bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-κB Decoy ODN-Loaded Poly lactic-co-glycolic Acid Nanospheres Inhibit Alveolar Ridge Resorption
Authors: Huang Albert Chun Shuo , Ishida Yuji , Li Kai , Rintanalert Duantawan , Hatano-sato Kasumi , Oishi Shuji , Hosomichi Jun , Usumi-Fujita Risa , Yamaguchi Hiroyuki , Tsujimoto Hiroyuki , Sasai Aiko , Ochi Ayaka , Watanabe Hajime , Ono Takashi 
Published: September 2022

AbstractResidual ridge resorption combined with dimensional loss resulting from tooth extraction has a prolonged correlation with early excessive inflammation. Nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotide (ODN) is a member of a group of double-stranded DNA capable of downregulating the expression of downstream genes of the NF-κB pathway. The healing action of its embellished effect combined with poly(lactic-co-glycolic acid) (PLGA) nanospheres on tooth extraction socket still remains unknown. Hence, the aim of this study was to investigate the therapeutic effect of NF-κB decoy ODN-loaded PLGA nanospheres (PLGA-NfD) transfected into extraction sockets in Wistar/ST rats. Micro-computed tomography and trabecular bone analysis following treatment with PLGA-NfD demonstrated inhibition of vertical alveolar bone loss with increased bone volume, smoother trabecular bone surface, thicker trabecular bone, larger trabecular number and separation, and fewer bone porosities. Histomorphometric and reverse transcription-quantitative polymerase chain reaction analysis revealed reduced tartrate-resistant acid phosphatase-expressing osteoclasts, interleukin-1β, tumor necrosis factor-α, receptor activator of NF-κB ligand, turnover rate and increased transforming growth factor-β1 immunopositive reactions and relative gene expressions. These data demonstrate that local delivery of PLGA-NfD could be used as a substantial suppressor of inflammation during the healing process in a tooth extraction socket, with the potential of accelerated new bone formation.
Honeybees vary communication and collective decision making across landscapes
Authors: Palmer Joseph , Samuelson Ash E. , Gill Richard J. , Leadbeater Ellouise , Jansen Vincent A.A. 
Published: September 2022

AbstractHoneybee (Apis mellifera) colony foraging decisions arise from the waggle dances of individual foragers, processed and filtered through a series of feedback loops that produce emergent collective behaviour. This process is an example of animal communication at the height of eusociality, yet a growing body of evidence suggests that its value for colony foraging success is heavily dependent on local ecology. Although colonies are thought to vary their use of the waggle dance in response to local ecological conditions, this is yet to be empirically established. Here, we quantify waggle dance use based on colony level dance-decoding and show that the impact of dance use on collective foraging is clear in some colonies but nearly negligible in others. We outline how these estimates of dance use can be combined with land-use data to explore the landscape characteristics that drive collective foraging. Our methodology provides a means to quantify the real-world importance of a celebrated example of animal communication and opens the door to the exploration of the selection pressures that may have driven the evolution of this remarkable collective behaviour.
Kmer-Node2Vec: a Fast and Efficient Method for Kmer Embedding from the Kmer Co-occurrence Graph, with Applications to DNA Sequences
Authors: Yu Zhaochong , Yang Zihang , Lan Qingyang , Wang Yuchuan , Huang Feijuan , Cai Yuanzhe 
Published: September 2022

AbstractLearning low-dimensional continuous vector representation for short k-mers divided from long DNA sequences is key to DNA sequence modeling that can be utilized in many bioinformatics investigations, such as DNA sequence classification and retrieval. DNA2Vec is the most widely used method for DNA sequence embedding. However, it poorly scales to large data sets due to its extremely long training time in kmer embedding. In this paper, we propose a novel efficient graph-based kmer embedding method, named Kmer-Node2Vec, to tackle this concern. Our method converts the large DNA corpus into one kmer co-occurrence graph and extracts kmer relation on the graph by random walks to learn fast and high-quality kmer embedding. Extensive experiments show that our method is faster than DNA2Vec by 29 times for training on a 4GB data set, and on par with DNA2Vec in terms of task-specific accuracy of sequence retrieval and classification.
HADEG: A Curated Hydrocarbon Aerobic Degradation Enzymes and Genes Database
Authors: Rojas-Vargas Jorge , Castelán-Sánchez Hugo G. , Pardo-López Liliana 
Published: September 2022

