Blockade of AMPA receptors by nickel in cultured rat astrocytes

The effect of Ni²⁺ on glial α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors was studied using the whole-cell patch-clamp technique in cultured rat cerebellar astrocytes. The application of kainate (10 μM-5 mM) evoked inward currents at a holding potential of −70 mV. These currents were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and Evans Blue, and potentiated by cyclothiazide, suggesting that they were primarily mediated by the AMPA receptor subtype. Analysis of the kainate concentration-response relation in cultured astrocytes revealed a maximal current of 488 pA, a half-maximal effective concentration of 137 μM and a Hill coefficient of 1.43, indicating more than one agonist binding site. Ni²⁺ inhibited the current activated by 300 μM kainate in a concentration-dependent manner, displaying a half-maximal inhibition at 860 μM Ni²⁺ and a Hill coefficient of 1.07. In the presence of 700 μM Ni²⁺ the kainate-induced concentration-response curve was shifted towards higher concentrations, increasing the half-maximal effective concentration to 300 μM, without significantly changing the Hill coefficient. The blocking effect of Ni²⁺ was counteracted by increasing kainate concentrations, suggesting a competitive mechanism. © 1996 Wiley-Liss, Inc.     

Phase separation of blends of polydisperse polymers: Comparison between experiment and theory for the system poly(dimethylsiloxane)/poly(ethylmethylsiloxane)

Cloud point curves were measured turbidimetrically for blends (upper critical solution temperatures; UCSTs) of poly(ethylmethylsiloxane) (PEMS) and four different samples of poly(dimethylsiloxane) (PDMS); the weight average molar masses in kg/mol are 31.2 for PEMS and 10.4, 15.5, 18.1 and 24.0 for PDMS; all components have polydispersity indices D (= M̄_w/M̄_n) within the range from 1.82 to 2.67. Corresponding calculations on the basis of the Flory-Huggins theory (three adjustable parameters) account for the poly-dispersity; molecular weight distributions are represented by the generalized Schulz-Flory equation. Calculated cloud point curves agree very well with those measured, if individual sets of parameters are admitted for each of the different mixtures. Even for an identical set of parameters the maximum deviations remain moderate. Realistic model calculations concerning the influences of D on cloud points and on critical points were performed with this set of parameters. For the present (only slightly endothermal) system, the precipitation threshold increases from 318 to 558.6 K as D_PEMS is raised from 1.87 to 4.00, keeping the number average degree of polymerization constant.     

Tumor mutational burden and purity adjustment before and after treatment with temozolomide in 27 paired samples of glioblastoma: a prospective study

Treatment of glioblastoma (GBM) remains a challenging task, with limited treatment options, none offering a cure. Immune therapy has proven effective across different cancers with remarkable response rates. Tumor mutational burden (TMB) is a marker of response, but technical and methodological differences in TMB estimates have made a proper assessment and comparison challenging. Here, we analyzed a prospective collection of paired samples from 35 patients with newly diagnosed GBM, all of whom were wild‐type (WT) for isocitrate dehydrogenase, before and after treatment with radiotherapy and temozolomide. Seven patients (20%) had O6‐methylguanine‐DNA methyltransferase‐methylated tumors. Six patients (17%) had two relapse surgeries, and tissue from all three surgeries was collected. We found that accurate evaluation of TMB was confounded by high variability in the cancer cell fraction of relapse samples. To ameliorate this, we developed a model to adjust for tumor purity based on the relative density distribution of variant allele frequencies in each primary–relapse pair. Additionally, we examined the mutation spectra of shared and private mutations. After tumor purity adjustment, we found TMB comparison reliable in tumors with tumor purity between 15% and 40%, resulting in 27/35 patients (77.1%). TMB remained unchanged from 0.65 mutations per megabase (Mb) to 0.67/Mb before and after treatment, respectively. Examination of the mutation spectra revealed a dominance of C > T transitions at CpG sites in both shared and relapse‐private mutations, consistent with cytosine deamination and the clock‐like mutational signature 1. We present and apply a cellularity correction approach that enables more accurate assessment of TMB in paired tumor samples. We did not find a significant increase in TMB after correcting for cancer cell fraction. Our study raises significant concerns when determining TMB. Although a small sample size, corrected TMB can have a clinical significance when stratifying patients to experimental treatment, for example, immune checkpoint therapy.     

Immunotherapy and immunotherapy biomarkers for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is increasing in prevalence and has the potential to be a highly lethal malignancy. Patients with early-stage HCC have potentiall...     

Cobalt-modified palladium nanocatalyst on nitrogen-doped reduced graphene oxide for direct hydrazine fuel cell

Nitrogen-doped reduced graphene oxide-supported palladium–cobalt nanoparticles (PdCo NPs/NrGO NSs) are synthesized and used as a high-performance and low-cost anodic catalyst for direct hydrazine–hydrogen peroxide fuel cells. The SEM and TEM images of PdCo NPs/NrGO NSs show the uniform metal nanoparticle distribution on the NrGO NSs. The reduction of the oxygen functional groups and the doping of the nitrogen atoms in the GO framework are confirmed by FT-IR and XRD spectroscopic studies. The Pd catalysts modified by Co exhibit a higher catalytic activity, lower onset potential, better durability, and lower impedance values than unmodified Pd catalysts for the electro-oxidation of hydrazine. The kinetic studies show a first-order reaction with an activation energy of 12.51 kJ mol⁻¹. A direct hydrazine–hydrogen peroxide fuel cell with PdCo NPs/NrGO NSs as anode and Pt/C as cathode provides an open circuit voltage of 1.76 V and a maximum power density of 148.58 mW cm⁻² at 60 °C, indicating that the PdCo NPs/NrGO NSs are an economical, high performance and reliable anode catalyst for the direct hydrazine–hydrogen peroxide fuel cell.

The superior catalytic activity and stability of a novel anodic PdCo NPs/NrGO NSs for HzOR are confirmed by half and signal cell investigations.