Persistence of neutral polymorphisms in Lake Victoria cichlid fish

Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period.     

Renaming Detection

Finding changed identifiers is important for understanding the difference between two versions of a program and for detecting and resolving conflicts while merging variants of a program together. Standard practice for differencing and merging relies on line based techniques that do not recognize renamed identifiers. The design and implementation of a tool to automatically detect renamed identifiers between two versions of a program is presented. The system uses an abstract representation of language constructs to enable language awareness without introducing language dependence. Modules for Java and Scheme have been written. The detector works with multiple file pairs, taking into account renamings that span several files. A case study is presented that demonstrates proof of concept. The detector is part of a suite of intelligent differencing and merging programs that exploit the static semantics of programming languages.     

Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis

DNA damaging agents such as ionizing radiation or chemotherapy are frequently used in oncology. DNA damage response (DDR)—triggered by radiation-induced double strand breaks—is orchestrated mainly by three Phosphatidylinositol 3-kinase-related kinases (PIKKs): Ataxia teleangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK) and ATM and Rad3-related kinase (ATR). Their activation promotes cell-cycle arrest and facilitates DNA damage repair, resulting in radioresistance. Recently developed specific ATR inhibitor, VE-821 (3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide), has been reported to have a significant radio- and chemo-sensitizing effect delimited to cancer cells (largely p53-deficient) without affecting normal cells. In this study, we employed SILAC-based quantitative phosphoproteomics to describe the mechanism of the radiosensitizing effect of VE-821 in human promyelocytic leukemic cells HL-60 (p53-negative). Hydrophilic interaction liquid chromatography (HILIC)-prefractionation with TiO₂-enrichment and nano-liquid chromatography—tandem mass spectrometry (LC-MS/MS) analysis revealed 9834 phosphorylation sites. Proteins with differentially up-/down-regulated phosphorylation were mostly localized in the nucleus and were involved in cellular processes such as DDR, all phases of the cell cycle, and cell division. Moreover, sequence motif analysis revealed significant changes in the activities of kinases involved in these processes. Taken together, our data indicates that ATR kinase has multiple roles in response to DNA damage throughout the cell cycle and that its inhibitor VE-821 is a potent radiosensitizing agent for p53-negative HL-60 cells.     

Constitution of the metabolic type of streptomycetes during the first hours of cultivation

Using the examples of biosynthesis of streptomycin, bialaphos, actinorhodin, oligoketides and autoregulators during the first hours of streptomycete cultivation, it is stressed that the external environment in cooperation with the internal metabolic abilities of the cell determines the metabolic type that would develop during the life cycle of the producing streptomycetes. If we accept that a certain metabolic type (from the point of view of the production of secondary metabolites) was determined already during the first hours of cultivation of the microorganisms, we must also admit that the availability of primary metabolites in the so-called production phase of growth (stationary phase, idiophase, etc.) is to a certain extent determined by the very early stages of strain development.     

Lubricating films of a viscoelastic fluid,including fluid inertia,studied by a linearization method

This study is concerned with the influence of fluid inertia in thin laminar transient or steady flows of a second order Rivlin-Ericksen fluid, predicting the combined effects of inertia and viscoelasticity. In the present study, a linearized approximation for both the convective inertia terms and the nonlinear terms involved in the fluid constitutive law is used. The problem is transformed to a coordinate system in such a way as to result in a linear diffusion-type equation for the vorticity in the Newtonian case, and for the vorticity Laplacian in the viscoelastic case. Having prescribed adequate initial or entrance conditions, closed-form solutions are obtained and tested in three cases for which solutions exist in the literature and excellent agreement is found.In the viscoelastic fluid case three examples are presented showing: 1) The influence of weak inertia effects on the steady flow of a second-order fluid. 2) The behavior in squeezing flow of a slightly viscoelastic fluid. 3) The behavior of a viscoelastic fluid undergoing large amplitude oscillatory squeezing in the presence of weak inertia effects.     

Native CSF spectrophotometry--contribution to the differential diagnosis of closed cranial injuries

The development of postoperative peritoneal adhesions was studied in rats and rabbits, the frequency of adhesions in the experimental model used being very high. In the development of an adhesion, fibrin seems to be an important contributor to the bridge between different tissues. Dextran, which modifies the fibrin network and makes it more susceptible to lysis, was used as a possible prophylactic agent, but we found no difference between treated and control groups. It is concluded that the stimulus for fibrin formation in the peritoneal adhesions using this atraumatic model was too strong to be overcome by the normal fibrinolytic system. The anti-inflammatory reaction of hyaluronic acid did not diminish the frequency or degree of adhesions.