ABSTRACTDatabases of genes and enzymes involved in hydrocarbon degradation have been previously reported. However, these databases specialize on only a specific group of hydrocarbons and/or are constructed partly based on enzyme sequences with putative functions indicated byin silicoresearch, with no experimental evidence. Here, we present a curated database of Hydrocarbon Aerobic Degradation Enzymes and Genes (HADEG) containing proteins and genes involved in alkane, alkene, aromatic, and plastic aerobic degradation and biosurfactant production based solely on experimental evidence, which are present in bacteria, and fungi. HADEG includes 259 proteins for petroleum hydrocarbon degradation, 160 for plastic degradation, and 32 for biosurfactant production. This database will help identify and predict hydrocarbon degradation genes/pathways and biosurfactant production in genomes.Graphical abstractData summaryThe HADEG database repository ishttps://github.com/jarojasva/HADEG. All Supplementary Material file is available on:https://figshare.com/articles/dataset/Supplementary_Material_HADEG/20752642.
The cancer-associated RBM39 bridges the pre-mRNA, U1 and U2 snRNPs to regulate alternative splicing
Authors: Campagne Sébastien , Jutzi Daniel , Malard Florian , Matoga Maja , Romane Ksenija , Feldmuller Miki , Colombo Martino , Ruepp Marc-David , Allain Frédéric H-T. 
Published: August 2022

SummaryPharmacologic depletion of RNA-binding motif 39 (RBM39) using aryl sulfonamides represents a promising anti-cancer therapy. However, its efficiency correlates with the expression level of DCAF15 which acts at the interface between RBM39, the drug and the E3-ubiquitin ligase. Consequently, the identification of alternative approaches to deplete RBM39 independently of DCAF15 is required. Here, we combined transcriptomic analysis, functional assays, and structural biology to elucidate the molecular mechanisms governing RBM39 homeostasis. Our data revealed that RBM39 autoregulates the splicing of its own pre-mRNA by triggering the inclusion of a poison exon. During this process, RBM39 selects the 3’-splice site of the toxic exon, helps the recruitment of U1 snRNP on its weak 5’-splice site and bridges the 3’-splice site recognition machinery. The elucidation of the molecular mechanisms controlling RBM39 homeostasis provides unprecedented insights into alternative 3’-splice site selection and a solid frame to design alternative anti-cancer therapies.
Chitosan diet alters the microbiome of adult house flies
Authors: Schaal Hila , Choudoir Mallory J. , Diwanji Vedang , Stoffolano John , DeAngelis Kristen M. 
Published: September 2022

AbstractHouse flies are disease vectors, carrying human pathogens which include Escherichia coli and Vibrio cholera. To explore the use of chitosan as a bioinsecticide, we evaluated the effects of a chitosan-amended diet on Musca domestica (house fly). We first conducted longevity experiments to understand the impact of chitosan on house fly longevity. We confirmed that chitosan diet amendment is associated with reduced longevity and that this is not due to starvation. We then extracted fly microbiome DNA and used 16S ribosomal RNA gene amplicon sequencing and quantitative PCR to assess the composition and load of the microbiome for flies fed chitosan-amended diets compared to controls. Diversity of the chitosan-fed fly microbiomes was lower than the control, with significant dissimilarities in community composition. Chitosan-fed flies showed lower Ralstonia relative abundance but increased relative abundance of Serratia. Both control and chitosan-fed flies had highly uneven communities, but the control flies were dominated by genera Ralstonia and Providencia, while the chitosan-fed flies were dominated by genera Serratia, Kosakonia, and Providencia. Contrary to our expected results, chitosan-fed flies also contained 56% more bacteria compared to controls. Gut microbiome changes appear to result from chitinolytic bacteria becoming more relatively abundant, and our results suggest that chitosan-amended diet alters the house fly microbiome resulting in higher fly mortality.
Plasmodium falciparum CRK4 links early mitotic events to the onset of S-phase during schizogony
Authors: Machado Marta , Klaus Severina , Klaschka Darius , Guizetti Julien , Ganter Markus 
Published: September 2022

