bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canine Mammary Tumours (CMTs) exploit Mitochondrial Cholesterol for aggressive reprogramming
Authors: Hardy Liana , Kannan Brindha , Rigon Manuel , Benton-Hawthorn Genevieve , L. Previdelli Renato , M. Reichler Iris , Guscetti Franco , P. Kowalewski Mariusz , Campanella Michelangelo 
Published: June 2024

AbstractIn human breast cancer the mitochondrial translocator protein (TSPO) aids pro-survival cellular response by facilitating the formation of mitochondrial contact sites with the nucleus termed Nucleus Associated Mitochondria (NAM). Here, we show that TSPO positively associates with the aggressiveness of tissues and cells isolated from Canine Mammary Tumours (CMTs). TSPO is also readily upregulated in reprogrammed mammary tumour cells following long-term deprivation of oestrogen or exposure to the endocrine chemotherapeutic (ET) agent Tamoxifen. The latter triggers mitochondrial handling of cholesterol which is facilitated by TSPO whose upregulation reduces susceptibility to Tamoxifen. TSPO binding ligands boost, on the other hand, the efficacy of Tamoxifen and Chemotherapy agents. In aggressive canine mammary tumour cells, TSPO repression impairs the NF-kB pattern thus confirming the pro-survival role of the NAM uncovered in the human counterpart.Mitochondrial cholesterol handling via TSPO emerges therefore as a signature in the aggressive reprogramming of CMTs thus advancing our understanding of the molecular mechanisms underpinning this pathology. A novel target mechanism to improve bio-marking and therapeutic protocols is here proposed.
Chromosome-level genome assembly of autotetraploidSelenicereus megalanthusand gaining genomic insights into the evolution of trait patterning in diploid and polyploid pitaya species
Authors: Zaman Qamar U , Hui Liu , Nazir Mian Faisal , Wang Guoqing , Garg Vanika , Ikram Muhammad , Raza Ali , Lv Wei , Khan Darya , Khokhar Aamir Ali , You Zhang , Chitikineni Annapurna , Usman Babar , Jianpeng Cui , Yang Xulong , Zuo Shiyou , Liu Peifeng , Kumar Sunjeet , Guo Mengqi , Zhu Zhi-Xin , Dwivedi Girish , Qin Yong-Hua , Varshney Rajeev K. , Wang Hua-Feng 
Published: June 2024

AbstractYellow pitaya (Selenicereus megalanthus, 2n=4x=44) breeding remains severely hindered due to lacking a reference genome. Here we report yellow pitaya’s high-quality chromosome-level genome assembly and link the phenotypic trait with genomic data, based on Hi-C, ATAC, and RNA-seq data of specific tissues. We declared yellow pitaya as an autotetraploid with a 7.16 Gb genome size (harboring 27,246 high confidence genes) and majorly evolved from diploid ancestors, which remains unknown. Beyond generating the genome assembly, we explored the 3D chromatin organization which revealed insights into the genome, compartments A (648 and 519), compartments B (728 and 1064), topologically associated domains-TADs (3376 and 2031), and varying numbers of structural variations (SVs) in diploid and polyploid pitaya species, respectively. Overall, TAD boundaries were enriched with the motifs ofAP2,WRKY18/60/75,MYB63/116,PHL2, andGATA8in both pitaya species. By linking the open chromatin genomic structure to function, we identified the major changes in betalains biosynthesis pathway in diploid and polyploid pitaya. Moreover, the higher genetic expression ofSmeADH1[Chr11, Compartment A (135400000 - 135500000), genes inside the TAD region (135480000 - 135520000)], and lower expression ofHuDOPA[Chr11, Compartment A (87100000 - 87200000), genes inside the TAD region (87160000-87200000)] acts as a key regulator of yellow and red color on the pericarp of polyploid and diploid pitaya, respectively. In addition, higher expression ofHuCYP76AD1genes in diploid pitaya and lower expression ofSmeCYP76AD1in polyploid pitaya potentially created the difference in the oxidase process that led to the production of betacyanin and betaxanthin, respectively. Furthermore, our results revealed not only the type of motifs that play a potential role in trait patterning but we also further uncovered that motif count in TAD-boundaries may impact the gene expression within the TAD regions of diploid and polyploid pitaya. Our valuable genomic resource and comparison of 3D euchromatin architecture of diploid and polyploid pitaya species will not only aid in the advancement of molecular breeding efforts but also offer insights into the organization of genomes, SVs, compartmentalization (A and B), and TADs, which have the potential to strengthen the idea of TADs-based trait improvement to achieve global food security.
Multiple Targets, One Goal: Compounding life‐extending effects through Polypharmacology
Authors: Avchaciov K. , Clay K. J. , Denisov K. , Burmistrova O. , Petrascheck M. , Fedichev P. 
Published: June 2024

