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Biomolecules May 2024Manganese (Mn) is an essential heavy metal in the human body, while excess leads to neurotoxicity, as observed in this study, where 100 µM of was administered to the...
Manganese (Mn) is an essential heavy metal in the human body, while excess leads to neurotoxicity, as observed in this study, where 100 µM of was administered to the human neuroblastoma (SH-SY5Y) cell model of dopaminergic neurons in neurodegenerative diseases. We quantitated pathway and gene changes in homeostatic cell-based adaptations to exposure. Utilizing the Gene Expression Omnibus, we accessed the GSE70845 dataset as a microarray of SH-SY5Y cells published by Gandhi et al. (2018) and applied statistical significance cutoffs at < 0.05. We report 74 pathway and 10 gene changes with statistical significance. ReactomeGSA analyses demonstrated upregulation of histones (5 out of 10 induced genes) and histone deacetylases as a neuroprotective response to remodel/mitigate -induced DNA/chromatin damage. Neurodegenerative-associated pathway changes occurred. NF-κB signaled protective responses via Sirtuin-1 to reduce neuroinflammation. Critically, activated three pathways implicating deficits in purine metabolism. Therefore, we validated that urate, a purine and antioxidant, mitigated -losses of viability in SH-SY5Y cells. We discuss as a hypoxia mimetic and trans-activator of HIF-1α, the central trans-activator of vascular hypoxic mitochondrial dysfunction. induced a 3-fold increase in mRNA levels for antioxidant metallothionein-III, which was induced 100-fold by hypoxia mimetics deferoxamine and zinc.
Topics: Humans; Manganese; Neuroblastoma; Cell Line, Tumor; Cell Survival; Neuroprotective Agents; Biomarkers
PubMed: 38927051
DOI: 10.3390/biom14060647 -
BMC Zoology Jun 2024The Middle Eastern endemic genus Asaccus comprises Southwest Asian leaf-toed geckos. To date, this genus includes 19 species of leaf-toed geckos (seven in Arabia and 12...
The Middle Eastern endemic genus Asaccus comprises Southwest Asian leaf-toed geckos. To date, this genus includes 19 species of leaf-toed geckos (seven in Arabia and 12 in the Zagros Mountains). Despite a recent study on the taxonomy and phylogeny of Asaccus species in Iran, controversies still remain surrounding the phylogeny and phylogeography of the genus. Here, we used an integrative approach to determine the phylogeny and phylogeography of Asaccus species using two mitochondrial genes (12 S and Cyt b), and one nuclear gene (c-mos). Our results uncovered 22 distinct lineages, demonstrating a significant cryptic diversity that challenges the current morphological classifications of these species. Phylogenetic analyses reinforce the monophyly of the Asaccus group, positioning A. montanus as a basal lineage, which supports a deep evolutionary divergence dating back to the Late Oligocene, approximately 27.94 million years ago. This genetic diversity also highlights the impact of historical climatic and geographical changes on species diversification. The findings advocate for an integrative approach combining both molecular and morphological data to resolve species identities accurately, thereby enhancing conservation strategies to protect these genetically distinct lineages.
PubMed: 38926885
DOI: 10.1186/s40850-024-00203-1 -
Scientific Data Jun 2024The plum fruit moth Grapholita funebrana (Tortricidae, Lepidoptera) is an important pest of many wild and cultivated stone fruits and other plants in the family...
The plum fruit moth Grapholita funebrana (Tortricidae, Lepidoptera) is an important pest of many wild and cultivated stone fruits and other plants in the family Rosaceae. Here, we assembled its nuclear and mitochondrial genomes using Illumina, Nanopore, and Hi-C sequencing technologies. The nuclear genome size is 570.9 Mb, with a repeat rate of 51.28%, and a BUCSO completeness of 97.7%. The karyotype for males is 2n = 56. We identified 17,979 protein-coding genes, 5,643 tRNAs, and 94 rRNAs. We also determined the mitochondrial genome of this species and annotated 13 protein-coding genes, 22 tRNAs, and 2 rRNA. These genomes provide resources to understand the genetics, ecology, and genome evolution of the tortricid moths.