AbstractPlasmodium falciparum proliferates through schizogony in the clinically relevant blood stage of infection. During schizogony, consecutive rounds of DNA replication and nuclear division give rise to multinucleated stages before cellularization occurs. Although these nuclei reside in a shared cytoplasm, DNA replication and nuclear division occur asynchronously. Here, by mapping the proteomic context of the S-phase-promoting kinase PfCRK4, we show that it has a dual role for nuclear-cycle progression: PfCRK4 orchestrates not only DNA replication, but also the rearrangement of intranuclear microtubules. Live-cell imaging of a reporter parasite showed that these microtubule rearrangements coincide with the onset of DNA replication. Together, our data render PfCRK4 the key factor for nuclear-cycle progression, linking entry into S-phase with the initiation of mitotic events. In part, such links may compensate for the absence of canonical cell cycle checkpoints in P. falciparum.
BNIP3L-mediated mitophagy triggered by Brucella in host cells is required for bacterial egress
Authors: Verbeke Jérémy , Fayt Youri , Martin Lisa , Yilmaz Oya , Sedzicki Jaroslaw , Reboul Angeline , Jadot Michel , Renard Patricia , Dehio Christoph , Renard Henri-François , Letesson Jean-Jacques , De Bolle Xavier , Arnould Thierry 
Published: September 2022

ABSTRACTThe facultative intracellular pathogen Brucella abortus interacts with several organelles of the host cell to reach its replicative niche inside the endoplasmic reticulum. However, little is known about the interplay between the bacteria and the host cell mitochondria. Here, we showed that B. abortus triggers a strong mitochondrial network fragmentation accompanied by mitophagy and the formation of mitochondrial Brucella-containing vacuoles in the late steps of cellular infection. The expression of the mitophagy receptor BNIP3L induced by B. abortus is essential for these events and relies on the iron-dependent stabilization of the hypoxia-inducible factor 1 alpha. Functionally, BNIP3L-mediated mitophagy appears to be advantageous for bacterial exit of the host cell as BNIP3L depletion drastically reduced the number of reinfection events. Altogether, these findings highlight the intricate link between Brucella trafficking and the mitochondria during host cell infection.
Mapping mitonuclear epistasis using a novel recombinant yeast population
Authors: Nguyen Tuc H.M. , Tinz-Burdick Austen , Lenhardt Meghan , Geertz Margaret , Ramirez Franchesca , Schwartz Mark , Toledano Michael , Bonney Brooke , Gaebler Benjamin , Liu Weiwei , Wolters John F. , Chiu Ken , Fiumera Anthony C. , Fiumera Heather L. 
Published: September 2022

