Transcriptologs: A Transcriptome-Based Approach to Predict Orthology Relationships

The detection of orthologs is a key approach in genomics, useful to understand gene evolution and phylogenetic relationships and essential for gene function prediction. However, a reliable annotation of the encoded protein regions is still a limiting aspect in genomics, mainly due to the lack of confirmatory experimental evidence at proteome level. Nevertheless, the current ortholog collections are generally based on protein sequence comparisons, in addition to the availability of large transcriptome sequence collections. We developed Transcriptologs , a method for the prediction of orthologs based on similarities of translated fragments from messenger RNAs of 2 species. We implemented a procedure to extend BLAST-based alignments and to define orthologs based on the Bidirectional Best Hit approach. Results from a test case on Arabidopsis thaliana and Sorghum bicolor transcript collections revealed in some cases outperformance of Transcriptologs in comparison with a classical protein-based analysis in terms of alignment quality, revealing similarities otherwise not detectable

Redesigning one's life when experiencing oncological problems: the role of resilience and a balanced time perspective on the quality of life.

openLe problematiche oncologiche sono ormai tra i fattori più comuni di mortalità prematura nella maggior parte dei paesi del mondo. Si prevede che il numero globale di persone che sperimentano questa condizione aumenterà nei prossimi 50 anni a causa della forte influenza dei cambiamenti demografici, come l'invecchiamento e la crescita della popolazione. (Soerjomataram e Bray, 2021) Per questo motivo, la medicina cerca sempre più di fare progressi in questo ambito attuando studi su cure sempre più all’avanguardia, oltre che cercando di implementare strategie che prendano di mira quei fattori comportamentali che aumentano il rischio di poter sviluppare eventuali problematiche oncologiche. L’insorgenza di una problematica oncologica, però, non mette solo a dura prova da un punto di vista fisico l’individuo, ma anche da un punto di vista psicologico; questo perché la persona si trova a mettere in discussione la propria vita e le proprie priorità. È solo negli ultimi anni, però, che la psicologia sta prestando attenzione a comprendere i cambiamenti che coinvolgono la persona; la lettura è ricca di ricerche che indagano l’impatto dei cambiamenti fisici sul benessere della persona. Con il presente studio ci si vuole concentrare sull’indagine di quelle risorse che possono aiutare l’individuo a vivere al meglio un percorso oncologico. Di sottofondo, quindi, a questo lavoro troviamo un concetto di salute mutuato alla psicologia positiva che non guarda solo ai deficit della persona, ma rivolge lo sguardo al funzionamento globale e alle potenzialità dell’individuo. A questo proposito, nello studio qui presentato, sono state coinvolte 34 persone che hanno affrontato un percorso oncologico, a cui è stato chiesto di rispondere alle domande di alcuni questionari volti ad indagare le risorse socio-emotive e altre risorse psicologiche, e il loro ruolo sul livello di benessere percepito nel continuum della gestione della malattia oncologica. I risultati dello studio sottolineano come le problematiche oncologiche abbiano una serie complessa di influenze sulle risorse e sul benessere della persona, che si estendono all’intero contesto e alle relazioni con le persone all’interno del contesto. Questo aspetto è di fondamentale importanza per gli operatori che assistono persone con problematiche oncologiche, in quanto nel progettare interventi mirati al benessere dell’individuo bisogna avere in mente che non ci si sta rapportando con la singola persona, ma anche con tutto il contesto in cui è inserita. Avere un approccio sistemico, può aiutare a non tralasciare aspetti esterni che influenzano la vita della persona e quindi avere un quadro completo della situazione

Precision Measurement of KS Meson Lifetime with the KLOE detector

Using a large sample of pure, slow, short lived K0 mesons collected with KLOE detector at DaFne, we have measured the KS lifetime. From a fit to the proper time distribution we find tau = (89.562 +- 0.029_stat +- 0.043_syst) ps. This is the most precise measurement today in good agreement with the world average derived from previous measurements. We observe no dependence of the lifetime on the direction of the Ks.Comment: 5 pages, 7 figure

Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of Kv7.2 potassium channel subunits

