CpG methylation recruits sequence specific transcription factors essential for tissue specific gene expression

CG methylation is an epigenetically inherited chemical modification of DNA found in plants and animals. In mammals it is essential for accurate regulation of gene expression and normal development. Mammalian genomes are depleted for the CG dinucleotide, a result of the chemical deamination of methyl-cytosine in CG resulting in TpG. Most CG dinucleotides are methylated, but ~ 15% are unmethylated. Five percent of CGs cluster into ~ 20,000 regions termed CG islands (CGI) which are generally unmethylated. About half of CGIs are associated with housekeeping genes. In contrast, the gene body, repeats and transposable elements in which CGs are generally methylated. Unraveling the epigenetic machinery operating in normal cells is important for understanding the epigenetic aberrations that are involved in human diseases including cancer. With the advent of high-throughput sequencing technologies, it is possible to identify the CG methylation status of all 30 million unique CGs in the human genome, and monitor differences in distinct cell types during differentiation and development. Here we summarize the present understanding of DNA methylation in normal cells and discuss recent observations that CG methylation can have an effect on tissue specific gene expression. We also discuss how aberrant CG methylation can lead to cancer. This article is part of a Special Issue entitled: Chromatin in time and space.     

The effect of heat treatment and meristem-tip culture on June Yellows in strawberry

Because there is some evidence that June Yellows (JY) of strawberry may be caused by a pathogenic agent, combinations of heat treatment and meristem-tip culture that are known to eliminate some viruses from tissues were used in attempts to cure affected Cambridge Favourite strawberry plants from JY. None of 397 propagants derived from JY-affected plants subjected to various combinations of these treatments were freed from JY. Indeed, all propagants showed more obvious JY symptoms than the parent plants from which they were derived, suggesting that such treatments may be useful for detecting incipient JY in symptomless strawberry stocks.     

Synthetic heat at mild temperatures

"Synthetic heat", also known as the heat grill illusion, occurs when contact with spatially adjacent warm and cold stimuli produce a sensation of "heat". This phenomenon has been explained as a painful perception that occurs when warm stimulation inhibits cold-sensitive neurons in the spinothalamic tract (STT), which in turn unmasks activity in the pain pathway caused by stimulation of C-polymodal nociceptors (CPNs). The "unmasking model" was tested in experiment 1 by combining warm (35-40°C) and cool ( &#83 27°C) stimuli that were too mild to stimulate CPNs. After discovering that these temperatures produced nonpainful heat, experiment 2 was designed to determine whether heat could be induced when near-threshold cooling was paired with mild warmth, and whether lowering the base temperature for cooling would increase the noxious (burning, stinging) components of heat for fixed cooling steps of 1-3°C. Cooling by just 1°C from a base temperature of 33°C led to reports of heat on more than 1/3 of trials, and cooling by just 3°C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29°C increased reports of heat and burning but did not produce significant reports of pain. Perception of nonpainful heat at such mild temperatures indicates either that cold-sensitive nociceptors with thresholds very similar to cold fibers innervate hairy skin in humans, or that heat can result from integration of warm fiber and cold fiber activity, perhaps via convergence on nonspecific (e.g., WDR) neurons in the STT.     

Long‐term non‐equilibrium dynamics of insular floras: a 17‐year record

Aim To document long‐term rates of immigration, extinction and turnover in insular floras and evaluate the relative impacts of recent hurricane activity and climate change. Location Three archipelagos of small islands, in the Exuma Cays, Andros and Abacos, Bahamas. Methods I surveyed the floras of 194 vegetated islands in three archipelagos over several multi‐year periods, spanning up to 17 years. Changes in abundance (foliar cover) of persistent populations were measured on a subset of 14 islands in the Exuma Cays over a 9‐year period. Results Rates of plant turnover were generally low compared with other organisms, but varied among archipelagos and time periods. Turnover rates were usually higher in the second decade of this study, and extinction rates were often dramatically higher than immigration rates in the second decade, resulting in overall decreases in species richness. Turnover did not differ significantly among island types based on generalized location and surrounding water depths, and extinctions were not more likely to occur on more exposed islands. The abundance (foliar cover) of populations that did not go extinct decreased steadily over the second decade of this study, indicating, along with higher extinction rates, a generalized decline in these insular floras. Main conclusions Although some islands may have been at or near a state of dynamic equilibrium in the first decade of this study, average species richness declined in all three archipelagos during the second decade, when extinctions greatly outnumbered immigrations. Four major hurricanes affected the study archipelagos in the second decade of this study, although the available evidence suggests that the hurricanes were not directly responsible for the declines. Indirect effects of hurricanes such as increased herbivory and possible decreased nutrient availability, along with a long‐term (25 years) increase in temperature and decline in rainfall are likely contributing factors.     

Insular avian adaptations on two Neotropical continental islands

Aim Most studies of avian insular adaptations have focused on oceanic islands, which may not allow characters that are insular adaptations to be teased apart from those that benefit dispersal and colonization. Using birds on continental islands, we investigated characters that evolved in situ in response to insular environments created by late Pleistocene sea level rise. Location Trinidad and Tobago and continental South America. Methods We weighed fresh flight muscles and measured museum skeletal specimens of seven species of birds common to the continental islands of Trinidad and Tobago. Results When corrected for body size, study species exhibited significantly smaller flight muscles, sterna and sternal keels on Tobago than on larger Trinidad and continental South America. Tobago populations were more ‘insular’ in their morphologies than conspecifics on Trinidad or the continent in other ways as well, including having longer bills, longer wings, longer tails and longer legs. Main conclusions We hypothesize that the longer bills enhance foraging diversity, the longer wings and tails compensate for the smaller pectoral assemblage (allowing for retention of volancy, but with a probable reduction in flight power and speed), and the longer legs expand perching ability. Each of these differences is likely to be related to the lower diversity and fewer potential predators and competitors on Tobago compared with Trinidad. These patterns of smaller flight muscles and larger bills, legs, wings and tails in island birds are not the results of selection for island dispersal and colonization, but probably arose from selection pressures acting on populations already inhabiting these islands.     