Topics: Animals; Female; Male; Genome, Insect; Genome, Mitochondrial; Moths; Prunus domestica
PubMed: 38926434
DOI: 10.1038/s41597-024-03522-7 -
Molecular Genetics & Genomic Medicine Jun 2024Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It...
BACKGROUND
Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It is a leading cause of heart failure and cardiac death at a young age. Cases with neonatal onset DCM were correlated with severe clinical presentation and poor prognosis. A monogenic molecular etiology accounts for nearly half of cases.
FAMILY DESCRIPTION
Here, we report a family with three deceased offspring at the age of 1 year old. The autopsy of the first deceased infant revealed a DCM. The second infant presented a DCM phenotype with a severely reduced Left Ventricular Ejection Fraction (LVEF) of 10%. Similarly, the third infant showed a severe DCM phenotype with LVEF of 30% as well, in addition to eccentric mitral insufficiency.
RESULTS
Exome sequencing was performed for the trio (the second deceased infant and her parents). Data analysis following the autosomal dominant and recessive patterns of inheritance was carried out along with a mitochondrial pathways-based analysis. We identified a homozygous frameshift variant in the TNNI3 gene (c.204delG; p.(Arg69AlafsTer8)). This variant has been recently reported in the ClinVar database in association with cardiac phenotypes as pathogenic or likely pathogenic and classified as pathogenic according to ACMG.
CONCLUSION
Genetic counseling was provided for the family and a prenatal diagnosis of choronic villus was proposed in the absence of pre-implantation genetic diagnosis possibilities. Our study expands the case series of early-onset DCM patients with a protein-truncating variant in the TNNI3 gene by reporting three affected infant siblings.
Topics: Humans; Cardiomyopathy, Dilated; Frameshift Mutation; Female; Homozygote; Pedigree; Consanguinity; Male; Infant; Phenotype; Troponin I
PubMed: 38924380
DOI: 10.1002/mgg3.2486 -
Journal of Cellular and Molecular... Jun 2024Mitochondrial dynamics has emerged as an important target for neuronal protection after cerebral ischaemia/reperfusion. Therefore, the aim of this study was to...
Mitochondrial dynamics has emerged as an important target for neuronal protection after cerebral ischaemia/reperfusion. Therefore, the aim of this study was to investigate the mechanism by which ARMC10 regulation of mitochondrial dynamics affects mitochondrial function involved in ischaemic stroke (IS). Mitochondrial morphology was detected by laser scanning confocal microscopy (LSCM), and mitochondrial ultrastructural alterations were detected by electron microscopy. The expression of mitochondrial dynamics-related genes Drp1, Mfn1, Mfn2, Fis1, OPA1 and ARMC10 and downstream target genes c-Myc, CyclinD1 and AXIN2 was detected by RT-qPCR. Western blot was used to detect the protein expression of β-catenin, GSK-3β, p-GSK-3β, Bcl-2 and Bax. DCFH-DA fluorescent probe was to detect the effect of ARMC10 on mitochondrial ROS level, Annexin V-FITC fluorescent probe was to detect the effect of ARMC10 on apoptosis, and ATP assay kit was to detect the effect of ARMC10 on ATP production. Mitochondrial dynamics was dysregulated in clinical IS samples and in the OGD/R cell model, and the relative expression of ARMC10 gene was significantly decreased in IS group (p < 0.05). Knockdown and overexpression of ARMC10 could affect mitochondrial dynamics, mitochondrial function and neuronal apoptosis. Agonist and inhibitor affected mitochondrial function and neuronal apoptosis by targeting Wnt/β-Catenin signal pathway. In the OGD/R model, ARMC10 affected mitochondrial function and neuronal apoptosis through the mechanism that regulates Wnt/β-catenin signalling pathway. ARMC10 regulates mitochondrial dynamics and protects mitochondrial function by activating Wnt/β-catenin signalling pathway, to exert neuroprotective effects.
