Photoluminescence Quenching Based Visual and Spectroscopic Method for Mercury Sensing by Surface-Modified Cadmium Sulphide Quantum Dots.

Here we present a simple yet efficient analytical method for sensing ultratrace levels of Hg2+ ions by highly water soluble CdS quantum dots functionalized with thiourea as a probe. The bluish photoluminescence emission of the probe responded to a systematic linear photoluminescence quenching in the presence of increasing concentration of Hg2+ ions. The photoluminescence quenching by Hg2+ ions was attributed to agglomeration of the quantum dots, which has been confirmed by zeta potential measurements. The sensitivity (31.38 L/mg) and LoD (0.11 µg/L) of Hg2+ ion detection by our method are two folds improved with respect to the existing data of CdS as sensor. The improved detection is attributable to synthesis of less than 3 nm diameter CdS quantum dots which rendered very high water solubility and hence facilitated better interaction with Hg2+ ions. The detection of Hg2+ ion was free from most interfering cations and anions, except for minor interference from Cu2+ and Pb2+ corresponding their concentrations expected in ground water. Further, the scope for visual detection of Hg2+ was explored, which revealed naked eye recognizable photoluminescence quenching of the probe treated 0.3 mg/L of Hg2+ ion when excited by a light source of 365 nm. The suitability of our probe to analyze Hg2+ in real samples has been demonstrated by Hg2+ spike analysis in groundwater and river water samples.

Functional characterisation of the methionine sulfoxide reductase repertoire in Trypanosoma brucei.

To combat the deleterious effects that oxidation of the sulfur atom in methionine to sulfoxide may bring, aerobic cells express repair pathways involving methionine sulfoxide reductases (MSRs) to reverse the above reaction. Here, we show that Trypanosoma brucei, the causative agent of African trypanosomiasis, expresses two distinct trypanothione-dependent MSRs that can be distinguished from each other based on sequence, sub-cellular localisation and substrate preference. One enzyme found in the parasite's cytosol, shows homology to the MSRA family of repair proteins and preferentially metabolises the S epimer of methionine sulfoxide. The second, which contains sequence motifs present in MSRBs, is restricted to the mitochondrion and can only catalyse reduction of the R form of peptide-bound methionine sulfoxide. The importance of these proteins to the parasite was demonstrated using functional genomic-based approaches to produce cells with reduced or elevated expression levels of MSRA, which exhibited altered susceptibility to exogenous H2O2. These findings identify new reparative pathways that function to fix oxidatively damaged methionine within this medically important parasite.

Distinct activation mechanisms trigger the trypanocidal activity of DNA damaging prodrugs.

Quinone-based compounds have been exploited to treat infectious diseases and cancer, with such chemicals often functioning as inhibitors of key metabolic pathways or as prodrugs. Here, we screened an aziridinyl 1,4-benzoquinone (ABQ) library against the causative agents of trypanosomiasis, and cutaneous leishmaniasis, identifying several potent structures that exhibited EC50 values of <100 nM. However, these compounds also displayed significant toxicity towards mammalian cells indicating that they are not suitable therapies for systemic infections. Using anti-T. brucei ABQs as chemical probes, we demonstrated that these exhibit different trypanocidal modes of action. Many functioned as type I nitroreductase (TbNTR) or cytochrome P450 reductase (TbCPR) dependent prodrugs that, following activation, generate metabolites which promote DNA damage, specifically interstrand crosslinks (ICLs). Trypanosomes lacking TbSNM1, a nuclease that specifically repairs ICLs, are hypersensitive to most ABQ prodrugs, a phenotype exacerbated in cells also engineered to express elevated levels of TbNTR or TbCPR. In contrast, ABQs that contain substituent groups on the biologically active aziridine do not function as TbNTR or TbCPR-activated prodrugs and do not promote DNA damage. By unravelling how ABQs mediate their activities, features that facilitate the desired anti-parasitic growth inhibitory effects could be incorporated into new, safer compounds targeting these neglected tropical diseases.

Rapid Photoluminescence Quenching Based Detection of Cu2+ in Aqueous Medium by CdS Quantum Dots Surface Passivated by Thiourea.

Presented here is a simple yet rapid and efficient analytical method for visual as well as spectroscopic method for sensing of trace concentrations of Cu2+ ions in aqueous medium by systematic photoluminescence quenching of a highly water soluble probe made of CdS quantum dots surface modified by thiourea. The salient features of this work describe rapid detection (2 min equilibration time) of Cu2+ ions at wider linear concentration range (0.025 - 10 mg/L) corresponding to a sensitivity of 2.81(mg/L)-1 and limit of quantification of 47.3 µg/L, respectively, suitable for Cu2+ sensing in drinking water and ground water. Further, the detection of Cu2+ ion was free from most interfering cations and anions, except for minor interference from Cr3+, Hg2+ and Pb2+. The robustness of our probe for Cu2+ sensing is demonstrated from efficient Cu2+ spike recovery analysis in groundwater and river water samples.

