Transcriptome structure variability in Saccharomyces cerevisiae strains determined with a newly developed assembly software

RNA-seq studies have an important role for both large-scale analysis of gene expression and for transcriptome reconstruction. However, the lack of software specifically developed for the analysis of the transcriptome structure in lower eukaryotes, has so far limited the comparative studies among different species and strains.Results: In order to fill this gap, an innovative software called ORA (Overlapped Reads Assembler) was developed. This software allows a simple and reliable analysis of the transcriptome structure in organisms with a low number of introns. It can also determine the size and the position of the untranslated regions (UTR) and of polycistronic transcripts. As a case study, we analyzed the transcriptional landscape of six S. cerevisiae strains in two different key steps of the fermentation process. This comparative analysis revealed differences in the UTR regions of transcripts. By extending the transcriptome analysis to yeast species belonging to the Saccharomyces genus, it was possible to examine the conservation level of unknown non-coding RNAs and their putative functional role.Conclusions: By comparing the results obtained using ORA with previous studies and with the transcriptome structure determined with other software, it was proven that ORA has a remarkable reliability. The results obtained from the training set made it possible to detect the presence of transcripts with variable UTRs between S. cerevisiae strains. Finally, we propose a regulatory role for some non-coding transcripts conserved within the Saccharomyces genus and localized in the antisense strand to genes involved in meiosis and cell wall biosynthesis

The architecture of the Rag GTPase signaling network

The evolutionarily conserved target of rapamycin complex 1 (TORC1) couples an array of intra- and extracellular stimuli to cell growth, proliferation and metabolism, and its deregulation is associated with various human pathologies such as immunodeficiency, epilepsy, and cancer. Among the diverse stimuli impinging on TORC1, amino acids represent essential input signals, but how they control TORC1 has long remained a mystery. The recent discovery of the Rag GTPases, which assemble as heterodimeric complexes on vacuolar/lysosomal membranes, as central elements of an amino acid signaling network upstream of TORC1 in yeast, flies, and mammalian cells represented a breakthrough in this field. Here, we review the architecture of the Rag GTPase signaling network with a special focus on structural aspects of the Rag GTPases and their regulators in yeast and highlight both the evolutionary conservation and divergence of the mechanisms that control Rag GTPases

Atrial Fibrillation Recurrence and Peri-Procedural Complication Rates in nMARQ vs. Conventional Ablation Techniques: A Systematic Review and Meta-Analysis

Background and Objectives: Atrial fibrillation is a common abnormal cardiac rhythm caused by disorganized electrical impulses. AF which is refractory to antiarrhythmic management is often treated with catheter ablation. Recently a novel ablation system (nMARQ) was introduced for PV isolation. However, there has not been a systematic review of its efficacy or safety compared to traditional ablation techniques. Therefore, we conducted this meta-analysis on the nMARQ ablation system. Methods: PubMed and EMBASE were searched up until 1st of September 2017 for articles on nMARQ. A total of 136 studies were found, and after screening, 12 studies were included in this meta-analysis. Results: Our meta-analysis shows that the use of nMARQ was associated with higher odds of AF non-recurrence (n = 1123, odds ratio = 6.79, 95% confidence interval 4.01–11.50; P 0.05). There were four reported mortalities in the nMARQ group compared to none in the conventional ablation group (relative risk: 1.58; 95% CI: 0.09–29.24; P > 0.05). Conclusions: AF recurrence rates are comparable between nMARQ and conventional ablation techniques. Although general complication rates are similar for both groups, the higher mortality with nMARQ suggests that conventional techniques should be used for resistant AF until improved safety profiles of nMARQ can be demonstrated

Combining HLA-DRB1-DQB1 and <i>Mycobacterium avium subspecies paratubercolosis</i> (MAP) antibodies in Sardinian multiple sclerosis patients: associated or independent risk factors?

