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Background: Post-intensive care syndrome (PICS) poses a notable public health concern, with survivors of critical illness experiencing long-term physical, psychological, and cognitive challenges. Mitochondrial dysfunction has gained attention for its potential involvement in PICS. However, the long-term impact of mitochondrial status on patient recovery remains uncertain. A single-centre retrospective analysis was conducted in Leeuwarden, the Netherlands, between May and November 2019, within a mixed ICU survivor cohort. Patients were assessed for mitochondrial markers (mtDNA damage represented by the presence of mtDNA fragmentation and mitochondrial DNA levels evaluated by the ratio of mtDNA and nuclear DNA), clinical factors, and long-term outcomes measured by the physical functioning (PF) domain of health-related quality of life. Results: A total of 43 patients were included in this study divided into recovery and non-recovery groups based on age-adjusted PF scores at 12 months post-ICU. Nineteen patients scored below these thresholds. No significant differences in mitochondrial markers between groups were identified. Furthermore, no significant correlations were found between mtDNA levels and mtDNA damage at baseline and 12 months with PF scores. However, mtDNA levels decreased over time in the recovery (p-value < < 0.01) and non-recovery groups (p-value < 0.01). Conclusion: No significant correlation was found between mitochondrial markers and physical functioning scores. This study underscores the multifactorial nature of PICS and the need for a comprehensive understanding of its metabolic and cellular components. While mitochondrial markers may play a role in PICS, they operate within a framework influenced by various factors. This exploratory study serves as a foundation for future investigations aimed at developing targeted interventions to enhance the quality of life for ICU survivors grappling with PICS. [ABSTRACT FROM AUTHOR]

This study evaluates long-read and short-read sequencing for mitochondrial DNA (mtDNA) heteroplasmy detection. 592,315 bootstrapped datasets generated from two single-nucleotide mismatched ultra-deep sequenced mtDNA samples were used to assess basecalling error and accuracy, limit of heteroplasmy detection, and heteroplasmy detection across various coverage depths. Results showed high Phred scores of data with GC-rich sequence bias for long reads. Limit of detection of 12% heteroplasmy was identified, showing strong correlation (R2 ≥ 0.955) with expected heteroplasmy but underreporting tendency of high-level variants. Nanopore sequencing shows potential for direct applicability in mitochondrial diseases diagnostics, but stringent validation processes to ensure diagnostic result quality are required. [ABSTRACT FROM AUTHOR]

The Chinese Grouse (Tetrastes sewerzowi), a rare endemic bird in China, belongs to the Galliformes order and Tetraonidae family. Despite extensive research, subspecies classification remains inadequate, especially in Pingwu, Sichuan. This study sequenced the mitochondrial genome of T. sewerzowi in Wanglang Nature Reserve, Sichuan, analyzed its structural features, and reconstructed phylogenetic relationships within Tetraonidae. The results indicate that the high conservation in mitochondrial genome structure and sequence between the T. sewerzowi from Wanglang, Sichuan and Lianhuashan, Gansu indicates that they may belong to the same subspecies. Furthermore, we observed significant differences in the length of the mitochondrial control region between T. sewerzowi and Tetrastes bonasia. Based on the phylogenetic tree constructed using a comprehensive mitochondrial dataset, we propose the reclassification of the Hazel Grouse genus into two independent genera: Tetrastes and Bonasa. This study is the first to sequence the mitochondrial genome of T. sewerzowi from Sichuan and compare it with populations from Gansu, providing important insights into the distribution pattern of T. sewerzowi subspecies and facilitating the formulation of effective conservation strategies. [ABSTRACT FROM AUTHOR]

Near the southern limit of its Japanese distribution range, the white-spotted charr Salvelinus leucomaenis inhabits headwater tributaries of inlet rivers to Lake Biwa, Shiga Prefecture, although failing to migrate to the lake from those tributaries. Even though lower depths (>30 m) of the north basin of the lake are cold throughout the year, the only salmonid inhabiting the lake is the Biwa salmon Oncorhynchus sp. However, between 2018 and 2021, five white-spotted charr were caught in Lake Biwa, their phenotype being characterized by large whitish spots, reminiscent of the anadromous form off northern Japan. Mitochondrial DNA Cyt b haplotype analysis data supported their origin as hatchery-reared specimens from Samegai Trout Farm (Shiga Prefecture), the latter having sourced white-spotted charr from several Japanese populations, including northern Japan (descending anadromous exists). Such white-spotted charr, upon release from the hatchery, may have migrated to the lake during winter, due to a retained migration instinct. [ABSTRACT FROM AUTHOR]

Salmonid fish are known to have the potential to induce allergies. Therefore, from the perspective of food safety, it is crucial to assess the contamination of salmonid components in food. In this study, we aimed to develop a highly sensitive detection method using real-time polymerase chain reaction (PCR) for the accurate identification of minute quantities of salmonid DNA in food. To enhance detection sensitivity, three types of repetitive DNA elements with high copy numbers per genome, that is, the Hpa I element, ribosomal DNA (rDNA), and mitochondrial DNA (mtDNA), were initially selected as candidate PCR targets. The copy numbers of these elements across 11 salmonid species were quantified using real-time PCR. The salmonid-specific retrotransposon with the highest copy number, Hpa I, was chosen as the target gene for the highly sensitive salmonid detection method. By conducting real-time PCR using DNA templates from 11 salmonid species and 71 non-salmonid species, the method demonstrated exceptional specificity to salmonids. By optimizing the conditions of the real-time PCR, the detection limit of salmonid DNA reached 20 fg, and the limit remained unaffected even in the presence of mixed DNA from other species. Compared with existing detection methods for salmonid fish, our approach signifies a substantial 250-fold advancement in detection limits. Application of our method to 16 processed foods containing components of salmonid fish and 5 processed foods devoid of salmonid fish components resulted in successful determination of the presence or absence of salmonid fish in all tested food samples. [ABSTRACT FROM AUTHOR]

Glaucoma is a sight threatening neurodegenerative condition of the optic nerve head associated with ageing and marked by the loss of retinal ganglion cells. Mitochondrial dysfunction plays a crucial role in the pathogenesis of neurodegeneration in the most prevalent type of glaucoma: primary open angle glaucoma (POAG). All previous mitochondrial genome sequencing studies in POAG analyzed mitochondrial DNA (mtDNA) isolated from peripheral blood leukocytes and have not evaluated cells derived from ocular tissue, which better represent the glaucomatous disease context. In this study, we evaluated mitochondrial genome variation and heteroplasmy using massively parallel sequencing of mtDNA in a cohort of patients with POAG, and in a subset assess the role of somatic mitochondrial genome mutations in disease pathogenesis using paired samples of peripheral blood leukocytes and ocular tissue (Tenon's ocular fibroblasts). An enrichment of potentially pathogenic nonsynonymous mtDNA variants was identified in Tenon's ocular fibroblasts from participants with POAG. The absence of oxidative DNA damage and predominance of transition variants support the concept that errors in mtDNA replication represent the predominant mutation mechanism in Tenon's ocular fibroblasts from patients with POAG. Pathogenic somatic mitochondrial genome mutations were observed in people with POAG. This supports the role of somatic mitochondrial genome variants in the etiology of glaucoma. [ABSTRACT FROM AUTHOR]

Accurate species delimitation and phylogenetic reconstruction are vital to understand biodiversity assessments, conservation management, evolutionary patterns, evolutionary processes, and historical biogeography. The taxonomy and phylogeny of the genus Neolissochilus (Cyprinidae) have a confusing history. We investigated the taxonomy and phylogeny of this group and related lineages using complete mitochondrial genome sequence data from 53 Cyprinidae species and one outgroup species. These analyses show that the monophyly of Neolissochilus and Tor is not supported. N. benasi might represent a new genus, and T. qiaojiensis should be moved into Neolissochilus. We estimated divergence times, evaluated the monophyly of this group, their relationship to other cyprinids, as well as the time course and geography of speciation. The results indicated that the family Cyprinidae likely diverged from other taxa during the Eocene (ca. 54.78 Mya), and species of various genera began to undergo massive diversification events during the Cenozoic Tertiary. The differentiation and diffusion of the family Cyprinidae might be attributed to the Qinghai–Tibet Plateau uplift events, one of the geological events marking the Cenozoic Tertiary period, which cut off genetic exchange between populations through geographic isolation, thus facilitating genetic divergence between populations and eventually leading to the formation of new species. In addition, the results of this study still need further improvement. The limitations are mainly due to the small sample size and the use of only mitochondrial data; therefore, it still needs to be further verified by combining nuclear genome data. [ABSTRACT FROM AUTHOR]

