Mechanisms Contributing To Differential Regulation of PAX3 Downstream Target Genes in Normal Human Epidermal Melanocytes Versus Melanoma Cells

Melanoma is a highly aggressive and drug resistant form of skin cancer. It arises from melanocytes, the pigment producing cells of the skin. The formation of these melanocytes is driven by the transcription factor PAX3 early during embryonic development. As a result of alternative splicing, the PAX3 gene gives rise to eight different transcripts which encode isoforms that have different structures and activate different downstream target genes involved in pathways of cell proliferation, migration, differentiation and survival. Furthermore, posttranslational modifications have also been shown to alter the functions of PAX3.We previously identified PAX3 downstream target genes in melanocytes and melanoma cells. Here we assessed the effects of PAX3 down-regulation on this panel of target genes in primary melanocytes versus melanoma cells. We show that PAX3 differentially regulates various downstream target genes involved in cell proliferation in melanoma cells compared to melanocytes. To determine mechanisms behind this differential downstream target gene regulation, we performed immunoprecipitation to assess post-translational modifications of the PAX3 protein as well as RNAseq to determine PAX3 transcript expression profiles in melanocytes compared to melanoma cells. Although PAX3 was found to be post-translationally modified, there was no qualitative difference in phosphorylation and ubiquitination between melanocytes and melanoma cells, while acetylation of PAX3 was reduced in melanoma cells. Additionally, there were differences in PAX3 transcript expression profiles between melanocytes and melanoma cells. In particular the PAX3E transcript, responsible for reducing melanocyte proliferation and increasing apoptosis, was found to be down-regulated in melanoma cells compared to melanocytes. These results suggest that alternate transcript expression profiles activate different downstream target genes leading to the melanoma phenotype

Characterization of fiber-generated entangled photon pairs with superconducting single-photon detectors

We demonstrate the suitability of fiber-generated entangled photon pairs for practical quantum communications in the telecom band by measuring their properties with superconducting single-photon detectors that produce negligible dark counts. The photon pairs are created in approximately 5-ps duration windows at 50 MHz rate while the detectors are operated in ungated free running mode. We obtain a coincidence to accidental-coincidence ratio >80 with raw photon-counting data, i.e., without making any post-measurement corrections. Using a previously demonstrated counter-propagating scheme we also produce polarizationentangled photon pairs at 50-MHz rate, which in coincidence detection directly yield two-photon interference with a fringe visibility >98%

Efecto del injerto en las propiedades antioxidantes del tomate (Solanum lycopersicum L.)

The use of grafted plants in vegetable crop production is now being expanded greatly. However, few data are available on the nutritional composition of grafted vegetables with emphasis on antioxidant properties. Therefore, the major objective of this study was to evaluate antioxidant components of tomatoes influenced by grafting technique. The tomato plants were grown in a greenhouse located at Kriz˘evci, Croatia. The cultivars ‘Efialto’, ‘Heman’, and ‘Maxifort’ were used as rootstocks, while ‘Tamaris’ was used as scion. Grafting resulted in increase of number of marketable fruits per plant by 30%. Content of total vitamin C and total phenolics significantly decreased after grafting. The concentration of total extractable phenolics in tomatoes ranged from 287.1 to 977.4 mg gallic acid equivalents (GAE) kg–1 fresh weight, whereas lycopene content ranged from 11.44 to 60.99 mg kg–1 fresh weight. Antioxidant activities determined by 1,1-diphenyl-2 picrylhydrazyl (DPPH) method of grafts were significantly different compared to their respective rootstocks. The overall results showed that tomato grafting on suitable rootstocks has positive effects on the cultivation performance, but decreases nutritional quality of tomatoes. En la producción de cultivos hortícolas se está expandiendo actualmente de forma considerable el uso de plantas injertadas. Sin embargo, hay pocos datos disponibles sobre la composición nutricional de las hortícolas injertadas, especialmente sobre sus propiedades antioxidantes. El principal objetivo de este estudio fue evaluar los componentes antioxidantes de tomates influenciados por la técnica de injerto. Se cultivaron plantas de tomate en un invernadero de Kriz˘evcii, Croacia. Se utilizaron como portainjertos los cultivares ‘Efialto’, ‘Heman’, y ‘Maxifort’, mientras que ‘Tamaris’ fue utilizado como injerto. El resultado del injerto fue un aumento del 30% en el número de frutos comerciales por planta, mientras que el contenido de vitamina C y de fenoles totales disminuyó significativamente. La concentración del total de fenoles extraíbles en los tomates varió entre 287,1 y 977,4 mg de equivalentes de ácido gálico (GAE) por kilo sobre la base de peso fresco, mientras que el contenido de licopeno varió desde 11,44 hasta 60,99 mg kg–1 de peso fresco. Las actividades antioxidantes determinadas por el método DPPH (2,2-difenil-1-picrilhidrazilo) de los injertos fueron significativamente diferentes respecto de sus respectivos patrones. Los resultados globales muestran que el injerto de tomate sobre patrones adecuados tiene efectos positivos sobre el rendimiento de cultivo, pero la calidad nutricional de los frutos disminuye

