Size- and Age-Dependent Neurotoxicity of Engineered Metal Nanoparticles in Rats

Earlier we showed that chronic administration of engineered nanoparticles (NPs) from metals, e.g., Cu, Ag, or Al (50–60 nm, 50 mg/kg, i.p. daily for 1 week) alter blood–brain barrier (BBB) disruption and induce brain pathology in adult rats (age 18 to 22 weeks). However, effects of size-dependent neurotoxicity of NPs in vivo are still largely unknown. In present investigation, we examined the effects of different size ranges of the above-engineered NPs on brain pathology in rats. Furthermore, the fact that age is also an important factor in brain pathology was also investigated in our rat model. Our results showed that small-sized NPs induced the most pronounced BBB breakdown (EBA +480 to 680 %; radioiodine +850 to 1025 %), brain edema formation (+4 to 6 %) and neuronal injuries (+30 to 40 %), glial fibrillary acidic protein upregulation (+40 to 56 % increase), and myelin vesiculation (+30 to 35 % damage) in young animals as compared to controls. Interestingly, the oldest animals (30 to 35 weeks of age) also showed massive brain pathology as compared to young adults (18 to 20 weeks old). The Ag and Cu exhibited greater brain damage compared with Al NPs in all age groups regardless of their size. This suggests that apart from the size, the composition of NPs is also important in neurotoxicity. The very young and elderly age groups exhibited greater neurotoxicity to NPs suggests that children and elderly are more vulnerable to NPs-induced brain damage. The NPs-induced brain damage correlated well with the upregulation of neuronal nitric oxide synthase activity in the brain indicating that NPs-induced neurotoxicity may be mediated via increased production of nitric oxide, not reported earlier.     

Development and validation of multiplex-PCR assay for simultaneous detection of rare alleles of <Emphasis Type="Italic">crtRB1</Emphasis> and <Emphasis Type="Italic">lcyE</Emphasis> governing higher accumulation of provitamin A in maize

Vitamin A deficiency is a widely prevalent health disorder among millions of people worldwide. Introgression of crtRB1 and lcyE favourable alleles that enhance concentration of provitamin A in maize endosperm have been employed in maize biofortification programmes. To make marker-assisted selection (MAS) more effective, we have developed rapid and convenient multiplex-polymerase chain reaction (PCR) assay to simultaneously discover the allelic combinations among the segregants. Validation of the multiplex assay was done in two backcross-derived populations developed using elite inbreds viz., HKI193-1 and HKI193-2 carrying unfavourable alleles of crtRB1 (296 bp) and lcyE (300 bp) and HarvestPlus inbreds viz., HP704-22 and HP704-23 possessing favourable alleles of crtRB1 (543 bp) and lcyE (650 bp). We also standardized the uniplex-PCR assays for both the genes that gave robust and reproducible results in sub-tropical populations. Gel profiles of BC₁F₁, BC₂F₁ and BC₂F₂ revealed that these assays identified the backcross progenies homo-or hetero-zygous for the favourable- or unfavourable-alleles. Multiplex-PCR assay also precisely confirmed the results of individual uniplex assays in different backcross generations. Cost and time analyses showed that multiplex-PCR assay has potential to save 41% of cost, and 50% of time compared to two uniplex assays in a MAS programme. It has also saved 50% of the manpower. The multiplex assay possesses significant advantage over uniplex assays and enhances the efficiency of selection. This is the first report of development and validation of multiplex-PCR assay of crtRB1 and lcyE for utilization in maize biofortification programme.     

Structural and Functional Analysis of E. coli Cyclopropane Fatty Acid Synthase

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Synthesis of DNA interactive C3-trans-cinnamide linked β-carboline conjugates as potential cytotoxic and DNA topoisomerase I inhibitors

A series of new C3-trans-cinnamide linked β-carboline conjugates has been synthesized by coupling between various β-carboline amines and substituted cinnamic acids. Evaluation of their anti-proliferative activity against a panel of selected human cancer cell lines such as A549 (lung cancer), MCF-7 (breast cancer), B16 (melanoma), HeLa (cervical cancer) and a normal cell line NIH3T3 (mouse embryonic fibroblast cell line), suggested that the newly designed conjugates are considerably active against all the tested cancer cell lines with IC₅₀ values 13–45?nM. Moreover, the conjugates 8v and 8x were the most active against MCF-7 cells (14.05?nM and 13.84?nM respectively) and also even potent on other cell lines tested. Further, detailed investigations such as cell cycle analysis, apoptosis induction study, topoisomerase I inhibition assay, DNA binding affinity and docking studies revealed that these new conjugates are DNA interactive topoisomerase I inhibitors.     

Identification of main effect and epistatic quantitative trait loci for morphological and yield-related traits in peanut (<Emphasis Type="Italic">Arachis hypogaea</Emphasis> L.)

