bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding the genomic landscape of chromatin-associated biomolecular condensates
Authors: Yu Zhaowei , Wang Qi , Zhu Guangya , Zhu Jidong , Zhang Yong 
Published: August 2023

AbstractBiomolecular condensates play a significant role in chromatin activities, primarily by concentrating and compartmentalizing proteins and/or nucleic acids. However, their genomic landscapes and compositions remain largely unexplored due to a lack of dedicated computational tools for systematic identificationin vivo. To address this, we developed CondSigDetector, a computational framework designed to detect condensate-like chromatin-associated protein co-occupancy signatures (CondSigs), to predict genomic loci and component proteins of distinct chromatin-associated biomolecular condensates. Applying this framework to mouse embryonic stem cells (mESC) and human K562 cells enabled us to depict the high-resolution genomic landscape of chromatin-associated biomolecular condensates, and uncover both known and potentially novel biomolecular condensates. Multi-omics analysis and experimental validation further verified the condensation properties of CondSigs. Additionally, our investigation shed light on the impact of chromatin-associated biomolecular condensates on chromatin activities. Collectively, CondSigDetector provides a novel approach to decode the genomic landscape of chromatin-associated condensates, facilitating a deeper understanding of their biological functions and underlying mechanisms in cells.
A fluorescence viewer for rapid molecular assay readout in space and low-resource terrestrial environments
Authors: Misquitta Kristoff , Miller Bess M. , Malecek Kathryn , Gleason Emily , Martin Kathryn , Walesky Chad M. , Foley Kevin , Copeland D. Scott , Saavedra Ezequiel Alvarez , Kraves Sebastian 
Published: August 2023

AbstractFluorescence-based assays provide sensitive and adaptable methods for point of care testing, environmental monitoring, studies of protein abundance and activity, and a wide variety of additional applications. Currently, their utility in remote and low-resource environments is limited by the need for technically complicated or expensive instruments to read out fluorescence signal. Here we describe the Genes in Space Fluorescence Viewer (GiS Viewer), a portable, durable viewer for rapid molecular assay readout that can be used to visualize fluorescence in the red and green ranges. The GiS Viewer can be used to visualize any assay run in standard PCR tubes and contains a heating element. Results are visible by eye or can be imaged with a smartphone or tablet for downstream quantification. We demonstrate the capabilities of the GiS Viewer using two case studies – detection of SARS-CoV-2 RNA using RT-LAMP and quantification of drug-induced changes in gene expression via qRT-PCR on Earth and aboard the International Space Station. We show that the GiS Viewer provides a reliable method to visualize fluorescence in space without the need to return samples to Earth and can further be used to assess the results of RT-LAMP and qRT-PCR assays on Earth.
The Risk of Mpox (Monkeypox) Importation and Subsequent Outbreak Potential in Mainland China: A Retrospective Statistical Modelling Study
Authors: Deng Xiaowei , Tian Yuyang , Zou Junyi , Yang Juan , Sun Kaiyuan , Yu Hongjie 
Published: August 2023

AbstractThe 2022 mpox outbreak has spread rapidly across multiple countries in the non-endemic region, mainly among men who have sex with men (MSM), while China only has limited recorded importation and no local outbreak. We constructed probabilistic models to simulate the risk of mpox importation in mainland China, with the help of reported monkeypox cases during this multi-country outbreak and the international air-travel data. And we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men, considering different transmissibility, population immunity and population activity. We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations respectively. Once a mpox case is introduced into active MSM population with almost no population immunity, the risk of triggering local transmission is estimated at 42%, and would rise to >95% with over six cases. Our study demonstrates the key role of the reduced international air-travel volume and stringent border entry policy during the COVID-19 pandemic on reducing mpox importations, and the subsequent risk of triggering local outbreaks among MSM.
Smoking during pregnancy and its effect on placental weight: A Mendelian randomization study
Authors: Jaitner Annika , Vaudel Marc , Tsaneva-Atanasova Krasimira , Njølstad Pål R. , Jacobsson Bo , Bowden Jack , Johansson Stefan , Freathy Rachel M. 
Published: August 2023

