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Intra- and intermolecular studies on the molten L-sorbose have been carried out at variable temperature conditions to determine the crosover temperature ( T c ). In addition, isothermal time-dependent FTIR and Raman measurements were performed to probe the pace of mutarotation and activation energy of this reaction in the studied saccharide, which varied from 53–62 kJ/mol up to 177–192 kJ/mol below and above T c , respectively. To explain the change in activation barrier for the mutarotation a complementary analysis using difference FTIR spectra collected around T c = 365 K in the hydroxyl region has been done. It was found that the alteration of kinetic parameters and molecular dynamics around T c are strictly related to the variation in the strength of H-bonds which above T c are significantly weaken, increasing the freedom of rotation of functional groups and movement of individual molecules. That phenomenon most likely affects the proton transfer, underlying molecular mechanism of mutarotation, which may lead to the significant increase in activation barrier. The new insight into a molecular aspect of the mutarotation around T c has created an opportunity to better understanding the relationship between physics of condensed matter and the potential role of H-bonds dynamics on the progress of the chemical reaction in highly viscous systems.
We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2. fed HFD and 3. fed HFD and treated with metformin. The animals were infused with a [U- 13 C]palmitate to measure fractional lipid synthesis rate. This allowed for the calculation of fractional synthesis rate of signaling lipids (FSR) through the estimation of their isotopic enrichment. Liver ceramide (Cer), diacylglycerol (DAG) and acyl-carnitine concentration and enrichment were analyzed by LC/MS/MS. The content of proteins involved in lipid metabolism and insulin signaling were analyzed by Western Blot. HFD treatment increased the content and FSR of DAG and Cer in the liver which was accompanied by systemic insulin resistance and inhibition of hepatic insulin signaling pathway under insulin stimulation. Metformin treatment ameliorated systemic insulin resistance and augmented the hepatic insulin signaling cascade. It reduced both the concentration and FSR of Cer, DAG, and increased acyl-carnitine content and the expression of mitochondrial markers. We postulate, that in liver, the insulin sensitizing effect of metformin depends on augmentation of mitochondrial β-oxidation, which protects from hepatic accumulation of both the Cer and DAG and preserves insulin sensitivity under HFD consumption. Moreover, we showed that hepatic content of Cer and DAG corresponds with their respective FSR.
We compare two approaches for deriving corrections to the “linear model” of cavity optomechanics, in order to describe effects that are beyond first order in the radiation pressure coupling. In the regime where the mechanical frequency is much lower than the cavity one, we compare: (I) a widely used phenomenological Hamiltonian conserving the photon number; (II) a two-mode truncation of C. K. Law’s microscopic model, which we take as the “true” system Hamiltonian. While these approaches agree at first order, the latter model does not conserve the photon number, resulting in challenging computations. We find that approach (I) allows for several analytical predictions, and significantly outperforms the linear model in our numerical examples. Yet, we also find that the phenomenological Hamiltonian cannot fully capture all high-order corrections arising from the C. K. Law model.
Mitochondria are central key players in cell metabolism, and mitochondrial DNA (mtDNA) instability has been linked to metabolic changes that contribute to tumorigenesis and to increased expression of pro-tumorigenic genes. Here, we use melanoma cell lines and metastatic melanoma tumors to evaluate the effect of mtDNA alterations and the expression of the mtDNA packaging factor, TFAM, on energetic metabolism and pro-tumorigenic nuclear gene expression changes. We report a positive correlation between mtDNA copy number, glucose consumption, and ATP production in melanoma cell lines. Gene expression analysis reveals a down-regulation of glycolytic enzymes in cell lines and an up-regulation of amino acid metabolism enzymes in melanoma tumors, suggesting that TFAM may shift melanoma fuel utilization from glycolysis towards amino acid metabolism, especially glutamine. Indeed, proliferation assays reveal that TFAM-down melanoma cell lines display a growth arrest in glutamine-free media, emphasizing that these cells rely more on glutamine metabolism than glycolysis. Finally, our data indicate that TFAM correlates to VEGF expression and may contribute to tumorigenesis by triggering a more invasive gene expression signature. Our findings contribute to the understanding of how TFAM affects melanoma cell metabolism, and they provide new insight into the mechanisms by which TFAM and mtDNA copy number influence melanoma tumorigenesis.