AbstractAnalysis of lifespan‐extending compounds suggested the most effective geroprotectors target multiple biogenic amine receptors. To test this hypothesis, we used graph neural networks to predict such polypharmacological compounds and evaluated them inC. elegans. Over 70% of the selected compounds extended lifespan, with effect sizes in the top 5% compared to the DrugAge database. This reveals that rationally designing polypharmacological compounds enables the design of geroprotectors with exceptional efficacy.Key takeawaysThe most effective known geroprotectors act by polypharmacological mechanisms.Graph neural networks predicted polypharmacological geroprotectors with a hit rate of 70%.The predicted polypharmacological geroprotectors are exceptionally effective.The predicted polypharmacological mechanism was experimentally confirmed.Rationally designing polypharmacological compounds results in geroprotectors with exceptional efficacy.
INCREASED CHLOROPLAST OCCUPANCY IN BUNDLE SHEATH CELLS OF RICEhap3HMUTANTS REVEALED BY CHLORO-COUNT, A NEW DEEP LEARNING-BASED TOOL
Authors: Lambret-Frotte Julia , Buarque de Gusmão Pedro P. , Smith Georgia , Lo Shuen-Fang , Yu Su-May , Hendron Ross W. , Kelly Steven , Langdale Jane A. 
Published: June 2024

SUMMARYThere is an increasing demand to boost photosynthesis in rice to increase yield potential. Chloroplasts are the site of photosynthesis, and increasing the number and size of these organelles in the in leaf is a potential route to elevate leaf-level photosynthetic activity. Notably, bundle sheath cells do not make a significant contribution to overall carbon fixation in rice and thus various attempts are being made to increase chloroplast content in this cell type. In this study we developed and applied a deep learning tool named Chloro-Count to demonstrate that loss ofOsHAP3Hfunction in rice increases chloroplast occupancy in bundle sheath cells by 50%. Although limited to a single season, when grown in the fieldOshap3Hmutants exhibited increased numbers of tillers and panicles as compared to controls or gain of function mutants. The implementation of Chloro-Count enabled precise quantification of chloroplasts in loss- and gain-of-functionOsHAP3Hmutants and facilitated a comparison between 2D and 3D quantification methods. In wild-type rice, as the dimensions of bundle sheath cells increase, the volume of individual chloroplasts also increases. However, the larger the chloroplasts the fewer there are per bundle sheath cell. This observation revealed that a mechanism operates in bundle sheath cells to restrict chloroplast occupancy as cell dimensions increase. That mechanism is unperturbed inOshap3Hmutants. The use of Chloro-Count also revealed that 2D quantification, upon which most previous studies have relied, is compromised by the positioning of chloroplasts within the cell. Chloro-Count is therefore a valuable tool for accurate and high-throughput quantification of chloroplasts that has enabled the robust characterization ofOsHAP3Heffects on chloroplast biogenesis in rice. Whereas previous studies have increased chloroplast occupancy in bundle sheath cells by increasing the size of individual chloroplasts, loss ofOsHAP3Hfunction leads to an increase in chloroplast numbers.
Eco-evolutionary Guided Pathomics Analysis to Predict DCIS Upstaging
Authors: Xiao Yujie , Elmasry Manal , Bai Ji Dong K. , Chen Andrew , Chen Yuzhu , Jackson Brooke , Johnson Joseph O. , Gillies Robert J. , Prasanna Prateek , Chen Chao , Damaghi Mehdi 
Published: June 2024

