Malaria Parasite Invasion of the Mosquito Salivary Gland Requires Interaction between the Plasmodium TRAP and the Anopheles Saglin Proteins

SM1 is a twelve-amino-acid peptide that binds tightly to the Anopheles salivary gland and inhibits its invasion by Plasmodium sporozoites. By use of UV-crosslinking experiments between the peptide and its salivary gland target protein, we have identified the Anopheles salivary protein, saglin, as the receptor for SM1. Furthermore, by use of an anti-SM1 antibody, we have determined that the peptide is a mimotope of the Plasmodium sporozoite Thrombospondin Related Anonymous Protein (TRAP). TRAP binds to saglin with high specificity. Point mutations in TRAP's binding domain A abrogate binding, and binding is competed for by the SM1 peptide. Importantly, in vivo down-regulation of saglin expression results in strong inhibition of salivary gland invasion. Together, the results suggest that saglin/TRAP interaction is crucial for salivary gland invasion by Plasmodium sporozoites

Synthesis and Spectroscopic Studies of Isosteviol-Calix[4]arene and -Calix[6]arene Conjugates

Novel calix[4]arene derivatives functionalized with two or four isosteviol units at the upper rim and a new calix[6]arene having six isosteviol moieties at the lower run have been synthesized. The structures of these compounds have been confirmed by NMR and mass spectrometry data. All H-1 and C-13 NMR chemical shifts of isosteviol were fully assigned by extensive NMR spectroscopic methods, and used to clarify the structures and conformations of isosteviol-calixarene, conjuates

Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid

The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the help of intravitreal in situ injection systems, which are injected with a syringe into the vitreous body and provide prolonged action of the drug at the focus of inflammation. Under the influence of temperature, the liquid drug undergoes a phase transition and turns into a gel after injection. This ensures its prolonged action. The study aimed to develop an intravitreal in situ cefuroxime delivery system for the treatment of endophthalmitis based on a thermosensitive biodegradable composition of poloxamer 407 and hyaluronic acid. A combination of poloxamer Kolliphor® P407, Kolliphor® P188, and PrincipHYAL® hyaluronic acids of different molecular weights was used as a delivery system. The potency of cefuroxime solid dispersion with polyvinylpyrrolidone-10000, polyethylene glycol-400, and polyethylene glycol-1500 in a 1:2 ratio was studied for prolonged action compared to cefuroxime substance. The experimental formulations were studied for the parameters of gelation temperature in a long-term test (4 months), pH, and release of cefuroxime using dialysis bags. To study the distribution parameter in the vitreous body, an in vitro model (1/13) was developed, which was a hollow agar sphere filled with 1% (w/v) polyacrylate gel. For the superior formulations, a HET-CAM test (chorioallantoic membrane test) was performed to determine the absence of irritant effects. According to the study results, a formulation containing a solid dispersion of cefuroxime:PEG-400 (1:2), the matrix of which contained 18% (w/v) Kolliphor® P407 poloxamer, 3% (w/v) Kolliphor® P188 poloxamer, and 0.5% (w/v) hyaluronic acid (1400–1800), was selected. This sample had an average gelation temperature of 34.6 °C, pH 6.7 ± 0.5, and a pronounced prolonged effect. Only 7.6% was released in 3 h of the experiment, whereas about 38% of cefuroxime was released in 72 h. No irritant effect on the chorioallantoic membrane was observed for any formulations studied

The unseen water: Experimentation with scientific photomicrography and creative coding

This research involves aesthetic approaches to scientific photomicrography. Specifically, this project investigates the reinterpretation of photomicrographic images of micro-scale drops of water made by a Scanning Electron Microscope (SEM), a tool that has expanded the boundaries of observation and representation of the micro world since it was introduced to scientific research in the mid-1960s. I was not aiming to produce scientific records through my use of the SEM; instead, like several artists before me, I used scientific photography methods to create aesthetic images. By exploring the interplay between the indexical and iconic modalities in the process of creating photomicrographs, I seek to imbue them with new meanings and re-appropriate scientific photography as a creative practice and a source of science communication to the general public. Building on the fact that scientific and digital tools have brought new ways of seeing the world, my artistic application of them seeks to extend our perception. This paper provides an explanation of the production of interactive artworks for my project. In these works, viewers are encouraged to engage with photomicrographs of water through touch and movement, which resembles human interaction with water

A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma

Background: Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs.Methods: Binding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFN gamma- or Granzyme B-generating CD3(+)CD8(+) T cells were detected by flow cytometry. To examine the role of CD8(+) T cells in the antitumor effect, we performed in vivo CD8(+) cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs.Results: We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8(+) T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs.Conclusions: This new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin