Modelling Cancer Metastasis in Drosophila melanogaster.

Cancer metastasis, the process by which tumour cells spread throughout the body and form secondary tumours at distant sites, is the leading cause of cancer-related deaths. The metastatic cascade is a highly complex process encompassing initial dissemination from the primary tumour, travel through the blood stream or lymphatic system, and the colonisation of distant organs. However, the factors enabling cells to survive this stressful process and adapt to new microenvironments are not fully characterised. Drosophila have proven a powerful system in which to study this process, despite important caveats such as their open circulatory system and lack of adaptive immune system. Historically, larvae have been used to model cancer due to the presence of pools of proliferating cells in which tumours can be induced, and transplanting these larval tumours into adult hosts has enabled tumour growth to be monitored over longer periods. More recently, thanks largely to the discovery that there are stem cells in the adult midgut, adult models have been developed. We focus this review on the development of different Drosophila models of metastasis and how they have contributed to our understanding of important factors determining metastatic potential, including signalling pathways, the immune system and the microenvironment.

Identification and Monitoring of Nucleotide Repeat Expansions Using Southern Blotting in Drosophila Models of C9orf72 Motor Neuron Disease and Frontotemporal Dementia.

Repeat expansion diseases, including fragile X syndrome, Huntington's disease, and C9orf72-related motor neuron disease and frontotemporal dementia, are a group of disorders associated with polymorphic expansions of tandem repeat nucleotide sequences. These expansions are highly repetitive and often hundreds to thousands of repeats in length, making accurate identification and determination of repeat length via PCR or sequencing challenging. Here we describe a protocol for monitoring repeat length in Drosophila models carrying 1,000 repeat C9orf72-related dipeptide repeat transgenes using Southern blotting. This protocol has been used regularly to check the length of these lines for over 100 generations with robust and repeatable results and can be implemented for monitoring any repeat expansion in Drosophila.

The acquisitive-conservative axis of leaf trait variation emerges even in homogeneous environments.

BACKGROUND AND AIMS: The acquisitive-conservative axis of plant ecological strategies results in a pattern of leaf trait covariation that captures the balance between leaf construction costs and plant growth potential. Studies evaluating trait covariation within species are scarcer, and have mostly dealt with variation in response to environmental gradients. Little work has been published on intraspecific patterns of leaf trait covariation in the absence of strong environmental variation. METHODS: We analysed covariation of four leaf functional traits [specific leaf area (SLA) leaf dry matter content (LDMC), force to tear (Ft) and leaf nitrogen content (Nm)] in six Poaceae and four Fabaceae species common in the dry Chaco forest of Central Argentina, growing in the field and in a common garden. We compared intraspecific covariation patterns (slopes, correlation and effect size) of leaf functional traits with global interspecific covariation patterns. Additionally, we checked for possible climatic and edaphic factors that could affect the intraspecific covariation pattern. KEY RESULTS: We found negative correlations for the LDMC-SLA, Ft-SLA, LDMC-Nm and Ft-Nm trait pairs. This intraspecific covariation pattern found both in the field and in the common garden and not explained by climatic or edaphic variation in the field follows the expected acquisitive-conservative axis. At the same time, we found quantitative differences in slopes among different species, and between these intraspecific patterns and the interspecific ones. Many of these differences seem to be idiosyncratic, but some appear consistent among species (e.g. all the intraspecific LDMC-SLA and LDMC-Nm slopes tend to be shallower than the global pattern). CONCLUSIONS: Our study indicates that the acquisitive-conservative leaf functional trait covariation pattern occurs at the intraspecific level even in the absence of relevant environmental variation in the field. This suggests a high degree of variation-covariation in leaf functional traits not driven by environmental variables.

Modeling C9orf72-Related Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Drosophila.

An intronic hexanucleotide (GGGGCC) expansion in the C9orf72 gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In the decade following its discovery, much progress has been made in enhancing our understanding of how it precipitates disease. Both loss of function caused by reduced C9orf72 transcript levels, and gain of function mechanisms, triggered by the production of repetitive sense and antisense RNA and dipeptide repeat proteins, are thought to contribute to the toxicity. Drosophila models, with their unrivaled genetic tractability and short lifespan, have played a key role in developing our understanding of C9orf72-related FTD/ALS. There is no C9orf72 homolog in fly, and although this precludes investigations into loss of function toxicity, it is useful for elucidating mechanisms underpinning gain of function toxicity. To date there are a range of Drosophila C9orf72 models, encompassing different aspects of gain of function toxicity. In addition to pure repeat transgenes, which produce both repeat RNA and dipeptide repeat proteins (DPRs), RNA only models and DPR models have been generated to unpick the individual contributions of RNA and each dipeptide repeat protein to C9orf72 toxicity. In this review, we discuss how Drosophila models have shaped our understanding of C9orf72 gain of function toxicity, and address opportunities to utilize these models for further research.

