Mitonuclear compatibility is maintained despite relaxed selection on male mitochondrial DNA in bivalves with doubly uniparental inheritance.

Mitonuclear coevolution is common in eukaryotes, but bivalve lineages that have doubly uniparental inheritance (DUI) of mitochondria may be an interesting example. In this system, females transmit mtDNA (F mtDNA) to all offspring, while males transmit a different mtDNA (M mtDNA) solely to their sons. Molecular evolution and functional data suggest oxidative phosphorylation (OXPHOS) genes encoded in M mtDNA evolve under relaxed selection due to their function being limited to sperm only (vs. all other tissues for F mtDNA). This has led to the hypothesis that mitonuclear coevolution is less important for M mtDNA. Here, we use comparative phylogenetics, transcriptomics, and proteomics to understand mitonuclear interactions in DUI bivalves. We found nuclear OXPHOS proteins coevolve and maintain compatibility similarly with both F and M mtDNA OXPHOS proteins. Mitochondrial recombination did not influence mitonuclear compatibility and nuclear-encoded OXPHOS genes were not upregulated in tissues with M mtDNA to offset dysfunction. Our results support that selection maintains mitonuclear compatibility with F and M mtDNA despite relaxed selection on M mtDNA. Strict sperm transmission, lower effective population size, and higher mutation rates may explain the evolution of M mtDNA. Our study highlights that mitonuclear coevolution and compatibility may be broad features of eukaryotes.

Comparison of Propofol and Alfaxalone as Anesthesic Drugs in Bitches Undergoing Ovariohysterectomies (Healthy Bitches and with Pyometra) and Cesarean Sections.

This study evaluated the efficacy and safety of two anesthetic agents, alfaxalone and propofol, on maternal physiological parameters (heart and respiratory rates, blood pressure, and temperature) on either ovariohysterectomies or cesarean sections in bitches. A total of 34 healthy and pyometra-affected females (classified as ASA II), were induced with IV propofol (4 mg/kg), while 35 females, both healthy and pyometra affected, were induced with IV alfaxalone (1 mg/kg). For cesarean sections, females (ASA II) were induced with propofol (n = 14) or alfaxalone (n = 14). Additionally, the neonatal viability and modified Apgar score were recorded at 5, 60, and 120 min post-delivery. There were no significant differences in the physiological parameters when comparing the use of propofol and alfaxalone in bitches undergoing ovariohysterectomies, regardless of their health status, nor when comparing cesarean sections. It was observed that bitches induced with propofol occasionally required an additional dose for maintenance of the anesthesia. Neonatal mortality rates were similar for both groups; however, alfaxalone was associated with higher neonatal viability as indicated by the Apgar scores. The findings suggest that both anesthetic protocols are effective and safe for use in canine reproductive surgeries, with no major differences in basic physiological parameters' alteration or neonatal outcomes between the two agents.

Cytosolic Ribosomal Protein Haploinsufficiency affects Mitochondrial Morphology and Respiration.

The interplay between ribosomal protein composition and mitochondrial function is essential for sustaining energy homeostasis. Precise stoichiometric production of ribosomal proteins is crucial to maximize protein synthesis efficiency while reducing the energy costs to the cell. However, the impact of this balance on mitochondrial ATP generation, morphology and function remains unclear. Particularly, the loss of a single copy ribosomal protein gene is observed in Mendelian disorders like Diamond Blackfan Anemia and is common in somatic tumors, yet the implications of this imbalance on mitochondrial function and energy dynamics are still unclear. In this study, we investigated the impact of haploinsufficiency for four ribosomal protein genes implicated in ribosomopathy disorders (rps-10, rpl-5, rpl-33, rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells. Our findings uncover significant, albeit variably penetrant, mitochondrial morphological differences across these mutants, alongside an upregulation of glutathione transferases, and SKN-1 dependent increase in oxidative stress resistance, indicative of increased ROS production. Specifically, loss of a single copy of rps-10 in C. elegans led to decreased mitochondrial activity, characterized by lower energy levels and reduced oxygen consumption. A similar reduction in mitochondrial activity and energy levels was observed in human leukemia cells with a 50% reduction in RPS10 transcript levels. Importantly, we also observed alterations in the translation efficiency of nuclear and mitochondrial electron transport chain components in response to reductions in ribosomal protein genes' expression in both C. elegans and human cells. This suggests a conserved mechanism whereby the synthesis of components vital for mitochondrial function are adjusted in the face of compromised ribosomal machinery. Finally, mitochondrial membrane and cytosolic ribosomal components exhibited significant covariation at the RNA and translation efficiency level in lymphoblastoid cells across a diverse group of individuals, emphasizing the interplay between the protein synthesis machinery and mitochondrial energy production. By uncovering the impact of ribosomal protein haploinsufficiency on the translation efficiency of electron transport chain components, mitochondrial physiology, and the adaptive stress responses, we provide evidence for an evolutionarily conserved strategy to safeguard cellular functionality under genetic stress.

Mitonuclear Sex Determination? Empirical Evidence from Bivalves.

