Cytokeratin immunoreactivity in lobular intraepithelial neoplasia.

Eighteen commercially available antibodies reactive against different cytokeratin proteins were tested on classic examples of lobular intraepithelial neoplasia (LIN) and of ductal intraepithelial neoplasia (DIN) of the breast. About 90% of higher-grade DIN (AIDH and DCIS) show no or substantially diminished reaction with clone 34betaE12 (specified as reactive against keratins 1, 5, 10, and 14 as determined by the manufacturer), while the cells of LIN were found to express the antigen reactive with this antibody. To determine which of these four keratins are present in the cells of LIN, antibodies reactive against these individual four keratins were tested. None of the four antibodies to keratins 1, 5, 10, or 14 reacted with the cells of LIN. To investigate this further, 13 additional monoclonal antibodies to various other keratin proteins were tested on the cells of LIN. Those that successfully reacted with the cells of LIN were further tested on the cells of DIN. All of the individual antibodies reactive with the cells of LIN were also reactive with the cells of DIN to a degree, with clone RCK108 (reactive against keratin 19) coming the closest to demonstrating the reactivity seen with 34betaE12. We conclude that the reactivity seen in the cells of LIN with 34betaE12 is due to either (a) a crossreaction with keratin 19 that is slightly less prominent than the reaction of the individual clone RCK108, (b) a crossreaction with a keratin protein that was not tested (3, 11, 12), (c) a crossreaction with a protein closely resembling keratin in formalin-fixed, paraffin-embedded tissue, or (d) the detection of a mutated or truncated form of keratin 1, 5, 10, or 14 that cannot be detected by the individual monoclonal antibody.     

Synthesis, characterization and ethylene polymerization activity of titanium aminopyridinato complexes

Three titanium complexes derived from 2-(2,6-difluoroanilino)pyridine and 2-(2-chloroanilino)pyridine were synthesized and characterized by X-ray diffraction or spectroscopic methods. All titanium complexes have been used to catalyze the polymerization of ethylene in the presence of MAO as cocatalyst. The mono(2,6-difluorophenylaminopyridinato) titanium catalyst was found to be more active in ethylene polymerization than the bis(2,6-difluorophenylaminopyridinato) and bis(2-chlorophenylaminopyridinato) titanium catalysts. ortho-Halogens disturbed the β-elimination transition state of ethylene polymerization and formed higher molar mass polyethylene than their unhalogenated congener. Due to fluxionality, the bis(2-chlorophenylaminopyridinato) titanium catalyst formed broader molar mass distribution than the bis(2,6-difluorophenylaminopyridinato) titanium catalysts.     

The breeding biology of the starling Sturnus vulgaris in northern Finland

The breeding biology of the starling Sturnus vulgaris was studied in three populations in northern Finland, with additional reference localities in nearby areas. Results from a total of 329 nests are presented from years 1962-1976.
The onset of laying in the Oulu area took place on 5 May, the median date being 10 May, about one week later than in southern Finland and 2–3 weeks later than in central Europe. The clutch-size was 5.29 ± 0.05 in the first nests and 5.06 ± 0.26 in later ones. Incubation time was 12.1 ± 0.6 d. An average of 3.31 ± 0.10 fledglings was produced per pair, 3.69 ± 0.08 in succesful clutches, which is significantly less than usually reported from central Europe. Most of the losses were due to starvation of the young.
No second broods were observed in the Oulu area, and repeated nesting was not common, probably because of the general late start of laying.
The reasons for the recent decline in several Finnish starling populations do not lie in the production capacity but must be sought for elsewhere.     

