Recent Submissions

  • Preparation of a novel metallothionein-AuNP composite material by genetic modification and Au–S covalent combination

    Li, Xuefen; Liu, Hui; Wang, Yuxia; Crabbe, M. James C.; Wang, Lan; Ma, Wenli; Ren, Zhumei; Shanxi University; University of Oxford; University of Bedfordshire (Elsevier, 2024-02-05)
    Metallothionein (MTs) can be used in the prevention and treatment of tumors and diabetes due to its antioxidant properties. However, it is necessary to solve its non-transmembrane properties and further improve its antioxidant activity, increase its fluorescence visualization and enhance its stability to meet practical applications in the biomedical field. Here, we report the preparation of a novel metallothionein-AuNP composite material with high transmembrane ability, fluorescence visualization, antioxidant activity, and stability by genetic modification (introducing transduction peptide TAT, fluorescence tag GFP and increasing sulfydryl groups) and immobilization technology (covalently bonding with AuNPs). The transmembrane activity of modified proteins was verified by immunofluorescence. Increasing the sulfhydryl content within a certain range can enhance the antioxidant activity of the protein. In addition, GFP were used to further simplify the imaging of the metallothionein-AuNP composite in cells. XPS results indicated that AuNPs can immobilize metallothionein through Au–S covalent bonds. TGA characterization and degradation experiments showed that thermal and degradation stability of the immobilized material was significantly improved. This work provides new ideas to construct metallothionein composites with high transmembrane ability, antioxidant activity, fluorescence visualization and stability to meet novel applications in the biomedical field.
  • Cancer development in hepatocytes by long-term induction of hypoxic hepatocellular carcinoma cell (HCC)-derived exosomes in vivo and in vitro

    Ju, Tuoyu; Dong, Jianjun; Wang, Bowei; Qu, Kaige; Cheng, Can; He, Xiuxia; Tian, Yanling; Crabbe, M. James C.; Wang, Zuobin; Chen, Yujuan (ACS, 2023-10-16)
    Hypoxic tumor cell-derived exosomes play a key role in the occurrence, development, and metastasis of tumors. However, the mechanism of hypoxia-mediated metastasis remains unclear. In this study, hypoxic hepatocellular carcinoma cell (HCC-LM3)-derived exosomes (H-LM3-exos) were used to induce hepatocytes (HL-7702) over a long term (40 passages in 120 days). A nude mouse experiment further verified the effect of H-LM3-exos on tumor growth and metastasis. The process of cancer development in hepatocytes induced by H-LM3-exos was analyzed using both biological and physical techniques, and the results showed that the proliferation and soft agar growth abilities of the transformed cells were enhanced. The concentration of tumor markers secreted by transformed cells was increased, the cytoskeleton was disordered, and the migration ability was enhanced and was accompanied by epithelial−mesenchymal transition (EMT). Transcriptome results showed that differentially expressed genes between transformed cells and hepatocytes were enriched in cancer-related signaling pathways. The degree of cancer development in transformed cells was enhanced by an increase in H-LM3-exos-induced passages. Nude mice treated with different concentrations of H-LM3-exos showed different degrees of tumor growth and liver lesions. The physical properties of the cells were characterized by atomic force microscopy. Compared with the hepatocytes, the height and roughness of the transformed cells were increased, while the adhesion and elastic modulus were decreased. The changes in physical properties of primary tumor cells and hepatocytes in nude mice were consistent with this trend. Our study linking omics with the physical properties of cells provides a new direction for studying the mechanisms of cancer development and metastasis.
  • Impacts of marine cloud brightening scheme on climatic extremes in the Tibetan Plateau

