ALBERT

Description: A halo merger tree forms the essential backbone of a semi-analytic model for galaxy formation and evolution. Recent studies have pointed out that extracting merger trees from numerical simulations of structure formation is non-trivial; different tree building algorithms can give differing merger histories. These differences should be carefully understood before merger trees are used as input for models of galaxy formation. We investigate the impact of different halo merger trees on a semi-analytic model. We find that the z  = 0 galaxy properties in our model show differences between trees when using a common parameter set. The star formation history of the universe and the properties of satellite galaxies can show marked differences between trees with different construction methods. Independently calibrating the semi-analytic model for each tree can reduce the discrepancies between the z  = 0 global galaxy properties, at the cost of increasing the differences in the evolutionary histories of galaxies. Furthermore, the underlying physics implied can vary, resulting in key quantities such as the supernova feedback efficiency differing by factors of 2. Such a change alters the regimes where star formation is primarily suppressed by supernovae. Therefore, halo merger trees extracted from a common halo catalogue using different, but reliable, algorithms can result in a difference in the semi-analytic model. Given the uncertainties in galaxy formation physics, however, these differences may not necessarily be viewed as significant.

Description: All commonly considered dark matter scenarios are based on hypothetical particles with small but non-zero thermal velocities and tiny interaction cross-sections. A generic consequence of these attributes is the suppression of small-scale matter perturbations either due to free-streaming or due to interactions with the primordial plasma. The suppression scale can vary over many orders of magnitude depending on particle candidate and production mechanism in the early Universe. While non-linear structure formation has been explored in great detail well above the suppression scale, the range around suppressed perturbations is still poorly understood. In this paper, we study structure formation in the regime of suppressed perturbations using both analytical techniques and numerical simulations. We develop simple and theoretically motivated recipes for the halo mass function , the expected number of satellites , and the halo concentrations , which are designed to work for power spectra with suppression at arbitrary scale and of arbitrary shape. As case studies, we explore warm and mixed dark matter scenarios where effects are most distinctive. Additionally, we examine the standard dark matter scenario based on weakly interacting massive particles (WIMP) and compare it to pure cold dark matter with zero primordial temperature. We find that our analytically motivated recipes are in good agreement with simulations for all investigated dark matter scenarios, and we therefore conclude that they can be used for generic cases with arbitrarily suppressed small-scale perturbations.

Description: We explore fundamental properties of the distribution of low-mass dark matter haloes within the cosmic web using warm dark matter (WDM) and cold dark matter (CDM) cosmological simulations. Using self-abundance-matched mock galaxy catalogues, we show that the distribution of dwarf galaxies in a WDM universe, wherein low-mass halo formation is heavily suppressed, is nearly indistinguishable to that of a CDM universe whose low-mass haloes are not seen because galaxy formation is suppressed below some threshold halo mass. However, if the scatter between dwarf galaxy luminosity and halo properties is large enough, low-mass CDM haloes would sometimes host relatively bright galaxies thereby populating CDM voids with the occasional isolated galaxy and reducing the numbers of completely empty voids. Otherwise, without high mass to light scatter, all mock galaxy clustering statistics that we consider – the auto-correlation function, the numbers and radial profiles of satellites, the numbers of isolated galaxies, and the probability distribution function of small voids – are nearly identical in CDM and WDM. WDM voids are neither larger nor emptier than CDM voids, when constructed from abundance-matched halo catalogues. It is thus a challenge to determine whether the CDM problem of the overabundance of small haloes with respect to the number density of observed dwarf galaxies has a cosmological solution or an astrophysical solution. However, some clues about the dark matter particle and the scatter between the properties of dwarf galaxies and their dark matter halo hosts might be found in the cosmic web of galaxies in future surveys of the local volume.

Description: The RecQL4 helicase is involved in the maintenance of genome integrity and DNA replication. Mutations in the human RecQL4 gene cause the Rothmund–Thomson, RAPADILINO and Baller–Gerold syndromes. Mouse models and experiments in human and Xenopus have proven the N-terminal part of RecQL4 to be vital for cell growth. We have identified the first 54 amino acids of RecQL4 (RecQL4_N54) as the minimum interaction region with human TopBP1. The solution structure of RecQL4_N54 was determined by heteronuclear liquid–state nuclear magnetic resonance (NMR) spectroscopy (PDB 2KMU; backbone root-mean-square deviation 0.73 Å). Despite low-sequence homology, the well-defined structure carries an overall helical fold similar to homeodomain DNA-binding proteins but lacks their archetypical, minor groove-binding N-terminal extension. Sequence comparison indicates that this N-terminal homeodomain-like fold is a common hallmark of metazoan RecQL4 and yeast Sld2 DNA replication initiation factors. RecQL4_N54 binds DNA without noticeable sequence specificity yet with apparent preference for branched over double-stranded (ds) or single-stranded (ss) DNA. NMR chemical shift perturbation observed upon titration with Y-shaped, ssDNA and dsDNA shows a major contribution of helix α3 to DNA binding, and additional arginine side chain interactions for the ss and Y-shaped DNA.

Description: Mitochondria are essential for eukaryotic life and more than 95% of their proteins are imported as precursors from the cytosol. The targeting signals for this posttranslational import are conserved in all eukaryotes. However, this conservation does not hold true for the protein translocase of the mitochondrial outer membrane that serves as entry gate for essentially all precursor proteins. Only two of its subunits, Tom40 and Tom22, are conserved and thus likely were present in the last eukaryotic common ancestor. Tom7 is found in representatives of all supergroups except the Excavates. This suggests that it was added to the core of the translocase after the Excavates segregated from all other eukaryotes. A comparative analysis of the biochemically and functionally characterized outer membrane translocases of yeast, plants, and trypanosomes, which represent three eukaryotic supergroups, shows that the receptors that recognize the conserved import signals differ strongly between the different systems. They present a remarkable example of convergent evolution at the molecular level. The structural diversity of the functionally conserved import receptors therefore provides insight into the early evolutionary history of mitochondria.

