated receptor gamma coactivator 1 alpha (PCG-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM). Mechanically, after the administration of Compound C (dorsomorphin), an AMPK inhibitor, these effects of myocardial protection produced by ES were reversed.

Conclusions

Collectively, these results demonstrated that ES could improve myocardial mitochondrial function and reduce ischemic injury by activating AMPK/PCG-1α signaling pathway, while indicating its potential advantages as a dietary supplement.
A Forty-Year-Old Campaign: Anne Frank’s Diary and the Holocaust Deniers, 1958–1998
Authors: Porat Dina
Published: October 2023

On December 9, 1998, the Dutch court in Amsterdam ruled Anne Frank’s diary to be authentic, and that anyone who cast doubt on its authenticity was breaking the law and would be fined. This article examines the ongoing battle between those who view themselves as charged with the legacy of the diary and the Holocaust deniers; it also examines the methods used by the latter and their possible influence on society. The first half deals with the events leading to the writing of the diary, its publication, theatrical and cinematic adaptations, and examines how the Holocaust deniers came to use those events in their claims. The second half deals with the claims themselves and their development over the years, and the deniers’ attempts to reach the widest possible audience in an attempt to sully the image of one of the central symbols of the Holocaust period, Anne Frank, The Diary of a Young Girl.
Compact binary formation in open star clusters – I. High formation efficiency of Gaia BHs and their multiplicities
Authors: Tanikawa Ataru , Cary Savannah , Shikauchi Minori , Wang Long , Fujii Michiko S
Published: October 2023

Gaia BHs, black hole (BH) binaries discovered from data base of an astrometric telescope Gaia, pose a question to the standard binary evolution model. We have assessed whether Gaia BHs can be formed through dynamical capture in open clusters rather than through isolated binary evolution. We have performed gravitational N-body simulations of 100 open clusters with $10^5 \, \mathrm{M}_\odot$ in total for each metallicity Z = 0.02, 0.01, and 0.005. We have discovered one Gaia BH-like binary escaping from an open cluster, and found that the formation efficiency of Gaia BHs in open clusters ($\sim 10^{-5} \, \mathrm{M}_\odot ^{-1}$) is larger than in isolated binaries ($\sim 10^{-8} \, \mathrm{M}_\odot ^{-1}$) by 3 orders of magnitude. The Gaia BH-like binary is the inner binary of a triple star system. Gaia BHs can have tertiary stars frequently, if they are formed in open clusters. Combining additional N-body simulations with 8000 open clusters with $8 \times 10^6 \, \mathrm{M}_\odot$, we have estimated the number of Gaia BHs in the Milky Way disc to 104–105 (depending on the definitions of Gaia BHs), large enough for the number of Gaia BHs discovered so far. Our results indicate that the discoveries of Gaia BHs do not request the reconstruction of the standard binary evolution model, and that Gaia BHs are a probe for the dynamics of open clusters already evaporated.
MACC: a visual interactive knowledgebase of metabolite-associated cell communications
Authors: Gao Jian , Mo Saifeng , Wang Jun , Zhang Mou , Shi Yao , Zhu Chuhan , Shang Yuxuan , Tang Xinyue , Zhang Shiyue , Wu Xinwen , Xu Xinyan , Wang Yiheng , Li Zihao , Zheng Genhui , Chen Zikun , Wang Qiming , Tang Kailin , Cao Zhiwei
Published: October 2023

