In situ quantification of aberrant p53 in colorectal neoplasia

Aberrant p53 protein accumulation was measured immunohistologically in 342 colorectal paraffin-embedded tissue sections from 115 patients (24 with adenocarcinoma, 59 with adenoma and 32 'hospital controls'). Subjective scoring was compared with quantitative cell imaging, including dichotomous (p53⁺/p53^-) status, ng p53^mut mg^-1 enterocyte protein, and tumour burden and patient body 'burden' of aberrant p53. A total of 62.5% cancer patients, 23.7% adenoma patients and 3.1% hospital controls were accorded p53⁺ status on the basis of p53 quantification. Quantitative p53⁺/p53^- assignment had a stronger inverse association with survival (χ²=6.17, p=0.013, Kaplan-Meier test) than subjective 'visual estimation' (χ²=0.57, p=0.449). There was a strong inverse relationship between the p53 'body burden' and the months of post-diagnosis survival (hazard ratio=1.42, p=0.0004, Cox proportional hazards). Absolute quantification for inactivated p53 permits objective and reproducible scoring, adjusts for intra-laboratory immunostaining 'batch effects', corrects for fixation artefacts, and standardizes for inter-laboratory differences in fixation, antibody selection and staining method. Clinically, in situ quantification of p53 will permit more accurate survival prognoses and will inform therapy selection and dose. Ultimately, accurate quantitative tissue/blood p53 correlations may provide a minimally invasive and systemic surrogate measure for these same clinical purposes.     

Species-Rich Scandinavian Grasslands are Inherently Open to Invasion

Invasion of native habitats by alien or generalist species is recognized worldwide as one of the major causes behind species decline and extinction. One mechanism determining community invasibility, i.e. the susceptibility of a community to invasion, which has been supported by recent experimental studies, is species richness and functional diversity acting as barriers to invasion. We used Scandinavian semi-natural grasslands, exceptionally species-rich at small spatial scales, to examine this mechanism, using three grassland generalists and one alien species as experimental invaders. Removal of two putative functional groups, legumes and dominant non-legume forbs, had no effect on invasibility except a marginally insignificant effect of non-legume forb removal. The amount of removed biomass and original plot species richness had no effect on invasibility. Actually, invasibility was high already in the unmanipulated community, leading us to further examine the relationship between invasion and propagule pressure, i.e. the inflow of seeds into the community. Results from an additional experiment suggested that these species-rich grasslands are effectively open to invasion and that diversity may be immigration driven. Thus, species richness is no barrier to invasion. The high species diversity is probably in itself a result of the community being highly invasible, and species have accumulated at small scales during centuries of grassland management.     

Serological analysis and pathogenic potentials of Wangiella dermatitidis isolated from bats

Methods for the preparation of antigens from clinically isolated cultures of Aspergillus were standardized. Sera from 25 suspected cases of pulmonary aspergillosis were tested against antigens prepared by us, from 4 strains of A. fumigatus and one strain of A. flavus, using the Ouchterlony double diffusion and immunoelectrophoretic techniques.Of the 25 sera tested, 18 reacted positively with antigens of A. fumigatus, one with A. flavus and 2 with both these species. Antigens of two non-pathogenic Aspergilli included in the study failed to react with any of the sera. Our antigen preparations gave more numerous as well as sharper precipitin lines than the commercial Bencard antigens which were used for comparison. Moreover, mycelial antigens from 48 to 96 h old cultures revealed precipitin lines comparable to that of the routine, 4 week old culture filtrate antigens, thus suggesting that the incubation period for obtaining antigens could be cut down considerably.Memoir No. 323 from the Centre of Advanced Study in Botany.Deceased     

Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations.     

Environmental (in)dependence of a hybrid zone: Insights from molecular markers and ecological niche modeling in a hybrid zone of Origanum (Lamiaceae) on the island of Crete

The role of environment and the relative significance of endogenous versus exogenous selection in shaping hybrid zones have been crucial issues in the studies of hybridization. Recent advances in ecological niche modeling (ENM) offer new methodological tools, especially in combination with the genotyping of individuals in the hybrid zone. Here, we study the hybrid zone between the widely known spices Origanum onites and Origanum vulgare ssp. hirtum in Crete. We analyze the genetic structure of both parental taxa and their hybrid Origanum × intercendens using AFLP markers on 15 sympatric and 12 allopatric populations and employ ecological niche modeling and niche similarity tests to study their niche patterns. We complement these analyses with seed viability measurements. Our study revealed that the hybridizing taxa O. onites and O. vulgare ssp. hirtum and the resulting genotypic classes showed geographical and environmental niche similarities based on the predictions of ENMs and the subsequent similarity tests. The occurrence of the hybrid zone is not directly dependent on environmental factors which favor the fitness of the hybrid compared to the parental taxa, but rather on aspects such as historical factors and management practices, which may contribute to the localization and maintenance of the contact zone between parental species. Our results suggest that if a minimum required niche differentiation between genotypic classes is not achieved, environmental dependence might not have a prominent role on the outcome of the hybridization.     