    Zhang, Zhihua; Zhu, Yuanzhuo; Crabbe, M. James C. (De Gruyter, 2023-09-29)
    As an ecologically fragile plateau and major water source in Asia, the Tibetan Plateau (TP) has grown warmer over recent decades, contributing to frequent occurrence of extreme climate events. It is urgently needed to find a suitable option to mitigate climate change impacts in the TP. The marine cloud brightening (MCB) scheme is proposed to mitigate global warming through the increasing cloud droplet number concentration of low marine clouds to reflect some solar radiation back into space. Until now, impacts of MCB scheme on the TP have not been investigated. In this study, we utilized 13 Expert Team on Climate Change Detection and Indices to assess the evolution of climate extremes over the TP with/without MCB implementation. We found that although the MCB is implemented over ocean only, it would cause significant changes on climate extremes in the TP which is very far from oceans and much higher than sea level. During 2030–2059, MCB implementation can decrease warm temperature extremes, leading to a significant decrease in the TXx index by 6–18°C, the TX90p index by 15–45 days, and the TN90p index by 15–50 days. MCB implementation would also have some cooling effects on cold temperature extremes, leading to an increase in the ID index by 30–80 days, the TX10p index by 22–32 days, and the TN10p index by about 12 days and a decrease in the TNn index by 0.5–1.5°C. Although MCB implementation would not have much impacts on precipitation extremes, it would significantly increase the area of the region with <10% drought frequency, and increase the drought intensity in the west of Lhasa city.
  • Effect of vegetation blanket cover with different materials on soil microbial community structure of opencast coal mines in arid areas

    Wang, Ziyin; Liu, Huili; Crabbe, M. James C.; Zhao, Xiaoyu; Liu, Bingru; North Minzu University; Oxford University; University of Bedfordshire; Shanxi University (John Wiley and Sons Ltd, 2023-09-04)
    Vegetation blanket restoration of mine soils provides a diverse environment for soil microbes, but the effects of vegetation blanket cover on soil physicochemical properties, microbial structure, and diversity are not well understood, particularly in arid areas. In this study, high-throughput sequencing was used to examine the microbial community at Dafeng Mine, the Helan Mountains, Ningxia, China. Soil microbial communities were analyzed with four different materials: 100% straw, 50% straw–50% coconut, and 100% coconut vegetation blanket types, and a bare ground control (CK). The results showed that the contents of soil total nitrogen (TN), available potassium (AP), urease, and catalase were significantly increased in different types of vegetation blankets. High-throughput sequencing showed that the straw vegetation blanket increased bacterial diversity, while the coconut vegetation blanket increased fungal diversity. The main influencing factors of the dominant bacterial phylum were total nitrogen, catalase, urease, protease, soil water content (WC), soil organic carbon (SOC), and electrical conductivity (EC). The main influencing factor of the dominant fungal phylum was soil water content. These results show that compared with straw vegetation blankets, coconut, and straw–coconut vegetation blanket mulches are more likely to improve soil physicochemical properties, increase the diversity and abundance of soil microorganisms and improve the structural composition of the community, thus improving the soil environment in dryland mining areas. However, further research is needed as to which is the more significant environmental improvement, coconut or straw–coconut vegetation blankets.
  • Integrative analysis of the metabolome and transcriptome reveals the potential mechanism of fruit flavor formation in wild hawthorn Crataegus chungtienensis

    Wu, Xien; Luo, Dengli; Zhang, Yingmin; Jin, Ling; Crabbe, M. James C.; Qiao, Qin; Li, Guodong; Zhang, Ti-Cao; ; Yunnan University of Chinese Medicine; et al. (Elsevier, 2023-02-24)
    Hawthorns are important medicinal and edible plants with a long history of health protection in China. Besides cultivated hawthorn, other wild hawthorns may also have excellent medicinal and edible value, such as Crataeguschungtienensis, an endemic species distributed in the Southwest of China. In this study, by integrating the flavor-related metabolome and transcriptome data of the ripening fruit of C. chungtienensis, we have developed an understanding of the formation of hawthorn fruit quality. The results show that a total of 849 metabolites were detected in the young and mature fruit of C. chungtienensis, of which flavonoids were the most detected metabolites. Among the differentially accumulated metabolites, stachyose, maltotetraose and cis-aconitic acid were significantly increased during fruit ripening, and these may be important metabolites affecting fruit flavor change. Moreover, several flavonoids and terpenoids were reduced after fruit ripening compared with young fruit. Therefore, using the unripe fruit of C. chungtienensis may allow us to obtain more medicinal active ingredients such as flavonoids and terpenoids. Furthermore, we screened out some differentially expressed genes (DEGs) related to fruit quality formation, which had important relationships with differentially accumulated sugars, acids, flavonoids and terpenoids. Our study provides new insights into flavor formation in wild hawthorn during fruit development and ripening, and at the same time this study lays the foundation for the improvement of hawthorn fruit flavor.
  • The effect of high altitude on ephedrine content and metabolic variations in two species of Ephedra

