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The mTOR pathway is a well-known regulator of cell size, and deregulation of mTOR has been observed in cilia-related diseases. Cilia modulate cell size by restricting LKB-1-mediated activation of AMPK to the basal body, which subsequently affects mTOR signalling. The mTOR pathway is the central regulator of cell size 1 . External signals from growth factors and nutrients converge on the mTORC1 multi-protein complex to modulate downstream targets, but how the different inputs are integrated and translated into specific cellular responses is incompletely understood 2 , 3 , 4 . Deregulation of the mTOR pathway occurs in polycystic kidney disease (PKD) 5 , 6 , 7 , where cilia (filiform sensory organelles) fail to sense urine flow because of inherited mutations in ciliary proteins 8 . We therefore investigated if cilia have a role in mTOR regulation. Here, we show that ablation of cilia in transgenic mice results in enlarged cells when compared with control animals. In vitro analysis demonstrated that bending of the cilia by flow is required for mTOR downregulation and cell-size control. Surprisingly, regulation of cell size by cilia is independent of flow-induced calcium transients, or Akt. However, the tumour-suppressor protein Lkb1 localises in the cilium, and flow results in increased AMPK phosphorylation at the basal body. Conversely, knockdown of Lkb1 prevents normal cell-size regulation under flow conditions. Our results demonstrate that the cilium regulates mTOR signalling and cell size, and identify the cilium-basal body compartment as a spatially restricted activation site for Lkb1 signalling.

Purpose Research to date suggests that physical activity is associated with improved sleep, but studies have predominantly relied on self-report measures and have not accounted for school day/free day variability. To address these gaps in the literature, the aim of the present study was to (a) quantify physical activity in adolescents using long-term daily actigraphy measurement and (b) to examine the association between actigraphically assessed steps and sleep behavior in a sample of healthy adolescents. To be able to capture intra- and inter-individual differences in the daily physical activity of adolescents, we examined within as well as between subjects effects and its association with sleep. Methods Fifty adolescents between 10 and 14 years of age were included in the present study. In total 5989 days of actigraphy measurement (average of 119 ± 40 days per participant; range = 39–195 days) were analyzed. We use multilevel modeling to disentangle the within and between subject effects of physical activity on sleep. In this way, we examine within an individual, the association between steps during the day and subsequent sleep on a day-to-day basis. On the other hand, our between subjects’ analysis allows us to ascertain whether individuals with more overall physical activity have better sleep. Results Within a subject more steps on school and free days were associated with later bed times on school and free days as well as later rise times on school days only. On the other hand, comparing between subjects’ effects, more steps were associated with lower sleep efficiency on free and school days. No other significant associations were found for the other sleep variables. Conclusion Our results obtained through objective and long-term measurement of both sleep and number of steps suggest weak or non-significant associations between these measures for most sleep variables. We emphasize the importance of the methodology and the separation of within subject from between subject features when examining the relationship between physical activity and sleep.

Ift88 is a central component of the intraflagellar transport (Ift) complex B, essential for the building of cilia and flagella from single cell organisms to mammals. Loss of Ift88 results in the absence of cilia and causes left-right asymmetry defects, disordered Hedgehog signaling, and polycystic kidney disease, all of which are explained by aberrant ciliary function. In addition, a number of extraciliary functions of Ift88 have been described that affect the cell-cycle, mitosis, and targeting of the T-cell receptor to the immunological synapse. Similarly, another essential ciliary molecule, the kinesin-2 subunit Kif3a, which transports Ift-B in the cilium, affects microtubule (MT) dynamics at the leading edge of migrating cells independently of cilia. We now show that loss of Ift88 impairs cell migration irrespective of cilia. Ift88 is required for the polarization of migrating MDCK cells, and Ift88 depleted cells have fewer MTs at the leading edge. Neither MT dynamics nor MT nucleation are dependent on Ift88. Our findings dissociate the function of Ift88 from Kif3a outside the cilium and suggest a novel extraciliary function for Ift88. Future studies need to address what unifying mechanism underlies the different extraciliary functions of Ift88.

