ANALISI DI PROCESSI DI DISPERSIONE LAGRANGIANO ED EULERIANO DI PARTICELLE IN FLUSSI TURBOLENTI

2001/2002XV Ciclo1973Versione digitalizzata della tesi di dottorato cartacea

Derivation of HLA Types from Shotgun Sequence Datasets

The human leukocyte antigen (HLA) is key to many aspects of human physiology and medicine. All current sequence-based HLA typing methodologies are targeted approaches requiring the amplification of specific HLA gene segments. Whole genome, exome and transcriptome shotgun sequencing can generate prodigious data but due to the complexity of HLA loci these data have not been immediately informative regarding HLA genotype. We describe HLAminer, a computational method for identifying HLA alleles directly from shotgun sequence datasets (http://www.bcgsc.ca/platform/bioinfo/software/hlaminer webcite). This approach circumvents the additional time and cost of generating HLA-specific data and capitalizes on the increasing accessibility and affordability of massively parallel sequencing

Non-Coding-Regulatory Regions Of Human Brain Genes Delineated By Bacterial Artificial Chromosome Knock-In Mice

Background The next big challenge in human genetics is understanding the 98% of the genome that comprises non-coding DNA. Hidden in this DNA are sequences critical for gene regulation, and new experimental strategies are needed to understand the functional role of gene-regulation sequences in health and disease. In this study, we build upon our HuGX (\u27high-throughput human genes on the X chromosome’) strategy to expand our understanding of human gene regulation in vivo. Results In all, ten human genes known to express in therapeutically important brain regions were chosen for study. For eight of these genes, human bacterial artificial chromosome clones were identified, retrofitted with a reporter, knocked single-copy into the Hprt locus in mouse embryonic stem cells, and mouse strains derived. Five of these human genes expressed in mouse, and all expressed in the adult brain region for which they were chosen. This defined the boundaries of the genomic DNA sufficient for brain expression, and refined our knowledge regarding the complexity of gene regulation. We also characterized for the first time the expression of human MAOA and NR2F2, two genes for which the mouse homologs have been extensively studied in the central nervous system (CNS), and AMOTL1 and NOV, for which roles in CNS have been unclear. Conclusions We have demonstrated the use of the HuGX strategy to functionally delineate non-coding-regulatory regions of therapeutically important human brain genes. Our results also show that a careful investigation, using publicly available resources and bioinformatics, can lead to accurate predictions of gene expression

Towards a scientific interpretation of the terroir concept: plasticity of the grape berry metabolome

BACKGROUND: The definition of the terroir concept is one of the most debated issues in oenology and viticulture. The dynamic interaction among diverse factors including the environment, the grapevine plant and the imposed viticultural techniques means that the wine produced in a given terroir is unique. However, there is an increasing interest to define and quantify the contribution of individual factors to a specific terroir objectively. Here, we characterized the metabolome and transcriptome of berries from a single clone of the Corvina variety cultivated in seven different vineyards, located in three macrozones, over a 3-year trial period. RESULTS: To overcome the anticipated strong vintage effect, we developed statistical tools that allowed us to identify distinct terroir signatures in the metabolic composition of berries from each macrozone, and from different vineyards within each macrozone. We also identified non-volatile and volatile components of the metabolome which are more plastic and therefore respond differently to terroir diversity. We observed some relationships between the plasticity of the metabolome and transcriptome, allowing a multifaceted scientific interpretation of the terroir concept. CONCLUSIONS: Our experiments with a single Corvina clone in different vineyards have revealed the existence of a clear terroir-specific effect on the transcriptome and metabolome which persists over several vintages and allows each vineyard to be characterized by the unique profile of specific metabolites.Andrea Anesi, Matteo Stocchero, Silvia Dal Santo, Mauro Commisso, Sara Zenoni, Stefania Ceoldo, Giovanni Battista Tornielli, Tracey E. Siebert, Markus Herderich, Mario Pezzotti and Flavia Guzz

Christina Komi Kallinikos, Digressions sur la métropole. Roberto Arlt, Juan Carlos Onetti, autour de Buenos Aires

Mauro Castellarin Teresita. Christina Komi Kallinikos, Digressions sur la métropole. Roberto Arlt, Juan Carlos Onetti, autour de Buenos Aires. In: Caravelle, n°88, 2007. Chanter le bandit. Ballades et complaintes d'Amérique latine. pp. 347-348

The identification and sequence analysis of new regenerating (Reg) gene members in rats and hamsters /

