pH-dependent complex formation with TAR RNA and DNA: application towards logic gates.

Nucleic acid-based logic gates have shown great potential in biotechnology, medicine as well as diagnostics. Herein, we have constructed pH-responsive logic devices by utilizing HIV-1 TAR hairpins in combination with a thiazole peptide that exhibits turn-on fluorescence upon interacting with TAR RNA or DNA. Based on this, INHIBIT-AND and YES-INHIBIT-AND logic gates were constructed in parallel. The pH alteration leads to conformational changes of the hairpin structure, enabling the construction of a multi-reset reusable logic system which could be developed for in vitro sensing of the HIV-1 viral RNA.

Frequency and risk factors stratification of hypertension among the rural population of Bangladesh.

Background and Objectives: Hypertension is one of the major risk factors of premature morbidity and mortality in our daily clinical practice. Various studies carried out in the urban settings, but there is scarcity of epidemiological data regarding hypertension among the rural people in Bangladesh. Therefore, this current study has been designed to find out the frequency and risk factors stratification of hypertension among the rural people in Jashore, Bangladesh. Materials and Methods: A cross-sectional study recruited 1812 participants above 18 years attending on national hypertensive week of 2019 in Bagherpara and Keshabpur upazila (subdistrict) health complex in Jashore, Bangladesh. 2020 International Society of Hypertension Global Hypertension Practice Guidelines had been demonstrated to classify hypertension. Results: Out of the total study population, the frequency of hypertension was 20.6% (Grade 1 and Grade 2 hypertensive patients 15.8% and 4.9%, respectively), and high normal blood pressure was 9.0%. The mean age of the study population, Grade 1 hypertensive and Grade 2 hypertensive cohorts were 42 ± 16, 49 ± 15 and 51 ± 14 years, respectively, with a male and female ratio was 1:2. Progressive rise of mean systolic and diastolic blood pressure were noticed with increasing age. Age (P: <0.001), sex (P: 0.004), occupation (P: <0.001), BMI (P: <0.001), family (P: <0.001) and past history (P: <0.001) of hypertension, sedentary life style (P: 0.004), additional salt intake (P: <0.001) and smoking (P: 0.011) were significantly associated with hypertension following bivariate analysis. Multivariate logistic regression analysis revealed that age after 50 years (AOR = 1.866, 95% CI: 1.210-2.876), positive past history of hypertension (AOR = 3.493, 95% CI: 2.676-4.558), additional salt intake (AOR = 0.591, 95% CI: 0.453-0.770) and obesity (AOR = 3.389, 95% CI: 1.830-6.274) were significantly associated with developing hypertension. Conclusion: High frequency of hypertension was found among the rural population in Bangladesh where presence with a lot of significantly associated risk factors. The data would be helpful for the health policymakers dealing noncommunicable diseases to reach the sustainable goal and mitigate morbidity and mortality of cardiovascular diseases in Bangladesh.

G4 Sensing Pyridyl-Thiazole Polyamide Represses c-KIT Expression in Leukemia Cells.

Specific sensing and functional tuning of nucleic acid secondary structures remain less explored to date. Herein, we report a thiazole polyamide TPW that binds specifically to c-KIT1 G-quadruplex (G4) with sub-micromolar affinity and ∼1 : 1 stoichiometry and represses c-KIT proto-oncogene expression. TPW shows up to 10-fold increase in fluorescence upon binding with c-KIT1 G4, but shows weak or no quantifiable binding to other G4s and ds26 DNA. TPW can increase the number of G4-specific antibody (BG4) foci and mark G4 structures in cancer cells. Cell-based assays reveal that TPW can efficiently repress c-KIT expression in leukemia cells via a G4-dependent process. Thus, the polyamide can serve as a promising probe for G-quadruplex recognition with the ability to specifically alter c-KIT oncogene expression.

Target-Directed Azide-Alkyne Cycloaddition for Assembling HIV-1 TAR RNA Binding Ligands.

The highly conserved HIV-1 transactivation response element (TAR) binds to the trans-activator protein Tat and facilitates viral replication in its latent state. The inhibition of Tat-TAR interactions by selectively targeting TAR RNA has been used as a strategy to develop potent antiviral agents. Therefore, HIV-1 TAR RNA represents a paradigmatic system for therapeutic intervention. Herein, we have employed biotin-tagged TAR RNA to assemble its own ligands from a pool of reactive azide and alkyne building blocks. To identify the binding sites and selectivity of the ligands, the in situ cycloaddition has been further performed using control nucleotide (TAR DNA and TAR RNA without bulge) templates. The hit triazole-linked thiazole peptidomimetic products have been isolated from the biotin-tagged target templates using streptavidin beads. The major triazole lead generated by the TAR RNA presumably binds in the bulge region, shows specificity for TAR RNA over TAR DNA, and inhibits Tat-TAR interactions.

Cell penetrating thiazole peptides inhibit c-MYC expression via site-specific targeting of c-MYC G-quadruplex.

The structural differences among different G-quadruplexes provide an opportunity for site-specific targeting of a particular G-quadruplex structure. However, majority of G-quadruplex ligands described thus far show little selectivity among different G-quadruplexes. In this work, we delineate the design and synthesis of a crescent-shaped thiazole peptide that preferentially stabilizes c-MYC quadruplex over other promoter G-quadruplexes and inhibits c-MYC oncogene expression. Biophysical analysis such as Förster resonance energy transfer (FRET) melting and fluorescence spectroscopy show that the thiazole peptide TH3 can selectively interact with the c-MYC G-quadruplex over other investigated G-quadruplexes and duplex DNA. NMR spectroscopy reveals that peptide TH3 binds to the terminal G-quartets and capping regions present in the 5'- and 3'-ends of c-MYC G-quadruplex with a 2:1 stoichiometry; whereas structurally related distamycin A is reported to interact with quadruplex structures via groove binding and end stacking modes with 4:1 stoichiometry. Importantly, qRT-PCR, western blot and dual luciferase reporter assay show that TH3 downregulates c-MYC expression by stabilizing the c-MYC G-quadruplex in cancer cells. Moreover, TH3 localizes within the nucleus of cancer cells and exhibits antiproliferative activities by inducing S phase cell cycle arrest and apoptosis.

Equilibrium and kinetics study on removal of arsenate ions from aqueous solution by CTAB/TiO2 and starch/CTAB/TiO2 nanoparticles: a comparative study.

We present a comparative study on the efficacy of TiO2 nanoparticles for arsenate ion removal after modification with CTAB (N-cetyl-N,N,N-trimethyl ammonium bromide) followed by coating with starch biopolymer. The prepared nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), thermogravimetry, scanning electron microscopy (SEM) and electron dispersive X-ray analysis (EDX). The removal efficiency was studied as a function of contact time, material dose and initial As(V) concentration. CTAB-modified TiO2 showed the highest arsenate ion removal rate (∼99% from 400 µg/L). Starch-coated CTAB-modified TiO2 was found to be best for regeneration. For a targeted solution of 400 µg/L, a material dose of 2 g/L was found to be sufficient to reduce the As(V) concentration below 10 µg/L. Equilibrium was established within 90 minutes of treatment. The sorption pattern followed a Langmuir monolayer pattern, and the maximum sorption capacity was found to be 1.024 mg/g and 1.423 mg/g after starch coating and after CTAB modification, respectively. The sorption mechanisms were governed by pseudo second order kinetics.