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Pyridoxal-5′-phosphate (PLP) is a versatile cofactor that assists in different types of enzymatic reactions. PLP has also been reported to react with substrates and catalyze some of these reactions independent of enzymes. One such catalytic reaction is the breakdown of cysteine to produce hydrogen sulfide (H2S) in the presence of multivalent metal ions. However, the enzyme-independent catalytic activity of PLP in catabolizing cysteine in the absence of multivalent ions is unknown. In this study, we show that PLP reacts with cysteine to form a thiazolidine product, which is supported by quantum chemical calculations of the absorption spectrum. The reaction of PLP with cysteine is dependent on ionic strength and pH. The thiazolidine product slowly decomposes to produce H2S and the PLP regenerates to its active form with longer reaction times (> 24 h), suggesting that PLP can act as a catalyst. We propose an enzyme-independent plausible reaction mechanism for PLP catalyzed cysteine breakdown to produce H2S, which proceeds through the formation of thiazolidine ring intermediates that later hydrolyzes slowly to regenerate the PLP. This work demonstrates that PLP catalyzes cysteine breakdown in the absence of enzymes, base, and multivalent metal ions to produce H2S.

Background:Hydroxyurea (HU) is found to be beneficial in Sickle cell Anaemia (SCA) patients, due to its ability to increase foetal haemoglobin (HbF), however, patients show a variable response. Differences in HbF levels are attributed to many factors; but, the role of miRNA in HbF regulation is sparsely investigated.Materials and Methods:In this study, we evaluated the effect of miRNA expression on HbF induction in relation to hydroxyurea therapy in 30 normal controls, 30 SCA patients at baseline, 20 patients after 3 and 6 months of hydroxyurea (HU) therapy. HbF levels were measured by HPLC. Total RNA and miRNA were extracted from CD71+ erythroid cells and the expression was determined using Taqman probes. Results:The mean HbF level increased 7.54 ±2.44 fold, after 3 months of HU therapy. After the HU therapy 8 miRNAs were significantly up-regulated while 2 were down-regulated. The increase in miR-210, miR16-1, and miR-29a expression and decrease in miR-96 expression were strongly associated with the HU mediated HbF induction. Post HU therapy, decreased miR-96 expression was observed; which might be due to interference of miR-96 binding to g-globin mRNA by HU, facilitating HbF expression. The miR-210 expression was enhanced in association with erythroid differentiation and induction to HbF production. Conclusions:The study suggests the role of miR-210, miR16-1, miR-29a, and miR-96 in g-globin gene regulation leading to HbF induction. Identification of the relevant protein targets might be useful for understanding the HU mediated HbF induction.

The proteasome is essential for the selective degradation of most cellular proteins and is fine-tuned according to cellular needs. Proteasome activators serve as building blocks to adjust protein turnover in cell growth and differentiation. Understanding the cellular function of proteasome activation in more detail offers a new strategy for therapeutic targeting of proteasomal protein breakdown in disease. The role of the proteasome activator PA200 in cell function and its regulation in disease is unknown. In this study, we investigated the function of PA200 in myofibroblast differentiation and fibrotic tissue remodeling. PA200 was upregulated in hyperplastic basal cells and myofibroblasts of fibrotic lungs from patients with idiopathic pulmonary fibrosis. Increased expression of PA200 and enhanced formation of PA200-proteasome complexes was also evident in experimental fibrosis of the lung and kidney in vivo and in activated primary human myofibroblasts of the lung in vitro. Transient silencing and overexpression revealed that PA200 functions as a negative regulator of myofibroblast differentiation of human but not mouse cells. Our data thus suggest an unexpected and important role for PA200 in adjusting myofibroblast activation in response to pro-fibrotic stimuli, which fails in idiopathic pulmonary fibrosis.

Scientific reports 7(1), 15523 (2017). doi:10.1038/s41598-017-15804-9, Published by Nature Publishing Group, London

Metasurfaces with sub-wavelength features are useful in modulating the phase, amplitude or polarization of electromagnetic fields. While several applications are reported for light manipulation and control, the sharp phase changes would be useful in enhancing the beam shifts at reflection from a metasurface. In designed periodic patterns on metal film, at surface plasmon resonance, we demonstrate Goos-Hanchen shift of the order of 70 times the incident wavelength and the angular shifts of several hundred microradians. We have designed the patterns using rigorous coupled wave analysis (RCWA) together with S-matrices and have used a complete vector theory to calculate the shifts as well as demonstrate a versatile experimental setup to directly measure the shifts. The giant shifts demonstrated could prove to be useful in enhancing the sensitivity of experiments ranging from atomic force microscopy to gravitational wave detection.

Metasurfaces with sub-wavelength features are useful in modulating the phase, amplitude or polarization of electromagnetic fields. While several applications are reported for light manipulation and control, the sharp phase changes would be useful in enhancing the beam shifts at reflection from a metasurface. In designed periodic patterns on metal film, at surface plasmon resonance, we demonstrate Goos-Hanchen shift of the order of 70 times the incident wavelength and the angular shifts of several hundred microradians. We have designed the patterns using rigorous coupled wave analysis (RCWA) together with S-matrices and have used a complete vector theory to calculate the shifts as well as demonstrate a versatile experimental setup to directly measure the shifts. The giant shifts demonstrated could prove to be useful in enhancing the sensitivity of experiments ranging from atomic force microscopy to gravitational wave detection.

Plasmonic quasicrystals (PlQCs), by integrating the properties of quasicrystals (rotational symmetry and long range ordering but lack translational symmetry) and surface plasmon polariton mediated effects, offer several advantages over plasmonic crystals (PlCs). For example, in PlQCs one could have broadband, polarization independent response. However, large area patterning by electron beam lithography requires precise lattice coordinates as well as a practical way to design the structures for specific spectral response. We demonstrate design and fabrication of large area quasicrystal air hole patterns of π/5 symmetry in metal film in which broadband, polarization and launch angle independent transmission enhancement is observed. We demonstrate bi-grating quasicrystals to show that designable transmission response is possible over visible to near infrared wavelength regions with about 15 times enhancement. These would be useful in many applications like energy harvesting, nonlinear optics and quantum plasmonics.