Optomechanical trampoline resonators

Quantum Matter and Optic

Habituation Learning Is a Widely Affected Mechanism in Drosophila Models of Intellectual Disability and Autism Spectrum Disorders

BACKGROUND: Although habituation is one of the most ancient and fundamental forms of learning, its regulators and its relevance for human disease are poorly understood. METHODS: We manipulated the orthologs of 286 genes implicated in intellectual disability (ID) with or without comorbid autism spectrum disorder (ASD) specifically in Drosophila neurons, and we tested these models in light-off jump habituation. We dissected neuronal substrates underlying the identified habituation deficits and integrated genotype-phenotype annotations, gene ontologies, and interaction networks to determine the clinical features and molecular processes that are associated with habituation deficits. RESULTS: We identified >100 genes required for habituation learning. For 93 of these genes, a role in habituation learning was previously unknown. These genes characterize ID disorders with macrocephaly and/or overgrowth and comorbid ASD. Moreover, individuals with ASD from the Simons Simplex Collection carrying damaging de novo mutations in these genes exhibit increased aberrant behaviors associated with inappropriate, stereotypic speech. At the molecular level, ID genes required for normal habituation are enriched in synaptic function and converge on Ras/mitogen-activated protein kinase (Ras/MAPK) signaling. Both increased Ras/MAPK signaling in gamma-aminobutyric acidergic (GABAergic) neurons and decreased Ras/MAPK signaling in cholinergic neurons specifically inhibit the adaptive habituation response. CONCLUSIONS: Our work supports the relevance of habituation learning to ASD, identifies an unprecedented number of novel habituation players, supports an emerging role for inhibitory neurons in habituation, and reveals an opposing, circuit-level-based mechanism for Ras/MAPK signaling. These findings establish habituation as a possible, widely applicable functional readout and target for pharmacologic intervention in ID/ASD

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination 'as a public health problem' when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models' predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020

Intrasexual competition and throat color evolution in female three-spined sticklebacks

Interest in the evolution of female ornaments has been growing but explaining their presence remains a challenge for many animal taxa. Although female ornaments may be sexually selected via male choice, they can also function in female–female competition. Here, we studied a stream-resident population of three-spined sticklebacks (Gasterosteus aculeatus), in which females possess male-typical red throat coloration, and a nearby anadromous population that lacks such coloration and is thought to possess ancestral character states for most traits in this species complex. We asked first whether there were population-level differences in agonism that might be associated with the evolution of female ornaments. We tested if the derived population possessing some red-throated females exhibited relatively higher levels and clearer patterns of within-population aggression and dominance in dyadic trials and more frequent behavioral dominance over individuals of the population lacking red females. Second, to address the relationship between the derived coloration and female–female competition, we tested whether red-throated stream females were more aggressive and dominant toward dull-throated stream females in both dyadic and socially complex contexts. We found that clear dominance was established more often in pairs of stream females, and stream females were more often dominant in stream-anadromous dyads. However, we found no clear evidence that the red throat coloration was directly linked to a female competitive advantage within the stream population, suggesting alternative untested signaling or perhaps nonadaptive functions. Our study represents the first evaluation of the potential relationship between a male-typical nuptial trait and intrasexual competition in female three-spined sticklebacks

Data from: Conspicuous female ornamentation and tests of male mate preference in threespine sticklebacks (Gasterosteus aculeatus)

Sexual selection drives the evolution of exaggerated male ornaments in many animal species. Female ornamentation is now acknowledged also to be common but is generally less well understood. One example is the recently documented red female throat coloration in some threespine stickleback (Gasterosteus aculeatus) populations. Although female sticklebacks often exhibit a preference for red male throat coloration, the possibility of sexual selection on female coloration has been little studied. Using sequential and simultaneous mate choice trials, we examined male mate preferences for female throat color, as well as pelvic spine color and standard length, using wild-captured threespine sticklebacks from the Little Campbell River, British Columbia. In a multivariate analysis, we found no evidence for a population-level mate preference in males, suggesting the absence of directional sexual selection on these traits arising from male mate choice. Significant variation was detected among males in their preference functions, but this appeared to arise from differences in their mean responsiveness across mating trials and not from variation in the strength (i.e., slope) of their preference, suggesting the absence of individual-level preferences as well. When presented with conspecific intruder males, male response decreased as intruder red throat coloration increased, suggesting that males can discriminate color and other aspects of phenotype in our experiment and that males may use these traits in intrasexual interactions. The results presented here are the first to explicitly address male preference for female throat color in threespine sticklebacks

The Role of Nitric oxide in IL-1β-mediated Dysfunction of Rodent Islets of Langerhans: Implications for the Function of Intrahepatic Islet Grafts