    Lu, Mengnan; He, Wenjia; Xu, Ziyan; Lu, Yan; Crabbe, M. James C.; De, Ji; ; Tibet University; Tibet Academy of Agricultural and Animal Husbandry Sciences; Fudan University; et al. (Frontiers, 2023-10-16)
    Ephedra is an important plant in Chinese medicine; however, there are few reports on two species of Ephedra which are distributed at high altitudes from 3000 to 5200 meters. We collected a total of 84 individuals representing five Ephedra gerardiana and nine Ephedra saxatilis populations respectively located from 3158 to 5200 meters altitude, and determined the relative content of 213 metabolites using UHPLC-MS/MS (Ultra-High-Performance Liquid Chromatography-tandem mass spectrometry). 37 Chemical compositions were annotated using the KEGG (Kyoto Encyclopaedia of Genes and Genomes) database. From the top five significant enrichments in metabolic KEGG pathway analysis, we found a total of 166 compounds belonging to phenylpropanoids, 123 flavonoids, 67 metabolites carried by ABC transporters, and 61 in purine metabolism. We identified the top 8 altitude-related compounds in two species. Ephedrine and pseudoephedrine were found to be associated with altitude in both E. saxatilis and E. gerardiana. To verify which environmental factors influenced the metabolic content, the soil moisture and temperature of each population site were collected, and quantitative analysis of ephedrine and pseudoephedrine was performed using UHPLC-MS (Ultra-High-Performance liquid chromatography-tandem mass spectrometry). After detection, soil moisture ranged from 0.074 to 0.177 mm3/mm3, and temperature ranged from 9.7°C to 23.9°C. The content of ephedrine ranged from (0.84 ± 0.49)% to (2.01 ± 0.41)% in E. saxatilis, which was positively correlated with soil moisture; the content of pseudoephedrine ranged from (0.72 ± 0.45)% to (1.11 ± 0.57)% and was negatively correlated with soil moisture. In contrast to these results, in E. gerardiana, the content of ephedrine and pseudoephedrine was negatively correlated with soil moisture. Furthermore, the trends of alkaloid contents in two kinds of Ephedra were similar when the temperature was lower than 17°C even if the sum was various. With the increase in soil moisture and temperature, the total alkaloid content of E. saxatilis was higher than that of E. gerardiana. When the soil moisture was lower, the alkaloid content of the two Ephedra species was higher. These results provide useful data for the future separation of new compounds, and for seed homogeneous growth to determine artificial breeding of Ephedra located at high altitudes.
  • Use of atomic force microscopy in UVB-induced chromosome damage provides important bioinformation for cell damage assessment

    Wang, Bowei; Dong, Jianjun; Yang, Fan; Ju, Tuoyu; Li, Jiani; Crabbe, M. James C.; Wang, Ying; Tian, Yanling; Wang, Zuobin (ACS, 2023-09-08)
    The chromosomal structure derived from UVB-stimulated HaCaT cells was detected by atomic force microscopy (AFM) to evaluate the effect of UVB irradiation. The results showed that the higher the UVB irradiation dose, the more the cells that had chromosome aberration. At the same time, different representative types of chromosome structural aberrations were investigated. We also revealed damage to both DNA and cells under the corresponding irradiation doses. It was found that the degree of DNA damage was directly proportional to the irradiation dose. The mechanical properties of cells were also changed after UVB irradiation, suggesting that cells experienced a series of chain reactions from inside to outside after irradiation. The highresolution imaging of chromosome structures by AFM after UVB irradiation enables us to relate the damage between chromosomes, DNA, and cells caused by UVB irradiation and provides specific information on genetic effects.
  • Large-scale biomedical relation extraction across diverse relation types: model development and usability study on COVID-19

