Proteome changes in lamb semimembranosus muscles associated with the inclusion of sunflower cake in their diet

A diet based on sunflower cake for lambs was assayed in order to reuse biodiesel industrial by-products with the aim of reducing livestock costs and evaluating their influence on meat quality. To achieve these goals, sixteen male lambs were fed diets containing different levels of sunflower cake (control, 5%, 10% and 15%). Afterwards, their semimembranosus muscles were analysed by two-dimensional electrophoresis coupled to mass spectrometry and their functional protein association was examined using STRING. Structural and metabolic proteins in the lambs’ proteomes changed significantly according to their diet. Fifteen proteins showed significant changes caused by the inclusion of sunflower cake, and the most differentially abundant structural proteins were detected in 2-DE gels from the lambs. Differentially abundant metabolic proteins such as ENO3 (enolase 3), MDH1 (malate dehydrogenase) and ALDH1A1 (retinal dehydrogenase) have been proposed as biomarkers of quality parameters in other species.     

Endothelial Progenitor Cells and Rheumatoid Arthritis: Response to Endothelial Dysfunction and Clinical Evidences

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the swelling of multiple joints, pain and stiffness, and accelerated atherosclerosis. Sustained immune response and chronic inflammation, which characterize RA, may induce endothelial activation, damage and dysfunction. An equilibrium between endothelial damage and repair, together with the preservation of endothelial integrity, is of crucial importance for the homeostasis of endothelium. Endothelial Progenitor Cells (EPCs) represent a heterogenous cell population, characterized by the ability to differentiate into mature endothelial cells (ECs), which contribute to vascular homeostasis, neovascularization and endothelial repair. A modification of the number and function of EPCs has been described in numerous chronic inflammatory and auto-immune conditions; however, reports that focus on the number and functions of EPCs in RA are characterized by conflicting results, and discrepancies exist among different studies. In the present review, the authors describe EPCs’ role and response to RA-related endothelial modification, with the aim of illustrating current evidence regarding the level of EPCs and their function in this disease, to summarize EPCs’ role as a biomarker in cardiovascular comorbidities related to RA, and finally, to discuss the modulation of EPCs secondary to RA therapy.     

Mechanisms of Sensitivity and Resistance of Primary Effusion Lymphoma to Dimethyl Fumarate (DMF)

PEL is a rare B cell lymphoma associated with KSHV that mainly arises in immune-deficient individuals. The search for new drugs to treat this cancer is still ongoing given its aggressiveness and the poor response to chemotherapies. In this study, we found that DMF, a drug known for its anti-inflammatory properties which is registered for the treatment of psoriasis and relapsing–remitting MS, could be a promising therapeutic strategy against PEL. Indeed, although some mechanisms of resistance were induced, DMF activated NRF2, reduced ROS and inhibited the phosphorylation of STAT3 and the release of the pro-inflammatory and immune suppressive cytokines IL-6 and IL-10, which are known to sustain PEL survival. Interestingly, we observed that DMF displayed a stronger cytotoxic effect against fresh PEL cells in comparison to PEL cell lines, due to the activation of ERK1/2 and autophagy in the latter cells. This finding further encourages the possibility of using DMF for the treatment of PEL.     

Deleting files in the Celeste peer-to-peer storage system

Celeste is a robust peer-to-peer object store built on top of a distributed hash table (DHT). Celeste is a working system, developed by Sun Microsystems Laboratories. During the development of Celeste, we faced the challenge of complete object deletion, and moreover, of deleting “files” composed of several different objects. This important problem is not solved by merely deleting meta-data, as there are scenarios in which all file contents must be deleted, e.g., due to a court order. Complete file deletion in a realistic peer-to-peer storage system has not been previously dealt with due to the intricacy of the problem — the system may experience high churn rates, nodes may crash or have intermittent connectivity, and the overlay network may become partitioned at times. We present an algorithm that eventually deletes all file contents, data and meta-data, in the aforementioned complex scenarios. The algorithm is fully functional and has been successfully integrated into Celeste.     

Modeling Lung Carcinoids with Zebrafish Tumor Xenograft

Lung carcinoids are neuroendocrine tumors that comprise well-differentiated typical (TCs) and atypical carcinoids (ACs). Preclinical models are indispensable for cancer drug screening since current therapies for advanced carcinoids are not curative. We aimed to develop a novel in vivo model of lung carcinoids based on the xenograft of lung TC (NCI-H835, UMC-11, and NCI-H727) and AC (NCI-H720) cell lines and patient-derived cell cultures in Tg(fli1a:EGFP)^y1 zebrafish embryos. We exploited this platform to test the anti-tumor activity of sulfatinib. The tumorigenic potential of TC and AC implanted cells was evaluated by the quantification of tumor-induced angiogenesis and tumor cell migration as early as 24 h post-injection (hpi). The characterization of tumor-induced angiogenesis was performed in vivo and in real time, coupling the tumor xenograft with selective plane illumination microscopy on implanted zebrafish embryos. TC-implanted cells displayed a higher pro-angiogenic potential compared to AC cells, which inversely showed a relevant migratory behavior within 48 hpi. Sulfatinib inhibited tumor-induced angiogenesis, without affecting tumor cell spread in both TC and AC implanted embryos. In conclusion, zebrafish embryos implanted with TC and AC cells faithfully recapitulate the tumor behavior of human lung carcinoids and appear to be a promising platform for drug screening.     

A -80 dB THD, 4 Vpp switched capacitor filter for 1.5 Vbattery-operated systems

A fully differential fifth-order SC filter that can operate from power supplies as low as 1.5 V featuring a -80 dB THD up to 4 V_pp output voltage is presented. A measured p-weighted noise of 120 μV_rms leads to a dynamic range of 81.5 dB. This circuit is used as reconstruction filter for a low voltage 14-b DAC. The very low voltage operation has been possible by integrating a regulated voltage-multiplier on the same chip. The filter active area is 0.54 mm ² in a 0.8 μm CMOS technology. Typical power consumption is 0.8 mW at 1.5 V supply     

Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages

The enzyme Zmp1 is a zinc‐containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8‐hydroxyquinoline‐2‐hydroxamate scaffold. Among the synthesized compounds, N‐(benzyloxy)‐8‐hydroxyquinoline‐2‐carboxamide ( 1 c ) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site. The effect of 1 c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte‐derived macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor 1 c displays interesting in vitro antitubercular properties worthy of further investigation.     

Electrode passivation caused by polymerization of different phenolic compounds

An electrochemical quartz crystal microbalance (EQCM) was used to investigate the formation of polymeric products resulting from electrooxidation in aqueous solutions of phenolic compounds on the surface of Au and Pt electrodes. The studied compounds were phenol; m-cresol; 2,5-dimethylphenol and 2,3,5-trimethylphenol. The polymerization process was studied as a function of the methyl substitution in the phenolic structure. Electrochemical quartz crystal microbalance studies show that the polymer formed from substituted phenols is more passivating than that from the non-substituted phenol. In any case, the largest amount of mass was deposited during the first voltammetric cycle and the Pt electrode was more active than the Au electrode for the organic electrooxidation process. FT-IR spectroscopy showed that the films formed upon phenol and m-cresol electrolysis were also oxidized.