Imbalanced functional link between executive control network and reward network explain the online-game seeking behaviors in Internet gaming disorder

Literatures have shown that Internet gaming disorder (IGD) subjects show impaired executive control and enhanced reward sensitivities than healthy controls. However, how these two networks jointly affect the valuation process and drive IGD subjects' online-game-seeking behaviors remains unknown. Thirty-five IGD and 36 healthy controls underwent a resting-states scan in the MRI scanner. Functional connectivity (FC) was examined within control and reward network seeds regions, respectively. Nucleus accumbens (NAcc) was selected as the node to find the interactions between these two networks. IGD subjects show decreased FC in the executive control network and increased FC in the reward network when comparing with the healthy controls. When examining the correlations between the NAcc and the executive control/reward networks, the link between the NAcc - executive control network is negatively related with the link between NAcc - reward network. The changes (decrease/increase) in IGD subjects' brain synchrony in control/reward networks suggest the inefficient/overly processing within neural circuitry underlying these processes. The inverse proportion between control network and reward network in IGD suggest that impairments in executive control lead to inefficient inhibition of enhanced cravings to excessive online game playing. This might shed light on the mechanistic understanding of IGD

Activation of the PIK3CA/AKT Pathway Suppresses Senescence Induced by an Activated RAS Oncogene to Promote Tumorigenesis

Mutations in both RAS and the PTEN/PIK3CA/AKT signaling module are found in the same human tumors. PIK3CA and AKT are downstream effectors of RAS, and the selective advantage conferred by mutation of two genes in the same pathway is unclear. Based on a comparative molecular analysis, we show that activated PIK3CA/AKT is a weaker inducer of senescence than is activated RAS. Moreover, concurrent activation of RAS and PIK3CA/AKT impairs RAS-induced senescence. In vivo, bypass of RAS-induced senescence by activated PIK3CA/AKT correlates with accelerated tumorigenesis. Thus, not all oncogenes are equally potent inducers of senescence, and, paradoxically, a weak inducer of senescence (PIK3CA/AKT) can be dominant over a strong inducer of senescence (RAS). For tumor growth, one selective advantage of concurrent mutation of RAS and PTEN/PIK3CA/AKT is suppression of RAS-induced senescence. Evidence is presented that this new understanding can be exploited in rational development and targeted application of prosenescence cancer therapies

Rising temperatures advance the main flight period of Bombus bumblebees in agricultural landscapes of the Central European Plain

Funder: Poznan University of Life SciencesAbstractThis study examined shifts over a 35-year period in the phenology of the four most important bumblebee species (Bombus terrestris, B. lapidarius, B. pascuorum and B. hortorum) in Central Europe. The species showed similar temporal trends, significantly advancing components of their main flight period in association with rising temperatures such that, for example, mid-dates of the main flight period advanced by 10–23 days over the study period. Drivers of this change differed between the four species. Trends in, and drivers of, the timing of first queens, first workers and first males were less consistent. Aspects of the phenology of the least common species, B. hortorum, were up to a month earlier than the other species and climatic effects less clear cut. There were some suggestions of differences between species trends. These results stress the importance of considering changes and drivers of change for the Bombus family on a species-specific basis with the need to pay more attention to the life history traits of the study organisms.</jats:p

MEK inhibition appears to improve symptom control in primary NRAS-driven CNS melanoma in children

BACKGROUND: Primary melanoma of the CNS in children is extremely rare, and usually linked to congenital melanocytic naevus syndrome, caused by mosaicism for oncogenic NRAS mutations. Outcome is fatal in all cases. Data from murine and in vitro studies suggest that MEK inhibition is a possible therapeutic option. METHODS: Four children with NRAS-mutated CNS melanoma were treated with Trametinib on a compassionate basis. RESULTS: All four had an improvement in symptoms and objectively in signs. These varied from mild improvement for 1 month, to a sustained symptom-free period of 9 months in one case. In all cases there was eventual disease progression through treatment, followed by rapid death after discontinuation. There were no clinically-significant side effects. CONCLUSIONS: Trametinib is the first therapy to show any objective or measurable effect in NRAS-mutated primary CNS melanoma, with few side effects in this small series. The role of this therapy should be explored further in this rare paediatric tumour.British Journal of Cancer advance online publication, 2 March 2017; doi:10.1038/bjc.2017.49 www.bjcancer.com