Genetic parameters in a rubber tree population: heritabilities,genotype-by-environment interactions and multi-trait correlations

Rubber tree breeding programs are mainly driven by selection of individuals with high yield and quality of rubber. Data from 51 open-pollinated progenies tested on six sites in Brazil were analyzed over several traits to estimate the following: genetic parameters such as narrow-sense heritability and additive genetic variance in single- and multi-site analyses, type B correlations to determine the relevance of genotype-by-environment interactions and its effects on alternative selection strategies, additive genetic repeatability correlation for rubber yield based on three consecutive yearly measurements, and type A correlations to evaluate trait-to-trait genetic associations for all measured traits. Average rubber yield (RYm) showed an estimated narrow-sense heritability of 0.31, with an estimated type B correlation of 0.84, indicating low levels of genotype-by-environment interaction. The trait survival and number of latex vessel rings (RG) showed larger genotype-by-environment interaction and the lowest heritabilites. High to moderate type B correlation was found for most traits, with a value of 0.85 between diameter (or girth) and RYm; therefore, it is possible to achieve interesting rubber yield genetic gains (over 3 years of measurements) from indirect selection based on diameter at age 2.     

Plant communities on ironstone outcrops: a diverse and endangered Brazilian ecosystem

Mountain areas are recognized centres of endemism and diversity on account of their isolation and altitudinal diversity. In tropical regions, mountain tops usually stand as islands of xeric vegetation among mesophytic assemblages. Unlike the vegetation growing on other rock outcrops lithologies, such as inselbergs (granite/gneiss) or campos rupestres (quartz/arenite), ironstone outcrop plant communities still lack systematic studies in Brazil. These outcrops (locally known as canga) share most of the characteristics of other rock outcrops, such as isolation and edapho-climatic harshness, but differ in that they are the object of opencast mining, and thus subjected to irrecoverable degradation. In addition, they are expected to harbour metal-tolerant and hyperaccumulator plant species. A botanical survey of two ironstone outcrop locations in the most important mining region of southeastern Brazil, the Iron Quadrangle, revealed a high within-site (138 and 160 species per site), and between-site diversity (only 27% of common species), totaling 64 families and 234 species among basal families and eudicots (154 species), monocots (68 species), and ferns (12 species). Canga crusts are rich in dicots, several of which play an important role in community structuring, together with the more usual monocot aggregations. Distinct plant communities are found associated to different microhabitats within the iron crust, depending primarily on the amount of soil and moisture retention in the different microtopographies. The environmental uniqueness, high diversity, lack of studies and rapid destruction of these ecosystems pose an immediate challenge for their conservation.     

Changes in ectonucleotidase activities in rat Sertoli cells during sexual maturation

Sertoli cell maturation is a complex process involving both morphological and biochemical changes. These cells have previously been shown to be targets for extracellular purine structures such as ATP and adenosine. These compounds evoke responses in rat Sertoli cells through the purinoceptor families, P₂X and P₂Y and PA₁. The signals to purinoceptors are usually terminated by the action of ectonucleotidases. In a previous work, we demonstrated that rat Sertoli cells have ecto-ATPdiphosphohydrolase (EC 3.6.1.5), ecto-5-nucleotidase (EC 3.1.3.5) and ecto-adenosine deaminase (ecto-ADA) (EC 3.5.4.4) activities. Here we investigated whether some changes occur during rat Sertoli cell maturation in these activities. Rat Sertoli cells obtained from rats of different ages representing the pre pubertal, mid pubertal and young adult (10-, 18- and 35-day-old, respectively) were cultured and used for different assays. The nucleotide hydrolysis was estimated by measuring the Pi released using a colorimetric method and by HPLC analysis. ATP and ADP hydrolysis was increased 3-fold during sexual maturation. AMP hydrolysis increased 4-fold in 10- to 35-day-old Sertoli cells. Similar results were obtained when we used other substrates to measure the extracellular hydrolysis of nucleotides (GTP, GDP, GMP and IMP). The ecto-ADA activity showed a 2-fold increase in the specific activity (18- to 35-day-old Sertoli cells). The termination of the purine cascade by adenosine degradation was faster in the 35- than in 18-day-old Sertoli cells. Follicle Stimulating Hormone (FSH) influences on the ectonucleotidase activities were investigated in 10- and 18-day-old Sertoli cells and a significant increase in the ATP and ADP hydrolysis was observed. Our results show an increase in the extracellular purine cascade during the Sertoli cell development, indicating a rise in the purine communication inside the seminiferous tubules with rat sexual maturation.     

What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.