The curious case of offset bars : markers for a baby galaxy disk or signposts of an interaction with dark matter sub halos?

>Magister Scientiae - MScWe have used the Spitzer Survey of Stellar Structure in Galaxies (S⁴G) as a representative sample of the local universe (total of 2352 galaxies in S⁴G) to make a catalog of offset disk barred galaxies. Using the combined variation of the position angle and the ellipticity (provided by ellipse fit) and also through visual inspection, we have been able to identify all offset structures in S⁴G. While primary bars are present in 2=3 of the disk galaxies in the visible universe, offset bars have a much lower fraction. Of the ̴ 1500 (3.6µm images) disk galaxies available in S⁴G, we classified only 49 as offset barred disk galaxies. We have determined basic properties (bar to total luminosity ratio, bar length, disk scale-length and bars of offset bars shape) using GALFIT, a widely used galaxy decomposition software package. Our main conclusion is that all the offset bars are boxy, independent of their offset from the galaxy center, or the mass of the host galaxy. Additionally we find that, the early type offset bars seem to be more boxy than the late types. The comparison of our offset sample with two other samples, respectively, low mass and high mass normal barred galaxies ("normal" for bars located at the photometric center of the host galaxy), reveals them to be at an intermediate position between the two normal samples. The bar length, disk scale-length and bar to total luminosity ratio are on average larger than the low mass normal and smaller than high mass normal barred galaxies. We have found, overall, a tighter correlation between the disk and bar properties for offset bars in comparison to the two normal samples. Our explanation is that, although the offset has no visible impact on the global shape of the bars, the process responsible for these disturbances seems to affect the star formation rate such that their disk and bars are on average more active than the normal barred galaxies in the same mass range, but not enough to surpass normal barred galaxies with much higher mass

Image_1_Compressed variance component mixed model reveals epistasis associated with flowering in Arabidopsis.pdf

IntroductionEpistasis is currently a topic of great interest in molecular and quantitative genetics. Arabidopsis thaliana, as a model organism, plays a crucial role in studying the fundamental biology of diverse plant species. However, there have been limited reports about identification of epistasis related to flowering in genome-wide association studies (GWAS). Therefore, it is of utmost importance to conduct epistasis in Arabidopsis.MethodIn this study, we employed Levene’s test and compressed variance component mixed model in GWAS to detect quantitative trait nucleotides (QTNs) and QTN-by-QTN interactions (QQIs) for 11 flowering-related traits of 199 Arabidopsis accessions with 216,130 markers.ResultsOur analysis detected 89 QTNs and 130 pairs of QQIs. Around these loci, 34 known genes previously reported in Arabidopsis were confirmed to be associated with flowering-related traits, such as SPA4, which is involved in regulating photoperiodic flowering, and interacts with PAP1 and PAP2, affecting growth of Arabidopsis under light conditions. Then, we observed significant and differential expression of 35 genes in response to variations in temperature, photoperiod, and vernalization treatments out of unreported genes. Functional enrichment analysis revealed that 26 of these genes were associated with various biological processes. Finally, the haplotype and phenotypic difference analysis revealed 20 candidate genes exhibiting significant phenotypic variations across gene haplotypes, of which the candidate genes AT1G12990 and AT1G09950 around QQIs might have interaction effect to flowering time regulation in Arabidopsis.DiscussionThese findings may offer valuable insights for the identification and exploration of genes and gene-by-gene interactions associated with flowering-related traits in Arabidopsis, that may even provide valuable reference and guidance for the research of epistasis in other species.</p

DataSheet_1_Compressed variance component mixed model reveals epistasis associated with flowering in Arabidopsis.zip

IntroductionEpistasis is currently a topic of great interest in molecular and quantitative genetics. Arabidopsis thaliana, as a model organism, plays a crucial role in studying the fundamental biology of diverse plant species. However, there have been limited reports about identification of epistasis related to flowering in genome-wide association studies (GWAS). Therefore, it is of utmost importance to conduct epistasis in Arabidopsis.MethodIn this study, we employed Levene’s test and compressed variance component mixed model in GWAS to detect quantitative trait nucleotides (QTNs) and QTN-by-QTN interactions (QQIs) for 11 flowering-related traits of 199 Arabidopsis accessions with 216,130 markers.ResultsOur analysis detected 89 QTNs and 130 pairs of QQIs. Around these loci, 34 known genes previously reported in Arabidopsis were confirmed to be associated with flowering-related traits, such as SPA4, which is involved in regulating photoperiodic flowering, and interacts with PAP1 and PAP2, affecting growth of Arabidopsis under light conditions. Then, we observed significant and differential expression of 35 genes in response to variations in temperature, photoperiod, and vernalization treatments out of unreported genes. Functional enrichment analysis revealed that 26 of these genes were associated with various biological processes. Finally, the haplotype and phenotypic difference analysis revealed 20 candidate genes exhibiting significant phenotypic variations across gene haplotypes, of which the candidate genes AT1G12990 and AT1G09950 around QQIs might have interaction effect to flowering time regulation in Arabidopsis.DiscussionThese findings may offer valuable insights for the identification and exploration of genes and gene-by-gene interactions associated with flowering-related traits in Arabidopsis, that may even provide valuable reference and guidance for the research of epistasis in other species.</p