Highly Sensitive and Selective Method for Detecting Ultratrace Levels of Aqueous Uranyl Ions by Strongly Photoluminescent-Responsive Amine-Modified Cadmium Sulfide Quantum Dots.

Detection of ultratrace levels of aqueous uranyl ions without using sophisticated analytical instrumentation and a tedious sample preparation method is a challenge for environmental monitoring and mitigation. Here we present a novel yet simple analytical method for highly sensitive and specific detection of uranyl ions via photoluminescence quenching of CdS quantum dots. We have demonstrated a new approach for synthesizing highly water-soluble and strong photoluminescence-emitting CdS quantum dots (i.e., CdS-MAA and CdS-MAA-TU) of sizes less than 3 nm. The structural, morphological, and optical properties of both the batches of CdS quantum dots were thoroughly characterized by XRD, high-resolution transmission electron microscopy (HRTEM), zeta potential, UV-visible absorption, and photoluminescence spectroscopy. Compared to the batch of CdS quantum dots prepared by capping with only mercaptoacetic acid (CdS-MAA), the batch prepared by capping with mercaptoacetic acid and thiourea in tandem (CdS-MAA-TU) exhibited higher quantum yield= 16.64 ± 1.02%, and more importantly, CdS-MAA-TU exhibited significantly a higher order of photoluminescence quenching responses when treated with ultratrace concentrations of uranyl ions. Under the optimized conditions, the sensitivity of detecting uranyl ion by CdS-MAA-TU was several folds better (0.316 L/ µg) than that of CdS-MAA (0.0053 (L/µg/), as determined from their respective Stern-Volmer plots. Qualitatively, CdS-MAA-TU probe can be used for visual detection of uranyl ions of concentration greater than 5 µg/L. However, the instrumental method of analysis based on photoluminescence spectroscopy confirmed the feasibility for quantitative analysis of ultratrace concentrations of uranyl ions as implied from a very low limit of detection (LoD = 0.07 µg/L) and limit of quantification (LoQ = and 0.231 µg/L). Systematic studies revealed very high selectivity for uranyl ion detection, though minor interference from Cu(2+), Pb(2+), Hg(2+), CO3(2-), and SO4(2-) was found. The recovery analysis performed by spiking uranyl ions (0.5 µg/L to 10.0 µg/L) in groundwater and river water samples, confirmed the robustness of the as-developed CdS-MAA-TU QDs for detecting ultratrace levels of uranyl ions in real water sample matrix. The very simple and effective strategy reported here should facilitate developing reliable sensors for detecting uranyl ion contamination in drinking water.

Unravelling the role of SNM1 in the DNA repair system of Trypanosoma brucei.

All living cells are subject to agents that promote DNA damage. A particularly lethal lesion are interstrand cross-links (ICL), a property exploited by several anti-cancer chemotherapies. In yeast and humans, an enzyme that plays a key role in repairing such damage are the PSO2/SNM1 nucleases. Here, we report that Trypanosoma brucei, the causative agent of African trypanosomiasis, possesses a bona fide member of this family (called TbSNM1) with expression of the parasite enzyme able to suppress the sensitivity yeast pso2Δ mutants display towards mechlorethamine, an ICL-inducing compound. By disrupting the Tbsnm1 gene, we demonstrate that TbSNM1 activity is non-essential to the medically relevant T. brucei life cycle stage. However, trypanosomes lacking this enzyme are more susceptible to bi- and tri-functional DNA alkylating agents with this phenotype readily complemented by ectopic expression of Tbsnm1. Genetically modified variants of the null mutant line were subsequently used to establish the anti-parasitic mechanism of action of nitrobenzylphosphoramide mustard and aziridinyl nitrobenzamide prodrugs, compounds previously shown to possess potent trypanocidal properties while exhibiting limited toxicity to mammalian cells. This established that these agents, following activation by a parasite specific type I nitroreductase, produce metabolites that promote formation of ICLs leading to inhibition of trypanosomal growth.

Camouflage for patients with vitiligo.

Vitiligo is known to be associated with social stigma and a decreased quality of life, especially when lesions are located over the face. While there are numerous treatment options for vitiligo, most of these need a long time to produce good cosmetic results. Camouflaging the skin lesions can be a useful option in such patients. The proper use of camouflage has been shown to improve the quality of life in patients with vitiligo. In this article, we discuss the different camouflage options available in vitiligo - products and techniques with their relative advantages and disadvantages.