Cloning and Expression of the Green Fluorescent Protein (GvFP) from the Clinging Jellyfish (Gonionemus vertens) Using RNA-Seq

We have discovered a novel GFP in the clinging jellyfish (Gonionemus vertens), a protein we have named GvFP (Gonionemus vertens Fluorescent Protein). This protein is responsible for the bright green fluorescence seen in the rhopalia along the margin of the bell, the gonads associated with the radial canals, and the manubrium when illuminated with blue light (470 nm). GvFP was first identified by Nextgen sequencing (RNA-Seq) of libraries made from mRNA of mature medusa collected from a salt pond on Martha’s Vineyard, MA. The full-length GvFP gene is 690 bp, encoding a protein of 230 AA (25.95 kDa; pI = 5.74). This protein shows low homology (43%) to the classic wtGFP from Aequorea victoria, but higher homology (86%) to another GFP (ScSuFP) from the Hydrozoan Scolionema suvaence. The tripeptide chromophore in GvFP - MYG - is unique among hydrozoans and has only been reported once before in Anemonia sulcata (Class Anthozoa). PHYRE2 analysis of GvFP predicts a β-barrel conformation and a 2° structure of 55% β-sheet, 7% alpha-helix, and 13% disordered structure, modelled at \u3e90% confidence. The dimensions of the protein are 6.8 nm x 5.4 nm x 3.8 nm. Cloning of the full-length GvFP (Contig 6770) into the pET-SUMO expression vector and transformation into E. coli (BL21(DE3)) has expressed a recombinant GvFP that is a near perfect match in excitation and emission maxima of the native in vivo GvFP. Future work on this novel GFP may shed light on its unique chromophore and further our understanding of the ecological consequences of biological fluorescence in this jellyfish

Efficacy of interferon in multiple sclerosis

Introduction of interferon b-1b in the therapeutic strategy against Multiple Sclerosis has resulted in a great amelioration of treatment in various terms. Relapse rates, delaying progression of the activity, improvement of imaging outcomes as well as reduction of disease activity itself consist great achievements against a pathological condition that challenged medical effectiveness throughout decades. Two recombinant human IFN-1a and an IFN-1b preparations have been proved effected and well tolerated. We reviewed the most important literature concerning pharmacodynamics, medical efficacy, tolerability and adverse effects of interferon-b usage. In parallel, despite the wide range of trials referring to INF-b treatment, we tried to categorize results of main trials in order to present our conclusions systematicall

Potentially inappropriate medication use in older adults with mild-moderate Alzheimer's disease:Prevalence and associations with adverse events

Aim: Potentially inappropriate medication (PIM) use is prevalent in older adults and is associated with adverse events, hospitalisation and mortality. We assessed the patterns and associations of PIM use in older adults with mild-to-moderate Alzheimer's Disease (AD), who may represent a particularly vulnerable group. Design: Analysis of data from NILVad, an 18-month Randomised Control Trial of Nilvadapine in mild-to-moderate AD. The v2 STOPP criteria were applied in duplicate to identify PIM use. Associations between PIM use and adverse events/unscheduled healthcare visits in addition to the associations between PIM use and AD progression were evaluated. Setting and Participants: 448 older adults with mild-to-moderate AD from 23 centres in nine European countries. Results: Of 448 participants (mean age: 72.56 ± 8.19 years), over half (55.8%) were prescribed a PIM with 30.1% being prescribed 2+ PIMs. The most frequent PIMs were (i) long-term benzodiazepines (11.6% N = 52/448), (ii) selective serotonin reuptake inhibitors without appropriate indication (11.1% N = 50/448), and (iii) Proton-Pump Inhibitors (PPIs) without appropriate indication (10.7% N = 48/448). Increasing number of PIMs was associated with a greater risk of adverse events (IRR 1.17, 1.13-1.19, P < 0.001), serious adverse events (IRR 1.27; 1.17-1.37, P < 0.001), unscheduled hospitalisations (IRR 1.16, 1.03-1.30, P = 0.016) and GP visits (IRR 1.22, 1.15-1.28, P < 0.001). PIM use was not associated with dementia progression. Conclusions and Implications: PIM use is highly prevalent in mild-to-moderate AD and is associated with adverse events and unscheduled healthcare utilisation. Further attention to de-prescribing in this vulnerable group is warranted

Multiple sclerosis registries in Europe – An updated mapping survey

Highlights Nineteen questionnaires from European MS registries were analysed. Aim and focus as well as number of patients and inclusion criteria vary considerably. Most of the MS registries collect data within common general categories. There are more pronounced differences regarding specific subcategories

Ex vivo models simulating the bone marrow environment and predicting response to therapy in multiple myeloma

