Arthrographis curvata and Rhodosporidium babjevae as New Potential Fungal Lipase Producers for Biotechnological Applications

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PARP-14 Promotes Survival of Mammalian α but Not β Pancreatic Cells Following Cytokine Treatment

PARP-14 (poly-ADP Ribose Polymerase-14), a member of the PARP family, belongs to the group of Bal proteins (B Aggressive Lymphoma). PARP-14 has recently appeared to be involved in the transduction pathway mediated by JNKs (c Jun N terminal Kinases), among which JNK2 promotes cancer cell survival. Several pharmacological PARP inhibitors are currently used as antitumor agents, even though they have also proved to be effective in many inflammatory diseases. Cytokine release from immune system cells characterizes many autoimmune inflammatory disorders, including type I diabetes, in which the inflammatory state causes β cell loss. Nevertheless, growing evidence supports a concomitant implication of glucagon secreting α cells in type I diabetes progression. Here, we provide evidence on the activation of a survival pathway, mediated by PARP-14, in pancreatic α cells, following treatment of αTC1.6 glucagonoma and βTC1 insulinoma cell lines with a cytokine cocktail: interleukin 1 beta (IL-1β), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). Through qPCR, western blot and confocal analysis, we demonstrated higher expression levels of PARP-14 in αTC1.6 cells with respect to βTC1 cells under inflammatory stimuli. By cytofluorimetric and caspase-3 assays, we showed the higher resistance of α cells compared to β cells to apoptosis induced by cytokines. Furthermore, the ability of PJ-34 to modulate the expression of the proteins involved in the survival pathway suggests a protective role of PARP-14. These data shed light on a poorly characterized function of PARP-14 in αTC1.6 cells in inflammatory contexts, widening the potential pharmacological applications of PARP inhibitors

Invasive Infections due to: Species Distribution, Genotyping, and Antifungal Susceptibilities from a Multi-center Study in China

One hundred and thirty-three clinical Trichosporon isolates were collected in the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program (2009 to 2016). Accurate identification was performed by sequencing of the intergenic spacer (IGS) 1 region. Among these isolates T. asahii (108, 81.2%) was the leading species, followed by T. dermatis (7, 5.3%), T. asteroides (5, 3.8%), T. inkin (5, 3.8%), T. dohaense (3, 2.3%), and one (0.7%) each of T. faecale, T. jirovecii, T. mucoides, T. coremiiforme and T. montevideense Both the VITEK MS (bioMérieux, Marcy l'Etoile, France) and Bruker Biotyper MS (Bruker Daltonics GmbH, Germany) platforms gave a high level (>97.5%) of correct identification when the species were present in the database. Geometric mean (GM) of amphotericin B MICs for T. asahii was 2-fold higher than for non-asahii Trichosporon High fluconazole MICs (≥8 μg/ml) were observed in 25% (27/108) of T. asahii and 16% (4/25) of non-asahii Trichosporon isolates. Itraconazole MICs were ≤0.5 μg/ml for 89.5% of the isolates. Voriconazole was the most potent antifungal agent in vitro, with GM of 0.09 μg/ml. Genotyping of the isolates using the IGS1 sequences alignment revealed that genotype1 was most common (41.7%), followed by genotype 4 (31.5%), 3 (23.1%), 5 (0.9%), 6 (0.9%) and 7 (1.8%). Our data of species distribution, genotypes and antifungal susceptibilities may contribute to a better understanding of the epidemiology of invasive Trichosporon infections throughout China

First external quality assurance program of the Italian HLA-B*57:01 Network assessing the performance of clinical virology laboratories in HLA-B*57:01 testing

