Mckinneychurch4342

Combined treatment of either SK-N-B-E(2) or IMR-32 cells with ISLQ and the anticancer agent cisplatin resulted in loss of cell viability that was greater than that induced by cisplatin alone. This study provides proof-of-principle that ISLQ is a potent cytotoxin for MYCN-amplified human NB cells. This is an important first step in rationalizing the further study of ISLQ as a potential adjunct therapy for high-risk NB. © 2019 The Author(s).Microglia are an essential component of the neurogenic niche in the adult hippocampus and are involved in the control of neural precursor cell (NPC) proliferation, differentiation and the survival and integration of newborn neurons in hippocampal circuitry. Microglial and neuronal cross-talk is mediated in part by the chemokine fractalkine/chemokine (C-X3-C motif) ligand 1 (CX3CL1) released from neurons, and its receptor CX3C chemokine receptor 1 (CX3CR1) which is expressed on microglia. A disruption in this pathway has been associated with impaired neurogenesis yet the specific molecular mechanisms by which this interaction occurs remain unclear. The orphan nuclear receptor TLX (Nr2e1; homologue of the Drosophila tailless gene) is a key regulator of hippocampal neurogenesis, and we have shown that in its absence microglia exhibit a pro-inflammatory activation phenotype. However, it is unclear whether a disturbance in CX3CL1/CX3CR1 communication mediates an impairment in TLX-related pathways which may have subsequent effects on neurogenesis. To this end, we assessed miRNA expression of up- and down-stream signalling molecules of TLX in the hippocampus of mice lacking CX3CR1. Our results demonstrate that a lack of CX3CR1 is associated with altered expression of TLX and its downstream targets in the hippocampus without significantly affecting upstream regulators of TLX. Thus, TLX may be a potential participant in neural stem cell (NSC)-microglial cross-talk and may be an important target in understanding inflammatory-associated impairments in neurogenesis. © 2019 The Author(s).Cholinergic basal forebrain (cBF) neurons are defined by their expression of the p75 neurotrophin receptor (p75NTR) and tropomyosin-related kinase (Trk) neurotrophin receptors in addition to cholinergic markers. It is known that the neurotrophins, particularly nerve growth factor (NGF), mediate cholinergic neuronal development and maintenance. However, the role of neurotrophin signalling in regulating adult cBF function is less clear, although in dementia, trophic signalling is reduced and p75NTR mediates neurodegeneration of cBF neurons. Here we review the current understanding of how cBF neurons are regulated by neurotrophins which activate p75NTR and TrkA, B or C to influence the critical role that these neurons play in normal cortical function, particularly higher order cognition. Specifically, we describe the current evidence that neurotrophins regulate the development of basal forebrain neurons and their role in maintaining and modifying mature basal forebrain synaptic and cortical microcircuit connectivity. Understanding the role neurotrophin signalling plays in regulating the precision of cholinergic connectivity will contribute to the understanding of normal cognitive processes and will likely provide additional ideas for designing improved therapies for the treatment of neurological disease in which cholinergic dysfunction has been demonstrated. © 2019 The Author(s).Objectives Our aim was to conduct a systematic review to determine which technology-driven diabetes prevention interventions were effective in producing clinically significant weight loss, and to identify the behaviour change techniques and digital features frequently used in effective interventions. Methods We searched five databases (CINAHL, EMBASE, MEDLINE, PsychINFO, and Pubmed) from inception to September 2018 and reviewed 19 experimental and non-experimental studies of 21 technology-driven diet plus physical activity interventions for adults (≥18 years) at risk of developing type 2 diabetes. Behaviour change techniques were coded using the BCT taxonomy v1, and digital features were identified via thematic analysis of intervention descriptions. Rapamycin research buy Results Sixty-three per cent of interventions were effective in the short term (achieving ≥3% weight loss at ≤6 months), using an average of 5.6 more behaviour change techniques than non-effective interventions, and 33% were effective in the long term (achieving ≥5% weight loss at ≥12 months), using 3.7 more behaviour change techniques than non-effective interventions. The techniques of social support (unspecified), goal setting (outcome/behaviour), feedback on behaviour, and self-monitoring of outcome(s) of behaviour were identified in over 90% of effective interventions. Interventions containing digital features that facilitated health and lifestyle education, behaviour/outcome tracking, and/or online health coaching were most effective. Conclusion The integration of specific behaviour change techniques and digital features may optimise digital diabetes prevention interventions to achieve clinically significant weight loss. Additional research is needed to identify the mechanisms in which behaviour change techniques and digital features directly influence physical activity, dietary behaviours, and intervention engagement. © The Author(s) 2020.The purpose of this study was to develop a statistical model of anhedonia of depression. The study included 748 healthy controls (350 women, 46.79%, age 21.27 ± 4.72) and 80 patients (32 women, 40%, age 38.36 ± 16.42). The Physical Anhedonia Scale (PhAS), the Social Anhedonia Scale (CSAS), the Positive and Negative Affect Scale (PANAS) and the Beck Depression Inventory(BDI) were administered. Classical Measurement Theory (CTT) and Item Response Theory (IRT) were applied to the collected data. We observed that the general factor of depression status was significantly related with positive emotion (r = -0.37, P less then 0.05), negative emotion (r = 0.62, P less then 0.05) and BDI (r = 0.48, P less then 0.01). A significant difference also was observed between controls and patients. The bifactor model of anhedonia of depression provided a better fit to the data than a unidimensional model. The bifactor model appears to be useful to describe anhedonia in depression. Copyright © 2020 The Author(s).