Internal translational initiation in the mRNA from the Neurospora crassa albino-3 gene.

The "ribosome scanning model" for translational initiation predicts that eukaryotic mRNAs should, as a rule, be monocistronic. However, cases have recently been described of eukaryotic mRNAs producing more than one protein through alternative translational initiation at several different AUG codons. The present work reports the occurrence of multiple translational start sites on the mRNA of the Neurospora crassa gene albino-3 (al-3), encoding the carotenoid biosynthetic enzyme geranylgeranyl-pyrophosphate synthase. This was revealed by the molecular analysis of an al-3 mutant carrying a deletion within the coding sequence, which was expected to prevent the synthesis of a functional geranylgeranyl-pyrophosphate synthase because of ribosome frameshifting and premature translational termination. However, the mutants could maintain appreciable geranylgeranyl-pyrophosphate synthase activity through a mechanism operating at the translational level, whereby a fraction of ribosomes initiated protein synthesis from either of two internal in-frame AUG codons located downstream of the deletion, thus producing a shortened but still active version of the geranylgeranyl-pyrophosphate synthase. The results presented indicate that the internal AUG codons are recognized mainly or solely by direct ribosome binding rather than by "leaky scanning" from the 5' end of the mRNA

Finding Exogenous Variables in Data with Many More Variables than Observations

Many statistical methods have been proposed to estimate causal models in classical situations with fewer variables than observations (p<n, p: the number of variables and n: the number of observations). However, modern datasets including gene expression data need high-dimensional causal modeling in challenging situations with orders of magnitude more variables than observations (p>>n). In this paper, we propose a method to find exogenous variables in a linear non-Gaussian causal model, which requires much smaller sample sizes than conventional methods and works even when p>>n. The key idea is to identify which variables are exogenous based on non-Gaussianity instead of estimating the entire structure of the model. Exogenous variables work as triggers that activate a causal chain in the model, and their identification leads to more efficient experimental designs and better understanding of the causal mechanism. We present experiments with artificial data and real-world gene expression data to evaluate the method.Comment: A revised version of this was published in Proc. ICANN201

Emergency Department as an epidemiological observatory of Human Mobility: the experience of the Moroccan population

We conducted a retrospective study of the accesses to the Emergency Department registered from January 2000 to December 2014 in 5 major hospitals in the Metropolitan Area of Rome. We extrapolated data relating to patients of Moroccan origin from about 5 million total accesses, so we compared with Italians data which, in the same period, came to ED. The Moroccan population is distinguished by a larger number of diagnoses belonging to the ICD-9 code of Infectious Diseases and, more precisely, to Respiratory Infectious Diseases. There are also no differences in the assignment of such diagnoses to Moroccans with Italian citizenship, and this led to think that this could play an important role in the use of the ED and moreover that enrollment to the National Health Service may reduce its inappropriate use. Regarding to Degenerative Disorders, the result of our analysis is quite emblematic, showing that the accesses to the ED is due to Cardiovascular Diseases: 6.33% of Italians' accesses against 1.81% of Moroccans and 2.36% of Moroccans with Italian citizenship. The main explanation for this difference is, obviously, due to the age of the population: about 60% of Moroccans who accessed to ED was less than 40 years old. It is interesting how, in the field of ​​Cardiovascular Diseases, Moroccans have a lower percentage of diagnosis compared to Italians for acute diseases and a greater percentage of diagnoses for chronic diseases, suggesting once again that accesses to ED for migrants often is due to the inability to use the general services of the National Health Service. In conclusion, from the point of view of the Emergency Department, Migration Medicine still has Infectious Diseases as the main reason for access. Degenerative Disorders remain a prerogative of the Italians, but we could certainly assume that the Moroccan population would develop at some point with the aging

ProTISA: a comprehensive resource for translation initiation site annotation in prokaryotic genomes

Correct annotation of translation initiation site (TIS) is essential for both experiments and bioinformatics studies of prokaryotic translation initiation mechanism as well as understanding of gene regulation and gene structure. Here we describe a comprehensive database ProTISA, which collects TIS confirmed through a variety of available evidences for prokaryotic genomes, including Swiss-Prot experiments record, literature, conserved domain hits and sequence alignment between orthologous genes. Moreover, by combining the predictions from our recently developed TIS post-processor, ProTISA provides a refined annotation for the public database RefSeq. Furthermore, the database annotates the potential regulatory signals associated with translation initiation at the TIS upstream region. As of July 2007, ProTISA includes 440 microbial genomes with more than 390 000 confirmed TISs. The database is available at http://mech.ctb.pku.edu.cn/protis

Artificial Sequences and Complexity Measures

In this paper we exploit concepts of information theory to address the fundamental problem of identifying and defining the most suitable tools to extract, in a automatic and agnostic way, information from a generic string of characters. We introduce in particular a class of methods which use in a crucial way data compression techniques in order to define a measure of remoteness and distance between pairs of sequences of characters (e.g. texts) based on their relative information content. We also discuss in detail how specific features of data compression techniques could be used to introduce the notion of dictionary of a given sequence and of Artificial Text and we show how these new tools can be used for information extraction purposes. We point out the versatility and generality of our method that applies to any kind of corpora of character strings independently of the type of coding behind them. We consider as a case study linguistic motivated problems and we present results for automatic language recognition, authorship attribution and self consistent-classification.Comment: Revised version, with major changes, of previous "Data Compression approach to Information Extraction and Classification" by A. Baronchelli and V. Loreto. 15 pages; 5 figure

Regulation of Translation in Haloarchaea: 5′- and 3′-UTRs Are Essential and Have to Functionally Interact In Vivo

Recently a first genome-wide analysis of translational regulation using prokaryotic species had been performed which revealed that regulation of translational efficiency plays an important role in haloarchaea. In fact, the fractions of genes under differential growth phase-dependent translational control in the two species Halobacterium salinarum and Haloferax volcanii were as high as in eukaryotes. However, nothing is known about the mechanisms of translational regulation in archaea. Therefore, two genes exhibiting opposing directions of regulation were selected to unravel the importance of untranslated regions (UTRs) for differential translational control in vivo

The Translation Factor eIF6 Is a Notch-Dependent Regulator of Cell Migration and Invasion

A growing body of evidence indicates that protein factors controlling translation play an important role in tumorigenesis. The protein known as eIF6 is a ribosome anti-association factor that has been implicated in translational initiation and in ribosome synthesis. Over-expression of eIF6 is observed in many natural tumours, and causes developmental and differentiation defects in certain animal models. Here we show that the transcription of the gene encoding eIF6 is modulated by the receptor Notch-1, a protein involved in embryonic development and cell differentiation, as well as in many neoplasms. Inhibition of Notch-1 signalling by γ-secretase inhibitors slowed down cell-cycle progression and reduced the amount of eIF6 in lymphoblastoid and ovarian cancer cell lines. Cultured ovarian cancer cell lines engineered to stably over-expressing eIF6 did not show significant changes in proliferation rate, but displayed an enhanced motility and invasive capacity. Inhibition of Notch-1 signalling in the cells over-expressing eIF6 was effective in slowing down the cell cycle, but did not reduce cell migration and invasion. On the whole, the results suggest that eIF6 is one of the downstream effectors of Notch-1 in the pathway that controls cell motility and invasiveness

The SPINK gene family and celiac disease susceptibility

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n = 15) and diet-treated patients (n = 31) and controls (n = 16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population