Correlation between two components of parental investment: nest defence intensity and nestling provisioning effort of willow tits

Nest defence intensity and nestling provisioning effort of female willow tits (Parus montanus) were significantly correlated at the end of nestling period: well-fed young were defended most intensely. Increased effort was rewarded, since broods with the highest female per-offspring provisioning rates were the most likely to produce local recruits. This suggests that the feeding ability is an important cue for parental investment decisions, at least in a species like the willow tit which has adopted the clutch adjustment strategy. Thus, the most valuable broods would not necessarily be the largest ones, but the ones in which the original number of young could be fed most adequately. However, no associations were found between the level of parental effort and offspring weight, size or condition, nor did the broods producing recruits differ from other broods in timing of breeding or number and size of offspring. The female behaviour may suggest that they invest the most time, energy and risk in the young whose chances of joining the winter flock are the best. The first well-fed young also gain an advantage of prior residency in joining the flock. The first to join normally obtain higher social status, and hence better winter survival, than latecomers. The corresponding patterns in male parental investment behaviour were weak or absent, which suggested that the male effort was affected by the female behaviour. Males seemed to invest in nestling provisioning in such a way as to supplement the female effort. During nest defence action males also seemed to invest in protection of females against predation.     

Systems pathology analysis identifies neurodegenerative nature of age‐related vitreoretinal interface diseases

Aging is a phenomenon that is associated with profound medical implications. Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision‐threatening vitreoretinal diseases affecting millions of aging people globally, making these conditions an important public health issue. iERM is characterized by fibrous tissue developing on the surface of the macula, which leads to biomechanical and biochemical macular damage. MH is a small breakage in the macula and is associated with many ocular conditions. Although several individual factors and pathways are suggested, a systems pathology level understanding of the molecular mechanisms underlying these disorders is lacking. Therefore, we performed mass spectrometry‐based label‐free quantitative proteomics analysis of the vitreous proteomes from patients with iERM and MH to identify the key proteins, as well as the multiple interconnected biochemical pathways, contributing to the development of these diseases. We identified a total of 1,014 unique proteins, many of which are linked to inflammation and the complement cascade, revealing the inflammation processes in retinal diseases. Additionally, we detected a profound difference in the proteomes of iEMR and MH compared to those of diabetic retinopathy with macular edema and rhegmatogenous retinal detachment. A large number of neuronal proteins were present at higher levels in the iERM and MH vitreous, including neuronal adhesion molecules, nervous system development proteins, and signaling molecules, pointing toward the important role of neurodegenerative component in the pathogenesis of age‐related vitreoretinal diseases. Despite them having marked similarities, several unique vitreous proteins were identified in both iERM and MH, from which candidate targets for new diagnostic and therapeutic approaches can be provided.     

Outside-host phage therapy as a biological control against environmental infectious diseases

Background

Environmentally growing pathogens present an increasing threat for human health, wildlife and food production. Treating the hosts with antibiotics or parasitic bacteriophages fail to eliminate diseases that grow also in the outside-host environment. However, bacteriophages could be utilized to suppress the pathogen population sizes in the outside-host environment in order to prevent disease outbreaks. Here, we introduce a novel epidemiological model to assess how the phage infections of the bacterial pathogens affect epidemiological dynamics of the environmentally growing pathogens. We assess whether the phage therapy in the outside-host environment could be utilized as a biological control method against these diseases. We also consider how phage-resistant competitors affect the outcome, a common problem in phage therapy. The models give predictions for the scenarios where the outside-host phage therapy will work and where it will fail to control the disease. Parameterization of the model is based on the fish columnaris disease that causes significant economic losses to aquaculture worldwide. However, the model is also suitable for other environmentally growing bacterial diseases.

Results

Transmission rates of the phage determine the success of infectious disease control, with high-transmission phage enabling the recovery of the host population that would in the absence of the phage go asymptotically extinct due to the disease. In the presence of outside-host bacterial competition between the pathogen and phage-resistant strain, the trade-off between the pathogen infectivity and the phage resistance determines phage therapy outcome from stable coexistence to local host extinction.

Conclusions

We propose that the success of phage therapy strongly depends on the underlying biology, such as the strength of trade-off between the pathogen infectivity and the phage-resistance, as well as on the rate that the phages infect the bacteria. Our results indicate that phage therapy can fail if there are phage-resistant bacteria and the trade-off between pathogen infectivity and phage resistance does not completely inhibit the pathogen infectivity. Also, the rate that the phages infect the bacteria should be sufficiently high for phage-therapy to succeed.

