Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene-hopene cyclases

Various (1E,3E)- and (1Z,3E)-conjugated methylthio derivatives of oxidosqualene (OS) and conjugated and non-conjugated phenylthio derivatives of OS were obtained. These compounds, designed as inhibitors of pig liver and Saccharomyces cerevisiae 2,3-oxidosqualene-lanosterol cyclases (OSC) (EC 5.4.99.7) and of Alicyclobacillus acidocaldarius squalenehopene cyclase (SHC) (EC 5.4.99.-), contain the reactive function adjacent to carbons involved in the formation of the third and the fourth cycle during OS cyclization. All the new compounds are inhibitors of OSC and SHC, with various degrees of selectivity. The conjugated methylthio derivatives behaved as potent inhibitors of S. cerevisiae OSC, whereas most of the phenylthio derivatives were especially active toward SHC.     

Using thermogravimetry for weight loss monitoring of permeation tubes used for generation of trace concentration gas standards.

Permeation tubes are convenient analyte sources for generating standard gas mixtures (containing, in particular, volatile organic compounds) used in the calibration of analytical instruments. For small permeation rates, corresponding to trace levels of analytes, the calibration of permeation tubes is time-consuming. The use of thermogravimetry as a means to measure rapidly the weight loss at constant temperature was investigated. An attempt to apply this technique to calibrating a permeation tube filled with benzene is described. In the 20 ng/min range of permeation rate, day-to-day variations of <5% were observed. The continuous weight loss monitoring of permeation tubes by thermogravimetry allows their rapid characterization.     

Contemporary Production and Urban Change: The Case of Milan

ABSTRACT

How do new sites of production and workplaces relate to the making of urban change in Milan’s peripheral areas? The paper answers this question by looking at two different fields of investigation related to peripheral areas. On one hand, the paper examines the policies promoted by the public administration at the municipal level to enhance urban innovation through new workplaces within the smart city agenda. On the other hand, the urban innovation brought by the establishment of cultural and creative industries promoted by private actors will be examined, ranging from the new geography of creative places to the creation of temporary transformations. Starting from these two fields of analysis, the paper identifies areas of difference and potential combined effects between public action and private initiative. These are placed against the backdrop of a conception of contemporary production that has worked as a tool for social inclusion and place-making in peripheral contexts in Milan.     

The effect of lighting changes on simultaneous colour contrast: a new aspect of colour rendition

Among the many metrics used to compute the colour rendition of a light source which have been investigated in recent years, most consider only the spectral power distribution of the light source being tested. To highlight aspects not usually considered in the development of colour rendition metrics, and to propose future directions for alternative approaches consistent with human visual perception, an experiment was conducted to examine colour appearance variations on certain spatial visual content configurations, in other words the effects of illusions under different light sources. Results indicate that stronger simultaneous contrast configurations have a more unpredictable variation in appearance. Therefore, it is proposed that colour spatial distribution should be considered for the future generation of rendering metrics.     

Genetic and Epigenetic Characterization of a Discordant KMT2A/AFF1-Rearranged Infant Monozygotic Twin Pair

The KMT2A/AFF1 rearrangement is associated with an unfavorable prognosis in infant acute lymphocytic leukemia (ALL). Discordant ALL in monozygotic twins is uncommon and represents an attractive resource to evaluate intrauterine environment–genetic interplay in ALL. Mutational and epigenetic profiles were characterized for a discordant KMT2A/AFF1-rearranged infant monozygotic twin pair and their parents, and they were compared to three independent KMT2A/AFF1-positive ALL infants, in which the DNA methylation and gene expression profiles were investigated. A de novo Q61H NRAS mutation was detected in the affected twin at diagnosis and backtracked in both twins at birth. The KMT2A/AFF1 rearrangement was absent at birth in both twins. Genetic analyses conducted at birth gave more insights into the timing of the mutation hit. We identified correlations between DNA methylation and gene expression changes for 32 genes in the three independent affected versus remitted patients. The strongest correlations were observed for the RAB32, PDK4, CXCL3, RANBP17, and MACROD2 genes. This epigenetic signature could be a putative target for the development of novel epigenetic-based therapies and could help in explaining the molecular mechanisms characterizing ALL infants with KMT2A/AFF1 fusions.     