AbstractCancers evolve in a dynamic ecosystem. Thus, characterizing cancer’s ecological dynamics is crucial to understanding cancer evolution and can lead to discovering novel biomarkers to predict disease progression. Ductal carcinoma in situ (DCIS) is an early-stage breast cancer characterized by abnormal epithelial cell growth confined within the milk ducts. In this study, we show that ecological analysis of hypoxia and acidosis biomarkers can significantly improve prediction of DCIS upstaging. First, we developed a novel eco-evolutionary designed approach to define habitats in the tumor intraductal microenvironment based on oxygen diffusion distance. Then, we identified cancer cells with metabolic phenotypes attributed to their habitats, including CA9 for hypoxia responding phenotype, and LAMP2b for acid adapted phenotype. Traditionally these markers have shown limited predictive capabilities for DCIS progression, if any. However, when analyzed from an ecological perspective, their power to differentiate between non-upstaged and upstaged DCIS increased significantly. Second, we discovered distinct niches with spatial patterns of these biomarkers and used the distribution of such niches to predict patient upstaging. The niches were characterized by pattern analysis of both cellular and spatial features. With a 5-fold validation on the biopsy cohort, we trained a random forest classifier to achieve the area under curve (AUC) of 0.74. Our results affirm the importance of tumor ecological features in eco-evolutionary-designed approaches for novel biomarkers discovery.SignificanceOur results affirm the importance of spatial and ecological features in eco-evolutionary-designed biomarkers discovery studies in the era of digital pathology.
ReducedSH3RF3may protect against Alzheimer’s disease by lowering microglial pro-inflammatory responses via modulation of JNK and NFkB signaling
Authors: Patel Ronak , Cheng Rong , Cardona Christopher L. , Angeles Ellen , Singh Gunjandeep , Miller Sabrina , Ashok Archana , Teich Andrew F. , Piriz Angel , Maldonado Aleyda , Jiménez-Velázquez Ivonne , Mayeux Richard , Lee Joseph H. , Sproul Andrew A. 
Published: June 2024

SummaryUnderstanding how high-risk individuals are protected from Alzheimer’s disease (AD) may illuminate potential therapeutic targets. We identified protective genetic variants inSH3RF3/POSH2that delayed the onset of AD among individuals carrying thePSEN1G206Amutation.SH3RF3acts as a JNK pathway scaffold and activates NFκB signaling. While effects ofSH3RF3knockdown in human neurons were subtle, including decreased ptau S422, knockdown in human microglia significantly reduced inflammatory cytokines in response to either a viral mimic or oAβ42. This was associated with reduced activation of JNK and NFκB pathways in response to these stimuli. Pharmacological inhibition of JNK or NFκB signaling phenocopiedSH3RF3knockdown. We also foundPSEN1G206Amicroglia had reduced inflammatory response to oAβ42. Thus, further reduction of microglial inflammatory responses inPSEN1G206Amutant carriers by protective variants inSH3RF3might reduce the link between amyloid and neuroinflammation to subsequently delay the onset of AD.Graphical Abstract
Recurrent disruption of tumour suppressor genes in cancer by somatic mutations in cleavage and polyadenylation signals
Authors: Kainov Yaroslav , Hamid Fursham , Makeyev Eugene V. 
Published: June 2024

AbstractThe expression of eukaryotic genes relies on the precise 3’-terminal cleavage and polyadenylation of newly synthesized pre-mRNA transcripts. Defects in these processes have been associated with various diseases, including cancer. While cancer-focused sequencing studies have identified numerous driver mutations in protein-coding sequences, noncoding drivers – particularly those affecting the cis-elements required for pre-mRNA cleavage and polyadenylation – have received less attention. Here, we systematically analysed cancer somatic mutations affecting 3’UTR polyadenylation signals using the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset. We found a striking enrichment of cancer-specific somatic mutations that disrupt strong and evolutionarily conserved cleavage and polyadenylation signals within tumour suppressor genes. Further bioinformatics and experimental analyses conducted as a part of our study suggest that these mutations have a profound capacity to downregulate the expression of tumour suppressor genes. Thus, this work uncovers a novel class of noncoding somatic mutations with significant potential to drive cancer progression.
A Host Enzyme Reduces Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) by Inactivating Intestinal Lipopolysaccharide
Authors: Wang Zhiyan , Ojogun Nore , Liu Yiling , Gan Lu , Xiao Zeling , Feng Jintao , Jiang Wei , Chen Yeying , Zou Benkun , Yu Cheng-Yun , Li Changshun , Ashuo Asha , Li Xiaobo , Fu Mingsheng , Wu Jian , Chu Yiwei , Munford Robert , Lu Mingfang 
Published: June 2024