Metabolite-associated cell communications play critical roles in maintaining the normal biological function of human through coordinating cells, organs and physiological systems. Though substantial information of MACCs has been continuously reported, no relevant database has become available so far. To address this gap, we here developed the first knowledgebase (MACC), to comprehensively describe human metabolite-associated cell communications through curation of experimental literatures. MACC currently contains: (a) 4206 carefully curated metabolite-associated cell communications pairs involving 244 human endogenous metabolites and reported biological effects in vivo and in vitro; (b) 226 comprehensive cell subtypes and 296 disease states, such as cancers, autoimmune diseases, and pathogenic infections; (c) 4508 metabolite-related enzymes and transporters, involving 542 pathways; (d) an interactive tool with user-friendly interface to visualize networks of multiple metabolite-cell interactions. (e) overall expression landscape of metabolite-associated gene sets derived from over 1500 single-cell expression profiles to infer metabolites variations across different cells in the sample. Also, MACC enables cross-links to well-known databases, such as HMDB, DrugBank, TTD and PubMed etc. In complement to ligand-receptor databases, MACC may give new perspectives of alternative communication between cells via metabolite secretion and adsorption, together with the resulting biological functions. MACC is publicly accessible at: http://macc.badd-cao.net/
CMAUP database update 2024: extended functional and association information of useful plants for biomedical research
Authors: Hou Dongyue , Lin Hanbo , Feng Yuhan , Zhou Kaicheng , Li Xingxiu , Yang Yuan , Wang Shuaiqi , Yang Xue , Wang Jiayu , Zhao Hui , Zhang Xuyao , Fan Jiajun , Lu SongLin , Wang Dan , Zhu Lyuhan , Ju Dianwen , Chen Yu Zong , Zeng Xian
Published: October 2023

Knowledge of the collective activities of individual plants together with the derived clinical effects and targeted disease associations is useful for plant-based biomedical research. To provide the information in complement to the established databases, we introduced a major update of CMAUP database, previously featured in NAR. This update includes (i) human transcriptomic changes overlapping with 1152 targets of 5765 individual plants, covering 74 diseases from 20 027 patient samples; (ii) clinical information for 185 individual plants in 691 clinical trials; (iii) drug development information for 4694 drug-producing plants with metabolites developed into approved or clinical trial drugs; (iv) plant and human disease associations (428 737 associations by target, 220 935 reversion of transcriptomic changes, 764 and 154121 associations by clinical trials of individual plants and plant ingredients); (v) the location of individual plants in the phylogenetic tree for navigating taxonomic neighbors, (vi) DNA barcodes of 3949 plants, (vii) predicted human oral bioavailability of plant ingredients by the established SwissADME and HobPre algorithm, (viii) 21–107% increase of CMAUP data over the previous version to cover 60 222 chemical ingredients, 7865 plants, 758 targets, 1399 diseases, 238 KEGG human pathways, 3013 gene ontologies and 1203 disease ontologies. CMAUP update version is freely accessible at https://bidd.group/CMAUP/index.html.
AnimalMetaOmics: a multi-omics data resources for exploring animal microbial genomes and microbiomes
Authors: Hu Ruirui , Li Fulin , Chen Yifan , Liu Chuyang , Li Jiawei , Ma Zhongchen , Wang Yue , Cui Chaowen , Luo Chengfang , Zhou Ping , Ni Wei , Yang Qing-Yong , Hu Shengwei
Published: October 2023

The Animal Meta-omics landscape database (AnimalMetaOmics, https://yanglab.hzau.edu.cn/animalmetaomics#/) is a comprehensive and freely available resource that includes metagenomic, metatranscriptomic, and metaproteomic data from various non-human animal species and provides abundant information on animal microbiomes, including cluster analysis of microbial cognate genes, functional gene annotations, active microbiota composition, gene expression abundance, and microbial protein identification. In this work, 55 898 microbial genomes were annotated from 581 animal species, including 42 924 bacterial genomes, 12 336 virus genomes, 496 archaea genomes and 142 fungi genomes. Moreover, 321 metatranscriptomic datasets were analyzed from 31 animal species and 326 metaproteomic datasets from four animal species, as well as the pan-genomic dynamics and compositional characteristics of 679 bacterial species and 13 archaea species from animal hosts. Researchers can efficiently access and acquire the information of cross-host microbiota through a user-friendly interface, such as species, genomes, activity levels, expressed protein sequences and functions, and pan-genome composition. These valuable resources provide an important reference for better exploring the classification, functional diversity, biological process diversity and functional genes of animal microbiota.
Mutual promotion of co-condensation of KRAS G-quadruplex and a well-folded protein HMGB1
Authors: Wang Yu , Cao Kaiming , Zong Mingxi , Yuan Siming , Zhang Na , Liu Yangzhong
Published: October 2023

