Population genetics of the wood-decay fungus Phlebia centrifuga P. Karst. in fragmented and continuous habitats

The basidiomycete Phlebia centrifuga is a wood-decay fungus characteristic for unmanaged old-growth forests of spruce, a habitat that has become increasingly fragmented due to forest management. The aim of this study was to investigate the genetic population structures of P. centrifuga in both continuous and fragmented habitats, and estimate the potential impact of fragmentation on the genetic diversity of the fungus. Three hundred fifteen single spore isolates (representing 47 spore families and 33 single isolates) from eight populations across northern Europe (Russia, Finland, and Sweden) were screened with seven microsatellite markers and arbitrary primed polymerase chain reaction with the M13 minisatellite. The two molecular methods generally gave the same pattern for the genetic population structure. There were no significant differences between the observed and the expected heterozygosities, and the inbreeding coefficient (FIS) did not indicate any inbreeding. The fixation index (FST) revealed a general pattern with little to moderate genetic differentiation for the majority of populations, while the southernmost Swedish population Norra Kvill was the only one showing high differentiation from about half of the other populations. Swedish population Fiby with the shortest distance to the continuous habitat was moderately differentiated from most of the others and to the largest extent differed from geographically closest population of Norra Kvill. The results indicate that the fragmentation of old-growth forest in Russia and Finland is more recent than the fragmentation in Sweden, and the genetic population structures of P. centrifuga in northern Europe might be related to differences in forest landscape dynamics between the two areas.     

CYP17 inhibitors for prostate cancer therapy

Prostate cancer (PC) is now the second most prevalent cause of death in men in the USA and Europe. At present, the major treatment options include surgical or medical castration. These strategies cause ablation of the production of testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes. However, because these procedures do not affect adrenal, prostate and other tissues' androgen production, they are often combined with androgen receptor antagonists to block their action. Indeed, recent studies have unequivocally established that in castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Clearly, inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17α-hydroxy/17,20-lyase (hereafter referred to as CYP17) could prevent androgen production from all sources. Thus, total ablation of androgen production by potent CYP17 inhibitors may provide effective treatment of prostate cancer patients. This review highlights the role of androgen biosynthesis in the progression of prostate cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical development. Article from the special issue on Targeted Inhibitors.     

Initial fungal colonizer affects mass loss and fungal community development in Picea abies logs 6 yr after inoculation

Picea abies logs were inoculated with Resinicium bicolor, Fomitopsis pinicola or left un-inoculated and placed in an old-growth boreal forest. Mass loss and fungal community data were collected after 6 yr to test whether simplification of the fungal community via inoculation affects mass loss and fungal community development. Three techniques were used to survey communities: (1) observation of fruiting structures; (2) culturing on media; and (3) cloning and sequencing of ITS rDNA. Fruit body surveys detected the smallest number of species (18, 3.8 per log), DNA-based methods detected the most species (72, 31.7 per log), and culturing detected an intermediate number (23, 7.2 per log). Initial colonizer affected community development and inoculation with F. pinicola led to significantly greater mass loss. Relationships among fungal community composition, community richness and mass loss are complex and further work is needed to determine whether simplification of fungal communities affects carbon sequestration in forests.     

Retracing the routes of introduction of invasive species: the case of the Sirex noctilio woodwasp

Understanding the evolutionary histories of invasive species is critical to adopt appropriate management strategies, but this process can be exceedingly complex to unravel. As illustrated in this study of the worldwide invasion of the woodwasp Sirex noctilio, population genetic analyses using coalescent‐based scenario testing together with Bayesian clustering and historical records provide opportunities to address this problem. The pest spread from its native Eurasian range to the Southern Hemisphere in the 1900s and recently to Northern America, where it poses economic and potentially ecological threats to planted and native Pinus spp. To investigate the origins and pathways of invasion, samples from five continents were analysed using microsatellite and sequence data. The results of clustering analysis and scenario testing suggest that the invasion history is much more complex than previously believed, with most of the populations being admixtures resulting from independent introductions from Europe and subsequent spread among the invaded areas. Clustering analyses revealed two major source gene pools, one of which the scenario testing suggests is an as yet unsampled source. Results also shed light on the microevolutionary processes occurring during introductions, and showed that only few specimens gave rise to some of the populations. Analyses of microsatellites using clustering and scenario testing considered against historical data drastically altered our understanding of the invasion history of S. noctilio and will have important implications for the strategies employed to fight its spread. This study illustrates the value of combining clustering and ABC methods in a comprehensive framework to dissect the complex patterns of spread of global invaders.     