Environmental margin and island evolution in Middle Eastern populations of the Egyptian fruit bat

Here, we present a study of the population genetic architecture and microevolution of the Egyptian fruit bat (Rousettus aegyptiacus) at the environmental margins in the Middle East using mitochondrial sequences and nuclear microsatellites. In contrast to the rather homogenous population structure typical of cave‐dwelling bats in climax tropical ecosystems, a relatively pronounced isolation by distance and population diversification was observed. The evolution of this pattern could be ascribed to the complicated demographic history at higher latitudes related to the range margin fragmentation and complex geomorphology of the studied area. Lineages from East Africa and Arabia show divergent positions. Within the northwestern unit, the most marked pattern of the microsatellite data set is connected with insularity, as demonstrated by the separate status of populations from Saharan oases and Cyprus. These demes also exhibit a reduction in genetic variability, which is presumably connected with founder effects, drift and other potential factors related to island evolution as site‐specific selection. Genetic clustering indicates a semipermeability of the desert barriers in the Sahara and Arabian Peninsula and a corridor role of the Nile Valley. The results emphasize the role of the island environment in restricting the gene flow in megabats, which is also corroborated by biogeographic patterns within the family, and suggests the possibility of nascent island speciation on Cyprus. Demographic analyses suggest that the colonization of the region was connected to the spread of agricultural plants; therefore, the peripatric processes described above might be because of or strengthened by anthropogenic changes in the environment.     

Seasonal changes in circadian rhythms of body temperatures in humans living in a dry tropical climate

Seven volunteers (3 females and 4 males; 3 Caucasians and 4 Africans) participated in two 24 h sessions during the cool dry (CD) and the hot dry (HD) seasons of the sahelian tropical climate. Body temperatures were taken on portable cassette recorders for 24 h. Rectal (Tre) and mean skin (Tsk) temperatures decreased in the HD compared to the CD conditions, meeting one of the criteria for adaptation to heat. No ethnic differences in thermal responses were found. Males and females differed in their body temperature rhythms and in their reactions to heat. Body temperatures were higher in females than in males. Males reacted to heat with a decrease in Tre, without change in the Tre-Tsk gradient. Females showed a decrease in both Tre and Tsk, more marked for Tsk, with an increase in the Tre-Tsk gradient. It was concluded that males showed seasonal acclimatization to heat via a decrease in metabolism confirmed by a decrease in plasma levels of thyroid stimulating hormone (TSH) in the HD condition. Females showed a mixed metabolic and thermolytic type of acclimatization, with an absence of variation in plasma TSH levels. In conclusion, the steady rise in temperature between the CD and HD conditions was sufficient to trigger an acclimatization to heat similar in Caucasian and African subjects, although exposure to the external climate differed widely.     

HSP90 mRNA在胃癌和大肠癌中表达的研究

目的为探讨胃癌和大肠癌细胞HSP90 mRNA表达的特点.方法利用核酸原位杂交技术,对79例胃肠癌组织进行检测.结果表明HSP90 mRNA在胃癌和大肠癌中的阳性率分别为55.56%(15/27)和69.23%(36/52).mRNA表达与病理类型、分化程度和有否淋巴结转移有相关性.结论 HSP90 mRNA在胃肠癌中有较高表达,检测HSP90 mRNA可以作为提示预后的重要临床指标.     

THE EFFECTIVE SIZE OF A HIERARCHICALLY STRUCTURED POPULATION

A knowledge of the effective size of a population (N_e) is important in understanding its current and future evolutionary potential. Unfortunately, the effective size of a hierarchically structured population is not, in general, equal to the sum of its parts. In particular, the inbreeding structure has a major influence on N_e. Here I link N_e to Wright's hierarchical measures of inbreeding, F_IS and F_ST, for an island-structured population (or metapopulation) of size N_T. The influence of F_ST depends strongly on the degree to which island productivity is regulated. In the absence of local regulation (the interdemic model), interdemic genetic drift reduces N_e. When such drift is combined with local inbreeding under otherwise ideal conditions, the effects of F_IS and F_ST are identical: increasing inbreeding either within or between islands reduces N_e, with N_e = N_T/[(1 + F_IS)(1 + F_ST) ? 2F_ISF_ST]. However, if islands are all equally productive because of local density regulation (the traditional island model), then N_e = N_T/[(1 + F_IS)(1 –F_ST)] and the effect of F_ST is reversed. Under the interdemic model, random variation in the habitat quality (and hence productivity) of islands act to markedly decrease N_e. This variation has no effect under the island model because, by definition, all islands are equally productive. Even when no permanent island structure exists, spatial differences in habitat quality can significantly increase the overall variance in reproductive success of both males and females and hence lower N_e. Each of these basic results holds when other nonideal factors are added to the model. These factors, deviations from a 1:1 sex ratio, greater than Poisson variance in female reproductive success, and variation in male mating success due to polygynous mating systems, all act to lower N_e. The effects of male and female variance on N_e have important differences because only females affect island productivity. Finally, it is noted that to use these relationships, F_IS and F_ST must be estimated according to Wright's definition (and corrected to have a zero expectation under the null model). A commonly used partitioning (θ, θ_g) can be biased if either island size or the number of islands is small.