    Zhang, Zeyu; Fang, Meng; Wu, Rebecca; Zong, Hui; Huang, Honglian; Tong, Yuantao; Xie, Yujia; Cheng, Shiyang; Wei, Ziyi; Crabbe, M. James C.; et al. (JMIR Publications, 2023-09-20)
    Biomedical relation extraction (RE) is of great importance for researchers to conduct systematic biomedical studies. It not only helps knowledge mining, such as knowledge graphs and novel knowledge discovery, but also promotes translational applications, such as clinical diagnosis, decision-making, and precision medicine. However, the relations between biomedical entities are complex and diverse, and comprehensive biomedical RE is not yet well established. We aimed to investigate and improve large-scale RE with diverse relation types and conduct usability studies with application scenarios to optimize biomedical text mining. Data sets containing 125 relation types with different entity semantic levels were constructed to evaluate the impact of entity semantic information on RE, and performance analysis was conducted on different model architectures and domain models. This study also proposed a continued pretraining strategy and integrated models with scripts into a tool. Furthermore, this study applied RE to the COVID-19 corpus with article topics and application scenarios of clinical interest to assess and demonstrate its biological interpretability and usability. The performance analysis revealed that RE achieves the best performance when the detailed semantic type is provided. For a single model, PubMedBERT with continued pretraining performed the best, with an F1-score of 0.8998. Usability studies on COVID-19 demonstrated the interpretability and usability of RE, and a relation graph database was constructed, which was used to reveal existing and novel drug paths with edge explanations. The models (including pretrained and fine-tuned models), integrated tool (Docker), and generated data (including the COVID-19 relation graph database and drug paths) have been made publicly available to the biomedical text mining community and clinical researchers. This study provided a comprehensive analysis of RE with diverse relation types. Optimized RE models and tools for diverse relation types were developed, which can be widely used in biomedical text mining. Our usability studies provided a proof-of-concept demonstration of how large-scale RE can be leveraged to facilitate novel research.
  • Multifractal features and dynamical thresholds of temperature extremes in Bangladesh

    Liu, Anxin; Zhang, Zhihua; Crabbe, M. James C.; Das, Lipon Chandra; Shandong University; Beijing Normal University; Oxford Universi; University of Bedfordshire; University of Chittagong (MDPI, 2023-07-13)
    Multifractal detrended fluctuation analysis (DFA) can extract multi-scaling behavior and measure long-range correlations in climatic time series. In this study, with the help of multifractal DFA, we investigated the scaling behavior of daily minimum/maximum temperatures during the years 1989–2019 from 34 meteorological stations in Bangladesh. We revealed spatial patterns, topographic impacts and global warming impacts of long-range correlations embedded in small and large fluctuations in temperature time series. Meanwhile, we developed a multifractal DFA-based algorithm to dynamically determine thresholds to discriminate extreme and non-extreme events in climate systems and applied it to analyze the frequency and trends of temperature extremes in Bangladesh. Compared with widely-used percentile thresholds, the extreme climate events captured in our algorithm are more reliable since they are determined dynamically by the climate system itself.
  • Do research incentives promote researchers’ mental health?

    Gu, Liujian; Wang, Tao; Wang, Chuanyi; Crabbe, M. James C.; Yue, Xiao-Guang; Tsinghua University; Oxford University; University of Bedfordshire (Tech Science Press, 2023-07-10)
    Researchers have a higher risk of anxiety and depression than the general population, so it is important to promote researchers’ mental health. Method: Based on the data from 3210 global researchers surveyed by the journal Nature in 2021, confirmatory factor analysis, OLS regression and other regressions were used to explore the research incentive dimensions and their effects on researchers’ mental health. Results: (1) Material incentive factors, work-family life balance factors, good organizational environment and spiritual motivation had significant positive effects on researchers’ mental health. (2) The spiritual motivation could better promote researchers’ mental health than the other factors. (3) Heterogeneity analysis showed that material incentive factors and spiritual motivation created more significant stimulating effects on the mental health of humanities and social sciences researchers. Work-family life balance factors were more effective in promoting the mental health of the mid-career group and the overtime group. Conclusion: Application of the four research incentives resulted in lower likelihood of anxiety or depression among researchers, and special attention should be paid to the role of the spiritual motivation. In order to promote researchers’ mental health, different incentives should be applied to different researcher groups to better improve researchers’ mental health.
  • Interaction between gut microbiota metabolites and dietary components in lipid metabolism and metabolic diseases

