Genome-Wide Transcription Factor Binding in Leaves from C3 and C4 Grasses.

The majority of plants use C3 photosynthesis, but over 60 independent lineages of angiosperms have evolved the C4 pathway. In most C4 species, photosynthesis gene expression is compartmented between mesophyll and bundle-sheath cells. We performed DNaseI sequencing to identify genome-wide profiles of transcription factor binding in leaves of the C4 grasses Zea mays, Sorghum bicolor, and Setaria italica as well as C3 Brachypodium distachyon In C4 species, while bundle-sheath strands and whole leaves shared similarity in the broad regions of DNA accessible to transcription factors, the short sequences bound varied. Transcription factor binding was prevalent in gene bodies as well as promoters, and many of these sites could represent duons that influence gene regulation in addition to amino acid sequence. Although globally there was little correlation between any individual DNaseI footprint and cell-specific gene expression, within individual species transcription factor binding to the same motifs in multiple genes provided evidence for shared mechanisms governing C4 photosynthesis gene expression. Furthermore, interspecific comparisons identified a small number of highly conserved transcription factor binding sites associated with leaves from species that diverged around 60 million years ago. These data therefore provide insight into the architecture associated with C4 photosynthesis gene expression in particular and characteristics of transcription factor binding in cereal crops in general.BBSRC ERC CONACy

Dual codon usage in germline variants of prostate cancer genomes

This thesis work builds on the recent discovery by Stergachis and his colleagues, which describes the process the genome uses to write genetic code. This work extends the previous vision in genome research, which states, that codons and regulatory elements work independently. Codons are a triplet of nucleotides that encode amino acids; and regulatory elements are responsible for regulation of the gene expression. However, as discovered by Stergachis and his colleagues in 2013, around 15% of codons within 85% of human genes are occupied by transcription factor binding sites (TFBSs) (see Stergachis et al., 2013). Consequently, these type of codons encode two types of information. They were labelled ‘duons’ and described as highly conserved entities with low levels of genetic variation. Overall, regulatory proteins bind to the same stretches of As, Cs, Ts and Gs and influence the process of gene expression, and also specify the amino acids of the protein that is made. This work applies Stergachis findings of ‘duons’ to analyse a variant data. An interesting fact of Stregachis work is that a mutation may occur without affecting a protein. This happens due to the ability of some amino acids to be encoded by a multiple combination of nucleotides (codons). Obviously, if an alteration occurs in the codon, which still encodes for the same amino acid, the functionality of the produced protein remains the same. In this case, transcription factors (TFs) bind to an altered (mutated) region, implicating a change of activity of TFs due to the fact, that the genetic pattern has been modified. As a result, wrong instructions are given to the expression of a gene, as Stergachis and his colleagues discovered (Stergachis et al., 2013). His discoveries led to the finding, that 13% of the deoxyribonucleic acid (DNA) mutations leading to a disease development are located in ‘duons’. Thus it is important to investigate disease-associated variants within ‘duons’ that increase the risk of disrupting both regulatory and protein-structural function. A finding by Kircher in 2014 - the application of a method that aimed at the interpretation of pathogenicity of human genetic variations – lead to a new method. This method developed by Kircher in 2014 is called the combined annotation dependent depletion (CADD) tool. It uses a single C score to annotate a variant as pathogenic. In contrast to other methods the CADD takes into consideration regulatory elements, thus the CADD tool was selected for this project work. These two research findings are used in the thesis work. The goal of this work was therefore the extraction and recording of variants from provided data, which have potential for ‘duons’. To achieve this goal, the thesis applied the techniques of the C score, the position weight matrix (PWMs), and p value estimation. The aim of this study was to apply the PWMs framework, and C score on provided data, in order to extract and record those variants from the data that have potential for’ duons’. Thus they could be putative causes of a disease development. First of all, the provided data was filtered to identify pathogenic variants based on C score. Afterwards, the above presented concept was used to compute the TFBSs for original reference and mutated nucleotide sequences, where the maximum and minimum difference between these scores were found and used as a criteria for computing p value. Eventually, the resulting set of genes was submitted to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and analysed for correlation of mutations to the type of a disease. The outcome of the KEGG database analysis represents the main pathways where resulting genes are involved into metabolic, cancer, and neuroactive ligand-receptor interaction pathways

Bounded Rationality and Strategic Complementarity in a Macroeconomic Model: Policy Effects, Persistence and Multipliers

Motivated by recent developments in the bounded rationality and strategic complementarity literatures, we examine an intentionally simple and stylized aggregative economic model, when the assumptions of fully rational expectations and no strategic interactions are relaxed. We show that small deviations from rational expectations, taken alone, lead only to small deviations from classical policy- ineffectiveness, but that the situation can change dramatically when strategic complementarity is introduced. Strategic complementarity magnifies the effects of even small departures from rational expectations, producing equilibria with policy effectiveness, output persistence and multiplier effects.

AN ALTERNATIVE APPROACH OF THE E-NOSE TRAINING PHASE IN ODOUR IMPACT ASSESSMENT

peer reviewe

Multi-scale drivers of community diversity and composition across tidal heights: an example on temperate seaweed communities

International audienc

GANAB and PKD1 Variations in a 12 Years Old Female Patient With Early Onset of Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) typically results from a mutation in the PKD1 and PKD2 genes, which code for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Mutations in these genes promote renal cystic dysplasia and are a significant cause of End-Stage Kidney Disease (ESKD). Polycystic kidney disease-3 (PKD3), another form of ADPKD, is caused by mutations in glucosidase II alpha subunit (GANAB) gene and present in mid- and late adulthood. We report a description of an ADPKD case in a 12-year-old female presented bilateral renal cysts in adolescence. Two mutations in two genes PKD1 and GANAB were identified by targeted capture and next-generation sequencing (NGS) on an Illumina sequencing system. The identified PKD1 mutation p.Pro61Leu: c.182C > T (CCC > CTC) a missense type of uncertain clinical significance. However, the identified PKD1 mutation can alter transcription factors motifs and consequently disturb the transcription process. The second mutation identified in GANAB locus, p.Arg61Ter: c.181C > T, a nonsense type, CGA > TGA. The mutation is unreported pathogenic variant can cause loss of the glucosidase II alpha subunit normal protein function. Both the patient father and paternal grandmother had a history of ADPKD but never were tested. This case is the first case of combine presentation on PKD1 and PKD3 in a pediatric patient with nephrolithiasis

Comparison of several inflow control devices for flight simulation of fan tone noise using a JT15D-1 engine

To enable accurate simulation of in-flight fan tone noise during ground static tests, four devices intended to reduce inflow disturbances and turbulence were tested with a JT15D-1 turbofan engine. These inflow control devices (ICD's) consisted of honeycomb/screen structures mounted over the engine inlet. The ICD's ranged from 1.6 to 4 fan diameters in size, and differed in shape and fabrication method. All the ICD's significantly reduced the BPF tone in the far-field directivity patterns, but the smallest ICD's apparently introduced propagating modes which could be recognized by additional lobes in the speeds; at supersonic fan tip speed the smallest ICD's had some measurable loss, but the largest had no loss. Data from a typical transducer show that the unsteady inflow distortion modes (turbulence) were eliminated or significantly reduced when either of the ICD's was installed. However, some steady inflow distortion modes remained