Members of the zinc finger protein gene family sharing a conserved N-terminal module

We report the isolation of human members of a subfamily of structurally related finger protein genes. These potentially encode polypeptides containing finger motifs of the Krüppel type at the C-terminus, and a conserved amino acid module at the N-terminus; because of its invariant location the latter is referred to as finger preceding box (FPB). The FPB, detected also in previously described finger proteins from human, mouse and Xenopus, extends over approximately 65 amino acids and appears to be composed of two contiguous modules: FPB-A (residues 1-42) and FPB-B (residues 43-65). The latter is absent in some of the members analyzed. Elements A and B and the zinc finger domain are encoded by separate exons in the ZNF2 gene, a human member of this sub-family. The positioning of introns within this gene is remarkable. One intron flanks and a second interrupts the first codon of the FPB-A and FPB-B modules, respectively. A third intron occurs a few nucleotides downstream of FPB-B marking its separation from the remainder of the coding sequences. This organization, together with the absence of FPB-B in some cDNAs, supports the hypothesis that mRNAs encoding polypeptides that include one, both or none of the FPB-A and FPB-B modules may be assembled through alternative splicing pathways. Northern analyses showed that members of his sub-family are expressed as multiple transcripts in several cell lines. The sequences of distinct cDNAs homologous to the ZNF2 gene indicate that alternative splicing events adjoin either coding or non oding xons to the FPB sequences. © 1991 Oxford University Press

Molecular anatomy of the human glucose 6-phosphate dehydrogenase core promoter

The gene encoding glucose 6-phosphate dehydrogenase (G6PD), which plays a pivotal role in cell defense against oxidative stress, is ubiquitously expressed at widely different levels in various tissues; moreover, G6PD expression is regulated by a number of stimuli. In this study we have analyzed the molecular anatomy of the G6PD core promoter. Our results indicate that the G6PD promoter is more complex than previously assumed; G6PD expression is under the control of several elements that are all required for correct promoter functioning and, furthermore, a still unidentified mammalian specific factor is needed. Copyright (C) 1998 Federation of European Biochemical Societies

Integrated Bimodal Fitting for Unilateral CI Users with Residual Contralateral Hearing

Background: The aim of this study was to compare, in users of bimodal cochlear implants, the performance obtained using their own hearing aids (adjusted with the standard NAL-NL1 fitting formula) with the performance using the Phonak Naìda Link Ultra Power hearing aid adjusted with both NAL-NL1 and a new bimodal system (Adaptive Phonak Digital Bimodal (APDB)) developed by Advanced Bionics and Phonak Corporations. Methods: Eleven bimodal users (Naìda CI Q70 + contralateral hearing aid) were enrolled in our study. The users’ own hearing aids were replaced with the Phonak Naìda Link Ultra Power and fitted following the new formula. Speech intelligibility was assessed in quiet and noisy conditions, and comparisons were made with the results obtained with the users’ previous hearing aids and with the Naída Link hearing aids fitted with the NAL-NL1 generic prescription formula. Results: Using Phonak Naìda Link Ultra Power hearing aids with the Adaptive Phonak Digital Bimodal fitting formula, performance was significantly better than that with the users’ own rehabilitation systems, especially in challenging hearing situations for all analyzed subjects. Conclusions: Speech intelligibility tests in quiet settings did not reveal a significant difference in performance between the new fitting formula and NAL-NL1 fittings (using the Naída Link hearing aids), whereas the performance difference between the two fittings was very significant in noisy test conditions

Interleukin-21 sustains inflammatory signals that contribute to sporadic colon tumorigenesis

