Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model

Glioblastoma is an aggressive brain tumour found in adults, and the therapeutic approaches available have not significantly increased patient survival. Recently, we discovered that ELTD1, an angiogenic biomarker, is highly expressed in human gliomas. Polyclonal anti‐ELTD1 treatments were effective in glioma pre‐clinical models, however, pAb binding is potentially promiscuous. Therefore, the aim of this study was to determine the effects of an optimized monoclonal anti‐ELTD1 treatment in G55 xenograft glioma models. MRI was used to assess the effects of the treatments on animal survival, tumour volumes, perfusion rates and binding specificity. Immunohistochemistry and histology were conducted to confirm and characterize microvessel density and Notch1 levels, and to locate the molecular probes. RNA‐sequencing was used to analyse the effects of the mAb treatment. Our monoclonal anti‐ELTD1 treatment significantly increased animal survival, reduced tumour volumes, normalized the vasculature and showed higher binding specificity within the tumour compared with both control‐ and polyclonal‐treated mice. Notch1 positivity staining and RNA‐seq results suggested that ELTD1 has the ability to interact with and interrupt Notch1 signalling. Although little is known about ELTD1, particularly about its ligand and pathways, our data suggest that our monoclonal anti‐ELTD1 antibody is a promising anti‐angiogenic therapeutic in glioblastomas.     

Molecular properties of metal difluorides and their interactions with CO<Subscript>2</Subscript> and H<Subscript>2</Subscript>O molecules: a DFT investigation

A computational study of metal difluorides (MF₂; M = Ca to Zn) and their interactions with carbon dioxide and water molecules was performed. The structural parameter values obtained and the results of AIM analysis and energy decomposition analysis indicated that the Ca–F bond is weaker and less ionic than the bonds in the transition metal difluorides. A deformation density plot revealed the stablizing influence of the Jahn–Teller effect in nonlinear MF₂ molecules (e.g., where M= Sc, Ti, Cr). An anaysis of the metal K-edge peaks of the difluorides showed that shifts in the edge energy were due to the combined effects of the ionicity, effective nuclear charge, and the spin state of the metal. The interactions of CO₂ with ScF₂ (Scc3 geometry) and TiF₂ (Tic2 geometry) caused CO₂ to shift from its usual linear geometry to a bent geometry (η²(C=O) binding mode), while it retained its linear geometry (η¹(O) binding mode) when it interacted with the other metal difluorides. Energy decomposition analysis showed that, among the various geometries considered, the Scc3 and Tic2 geometries possessed the highest interaction energies and orbital interaction energies. Heavier transition metal difluorides showed stronger affinities for H₂O, whereas the lighter transition metal (Sc and Ti) difluorides preferred CO₂. Overall, the results of this study suggest that fluorides of lighter transition metals with partially filled d orbitals (e.g., Sc and Ti) could be used for CO₂ capture under moist conditions.

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Graphical abstract Interaction of metal difluorides with carbon dioxide and water

     

Natural occurrence of trichothecene-producing Fusaria isolated from India with particular reference to sorghum

In this study a total of 167 isolates collected from different food materials (68.8% from sorghum and the remaining from various other food materials) were assayed by PCR for amplification of the tri 5 gene present in trichothecene-producing Fusaria. Amplification of the tri 5 fragment was observed in 45 isolates (39 isolates from sorghum and 6 isolates from vegetables). Isolates found positive for presence of the tri 5 gene were classified into different morphological groups based on their cultural and conidial characters; 11 of the tri 5 positive isolates from moldy grains of sorghum, one from each morphology group were selected for further analyses. Five deoxynivalenol producers and three deoxynivalenol and Fusarenon-X producers were detected by analysing culture filtrates of the 11 isolates using GC-MS. One isolate each were identified as producers of NIV alone, or NIV along with DON or DAS toxins. Identification of these isolates to the species level was carried out using spore morphology and sequence comparison of the translation elongation factor 1-alpha (EF-1α) gene against the database as well as using phylogenetic analyses. The isolates were identified as Fusarium proliferatum (6), F. nelsonii (2), F. equiseti (1), F. thapsinum (1) and F. sacchari (1). Amplified Fragment Length Polymorphism (AFLP) based grouping clustered the isolates of same species together. This is the first detailed study of trichothecene production by Fusarium spp. associated with sorghum grain mold in India and the identification of F. nelsonii and F. thapsinum as producers of trichothecenes.