A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies

A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data. We also quantitatively describe the parameter space in which binding occurs. Our results point toward mechanisms relating epitope immobility to cell adhesion and offer insight into the activity of an important class of drugs.Comment: 13 pages, 5 figure

Improvement of the Trivalent Inactivated Flu Vaccine Using PapMV Nanoparticles

Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic

Immune inhibitory proteins and their pathogenic and therapeutic implications in autoimmunity and autoimmune hepatitis

Key inhibitory proteins can blunt immune responses to self-antigens, and deficiencies in this repertoire may promote autoimmunity. The goals of this review are to describe the key immune inhibitory proteins, indicate their possible impact on the development of autoimmune disease, especially autoimmune hepatitis, and encourage studies to clarify their pathogenic role and candidacy as therapeutic targets. English abstracts were identified in PubMed by multiple search terms. Full length articles were selected for review, and secondary and tertiary bibliographies were developed. Cytotoxic T lymphocyte antigen-4 impairs ligation of CD28 to B7 ligands on antigen presenting cells and inhibits the adaptive immune response by increasing anti-inflammatory cytokines, generating regulatory T cells, and reducing T cell activation and proliferation. Programed cell death antigen-1 inhibits T cell selection, activation, and proliferation by binding with two ligands at different phases and locations of the immune response. A soluble alternatively spliced variant of this protein can dampen the inhibitory signal. Autoimmune hepatitis has been associated with polymorphisms of the cytotoxic T lymphocyte antigen-4 gene, reduced hepatic expression of a ligand of programed cell death antigen-1, an interfering soluble variant of this key inhibitory protein, and antibodies against it. Findings have been associated with laboratory indices of liver injury and suboptimal treatment response. Abatacept, belatacept, CD28 blockade, and induction of T cell exhaustion are management considerations that require scrutiny. In conclusion, deficiencies in key immune inhibitory proteins may promote the occurrence of autoimmune diseases, such as autoimmune hepatitis, and emerging interventions may overcome these deficiencies. Investigations should define the nature, impact and management of these inhibitory disturbances in autoimmune hepatitis

Exploring PEGylated and immobilized laccases for catechol polymerization

Laccases have been reported for their ability to eliminate hazardous phenolic compounds by oxidative polymerization. The exploitation of the oxidative behavior of different laccase forms, namely free/native, free/PEGylated, immobilized/native and immobilized/PEGylated, was assessed in this study. We found that PEGylated and immobilized laccase forms have differentiated catalytic behavior revealing distinct conversion rates and differentiated poly(catechol) chains, as confirmed by UV--Visible spectroscopy, by the total content of OH groups and by MALDI-TOF spectroscopy. The synergy underlying on the immobilized/PEGylated enzyme forms reveal to be responsible for the highest conversion rates and for the longer polymers produced.This study was supported by Chinese Government Scholarship under China Scholarship Council (No. 201606790036) and Chinese Foundation Key projects of governmental cooperation in international scientific and technological innovation (No. 2016 YFE0115700) and by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI‑01‑0145‑FEDER‑006684) and BioTecNorte operation (NORTE‑01‑0145‑FEDER‑000004) funded by European Regional Development Fund under the scope of Norte2020—Programa Oper‑ acional Regional do Norte. Jennifer Noro also thanks to FCT‑ Fundação para a Ciência e a Tecnologia for funding her scholarship (SFRH/BD/121673/2016). Carla Silva is an investigator FCT (SFRH/IF/00186/2015).info:eu-repo/semantics/publishedVersio

A hybrid life cycle assessment of public transportation buses with alternative fuel options

Purpose: Alternative fuel options are gaining popularity in the vehicle market. Adopting alternative fuel options for public transportation compared to passenger vehicles contributes exponentially to reductions in transportation-related environmental impacts. Therefore, this study aims to present total air pollutant emissions and water withdrawal impacts through the lifetime of a transit bus with different fuel options. Methods: In consideration of market share and future development trends, diesel, biodiesel, compressed natural gas (CNG), liquefied natural gas (LNG), hybrid (diesel-electric), and battery electric (BE) transit buses are analyzed with an input-output (IO)-based hybrid life cycle assessment (LCA) model. In order to accommodate the sensitivity of total impacts to fuel economy, three commonly used driving cycles are considered: Manhattan, Central Business District (CBD), and Orange County Transit Authority (OCTA). Fuel economy for each of these driving cycles varies over the year with other impacts, so a normal distribution of fuel economy is developed with a Monte Carlo simulation model for each driving cycle and corresponding fuel type. Results and discussion: Impacts from a solar panel (photovoltaic, PV) charging scenario and different grid mix scenarios are evaluated and compared to the nation’s average grid mix impacts from energy generation to accommodate the lifetime electricity needs for the BE transit bus. From these results, it was found that the BE transit bus causes significantly low CO2 emissions than diesel and other alternative fuel options, while some of the driving cycles of the hybrid-powered transit bus cause comparable emissions to BE transit bus. On the other hand, lifetime water withdrawal impacts of the diesel and hybrid options are more feasible compared to other options, since electricity generation and natural gas manufacturing are both heavily dependent on water withdrawal. In addition, the North American Electricity Reliability Corporation’s (NERC) regional electricity grid mix impacts on CO2 emissions and water withdrawal are presented for the BE transit bus. Conclusions: As an addition of current literature, LCA of alternative fuel options was performed in this paper for transit buses with the consideration of a wide variety of environmental indicators. Although the results indicate that BE and hybrid-powered buses have less environmental emissions, the US’s dependency on fossil fuel for electricity generation continues to yield significant lifetime impacts on BE transit bus operation. With respect to water withdrawal impacts, we believe that the adoption of BE transit buses will be faster and more environmentally feasible for some NREC regions than for others