Ribosomal RNA Pseudouridylation: Will Newly Available Methods Finally Define the Contribution of This Modification to Human Ribosome Plasticity?

In human rRNA, at least 104 specific uridine residues are modified to pseudouridine. Many of these pseudouridylation sites are located within functionally important ribosomal domains and can influence ribosomal functional features. Until recently, available methods failed to reliably quantify the level of modification at each specific rRNA site. Therefore, information obtained so far only partially explained the degree of regulation of pseudouridylation in different physiological and pathological conditions. In this focused review, we provide a summary of the methods that are now available for the study of rRNA pseudouridylation, discussing the perspectives that newly developed approaches are offering

Psychometric properties of the Italian Tinnitus Functional Index (TFI)

Diversi questionari sono utilizzati per valutare l\u2019impatto dell\u2019acufene sulla qualit\ue0 della vita. Il Tinnitus Functional Index (TFI) proposto da Meikle et al, nel 2012, ha dimostrato propriet\ue0 eccellenti per misurare la gravit\ue0 e le modificazioni indotte dal trattamento degli acufeni, sia in ambito clinico che di ricerca. Lo scopo di questo studio \ue8 stato valutare le propriet\ue0 psicometriche della versione italiana del TFI, in particolare, l\u2019analisi fattoriale, la consistenza interna, l\u2019affidabilit\ue0 e la validit\ue0. La versione originale inglese del TFI \ue8 stata tradotta in italiano secondo la procedura translation - back translation; 137 partecipanti con acufeni da almeno 3 mesi (39,4% femmine, et\ue0: 18-80 anni, et\ue0 media: 48,26, SD: 14,08), reclutati presso la Tinnitus Clinic di Milano, hanno completato la versione italiana del TFI, il Tinnitus Handicap Inventory, la Beck Depression Inventory - Versione Primary Care e la scala di valutazione numerica per il fastidio. Una parte del campione, 57 pazienti, ha completato la versione italiana del TFI in una seconda visita, dopo 7-14 giorni, prima di ricevere qualsiasi tipo di trattamen- to, per ricavare i dati per la valutazione della riproducibilit\ue0. Le propriet\ue0 psicometriche sono state studiate attraverso un\u2019analisi fattoriale esplorativa ed il calcolo di misure di consistenza interna e affidabilit\ue0 test-retest. La validit\ue0 convergente \ue8 stata valutata mediante i coefficienti di correlazione con le restanti misure. La versione italiana del TFI ha mostrato una struttura a quattro fattori, parzialmente diversa dalla struttura originale a otto fattori. L\u2019adattamento italiano del TFI ha rivelato buoni livelli di consistenza interna (0,92 64 \u3b1 64 0,96) e affidabilit\ue0 test-retest (0,79 64 \u3b1 64 0,85). In termini di validit\ue0 convergente, ha mostrato buone correlazioni con i punteggi del THI (r = 0,77) e della scala del fastidio (r = 0,70) e correlazioni medie con i punteggi del BDI (r = 0,46). Le difficolt\ue0 nel riprodurre la struttura originale a otto fattori sono coerenti con altri studi di validazione del TFI nelle lingue europee. Nonostante tali discrepanze, la versione italiana del TFI ha mostrato una struttura fattoriale caratterizzata da alti livelli di affidabilit\ue0 e validit\ue0. Nel complesso, l\u2019adattamento italiano di TFI si \ue8 rivelato idoneo a misurare l\u2019impatto degli acufeni sulla vita quotidiana degli individui.Various questionnaires are used to assess the impact of tinnitus on the quality of life. The Tinnitus Functional Index (TFI) has excellent properties for scaling the severity of tinnitus and treatment-related changes in both clinical and research settings. The aim of this study was to evaluate the psychometric properties of the Italian version of the TFI with particular emphasis on factor analysis, internal consistency, reliability and validity. The original English version of the TFI was translated into Italian using the translation/back - translation process; 137 participants who were re- cruited at the Tinnitus Clinic in Milan and had suffered from tinnitus for at least three months (39.4% females, age: 18-80 years, mean age: 48.26, SD: 14.08) completed the Italian version of the TFI, the Tinnitus Handicap Inventory (THI), the Beck Depression Inventory - Primary Care Version (BDI-PC) and the Numeric Rating Scale of annoyance (NRS-A). Of these patients, 57 completed the TFI again at a second visit 7-14 days later, before undergoing any intervention, in order to provide data for reproducibility assessment. The psychometric properties were investigated using exploratory factor analysis and internal consistency and test-retest reliability instruments. The convergent validity of the TFI was evalu- ated using correlation coefficients obtained from the remaining measurements. The Italian TFI has a four-factor structure that was somewhat different from the original. The internal consistency proved to be good (0.92 64 \u3b1 64 0.96) as did the test-retest reliability (0.79 64 \u3b1 64 0.85). In terms of convergent validity, the TFI showed high correlations with the THI (r = 0.77) and the NRS-A (r = 0.70) scores, and moderate correlations with the BDI-PC scores (r = 0.46). The difficulties encountered when attempting to reproduce the original eight-factor structure were consistent with other studies in which the TFI was translated into European languages. In spite of this, the factorial structure of the Italian version of the TFI was characterised by high levels of reliability and validity. Overall, the Italian adaptation of the TFI was shown to be suitable to measure the impact of tinnitus on the daily lives of individuals

