TLR4‐mediated skin carcinogenesis is dependent on immune and radioresistant cells

Skin cancers are the most commonly diagnosed cancers. Understanding what are the factors contributing to skin tumour development can be instrumental to identify preventive therapies. The myeloid differentiation primary response gene (MyD)88, the downstream adaptor protein of most Toll‐like receptors (TLR), has been shown to be involved in several mouse tumourigenesis models. We show here that TLR4, but not TLR2 or TLR9, is upstream of MyD88 in skin tumourigenesis. TLR4 triggering is not dependent on lipopolysaccharide associated to skin‐colonizing bacteria, but on the high mobility group box‐1 protein (HMGB1), an endogenous ligand of TLR4. HMGB1 is released by necrotic keratinocytes and is required for the recruitment of inflammatory cells and for the initiation of inflammation. The expression of TLR4 on both bone marrow‐derived and radioresistant cells is necessary for carcinogenesis. Consistently, a human tissue microarray analysis showed that melanoma and colon cancer display an over‐expression of TLR4 and its downstream adaptor protein MyD88 within tumours. Together, our results suggest that the initial release of HMGB1 triggers a TLR4‐dependent inflammatory response that leads to tumour development.     

Evolutionary dynamics of multilocus microsatellite arrangements in the genome of the butterfly Bicyclus anynana, with implications for other Lepidoptera

The sequences flanking microsatellites isolated from the butterfly Bicyclus anynana display high levels of similarity among different loci. We examined sequence data for evidence of the two mechanisms most likely to generate these similarities, namely recombination mediated events, such as unequal crossing over or gene conversion and through transposition of mobile elements (MEs). Many sequences contained tandemly arranged microsatellites, lending support to recombination as the multiplication mechanism. There is, however, also support for ME-mediated multiplication of microsatellites and their flanking sequences. Homology with a known Lepidopteran ME was found in B. anynana microsatellite regions, and polymorphic microsatellite markers with partial similarities in their flanking sequences were passed on to the next generation independently, indicating that they are not linked. Therefore, the rise of these similarities appears to be mediated through both processes, either as an interaction between the two, or by each being responsible for part of the observations. A large proportion of microsatellites embedded in repetitive DNA is representative for most studied butterflies and moths, and a BLAST survey of the B. anynana sequences revealed four short microsatellite-associated sequences that were present in many species of Lepidoptera. The similarities usually start to deviate beyond these sequences, which suggests that they define the extremes of a repeated unit. Further study of these conserved sequences may help to understand the mechanism underlying the multiplication events, and answer the question of why these redundancies are predominantly found in this insect group.     

Compatible genetic and ecological estimates of dispersal rates in insect (Coenagrion mercuriale: Odonata: Zygoptera) populations: analysis of 'neighbourhood size' using a more precise estimator

Genetic and demographic estimates of dispersal are often thought to be inconsistent. In this study, we use the damselfly Coenagrion mercuriale (Odonata: Zygoptera) as a model to evaluate directly the relationship between estimates of dispersal rate measured during capture-mark-recapture fieldwork with those made from the spatial pattern of genetic markers in linear and two-dimensional habitats. We estimate the 'neighbourhood size' (Nb) - the product of the mean axial dispersal rate between parent and offspring and the population density - by a previously described technique, here called the regression method. Because C. mercuriale is less philopatric than species investigated previously by the regression method we evaluate a refined estimator that may be more applicable for relatively mobile species. Results from simulations and empirical data sets reveal that the new estimator performs better under most situations, except when dispersal is very localized relative to population density. Analysis of the C. mercuriale data extends previous results which demonstrated that demographic and genetic estimates of Nb by the regression method are equivalent to within a factor of two at local scales where genetic estimates are less affected by habitat heterogeneity, stochastic processes and/or differential selective regimes. The corollary is that with a little insight into a species' ecology the pattern of spatial genetic structure provides quantitative information on dispersal rates and/or population densities that has real value for conservation management.     

不同胁迫预处理提高水稻幼苗抗寒性期间蛋白质的变化

水稻(Oryza sativa L.)幼苗经盐、热激和冷三种不同胁迫预处理均提高了幼苗的抗寒性。与未预处理苗相比,在处理后、低温伤害后和常温下恢复2d的三个时期,不同胁迫预处理苗的可溶性和热不稳定蛋白含量变化趋势甚为相似,但热稳定蛋白含量变化则各有异同。SDS-PAGE图谱分析显示,不同胁迫预处理提高水稻幼苗抗寒性时,其可溶性蛋白、热稳定和热不稳定蛋白组成变化亦各有异同。除诱导出共有的新多肽外,还各自诱导出特有的新多肽。结果表明,植物对不同胁迫的交叉适应存在一定的共同机理,但亦可看出植物对同一种环境胁迫似乎不是以同一的机理去适应。     