The Presence of Real Food Usurps Hypothetical Health Value Judgment in Overweight People.

To develop more ecologically valid models of the neurobiology of obesity, it is critical to determine how the neural processes involved in food-related decision-making translate into real-world eating behaviors. We examined the relationship between goal-directed valuations of food images in the MRI scanner and food consumption at a subsequent ad libitum buffet meal. We observed that 23 lean and 40 overweight human participants showed similar patterns of value-based neural responses to health and taste attributes of foods. In both groups, these value-based responses in the ventromedial PFC were predictive of subsequent consumption at the buffet. However, overweight participants consumed a greater proportion of unhealthy foods. This was not predicted by in-scanner choices or neural response. Moreover, in overweight participants alone, impulsivity scores predicted greater consumption of unhealthy foods. Overall, our findings suggest that, while the hypothetical valuation of the health of foods is predictive of eating behavior in both lean and overweight people, it is only the real-world food choices that clearly distinguish them.This study was supported by the Bernard Wolfe Health Neuroscience Fund (HZ, PCF), the Wellcome Trust (NM, HZ, PCF), the Medical Research Council grant U105960389 (ALA, KMD, SAJ) and the Department of Health Policy Research Program (Policy Research Unit in Behaviour and Health [PR-UN-0409-10109]) (TMM, SEF).This is the final version of the article. It first appeared from the Society for Neuroscience via https://doi.org/10.1523/ENEURO.0025-16.201

The importance of clonal selection of grapevine and the role of selected clones in production of healthy propagating stocks

Genetical alterations and phytosanitary status promote the variability and modify the appearance of vine. Old vine varieties in oldvineyards are highly variable and well adapted to selection. Clonal selektion is based on a visual performance: valuable individuals (clones)are picked out according to visible symptoms or characters. The genetical stability of clones is proved by testing the vegetatively propagatedprogenies on the basis of morphological and molekular (SSR, AFLP, SMPL, RAPD) markes.Authors take great care of the visual phytosanitary selection as part of the clonal selection being the preliminary step to develop pathogen-freepropagation stocks.In Serbia (Vojvodina) the selection breeding has been carried on for several decades resulted in comparative clone trials with home andimported clones of Welsch Riesling, Chardonnay, Pinot gris, White Riesling. Among the clones of home selection SK.54 Welsch Rieslingclone is the most valuable. Its clearing from pathogene is being carried on in an interregional IPA programme (HUSRB/0901/214/123) inKecskemét.In Kecskemét, the centre of the Hungarian Danube vine region 5 vine clones have been registered (Cegléd szépe K.73, Irsai Olivér K.11,Kövidinka K.8, Hárslevelû K.9, Pannónia kincse K.56). Besides them 18 virus-tested clones have also been qualified.Works aiming at theircomplete exemption are going on in order to obtain clones free of propagation wood-borne diseases

The importance of clonal selection of grapevine and the role of selected clones in production of healthy propagating stocks

Genetical alterations and phytosanitary status promote the variability and modify the appearance of vine. Old vine varieties in old vineyards are highly variable and well adapted to selection. Clonal selektion is based on a visual performance: valuable individuals (clones) are picked out according to visible symptoms or characters. The genetical stability of clones is proved by testing the vegetatively propagated progenies on the basis of morphological and molekular (SSR, AFLP, SMPL, RAPD) markes. Authors take great care of the visual phytosanitary selection as part of the clonal selection being the oreliminary step to develop pathogen-free propagation stocks. In Serbia (Vojvodina) the selection breeding has been carried on for several decades resulted in comparative clone trials with home and imported clones of Welsch Riesling, Chardonnay, Pinot gris, White Riesling. Among the clones of home selection SK.54 Welsch Riesling clone is the most valuable. Its clearing from pathogene is being carried on in an interregional IPA programme (HUSRB/0901/214/123) in Kecskemét. In Kecskemét, the centre of the Hungarian Danube vine region 5 vine clones have been registered (Cegléd szépe K.73, Irsai Olivér K.11, Kövidinka K.8, Hárslevelû K.9, Pannónia kincse K.56). Besides them 18 virus-tested clones have also been qualified.Works aiming at their complete exemption are going on in order to obtain clones free of propagation wood-borne diseases

Failure of sucrose replacement with the non-nutritive sweetener erythritol to alter GLP-1 or PYY release or test meal size in lean or obese people.

