A gut-derived hormone suppresses sugar appetite and regulates food choice in Drosophila.

Animals must adapt their dietary choices to meet their nutritional needs. How these needs are detected and translated into nutrient-specific appetites that drive food-choice behaviours is poorly understood. Here we show that enteroendocrine cells of the adult female Drosophila midgut sense nutrients and in response release neuropeptide F (NPF), which is an ortholog of mammalian neuropeptide Y-family gut-brain hormones. Gut-derived NPF acts on glucagon-like adipokinetic hormone (AKH) signalling to induce sugar satiety and increase consumption of protein-rich food, and on adipose tissue to promote storage of ingested nutrients. Suppression of NPF-mediated gut signalling leads to overconsumption of dietary sugar while simultaneously decreasing intake of protein-rich yeast. Furthermore, gut-derived NPF has a female-specific function in promoting consumption of protein-containing food in mated females. Together, our findings suggest that gut NPF-to-AKH signalling modulates specific appetites and regulates food choice to ensure homeostatic consumption of nutrients, providing insight into the hormonal mechanisms that underlie nutrient-specific hungers.

Canalized gene expression during development mediates caste differentiation in ants.

Ant colonies are higher-level organisms consisting of specialized reproductive and non-reproductive individuals that differentiate early in development, similar to germ-soma segregation in bilateral Metazoa. Analogous to diverging cell lines, developmental differentiation of individual ants has often been considered in epigenetic terms but the sets of genes that determine caste phenotypes throughout larval and pupal development remain unknown. Here, we reconstruct the individual developmental trajectories of two ant species, Monomorium pharaonis and Acromyrmex echinatior, after obtaining >1,400 whole-genome transcriptomes. Using a new backward prediction algorithm, we show that caste phenotypes can be accurately predicted by genome-wide transcriptome profiling. We find that caste differentiation is increasingly canalized from early development onwards, particularly in germline individuals (gynes/queens) and that the juvenile hormone signalling pathway plays a key role in this process by regulating body mass divergence between castes. We quantified gene-specific canalization levels and found that canalized genes with gyne/queen-biased expression were enriched for ovary and wing functions while canalized genes with worker-biased expression were enriched in brain and behavioural functions. Suppression in gyne larvae of Freja, a highly canalized gyne-biased ovary gene, disturbed pupal development by inducing non-adaptive intermediate phenotypes between gynes and workers. Our results are consistent with natural selection actively maintaining canalized caste phenotypes while securing robustness in the life cycle ontogeny of ant colonies.

Insulin signaling couples growth and early maturation to cholesterol intake in Drosophila.

Nutrition is one of the most important influences on growth and the timing of maturational transitions including mammalian puberty and insect metamorphosis. Childhood obesity is associated with precocious puberty, but the assessment mechanism that links body fat to early maturation is unknown. During development, the intake of nutrients promotes signaling through insulin-like systems that govern the growth of cells and tissues and also regulates the timely production of the steroid hormones that initiate the juvenile-adult transition. We show here that the dietary lipid cholesterol, which is required as a component of cell membranes and as a substrate for steroid biosynthesis, also governs body growth and maturation in Drosophila via promoting the expression and release of insulin-like peptides. This nutritional input acts via the nutrient sensor TOR, which is regulated by the Niemann-Pick-type-C 1 (Npc1) cholesterol transporter, in the glia of the blood-brain barrier and cells of the adipose tissue to remotely drive systemic insulin signaling and body growth. Furthermore, increasing intracellular cholesterol levels in the steroid-producing prothoracic gland strongly promotes endoreduplication, leading to an accelerated attainment of a nutritional checkpoint that normally ensures that animals do not initiate maturation prematurely. These findings, therefore, show that a Npc1-TOR signaling system couples the sensing of the lipid cholesterol with cellular and systemic growth control and maturational timing, which may help explain both the link between cholesterol and cancer as well as the connection between body fat (obesity) and early puberty.

The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress.

The intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the gut-derived hormones affecting metabolic and behavioral responses are poorly defined. Here we show that the endocrine cells of the Drosophila gut sense nutrient stress through a mechanism that involves the TOR pathway and in response secrete the peptide hormone allatostatin C, a Drosophila somatostatin homolog. Gut-derived allatostatin C induces secretion of glucagon-like adipokinetic hormone to coordinate food intake and energy mobilization. Loss of gut Allatostatin C or its receptor in the adipokinetic-hormone-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.

Regulation of Body Size and Growth Control.

The control of body and organ growth is essential for the development of adults with proper size and proportions, which is important for survival and reproduction. In animals, adult body size is determined by the rate and duration of juvenile growth, which are influenced by the environment. In nutrient-scarce environments in which more time is needed for growth, the juvenile growth period can be extended by delaying maturation, whereas juvenile development is rapidly completed in nutrient-rich conditions. This flexibility requires the integration of environmental cues with developmental signals that govern internal checkpoints to ensure that maturation does not begin until sufficient tissue growth has occurred to reach a proper adult size. The Target of Rapamycin (TOR) pathway is the primary cell-autonomous nutrient sensor, while circulating hormones such as steroids and insulin-like growth factors are the main systemic regulators of growth and maturation in animals. We discuss recent findings in Drosophila melanogaster showing that cell-autonomous environment and growth-sensing mechanisms, involving TOR and other growth-regulatory pathways, that converge on insulin and steroid relay centers are responsible for adjusting systemic growth, and development, in response to external and internal conditions. In addition to this, proper organ growth is also monitored and coordinated with whole-body growth and the timing of maturation through modulation of steroid signaling. This coordination involves interorgan communication mediated by Drosophila insulin-like peptide 8 in response to tissue growth status. Together, these multiple nutritional and developmental cues feed into neuroendocrine hubs controlling insulin and steroid signaling, serving as checkpoints at which developmental progression toward maturation can be delayed. This review focuses on these mechanisms by which external and internal conditions can modulate developmental growth and ensure proper adult body size, and highlights the conserved architecture of this system, which has made Drosophila a prime model for understanding the coordination of growth and maturation in animals.

Designing an Information and Communications Technology Tool With and for Victims of Violence and Their Case Managers in San Francisco: Human-Centered Design Study.

BACKGROUND: Violence is a public health problem. Hospital-based violence intervention programs such as the San Francisco Wraparound Project (WAP) have been shown to reduce future violent injury. The WAP model employs culturally competent case managers who recruit and enroll violently injured patients as clients. Client acceptance of the WAP intervention is variable, and program success depends on streamlined, timely communication and access to resources. High rates of smartphone usage in populations who are at risk for violent reinjury create an opportunity to design a tailored information and communications technology (ICT) tool to support hospital-based violence intervention programs. OBJECTIVE: Current evidence shows that ICT tools developed in the health care space may not be successful in engaging vulnerable populations. The goal of this study was to use human-centered design methodology to identify the unique communication needs of the clients and case managers at WAP to design a mobile ICT. METHODS: We conducted 15 semi-structured interviews with users: clients, their friends and families, case managers, and other stakeholders in violence intervention and prevention. We used a human-centered design and general inductive approach to thematic analysis to identify themes in the qualitative data, which were extrapolated to insight statements and then reframed into design opportunities. Wireframes of potential mobile ICT app screens were developed to depict these opportunities. RESULTS: Thematic analysis revealed four main insights that were characterized by the opposing needs of our users. (1) A successful relationship is both professional and personal. Clients need this around the clock, but case managers can only support this while on the clock. (2) Communications need to feel personal, but they do not always need to be personalized. (3) Healing is a journey of skill development and lifestyle changes that must be acknowledged, monitored, and rewarded. (4) Social networks need to provide peer support for healing rather than peer pressure to propagate violence. These insights resulted in the following associated design opportunities: (1) Maximize personal connection while controlling access, (2) allow case managers to personalize automated client interactions, (3) hold clients accountable to progress and reward achievements, and (4) build a connected, yet confidential community. CONCLUSIONS: Human-centered design enabled us to identify unique insights and design opportunities that may inform the design of a novel and tailored mobile ICT tool for the WAP community.

Ecdysone-dependent feedback regulation of prothoracicotropic hormone controls the timing of developmental maturation.