Liquid−liquid phase separation (LLPS) of G-quadruplex (GQ) is involved in many crucial cellular processes, while the quadruplex-folding and their functions are typically modulated by specific DNA-binding proteins. However, the regulatory mechanism of binding proteins, particularly the well-folded proteins, on the LLPS of GQs is largely unknown. Here, we investigated the effect of HMGB1 on the condensation of a G-quadruplex of KRAS promoter (GQKRAS). The results show that these two rigid macro-biomolecules undergo co-condensation through a mutual promotion manner, while neither of them can form LLPS alone. Fluidity measurements confirm that the liquid-like droplets are highly dynamic. HMGB1 facilitates and stabilizes the quadruplex folding of GQKRAS, and this process enhances their co-condensation. The KRAS promoter DNA retains quadruplex folding in the droplets; interference with the GQ-folding disrupts the co-condensation of GQKRAS/HMGB1. Mechanistic studies reveal that electrostatic interaction is a key driving force of the interaction and co-condensation of GQKRAS/HMGB1; meanwhile, the recognition of two macro-biomolecules plays a crucial role in this process. This result indicates that the phase separation of GQs can be modulated by DNA binding proteins, and this process could also be an efficient way to recruit specific DNA binding proteins.
Human HELQ regulates DNA end resection at DNA double-strand breaks and stalled replication forks
Authors: Zhao Yuqin , Hou Kaiping , Li Youhang , Hao Shuailin , Liu Yu , Na Yinan , Li Chao , Cui Jian , Xu Xingzhi , Wu Xiaohua , Wang Hailong
Published: October 2023

Following a DNA double strand break (DSB), several nucleases and helicases coordinate to generate single-stranded DNA (ssDNA) with 3′ free ends, facilitating precise DNA repair by homologous recombination (HR). The same nucleases can act on stalled replication forks, promoting nascent DNA degradation and fork instability. Interestingly, some HR factors, such as CtIP and BRCA1, have opposite regulatory effects on the two processes, promoting end resection at DSB but inhibiting the degradation of nascent DNA on stalled forks. However, the reason why nuclease actions are regulated by different mechanisms in two DNA metabolism is poorly understood. We show that human HELQ acts as a DNA end resection regulator, with opposing activities on DNA end resection at DSBs and on stalled forks as seen for other regulators. Mechanistically, HELQ helicase activity is required for EXO1-mediated DSB end resection, while ssDNA-binding capacity of HELQ is required for its recruitment to stalled forks, facilitating fork protection and preventing chromosome aberrations caused by replication stress. Here, HELQ synergizes with CtIP but not BRCA1 or BRCA2 to protect stalled forks. These findings reveal an unanticipated role of HELQ in regulating DNA end resection at DSB and stalled forks, which is important for maintaining genome stability.
A3D Model Organism Database (A3D-MODB): a database for proteome aggregation predictions in model organisms
Authors: Badaczewska-Dawid Aleksandra E , Kuriata Aleksander , Pintado-Grima Carlos , Garcia-Pardo Javier , Burdukiewicz Michał , Iglesias Valentín , Kmiecik Sebastian , Ventura Salvador
Published: October 2023

Protein aggregation has been associated with aging and different pathologies and represents a bottleneck in the industrial production of biotherapeutics. Numerous past studies performed in Escherichia coli and other model organisms have allowed to dissect the biophysical principles underlying this process. This knowledge fuelled the development of computational tools, such as Aggrescan 3D (A3D) to forecast and re-design protein aggregation. Here, we present the A3D Model Organism Database (A3D-MODB) http://biocomp.chem.uw.edu.pl/A3D2/MODB, a comprehensive resource for the study of structural protein aggregation in the proteomes of 12 key model species spanning distant biological clades. In addition to A3D predictions, this resource incorporates information useful for contextualizing protein aggregation, including membrane protein topology and structural model confidence, as an indirect reporter of protein disorder. The database is openly accessible without any need for registration. We foresee A3D-MOBD evolving into a central hub for conducting comprehensive, multi-species analyses of protein aggregation, fostering the development of protein-based solutions for medical, biotechnological, agricultural and industrial applications.
SPIRE: a Searchable, Planetary-scale mIcrobiome REsource
Authors: Schmidt Thomas S B , Fullam Anthony , Ferretti Pamela , Orakov Askarbek , Maistrenko Oleksandr M , Ruscheweyh Hans-Joachim , Letunic Ivica , Duan Yiqian , Van Rossum Thea , Sunagawa Shinichi , Mende Daniel R , Finn Robert D , Kuhn Michael , Pedro Coelho Luis , Bork Peer
Published: October 2023

