Mechanism of Evolution Shared by Gene and Language

We propose a general mechanism for evolution to explain the diversity of gene and language. To quantify their common features and reveal the hidden structures, several statistical properties and patterns are examined based on a new method called the rank-rank analysis. We find that the classical correspondence, "domain plays the role of word in gene language", is not rigorous, and propose to replace domain by protein. In addition, we devise a new evolution unit, syllgram, to include the characteristics of spoken and written language. Based on the correspondence between (protein, domain) and (word, syllgram), we discover that both gene and language shared a common scaling structure and scale-free network. Like the Rosetta stone, this work may help decipher the secret behind non-coding DNA and unknown languages.Comment: 15 pages, 13 figures, 3 tabl

Panax notoginseng Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

Panax notoginseng (PN) is a traditional Chinese herb experimentally proven to have anti-inflammatory effects, and it is used clinically for the treatment of atherosclerosis, cerebral infarction, and cerebral ischemia. This study aimed to determine the anti-inflammatory effects of PN against bleomycin-induced pulmonary fibrosis in mice. First, in an in vitro study, culture media containing lipopolysaccharide (LPS) was used to stimulate macrophage cells (RAW 264.7 cell line). TNF-α and IL-6 levels were then determined before and after treatment with PN extract. In an animal model (C57BL/6 mice), a single dose of PN (0.5 mg/kg) was administered orally on Day 2 or Day 7 postbleomycin treatment. The results showed that TNF-α and IL-6 levels increased in the culture media of LPS-stimulated macrophage cells, and this effect was significantly inhibited in a concentration-dependent manner by PN extract. Histopathologic examination revealed that PN administered on Day 7 postbleomycin treatment significantly decreased inflammatory cell infiltrates, fibrosis scores, and TNF-α, TGF-β, IL-1β, and IL-6 levels in bronchoalveolar lavage fluid when compared with PN given on Day 2 postbleomycin treatment. These results suggest that PN administered in the early fibrotic stage can attenuate pulmonary fibrosis in an animal model of idiopathic pulmonary fibrosis

The C-Terminus of Histone H2B Is Involved in Chromatin Compaction Specifically at Telomeres, Independently of Its Monoubiquitylation at Lysine 123

Telomeric heterochromatin assembly in budding yeast propagates through the association of Silent Information Regulator (SIR) proteins with nucleosomes, and the nucleosome array has been assumed to fold into a compacted structure. It is believed that the level of compaction and gene repression within heterochromatic regions can be modulated by histone modifications, such as acetylation of H3 lysine 56 and H4 lysine 16, and monoubiquitylation of H2B lysine 123. However, it remains unclear as to whether or not gene silencing is a direct consequence of the compaction of chromatin. Here, by investigating the role of the carboxy-terminus of histone H2B in heterochromatin formation, we identify that the disorderly compaction of chromatin induced by a mutation at H2B T122 specifically hinders telomeric heterochromatin formation. H2B T122 is positioned within the highly conserved AVTKY motif of the αC helix of H2B. Heterochromatin containing the T122E substitution in H2B remains inaccessible to ectopic dam methylase with dramatically increased mobility in sucrose gradients, indicating a compacted chromatin structure. Genetic studies indicate that this unique phenotype is independent of H2B K123 ubiquitylation and Sir4. In addition, using ChIP analysis, we demonstrate that telomere structure in the mutant is further disrupted by a defect in Sir2/Sir3 binding and the resulting invasion of euchromatic histone marks. Thus, we have revealed that the compaction of chromatin per se is not sufficient for heterochromatin formation. Instead, these results suggest that an appropriately arrayed chromatin mediated by H2B C-terminus is required for SIR binding and the subsequent formation of telomeric chromatin in yeast, thereby identifying an intrinsic property of the nucleosome that is required for the establishment of telomeric heterochromatin. This requirement is also likely to exist in higher eukaryotes, as the AVTKY motif of H2B is evolutionarily conserved

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Fha Interaction with Phosphothreonine of TssL Activates Type VI Secretion in <i>Agrobacterium tumefaciens</i>

<div><p>The type VI secretion system (T6SS) is a widespread protein secretion system found in many Gram-negative bacteria. T6SSs are highly regulated by various regulatory systems at multiple levels, including post-translational regulation via threonine (Thr) phosphorylation. The Ser/Thr protein kinase PpkA is responsible for this Thr phosphorylation regulation, and the forkhead-associated (FHA) domain-containing Fha-family protein is the sole T6SS phosphorylation substrate identified to date. Here we discovered that TssL, the T6SS inner-membrane core component, is phosphorylated and the phosphorylated TssL (<i>p-</i>TssL) activates type VI subassembly and secretion in a plant pathogenic bacterium, <i>Agrobacterium tumefaciens</i>. Combining genetic and biochemical approaches, we demonstrate that TssL is phosphorylated at Thr 14 in a PpkA-dependent manner. Further analysis revealed that the PpkA kinase activity is responsible for the Thr 14 phosphorylation, which is critical for the secretion of the T6SS hallmark protein Hcp and the putative toxin effector Atu4347. TssL phosphorylation is not required for the formation of the TssM-TssL inner-membrane complex but is critical for TssM conformational change and binding to Hcp and Atu4347. Importantly, Fha specifically interacts with phosphothreonine of TssL via its pThr-binding motif <i>in vivo</i> and <i>in vitro</i> and this interaction is crucial for TssL interaction with Hcp and Atu4347 and activation of type VI secretion. In contrast, pThr-binding ability of Fha is dispensable for TssM structural transition. In conclusion, we discover a novel Thr phosphorylation event, in which PpkA phosphorylates TssL to activate type VI secretion via its direct binding to Fha in <i>A. tumefaciens</i>. A model depicting an ordered TssL phosphorylation-induced T6SS assembly pathway is proposed.</p></div

