Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate

Resveratrol, a natural phytoalexin found in grapes and red wine, increases longevity in the short-lived invertebrates Caenorhabditis elegans and Drosophila and exerts a variety of biological effects in vertebrates, including protection from ischemia and neurotoxicity. Its effects on vertebrate lifespan were not yet known. The relatively long lifespan of mice, which live at least 2.5 years, is a hurdle for life-long pharmacological trials. Here, the authors used the short-lived seasonal fish Nothobranchius furzeri with a maximum recorded lifespan of 13 weeks in captivity. Short lifespan in this species is not the result of spontaneous or targeted genetic mutations, but a natural trait correlated with the necessity to breed in an ephemeral habitat and tied with accelerated development and expression of ageing biomarkers at a cellular level. Resveratrol was added to the food starting in early adulthood and caused a dose-dependent increase of median and maximum lifespan. In addition, resveratrol delays the age-dependent decay of locomotor activity and cognitive performances and reduces the expression of neurofibrillary degeneration in the brain. These results demonstrate that food supplementation with resveratrol prolongs lifespan and retards the expression of age-dependent traits in a short-lived vertebrate.     

Mapping Loci Associated With Tail Color and Sex Determination in the Short-Lived Fish Nothobranchius furzeri

The African fish Nothobranchius furzeri is the shortest-lived vertebrate species that can reproduce in captivity, with a median life span of 9–11 weeks for the shortest-lived strain. Natural populations of N. furzeri display differences in life span, aging biomarkers, behavior, and color, which make N. furzeri a unique vertebrate system for studying the genetic basis of these traits. We mapped regions of the genome involved in sex determination and tail color by genotyping microsatellite markers in the F₂ progeny of a cross between a short-lived, yellow-tailed strain and a long-lived, red-tailed strain of N. furzeri. We identified one region linked with the yellow/red tail color that maps close to melanocortin 1 receptor (mc1r), a gene involved in pigmentation in several vertebrate species. Analysis of the segregation of sex-linked markers revealed that N. furzeri has a genetic sex determination system with males as the heterogametic sex and markedly reduced recombination in the male sex-determining region. Our results demonstrate that both naturally-evolved pigmentation differences and sex determination in N. furzeri are controlled by simple genetic mechanisms and set the stage for the molecular genetic dissection of factors underlying such traits. The microsatellite-based linkage map we developed for N. furzeri will also facilitate analysis of the genetic architecture of traits that characterize this group of vertebrates, including short life span and adaptation to extreme environmental conditions.THE Nothobranchius fish species are present in eastern and southeastern Africa, where they populate ephemeral water pools that often undergo complete desiccation during the dry season (Terzibasi et al. 2008; Reichard et al. 2009; Wildekamp 2009). Nothobranchius species tend to live in extreme habitats and have evolved unique adaptations to harsh environmental conditions, including extremely short life cycles, resistance to a wide range of temperatures and water salinity, embryonic development that does not require the presence of water, and a developmental diapause that allows embryos to survive for months in dry conditions (Wourms 1972; Inglima et al. 1981; Genade et al. 2005).Nothobranchius furzeri is the shortest-lived species of the Nothobranchius genus, with an intergeneration time of 40 days, a median life span of 9–11 weeks, and a maximum life span of 12–15 weeks for the shortest-lived strain GRZ (Valdesalici and Cellerino 2003; Genade et al. 2005; Valenzano et al. 2006; Terzibasi et al. 2008, 2009; Hartmann et al. 2009). Natural populations of N. furzeri can vary substantially in phenotypic traits. For example, N. furzeri strains derived from Zimbabwe and northern Mozambique (e.g., GRZ) exhibit a shorter life span than strains derived from more humid areas in southern Mozambique (e.g., MZM-0403) under controlled conditions (Terzibasi et al. 2008). The extremely short life cycle of N. furzeri and the presence of natural populations with phenotypic variations make this species a promising model system for studying aging and adult-specific traits, including color and behavior.The color pattern of the adult male tail differs among N. furzeri strains. GRZ males show a yellow submarginal band and a black marginal band (yellow morph) whereas MZM-0403 males display a broad red band (red morph) in the caudal fin (Figure 1A). This dichromatism is present in natural populations of N. furzeri (Terzibasi et al. 2008; Reichard et al. 2009). Similar color polymorphism among males is also observed in other species of Nothobranchius (Wildekamp 2009) and in other fish species, including guppies and cichlids (Hughes et al. 1999; Brooks and Endler 2001; Maan et al. 2004). Differences in male color morphs within the same species are associated with sexual preference by females, different recognition by predators depending on the habitat, and differential susceptibility to pathogens (Price et al. 2008), which could all influence the evolution of this trait. Despite the widespread variation in Nothobranchius coloration, the genetic basis of this trait is unknown.Open in a separate windowFigure 1.—Cross between two strains of N. furzeri that differ in color and life span (A) Color phenotypes of GRZ and MZM-0403. (B) A yellow-tailed, short-lived male GRZ and a red-tailed, long-lived female MZM-0403 were the founders of cross 1.Genetic information on N. furzeri is still limited. The N. furzeri genome is 1.6–1.9 Gb in size and is characterized by a high repeat content (45%) (Reichwald et al. 2009). N. furzeri has 19 chromosomes, but no morphologically discernible sex chromosomes (Reichwald et al. 2009). The sex determination system in N. furzeri has not been characterized yet. Sex can be determined either genetically or environmentally in fish (Volff 2005; Marshall Graves 2008). For example, medaka, platyfish, guppy, and sticklebacks all have recently evolved genetic sex-determining systems (Volff and Schartl 2002; Peichel et al. 2004; Shapiro et al. 2009; Tripathi et al. 2009a), whereas zebrafish do not have a clear genetic basis of sex determination (von Hofsten and Olsson 2005).Genetic studies in N. furzeri would greatly benefit from the building of a linkage map in this species of fish. However, to date there is no linkage map available for N. furzeri or for any Nothobranchius species, although linkage maps have been generated for fish of the same order, e.g., Poecilia reticulata (guppy) and Xiphophorus maculatus (platyfish) (Khoo et al. 2003; Walter et al. 2004; Tripathi et al. 2009b), and of the same superorder, e.g., Oryzias latipes (medaka) (Wada et al. 1995).Here, we report a microsatellite-based linkage map for N. furzeri using a genetic cross between the short-lived yellow-tailed GRZ strain and the long-lived red-tailed MZM-0403 strain. This N. furzeri linkage map allowed us to map the male-specific tail color trait on linkage group (LG) V. Synteny analysis revealed that LG V has homology to a region of the medaka genome that contains the melanocortin 1 receptor (mc1r) gene, which is known to play a key role in vertebrate pigmentation. We identified a sequence polymorphism in mc1r between the two strains of N. furzeri, allowing us to map mc1r on LG V. This analysis revealed that mc1r is located in close proximity to the color locus, but that the sequence polymorphism is probably not causative for the color difference. We also found that sex is genetically determined in N. furzeri, with males as the heterogametic sex. The sex-determining region is located on LG XIII and is characterized by male-specific suppression of recombination. Our findings will be pivotal for the identification of the genetic determinants of color in N. furzeri and for expanding our knowledge about sex-determination mechanisms in vertebrates. Due to the array of intraspecific phenotypic differences displayed by the various populations of N. furzeri, this linkage map will also be a key tool for mapping phenotypic variation in this short-lived vertebrate species, including differences in life span.     