Angiotensin 1–7 (Ang1–7) is an endogenous bioactive component of the renin-angiotensin system (RAS). In addition to its cardiovascular properties, its anti-proliferative and anti-angiogenic traits are believed to play important roles in carcinogenesis. The present study examines the influence of Ang1–7 on processes associated with development and progression of prostate cancer cells. Our findings indicate that while Ang1–7 (1 nM; 48 h) can effectively reduce cell proliferation in DU-145, it can induce a significant decrease in the expression of MKI67 in LNCaP. In both cell lines we also observed a reduction in colony size in soft agar assay. A various changes in gene expression were noted after exposure to Ang1–7: those of anti- and pro-apoptotic agents and the NF-kB family of transcription factors, as well as mesenchymal cell markers and vascular endothelial growth factor A ( VEGFA ). In addition, Ang1–7 was found to modulate cell adhesion and matrix metallopeptidase (MMP) activity. Changes were also observed in the levels of angiotensin receptors and sex steroid hormone receptors. Ang1–7 reduced the levels of estrogen receptor alpha gene ( ESR1 ) and increased the expression of estrogen receptor beta gene ( ESR2 ) in all prostate cancer cells; it also up-regulated androgen receptor ( AR ) expression in androgen-sensitive cells but contradictory effect was observed in androgen- irresponsive cell lines. In summary, the results confirm the existence of complex network between the various elements of the local RAS and the molecular and cellular mechanisms of prostate cancerogenesis. The response of cancer cells to Ang1–7 appears to vary dependently on the dose and time of incubation as well as the aggressiveness and the hormonal status of cells.
Disseminated diseases of the central nervous system such as amyotrophic lateral sclerosis (ALS) require that therapeutic agents are delivered and distributed broadly. Intrathecal route is attractive in that respect, but to date there was no methodology available allowing for optimization of this technique to assure safety and efficacy in a clinically relevant setting. Here, we report on interventional, MRI-guided approach for delivery of hydrogel-embedded glial progenitor cells facilitating cell placement over extended surface of the spinal cord in pigs and in naturally occurring ALS-like disease in dogs. Glial progenitors used as therapeutic agent were embedded in injectable hyaluronic acid-based hydrogel to support their survival and prevent sedimentation or removal. Intrathecal space was reached through lumbar puncture and the catheter was advanced under X-ray guidance to the cervical part of the spine. Animals were then transferred to MRI suite for MRI-guided injection. Interventional and follow-up MRI as well as histopathology demonstrated successful and predictable placement of embedded cells and safety of the procedure.
Surface-enhanced Raman spectroscopy (SERS) is well known for its high sensitivity that emerges due to the plasmonic enhancement of electric fields typically on gold and silver nanostructures. However, difficulties associated with the preparation of nanostructured substrates with uniform and reproducible features limit reliability and quantitation using SERS measurements. In this work we use layer-by-layer (LbL) self-assembly to incorporate multiple functional building blocks of collaborative assemblies of nanoparticles on colloidal spheres to fabricate SERS sensors. Gold nanoparticles (AuNPs) are packaged in discrete layers, effectively 'freezing nano-gaps', on spherical colloidal cores to achieve multifunctionality and reproducible sensing. Coupling between layers tunes the plasmon resonance for optimum SERS signal generation to achieve a 10 nM limit of detection. Significantly, using the layer-by-layer construction, SERS-active AuNP layers are spaced out and thus optically isolated. This uniquely allows the creation of an internal standard within each colloidal sensor to enable highly reproducible self-calibrated sensing. By using 4-mercaptobenzoic acid (4-MBA) as the internal standard adenine concentrations are quantified to an accuracy of 92.6-99.5%. Our versatile approach paves the way for rationally designed yet quantitative colloidal SERS sensors and their use in a variety of sensing applications.
In this work, we extracted 95% of the electrochemically available Li from LiNi0.8Co0.15Al0.05O2 (NCA) by galvanostatically charging the NCA/MCMB full cell to 4.7 V. Joint powder X-ray and neutron diffraction (XRD & ND) studies were undertaken for NCA at highly charged states at the first cycle, and discharged states at different cycles. The results indicate that the bulk structure of NCA maintains the O3 structure up to the extraction of 0.90 Li per formula unit. In addition, we found that the transition metal layer becomes more disordered along the c-axis than along the a- and b-axes upon charging. This anisotropic disorder starts to develop no later than 4.3 V on charge and continues to grow until the end of charge. As Li is re-inserted during discharge, the structure that resembles the pristine NCA is recovered. The irreversible loss of Li and the migration of Ni to the Li layer have been quantified by the joint XRD and ND refinement and the results were further verified by solid state 7Li NMR and magnetic measurements. Our work clearly demonstrates that the NCA bulk retains a robust, single phase O3 structure throughout the wide delithiation range (up to 0.9 Li per formula unit of NCA) and is suitable for higher energy density usage with proper modifications.