The activation of a neuroendocrine system that induces a surge in steroid production is a conserved initiator of the juvenile-to-adult transition in many animals. The trigger for maturation is the secretion of brain-derived neuropeptides, yet the mechanisms controlling the timely onset of this event remain ill-defined. Here, we show that a regulatory feedback circuit controlling the Drosophila neuropeptide Prothoracicotropic hormone (PTTH) triggers maturation onset. We identify the Ecdysone Receptor (EcR) in the PTTH-expressing neurons (PTTHn) as a regulator of developmental maturation onset. Loss of EcR in these PTTHn impairs PTTH signaling, which delays maturation. We find that the steroid ecdysone dose-dependently affects Ptth transcription, promoting its expression at lower concentrations and inhibiting it at higher concentrations. Our findings indicate the existence of a feedback circuit in which rising ecdysone levels trigger, via EcR activity in the PTTHn, the PTTH surge that generates the maturation-inducing ecdysone peak toward the end of larval development. Because steroid feedback is also known to control the vertebrate maturation-inducing hypothalamic-pituitary-gonadal axis, our findings suggest an overall conservation of the feedback-regulatory neuroendocrine circuitry that controls the timing of maturation initiation.

"You don't want anyone who hasn't been through anything telling you what to do, because how do they know?": Qualitative analysis of case managers in a hospital-based violence intervention program.

STATEMENT OF PURPOSE: Intentional violent injury is a leading cause of disability and death among young adults in the United States. Hospital-based violence intervention programs (HVIPs), which strive to prevent re-injury through intensive case management, have emerged as a successful and cost-effective strategy to address this issue. Despite the importance of strong therapeutic relationships between clients and their case managers, specific case manager behaviors and attributes that drive the formation of these relationships have not been elucidated. METHODS: A qualitative analysis with a modified grounded theory approach was conducted to gain insight into what clients perceive to be crucial to the formation of a strong client-case manager relationship. Twenty-four semi-structured interviews were conducted with prior clients of our hospital's HVIP. The interviews were analyzed using constant comparison method for recurrent themes. RESULTS: Several key themes emerged from the interviews. Clients emphasized that their case managers must: 1) understand and relate to their sociocultural contexts, 2) navigate the initial in-hospital meeting to successfully create connection, 3) exhibit true compassion and care, 4) serve as role models, 5) act as portals of opportunity, and 6) engender mutual respect and pride. CONCLUSIONS: This study identifies key behaviors of case managers that facilitate the formation of strong therapeutic relationships at the different stages of client recovery. This study's findings emphasize the importance of case managers being culturally aligned with and embedded in their clients' communities. This work can provide a roadmap for case managers to form optimally effective relationships with clients.

Metabolism and growth adaptation to environmental conditions in Drosophila.

Organisms adapt to changing environments by adjusting their development, metabolism, and behavior to improve their chances of survival and reproduction. To achieve such flexibility, organisms must be able to sense and respond to changes in external environmental conditions and their internal state. Metabolic adaptation in response to altered nutrient availability is key to maintaining energy homeostasis and sustaining developmental growth. Furthermore, environmental variables exert major influences on growth and final adult body size in animals. This developmental plasticity depends on adaptive responses to internal state and external cues that are essential for developmental processes. Genetic studies have shown that the fruit fly Drosophila, similarly to mammals, regulates its metabolism, growth, and behavior in response to the environment through several key hormones including insulin, peptides with glucagon-like function, and steroid hormones. Here we review emerging evidence showing that various environmental cues and internal conditions are sensed in different organs that, via inter-organ communication, relay information to neuroendocrine centers that control insulin and steroid signaling. This review focuses on endocrine regulation of development, metabolism, and behavior in Drosophila, highlighting recent advances in the role of the neuroendocrine system as a signaling hub that integrates environmental inputs and drives adaptive responses.

Analysis of genes within the schizophrenia-linked 22q11.2 deletion identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep control.