AbstractThe incidence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been increasing world-wide. Since gut-derived bacterial lipopolysaccharides (LPS) can travel via the portal vein to the liver and play an important role in producing hepatic pathology, it seemed possible that (1) LPS stimulates hepatic cells to accumulate lipid, and (2) inactivating LPS can be preventive. Acyloxyacyl hydrolase (AOAH), the eukaryotic lipase that inactivates LPS and oxidized phospholipids, is produced in the intestine, liver, and other organs. We fed mice either normal chow or a high-fat diet for 28 weeks and found thatAoah−/−mice accumulated more hepatic lipid than didAoah+/+mice. In young mice, before increased hepatic fat accumulation was observed,Aoah−/−mouse livers increased their abundance of Sterol Regulatory Element-Binding Protein 1 (SREBP1) and the expression of its target genes that promote fatty acid synthesis.Aoah−/−mice also increased hepatic expression of CD36 and Fabp3, which mediate fatty acid uptake, and decreased expression of fatty acid oxidation-related genes Acot2 and Ppar-α. Our results provide evidence that increasing AOAH abundance in the gut, bloodstream and/or liver may be an effective strategy for preventing or treating MASLD.
Chemical mate choice copying inDrosophila melanogaster
Authors: Mitchell Bloo , Abbott Alexandria , Brown Ashanti , Skinner Lacy , Umarova Elmira , Kohlmeier Philip 
Published: June 2024

AbstractMate choice is a critical decision especially for females that requires time and energy to assess potential partners’ genetic quality. Consequently, in many species, females have evolved the ability to utilize social information by copying the mate choices of others, usually based on visual cues. However, many species, especially invertebrates, primarily rely on chemical not visual cues. Using chemical rather than visual cues provides several advantages such as not requiring active observation of copulations. Despite of that, empirical evidence for the existence of chemical mate choice copying is scarce. UsingDrosophila melanogaster, we provide the first demonstration of chemical mate choice copying. Females exposed to a recently mated select the same male genotype as the teacher female mated with at a higher frequency than expected by chance. Chemical mate choice copying requires sensing both male and female cues, which might indicate that other females have chosen that male genotype. Our work suggests that females, in the presence of mated females, increase choosiness at the virgin stage, elevating sexual selection on male traits. This study provides novel evidence that exploiting social information is more prevalent in flies than previously assumed.
Different resource partitioning explains plant species richness patterns in tropical alpine ecosystems
Authors: Kandziora Martha , Vásquez Diana L. A. , Brochmann Christian , Gizaw Abel , Gustafsson Lovisa , Chala Desalegn , Galbany-Casals Mercè , Kolář Filip , Sklenář Petr , Nürk Nicolai M. , Schmickl Roswitha 
Published: June 2024

AbstractSpecies co-existence based on resource partitioning modulates biodiversity patterns across latitudes and altitudes. Resource partitioning can occur via specialisation or separation in the geographic range or niche. Here, we compare two tropical alpine ecosystems with similar climates to test for geographic range and climatic niche partitioning strategies in explaining species richness difference. We compare the species-rich tropical alpine ecosystem in the South American Andes with the more species-poor one in the eastern African mountains. We combine phylogenomic data for three locally diversified plant lineages in each region with occurrence records and estimate climatic niche and geographic range metrics (size and overlap). We found that the Andean species have overall larger niches than the African species, thus smaller niches indicating specialisation is not the explanation for the higher species richness in the Andes. Instead, for species with overlapping geographic ranges, we found that the Andean species tend to show less niche overlap than the African species, indicating more effective niche separation. Taken together, we propose that different degrees of niche separation in geographically overlapping species, and hence, a different pattern of resource partitioning, explain the differences in species richness between the two tropical alpine ecosystems.
Allopolyploidy enhances survival advantages for urban environments in the native plant genusCommelina
Authors: Shimomai Hina , Taichi Nakata , Katsuhara Koki R. , Kato Seiji , Ushimaru Atushi , Ohmido Nobuko 
Published: June 2024