The inference of body fluids and tissues is critical in reconstructing crime scenes and inferring criminal behaviors. Nevertheless, present methods are incompatible with conventional DNA genotyping, and additional testing might result in excessive consumption of forensic scene materials. This study aims to investigate the feasibility of distinguishing common body fluids/tissues through the difference in mitochondrial DNA copy number (mtDNAcn). Four types of body fluids/tissues were analyzed in this study - hair, saliva, semen, and skeletal muscle. MtDNAcn was estimated by dividing the read counts of mitochondrial DNA to that of nuclear DNA (RRmt/nu). Results indicated that there were significant differences in RRmt/nu between different body fluids/tissues. Specifically, hair samples exhibited the highest RRmt/nu (log10RRmt/nu: 4.3 ± 0.28), while semen samples showed the lowest RRmt/nu (log10RRmt/nu: -0.1 ± 0.28). RRmt/nu values for DNA samples without extraction were notably higher (approximately 2.9 times) than those obtained after extraction. However, no significant difference in RRmt/nu was observed between various age and gender groups. Hierarchical clustering and Kmeans clustering analyses showed that body fluids/tissues of the same type clustered closely to each other and could be inferred with high accuracy. In conclusion, this study demonstrated that the simultaneous detection of nuclear and mitochondrial DNA made it possible to perform conventional DNA analyses and body fluid/tissue inference at the same time, thus killing two birds with one stone. Furthermore, mtDNAcn has the potential to serve as a novel and promising biomarker for the identification of body fluids/tissues. [ABSTRACT FROM AUTHOR]

STR loci localized on the X chromosome provide information additional to the autosomal markers routinely analyzed in forensic genetics, integrating genetic systems as Y-STRs and mitochondrial DNA in the investigation of complex kinship scenarios and mass disaster cases. In this study we genotyped 12 X-STR loci in 251 male samples from four populations of Namibia in southern Africa using the Investigator Argus X-12 kit (Qiagen, Hilden, Germany). Forensic efficiency parameters indicated high power of discrimination in the considered populations. As part of our investigation, we highlighted partial linkage associations between loci within known linkage groups (LGs) and identified several occurrences of previously unreported out-of-ladder (OL) alleles. Genetic distances between the Namibian populations here investigated and other African (Eritrea, Ethiopia, Somalia, Guinea, Cape Verde) and non-African (Germany, China, Philippines) populations using loci grouped in LGs mirrored their biogeographical distribution differently for each linkage group. Haplotype sharing within each LG revealed a high degree of population-specific types, hinting to the potential of these markers for ancestry applications. These results highlight the importance to produce specific and freely available population databases especially for multi-ethnic countries. This novel dataset is expected to be of interest for population studies that need an accessible reference dataset of African regions not currently well represented, as well as possible relevance for forensic applications focusing on the biogeographic origin of samples. [ABSTRACT FROM AUTHOR]

Objective: Identify the genotype and clinical characteristics of mitochondrial epilepsy caused by nDNA mutations in Chinese children and explore the treatment and prognosis of the condition. Study design: This is a retrospective cohort study conducted at a single center, including patients diagnosed with an established nDNA mutation-associated primary mitochondrial disease between October 2012 and March 2023 who also met the practical clinical definition of epilepsy published by the ILAE in 2014. Results: Of the 58 patients identified, 74.1% had an onset before the age of 1 year and 63.8% had seizures as their initial symptom. Developmental and epileptic encephalopathy (DEE) (31%) are the most common phenotypes. The most frequently observed MRI abnormalities include abnormal signal asymmetry in the bilateral basal ganglia and/or brainstem (34.7%), as well as brain atrophy, myelin sheath dysplasia, and corpus callosum dysplasia (32.7%). Of the 40 patients followed, seizure treatment was effective in 18 of the cases, while it was ineffective in 22. The mitochondrial DNA depletion syndrome (MDS) was found to be more difficult to control seizures than other phenotypes (P < 0.05). Additionally, the MDS was associated with a significantly higher mortality rate compared to alternative phenotypes (P < 0.05). Conclusions: The onset of mitochondrial epilepsy due to nDNA mutations is early and seizures are the most common initial symptom. DEE is the most common phenotype. Characteristic MRI abnormalities in the brain may be helpful in the diagnosis of primary mitochondrial disease. People with MDS typically face challenges in seizure control and have a poor prognosis. [ABSTRACT FROM AUTHOR]

Mitochondria serve as the cellular powerhouse, and their distinct DNA makes them a prospective target for gene editing to treat genetic disorders. However, the impact of genome editing on mitochondrial DNA (mtDNA) stability remains a mystery. Our study reveals previously unknown risks of genome editing that both nuclear and mitochondrial editing cause discernible transfer of mitochondrial DNA segments into the nuclear genome in various cell types including human cell lines, primary T cells, and mouse embryos. Furthermore, drug-induced mitochondrial stresses and mtDNA breaks exacerbate this transfer of mtDNA into the nuclear genome. Notably, we observe that mitochondrial editors, including mitoTALEN and recently developed base editor DdCBE, can also enhance crosstalk between mtDNA and the nuclear genome. Moreover, we provide a practical solution by co-expressing TREX1 or TREX2 exonucleases during DdCBE editing. These findings imply genome instability of mitochondria during induced DNA breaks and explain the origins of mitochondrial-nuclear DNA segments. Emerging genome editing tools have been reported to possess threats to genome stability, while their impact on mitochondrial DNA (mtDNA) remains unknown. Here, authors report that genome editing of both nuclear and mitochondrial genome triggers transfer of mtDNA fragments into the nuclear genome. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is a debilitating mitochondrial disease associated with mutations in mitochondrial DNA (mtDNA). Unfortunately, the available treatment options for LHON patients are limited due to challenges in mitochondrial replacement. In our study, we reprogramming LHON urine cells into induced pluripotent stem cells (iPSCs) and differentiating them into neural progenitor cells (NPCs) and neurons for disease modeling. Our research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function, confirming the disease phenotype. However, through co-culturing LHON iPSC-derived NPCs with mesenchymal stem cells (MSCs), we observed a remarkable rescue of mutant mtDNA and a significant improvement in mitochondrial metabolic function in LHON neurons. These findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs, even after their differentiation into neurons. This discovery holds promise as a potential therapeutic strategy for LHON patients. [ABSTRACT FROM AUTHOR]

The MELAS/Leigh overlap syndrome manifests with a blend of clinical and radiographic traits from both MELAS and LS. However, the association of MELAS/Leigh overlap syndrome with MT-CO1 gene variants has not been previously reported. In this study, we report a patient diagnosed with MELAS/Leigh overlap syndrome harboring the m.5906G > A variant in MT-CO1, with biochemical evidence supporting the pathogenicity of the variant. The variant m.5906G > A that led to a synonymous variant in the start codon of MT-CO1 was filtered as the candidate disease-causing variant of the patient. Patient-derived fibroblasts were used to generate a series of monoclonal cells carrying different m.5906G > A variant loads for further functional assays. The oxygen consumption rate, ATP production, mitochondrial membrane potential and lactate assay indicated an impairment of cellular bioenergetics due to the m.5906G > A variant. Blue native PAGE analysis revealed that the m.5906G > A variant caused a deficiency in the content of mitochondrial oxidative phosphorylation complexes. Furthermore, molecular biology assays performed for the pathogenesis, mtDNA copy number, mtDNA-encoded subunits, and recovery capacity of mtDNA were all deficient due to the m.5906G > A variant, which might be caused by mtDNA replication deficiency. Overall, our findings demonstrated the pathogenicity of m.5906G > A variant and proposed a potential pathogenic mechanism, thereby expanding the genetic spectrum of MELAS/Leigh overlap syndrome. [ABSTRACT FROM AUTHOR]