The human 22q11.2 chromosomal deletion is one of the strongest identified genetic risk factors for schizophrenia. Although the deletion spans a number of known genes, the contribution of each of these to the 22q11.2 deletion syndrome (DS) is not known. To investigate the effect of individual genes within this interval on the pathophysiology associated with the deletion, we analyzed their role in sleep, a behavior affected in virtually all psychiatric disorders, including the 22q11.2 DS. We identified the gene LZTR1 (night owl, nowl) as a regulator of night-time sleep in Drosophila. In humans, LZTR1 has been associated with Ras-dependent neurological diseases also caused by Neurofibromin-1 (Nf1) deficiency. We show that Nf1 loss leads to a night-time sleep phenotype nearly identical to that of nowl loss and that nowl negatively regulates Ras and interacts with Nf1 in sleep regulation. Furthermore, nowl is required for metabolic homeostasis, suggesting that LZTR1 may contribute to the genetic susceptibility to obesity associated with the 22q11.2 DS. Knockdown of nowl or Nf1 in GABA-responsive sleep-promoting neurons elicits the sleep phenotype, and this defect can be rescued by increased GABAA receptor signaling, indicating that Nowl regulates sleep through modulation of GABA signaling. Our results suggest that nowl/LZTR1 may be a conserved regulator of GABA signaling important for normal sleep that contributes to the 22q11.2 DS.

Autophagy regulates steroid production by mediating cholesterol trafficking in endocrine cells.

Steroid hormones are made from cholesterol and are essential for many developmental processes and disease conditions. The production of these hormones is nutrient dependent and tightly controlled by mechanisms that involve delivery of the precursor molecule cholesterol stored in lipid droplets (LDs). Recent studies have implicated macroautophagy/autophagy, a process regulated by nutrition, in the degradation of LDs and the mobilization of stored lipids. We recently identified an autophagy-dependent mechanism that regulates steroid production via effects on cholesterol trafficking. Through gain- and loss-of-function studies in Drosophila, we found that essential autophagy-related (Atg) genes are required in steroidogenic cells for normal steroid production. Inhibition of autophagy in these cells by knockdown of Atg genes causes strong accumulation of cholesterol in LDs and reduces steroid production, resembling effects seen in some lipid-storage disorders and steroid-dependent cancer conditions. This autophagy-dependent steroid hormone regulation (ASHR) process is regulated by the wts-yki/Warts-Yorkie tumor-suppressor pathway downstream of nutrition, coupling nutrient intake with steroid-dependent developmental growth. This mechanism potentially contributes to the development of certain cancers and lipid-storage disorders and thus may be of great therapeutic relevance.

A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion.

Organisms adapt their metabolism and growth to the availability of nutrients and oxygen, which are essential for development, yet the mechanisms by which this adaptation occurs are not fully understood. Here we describe an RNAi-based body-size screen in Drosophila to identify such mechanisms. Among the strongest hits is the fibroblast growth factor receptor homolog breathless necessary for proper development of the tracheal airway system. Breathless deficiency results in tissue hypoxia, sensed primarily in this context by the fat tissue through HIF-1a prolyl hydroxylase (Hph). The fat relays its hypoxic status through release of one or more HIF-1a-dependent humoral factors that inhibit insulin secretion from the brain, thereby restricting systemic growth. Independently of HIF-1a, Hph is also required for nutrient-dependent Target-of-rapamycin (Tor) activation. Our findings show that the fat tissue acts as the primary sensor of nutrient and oxygen levels, directing adaptation of organismal metabolism and growth to environmental conditions.

Autophagy-Mediated Cholesterol Trafficking Controls Steroid Production.

Steroid hormones are important signaling molecules that regulate growth and drive the development of many cancers. These factors act as long-range signals that systemically regulate the growth of the entire organism, whereas the Hippo/Warts tumor-suppressor pathway acts locally to limit organ growth. We show here that autophagy, a pathway that mediates the degradation of cellular components, also controls steroid production. This process is regulated by Warts (in mammals, LATS1/2) signaling, via its effector microRNA bantam, in response to nutrients. Specifically, autophagy-mediated mobilization and trafficking of the steroid precursor cholesterol from intracellular stores controls the production of the Drosophila steroid ecdysone. Furthermore, we also show that bantam regulates this process via the ecdysone receptor and Tor signaling, identifying pathways through which bantam regulates autophagy and growth. The Warts pathway thus promotes nutrient-dependent systemic growth during development by autophagy-dependent steroid hormone regulation (ASHR). These findings uncover an autophagic trafficking mechanism that regulates steroid production.

