Biophysical characterization of melanoma cell phenotype markers during metastatic progression

Melanoma is the most fatal form of skin cancer, with increasing prevalence worldwide. The most common melanoma genetic driver is mutation of the proto-oncogene serine/threonine kinase BRAF; thus, the inhibition of its MAP kinase pathway by specific inhibitors is a commonly applied therapy. However, many patients are resistant, or develop resistance to this type of monotherapy, and therefore combined therapies which target other signaling pathways through various molecular mechanisms are required. A possible strategy may involve targeting cellular energy metabolism, which has been recognized as crucial for cancer development and progression and which connects through glycolysis to cell surface glycan biosynthetic pathways. Protein glycosylation is a hallmark of more than 50% of the human proteome and it has been recognized that altered glycosylation occurs during the metastatic progression of melanoma cells which, in turn facilitates their migration. This review provides a description of recent advances in the search for factors able to remodel cell metabolism between glycolysis and oxidative phosphorylation, and of changes in specific markers and in the biophysical properties of cells during melanoma development from a nevus to metastasis. This development is accompanied by changes in the expression of surface glycans, with corresponding changes in ligand-receptor affinity, giving rise to structural features and viscoelastic parameters particularly well suited to study by label-free biophysical methods

A novel bacterial l-arginine sensor controlling c-di-GMP levels in Pseudomonas aeruginosa

Nutrients such as amino acids play key roles in shaping the metabolism of microorganisms in natural environments and in host–pathogen interactions. Beyond taking part to cellular metabolism and to protein synthesis, amino acids are also signaling molecules able to influence group behavior in microorganisms, such as biofilm formation. This lifestyle switch involves complex metabolic reprogramming controlled by local variation of the second messenger 3′, 5′-cyclic diguanylic acid (c-di-GMP). The intracellular levels of this dinucleotide are finely tuned by the opposite activity of dedicated diguanylate cyclases (GGDEF signature) and phosphodiesterases (EAL and HD-GYP signatures), which are usually allosterically controlled by a plethora of environmental and metabolic clues. Among the genes putatively involved in controlling c-di-GMP levels in P. aeruginosa, we found that the multidomain transmembrane protein PA0575, bearing the tandem signature GGDEF-EAL, is an l-arginine sensor able to hydrolyse c-di-GMP. Here, we investigate the basis of arginine recognition by integrating bioinformatics, molecular biophysics and microbiology. Although the role of nutrients such as l-arginine in controlling the cellular fate in P. aeruginosa (including biofilm, pathogenicity and virulence) is already well established, we identified the first l-arginine sensor able to link environment sensing, c-di-GMP signaling and biofilm formation in this bacterium

A 3D-printed blood-brain barrier model with tunable topology and cell-matrix interactions.

Recent developments in digital light processing (DLP) can advance the structural and biochemical complexity of perfusable in vitro models of the blood–brain barrier. Here, we describe a strategy to functionalize complex, DLP-printed vascular models with multiple peptide motifs in a single hydrogel. Different peptides can be clicked into the walls of distinct topologies, or the peptide motifs lining channel walls can differ from those in the bulk of the hydrogel. The flexibility of this approach is used to both characterize the effects of various bioactive domains on endothelial coverage and tight junction formation, in addition to facilitating astrocyte attachment in the hydrogel surrounding the endothelialized vessel to mimic endothelial–astrocyte interaction. Peptides derived from proteins mediating cell-extracellular matrix (e.g. RGD and IKVAV) and cell–cell (e.g. HAVDI) adhesions are used to mediate endothelial cell attachment and coverage. HAVDI and IKVAV-lined channels exhibit significantly greater endothelialization and increased zonula-occluden-1 (ZO-1) localization to cell–cell junctions of endothelial cells, indicative of tight junction formation. RGD is then used in the bulk hydrogel to create an endothelial–astrocyte co-culture model of the blood–brain barrier that overcomes the limitations of previous platforms incapable of complex topology or tunable bioactive domains. This approach yields an adjustable, biofabricated platform to interrogate the effects of cell-matrix interaction on blood–brain barrier mechanobiology

Alexithymia and obesity: controversial findings from a multimethod assessment

OBJECTIVE: The aim of the study is to assess alexithymia levels in obese patients using a multimethod measurement (TAS-20 and TSIA) to evaluate both possible differences between the two instruments and their relationship with body weight. PATIENTS AND METHODS: 54 obese patients, seeking surgical treatment, were enrolled. They completed a socio-demographic questionnaire, 20-items Toronto Alexithymia Scale and the Toronto Structured Interview for Alexithymia. RESULTS: Data analysis showed a significant positive association between TAS-20 and TSIA total scores (r=.28, p<.05), but only the TSIA score was positively related to body weight (r=.39; p<.001). Multivariable linear regression models showed the predictive effects of TSIA total score (beta=.41; p<.001) and difficulty in identifying feelings (DIF) (beta=.56; p<.001) respectively on weight. CONCLUSIONS: The findings showed a different association between body weight and alexithymia according to the instrument employed to evaluate alexithymia, supporting the importance of a multimethod assessment in some clinical conditions