Meta’omic data on microbial diversity and function accrue exponentially in public repositories, but derived information is often siloed according to data type, study or sampled microbial environment. Here we present SPIRE, a Searchable Planetary-scale mIcrobiome REsource that integrates various consistently processed metagenome-derived microbial data modalities across habitats, geography and phylogeny. SPIRE encompasses 99 146 metagenomic samples from 739 studies covering a wide array of microbial environments and augmented with manually-curated contextual data. Across a total metagenomic assembly of 16 Tbp, SPIRE comprises 35 billion predicted protein sequences and 1.16 million newly constructed metagenome-assembled genomes (MAGs) of medium or high quality. Beyond mapping to the high-quality genome reference provided by proGenomes3 (http://progenomes.embl.de), these novel MAGs form 92 134 novel species-level clusters, the majority of which are unclassified at species level using current tools. SPIRE enables taxonomic profiling of these species clusters via an updated, custom mOTUs database (https://motu-tool.org/) and includes several layers of functional annotation, as well as crosslinks to several (micro-)biological databases. The resource is accessible, searchable and browsable via http://spire.embl.de.
circRNADisease v2.0: an updated resource for high-quality experimentally supported circRNA-disease associations
Authors: Sun Zhi-Yan , Yang Chang-Lin , Huang Li-Jie , Mo Zong-Chao , Zhang Ke-Nan , Fan Wen-Hua , Wang Kuan-Yu , Wu Fan , Wang Ji-Guang , Meng Fan-Lin , Zhao Zheng , Jiang Tao
Published: October 2023

circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.
HHCDB: a database of human heterochromatin regions
Authors: Wang Hongli , Su Mu , Xing Jie , Zhou Jie , Wang Jinzhang , Chen Long , Dong Haomin , Xue Wenhui , Liu Yubo , Wu Qiong , Zhang Yan
Published: October 2023

Heterochromatin plays essential roles in eukaryotic genomes, such as regulating genes, maintaining genome integrity and silencing repetitive DNA elements. Identifying genome-wide heterochromatin regions is crucial for studying transcriptional regulation. We propose the Human Heterochromatin Chromatin Database (HHCDB) for archiving heterochromatin regions defined by specific or combined histone modifications (H3K27me3, H3K9me2, H3K9me3) according to a unified pipeline. 42 839 743 heterochromatin regions were identified from 578 samples derived from 241 cell-types/cell lines and 92 tissue types. Genomic information is provided in HHCDB, including chromatin location, gene structure, transcripts, distance from transcription start site, neighboring genes, CpG islands, transposable elements, 3D genomic structure and functional annotations. Furthermore, transcriptome data from 73 single cells were analyzed and integrated to explore cell type-specific heterochromatin-related genes. HHCDB affords rich visualization through the UCSC Genome Browser and our self-developed tools. We have also developed a specialized online analysis platform to mine differential heterochromatin regions in cancers. We performed several analyses to explore the function of cancer-specific heterochromatin-related genes, including clinical feature analysis, immune cell infiltration analysis and the construction of drug-target networks. HHCDB is a valuable resource for studying epigenetic regulation, 3D genomics and heterochromatin regulation in development and disease. HHCDB is freely accessible at http://hhcdb.edbc.org/.
Financial Toxicity: Unveiling the Burden of Cancer Care on Patients in Rwanda
Authors: Rubagumya Fidel , Wilson Brooke , Manirakiza Achille , Mutabazi Emmanuel , A. Ndoli Diane , Rudakemwa Emmanuel , Chamberlin Mary D , Hopman Wilma M , Booth Christopher M
Published: October 2023

Introduction

Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda.

Methods

This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country’s cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin’s and non-Hodgkin’s lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics.

Results

239 patients were included; 75% (n = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n = 106/239) of respondents sold property, 29% (n = 70/239) asked for charity from public, family, or friends, and 16% (n = 37/239) took loans with interest to fund cancer treatment.