Variants in mitochondrial genomes (mtDNA) can cause various neurological and mitochondrial diseases such as mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes (MELAS). Given the 16 kb length of mtDNA, continuous sequencing is feasible using long-read sequencing (LRS). Herein, we aimed to show a simple and accessible method for comprehensive mtDNA sequencing with potential diagnostic applications for mitochondrial diseases using the compact and affordable LRS flow cell "Flongle." Whole mtDNA amplification (WMA) was performed using genomic DNA samples derived from four patients with mitochondrial diseases, followed by LRS using Flongle. We compared these results to those obtained using Cas9 enrichment. Additionally, the accuracy of heteroplasmy rates was assessed by incorporating mtDNA variants at equimolar levels. Finally, mtDNA from 19 patients with Parkinson's disease (PD) was sequenced using Flongle to identify disease risk-associated variants. mtDNA variants were detected in all four patients with mitochondrial diseases, with results comparable to those obtained from Cas9 enrichment. Heteroplasmy levels were accurately detected (r2 > 0.99) via WMA using Flongle. A reported variant was identified in three patients with PD. In conclusion, Flongle can simplify the traditionally cumbersome and expensive mtDNA sequencing process, offering a streamlined and accessible approach to diagnosing mitochondrial diseases. [ABSTRACT FROM AUTHOR]

Sea cucumbers are deposit feeding members of marine benthic communities. The over-exploitation of sea cucumber natural stocks, especially in the Mediterranean basin, is having negative impacts on the marine ecosystem. This concerns had led the Italian government to take legal actions to preserve these important marine resources. The aim of this study was to evaluate the level of genetic diversity and population structures within two sympatric Holothuria sea cucumber species, H. polii and H. tubulosa, across ten Mediterranean areas along Italy. A 323 bp portion of the COI mitochondrial gene was sequenced in a total of 441 holothurians (251 H. polii, 177 H. tubulosa and 13 from other species). Genetic diversity analyses and analysis of molecular variance (AMOVA) suggest that H. polii and H. tubulosa species are distinct, but within and among populations are homogeneous, indicating active gene flows across the Mediterranean areas investigated. H. polii showed a lower genetic diversity than H. tubulosa, probably related to differences in life history traits. Phylogenetic analyses showed a clear differentiation between the two species, even if six specimens morphologically assigned to a species clustered within the other species, indicating a possible occurrence of hybridization events. These data will be useful in implementing conservation actions for these holothurian genetic resources. [ABSTRACT FROM AUTHOR]

The Indian spot-billed duck, Anas poecilorhyncha is a large dabbling and non-migratory breeding bird. The identification and phylogenetic relationship of A. poecilorhyncha remain uncertain due to the presence of overlapping meristic characters and hybridization with closely related species. Molecular data aids when there are challenges in morphological identification. However, genetic characterization of A. poecilorhyncha has been paid less attention. Apart from their functional and physiological role, mitochondrial genome can also be used for various purposes, including species identification, phylogenetic analysis, understanding the domestication history of species etc. Therefore, the present study aimed to sequence the mitochondrial genome of A. poecilorhyncha and its closely related domestic species A. platyrhynchos (mallard duck) to understand their mitochondrial genome structure and phylogenetic relationships. The length of mitochondrial genome of A. poecilorhyncha and A. platyrhynchos was 16,608 and 16,604 bp respectively. Mitochondrial genome contained 37 genes and a non-coding control region. Overall, the characteristics of mitochondrial genome of both species were found to be conserved. The phylogenetic tree exhibited seven major clades (A to G) with a high bootstrap support. Notably, the Indian A. poecilorhyncha population formed a distinct clade (C) whereas the A. poecilorhyncha that were probably sampled from China grouped along with A. zonorhyncha (clade B). Besides, one of the A. poecilorhyncha probably sampled from China was placed in the clade A, which predominantly consisted of A. platyrhynchos. It suggests that Indian A. poecilorhyncha population is genetically different from Chinese A. poecilorhyncha population. Further, it sheds light on the importance of conducting a comprehensive phylogenetic study on these species. The newly sequenced mitochondrial genome of A. poecilorhyncha and A. platyrhynchos would be useful not only to have a better understanding of the phylogeny and evolution of Anas species but also to help in the conservation of A. poecilorhyncha which is under constant threat from rapid urbanization, interspecific hybridization and other human activities. [ABSTRACT FROM AUTHOR]

Cancer cells are constantly evolving to adapt to environmental changes, particularly during exposure to drug treatment. In this work, we aimed to characterize genetic and epigenetic changes in mitochondrial DNA (mtDNA) that may increase the resistance of oral squamous cell carcinoma (OSCC) to cisplatin. We first derived drug-resistant cells from two human OSCC cell lines, namely SAS and H103, by continual cisplatin treatments for about 4 months. To determine mtDNA changes induced by cisplatin, we performed nanopore sequencing and quantitative polymerase chain reaction analysis of mtDNA extracted from the cells pre- and post-treatment. We also assessed the mitochondrial functions of the cells and their capacity to generate intracellular reactive oxygen species (ROS). We found that in the cisplatin-resistant cells derived from SAS, there was a reduction in mtDNA content and significant enrichment of a m.3910G > C mutation in the MT-ND1 gene. However, such changes were not detected in cisplatin-resistant H103 cells. The cisplatin treatment also altered methylation patterns in both SAS and H103 cells and decreased their sensitivity to ROS-induced cytotoxicity. We suggest that the sequence alterations and epigenetic changes in mtDNA and the reduction in mtDNA content could be key drivers of cisplatin resistance in OSCC. These mtDNA alterations may participate in cellular adaptation that serves as a response to adverse changes in the environment, particularly exposure to cytotoxic agents. Importantly, the observed mtDNA changes may be influenced by the distinct genetic landscapes of various cancer subtypes. Overall, this study reveals significant insights into cisplatin resistance driven by complex mtDNA dynamics, particularly in OSCC. This underscores the need for targeted therapies tailored to the genetic profiles of individual OSCC patients to improve disease prognosis. [ABSTRACT FROM AUTHOR]

Background: Mobulidae is a monophyletic family within the Myliobatiformes that comprises pelagic species represented by manta and devil rays. Among the genus Mobula, the Atlantic Pygmy Devil Ray - Mobula hypostoma - is reported in coastal regions exclusively in tropical and subtropical Atlantic Ocean from 1 to 100 m deep. In Brazil, M. hypostoma is one of the least studied Mobula species. It is regularly misidentified, especially as Mobula thurstoni, and is commonly listed as bycatch, in fishery inventories, or related to opportunistic sightings in the national territory. Methods and results: Here, we describe the complete nucleotide sequence of the mitochondrial genome (mitogenome) from Mobula hypostoma, which is 18,141 bp in length and comprises 13 protein-coding, two ribosomal RNA, and 22 transfer RNA genes. The M. hypostoma mitochondrial genes organisation and mitochondrial genome length are similar to other Mobula species, and the phylogenetic reconstruction indicates M. hypostoma as closely related to Mobula munkiana. Conclusions: The Brazilian mitogenome of M. hypostoma is expected to be a valuable resource for molecular-based species identification, and evolutionary and phylogeography studies. [ABSTRACT FROM AUTHOR]

Understanding host-microbe interactions in planta is an expanding area of research. Amplicon sequencing of the 16S rRNA gene is a powerful and common method to study bacterial communities associated with plants. However, the co-amplification of mitochondrial and plastid 16S rRNA genes by universal primers impairs the sensitivity and performance of 16S rRNA sequencing. In 2020, a new method, Cas-16S-seq, was reported in the literature to remove host contamination for profiling the microbiota in rice, a well-studied domestic plant, by engineering RNA-programmable Cas9 nuclease in 16S rRNA sequencing. For the first time, we tested the efficiency and applicability of the Cas-16S-seq method on foliage, flowers, and seed of a non-domesticated wild plant for which there is limited genomic information, Leptospermum scoparium (mānuka). Our study demonstrated the efficiency of the Cas-16S-seq method for L. scoparium in removing host contamination in V4-16S amplicons. An increase of 46% in bacterial sequences was found using six guide RNAs (gRNAs), three gRNAs targeting the mitochondrial sequence, and three gRNAs targeting the chloroplast sequence of L. scoparium in the same reaction. An increase of 72% in bacterial sequences was obtained by targeting the mitochondrial and chloroplast sequences of L. scoparium in the same sample at two different steps of the library preparation (DNA and 1st step PCR). The number of OTUs (operational taxonomic units) retrieved from soil samples was consistent when using the different methods (Cas-16S-seq and 16S-seq) indicating that the Cas-16S-seq implemented for L. scoparium did not introduce bias to microbiota profiling. Our findings provide a valuable tool for future studies investigating the bacterial microbiota of L. scoparium in addition to evaluating an important tool in the plant microbiota research on other non-domesticated wild species. [ABSTRACT FROM AUTHOR]

