Emerging roles of PHLPP phosphatases in the nervous system.

It has been more than a decade since the discovery of a novel class of phosphatase, the Pleckstrin Homology (PH) domain Leucine-rich repeat Protein Phosphatases (PHLPP). Over time, they have been recognized as crucial regulators of various cellular processes, such as memory formation, cellular survival and proliferation, maintenance of circadian rhythm, and others, with any deregulation in their expression or cellular localization causing havoc in any cellular system. With the ever-growing number of downstream substrates across multiple tissue systems, a web is emerging wherein the central point is PHLPP. A slight nick in the normal signaling cascade of the two isoforms of PHLPP, namely PHLPP1 and PHLPP2, has been recently found to invoke a variety of neurological disorders including Alzheimer's disease, epileptic seizures, Parkinson's disease, and others, in the neuronal system. Improper regulation of the two isoforms has also been associated with various disease pathologies such as diabetes, cardiovascular disorders, cancer, musculoskeletal disorders, etc. In this review, we have summarized all the current knowledge about PHLPP1 (PHLPP1α and PHLPP1ß) and PHLPP2 and their emerging roles in regulating various neuronal signaling pathways to pave the way for a better understanding of the complexities. This would in turn aid in providing context for the development of possible future therapeutic strategies.

Prognostic Value of Metabolic Tumor Parameters in Pretreatment 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Scan in Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: This retrospective study aimed to investigate whether metabolic parameters of primary tumour i.e. maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) predict overall survival (OS) in patients with advanced stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: SUVmax, MTV and TLG of the primary tumors were measured in staging 18F-Fluorodeoxyglucose Positron emission tomography- Computed tomography (18F-FDG PET/CT) scan of 97 NSCLC patients by gradient based tumour segmentation method. Prognostic ability was assessed for overall survival (OS) of the patients. RESULT: The median follow-up period of the study was 15.84 months (range 1.3 to 47.97 months).The estimated median OS was 11.29 months (range 1.37 to 38.63 months). Total of 40 (41.24%) patients had progressive disease and 21 (21.65%) patients died during the follow up period. Receiver Operating Characteristic (ROC) analysis showed that the area under the curve (AUC) for MTV was significant (area = 0.652 ± 0.065; 95% CI = 0.548 - 0.746; P = 0.020). Kaplan-Meier survival curves showed that the OS differences between the groups of patients who were dichotomized by the median value of MTV (38.76 ml, P = 0.0150) and TLG (301.69 ml, P = 0.0046) were significant. MTV (hazard ratio = 4.524; 95% CI = 1.244 - 16.451; P = 0.022) was found to be an independent prognostic factor for OS in multivariate analysis. CONCLUSION: MTV of the primary tumor is a potential prognostic parameter for OS in our population of advanced NSCLC patients independent of other risk factors.

Contrasting spectroscopic response of human hemoglobin in presence of graphene oxides and its reduced form: Comparative approach with carbon quantum dots.

Recently, a considerable amount of research is being directed towards study of graphene oxide (GO) and its reduced form (RGO) since their exposed functional groups make them better candidates in nanobiotechnolgy. In order to assess their biocompatibility, the nature of interactions between Human Hemoglobin (HHb) and GO/RGO are monitored since a comparative spectroscopic approach towards understanding their nature of interactions has not been investigated previously. UV-vis spectroscopy reveals hyperchromicity for HHb-GO system and hypochromicity for HHb-RGO system in the region of absorption of tryptophan/tyrosine residues. Notably, although steady-state fluorescence static quenching of HHb for GO and enhancement of fluorescence for RGO is noticed, but average fluorescence-lifetime is remaining unchanged in presence of GO/RGO. Calorimetric data illustrates three-site and five-site binding model to be the best-fit model for GO and RGO respectively. Also, synchronous fluorescence quenching corresponding to alterations in microenvironment of tryptophan/ tyrosine residues is observed only in presence of GO. Likewise FTIR spectroscopy elucidates involvement of both amide I and amide II bond of HHb backbone through H-bonding interaction only for GO. Furthermore RLS spectra demonstrate an increase and a decrease in signal for GO and RGO respectively. Surprisingly, secondary structure of HHb is maintained upon interaction with both GO/RGO, as revealed by CD spectroscopy, thus supporting their potential application in biological microenvironment. Thus it appears that the spectroscopic properties of HHb upon interaction with GO is altered upon its reduction to RGO. Furthermore the role of HHb as good candidate for bimolecular interaction has been highlighted.

Correlation of cation distribution with the hyperfine and magnetic behaviour of Ni0.3Zn0.4Co0.2Cu0.1Fe2O4 nanoparticles and their microwave absorption properties when encapsulated in multi-walled carbon nanotubes.

Nanocrystalline samples of Ni0.3Zn0.4Co0.2Cu0.1Fe2O4 (NZCCF) are prepared by a simple co-precipitation method. To obtain nanoparticles of different sizes, the as prepared sample is annealed at 400, 600, 800 and 1000 °C. Nanoparticles of the sample annealed at 600 °C are encapsulated in multi-walled carbon nanotubes (MWCNT). To confirm the crystallographic phase, x-ray diffraction (XRD) patterns are analyzed by the Rietveld method and cation distribution in A- and B-sites is estimated from the analysis. Occupancy of Zn2+ ions in A-site and that of Fe3+ ions in B-site increase with the increase of annealing temperature (T A) and lattice parameters lie within 8.365-8.398 Å. Morphology of the encapsulated sample is examined by taking micrographs in high resolution transmission electron microscope (HRTEM). Hyperfine behaviour of the prepared samples is studied by analyzing Mössbauer spectra recorded at room temperature (RT) and 77 K. Average values of isomer shift (IS) are found to decrease with the increase of crystallite size. Static and dynamic magnetic hysteresis loops are recorded to analyze the magnetic properties of the sample. Maximum saturation magnetization of ~75 emu g-1 is obtained for the sample of NZCCF annealed at 800 °C with crystallite size of ~48 nm. Microwave absorption capability of the encapsulated sample is measured by recording the reflection loss in X and K u bands of microwave region of frequency. Maximum value of reflection loss is -25.71 dB observed at 15.24 GHz for a sample layer thickness of 1 mm. Moreover, the reflection loss is less than -10 dB for the entire range of observation (8-18 GHz) which shows that MWCNT encapsulated NZCCF could be considered as a potential candidate for applications in microwave devices.