Mutations in the K(V)7.2 gene encoding for voltage-dependent K(+) channel subunits cause neonatal epilepsies with wide phenotypic heterogeneity. Two mutations affecting the same positively charged residue in the S(4) domain of K(V)7.2 have been found in children affected with benign familial neonatal seizures (R213W mutation) or with neonatal epileptic encephalopathy with severe pharmacoresistant seizures and neurocognitive delay, suppression-burst pattern at EEG, and distinct neuroradiological features (R213Q mutation). To examine the molecular basis for this strikingly different phenotype, we studied the functional characteristics of mutant channels by using electrophysiological techniques, computational modeling, and homology modeling. Functional studies revealed that, in homomeric or heteromeric configuration with K(V)7.2 and/or K(V)7.3 subunits, both mutations markedly destabilized the open state, causing a dramatic decrease in channel voltage sensitivity. These functional changes were (i) more pronounced for channels incorporating R213Q- than R213W-carrying K(V)7.2 subunits; (ii) proportional to the number of mutant subunits incorporated; and (iii) fully restored by the neuronal K(v)7 activator retigabine. Homology modeling confirmed a critical role for the R213 residue in stabilizing the activated voltage sensor configuration. Modeling experiments in CA1 hippocampal pyramidal cells revealed that both mutations increased cell firing frequency, with the R213Q mutation prompting more dramatic functional changes compared with the R213W mutation. These results suggest that the clinical disease severity may be related to the extent of the mutation-induced functional K(+) channel impairment, and set the preclinical basis for the potential use of K(v)7 openers as a targeted anticonvulsant therapy to improve developmental outcome in neonates with K(V)7.2 encephalopathy

Effects of Abrupt Variations of Solar Wind Dynamic Pressure on the High-Latitude Ionosphere

We show the results of a statistical study on the effects in the high-latitude ionosphere of abrupt variations of solar wind dynamic pressure, using Super Dual Auroral Radar Network (SuperDARN) data in both hemispheres. We find that, during periods of quiet ionospheric conditions, the amount of radar backscatter increases when a variation in the dynamic pressure occurs, both positive (increase of the pressure) and negative (decrease of the pressure). We also investigate the behaviour of the Cross-Polar Cap Potential (CPCP) during pressure variations and show preliminary results

Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine

Despite the availability of over 20 antiepileptic drugs, about 30% of epileptic patients do not achieve seizure control. Thus, identification of additional molecules targeting novel molecular mechanisms is a primary effort in today’s antiepileptic drug research. This paper reviews the pharmacological development of retigabine, an antiepileptic drug with a novel mechanism of action, namely the activation of voltage-gated potassium channels of the Kv7 subfamily. These channels, which act as widespread regulators of intrinsic neuronal excitability and of neurotransmitter-induced network excitability changes, are currently viewed among the most promising targets for anticonvulsant pharmacotherapy. In particular, the present work reviews the pathophysiological role of Kv7 channels in neuronal function, the molecular mechanisms involved in the Kv7 channel-opening action of retigabine, the activity of retigabine in preclinical in vitro and in vivo studies predictive of anticonvulsant activities, and the clinical status of development for this drug as an add-on treatment for pharmacoresistant epilepsy. Particular efforts are devoted to highlighting the potential advantages and disadvantages of retigabine when compared with currently available compounds, in order to provide a comprehensive assessment of its role in therapy for treatment-resistant epilepsies

Gender differences in treatment of Coronavirus Disease-2019

Coronavirus Disease-2019 (COVID-19) is the worst worldwide pandemic with more than 12,000,000 cases and 560,000 deaths until 14th July 2020. Men were more infected by COVID-19 than women, and male subjects with underlying conditions, including diabetes, hypertension, and cardiovascular diseases developed a severe form of the affection, with increased mortality rate. Many factors can contribute to the disparity in disease outcomes, such as hormone-specific reaction and activity of X-linked genes, which modulate the innate and adaptive immune response to virus infection. Until now, only the Remdesivir was approved by FDA (Food Drug Administration) for COVID-19 treatment, although several clinical trials are ongoing worldwide also on other drugs. In this review, we analyzed published studies on several drugs (chloroquine or hydroxychloroquine, remdesivir, favipiravir, lopinavir-ritonavir in combination, tocilizumab, plasma, and immunoglobulins) with some efficacy to COVID-19 in humans, and evaluated if there were a gender analysis of the available data. In our opinion, it is essential to report data about COVID-19 disaggregated by sex, age, and race, because the knowledge of gender differences is fundamental to identify effective and customized treatments to reduce hospitalizations, admissions to intensive care units, and mortality

pATsi: Paralogs and singleton genes from Arabidopsis thaliana

Arabidopsis thaliana is widely accepted as a model species in plant biology. Its genome, due to its small size and diploidy, was the first to be sequenced among plants, making this species also a reference for plant comparative genomics. Nevertheless, the evolutionary mechanisms that shaped the Arabidopsis genome are still controversial. Indeed, duplications, translocations, inversions, and gene loss events that contributed to the current organization are difficult to be traced. A reliable identification of paralogs and single-copy genes is essential to understand these mechanisms. Therefore, we implemented a dedicated pipeline to identify paralog genes and classify single-copy genes into opportune categories. PATsi, a web-accessible database, was organized to allow the straightforward access to the paralogs organized into networks and to the classification of single-copy genes. This permits to efficiently explore the gene collection of Arabidopsis for evolutionary investigations and comparative genomics

