Identification of Novel Wsf1 Mutations in a Sicilian Child with Wolfram Syndrome

Wolfram Syndrome (WS) is a rare hereditary disease with autosomal recessive inheritance with incomplete penetrance. It is characterized by diabetes mellitus associated with progressive optic atrophy. The diagnosis is essentially clinical and mutation analysis is used to confirm the diagnosis. In the present study we describe the clinical and molecular features of a diabetic child carrying two novel WFS1 mutations. The Sicilian proband and his non-affected family were studied. Ophthalmologic examination included: visual acuity determination and funduscopy, optical coherent tomography, retinal fluorangiography, perimetry and electroretinogram. Molecular methods: automatic sequencing of PCR amplified WFS1 gene fragments and qRT-PCR analysis of WFS1 transcripts. 3 WSF1 mutations have been identified in the proband. One allele carries 2 paternally inherited mutations (c.1332 C>G and c.1631C>G) in exon-8, never annotated before, in heterozygosis with one “de novo” classic mutation (c.505 G>A) in exon-5. In addition, we report an unexpected molecular feature: higher WFS1 mRNA levels in the proband compared to the father

Blocking the APRIL circuit enhances acute myeloid leukemia cell chemosensitivity.

Resistance to chemotherapy-induced cell death represents a major obstacle in the treatment of acute myeloid leukemia. APRIL (A Proliferation Inducing Ligand) is a member of the tumor necrosis factor superfamily that plays a key role in normal B-cell development, while promoting survival and proliferation of malignant B cells. We investigated APRIL expression and activity in acute myeloid leukemia. We found that APRIL mRNA and protein, including the secreted form, are expressed in leukemic cells of patients with M0, M2 and M4 acute myeloid leukemia subtypes but not in normal hematopoietic progenitors. Retrovirus-mediated APRIL expression in normal hematopoietic progenitors confers resistance to chemotherapeutic drugs-induced apoptosis. Conversely, blocking APRIL function by recombinant soluble APRIL receptors increased chemotherapeutic drugs-induced cell adeath in acute myeloid leukemia cells. These results indicate that APRIL acts in an autocrine fashion to protect acute myeloid leukemia cells from drug-induced death and foresee a therapeutic potential of APRIL antagonists in the treatment of acute myeloid leukemia

An updated checklist of chondrichthyans of Calabria (Central Mediterranean, southern Italy), with emphasis on rare species

In this contribution the checklist of chondrichthyans of Calabria (Central Mediterranean, southern Italy) is reported. Data presented is derived from twenty years of opportunistic and active surveys from 2000 to 2020. A total of 55 species of chondrichthyans is present in Calabrian seas: 33 sharks, 20 rays, and 2 chimaeras. These species represent approximately 62% of the total reported for the Mediterranean. Approximately 71% of Calabrian species have been reported in the Tyrrhenian Sea, 49% in the Ionian Sea, and 33% in the Strait of Messina. According to IUCN criteria, new records of Endangered and Critically Endangered species (i.e., Carcahrodon carcharias [Linnaeus, 1758], Lamna nasus [Bonnaterre, 1788], Cetorhinus maximus [Gunnerus, 1765], Mobula mobular [Bonnaterre, 1788], Sphyrna zygaena [Linnaeus, 1758]) are reported, together with the first record of Raya brachyura Lafont, 1873 for the Ionian coasts and probably third confirmed record of the rare chimaera Hydrolagus mirabilis (Collett, 1904) for the Mediterranean

Combination of the Systemin peptide with the beneficial fungus Trichoderma afroharzianum T22 improves plant defense responses against pests and diseases

Trichoderma spp. are among the most widely used plant beneficial fungi in agriculture. Its interaction with the plant triggers resistance responses by the activation of Induced Systemic Resistance mediated by Jasmonic acid and Ethylene and/or Systemic Acquired Resistance, which involves Salicylic acid, with the consequent control of a wide range of plant parasites. However, the benefit they can confer to plants may be reduced or nullified by environmental conditions or fungal ecological fitness. A novel approach to enhance their effectiveness in plant defense is to combine them with bioactive molecules including plant-derived compounds. Here, we show that plant treatment with Trichoderma afroharzianum (strain T22) and Systemin, a tomato peptide active in triggering plant defense, confers protection against the fungal pathogens Fusarium oxysporum, Botrytis cinerea and the insect pest Tuta absoluta. The observed defensive response was associated with an increase of Jasmonic acid and related metabolites and a decrease of Salicili acid