Study of the respiratory sensation on high-altitude andeans

The respiratory sensation and some routine cardiorespiratory parameters were studied on native Highlanders from the Argentine Andes and on Lowlanders from Europe, already tested during previous high altitude expeditions. The tests were performed at various altitude levels from 2688m e.i., the village altitude for Highlanders, to 5600m during an expedition to Mt. Aconcagua (6990m). At rest, the perception of 4 external inspiratory resistive loads (ranged between 2.5 and 13 cm.H2O.L-1.s) can allow us to fix by discrimination the sensitivity index P(A) independently of response bias (B) according to Sensory Decision Theory (SDT). The Andean highlanders did not experience the respiratory sensation at the same limits as the European lowlanders well adaptated to high altitude. At higher altitudes than their village altitude, their respiratory sensation presented a lower threshold of perception and a weaker discrimination which might be partly explained by the evolution of some parameters of their cardio-respiratory function when altitude increased. Indeed, in response to high altitude hypoxia (5600m), they increased their respiratory frequency and not their minuteventilation or mouth pressure. This chosen ventilatory pattern was opposite to the one chosen by the Lowlanders and did not allow for sufficient adaptation to a more important altitude hypoxia than that of their village altitude. In conclusion, the Andean highlanders wellbeing adapted to their village altitude, exhibited a difficult acclimatization to higher altitudes which might be due to the characteristics of their respiratory sensation. These results might explain their weak physical performances during ascent to the Mt. Aconcagua summit in spite of special training.     

Migalastat HCl Reduces Globotriaosylsphingosine (Lyso-Gb3) in Fabry Transgenic Mice and in the Plasma of Fabry Patients

Fabry disease (FD) results from mutations in the gene (GLA) that encodes the lysosomal enzyme α-galactosidase A (α-Gal A), and involves pathological accumulation of globotriaosylceramide (GL-3) and globotriaosylsphingosine (lyso-Gb₃). Migalastat hydrochloride (GR181413A) is a pharmacological chaperone that selectively binds, stabilizes, and increases cellular levels of α-Gal A. Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. A liquid chromatography-tandem mass spectrometry method was developed to measure lyso-Gb₃ in mouse tissues and human plasma. Oral administration of migalastat HCl to transgenic mice reduced elevated lyso-Gb₃ levels up to 64%, 59%, and 81% in kidney, heart, and skin, respectively, generally equal to or greater than observed for GL-3. Furthermore, baseline plasma lyso-Gb₃ levels were markedly elevated in six male FD patients enrolled in Phase 2 studies. Oral administration of migalastat HCl (150 mg QOD) reduced urine GL-3 and plasma lyso-Gb₃ in three subjects (range: 15% to 46% within 48 weeks of treatment). In contrast, three showed no reductions in either substrate. These results suggest that measurement of tissue and/or plasma lyso-Gb₃ is feasible and may be warranted in future studies of migalastat HCl or other new potential therapies for FD.     

Higher number of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> CagA EPIYA C phosphorylation sites increases the risk of gastric cancer,but not duodenal ulcer

Background  

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis.     

Induced plant volatiles allow sensitive monitoring of plant health status in greenhouses

A novel approach to support the inspection of greenhouse crops is based on the measurement of volatile organic compounds emitted by unhealthy plants.This approach has attracted some serious interest over the last decade. In pursuit of this interest, we performed several experiments at the laboratory-scale to pinpoint marker volatiles that can be used to indicate certain health problems. In addition to these laboratory experiments, pilot and model studies were performed in order to verify the validity of these marker volatiles under real-world conditions. This paper provides an overview of results and gives an outlook on the use of plant volatiles for plant health monitoring.Key words: plant health, volatiles, plant pathogens, plant infection