Comparison of Open-Source Reverse Vaccinology Programs for Bacterial Vaccine Antigen Discovery

Reverse Vaccinology (RV) is a widely used approach to identify potential vaccine candidates (PVCs) by screening the proteome of a pathogen through computational analyses. Since its first application in Group B meningococcus (MenB) vaccine in early 1990's, several software programs have been developed implementing different flavors of the first RV protocol. However, there has been no comprehensive review to date on these different RV tools. We have compared six of these applications designed for bacterial vaccines (NERVE, Vaxign, VaxiJen, Jenner-predict, Bowman-Heinson, and VacSol) against a set of 11 pathogens for which a curated list of known bacterial protective antigens (BPAs) was available. We present results on: (1) the comparison of criteria and programs used for the selection of PVCs (2) computational runtime and (3) performances in terms of fraction of proteome identified as PVC, fraction and enrichment of BPA identified in the set of PVCs. This review demonstrates that none of the programs was able to recall 100% of the tested set of BPAs and that the output lists of proteins are in poor agreement suggesting in the process of prioritize vaccine candidates not to rely on a single RV tool response. Singularly the best balance in terms of fraction of a proteome predicted as good candidate and recall of BPAs has been observed by the machine-learning approach proposed by Bowman (1) and enhanced by Heinson (2). Even though more performing than the other approaches it shows the disadvantage of limited accessibility to non-experts users and strong dependence between results and a-priori training dataset composition. In conclusion we believe that to significantly enhance the performances of next RV methods further studies should focus on the enhancement of accuracy of the existing protein annotation tools and should leverage on the assets of machine-learning techniques applied to biological datasets expanded also through the incorporation and curation of bacterial proteins characterized by negative experimental results

Complex Loci in Human and Mouse Genomes

Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis–antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis–antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units (TUs), along with 6,141 cis–antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human TUs. In both human and mouse, 25% of TUs resided in cis–antisense pairs, only 17% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40% of all TUs might actually be in cis–antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis–antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes

Incoherence correction strategies in statistical matching

Several economic applications require to consider different data sources and to integrate the information coming from them. This paper focuses on statistical matching, in particular we deal with incoherences. In fact, when logical constraints among the variables are present incoherencies on the probability evaluations can arise. The aim of this paper is to remove such incoherences by using different methods based on distances minimization or least commitment imprecise probabilities extensions. An illustrative example shows peculiarities of the different correction methods. Finally, limited to pseudo distance minimization, we performed a systematic comparison through a simulation study. (c) 2012 Elsevier Inc. All rights reserved

Autoimmune pancreatitis not otherwise specified (NOS): Clinical features and outcomes of the forgotten type

Background: Autoimmune pancreatitis (AIP) is a well-recognized fibroinflammatory disease of the pancreas. Despite the significant number of studies published on AIP type 1 and 2, no studies have been focused on AIP type not otherwise specified (NOS) and therefore very little is known about clinical features and long-term outcomes of these patients. The aim of this study was to investigate clinical and radiological features of AIP type NOS-patients.Methods: Patients classified as AIP type NOS at clinical onset included in our database prospectively maintained since 1995 were evaluated. Epidemiological, clinical data were collected and analyzed.Results: Forty-six patients were included in the study. The clinical onset was mainly characterized by weight loss, jaundice and acute pancreatitis. Eight patients (17.4%) were reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. Seven patients (15.2%) experienced relapse after steroid treatment but only one (2.2%) needed immunosuppressive drugs because of recurrent relapses.Conclusions: AIP type NOS shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. The risk of relapse is low but not irrelevant. (C) 2019 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved

Oncogenic H-Ras up-regulates acid β-hexosaminidase by a mechanism dependent on the autophagy regulator TFEB.

The expression of constitutively active H-RasV12 oncogene has been described to induce proliferative arrest and premature senescence in many cell models. There are a number of studies indicating an association between senescence and lysosomal enzyme alterations, e.g. lysosomal β-galactosidase is the most widely used biomarker to detect senescence in cultured cells and we previously reported that H-RasV12 up-regulates lysosomal glycohydrolases enzymatic activity in human fibroblasts. Here we investigated the molecular mechanisms underlying lysosomal glycohydrolase β-hexosaminidase up-regulation in human fibroblasts expressing the constitutively active H-RasV12. We demonstrated that H-Ras activation increases β-hexosaminidase expression and secretion by a Raf/extracellular signal-regulated protein kinase dependent pathway, through a mechanism that relies on the activity of the transcription factor EB (TFEB). Because of the pivotal role of TFEB in the regulation of lysosomal system biogenesis and function, our results suggest that this could be a general mechanism to enhance lysosomal enzymes activity during oncogene-induced senescence

HEXA and HEXB gene expression analysis by qRT-PCR.

<p>About 10-Ras mutants, with respect to those infected with the vector alone as control, is represented. The value is expressed as Relative Quantity (RQ). Analysis was repeated three times. The mean±s.d. of a representative experiment is reported. ** P<0.01 vs empty vector.</p

"Alter Elios". The 2016 MNPG International Arch Competition for the design of a tech port beacon that infuses architecture, technology, ecology and modern living. Sapphire Coast, Australia. MNPG LTD.

Designed by two architects and ten students, the natural setting is what this is really all about. And then there is a new approach to magnetic levitation light projection from inside the building. A zero cost plan for the transference of the beacon, which acts as the nucleus for further scientific and experimental thought. Inventing not just a new way to perceive energy, but also the display of the possibility of architecture as more than a field of design, but that of an arena that can infuse other disciplines to create the next breakthrough. Il progetto proposto, condotto all’interno della ricerca sviluppata nell’insegnamento di Architettura Tecnica 2 presso il Corso di Laurea in Ingegneria Edile-Architettura dell’Università di Pisa, tenuto dal sottoscritto G. Santi, consiste nella sperimentazione edilizia di un modello di faro sostenibile, sia come impatto ambientale che come consumo delle risorse energetiche, a lievitazione magnetica