The dynamics of cardiolipin synthesis post-mitochondrial fusion

AbstractAlteration in mitochondrial fusion may regulate mitochondrial metabolism. Since the phospholipid cardiolipin (CL) is required for function of the mitochondrial respiratory chain, we examined the dynamics of CL synthesis in growing Hela cells immediately after and 12h post-fusion. Cells were transiently transfected with Mfn-2, to promote fusion, or Mfn-2 expressing an inactive GTPase for 24h and de novo CL biosynthesis was examined immediately after or 12h post-fusion. Western blot analysis confirmed elevated Mfn-2 expression and electron microscopic analysis revealed that Hela cell mitochondrial structure was normal immediately after and 12h post-fusion. Cells expressing Mfn-2 exhibited reduced CL de novo biosynthesis from [1,3-3H]glycerol immediately after fusion and this was due to a decrease in phosphatidylglycerol phosphate synthase (PGPS) activity and its mRNA expression. In contrast, 12h post-mitochondrial fusion cells expressing Mfn-2 exhibited increased CL de novo biosynthesis from [1,3-3H]glycerol and this was due to an increase in PGPS activity and its mRNA expression. Cells expressing Mfn-2 with an inactive GTPase activity did not exhibit alterations in CL de novo biosynthesis immediately after or 12h post-fusion. The Mfn-2 mediated alterations in CL de novo biosynthesis were not accompanied by alterations in CL or monolysoCL mass. [1-14C]Oleate incorporation into CL was elevated at 12h post-fusion indicating increased CL resynthesis. The reason for the increased CL resynthesis was an increased mRNA expression of tafazzin, a mitochondrial CL resynthesis enzyme. Ceramide-induced expression of PGPS in Hela cells or in CHO cells did not alter expression of Mfn-2 indicating that Mfn-2 expression is independent of altered CL synthesis mediated by elevated PGPS. In addition, Mfn-2 expression was not altered in Hela cells expressing phospholipid scramblase-3 or a disrupted scramblase indicating that proper CL localization within mitochondria is not essential for Mfn-2 expression. The results suggest that immediately post-mitochondrial fusion CL de novo biosynthesis is “slowed down” and then 12h post-fusion it is “upregulated”. The implications of this are discussed

Common bean SNP alleles and candidate genes affecting photosynthesis under contrasting water regimes

Water deficit is a major worldwide constraint to common bean (Phaseolus vulgaris L.) production, being photosynthesis one of the most affected physiological processes. To gain insights into the genetic basis of the photosynthetic response of common bean under water-limited conditions, a collection of 158 Portuguese accessions was grown under both well-watered and water-deficit regimes. Leaf gas-exchange parameters were measured and photosynthetic pigments quantified. The same collection was genotyped using SNP arrays, and SNP-trait associations tested considering a linear mixed model accounting for the genetic relatedness among accessions. A total of 133 SNPtrait associations were identified for net CO2 assimilation rate, transpiration rate, stomatal conductance, and chlorophylls a and b, carotenes, and xanthophyll contents. Ninety of these associations were detected under waterdeficit and 43 under well-watered conditions, with only two associations common to both treatments. Identified candidate genes revealed that stomatal regulation, protein translocation across membranes, redox mechanisms, hormone, and osmotic stress signaling were the most relevant processes involved in common bean response to water-limited conditions. These candidates are now preferential targets for common bean water-deficit-tolerance breeding. Additionally, new sources of water-deficit tolerance of Andean, Mesoamerican, and admixed origin were detected as accessions valuable for breeding, and not yet exploredinfo:eu-repo/semantics/publishedVersio

Integrating Clinical Phenotype With Multiomics Analyses of Human Cardiac Tissue Unveils Divergent Metabolic Remodeling in Genotype-Positive and Genotype-Negative Patients With Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by sarcomere gene mutations (genotype-positive HCM) in ≈50% of patients and occurs in the absence of mutations (genotype-negative HCM) in the other half of patients. We explored how alterations in the metabolomic and lipidomic landscape are involved in cardiac remodeling in both patient groups. METHODS: We performed proteomics, metabolomics, and lipidomics on myectomy samples (genotype-positive N=19; genotype-negative N=22; and genotype unknown N=6) from clinically well-phenotyped patients with HCM and on cardiac tissue samples from sex- and age-matched and body mass index-matched nonfailing donors (N=20). These data sets were integrated to comprehensively map changes in lipid-handling and energy metabolism pathways. By linking metabolomic and lipidomic data to variability in clinical data, we explored patient group-specific associations between cardiac and metabolic remodeling. RESULTS:HCM myectomy samples exhibited (1) increased glucose and glycogen metabolism, (2) downregulation of fatty acid oxidation, and (3) reduced ceramide formation and lipid storage. In genotype-negative patients, septal hypertrophy and diastolic dysfunction correlated with lowering of acylcarnitines, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines. In contrast, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines were positively associated with septal hypertrophy and diastolic impairment in genotype-positive patients. CONCLUSIONS: We provide novel insights into both general and genotype-specific metabolic changes in HCM. Distinct metabolic alterations underlie cardiac disease progression in genotype-negative and genotype-positive patients with HCM.</p

Ramsay Hunt Syndrome: A Histopathologic Observation Of A Facial Sequelae.

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Root Resorption in Orthodontics - Genetic Susceptibility?

OBJECTIVES: External root resorption (ERR) is a condition that can be observed in association with orthodontic treatment. The etiology of root resorption is complex, related with several factors. Some inflammatory mediators, controlled by specific genes, have been associated with bone resorption and in the recruitment of osteoclasts during orthodontic movement (Lee et al., 2007; Abass et al., 2008; Bastos et al., 2009). Particularly the association between polymorphisms in the IL-1B gene and ERR during orthodontic treatment has been referenced in literature. The present paper as the principal objective to present a case of an orthodontic patient, Caucasian, gender male, 15 years old, with positive family history of generalized ERR associated to orthodontic treatment (one sister), and there was therefore need to clarify the role of genetic susceptibility in its pathogenesis. MATERIALS AND METHODS: It was performed a literature review on PUBMED with the key words dental orthodontics resorption genetics, 12 articles were obtained and were included 8 of these. There were also associated with the theme 7 more articles, from the list of related articles. The search was limited to the last 10 years and the English, French and Spanish. RESULTS: As there was positive family history of the ERR was decided to perform a genetic test for determination of single polymorphisms for IL1B gene (TGP, CGC Clinical Genetics Center, Portugal), which revealed the presence of an allele of the IL1B gene - positive result for ERR. The absence of external etiological factors associated with orthodontic treatment was suggestive of possible individual genetic susceptibility. CONCLUSIONS: The identification of individuals with increased susceptibility to ERR should be considered during the orthodontic treatment plan, to allow adjustments necessary in terms of magnitude of the force to be applied, both in terms of duration of treatment

BioSTEC 2017: 10th International Joint Conference on Biomedical Engineering Systems and Technologies: Proceedings Volume 5: HealthInf

This book contains the proceedings of the 10th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2017). This conference is sponsored by the Institute for Systems and Technologies of Information, Control and Communication (INSTICC), in cooperation with the ACM Special Interest Group on Knowledge Discovery and Data Mining (ACM SIGKDD), the EUROMICRO, the International Society for Telemedicine & eHealth (ISfTeH), the Association for the Advancement of Artificial Intelligence (AAAI), the International Society for Computational Biology (iSCB) and the Biomedical Engineering Society (BMES)