Characterization of glycerophosphocholine phosphodiesterase activity and phosphatidylcholine biosynthesis in cultured retinal microcapillary pericytes. Effect of adenosine and endothelin-1

In pericytes from bovine retina, the enzyme glycerophosphocholine phosphodiesterase, catalyzing the hydrolysis of sn-glycero-3-phosphocholine to glycero-3-phosphate and choline, has been characterized with respect to pH optimum, metal ion dependence, K _m, inhibitors, and subcellular localization. In these cells, the natural substrate sn-glycero-3-phosphocholine was present at relatively high concentration (6.4±1.2 nmol/mg protein), and the EDTA-sensitive phosphodiesterase activity was also found to be markedly high (9.80±1.5 nmol/min/mg protein) compared to the estimated in liver and brain (1–3 nmol/min/mg protein) or in renal epithelial cell culture (0.27 nmol/min/mg protein). The reaction conditions were in general agreement with those found earlier in brain and other tissues. The majority of the enzyme specific activity was located in the plasma membrane, whereas a minor part was present in the microsomal fraction. The physiological significance of the high catabolic phosphodiesterase activity in these cells may be related to the tranfer, followed by deacylation, of lysophosphatidylcholine from the bloodstream to nervous tissue. In addition, capillary pericytes in culture were able to incorporate ³H-choline rapidly into choline-containing soluble phosphorylated intermediates and into phosphatidylcholine. To find a positive and negative effector on phosphatidylcholine formation, adenosine, an important intercellular mediator in the retina in response to alterations in oxygen delivery, and endothelin-1, a potent paracrine mediator present at the blood-brain and blood-retina barrier, were tested. The cells cultured for 1 or 24 h in a medium containing adenosine at concentrations of 10⁻⁶ and 10⁻⁴ M showed significant reduction in ³H-choline incorporation compared to control cultures, whereas endothelin-1, at a concentration of 10 and 100 nM, caused stimulation of phosphatidylcholine biosynthesis. These findings provide evidence that both agonists may modulate phosphatidylcholine metabolism in pericytes.     

Opportunities and barriers for international bioenergy trade

Recently, the international trade of various bioenergy commodities has grown rapidly, yet this growth is also hampered by some barriers. The aim of this paper is to obtain an overview of what market actors currently perceive as major opportunities and barriers for the development of international bioenergy trade. The work focuses on three bioenergy commodities: bioethanol, biodiesel and wood pellets. Data were collected through an internet-based questionnaire. The majority of the 141 respondents had an industrial background. Geographically, two-thirds were from (mainly Western) Europe, with other minor contributions from all other continents. Results show that import tariffs and the implementation of sustainability certification systems are perceived as (potentially) major barriers for the trade of bioethanol and biodiesel, while logistics are seen mainly as an obstacle for wood pellets. Development of technical standards was deemed more as an opportunity than a barrier for all commodities. Most important drivers were high fossil fuel prices and climate change mitigation policies. Concluding, to overcome some of the barriers, specific actions will be required by market parties and policy makers. Import tariffs for biofuels could be reduced or abolished, linked to multinational trade agreements and harmonization (including provisions on technical standards and sustainability requirements).     

Autophagy in Prostate Cancer and Androgen Suppression Therapy

The role of autophagy is known to be highly complex and context-dependent, leading to both cancer suppression and progression in several tumors including melanoma, breast and prostate cancer. In the present review, recent advances in an understanding of the involvement of autophagy in prostate cancer treatment are described. The regulatory effects of androgens on prostate cancer cell autophagy are particularly discussed in order to highlight the effects of autophagy modulation during androgen deprivation. A critical evaluation of the studies examined in the present review suggests the attractive possibility of autophagy inhibition combined with hormonal therapy as a promising approach for prostate cancer treatment.