Habitat destruction, land conversion, and forest fragmentation over the past several decades have resulted in major declines and local extirpation of wild animal and plant species. The gray snub-nosed monkey (Rhinopithecus brelichi) is currently listed among the 25 most endangered primate species in the world, with an estimated remaining wild population of less than 400 individuals. Given the potential negative effects of small population size on genetic diversity, we investigated how factors, such as climate, inbreeding, kinship, population structure, and effective population size, have contributed to their genetic status. We extracted DNA from 307 fecal samples and analyzed microsatellite diversity, sex-identifying genes, and the mtDNA control region in 179 wild individuals. Our analyses suggest that gray snub-nosed monkeys experienced an initial population decline during the Last Glacial Maximum, some 20,000 years ago. During the past 70 years, this species experienced a second, steeper population decline, coinciding with human activities. Their current effective population size (± SD) of 675 ± 292 exceeds the remaining number of individuals in the population and has declined by 93.9%—96.7% over the past 20,000 years. Our findings highlight the need for immediate conservation and management strategies to protect this endemic and Critically Endangered primate species. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the current study was to investigate the mtDNA methylation levels and mtDNA copy numbers in the sperm of patients with asthenozoospermia and compare them to those observed in controls with normozoospermia. Methods: Pyrosequencing analysis of the methylation levels of the mitochondrial D-loop and MT-CO1/chr1:631,907–632083/chrX:26,471,887–126,472,063 (hereinafter referred to as "MT-CO1-AVG") region and quantitative PCR analysis of the mtDNA copy number were performed on sperm from 30 patients with asthenozoospermia and 30 controls with normozoospermia. Results: Compared with those of controls with normozoospermia, the methylation levels of D-loop and MT-CO1-AVG regions and mtDNA copy number were significantly higher in patients with asthenozoospermia. The methylation level of the D-loop region in patients with asthenozoospermia and controls with normozoospermia and that of MT-CO1-AVG region in patients with asthenozoospermia showed a decreasing tendency with increasing total sperm motility. A significant inverse correlation between the mtDNA copy number and total sperm motility was observed in patients with asthenozoospermia but not in controls with normozoospermia. In patients with asthenozoospermia, but not in controls with normozoospermia, we observed a significant inverse correlation between D-loop methylation levels and mtDNA copy number, while no significant correlation was observed between MT-CO1-AVG methylation levels and mtDNA copy number. Conclusion: These results reveal the occurrence of mtDNA methylation in human sperm and altered D-loop and MT-CO1-AVG methylation levels in patients with asthenozoospermia. Additional research is needed to determine the function of these features in the etiology and course of asthenozoospermia. [ABSTRACT FROM AUTHOR]

Characterizing the genetic diversity of a species is crucial for understanding the factors that influence its local dispersion and population dynamics. Additionally, it provides insights into local processes that may affect the distribution of other species. Lineus sanguineus (Rathke, 1799) is a widely distributed species commonly found on fouling fauna along rocky shores. This species can reproduce asexually by fissiparity, and its pilidium larva facilitates dispersal, similar to other heteronemerteans. The present study utilized a population genetics approach combined with Ecological Niche Modeling analysis to evaluate L. sanguineus populations along the Brazilian coast. We used sequences from two mtDNA regions, 16S ribosomal RNA (16SrRNA) and cytochrome c oxidase subunit 1 (COI), and one nuclear region, Internal Transcribed Spacer 1 (ITS-1), from 85 specimens sampled in nine locations. Genetic diversity analysis revealed greater genetic variation for the ITS-1 marker compared to mtDNA, as evidenced by higher intrapopulation diversity values. There was no clear geographic pattern, and the AMOVA analysis revealed low to moderate genetic structuring and high connectivity among sampled localities, with most of the genetic variation contained within populations. The pairwise FST results indicate high genetic structuring between the Northeast and localities along the South and Southeast of Atlantic coastlines. This pattern suggests that Brazilian oceanic currents play an important role in species connectivity. The paleodistribution pattern demonstrated that the colonization could have occured from the South to the Northeast of the continent. These results reinforce that sexual reproduction and larval dispersion play a vital role in the connectivity of these Southwest Atlantic populations and that oceanographic currents, rafting and artificial transport facilitate these processes. [ABSTRACT FROM AUTHOR]

Brachidontes variabilis (Krauss, 1848) is a common small mussel widely distributed in the intertidal zone of southern China. Firstly, we characterized four complete mitochondrial genomes of B. variabilis from four populations (Wanning, Yangjiang, Zhangzhou, and Shanwei) in Chinese waters. This study was the first to sequence and discribe the mitochondrial genome of B. variabilis, which comprised of 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and 12 protein-coding genes (PCGs, lacking atp8). And then three PCGs fragments, including cytochrome oxidase subunit I (cox1, 558 bp), NADH dehydrogenase subunit 5 (nad5, 754 bp), and NADH dehydrogenase subunit 4 (nad4, 879 bp), were utilized to investigate the population genetics and demography. The cox1, nad5 and nad4 fragments revealed 55, 81, and 103 haplotypes, respectively. Results indicated high genetic diversity within populations (Hd > 0.5, Pi > 0.005) and little genetic differentiation among populations (FST<0.05), suggesting frequent gene exchanges. Further, the neutrality test and Extended Bayesian skyline plots (EBSPs) suggested that the four populations underwent population expansion at 0.9–1.1 Ma during the Pleistocene. In summary, this study on the mitochondrial genomes and population genetics of B. variabilis provides insights into the evolutionary history and demographic dynamics of this species in southern China. [ABSTRACT FROM AUTHOR]

Museum specimens preserve genetic information that can help resolve phylogenetic relationships of now extinct species. The Caribbean monk seal, Neomonachus tropicalis, is the only marine mammal driven to extinction in tropical seas and one of the few marine mammals to go extinct in historical times. Prior to 1700 it was widely distributed throughout the coasts of North, Central and South America, and in the Bahamas, Greater and Lesser Antilles. The species was first taxonomically placed in the genus Monachus, along with the Hawaiian and Mediterranean monk seals and it was later moved together with the Hawaiian monk seal into the newly described genus Neomonachus. Here, we present the complete mitochondrial genome of the Caribbean monk seal and a phylogenetic reconstruction, confirming its sister taxa relationship with the Hawaiian monk seal, and thus the monophyly of the genus Neomonachus. Our estimates of divergence times are contemporaneous with or predate the emergence of the Isthmus of Panama. We also identify limited genetic variation among five specimens of Caribbean monk seal. [ABSTRACT FROM AUTHOR]

Background: Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of in vivo radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies. Objective: Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography. Materials and methods: Prospective single-site study of 27 children. Blood collected pre and post neuroangiography, from which PBMC were isolated and assayed for biomarkers of mitochondrial stress (mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial DNA (mtDNA)) and DNA damage (γH2AX). Dose response of biomarkers vs. radiation dose was analyzed using linear regressions. The cohort was divided into higher (HD) and lower dose (LD) groups and analyzed using linear mixed models and compared using Welch's t-tests. Results: No biomarker exhibited a dose-dependent response following radiation (γH2AX: R2 = 0.0012, P = 0.86; MMP: R2 = 0.016, P = 0.53; mtDNA: R2 = 0.10, P = 0.11; ROS: R2 = 0.0023, P = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, P = 0.92; HD: -7.5 ± 6.3 AU, P = 0.24; ROS: LD: 1.3 ± 2.8, P = 0.64; HD: -3.6 ± 3.0 AU, P = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, P = 0.0014) and mtDNA (-1.1 ± 0.4 AU, P = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, P = 0.090; mtDNA: 0.2 ± 0.4, P = 0.65). Conclusions: Biomarkers of mitochondrial stress in PBMC were identified during pediatric neuroangiography and warrant further investigation for radiation biodosimetry. However, isolating radiation-specific effects from those of procedural stress and general anesthesia requires further investigation. [ABSTRACT FROM AUTHOR]