ABSTRACTBackgroundThe causal relationship between maternal smoking in pregnancy and reduced offspring birth weight is well established and is likely due to impaired placental function. However, observational studies have given conflicting results on the association between smoking and placental weight. We aimed to estimate the causal effect of newly pregnant mothers quitting smoking on their placental weight at the time of delivery.MethodsWe used one-sample Mendelian randomization, drawing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (up to N = 805) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (up to N = 4475). The analysis was performed in pre-pregnancy smokers only, due to the specific role of the genetic instrument SNP rs1051730 (CHRNA5 – CHRNA3 – CHRNB4) in affecting smoking cessation but not initiation.ResultsFixed effect meta-analysis showed a 175 g [95%CI: 16, 334] higher placental weight for pre-pregnancy smoking mothers who continued smoking at the beginning of pregnancy, compared with those who stopped smoking. Using the number of cigarettes smoked per day in the first trimester as the exposure, the causal estimate was a 12 g [95%CI: 2,22] higher placental weight per cigarette per day. Results were similar when the smoking exposures were measured at the end of pregnancy. Using the residuals of birth weight regressed on placental weight as the outcome, we showed weak evidence of lower offspring birth weight relative to the placental weight for continuing smoking.ConclusionOur results suggest that continued smoking during pregnancy causes higher placental weights.Key MessagesIt is well known that maternal smoking in pregnancy causes a lower birth weight on average, but the relationship between maternal smoking and placental weight is less clear, with observational studies showing conflicting results.Our Mendelian randomization study suggests that for pre-pregnancy smokers, continuing smoking during pregnancy causes higher placental weight at term than quitting smoking.Our study also suggests that a greater number of cigarettes smoked per day during pregnancy causes a larger placental weight at term.A possible explanation for our findings is that the placenta grows larger in mothers who smoke during pregnancy to compensate for the lower oxygen availability, but further work is needed to confirm and further investigate this hypothesis.
Participatory Approaches in Community Health in light of the COVID-19 Pandemic: A Scoping Review Protocol
Authors: Frahsa Annika , Liwanag Harvy Joy , Kobler Cristopher , Ipekci Aziz Mert , Minder Beatrice , Schow Diana 
Published: August 2023

ABSTRACTBackgroundParticipatory approaches are considered essential to ensure community health in the context of the COVID-19 pandemic. Previous reviews on community participation have explored different aspects of participation in specific contexts, such as public health emergencies, but none has examined participatory approaches both in depth and in breadth across diverse activities during the COVID-19 pandemic and considering diverse communities in all country contexts. This scoping review seeks to: (a) provide an overview of participatory approaches in terms of the features and depth of participation, the breadth of the communities and stakeholders involved, and for what types of activities and interventions in light of the COVID-19 pandemic across all country contexts; (b) explore the challenges and facilitators of participation processes; and (c) analyse to what extent participation impacts community health, including health equity, in the context of a public health emergency.MethodsWe developed this protocol following the latest JBI guidance on scoping reviews. A comprehensive search strategy combining the concepts of participation, community health, and COVID-19 was used to search the databases of Medline/Ovid, Embase.com, Cochrane CENTRAL, Web of Science, APA PsycInfo/Ovid, Global Health/Ovid, ERIC/OvidSP, CINAHL/EBSCOhost, ClinTrials.gov, and the grey literature through Google Scholar. At least two reviewers will perform screening of titles/abstracts and full text using the inclusion and exclusion criteria defined in this protocol. Article characteristics and data on participatory approaches and community health will be charted to provide an overview of the literature, map the variations in participatory approaches and community health, and explore patterns in the links between participation, community health, and the type of activities to address the challenges related to the COVID-19 pandemic.DiscussionWe anticipate that review findings will contribute to advance innovative thinking about community participation and facilitating better application and integration of participatory approaches to ensure community health in a future public health emergency or in building back better fairer in the new normal.
Regulation of Lung Immune Tone by the Gut-Lung Axis via Dietary Fiber, Gut Microbiota, and Short-Chain Fatty Acids
Authors: Maruyama Daisuke , Liao Wen-I , Tian Xiaoli , Bredon Marius , Knapp Johannes , Tat Christine , Doan Thien N. M. , Chassaing Benoit , Bhargava Aditi , Sokol Harry , Prakash Arun 
Published: August 2023

