Phylogeographic history of the genus Tropheus,a lineage of rock-dwelling cichlid fishes endemic to Lake Tanganyika

Lake Tanganyika contains the oldest and most complex flock of cichlid fishes counting about 200 endemic species. It is comprised of 16 ecologically, morphologically and genetically highly distinct tribes. Many species are further subdivided into arrays of geographic morphs, each colonizing particular sections of the shore line. The genus Tropheus represents the most spectacular and best studied example for this phenomenon, counting more than 100 distinctly colored populations and sister species, some living in sympatry. Their present distribution and genetic structure was shaped by a series of lake level fluctuations which caused cycles of isolation and secondary admixis. The present study extends previous work on the phylogeography of Tropheus and aims at the fine-scale reconstruction of the origin and spread of lineages in the central and southern basin of the lake. The previously defined mtDNA lineages were evaluated on the basis of statistical parsimony networks. Haplotype networks were created for each lineage and related to their centers of diversity in terms of present distribution. A linearized tree analysis and a mismatch distribution analysis corroborate two of the three radiation waves suggested in earlier works, but the new data suggest a different primary colonization scenario for the southern basin.     

The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin

Alpha-actinin is the major F-actin crosslinking protein in both muscle and non-muscle cells. We report the crystal structure of the actin binding domain of human muscle alpha-actinin-3, which is formed by two consecutive calponin homology domains arranged in a "closed" conformation. Structural studies and available biochemical data on actin binding domains suggest that two calponin homology domains come in a closed conformation in the native apo-form, and that conformational changes involving the relative orientation of the two calponin homology domains are required for efficient binding to actin filaments. The actin binding activity of muscle isoforms is supposed to be regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), which binds to the second calponin homology domain. On the basis of structural analysis we propose a distinct binding site for PtdIns(4,5)P2, where the fatty acid moiety would be oriented in a direction that allows it to interact with the linker sequence between the actin binding domain and the first spectrin-like repeat, regulating thereby the binding of the C-terminal calmodulin-like domain to this linker.     

Relative strength of resource and predation limitation of heterotrophic nanoflagellates in a low-productive sea area

The magnitude of resource and predation limitation of heterotrophicnanoflagellates (HNF) was studied in two short-term enclosureexperiments performed in a low-productive sea area in the northernBaltic Sea in 2001. A cross-factorial design was used to simultaneouslyassess the relative importance of the two factors. Resourcelimitation was removed by adding bacteria, and predation limitationwas eliminated by selective filtration. The first experimentwas performed in June just after the spring bloom decline andthe second in September at the end of the productive season.Resource limitation prevailed during both experiments, contributingto 60% of the net growth increase in June and 74% in September.Removal of predators had a significant effect only in June.Evidence for simultaneous resource and predation limitationwas thus found only during the post-bloom situation. The resultswere applied to a model on resource and predation control ofHNF abundances. To evaluate seasonal differences, field dataon HNF and bacteria from a whole year study were applied tothe model. Except for a few occasions during spring, the modelindicated prevailing resource control of HNF at two locationswith slightly different productivity.     

Involvement of AMP-activated protein kinase in fat depot-specific metabolic changes during starvation

The mechanisms controlling fat depot-specific metabolism are poorly understood. During starvation of mice, downregulation of lipogenic genes, suppression of fatty acid synthesis, and increases in lipid oxidation were all more pronounced in epididymal than in subcutaneous fat. In epididymal fat, relatively strong upregulation of uncoupling protein 2 and phosphoenolpyruvate carboxykinase genes was found. In mice maintained both at 20 and 30 degrees C, AMP-activated protein kinase was activated in epididymal but did not change in subcutaneous fat. Our results suggest that AMPK may have a role in the different response of various fat depots to starvation.     

Synthesis and SAR of highly selective MMP-13 inhibitors

The structure-based design and synthesis of a series of novel biphenyl sulfonamide carboxylic acids as potent MMP-13 inhibitors with selectivity over MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-14, Aggrecanase 1, and TACE are described.     

Towards a label-free optical porous silicon DNA sensor

We report on the fabrication of an optical silicon-based label-free DNA sensor. n-Type crystalline silicon wafers have been electrochemically etched to form porous silicon layers and characterized in terms of porosity, pore distribution, surface composition and photoluminescence. Samples (0.25 cm(2)) have been cut and properly derivatized using trimethoxy-3-bromoacetamidopropylsilane in order to link single strand DNA (ss-DNA). Such a molecule is not commercially available and has been ad-hoc prepared by reacting hydrobromic acid and 3-aminopropyltrimethoxysilane in presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide as coupling agent. Trimethoxy-3-bromoacetamidopropylsilane acts as a bridge anchored to the porous silicon surface through the silane group while immobilizing ss-DNA by means of the bromoacetamido moiety. We have found that derivatized samples exhibit a photoluminescence that is stable in time and is not modified after exposure to non-complementary DNA strand. On the other hand, a sensible enhancement of the light emission has been observed when the derivatized samples react with the complementary strand, showing that the specific ss-DNA/complementary DNA (c-DNA) interaction can be optically sensed without using further labeling steps. This strongly strengthens the possible role of silicon as a material for biosensors.     

When medical cure is not an unmitigated good

The impact of chronic illness on patients has been discussed extensively, but little attention has been paid to the reverse situation: the need for patients who have been chronically ill since childhood to adjust to health and normality in adulthood. Drawing upon the narratives of two adults with childhood onset diseases, this paper provides a new perspective about the transition from chronic illness to health after a successful transplantation. We analyze from the patients' perspective the unusual disruptive impact of overcoming illness in such situations. The process of becoming cured affects their identity, leaving them unable to restructure their self within health and normality, in the same way as others are unable to adjust to chronic illness. Health care providers and families must pay more attention to the losses and life changes these patients undergo after being cured, and to their specific needs in the post-transplantation situation. We hope to offer insight into ways to prevent and address the difficulties and suffering in such situations, which may become more frequent as more therapeutic options become available for adults with childhood onset diseases.