Conclusion

Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care.
A targeted approach to vaccine hesitancy
Authors: Leston Meredith , de Lusignan Simon , Hobbs F D Richard
Published: October 2023

This short communication makes the case for targeted vaccine research when attempting to counter hesitancy, especially amongst vulnerable or rarefied patient groups. Far from disincentivizing vaccination, the freedom to research and publicize the limitations of these technologies for certain groups and personalizing dosing, pacing, adjuvants, and time-sensitive alternatives in response is essential for optimizing health outcomes while neutralizing the vaccine research landscape itself. Vaccine evangelism only arouses suspicion when it is not tempered by rigorous research into differential vaccine benefit-risk in this way. That said, the long-standing politicization of vaccination—a topic vulnerable to misinterpretation and media sensationalism—along with the commercial incentives associated with universal adoption makes more comparative and critical research difficult to fund and promote in practice. Likewise, a prescriptive approach to vaccination does little to address the issues of vaccine inequality that contribute to both hesitancy and conspiracy globally and will likely prove financially prohibitive in certain markets. These obstacles are not insurmountable, however, provided that comparative research is centrally subsidized, regulations ensure that vaccine development trials explore differentiated outcomes, especially amongst high-risk or rare groups, and findings are used to prioritize global vaccine allocation to those that stand to benefit most from them.
A Fitting Definition of Epistemic Emotions
Authors: Deigan Michael , Piñeros Glasscock Juan S
Published: October 2023

Philosophers and psychologists sometimes categorize emotions like surprise and curiosity as specifically epistemic. Is there some reasonably unified and interesting class of emotions here? If so, what unifies it? This paper proposes and defends an evaluative account of epistemic emotions: What it is to be an epistemic emotion is to have fittingness conditions that distinctively involve some epistemic evaluation. We argue that this view has significant advantages over alternative proposals and is a promising way to identify a limited and interesting class of emotions.
‘I am afraid you will see the stain on my soul’: Direct gaze neural processing in individuals with PTSD after moral injury recall
Authors: Andrews Krysta , Lloyd Chantelle S , Densmore Maria , Kearney Breanne E , Harricharan Sherain , McKinnon Margaret C , Théberge Jean , Jetly Rakesh , Lanius Ruth A
Published: October 2023

Direct eye contact is essential to understanding others’ thoughts and feelings in social interactions. However, those with post-traumatic stress disorder (PTSD) and exposure to moral injury (MI) may exhibit altered theory-of-mind (ToM)/mentalizing processes and experience shame which precludes one’s capacity for direct eye contact. We investigated blood oxygenation level-dependent (BOLD) responses associated with direct vs averted gaze using a virtual reality paradigm in individuals with PTSD (n = 28) relative to healthy controls (n = 18) following recall of a MI vs a neutral memory. Associations between BOLD responses and clinical symptomatology were also assessed. After MI recall, individuals with PTSD showed greater activation in the right temporoparietal junction as compared to controls (T = 4.83; pFDR < 0.001; k = 237) during direct gaze. No significant activation occurred during direct gaze after neutral memory recall. Further, a significant positive correlation was found between feelings of distress and right medial superior frontal gyrus activation in individuals with PTSD (T = 5.03; pFDR = 0.049; k = 123). These findings suggest that direct gaze after MI recall prompts compensatory ToM/mentalizing processing. Implications for future interventions aimed at mitigating the effects of PTSD on social functioning are discussed.
Exercise intensity-dependent lactate elevation in skin interstitial fluid and its long-lasting effect
Authors: Dobashi Shohei , Funabashi Daisuke , Sameshima Kazuki , Tsuruoka Noriko , Matsui Takashi
Published: October 2023

Regular exercise promotes various anti-ageing adaptations in skin tissue. Although the underlying mechanisms of that might associate to the acute exercise-induced lactate signaling in the skin, it remains uncertain the profile of skin interstitial fluid (ISF) lactate dynamics during and following acute exercise. Here, we investigated whether the skin ISF lactate level increases in association with blood lactate during acute incremental exercise using a single microneedle perfusion system. The rats were acclimated to treadmill running exercise and underwent external jugular vein cannulation. Following comprehensive recovery, a 1 mm single microneedle was implanted into the back skin. Skin ISF lactate progressively increased in tandem with blood lactate during the incremental exercise but did not decrease to baseline levels until 30 minutes following the exercise unlike blood. Moreover, lactate threshold (LT), is a crucial marker of athletic aerobic performance during acute exercise, extrapolated from skin ISF showed significant alignment with blood LT. Our findings reveal that the skin ISF lactate increases associated with blood lactate and the long-lasting elevation state following acute exercise. Moreover, lactate dynamics in skin ISF can predict LT. These findings would be a milestone for elucidating regular exercise-induced physiological adaptations in the skin and evaluating athletic performance.

