Signatures of Extreme Longevity: A Perspective from Bivalve Molecular Evolution

Among Metazoa, bivalves have the highest lifespan disparity, ranging from 1 to 500+ years, making them an exceptional testing ground to understand mechanisms underlying aging and the evolution of extended longevity. Nevertheless, comparative molecular evolution has been an overlooked approach in this instance. Here, we leveraged transcriptomic resources spanning 30 bivalve species to unravel the signatures of convergent molecular evolution in four long-lived species: Margaritifera margaritifera, Elliptio complanata, Lampsilis siliquoidea, and Arctica islandica (the latter represents the longest-lived noncolonial metazoan known so far). We applied a comprehensive approach-which included inference of convergent dN/dS, convergent positive selection, and convergent amino acid substitution-with a strong focus on the reduction of false positives. Genes with convergent evolution in long-lived bivalves show more physical and functional interactions to each other than expected, suggesting that they are biologically connected; this interaction network is enriched in genes for which a role in longevity has been experimentally supported in other species. This suggests that genes in the network are involved in extended longevity in bivalves and, consequently, that the mechanisms underlying extended longevity are-at least partially-shared across Metazoa. Although we believe that an integration of different genes and pathways is required for the extended longevity phenotype, we highlight the potential central roles of genes involved in cell proliferation control, translational machinery, and response to hypoxia, in lifespan extension

Quinupristin/dalfopristin Bonding in Combination with Intraperitoneal Antibiotics Prevent Infection of Knitted Polyester Graft Material in a Subcutaneous Rat Pouch Model Infected with Resistant Staphylococcus epidermidis

AbstractObjective: to investigate the efficacy of quinupristin/dalfopristin in the prevention of prosthetic graft infection in a rat subcutaneous pouch model.Methods: graft infections were established in the subcutaneous tissue of 140 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation withStaphylococcus epidermidis with intermediate resistance to glycopeptides. The study included one group without contamination, one contaminated group without prophylaxis, one contaminated group that received 50mg/l quinupristin/dalfopristin-soaked graft, one contaminated group that received 10mg/kg intraperitoneal levofloxacin, one contaminated group that received 3mg/kg intraperitoneal doxycycline, and two contaminated groups that received 50mg/l quinupristin/dalfopristin-soaked plus 10mg/kg intraperitoneal levofloxacin or 3mg/kg intraperitoneal doxycycline. Each group included 20 animals. The grafts were removed after 7 days and evaluated by quantitative culture.Results: quinupristin/dalfopristin showed a significantly higher efficacy than levofloxacin and doxycycline, even though quantitative graft cultures for rats that received only quinupristin/dalfopristin-soaked graft showed bacterial growth. Otherwise, the efficacy of levofloxacin was similar to that of doxycycline. Only the group treated with quinupristin/dalfopristin combined with levofloxacin or doxycycline showed no evidence of staphylococcal infection.Conclusions: quinupristin/dalfopristin as adjunctive topical antibiotic prophylaxis can be useful for the prevention of vascular graft infections caused by staphylococcal strains with high levels of resistance

RNAIII-inhibiting Peptide and/or Nisin Inhibit Experimental Vascular Graft Infection with Methicillin-susceptible and Methicillin-resistant Staphylococcus epidermidis

AbstractObjective. To investigate the efficacy of RNAIII-inhibiting peptide (RIP) and nisin as prophylactic agents in a rat model of vascular graft infection.Design. Prospective, randomized, controlled animal study.Materials. Two hundred and twenty adult male Wistar rats. Staphylococcus epidermidis ATCC 12228 and one clinical isolate of methicillin-resistant S. epidermidis. Drugs: RIP, nisin and rifampin.Methods. Graft infections were established in the dorsal subcutaneous tissue by implantation of 1 cm2 sterile Dacron grafts, followed by topical bacterial inoculation: grafts were retrieved at 7 days. The study included a control group (without inoculation) and two series composed of five groups for each staphylococcal strain: one contaminated group that did not receive any antibiotic prophylaxis, three contaminated groups that received grafts soaked with 10 mg/l RIP, 10 mg/l nisin, 10 mg/l rifampin, or RIP+nisin. The main outcome measure was the extent of bacterial at graft harvest.Results. The bacterial counts for methicillin-resistant S. epidermidis on explanted grafts were 6.1±2.8×102, 7.8±3.0×103 and 5.5±2.9×104 for RIP, nisin and rifampin, respectively. RIP and nisin used in combination reduced the bacterial count to <10. The results for S. epidermidis were similar.Conclusions. RIP and nisin could be used in combination to coat medical devices to prevent drug resistant S. epidermidis infections

A importância do gerenciamento de resíduos nos laboratórios de pesquisa.

