Given the global burden of diarrheal diseases on healthcare it is surprising how little is known about the drivers of disease severity. Colitis caused by infection and inflammatory bowel disease ...(IBD) is characterised by neutrophil infiltration into the intestinal mucosa and yet our understanding of neutrophil responses during colitis is incomplete. Using infectious (Citrobacter rodentium) and chemical (dextran sulphate sodium; DSS) murine colitis models, as well as human IBD samples, we find that faecal neutrophil elastase (NE) activity reflects disease severity. During C. rodentium infection intestinal epithelial cells secrete the serine protease inhibitor SerpinA3N to inhibit and mitigate tissue damage caused by extracellular NE. Mice suffering from severe infection produce insufficient SerpinA3N to control excessive NE activity. This activity contributes to colitis severity as infection of these mice with a recombinant C. rodentium strain producing and secreting SerpinA3N reduces tissue damage. Thus, uncontrolled luminal NE activity is involved in severe colitis. Taken together, our findings suggest that NE activity could be a useful faecal biomarker for assessing disease severity as well as therapeutic target for both infectious and chronic inflammatory colitis.
Silurian source rocks are among the least studied in the Timan-Pechora basin. This is mainly due to their occurrence at great depths (3.0–4.5 km) and the limited penetration of this stratigraphic ...interval by wells. Another source of information is the outcrops of the Silurian, which are known in the eastern and northeastern parts of the Timan-Pechora basin. The studied section of the Silurian deposits is exposed on the Padimeityvis River, located on the Chernov swell in the northeastern part of the basin. This article is devoted to the study of Silurian source rocks based on the results of lithological, coal petrographic studies and geochemistry of organic matter. The studied section is composed of carbonate and clay-carbonate deposits formed in shallow-water shelf conditions. Most of the section, composed of microcrystalline and microcrystalline with bioclasts limestones, is characterized by low concentrations of organic matter (Corg is generally less than 0.3 %). Elevated Corg contents (up to 1.16 %) are characteristic of clay-carbonate rock varieties, which make up about 20 % of the section. Sediments with increased concentrations of organic matter were formed in isolated and deepened areas of the bottom of the shallow-water basin as a whole. Assessment of the catagenetic transformation based on Rock-Eval pyrolysis data, coal petrographic studies, and conodont color indices showed that organic matter reached the conditions of the middle-end of the main oil generation zone (gradation MC2‑MC3). The obtained geochemical characteristics (Corg, S2, HI), taking into account a certain level of organic matter maturity, indicate that the Silurian source rocks had an average hydrocarbon potential.
Defining the roles and interactions of PTB Kafasla, Panagiota; Mickleburgh, Ian; Llorian, Miriam ...
Biochemical Society transactions,
08/2012, Letnik:
40, Številka:
4
Journal Article
Recenzirano
Odprti dostop
PTB (polypyrimidine tract-binding protein) is an abundant and widely expressed RNA-binding protein with four RRM (RNA recognition motif) domains. PTB is involved in numerous post-transcriptional ...steps in gene expression in both the nucleus and cytoplasm, but has been best characterized as a regulatory repressor of some ASEs (alternative splicing events), and as an activator of translation driven by IRESs (internal ribosome entry segments). We have used a variety of approaches to characterize the activities of PTB and its molecular interactions with RNA substrates and protein partners. Using splice-sensitive microarrays we found that PTB acts not only as a splicing repressor but also as an activator, and that these two activities are determined by the location at which PTB binds relative to target exons. We have identified minimal splicing repressor and activator domains, and have determined high resolution structures of the second RRM domain of PTB binding to peptide motifs from the co-repressor protein Raver1. Using single-molecule techniques we have determined the stoichiometry of PTB binding to a regulated splicing substrate in whole nuclear extracts. Finally, we have used tethered hydroxyl radical probing to determine the locations on viral IRESs at which each of the four RRM domains bind. We are now combining tethered probing with single molecule analyses to gain a detailed understanding of how PTB interacts with pre-mRNA substrates to effect either repression or activation of splicing.
This article complements the description of the informative-motivational text, which has recently been gaining great popularity among other types of scientific texts. The research material of the ...article allows not to limit the study of this type of text to the texts of natural-science orientation. It is noted that the texts of legal orientation are also important for understanding the features of style. A large thematic variety of legal scientific articles with different tasks in relation to the reader is revealed. The type of the text researched by the authors shows rather high level of expressiveness due to the frequent use of lexical stylistic means. The terms “lexical stylistic means” and “epithet” are defined in the article from the point of view of their functioning in an informative-motivational type of the text. The importance of lexical stylistic means and other expressive means is explained by appealing to a wide range of addressees in this type of text in order to influence the public consciousness and to form images and stereotypes required by the author of the legal text. The creation of such images becomes possible through the use of various means of expressive devices. The main feature of the figurative presentation of legal material is the absence of a direct nomination between the described scientific denotation and the lexeme. The analysis of the material has shown the great prevalence of derivatives formed by suffixation in the legal texts. The paper highlights the idea that the presence, along with professional vocabulary, lexical stylistic means in the informative-motivational text of the legal language allows to emphasize the validity of attributing this type of text to a special type, namely informative-motivational type of scientific text. The presence of expressive means can be considered its characteristic feature, which is innovative in the study of scientific text.
The eukaryotic La protein recognizes the 3′ poly(U) sequences of nascent RNA polymerase III transcripts to assist folding and maturation. The 3′ ends of such RNAs are bound by the N-terminal domain ...of La (LaNTD). We have solved the crystal structures of four LaNTD:RNA complexes, each containing a different single-stranded RNA oligomer, and compared them to the structure of a previously published LaNTD:RNA complex containing partially duplex RNA. The presence of purely single-stranded RNA in the binding pocket at the interface between the La motif and RRM domains allows significantly closer contact with the 3′ end of the RNA. Comparison of the different LaNTD:RNA complexes identifies a conserved set of interactions with the last two nucleotides at the 3′ end of the RNA ligand that are key to binding. Strikingly, we also observe two alternative conformations of bound ssRNA, indicative of an unexpected degree of plasticity in the modes of RNA binding.