Topics: Wnt Signaling Pathway; Mitochondria; Humans; Ischemic Stroke; Mitochondrial Dynamics; Apoptosis; Armadillo Domain Proteins; Male; beta Catenin; Reactive Oxygen Species; Brain Ischemia; Animals
PubMed: 38924214
DOI: 10.1111/jcmm.18449 -
PloS One 2024Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelium, particularly prevalent in Asian countries with liver fluke infections. Current...
Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelium, particularly prevalent in Asian countries with liver fluke infections. Current chemotherapy for CCA often fails due to drug resistance, necessitating novel anticancer agents. This study investigates the potential of 5'-deoxy-5'-methylthioadenosine (MTA), a naturally occurring nucleoside, against CCA. While MTA has shown promise against various cancers, its effects on CCA remain unexplored. We evaluated MTA's anticancer activity in CCA cell lines and drug-resistant sub-lines, assessing cell viability, migration, invasion, and apoptosis. The potential anticancer mechanisms of MTA were explored through proteomic analysis using LC-MS/MS and bioinformatic analysis. The results show a dose-dependent reduction in CCA cell viability, with enhanced effects on cancer cells compared to normal cells. Moreover, MTA inhibits growth, induces apoptosis, and suppresses cell migration and invasion. Additionally, MTA enhanced the anticancer effects of gemcitabine on drug-resistant CCA cells. Proteomics revealed the down-regulation of multiple proteins by MTA, affecting various molecular functions, biological processes, and cellular components. Network analysis highlighted MTA's role in inhibiting proteins related to mitochondrial function and energy derivation, crucial for cell growth and survival. Additionally, MTA suppressed proteins involved in cell morphology and cytoskeleton organization, important for cancer cell motility and metastasis. Six candidate genes, including ZNF860, KLC1, GRAMD1C, MAMSTR, TANC1, and TTC13, were selected from the top 10 most down-regulated proteins identified in the proteomics results and were subsequently verified through RT-qPCR. Further, KLC1 protein suppression by MTA treatment was confirmed through Western blotting. Additionally, based on TCGA data, KLC1 mRNA was found to be upregulated in the tissue of CCA patients compared to that of normal adjacent tissues. In summary, MTA shows promising anticancer potential against CCA by inhibiting growth, inducing apoptosis, and suppressing migration and invasion, while enhancing gemcitabine's effects. Proteomic analysis elucidates possible molecular mechanisms underlying MTA's anticancer activity, laying the groundwork for future research and development of MTA as a treatment for advanced CCA.
Topics: Cholangiocarcinoma; Humans; Proteomics; Cell Line, Tumor; Deoxyadenosines; Bile Duct Neoplasms; Apoptosis; Cell Movement; Thionucleosides; Antineoplastic Agents; Gemcitabine; Deoxycytidine; Cell Survival; Cell Proliferation; Drug Resistance, Neoplasm
PubMed: 38923999
DOI: 10.1371/journal.pone.0306060 -
Veterinary Sciences May 2024Cattle ticks are a significant health concern in tropical livestock production due to their hematophagous behavior and potential as vectors for human and animal...
Cattle ticks are a significant health concern in tropical livestock production due to their hematophagous behavior and potential as vectors for human and animal pathogens. In this study, we investigated the tick population present in dairy cattle production, calves, and grazing areas of livestock systems in the northwestern Colombian Amazon. Identification was based on taxonomic keys and molecular markers. Phylogenetic relationships were established using mitochondrial and 16S genes. Population structure analysis was performed considering age, racial type ( vs. ), and the influence of environmental factors and the geomorphological landscape on tick population dynamics. Our findings revealed the presence of a single tick species, with a unique haplotype identified for each mitochondrial gene assessed. Phylogenetic analysis classified the found species within Clade A of the complex. Ticks were more prevalent during periods of low rainfall and high temperature, and cows exhibited the highest tick abundance. Thus, these results provide insights into the population characteristics and distribution of the tick species present in dairy cattle production systems in the northwestern part of the Colombian Amazon. This information is fundamental for developing targeted strategies based on seasonal variation and host characteristics to mitigate tick infestation severity in the region.
