Diversity and Applications of Endophytic Actinobacteria of Plants in Special and Other Ecological Niches

Actinobacteria are wide spread in nature and represent the largest taxonomic group within the domain Bacteria. They are abundant in soil and have been extensively explored for their therapeutic applications. This versatile group of bacteria has adapted to diverse ecological habitats, which has drawn considerable attention of the scientific community in recent times as it has opened up new possibilities for novel metabolites that may help in solving some of the most challenging problems of the day, for example, novel drugs for drug-resistant human pathogens, affordable means to maintain ecological balance in various habitats, and alternative practices for sustainable agriculture. Traditionally, free dwelling soil actinobacteria have been the subject of intensive research. Of late, symbiotic actinobacteria residing as endophytes within the plant tissues have generated immense interest as potential source of novel compounds, which may find applications in medicine, agriculture, and environment. In the light of these possibilities, this review focuses on the diversity of endophytic actinobacteria isolated from the plants of extreme habitats and specific ecological niches. Furthermore, an attempt has been made to assign chemical class to the compounds obtained from endophytic actinobacteria. Potential therapeutic applications of these compounds and the utility of endophytic actinobacteria in agriculture and environment are discussed

Repurposed Therapeutic Strategies towards COVID-19 Potential Targets Based on Genomics and Protein Structure Remodeling

Target recognition is important for the identification of drugs with a high target specificity and/or for the development of existing drugs that could be replicated for the treatment of SARS-CoV-2 infections. Since SARS-CoV-2 is a pathogen recently discovered, no specific medicines have been identified or are available at present. The scientific community had proposed list of current drugs with therapeutic potential for COVID-19 on the basis of genomic sequence information coupled with protein structure modeling, posing an effective and productive therapeutic approach for repurposing existing drugs. The possible therapeutics for the treatment of COVID-19 involves a wide range of alternatives, encompassing nucleic acid-based treatments directed at the expression of genes of viruses, cytokine therapy, genetic engineered and vectored antibodies, and different formulations of vaccines. The future prospective in the treatment approaches the exploration of antiviral therapy, such as screening of prevailing molecules or libraries, testing of existing broad-spectrum antiviral medications, modern drug discovery focused on genomic knowledge and biochemical properties of various coronaviruses to create new targeted drugs

Review of Graphene Technology and Its Applications for Electronic Devices

Graphene has amazing abilities due to its unique band structure characteristics defining its enhanced electrical capabilities for a material with the highest characteristic mobility known to exist at room temperature. The high mobility of graphene occurs due to electron delocalization and weak electron–phonon interaction, making graphene an ideal material for electrical applications requiring high mobility and fast response times. In this review, we cover graphene’s integration into infrared (IR) devices, electro-optic (EO) devices, and field effect transistors (FETs) for radio frequency (RF) applications. The benefits of utilizing graphene for each case are discussed, along with examples showing the current state-of-the-art solutions for these applications

CTL Responses of High Functional Avidity and Broad Variant Cross-Reactivity Are Associated with HIV Control

Cytotoxic T lymphocyte (CTL) responses targeting specific HIV proteins, in particular Gag, have been associated with relative control of viral replication in vivo. However, Gag-specific CTL can also be detected in individuals who do not control the virus and it remains thus unclear how Gag-specific CTL may mediate the beneficial effects in some individuals but not in others. Here, we used a 10mer peptide set spanning HIV Gag-p24 to determine immunogen-specific T-cell responses and to assess functional properties including functional avidity and cross-reactivity in 25 HIV-1 controllers and 25 non-controllers without protective HLA class I alleles. Our data challenge the common belief that Gag-specific T cell responses dominate the virus-specific immunity exclusively in HIV-1 controllers as both groups mounted responses of comparable breadths and magnitudes against the p24 sequence. However, responses in controllers reacted to lower antigen concentrations and recognized more epitope variants than responses in non-controllers. These cross-sectional data, largely independent of particular HLA genetics and generated using direct ex-vivo samples thus identify T cell responses of high functional avidity and with broad variant reactivity as potential functional immune correlates of relative HIV control

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Resolution of a complex ionic mixture of an apparently homogenous protein preparation by preparative electrophoresis

279-283Preparations of recombinant envelope glycoprotein E2 of hepatitis C virus (r-HCV E2), found to be homogeneous by N-terminal amino acid sequencing and mass spectrometry, resolved into multiple ionic species (isoforms) when analysed by isoelectric focusing (IEF) gel electrophoresis in the pI range of 3-10. These isoforms possessed pI &nbsp;values in the range or 4.5-8.2. The major isoform with p<i style="mso-bidi-font-style: normal">I value of approximately 7. 1 was separated from the rest of them by employing a method developed on Gradiflow BF 200, a device based on preparative electrophoresis. This isoform was adjudged to be homogenous by IEF and by native polyacrylamide gel electrophoresis (PAGE)