There is considerable interest in the effect of foods containing high intensity sweeteners on satiation. However, less is known about low-calorie bulk sweeteners such as erythritol. In this randomized three-way crossover study, we studied 10 lean and 10 obese volunteers who consumed three test meals on separate occasions: (a) control sucrose meal; (b) isovolumic meal with partial replacement of sucrose by erythritol; (c) isocaloric meal which contained more erythritol but equivalent calories to the control meal. We measured gut hormone levels, hunger and satiety scores, ad libitum food intake, sucrose preference and intake after the manipulations. There was a greater post-prandial excursion in glucose and insulin levels after sucrose than after the erythritol meals. There was no difference in GLP-1/PYY levels or subsequent energy intake and sucrose preference between sucrose control and isovolumic erythritol meals. In lean (but not obese) participants, hunger decreased to a greater extent after the isocaloric erythritol meal compared to the control meal (p = 0.003) reflecting the larger volume of this meal. Replacing sucrose with erythritol leads to comparable hunger and satiety scores, GLP-1 and PYY levels, and subsequent sucrose preference and intake.Wellcome Trust, National Institute for Health Research Cambridge Biomedical Research Centre, Bernard Wolfe Health Neuroscience Fund, Swiss National Science Foundation (Grant IDs: PBLAP3-145870, P3SMP3-155318), NeuroFAST consortium, European Union's Seventh Framework Programme (FP7/ 2007e2013) Grant ID: 245009), Cargill, Sas van Gent, The NetherlandsThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.appet.2016.09.00

A Review of Controlling Motivational Strategies from a Self-Determination Theory Perspective: Implications for Sports Coaches

The aim of this paper is to present a preliminary taxonomy of six controlling strategies, primarily based on the parental and educational literatures, which we believe are employed by coaches in sport contexts. Research in the sport and physical education literature has primarily focused on coaches’ autonomysupportive behaviours. Surprisingly, there has been very little research on the use of controlling strategies. A brief overview of the research which delineates each proposed strategy is presented, as are examples of the potential manifestation of the behaviours associated with each strategy in the context of sports coaching. In line with self-determination theory (Deci & Ryan, 1985; Ryan & Deci, 2002), we propose that coach behaviours employed to pressure or control athletes have the potential to thwart athletes’ feelings of autonomy, competence,and relatedness, which, in turn, undermine athletes’ self-determined motivation and contribute to the development of controlled motives. When athletes feel pressured to behave in a certain way, a variety of negative consequences are expected to ensue which are to the detriment of the athletes’ well-being. The purpose of this paper is to raise awareness and interest in the darker side of sport participation and to offer suggestions for future research in this area

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON).

In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs). Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy. PROs (prespecified secondary endpoints) were assessed using the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire version 3 (QLQ-C30) and its 13-item lung cancer module (QLQ-LC13). We analyzed time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization by log-rank test and improvement rates by logistic regression. 972/1013 (96 %) patients randomized completed baseline QLQ-C30 and QLQ-LC13 questionnaires, with scores comparable between treatment arms. Patients receiving tremelimumab plus durvalumab and chemotherapy versus chemotherapy had longer median TTD for all PRO items. Hazard ratios for TTD favored tremelimumab plus durvalumab and chemotherapy for all items except diarrhea; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, cognitive functioning, pain, nausea/vomiting, insomnia, constipation, hemoptysis, dyspnea, and pain in other parts. For durvalumab plus chemotherapy, median TTD was longer versus chemotherapy for all items except nausea/vomiting and diarrhea. Hazard ratios favored durvalumab plus chemotherapy for all items except appetite loss; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, role functioning, dyspnea, and pain in other parts. For both immunotherapy plus chemotherapy arms, improvement rates in all PRO items were numerically higher versus chemotherapy, with odds ratios > 1. Tremelimumab plus durvalumab and chemotherapy delayed deterioration in symptoms, functioning, and global health status/QoL compared with chemotherapy. Together with significant improvements in survival, these results support tremelimumab plus durvalumab and chemotherapy as a first-line treatment option in metastatic NSCLC