Graphical Abstract

Lactate levels in rat skin interstitial fluid (ISF) increased in association with blood lactate during acute incremental exercise, but the increase in skin ISF lactate lasted 30 min following acute exercise. Lactate threshold (LT), a crucial marker of aerobic athletic performance, can be predicted from skin fluid dynamics during acute exercise. These findings would be a milestone for elucidating regular exercise-induced physiological adaptations in the skin and evaluating athletic performance.
Low relative air humidity and increased stomatal density independently hamper growth in young Arabidopsis
Authors: Tulva Ingmar , Koolmeister Kaspar , Hõrak Hanna
Published: October 2023

Stomatal pores in plant leaves mediate CO2uptake for photosynthesis and water loss via transpiration. Altered stomatal density can affect plant photosynthetic capacity, water use efficiency, and growth, potentially providing either benefits or drawbacks depending on the environment. Here we explore, at different air humidity regimes, gas exchange, stomatal anatomy, and growth of Arabidopsis lines designed to combine increased stomatal density (epf1,epf2) with high stomatal sensitivity (ht1-2,cyp707a1/a3). We show that the stomatal density and sensitivity traits combine as expected: higher stomatal density increases stomatal conductance, whereas the effect is smaller in the high stomatal sensitivity mutant backgrounds than in theepf1epf2double mutant. Growth under low air humidity increases plant stomatal ratio with relatively more stomata allocated to the adaxial epidermis. Low relative air humidity and high stomatal density both independently impair plant growth. Higher evaporative demand did not punish increased stomatal density, nor did inherently low stomatal conductance provide any protection against low relative humidity. We propose that the detrimental effects of high stomatal density on plant growth at a young age are related with the cost of producing stomata; future experiments need to test if high stomatal densities might pay off in later life stages.

Significance statement

This study delves into the relationship between stomatal density, sensitivity, and environment in Arabidopsis. These findings not only enhance our comprehension of plant responses to humidity but also lay the groundwork for future studies aimed at optimising plant adaptability to varying environmental conditions.
Adipokinetic hormone signaling mediates the enhanced fecundity ofDiaphorina citriinfected by ‘CandidatusLiberibacter asiaticus’
Authors: Li Jiayun , Holford Paul , Beattie George Andrew Charles , Wu Shujie , He Jielan , Tan Shijian , Wang Desen , He Yurong , Cen Yijing , Nian Xiaoge
Published: October 2023

Diaphorina citriserves as the primary vector for ‘CandidatusLiberibacter asiaticus’ (CLas), the bacterium associated with the severe Asian form of huanglongbing.CLas-positiveD. citriare more fecund than theirCLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response toCLas infection inD. citri.Knockdown ofDcAKHandDcAKHRnot only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity andCLas titer in ovaries. Combinedin vivoandin vitroexperiments showed that miR-34 suppressesDcAKHRexpression by binding to its 3’ untranslated region, whilst overexpression of miR-34 resulted in a decline ofDcAKHRexpression andCLas titer in ovaries and caused defects that mimickedDcAKHRknockdown phenotypes. Additionally, knockdown ofDcAKHandDcAKHRsignificantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor,methoprene-tolerant(DcMet), and the transcription factor,Krüppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genesvitellogenin 1-like(DcVg-1-like),vitellogenin A1-like(DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result,CLas hijacks AKH/AKHR-miR-34-JH signaling to improveD. citrilipid metabolism and fecundity, while simultaneously increasing the replication ofCLas, suggesting a mutualistic interaction betweenCLas andD. citriovaries.
A fuzzy sequencer for rapid DNA fragment counting and genotyping
Authors: Zhou Wenxiong , Kang Li , Qiao Shuo , Duan Haifeng , Yin Chenghong , Liu Chao , Liao Zhizhao , Tang Mingchuan , Zhang Ruiying , Li Lei , Shi Lei , Du Meijie , Wang Yipeng , Yue Wentao , Xiao Yan , Di Lin , Zhang Xiannian , Pang Yuhong , Li Mingkun , Ren Lili , Wang Jianbin , Chen Zitian , Huang Yanyi
Published: October 2023