Tropical understory herbaceous community responds more strongly to hurricane disturbance than to experimental warming.

The effects of climate change on tropical forests may have global consequences due to the forests' high biodiversity and major role in the global carbon cycle. In this study, we document the effects of experimental warming on the abundance and composition of a tropical forest floor herbaceous plant community in the Luquillo Experimental Forest, Puerto Rico. This study was conducted within Tropical Responses to Altered Climate Experiment (TRACE) plots, which use infrared heaters under free-air, open-field conditions, to warm understory vegetation and soils + 4°C above nearby control plots. Hurricanes Irma and María damaged the heating infrastructure in the second year of warming, therefore, the study included one pretreatment year, one year of warming, and one year of hurricane response with no warming. We measured percent leaf cover of individual herbaceous species, fern population dynamics, and species richness and diversity within three warmed and three control plots. Results showed that one year of experimental warming did not significantly affect the cover of individual herbaceous species, fern population dynamics, species richness, or species diversity. In contrast, herbaceous cover increased from 20% to 70%, bare ground decreased from 70% to 6%, and species composition shifted pre to posthurricane. The negligible effects of warming may have been due to the short duration of the warming treatment or an understory that is somewhat resistant to higher temperatures. Our results suggest that climate extremes that are predicted to increase with climate change, such as hurricanes and droughts, may cause more abrupt changes in tropical forest understories than longer-term sustained warming.

Co-expression of C9orf72 related dipeptide-repeats over 1000 repeat units reveals age- and combination-specific phenotypic profiles in Drosophila.

A large intronic hexanucleotide repeat expansion (GGGGCC) within the C9orf72 (C9orf72-SMCR8 Complex Subunit) locus is the most prevalent genetic cause of both Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND). In patients this expansion is typically hundreds to thousands of repeat units in length. Repeat associated non-AUG translation of the expansion leads to the formation of toxic, pathological Dipeptide-Repeat Proteins (DPRs). To date there remains a lack of in vivo models expressing C9orf72 related DPRs with a repeat length of more than a few hundred repeats. As such our understanding of how physiologically relevant repeat length DPRs effect the nervous system in an ageing in vivo system remains limited. In this study we generated Drosophila models expressing DPRs over 1000 repeat units in length, a known pathological length in humans. Using these models, we demonstrate each DPR exhibits a unique, age-dependent, phenotypic and pathological profile. Furthermore, we show co-expression of specific DPR combinations leads to distinct, age-dependent, phenotypes not observed through expression of single DPRs. We propose these models represent a unique, in vivo, tool for dissecting the molecular mechanisms implicated in disease pathology, opening up new avenues in the study of both MND and FTD.

Psychiatric hospital treatment of children and adolescents in New South Wales, Australia: 12-year trends.

BACKGROUND: It is preferable that children and adolescents requiring in-patient care for mental health problems are managed in age-appropriate facilities. To achieve this, nine specialist Child and Adolescent Mental Health Services (CAMHS) in-patient units have been commissioned in New South Wales (NSW) since 2002. AIMS: To examine trends in child and adolescent in-patient admissions since the opening of these CAMHS units. METHOD: Analysis of separation data for under 18-year-olds to CAMHS, adult mental health and paediatric units for the period 2002 to 2013 in NSW, comparing districts with and without specialist CAMHS units. RESULTS: Separations from CAMHS, adult and paediatric units rose with time, but there was no interaction between time and health district type (with/without CAMHS unit). Five of eight health districts experienced increased separations of under 18-year-olds from adult units in the year of opening a CAMHS unit. Separations from related paediatric units increased in three of seven health districts. CONCLUSIONS: Opening CAMHS units may be followed by a temporary increase in separations of young people from adult units, but it does not influence the flow of patients to non-CAMHS facilities in the longer term. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Multinational experiences in reducing and preventing the use of restraint and seclusion.

Restraint and seclusion (R/S) have been used in many countries and across service sectors for centuries. With the recent and increasing recognition of the harm associated with these procedures, efforts have been made to reduce and prevent R/S. Following a scathing media exposé in 1998 and congressional scrutiny, the United States began a national effort to reduce and prevent R/S use. With federal impetus and funding, an evidence-based practice, the Six Core Strategies to Prevent Conflict, Violence and the Use of Seclusion and Restraint, was developed. This model was widely and successfully implemented in a number of U.S. states and is being adopted by other countries, including Finland, Australia, and the United Kingdom. Recently, the first cluster randomized controlled study of the Six Core Strategies in Finland provided the first evidence-based data of the safety and effectiveness of a coercion prevention methodology. Preliminary findings of some of the international efforts are discussed. Reduction in R/S use and other positive outcomes are also reported.