Background and AimsUrbanization-induced environmental changes have profound effects on the geographical distribution limits in natural plant species. Polyploidization, an influential dynamic genome change, may determine survival potentials of plant species in urban environments. This study focused on the native plants,Commelina communisL. (Cc) and closely related subspecies,C. communisf.ciliata(Masam.) Murata (Ccfc) which have different chromosome numbers (e.g. Cc: 2n = 88, Ccfc: 2n = 46). The aim is to investigate polyploidization effects on natural plant distribution in urban environments.MethodsThe geographical distribution across urban-rural gradients was investigated at a total of 218 sites in Japan. Stomata size and density were measured and compared between Cc and Ccfc. Flow cytometry was used to determine genome size and polyploidy. Chromosome karyotyping was performed by using the GISH method.Key resultsUrban areas were exclusively dominated by Cc, while Cc and Ccfc coexisted in rural areas. Cc had larger and fewer stomata and more than twice genome size than Ccfc. GISH results indicated that Cc possesses Ccfc and another unknown genome, suggesting allopolyploidy.ConclusionsThese results show that the ploidy difference affects the geographical distribution, the stomata traits, and genome size between Cc and Ccfc. In addition, GISH results indicate that Cc has Ccfc and another unknown genome, suggesting Cc is an allopolyploid and these two species of the genusCommelinaare distinct. Therefore, not only polyploid but also allopolyploid contributes to Cc to enhance survival potentials in urban environments compared to Ccfc. This is the first investigation to clarify the distribution difference related to urban environments, the difference in stomata traits and genome size, and to conduct chromosome composition inCommelinaspecies.
RNA-Protein Interaction Prediction without High-Throughput Data: An Overview and Benchmark ofin silicoTools
Authors: Krautwurst Sarah , Lamkiewicz Kevin 
Published: June 2024

AbstractRNA-protein interactions (RPIs) are crucial for accurately operating various processes in and between organisms across kingdoms of life. Mutual detection of RPI partner molecules depends on distinct sequential, structural, or thermodynamic features, which can be determined via experimental and bioinformatic methods. Still, the underlying molecular mechanisms of many RPIs are poorly understood. It is further hypothesized that many RPIs are not even described yet. Computational RPI prediction is continuously challenged by the lack of data and detailed research of very specific examples. With the discovery of novel RPI complexes in all kingdoms of life, adaptations of existing RPI prediction methods are necessary. Continuously improving computational RPI prediction is key in advancing the understanding of RPIs in detail and supplementing experimental RPI determination. The growing amount of data covering more species and detailed mechanisms support the accuracy of prediction tools, which in turn support specific experimental research on RPIs. Here, we give an overview of RPI prediction tools that do not use high-throughput data as the user’s input. We review the tools according to their input, usability, and output. We then apply the tools to known RPI examples across different kingdoms of life. Our comparison shows that the investigated prediction tools do not favor a certain species and equip the user with results varying in degree of information, from an overall RPI score to detailed interacting residues. Furthermore, we provide a guide tree to assist users which RPI prediction tool is appropriate for their available input data and desired output.Contactsarah.krautwurst@uni-jena.de
A system biology-oriented investigation of Arabidopsis proteomes altered in chloroplast biogenesis and retrograde signaling reveals adaptive responses at whole cell level
Authors: Di Silvestre Dario , Jeran Nicolaj , Domingo Guido , Vannini Candida , Marsoni Milena , Fortunato Stefania , de Pinto Maria Concetta , Tamborrino Alberto , Negroni Yuri Luca , Zottini Michela , Hong Lien Tran , Lomagno Andrea , Mauri Pierluigi , Pesaresi Paolo , Tadini Luca 
Published: June 2024

AbstractCommunication across different plant cell compartments relies on an intricate network of molecular interactions, required for the orchestration of organelle development and adaptation to the environment. In this scenario, the Pentatricopeptide Repeat (PPR) Protein GENOMES UNCOUPLED1 (GUN1) plays a key role in transferring information from both developing and mature chloroplasts to the nucleus with the aim to coordinate gene expression between the two genomes. However, its role and the related signaling molecules are still under debate. To help shed light on this matter, we attempted the holistic description ofArabidopsis thalianaproteome upon perturbation of chloroplast biogenesis by lincomycin (Lin), in a genetic context devoid of GUN1-dependent plastid-to-nucleus signaling pathway. Furthermore, the topological analysis of protein-protein interaction (PPI) and protein co-expression networks allowed the identification of protein hubs/bottlenecks characterizing genotypes and conditions, such as proteases, HSPs/Chaperones and redox proteins. Taken together, our findings indicate that GUN1 is required to orchestrate a plastid-located response to plastid protein synthesis inhibition while, in its absence, the reorganization of the activities associated with extra-plastid compartments, such as cytosol, vacuole and mitochondria, prevails. From this landscape, we documented a new role of the Oxygen Evolving Complex subunit PsbO, which appears to be an unconventional photosynthetic protein, as it accumulates in non-photosynthetic plastids and plays a central role in promoting chloroplast breakdown when plastid functions are altered.