Kinetics & Mechanism of Oxidation of Toluenes by Lead Tetraacetate

478-48

Kinetic Evidence for Radical Anions in the Oxidation of p-Nitrotoluene & 2,4-Dinitrotoluene by Alkaline Hexacyanoferrate(III) in Aqueous Dimethyl Sulphoxide

613-61

The EMT transcription factor ZEB1 governs a fitness-promoting but vulnerable DNA replication stress response

The DNA damage response (DDR) and epithelial-to-mesenchymal transition (EMT) are two crucial cellular programs in cancer biology. While the DDR orchestrates cell cycle progression, DNA repair and cell death, EMT promotes invasiveness, cellular plasticity and intratumor heterogeneity. Therapeutic targeting of EMT transcription factors, such as ZEB1, remains challenging, but tumor-promoting DDR alterations elicit specific vulnerabilities. Using multi-omics, inhibitors and high-content microscopy, we discover a chemoresistant ZEB1 high expressing sub-population (ZEB1hi) with co-rewired cell cycle progression and proficient DDR across tumor entities. ZEB1 stimulates accelerated S-phase entry via CDK6, inflicting endogenous DNA replication stress. However, DDR buildups involving constitutive MRE11-dependent fork resection allow homeostatic cycling and enrichment of ZEB1hi cells during TGFβ-induced EMT and chemotherapy. Thus, ZEB1 promotes G1/S transition to launch a progressive DDR benefitting stress tolerance, which concurrently manifests a targetable vulnerability in chemoresistant ZEB1hi cells. Our study thus highlights the translationally relevant intercept of the DDR and EMT

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

Poly-lactic acid nanoparticles (PLA-NP) promote physiological modifications in lung epithelial cells and are internalized by clathrin-coated pits and lipid rafts

BackgroundPoly-lactic acid nanoparticles (PLA-NP) are a type of polymeric NP, frequently used as nanomedicines, which have advantages over metallic NP such as the ability to maintain therapeutic drug levels for sustained periods of time. Despite PLA-NP being considered biocompatible, data concerning alterations in cellular physiology are scarce.MethodsWe conducted an extensive evaluation of PLA-NP biocompatibility in human lung epithelial A549 cells using high throughput screening and more complex methodologies. These included measurements of cytotoxicity, cell viability, immunomodulatory potential, and effects upon the cells’ proteome. We used non- and green-fluorescent PLA-NP with 63 and 66 nm diameters, respectively. Cells were exposed with concentrations of 2, 20, 100 and 200 µg/mL, for 24, 48 and 72 h, in most experiments. Moreover, possible endocytic mechanisms of internalization of PLA-NP were investigated, such as those involving caveolae, lipid rafts, macropinocytosis and clathrin-coated pits.ResultsCell viability and proliferation were not altered in response to PLA-NP. Multiplex analysis of secreted mediators revealed a low-level reduction of IL-12p70 and vascular epidermal growth factor (VEGF) in response to PLA-NP, while all other mediators assessed were unaffected. However, changes to the cells’ proteome were observed in response to PLA-NP, and, additionally, the cellular stress marker miR155 was found to reduce. In dual exposures of staurosporine (STS) with PLA-NP, PLA-NP enhanced susceptibility to STS-induced cell death. Finally, PLA-NP were rapidly internalized in association with clathrin-coated pits, and, to a lesser extent, with lipid rafts.ConclusionsThese data demonstrate that PLA-NP are internalized and, in general, tolerated by A549 cells, with no cytotoxicity and no secretion of pro-inflammatory mediators. However, PLA-NP exposure may induce modification of biological functions of A549 cells, which should be considered when designing drug delivery systems. Moreover, the pathways of PLA-NP internalization we detected could contribute to the improvement of selective uptake strategies

On the Origin of OSO4 Catalysis in Homogeneous Redox Reactions of Organic Substrates with IO<img src='http://www.niscair.res.in/jinfo/Subscript4.gif' border=0> , Fe(CN)<img src='http://www.niscair.res.in/jinfo/threebysix.gif' border=0> , CIO<img src='/image/spc_char/3_bar.gif' border=0> & Chloramine-T

404-40

Hydrolysis of Peroxodiphosphate by Acid Phosphatase

834-83

Archaean granulite facies metamorphism at the Singhbhum Craton-Eastern Ghats Mobile Belt interface: implication for the Ur supercontinent assembly

In this study, we investigate the geological significance and the antiquity of lower crustal granulite facies metamorphism from the Rengali Domain, which lies in between the Singhbhum Craton in the north and the Eastern Ghats Mobile Belt in the south. Petrographic, mineral compositional, metamorphic reaction history and geothermobarometric studies of two representative metapelite granulite samples reveal widespread biotite melting at peak granulite facies metamorphic conditions of 7.8 &#177; 0.13 kbar, 849 &#177; 31 °C and subsequent melt extraction, producing a mixture of residual granulites and melts in the Rengali Province. Depending on local bulk rock compositional variations, biotite melting produced peak metamorphic assemblages of garnet + cordierite in the more aluminous compositional domain, while garnet + orthopyroxene + cordierite resulted in domains of intermediate alumina. During post-peak cooling, there were localized developments of biotite + sillimanite + quartz symplectites replacing garnet and cordierite and biotite + quartz intergrowths after orthopyroxene. Application of garnet-orthopyroxene and garnet-biotite Fe–Mg exchange thermometers to co-existing garnet rim and symplectitic biotite show the extent of cooling to 610–660 °C. Electron microprobe geochronology of texturally well constrained monazites indicates the timing of peak granulite metamorphism at 3057 &#177; 17 Ma and its metamorphic reheating at 2781 &#177; 16 Ma. The present findings when collated with available geological and geophysical data appear to indicate that the studied granulites and the associated granite gneisses, charnockite and enderbite suite of rocks of the Rengali Domain are part of the exhumed lower continental crust of the Singhbhum Craton. The significance of this Neoarchaean orogenesis in the ‘Ur’ supercontinent assembly is discussed