Body size and craniometry of the herb field mouse from Lithuania in the context of species range

We present morphometric and craniometric measurements of the herb field mouse (Apodemus uralensis) from Lithuania and analyze variation of body and skull size across species range. We suppose species is characterized by high size variability, not following Bergmann’s or Murphy’s rules. Preliminary, distinct size differences have been registered in the eastern and southern edges of the distribution range, with these populations having largest individuals according to average body and skull size. In terms of tail length and condylobasal length of the skull, Lithuanian mice on the north-western edge of the species range are among the largest, but in terms of body weight, body length, zygomatic skull width and the length of maxillary toothrow, adult A. uralensis from Lithuania are small and correspond to those from populations on the western edge of the range. The relative skull width (ratio of zygomatic skull width to condylobasal length) of Lithuanian A. uralensis is the smallest across the entire range. In A. uralensis from Lithuania, sex dimorphism is weakly expressed, with hind foot length and postorbital constriction larger in adult males, while the height of the mandibula and length of the mandibular diastema is larger in adult females. Juvenile and subadult A. uralensis from Lithuania differ in body weight, but not in size.     

Impact of <Emphasis Type="Italic">Heterobasidion</Emphasis> root-rot on fine root morphology and associated fungi in <Emphasis Type="Italic">Picea abies</Emphasis> stands on peat soils

We examined differences in fine root morphology, mycorrhizal colonisation and root-inhabiting fungal communities between Picea abies individuals infected by Heterobasidion root-rot compared with healthy individuals in four stands on peat soils in Latvia. We hypothesised that decreased tree vitality and alteration in supply of photosynthates belowground due to root-rot infection might lead to changes in fungal communities of tree roots. Plots were established in places where trees were infected and in places where they were healthy. Within each stand, five replicate soil cores with roots were taken to 20 cm depth in each root-rot infected and uninfected plot. Root morphological parameters, mycorrhizal colonisation and associated fungal communities, and soil chemical properties were analysed. In three stands root morphological parameters and in all stands root mycorrhizal colonisation were similar between root-rot infected and uninfected plots. In one stand, there were significant differences in root morphological parameters between root-rot infected versus uninfected plots, but these were likely due to significant differences in soil chemical properties between the plots. Sequencing of the internal transcribed spacer of fungal nuclear rDNA from ectomycorrhizal (ECM) root morphotypes of P. abies revealed the presence of 42 fungal species, among which ECM basidiomycetes Tylospora asterophora (24.6 % of fine roots examined), Amphinema byssoides (14.5 %) and Russula sapinea (9.7 %) were most common. Within each stand, the richness of fungal species and the composition of fungal communities in root-rot infected versus uninfected plots were similar. In conclusion, Heterobasidion root-rot had little or no effect on fine root morphology, mycorrhizal colonisation and composition of fungal communities in fine roots of P. abies growing on peat soils.     

Synthesis and biological evaluations of putative metabolically stable analogs of VN/124-1 (TOK-001): head to head anti-tumor efficacy evaluation of VN/124-1 (TOK-001) and abiraterone in LAPC-4 human prostate cancer xenograft model

In a continuing study of our clinical candidate 5 VN/124-1 (TOK-001) and analogs as potential agents for prostate cancer therapy, putative metabolites (10, 15 and 18) of compound 5 were rationally designed and synthesized. However, none of these agents were as efficacious as 5 in several in vitro studies. Using western blot analysis, we have generated a preliminary structure–activity relationship (SAR) of 5 and related analogs as androgen receptor ablative agents (ARAAs). In vivo using the androgen-dependent LAPC-4 prostate cancer xenograft model, we demonstrated for the first time that 5 is more efficacious than the 17-lyase inhibitor 3 (abiraterone)/4 (abiraterone acetate) that is currently in phase III clinical trials. In our desire to optimize the potency of 5, compounds 6 (3ξ-fluoro-) and 9 (3β-sulfamate-) designed to increase the stability and oral bioavailability of 5, respectively were evaluated in vivo. We showed, that on equimolar basis, compound 6 was ∼2-fold more efficacious versus LAPC-4 xenografts than 5, but the toxicity observed with 6 is of concern. These studies further demonstrate the efficacy of 5 in a clinically relevant prostate cancer model and justify its current clinical development as a potential treatment of prostate cancer.     

Identification of rheological properties of human body surface tissue

According to World Health Organization obesity is one of the greatest public health challenges of the 21st century. It has tripled since the 1980s and the numbers of those affected continue to rise at an alarming rate, especially among children. There are number of devices that act as a prevention measure to boost person?s motivation for physical activity and its levels. The placement of these devices is not restricted thus the measurement errors that appear because of the body rheology, clothes, etc. cannot be eliminated. The main objective of this work is to introduce a tool that can be applied directly to process measured accelerations so human body surface tissue induced errors can be reduced. Both the modeling and experimental techniques are proposed to identify body tissue rheological properties and prelate them to body mass index. Multi-level computational model composed from measurement device model and human body surface tissue rheological model is developed. Human body surface tissue induced inaccuracies can increase the magnitude of measured accelerations up to 34% when accelerations of the magnitude of up to 27 m/s² are measured. Although the timeframe of those disruptions are short – up to 0.2 s – they still result in increased overall measurement error.