Candida drug resistance protein 1, a major multidrug ATP binding cassette transporter of Candida albicans, translocates fluorescent phospholipids in a reconstituted system

Candida albicans drug resistance protein 1 (Cdr1p), an ATP-dependent drug efflux pump, contributes to multidrug resistance in Candida-infected immunocompromised patients. Previous cell-based assays suggested that Cdr1p also acts as a phospholipid translocator. To investigate this, we reconstituted purified Cdr1p into sealed membrane vesicles. Comparison of the ATPase activities of sealed and permeabilized proteoliposomes indicated that Cdr1p was asymmetrically reconstituted such that ~70% of the molecules had their ATP binding sites accessible to the extravesicular space. Fluorescent glycerophospholipids were incorporated into the outer leaflet of the proteoliposomes, and their transport into the inner leaflet was tracked with a quenching assay using membrane-impermeant dithionite. We observed ATP-dependent transport of the fluorescent lipids into the inner leaflet of the vesicles. With 6 molecules of Cdr1p per vesicle on average, the half-time to reach the maximal extent of transport was ~15 min. Transport was reduced in vesicles reconstituted with Cdr1p variants with impaired ATPase activity and could be competed out to different levels by a molar excess of drugs such as fluconazole and miconazole that are known to be effluxed by Cdr1p. Transport was not affected by ampicillin, a compound that is not effluxed by Cdr1p. Our results suggest a direct link between the ability of Cdr1p to translocate fluorescent phospholipids and efflux drugs. We note that only a few members of the ABC superfamily of Candida have a well-defined role as drug exporters; thus, lipid translocation mediated by Cdr1p could reflect its cellular function

Quest for lead free relaxors in YIn<SUB>1–x</SUB>Fe<SUB>x</SUB>O<SUB>3</SUB>(0.0 ≤x≤ 1.0) system: role of synthesis and structure

The B-site tailored YIn1–xFexO3 (0.0≤ x≤ 1.0) series was synthesized by glycine-aided gel-combustion technique and subjected to extensive structural and electrical investigations. The temperature had tremendous bearing on the phase evolution exhibited by the system. The entire system crystallized as C-type metastable polymorph in the as–synthesized form. Hexagonal polymorphs of Fe3+-rich compositions could be isolated by controlled heat treatment at 750 °C. Raman spectroscopic investigations showed that, while there is a general shrinkage of the lattice due to substitution of a smaller ion at In3+-site, there is an apparent dilation of the Y–O bond, and this anomaly reflects in the electrical behavior exhibited by the system. The single-phasic hexagonal nominal compositions, YIn1–xFexO3 (0.0 ≤ x ≤ 0.3), were also studied by impedance spectroscopy. The dielectric constant was found to drastically increase from 10 for YInO3 to 1000 for YIn0.7Fe0.3O3 at room temperature stressing the role of B-site tailoring on electrical behavior. More interestingly, careful substitution of Fe into YInO3 could tune the electrical behavior from a dielectric to relaxor ferroelectric in the temperature range studied. The nominal composition YIn0.7Fe0.3O3 showed a classical relaxor ferroelectric like behavior which is an important observation in context of the search for new lead free relaxor materials

Heparan Sulfate Binding Cationic Peptides Restrict SARS-CoV-2 Entry

A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. While the world is striving for a treatment modality against SARS-CoV-2, our understanding about the virus entry mechanisms may help to design entry inhibitors, which may help to limit the virus spreading. Owing to the importance of cellular ACE2 and heparan sulfate in SARS-CoV-2 entry, we aimed to evaluate the efficacy of cationic G1 and G2 peptides in virus entry inhibition. In silico binding affinity studies revealed possible binding sites of G1 and G2 peptides on HS and ACE2, which are required for the spike–HS and spike–ACE2 interactions. Prophylactic treatment of G1 and G2 peptide was also proved to decrease the cell surface HS, an essential virus entry receptor. With these two mechanisms we confirm the possible use of cationic peptides to inhibit the entry of SARS-CoV-2

Multifunctional nanocrystalline CeCrO<SUB>3</SUB>: antiferromagnetic, relaxor, and optical properties

Nanocrystalline phase pure CeCrO<SUB>3</SUB> was synthesized by a two-step synthesis. The compound was investigated by a host of characterization techniques such as X-ray diffraction, high-temperature X-ray diffraction, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric−differential thermal analysis, magnetic and specific heat capacity data, ac impedance spectroscopy, diffuse reflectance DR UV−visible spectrophotometer, and dynamic light scattering. The magnetic structure of CeCrO<SUB>3</SUB> was established using variable-temperature neutron diffraction data. On the basis of the detailed studies, this compound was found to exhibit multifunctionalities such as antiferromagnetism, relaxor behavior, and an optical band gap in the visible region. This newly developed synthesis route opens the immense possibilities of preparation of the hitherto unknown Ce<SUP>3+</SUP>-based mixed oxides, analogous to other rare earth (RE<SUP>3+</SUP>) counterparts

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

IDH1 Mutations in Diffusely Infiltrating Astrocytomas Grade Specificity, Association With Protein Expression, and Clinical Relevance

IDH1 mutations are frequent genetic alterations in low-grade diffuse gliomas and secondary glioblastoma (GBM). To validate mutation frequency, IDH1 gene at codon 132 was sequenced in 74 diffusely infiltrating astrocytomas: diffuse astrocytoma (DA; World Health Organization WHO] grade II), anaplastic astrocytoma (AA; WHO grade III), and GBM (WHO grade IV). All cases were immunostained with IDH1-R132H monoclonal antibody. Mutational status was correlated with mutant protein expression, patient age, duration of symptoms, and prognosis of patients with GBM. We detected 31 (41.9%) heterozygous IDH1 mutations resulting in arginine-to-histidine substitution (R132H;CGT-CAT). All 12 DAs (100%), 13 of 14 AAs (92.9%), and 6 of 48 GBMs (12.5%) (5/6 83.3%] secondary, and 1/42 2.4%] primary) harbored IDH1 mutations. The correlation between mutational status and protein expression was significant (P < .001). IDH1 mutation status, though not associated with prognosis of patients with GBM, showed significant association with younger age and longer duration of symptoms in the whole cohort (P < .001). Our study validates IDH1 mutant protein expression across various grades of astrocytoma, and demonstrates a high incidence of IDH1 mutations in DA, AA, and secondary GBM

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