Background: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. Methods: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1-DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. Results: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). Conclusions: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP

The I-BAR protein Ivy1 is an effector of the Rab7 GTPase Ypt7 involved in vacuole membrane homeostasis

Membrane fusion at the vacuole depends on a conserved machinery that includes SNAREs, the Rab7 homolog Ypt7 and its effector HOPS. Here, we demonstrate that Ypt7 has an unexpected additional function by controlling membrane homeostasis and nutrient-dependent signaling on the vacuole surface. We show that Ivy1, the yeast homolog of mammalian missing-in-metastasis (MIM), is a vacuolar effector of Ypt7-GTP and interacts with the EGO/ragulator complex, an activator of the target of rapamycin kinase complex 1 (TORC1) on vacuoles. Loss of Ivy1 does not affect EGO vacuolar localization and function. In combination with the deletion of individual subunits of the V-ATPase, however, we observed reduced TORC1 activity and massive enlargement of the vacuole surface. Consistent with this, Ivy1 localizes to invaginations at the vacuole surface and on liposomes in a phosphoinositide- and Ypt7-GTP-controlled manner, which suggests a role in microautophagy. Our data, thus, reveal that Ivy1 is a novel regulator of vacuole membrane homeostasis with connections to TORC1 signaling

Creating with Anger: Contemplating Vendetta. An Analysis of Anger in Italian and Spanish Women Writers of the Early Modern Era

In the vast gamut of human emotions, anger is one of the most complex, provocative, and enduring. From Greek philosophers working in antiquity to today’s most recent theories on emotions, most scholars agree that anger has a multifaceted nature. This near universal agreement across the barriers of time and geography stems from the following facts: in order to exist, anger involves the participation of other emotions; anger does not have an opposite; anger leads an individual to engage in an act of self-analysis and in an evaluation of other individuals; and, finally, anger inspires action to right a wrong that has been perceived as injustice. This sense of perceived injustice is what leads to the creation of vendetta for the women writers I analyze in my dissertation. They achieve their vendetta through their act of writing, as they themselves often assert. Like all vendetta, theirs grows from a sense of constant injustice and systematic subjugation. Unlike traditional vendetta however, these women, because of their status within society as women, could not take direct action to right these perceived wrongs. Their need for revenge therefore had to be fulfilled entirely through the written word, with their poems, plays, novels and short stories serving as the vehicles through which their anger could be delivered. This dissertation investigates the connection between anger and the act of writing. Specifically, it attempts to explore how anger served as a vital catalyst that prompted early modern women writers to engage in the act of writing

Review on significance debate

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Journey Map Guidelines

The Journey Map tool provides a graphic and structured visualization about all the factors that can influence the User Experience, directly constructed from the user's perspective. Basically it is a schematization of the user path, crossing different service touchpoints1, as the user starts to use a service until some goals are achieved. Into the user journey also the emotional aspects that affect the quality of the user experience and its level of satisfaction are considered. Graphically the Journey Map is a matrix composed by columns and rows. The columns, from left to right, show all the steps that form the user journey, a timeline that provides a sequential and chronological disposition of each stage for further details. In horizontal are displayed several rows, representing the research areas of interests (eg. Where the action takes place, the touchpoints involved in the context considered, the unexpressed needs of the user, his/her level of confidence to technology, etc…). All these elements together usually have different impacts along the journey steps; in this way the Journey Map can better track them and represent and identify these changes that interact with the user experience. In this specific occasion, the Journey Map will be used with the purpose to extrapolate qualitative and quantitative data about the User Experience of children with T1DM aged 8-10 in using the first prototype of the MyPAL app , as a graphical facilitator for an interactive discussion. In order to obtain reliable proofs of children’s experience, the Journey Map activity will be exploited with a co-creation methodological approach, where interactivity is essential and represents a great tool to collect insights in a playful and stimulating environment. In fact, this activity will involve directly our users (children) by mapping his/her experience and telling indirectly to us his/her feedbacks and expectations. This tool allows both individual and choral sessions and participatory techniques between deductive and analytical thinking. In this context, the Journey Map will be used as an individual explorative tool of investigation (one child per time)