Oocytes play a crucial role in transmitting maternal mitochondrial DNA (mtDNA), essential for the continuation of species. However, the effects of mitochondrial reactive oxygen species (ROS) on mammalian oocyte maturation and mtDNA maintenance remain unclear. We investigated this by conditionally knocking out the Sod2 gene in primordial follicles, elevating mitochondrial matrix ROS levels from early oocyte stages. Our data indicates that reproductive aging in Sod2 conditional knockout females begins at 6 months, with oxidative stress impairing oocyte quality, particularly affecting OXPHOS complex II and mtDNA-encoded mRNA levels. Despite unchanged mtDNA mutation load, mtDNA copy numbers exhibited significant variations. Strikingly, reducing mtDNA copy numbers by reducing mtSSB protein, crucial for mtDNA replication, accelerated reproductive aging onset to three months, underscoring the critical role of mtDNA copy number maintenance under oxidative stress conditions. This research provides new insights into the relationship among mitochondrial ROS, mtDNA, and reproductive aging, offering potential strategies for delaying aging-related fertility decline. Elevating mitochondrial ROS induces female reproductive aging without increasing maternal mtDNA mutation load where deducing mtDNA copy numbers accelerates this phenomenon, highlighting the importance of maintaining mtDNA quantity under oxidative stress. [ABSTRACT FROM AUTHOR]

Sound management of coastal resources is based on science-based decisions. Bottlenose dolphins are found around Puerto Rico; however, limited information exists on the ecology, behavior, sex ratio, distribution patterns, and population structure presenting, challenges in managing the bottlenose dolphin as defined in the Marine Mammal Protection Act of 1972. We sequenced the mitochondrial control region (mtDNA-CR) of 27 live and 11 stranded dolphins from Puerto Rico, five stranded dolphins from Guadeloupe and included sequences from the North Atlantic and the Pacific Ocean. Our genetic data from the new samples indicates the presence of distinct genetic lineages (inshore—represented by coastal individuals) and worldwide-distributed form (represented by both coastal and offshore individuals) in Puerto Rico. DNA divergence between inshore/coastal and offshore haplotypes ranged from 4.34 to 6.58%. All haplotypes from Puerto Rico have been previously reported from the Caribbean and North Atlantic. Genetic analysis yielded a complex population structure without a clear geographic signal; an expected result from a highly mobile marine mammal. A clade consisting exclusively of coastal dolphins of the Caribbean and the western North Atlantic was recovered. Offshore haplotypes from the eastern and western North Atlantic were generally clustered with offshore haplotypes of the Caribbean. Coastal and offshore haplotypes from the Pacific differed from those from the Atlantic. When we partitioned the data by form (coastal vs. offshore) and ocean (Atlantic vs. Pacific), we detected significant population differentiation (FST = 0.4089), indicating limited gene flow between forms and across oceans. [ABSTRACT FROM AUTHOR]

Metabolic rewiring promotes cancer cell adaptation to a hostile microenvironment, representing a hallmark of cancer. This process involves mitochondrial function and is mechanistically linked to the balance between mitochondrial biogenesis (MB) and mitophagy. The molecular chaperone TRAP1 is overexpressed in 60–70% of human colorectal cancers (CRC) and its over-expression correlates with poor clinical outcome, being associated with many cancer cell functions (i.e. adaptation to stress, protection from apoptosis and drug resistance, protein synthesis quality control, metabolic rewiring from glycolysis to mitochondrial respiration and vice versa). Here, the potential new role of TRAP1 in regulating mitochondrial dynamics was investigated in CRC cell lines and human CRCs. Our results revealed an inverse correlation between TRAP1 and mitochondrial-encoded respiratory chain proteins both at transcriptional and translational levels. Furthermore, TRAP1 silencing is associated with increased mitochondrial mass and mitochondrial DNA copy number (mtDNA-CN) as well as enhanced MB through PGC-1α/TFAM signalling pathway, promoting the formation of new functioning mitochondria and, likely, underlying the metabolic shift towards oxidative phosphorylation. These results suggest an involvement of TRAP1 in regulating MB process in human CRC cells. Key messages: TRAP1 inversely correlates with protein-coding mitochondrial gene expression in CRC cells and tumours. TRAP1 silencing correlates with increased mitochondrial mass and mtDNA copy number in CRC cells. TRAP1 silencing favours mitochondrial biogenesis in CRC cells. [ABSTRACT FROM AUTHOR]

The day gecko Phelsuma borbonica displays marked differences in coloration and occupies a variety of habitats across its very small range on the volcanic oceanic island of Reunion in the southwestern Indian Ocean. Such differences might reflect geographic and ecological divergence and thus be associated with an underlying genetic differentiation. We examined the partitioning of genetic diversity in Phelsuma borbonica across Reunion at a very small spatial scale (< 10 km) using mtDNA and nuDNA sequences, along with microsatellite genotype data. This study provides an account of the evolutionary history of Phelsuma borbonica, along with a quantification of effective population sizes, which constitute important information for the conservation of this endangered species, which may represent a previously unrecognized case of incipient speciation. We found that populations of Phelsuma borbonica are genetically strongly differentiated, highlighting historically low levels of gene flow. Phylogenetic analyses suggest that Phelsuma borbonica reached its present range through two parallel southward expansions from an ancestral population located in the northern part of the island. [ABSTRACT FROM AUTHOR]

Genetic connectivity and historical population expansion are characteristics that have largely been studied and observed in several members of the Lutjanidae family throughout the Western South Atlantic, particularly in Brazilian waters. In this study, the population genetic structure of Lutjanus jocu was investigated using four genomic regions: two from mitochondrial DNA (Control Region and Cytochrome B) and two nuclear genes (Delta 6 desaturase—intron 8 and Ribosomal Protein S7—intron 1), in 144 specimens distributed in six locations on the Atlantic coast of Brazil. The results revealed high levels of genetic diversity for both mtDNA and nuDNA markers, and intense gene flow, indicating, consistent with other studies, that this species is represented by a single genetic stock along the Brazilian coast. This is likely due to the high dispersal capacity of L. jocu larvae, driven by the main equatorial currents, as well as biological and ecological factors, contributing to a genetically homogeneous population. Historical demographic analysis and neutrality tests suggest that the species experienced population expansion, possibly during the Pleistocene. Information regarding the genetic structure of populations is extremely important, especially for species of high economic and fishing importance, and can be very useful in guiding stock management and management measures. [ABSTRACT FROM AUTHOR]

We collected 56 specimens of Laelaps chini from the endemic Hengduan Mountain rat species (Eothenomys miletus) and obtained the first complete mitochondrial genome of L. chini by next-generation sequencing (NGS). The L. chini mitogenome is 16,507 bp in size and contains 37 genes and a control region of 2380 bp in length. The L. chini mitogenome has a high AT content and a compact arrangement with four overlapping regions ranging from 1 to 2 bp and 16 spacer regions ranging from 1 to 48 bp. We analyzed 13 protein-coding genes of L. chini mitogenome and found that protein-coding genes in the L. chini mitogenome preferred codons ending in A/U and codon usage pattern was mainly influenced by natural selection. Cox1 has the slowest evolution rate and cox3 has the fastest evolution rate. We combined the mitochondrial genome of eight species of gamasid mites in the superfamily Dermanyssoidea from Genbank and the L. chini mitochondrial genome to analyze its rearrangement patterns and breakpoint numbers. We found that the L. chini mitogenome showed a novel arrangement pattern and nine species of gamasid mites in the superfamily Dermanyssoidea, which have been sequenced complete mitochondrial genomes to date, all showed different degrees of rearrangement. Laelaps chini, Echinolaelaps echidninus and Echinolaelaps fukinenensis were closely related species based on genetic distance and phylogenetic analyses. Notably they are clustered with Varroa destructor of the family Varroidae, suggesting that the family Varroidae is more closely related to the family Laelapidae, but more data are needed to test whether Varroa can be classified under the family Laelapidae. The L. chini mitogenome is the first complete mitochondrial genome for the genus Laelaps, and contributes to further exploration of the mitochondrial gene rearrangements and phylogeny for the superfamily Dermanyssoidea. [ABSTRACT FROM AUTHOR]

