ALBERT

Description: CsrA/RsmA homologs are an extensive family of ribonucleic acid (RNA)-binding proteins that function as global post-transcriptional regulators controlling important cellular processes such as secondary metabolism, motility, biofilm formation and the production and secretion of virulence factors in diverse bacterial species. While direct messenger RNA binding by CsrA/RsmA has been studied in detail for some genes, it is anticipated that there are numerous additional, as yet undiscovered, direct targets that mediate its global regulation. To assist in the discovery of these targets, we propose a sequence-based approach to predict genes directly regulated by these regulators. In this work, we develop a computer code (CSRA_TARGET) implementing this approach, which leads to predictions for several novel targets in Escherichia coli and Pseudomonas aeruginosa . The predicted targets in other bacteria, specifically Salmonella enterica serovar Typhimurium , Pectobacterium carotovorum and Legionella pneumophila , also include global regulators that control virulence in these pathogens, unraveling intricate indirect regulatory roles for CsrA/RsmA. We have experimentally validated four predicted RsmA targets in P. aeruginosa . The sequence-based approach developed in this work can thus lead to several testable predictions for direct targets of CsrA homologs, thereby complementing and accelerating efforts to unravel global regulation by this important family of proteins.

Description: Although homologous recombination (HR) is an important pathway for DNA repair, it can also be a cause for deleterious genomic rearrangements leading to carcinogenesis. Therefore, cells have evolved elaborate mechanisms to regulate HR, positively as well as negatively. Among many molecular components that regulate HR are tumour suppressors p53, a negative regulator and breast cancer early-onset (BRCA)2, a positive regulator. Both the players not only interact with each other but also directly interact with human RAD51 (hRAD51), the key recombinase in HR. Here, for the first time we studied HR regulation by the combined action of p53 and BRCA2, in vitro . While BRC4 peptide inhibits ATP hydrolysis by hRAD51, BRCA2 BRC1-8 stimulates DNA-independent and double-stranded DNA-dependent ATPase several fold and only marginally single-stranded DNA-dependent ATPase. Pull down assays demonstrated the occurrence of complex comprising of all three proteins and DNA, where p53 tends to compete out hRAD51 and BRCA2 BRC1-8 , leading to not only the decline in ATP hydrolysis but also the strand exchange function of hRAD51 that was stimulated by BRCA2 BRC1-8 . Our findings suggest a rigorous p53-mediated regulation on hRAD51 functions in HR even in the presence of BRCA2.

Description: Long non coding RNAs (lncRNAs) have emerged as important regulators of various biological processes. LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regulates canonical Wnt pathway and gets down regulated upon Wnt signaling activation in mouse spermatogonial cells. Also, mrhl RNA regulates expression of genes pertaining to Wnt pathway and spermatogenesis by binding to chromatin. In the present study, we delineate the detailed molecular mechanism of Wnt signaling induced mrhl RNA down regulation in mouse spermatogonial cells. Mrhl RNA has an independent transcription unit and our various experiments like Chromatin Immunoprecipitation (in cell line as well as mouse testis) and shRNA mediated down regulation convincingly show that β-catenin and TCF4, which are the key effector proteins of the Wnt signaling pathway are required for down regulation of mrhl RNA. We have identified Ctbp1 as the co-repressor and its occupancy on mrhl RNA promoter depends on both β-catenin and TCF4. Upon Wnt signaling activation, Ctbp1 mediated histone repression marks increase at the mrhl RNA promoter. We also demonstrate that Wnt signaling induced mrhl RNA down regulation results in an up regulation of various meiotic differentiation marker genes.

Description: We present measurements of element abundance ratios and dust in Ca ii absorbers identified in Sloan Digital Sky Survey DR7+DR9. In an earlier paper we formed a statistical sample of 435 Ca ii absorbers and postulated that their statistical properties might be representative of at least two populations of absorbers. Here, we show that if the absorbers are roughly divided into two subsamples with Ca ii rest equivalent widths larger and smaller than $W_0^{\lambda 3934} = 0.7$ Å, they are then representative of two physically different populations. Comparisons of abundance ratios between the two Ca ii absorber populations indicate that the weaker $W_0^{\lambda 3934}$ absorbers have properties consistent with halo-type gas, while the stronger absorbers have properties intermediate between halo- and disc-type gas. We also show that, on average, the dust-extinction properties of the overall sample is consistent with a Large Magellanic Cloud or Small Magellanic Cloud dust law, and the stronger absorbers are nearly six times more reddened than their weaker counterparts. The absorbed-to-unabsorbed composite flux ratio at rest  = 2200 Å is $\mathcal {R} \approx 0.73$ and E ( B – V )  0.046 for the stronger Ca ii absorbers ( $W_0^{\lambda 3934} \ge 0.7$ Å), and $\mathcal {R} \approx 0.95$ and E ( B – V )  0.011 for the weaker Ca ii absorbers ( $W_0^{\lambda 3934} 〈 0.7$ Å).