Modulation of Drosophila post-feeding physiology and behavior by the neuropeptide leucokinin.

Behavior and physiology are orchestrated by neuropeptides acting as central neuromodulators and circulating hormones. An outstanding question is how these neuropeptides function to coordinate complex and competing behaviors. In Drosophila, the neuropeptide leucokinin (LK) modulates diverse functions, but mechanisms underlying these complex interactions remain poorly understood. As a first step towards understanding these mechanisms, we delineated LK circuitry that governs various aspects of post-feeding physiology and behavior. We found that impaired LK signaling in Lk and Lk receptor (Lkr) mutants affects diverse but coordinated processes, including regulation of stress, water homeostasis, feeding, locomotor activity, and metabolic rate. Next, we sought to define the populations of LK neurons that contribute to the different aspects of this physiology. We find that the calcium activity in abdominal ganglia LK neurons (ABLKs), but not in the two sets of brain neurons, increases specifically following water consumption, suggesting that ABLKs regulate water homeostasis and its associated physiology. To identify targets of LK peptide, we mapped the distribution of Lkr expression, mined a brain single-cell transcriptome dataset for genes coexpressed with Lkr, and identified synaptic partners of LK neurons. Lkr expression in the brain insulin-producing cells (IPCs), gut, renal tubules and chemosensory cells, correlates well with regulatory roles detected in the Lk and Lkr mutants. Furthermore, these mutants and flies with targeted knockdown of Lkr in IPCs displayed altered expression of insulin-like peptides (DILPs) and transcripts in IPCs and increased starvation resistance. Thus, some effects of LK signaling appear to occur via DILP action. Collectively, our data suggest that the three sets of LK neurons have different targets, but modulate the establishment of post-prandial homeostasis by regulating distinct physiological processes and behaviors such as diuresis, metabolism, organismal activity and insulin signaling. These findings provide a platform for investigating feeding-related neuroendocrine regulation of vital behavior and physiology.

Midgut-derived neuropeptide F controls germline stem cell proliferation in a mating-dependent manner.

Stem cell maintenance is established by neighboring niche cells that promote stem cell self-renewal. However, it is poorly understood how stem cell activity is regulated by systemic, tissue-extrinsic signals in response to environmental cues and changes in physiological status. Here, we show that neuropeptide F (NPF) signaling plays an important role in the pathway regulating mating-induced germline stem cell (GSC) proliferation in the fruit fly Drosophila melanogaster. NPF expressed in enteroendocrine cells (EECs) of the midgut is released in response to the seminal-fluid protein sex peptide (SP) upon mating. This midgut-derived NPF controls mating-induced GSC proliferation via ovarian NPF receptor (NPFR) activity, which modulates bone morphogenetic protein (BMP) signaling levels in GSCs. Our study provides a molecular mechanism that describes how a gut-derived systemic factor couples stem cell behavior to physiological status, such as mating, through interorgan communication.

Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster males.

Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them. Olfactory conditioning experiments showed that winning is perceived as rewarding, while losing is perceived as aversive. Moreover, the effect of chronic fighting experience generalized to other behaviors, such as gap-crossing and courtship. We propose that in response to repeatedly winning or losing aggressive encounters, male flies form an internal state that displays persistence and generalization; fight outcomes can also have positive or negative valence. Furthermore, we show that the activities of the PPL1-γ1pedc dopaminergic neuron and the MBON-γ1pedc>α/ß mushroom body output neuron are required for aversion to an olfactory cue associated with losing fights.

Warts Signaling Controls Organ and Body Growth through Regulation of Ecdysone.

