Summary Based on electrophysiological, neurochemical, genetic and neuropharmacological approaches, it is currently accepted that serotonin (5-HT) functions predominantly to promote wakefulness (W) ...and to inhibit REM (rapid eye movement) sleep (REMS). Yet, under certain circumstances the neurotransmitter contributes to the increase in sleep propensity. Most of the serotonergic innervation of the cerebral cortex, amygdala, basal forebrain (BFB), thalamus, preoptic and hypothalamic areas, raphe nuclei, locus coeruleus and pontine reticular formation comes from the dorsal raphe nucleus (DRN). The 5-HT receptors can be classified into at least seven classes, designated 5-HT1–7 . The 5-HT1A and 5-HT1B receptor subtypes are linked to the inhibition of adenylate cyclase, and their activation evokes a membrane hyperpolarization. The actions of the 5-HT2A , 5-HT2B and 5-HT2C receptor subtypes are mediated by the activation of phospholipase C, with a resulting depolarization of the host cell. The 5-HT3 receptor directly activates a 5-HT-gated cation channel which leads to the depolarization of monoaminergic, aminoacidergic and cholinergic cells. The primary signal transduction pathway of 5-HT6 and 5-HT7 receptors is the stimulation of adenylate cyclase which results in the depolarization of the follower neurons. Mutant mice that do not express 5-HT1A or 5-HT1B receptor exhibit greater amounts of REMS than their wild-type counterparts, which could be related to the absence of a postsynaptic inhibitory effect on REM-on neurons of the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT). 5-HT2A and 5-HT2C receptor knock-out mice show a significant increase of W and a reduction of slow wave sleep (SWS) which has been ascribed to the increase of catecholaminergic neurotransmission involving mainly the noradrenergic and dopaminergic systems. Sleep variables have been characterized, in addition, in 5-HT7 receptor knock-out mice; the mutants spend less time in REMS that their wild-type counterparts. Direct infusion of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan into the DRN significantly enhances REMS in the rat. In contrast, microinjection of the 5-HT1B (CP-94253), 5-HT2A/2C (DOI), 5-HT3 (m-chlorophenylbiguanide) and 5-HT7 (LP-44) receptor agonists into the DRN induces a significant reduction of REMS. Systemic injection of full agonists at postsynaptic 5-HT1A (8-OH-DPAT, flesinoxan), 5-HT1B (CGS 12066B, CP-94235), 5-HT2C (RO 60-0175), 5-HT2A/2C (DOI, DOM), 5-HT3 (m-chlorophenylbiguanide) and 5-HT7 (LP-211) receptors increases W and reduces SWS and REMS. Of note, systemic administration of the 5-HT2A/2C receptor antagonists ritanserin, ketanserin, ICI-170,809 or sertindole at the beginning of the light period has been shown to induce a significant increase of SWS and a reduction of REMS in the rat. Wakefulness was also diminished in most of these studies. Similar effects have been described following the injection of the selective 5-HT2A receptor antagonists volinanserin and pruvanserin and of the 5-HT2A receptor inverse agonist nelotanserin in rodents. In addition, the effects of these compounds have been studied on the sleep electroencephalogram of subjects with normal sleep. Their administration was followed by an increase of SWS and, in most instances, a reduction of REMS. The administration of ritanserin to poor sleepers, patients with chronic primary insomnia and psychiatric patients with a generalized anxiety disorder or a mood disorder caused a significant increase in SWS. The 5-HT2A receptor inverse agonist APD-125 induced also an increase of SWS in patients with chronic primary insomnia. It is known that during the administration of benzodiazepine (BZD) hypnotics to patients with insomnia there is a further reduction of SWS and REMS, whereas both variables tend to remain decreased during the use of non-BZD derivatives (zolpidem, zopiclone, eszopiclone, zaleplon). Thus, the association of 5-HT2A antagonists or 5-HT2A inverse agonists with BZD and non-BZD hypnotics could be a valid alternative to normalize SWS in patients with primary or comorbid insomnia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This paper investigates direct and spillover effects of a social information campaign aimed at encouraging residential water savings in Colombia. The campaign was organized as a randomized field ...experiment, consisting of monthly delivery of consumption reports, including normative messages, for one year. Results indicate that social information and appeals to norm-based behavior reduce water use by up to 6.8% in households directly targeted by the campaign. In addition, we find evidence of spillover effects: households that were not targeted by the campaign reduced water use by 5.8% in the first six months following the intervention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer ...cells from diverse lineages. Pan-cancer analyses have been performed for adult but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.