    Basnet, Til Bahadur; GC, Srijana; Basnet, Rajesh; Fatima, Sadia; Safdar, Mahpara; Sehar, Bismillah; Alsubaie, Ali Saad R.; Zeb, Falak; ; Fujian Medical University; et al. (Microbiology Society, 2023-06-23)
    Gut microbiota composition has caused perplexity in developing precision therapy to cure metabolic disorders. However, recent research has focused on using daily diet and natural bioactive compounds to correct gut microbiota dysbiosis and regulate host metabolism. Complex interactions between the gut microbiota and dietary compounds disrupt or integrate the gut barrier and lipid metabolism. In this review, we investigate the role of diet and bioactive natural compounds in gut microbiota dysbiosis and also the modulation of lipid metabolism by their metabolites. Recent studies have revealed that diet, natural compounds and phytochemicals impact significantly on lipid metabolism in animals and humans. These findings suggest that dietary components or natural bioactive compounds have a significant impact on microbial dysbiosis linked to metabolic diseases. The interaction between dietary components or natural bioactive compounds and gut microbiota metabolites can regulate lipid metabolism. Additionally, natural products can shape the gut microbiota and improve barrier integrity by interacting with gut metabolites and their precursors, even in unfavourable conditions, potentially contributing to the alignment of host physiology.
  • RNA-binding proteins and their emerging roles in cancer: beyond the tip of the iceberg

    Murphy, John J.; Surendranath, Kalpana; Kanagaraj, Radhakrishnan; University of Westminster; University of Bedfordshire; Sathyabama Institute of Science and Technology (MDPI, 2023-06-01)
    RNA-binding proteins (RBPs) represent a large family of proteins with an extensive array of roles that contribute to coordinating and directing multiple functions in RNA metabolism and transcription [...].
  • Thyroid-disrupting effects of exposure to fipronil and its metabolites from drinking water based on human thyroid follicular epithelial Nthy-ori 3‑1 cell lines

    Zhuang, Jianhui; Jiang, Zhiqiang; Chen, Dawei; Li, Jingguang; Crabbe, M. James C.; Qiu, Meiyue; Zheng, Yuxin; Qu, Weidong; Fudan University; China National Center for Food Safety Risk Assessment; et al. (ACS, 2023-04-06)
    Fipronil is a broad-spectrum insecticide used for plants and poultry. Owing to its widespread use, fipronil and its metabolites (fipronil sulfone, fipronil desulfinyl, and fipronil sulfide), termed FPM, can be frequently detected in drinking water and food. Fipronil can affect the thyroid function of animals, but the effects of FPM on the human thyroid remain unclear. We employed human thyroid follicular epithelial Nthy-ori 3-1 cells to examine combined cytotoxic responses, thyroid-related functional proteins including the sodium-iodide symporter (NIS), thyroid peroxidase (TPO), deiodinases I−III (DIO I−III), and the nuclear factor erythroid-derived factor 2−related factor 2 (NRF2) pathway induced by FPM of 1−1000-fold concentrations detected in school drinking water collected from a heavily contaminated area of the Huai River Basin. Thyroid-disrupting effects of FPM were evaluated by examining biomarkers of oxidative stress and thyroid function and tetraiodothyronine (T4) levels secreted by Nthy-ori 3-1 cells after FPM treatment. FPM activated the expression of NRF2, HO-1 (heme oxygenase 1), TPO, DIO I, and DIO II but inhibited NIS expression and increased the T4 level of thyrocytes, indicating that FPM can disrupt the function of human thyrocytes through oxidative pathways. Given the adverse impact of low FPM concentrations on human thyrocytes, supportive evidence from rodent studies, and the critical importance of thyroid hormones on development, the effects of FPM on the neurodevelopment and growth of children warrant priority attention.
  • Genome-wide identification and characterization of the chemosensory relative protein genes in Rhus gall aphid Schlechtendalia chinensis.

    He, Hongli; Crabbe, M. James C.; Ren, Zhumei; Shanxi University; Oxford University; University of Bedfordshire (BMC, 2023-04-28)
    The Rhus gall aphid Schlechtendalia chinensis specially uses the only species Rhus chinensis and certain moss species (Mniaceae) as its primary host plant and secondary host plants, respectively. Rhus galls are formed on the primary host by the sucking of aphids, and used in traditional medicine as well as other various areas due to their high tannin contents. Chemoreception is critical for insect behaviors such as host searching, location and identification of mates and reproductive behavior. The process of chemoreception is mediated by a series of protein gene families, including odorant-binding proteins (OBPs), chemosensory proteins (CSPs), olfactory receptors (ORs), gustatory receptors (GRs), ionotropic receptors (IRs), and sensory neuron membrane proteins (SNMPs). However, there have been no reports on the analysis of molecular components related to the chemoreception system of S. chinensis at the genome level. We examined the genes of eight OBPs, nine CSPs, 24 ORs, 16 GRs, 22 IRs, and five SNMPs in the S. chinensis genome using homological searches, and these chemosensory genes appeared mostly on chromosome 1. Phylogenetic and gene number analysis revealed that the gene families, e.g., ORs, GRs, CSPs and SNMPs in S. chinensis, have experienced major contractions by comparing to Myzus persicae, while the two gene families OBPs and IRs had slight expansion. The current results might be related to the broader host range of M. persicae versus the specialization of S. chinensis on only a host plant. There were 28 gene pairs between genomes of S. chinensis and Acyrthosiphon pisum in the chemoreceptor gene families by collinear comparison. Ka/Ks ratios (< 1) indicated that the genes of S. chinensis were mainly affected by purification selection during evolution. We also found the lower number and expression level of chemoreception genes in S. chinensis than in other 11 aphid species, such as ORs, GRs and IRs, which play an important role in host search. Our study firstly identified the genes of the different chemosensory protein gene families in the S. chinensis genome, and analyzed their general features and expression profile, demonstrating the importance of chemoreception in the aphid and providing new information for further functional research.
  • Excessive reactive oxygen species induce transcription-dependent replication stress