AbstractNatural genetic variation in mitochondrial and nuclear genomes can influence phenotypes by perturbing coadapted mitonuclear interactions. Mitonuclear epistasis, i.e. non-additive phenotype effects of interacting mitochondrial and nuclear alleles, is emerging as a general feature in eukaryotes, yet very few mitonuclear loci have been identified. Here, we present a novel advanced intercrossed population of S. cerevisiae yeasts, called the Mitonuclear Recombinant Collection (MNRC), designed explicitly for detecting mitonuclear loci contributing to complex traits, and use this population to map the genetic basis to mtDNA loss. In yeast, spontaneous deletions within mtDNAs lead to the petite phenotype that heralded mitochondrial research. We show that in natural populations, rates of petite formation are variable and influenced by genetic variation in nuclear, mtDNAs and mitonuclear interactions. We then mapped nuclear and mitonuclear alleles contributing mtDNA stability using the MNRC by integrating mitonuclear epistasis into a genome-wide association model. We found that associated mitonuclear loci play roles in mitotic growth most likely responding to retrograde signals from mitochondria, while associated nuclear loci with main effects are involved in genome replication. We observed a positive correlation between growth rates and petite frequencies, suggesting a fitness tradeoff between mitotic growth and mtDNA stability. We also found that mtDNA stability was influenced by a mobile mitochondrial GC-cluster that is expanding in certain populations of yeast and that selection for nuclear alleles that stabilize mtDNA may be rapidly occurring. The MNRC provides a powerful tool for identifying mitonuclear interacting loci that will help us to better understand genotype-phenotype relationships and coevolutionary trajectories.Author SummaryGenetic variation in mitochondrial and nuclear genomes can perturb mitonuclear interactions and lead to phenotypic differences between individuals and populations. Despite their importance to most complex traits, it has been difficult to identify the interacting loci. Here, we created a novel population of yeast designed explicitly for mapping mitonuclear loci contributing to complex traits and used this population to map genes influencing the stability of mitochondrial DNA (mtDNA). We found that mitonuclear interacting loci were involved in mitotic growth while non-interacting loci were involved in genome replication. We also found evidence that selection for mitonuclear loci that stabilize mtDNAs occurs rapidly. This work provides insight into mechanisms underlying maintenance of mtDNAs. The mapping population presented here is an important new resource that will help to understand genotype/phenotype relationships and coevolutionary trajectories.
Transcriptional response of circadian clock genes to an ‘artificial light at night’ pulse in the cricketGryllus bimaculatus
Authors: Levy Keren , Fishman Bettina , Barnea Anat , Ayali Amir , Tauber Eran 
Published: September 2022

ABSTRACTLight is the major signal entraining the circadian clock that regulates physiological and behavioral rhythms in most organisms, including insects. Artificial Light at Night (ALAN) disrupts the natural light-dark cycle and negatively impacts animals at various levels. We simulated ALAN using dim light stimuli and tested their impact on gene expression in the cricketGryllus bimaculatus, a model of insect physiology and chronobiology. At night, adult LD crickets were exposed for 30 minutes to a light pulse of 2-40 lx. The relative expression of five circadian clock associated genes was compared using qPCR. A dim ALAN pulse elicited tissue-dependent differential expression in some of these genes. The strongest effect was observed in the brain and in the optic lobe, the cricket’s circadian pacemaker. Expression ofopsin-Long Wave(opLW)was upregulated, as well ascryptochrome1-2 (cry), andperiod(per). Our findings demonstrate that even a dim ALAN exposure may affect insects at the molecular level, underscoring the detrimental impact of ALAN on the circadian clock system.
Genetic control of RNA editing in Neurodegenerative disease
Authors: Wu Sijia , Xue Qiuping , Yang Mengyuan , Wang Yanfei , Kim Pora , Zhou Xiaobo , Huang Liyu 
Published: September 2022

ABSTRACTA-to-I RNA editing diversifies human transcriptome to confer its functional effects on the downstream genes or regulations, potentially involving in neurodegenerative pathogenesis. Its variabilities are attributed to multiple regulators, including the key factor of genetic variant. To comprehensively investigate the potentials of neurodegenerative disease-susceptibility variants from the view of A-to-I RNA editing, we analyzed matched genetic and transcriptomic data of 1,596 samples across nine brain tissues and whole blood from two large consortiums, Accelerating Medicines Partnership - Alzheimer’s Disease (AMP-AD) and Parkinson’s Progression Markers Initiative (PPMI). The large-scale and genome-wide identification of 95,637 RNA editing quantitative trait loci revealed the preferred genetic effects on adjacent editing events. Furthermore, to explore the underlying mechanisms of the genetic controls of A-to-I RNA editing, several top RNA binding proteins were pointed out, such as EIF4A3, U2AF2, NOP58, FBL, NOP56, and DHX9, since their regulations on multiple RNA editing events probably interfered by these genetic variants. Moreover, these variants may also contribute to the variability of other molecular phenotypes associated with RNA editing, including the functions of four proteins, expressions of 148 genes, and splicing of 417 events. All the analyses results shown in NeuroEdQTL (https://relab.xidian.edu.cn/NeuroEdQTL/) constituted a unique resource for the understanding of neurodegenerative pathogenesis from genotypes to phenotypes related to A-to-I RNA editing.
Physical association of low density lipoprotein particles and extracellular vesicles unveiled by single particle analysis
Authors: Lozano-Andrés Estefanía , Enciso-Martinez Agustin , Gijsbers Abril , Libregts Sten F.W.M. , Pinheiro Cláudio , Van Niel Guillaume , Hendrix An , Peters Peter J. , Otto Cees , Arkesteijn Ger J.A. , Wauben Marca H.M. 
Published: September 2022