ABSTRACTLung immune tone, i.e. the immune state of the lung, can vary between individuals and over a single individual’s lifetime, and its basis and regulation in the context of inflammatory responses to injury is poorly understood. The gut microbiome, through the gut-lung axis, can influence lung injury outcomes but how the diet and microbiota affect lung immune tone is also unclear. We hypothesized that lung immune tone would be influenced by the presence of fiber-fermenting short-chain fatty acid (SCFA)-producing gut bacteria. To test this hypothesis, we conducted a fiber diet intervention study followed by lung injury in mice and profiled gut microbiota using 16S sequencing, metabolomics, and lung immune tone. We also studied germ-free mice to evaluate lung immune tone in the absence of microbiota and performedin vitromechanistic studies on immune tone and metabolic programming of alveolar macrophages exposed to the SCFA propionate (C3). Mice on high-fiber diet were protected from sterile lung injury compared to mice on a fiber-free diet. This protection strongly correlated with lower lung immune tone, elevated propionate levels and enrichment of specific fecal microbiota taxa; conversely, lower levels of SCFAs and an increase in other fatty acid metabolites and bacterial taxa correlated with increased lung immune tone and increased lung injury in the fiber-free group.In vitro, C3 reduced lung alveolar macrophage immune tone (through suppression of IL-1β and IL-18) and metabolically reprogrammed them (switching from glycolysis to oxidative phosphorylation after LPS challenge). Overall, our findings reveal that the gut-lung axis, through dietary fiber intake and enrichment of SCFA-producing gut bacteria, can regulate innate lung immune tone via IL-1β and IL-18 pathways. These results provide a rationale for the therapeutic development of dietary interventions to preserve or enhance specific aspects of host lung immunity.
Structure basis of the phytoplasma effector SAP05 recognition specificities to plant Rpn10 in ubiquitin-independent protein degradation
Authors: Zhang Liying , Du Yunxiang , Zheng Qingyun 
Published: August 2023

AbstractRecent research reported an effector protein SAP05 secreted by phytoplasma could hijack hostage Rpn10 subunit of proteasome and target degradation of GATA or SPL transcription factors (TFs) without ubiquitin. As a result, plant phenotypes will be reprogrammed to a state suitable for phytoplasma amplification and insect vector propagation which present prolonged growth cycles, witches’ broom-like proliferations of leaves and sterile shoots. We are curious about how could SAP05 target degradation bypassing the ubiquitin pathway and if there is any conserved interaction between different species of SAP05 with AtRpn10. Here, we have determined the crystal structure of the AtRpn10 complex with AY-WB or OY SAP05. Structure alignment revealed similar recognition patterns through sequences of two species SAP05 are poor homologous, which suggested phytoplasma may conduct resemble mode in plant infection. After docking the complex structure to the plant proteasome, we found that SAP05’s location is near the ATPase central pore, which may be close enough to submit substrate with no need for ubiquitin in the degradation process.
Recurrent Neural Network-based Prediction of O-GlcNAcylation Sites in Mammalian Proteins
Authors: Seber Pedro , Braatz Richard D. 
Published: August 2023

AbstractO-GlcNAcylation has the potential to be an important target for therapeutics, but a motif or an algorithm to reliably predict O-GlcNAcylation sites is not available. In spite of the importance of O-GlcNAcylation, current predictive models are insufficient as they fail to generalize, and many are no longer available. This article constructs MLP and RNN models to predict the presence of O-GlcNAcylation sites based on protein sequences. Multiple different datasets are evaluated separately and assessed in terms of strengths and issues. The models trained in this work achieve considerably better metrics than previously published models, with at least a two-fold increase in F1score relative to previously published models; the specific gains vary depending on the dataset. Within a given dataset, the results are robust to changes in cross-validation and test data as determined by nested validation. The best model achieves an F1score of 36% (more than 3.5-fold greater than the previous best model) and a Matthews Correlation Coefficient of 35% (more than 4.5-fold greater than the previous best model), and, for the F1score, 7.6-fold higher than when not using any model. Shapley values are used to interpret the model ‘s predictions and provide biological insight into O-GlcNAcylation.
HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells
Authors: Kou Xinxin , Yang Xiaoxia , Zhao Zheng , Li Lei 
Published: August 2023

