Tumor tissue inhibitor of metalloproteinases-1 (TIMP-1) in hormone-independent breast cancer might originate in stromal cells, and improves stratification of prognosis together with nodal status

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is shown to be a potential marker for poor prognosis in breast cancer, but the biology of TIMP-1 is only partially understood. In this study, TIMP-1 production was studied in a co-culture model of hormone-independent breast cancer cell lines and mesenchymal stem cells mimicking the stromal components of the tumor. In addition, the prognostic value of TIMP-1 was histologically evaluated in a clinical material of 168 patients with hormone-independent breast tumors. The hormone-independent breast cancer (BC) cell lines MDA-MB-231, M4A4 and NM2C5 did not produce TIMP-1 protein in measureable quantities. Six tested primary mesenchymal stem cell lines all produced TIMP-1. Co-culturing of mesenchymal stem cells and breast cancer cells resulted in positive immunocytochemical diffuse staining for TIMP-1 for both cell types. Culturing breast cancer cells with MSC-conditioned media resulted in a positive cytoplasmic immunoreactivity for TIMP-1, and TIMP-1 protein concentration in cell lysates increased 2.7-fold (range 1.1-4.7). The TIMP-1 mRNA levels remained unaffected in BC cells. This might suggest that breast cancer cells can take up TIMP-1 produced by stromal cells and are thus displaying cellular immunoreactivity. In addition, TIMP-1 was shown to improve stratification of prognosis in clinical material.     

Perennial polypores as indicators of annual and red-listed polypores

Many polypores are specialized in their requirements for substrate and environment, and they have been suggested to indicate the continuity of coarse woody debris or naturalness of a forest stand. However, the use of polypores as indicators of conservation value is restricted by the temporally limited appearance of annual fruit bodies. We studied whether the species richness of perennial polypores (perennials) can be used to predict the species richness of annual or annual red-listed polypores (annuals). Our data included 1471 separate datasets (sample plots or larger inventoried areas) in different parts of Finland and Russian Karelia, ranging from the southern to northern boreal zone. At the large scale (the whole area) the number of perennials explained about 70% of the variation in the number of annuals, and about 67% in the number of red-listed annuals. A minimum set of 40–60 perennial occurrences gave a reliable estimate on the species richness of annuals, and 60–80 occurrences on the species richness of red-listed annuals. The richness of perennials predicted the richness of annuals and, in particular, richness of red-listed annuals, better than the size of inventoried area. According to our results, perennial polypores can be used as a surrogate for overall polypore species richness in natural and seminatural boreal forests, but the predictive power is weaker in managed forests. In addition, the relationship between the perennial and annual species seems to differ in different vegetation zones, management types and forest types. Due to this variation direct application of the indicator values derived from different vegetation zones and management or forest types are not recommended. Since perennials are easier to identify than annuals, detectable throughout the year, and have much smaller year-to-year variation, their use as an indicator group seems to offer advantages regarding the timing and cost-efficiency of inventories.     

BODIPY-cholesterol: a new tool to visualize sterol trafficking in living cells and organisms

Analysis of sterol distribution and transport in living cells has been hampered by the lack of bright, photostable fluorescent sterol derivatives that closely resemble cholesterol. In this study, we employed atomistic simulations and experiments to characterize a cholesterol compound with fluorescent boron dipyrromethene difluoride linked to sterol carbon-24 (BODIPY-cholesterol). This probe packed in the membrane and behaved similarly to cholesterol both in normal and in cholesterol-storage disease cells and with trace amounts allowed the visualization of sterol movement in living systems. Upon injection into the yolk sac, BODIPY-cholesterol did not disturb zebrafish development and was targeted to sterol-enriched brain regions in live fish. We conclude that this new probe closely mimics the membrane partitioning and trafficking of cholesterol and, because of its excellent fluorescent properties, enables the direct monitoring of sterol movement by time-lapse imaging using trace amounts of the probe. This is, to our knowledge, the first cholesterol probe that fulfills these prerequisites.     