     

Adaptation to fluctuations in temperature by nine species of bacteria

Rapid environmental fluctuations are ubiquitous in the wild, yet majority of experimental studies mostly consider effects of slow fluctuations on organism. To test the evolutionary consequences of fast fluctuations, we conducted nine independent experimental evolution experiments with bacteria. Experimental conditions were same for all species, and we allowed them to evolve either in fluctuating temperature alternating rapidly between 20°C and 40°C or at constant 30°C temperature. After experimental evolution, we tested the performance of the clones in both rapid fluctuation and in constant environments (20°C, 30°C and 40°C). Results from experiments on these nine species were combined meta‐analytically. We found that overall the clones evolved in the fluctuating environment had evolved better efficiency in tolerating fluctuations (i.e., they had higher yield in fluctuating conditions) than the clones evolved in the constant environment. However, we did not find any evidence that fluctuation‐adapted clones would have evolved better tolerance to any measured constant environments (20°C, 30°C, and 40°C). Our results back up recent empirical findings reporting that it is hard to predict adaptations to fast fluctuations using tolerance curves.     

Brood rearing costs affect future reproduction in the precocial common goldeneye Bucephala clangula

Life-history theory assumes a trade-off between current reproductive effort and future reproductive success. There are a large number of studies demonstrating reproductive trade-offs in different animal taxa, particularly in birds. Most bird studies have focused on the costs of chick rearing in altricial species. These costs have been assumed to be low in precocial species, but this aspect has been little studied. We used long-term individual reproductive data from the common goldeneye Bucephala clangula , an iteroparous precocial duck with uniparental female care, to examine whether brood rearing carries costs that affect future reproductive performance. All females were experienced breeders, and possible differences in female quality were ruled out. We compared within-individual (between-year) changes in clutch size, hatching date and body mass between females that had reared a brood in the previous year and females that had not. It turned out that brood rearing involved a cost in terms of clutch size and hatching date the next year, but not in terms of body mass: females that had reared a brood in the previous year laid relatively smaller clutches and laid relatively later than females that had not reared a brood. Our results show that normal brood rearing in a precocial species involves costs that affect future reproduction.     

Evidence for Natural Horizontal Transfer of the pcpB Gene in the Evolution of Polychlorophenol-Degrading Sphingomonads

The chlorophenol degradation pathway in Sphingobium chlorophenolicum is initiated by the pcpB gene product, pentachlorophenol-4-monooxygenase. The distribution of the gene was studied in a phylogenetically diverse group of polychlorophenol-degrading bacteria isolated from contaminated groundwater in Kärkölä, Finland. All the sphingomonads isolated were shown to share pcpB gene homologs with 98.9 to 100% sequence identity. The gene product was expressed when the strains were induced by 2,3,4,6-tetrachlorophenol. A comparative analysis of the 16S rDNA and pcpB gene trees suggested that a recent horizontal transfer of the pcpB gene was involved in the evolution of the catabolic pathway in the Kärkölä sphingomonads. The full-length Kärkölä pcpB gene allele had approximately 70% identity with the three pcpB genes previously sequenced from sphingomonads. It was very closely related to the environmental clones obtained from chlorophenol-enriched soil samples (M. Beaulieu, V. Becaert, L. Deschenes, and R. Villemur, Microbiol. Ecol. 40:345-355, 2000). The gene was not present in polychlorophenol-degrading nonsphingomonads isolated from the Kärkölä source.     

Genetic and environmental factors in complex diseases: the older Finnish Twin Cohort.

In studies on the Finnish Twin Cohort, we investigate genetic and environmental determinants of common, complex diseases, and their behavioral risk factors in Finland, a genetically unique and culturally homogenous population. We have formed the following databases: 1) Like-sexed twin pairs (13,888 pairs of known zygosity) form the older Twin Cohort. They have participated since 1975 in mail surveys, in clinical examinations for subsamples, and have been followed-up for morbidity using national medical registers; 2) The older Twin Cohort was expanded in 1996 to include opposite-sex pairs born 1938-1957 (c. 8000 pairs); 3) Two, new longitudinal studies of adolescent twins and their families, form a complementary, ongoing study base described in more detail in an accompanying article. Genetic and environmental effects vary over the life-span, and only longitudinal studies in genetically informative data sets permits the evaluation of such effects. Finally, the inclusion of DNA-based genetic information in a phenotypically rich family data base will offer a unique resource for research in genetic epidemiology and behavioral medicine.