Short and long term outcomes of 200 patients supported by continuous-flow left ventricular assist devices

AIM: To study the institutional experience over 8 years with 200 continuous-flow (CF) - left ventricular assist devices (LVAD). METHODS: We evaluated our institution\u27s LVAD database and analyzed all patients who received a CF LVAD as a bridge to transplant (BTT) or destination therapy from March 2006 until June 2014. We identified 200 patients, of which 179 were implanted with a HeartMate II device (Thoratec Corp., Pleasanton, CA) and 21 received a Heartware HVAD (HeartWare Inc., Framingham, MA). RESULTS: The mean age of our LVAD recipients was 59.3 years (range 17-81), 76% (152/200) were males, and 49% were implanted for the indication of BTT. The survival rate for our LVAD patients at 30 d, 6 mo, 12 mo, 2 years, 3 years, and 4 years was 94%, 86%, 78%, 71%, 62% and 45% respectively. The mean duration of LVAD support was 581 d (range 2-2595 d). Gastrointestinal bleeding (was the most common adverse event (43/200, 21%), followed by right ventricular failure (38/200, 19%), stroke (31/200, 15%), re exploration for bleeding (31/200, 15%), ventilator dependent respiratory failure (19/200, 9%) and pneumonia (15/200, 7%). Our driveline infection rate was 7%. Pump thrombosis occurred in 6% of patients. Device exchanged was needed in 6% of patients. On multivariate analysis, preoperative liver dysfunction, ventilator dependent respiratory failure, tracheostomy and right ventricular failure requiring right ventricular assist device support were significant predictors of post LVAD survival. CONCLUSION: Short and long term survival for patients on LVAD support are excellent, although outcomes still remain inferior compared to heart transplantation. The incidence of driveline infections, pump thrombosis and pump exchange have declined significantly in recent years

Research on Experiential Marketing from the Qingdao International Beer Festival

近年来，“体验”一词成为营销界出现频率越来越高的词汇。在学术界，早在上世纪70年代就有学者提出，但较为集中和富有成果的研究基本都在2000以后才出现，并且长期以来都以约瑟夫·派恩、詹姆斯·吉尔摩和伯德·施密特博士的研究为奠基之作；在业界，体验营销作为一种新型的营销方式，在国外的很多企业，尤其是很多跨国企业中已经得到了很成熟的应用，并且取得了很好的效果，而在国内，由于多种原因，只在小部分企业当中得以应用，普及程度并不高。不管未来如何，现如今体验式营销作为一种为消费者带来个性化消费体验的营销手段，已经逐渐开始流行并被商家所接受和采用，研究体验营销及其应用，对国内产品品牌建设方面有很高的借鉴价值。 ...In recent years, the word “experiencing” appears more and more frequently in the marketing area. As a matter of fact,the concept of experiential marketing had been mentioned during the 1970s. As a new way of marketing, experiential marketing has already been widely used in foreign enterprises, especially in the transnational enterprises. Howerer, in china, as a result of several things, experienti...学位：文学硕士院系专业：新闻传播学院广告学系_传播学学号：1052006115025

A first attempt to evaluate the toxicity to Phaeodactylum tricornutum Bohlin exposed to rare earth elements

The increasing use and demand of rare earth elements in many emerging technologies is leading to a potentially higher input to the marine environment. This study compared for the first time the effect of lanthanum (La), cerium (Ce), neodymium (Nd), samarium (Sm), europium (Eu), gadolinium (Gd), dysprosium (Dy), and erbium (Er) to the microalga Phaeodactylum tricornutum Bohlin. The algal growth inhibition was investigated after 72 h of exposure. The median effect concentrations (EC50) ranged from 0.98 mg/L to 13.21 mg/L and elements were ranked as follows: Gd > Ce > Er > La > Eu > Nd > Dy > Sm. The comparison of predicted no effect concentrations (PNEC) for hazard and risk assessment with measured environmental concentrations showed that ecological risks deriving from REEs could be present, but limited to specific environments like estuarine waters. The results support evidence of actions to manage the REE impact in seawater environments, looking to improve the monitoring tailored to the different and dynamic nature of ecosystems