There is great cultural diversity across Europe. This is reflected in the organisation of child and adolescent mental health (CAMH) services and the training of the respective professionals in different countries in Europe. Patients and their parents will want a high quality, knowledgeable, and skillful service from child and adolescent psychiatrists (CAPs) wherever they see them in Europe. A European comparison of training programs allows all stakeholders in different European countries to assess the diversity and to initiate discussions as to the introduction of improvements within national training programs. Major issues to be addressed in comparing child and adolescent psychiatric training programs across Europe include: (1) formal organisation and content of training programs and the relationship to adult psychiatry and paediatrics; (2) flexibility of training, given different trainee interests and that many trainees will have young families; (3) quality of governance of training systems; (4) access to research; and (5) networking. The Child and Adolescent Psychiatry—Study of Training in Europe (CAP-State) is a survey of training for child and adolescent psychiatrists (CAPs) across European countries. It aims to revisit and extend the survey carried out in 2006 by Karabekiroglu and colleagues. The current article is embedded in a special issue of European Child + Adolescent Psychiatry attempting to for the first time address training in CAP at the European and global levels. Structured information was sought from each of 38 European and neighboring countries (subsequently loosely referred to as Europe) and obtained from 31. The information was provided by a senior trainee or recently qualified specialist and their information was checked and supplemented by information from a senior child and adolescent psychiatry trainer. Results showed that there is a very wide range of provision of training in child and adolescent psychiatry in different countries in Europe. There remains very substantial diversity in training across Europe and in the degree to which it is subject to national oversight and governance. Some possible reasons for this variation are discussed and some recommendations made.

The original article has been corrected.

The ever-increasing use of the Internet among adolescents represents an emerging opportunity for researchers to gain access to larger samples, which can be queried over several years longitudinally. Among adolescents, young adolescents (ages 11 to 13 years) are of particular interest to clinicians as this is a transitional stage, during which depressive and anxiety symptoms often emerge. However, it remains unclear whether these youngest adolescents can accurately answer questions about their mental well-being using a Web-based platform. The aim of the study was to examine the accuracy of responses obtained from Web-based questionnaires by comparing Web-based with paper-and-pencil versions of depression and anxiety questionnaires. The primary outcome was the score on the depression and anxiety questionnaires under two conditions: (1) paper-and-pencil and (2) Web-based versions. Twenty-eight adolescents (aged 11-13 years, mean age 12.78 years and SD 0.78; 18 females, 64%) were randomly assigned to complete either the paper-and-pencil or the Web-based questionnaire first. Intraclass correlation coefficients (ICCs) were calculated to measure intrarater reliability. Intraclass correlation coefficients were calculated separately for depression (Children's Depression Inventory, CDI) and anxiety (Spence Children's Anxiety Scale, SCAS) questionnaires. On average, it took participants 17 minutes (SD 6) to answer 116 questions online. Intraclass correlation coefficient analysis revealed high intrarater reliability when comparing Web-based with paper-and-pencil responses for both CDI (ICC=.88; P<.001) and the SCAS (ICC=.95; P<.001). According to published criteria, both of these values are in the \"almost perfect\" category indicating the highest degree of reliability. The results of the study show an excellent reliability of Web-based assessment in 11- to 13-year-old children as compared with the standard paper-pencil assessment. Furthermore, we found that Web-based assessments with young adolescents are highly feasible, with all enrolled participants completing the Web-based form. As early adolescence is a time of remarkable social and behavioral changes, these findings open up new avenues for researchers from diverse fields who are interested in studying large samples of young adolescents over time.

The mTOR pathway is the central regulator of cell size (1). External signals from growth factors and nutrients converge on the mTORC1 multi-protein complex to modulate downstream targets, but how the different inputs are integrated and translated into specific cellular responses is incompletely understood (2-4). Deregulation of the mTOR pathway occurs in polycystic kidney disease (PKD) (5-7), where cilia (filiform sensory organelles) fail to sense urine flow because of inherited mutations in ciliary proteins (8). We therefore investigated if cilia have a role in mTOR regulation. Here, we show that ablation of cilia in transgenic mice results in enlarged cells when compared with control animals. In vitro analysis demonstrated that bending of the cilia by flow is required for mTOR downregulation and cell-size control. Surprisingly, regulation of cell size by cilia is independent of flow-induced calcium transients, or Akt. However, the tumour-suppressor protein Lkbl localises in the cilium, and flow results in increased AMPK phosphorylation at the basal body. Conversely, knockdown of Lkb1 prevents normal cell-size regulation under flow conditions. Our results demonstrate that the cilium regulates mTOR signalling and cell size, and identify the cilium-basal body compartment as a spatially restricted activation site for Lkb1 signalling.