The ethics of uncertainty for data subjects

Modern health data practices come with many practical uncertainties. In this paper, I argue that data subjects’ trust in the institutions and organizations that control their data, and their ability to know their own moral obligations in relation to their data, are undermined by significant uncertainties regarding the what, how, and who of mass data collection and analysis. I conclude by considering how proposals for managing situations of high uncertainty might be applied to this problem. These emphasize increasing organizational flexibility, knowledge, and capacity, and reducing hazard

A framework for integrated environmental health impact assessment of systemic risks

Traditional methods of risk assessment have provided good service in support of policy, mainly in relation to standard setting and regulation of hazardous chemicals or practices. In recent years, however, it has become apparent that many of the risks facing society are systemic in nature – complex risks, set within wider social, economic and environmental contexts. Reflecting this, policy-making too has become more wide-ranging in scope, more collaborative and more precautionary in approach. In order to inform such policies, more integrated methods of assessment are needed. Based on work undertaken in two large EU-funded projects (INTARESE and HEIMTSA), this paper reviews the range of approaches to assessment now in used, proposes a framework for integrated environmental health impact assessment (both as a basis for bringing together and choosing between different methods of assessment, and extending these to more complex problems), and discusses some of the challenges involved in conducting integrated assessments to support policy

Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body

In humans and many other animals, memory consolidation occurs through multiple temporal phases and usually involves more than one neuroanatomical brain system. Genetic dissection of Pavlovian olfactory learning in Drosophila melanogaster has revealed multiple memory phases, but the predominant view holds that all memory phases occur in mushroom body neurons. Here, we demonstrate an acute requirement for NMDA receptors (NMDARs) outside of the mushroom body during long-term memory (LTM) consolidation. Targeted dsRNA-mediated silencing of Nmdar1 and Nmdar2 (also known as dNR1 or dNR2, respectively) in cholinergic R4m-subtype large-field neurons of the ellipsoid body specifically disrupted LTM consolidation, but not retrieval. Similar silencing of functional NMDARs in the mushroom body disrupted an earlier memory phase, leaving LTM intact. Our results clearly establish an anatomical site outside of the mushroom body involved with LTM consolidation, thus revealing both a distributed brain system subserving olfactory memory formation and the existence of a system-level memory consolidation in Drosophila

Moving towards a population health approach to the primary prevention of common mental disorders

There is a need for the development of effective universal preventive approaches to the common mental disorders, depression and anxiety, at a population level. Poor diet, physical inactivity and smoking have long been recognized as key contributors to the high prevalence noncommunicable diseases. However, there are now an increasing number of studies suggesting that the same modifiable lifestyle behaviors are also risk factors for common mental disorders. In this paper we point to the emerging data regarding lifestyle risk factors for common mental disorders, with a particular focus on and critique of the newest evidence regarding diet quality. On the basis of this most recent evidence, we consequently argue for the inclusion of depression and anxiety in the ranks of the high prevalence noncommunicable diseases influenced by habitual lifestyle practices. We believe that it is both feasible and timely to begin to develop effective, sustainable, population-level prevention initiatives for the common mental illnesses that build on the established and developing approaches to the noncommunicable somatic diseases.<br /

A Functional Misexpression Screen Uncovers a Role for Enabled in Progressive Neurodegeneration

Drosophila is a well-established model to study the molecular basis of neurodegenerative diseases. We carried out a misexpression screen to identify genes involved in neurodegeneration examining locomotor behavior in young and aged flies. We hypothesized that a progressive loss of rhythmic activity could reveal novel genes involved in neurodegenerative mechanisms. One of the interesting candidates showing progressive arrhythmicity has reduced enabled (ena) levels. ena down-regulation gave rise to progressive vacuolization in specific regions of the adult brain. Abnormal staining of pre-synaptic markers such as cystein string protein (CSP) suggest that axonal transport could underlie the neurodegeneration observed in the mutant. Reduced ena levels correlated with increased apoptosis, which could be rescued in the presence of p35, a general Caspase inhibitor. Thus, this mutant recapitulates two important features of human neurodegenerative diseases, i.e., vulnerability of certain neuronal populations and progressive degeneration, offering a unique scenario in which to unravel the specific mechanisms in an easily tractable organism

dyschronic, a Drosophila Homolog of a Deaf-Blindness Gene, Regulates Circadian Output and Slowpoke Channels

Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc). dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause of deaf-blindness in humans. Whirlin and other Usher proteins are expressed in the mammalian central nervous system, yet their function in the CNS has not been investigated. We show that DYSC is expressed in major neuronal tracts and regulates expression of the calcium-activated potassium channel SLOWPOKE (SLO), an ion channel also required in the circadian output pathway. SLO and DYSC are co-localized in the brain and control each other's expression post-transcriptionally. Co-immunoprecipitation experiments demonstrate they form a complex, suggesting they regulate each other through protein–protein interaction. Furthermore, electrophysiological recordings of neurons in the adult brain show that SLO-dependent currents are greatly reduced in dysc mutants. Our work identifies a Drosophila homolog of a deaf-blindness gene as a new component of the circadian output pathway and an important regulator of ion channel expression, and suggests novel roles for Usher proteins in the mammalian nervous system

Revisiting in vivo staining with alizarin red S - a valuable approach to analyse zebrafish skeletal mineralization during development and regeneration

Background The correct evaluation of mineralization is fundamental for the study of skeletal development, maintenance, and regeneration. Current methods to visualize mineralized tissue in zebrafish rely on: 1) fixed specimens; 2) radiographic and μCT techniques, that are ultimately limited in resolution; or 3) vital stains with fluorochromes that are indistinguishable from the signal of green fluorescent protein (GFP)-labelled cells. Alizarin compounds, either in the form of alizarin red S (ARS) or alizarin complexone (ALC), have long been used to stain the mineralized skeleton in fixed specimens from all vertebrate groups. Recent works have used ARS vital staining in zebrafish and medaka, yet not based on consistent protocols. There is a fundamental concern on whether ARS vital staining, achieved by adding ARS to the water, can affect bone formation in juvenile and adult zebrafish, as ARS has been shown to inhibit skeletal growth and mineralization in mammals. Results Here we present a protocol for vital staining of mineralized structures in zebrafish with a low ARS concentration that does not affect bone mineralization, even after repetitive ARS staining events, as confirmed by careful imaging under fluorescent light. Early and late stages of bone development are equally unaffected by this vital staining protocol. From all tested concentrations, 0.01 % ARS yielded correct detection of bone calcium deposits without inducing additional stress to fish. Conclusions The proposed ARS vital staining protocol can be combined with GFP fluorescence associated with skeletal tissues and thus represents a powerful tool for in vivo monitoring of mineralized structures. We provide examples from wild type and transgenic GFP-expressing zebrafish, for endoskeletal development and dermal fin ray regeneration

Mapping Peptidergic Cells in Drosophila: Where DIMM Fits In

The bHLH transcription factor DIMMED has been associated with the differentiation of peptidergic cells in Drosophila. However, whether all Drosophila peptidergic cells express DIMM, and the extent to which all DIMM cells are peptidergic, have not been determined. To address these issues, we have mapped DIMM expression in the central nervous system (CNS) and periphery in the late larval stage Drosophila. At 100 hr after egg-laying, DIMM immunosignals are largely congruent with a dimm-promoter reporter (c929-GAL4) and they present a stereotyped pattern of 306 CNS cells and 52 peripheral cells. We assigned positional values for all DIMM CNS cells with respect to reference gene expression patterns, or to patterns of secondary neuroblast lineages. We could assign provisional peptide identities to 68% of DIMM-expressing CNS cells (207/306) and to 73% of DIMM-expressing peripheral cells (38/52) using a panel of 24 markers for Drosophila neuropeptide genes. Furthermore, we found that DIMM co-expression was a prevalent feature within single neuropeptide marker expression patterns. Of the 24 CNS neuropeptide gene patterns we studied, six patterns are >90% DIMM-positive, while 16 of 22 patterns are >40% DIMM-positive. Thus most or all DIMM cells in Drosophila appear to be peptidergic, and many but not all peptidergic cells express DIMM. The co-incidence of DIMM-expression among peptidergic cells is best explained by a hypothesis that DIMM promotes a specific neurosecretory phenotype we term LEAP. LEAP denotes Large cells that display Episodic release of Amidated Peptides

Gene expression patterns associated with blood-feeding in the malaria mosquito Anopheles gambiae

BACKGROUND: Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of the blood meal and compared their expression to transcript levels in mosquitoes with access only to a sugar solution. RESULTS: In blood-fed mosquitoes, 413 unique transcripts, approximately 25% of the total, were expressed at least two-fold above or below their levels in the sugar-fed mosquitoes, at one or more time points. These differentially expressed gene products were clustered using k-means clustering into Early Genes, Middle Genes, and Late Genes, containing 144, 130, and 139 unique transcripts, respectively. Several genes from each group were analyzed by quantitative real-time PCR in order to validate the microarray results. CONCLUSION: The expression patterns and annotation of the genes in these three groups (Early, Middle, and Late genes) are discussed in the context of female mosquitoes' physiological responses to blood feeding, including blood digestion, peritrophic matrix formation, egg development, and immunity