Outer Membrane Vesicles Derived from Klebsiella pneumoniae Influence the miRNA Expression Profile in Human Bronchial Epithelial BEAS-2B Cells

: Klebsiella pneumoniae is an opportunistic pathogen that causes nosocomial and community-acquired infections. The spread of resistant strains of K. pneumoniae represents a growing threat to human health, due to the exhaustion of effective treatments. K. pneumoniae releases outer membrane vesicles (OMVs). OMVs are a vehicle for the transport of virulence factors to host cells, causing cell injury. Previous studies have shown changes of gene expression in human bronchial epithelial cells after treatment with K. pneumoniae OMVs. These variations in gene expression could be regulated through microRNAs (miRNAs), which participate in several biological mechanisms. Thereafter, miRNA expression profiles in human bronchial epithelial cells were evaluated during infection with standard and clinical K. pneumoniae strains. Microarray analysis and RT-qPCR identified the dysregulation of miR-223, hsa-miR-21, hsa-miR-25 and hsa-let-7g miRNA sequences. Target gene prediction revealed the essential role of these miRNAs in the regulation of host immune responses involving NF-ĸB (miR-223), TLR4 (hsa-miR-21), cytokine (hsa-miR-25) and IL-6 (hsa-let-7g miRNA) signalling pathways. The current study provides the first large scale expression profile of miRNAs from lung cells and predicted gene targets, following exposure to K. pneumoniae OMVs. Our results suggest the importance of OMVs in the inflammatory response

Blocking the APRIL circuit enhances acute myeloid leukemia cell chemosensitivity

Resistance to chemotherapy-induced cell death represents a major obstacle in the treatment of acute myeloid leukemia. APRIL (A Proliferation Inducing Ligand) is a member of the tumor necrosis factor superfamily that plays a key role in normal B-cell development, while promoting survival and proliferation of malignant B cells. We investigated APRIL expression and activity in acute myeloid leukemia. We found that APRIL mRNA and protein, including the secreted form, are expressed in leukemic cells of patients with M0, M2 and M4 acute myeloid leukemia subtypes but not in normal hematopoietic progenitors. Retrovirus-mediated APRIL expression in normal hematopoietic progenitors confers resistance to chemotherapeutic drugs-induced apoptosis. Conversely, blocking APRIL function by recombinant soluble APRIL receptors increased chemotherapeutic drugs-induced cell adeath in acute myeloid leukemia cells. These results indicate that APRIL acts in an autocrine fashion to protect acute myeloid leukemia cells from drug-induced death and foresee a therapeutic potential of APRIL antagonists in the treatment of acute myeloid leukemia. \uc2\ua92008 Ferrata Storti Foundation

Perioperative Antibiotic Prophylaxis: Knowledge and Attitudes among Resident Physicians in Italy

The aim of this study is to evaluate knowledge and attitudes on the perioperative antibiotic prophylaxis (PAP) among surgery and anesthesiology resident physicians in Italy. A Web-based national survey of Italian surgery and anesthesiology resident physicians was conducted between March 2018 and January 2019. Participants completed a questionnaire and three case vignettes for each specialty. Of the 1282 resident physicians selected, 466 completed the online questionnaire for a response rate of 36.3%. More than half of the sample were female (52.9%), and the mean age was 30 years. A total of 36.3% of the participants had an adequate knowledge score about PAP. Multiple logistic regression analysis showed that resident physicians in general surgery compared to those in anesthesiology, those who agreed that PAP must be performed within 60 min before surgical incision, and those who were aware regarding the availability about the availability of national guidelines on PAP, were significantly more likely to have adequate knowledge about PAP. Moreover, 14% of participants were very concerned that patients may contract surgical site infections during hospitalization. These findings should be useful to promote educational intervention specifically targeted for surgery and anesthesiology resident physicians organizing training course on PAP, to improve the correct antibiotic use and to prevent healthcare-associated infections