Interleukin (IL)-21 triggers inflammatory signals that contribute to the growth of neoplastic cells in mouse models of colitis-associated colorectal cancer (CRC). Because most CRCs are sporadic and arise in the absence of overt inflammation we have investigated the role of IL-21 in these tumors in mouse and man. IL-21 was highly expressed in human sporadic CRC and produced mostly by IFN-γ-expressing T-bet/RORγt double-positive CD3+CD8- cells. Stimulation of human CRC cell lines with IL-21 did not directly activate the oncogenic transcription factors STAT3 and NF-kB and did not affect CRC cell proliferation and survival. In contrast, IL-21 modulated the production of protumorigenic factors by human tumor infiltrating T cells. IL-21 was upregulated in the neoplastic areas, as compared with non-tumor mucosa, of Apc(min/+) mice, and genetic ablation of IL-21 in such mice resulted in a marked decrease of both tumor incidence and size. IL-21 deficiency was associated with reduced STAT3/NF-kB activation in both immune cells and neoplastic cells, diminished synthesis of protumorigenic cytokines (that is, IL-17A, IL-22, TNF-α and IL-6), downregulation of COX-2/PGE2 pathway and decreased angiogenesis in the lesions of Apc(min/+) mice. Altogether, data suggest that IL-21 promotes a protumorigenic inflammatory circuit that ultimately sustains the development of sporadic CRC

Simplified tabu search with random-based searches for bound constrained global optimization

This paper proposes a simplified version of the tabu search algorithm that solely uses randomly generated direction vectors in the exploration and intensification search procedures, in order to define a set of trial points while searching in the neighborhood of a given point. In the diversification procedure, points that are inside any already visited region with a relative small visited frequency may be accepted, apart from those that are outside the visited regions. The produced numerical results show the robustness of the proposed method. Its efficiency when compared to other known metaheuristics available in the literature is encouraging.FCT - Fundação para a Ciência e a Tecnologia(UIDB/00013/2020); FCT – Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020, UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM

Natural Course of COVID-19 and Independent Predictors of Mortality.

Background: During the SARS-CoV-2 pandemic, several biomarkers were shown to be helpful in determining the prognosis of COVID-19 patients. The aim of our study was to evaluate the prognostic value of N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) in a cohort of patients with COVID-19. Methods: One-hundred and seven patients admitted to the Covid Hospital of Messina University between June 2022 and January 2023 were enrolled in our study. The demographic, clinical, biochemical, instrumental, and therapeutic parameters were recorded. The primary outcome was in-hospital mortality. A comparison between patients who recovered and were discharged and those who died during the hospitalization was performed. The independent parameters associated with in-hospital death were assessed by multivariable analysis and a stepwise regression logistic model. Results: A total of 27 events with an in-hospital mortality rate of 25.2% occurred during our study. Those who died during hospitalization were older, with lower GCS and PaO2/FiO2 ratio, elevated D-dimer values, INR, creatinine values and shorter PT (prothrombin time). They had an increased frequency of diagnosis of heart failure (p < 0.0001) and higher NT-pro-BNP values. A multivariate logistic regression analysis showed that higher NT-pro-BNP values and lower PT and PaO2/FiO2 at admission were independent predictors of mortality during hospitalization. Conclusions: This study shows that NT-pro-BNP levels, PT, and PaO2/FiO2 ratio are independently associated with in-hospital mortality in subjects with COVID-19 pneumonia. Further longitudinal studies are warranted to confirm the results of this study

Genetica della funzione uditiva normale e patologica

Questo libro, frutto della collaborazione delle principali Scuole italiane di Audiologia-Foniatria e Otorinolaringoiatria, con il contributo di genetisti, biologi molecolari ed esperti in neuroscienze di vari paesi, offre un panorama delle più aggiornate conoscenze in tema di sordità genetica. La sordità rappresenta il più comune deficit sensoriale nella popolazione mondiale: infatti circa 1 bambino su 1000 nasce con ipoacusia e questa in più della metà dei casi è su base genetica. Negli ultimi vent’anni si è avuto un grande sviluppo delle ricerche in questo campo e molti dei geni e dei loci associati a ipoacusia sono stati identificati. I vari capitoli del libro, esposti in modo monografico, sono suddivisi in tre sezioni: la prima, genetica e ipoacusia, verte sui concetti base relativi a genotipo, fenotipo, epidemiologia, della sordità, ipoacusie ereditarie sindromiche e non sindromiche, presbiacusia e sordità da rumore. La seconda sezione è dedicata al trattamento e comprende diagnostica per immagini, screening uditivi neonatali, riabilitazione in caso di handicap multipli, protesizzazione e chirurgia. La terza sezione tratta delle prospettive terapeutiche future, incluse la terapia farmacologia sistemica e locale, la terapia genica e con cellule staminali e i trapianti