The bay scallop, Argopecten irradians, is a species of major commercial, cultural, and ecological importance. It is endemic to the eastern coast of the United States, but has also been introduced to China, where it supports a significant aquaculture industry. Here, we provide an annotated chromosome-level reference genome assembly for the bay scallop, assembled using PacBio and Hi-C data. The total genome size is 845.9 Mb, distributed over 1,503 scaffolds with a scaffold N50 of 44.3 Mb. The majority (92.9%) of the assembled genome is contained within the 16 largest scaffolds, corresponding to the 16 chromosomes confirmed by Hi-C analysis. The assembly also includes the complete mitochondrial genome. Approximately 36.2% of the genome consists of repetitive elements. The BUSCO analysis showed a completeness of 96.2%. We identified 33,772 protein-coding genes. This genome assembly will be a valuable resource for future research on evolutionary dynamics, adaptive mechanisms, and will support genome-assisted breeding, contributing to the conservation and management of this iconic species in the face of environmental and pathogenic challenges. [ABSTRACT FROM AUTHOR]

Pygmy jerboas are one of the smallest taxa of rodents. They exhibit distinctly different morphological and biological characteristics from other subfamilies, such as more restricted distribution, species richness, reproductive ability, and population size. Agricultural expansion and the development of new energy projects in recent years lead to sharp decline of their natural populations. Here, we assembled and annotated the first reference genome for the subfamily Cardiocraniinae using Illunima and Nanopore sequencing from the thick-tailed pygmy jerboa, Salpingotus crassicauda. The final genome is 2.44 Gb in size, with a contig N50 length of 13.71 Mb and a BUSCO completeness of 96.35%. A total of 23,344 protein-coding genes were annotated in the final genome. We also determined the mitochondrial genome of this species and annotated 13 protein-coding genes, 22 tRNAs, and 2 rRNA. These genomic assemblies provide resources in studying phylogeny and adaptive evolution of Dipodidae, as well as implementing conservation management of jerboas. [ABSTRACT FROM AUTHOR]

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway in productively infected cells. Pharmacological inhibition of STING in primary airway cells enhances SARS-CoV-2 replication and reduces virus-induced innate immune activation. Together, our study highlights that tonic activation of the cGAS-STING and IFN pathways can impact SARS-CoV-2 cellular tropism in a manner dependent on ACE2 expression levels. Factors that determine the cellular tropism of SARS-CoV-2 beyond the host cell receptor, ACE2, are poorly defined. Here, the authors show that tonic activation of the cGAS-STING sensing pathway potently blocks SARS-CoV-2 replication in a subset of ACE2-expressing airway-derived cells. [ABSTRACT FROM AUTHOR]

Cells possess multiple mitochondrial DNA (mtDNA) copies, which undergo semi-autonomous replication and stochastic inheritance. This enables mutant mtDNA variants to arise and selfishly compete with cooperative (wildtype) mtDNA. Selfish mitochondrial genomes are subject to selection at different levels: they compete against wildtype mtDNA directly within hosts and indirectly through organism-level selection. However, determining the relative contributions of selection at different levels has proven challenging. We overcome this challenge by combining mathematical modeling with experiments designed to isolate the levels of selection. Applying this approach to many selfish mitochondrial genotypes in Caenorhabditis elegans reveals an unexpected diversity of evolutionary mechanisms. Some mutant genomes persist at high frequency for many generations, despite a host fitness cost, by aggressively outcompeting cooperative genomes within hosts. Conversely, some mutant genomes persist by evading inter-organismal selection. Strikingly, the mutant genomes vary dramatically in their susceptibility to genetic drift. Although different mechanisms can cause high frequency of selfish mtDNA, we show how they give rise to characteristically different distributions of mutant frequency among individuals. Given that heteroplasmic frequency represents a key determinant of phenotypic severity, this work outlines an evolutionary theoretic framework for predicting the distribution of phenotypic consequences among individuals carrying a selfish mitochondrial genome. Selfish mitochondrial genomes undergo selection at different levels, within and between hosts. Here, the authors combine mathematical modeling and empirical experimentation to determine the strength of selection at these different levels and to predict selfish mtDNA frequency in C. elegans. [ABSTRACT FROM AUTHOR]

Primordial germ cells (PGCs) are vital for producing sperm and eggs and are crucial for conserving chicken germplasm and creating genetically modified chickens. However, efforts to use PGCs for preserving native chicken germplasm and genetic modification via CRISPR/Cas9 are limited. Here we show that we established 289 PGC lines from eight Chinese chicken populations with an 81.6% success rate. We regenerated Piao chickens by repropagating cryopreserved PGCs and transplanting them into recipient chickens, achieving a 12.7% efficiency rate. These regenerated chickens carried mitochondrial DNA from female donor PGC and the rumplessness mutation from both male and female donors. Additionally, we created the TYRP1 (tyrosinase-related protein 1) knockout (KO) PGC lines via CRISPR/Cas9. Transplanting KO cells into male recipients and mating them with wild-type hens produced four TYRP1 KO chickens with brown plumage due to reduced eumelanin production. Our work demonstrates efficient PGC culture, cryopreservation, regeneration, and gene editing in chickens. The combination of efficient PGC culture, practical cryopreservation, regeneration from recipient chickens, and CRISPR/Cas9 gene-editing to create knockout chickens for conserving and genetically improving rare native breeds. [ABSTRACT FROM AUTHOR]

Plastic waste has recently become a major global environmental concern and one of the biggest challenges has been seeking for alternative management options. Several studies have revealed the potential of several coleopteran species to degrade plastics, and this is the first research paper on plastic-degradation potential by lesser mealworms from Africa. This study evaluated the whole mitogenomic profile of the lesser mealworm to further identify the insect. The ability of the mealworm to consume Polystyrene (PS) was also evaluated alongside its associated gut microbiota diversity. Our results showed a complete circular mitochondrial genome which clustered closely to the Alphitobius genus but also suggested that our insect might be a new subspecies which require further identification. During the PS feeding trials, overall survival rates of the larvae decreased when fed a sole PS diet while PS intake was observed to increase over a 30-day period. The predominant bacteria observed in larvae fed PS diets were Kluyvera, Lactococcus, Klebsiella, Enterobacter, and Enterococcus, while Stenotrophomonas dominated the control diet. These findings demonstrated that the newly identified lesser mealworm can survive on a PS diet and has a consortium of important bacteria strongly associated with PS degradation. This work provides a better understanding of bioremediation applications, paving the way for further research into the metabolic pathways of plastic-degrading microbes and bringing hope to solving plastic waste pollution while providing high-value insect protein towards a circular economy. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), but resistance to ICB occurs and patient responses vary. Here, we uncover protein arginine methyltransferase 3 (PRMT3) as a driver for immunotherapy resistance in HCC. We show that PRMT3 expression is induced by ICB-activated T cells via an interferon-gamma (IFNγ)-STAT1 signaling pathway, and higher PRMT3 expression levels correlate with reduced numbers of tumor-infiltrating CD8+ T cells and poorer response to ICB. Genetic depletion or pharmacological inhibition of PRMT3 elicits an influx of T cells into tumors and reduces tumor size in HCC mouse models. Mechanistically, PRMT3 methylates HSP60 at R446 to induce HSP60 oligomerization and maintain mitochondrial homeostasis. Targeting PRMT3-dependent HSP60 methylation disrupts mitochondrial integrity and increases mitochondrial DNA (mtDNA) leakage, which results in cGAS/STING-mediated anti-tumor immunity. Lastly, blocking PRMT3 functions synergize with PD-1 blockade in HCC mouse models. Our study thus identifies PRMT3 as a potential biomarker and therapeutic target to overcome immunotherapy resistance in HCC. Resistance to immune checkpoint blockade (ICB) is a challenge in hepatocellular carcinoma therapy. Here, the authors show that targeting PRMT3 markedly improves the anticancer efficacy of ICB via interrupting HSP60 methylation and oligomerization, damaging mitochondrial integrity, and thereby activating cGAS/STING-mediated anti-tumor immunity. [ABSTRACT FROM AUTHOR]