PubMed: 38921991
DOI: 10.3390/vetsci11060244 -
Insects Jun 2024Currently, the subfamily Meconematinae encompasses 1029 species, but whole-mitochondrial-genome assemblies have only been made available for 13. In this study, the whole...
Currently, the subfamily Meconematinae encompasses 1029 species, but whole-mitochondrial-genome assemblies have only been made available for 13. In this study, the whole mitochondrial genomes (mitogenomes) of nine additional species in the subfamily Meconematinae were sequenced. The size ranged from 15,627 bp to 17,461 bp, indicating double-stranded circular structures. The length of the control region was the main cause of the difference in mitochondrial genome length among the nine species. All the mitogenomes including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs) and a control region (CR). The majority strand encoded 23 genes, and the minority strand encoded 14 genes. A phylogenetic analysis reaffirmed the monophyletic status of each subfamily, but the monophysitism of , and was not supported.
PubMed: 38921128
DOI: 10.3390/insects15060413 -
Insects May 2024Using Illumina sequencing technology, we generated complete mitochondrial genomes (mitogenomes) of three constituent species of the aphid genus Koch, (Blanchard),...
Using Illumina sequencing technology, we generated complete mitochondrial genomes (mitogenomes) of three constituent species of the aphid genus Koch, (Blanchard), Ghulamullah, and (Geoffroy). The sizes of the mitogenomes range from 15,306 to 15,410 bp, primarily due to variations in the length of non-coding regions. The mitogenomes consist of 37 coding genes arranged in the order of the ancestral insect mitogenome, a control region, and a repeat region between and According to the COI-based analysis, one previously reported mitogenome of should be assigned to . The gene order, nucleotide composition, and codon usage in the mitogenomes are highly conserved and similar to those of other species of Aphidinae. The tandem repeat units differ in nucleotide composition, length, and copy number across three species. Within the widespread Eurasian species , variation in repeat units among different geographic populations is observed, indicating that the repeat region may provide valuable insights for studying the intraspecific diversification of aphids. Phylogenetic analyses based on 28 complete mitogenomes of Aphidinae supported the monophyly of Aphidinae, Aphidini, Macrosiphini, and two subtribes of Aphidini. was monophyletic. and formed a sister group, while was placed basally. Characterization of the mitogenomes of provides valuable resources for further comparative studies and for advancing our understanding of the aphid mitogenome architecture.
PubMed: 38921104
DOI: 10.3390/insects15060389 -
Current Issues in Molecular Biology Jun 2024The family Scolopacidae presents a valuable subject for evolutionary research; however, molecular studies of Scolopacidae are still relatively understudied, and the...
The family Scolopacidae presents a valuable subject for evolutionary research; however, molecular studies of Scolopacidae are still relatively understudied, and the phylogenetic relationships of certain species remain unclear. In this study, we sequenced and obtained complete mitochondrial DNA (mtDNA) from and partial mtDNA from , and . The complete mtDNA contained 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 tRNA genes, and a control region. Scolopacidae contained three types of start codons and five types of stop codons (including one incomplete stop codon, T--). In 13 protein-coding genes, average uncorrected pairwise distances (Aupd) revealed that was the least conserved while had the lowest evolutionary rate. The ratio of Ka/Ks suggested that all PCGs were under purifying selection. Using two methods (maximum likelihood and Bayesian inference) to analyze the phylogenetic relationships of the family Scolopacidae, it was found that the genera and were clustered into another sister group, while the genus is more closely related to the genus . The genera , and form a monophyletic group. This study improves our understanding of the evolutionary patterns and phylogenetic relationships of the family Scolopacidae.
PubMed: 38921040
DOI: 10.3390/cimb46060369