Acute inhibition of MEK suppresses congenital melanocytic nevus syndrome in a murine model driven by activated NRAS and Wnt signaling

Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRASQ61K and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition

Thirty years of vegetation dynamics in the Rospuda fen (NE Poland)

Little is known about the vegetation dynamics of fens, and especially of hydrologically undisturbed examples. We described the vegetation of an undisturbed mesotrophic rich fen (percolation mire) in 2006–2008 and 2016 and compared our results with vegetation records from the 1980s to identify any longer-term changes. Eight vegetation types were distinguished. On the whole, the vegetation of the mire has remained very stable throughout the last 30 years. However, detailed comparisons of permanent plots recorded twice in the last ten years indicated an expansion of shrubs in patches of Sphagnum - small sedge vegetation. There were also several less prominent changes in the abundance of particular species in other mire vegetation types: (1) an increase of sedges, reeds and Calliergonella cuspidata at the expense of rich-fen moss species in communities of brown moss - small sedge; (2) a change in composition of the moss layer in pine - birch fen woodland; (3) an increase of reedbed species and reduced Alnus glutinosa abundance in flooded riparian alder woodland; and (4) a decline of wetland herbs and mosses in alder spring fen woodland at the edges of the valley

Exploring the Trade-offs of Aggregated versus Disaggregated Architectures for Environmental Monitoring in Low-Earth Orbit

Traditionally, government space agencies have developed aggregated systems that co-host multiple capabilities on shared spacecraft buses. However, in response to cost growth and schedule delays on past programs, leaders in the government space community have expressed an interest in disaggregation, or distributing their capabilities across multiple spacecraft. Since their aggregated National Polar-orbiting Operational Satellite System (NPOESS) program was cancelled in 2010, both the National Oceanic and Atmospheric Administration (NOAA) and the Department of Defense (DoD) have investigated opportunities to reduce program costs through disaggregation. This paper expands their initial investigation and explores the cost impacts of aggregation and disaggregation across a large trade space of candidate architectures for environmental monitoring in low-Earth orbit. We find that on average, aggregated architectures are less costly than fully disaggregated ones but also find opportunities for cost savings by developing semi-aggregated systems, or systems with one or two satellites per orbital plane. Finally, we investigate several trades that are currently under consideration by NOAA and the DoD and make recommendations for future environmental monitoring systems in low-Earth orbit.Massachusetts Institute of Technology (Sandia Corporation Excellence in Engineering Graduate Fellowship)Skolkovo Institute of Science and Technolog

Nest-site competition between bumblebees (Bombidae), social wasps (Vespidae) and cavity-nesting birds in Britain and the Western Palearctic

Capsule: There is no evidence of widespread significant nest-site competition in Britain or the Western Palearctic between cavity-nesting birds and bumblebees or social wasps. Aims: To investigate competition between cavity-nesting birds and bumblebees and wasps, particularly the range-expanding Tree Bumblebee, Saxon Wasp and European Hornet in Britain, and review evidence throughout the Western Palearctic. Methods: We compared field data from English and Polish studies of tits and woodpeckers breeding in nest-boxes and/or tree holes to assess nest-site competition with bumblebees and wasps. We reviewed the literature quantifying nest-site competition between birds and these insects in the Western Palearctic. Results: Bumblebees and wasps are capable of usurping small passerines from nests. In England, these insects commandeered a mean annual 4.1% of tit nests initiated in nest-boxes; occurrence of hornets showed a long-term increase, but not other wasps or bumblebees. Across the Western Palearctic, insect occupation of nest-boxes was generally low, and was lower in England than in Poland. No insects were discovered in tree cavities, including those created by woodpeckers (Picidae). Conclusion: Nest-site competition between cavity-nesting birds and bumblebees and wasps appears to be a ‘nest-box phenomenon’, which may occasionally interfere with nest-box studies, but appears negligible in natural nest-sites

Religious identity in the workplace : a systematic review, research agenda, and practical implications