High-throughput sequencing technologies generate a vast number of DNA sequence reads simultaneously, which are subsequently analyzed using the information contained within these fragmented reads. The assessment of sequencing technology relies on information efficiency, which measures the amount of information entropy produced per sequencing reaction cycle. In this study, we propose a fuzzy sequencing strategy that exhibits information efficiency more than twice of currently prevailing cyclic reversible terminator sequencing methods. To validate our approach, we developed a fully functional and high-throughput fuzzy sequencer. This sequencer implements a highly efficient fluorogenic sequencing-by-synthesis chemistry and underwent testing across various application scenarios, including copy-number variation detection, noninvasive prenatal testing, transcriptome profiling, mutation genotyping, and metagenomic profling. Our findings unequivocally demonstrate that the fuzzy sequencing strategy outperforms existing methods in terms of information efficiency and delivers accurate resequencing results with faster turnaround times.

One Sentence Summary

A fuzzy sequencer can exceed current limit of information efficiency of DNA sequencers for resequencing applications.
Rapid and Inducible Mislocalization of Endogenous TDP43 in a Novel Human Model of Amyotrophic Lateral Sclerosis
Authors: Ganssauge Johanna , Hawkins Sophie , Namboori Seema , Leung Szi-Kay , Mill Jonathan , Bhinge Akshay
Published: October 2023

Transactive response DNA binding protein 43 kDa (TDP43) proteinopathy, characterized by the mislocalization and aggregation of TDP43, is a hallmark of several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). In this study, we describe the development of a new model of TDP43 proteinopathy using human induced pluripotent stem cell (iPSC)-derived neurons. Utilizing a genome engineering approach, we induced the mislocalization of endogenous TDP43 from the nucleus to the cytoplasm without mutating the TDP43 gene or using chemical stressors. Our model successfully recapitulates key early and late pathological features of TDP43 proteinopathy, including neuronal loss, reduced neurite complexity, and cytoplasmic accumulation and aggregation of TDP43. Concurrently, the loss of nuclear TDP43 leads to splicing defects, while its cytoplasmic gain adversely affects microRNA expression. Strikingly, our observations suggest that TDP43 is capable of sustaining its own mislocalization, thereby perpetuating and further aggravating the proteinopathy. This innovative model provides a valuable tool for the in-depth investigation of the consequences of TDP43 proteinopathy. It offers a clinically relevant platform that will accelerate identification of potential therapeutic targets for the treatment of TDP43-associated neurodegenerative diseases including sporadic ALS.
Systematic identification of cargo-carrying genetic elements reveals new dimensions of eukaryotic diversity
Authors: Gluck-Thaler Emile , Vogan Aaron A.
Published: October 2023

Cargo-carrying mobile elements (CCEs) are genetic entities that transpose diverse protein coding sequences. Although common in bacteria, we know little about the biology of eukaryotic CCEs because no appropriate tools exist for their annotation. For example,Starshipsare fungal CCEs whose functions are largely unknown because they require time-intensive manual curation. To address this knowledge gap, we developed starfish, a computational workflow for high-throughput eukaryotic CCE annotation. We applied starfish to 2, 899 genomes of 1, 649 fungal species and found that starfish recovers knownStarshipswith >95% precision and accuracy while expanding the number of annotated elements ten-fold. ExtantStarshipdiversity is partitioned into 11 families that differ in their enrichment patterns across fungal classes.Starshipcargo changes rapidly such that elements from the same family differ substantially in their functional repertoires, which are predicted to contribute to diverse biological processes such as metabolism. Many elements have convergently evolved to insert into 5S rDNA and AT-rich sequence while others integrate into random locations, revealing both specialist and generalist strategies for persistence. Our work establishes a framework for advancing mobile element biology and provides the means to investigate an emerging dimension of eukaryotic genetic diversity, that of genomes within genomes.