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Wellcome Open Research 2023We present a genome assembly from an individual male (hoverfly, Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence is 523.3 megabases in span. Most of the...
We present a genome assembly from an individual male (hoverfly, Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence is 523.3 megabases in span. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.24 kilobases in length.
PubMed: 38938786
DOI: 10.12688/wellcomeopenres.19622.1 -
Frontiers in Pediatrics 2024The mitochondrion is a multifunctional organelle that modulates multiple systems critical for homeostasis during pathophysiological stress. Variation in mitochondrial...
The mitochondrion is a multifunctional organelle that modulates multiple systems critical for homeostasis during pathophysiological stress. Variation in mitochondrial DNA (mtDNA) copy number (mtDNAcn), a key mitochondrial change associated with chronic stress, is an emerging biomarker for disease pathology and progression. mtDNAcn can be quantified from whole blood samples using qPCR to determine the ratio of mtDNA to nuclear DNA. However, the collection of blood samples in pediatric populations, particularly in infants and young children, can be technically challenging, yield much smaller volume samples, and can be distressing for the patients and their caregivers. Therefore, we have validated a mtDNAcn assay utilizing DNA from simple buccal swabs (Isohelix SK-2S) and report here it's performance in specimens from infants (age = <12 months). Utilizing qPCR to amplify ∼200 bp regions from two mitochondrial () and two nuclear () genes, we demonstrated absolute (100%) concordance with results from low-pass whole genome sequencing (lpWGS). We believe that this method overcomes key obstacles to measuring mtDNAcn in pediatric populations and creates the possibility for development of clinical assays to measure mitochondrial change during pathophysiological stress.
PubMed: 38938506
DOI: 10.3389/fped.2024.1401737 -
Animal Bioscience Jun 2024Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the...
OBJECTIVE
Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear.
METHODS
In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine CSO22 (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine CSO22 (pVAX-asd) orally.
RESULTS
The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p < 0.05). SS-14 DNA vaccine immunisation resulted in significantly higher concentrations of growth-related hormones such as GH-releasing hormone and IGF-1 in the serum of goats (p < 0.05). RNA-seq analysis of hypothalamus of oral SS-14 DNA vaccine and negative control DBGs identified 31 differentially expressed genes (DEGs). Pituitary gland identified 164 DEGs. A total of 246 DEGs were detected in the liver by RNA-seq. Gene ontology (GO) of DEGs was enriched in mitochondrial envelope, extracellular region, receptor binding and cell proliferation. The biological metabolic pathways associated with DEGs were explored by Kyoto Encyclopedia of Genes and Genomes analysis. DEGs were associated with metabolic pathways, oxidative phosphorylation, vitamin digestion and absorption and galactose metabolism. These candidate genes (e.g. DGKK, CYTB, DUSP1 and LRAT) may provide references for exploring the molecular mechanisms by which SS promotes growth and development.
CONCLUSION
Overall, these results demonstrated that the SS DNA vaccine enhanced the growth of DBGs by altering growth-related hormone concentrations and regulating the expression of growth-related genes in the hypothalamic-pituitary-liver axis.
PubMed: 38938026
DOI: 10.5713/ab.24.0121 -
Journal of Biophotonics Jun 2024Photobiomodulation (PBM) using 460 nm blue light has been shown to have an inhibitory effect on skin cancer cells. In this study, we used a continuous LED light source...
Photobiomodulation (PBM) using 460 nm blue light has been shown to have an inhibitory effect on skin cancer cells. In this study, we used a continuous LED light source with a wavelength of 460 nm and designed various combinations of power density (ranging from 6.4 to 25.6 mW) and dose (ranging from 0.96 to 30.72 J/cm) to conduct treatment experiments on MeWo cells to investigate the effects of blue light on MeWo melanoma cells. We are focusing on cell viability, cytotoxicity, mitochondrial function, oxidative stress, and apoptosis. We found that blue light inhibits these melanoma cells through oxidative stress and DNA damage, and this inhibition intensifies at higher irradiance levels. Although the cells initially attempt to resist the stress induced by the treatment, they eventually undergo apoptosis over time. These findings contribute to understanding melanoma's molecular response to blue light PBM, lay the groundwork for future clinical applications.