Products of inflammation, such as interleukin-1β (IL-1β) and nitric oxide (NO), may impair early function of pancreatic islet grafts. In in vitro studies, freshly isolated rat islets of Langerhans cultured for 24 hr (10 islets/well) in the presence of 20 IU/ml of IL-1β released 57% less insulin (mean ± S.E. of 151±61 μU) on the average than control (385±89 μU) cultures (n=9, P=0.08). Nitrite levels in the medium (indirect measure of NO) after islets were cultured for a 24-hr period were nearly 3-fold greater in IL-1β-exposed islets than control islet cultures (5.8±1.0 μM vs. 2.2±0.3 μM, P=0.03). Production of nitrite by islet cells in the presence of IL-1β was inhibited in cultures also containing 2 mM L-NG-monomethyl-Arginine (L- NMMA) (3.4±0.4 μM, n=9, P=0.09 vs. control). When islets were maintained for 1 hr in 30 mg/dl glucose followed by 300 mg/dl for 1 hr, insulin release (stimulated) increased 6-fold (from 7±2 to 45±11 μU) in control cultures but only 3-fold (from 4±2 to 12±4 μU) in IL-1β-exposed cultures (n=9, P=.01). Addition of 2 mM L-NMMA to islet cultures in the presence of IL-1β (20 IU/ml) (n=9) restored insulin release to normal (from 6±2 to 38±9 μU, P≥0.6), suggesting that NO mediates the inhibitory effect of IL-1β on beta- cell function. In in vivo studies, rats with streptozotocin-induced diabetes (blood glucose \u3e400 mg/dl) received minimal (750 hand-picked islets) intraportal beta cell mass isografts with (n=5) or without (n=9) treatment with 100 mg/7 days of L-NMMA from 3 days before transplantation to 4 days after transplantation (POD -3 to +4). L-NMMA-treated rats became euglycemic (glucose \u3c200 mg/dl) earlier than nontreated rats (mean ± SD of 6.4±2.5 vs. 16.7±4.7 days posttransplant, P=0.001). These findings support the hypothesis that NO is a mediator of beta cell dysfunction after intraportal transplantation of freshly isolated islets of Langerhans

The Role of Nitric oxide in IL-1β-mediated Dysfunction of Rodent Islets of Langerhans: Implications for the Function of Intrahepatic Islet Grafts

Products of inflammation, such as interleukin-1β (IL-1β) and nitric oxide (NO), may impair early function of pancreatic islet grafts. In in vitro studies, freshly isolated rat islets of Langerhans cultured for 24 hr (10 islets/well) in the presence of 20 IU/ml of IL-1β released 57% less insulin (mean ± S.E. of 151±61 μU) on the average than control (385±89 μU) cultures (n=9, P=0.08). Nitrite levels in the medium (indirect measure of NO) after islets were cultured for a 24-hr period were nearly 3-fold greater in IL-1β-exposed islets than control islet cultures (5.8±1.0 μM vs. 2.2±0.3 μM, P=0.03). Production of nitrite by islet cells in the presence of IL-1β was inhibited in cultures also containing 2 mM L-NG-monomethyl-Arginine (L- NMMA) (3.4±0.4 μM, n=9, P=0.09 vs. control). When islets were maintained for 1 hr in 30 mg/dl glucose followed by 300 mg/dl for 1 hr, insulin release (stimulated) increased 6-fold (from 7±2 to 45±11 μU) in control cultures but only 3-fold (from 4±2 to 12±4 μU) in IL-1β-exposed cultures (n=9, P=.01). Addition of 2 mM L-NMMA to islet cultures in the presence of IL-1β (20 IU/ml) (n=9) restored insulin release to normal (from 6±2 to 38±9 μU, P≥0.6), suggesting that NO mediates the inhibitory effect of IL-1β on beta- cell function. In in vivo studies, rats with streptozotocin-induced diabetes (blood glucose \u3e400 mg/dl) received minimal (750 hand-picked islets) intraportal beta cell mass isografts with (n=5) or without (n=9) treatment with 100 mg/7 days of L-NMMA from 3 days before transplantation to 4 days after transplantation (POD -3 to +4). L-NMMA-treated rats became euglycemic (glucose \u3c200 mg/dl) earlier than nontreated rats (mean ± SD of 6.4±2.5 vs. 16.7±4.7 days posttransplant, P=0.001). These findings support the hypothesis that NO is a mediator of beta cell dysfunction after intraportal transplantation of freshly isolated islets of Langerhans

Expression of Intrahepatic Inducible Nitric oxide Synthetase mRNA Correlates With Production of Nitric Oxide During Intraportal Isogeneic and Allogeneic Rat Islet Transplantation

Intrahepatic NO production is related to the islet mass transplanted. Nitric oxide production is higher in recipients of allogeneic rather than syngeneic islets. In addition, in allogeneic recipients a possible second peak of NO production was observed at 120 hours corresponding to the time of cellular rejection of the islet grafts (P = .22 vs 96 hours). Finally, the time to rejection of Wistar rat donor islets transplanted into Lewis rat diabetic recipients treated with NMA was not affected. However, inhibiting NO production in the minimal islet transplant model decreased the time to islet function, it does not affect the time to clinical rejection in recipients of a high number of allogeneic islet, which functions immediately. High-level NO has been shown to inhibit T-cell activation in vitro, and thus decreasing the levels by administrating NMA may accentuate the rejection response, canceling out the beneficial effect that might otherwise have occurred on islet function. Further experiments are required to clarify these issues