Genetic elements encoded in nuclear DNA determine the sex of an individual in many animals. In certain bivalve lineages that possess doubly uniparental inheritance (DUI), mitochondrial DNA (mtDNA) has been hypothesized to contribute to sex determination. In these cases, females transmit a female mtDNA to all offspring, while male mtDNA (M mtDNA) is transmitted only from fathers to sons. Because M mtDNA is inherited in the same way as Y chromosomes, it has been hypothesized that mtDNA may be responsible for sex determination. However, the role of mitochondrial and nuclear genes in sex determination has yet to be validated in DUI bivalves. In this study, we used DNA, RNA, and mitochondrial short noncoding RNA (sncRNA) sequencing to explore the role of mitochondrial and nuclear elements in the sexual development pathway of the freshwater mussel Potamilus streckersoni (Bivalvia: Unionida). We found that the M mtDNA sheds a sncRNA partially within a male-specific mitochondrial gene that targets a pathway hypothesized to be involved in female development and mitophagy. RNA-seq confirmed the gene target was significantly upregulated in females, supporting a direct role of mitochondrial sncRNAs in gene silencing. These findings support the hypothesis that M mtDNA inhibits female development. Genome-wide patterns of genetic differentiation and heterozygosity did not support a nuclear sex-determining region, although we cannot reject that nuclear factors are involved with sex determination. Our results provide further evidence that mitochondrial loci contribute to diverse, nonrespiratory functions and additional insights into an unorthodox sex-determining system.

Mitonuclear sex determination? Empirical evidence from bivalves.

Genetic elements encoded in nuclear DNA determine the sex of an individual in many animals. In bivalves, however, mitochondrial DNA (mtDNA) has been hypothesized to contribute to sex determination in lineages that possess doubly uniparental inheritance (DUI). In these cases, females transmit a female mtDNA (F mtDNA) to all offspring, while male mtDNA (M mtDNA) is transmitted only from fathers to sons. Because M mtDNA is inherited in the same way as Y chromosomes, it has been hypothesized that mtDNA may be responsible for sex determination. However, the role of mitochondrial and nuclear genes in sex determination has yet to be validated in DUI bivalves. In this study, we used DNA, RNA, and mitochondrial short non-coding RNA (sncRNA) sequencing to explore the role of mitochondrial and nuclear elements in the sexual development pathway of the freshwater mussel Potamilus streckersoni (Bivalvia: Unionida). We found that the M mtDNA shed a sncRNA partially within a male-specific mitochondrial gene that targeted pathways hypothesized to be involved in female development and mitophagy. RNA-seq confirmed the gene target was significantly upregulated in females, supporting a direct role of mitochondrial sncRNAs in gene silencing. These findings support the hypothesis that M mtDNA inhibits female development. Genome-wide patterns of genetic differentiation and heterozygosity did not support a nuclear sex determining region, although we cannot reject that nuclear factors are involved with sex determination. Our results provide further evidence that mitochondrial loci contribute to diverse, non-respiratory functions and provide a first glimpse into an unorthodox sex determining system.

The male-type mitochondrial genome of the freshwater mussel Potamilus streckersoni Smith, Johnson, Inoue, Doyle, & Randklev, 2019 (Bivalvia: Unionidae).

The global decline of freshwater mussels emphasizes the need to establish genetic resources to better understand their biology, including a unique mitochondrial biology known as doubly uniparental inheritance. In this study, we present the complete male-type (M-type) mitochondrial genome of the freshwater mussel, Potamilus streckersoni Smith, Johnson, Inoue, Doyle, & Randklev, 2019. The M-type mtDNA is approximately 16 kilobases and contains 22 tRNAs, two rRNAs, and 14 protein-coding genes, including a male-specific open reading frame. Read coverage revealed that M-type mtDNA was more abundant than female-type mtDNA in male gonadal tissue, with respect to a non-spawning male individual. Novel mitogenomes were resolved within previously described sex-specific monophyletic clades across the subfamily Ambleminae. The availability of high-quality nuclear and mitochondrial genomic data for P. streckersoni makes it a model for future research into the potential role of mtDNA in sex determination or sexual development in freshwater mussels.

Knowledge, Attitude, and Practice (KAP) Survey toward Skin Cancer among Ecuadorian Population.

BACKGROUND: Skin cancer is one of the most common cancers, and melanoma is a highly preventable cancer. In Ecuador, few studies have evaluated the awareness levels of the population about the disease. For this reason, the objective of this study was to measure the level of knowledge, attitudes, and practices regarding skin cancer and its determining factors. METHODS: A cross-sectional analysis using an online self-assessment questionnaire containing 40 questions was delivered. A total of 537 participants were included in this study. Knowledge, attitude, and practice scores were assigned to each participant based on the number of correct or appropriate responses. Logistic regression analysis was used to calculate crude and adjusted odds ratios. RESULTS: In total, 75% of participants referenced knowledge of the harmful effects related to noncontrolled solar exposure. Concerning sunscreen, 76.7% knew the reason for using it. The female group was 1.68 times more likely to get a higher score than the male group, and the groups between 61-70 and 71-80 years were 0.30 and 0.17 times less likely to get a higher score compared with the less than 20-years-old group, respectively. CONCLUSIONS: The findings of this study indicate the requirement to increase the population's knowledge about skin cancer and possible protection measures. For this reason, the prevention and health promotion programs at a national level from primary healthcare centers are recommended. Due to the limitation of the representativeness of the sample, the use of more studies among Ecuadorian residents of the low socioeconomic level and replication in different provinces of Ecuador is justified.