Table_1_Compressed variance component mixed model reveals epistasis associated with flowering in Arabidopsis.xlsx

IntroductionEpistasis is currently a topic of great interest in molecular and quantitative genetics. Arabidopsis thaliana, as a model organism, plays a crucial role in studying the fundamental biology of diverse plant species. However, there have been limited reports about identification of epistasis related to flowering in genome-wide association studies (GWAS). Therefore, it is of utmost importance to conduct epistasis in Arabidopsis.MethodIn this study, we employed Levene’s test and compressed variance component mixed model in GWAS to detect quantitative trait nucleotides (QTNs) and QTN-by-QTN interactions (QQIs) for 11 flowering-related traits of 199 Arabidopsis accessions with 216,130 markers.ResultsOur analysis detected 89 QTNs and 130 pairs of QQIs. Around these loci, 34 known genes previously reported in Arabidopsis were confirmed to be associated with flowering-related traits, such as SPA4, which is involved in regulating photoperiodic flowering, and interacts with PAP1 and PAP2, affecting growth of Arabidopsis under light conditions. Then, we observed significant and differential expression of 35 genes in response to variations in temperature, photoperiod, and vernalization treatments out of unreported genes. Functional enrichment analysis revealed that 26 of these genes were associated with various biological processes. Finally, the haplotype and phenotypic difference analysis revealed 20 candidate genes exhibiting significant phenotypic variations across gene haplotypes, of which the candidate genes AT1G12990 and AT1G09950 around QQIs might have interaction effect to flowering time regulation in Arabidopsis.DiscussionThese findings may offer valuable insights for the identification and exploration of genes and gene-by-gene interactions associated with flowering-related traits in Arabidopsis, that may even provide valuable reference and guidance for the research of epistasis in other species.</p

Image_2_Compressed variance component mixed model reveals epistasis associated with flowering in Arabidopsis.tif

IntroductionEpistasis is currently a topic of great interest in molecular and quantitative genetics. Arabidopsis thaliana, as a model organism, plays a crucial role in studying the fundamental biology of diverse plant species. However, there have been limited reports about identification of epistasis related to flowering in genome-wide association studies (GWAS). Therefore, it is of utmost importance to conduct epistasis in Arabidopsis.MethodIn this study, we employed Levene’s test and compressed variance component mixed model in GWAS to detect quantitative trait nucleotides (QTNs) and QTN-by-QTN interactions (QQIs) for 11 flowering-related traits of 199 Arabidopsis accessions with 216,130 markers.ResultsOur analysis detected 89 QTNs and 130 pairs of QQIs. Around these loci, 34 known genes previously reported in Arabidopsis were confirmed to be associated with flowering-related traits, such as SPA4, which is involved in regulating photoperiodic flowering, and interacts with PAP1 and PAP2, affecting growth of Arabidopsis under light conditions. Then, we observed significant and differential expression of 35 genes in response to variations in temperature, photoperiod, and vernalization treatments out of unreported genes. Functional enrichment analysis revealed that 26 of these genes were associated with various biological processes. Finally, the haplotype and phenotypic difference analysis revealed 20 candidate genes exhibiting significant phenotypic variations across gene haplotypes, of which the candidate genes AT1G12990 and AT1G09950 around QQIs might have interaction effect to flowering time regulation in Arabidopsis.DiscussionThese findings may offer valuable insights for the identification and exploration of genes and gene-by-gene interactions associated with flowering-related traits in Arabidopsis, that may even provide valuable reference and guidance for the research of epistasis in other species.</p

Adamantane-Resistant Influenza A Viruses in the World (1902–2013): Frequency and Distribution of M2 Gene Mutations