    Andrs, Martin; Stoy, Henriette; Boleslavska, Barbora; Chappidi, Nagaraja; Kanagaraj, Radhakrishnan; Nascakova, Zuzana; Menon, Shruti; Rao, Satyajeet; Oravetzova, Anna; Dobrovolna, Jana; et al. (SpringerNature, 2023-03-30)
    Elevated levels of reactive oxygen species (ROS) reduce replication fork velocity by causing dissociation of the TIMELESS-TIPIN complex from the replisome. Here, we show that ROS generated by exposure of human cells to the ribonucleotide reductase inhibitor hydroxyurea (HU) promote replication fork reversal in a manner dependent on active transcription and formation of co-transcriptional RNA:DNA hybrids (R-loops). The frequency of R-loop-dependent fork stalling events is also increased after TIMELESS depletion or a partial inhibition of replicative DNA polymerases by aphidicolin, suggesting that this phenomenon is due to a global replication slowdown. In contrast, replication arrest caused by HU-induced depletion of deoxynucleotides does not induce fork reversal but, if allowed to persist, leads to extensive R-loop-independent DNA breakage during S-phase. Our work reveals a link between oxidative stress and transcription-replication interference that causes genomic alterations recurrently found in human cancer.
  • Effect of Ajwa date pits powder (Phoenix dactylifera L.) on body composition, lipid profile and blood pressure in patients with hyperlipidemia: a randomized clinical trial

    Nasrullah, Parkha Riaz; Sehar, Bismillah; Safdar, Mahpara; Fatima, Sadia; Zeb, Falak; Shah, Jahan; Khalil, Atif Ali Khan; Ahmed, Bilal; Alsubaie, Ali Saad R.; Zaman, Muhammad Haidar; et al. (Mashhad University of Medical Sciences, 2023-04-30)
    Objective: To evaluate the effect of Ajwa dates pit powder (ADP) on lipid profile, body composition and blood pressure in patients with hyperlipidemia. Materials and Methods: This randomized controlled clinical study was carried out on 40 patients with total cholesterol >200 mg/dl, triglycerides >150 mg/dl and BMI >25, of either sex, aged 30-50 years, who were recruited through written consent. The patients were divided into two groups (n=20 each): the ADP and the control group (CG). All patients received the doctor’s prescribed class A statin (Rosuvastatin/ Atorvastatin) 10 mg/day, while 2.7 g ADP was given on daily basis before breakfast with lukewarm water for 40 days and the control group received the same amount of wheat flour. Body composition, blood pressure and lipid profile were determined at baseline, and after 20 and 40 days. Data were analyzed by using SPSS and GraphPad Prism. Results: ADP significantly reduced body weight (p<0.001), BMI (p<0.001), fat mass, body fat percentage, visceral fat area and waist circumference compared to the control group. Similarly, ADP significantly (p=0.000) decreased the serum level of total cholesterol and low-density lipoprotein. Conclusion: ADP may have the potential to improve dyslipidemia and obesity.
  • A knowledge empowered explainable gene ontology fingerprint approach to improve gene functional explication and prediction.

