Transfer RNA-derived fragments: Origins, processing, and functions

Deep sequencing approaches have revealed multiple types of small RNAs with known and unknown functions. In this review we focus on a recently identified group of small RNAs that are derived from transfer RNAs (tRNAs), tRNA fragments (tRFs). We review the mechanism of their processing and their functions in mammalian cells, and highlight points of possible cross-talk between tRFs and the canonical small RNA pathway characterized by small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). We also propose a nomenclature that is based on their processing characteristics. © 2011 John Wiley & Sons, Ltd

ChtVis-Tomato, a genetic reporter for in vivo visualization of chitin deposition in Drosophila

Chitin is a polymer of N-acetylglucosamine that is abundant and widely found in the biological world. It is an important constituent of the cuticular exoskeleton that plays a key role in the insect life cycle. To date, the study of chitin deposition during cuticle formation has been limited by the lack of a method to detect it in living organisms. To overcome this limitation, we have developed ChtVis-Tomato, an in vivo reporter for chitin in Drosophila. ChtVis-Tomato encodes a fusion protein that contains an apical secretion signal, a chitin-binding domain (CBD), a fluorescent protein and a cleavage site to release it from the plasma membrane. The chitin reporter allowed us to study chitin deposition in time lapse experiments and by using it we have identified unexpected deposits of chitin fibers in Drosophila pupae. ChtVis-Tomato should facilitate future studies on chitin in Drosophila and other insects

A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis

Funding: The study was supported by the European Cooperation in Science and Technology, who provided funds for publication. KMG is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre and by the European Union's Seventh Framework Programme (FP7/2007-2013), projects Early Nutrition and ODIN under grant agreement numbers 289346 and 613977.Peer reviewedPublisher PD

Pasture landscape durability in the Beskid Mountains (Western Carpathians, Poland)

The agricultural abandonment and reforestation taking place over the last few decades in the Carpathians has led to accelerated transformation of pasture landscape. The trajectories of pasture landscape changes, the factors threatening and supporting the pastures’ traditional use have been established on the basis of archival and contemporary cartographic materials, historical scientific works and archival photographs. An attempt has also been made to assess pasture landscape durability. The major part of the former pasture landscape has evolved into forest or settlement landscapes. The pasture landscape durability will only be possible if the operations supporting the traditional mountain grazing are continued

Landscape effects of conflicts in space management. A historical approach based on the Silesian and Żywiec Beskids (West Carpathians, Poland)

A land use regime undergoes much change over time depending on the growth in the importance of various interest groups. Spatial conflicts repeatedly accompany this growth. The aim of the article is to determine the relationship between spatial conflicts and landscape changes. On the basis of the Silesian and Żywiec Beskid mountain ranges, it has been proven that conflicts arising between mountain grazing, agriculture, forest management, contemporary building and tourism development have significant impacts on the landscape. To this end, archive and contemporary cartographic materials, historical scientific works and archive photographs were used. The conflicts between mountain grazing and other types of human activity in the study area were analysed. Subsequently, their influence on the landscape was determined. As a result of the study, the primary sources of conflicts were indicated and correlated with historical periods and the predominant landscape use regime. The imprints of historical space conflicts and the rivalry for land use between different entities for their own purposes are still visible in the landscape. The historical conflicts have arisen between entities seeking ways to use different environmental resources occurring in the same area. Contemporary conflicts arise between entities seeking ways to use environmental resources (tourism) and between entities conscious of the hazards of the landscape sustainability resulting from the utilization of environmental resources (nature conservation services). Both historical and contemporary conflicts usually have a violent course resulting from the lack, or deficiency of, legislation concerning land management

Mountain Meadows and Glades of the Carpathians - Type or Element of Landscape? The Problem of Delimitation and Typology of Mountain Pasture Landscapes

The typologies of landscapes of individual states that have ratified the European Landscape Convention do not include mountain pasture landscapes. Pasture landscapes in the Carpathians are preserved in a relatively good condition, although their spatial extent has considerably shrunk over the last few decades. The article demonstrates that mountain meadows and glades in the Carpathians meet all the conditions that allow them to be classified as a type of landscape, and thus they should be included in national typologies of landscapes. Firstly, they constitute a set of natural (non-forest vegetation) and anthropogenic (traditional shepherding buildings) objects. Secondly, they are a dynamic system in which natural, social and economic processes take place. They are also a source of stimuli, affecting different human senses and values and are a system that provides various real and potential services. The inclusion of mountain pasture landscapes in national typologies may provide a stronger basis for their protection

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

Structural, mechanistic and functional characterization of glycoside hydrolases of family GH99

Glycosylation is a very common post-translational modification and the glycans can be attached to oxygen (O-linked), nitrogen (N-linked) or carbon (C-linked). N-linked glycosylation has implications for protein folding and is also essential in viral infectivity and cell-cell signalling. Endo-α-1,2-mannosidase from family GH99 is a unique enzyme within the N-glycosylation pathway as it is the only one which does not cleave the terminal sugar from the reducing end of the glycan, but instead releases an α-Glc-1,3-Man disaccharide, with overall retention of stereochemistry at the anomeric carbon. Previously it was proposed that GH99 endo-acting mannosidases and mannanases proceed through a neighbouring group participation mechanism with a 1,2-anhydrosugar as a reaction intermediate. This Thesis contains evidence supporting this hypothesis. Chapter 2 presents structures of the bacterial GH99 with its substrate, with mimics of the reaction intermediate and with the products of the reaction. Kinetic and structural data on various intermediate mimics show that the compound whose structure is the closest to the intermediate is turned over by the enzyme. In Chapter 3, analysis of different designs of GH99 inhibitors and their conformation on-enzyme is presented. Chapter 4 presents purification and solution of the crystal structure of the catalytic domain of the human endomannosidase (MANEA). Multiple crystal forms were obtained, which made it possible to look at the conformation of a feature present in the eukaryotic but not bacterial GH99: a loop spanning residues 191–201. This loop was disordered when no ligand was present in the –2/–1 sites, and ordered when these sites were occupied. Chapter 5 explores attempts at producing MANEAL, a paralog of MANEA which is found in bony vertebrates. The Thesis concludes with an analysis of the phylogeny of endomannosidase genes and perspectives for future research: studies of endomannosidase in mammalian model organisms are needed to understand its significance

Use of bauxite residue (red mud) as a low cost sorbent for sulfide removal in polluted water remediation

Sulfide is an important pollutant in aqueous systems. Sulfide removal from polluted waters is required prior to discharge. Red mud RM) is a solid waste of bauxite processing that is rich in reactive iron oxides and consequently has the potential to be used to remove sulfide from aqueous systems. A series of experiments were undertaken using raw and sintered RM to remove sulfide from waters. RM was highly efficient at sulfide removal (average 75% sulfide removal at initial concentration of ~5 mg L-1, with 500 mg L-1 RM addition) due to both physical adsorption (high specific area) and chemical reaction (with amorphous Fe). Sintered RM, which has a lower surface area and lower mineral reactivity, was much less efficient at removing sulfide (~20% removal under equivalent experimental conditions). Furthermore, concomitant metal release from raw RM was lower than for sintered RM during the sulfide removal process. The results showed that raw RM is a potentially suitable material for sulfide removal from polluted waters and consequently could be used as a low cost alternative treatment in certain engineering applications

Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut

The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta) genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-L-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins