The HOX Gene Cluster in the Bivalve Mollusc Mytilus galloprovincialis

The clustered Hox genes play a central role in the regulation of development in bilaterian animals. In this study, we analyzed the homeobox-containing genes in a bivalve mollusc, the mussel Mytilus galloprovincialis, an unsegmented spiralian lophotrochozoan. We isolated and characterized four Hox cluster genes using the polymerase chain reaction with specific primers. Molecular alignments and phylogenetic analysis indicate that these mussel genes are homologs of the anterior group (pb ortholog), paralog group 3, and central group (PG4/Dfd and PG5/Scr) genes. The putative homeodomain sequences were designated Mgox1, Mgox2, Mgox3, and Mgox4.     

The new face of nucleolin in human melanoma

Nucleolin is multifunctional protein mainly present in nucleoli but also detected in cytoplasm and plasma membranes. Extranuclear nucleolin differs from the nuclear form by its glycosylation. Studies on expression of nucleolin in breast cancer suggest a possible association to the metastatic cascade. In the present study, Vicia villosa lectin (VVL) precipitation followed by subsequent polyacrylamide gel electrophoresis and mass spectrometry analysis demonstrates nucleolin as a VVL-positive glycoprotein expressed in melanoma. The presence of VVL-positive nucleolin in the melanoma cell membrane and cytoplasm was confirmed by confocal microscopy. Using bioinformatic peptide prediction programs, nucleolin was shown to contain multiple possible MHC class-I binding peptides in its sequence which makes nucleolin an interesting melanoma marker and target for immunodiagnostic and possibly therapeutic purposes. This paper is an original contribution from the meeting which took place on 28–and 29 May, 2008, in Nottingham, UK, celebrating the contribution of Professor I.A. “Tony” Dodi (+29.1.2008) to the EU project “Network for the identification and validation of antigens and biomarkers in cancer and their application in clinical tumour immunology (ENACT)”.     

Relationship between serum Se concentration in dogs and incidence of some disease conditions

The aim of the study was to determine if there is a relationship between serum selenium concentration in dogs and their health, and to assess the relationship between selenium concentration and morphological parameters of blood. Mean serum selenium concentration in dogs ranged from 0.169 to 0.273 mg/ml. Dogs diagnosed with malignant neoplasm had a significantly lower mean concentration of serum selenium compared to healthy dogs and those from the groups studied. The present study showed no statistically significant differences in Se serum content according to sex, age, and food type. Dogs diagnosed with malignant neoplasm had a significantly lower mean serum selenium concentration compared to healthy dogs and those from the other groups analysed, namely with hip dysplasia, allergy and fractures and with non-malignant tumour. Healthy dogs were characterized by the highest mean serum selenium concentration, significantly higher compared to dogs with non-malignant tumour, malignant neoplasm, allergy and fractures. Low levels of selenium contribute to the incidence of neoplasms and allergies and increase the risk of bone fractures in dogs. Additional laboratory tests should be conducted when certain diseases are diagnosed to determine Se concentration in dogs, thus making it possible to take preventive measures or therapeutic action.     

Accommodating receptor flexibility and free energy calculation to reduce false positive binders in the discovery of natural products blockers of SARS-COV-2 spike RBD-ACE2 interface

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which causes coronavirus disease-19 (COVID-19) has caused more than 2 million deaths around the globe. The high transmissibility rate of the disease is related to the strong interaction between the virus spike receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) as documented in several reports. In this study, using state-of-the-art computational methods, natural products were screened and their molecular mechanism to disrupt spike RBD-ACE2 recognition was evaluated. There is the sensitivity of results to receptor ensemble docking calculations. Binding free energy and MD simulation are important tools to evaluate the thermodynamics of binding stability and the capacity of top hits to disrupt RBD-ACE2 recognition. The free energy profiles provide a slight decrease in binding affinity of the virus-receptor interaction. Three flavonoids parvisoflavone B (3), alpinumisoflavone (5) and norisojamicin (2) were effective in blocking the viral entry by binding strongly at the spike RBD-ACE2 interface with the inhibition constant of 0.56, 0.78 and 0.93 μM, respectively. The same compounds demonstrated similar effect on free ACE2 protein. Compound (2), also demonstrated ability to bind strongly on free spike RBD. Well-tempered metadynamics established that parvisoflavone B (3) works by binding to three sites namely interface α, β and loop thereby inhibiting viral cell entry. Owing to their desirable pharmacokinetic properties, the presented top hit natural products are suggested for further SARS-COV-2 molecular targets and subsequent in vitro and in vivo evaluations.