Antitumor Effects of Vitamin D Analogs on Hamster and Mouse Melanoma Cell Lines in Relation to Melanin Pigmentation

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)₂D₃) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH)₂D₃ and 25(OH)D₃), and novel relatively non-calcemic ones (20(OH)D₃, calcipotriol, 21(OH)pD, pD and 20(OH)pL), on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells. Murine B16-F10 and hamster Bomirski Ab cell lines were shown to be effective models to study how melanogenesis affects anti-melanoma treatment. Novel Vitamin D analogs with a short side-chain and lumisterol-like 20(OH)pL efficiently inhibited rodent melanoma growth. Moderate pigmentation sensitized rodent melanoma cells towards Vitamin D analogs, and altered expression of key genes involved in Vitamin D signaling, which was opposite to the effect on heavily pigmented cells. Interestingly, melanogenesis inhibited ligand-induced Vitamin D receptor translocation and ligand-induced expression of VDR and CYP24A1 genes. These findings indicate that melanogenesis can affect the anti-melanoma activity of Vitamin D analogs in a complex manner.     

Target Score—A Proteomics Data Selection Tool Applied to Esophageal Cancer Identifies GLUT1-Sialyl Tn Glycoforms as Biomarkers of Cancer Aggressiveness

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.     

Scales to measure parents and caretakers satisfaction with the food and nutrition component of Child care Centers

Two Likert-type scales for measuring parents' and caretakers' level of satisfaction with the food and nutrition services offered at childcare multi-centers in a peri-urban community in Caracas, were developed and validated. An intentional sample of 20 parents and caretakers were interviewed within the naturalistic-constructivist perspective, to capture their perceptions of distinct aspects of the food and nutrition components of the program. Categories emerged from the interviews that served to construct the items for two scales that measure level of satisfaction of parents and caretakers with the food and nutrition aspects of the program. To validate the scales, they were applied to 73 parents and 32 caretakers. Factor and multiple components analysis showed that overall, the scales explained 61% and 69% of the variation in level of satisfaction of parents and caretakers respectively. Confiability measured with Alpha Cronbach coefficient was 0.74 and 0.77 for parents' and caretakers' scales respectively. These results reveal scales that have content validity and good reliability. Besides, the scales detect specific aspects of the food and nutrition service that should be reinforced or modified, to make the Child-care Centers program more effective and efficient. External validation of the scales is recommended, since they provide an instrument capable of capturing useful information for monitoring and evaluating the Child-care Centers program nation-wide, from the perspective of program managers and parents of program users.     

High‐retention properties for Hg(II) ions of a resin containing ammonium and pyridine groups

The metal‐ion uptake behavior of the chelating resin poly([(3‐(methacryloylamino)propyl] trimethyl ammonium chloride‐co‐4‐vinyl pyridine) has been investigated. The resin is obtained by radical copolymerization in a yield of 99.6%. The hydrophilic resin shows a high retention capacity and selectivity toward Hg(II) ions in the presence of Cu(II), Pb(II), Cd(II), Zn(II), and Cr(III) ions. A retention of Hg(II) higher than 99% is observed after 5 min. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 2595–2599, 2002     

Comparison of 2D simultaneous multi-slice and 3D GRASE readout schemes for pseudo-continuous arterial spin labeling of cerebral perfusion at 3 T

Objective

In this perfusion magnetic resonance imaging study, the performances of different pseudo-continuous arterial spin labeling (PCASL) sequences were compared: two-dimensional (2D) single-shot readout with simultaneous multislice (SMS), 2D single-shot echo-planar imaging (EPI) and multishot three-dimensional (3D) gradient and spin echo (GRASE) sequences combined with a background-suppression (BS) module.

Materials and methods

Whole-brain PCASL images were acquired from seven healthy volunteers. The performance of each protocol was evaluated by extracting regional cerebral blood flow (rCBF) measures using an inline morphometric segmentation prototype. Image data postprocessing and subsequent statistical analyses enabled comparisons at the regional and sub-regional levels.

