Taste and pheromonal inputs govern the regulation of time investment for mating by sexual experience in male Drosophila melanogaster.

Males have finite resources to spend on reproduction. Thus, males rely on a 'time investment strategy' to maximize their reproductive success. For example, male Drosophila melanogaster extends their mating duration when surrounded by conditions enriched with rivals. Here we report a different form of behavioral plasticity whereby male fruit flies exhibit a shortened duration of mating when they are sexually experienced; we refer to this plasticity as 'shorter-mating-duration (SMD)'. SMD is a plastic behavior and requires sexually dimorphic taste neurons. We identified several neurons in the male foreleg and midleg that express specific sugar and pheromone receptors. Using a cost-benefit model and behavioral experiments, we further show that SMD behavior exhibits adaptive behavioral plasticity in male flies. Thus, our study delineates the molecular and cellular basis of the sensory inputs required for SMD; this represents a plastic interval timing behavior that could serve as a model system to study how multisensory inputs converge to modify interval timing behavior for improved adaptation.

Nod-like receptors are critical for gut-brain axis signalling in mice.

KEY POINTS: •Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. •Nod-like receptors regulate central and peripheral serotonergic biology. •Nod-like receptors are important for maintenance of gastrointestinal physiology. •Intestinal epithelial cell expression of Nod1 receptors regulate behaviour. ABSTRACT: Gut-brain axis signalling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addition, NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioural impairments and restored serotonin signalling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre+ Nod1f/f ), but not Nod2, increased susceptibility to stress-induced anxiety-like behaviour and cognitive impairment following exposure to stress. Together, these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for the treatment of gut-brain disorders.

The astrocyte-enriched gene deathstar plays a crucial role in the development, locomotion, and lifespan of D. melanogaster.

The Drosophila melanogaster brain is a complex organ with various cell types, orchestrating the development, physiology, and behaviors of the fly. While each cell type in Drosophila brain is known to express a unique gene set, their complete genetic profile is still unknown. Advances in the RNA sequencing techniques at single-cell resolution facilitate identifying novel cell type markers and/or re-examining the specificity of the available ones. In this study, exploiting a single-cell RNA sequencing data of Drosophila optic lobe, we categorized the cells based on their expression pattern for known markers, then the genes with enriched expression in astrocytes were identified. CG11000 was identified as a gene with a comparable expression profile to the Eaat1 gene, an astrocyte marker, in every individual cell inside the Drosophila optic lobe and midbrain, as well as in the entire Drosophila brain throughout its development. Consistent with our bioinformatics data, immunostaining of the brains dissected from transgenic adult flies showed co-expression of CG11000 with Eaat1 in a set of single cells corresponding to the astrocytes in the Drosophila brain. Physiologically, inhibiting CG11000 through RNA interference disrupted the normal development of male D. melanogaster, while having no impact on females. Expression suppression of CG11000 in adult flies led to decreased locomotion activity and also shortened lifespan specifically in astrocytes, indicating the gene's significance in astrocytes. We designated this gene as 'deathstar' due to its crucial role in maintaining the star-like shape of glial cells, astrocytes, throughout their development into adult stage.

Evidence that Relationship Quality, Social Support, and SSRI Use Do Not Account for the Shared Underlying Relationships among Symptoms of Depression, Anxiety, and Female Sexual Dysfunction.

Recent research has suggested that the shared characteristics and co-occurrence among depression, anxiety, and female sexual dysfunction may represent a shared underlying liability (i.e., the internalizing spectrum, which traditionally accounts for the overlap between depression and anxiety in psychopathology research). To date, however, whether common covariates shared by these symptom domains might instead account for the interrelationships has not been examined. Three such potential confounders include intimate relationship quality, social support, and selective serotonin reuptake inhibitor (SSRI) use. We therefore aimed to examine whether and to what extent controlling for these covariates affects the structure of an internalizing spectrum model that includes sexual problems. Participants (n = 525, mean [SD] age = 32 [11.1]) were women who participated in an online self-report survey and were in a current intimate relationship. Hierarchical exploratory structural equation models of the internalizing spectrum were compared before and after controlling for relationship quality, social support, and SSRI use and were markedly similar, indicating that the model was robust. This study provides further evidence that the internalizing spectrum can account for the relationships among depression, anxiety, and low sexual function in women, which has potential implications for diagnosis and treatment.

Attending, learning, and socioeconomic disadvantage: developmental cognitive and social neuroscience of resilience and vulnerability.

We review current findings associating socioeconomic status (SES), development of neurocognitive functions, and neurobiological pathways. A sizeable interdisciplinary literature was organized through a bifurcated developmental trajectory (BiDeT) framework, an account of the external and internal variables associated with low SES that may lead to difficulties with attention and learning, along with buffers that may protect against negative outcomes. A consistent neurocognitive finding is that low-SES children attend to information nonselectively, and engage in late filtering out of task-irrelevant information. Attentional preferences influence the development of latent inhibition (LI), an aspect of learning that involves reassigning meaningful associations to previously learned but irrelevant stimuli. LI reflects learning processes clarifying the relationship between neurobiological mechanisms related to attention and socioeconomic disadvantage during child development. Notably, changes in both selective attention and typical LI development may occur via the mesocorticolimbic dopamine (MsCL-DA) system. Chaotic environments, social isolation, and deprivation associated with low SES trigger stress responses implicating imbalances in the MsCL-DA and consolidating anxiety traits. BiDeT describes plausible interactions between socioemotional traits and low-SES environments that modify selective attention and LI, predisposing individuals to vulnerability in cognitive development and academic achievement. However, positive role models, parental style, and self-regulation training are proposed as potential promoters of resilience.

Practice patterns of canadian physiotherapists mobilizing patients with external ventricular drains.

PURPOSE: To describe current mobilization practices of Canadian physiotherapists when treating patients with external ventricular drains (EVDs). METHODS: A quantitative, descriptive, cross-sectional study design using an online questionnaire via SurveyMonkey. An email invitation and questionnaire link was distributed in March 2010 to physiotherapists currently working with this patient population in Neurosurgical Centres across Canada. RESULTS: Respondents were 25 physiotherapists (21 full-time, 2 part-time, and 2 who did not disclose work status) working in 5 different provinces who treated ≥1 patient/month with an EVD (n=9). Slightly more than half of respondents had ≤10 years' clinical physiotherapy experience (n=14); the remainder had >10 years' experience (n=11). The majority of respondents indicated that they felt comfortable mobilizing patients with EVDs (n =19) and that it was safe to do so (n=20). Clinical experience (n=23) and safety concerns (n=25) were most commonly cited as guiding practice. More experienced physiotherapists were more likely to use out-of-bed mobilization practices. Regardless of experience, the majority of physiotherapists (20/25) ranked intracranial pressure (ICP) as the most important factor and saturation of oxygen (Spo2) as the least important factor to consider before mobilization. CONCLUSIONS: Canadian physiotherapists are mobilizing patients with EVDs, and the intensity level of their mobilization practices appears to be related to their experience level. Data from the current study may be used in developing future best-practice guidelines for the mobilization of patients with EVDs.

Objectif : Décrire les méthodes actuelles de mobilisation pratiquées par les physiothérapeutes canadiens qui traitent des patients avec des drains ventriculaires externes (DVE). Méthodes   : Étude transversale descriptive quantitative basée sur un questionnaire en ligne administré via SurveyMonkey. Une invitation électronique comportant un lien vers le questionnaire a été distribuée en mars 2010 aux physiothérapeutes qui travaillent actuellement avec cette population dans les centres de neurochirurgie du Canada. Résultats : Les répondants étaient 25 physiothérapeutes travaillant (21 à temps plein, 2 à temps partiel, 2 qui n'ont pas révélé leur statut) dans cinq provinces différentes qui ont traité ≥1 patient/mois au moyen de DVE (n=9). Un peu plus de la moitié des répondants comptaient ≤10 ans d'expérience de la physiothérapie clinique (n=14); les autres en comptaient >10 (n=11). La majorité des répondants ont indiqué se sentir à l'aise de mobiliser cette population (n=19) et qu'il était sécuritaire de le faire (n=20). L'expérience clinique (n=23) et les préoccupations en matière de sécurité (n=25) ont été les facteurs mentionnés le plus souvent comme guide de pratique. La plupart des physiothérapeutes chevronnés étaient plus susceptibles d'utiliser des méthodes de mobilisation hors du lit. Sans égard à l'expérience, la majorité des physiothérapeutes (20/25) a classé la pression intracrânienne (PIC) comme facteur le plus important et la saturation en oxygène (Spo2) comme facteur le moins important dont il faut tenir compte avant la mobilisation. Conclusions : Les physiothérapeutes canadiens mobilisent les patients en utilisant le DVE et l'intensité de leurs méthodes de mobilisation semble liée à leur expérience. Les données tirées de l'étude en cours pourront servir à établir de futurs guides de pratique clinique sur la mobilité des patients au moyen de DVE.

Spatial control of cell-mediated degradation to regulate vasculogenesis and angiogenesis in hyaluronan hydrogels.

Matrix remodeling is crucial for neovascularization, however its utilization to control this process in synthetic biomaterials has been limited. Here, we utilized hyaluronic acid (HA) hydrogels to spatially control cellular remodeling during vascular network formation. Specifically, we exploited a secondary radical polymerization to alter the ability of cells to degrade the hydrogel and utilized it to create spatial patterning using light initiation. We first demonstrated the ability of the hydrogel to either support or inhibit in vitro vasculogenesis of endothelial colony-forming cells (ECFCs) or angiogenesis from ex ovo chorioallantoic membranes. We showed that vascular tube branching and sprouting, which required matrix metalloproteinases (MMPs)-dependent remodeling, could be achieved in hydrogels formed by primary addition-crosslinking only. Although ECFCs expressed higher levels of MMPs in the hydrogels with the secondary radical crosslinking, the generated kinetic chains disabled cell-mediated remodeling and therefore vascular formation was arrested at the vacuole and lumen stage. We then patterned hydrogels to have regions that either permitted or inhibited cell-mediated degradation during in vitro vasculogenesis or angiogenesis. Our ability to control degradation cues that regulate vascular tube formation is important for the study of vascular biology and the application of synthetic biomaterials in tissue regeneration.