An effort was made in the present study to identify the main effect and epistatic quantitative trait locus (QTL) for the morphological and yield-related traits in peanut. A recombinant inbred line (RIL) population derived from TAG 24 × GPBD 4 was phenotyped in seven environments at two locations. QTL analysis with available genetic map identified 62 main-effect QTLs (M-QTLs) for ten morphological and yield-related traits with the phenotypic variance explained (PVE) of 3.84–15.06%. Six major QTLs (PVE >?10%) were detected for PLHT, PPP, YPP, and SLNG. Stable M-QTLs appearing in at least two environments were detected for PLHT, LLN, YPP, YKGH, and HSW. Five M-QTLs governed two traits each, and 16 genomic regions showed co-localization of two to four M-QTLs. Intriguingly, a major QTL reported to be linked to rust resistance showed pleiotropic effect for yield-attributing traits like YPP (15.06%, PVE) and SLNG (13.40%, PVE). Of the 24 epistatic interactions identified across the traits, five interactions involved six M-QTLs. Three interactions were additive × additive and remaining two involved QTL × environment (QE) interactions. Only one major M-QTL governing PLHT showed epistatic interaction. Overall, this study identified the major M-QTLs for the important productivity traits and also described the lack of epistatic interactions for majority of them so that they can be conveniently employed in peanut breeding.     

Distal Lateral Subungual Onychomycosis Owing to <Emphasis Type="Italic">Tritirachium oryzae</Emphasis>: A Bystander or Invader?

The genus Tritirachium is a mitosporic fungus which inhabits in soil and decaying plant material and also a notable insect pathogen. Human infections with Tritirachium species though rare were previously reported to cause corneal ulcers, otomycosis, onychomycosis, and dermatomycosis of the scalp and hence may be considered as a potential pathogen. Here we report a case of distal lateral subungual onychomycosis involving right great toenail in a 22-year-old female, wherein direct potassium hydroxide preparations, fungal cultures, and molecular sequencing of the isolate established Tritirachium oryzae as the etiological agent. Antifungal susceptibility performed by the microbroth technique of CLSI revealed increased MICs to amphotericin B and low MICs to azoles and echinocandins. The case was managed with surgical nail avulsion followed by topical application of 2% ketoconazole cream resulting regrowth of normal nail. To the best of our knowledge, this is the first report of non-dermatophytic mold T. oryzae causing onychomycosis in India.     

Imidacloprid impedes mitochondrial function and induces oxidative stress in cotton bollworm, <Emphasis Type="Italic">Helicoverpa armigera</Emphasis> larvae (Hubner: Noctuidae)

Neonicotinoids have high agonistic affinity to insect nicotinic acetylcholine receptors (nAChR) and are frequently used as insecticides against most devastating lepidopteran insect pests. Imidacloprid influenced dose-dependent decline in the state III and IV respiration, respiration control index (RCI), and P/O ratios, in vitro and in vivo. The bioassay indicated its LD₅₀ value to be 531.24 μM. The insecticide exhibited a dose-dependent inhibition on F₀F₁-ATPase and complex IV activity. At 600 μM, the insecticide inhibited 83.62 and 27.13% of F₀F₁-ATPase and complex IV activity, respectively, and induced the release of 0.26 nmoles/min/mg protein of cytochrome c. A significant dose- and time-dependent increase in oxidative stress was observed; at 600 μM, the insecticide correspondingly induced lipid peroxidation, LDH activity, and accumulation of H₂O₂ content by 83.33, 31.51 and 223.66%. The stress was the maximum at 48 h of insecticide treatment (91.58, 35.28, and 189.80%, respectively). In contrast, catalase and superoxide dismutase were reduced in a dose- and time-dependent manner in imidacloprid-fed larvae. The results therefore suggest that imidacloprid impedes mitochondrial function and induces oxidative stress in H. armigera, which contributes to reduced growth of the larvae along with its neurotoxic effect.     

Human parieto-occipital visual cortex: lack of retinotopy and foveal magnification.

We studied visual representation in the parietal cortex by recording whole-scalp neuromagnetic responses to luminance stimuli of varying eccentricities. The stimuli were semicircles (5.5 degrees in radius) presented at horizontal eccentricities from 0 degree to 16 degrees, separately in the right and left hemifields. All stimuli evoked responses in the contralateral occipital and medial parietal areas. The waveforms and distributions of the occipital responses varied with stimulus side (left, right) and eccentricity, whereas the parietal responses were remarkably similar to all stimuli. The equivalent sources of the parietal signals clustered within 1 cm3 in the medial parieto-occipital sulcus and did not differ significantly between the stimuli. The strength of the parietal activation remained practically constant with increasing stimulus eccentricity, suggesting that the visual areas in the parieto-occipital sulcus lack the enhanced foveal representation typical of most other visual areas. This result strengthens our previous suggestion that the medial parieto-occipital sulcus is the human homologue of the monkey V6 complex, characterized by, for example, lack of retinotopy and the absence of relative foveal magnification.