PubMed: 38937982
DOI: 10.1002/jbio.202400071 -
Journal of Experimental & Clinical... Jun 2024Triple-negative breast cancer (TNBC) is characterized by its high metastatic potential, which results in poor patient survival. Cancer-associated fibroblasts (CAFs) are...
BACKGROUND
Triple-negative breast cancer (TNBC) is characterized by its high metastatic potential, which results in poor patient survival. Cancer-associated fibroblasts (CAFs) are crucial in facilitating TNBC metastasis via induction of mitochondrial biogenesis. However, how to inhibit CAF-conferred mitochondrial biogenesis is still needed to explore.
METHODS
We investigated metastasis using wound healing and cell invasion assays, 3D-culture, anoikis detection, and NOD/SCID mice. Mitochondrial biogenesis was detected by MitoTracker green FM staining, quantification of mitochondrial DNA levels, and blue-native polyacrylamide gel electrophoresis. The expression, transcription, and phosphorylation of peroxisome-proliferator activated receptor coactivator 1α (PGC-1α) were detected by western blotting, chromatin immunoprecipitation, dual-luciferase reporter assay, quantitative polymerase chain reaction, immunoprecipitation, and liquid chromatography-tandem mass spectrometry. The prognostic role of PGC-1α in TNBC was evaluated using the Kaplan-Meier plotter database and clinical breast cancer tissue samples.
RESULTS
We demonstrated that PGC-1α indicated lymph node metastasis, tumor thrombus formation, and poor survival in TNBC patients, and it was induced by CAFs, which functioned as an inducer of mitochondrial biogenesis and metastasis in TNBC. Shikonin impeded the CAF-induced PGC-1α expression, nuclear localization, and interaction with estrogen-related receptor alpha (ERRα), thereby inhibiting PGC-1α/ERRα-targeted mitochondrial genes. Mechanistically, the downregulation of PGC-1α was mediated by synthase kinase 3β-induced phosphorylation of PGC-1α at Thr295, which associated with neural precursor cell expressed developmentally downregulated 4e1 recognition and subsequent degradation by ubiquitin proteolysis. Mutation of PGC-1α at Thr295 negated the suppressive effects of shikonin on CAF-stimulated TNBC mitochondrial biogenesis and metastasis in vitro and in vivo.
CONCLUSIONS
Our findings indicate that PGC-1α is a viable target for blocking TNBC metastasis by disrupting mitochondrial biogenesis, and that shikonin merits potential for treatment of TNBC metastasis as an inhibitor of mitochondrial biogenesis through targeting PGC-1α.
Topics: Humans; Triple Negative Breast Neoplasms; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Mice; Animals; Organelle Biogenesis; Phosphorylation; Glycogen Synthase Kinase 3 beta; Naphthoquinones; Female; Cancer-Associated Fibroblasts; Cell Line, Tumor; Mice, SCID; Neoplasm Metastasis; Mice, Inbred NOD; Mitochondria; Xenograft Model Antitumor Assays
PubMed: 38937832
DOI: 10.1186/s13046-024-03101-z -
BMC Plant Biology Jun 2024Caryodaphnopsis, a group of tropical trees (ca. 20 spp.) in the family Lauraceae, has an amphi-Pacific disjunct distribution: ten species are distributed in Southeast...
BACKGROUND
Caryodaphnopsis, a group of tropical trees (ca. 20 spp.) in the family Lauraceae, has an amphi-Pacific disjunct distribution: ten species are distributed in Southeast Asia, while eight species are restricted to tropical rainforests in South America. Previously, phylogenetic analyses using two nuclear markers resolved the relationships among the five species from Latin America. However, the phylogenetic relationships between the species in Asia remain poorly known.
RESULTS
Here, we first determined the complete mitochondrial genome (mitogenome), plastome, and the nuclear ribosomal cistron (nrDNA) sequences of C. henryi with lengths of 1,168,029 bp, 154,938 bp, and 6495 bp, respectively. We found 2233 repeats and 368 potential SSRs in the mitogenome of C. henryi and 50 homologous DNA fragments between its mitogenome and plastome. Gene synteny analysis revealed a mass of rearrangements in the mitogenomes of Magnolia biondii, Hernandia nymphaeifolia, and C. henryi and only six conserved clustered genes among them. In order to reconstruct relationships for the ten Caryodaphnopsis species in Asia, we created three datasets: one for the mitogenome (coding genes and ten intergenic regions), another for the plastome (whole genome), and the other for the nuclear ribosomal cistron. All of the 22 Caryodaphnopsis individuals were divided into four, five, and six different clades in the phylogenies based on mitogenome, plastome, and nrDNA datasets, respectively.
