Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings

Cataloged from PDF version of article.Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon alpha (IFN alpha) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity

Potential Role of Phosphatidylinositol 3 Kinase, rather than DNA-dependent Protein Kinase, in CpG DNA–induced Immune Activation

Unmethylated CpG motifs present in bacterial DNA stimulate a strong innate immune response. There is evidence that DNA-dependent protein kinase (DNA-PK) mediates CpG signaling. Specifically, wortmannin (an inhibitor of phosphatidylinositol 3 kinase [PI3]-kinases including DNA-PK) interferes with CpG-dependent cell activation, and DNA-PK knockout (KO) mice fail to respond to CpG stimulation. Current studies establish that wortmannin actually inhibits the uptake and colocalization of CpG DNA with toll-like receptor (TLR)-9 in endocytic vesicles, thereby preventing CpG-induced activation of the NF-κB signaling cascade. We find that DNA-PK is not involved in this process, since three strains of DNA-PK KO mice responded normally to CpG DNA. These results support a model in which CpG signaling is mediated through TLR-9 but not DNA-PK, and suggest that wortmannin-sensitive member(s) of the PI3-kinase family play a critical role in shuttling CpG DNA to TLR-9

Biosorption of phenol and 2-chlorophenol by Funalia trogii pellets

Cataloged from PDF version of article.The removal of phenol (Ph) and 2-chlorophenol (2-CPh) from aqueous solution by native and heat inactivated fungus Funalia trogii pellets were investigated. The effects of contact time, solid/liquid ratio, optimum pH and temperature on the phenols removal capacity by the pellets were established. The removal efficiency of phenols increased significantly with increasing biomass dose. The optimum pH was detected to be 8.0. The second-order equations are described and evaluated on the basis of a comparative estimation of the corresponding coefficients. The phenol removal equilibrium isotherm was modeled by the Langmuir equations. The enthalpy change values were obtained between -7.62 and -10.64 kJ/mol. This indicated that the uptake of phenols either on native or heat inactivated fungal pellets was based on a physical adsorption process. © 2008 Elsevier Ltd. All rights reserved

Fuel-cell performance of multiply-crosslinked polymer electrolyte membranes prepared by two-step radiation technique

A multiply-crosslinked polymer electrolyte membrane was prepared by the radiation-induced co-grafting of styrene and a bis(vinyl phenyl)ethane (BVPE) crosslinker into a radiation-crosslinked polytetrafluoroethylene (cPTFE) film. We then investigated its H2/O2 fuel-cell performance at 60 and 80ºC in terms of the effect of radiation and chemical crosslinking. At 60ºC, all the membranes initially exhibited similar performance, but only the cPTFE-based membranes were durable at 80ºC, indicating the necessity of radiation crosslinking in the PTFE main chains. Importantly, cell performance of the multiply-crosslinked membrane was found high enough to reach that of a Nafion112 membrane. This is probably because the BVPE crosslinks in the graft component improved the membrane-electrode interface in addition to membrane durability. After severe OCV hold tests at 80 and 95ºC, the performance deteriorated, while no significant change was observed in ohmic resistivity. Accordingly, our membranes seemed so chemically stable that an influence on overall performance loss could be negligible

Intestinal microbiota in patients with spinal cord injury

Human intestinal flora comprises thousands of bacterial species. Growth and composition of intestinal microbiota is dependent on various parameters, including immune mechanisms, dietary factors and intestinal motility. Patients with spinal cord injury (SCI) frequently display neurogenic bowel dysfunction due to the absence of central nervous system control over the gastrointestinal system. Considering the bowel dysfunction and altered colonic transit time in patients with SCI, we hypothesized the presence of a significant change in the composition of their gut microbiome. The objective of this study was to characterize the gut microbiota in adult SCI patients with different types of bowel dysfunction. We tested our hypothesis on 30 SCI patients (15 upper motor neuron [UMN] bowel syndrome, 15 lower motor neuron [LMN] bowel syndrome) and 10 healthy controls using the 16S rRNA sequencing. Gut microbial patterns were sampled from feces. Independent of study groups, gut microbiota of the participants were dominated by Blautia, Bifidobacterium, Faecalibacterium and Ruminococcus. When we compared all study groups, Roseburia, Pseudobutyrivibrio, Dialister, Marvinbryantia and Megamonas appeared as the genera that were statistically different between groups. In comparison to the healthy group, total bacterial counts of Pseudobutyrivibrio, Dialister and Megamonas genera were significantly lower in UMN bowel dysfunction group. The total bacterial count of Marvinbryantia genus was significantly lower in UMN bowel dysfunction group when compared to the LMN group. Total bacterial counts of Roseburia, Pseudobutyrivibrio and Megamonas genera were significantly lower in LMN bowel dysfunction group when compared to healthy groups. Our results demonstrate for the first time that butyrate-producing members are specifically reduced in SCI patients when compared to healthy subjects. The results of this study would be of interest since to our knowledge, microbiome-associated studies targeting SCI patients are non-existent and the results might help explain possible implications of gut microbiome in SCI. Copyright © 2016 Gungor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