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KISLJ, NUK, SBMB, UL, UM, UPUK
Urban Green Space and Its Impact on Human Health Kondo, Michelle C; Fluehr, Jaime M; McKeon, Thomas ...
International journal of environmental research and public health,
03/2018, Volume:
15, Issue:
3
Journal Article
Peer reviewed
Open access
: Over half of the world's population now lives in urban areas, and this proportion is expected to increase. While there have been numerous reviews of empirical studies on the link between nature and ...human health, very few have focused on the urban context, and most have examined almost exclusively cross-sectional research. This review is a first step toward assessing the possibility of causal relationships between nature and health in urban settings.
: Through systematic review of published literature, we explored the association between urban green space and human health.
: We found consistent negative association between urban green space exposure and mortality, heart rate, and violence, and positive association with attention, mood, and physical activity. Results were mixed, or no association was found, in studies of urban green space exposure and general health, weight status, depression, and stress (via cortisol concentration). The number of studies was too low to generalize about birth outcomes, blood pressure, heart rate variability, cancer, diabetes, or respiratory symptoms.
: More studies using rigorous study design are needed to make generalizations, and meta-analyses, of these and other health outcomes possible. These findings may assist urban managers, organizations, and communities in their efforts to increase new or preserve existing green space.
We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition ...to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.
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IJS, NUK, SBMB, UL, UM, UPUK
Research examining the role of place in Black adolescents’ health behaviors typically examines neighborhoods, with little attention paid to micro geographies such as activity spaces. Understanding ...experiences in activity spaces may be especially important for Black adolescents living in neighborhoods traditionally characterized as disadvantaged. The SPIN project recruited 75 Black adolescents living in a single neighborhood to complete ecological momentary assessments (EMA) about the activity spaces they encountered over a month. Perceptions of violence and social support in activity spaces in a day are related to marijuana use during the day, relationships partially explained by negative momentary emotions.
•For Black adolescents, spending time in activity spaces perceived as violent/racist correlates with reported marijuana use that day.•For Black adolescents, perceived social support in daily activity spaces indirectly relates to marijuana use via momentary negative emotions.•Negative momentary emotions explain the correlation between adolescents' exposure to violent activity spaces and reported marijuana use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer ...Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults. Conversely, mutations in DNMT3A and TP53, which were common in adults, were conspicuously absent from virtually all pediatric cases. New mutations in GATA2, FLT3 and CBL and recurrent mutations in MYC-ITD, NRAS, KRAS and WT1 were frequent in pediatric AML. Deletions, mutations and promoter DNA hypermethylation convergently impacted Wnt signaling, Polycomb repression, innate immune cell interactions and a cluster of zinc finger-encoding genes associated with KMT2A rearrangements. These results highlight the need for and facilitate the development of age-tailored targeted therapies for the treatment of pediatric AML.
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IJS, NUK, SBMB, UL, UM, UPUK
The exclusive
ρ
,
ω
and
J
/
Ψ
photoproduction in fixed-target collisions at the LHC is investigated. We estimate, for the first time, the rapidity and transverse momentum distributions of the vector ...meson photoproduction in
pHe
,
pAr
,
PbHe
and
PbAr
fixed-target collisions at the LHC using the STARlight Monte Carlo and present our results for the total cross sections. Predictions for the kinematical range probed by the LHCb detector are also presented. Our results indicate that the experimental analysis of this process in fixed-target collisions at the LHC is feasible. Such future analysis will probe the QCD dynamics in a kinematical range complementary to that studied in the collider mode.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Organismal ageing is accompanied by progressive loss of cellular function and systemic deterioration of multiple tissues, leading to impaired function and increased vulnerability to death. ...Mitochondria have become recognized not merely as being energy suppliers but also as having an essential role in the development of diseases associated with ageing, such as neurodegenerative and cardiovascular diseases. A growing body of evidence suggests that ageing and age-related diseases are tightly related to an energy supply and demand imbalance, which might be alleviated by a variety of interventions, including physical activity and calorie restriction, as well as naturally occurring molecules targeting conserved longevity pathways. Here, we review key historical advances and progress from the past few years in our understanding of the role of mitochondria in ageing and age-related metabolic diseases. We also highlight emerging scientific innovations using mitochondria-targeted therapeutic approaches.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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