CONCLUSIONS
The study showed phylogenetic conflicts within and between nuclear and organellar genome data of Caryodaphnopsis species. The sympatric Caryodaphnopsis species in Hekou and Malipo SW China may be related to the incomplete lineage sorting, chloroplast capture, and/or hybridization, which mixed the species as a complex in their evolutionary history.
Topics: Phylogeny; Genome, Mitochondrial; Lauraceae; Genome, Plant
PubMed: 38937691
DOI: 10.1186/s12870-024-05050-3 -
Nature Communications Jun 2024Mitochondrial transcription factor A (TFAM) employs DNA bending to package mitochondrial DNA (mtDNA) into nucleoids and recruit mitochondrial RNA polymerase (POLRMT) at...
Mitochondrial transcription factor A (TFAM) employs DNA bending to package mitochondrial DNA (mtDNA) into nucleoids and recruit mitochondrial RNA polymerase (POLRMT) at specific promoter sites, light strand promoter (LSP) and heavy strand promoter (HSP). Herein, we characterize the conformational dynamics of TFAM on promoter and non-promoter sequences using single-molecule fluorescence resonance energy transfer (smFRET) and single-molecule protein-induced fluorescence enhancement (smPIFE) methods. The DNA-TFAM complexes dynamically transition between partially and fully bent DNA conformational states. The bending/unbending transition rates and bending stability are DNA sequence-dependent-LSP forms the most stable fully bent complex and the non-specific sequence the least, which correlates with the lifetimes and affinities of TFAM with these DNA sequences. By quantifying the dynamic nature of the DNA-TFAM complexes, our study provides insights into how TFAM acts as a multifunctional protein through the DNA bending states to achieve sequence specificity and fidelity in mitochondrial transcription while performing mtDNA packaging.
Topics: DNA-Binding Proteins; Mitochondrial Proteins; Transcription Factors; DNA, Mitochondrial; DNA Packaging; Promoter Regions, Genetic; Fluorescence Resonance Energy Transfer; Humans; Nucleic Acid Conformation; Transcription Initiation, Genetic; Mitochondria; Single Molecule Imaging; DNA-Directed RNA Polymerases; Base Sequence; Protein Binding
PubMed: 38937458
DOI: 10.1038/s41467-024-49728-6 -
Life Sciences Jun 2024Infertility is intricately linked with alterations in circadian rhythms along with physiological decline and stem cell senescence. Yet, the direct involvement of...
Nicotine induces senescence in spermatogonia stem cells by disrupting homeostasis between circadian oscillation and rhythmic mitochondrial dynamics via the SIRT6/Bmal1 pathway.
Infertility is intricately linked with alterations in circadian rhythms along with physiological decline and stem cell senescence. Yet, the direct involvement of circadian mechanisms in nicotine-induced injury to the testes, especially the senescence of spermatogonia stem cells (SSCs), is not well comprehended. This study revealed that nicotine exposure induced testis injury by triggering SSCs senescence along with the upregulation of senescence marker genes and senescence-associated secretory phenotype components. Moreover, nicotine treatment caused mitochondrial hyper-fusion, increased oxidative stress, and DNA damage. Exposure to nicotine was found to suppress the expression of sirtuin 6 (SIRT6), which accelerated the senescence of spermatogonia stem cells (SSCs). This acceleration led to increased acetylation of brain and muscle ARNT-like protein (Bmal1), consequently reducing the expression of Bmal1 protein. Conversely, the overexpression of Bmal1 alleviated mitochondrial hyper-fusion and senescence phenotypes induced by nicotine. Overall, this study unveiled a novel molecular mechanism behind nicotine-induced disorders in spermatogenesis and highlighted the SIRT6/Bmal1 regulatory pathway as a potential therapeutic target for combating nicotine-associated infertility.
PubMed: 38936603
DOI: 10.1016/j.lfs.2024.122860 -
Infection, Genetics and Evolution :... Jun 2024Hydatigera kamiyai (H. kamiyai) is a new species within Hydatigera that has recently been resurrected. Voles and cats are hosts of H. kamiyai and have a certain impact...