Results

The main findings were as follows: (i) Mean global CBF obtained across methods was were highly correlated, and these correlations were significantly higher among the same readout sequences. (ii) Temporal signal-to-noise ratio and gray-matter-to-white-matter CBF ratio were found to be equivalent for all 2D variants but lower than those of 3D-GRASE.

Discussion

Our study demonstrates that the accelerated SMS readout can provide increased acquisition efficiency and/or a higher temporal resolution than conventional 2D and 3D readout sequences. Among all of the methods, 3D-GRASE showed the lowest variability in CBF measurements and thus highest robustness against noise.

     

Iterative global and local methods of image restoration

Most of the reconstruction algorithms smooth out the edges of the reconstructed images but iterative total variation regularization and local adaptive methods preserve the edge information without any prior knowledge about the image geometric details. The restoration performance of the proposed algorithms for image deblurring is compared in terms of the mean squared error. Computer simulation results are provided and discussed.     

Reinforcement learning to adjust parametrized motor primitives to new situations

Humans manage to adapt learned movements very quickly to new situations by generalizing learned behaviors from similar situations. In contrast, robots currently often need to re-learn the complete movement. In this paper, we propose a method that learns to generalize parametrized motor plans by adapting a small set of global parameters, called meta-parameters. We employ reinforcement learning to learn the required meta-parameters to deal with the current situation, described by states. We introduce an appropriate reinforcement learning algorithm based on a kernelized version of the reward-weighted regression. To show its feasibility, we evaluate this algorithm on a toy example and compare it to several previous approaches. Subsequently, we apply the approach to three robot tasks, i.e., the generalization of throwing movements in darts, of hitting movements in table tennis, and of throwing balls where the tasks are learned on several different real physical robots, i.e., a Barrett WAM, a BioRob, the JST-ICORP/SARCOS CBi and a Kuka KR?6.     

How important is tryptophan in human health?

Tryptophan (Trp) is an amino acid and an essential component of the human diet. It plays a crucial role in many metabolic functions. Clinicians can use Trp levels in the course of diagnosing various metabolic disorders and the symptoms associated with those diseases. Furthermore, supplementation with this amino acid is considered in the treatment of depression and sleep disorders, mainly due to the Trp relationship with the synthesis of serotonin (5-HT) and melatonin. It is also used in helping to resolve cognitive disorders, anxiety, or neurodegenerative diseases. Reduced secretion of serotonin is associated with autism spectrum disorder, obesity, anorexia and bulimia nervosa, and other diseases presenting peripherals symptoms. The literature strongly suggests that Trp has a significant role in the correct functionality of the brain-gut axis and immunology. This information leads to the consideration of Trp as an essential dietary component due to its role in the serotonin pathway. A reduced availability of Trp in diet and nutraceutical supplementation should be considered with greater concern than one might expect. This paper constitutes a review of the more salient aspects gleaned from the current knowledge base about the role of Trp in diseases, associated nutritional disorders, and food science, in general.     

Sex‐related differences in the nutritional value of Japanese quail meat

The objective of the study was to evaluate the impact of birds’ sex on the carcass composition and meat (breast muscle) nutritional value in Japanese quails in a large‐scale four‐generation study. Standard poultry feed was used, based on maize, soya bean meal and wheat. Four generations of quails were housed up to the age of 17 weeks each. Then samples of breast muscle were collected after dissection and analysed for basic nutrient content and for fatty acids composition. Results were analysed by GLM procedure in SAS, and significance of differences between birds of different sex was estimated by Duncan's test. Dissection revealed marked differences between birds’ of different sex in case of relative organ weight. Results of meat analyses showed no differences in the basic composition. Fatty acids analyses showed a more advantageous profile in female meat.     

Comparison of different failure criteria for fiber-reinforced plastics in terms of fracture curves for arbitrary stress combinations

For fiber-reinforced plastics exists a big number of different criteria for the failure prediction. The intention of this paper is to compare the TSAI-HIL-, the LaRC04- and PUCK’s criterion in terms of their fracture curves for a unidirectional glass-fiber reinforced composite layer. Therefore after the implementation of these three criteria, the two-dimensional fracture curves for all possible stress combinations, which can be derived from a general spatial stress tensor, are computed. In this way, the characteristics of the criteria, similarities and differences and possible weak points become obvious.