AbstractExtracellular vesicles (EVs) in blood plasma are recognized as potential biomarkers for disease. Although blood plasma is easily obtainable, analysis of EVs at the single particle level is still challenging due to the biological complexity of this body fluid. Besides EVs, plasma contains different types of lipoproteins particles (LPPs), that outnumber EVs by orders of magnitude and which partially overlap in biophysical properties such as size, density and molecular makeup. Consequently, during EV isolation LPPs are often co-isolated. Furthermore, physical EV-LPP complexes have been observed in purified EV preparations. Since co-isolation or association of LPPs can impact single EV-based analysis and biomarker profiling, we investigated whether under physiological conditions LPPs and EVs can associate by using cryo-electron tomography, label-free synchronous Rayleigh and Raman scattering analysis of optically trapped particles and fluorescence-based high resolution single particle flow cytometric analysis. Furthermore, we evaluated the impact on flow cytometric analysis in the absence or presence of different types of LPPs usingin vitrospike-in experiments of purified tumor cell line-derived EVs in different classes of purified human LPPs. Based on orthogonal single-particle analysis techniques we demonstrated that EV-LPP complexes can form under physiological conditions. Furthermore, we show that in fluorescence-based flow cytometric EV analysis staining of LPPs, as well as EV-LPP associations can influence EV analysis in a quantitative and qualitative manner. Our findings demonstrate that the biological colloidal matrix of the biofluid in which EVs reside impacts their buoyant density, size and/or refractive index (RI), which may have consequences for down-stream EV analysis.
NRF2 activation induces NADH-reductive stress providing a metabolic vulnerability in lung cancer
Authors: Weiss-Sadan Tommy , Ge Maolin , de Groot Addriaan , Carlin Alexander , Gohar Magdy , Fischer Hannah , Shi Lei , Wei Ting-Yu , Adelmann Charles H. , Vornbäumen Tristan , Dürr Benedkit R. , Takahashi Mariko , Richter Marianne , Zhang Junbing , Yang Tzu-Yi , Vijay Vindhya , Hayashi Makiko , Fischer David E. , Hata Aaron N. , Papaginanakopoulos Thales , Mostoslavsky Raul , Bardeesy Nabeel , Bar-Peled Liron 
Published: September 2022

AbstractMultiple cancers regulate oxidative stress by activating the transcription factor NRF2 through mutation of its negative regulator KEAP1. NRF2 has been studied extensively in KEAP1-mutant cancers, however the role of this pathway in cancers with wildtype KEAP1 remains poorly understood. To answer this question, we induced NRF2 via pharmacological inactivation of KEAP1 in a panel of 50+ non-small lung cancer cell lines. Unexpectedly, marked decreases in viability were observed in >13% of the cell lines—an effect that was completely rescued by NRF2 ablation. Genome-wide and targeted CRISPR screens revealed that NRF2 induces NADH-reductive stress, through the upregulation of the NAD+-consuming enzyme ALDH3A1. Leveraging these findings, we show that cells treated with KEAP1 inhibitors or those with endogenous KEAP1 mutations are selectively vulnerable to Complex I inhibition, which impairs NADH oxidation capacity and potentiates reductive stress. Thus, we identify reductive stress as a metabolic vulnerability in NRF2-activated lung cancers.