Hydatigera kamiyai (H. kamiyai) is a new species within Hydatigera that has recently been resurrected. Voles and cats are hosts of H. kamiyai and have a certain impact on its health and economy. Moreover, the Qinghai-Tibetan plateau (QTP) is a research hotspot representing Earth's biodiversity, as its unique geographical environment and climatic conditions support the growth of a variety of mammals and provide favorable conditions for various parasites to complete their life history. The aim of this study was to reveal the phylogenetic relationships and divergence times of H. kamiyai strains isolated from Neodon fuscus on the QTP using morphological and molecular methods. In this study, we morphologically observed H. kamiyai and sequenced the whole mitochondrial genome. Then, we constructed phylogenetic trees with the maximum likelihood (ML) and Bayesian inference (BI) methods. The GTR alternative model was selected for divergence time analysis. These data demonstrated that the results were consistent with the general morphological characteristics of Hydatigera. The whole genome of H. kamiyai was 13,822 bp in size, and the A + T content (73%) was greater than the G + C content (27%). The Ka/Ks values were all <1, indicating that all 13 protein-coding genes (13 PCGs) underwent purifying selection during the process of evolution. The phylogenetic tree generated based on the 13 PCGs, cytochrom oxidase subunit I (COI), 18S rRNA and 28S rRNA revealed close phylogenetic relationships between H. kamiyai and Hydatigera, with high node support for the relationship. The divergence time based on 13 PCGs indicated that H. kamiyai diverged approximately 11.3 million years ago (Mya) in the Miocene. Interestingly, it diverged later than the period of rapid uplift in the QTP. We also speculated that H. kamiyai differentiation was caused by host differentiation due to the favorable living conditions brought about by the uplift of the QTP. As there have been relatively few investigations on the mitochondrial genome of H. kamiyai, our study could provide factual support for further studies of H. kamiyai on the QTP. We also emphasized the importance of further studies of its hosts, Neodon fuscus and cats, which will be important for further understanding the life cycle of H. kamiyai.
PubMed: 38936527
DOI: 10.1016/j.meegid.2024.105629 -
Biomedicine & Pharmacotherapy =... Jun 2024Deciphering how hesperadin, a repurposed mammalian aurora kinase B inhibitor, affects the cellular pathways in Leishmania donovani might be beneficial. This...
Deciphering how hesperadin, a repurposed mammalian aurora kinase B inhibitor, affects the cellular pathways in Leishmania donovani might be beneficial. This investigation sought to assess the physiological effects of hesperadin on promastigotes of L. donovani, by altering the duration of treatment following exposure to hesperadin. Groups pre-treated with inhibitors such as EGTA, NAC, and z-VAD-fmk before hesperadin exposure were also included. Morphological changes by microscopy, ATP and ROS changes by luminometry; DNA degradation using agarose gel electrophoresis and metacaspase levels through RT-PCR were assessed. Flow cytometry was used to study mitochondrial depolarization using JC-1 and MitoTracker Red; mitochondrial-superoxide accumulation using MitoSOX; plasma membrane modifications using Annexin-V and propidium iodide, and lastly, caspase activation using ApoStat. Significant alterations in promastigote morphology were noted. Caspase activity and mitochondrial-superoxide rose early after exposure whereas mitochondrial membrane potential demonstrated uncharacteristic variations, with significant functional disturbances such as leakage of superoxide radicals after prolonged treatments. ATP depletion and ROS accumulation demonstrated inverse patterns, genomic DNA showed fragmentation and plasma membrane showed Annexin-V binding, soon followed by propidium iodide uptake. Multilobed macronuclei and micronuclei accumulated in hesperadin exposed cells before they disintegrated into necrotic debris. The pathologic alterations were unlike the intrinsic or extrinsic pathways of classical apoptosis and suggest a caspase-mediated cell death most akin to mitotic-catastrophe. Most likely, a G2/M transition block caused accumulation of death signals, disorganized spindles and mechanical stresses, causing changes in morphology, organellar functions and ultimately promastigote death. Thus, death was a consequence of mitotic-arrest followed by ablation of kinetoplast functions, often implicated in L. donovani killing.
PubMed: 38936193
DOI: 10.1016/j.biopha.2024.116960