Amplified spontaneous emission and gain in highly concentrated Rhodamine-doped peptide derivative

Bioinspired fluorescence, being widely explored for imaging purposes, faces challenges in delivering bright biocompatible sources. While quite a few techniques have been developed to reach this goal, encapsulation of high-quantum yield fluorescent dyes in natural biological forms suggest achieving superior light-emitting characteristics, approaching amplified spontaneous emission and even lasing. Here we compare gain capabilities of highly concentrated Rhodamine B solutions with a newly synthesized biocompatible peptide derivative hybrid polymer/peptide material, RhoB-PEG1300-F6, which contains the fluorescent covalently bound dye. While concentration quenching effects limit the maximal achievable gain of dissolved Rhodamine B, biocompatible conjugation allows elevating amplification coefficients towards moderately high values. In particular, Rhodamine B, anchored to the peptide derivative material, demonstrates gain of 22–23 cm−1 for a 10−2 M solution, while a pure dye solution possesses 25% smaller values at the same concentration. New biocompatible fluorescent agents pave ways to demonstrate lasing in living organisms and can be further introduced to therapeutic applications, if proper solvents are found

DJ-1 contributes to adipogenesis and obesity-induced inflammation

Adipose tissue functions as an endocrine organ, and the development of systemic inflammation in adipose tissue is closely associated with metabolic diseases, such as obesity and insulin resistance. Accordingly, the fine regulation of the inflammatory response caused by obesity has therapeutic potential for the treatment of metabolic syndrome. In this study, we analyzed the role of DJ-1 (PARK7) in adipogenesis and inflammation related to obesity in vitro and in vivo. Many intracellular functions of DJ-1, including oxidative stress regulation, are known. However, the possibility of DJ-1 involvement in metabolic disease is largely unknown. Our results suggest that DJ-1 deficiency results in reduced adipogenesis and the down-regulation of pro-inflammatory cytokines in vitro. Furthermore, DJ-1-deficient mice show a low-level inflammatory response in the high-fat diet-induced obesity model. These results indicate previously unknown functions of DJ-1 in metabolism and therefore suggest that precise regulation of DJ-1 in adipose tissue might have a therapeutic advantage for metabolic disease treatment.open0

Molecular Basis for Vulnerability to Mitochondrial and Oxidative Stress in a Neuroendocrine CRI-G1 Cell Line

Many age-associated disorders (including diabetes, cancer, and neurodegenerative diseases) are linked to mitochondrial dysfunction, which leads to impaired cellular bioenergetics and increased oxidative stress. However, it is not known what genetic and molecular pathways underlie differential vulnerability to mitochondrial dysfunction observed among different cell types.Starting with an insulinoma cell line as a model for a neuronal/endocrine cell type, we isolated a novel subclonal line (named CRI-G1-RS) that was more susceptible to cell death induced by mitochondrial respiratory chain inhibitors than the parental CRI-G1 line (renamed CRI-G1-RR for clarity). Compared to parental RR cells, RS cells were also more vulnerable to direct oxidative stress, but equally vulnerable to mitochondrial uncoupling and less vulnerable to protein kinase inhibition-induced apoptosis. Thus, differential vulnerability to mitochondrial toxins between these two cell types likely reflects differences in their ability to handle metabolically generated reactive oxygen species rather than differences in ATP production/utilization or in downstream apoptotic machinery. Genome-wide gene expression analysis and follow-up biochemical studies revealed that, in this experimental system, increased vulnerability to mitochondrial and oxidative stress was associated with (1) inhibition of ARE/Nrf2/Keap1 antioxidant pathway; (2) decreased expression of antioxidant and phase I/II conjugation enzymes, most of which are Nrf2 transcriptional targets; (3) increased expression of molecular chaperones, many of which are also considered Nrf2 transcriptional targets; (4) increased expression of β cell-specific genes and transcription factors that specify/maintain β cell fate; and (5) reconstitution of glucose-stimulated insulin secretion.The molecular profile presented here will enable identification of individual genes or gene clusters that shape vulnerability to mitochondrial dysfunction and thus represent potential therapeutic targets for diabetes and neurodegenerative diseases. In addition, the newly identified CRI-G1-RS cell line represents a new experimental model for investigating how endogenous antioxidants affect glucose sensing and insulin release by pancreatic β cells

Identification of Phosphoproteins as Possible Differentiation Markers in All-Trans-Retinoic Acid-Treated Neuroblastoma Cells

BACKGROUND: Neuroblastic tumors account for 9-10% of pediatric tumors and neuroblastoma (NB) is the first cause of death in pre-school age children. NB is classified in four stages, depending on the extent of spreading. A fifth type of NB, so-called stage 4S (S for special), includes patients with metastatic tumors but with an overall survival that approximates 75% at five years. In most of these cases, the tumor regresses spontaneously and regression is probably associated with delayed neuroblast cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS: In order to identify new early markers to follow and predict this process for diagnostic and therapeutics intents, we mimicked the differentiation process treating NB cell line SJ-NK-P with all-trans-retinoic acid (ATRA) at different times; therefore the cell proteomic pattern by mass spectrometry and the phosphoproteomic pattern by a 2-DE approach coupled with anti-phosphoserine and anti-phosphotyrosine western blotting were studied. CONCLUSIONS/SIGNIFICANCE: Proteomic analysis identified only two proteins whose expression was significantly different in treated cells versus control cells: nucleoside diphosphate kinase A (NDKA) and reticulocalbin-1 (RCN1), which were both downregulated after 9 days of ATRA treatment. However, phosphoproteomic analysis identified 8 proteins that were differentially serine-phosphorylated and 3 that were differentially tyrosine-phosphorylated after ATRA treatment. All proteins were significantly regulated (at least 0.5-fold down-regulated). Our results suggest that differentially phosphorylated proteins could be considered as more promising markers of differentiation for NB than differentially expressed proteins

Analysis of naturally etched surface of brass sheathing from a nineteenth-century shipwreck

The Akko Tower Wreck is ently the remains of a 25-m-long merchant brig, dated to the first half of the nineteenth century. During the 2015 underwater excavation, a piece of brass sheet was retrieved from the shipwreck and its surface and bulk were examined by metallurgical analyses. The examinations revealed a unique example of almost two hundred years’ natural etching, which took place in the sea underwater environment. The surface of the sheet was covered with different copper and zinc oxides, which were identified by XRD analysis. Observation of the naturally etched surface with multi-focal light microscopy and SEM-EDS analysis indicated a microstructure of annealed α-brass, similar to that of its bulk. S-OES chemical analysis of the bulk revealed a composition of 65.0 wt% Cu, 34.4 wt% Zn and 0.6 wt% Pb. Based on the thickness of the sheet and its good state of preservation, it is suggested that it was used as sheathing to protect the hull against marine organisms, and to improve the sailing qualities of the ship. The results provide further information about the Akko Tower shipwreck; and expand our knowledge regarding the corrosion processes and preservation of brass during a long burial period in marine environments