Crosstalk between Macrophages and Myxoid Liposarcoma Cells Increases Spreading and Invasiveness of Tumor Cells

Myxoid liposarcoma (MLPS) is the second most common subtype of liposarcoma and has tendency to metastasize to soft tissues. To date, the mechanisms of invasion and metastasis of MLPS remain unclear, and new therapeutic strategies that improve patients' outcomes are expected. In this study, we analyzed by immunohistochemistry the immune cellular components and microvessel density in tumor tissues from patients affected by MLPS. In order to evaluate the effects of primary human MLPS cells on macrophage polarization and, in turn, the ability of macrophages to influence invasiveness of MLPS cells, non-contact and 3D organotypic co-cultures were set up. High grade MLPS tissues were found heavily vascularized, exhibited a CD3, CD4, and CD8 positive T lymphocyte-poor phenotype and were massively infiltrated by CD163 positive M2-like macrophages. Conversely, low grade MLPS tissues were infiltrated by a discrete amount of CD3, CD4, and CD8 positive T lymphocytes and a scarce amount of CD163 positive macrophages. Kaplan–Meier analysis revealed a shorter Progression Free Survival in MLPS patients whose tumor tissues were highly vascularized and heavily infiltrated by CD163 positive macrophages, indicating a clear-cut link between M2-like macrophage abundance and poor prognosis in patients. Moreover, we documented that, in co-culture, soluble factors produced by primary human MLPS cells induce macrophage polarization toward an M2-like phenotype which, in turn, increases MLPS cell capability to spread into extracellular matrix and to cross endothelial monolayers. The identification of M2-like polarization factors secreted by MLPS cells may allow to develop novel targeted therapies counteracting MLPS progression.

Qualitative Aspects of Some Traditional Landraces of the Tomato “Piennolo” (Solanum lycopersicum L.) of the Campania Region, Southern Italy

Our study aimed to analyze some qualitative aspects of five landraces of the tomato “Piennolo,” typical of the Vesuvian area, Italy, and determine the in vitro antioxidant activity. All samples showed a high °Brix value and acidity, as well as a discrete amount of reducing sugars, indicating their good quality as fresh products. They showed a high content of lycopene (up to 218 μg g−1 of fresh product) and ascorbic acid (up to 238 μg g−1 of fresh product). The content of total polyphenols was never less than 278 μg g−1 of fresh product. Hyperoside, chlorogenic and gallic acids were the most abundant polyphenols. The interrelationships between the parameters analyzed and the different landraces showed that total polyphenols could have mostly affected (ρ = 0.76) the antioxidant activity more than lycopene (ρ = −0.96). The interrelationships between the most abundant polyphenols and antioxidant activity showed that hyperoside, although the most abundant, negatively affected (ρ = −0.93) the antioxidant activity. Due to the high content of lycopene, ascorbic acid, and hyperoside, the five landraces of the tomato “Piennolo” could be considered promising in terms of their potential healthy characteristics.

Potential prevention of diabetes and obesity by achieving macronutrient balance: a guide for diet and fast food

Protein is the most satiating macronutrient. Animal studies have indicated that there may be a discrete amount of protein that an individual seeks to consume each day. Given this to be true, a person will continue to eat until this amount of protein has been consumed. Once the target is met, hunger signals are switched off. By altering the proportion of protein in a diet, you can affect how many calories are required to meet this target. A diet with a protein content >15% drives weight loss through the reduction of calories consumed to meet protein needs. We hypothesise that changing the proportion of calories from protein in a person’s diet from 12% to 20% could alter their total intake by 1000 kcal each day. This equates to a weight change of 0.9 kg each week. Maintaining a healthy weight is not as simple as changing a single variable. Eating habits in the UK are governed by a range of complex interdependent factors including hunger, emotions, cost, accessibility, education and culture. However, we suggest that by addressing satiety, and thereby hunger, we may remove a significant barrier for those trying to alter their diet for weight loss.