    Wang, Ying; Zong, Hui; Yang, Fan; Tong, Yuantao; Xie, Yujia; Zhang, Zeyu; Huang, Honglian; Zheng, Rongbin; Wang, Shuangkuai; Huang, Danqi; et al. (Cell Press, 2023-03-07)
    Functional explication of genes is of great scientific value. However, conventional methods have challenges for those genes thatmay affect biological processes but are not annotated in public databases. Here, we developed a novel explainable gene ontology fingerprint (XGOF) method to automatically produce knowledge networks on biomedical literature in a given field which quantitatively characterizes the association between genes and ontologies. XGOF provides systematic knowledge for the potential function of genes and ontologically compares similarities and discrepancies in different disease-XGOFs integrating omics data. More importantly, XGOF can not only help to infer major cellular components in a disease microenvironment but also reveal novel gene panels or functions for in-depth experimental research where few explicit connections to diseases have previously been described in the literature. The reliability of XGOF is validated in four application scenarios, indicating a unique perspective of integrating text and data mining, with the potential to accelerate scientific discovery.
  • A deep learning workflow for quantification of micronuclei in DNA damage studies in cultured cancer cell lines: a proof of principle investigation.

    Panchbhai, Anand; Savash Ishanzadeh, Munuse C.; Sidali, Ahmed; Solaiman, Nadeen Shaikh; Pankanti, Smarana; Kanagaraj, Radhakrishnan; Murphy, John J.; Surendranath, Kalpana; Indian Institute of Technology Bhilai; University of Westminster; et al. (Elsevier, 2023-02-26)
    The cytokinesis block micronucleus assay is widely used for measuring/scoring/counting micronuclei, a marker of genome instability in cultured and primary cells. Though a gold standard method, this is a laborious and time-consuming process with person-to-person variation observed in quantification of micronuclei. We report in this study the utilisation of a new deep learning workflow for detection of micronuclei in DAPI stained nuclear images. The proposed deep learning framework achieved an average precision of >90% in detection of micronuclei. This proof of principle investigation in a DNA damage studies laboratory supports the idea of deploying AI powered tools in a cost-effective manner for repetitive and laborious tasks with relevant computational expertise. These systems will also help improving the quality of data and wellbeing of researchers.
  • GEN1 promotes common fragile site expression

    Benitez, Anaid; Sebald, Marie; Kanagaraj, Radhakrishnan; Rodrigo-Brenni, Monica C. R; Chan, Ying Wai; Liang, Chih-Chao; West, Stephen C; Francis Crick Institute; University of Westminster; University of Bedfordshire; et al. (Cell Press, 2023-01-31)
    Our genomes harbor conserved DNA sequences, known as common fragile sites (CFSs), that are difficult to replicate and correspond to regions of genome instability. Following replication stress, CFS loci give rise to breaks or gaps (termed CFS expression) where under-replicated DNA subsequently undergoes mitotic DNA synthesis (MiDAS). We show that loss of the structure-selective endonuclease GEN1 reduces CFS expression, leading to defects in MiDAS, ultrafine anaphase bridge formation, and DNA damage in the ensuing cell cycle due to aberrant chromosome segregation. GEN1 knockout cells also exhibit an elevated frequency of bichromatid constrictions consistent with the presence of unresolved regions of under-replicated DNA. Previously, the role of GEN1 was thought to be restricted to the nucleolytic resolution of recombination intermediates. However, its ability to cleave under-replicated DNA at CFS loci indicates that GEN1 plays a dual role resolving both DNA replication and recombination intermediates before chromosome segregation.
  • Repeat-sequence turnover shifts fundamentally in species with large genomes

    Novák, Petr; Guignard, Maite S.; Neumann, Pavel; Kelly, Laura J.; Mlinarec, Jelena; Koblížková, Andrea; Dodsworth, Steven; Kovařík, Aleš; Pellicer, Jaume; Wang, Wencai; et al. (Nature Research, 2020-10-19)
    Given the 2,400-fold range of genome sizes (0.06–148.9 Gbp (gigabase pair)) of seed plants (angiosperms and gymnosperms) with a broadly similar gene content (amounting to approximately 0.03 Gbp), the repeat-sequence content of the genome might be expected to increase with genome size, resulting in the largest genomes consisting almost entirely of repetitive sequences. Here we test this prediction, using the same bioinformatic approach for 101 species to ensure consistency in what constitutes a repeat. We reveal a fundamental change in repeat turnover in genomes above around 10 Gbp, such that species with the largest genomes are only about 55% repetitive. Given that genome size influences many plant traits, habits and life strategies, this fundamental shift in repeat dynamics is likely to affect the evolutionary trajectory of species lineages.

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