Advantages of the recursive operability analysis in updating the risk assessment

With the introduction of new regulations and sustainable technologies, revamping and upgrading already existing chemical plants is nowadays an important element in the framework of process engineering. Such important modifications must come along in parallel improvement of process safety. In this sense, risk assessment is a tool that should be versatile and easy to update by definition. However, even the most common methods currently used for accidental scenarios identification and risk assessment estimation (such as HazOp) may prove to be very time-consuming when discussing about safety from process modifications. The availability of a reliable and easy-to-update tool for safety engineering is crucial for process industries. In this work, we compare a risk analysis on a chemical plant subject of modifications performed with two different tools: HazOp and FTA vs Recursive Operability Analysis (ROA) and FTA. Both techniques have been applied to a tank dedicated to dust mixing that was subject of process modifications. Both methods come to the same conclusions, highlighting new failures and process criticalities, associated with the introduction of flow alarms and interlocks in case of excessive depressurizing. It is shown that the Recursive Operability Analysis, with its cause-consequence structure tied with process variable interactions, is much more effective in a risk assessment update

Actin and microtubules differently contribute to vacuolar targeting specificity during the export from the er

Plants rely on both actin and microtubule cytoskeletons to fine-tune sorting and spatial targeting of membranes during cell growth and stress adaptation. Considerable advances have been made in recent years in the comprehension of the relationship between the trans-Golgi network/early endosome (TGN/EE) and cytoskeletons, but studies have mainly focused on the transport to and from the plasma membrane. We address here the relationship of the cytoskeleton with different endoplasmic reticulum (ER) export mechanisms toward vacuoles. These emergent features of the plant endomembrane traffic are explored with an in vivo approach, providing clues on the traffic regulation at different levels beyond known proteins’ functions and interactions. We show how traffic of vacuolar markers, characterized by different vacuolar sorting determinants, diverges at the export from the ER, clearly involving different components of the cytoskeleton

Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes

Understanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs) and sub-TAD contact domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions. Here, we present a novel algorithm named CaTCH that identifies hierarchical trees of chromosomal domains in Hi-C maps, stratified through their reciprocal physical insulation, which is a single and biologically relevant parameter. By applying CaTCH to published Hi-C data sets, we show that previously reported folding layers appear at different insulation levels. We demonstrate that although no structurally privileged folding level exists, TADs emerge as a functionally privileged scale defined by maximal boundary enrichment in CTCF and maximal cell-type conservation. By measuring transcriptional output in embryonic stem cells and neural precursor cells, we show that the likelihood that genes in a domain are coregulated during differentiation is also maximized at the scale of TADs. Finally, we observe that regulatory sequences occur at genomic locations corresponding to optimized mutual interactions at the same scale. Our analysis suggests that the architectural functionality of TADs arises from the interplay between their ability to partition interactions and the specific genomic position of regulatory sequences

A possible role of inner ear melanocytes in tinnitus and audiovestibular disorders

