Using Immunoinformatics and Structural Approaches to Design a Novel HHV8 Vaccine

International Journal of Peptide Research and Therapeutics - Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) has caused infection in different parts of the...     

Programmable assembly of 2D crystalline protein arrays into covalently stacked 3D bionanomaterials

Rational embellishment of self-assembling two-dimensional (2D) proteins make it possible to build 3D nanomaterials with novel catalytic, optoelectronic and mechanical properties. However, introducing multiple sites of embellishment into 2D protein arrays without affecting the self-assembly is challenging, limiting the ability to program in additional functionality and new 3D configurations. Here we introduce two orthogonal covalent linkages at multiple sites in a 2D crystalline-forming protein without affecting its self-assembly. We first engineered the surface-layer protein SbsB from Geobacillus stearothermophilus pV72/p2 to display isopeptide bond-forming protein conjugation pairs, SpyTag or SnoopTag, at four positions spaced 5.7-10.5 nm apart laterally and 3 nm axially. The C-terminal and two newly-identified locations within SbsB monomer accommodated the short SpyTag or SnoopTag peptide tags without affecting the 2D lattice structure. Introducing tags at distinct locations enabled orthogonal and covalent binding of SpyCatcher- or SnoopCatcher-protein fusions to micron-sized 2D nanosheets. By introducing different types of bifunctional cross-linkers, the dual-functionalized nanosheets were programmed to self-assemble into different 3D stacks, all of which retain their nanoscale order. Thus, our work creates a modular protein platform that is easy to program to create dual-functionalized 2D and lamellar 3D nanomaterials with new catalytic, optoelectronic, and mechanical properties.     

Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment

Despite many advances and optimization in colon cancer treatment, tumor recurrence and metastases make the development of new therapies necessary. Colon cancer stem cells (CCSCs) are considered as the main triggering factor of cancer progression, recurrence, and metastasis. CCSCs as a result of accumulated genetic and epigenetic alterations and also complex interconnection with the tumor microenvironment (TME) can evolve and convert to full malignant cells. Mounting evidence suggests that in cancer therapy both CCSCs and non-CCSCs in TME have to be regarded to break through the limitation of current therapies. In this regard, stem cell capabilities of some non-CCSCs may arise inside the TME condition. Therefore, a deep knowledge of regulatory mechanisms, heterogeneity, specific markers, and signaling pathways of CCSCs and their interconnection with TME components is needed to improve the treatment of colorectal cancer and the patient's life quality. In this review, we address current different targeted therapeutic options that target cell surface markers and signaling pathways of CCSCs and other components of TME. Current challenges and future perspectives of colon cancer personalized therapy are also provided here. Taken together, based on the deep understanding of biology of CCSCs and using three-dimensional culture technologies, it can be possible to reach successful colon cancer eradication and improvise combination targeted therapies against CCSCs and TME.     

Elevated nutrient inputs to marshes differentially impact carbon and nitrogen cycling in two northern Gulf of Mexico saltmarsh plants

Peatlands have accumulated vast quantities of organic carbon over thousands of years but it is unclear how these sensitive ecosystems will respond to future climate change. If emissions of methane from peatlands increase, then they may contribute increasingly towards climatic warming due to the higher greenhouse warming potential of this gas. We investigated the radiocarbon concentration of methane emissions from a temperate bog over 1.5 years, which we supported with measurements of the surface flux of methane and carbon dioxide. The radiocarbon content of methane emissions varied greatly, from modern (i.e. fixed from the atmosphere within recent decades) to ~ 1400 years BP. Flux rates of methane were spatially and temporally highly variable. A vegetation clipping experiment showed that plants had a great influence on the carbon isotope composition and flux of methane emitted from the peat surface, consistent with earlier studies showing the key role of plants in peatland methane emissions. When plants were absent, emission rates were 70–94% lower and the radiocarbon age of methane emissions was much younger and less variable. Our radiocarbon measurements show that at this peatland, plant-associated methane emissions contain carbon originally fixed from the atmosphere up to hundreds of years earlier, consistent with a contribution from plant mediated transport of methane sourced from sub-surface layers.

     

CD133 suppression increases the sensitivity of prostate cancer cells to paclitaxel

Molecular Biology Reports - One of the major barriers in cancer therapy is the resistance to conventional therapies and cancer stem cells (CSCs) are among the main causes of this problem. CD133 as...     

Expression of recombinant human IFN-γ protein in soybean (Glycine max L.)

Plant Cell, Tissue and Organ Culture (PCTOC) - Globular androgenic haploid embryos of TV21 and TV19 cultivars of Camellia ssp., obtained on embryo induction medium (EIM), Murashige and Skoog medium...     

MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle,apoptosis, and proliferation

Molecular Biology Reports - Combination therapy has been considered as a potential method to overcome the BC chemoresistance. MicroRNAs (miRs) have been suggested as a therapeutic factor in the...     

Direct shoot regeneration from mature embryo as a rapid and genotype-independent pathway in tissue culture of heterogeneous diverse sets of cumin (Cuminum cyminum L.) genotypes

Summary A rapid and one-step protocol for direct regeneration of shoots from cumin embryo explants has been developed. Embryo explants with shoot meristems were cultured on shoot regeneration medium for 15–22 d. After embryo culture, shoots were regenerated from the area adjacent to the region between the cotyledons and embryo axis within 2 wk, without any intermediate callus phase. Shoot proliferation and elongation were achieved on shoot regeneration medium without subculture. Among the different combinations of 6-benzylaminopurine, α-naphthaleneacetic acid (NAA), and indole-3-acetic acid (IAA) tested, 0.8 mgl^−1 (4.3 μM) NAA in combination with 0.3 mgl^−1 (1.71 μM) IAA in the B5 medium resulted in the most efficient direct shoot regeneration. No significant difference was detected for the number of regenerated explants when different heterogeneous endemic varieties were compared. This plant regeneration procedure was applicable to different cumin genotypes and regenerated plants were phenotypically normal.     

Immunogenicity of Salmonella enterica serovar Enteritidis virulence protein,InvH, and cross-reactivity of its antisera with Salmonella strains

Acellular vaccines containing bacterial immunodominant components such as surface proteins may be potent alternatives to live attenuated vaccines in order to reduce salmonellosis risk to human health. invH gene, an important part of needle complex in type three secretion system (TTSS) plays important role in efficient bacterial adherence and entry into epithelial cells. In this work we hypothesize that use of a 15 kDa recombinant InvH as Salmonella enterica serovar Enteritidis surface protein could provoke antibody production in mouse and would help us study feasibility of its potential for diagnosis and/or a recombinant vaccine. The purified InvH provoked significant rise of IgG in mice. Active protection induced by immunization with InvH against variable doses of S. enterica serovar Enteritidis, indicated that the immunized mice were completely protected against challenge with 10⁴ LD₅₀. The immunoreaction of sera from immunized mice with other Salmonella strains or cross reaction with sera of Salmonella strains inoculated mice is indicative of possessing by Salmonella strains of the surface protein, InvH, that can be employed in both prophylactic and diagnostic measures against S. enterica. Bacteria free spleen and ileum of the immunized mice in this study indicate that the invH gene affects bacterial invasion. Efficacy of the virulence protein, InvH, in shuttling into host cells in injectisome of S. enterica serovar Enteritidis and inhibition of this phenomenon by active immunization was shown in this study. In conclusion immunization with InvH protein can develop protection against S. enterica serovar Enteritidis infections. InvH in Salmonella strains can be exploited in protective measures as well as a diagnostic tool in Salmonella infections.