Reference Values for Selected Ophthalmic Diagnostic Tests in the Caatinga Parakeet (Eupsittula Cactorum) and Yellow-Chevroned Parakeet (Brotogeris Chiriri)

The aim of the present study was to determine reference values for selected ophthalmic diagnostic tests in the Caatinga Parakeet ( Eupsittula cactorum) and Yellow-chevroned Parakeet ( Brotogeris chiriri). Healthy adults of undetermined gender (15 Caatinga Parakeets and 13 Yellow-chevroned Parakeets), kept at the Triage Center of Wild Animals (CETAS, Salvador, Bahia, Brazil), were used in this investigation. Ophthalmic diagnostic tests were conducted in both eyes, including culture of the conjunctival bacterial flora with antimicrobial susceptibility test, conjunctival cytology, evaluation of tear production by phenol red thread test (PRTT) and endodontic absorbent paper point tear test (EAPPTT), measurements of palpebral fissure length (PFL) and corneal touch threshold (CTT). There was bacterial growth in 97.5% of the evaluated samples, with predominance of Grampositive microorganisms. The antimicrobial susceptibility test showed ciprofloxacin to be the most effective antibiotic. The conjunctival cytology of Caatinga Parakeets demonstrated hypocellularity with a discrete amount of squamous cells, whereas for Yellow-chevroned Parakeets, it presented hypercellularity and predominance of lymphocytes. Medians ± semi-interquartile ranges in Caatinga and Yellow-chevroned Parakeets, respectively, were: 3.51±2.2 and 1.67±1.95 mm·15 s−1 for PRTT; 8.74±2.0 and 5.89±1.48 mm min−1 for EAPPTT; 6.24±3.5 and 6.35±0.27 mm for PFL; and 4.5±1.0 and 3.5±1.95 cm for CTT. The ophthalmic parameters determined in this study may help in the diagnosis of ocular diseases in Caatinga and Yellow-chevroned Parakeets.

A simple technique to control macromolecular crystal nucleation efficiently using a standard vapour-diffusion setup

Excessive nucleation often leads to a large number of small macromolecular crystals that are not useful for X-ray diffraction analysis. Crystals with dimensions suitable for data collection can be reproducibly obtained by releasing, for a discrete amount of time, the vapour pressure in both hanging- and sitting-drop experiments, set up at lower precipitant concentrations than those required for crystallization.

Polyamines directly induce release of cytochrome c from heart mitochondria

Cytochrome c release from mitochondria to the cytosol represents a critical step in apoptosis, correlated to the activation of the caspase cascade. In this report, we show that addition of micromolar concentrations of polyamines to isolated rat heart mitochondria induces the release of cytochrome c. Spermine, which is effective at concentrations of 10-100 μM, is more potent than spermidine, whereas putrescine has no effect up to 1 mM. The release of cytochrome c caused by spermine is a rapid, saturable and selective process that is independent of mitochondria damage. Spermine, unlike polylysine, is able to release a discrete amount of cytochrome c from intact, functional mitochondria. The cytochrome c-releasing power of spermine is not affected by cyclosporin A, differently from the effect of permeability transition inducers. In a cardiac cell-free model of apoptosis, the latent caspase activity of cytosolic extracts from cardiomyocytes could be activated by cytochrome c released from spermine-treated heart mitochondria. These data indicate a novel mechanism of cytochrome c release from the mitochondrion, and suggest that prolonged and sustained elevation of polyamines, characteristic of some pathologies such as heart hypertrophy, could be involved in the development of apoptosis.