Description: Over the last decade, warm dark matter (WDM) has been repeatedly proposed as an alternative scenario to the standard cold dark matter (CDM) one, potentially resolving several disagreements between the CDM model and observations on small scales. Here, we reconsider the most important CDM small-scale discrepancies in the light of recent observational constraints on WDM. As a result, we find that a conventional thermal (or thermal-like) WDM cosmology with a particle mass in agreement with Lyman α is nearly indistinguishable from CDM on the relevant scales and therefore fails to alleviate any of the small-scale problems. The reason for this failure is that the power spectrum of conventional WDM falls off too rapidly. To maintain WDM as a significantly different alternative to CDM, more evolved production mechanisms leading to multiple dark matter components or a gradually decreasing small-scale power spectrum have to be considered.

Description: Non-LTR retrotransposons are mobile genetic elements and play a major role in eukaryotic genome evolution and disease. Similar to retroviruses they encode a reverse transcriptase, but their genomic integration mechanism is fundamentally different, and they lack homologs of the retroviral nucleocapsid-forming protein Gag. Instead, their first open reading frames encode distinct multi-domain proteins (ORF1ps) presumed to package the retrotransposon-encoded RNA into ribonucleoprotein particles (RNPs). The mechanistic roles of ORF1ps are poorly understood, particularly of ORF1ps that appear to harbor an enzymatic function in the form of an SGNH-type lipolytic acetylesterase. We determined the crystal structures of the coiled coil and esterase domains of the ORF1p from the Danio rerio ZfL2-1 element. We demonstrate a dimerization of the coiled coil and a hydrolytic activity of the esterase. Furthermore, the esterase binds negatively charged phospholipids and liposomes, but not oligo-(A) RNA. Unexpectedly, the esterase can split into two dynamic half-domains, suited to engulf long fatty acid substrates extending from the active site. These properties indicate a role for lipids and membranes in non-LTR retrotransposition. We speculate that Gag-like membrane targeting properties of ORF1ps could play a role in RNP assembly and in membrane-dependent transport or localization processes.

Description: Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNAs with their cognate amino acids. They are an essential part of each translation system and in eukaryotes are therefore found in both the cytosol and mitochondria. Thus, eukaryotes either have two distinct genes encoding the cytosolic and mitochondrial isoforms of each of these enzymes or a single gene encoding dually localized products. Trypanosomes require trans- splicing of a cap containing leader sequence onto the 5'-untranslated region of every mRNA. Recently we speculated that alternative trans- splicing could lead to the expression of proteins having amino-termini of different lengths that derive from the same gene. We now demonstrate that alternative trans- splicing, creating a long and a short spliced variant, is the mechanism for dual localization of trypanosomal isoleucyl-tRNA synthetase (IleRS). The protein product of the longer spliced variant possesses an amino-terminal presequence and is found exclusively in mitochondria. In contrast, the shorter spliced variant is translated to a cytosol-specific isoform lacking the presequence. Furthermore, we show that RNA stability is one mechanism determining the differential abundance of the two spliced isoforms.

Description: We investigate the formation, growth, merger history, movement, and destruction of cosmic voids detected via the watershed transform code vide in a cosmological N -body dark matter cold dark matter simulation. By adapting a method used to construct halo merger trees, we are able to trace individual voids back to their initial appearance and record the merging and evolution of their progenitors at high redshift. For the scales of void sizes captured in our simulation, we find that the void formation rate peaks at scale factor 0.3, which coincides with a growth in the void hierarchy and the emergence of dark energy. Voids of all sizes appear at all scale factors, though the median initial void size decreases with time. When voids become detectable they have nearly their present-day volumes. Almost all voids have relatively stable growth rates and suffer only infrequent minor mergers. Dissolution of a void via merging is very rare. Instead, most voids maintain their distinct identity as annexed subvoids of a larger parent. The smallest voids are collapsing at the present epoch, but void destruction ceases after scale factor 0.3. In addition, voids centres tend to move very little, less than 10 –2 of their effective radii per ln a , over their lifetimes. Overall, most voids exhibit little radical dynamical evolution; their quiet lives make them pristine probes of cosmological initial conditions and the imprint of dark energy.

Description: We analyzed a multi-drug resistant (MR) HIV-1 reverse transcriptase (RT), subcloned from a patient-derived subtype CRF02_AG, harboring 45 amino acid exchanges, amongst them four thymidine analog mutations (TAMs) relevant for high-level AZT (azidothymidine) resistance by AZTMP excision (M41L, D67N, T215Y, K219E) as well as four substitutions of the AZTTP discrimination pathway (A62V, V75I, F116Y and Q151M). In addition, K65R, known to antagonize AZTMP excision in HIV-1 subtype B was present. Although MR-RT harbored the most significant amino acid exchanges T215Y and Q151M of each pathway, it exclusively used AZTTP discrimination, indicating that the two mechanisms are mutually exclusive and that the Q151M pathway is obviously preferred since it confers resistance to most nucleoside inhibitors. A derivative was created, additionally harboring the TAM K70R and the reversions M151Q as well as R65K since K65R antagonizes excision. MR-R65K-K70R-M151Q was competent of AZTMP excision, whereas other combinations thereof with only one or two exchanges still promoted discrimination. To tackle the multi-drug resistance problem, we tested if the MR-RTs could still be inhibited by RNase H inhibitors. All MR-RTs exhibited similar sensitivity toward RNase H inhibitors belonging to different inhibitor classes, indicating the importance of developing RNase H inhibitors further as anti-HIV drugs.