SIRT1 longevity factor suppresses NF‐κB ‐driven immune responses: regulation of aging via NF‐κB acetylation?

The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF-kappaB signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF-kappaB system in aging and immune responses. Adler et al showed that the NF-kappaB binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al studying HIV-1 infection and subsequent immune deficiency process demonstrated that HIV-1 Tat protein binds to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT1-mediated deacetylation of the p65 component of the NF-kappaB complex. As a consequence, the transactivation efficiency of the NF-kappaB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF-kappaB transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF-kappaB signaling, the major outcome of which is inflamm-aging via proinflammatory responses.     

Frequency and density-dependent selection on life-history strategies--a field experiment

Negative frequency-dependence, which favors rare genotypes, promotes the maintenance of genetic variability and is of interest as a potential explanation for genetic differentiation. Density-dependent selection may also promote cyclic changes in frequencies of genotypes. Here we show evidence for both density-dependent and negative frequency-dependent selection on opposite life-history tactics (low or high reproductive effort, RE) in the bank vole (Myodes glareolus). Density-dependent selection was evident among the females with low RE, which were especially favored in low densities. Instead, both negative frequency-dependent and density-dependent selection were shown in females with high RE, which were most successful when they were rare in high densities. Furthermore, selection at the individual level affected the frequencies of tactics at the population level, so that the frequency of the rare high RE tactic increased significantly at high densities. We hypothesize that these two selection mechanisms (density- and negative frequency-dependent selection) may promote genetic variability in cyclic mammal populations. Nevertheless, it remains to be determined whether the origin of genetic variance in life-history traits is causally related to density variation (e.g. population cycles).     

Mannose inhibits hyaluronan synthesis by down-regulation of the cellular pool of UDP-N-acetylhexosamines

We found that d-mannose dose-dependently decreases hyaluronan synthesis in cultured epidermal keratinocytes to approximately 50%, whereas glucose, galactose, and fructose up to 20 mm concentration had no effect. The full inhibition occurred within 3 h following introduction of mannose and did not involve down-regulation of hyaluronan synthase (Has1-3) mRNA. Following introduction of mannose, there was an approximately 50% reduction in the cellular concentration of UDP-N-acetylhexosamines (UDP-HexNAc, i.e. UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine). On the other hand, 2 mm glucosamine in the culture medium increased UDP-HexNAc content, stimulated hyaluronan secretion, and negated the effect of mannose, supporting the notion that the inhibition by mannose on hyaluronan synthesis was because of down-regulated UDP-HexNAc content. The content of UDP-glucuronic acid, the other building block for hyaluronan synthesis, was not reduced by mannose but declined from 39 to 14% of controls by 0.2-1.0 mm 4-methylumbelliferone, another compound that inhibits hyaluronan synthesis. Applying 4-methylumbelliferone and mannose together produced the expected reductions in both UDP sugars but no additive reduction in hyaluronan production, indicating that the concentration of each substrate alone can limit hyaluronan synthesis. Mannose is a potentially useful tool in studies on hyaluronan-dependent cell functions, as demonstrated by reduced rates of keratinocyte proliferation and migration, functions known to depend on hyaluronan synthesis.     

Hypoxia increases intensity of epidermal papillomatosis in roach Rutilus rutilus

Hypoxia, which occurs frequently in aquatic ecosystems and is mainly due to increasing eutrophication can cause severe environmental stress in fish. We investigated experimentally the hypothesis that hypoxia could be one of the environmental stress factors that can induce papillomatosis in fish. Male roach Rutilus rutilus exposed to periodic oxygen deficiency and accompanied temperature increases (OT group) showed the highest increase in the intensity of papillomatosis, as measured by the number of scales covered by papillomatosis tumors. The second highest increase in disease intensity was among male roach exposed to periodical temperature increases. The incidence of such tumors was lowest in the control group, which was exposed to neither hypoxia nor increased temperature. The mortality of fish during the 17 d experiment was highest and the condition factor was lowest in the OT group, indicating this group experienced a higher level of stress. The apparent interaction of hypoxia and temperature suggests that these environmental stressors are among the multifactorial elements leading to papillomatosis in roach. Furthermore, these results provide experimental evidence to indicate that hypoxia may contribute to tumor development in fish.     