Background: Since the HLA-B*57:01 allele is strongly associated with abacavir hypersensitivity reaction, testing for the presence of HLA-B*57:01 is mandatory before administration of abacavir. While HLA-B*57:01 testing is usually provided by pharmacogenetics, genetics or blood transfusion services, clinical virology laboratories can be an optimal opportunity for HLA-B*57:01 testing since they receive blood samples for routine HIV monitoring and have the expertise for convenient and less expensive PCR-based point mutation assays. Objectives: The Italian HLA-B*57:01 Network gathers accredited clinical virology laboratories offering HLA-B*57:01 testing in Italy with the aim to share protocols, test new methods, develop and maintain external quality assurance (EQA) programs. Study design: A panel of 9HLA-B*57:01-positive and 16HLA-B*57:01-negative frozen blood samples were blindly distributed to 10 units including 9 clinical virology laboratories and one reference pharmacology laboratory. Each laboratory was free to use its own routine method for DNA extraction and HLA-B*57:01 testing. Results: DNA was extracted by automated workstations in 6 units and by manual spin columns in 4. Eight units used the Duplicα Real Time HLA-B*57:01 kit by Euroclone and two units used two different PCR homemade protocols. All the 10 units correctly identified all the 25 samples. Conclusions: The first HLA-B*57:01 EQA program run in Italy showed that clinical virology units are equipped and proficient for providing HLA-B*57:01 testing by inexpensive assays easy to integrate into their routine

Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations

Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity. CC BY 4.0© 2023 The Author(s)Correspondence [email protected] work has received funding from the European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie grant agreement 754412 (to O.G.). O.G. was also supported by a personal fellowship from EFIS as well as research grants from the Wilhelm and Martina Lundgren Foundation (grants 2018-2300, 2019-2986, and 2020-3395), the Axel Linder Foundation, the Swedish Medical Society (grant SLS-593371), the Gunvor and Josef Anér Foundation (grant FB19-0054), the O.E. and Edla Johansson Science Foundation, the Elsa and Sigurd Memorial Foundation, the Pharmacist Hedberg Foundation for Medical Research, The Royal Society of Arts and Sciences in Gothenburg (grants 2018-184, 2020-422, and 2021-548), the Tore Nilsson Foundation (grants 2015-00218, 2018-00648, and 2020-00789), and The Healthcare Committee, Region Västra Götaland. This work was also supported by The Health &amp; Medical Care Committee of the Region Västra Götaland and by grants from the Swedish state under an agreement between the Swedish government and the country councils, the ALF agreement (73740) (to V.F.). The work of S.P.A. was supported by a grant from the Austrian Science Fund (FWF, project P32953). The work was also supported by the Italian Ministry of Health (grant RF2013-02358960) (to R.C.). A.N.D. was supported by the Ministry of Education, Youth and Sports of the Czech Republic (project CEITEC 2020 LQ1601). M.S. and D.M.C. were supported by the Ministry of Science and Higher Education of the Russian Federation (project 075-15-2019-1789). None of the funding sources had any involvement in the study design. We thank Dr. Mattias Svensson for critical input to the manuscript. We are also thankful to Dr. Vincent Collins for help with language editing of the manuscript.</p

White Paper of Italian Gastroenterology: Delivery of services for digestive diseases in Italy: Weaknesses and strengths

In 2011 the three major Italian gastroenterological scientific societies (AIGO, the Italian Society of Hospital Gastroenterologists and Endoscopists; SIED, the Italian Society of Endoscopy; SIGE, the Italian Society of Gastroenterology) prepared their official document aimed at analysing medical care for digestive diseases in Italy, on the basis of national and regional data (Health Ministry and Lombardia, Veneto, Emilia-Romagna databases) and to make proposals for planning of care. Digestive diseases were the first or second cause of hospitalizations in Italy in 1999-2009, with more than 1,500,000 admissions/year; however only 5-9% of these admissions was in specialized Gastroenterology units. Reported data show a better outcome in Gastroenterology Units than in non-specialized units: shorter average length of stay, in particular for admissions with ICD-9-CM codes proxying for emergency conditions (6.7 days versus 8.4 days); better case mix (higher average diagnosis-related groups weight in Gastroenterology Units: 1 vs 0.97 in Internal Medicine units and 0.76 in Surgery units); lower inappropriateness of admissions (16-25% versus 29-87%); lower in-hospital mortality in urgent admissions (2.2% versus 5.1%); for patients with urgent admissions due to gastrointestinnal haemorrhage, in-hospital mortality was 2.3% in Gastroenterology units versus 4.0% in others. The present document summarizes the scientific societies' official report, which constitutes the "White paper of Italian Gastroenterology". © 2014 Editrice Gastroenterologica Italiana S.r.l