<div><p>Adamantanes (amantadine and rimantadine) have been used to prevent and treat influenza A virus infections for many years; however, resistance to these drugs has been widely reported in the world. To investigate the frequency and distribution of M2 gene mutations in adamantane-resistant influenza variants circulated in the world between 1902 and 2013, 31251 available M2 protein sequences from different HA-subtype influenza A viruses (H1–H17) were analyzed and adamantane resistance-associated mutations were compared (L26F, V27A, A30T, A30V, S31N, G34E, and L38F). We find that 45.2% (n = 14132) of influenza A (H1–H17) viruses circulating globally were resistant to adamantanes, and the vast majority of resistant viruses (95%) bear S31N mutations. Whereas, only about 1% have V27A mutations and other mutations (L26F, A30T, G34E, and L38F) were extremely rare (their prevalence appeared to be < 0.2%). Our results confirm that H1, H3, H5, H7, H9, and H17 subtype influenza A viruses exhibit high-level resistance to adamantanes. In contrast, the appearance of adamantane-resistant mutants in H2, H4, H6, H10, and H11 subtypes was rare. However, no adamantane resistance viruses were identified among other HA subtypes (H8, H12–H16). Our findings indicate that the frequency and distribution of adamantane-resistant influenza variants varied among different HA subtypes, host species, years of isolation, and geographical areas. This comprehensive study raises concerns about the increasing prevalence of adamantane-resistant influenza A viruses and highlights the importance of monitoring the emergence and worldwide spread of adamantane-resistant variants.</p></div

The frequencies of adamantane-resistant variants among all influenza A (H1-H17) viruses used in this study.

<p>^a adamantane resistance-associated mutations present in the M2 Protein of viruses were at positions L26F, V27A, A30T, A30V, S31N, G34E, and L38F that confer resistance to adamantanes.</p><p>^b Appearance time to adamantane resistant variants.</p><p>^c The frequency of adamantane resistant variants among different HA subtypes.</p><p>The frequencies of adamantane-resistant variants among all influenza A (H1-H17) viruses used in this study.</p

Identification of a Small Molecule That Turns ON the Pluripotency Gene Circuitry in Human Fibroblasts

A nontransgenic approach to reprogram mouse somatic cells into induced pluripotent stem cells using only small molecules got achieved to propose a potential clinical-friendly cellular reprogramming strategy. Consequently, the screening and identification of small molecules capable of inducing pluripotency genes in human cells are increasingly a focus of research. Because cellular reprogramming is multifactorial in nature, there is a need for versatile small molecules capable of modulating the complicated gene networks associated with pluripotency. We have developed a targeting small molecule called SAHA-PIP comprising the histone deacetylase inhibitor SAHA and the sequence-specific DNA binding pyrrole-imidazole polyamides for modulating distinct gene networks. Here, we report the identification of a SAHA-PIP termed <b>I</b>̀ that could trigger genome-wide epigenetic reprogramming and turn ON the typically conserved core pluripotency gene network. Through independent lines of evidence, we report for the first time a synthetic small molecule inducer that target and activate the <i>OCT-3/4</i> regulated pluripotency genes in human dermal fibroblasts

Discovery of Diverse Human Dihydroorotate Dehydrogenase Inhibitors as Immunosuppressive Agents by Structure-Based Virtual Screening

This study applied an efficient virtual screening strategy integrating molecular docking with MM-GBSA rescoring to identify diverse human dihydroorotate dehydrogenase (<i>h</i>DHODH) inhibitors. Eighteen compounds with IC₅₀ values ranging from 0.11 to 18.8 μM were identified as novel <i>h</i>DHODH inhibitors that exhibited overall species-selectivity over <i>Plasmodium falciparum</i> dihydroorotate dehydrogenase (<i>pf</i>DHODH). Compound <b>8</b>, the most potent one, showed low micromolar inhibitory activity against <i>h</i>DHODH with an IC₅₀ value of 0.11 μM. Moreover, lipopolysaccharide-induced B-cell assay and mixed lymphocyte reaction assay revealed that most of the hits showed potent antiproliferative activity against B and T cells, which demonstrates their potential application as immunosuppressive agents. In particular, compound <b>18</b> exhibited potent B-cell inhibitory activity (IC₅₀ = 1.78 μM) and presents a B-cell-specific profile with 17- and 26-fold selectivities toward T and Jurkat cells, respectively

Design, Synthesis, X‑ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase

Human dihydroorotate dehydrogenase (<i>Hs</i>DHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound <b>4</b>, which was previously identified as potential <i>Hs</i>DHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues <b>12</b> and <b>33</b> confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds <b>44</b>, <b>46</b>, and <b>47</b> which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, <b>44</b> presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of <i>Hs</i>DHODH