Description: The circumgalactic medium (CGM) can be probed through the analysis of absorbing systems in the line of sight to bright background quasars. We present measurements of the metallicity of a new sample of 15 sub-damped Lyman α absorbers (sub-DLAs, defined as absorbers with 19.0 〈 log N(H I) 〈 20.3) with redshift 0.584 ≤ z abs ≤ 3.104 from the ESO Ultra-Violet Echelle Spectrograph (UVES) Advanced Data Products Quasar Sample (EUADP). We combine these results with other measurements from the literature to produce a compilation of metallicity measurements for 92 sub-DLAs as well as a sample of 362 DLAs. We apply a multi-element analysis to quantify the amount of dust in these two classes of systems. We find that either the element depletion patterns in these systems differ from the Galactic depletion patterns or they have a different nucleosynthetic history than our own Galaxy. We propose a new method to derive the velocity width of absorption profiles, using the modelled Voigt profile features. The correlation between the velocity width V 90 of the absorption profile and the metallicity is found to be tighter for DLAs than for sub-DLAs. We report hints of a bimodal distribution in the [Fe/H] metallicity of low redshift ( z 〈 1.25) sub-DLAs, which is unseen at higher redshifts. This feature can be interpreted as a signature from the metal-poor, accreting gas and the metal-rich, outflowing gas, both being traced by sub-DLAs at low redshifts.

Description: Quasar damped Lyα (DLA) absorption-line systems with redshifts z  〈 1.65 are used to trace neutral gas over approximately 70 per cent of the most recent history of the Universe. However, such systems fall in the UV and are rarely found in blind UV spectroscopic surveys. Therefore, it has been difficult to compile a moderate-sized sample of UV DLAs in any narrow cosmic time interval. However, DLAs are easy to identify in low-resolution spectra because they have large absorption rest equivalent widths. We have performed an efficient strong-Mg  ii -selected survey for UV DLAs at redshifts z  = [0.42, 0.70] using Hubble Space Telescope 's low-resolution ACS-HRC-PR200L prism. This redshift interval covers ~1.8 Gyr in cosmic time, i.e. t   [7.2, 9.0] Gyr after the big bang. A total of 96 strong Mg  ii absorption-line systems identified in Sloan Digital Sky Survey spectra were successfully observed with the prism at the predicted UV wavelengths of Lyα absorption. We found that 35 of the 96 systems had a significant probability of being DLAs. One additional observed system could be a very high $N_{\rm H\,\small {I}}$ DLA ( $N_{\rm H\,\small {I}} \sim 2\times 10^{22}$ atoms cm –2 or possibly higher), but since very high $N_{\rm H\,\small {I}}$ systems are extremely rare, it would be unusual for this system to be a DLA given the size of our sample. Here we present information on our prism sample, including our best estimates of $N_{\rm H\,\small {I}}$ and errors for the 36 systems fitted with DLA profiles. This list is valuable for future follow-up studies of low-redshift DLAs in a small redshift interval, although such work would clearly benefit from improved UV spectroscopy to more accurately determine their neutral hydrogen column densities.

Description: Identification of components essential to chromosome structure and behaviour remains a vibrant area of study. We have previously shown that invadolysin is essential in Drosophila , with roles in cell division and cell migration. Mitotic chromosomes are hypercondensed in length, but display an aberrant fuzzy appearance. We additionally demonstrated that in human cells, invadolysin is localized on the surface of lipid droplets, organelles that store not only triglycerides and sterols but also free histones H2A, H2Av and H2B. Is there a link between the storage of histones in lipid droplets and the aberrantly structured chromosomes of invadolysin mutants? We have identified a genetic interaction between invadolysin and nonstop , the de-ubiquitinating protease component of the SAGA (Spt-Ada-Gcn5-acetyltransferase) chromatin-remodelling complex. invadolysin and nonstop mutants exhibit phenotypic similarities in terms of chromosome structure in both diploid and polyploid cells. Furthermore, IX-14 1 / not 1 transheterozygous animals accumulate mono-ubiquitinated histone H2B (ubH2B) and histone H3 tri-methylated at lysine 4 (H3K4me3). Whole mount immunostaining of IX-14 1 / not 1 transheterozygous salivary glands revealed that ubH2B accumulates surprisingly in the cytoplasm, rather than the nucleus. Over-expression of the Bre1 ubiquitin ligase phenocopies the effects of mutating either the invadolysin or nonstop genes. Intriguingly, nonstop and mutants of other SAGA subunits ( gcn5, ada2b and sgf11 ) all suppress an invadolysin-induced rough eye phenotype. We conclude that the abnormal chromosome phenotype of invadolysin mutants is likely the result of disrupting the histone modification cycle, as accumulation of ubH2B and H3K4me3 is observed. We further suggest that the mislocalization of ubH2B to the cytoplasm has additional consequences on downstream components essential for chromosome behaviour. We therefore propose that invadolysin plays a crucial role in chromosome organization via its interaction with the SAGA complex.