Purification and characterization of Dolichos lablab lectin

The mannose/glucose-binding Dolichos lablab lectin (designated DLL) has been purified from seeds of Dolichos lablab (hyacinth bean) to electrophoretic homogeneity by affinity chromatography on an ovalbumin- Sepharose 4B column. The purified lectin gave a single symmetric protein peak with an apparent molecular mass of 67 kDa on gel filtration chromatography, and five bands ranging from 10 kDa to 22 kDa upon SDS-PAGE. N-Terminal sequence analysis of these bands revealed subunit heterogeneity due to posttranslational proteolytic truncation at different sites mostly at the carboxyl terminus. The carbohydrate binding properties of the purified lectin were investigated by three different approaches: hemagglutination inhibition assay, quantitative precipitation inhibition assay, and ELISA. On the basis of these studies, it is concluded that the Dolichos lablab lectin has neither an extended carbohydrate combining site, nor a hydrophobic binding site adjacent to it. The carbohydrate combining site of DLL appears to most effectively accommodate a nonreducing terminal alpha-d-mannosyl unit, and to be complementary to the C-3, C-4, and C-6 equatorial hydroxyl groups of alpha-d-mannopyranosyl and alpha-d-glucopyranosyl residues. DLL strongly precipitates murine IgM but not IgG, and the recent finding that this lectin interacts specifically with NIH 3T3 fibroblasts transfected with the Flt3 tyrosine kinase receptor and preserves human cord blood stem cells and progenitors in a quiescent state for prolonged periods in culture, make this lectin a valuable tool in biomedical research.      

The peppered moth and industrial melanism: evolution of a natural selection case study

From the outset multiple causes have been suggested for changes in melanic gene frequency in the peppered moth Biston betularia and other industrial melanic moths. These have included higher intrinsic fitness of melanic forms and selective predation for camouflage. The possible existence and origin of heterozygote advantage has been debated. From the 1950s, as a result of experimental evidence, selective predation became the favoured explanation and is undoubtedly the major factor driving the frequency change. However, modelling and monitoring of declining melanic frequencies since the 1970s indicate either that migration rates are much higher than existing direct estimates suggested or else, or in addition, non-visual selection has a role. Recent molecular work on genetics has revealed that the melanic (carbonaria) allele had a single origin in Britain, and that the locus is orthologous to a major wing patterning locus in Heliconius butterflies. New methods of analysis should supply further information on the melanic system and on migration that will complete our understanding of this important example of rapid evolution.     

Rapid spread of immigrant genomes into inbred populations

When local populations are genetically differentiated from one another and partially inbred, as typically occurs in subdivided populations, immigrant genomes are predicted to be at a frequency-dependent fitness advantage due to heterosis (hybrid vigour) in their descendants. We tested this prediction with pedigreed laboratory populations of the butterfly Bicyclus anynana and report here on a rapid increase over five generations in the contribution of an initially rare immigrant genome to the local population gene pool. The replicated experimental design, including immigrant controls, demonstrates that the mechanism underlying immigrant genome spread is heterosis, and that the advantage to the immigrant genes is sustained over several generations. Our result suggests that effective migration rates may often be much higher than the numbers of individual migrants assumed by classical population genetics models, with implications for the persistence and evolution of metapopulations.     

Genetic differentiation between alternate-year cohorts of Xestia tecta (Lepidoptera,Noctuidae) in Finnish Lapland

Several species in the noctuid genus Xestia exhibit periodic dynamics, with two coexisting cohorts flying in alternate years. The population dynamics and two-year life cycle of Xestia moths suggest that the two cohorts are more or less isolated in time. Typically one cohort is abundant and the other one is rare. Knowledge of the extent of isolation between the two cohorts is important to fully understand the population dynamics and the evolution of alternate-year flight in these species. We applied allozyme electrophoresis and mitochondrial genome sequencing to infer the extent of genetic differentiation among different cohorts of Xestia tecta (Hübner) within the same geographical area as well as between cohorts with opposite-phase flight pattern in different geographical regions. We found no evidence for substantial genetic differentiation and isolation between the even- and odd-year cohorts in eastern Lapland, nor between the cohorts in eastern and western Lapland. The most informative markers were the most polymorphic allozyme loci (Pgm and Mpi) and the AT-rich region in the mtDNA. However, owing to the generally low levels of genetic variation it was not possible to establish conclusively the degree of genetic isolation between the different cohorts. We discuss the implications of our results in relation to two different hypotheses which could account for this pattern: ongoing gene flow between different cohorts and recent common ancestry.