Pierce into the Native Structure of Ata,a Trimeric Autotransporter of Acinetobacter baumannii ATCC 17978

International Journal of Peptide Research and Therapeutics - Acinetobacter baumannii is an important pathogen responsible for nosocomial infections worldwide. Trimeric autotransporters, the...     

Quasi-Monopolar Stimulation: A Novel Electrode Design Configuration for Performance Optimization of a Retinal Neuroprosthesis

In retinal neuroprostheses, spatial interaction between electric fields from various electrodes – electric crosstalk – may occur in multielectrode arrays during simultaneous stimulation of the retina. Depending on the electrode design and placement, this crosstalk can either enhance or degrade the functional characteristics of a visual prosthesis. To optimize the device performance, a balance must be satisfied between the constructive interference of crosstalk on dynamic range and power consumption and its negative effect on artificial visual acuity. In the present computational modeling study, we have examined the trade-off in these positive and negative effects using a range of currently available electrode array configurations, compared to a recently proposed stimulation strategy – the quasi monopolar (QMP) configuration – in which the return current is shared between local bipolar guards and a distant monopolar electrode. We evaluate the performance of the QMP configuration with respect to the implantation site and electrode geometry parameters. Our simulation results demonstrate that the beneficial effects of QMP are only significant at electrode-to-cell distances greater than the electrode dimensions. Possessing a relatively lower activation threshold, QMP was found to be superior to the bipolar configuration in terms of providing a relatively higher visual acuity. However, the threshold for QMP was more sensitive to the topological location of the electrode in the array, which may need to be considered when programming the manner in which electrode are simultaneously activated. This drawback can be offset with a wider dynamic range and lower power consumption of QMP. Furthermore, the ratio of monopolar return current to total return can be used to adjust the functional performance of QMP for a given implantation site and electrode parameters. We conclude that the QMP configuration can be used to improve visual information-to-stimulation mapping in a visual prosthesis, while maintaining low power consumption.     

The Route of Leishmania tropica Infection Determines Disease Outcome and Protection against Leishmania major in BALB/c Mice

Leishmania tropica is one of the causative agents of leishmaniasis in humans. Routes of infection have been reported to be an important variable for some species of Leishmania parasites. The role of this variable is not clear for L. tropica infection. The aim of this study was to explore the effects of route of L. tropica infection on the disease outcome and immunologic parameters in BALB/c mice. Two routes were used; subcutaneous in the footpad and intradermal in the ear. Mice were challenged by Leishmani major, after establishment of the L. tropica infection, to evaluate the level of protective immunity. Immune responses were assayed at week 1 and week 4 after challenge. The subcutaneous route in the footpad in comparison to the intradermal route in the ear induced significantly more protective immunity against L. major challenge, including higher delayed-type hypersensitivity responses, more rapid lesion resolution, lower parasite loads, and lower levels of IL-10. Our data showed that the route of infection in BALB/c model of L. tropica infection is an important variable and should be considered in developing an appropriate experimental model for L. tropica infections.     

Glutamate metabolism in HIV-1 infected macrophages: Role of HIV-1 Vpr

HIV-1 infected macrophages play a significant role in the neuropathogenesis of AIDS. HIV-1 viral protein R (Vpr) not only facilitates HIV-1 infection but also contribute to long-lived persistence in macrophages. Our previous studies using SILAC-based proteomic analysis showed that the expression of critical metabolic enzymes in the glycolytic pathway and tricarboxylic acid (TCA) cycle were altered in response to Vpr expression in macrophages. We hypothesized that Vpr-induced modulation of glycolysis and TCA cycle regulates glutamate metabolism and release in HIV-1 infected macrophages.

We assessed the amount of specific metabolites induced by Vpr and HIV-1 in macrophages at the intracellular and extracellular level in a time-dependent manner utilizing multiple reaction monitoring (MRM) targeted metabolomics. In addition, stable isotope-labeled glucose and an MRM targeted metabolomics assay were used to evaluate the de novo synthesis and release of glutamate in Vpr overexpressing macrophages and HIV-1 infected macrophages, throughout the metabolic flux of glycolytic pathway and TCA cycle activation.

The metabolic flux studies demonstrated an increase in glucose uptake, glutamate release and accumulation of α-ketoglutarate (α-KG) and glutamine in the extracellular milieu in Vpr expressing and HIV-1 infected macrophages. Interestingly, glutamate pools and other intracellular intermediates (glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), citrate, malate, α-KG, and glutamine) showed a decreased trend except for fumarate, in contrast to the glutamine accumulation observed in the extracellular space in Vpr overexpressing macrophages.

Our studies demonstrate that dysregulation of mitochondrial glutamate metabolism induced by Vpr in HIV-1 infected macrophages commonly seen, may contribute to neurodegeneration via excitotoxic mechanisms in the context of NeuroAIDS.     

Bevacizumab Antibody Affinity Maturation to Improve Ovarian Cancer Immunotherapy: In Silico Approach

International Journal of Peptide Research and Therapeutics - Ovarian cancer is one of the most lethal gynecologic cancers. The high mortality rate is due to lack of early symptoms and developing...     

Diagnostic biomarker and therapeutic target applications of miR-326 in cancers: A systematic review

MicroRNAs (miRNAs) are endogenous mediators of RNA interference and have key roles in the modulation of gene expression under healthy, inflamed, stimulated, carcinogenic, or other cells, and tissues of a pathological state. Many studies have proved the association between miRNAs and cancer. The role of miR-326 as a tumor suppressor miRNA in much human cancer confirmed. We will explain the history and the role of miRNAs changes, especially miR-326 in cancers and other pathological conditions. Attuned with these facts, this review highlights recent preclinical and clinical research performed on miRNAs as novel promising diagnostic biomarkers of patients at early stages, prediction of prognosis, and monitoring of the patients in response to treatment. All related publications retrieved from the PubMed database, with keywords such as epigenetic, miRNA, microRNA, miR-326, cancer, diagnostic biomarker, and therapeutic target similar terms from 1899 to 2018 with limitations in the English language. Recently, researchers have focused on the impacts of miRNAs and their association in inflammatory, autoinflammatory, and cancerous conditions. Recent studies have suggested a major pathogenic role in cancers and autoinflammatory diseases. Investigations have explained the role of miRNAs in cancers, autoimmunity, and autoinflammatory diseases, and so on. The miRNA-326 expression has an important role in cancer conditions and other diseases.     

The roles of moonlight ribosomal proteins in the development of human cancers

“Moonlighting protein” is a term used to define a single protein with multiple functions and different activities that are not derived from gene fusions, multiple RNA splicing, or the proteolytic activity of promiscuous enzymes. Different proteinous constituents of ribosomes have been shown to have important moonlighting extra-ribosomal functions. In this review, we introduce the impact of key moonlight ribosomal proteins and dependent signal transduction in the initiation and progression of various cancers. As a future perspective, the potential role of these moonlight ribosomal proteins in the diagnosis, prognosis, and development of novel strategies to improve the efficacy of therapies for human cancers has been suggested.