The regenerating (Reg) genes have been associated with tissue repair and have been directly implicated in pancreatic beta-cell regeneration. Peptide administration of INGAP, a hamster Reg3, can reverse hyperglycaemia in rodents and stimulate new beta-cell growth in human epithelial cultures.New Reg genes in rats and hamsters were identified using homology reverse transcription polymerase chain reaction (RT-PCR) with degenerate Reg3 primers and selected products were further sequenced using rapid amplification of cDNA ends (RACE). This method resulted in no novel rat Regs, although a putative rat INGAP with 65% identity to the mouse INGAP protein was discovered by a BLAST homology search of the rat genome. The putative rat INGAP protein was shorter than both mouse and hamster INGAP and a mRNA transcript could not be amplified by PCR. It is thus concluded that this rat homologue of INGAP is a pseudogene.Homology RT-PCR did, however, result in the discovery of a new hamster Reg3 gene of 765 nucleotides (nt) that encodes a 174 amino acid (aa) protein. This protein sequence was identified as a novel hamster Reg3gamma with 78% and 75% identity to the rat Reg3gamma and mouse Reg3gamma protein, respectively. The hamster Reg1 gene coding region was fully sequenced from a reported partial sequence using RACE to yield a 756 nt transcript that encodes a deduced 173 aa protein. This protein was identified as hamster Reg2, rather than Reg1 as was initially reported, with an 81% identity to mouse Reg2.Mice and hamsters are the only species known to carry either of the functional INGAP or Reg2 genes. It remains to be determined whether these genes bestow mice and hamsters with special regenerative abilities in the pancreas

Genomic Analysis of Infectious Agents, Mutations and Immune Cells Associated with Cancer

Cancer is primarily a genetic disease that can be actuated by carcinogens, such as infectious agents, and attenuated by the body’s own immune response. This thesis is a multifaceted study of cancer genomics, metagenomics and immunogenomics. In our metagenomic study of colorectal cancer, we used RNA-seq followed by host sequence subtractions and found marked over-representation of Fusobacterium nucleatum sequences in tumours. We verified the overabundance of Fusobacterium sequences by quantitative PCR analysis from a total of 99 subjects, and we observed a positive association with lymph node metastasis. In our cancer genomics study of ovarian cancer, the clonal structure and evolution of tumours were profiled by whole exome sequencing of serial tumour samples in three patients. Tumours from all three patients harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight novel pathways that are mutated in ovarian cancer and shows that recurrent disease arises from multiple clones present in the primary tumour. In our immunogenomics study of ovarian cancer immunity, T and B cell clonality was surveyed by high-throughput sequencing of their antigen receptor. First, we characterized the errors in receptor sequencing and developed filtering strategies to reduce the false discovery rate. Errors were discovered in the form of substitutions and chimeras and additionally, sequence contamination and biases were observed between samples. We applied our error filtering model to survey the T and B cells in serial ovarian tumour samples and found that the tumour-associated immune repertoires diverged over time. Furthermore, we discovered that tumour-responsive lymphocytes can be recognized by in vitro expansions of T cells and by discovering B cells with highly mutated antigen receptor sequences. In conclusion, genomics approaches were employed first to study colorectal cancer, which revealed a tumour-associated bacteria. Secondly, genomics was used to study ovarian cancer tumours, which showed tumour clonal evolution, alterations in novel biological pathways and a dynamic adaptive immune response

Christina Komi Kallinikos, Digressions sur la métropole. Roberto Arlt, Juan Carlos Onetti, autour de Buenos Aires

Mauro Castellarin Teresita. Christina Komi Kallinikos, Digressions sur la métropole. Roberto Arlt, Juan Carlos Onetti, autour de Buenos Aires. In: Caravelle, n°88, 2007. Chanter le bandit. Ballades et complaintes d'Amérique latine. pp. 347-348

Vanadium on TiO2(110): adsorption site and sub-surface migration

The initial stages of the growth of vanadium overlayers on TiO2(1 1 0) at room temperature have been investigated with scanning tunneling microscopy. At very low coverages both individual vanadium adatoms and small vanadium clusters have been imaged with good resolution. The V adatoms adsorb preferentially on the so-called \u201cupper threefold hollow\u201d sites, as revealed by atomically resolved STM images: they are thus bonded to two bridging oxygen atoms and one threefold coordinated basal oxygen atom. At higher coverages the vanadium adlayers grow in form of poorly ordered three-dimensional islands. The number of V clusters at low coverages decreases by gentle annealing or with time even at room temperature. This kinetic effect has been interpreted in terms of sub-surface migration of V adatom