Fallout from the Chernobyl accident and overall cancer incidence in Finland

Aim: We studied whether incidence of all cancer sites combined was associated with the radiation exposure due to fallout from the Chernobyl accident in Finland. An emphasis was on the first decade after the accident to assess the suggested “promotion effect”. Methods: The segment of Finnish population with a stable residence in the first post-Chernobyl year (2 million people) was studied. The analyses were based on a 250 m × 250 m grid squares covering all of Finland and all cancer cases except cancers of the breast, prostate and lung. Cancer incidence in four exposure areas (based on first-year dose due to external exposure <0.1 mSv, 0.1–1.3, 0.3–0.5, or ≥0.5 mSv) was compared before the Chernobyl accident (1981–1985) and after it (1988–2007) taking into account cancer incidence trends for a longer period prior to the accident (since 1966). Results: There were no systematic differences in the cancer incidence in relation to radiation exposure in any calendar period, or any subgroup by sex or age at accident. Conclusion: The current large and comprehensive cohort analysis of the relatively low levels of the Chernobyl fallout in Finland did not observe a cancer promotion effect.     

Population fluctuations of the wood lemming<Emphasis Type="Italic">Myopus schisticolor</Emphasis> in eastern and western Finland

Olavi Eskelinen, Pertti Sulkava and Risto Sulkava From 1982 to 2003 we studied fluctuations in populations of the wood lemmingMyopus schisticolor (Liljeborg, 1844) in the Heinävesi (eastern Finland) and Keuruu regions (western Finland) by counting field signs and dead animals in standardized field surveys. We compared the population fluctuations of lemmings to those of other voles, owls and small mustelids in these regions. The lemming population in Heinävesi fluctuated regularly in 3-year cycles and in synchrony with the field vole population. Populations of owls also fluctuated in synchrony with wood lemming and field vole populations. In the Keuruu region, oscillations in the wood lemming population were irregular, and neither lemming and vole populations nor lemming and owl populations were correlated. Although direct mechanistic evidence is lacking, specialist predators such as weasels and owls probably cause the cyclicity in the field vole and wood lemming populations in the Heinävesi area. On the other hand, scarcity of high-quality habitats, unfavourable winter weather conditions and generalist predators may prevent the development of cyclicity in the wood lemming population of Keuruu.     

Impact of climate change and prey abundance on nesting success of a top predator, the goshawk

Contemporary research has documented a large number of shifts in spring phenology and changes in distribution range although the average spring temperatures have increased by only 0.3–0.6 °C over the past 100 years. Generally, earlier breeding birds have larger clutch sizes, and the advancing spring could thus potentially increase breeding success. Shifts in spring phenology can, however, be crucial for bird reproduction, and mistiming the breeding event may even have negative consequences for population development. Our aim was to explore how weather and prey abundance relates to the breeding performance of a north European top predator, the northern goshawk Accipiter gentilis. Our nationwide dataset from Finland, spanning the period 1989–2004, shows that ambient weather has a greater impact on the timing and success of breeding than the density of grouse Tetraonidae, the main prey of goshawks. Higher early spring temperatures were associated with advancing hatching date of goshawks. Correspondingly, grouse density and temperature during laying and brooding were positively associated with brood size, while precipitation showed a negative connection. Applying our models to a future scenario of climate warming, combined with a 50 % reduction in grouse density, suggests that average breeding dates will advance only 2.5 days and average breeding success would remain the same. Notably, breeding success was not spatially equal throughout Finland, as northern and eastern populations suffered most from declining grouse densities. The observed pattern is thus the opposite to what is expected from a population situated at the northern edge of its distribution range, and thus may help to understand why populations may not increase at the northern edge of their thermal distribution due to climate change.     

Genome-wide analysis of single nucleotide polymorphisms uncovers population structure in Northern Europe

Background

Genome-wide data provide a powerful tool for inferring patterns of genetic variation and structure of human populations.

