Radiation-Induced Alteration of the Brain Proteome: Understanding the Role of the Sirtuin 2 Deacetylase in a Murine Model

Whole brain radiotherapy (WBRT) produces unwanted sequelae, albeit via unknown mechanisms. A deacetylase expressed in the central nervous system, Sirtuin 2 (SIRT2), has been linked to neurodegeneration. Therefore, we sought to challenge the notion that a single disease pathway is responsible for radiation-induced brain injury in <i>Sirt2</i> wild-type (WT) and knockout (KO) mice at the proteomic level. We utilized isobaric tag for relative and absolute quantitation to analyze brain homogenates from <i>Sirt2</i> WT and KO mice with and without WBRT. Selected proteins were independently verified, followed by ingenuity pathway analysis. Canonical pathways for Huntington’s, Parkinson’s, and Alzheimer’s were acutely affected by radiation within 72 h of treatment. Although loss of <i>Sirt2</i> preferentially affected both Huntington’s and Parkinson’s pathways, WBRT most significantly affected Huntington’s-related proteins in the absence of <i>Sirt2</i>. Identical protein expression patterns were identified in Mog following WBRT in both <i>Sirt2</i> WT and KO mice, revealing a proteomic radiation signature; however, long-term radiation effects were found to be associated with altered levels of a small number of key neurodegeneration-related proteins, identified as Mapt, Mog, Snap25, and Dnm1. Together, these data demonstrate the principle that the presence of <i>Sirt2</i> can have significant effects on the brain proteome and its response to ionizing radiation

Radiation-Induced Alteration of the Brain Proteome: Understanding the Role of the Sirtuin 2 Deacetylase in a Murine Model

Whole brain radiotherapy (WBRT) produces unwanted sequelae, albeit via unknown mechanisms. A deacetylase expressed in the central nervous system, Sirtuin 2 (SIRT2), has been linked to neurodegeneration. Therefore, we sought to challenge the notion that a single disease pathway is responsible for radiation-induced brain injury in <i>Sirt2</i> wild-type (WT) and knockout (KO) mice at the proteomic level. We utilized isobaric tag for relative and absolute quantitation to analyze brain homogenates from <i>Sirt2</i> WT and KO mice with and without WBRT. Selected proteins were independently verified, followed by ingenuity pathway analysis. Canonical pathways for Huntington’s, Parkinson’s, and Alzheimer’s were acutely affected by radiation within 72 h of treatment. Although loss of <i>Sirt2</i> preferentially affected both Huntington’s and Parkinson’s pathways, WBRT most significantly affected Huntington’s-related proteins in the absence of <i>Sirt2</i>. Identical protein expression patterns were identified in Mog following WBRT in both <i>Sirt2</i> WT and KO mice, revealing a proteomic radiation signature; however, long-term radiation effects were found to be associated with altered levels of a small number of key neurodegeneration-related proteins, identified as Mapt, Mog, Snap25, and Dnm1. Together, these data demonstrate the principle that the presence of <i>Sirt2</i> can have significant effects on the brain proteome and its response to ionizing radiation

Modulating Cationic Ratios for High-Performance Transparent Solution-Processed Electronics

Amorphous oxide semiconductors such as indium zinc tin oxide (IZTO) are considered favorites to serve as channel materials for thin film transistors (TFTs) because they combine high charge carrier mobility with high optical transmittance, allowing for the development of transparent electronics. Although the influence of relative cationic concentrations in determining the electronic properties have been studied in sputtered and PLD films, the development of printed transparent electronics hinges on such dependencies being explored for solution-processed systems. Here, we study solution-processed indium zinc tin oxide thin film transistors (TFTs) to investigate variation in their electrical properties with change in cationic composition. Charge transport mobility ranging from 0.3 to 20.3 cm²/(V s), subthreshold swing ranging from 1.2 to 8.4 V/dec, threshold voltage ranging from −50 to 5 V, and drain current on–off ratio ranging from 3 to 6 orders of magnitude were obtained by examining different compositions of the semiconductor films. Mobility was found to increase with the incorporation of large cations such as In³⁺ and Sn⁴⁺ due to the vast s-orbital overlap they can achieve when compared to the intercationic distance. Subthreshold swing decreased with an increase in Zn²⁺ concentration due to reduced interfacial state formation between the semiconductor and dielectric. The optimized transistor obtained at a compositional ratio of In/Zn/Sn = 1:1:1, exhibited a high field-effect mobility of 8.62 cm²/(V s), subthreshold swing of 1.75 V/dec, and current on–off ratio of 10⁶. Such impressive performances reaffirm the promise of amorphous metal oxide semiconductors for printed electronics

Low-Temperature Chemical Transformations for High-Performance Solution-Processed Oxide Transistors

The challenges associated with low-temperature solution-processed metal oxide network formation have hindered the realization of high-performance solution-based electronic circuitry at temperatures lower than 200 °C. Here, UV irradiation is embarked upon as a route to effectively transform the chemical precursors to semiconducting metal oxides with high electrical quality. High-performance UV-irradiated indium oxide (In₂O₃) and indium zinc oxide (IZO) thin film transistors with mobility greater than 30 cm²/(V s) have been obtained from nitrate-based precursors. The chemical transformation has been monitored by detailed spectroscopic studies, physical characterization, and temperature-dependent electrical transport measurements. In comparison to thermal annealing, UV annealing seems to result in higher M–O–M network formation (depicted by M–O bonds in XPS), better removal of chemical impurities (depicted by FTIR and XPS), and structural relaxation driven electron doping, transforming the oxygen vacancies to act as shallow donors (depicted by TFT characteristics, XPS, XRD, and Urbach studies). Our results provide new insight into how UV irradiation drives metal oxide network formation and passivates the subgap density of states (DOS)

