In Vivo Tracking of Human Neural Stem Cells with 19F Magnetic Resonance Imaging

(c)The Author

Retromer and Its Role in Regulating Signaling at Endosomes.

The retromer complex is a key element of the endosomal protein sorting machinery being involved in trafficking of proteins from endosomes to the Golgi and also endosomes to the cell surface. There is now accumulating evidence that retromer also has a prominent role in regulating the activity of many diverse signaling proteins that traffic through endosomes and this activity has profound implications for the functioning of many different cell and tissue types from neuronal cells to cells of the immune system to specialized polarized epithelial cells of the retina. In this review, the protein composition of the retromer complex will be described along with many of the accessory factors that facilitate retromer-mediated endosomal protein sorting to detail how retromer activity contributes to the regulation of several distinct signaling pathways

Functional imaging using fluorine ((19)F) MR methods: basic concepts

Kidney-associated pathologies would greatly benefit from noninvasive and robust methods that can objectively quantify changes in renal function. In the past years there has been a growing incentive to develop new applications for fluorine ((19)F) MRI in biomedical research to study functional changes during disease states. (19)F MRI represents an instrumental tool for the quantification of exogenous (19)F substances in vivo. One of the major benefits of (19)F MRI is that fluorine in its organic form is absent in eukaryotic cells. Therefore, the introduction of exogenous (19)F signals in vivo will yield background-free images, thus providing highly selective detection with absolute specificity in vivo. Here we introduce the concept of (19)F MRI, describe existing challenges, especially those pertaining to signal sensitivity, and give an overview of preclinical applications to illustrate the utility and applicability of this technique for measuring renal function in animal models. This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis

Inhibition of influenza A virus replication by short double-stranded oligodeoxynucleotides

Influenza A virus causes prevalent respiratory tract infections in humans. Small interfering RNA (siRNA) and antisense oligonucleotides (asODNs) have been used previously for silencing the RNA genome of influenza virus. Here, we explored the use of partially double-stranded oligodeoxynucleotides (dsODNs) to suppress the production of influenza A virus in cell cultures and animal models. We were able to inhibit influenza A virus replication in cultured human lung cells as well as in the lungs of infected C57BL/6 mice by treatment with dsODN 3-h post-infection. In about 20% of the cases (15/77) the titer was reduced by 10- to 100-fold and in 10% up to 1,000-fold. The antiviral effects of dsODNs were dose-dependent, sequence-dependent and comparable to those of its antisense and siRNA analogues. Thus, dsODNs may be developed as an additional class of nucleic acids for the inhibition of influenza virus replication

Fluorine-19 nuclear magnetic resonance of chimeric antigen receptor T cell biodistribution in murine cancer model

Abstract Discovery of effective cell therapies against cancer can be accelerated by the adaptation of tools to rapidly quantitate cell biodistribution and survival after delivery. Here, we describe the use of nuclear magnetic resonance (NMR) ‘cytometry’ to quantify the biodistribution of immunotherapeutic T cells in intact tissue samples. In this study, chimeric antigen receptor (CAR) T cells expressing EGFRvIII targeting transgene were labeled with a perfluorocarbon (PFC) emulsion ex vivo and infused into immunocompromised mice bearing subcutaneous human U87 glioblastomas expressing EGFRvIII and luciferase. Intact organs were harvested at day 2, 7 and 14 for whole-sample fluorine-19 (19F) NMR to quantitatively measure the presence of PFC-labeled CAR T cells, followed by histological validation. NMR measurements showed greater CAR T cell homing and persistence in the tumors and spleen compared to untransduced T cells. Tumor growth was monitored with bioluminescence imaging, showing that CAR T cell treatment resulted in significant tumor regression compared to untransduced T cells. Overall, 19F NMR cytometry is a rapid and quantitative method to evaluate cell biodistribution, tumor homing, and fate in preclinical studies

Does One Size Fit All? Patents, the Right to Health and Access to Medicines

The question posed in this article is whether the right to health and patents conflict or coexist. This question is examined from the perspective of the issue of access to affordable medicines in developing countries focusing on the right to health as set out in the ICESCR and patent standards (and flexibilities) as required by the TRIPS Agreement. In the strict sense, there is no conflict between the right to health and patents. ICESCR and TRIPS do not contain mutually exclusive obligations. Yet, it is shown that tension between the two does exist. There are a number of ways in which such tension can be resolved. The UN Sub-Commission for the Promotion and Protection of Human Rights has contended that human rights should enjoy primacy over patents, yet there is no evidence to suggest that the right to health and/ or access to essential medicines are considered prioritised norms under international law. The WTO disagrees and views IPRs and human rights as complementary. In international law there is a strong presumption against conflict. In line with the principle of systemic integration a good faith interpretation of the relevant WTO and human rights provisions should lead to a reading of TRIPS' obligations which is coherent with human rights law. However, this balancing act must also take place at the domestic level and the success of such a coexistence approach, namely whether (developing) states are able to strike a balance between access to medicines and patent protection, will depend much on the actual implementation and interpretation by states. Consequently, some examples of state practice regarding the interpretation and implementation of TRIPS in light of the right to health are highlighted