ALBERT

Description: Thermodynamics of weakly screened (near the one-component-plasma limit) Yukawa fluids in two and three dimensions is analyzed in detail. It is shown that the thermal component of the excess internal energy of these fluids, when expressed in terms of the properly normalized coupling strength, exhibits the scaling pertinent to the corresponding one-component-plasma limit (the scalings differ considerably between the two- and three-dimensional situations). This provides us with a simple and accurate practical tool to estimate thermodynamic properties of weakly screened Yukawa fluids. Particular attention is paid to the two-dimensional fluids, for which several important thermodynamic quantities are calculated to illustrate the application of the approach.

Description: In an argon plasma of 20 W rf discharge at a pressure of 1.38 Pa, a stable highly ordered monolayer of microparticles is suspended. We observe spontaneous particle pairing when suddenly reducing the gas pressure. Special types of dynamical activity, in particular, entanglement and cooperative movements of coupled particles have been registered. In the course of the experiment first appeared single vertical pairs of particles, in further they gradually accumulated causing melting of the entire crystal. To record pairing events, the particle suspension is side-view imaged using a vertically extended laser sheet. The long-lasting pre-melting phase assured the credible recording and identification of isolated particle pairs. The high monolayer charge density is crucial to explain the spontaneous pairing events observed in our experiments as the mutual repulsion between the particles comprising the monolayer make its vertical extend thicker.

Description: A new approximate expression for the potential distribution around an absorbing particle in isotropic collisionless plasma is proposed. The approximate expression is given by the sum of the Debye-Hückel potential with an effective screening length and the far-field asymptote obtained from the solution of the linearized Poisson equation. In contrast to analogous models, the effective screening length is not fixed but depends on the distance from the particle. This allows us to obtain a more accurate approximation for the potential distribution in the entire range of distances. The dependence of the screening length on the distance is predicted from the analysis of the charge density distribution function. This dependence contains two adjustable parameters, which are calculated by applying the procedure based on charge balance considerations. Using the obtained results, simple expressions for the parameters of the model are proposed. In addition, a simple expression for the characteristic screening length, which can be used to approximate the potential distribution near the particle, is obtained. The developed model potential is shown to be in excellent agreement with the solution of the nonlinear Poisson equation for typical conditions used in experiments with complex plasmas.

Description: The buccal micronucleus cytome (BMCyt) assay is a minimally invasive approach for measuring DNA damage, cell proliferation, cell differentiation and cell death in exfoliated buccal cells. The main limitation for its use is the lack of knowledge about inter- and intra-laboratory variability in scoring micronuclei and other end points included in the cytome approach. In order to identify the main sources of variability across the BMCyt biomarkers, a scoring exercise was carried out between three experienced laboratories using the same set of slides and an identical set of detailed scoring criteria and associated images for the different end points. Single batches of slides were prepared from pooled samples of four groups of subjects characterised by different frequencies of cell types and micronuclei, namely Down syndrome patients, head and neck cancer patients undergoing radiotherapy and two age- and gender-matched control groups. A good agreement among the laboratories in the identification of normal differentiated cells and of micronuclei was obtained. A 3-fold and 20-fold increase in the frequency of micronucleated cells and micronuclei in differentiated cells of Down syndrome patients and in cancer patients, respectively, compared to matched controls, was a consistent result in the three laboratories. The scores of other cell types and nuclear anomalies, such as basal, binucleated, condensed chromatin and karyorrhectic cells showed significant disagreement between and within laboratories indicating that their evaluation using the current visual scoring protocol does not yield robust results for these parameters. The guidelines for BMCyt assay application could be improved by combining the anomalies associated with cell death (condensed chromatin and karyorrhectic cells) in a single category and by defining more stringent criteria in classifying basal cell, binucleated cells and buds.

Description: We have updated the Munich galaxy formation model to the Planck first-year cosmology, while modifying the treatment of baryonic processes to reproduce recent data on the abundance and passive fractions of galaxies from z  = 3 down to z  = 0. Matching these more extensive and more precise observational results requires us to delay the reincorporation of wind ejecta, to lower the surface density threshold for turning cold gas into stars, to eliminate ram-pressure stripping in haloes less massive than ${\sim }10^{14}{\rm \, M_{{\odot }}}$ , and to modify our model for radio mode feedback. These changes cure the most obvious failings of our previous models, namely the overly early formation of low-mass galaxies and the overly large fraction of them that are passive at late times. The new model is calibrated to reproduce the observed evolution both of the stellar mass function and of the distribution of star formation rate at each stellar mass. Massive galaxies (log M * /M  ≥ 11.0) assemble most of their mass before z  = 1 and are predominantly old and passive at z  = 0, while lower mass galaxies assemble later and, for log M * /M  ≤ 9.5, are still predominantly blue and star forming at z  = 0. This phenomenological but physically based model allows the observations to be interpreted in terms of the efficiency of the various processes that control the formation and evolution of galaxies as a function of their stellar mass, gas content, environment and time.

Description: Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY . Two sisters with c.137T〉C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (~20–50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G〉A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5'-UTR regions despite their typically low coverage in exome data.

Description: Leishmania infantum is a protozoan parasite that is phagocytized by human macrophages. The host macrophages kill the parasite by generating oxidative compounds that induce DNA damage. We have identified, purified and biochemically characterized a DNA polymerase from L. infantum ( Li Pol), demonstrating that it is a DNA-dependent DNA polymerase involved in translesion synthesis of 8oxoG, abasic sites and thymine glycol lesions. Stably transfected L. infantum parasites expressing Li Pol were significantly more resistant to oxidative and interstrand cross-linking agents, e.g. hydrogen peroxide, cisplatin and mitomycin C. Moreover, Li Pol-overexpressing parasites showed an increased infectivity toward its natural macrophage host. Therefore, we propose that Li Pol is a translesion synthesis polymerase involved in parasite DNA damage tolerance, to confer resistance against macrophage aggression.

Description: The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intriguingly, KorA and KorB can act as co-repressors at varying distances between their operators, even when they are moved to be on opposite sides of the DNA. KorA is a homodimer with the 101-amino acid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerization domain. In this study, we have determined the structures of the free KorA repressor and two complexes each bound to a 20-bp palindromic DNA duplex containing its consensus operator sequence. Using a combination of X-ray crystallography, nuclear magnetic resonance spectroscopy, SAXS and molecular dynamics calculations, we show that the linker between the two domains is very flexible and the protein remains highly mobile in the presence of DNA. This flexibility allows the DNA-binding domains of the dimer to straddle the operator DNA on binding and is likely to be important in cooperative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerization domain of the tumour suppressor p53.

Description: Simple practical approach to estimate thermodynamic properties of strongly coupled Yukawa systems, in both fluid and solid phases, is presented. The accuracy of the approach is tested by extensive comparison with direct computer simulation results (for fluids and solids) and the recently proposed shortest-graph method (for solids). Possible applications to other systems of softly repulsive particles are briefly discussed.

Description: We report the first observation of the Mach cones excited by a larger microparticle (projectile) moving through a cloud of smaller microparticles (dust) in a complex plasma with neon as a buffer gas under microgravity conditions. A collective motion of the dust particles occurs as propagation of the contact discontinuity. The corresponding speed of sound was measured by a special method of the Mach cone visualization. The measurement results are incompatible with the theory of ion acoustic waves. The estimate for the pressure in a strongly coupled Coulomb system and a scaling law for the complex plasma make it possible to derive an evaluation for the speed of sound, which is in a reasonable agreement with the experiments in complex plasmas.