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The incredible ULKs.

ABSTRACT: Macroautophagy (commonly abbreviated as autophagy) is an evolutionary conserved lysosome-directed vesicular trafficking pathway in eukaryotic cells that mediates the lysosomal degradation of intracellular components. The cytoplasmic cargo is initially enclosed by a specific double membrane vesicle, termed the autophagosome. By this means, autophagy either helps to remove damaged organelles, long-lived proteins and protein aggregates, or serves as a recycling mechanism for molecular building blocks. Autophagy was once invented by unicellular organisms to compensate the fluctuating external supply of nutrients. In higher eukaryotes, it is strongly enhanced under various stress conditions, such as nutrient and growth factor deprivation or DNA damage. The serine/threonine kinase Atg1 was the first identified autophagy-related gene (ATG) product in yeast. The corresponding nematode homolog UNC-51, however, has additional neuronal functions. Vertebrate genomes finally encode five closely related kinases, of which UNC-51-like kinase 1 (Ulk1) and Ulk2 are both involved in the regulation of autophagy and further neuron-specific vesicular trafficking processes. This review will mainly focus on the vertebrate Ulk1/2-Atg13-FIP200 protein complex, its function in autophagy initiation, its evolutionary descent from the yeast Atg1-Atg13-Atg17 complex, as well as the additional non-autophagic functions of its components. Since the rapid nutrient- and stress-dependent cellular responses are mainly mediated by serine/threonine phosphorylation, it will summarize our current knowledge about the relevant upstream signaling pathways and the altering phosphorylation status within this complex during autophagy induction.

SUBMITTER: Alers S

PROVIDER: S-EPMC3330011 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The incredible ULKs.

Alers Sebastian S Löffler Antje S AS Wesselborg Sebastian S Stork Björn B

Cell communication and signaling : CCS 20120313 1

Macroautophagy (commonly abbreviated as autophagy) is an evolutionary conserved lysosome-directed vesicular trafficking pathway in eukaryotic cells that mediates the lysosomal degradation of intracellular components. The cytoplasmic cargo is initially enclosed by a specific double membrane vesicle, termed the autophagosome. By this means, autophagy either helps to remove damaged organelles, long-lived proteins and protein aggregates, or serves as a recycling mechanism for molecular building bloc ...[more]

PMID: 22413737

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Project description:Infancy is an important period of life; adverse experiences during this stage can have both immediate and lifelong impacts on the child's mental health and well-being. This study evaluates the effects of offering the Incredible Years Parents and Babies (IYPB) program as a universal intervention.We conducted a pragmatic, two-arm, parallel pilot randomized controlled trial; 112 families with newborns were randomized to the IYPB program (76) or usual care (36) with a 2:1 allocation ratio. The primary outcome was parenting confidence at 20 weeks(Karitane Parenting Confidence Scale and Parental Stress Scale). Secondary outcomes include measures of parent health, parent-child relationship, infant development, parent-child activities, and network. Interviewers and data analysts were blind to allocation status. Multiple linear-regression analyses were used for evaluating the effects of the intervention.There were no intervention effects on the primary outcomes. Only one effect was detected for secondary outcomes, intervention mothers reported a significantly smaller network than control mothers (? = -0.15 [-1.85,-0.28]). When examining the lowest-functioning mothers in moderator analyses, we found that intervention mothers reported significantly higher parent stress (? = 5.33 [0.27,10.38]), lower parenting confidence (? = -2.37 [-4.45,-0.29]), and worse mental health than control mothers (? = -18.62 [-32.40,-4.84]). In contrast, the highest functioning intervention mothers reported significantly lower parent stress post-intervention (? = -6.11 [-11.07,-1.14]).Overall, we found no effects of the IYPB as a universal intervention for parents with infants. The intervention was developed to be used with groups of low functioning families and may need to be adapted to be effective with universal parent groups. The differential outcomes for the lowest and highest functioning families suggest that future research should evaluate the effects of delivering the IYPB intervention to groups of parents who have similar experiences with parenting and mental health.ClinicalTrials.gov NCT01931917.

Project description:BACKGROUND: School interventions such as the Incredible Years Classroom Dinosaur Programme targets pupil behaviour across whole classrooms, yet for some children a more intense approach is needed. The Incredible Years Therapeutic Dinosaur Programme is effective for clinically referred children by enhancing social, problem-solving skills, and peer relationship-building skills when delivered in a clinical setting in small groups. The aim of this trial is to evaluate the effectiveness of the Therapeutic Programme, delivered with small groups of children at high-risk of developing conduct disorder, delivered in schools already implementing the Classroom Programme. METHODS/DESIGN: This is a pragmatic, parallel, randomised controlled trial.Two hundred and forty children (aged 4-8 years) rated by their teacher as above the 'borderline cut-off' for concern on the Strengths and Difficulties Questionnaire, and their parents, will be recruited. Randomisation is by individual within blocks (schools); 1:1 ratio, intervention to waiting list control. Twenty schools will participate in two phases. Two teachers per school will deliver the programme to six intervention children for 2-hours/week for 18 weeks between baseline and first follow-up. The control children will receive the intervention after first follow up. Phase 1 comprises three data collection points - baseline and two follow-ups eight months apart. Phase 2 includes baseline and first follow-up.The Therapeutic Programme includes elements on; Learning school rules; understanding, identifying, and articulating feelings; problem solving; anger management; how to be friendly; how to do your best in school. Primary outcomes are; change in child social, emotional and behavioural difficulties. Secondary outcomes are; teacher and parent mental wellbeing, child academic attainment, child and teacher school attendance. Intervention delivery will be assessed for fidelity. Intention to treat analyses will be conducted. ANCOVA, effect sizes, mediator and moderator analyses will be applied to establish differences between conditions, and for whom the intervention works best for and why. DISCUSSION: This trial will provide information on the delivery and effectiveness of a child centred, school-based intervention delivered in small groups of children, at risk of developing more severe conduct problems. The effects on child behaviour in school and home environments, academic attainment, peer interactions, parent and teacher mental health will be assessed. TRIAL REGISTRATION: UK Clinical Research Network UKCRNID8615. Current Controlled Trials ISRCTN96803379.

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The incredible ULKs.

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The incredible ULKs.

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