Phos-tag SDS-PAGE for TssL phosphorylation analysis in various mutants.

<p>Detection of the phosphorylation status of TssL-His on Phos-tag gel. Western blot analysis of the same volumes of Ni-NTA resins (40 µl) associated with TssL-His from different strains treated with (+) or without (−) CIAP and examined with specific antibody against 6×His. Total proteins isolated from Δ<i>tssL</i> were a negative control. Phos-tag SDS-PAGE revealed the upper band indicating the phosphorylated TssL-His (<i>p</i>-TssL-His) and lower band indicating unphosphorylated TssL-His.</p

TssL-Strep pulldown and spheroplast protease susceptibility assays in <i>A. tumefaciens</i>.

<p>(<b>A</b>) Pulldown assay by TssL-Strep in various <i>A. tumefaciens</i> strains. Western blot analysis of the loaded Triton X-100 solublized protein fraction (L), wash (W), and elution (E) examined with specific antibodies. The soluble protein ActC and outer-membrane protein AopB <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003991#ppat.1003991-Jia1" target="_blank">[46]</a> were internal controls. (<b>B</b>) Spheroplasts from various <i>A. tumefaciens</i> strains were incubated with different protease concentrations as indicated. The degree of susceptibility or resistance to protease in various strains was analyzed by western blot analysis with specific antibodies. Cytoplasmic GroEL <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003991#ppat.1003991-Chang1" target="_blank">[47]</a> was an internal control for resistance to protease digestion. The amount of analyzed proteins was further quantified by use of UVP BioSpectrum 600 and normalized to the internal control GroEL. The relative intensity from TssM and TssL are shown at the bottom of analyzed strains by setting the wild-type C58 level to 100. The quantitative results shown with standard deviation were obtained and normalized from at least 2 independent experiments.</p

PpkA- and Fha-dependent post-translational regulation of Hcp secretion from <i>A. tumefaciens.</i>

<p>(<b>A</b>) The <i>imp</i> operon encoding 14 genes (<i>atu4343</i> to <i>atu4330</i> or <i>impA-N</i>) and the <i>hcp</i> operon encoding 9 genes (<i>atu4344</i> to <i>atu4352</i>) and <i>atu3642</i> (<i>vgrG-2</i>) encoded by <i>A. tumefaciens</i> strain C58 was designated <i>tss</i> or <i>tag</i> based on nomenclature proposed by Shalom et al. (2007) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003991#ppat.1003991-Shalom1" target="_blank">[18]</a> and common names <i>ppkA</i>, <i>tagF-pppA</i>, and <i>fha</i>. This schematic was from Lin et al. (2013) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003991#ppat.1003991-Lin1" target="_blank">[11]</a>. (<b>B</b>) Hcp secretion analysis. Western blot analysis of total (T) and secreted (S) proteins isolated from wild-type C58, Δ<i>ppkA</i>, and Δ<i>tagF-pppA</i> mutants harboring the vector pRL662 (V) or <i>ppkA</i> complemented plasmid (pPpkA) or <i>tagF-pppA</i> complemented plasmid (pTagF-PppA) with specific antibodies. (<b>C</b>) The amino acid sequence alignment of the FHA domain of Fha (Atu4335) and selected Fha-family proteins indicating the conserved pThr binding motif. Conserved amino acid residues are highlighted in black and marked below, and R30 and S46 used for mutagenesis are indicated with an asterisk. Sequences were aligned and highlighted by use of ClustalW2 (<a href="http://www.ebi.ac.uk/Tools/msa/clustalw2/" target="_blank">http://www.ebi.ac.uk/Tools/msa/clustalw2/</a>). (<b>D</b>) Hcp secretion assay for chromosomally encoded <i>fha</i> variants, including <i>fha</i> deletion (Δ<i>fha</i>), <i>fha</i> wild-type revertant with double crossover (<i>fha</i> R), <i>fha</i> with deletion of the entire FHA domain from 25 to 76 aa (<i>fha</i>^ΔFHA), and <i>fha</i> with substitutions of pThr binding motif (<i>fha</i>^R30A, <i>fha</i>^S46A, and <i>fha</i>^R30AS46A). For secretion assays in (B) and (D), the non-secreted protein ActC was an internal control. The proteins analyzed and sizes of molecular weight standards are on the left and right, respectively.</p