Effect of Salt Addition and Fermentation Time on Phenolics, Microbial Dynamics, Volatile Organic Compounds, and Sensory Properties of the PDO Table Olives of Gaeta (Italy)

‘Oliva di Gaeta’ is almost certainly the most important and well-known PDO denomination for table olives in Italy. Their production is based on a specific two-stage trade preparation called the ‘Itrana’ method. In this work, we investigated how variations in the duration of the initial water fermentation (i.e., 15 and 30 days) and the salt concentration (i.e., 6% and 8% NaCl) influence the chemical features, microbial dynamics, polyphenols, volatile organic compounds, and sensory features of ‘Oliva di Gaeta’. The time of the addition of salt did not affect the final concentration in the brine, but a longer initial water fermentation (before salt addition) led to lower pH values. The bacterial count constantly increased until the salt addition (i.e., either 15 or 30 days), while the yeast population peaked on day 30. Generally, the two different salt concentrations did not affect the count of microorganisms at the end of fermentation, with the only exception being a higher lactic acid bacteria count for the treatment with 6% salt added at 30 days. At commercial maturity, the crucial bitter tastant oleuropein was not completely removed from the drupes, and differences in salt concentration and the length of the first-stage water fermentation did not influence its content at the end of olive curing. Richer volatile profiles of olives were detected with higher-salt treatments, while the combination of low salt and early saline treatment provided a more distinct profile. Longer initial water fermentation caused a small increase in some phenolic compounds (e.g., iso-verbascoside, verbascoside, and hydroxytyrosol-glucoside). A panel test indicated that salt application at 30 days resulted in a more “Sour” and “Bitter” taste, irrespective of the salt concentration. The low salt concentration coupled with the late saline treatment resulted in more “Fruity” notes, probably due to the higher production of esters by lactobacilli. The slightly bitter perception of the olives was consistent with the partial removal of oleuropein. Our work revealed the characteristics of the ‘Itrana’ method and that the variation in salt concentration and its time of application changes parameters ranging from the microbial dynamics to the sensory profile. Specifically, our data indicate that 6% NaCl coupled with a longer initial water fermentation is the most different condition: it is less effective in blocking microbial growth but, at the same time, is more potent in altering the nutritional (e.g., polyphenols) and sensorial qualities (e.g., bitterness and fruitiness) of ‘Oliva di Gaeta’

Educational level, marital status and sex as social gender discharge determinants in chronic obstructive pulmonary disease exacerbations: a time-to-event analysis

The aim of this study is to evaluate, in patients hospitalized for COPD exacerbation, how educational level, marital status and sex (social gender indicators) affect the home discharge probability (main effects) and how interact with each other in affecting this probability (effect modification). Data for all patients discharged with a principal diagnosis of COPD with exacerbation (ICD-9 491.21) by Apulian hospitals between 2013 and 2017 were retrieved from the National Hospital Discharge Register Database. A multivariable multi-stratified frailty cox proportional-hazard regression with interaction terms was fitted in order to assess the effect of sex, educational level and marital status on the time-to-event for home discharge through the estimation of hazard ratios. Adjusting for several patient and hospitalization characteristics and for healthcare facilities, low educational level (<8 years of schooling) is associated with a lower probability of being discharged to home in both sexes and in all marital status categories (HR 0.92, 95%CI 0.87-0.97, p=0.0020). Female sex is associated with a lower probability of being discharged to home only in married patients (HR 0.83, 95%CI 0.78-0.88, p<0.0001). Marital status different from married is associated with a lower probability of being discharged to home only in male patients, in particular single patients (HR 0.82, 95%CI 0.74-0.92, p=0.0009), separated or divorced patients (HR 0.71, 95%CI 0.58-0.86, p=0.0005) and widowed patients (HR 0.87, 95%CI 0.80-0.95, p=0.0018). Differently from findings about protective effect of education, the evidence of different effects of sex on home discharge probability among civil statuses and of different effect of civil status among sexes is supposed to be a proxy for social gender health and healthcare inequalities