Heteroplasmic mitochondrial DNA (mtDNA) variants accumulate as humans age, particularly in the stem-cell compartments, and are an important contributor to age-related disease. Mitochondrial dysfunction has been observed in osteoporosis and somatic mtDNA pathogenic variants have been observed in animal models of osteoporosis. However, this has never been assessed in the relevant human tissue. Mesenchymal stem cells (MSCs) are the progenitors to many cells of the musculoskeletal system and are critical to skeletal tissues and bone vitality. Investigating mtDNA in MSCs could provide novel insights into the role of mitochondrial dysfunction in osteoporosis. To determine if this is possible, we investigated the landscape of somatic mtDNA variation in MSCs through a combination of fluorescence-activated cell sorting and single-cell next-generation sequencing. Our data show that somatic heteroplasmic variants are present in individual patient-derived MSCs, can reach high heteroplasmic fractions and have the potential to be pathogenic. The identification of somatic heteroplasmic variants in MSCs of patients highlights the potential for mitochondrial dysfunction to contribute to the pathogenesis of osteoporosis. [ABSTRACT FROM AUTHOR]

The conservation of the genetic integrity of Apis mellifera subspecies has emerged as an important objective. In 2019, the Emilia-Romagna region became the first Italian regional authority to issue a law specifically addressing the protection of the native Apis mellifera ligustica subspecies. In this study we analysed a highly informative portion of the mitochondrial DNA (mtDNA), widely used for assessing genetic diversity of honey bee populations. By analysing 1143 honey bees sampled after the introduction of this law, we provided a snapshot of the distribution of mtDNA haplotypes in this region. The two most frequent mtDNA haplotypes were C1 (characteristic of A. m. ligustica) and C2 (characteristic of A. m. carnica), reported in 86.5% and 11.0% of the analysed bees, respectively. About 1.3% and 1.1% of the analysed bees carried mtDNA haplotypes of the A and M lineages (haplotypes A1a, A1e, A4, A26, A65 and two novel ones, A2w and A6a; M3, M3a, M4 and M79). Continued genetic monitoring will be important to assess the impact of this regional law over the coming years. Based on the obtained results, we recommend a more stringent policy to prevent the erosion of the genetic integrity of the native subspecies A. m. ligustica. [ABSTRACT FROM AUTHOR]

The variability of the cytochrome b gene in 11 individuals of Korean field mouse from the Ussuri Nature Reserve located on the southern spurs of the Sikhote-Alin in the Przewalski Mountains has been analyzed. In the population, a high level of genetic diversity was identified owing to the discovery of individuals with haplotypes of three phylogenetic lineages, i.e., Amur, Korea, and Manchuria. The majority of individuals (72.73%) in the population had Amur haplotypes. A significantly lower frequency of occurrence of individuals with Korea haplotypes in the Ussuri Nature Reserve (9.09%) compared to the previously analyzed population of the Khasansky district (38.46%) located in the very south of the Primorsky krai was noted. In the Ussuri Nature Reserve, for the first time in the Russian Far East, two individuals with Manchuria haplotypes were discovered. Previously, only one finding of an individual with a similar haplotype was noted in the literature in the Heilongjiang province of Northeast China. It was suggested that individuals with haplotypes of the Korea phylogroup penetrate into the south of Sikhote-Alin from South Korea and with haplotypes of the Manchuria phylogroup from Northeast China. [ABSTRACT FROM AUTHOR]

Blind mole rats (Nannospalax) in Turkey, adapted to low-oxygen subterranean habitats, demonstrate considerable diploid chromosome number diversity, including species like Nannospalax xanthodon, Nannospalax leucodon, and Nannospalax ehrenbergi. However, uncertainties persist regarding the taxonomic status and nomenclature of populations with varying diploid chromosome numbers. Resolving these uncertainties is essential for effective biodiversity management and strategic conservation planning within the ecosystem. This study focuses on elucidating the phylogenetic relationships within the blind mole rat genus Nannospalax, particularly among individuals exhibiting the 2n = 54 cytotype across diverse Turkish geographical regions. Utilizing nuclear (IRBP gene region) and mitochondrial DNA (D-loop control region and 16S rRNA gene regions), the study addresses key questions regarding the phylogenetic relationships between allopatric cytotypes sharing the same diploid chromosome number. The analyses, employing Maximum Likelihood, Neighbor Joining, and Network phylogenetic methods, reveal a preliminary differentiation level suggesting the potential existence of at least three cryptic species within the 2n = 54 cytotypes in Anatolia. It is emphasized that these conclusions are preliminary due to the limited sample size, necessitating further investigation. Additionally, the research validates the morphologically based species Nannospalax tuncelicus among Turkish blind mole rats. Genetic distance values from sequence analyses indicate significant divergence, establishing Nannospalax tuncelicus as a distinct species from other recognized species in Turkey. The study underscores the importance of resolving uncertainties in taxonomic status for effective biodiversity management and conservation planning. Future studies should expand sample sizes and comprehensively address the phylogenetic background of cytotypes, especially the İmamoğlu-Adana (2n = 54) population within the Nannospalax ehrenbergi species, to enhance our understanding of the evolutionary dynamics within this genus. [ABSTRACT FROM AUTHOR]

Odontamblyopus sp. is a small burrowing fish widely distributed in coastal waters and intertidal zone of China. Due to the morphological similarity of Odontamblyopus and even Amblyopinae fish, their classification has always been controversial. The lack of genomic information is also not helpful for further analysis of classification and phylogenetics. In this study, we conducted a whole genomic survey of O. sp. based on next-generation sequencing (NGS). A total of 31.30 Gb of high-quality sequence data were obtained in this study. The estimated genome size of O. sp. was 984.05 Mb, with heterozygosity and repetitive sequence rates of 0.66 and 42.94%, and a GC content of approximately 40.23%. The total sequence length of the genome assembly is 920.03 Mb. A total of 227,271 simple sequence repeats (SSRs) were identified, with the highest frequency of repeated motifs being dinucleotide motifs at 58.00%, followed by trinucleotide motifs at 33.00%, tetranucleotide motifs at 7.10%, pentanucleotide motifs at 1.14%, and hexanucleotide motifs at 0.75%. The assembled complete mitochondrial genome sequence was 16,766 bp in length and the structure of its control region were detected and phylogenetic analysis was performed. The results of PSMC (pairwise sequentially Markovian coalescent) analysis showed that two population declines and a population expansion in the Pleistocene, which were consistent with the glacial and interglacial periods, indicating that the population dynamics of O. sp. was closely related to climate conditions. This is the first study on O. sp. genomic characteristics. [ABSTRACT FROM AUTHOR]

Carangidae is an economically important fish family comprised of 32 genera with more than 140 circumglobally distributed species. Its members exhibit vast differences in morphology and lifestyle, thus making them compelling subjects for evolutionary studies. Recently, more works on carangids have detected the presence of cryptic lineages through molecular and/or non-molecular techniques. Credited for its inherent amplification efficiency, mitophylogenomics became effective in opening avenues to further understand higher-level interrelationships in many fish groups. However, the mitophylogenomic approach has not yet been widely applied to infer evolutionary history at the lower-level interrelationships, especially on cryptic representatives. In this study, we evaluated the diagnostic applicability of mitogenomes in detecting population-level divergences within Carangidae. Using the mitogenomes, we detected intraspecific divergences on some taxa, namely Caranx melampygus, Selaroides leptolepis, Seriola lalandi, Decapterus maruadsi, and Trachurus trachurus, with divergences highly correspondent to that of their geographic origins. Additionally, a widespread Pacific arrangement was also detected for S. rivoliana. Our discoveries were highly corroborative with findings from other Carangidae studies which utilized different diagnostic markers (e.g., SNPs, microsatellites, morphometrics, parasites). Dated phylogeny also suggested that intraspecific diversifications occurred during the Late Neogene. Likewise, we characterized two mitogenomes from different cryptic lineages of Selaroides leptolepis and revealed that the two mitogenomes were K2P pairwise = 5.58% different from each other. Its genetic compositions included 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. These findings paved way for future evolutionary insights into the divergence histories of other fish populations. [ABSTRACT FROM AUTHOR]