Reaction of cis- and trans-Dichlorotetra(Dimethylsulfoxide)Ruthenium(II) With the Antiviral Drug Acyclovir

NMR was used to investigate the reaction of cis- and trans-[RuCl2(DMSO)4] with the antiviral drug acyclovir, a guanine derivative containing the acyclic (2-hydroxo) ethoxymethyl pendant linked to N(9). Studies were performed in aqueous solutions at ambient temperature and at 37 °C, and at various molar ratios. Both isomers yielded two compounds, a monoadduct and a bisadduct, the relative yields being dependent upon the metal to ligand concentration ratios. The products derived from the two Ru isomers displayed identical NMR spectra, suggesting that they have the same coordination environment, however the rate of formation of the monoadduct was higher in the case of the trans isomer than in the case of the cis isomer, while the rate of conversion of the monoadduct into the bisadduct appeared to be similar in both cases. As a consequence in the case of the trans isomer there is accumulation of monoadduct in the early stage of the reaction, whose concentration afterwards decreases with the progress of the reaction. As for platinum, also for ruthenium the preferred binding site is N(7) of the purine base, however, in the case of ruthenium a discrete amount of bisadduct is formed even in the presence of an excess of metallic substrate with respect to the acyclovir ligand; under similar conditions a platinum substrate would have given, nearly exclusively, the monoadduct.

Freeze-fracture TEM of the helical smectic A* phase

A new liquid crystal (called the smectic-A* phase) that combines cholesteric twist and smectic layering was a surprise as smectic phases preclude twist distortions. However, the twist grain boundary (TGB) model of Renn and Lubensky predicted a defect-mediated smectic phase that incorporates cholesteric twist by a lattice of screw dislocations. The TGB model for the liquid crystal analog of the Abrikosov phase of superconductors consists of regularly spaced grain boundaries of screw dislocations, parallel to each other within the grain boundary, but rotated by a fixed angle with respect to adjacent grain boundaries. The dislocations divide the layers into blocks which rotate by a discrete amount, Δθ, given by the ratio of the layer spacing, d, to the distance between grain boundaries, lb; Δθ ≈ d/lb (Fig. 1).

LENGTH VARIATION AND HETEROPLASMY ARE FREQUENT IN MITOCHONDRIAL DNA FROM PARTHENOGENETIC AND BISEXUAL LIZARDS (GENUS CNEMIDOPHORUS)

ABSTRACT Samples of mtDNA isolated from each of 92 lizards representing all color pattern classes of Cnemidophorus tesselatus and two populations of C. tigris marmoratus were digested with the restriction endonucleases MboI, TaqI, RsaI and MspI. The mtDNA fragment sizes were compared after radioactive labeling and gel electrophoresis. Three features were notable in the comparisons: (1) there was little variation due to gain or loss of cleavage sites, (2) two fragments varied noticeably in length among the samples, one by a variable amount up to a maximum difference of ∼370 base pairs (bp) and the other by a discrete amount of 35 bp, (3) these two fragments occasionally varied within, as well as between, samples. Two regions that corresponded in size to these variants were identified by restriction endonuclease cleavage mapping. One of these is adjacent to the D-loop. Heteroplasmy, heretofore rarely observed, occurred frequently in these same two regions. Variability in the copy number of a tandemly repeated 64-bp sequence appears to be one component of the variation, but others (e.g., base substitutions or small additions/deletions) must also be involved. The frequent occurrence of these length variations suggests either that they can be generated rapidly or that they were inherited from a highly polymorphic ancestor. The former interpretation is favored.

The inelastic scattering of slow electrons in gases.—IV

Recent investigations have shown that the inelastic scattering of electrons in gases exhibits some very interesting phenomena. In previous papas we have described the angular distribution of the scattering of electrons which have lost a discrete amount of energy. Papers I and II described preliminary results which established the existence of diffraction effects at large angles in a number of gases. In Paper III the measurements were carried out over a range of velocities lower than those previously studied, results being obtained for incident electron energies down to within a few volts of the excitation potential. angular distributions were obtained for the inelastic scattering of electrons in hydrogen, helium, and argon between the angles 10° and 155°. The present paper describes the extension of the measurements to methane, nitrogen, neon and mercury vapour.