We conducted a systematic review of relevant literature to address how religious and occupational identities relate to each other in the workplace. We identified 53 relevant publications for analysis and synthesis. Studies addressed value differences associated with religion and occupation, identity tensions, unmet expectations, and the connection of religious identity to well-being and work outcomes. Key variables in the connection between religious and occupational identities included personal preferences, the fit between religious identity and job-related concerns, and the organization’s policies, practices and expectations. We highlight the personal and organizational consequences of being able to express religious identity at work and the conditions that promote high congruence between religious identity and its expression in the workplace. From these findings, we develop a research agenda and offer recommendations for management practice that focus on support for expression of religious identity at work while maintaining a broader climate of inclusion

Carotid Body AT4 Receptor Expression and its Upregulation in Chronic Hypoxia

Hypoxia regulates the local expression of angiotensin-generating system in the rat carotid body and the me-tabolite angiotensin IV (Ang IV) may be involved in the modulation of carotid body function. We tested the hypothesis that Ang IV-binding angiotensin AT4 receptors play a role in the adaptive change of the carotid body in hypoxia. The expression and localization of Ang IV-binding sites and AT4 receptors in the rat carotid bodies were studied with histochemistry. Specific fluorescein-labeled Ang IV binding sites and positive staining of AT4 immunoreactivity were mainly found in lobules in the carotid body. Double-labeling study showed the AT4 receptor was localized in glomus cells containing tyrosine hydroxylase, suggesting the expression in the chemosensitive cells. Intriguingly, the Ang IV-binding and AT4 immunoreactivity were more intense in the carotid body of chronically hypoxic (CH) rats (breathing 10% oxygen for 4 weeks) than the normoxic (Nx) control. Also, the protein level of AT4 receptor was doubled in the CH comparing with the Nx group, supporting an upregulation of the expression in hypoxia. To examine if Ang IV induces intracellular Ca2+ response in the carotid body, cytosolic calcium ([Ca2+]i) was measured by spectrofluorimetry in fura-2-loaded glomus cells dissociated from CH and Nx carotid bodies. Exogenous Ang IV elevated [Ca2+]i in the glomus cells and the Ang IV response was significantly greater in the CH than the Nx group. Hence, hypoxia induces an upregulation of the expression of AT4 receptors in the glomus cells of the carotid body with an increase in the Ang IV-induced [Ca2+]i elevation. This may be an additional pathway enhancing the Ang II action for the activation of chemoreflex in the hypoxic response during chronic hypoxia

Validation and psychometric analysis of the Internet Addiction Test in Spanish among college students

BACKGROUND: The wide use of the Internet in the workplace, academic or social field, can have an impact on daily life. One of the most used questionnaires worldwide to analyse these problems is the Internet Addiction Test (IAT). Our aim was to validate a Spanish version of the IAT and analyse its psychometric properties. METHODS: Population of study were college students participating in the uniHcos project (Universities of Granada, Huelva, Jaén, León, Salamanca, and Vigo). The questionnaire was translated and back-translated by two native English speakers. Reliability of scores was analysed using Pearson's correlation coefficient and agreement was analysed using the Bland-Altman and Kappa techniques. Test dimensions were analysed by exploratory and confirmatory factor analysis. RESULTS: The reliability of scores was good (r = 0.899, Kappa = 0.650 and mean difference using Bland-Altman = -3.5). The psychometric assessment identified two factors (Emotional Investment; Performance and Time Management) which explained 55 % of the variance (total internal consistency of 0.91) and only 19 items. The confirmatory analysis showed an acceptable goodness of fit, especially when items 6 and 8 were related (RMSEA = 0.07 90%IC = 0.06 - 0.08; WRMR = 1.01, CFI = 0.96; TLI = 0.95). The two dimensions were negatively correlated with age and positively correlated with time spent online, especially for the purposes of leisure and entertainment. DISCUSSION: The results show good reliability and psychometric properties of the Spanish version of IAT with a two-dimensional solution. This result is partially in concordance with previous validations of the IAT in other languages that have found uni- and multi-dimensional solutions using different methodologies. Moreover, we want to highlight the possibility that some item of this questionnaire is outdated due to the technological and lifestyles changes and should be not taken into account. CONCLUSION: The reliability and psychometric properties obtained in this study support the conclusion that this Spanish short version of the IAT represents a useful tool for the analysis of problems arising from misuse of the Internet