Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/β-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of β-catenin, decreased GSK-3β levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3β. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/β-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism.
In the wake of the findings that Antarctic krills concentrate heavy metals at ppm level, (Yamamoto et al. 1987), the Antarctic waters from the Indian side were examined for the incidence of metal and antibiotic-resistant bacteria during the austral summer (13th Indian Antarctic expedition) along the cruise track extending from 50 degrees S and 18 degrees E to 65 degrees S and 30 degrees E. The bacterial isolates from these waters showed varying degrees of resistance to antibiotics (Chloramphenicol, ampicillin, streptomycin, tetracycline and kanamycin) and metals (K(2)CrO(4), CdCl(2), ZnCl(2) and HgCl(2)) tested. Of the isolates screened, about 29% and 16% were resistant to 100 ppm of cadmium and chromium salt respectively. Tolerance to lower concentration (10 ppm) of mercury (Hg) was observed in 68% of the isolates. Depending on the antibiotics the isolates showed different percentage of resistance. Multiple drug and metal-resistance were observed. High incidence of resistance to both antibiotics and metals were common among the pigmented bacterial isolates. Increased resistance decreased the ability of bacteria to express enzymes. The results reiterate previous findings by other researchers that the waters of southern ocean may not be exempt from the spread of metal and antibiotic-resistance.
Snow overlays the majority of Antarctica and is an important repository of dissolved organic matter (DOM). DOM transformations by supraglacial microbes are not well understood. We use ultrahigh resolution mass spectrometry to elucidate molecular changes in snowpack DOM by in situ microbial processes (up to 55 days) in a coastal Antarctic site. Both autochthonous and allochthonous DOM is highly bioavailable and is transformed by resident microbial communities through parallel processes of degradation and synthesis. DOM thought to be of a more refractory nature, such as dissolved black carbon and carboxylic-rich alicyclic molecules, was also rapidly and extensively reworked. Microbially reworked DOM exhibits an increase in the number and magnitude of N-, S-, and P-containing formulas, is less oxygenated, and more aromatic when compared to the initial DOM. Shifts in the heteroatom composition suggest that microbial processes may be important in the cycling of not only C, but other elements such as N, S, and P. Microbial reworking also produces photoreactive compounds, with potential implications for DOM photochemistry. Refined measurements of supraglacial DOM and their cycling by microbes is critical for improving our understanding of supraglacial DOM cycling and the biogeochemical and ecological impacts of DOM export to downstream environments.
Net ecosystem production was examined in the Mandovi and Zuari estuaries (southwestern India) and the adjoining coastal waters for a period of 1 yr (January to December 1998). The study period encompassed premonsoon, monsoon, and postmonsoon seasons. At the estuarine stations, net ecosystem production showed monthly variation and a transition from net autotrophy of 49 mmol C m Ϫ2 d Ϫ1 during the nonmonsoon seasons (premonsoon and postmonsoon) to net heterotrophy of Ϫ46 mmol C m Ϫ2 d Ϫ1 in the monsoon season. Seasonal monsoon-driven changes such as increased allochthonous inputs resulted in enhanced heterotrophic respiration and reduced primary production in the estuaries. In the coastal station, the monthly variation in net ecosystem production was not significant, and net heterotrophy was prevalent whenever measurements were made, thereby potentially serving as the net source of carbon dioxide to the atmosphere. Results suggest that the excess organic matter from these tropical estuaries supports heterotrophy in the adjacent coastal ecosystem.
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