Stochasticity of gene products from transcriptional pulsing

Transcriptional pulsing has been observed in both prokaryotes and eukaryotes and plays a crucial role in cell-to-cell variability of protein and mRNA numbers. An important issue is how the time constants associated with episodes of transcriptional bursting and mRNA and protein degradation rates lead to different cellular mRNA and protein distributions, starting from the transient regime leading to the steady state. We address this by deriving and then investigating the exact time-dependent solution of the master equation for a transcriptional pulsing model of mRNA distributions. We find a plethora of results. We show that, among others, bimodal and long-tailed (power-law) distributions occur in the steady state as the rate constants are varied over biologically significant time scales. Since steady state may not be reached experimentally we present results for the time evolution of the distributions. Because cellular behavior is determined by proteins, we also investigate the effect of the different mRNA distributions on the corresponding protein distributions using numerical simulations

Cell-Type Specific Transcriptomic Profiling to Dissect Mechanisms of Differential Dendritogenesis

The establishment, maintenance and modulation of cell-type specific neural architectures are critically important to the formation of functional neural networks. At the neuroanatomical level, differential patterns of dendritic arborization directly impact neural function and connectivity, however the molecular mechanisms underlying the specification of distinct dendrite morphologies remain incompletely understood. To address this question, we analyzed global gene expression from purified populations of wild-type class I and class IV Drosophila melanogaster dendritic arborization (da) sensory neurons compared to wild-type whole larval RNA using oligo DNA microarray expression profiling. Herein we present detailed experimental methods and bioinformatic anal- yses to correspond with our data reported in the Gene Expression Omnibus under accession number GSE46154. We further provide R code to facilitate data accession, perform quality controls, and conduct bioinformatic analyses relevant to this dataset. Our cell-type specific gene expression datasets provide a valuable resource for guiding further investigations designed to explore the molecular mechanisms underlying differential patterns of neuronal patterning

Pathways to mental health services for young people: a systematic review

Purpose: While early access to appropriate care can minimise the sequelae of mental illnesses, little is known about how youths come to access mental healthcare. We therefore conducted a systematic review to synthesise literature on the pathways to care of youths across a range of mental health problems. Methods: Studies were identified through searches of electronic databases (MEDLINE, PsycINFO, Embase, HealthSTAR and CINAHL), supplemented by backward and forward mapping and hand searching. We included studies on the pathways to mental healthcare of individuals aged 11–30 years. Two reviewers independently screened articles and extracted data. Results: Forty-five studies from 26 countries met eligibility criteria. The majority of these studies were from settings that offered services for the early stages of psychosis, and others included inpatient and outpatient settings targeting wide-ranging mental health problems. Generally, youths’ pathways to mental healthcare were complex, involved diverse contacts, and, sometimes, undue treatment delays. Across contexts, family/carers, general practitioners and emergency rooms featured prominently in care pathways. There was little standardization in the measurement of pathways. Conclusions: Except in psychosis, youths’ pathways to mental healthcare remain understudied. Pathways to care research may need to be reconceptualised to account for the often transient and overlapping nature of youth mental health presentations, and the possibility that what constitutes optimal care may vary. Despite these complexities, additional research, using standardized methodology, can yield a greater understanding of the help-seeking behaviours of youths and those acting on their behalf; service responses to help-seeking; and the determinants of pathways. This understanding is critical to inform ongoing initatives to transform youth mental healthcare

Our roles are not at ease: The work of engaging a youth advisory council in a mental health services delivery organization

Objectives: There is growing policy impetus for including youth voices in health services research and health system reform. This article examines the perspectives of professionals in a mental healthcare organization charged with engaging young people as advisors in service transformation. Methods: An institutional ethnography of a youth mental health services organization in Ontario, Canada, was conducted. Fieldwork consisted of twelve months of observation of meetings, interviews with youth advisors and adult service providers, with subsequent text analysis of engagement training and policy materials. The present article reports data from six adult professionals and related field observations. Results: Service providers’ efforts to engage youth were observed in three areas: a) supporting youth\u27s development as advisors, b) retaining and deepening youth participation while waiting for organizational change and c) embedding relationships between youth and adults at various levels within the system of care. This work denotes existing tensions between the values and ideals of youth engagement and the everyday demands of services delivery. Conclusion: In this setting, a fundamental dimension of this work consisted of negotiating tensions between the policy enthusiasm for engagement and its realization in a health services context. In describing these contextual challenges, we outline implications for consideration by other youth mental health services. Engagement efforts that are authentic and sustained require resources and flexibility, and leadership commitment to instil service users’ perspectives throughout multiple levels within the organization