Principal Findings

In this study, we analysed almost 250,000 SNPs from a total of 945 samples from Eastern and Western Finland, Sweden, Northern Germany and Great Britain complemented with HapMap data. Small but statistically significant differences were observed between the European populations (F_ST = 0.0040, p<10⁻⁴), also between Eastern and Western Finland (F_ST = 0.0032, p<10⁻³). The latter indicated the existence of a relatively strong autosomal substructure within the country, similar to that observed earlier with smaller numbers of markers. The Germans and British were less differentiated than the Swedes, Western Finns and especially the Eastern Finns who also showed other signs of genetic drift. This is likely caused by the later founding of the northern populations, together with subsequent founder and bottleneck effects, and a smaller population size. Furthermore, our data suggest a small eastern contribution among the Finns, consistent with the historical and linguistic background of the population.

Significance

Our results warn against a priori assumptions of homogeneity among Finns and other seemingly isolated populations. Thus, in association studies in such populations, additional caution for population structure may be necessary. Our results illustrate that population history is often important for patterns of genetic variation, and that the analysis of hundreds of thousands of SNPs provides high resolution also for population genetics.     

The effects of coffee consumption on lipid peroxidation and plasma total homocysteine concentrations: a clinical trial

Despite extensive research, the cardiovascular effects of coffee consumption in humans remain controversial. Our aim was to investigate the excretion of coffee phenols and the effects of filtered coffee consumption on oxidative stress and plasma homocysteine (tHcy) concentration in humans. The study consisted of a multiple-dose clinical supplementation trial and a single-dose study. In the long-term trial, 43 healthy nonsmoking men optionally consumed daily either no coffee, 3 cups (450 mL), or 6 cups (900 mL) of filtered coffee for 3 weeks, while in the short-term study 35 subjects consumed a single dose of 0, 1 (150 mL), or 2 cups (300 mL) of coffee. Long-term consumption of coffee increased the urinary excretion of caffeic and ferulic acid. The change in the total excretion of phenolic acids in 3 and 6 cups groups represented 3.8 and 2.5% of the amount ingested daily. Plasma tHcy concentrations increased nonsignificantly, but the consumption of coffee had neither short-nor long-term effects on lipid peroxidation or the activity of measured antioxidant enzymes. In conclusion, the consumption of filtered coffee does not have any detectable effects on lipid peroxidation in healthy nonsmoking men. The effect of coffee consumption on tHcy concentrations needs further investigation.     

Paired comparisons of carbon exchange between undisturbed and regenerating stands in four managed forests in Europe

The effects of harvest on European forest net ecosystem exchange (NEE) of carbon and its photosynthetic and respiratory components (GPP (gross primary production) and TER (total ecosystem respiration)) were examined by comparing four pairs of mature/harvested sites in Europe via a combination of eddy covariance measurements and empirical modeling. Three of the comparisons represented high coniferous forestry (spruce in Britain, and pines in Finland and France), while a coppice‐with‐standard oak plantation was examined in Italy. While every comparison revealed that harvesting converted a mature forest carbon sink into a carbon source of similar magnitude, the mechanisms by which this occurred were very different according to species or management practice. In Britain, Finland, and France the annual sink (source) strength for mature (clear‐cut) stands was estimated at 496 (112), 138 (239), and 222 (225) g C m^?2, respectively, with 381 (427) g C m^?2 for the mature (coppiced) stand in Italy. In all three cases of high forestry in Britain, Finland, and France, clear‐cutting crippled the photosynthetic capacity of the ecosystem – with mature (clear‐cut) GPP of 1970 (988), 1010 (363), and 1600 (602) g C m^?2– and also reduced ecosystem respiration to a lesser degree – TER of 1385 (1100), 839 (603), and 1415 (878) g C m^?2, respectively. By contrast, harvesting of the coppice oak system provoked a burst in respiration – with mature (clear‐cut) TER estimated at 1160 (2220) gC m^?2– which endured for the 3 years sampled postharvest. The harvest disturbance also reduced GPP in the coppice system – with mature (clear‐cut) GPP of 1600 (1420) g C m^?2– but to a lesser extent than in the coniferous forests, and with near‐complete recovery within a few years. Understanding the effects of harvest on the carbon balance of European forest systems is a necessary step towards characterizing carbon exchange for timberlands on large scales.