3D printed flexure hinges for soft monolithic prosthetic fingers

Mechanical compliance is one of the primary properties of structures in nature playing a key role in their efficiency. This study investigates a number of commonly used flexure hinges to determine a flexure hinge morphology, which generates large displacements under a lowest possible force input. The aim of this is to design a soft and monolithic robotic finger. Fused deposition modeling, a low-cost 3D printing technique, was used to fabricate the flexure hinges and the soft monolithic robotic fingers. Experimental and finite element analyses suggest that a nonsymmetric elliptical flexure hinge is the most suitable type for use in the soft monolithic robotic finger. Having estimated the effective elastic modulus, flexion of the soft monolithic robotic fingers was simulated and this showed a good correlation with the actual experimental results. The soft monolithic robotic fingers can be employed to handle objects with unknown shapes and are also potential low-cost candidates for establishing soft and one-piece prosthetic hands with light weight. A three-finger gripper has been constructed using the identified flexure hinge to handle objects with irregular shapes such as agricultural products

Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development

Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading. Furthermore, they protect cargo from enzymatic cleavage while providing stability, and enhancing biological activity. Herein, we aimed to develop a liposomal carrier system co-encapsulating TLR3 (polyinosinic-polycytidylic acid; poly(I:C)) and TLR9 (oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs; CpG ODN) ligands as immunoadjuvants together with protein antigen. To demonstrate that this depot system not only induce synergistic innate immune activation but also boost antigen-dependent immune response, we analyzed the potency of dual ligand encapsulated liposomes in long-term cancer protection assay. Data revealed that CpG ODN and poly(I:C) co-encapsulation significantly enhanced cytokine production from spleen cells. Activation and maturation of dendritic cells as well as bactericidal potency of macrophages along with internalization capacity of ligands were elevated upon incubation with liposomes co-encapsulating CpG ODN and poly(I:C). Immunization with co-encapsulated liposomes induced OVA-specific Th1-biased immunity which persisted for eight months post-booster injection. Subsequent challenge with OVA-expressing tumor cell line, E.G7, demonstrated that mice immunized with liposomes co-encapsulating dual ligands had significantly slower tumor progression. Tumor clearance was dependent on OVA-specific cytotoxic memory T-cells. These results suggest that liposomes co-encapsulating TLR3 and TLR9 ligands and a specific cancer antigen could be developed as a preventive cancer vaccine. � 2017 Elsevier B.V

A 3D-Printed Omni-Purpose Soft Gripper

Numerous soft grippers have been developed based on smart materials, pneumatic soft actuators, and underactuated compliant structures. In this article, we present a three-dimensional (3-D) printed omni-purpose soft gripper (OPSOG) that can grasp a wide variety of objects with different weights, sizes, shapes, textures, and stiffnesses. The soft gripper has a unique design that incorporates soft fingers and a suction cup that operate either separately or simultaneously to grasp specific objects. A bundle of 3-D-printable linear soft vacuum actuators (LSOVA) that generate a linear stroke upon activation is employed to drive the tendon-driven soft fingers. The support, fingers, suction cup, and actuation unit of the gripper were printed using a low-cost and open-source fused deposition modeling 3-D printer. A single LSOVA has a blocked force of 30.35 N, a rise time of 94 ms, a bandwidth of 2.81 Hz, and a lifetime of 26 120 cycles. The blocked force and stroke of the actuators are accurately predicted using finite element and analytical models. The OPSOG can grasp at least 20 different objects. The gripper has a maximum payload-to-weight ratio of 7.06, a grip force of 31.31 N, and a tip blocked force of 3.72 N

Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction

Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients. © 2017 Gucluler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited