Failure to mate enhances investment in behaviors that may promote mating reward and impairs the ability to cope with stressors via a subpopulation of Neuropeptide F receptor neurons.

Living in dynamic environments such as the social domain, where interaction with others determines the reproductive success of individuals, requires the ability to recognize opportunities to obtain natural rewards and cope with challenges that are associated with achieving them. As such, actions that promote survival and reproduction are reinforced by the brain reward system, whereas coping with the challenges associated with obtaining these rewards is mediated by stress-response pathways, the activation of which can impair health and shorten lifespan. While much research has been devoted to understanding mechanisms underlying the way by which natural rewards are processed by the reward system, less attention has been given to the consequences of failure to obtain a desirable reward. As a model system to study the impact of failure to obtain a natural reward, we used the well-established courtship suppression paradigm in Drosophila melanogaster as means to induce repeated failures to obtain sexual reward in male flies. We discovered that beyond the known reduction in courtship actions caused by interaction with non-receptive females, repeated failures to mate induce a stress response characterized by persistent motivation to obtain the sexual reward, reduced male-male social interaction, and enhanced aggression. This frustrative-like state caused by the conflict between high motivation to obtain sexual reward and the inability to fulfill their mating drive impairs the capacity of rejected males to tolerate stressors such as starvation and oxidative stress. We further show that sensitivity to starvation and enhanced social arousal is mediated by the disinhibition of a small population of neurons that express receptors for the fly homologue of neuropeptide Y. Our findings demonstrate for the first time the existence of social stress in flies and offers a framework to study mechanisms underlying the crosstalk between reward, stress, and reproduction in a simple nervous system that is highly amenable to genetic manipulation.

Decomposition of cyanobacterial light harvesting complexes: NblA-dependent role of the bilin lyase homolog NblB.

Phycobilisomes, the macromolecular light harvesting complexes of cyanobacteria are degraded under nutrient-limiting conditions. This crucial response is required to adjust light excitation to the metabolic status and avoid damage by excess excitation. Phycobilisomes are comprised of phycobiliproteins, apo-proteins that covalently bind bilin chromophores. In the cyanobacterium Synechococcus elongatus, the phycobiliproteins allophycocyanin and phycocyanin comprise the core and the rods of the phycobilisome, respectively. Previously, NblB was identified as an essential component required for phycocyanin degradation under nutrient starvation. This protein is homologous to bilin-lyases, enzymes that catalyze the covalent attachment of bilins to apo-proteins. However, the nblB-inactivated strain is not impaired in phycobiliprotein synthesis, but rather is characterized by aberrant phycocyanin degradation. Here, using a phycocyanin-deficient strain, we demonstrate that NblB is required for degradation of the core pigment, allophycocyanin. Furthermore, we show that the protein NblB is expressed under nutrient sufficient conditions, but during nitrogen starvation its level decreases about two-fold. This finding is in contrast to an additional component essential for degradation, NblA, the expression of which is highly induced under starvation. We further identified NblB residues required for phycocyanin degradation in vivo. Finally, we demonstrate phycocyanin degradation in a cell-free system, thereby providing support for the suggestion that NblB directly mediates pigment degradation by chromophore detachment. The dependence of NblB function on NblA revealed using this system, together with the results indicating presence of NblB under nutrient sufficient conditions, suggests a rapid mechanism for induction of pigment degradation, which requires only the expression of NblA.

The proteolysis adaptor, NblA, is essential for degradation of the core pigment of the cyanobacterial light-harvesting complex.

The cyanobacterial light-harvesting complex, the phycobilisome, is degraded under nutrient limitation, allowing the cell to adjust light absorbance to its metabolic capacity. This large light-harvesting antenna comprises a core complex of the pigment allophycocyanin, and rod-shaped pigment assemblies emanating from the core. NblA, a low-molecular-weight protein, is essential for degradation of the phycobilisome. NblA mutants exhibit high absorbance of rod pigments under conditions that generally elicit phycobilisome degradation, implicating NblA in degradation of these pigments. However, the vast abundance of rod pigments and the substantial overlap between the absorbance spectra of rod and core pigments has made it difficult to directly associate NblA with proteolysis of the phycobilisome core. Furthermore, lack of allophycocyanin degradation in an NblA mutant may reflect a requirement for rod degradation preceding core degradation, and does not prove direct involvement of NblA in proteolysis of the core pigment. Therefore, in this study, we used a mutant lacking phycocyanin, the rod pigment of Synechococcus elongatusPCC7942, to examine whether NblA is required for allophycocyanin degradation. We demonstrate that NblA is essential for degradation of the core complex of the phycobilisome. Furthermore, fluorescence lifetime imaging microscopy provided in situ evidence for the interaction of NblA with allophycocyanin, and indicated that NblA interacts with allophycocyanin complexes that are associated with the photosynthetic membranes. Based on these data, as well as previous observations indicating interaction of NblA with phycobilisomes attached to the photosynthetic membranes, we suggest a model for sequential phycobilisome disassembly by NblA.

The proteolysis adaptor, NblA, initiates protein pigment degradation by interacting with the cyanobacterial light-harvesting complexes.

Degradation of the cyanobacterial protein pigment complexes, the phycobilisomes, is a central acclimation response that controls light energy capture. The small protein, NblA, is essential for proteolysis of these large complexes, which may reach a molecular mass of up to 4 MDa. Interactions of NblA in vitro supported the suggestion that NblA is a proteolysis adaptor that labels the pigment proteins for degradation. The mode of operation of NblA in situ, however, remained unresolved. Particularly, it was unclear whether NblA interacts with phycobilisome proteins while part of the large complex, or alternatively interaction with NblA, necessitates dissociation of pigment subunits from the assembly. Fluorescence intensity profiles demonstrated the preferential presence of NblA::GFP (green fluorescent protein) at the photosynthetic membranes, indicating co-localization with phycobilisomes. Furthermore, fluorescence lifetime imaging microscopy provided in situ evidence for interaction of NblA with phycobilisome protein pigments. Additionally, we demonstrated the role of NblA in vivo as a proteolysis tag based on the rapid degradation of the fusion protein NblA::GFP compared with free GFP. Taken together, these observations demonstrated in vivo the role of NblA as a proteolysis adaptor. Additionally, the interaction of NblA with phycobilisomes indicates that the dissociation of protein pigment subunits from the large complex is not a prerequisite for interaction with this adaptor and, furthermore, implicates NblA in the disassembly of the protein pigment complex. Thus, we suggest that, in the case of proteolysis of the phycobilisome, the adaptor serves a dual function: undermining the complex stability and designating the dissociated pigments for degradation.

Cognitive traits in inpatient adolescents with and without prior suicide attempts and non-suicidal self-injury.

OBJECTIVE: Establishing a psychiatric diagnosis and assessing suicidal tendencies is often a challenging task particularly in the early stages of an illness. Cognitive impairments characterize different psychiatric entities, but there is no known specific cognitive deficit profile that could help the clinician in achieving the diagnostic task. This study's aim was to establish a cognitive profile and test its ability to differentiate psychiatric inpatient subgroups, in terms of suicidal risk and diagnosis. The sample constituted of 76 consecutive admissions to the psychiatric adolescent day-care unit, who were admitted for any diagnosis. Assessment included full psychiatric interview and cognitive evaluation, using the COGNISTAT test. RESULTS: Of the 76 participants, 58% reported having suicidal ideation and 29% reported a prior attempted suicide. Subjects who had a prior suicide attempt had better orientation and attention scores in the COGNISTAT. Other cognitive domains did not differentiate between groups or diagnoses. CONCLUSION: These preliminary results suggest a significant association between specific cognitive characteristics and suicidal behavior in adolescents. Those cognitive characteristics might prove clinically useful in the assessment of suicide risk. Further study is needed to establish this association and generalize the conclusion to different populations.

Transcriptome Analysis of NPFR Neurons Reveals a Connection Between Proteome Diversity and Social Behavior.

Social behaviors are mediated by the activity of highly complex neuronal networks, the function of which is shaped by their transcriptomic and proteomic content. Contemporary advances in neurogenetics, genomics, and tools for automated behavior analysis make it possible to functionally connect the transcriptome profile of candidate neurons to their role in regulating behavior. In this study we used Drosophila melanogaster to explore the molecular signature of neurons expressing receptor for neuropeptide F (NPF), the fly homolog of neuropeptide Y (NPY). By comparing the transcription profile of NPFR neurons to those of nine other populations of neurons, we discovered that NPFR neurons exhibit a unique transcriptome, enriched with receptors for various neuropeptides and neuromodulators, as well as with genes known to regulate behavioral processes, such as learning and memory. By manipulating RNA editing and protein ubiquitination programs specifically in NPFR neurons, we demonstrate that the proper expression of their unique transcriptome and proteome is required to suppress male courtship and certain features of social group interaction. Our results highlight the importance of transcriptome and proteome diversity in the regulation of complex behaviors and pave the path for future dissection of the spatiotemporal regulation of genes within highly complex tissues, such as the brain.

Early Life Experience Shapes Male Behavior and Social Networks in Drosophila.

Living in a group creates a complex and dynamic environment in which behavior of individuals is influenced by and affects the behavior of others. Although social interaction and group living are fundamental adaptations exhibited by many organisms, little is known about how prior social experience, internal states, and group composition shape behavior in groups. Here, we present an analytical framework for studying the interplay between social experience and group interaction in Drosophila melanogaster. We simplified the complexity of interactions in a group using a series of experiments in which we controlled the social experience and motivational states of individuals to compare behavioral patterns and social networks of groups under different conditions. We show that social enrichment promotes the formation of distinct group structure that is characterized by high network modularity, high inter-individual and inter-group variance, high inter-individual coordination, and stable social clusters. Using environmental and genetic manipulations, we show that visual cues and cVA-sensing neurons are necessary for the expression of social interaction and network structure in groups. Finally, we explored the formation of group behavior and structure in heterogenous groups composed of flies with distinct internal states and documented emergent structures that are beyond the sum of the individuals that constitute it. Our results demonstrate that fruit flies exhibit complex and dynamic social structures that are modulated by the experience and composition of different individuals within the group. This paves the path for using simple model organisms to dissect the neurobiology of behavior in complex social environments.

Risk factors for weight gain and metabolic syndrome in adolescents with psychiatric disorders: a historical prospective study.

OBJECTIVE: Adolescents with mental disorders are at increased risk for being overweight or obese, and subsequently developing metabolic syndrome. However, data regarding risk factors for weight gain during psychiatric hospitalization of adolescents are limited and inconsistent. The aim of this study was to investigate the sociodemographic, clinical, and pharmacological risk factors for weight gain during psychiatric treatment, in order to improve prevention of subsequent metabolic syndrome. METHODS: We conducted a historical prospective study of 146 adolescent patients (mean age 15.2±1.9 years, 52.7% males), consecutively admitted for day treatment in an adolescent day unit (length of stay 141±76 days). Anthropometric measurements and laboratory analyses of fasting glucose and lipid levels were conducted as part of the routine medical care at admission and discharge. Psychiatric diagnoses, medication histories, and sociodemographic data were obtained from the electronic medical records system. RESULTS: A significant increase in age- and gender adjusted body mass index (BMI) (i.e., z score) was observed (0.5±1.2 vs. 0.7±1.1 at admission and discharge, respectively, p<0.001). Male subjects were more prone to weight gain than females (odds ratio [OR]=3.5, 95% CI=1.2-10.3) and BMI z score at admission was inversely associated with weight gain (R (2)=0.2, p<0.0001). Surprisingly, age at admission, psychiatric diagnoses, length of stay, and number of medications were not associated with weight gain. Despite weight gain, fasting blood glucose and lipid profile did not change significantly during the study period. CONCLUSIONS: Hospitalization of adolescents in a psychiatric day unit may be associated with a significant weight gain, especially in male subjects and those with normal weight at admission. Efforts should be aimed to reduce weight gain among youth with psychiatric disorders during treatment, to avoid a subsequent metabolic syndrome.