Melanocytes are present in the skin and hair follicles, as well as in the eye, the leptomeninges, the anal canal and the inner ear. In the inner ear melanocytes are found both in the intermediate layer of the stria vascularis of the cochlea and in the dark cells of the vestibular organs. They are believed to play an important role in the production of endolymphatic potentials and in the maintenance of normal volumes of the inner ear fluids. Melanocytes disorders have been associated to some audiological abnormalities such as the Waardenburg syndrome and/or the Vogt-Kayanagi-Harada syndrome, characterized by both hearing impairment and pigmentation abnormalities. We propose that melanocytes could potentially be involved with inner ear fluid pressure dysfunction influencing conditions such as endolymphatic hydrops and M\ue9ni\ue8re\u2019s disease. Recently, we reported the case of a patient in whom the appearance of a choroidal melanoma coincided with the exacerbation of tinnitus and vertigo spells in a unilateral M\ue9ni\ue8re\u2019s disease that had been clinically silent for more than ten years. The symptoms disappeared after the radiotherapy treatment and did not show up again during the following three years. We suggest that inner ear melanocytes could be a target of an autoimmune process in patients affected by melanoma as well retinal melanocytes in melanoma-associated retinopathy. The immune system could produce antibodies that cross-react with both the melanoma cells and the labyrinth melanocytes, causing an altered homeostasis of endolymphatic liquids. In this perspective, audiovestibular disorders could be interpreted as an attempt by the individual immune system to develop anti-tumoral response. Autoimmune processes affecting inner ear melanocytes could be considered as a potential cause of tinnitus and audiovestibular disorders

MR Imaging in Menière Disease: Is the Contact between the Vestibular Endolymphatic Space and the Oval Window a Reliable Biomarker?

BACKGROUND AND PURPOSE: No reliable MR imaging marker for the diagnosis of Meniere disease has been reported. Our aim was to investigate whether the obliteration of the inferior portion of the vestibule and the contact with the stapes footplate by the vestibular endolymphatic space are reliable MR imaging markers in the diagnosis of Meniere disease. MATERIALS AND METHODS: We retrospectively enrolled 49 patients, 24 affected by unilateral sudden hearing loss and 25 affected by definite Meniere disease, who had undergone a 4-hour delayed 3D-FLAIR sequence. Two readers analyzed the MR images investigating whether the vestibular endolymphatic space bulged in the third inferior portion of the vestibule contacting the stapes footplate. This sign was defined as the vestibular endolymphatic space contacting the oval window. RESULTS: We analyzed 98 ears: 27 affected by Meniere disease, 24 affected by sudden sensorineural hearing loss, and 47 that were healthy. The vestibular endolymphatic space contacting the oval window showed an almost perfect interobserver agreement (Cohen κ = 0.87; 95% CI, 0.69–1). The vestibular endolymphatic space contacting oval window showed the following: sensitivity = 81%, specificity = 96%, positive predictive value = 88%, and negative predictive value = 93% in differentiating Meniere disease ears from other ears. The vestibular endolymphatic space contacting the oval window showed the following: sensitivity = 81%, specificity = 96%, positive predictive value = 96%, negative predictive value = 82% in differentiating Meniere disease ears from sudden sensorineural hearing loss ears. CONCLUSIONS: The vestibular endolymphatic space contacting the oval window has high specificity and positive predictive value in differentiating Meniere disease ears from other ears, thus resulting in a valid tool for ruling in Meniere disease in patients with mimicking symptoms

MYH9-related disease: Five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations

MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin-9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is limited. We report five families, each with a novel MYH9 mutation. Two mutations, p.Val34Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the other three, p.Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the coiled-coil tail domain of the protein. The motor domain mutations were associated with more severe clinical phenotypes than those in the tail domain.Fil: de Rocco, Daniela. Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo"; ItaliaFil: Zieger, Barbara. University of Freiburg; AlemaniaFil: Platokouki, Helen. “Aghia Sophia” Children; GreciaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pastore, Annalisa. National Institute for Medical Research; Reino UnidoFil: Bottega, Roberta. Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo"; ItaliaFil: Noris, Patrizia. Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo"; Italia. University of Pavia; ItaliaFil: Barozzi, Serena. Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo"; Italia. University of Pavia; ItaliaFil: Glembotsky, Ana Claudia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Pergantou, Helen. “Aghia Sophia” Children; GreciaFil: Balduini, Carlo L.. Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo"; Italia. University of Pavia; ItaliaFil: Savoia, Anna. Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo"; Italia. Universita Degli Studi Di Trieste; ItaliaFil: Pecci, Alessandro. Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo"; Italia. University of Pavia; Itali