The hypervariable region (HVR) in the control region of the mitochondrial DNA has frequently been used for population genetics and phylogeographic studies because of its highly variable nature. Although the HVR is beneficial for evaluating recent evolutionary history, including population demography, recent studies have implied the incidence of homoplasy in this region. To assess the accuracy of relying solely on the HVR for population genetics studies, molecular evolutionary analysis of the HVR, NADH-dehydrogenase subunit 2 (ND2), and cytochrome b genes were performed using 120 individuals of marbled flounder Pseudopleuronectes yokohamae. The HVR exhibited the highest genetic variability among the three regions, with sites showing high site-specific substitution rates. Considering the reticulate haplotype network structure and evolutionary linkages between regions, homoplastic mutations were indicated in the HVR in addition to ND2, underestimating genetic diversity. We found that homoplasy was less likely to affect coalescent-based demographic inferences in the population; however, there is still a potential risk of misinterpretation of population demography when solely using the HVR owing to its hypervariable nature. Collectively, we suggest analyzing other regions in addition to the HVR in fish population genetic research to improve accuracy and eliminate biases caused by homoplasy. [ABSTRACT FROM AUTHOR]

Tri(1,3-dichloro-2-propyl)phosphate (TDCPP) is one of the most widely used organophosphorus flame retardants in consumer products. TDCPP has been confirmed to be neurotoxic, but its mechanism has not been clarified and may be related to mitophagy. AMBRA1 can promote neurological autophagy, but whether AMBRA1 is involved in the mechanism of TDCPP-induced neurotoxicity has not been elucidated. In this study, the optimal neuronal damage model was established by exposing mice hippocampal neurons to TDCPP. Furthermore, on the basis of this model, siRNA was used to knock down AMBRA1. Combined with qRT-PCR and Western blot techniques, we identified AMBRA1-mediated mitophagy-induced neuronal damage in vitro mechanism. The experimental results indicated that TDCPP treatment for 24 h led to a decrease in the cell viability of mouse hippocampal neurons, causing neuronal damage. Meanwhile, TDCPP exposure increased autophagy marker proteins p62 and LC3B, and down-regulated mitochondrial DNA ND1 damage and TOMM20 protein, suggesting that TDCPP exposure promoted mitophagy. In addition, TDCPP exposure led to changes in the expression of AMBRA1 and the key factors of mitophagy, FUNDC1, PINK1, and PARKIN, whereas mitophagy was inhibited after knockdown of AMBRA1. The research results indicated that exposure to TDCPP induced neuronal damage and promoted mitophagy. The mechanism may be that AMBRA1 promoted mitophagy in neuronal cells through the PARKIN-dependent/non-dependent pathway. This study revealed the toxic effects of TDCPP on the nervous system and its potential molecular mechanisms, which provided important clues for further understanding the mechanism of action of AMBAR1-mediated mitophagy. [ABSTRACT FROM AUTHOR]

Georgia is part of two biodiversity hotspots, the Caucasus and the Irano-Anatolian, both of which are characterized by high biological diversity and endemism rates. Eighty-one species of small mammals (Eulipotyphla, Chiroptera, Rodentia, and Leporidae) have been recorded in Georgia so far based on morphological identification. However, a comprehensive understanding of small mammal diversity requires integrative taxonomic approaches due to the cryptic nature and sympatric distribution of some taxa. Here, to develop a DNA barcode library, we re-evaluated the small mammal diversity of Georgia. Samples for DNA studies were collected during the last nine years throughout Georgia. The Cytochrome Oxidase Subunit I (COI) region of the mitochondrial genome was barcoded for collected samples, and a DNA barcode library was assembled. As a result, nearly 80% of the known species of Georgian small mammals were covered. Two species, Microtus rossiaemeridionalis (Ognev, 1924) and Myotis tschuliensis (Kuzyakin, 1935), were detected for the first time in Georgia. Furthermore, several problems were identified within the Chiroptera and Rodentia orders, requiring further studies. [ABSTRACT FROM AUTHOR]

Bone homeostasis relies on the dynamic balance of osteoblast mediated bone construction and osteoclast-based bone resorption processes, which has been reported to be controlled by various mineral ions. However, there is no direct evidence of the effect and the underlying mechanism of high salt stimulation on bone metabolism. In this study, we demonstrated that high salt stimulation promoted excessive mitochondrial fission mediated by dynamin-related protein 1 in mesenchymal stem cells, which resulted in impaired mitochondrial morphology and function. Consequently, this impairment hindered the bone formation of mesenchymal stem cells, resulting in osteopenia in mice. Mechanically, the impaired property of mesenchymal stem cells which was caused by high salt was controlled by dynamin-related protein 1 mediated mitochondrial fission, which inhibited the classical Wnt signaling pathway. Furthermore, the osteogenic property of mesenchymal stem cells decreased by high salt could be restored by exosomes to transfer the mitochondrial DNA into the impaired mesenchymal stem cells. This study provides not only new strategies for promoting bone regeneration but also new insights into the effect and mechanism of exosome-mediated delivery. [ABSTRACT FROM AUTHOR]

Type-1 IFN (interferon)-associated innate immune response is increasingly getting attention in neurodegenerative and metabolic diseases like type 2 diabetes (T2DM). However, its significance in T2DM/lipotoxicity-induced neuroglia changes and cognitive impairment is missing. The present study aims to evaluate the involvement of cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon gene), IRF3 (interferon regulatory factor-3), TBK (TANK binding kinase)-mediated Type-1 IFN response in the diabetic brain, and lipotoxicity (palmitate-bovine serum albumin conjugate/PA-BSA)-induced changes in cells (neuro2a and BV2). T2DM was induced in C57/BL6 mice by feeding on a high-fat diet (HFD, 60% Kcal) for 16 weeks and injecting a single dose of streptozotocin (100 mg/kg, i.p) in the 12th week. Plasma biochemical parameter analysis, neurobehavioral assessment, protein expression, and quantitative polymerase chain reaction study were carried out to decipher the hypothesis. T2DM-associated metabolic and lipotoxic stress led to mitochondrial impairment causing leakage of mtDNA to the cytoplasm further commencing cGAS activation and its downstream signaling. The diseased hippocampus and cortex showed decreased expression of synaptophysin (p < 0.01) and PSD-95 (p < 0.01, p < 0.05) with increased expression of cGAS (p < 0.001), p-STING (p < 0.001), p-STAT1 (signal transducer and activator of transcription) (p < 0.01), and IFN-β (p < 0.001) compared to normal control. The IFN-β/p-STAT1-mediated microglia activation was executed employing a conditioned media approach. C-176, a selective STING inhibitor, alleviated cGAS/p-STING/IFN-β expression and proinflammatory microglia/M1-associated markers (CD16 expression, CXCL10, TNF-α, IL-1β mRNA fold change) in the diabetic brain. The present study suggests Type-1IFN response may result in neuroglia dyshomeostasis affecting normal brain function. Alleviating STING signaling has the potential to protect T2DM-associated central ailment. [ABSTRACT FROM AUTHOR]

Mosquitoes (Diptera: Culicidae) are one of the most studied groups of arthropods worldwide due to their high transmission capacity for pathogens, including viruses and parasites. During June to October 2022, the prevalence of mosquito species in 12 intensive pig farms from 12 representative administrative regions in Hunan province of China was investigated using traps with ultraviolet light. All collected mosquitoes were counted and identified to species according to morphological and molecular methods. A total of 4,443 mosquito specimens were collected in the pig farms, and they represented one family, four genera and nine species. Culex pipiens pipiens (24%) was the most common mosquito species, followed by Armigeres subalbatus (23.4%) and Culex tritaeniorhynchus (20.6%). Phylogenetic analyses based on mitochondrial cox1 sequences revealed all mosquito species from present study grouping into distinct monophyletic groups corresponding to nine known mosquito species with strongly supported. The results of the present investigation have implications for the ongoing control of mosquito infestation in pig farms in Hunan province, China. This is the first report of mosquito populations in intensive pig farms in Hunan province, China.Highlights: •This is the first report of mosquito populations in intensive pig farms in Hunan province, China. •A total of 4,443 mosquito specimens were collected and they represented one family, four genera and nine species. [ABSTRACT FROM AUTHOR]