AbstractBackgroundCurrently, platinum agents remain the mainstay of chemotherapy for ovarian cancer (OC). However, cisplatin (DDP) resistance is a major reason for chemotherapy failure. Thus, it is extremely important to elucidate the mechanism of resistance to DDP.MethodsWe establish 2 DDP-resistant ovarian cancer cell lines and find that caseinolytic protease P (CLPP) is significantly downregulated in the DDP-resistant cell lines when compared to wild-type ovarian cancer cell lines (SK-OV-3 and OVcar3). Next, we investigate the functions of CLPP in the DDP-resistant and wild-type ovarian cancer cells using various assays including cell counting kit-8 assays, western blotting, immunofluorescent staining, and reactive oxygen species (ROS) and apoptosis detection.ResultsOur experiments show that CLPP knockdown significantly increase the half maximal inhibitory concentration (IC50) and mitophagy of wild-type SK-OV-3 and OVcar3 cells, while CLPP overexpression reduces the IC50values and mitophagy of DDP-resistant SK-OV-3 and OVcar3 cells. Next, we perform database predictions and experiments to show that heat shock protein family A member 8 (HSPA8) regulates CLPP protein stability. The dynamic effects of the HSPA8/CLPP axis in the ovarian cancer cells were also examined. HSPA8 increases mitophagy and the IC50values of SK-OV-3 and OVcar3 cells, but inhibits their ROS production and apoptosis. In addition, CLPP partly reverses the effects induced by HSPA8 in the SK-OV-3 and OVcar3 cells.ConclusionsCLPP increases the DDP resistance of ovarian cancer by inhibiting mitophagy and promoting cellular stress. Meanwhile, HSPA8 promotes the degradation of CLPP protein by inducing its stability.
Beyond microRNAs: Analysis of chimeric reads characterises the diverse targetome of AGO2-mediated regulation
Authors: Hejret Vaclav , Varadarajan Nandan Mysore , Klimentova Eva , Gresova Katarina , Giassa Ilektra-Chara , Vanacova Stepanka , Alexiou Panagiotis 
Published: August 2023

AbstractArgonaute proteins are instrumental in regulating RNA stability and translation. AGO2, the major mammalian Argonaute protein, is known to primarily associate with microRNAs, a family of small RNA ‘driver’ sequences, and identifies its targets primarily via a ‘seed’ mediated partial complementarity process Despite numerous studies, a definitive experimental dataset of AGO2 ‘driver’-’target’ interactions remains elusive. Our study employs two experimental methods - AGO2 CLASH and AGO2 eCLIP, to generate thousands of AGO2 target sites verified by chimeric reads. These chimeric reads contain both the AGO2 loaded small RNA ‘driver’ and the target sequence, providing a robust resource for modeling AGO2 binding preferences. Our novel analysis pipeline reveals thousands of AGO2 target sites driven by microRNAs and a significant number of AGO2 ‘drivers’ derived from fragments of other small RNAs such as tRNAs, YRNAs, snoRNAs, rRNAs, and more. We utilize convolutional neural networks to train machine learning models that accurately predict the binding potential for each ‘driver’ class and experimentally validate several interactions. In conclusion, our comprehensive analysis of the AGO2 targetome broadens our understanding of its ‘driver’ repertoire and potential function in development and disease. Moreover, we offer practical bioinformatic tools for future experiments and the prediction of AGO2 targets. All data and code from this study are freely available athttps://github.com/ML-Bioinfo-CEITEC/HybriDetector/Contactpanagiotis.alexiou@um.edu.mt,stepanka.vanacova@ceitec.muni.cz
Diversity of Bathyarchaeia viruses in metagenomes and virus-encoded CRISPR system components
Authors: Duan Changhai , Liu Yang , Liu Ying , Liu Lirui , Cai Mingwei , Zhang Rui , Zeng Qinglu , Koonin Eugene V. , Krupovic Mart , Li Meng 
Published: August 2023