Aminoacyl-tRNA synthetases (aaRSs) exert control over the faithful transfer of amino acids onto cognate tRNAs. Since chemical structures of various amino acids closely resemble each other, it is ...difficult to discriminate between them. Editing activity has been evolved by certain aaRSs to resolve the problem. In this study, we determined the crystal structures of complexes of
T. thermophilus phenylalanyl-tRNA synthetase (PheRS) with L-tyrosine,
p-chloro-phenylalanine, and a nonhydrolyzable tyrosyl-adenylate analog. The structures demonstrate plasticity of the synthetic site capable of binding substrates larger than phenylalanine and provide a structural basis for the proofreading mechanism. The editing site is localized at the B3/B4 interface, 35 Å from the synthetic site. Gluβ334 plays a crucial role in the specific recognition of the Tyr moiety in the editing site. The tyrosyl-adenylate analog binds exclusively in the synthetic site. Both structural data and tyrosine-dependent ATP hydrolysis enhanced by tRNA
Phe provide evidence for a preferential posttransfer editing pathway in the phenylalanine-specific system.
The polypyrimidine tract-binding protein (PTB) is an important regulator of alternative splicing. PTB-regulated splicing of α-tropomyosin is enhanced by Raver1, a protein with four PTB-Raver1 ...interacting motifs (PRIs) that bind to the helical face of the second RNA recognition motif (RRM2) in PTB. We present the crystal structures of RRM2 in complex with PRI3 and PRI4 from Raver1, which—along with structure-based mutagenesis—reveal the molecular basis of their differential binding. High-affinity binding by Raver1 PRI3 involves shape-matched apolar contacts complemented by specific hydrogen bonds, a new variant of an established mode of peptide-RRM interaction. Our results refine the sequence of the PRI motif and place important structural constraints on functional models of PTB-Raver1 interactions. Our analysis indicates that the observed Raver1-PTB interaction is a general mode of binding that applies to Raver1 complexes with PTB paralogues such as nPTB and to complexes of Raver2 with PTB.
► First crystal structures of PTB reveals how it binds Raver1 via PRI motifs ► Observed mode of binding is general for PRIs and PTB paralogues ► Results place constraints on models of splicing repression by PTB-Raver1 complexes
Toponyms are a complex system, the semantic and structural features of which reflect the cultural and historical peculiarities of the nation. The toponyms of Norfolk Island stand out from other ...toponyms of the English language due to the isolated geographical location of the island and its violent history. This article discusses in detail the extralinguistic factors that determine the semantic features of geographical names of Norfolk Island. The historical factors that influenced the creation of a significant number of place names include the fact that the settlement of Norfolk Island was founded as a British penal colony. Other factors include political and economic dependence on the UK, and later on Australia. It is noted that the most important among such factors is the motivation of the residents who inhabited Norfolk Island after its discovery by Captain J. Cook. The historical factors we are considering influence the formation of certain connotations of the toponyms of Norfolk Island and Australia. The article proposes a structural and semantic classification of toponyms of Australia and Oceania. The criteria that served as the basis for describing the classification include the presence of positive or negative stylistic coloring. It is noted that some names change their stylistic coloring. This phenomenon is an example of historical rehabilitation. Among the most common anthropogenic factors affecting the structure of toponyms, we have identified the influence of historical figures on the development of the island and the difficult living conditions of the first settlers. Such factors determine the choice of a toponym and are reflected in the presence or absence of its stylistic coloring.
This article assesses the role of geographical and social factors that influenced the toponyms currently officially fixed on the maps of Australia and Oceania. It is noted that the fundamental reason ...for naming the toponyms of Australia and Oceania is the desire of speakers of different languages to leave a memory of themselves on geographical maps. The names of the largest number of Australian place names were given by the first settlers — navigators and discoverers. A significant number of them are English geographical names. Among the least common extralinguistic factors influencing the formation of toponyms, the names of vital objects by natives stand out. The instability of such toponyms in the language is noted. Such toponyms are mostly descriptive. Due to the wide field for research activities, a unified universal classification of toponyms has not yet been developed. The article analyzes the classifications of toponyms existing in linguistics and proposes its own classification of toponyms based on practical material from the geographical names of Australia and Oceania. The main criteria for highlighting the structural elements of the classification is the presence or absence of word-formation elements, many of which are typical for the sphere of toponymy. A large group is formed by phrases, which the authors of the article subdivide depending on the number of components. Particular attention is paid to the use of the article as part of the toponym, as well as graphic signs. The classification presented by the authors of the article also makes it possible to judge that the toponyms of Australia and Oceania are part of the lexical system of the general literary language.
The specific recognition by proteins of the 5′ and 3′ ends of RNA molecules is an important facet of many cellular processes, including RNA maturation, regulation of translation initiation and ...control of gene expression by degradation and RNA interference. The aim of this review is to survey recent structural analyses of protein binding domains that specifically bind to the extreme 5′ or 3′ termini of RNA. For reasons of space and because their interactions are also governed by catalytic considerations, we have excluded enzymes that modify the 5′ and 3′ extremities of RNA. It is clear that there is enormous structural diversity among the proteins that have evolved to bind to the ends of RNA molecules. Moreover, they commonly exhibit conformational flexibility that appears to be important for binding and regulation of the interaction. This flexibility has sometimes complicated the interpretation of structural results and presents significant challenges for future investigations.
PDF