Enhancement of Open-Circuit Voltage of Solution-Processed Cu₂ZnSnS₄ Solar Cells with 7.2% Efficiency by Incorporation of Silver

Recently, considerable attention in the development of Cu₂ZnSnS₄ (CZTS)-based thin-film solar cells has been given to the reduction of antisite defects via cation substitution. In this Letter, we report the substitution of copper atoms by silver, incorporated into the crystal lattice through a solution processable method. We observe an increase in open-circuit voltage (<i>V</i>_OC) by 50 mV and an accompanying rise in device efficiency from 4.9% to 7.2%. The incorporation of Ag is found to improve the grain size, enhance the depletion width of the pn-junction, and reduce the concentration of antisite defect states. This work demonstrates the promising role of Ag in reducing the <i>V</i>_OC deficit of Cu-kesterite thin-film solar cells

Origin of Photocarrier Losses in Iron Pyrite (FeS₂) Nanocubes

Iron pyrite has received significant attention due to its high optical absorption. However, the loss of open circuit voltage (<i>V</i>_oc) prevents its further application in photovoltaics. Herein, we have studied the photophysics of pyrite by ultrafast laser spectroscopy to understand fundamental limitation of low <i>V</i>_oc by quantifying photocarrier losses in high quality, stoichiometric, and phase pure {100} faceted pyrite nanocubes. We found that fast carrier localization of photoexcited carriers to indirect band edge and shallow trap states is responsible for major carrier loss. Slow relaxation component reflects high density of defects within the band gap which is consistent with the observed Mott-variable range hopping (VRH) conduction from transport measurements. Magnetic measurements strikingly show the magnetic ordering associated with phase inhomogeneity, such as FeS_2−δ (0 ≤ δ ≤ 1). This implies that improvement of iron pyrite solar cell performance lies in mitigating the intrinsic defects (such as sulfur vacancies) by blocking the fast carrier localization process. Photocarrier generation and relaxation model is presented by comprehensive analysis. Our results provide insight into possible defects that induce midgap states and facilitate rapid carrier relaxation before collection

Iron Pyrite Thin Film Counter Electrodes for Dye-Sensitized Solar Cells: High Efficiency for Iodine and Cobalt Redox Electrolyte Cells

Iron pyrite has been the material of interest in the solar community due to its optical properties and abundance. However, the progress is marred due to the lack of control on the surface and intrinsic chemistry of pyrite. In this report, we show iron pyrite as an efficient counter electrode (CE) material alternative to the conventional Pt and poly(3,4-ethylenedioxythiophene (PEDOT) CEs in dye-sensitized solar cells (DSSCs). Pyrite film CEs prepared by spray pyrolysis are utilized in I₃^–/I^– and Co(III)/Co(II) electrolyte-mediated DSSCs. From cyclic voltammetry and impedance spectroscopy studies, the catalytic activity is found to be comparable with that of Pt and PEDOT in I₃^–/I^– and Co(III)/Co(II) electrolyte, respectively. With the I₃^–/I^– electrolyte, photoconversion efficiency is found to be 8.0% for the pyrite CE and 7.5% for Pt, whereas with Co(III)/Co(II) redox DSSCs, efficiency is found to be the same for both pyrite and PEDOT (6.3%). The excellent performance of the pyrite CE in both the systems makes it a distinctive choice among the various CE materials studied

A Fourteen Gene GBM Prognostic Signature Identifies Association of Immune Response Pathway and Mesenchymal Subtype with High Risk Group

<div><p>Background</p><p>Recent research on glioblastoma (GBM) has focused on deducing gene signatures predicting prognosis. The present study evaluated the mRNA expression of selected genes and correlated with outcome to arrive at a prognostic gene signature.</p><p>Methods</p><p>Patients with GBM (n = 123) were prospectively recruited, treated with a uniform protocol and followed up. Expression of 175 genes in GBM tissue was determined using qRT-PCR. A supervised principal component analysis followed by derivation of gene signature was performed. Independent validation of the signature was done using TCGA data. Gene Ontology and KEGG pathway analysis was carried out among patients from TCGA cohort.</p><p>Results</p><p>A 14 gene signature was identified that predicted outcome in GBM. A weighted gene (WG) score was found to be an independent predictor of survival in multivariate analysis in the present cohort (HR = 2^.507; B = 0^.919; p<0^.001) and in TCGA cohort. Risk stratification by standardized WG score classified patients into low and high risk predicting survival both in our cohort (p = <0^.001) and TCGA cohort (p = 0^.001). Pathway analysis using the most differentially regulated genes (n = 76) between the low and high risk groups revealed association of activated inflammatory/immune response pathways and mesenchymal subtype in the high risk group.</p><p>Conclusion</p><p>We have identified a 14 gene expression signature that can predict survival in GBM patients. A network analysis revealed activation of inflammatory response pathway specifically in high risk group. These findings may have implications in understanding of gliomagenesis, development of targeted therapies and selection of high risk cancer patients for alternate adjuvant therapies.</p></div

Details about the genes that form part of the 14 gene prognostic signature.

*<p>SD - Standard deviation.</p

Gene Ontology terms significantly enriched (p<0.05) in the set of genes differentially expressed between high risk and low risk.

<p>Gene Ontology terms significantly enriched (p<0.05) in the set of genes differentially expressed between high risk and low risk.</p