Coordination of growth between individual organs and the whole body is essential during development to produce adults with appropriate size and proportions [1, 2]. How local organ-intrinsic signals and nutrient-dependent systemic factors are integrated to generate correctly proportioned organisms under different environmental conditions is poorly understood. In Drosophila, Hippo/Warts signaling functions intrinsically to regulate tissue growth and organ size [3, 4], whereas systemic growth is controlled via antagonistic interactions of the steroid hormone ecdysone and nutrient-dependent insulin/insulin-like growth factor (IGF) (insulin) signaling [2, 5]. The interplay between insulin and ecdysone signaling regulates systemic growth and controls organismal size. Here, we show that Warts (Wts; LATS1/2) signaling regulates systemic growth in Drosophila by activating basal ecdysone production, which negatively regulates body growth. Further, we provide evidence that Wts mediates effects of insulin and the neuropeptide prothoracicotropic hormone (PTTH) on regulation of ecdysone production through Yorkie (Yki; YAP/TAZ) and the microRNA bantam (ban). Thus, Wts couples insulin signaling with ecdysone production to adjust systemic growth in response to nutritional conditions during development. Inhibition of Wts activity in the ecdysone-producing cells non-autonomously slows the growth of the developing imaginal-disc tissues while simultaneously leading to overgrowth of the animal. This indicates that ecdysone, while restricting overall body growth, is limiting for growth of certain organs. Our data show that, in addition to its well-known intrinsic role in restricting organ growth, Wts/Yki/ban signaling also controls growth systemically by regulating ecdysone production, a mechanism that we propose controls growth between tissues and organismal size in response to nutrient availability.

Synaptic transmission parallels neuromodulation in a central food-intake circuit.

NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the Drosophila larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.

A decade of hospital-based violence intervention: Benefits and shortcomings.

INTRODUCTION: Initial analyses of hospital-based violence intervention programs (VIPs) have demonstrated decreased violent injury recidivism. Long-term VIP performance has not been assessed. Violence intervention program quality improvement requires evaluation to identify shortcomings and client subpopulations warranting additional resources. We evaluated our case manager-based VIPs to identify modifiable risk factors that most impact violent injury recidivism and determine subpopulations that need modification of targeted services. METHODS: Data on demographic variables, socioeconomic factors, needs, and injury recidivism from 2005 to 2014 were collected through our VIP database. Possible client needs included housing, education, employment, court advocacy, driver's license obtainment, and "other." Case managers assessed needs as "not needed," "identified (unmet)," and "met." χ And nonparametric tests were used to identify factors associated with recidivism reduction. RESULTS: Over the 10-year period, 466 clients were enrolled in VIP. During the program period, the violent reinjury rate was 4%, as compared with a historical control of 8% from 2000 to 2004. Women had lower rates of reinjury than men (3% vs 13%, respectively, p = 0.023). Blacks had the lowest recidivism (2%, p < 0.0001), whereas a higher rate (11%) was observed among Latinos. Although a minority of clients (5%), 100% of white clients were reinjured. Mental health services (51%), victim-of-crime compensation (48%), employment (36%), and housing (30%) were the most frequently identified needs. Expressing the need for education was significantly associated with likelihood of reinjury, an effect that was completely reversed when the need was met. CONCLUSION: This evaluation of a VIP demonstrates sustained recidivism reduction and success in addressing client needs from a traditionally underserved population. Efforts to identify and address root causes of Latino and white client reinjury should be increased. Violence intervention program prioritization of housing needs may reduce future reinjury. This study demonstrating sustainable success underscores the importance of increased integration of VIP into trauma centers nationally. LEVEL OF EVIDENCE: Therapeutic study, level III.

Drosophila larval to pupal switch under nutrient stress requires IP3R/Ca(2+) signalling in glutamatergic interneurons.

Neuronal circuits are known to integrate nutritional information, but the identity of the circuit components is not completely understood. Amino acids are a class of nutrients that are vital for the growth and function of an organism. Here, we report a neuronal circuit that allows Drosophila larvae to overcome amino acid deprivation and pupariate. We find that nutrient stress is sensed by the class IV multidendritic cholinergic neurons. Through live calcium imaging experiments, we show that these cholinergic stimuli are conveyed to glutamatergic neurons in the ventral ganglion through mAChR. We further show that IP3R-dependent calcium transients in the glutamatergic neurons convey this signal to downstream medial neurosecretory cells (mNSCs). The circuit ultimately converges at the ring gland and regulates expression of ecdysteroid biosynthetic genes. Activity in this circuit is thus likely to be an adaptation that provides a layer of regulation to help surpass nutritional stress during development.