Growth Inhibition of <Emphasis Type="Italic">Streptococcus mutans</Emphasis> with Low Xylitol Concentrations

No studies on the concentration dependency of the inhibition of Streptococcus mutans with xylitol are available. We studied xylitol-induced growth inhibition of two type strains, S. mutans NCTC 10449 and Ingbritt, and three clinical isolates of S. mutans. The strains were grown in Brain Hearth Infusion Medium in the presence of 0.001% (0.066 mM), 0.005% (0.33 mM), 0.01% (0.66 mM), 0.1% (6.6 mM), and 1% (66 mM) xylitol. Growth was followed by measuring the absorbance at a wavelength of 660 nm. The highest xylitol concentration tested in this study, 1%, showed mean inhibition percentages ranging from 61% to 76% when the growth inhibition of the five strains was compared to the control without xylitol at log-phase. For 0.1% xylitol, the inhibition percentages ranged from 22% to 59%. A concentration dependency was seen in the growth inhibition, with 0.01% xylitol being the lowest xylitol concentration inhibiting all five strains significantly (p < 0.001). The growth inhibition percentages determined for 0.01% xylitol, however, were low, and the inhibition was significantly weaker as compared to 0.1% and 1% xylitol. Our results suggest that low xylitol concentrations of 0.1% (6.6 mM) could inhibit mutans streptococci in vivo but even lower xylitol concentrations may be inhibitory.     

The Genome-wide Patterns of Variation Expose Significant Substructure in a Founder Population

Although high-density SNP genotyping platforms generate a momentum for detailed genome-wide association (GWA) studies, an offshoot is a new insight into population genetics. Here, we present an example in one of the best-known founder populations by scrutinizing ten distinct Finnish early- and late-settlement subpopulations. By determining genetic distances, homozygosity, and patterns of linkage disequilibrium, we demonstrate that population substructure, and even individual ancestry, is detectable at a very high resolution and supports the concept of multiple historical bottlenecks resulting from consecutive founder effects. Given that genetic studies are currently aiming at identifying smaller and smaller genetic effects, recognizing and controlling for population substructure even at this fine level becomes imperative to avoid confounding and spurious associations. This study provides an example of the power of GWA data sets to demonstrate stratification caused by population history even within a seemingly homogeneous population, like the Finns. Further, the results provide interesting lessons concerning the impact of population history on the genome landscape of humans, as well as approaches to identify rare variants enriched in these subpopulations.     

The role of zooplankton grazing in the formation of `clear water phase' in a shallow charophyte-dominated lake

In Chara-dominated shallow eutrophic Lake Prossa (Estonia), the collapse of spring phytoplankton community occurred in late May after which both primary production (PP) and phytoplankton biomass (B&pinf;) stayed at a very low level. By mid-June the Secchi depth had increased up to 2.6 m indicating the achievement of the `clear water phase', which persisted thoughout the rest of the vegetation period. The biomass of `edible' phytoplankton formed on average 53% of the total phytoplankton biomass, and the share of herbivorous zooplankton was on average 61% of the total zooplankton biomass. In spring zooplankton removed daily 27% of the total B&pinf; and 29% of PP by grazing while in summer these values rarely exceeded 5%. Zooplankton grazing was responsible for the decrease of `edible' (<31 μm) phytoplankton after its spring peak as well as for maintaining its biomass at a very low level during the whole vegetation period. Depletion of mineral forms of nitrogen and phosphorus that occurred most probably because of the development of charophytes by the end of May supported the collapse of the whole phytoplankton community and kept the water clear throughout the summer and autumn.

     

Luciferase-based reporter system for in vitro evaluation of elongation rate and processivity of ribosomes

The elongation step of translation is a key contributor to the abundance, folding and quality of proteins and to the stability of mRNA. However, control over translation elongation has not been thoroughly investigated. In this study, a Renilla–firefly luciferase fusion reporter system was further developed to investigate the in vitro elongation rate and processivity of ribosomes independent of the initiation and termination steps. The reporter mRNA was constructed to contain a single ORF encoding in-frame Renilla luciferase, a specific domain moiety and firefly luciferase. Such a reporter structure enables the quantitative and individual evaluation of the synthesis of a specific domain. As a proof of principle, the synthesis of three protein domains of different lengths and structures was analyzed. Using a cell-free translation assay, both the elongation rate and processivity of ribosomes were shown to vary depending on the domain synthesized. Additionally, a stalling sequence consisting of ten rare arginine codons notably reduced the elongation rate and the processivity of the ribosomes. All these results are consistent with the previously known dynamics of elongation in vivo. Overall, the methodology presented in this report provides a framework for studying aspects that contribute to the elongation step of translation.