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Systemic and local antibiotic prophylaxis in the prevention of Staphylococcus epidermidis graft infection

BACKGROUND: The aim of the study was to investigate the in vivo efficacy of local and systemic antibiotic prophylaxis in the prevention of Staphylococcus (S.) epidermidis graft infection in a rat model and to evaluate the bacterial adherence to frequently used prosthetic graft materials. METHODS: Graft infections were established in the subcutaneous tissue of 120 male Wistar rats by implantation of Dacron/ePTFE grafts followed by topical inoculation with 2 × 10(7 )CFUs of clinical isolate of methicillin-resistant S. epidermidis. Each of the graft series included a control group, one contaminated group that did not receive any antibiotic prophylaxis, two contaminated groups that received systemic prophylaxis with teicoplanin or levofloxacin and two contaminated groups that received teicoplanin-soaked or levofloxacin-soaked grafts. The grafts were removed 7 days after implantation and evaluated by quantitative culture. RESULTS: There was significant bacterial growth inhibition in the groups given systemic or local prophylaxis (P < 0.05). Methicillin-resistant S. epidermidis had greater affinity to Dacron graft when compared with ePTFE graft in the untreated contaminated groups (P < 0.05). CONCLUSION: The study demonstrated that the usage of systemic or local prophylaxis and preference of ePTFE graft can be useful in reducing the risk of vascular graft infections caused by staphylococcal strains with high levels of resistance

The INFN-grid testbed

The Italian INFN-Grid Project is committed to set-up, run and manage an unprecedented nation-wide Grid infrastructure. The implementation and use of this INFN-Grid Testbed is presented and discussed. Particular care and attention are devoted to those activities, relevant for the management of the Testbed, carried out by the INFN within international Grid Projects

Doubly Uniparental Inheritance of Mitochondria As a Model System for Studying Germ Line Formation

BACKGROUND: Doubly Uniparental Inheritance (DUI) of mitochondria occurs when both mothers and fathers are capable of transmitting mitochondria to their offspring, in contrast to the typical Strictly Maternal Inheritance (SMI). DUI was found in some bivalve molluscs, in which two mitochondrial genomes are inherited, one through eggs, the other through sperm. During male embryo development, spermatozoon mitochondria aggregate in proximity of the first cleavage furrow and end up in the primordial germ cells, while they are dispersed in female embryos. METHODOLOGY/PRINCIPAL FINDINGS: We used MitoTracker, microtubule staining and transmission electron microscopy to examine the mechanisms of this unusual distribution of sperm mitochondria in the DUI species Ruditapes philippinarum. Our results suggest that in male embryos the midbody deriving from the mitotic spindle of the first division concurs in positioning the aggregate of sperm mitochondria. Furthermore, an immunocytochemical analysis showed that the germ line determinant Vasa segregates close to the first cleavage furrow. CONCLUSIONS/SIGNIFICANCE: In DUI male embryos, spermatozoon mitochondria aggregate in a stable area on the animal-vegetal axis: in organisms with spiral segmentation this zone is not involved in cleavage, so the aggregation is maintained. Moreover, sperm mitochondria reach the same embryonic area in which also germ plasm is transferred. In 2-blastomere embryos, the segregation of sperm mitochondria in the same region with Vasa suggests their contribution in male germ line formation. In DUI male embryos, M-type mitochondria must be recognized by egg factors to be actively transferred in the germ line, where they become dominant replacing the Balbiani body mitochondria. The typical features of germ line assembly point to a common biological mechanism shared by DUI and SMI organisms. Although the molecular dynamics of the segregation of sperm mitochondria in DUI species are unknown, they could be a variation of the mechanism regulating the mitochondrial bottleneck in all metazoans

A new automated method for the determination of the Total Antioxidant Capacity (TAC) of human plasma, based on the crocin bleaching assay

BACKGROUND: Antioxidant molecules, which scavenge free radical species to prevent or delay oxidative damage of important macromolecules, membrane lipids and lipoproteins, are prevalent in plasma and other biological fluids. Among them, bilirubin, uric acid and protein thiols are the major endogenous antioxidants, while vitamins C and E, as well as a number of food-derived (poly)aromatic substances, belonging to stilbens, flavonoids and phenolic acids, are the main classes of nutritional antioxidants. Assays for total antioxidant capacity in plasma differ in their type of oxidation source, target and measurement used to detect the oxidized product. METHODS: In the present work we present an automated assay for the estimation of blood total antioxidant capacity (TAC assay), based on the crocin bleaching (oxidation) method. This method was adapted on a modern autoanalyzer, was linear over a wide range of values (0–3 mmol/L), and performed using an end point measurement. RESULTS: The TAC method presented a linear correlation with another automated commercial Total Antioxidant Status (TAS) test. Detection of the interference of different metabolites revealed a significant participation of TAC from uric acid, bilirubin, albumin, a minor interference from ascorbic acid, and no interference from hemoglobin. TAC was not modified by two freeze/thawing cycles, and was stable in samples stored at room temperature for 4 hours. K-EDTA and heparin were the best anticoagulants, while citrate decreased TAC by 20%. Reference values derived from samples of normal blood donors was 1.175 ± 0.007 mmol/L (mean ± SEM), while a diet rich in antioxidants more than doubled this value. CONCLUSIONS: The proposed TAC assay, is fully automated, stable and reliable, and could be of value in the estimation of the AC of plasma. It is further proposed to calculate the antioxidant capacity of plasma after a subtraction of all interference deriving from endogenous and/or exogenous metabolites. The antioxidant capacity of plasma thus calculated can be used as a useful indicator of the antioxidant value of foods and beverages in the daily diet