AbstractBathyarchaeia represent a class of archaea common and abundant in sedimentary ecosystems. The virome of Bathyarchaeia so far has not been characterized. Here we report 56 metagenome-assembled genomes of Bathyarchaeia viruses identified in metagenomes from different environments. Gene sharing network and phylogenomic analyses led to the proposal of four virus families, including viruses of the realmsDuplodnaviriaandAdnaviria, and archaea-specific spindle-shaped viruses. Genomic analyses uncovered diverse CRISPR elements in these viruses. Viruses of the proposed family ‘Fuxiviridae’ harbor an atypical type IV-B CRISPR-Cas system and a Cas4 protein that might interfere with host immunity. Viruses of the family ‘Chiyouviridae’ encode a Cas2-like endonuclease and two mini-CRISPR arrays, one with a repeat identical to that in the host CRISPR array, potentially allowing the virus to recruit the host CRISPR adaptation machinery to acquire spacers that could contribute to competition with other mobile genetic elements or to inhibition of host defenses. These findings present an outline of the Bathyarchaeia virome and offer a glimpse into their counter-defense mechanisms.
Diversity in Notch ligand-receptor signaling interactions
Authors: Kuintzle Rachael , Santat Leah A. , Elowitz Michael B. 
Published: August 2023

AbstractThe Notch signaling pathway uses families of ligands and receptors to transmit signals to nearby cells. These components are expressed in diverse combinations in different cell types, interact in a many-to-many fashion, both within the same cell (in cis) and between cells (in trans), and their interactions are modulated by Fringe glycosyltransferases. A fundamental question is how the strength of Notch signaling depends on which pathway components are expressed, at what levels, and in which cells. Here, we used a quantitative, bottom-up, cell-based approach to systematically characterize trans-activation, cis-inhibition, and cis-activation signaling efficiencies across a range of ligand and Fringe expression levels in two mammalian cell types. Each ligand (Dll1, Dll4, Jag1, and Jag2) and receptor variant (Notch1 and Notch2) analyzed here exhibited a unique profile of interactions, Fringe-dependence, and signaling outcomes. All four ligands were able to bind receptors in cis and in trans, and all ligands trans-activated both receptors, although Jag1-Notch1 signaling was substantially weaker than other ligand-receptor combinations. Cis-interactions were predominantly inhibitory, with the exception of the Dll1-and Dll4-Notch2 pairs, which exhibited cis-activation stronger than trans-activation. Lfng strengthened Delta-mediated trans-activation and weakened Jagged-mediated trans-activation for both receptors. Finally, cis-ligands showed diverse cis-inhibition strengths, which depended on the identity of the trans-ligand as well as the receptor. The map of receptor-ligand-Fringe interaction outcomes revealed here should help guide rational perturbation and control of the Notch pathway.
AKT2 Loss Impairs BRAF-Mutant Melanoma Metastasis
Authors: McRee Siobhan K. , Bayer Abraham L. , Pietruska Jodie , Tsichlis Philip N. , Hinds Philip W. 
Published: August 2023

AbstractDespite recent advances in treatment, melanoma remains the deadliest form of skin cancer, due to its highly metastatic nature. Melanomas harboring oncogenic BRAFV600Emutations combined with PTEN loss exhibit unrestrained PI3K/AKT signaling and increased invasiveness. However, the contribution of different AKT isoforms to melanoma initiation, progression, and metastasis has not been comprehensively explored, and questions remain whether individual isoforms play distinct or redundant roles in each step. We investigate the contribution of individual AKT isoforms to melanoma initiation using a novel mouse model of AKT isoform-specific loss in a murine melanoma model, and investigate tumor progression, maintenance, and metastasis among a panel of human metastatic melanoma cell lines using AKT-isoform specific knockdown studies. We elucidate that AKT2 is dispensable for primary tumor formation but promotes migration and invasionin vitroand metastatic seedingin vivo, while AKT1 is uniquely important for melanoma initiation and cell proliferation. We propose a mechanism whereby inhibition of AKT2 impairs glycolysis and reduces an EMT-related gene expression signature in PTEN-null BRAF-mutant human melanoma cells to limit metastatic spread. Our data suggest that elucidation of AKT2-specific functions in metastasis could inform therapeutic strategies to improve treatment options for melanoma patients.Graphical Abstract