Description: We present the results of a survey for Ca ii 3934, 3969 absorption-line systems culled from ~95 000 Sloan Digital Sky Survey (SDSS) Data Release 7 and Data Release 9 quasar spectra. With 435 doublets identified in the catalogue, this list is the largest Ca ii catalogue compiled to date, spanning redshifts z  〈 1.34, which corresponds to the most recent ~8.9 Gyr of the history of the Universe. We derive statistics on the Ca ii rest equivalent width distribution and incidence. We find that the 3934 rest equivalent width ( $W_{0}^{\lambda 3934}$ ) distribution cannot be described by a single exponential function. A double exponential function is required to produce a satisfactory description. The function can be written as a sum of weak and strong components: ${\mathrm{\partial} n}/{\mathrm{\partial} W_{0}^{\lambda 3934}}= ({N_{{\rm wk}}^{\ast }}/{W_{{\rm wk}}^{\ast }}) \exp ({ -{W_{0}^{\lambda 3934}}/{W_{{\rm wk}}^{\ast } } }) + ({N_{{\rm str}}^{\ast }}/{W_{{\rm str}}^{\ast }}) \exp ({ -{W_{0}^{\lambda 3934}}/{W_{{\rm str}}^{\ast } } })$ . A maximum likelihood fit to the unbinned data indicates $N_{{\rm wk}}^{\ast }=0.140\pm 0.029$ , $W_{{\rm wk}}^{\ast }=0.165\pm 0.020\ \mathrm{\unicode{197}}$ , $N_{{\rm str}}^{\ast }=0.024\pm 0.020$ , and $W_{{\rm str}}^{\ast }=0.427\pm 0.101\ \mathrm{\unicode{197}}$ . This suggests that the Ca ii absorbers are composed of at least two distinct populations. The incidence of the overall Ca ii absorber population does not show evidence for evolution in the standard cosmology. The normalization of the no-evolution curve, i.e. the value of the Ca ii incidence extrapolated to redshift z  = 0, for $W_{0}^{\lambda 3934} \ge 0.3$ Å, is n 0  = 0.017 ± 0.001. In comparison to Mg ii surveys, we found that only 3 per cent of Mg ii systems in the SDSS have Ca ii , confirming that Ca ii systems are rare. We also report on some preliminary investigations of the nature of the two populations of Ca ii absorbers, and show that they can likely be distinguished using their Mg ii properties.

Description: We present Hubble Space Telescope Cosmic Origins Spectrograph spectra of 10 quasars located behind M31, selected to investigate the properties of gas associated with its extended disc and high-velocity clouds (HVCs). The sightlines have impact parameters ranging between b  = 13 and 112 kpc. No absorption is detected in the four sightlines selected to sample any extended disc (or halo) gas that might be present in the outer regions of M31 beyond an impact parameter of b  〉 57 kpc. Of the six remaining sightlines, all of which lie at b 〈 32 kpc and within the N HI = 2 x 10 18  cm –2 boundary of the H i disc of M31, we detect low-ionization absorption at M31 velocities along four of them (three of which include Mg ii absorption). We also detect Mg ii absorption from an HVC. This HVC sightline does not pass through the 21 cm disc of M31, but we detect additional Mg ii absorption at velocities distinct from the HVC that presumably arises in the halo. We find that along sightlines where both are detected, the velocity location of the low-ion gas tracks the peak in 21 cm emission. High-ionization absorption is detected along the three inner sightlines, but not along the three outer sightlines, for which C iv data exist. As inferred from high-resolution 21 cm emission-line maps of M31's disc and extended regions, only one of the sightlines may be capable of harbouring a damped Lyα system, i.e. with N HI ≥ 2 x 10 20  cm –2 . This sightline has impact parameter b  = 17.5 kpc, and we detect both low- and high-ion absorption lines associated with it. The impact parameters of our observed sightlines through M31 are similar to the impact parameters of galaxies identified with Mg ii absorbers at redshifts 0.1 〈 z 〈 1.0 in a 2011 study by Rao et al. However, even if we only count cases where absorption due to M31 is detected, the Mg ii 2796 rest equivalent width values are significantly smaller. In comparison, moderate-to-strong Mg ii absorption from Milky Way gas is detected along all 10 sightlines. Thus, this study indicates that M31 does not present itself as an absorbing galaxy which is typical of higher-redshift galaxies inferred to give rise to moderate-strength quasar absorption lines. M31 also appears not to possess an extensive large gaseous cross-section, at least not along the direction of its major axis.