Multiple myeloma (MM) remains incurable despite the abundance of novel drugs. As it has been previously shown, preclinical 2D models fail to predict disease progression due to their inability to simulate the microenvironment of the bone marrow. In this review, we focus on 3D models and present all currently available ex vivo MM models that fulfil certain criteria, such as development of complex 3D environments using patients’ cells and ability to test different drugs in order to assess personalized MM treatment efficacy of various regimens and combinations. We selected models representing the top-notch ex vivo platforms and evaluated them in terms of cost, time-span, and feasibility of the method. Finally, we propose where such a model can be more informative in a patient’s treatment timeline. Overall, advanced 3D preclinical models are very promising as they may eventually offer the opportunity to precisely select the optimal personalized treatment for each MM patient. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

4th Summer School in Immuno-Oncology, July 1st-3rd, 2021, Athens, Greece

The 4th Summer School in Immuno-Oncology was held from July 1st-July 3rd as a web meeting. Many eminent researchers and leading oncologists from Europe and the USA working on basic, translational and clinical cancer research participated, presented, and discussed the most recent advances in cancer immunology and immunotherapy. Besides sharing the newest information in the field of cancer immunology and immunotherapy, the meeting also focused on the actual translation of new knowledge acquired in the lab to the clinical setting; particular emphasis was given to the mode of action of novel therapeutic modalities and to biomarkers helpful for treatment decision-making, as well as to means that may improve cancer immunotherapeutic protocols used for the treatment of a variety of malignancies. The main topics presented by the speakers included: (1) mechanisms of tumor immune evasion and resistance; (2) host-tumor interactions and means to regulate antitumor immunity; (3) exploitation of new biomarkers and tumor or immune signatures able to potentially guide therapeutic interventions; (4) emerging therapeutic modalities for cancer treatment and specific immunotherapeutics for thoracic, genito-urinary, gastrointestinal, skin and breast cancers; and (5) innovative treatment options and alternatives to minimize the toxic adverse events of cancer immunotherapy. © 2021 The Author(s). Published by BRI

Cysteinyl leukotriene receptors in tonsillar B- and T-lymphocytes from children with obstructive sleep apnea

Objectives: Cysteinyl leukotrienes have been implicated in the pathogenesis of adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). This study aimed to quantify the expression of cysteinyl leukotriene receptors (CysLT(1), CysLT(2)) by tonsillar lymphocyte subpopulations from children with OSA and to make comparisons to lymphocyte subpopulations from control subjects with recurrent tonsillitis (RT). Methods: Tonsillar tissue from children with OSA or RT was studied for CysLT(1) and CysLT(2) expression by RT-PCR, flow cytometry (FC), and immunofluorescence. Results: Ten children with OSA and 10 control subjects were recruited. In OSA participants, CysLT(1)+ fraction of small-size CD19+ B-lymphocytes was similar to the CysLT(1)+ CD3+ T-lymphocytes fraction (FC: 36.5 [16.5-55.4] vs. 14 [2.8-22.1]) (p > 0.05) and higher than the CysLT(1)+ moderate/large-size CD19+ B-lymphocytes fraction (6.6 [1.5-14.4]) (p < 0.01). Similar trends were recognized for CysLT(2). CysLT(1) and CysLT(2) immunoreactivity was detected by immunofluorescence in the tonsillar mantle zones (small B-lymphocytes) and the extrafollicular areas (T-lymphocytes). Compared to subjects with RT, children with OSA had significantly higher expression of CysLT(1) in small-size CD19+ B-lymphocytes (FC) and in CD3+ T-lymphocytes (RT-PCR and FC) (p < 0.05). Conclusions: Increased expression of leukotriene receptors by immunologically active tonsillar, areas in children with OSA is a potential therapeutic target for pediatric sleep apnea. (C) 2012 Elsevier B.V. All rights reserved

Ex vivo models simulating the bone marrow environment and predicting response to therapy in multiple myeloma

Multiple myeloma (MM) remains incurable despite the abundance of novel drugs. As it has been previously shown, preclinical 2D models fail to predict disease progression due to their inability to simulate the microenvironment of the bone marrow. In this review, we focus on 3D models and present all currently available ex vivo MM models that fulfil certain criteria, such as development of complex 3D environments using patients&rsquo; cells and ability to test different drugs in order to assess personalized MM treatment efficacy of various regimens and combinations. We selected models representing the top-notch ex vivo platforms and evaluated them in terms of cost, time-span, and feasibility of the method. Finally, we propose where such a model can be more informative in a patient&rsquo;s treatment timeline. Overall, advanced 3D preclinical models are very promising as they may eventually offer the opportunity to precisely select the optimal personalized treatment for each MM patient