Functional correlates of positional and gender-specific renal asymmetry in drosophila

Accordingly, the physical asymmetry of the tubules in the body cavity is directly adaptive. Now that the detailed machinery underlying internal asymmetry is starting to be delineated, our work invites the investigation, not just of tissues in isolation, but in the context of their unique physical locations and milieux

Structural Insights from Recent CB1 X-Ray Crystal Structures

Over the past 2 years, X-ray crystal structures of the antagonist- and agonist-bound CB1 receptor have been reported. Such structures are expected to accelerate progress in the understanding of CB1 and should provide an exceptional starting point for structure-based drug discovery. This chapter examines the consistency of these X-ray structures with the CB1 experimental literature, including mutation, NMR and covalent labeling studies. These comparisons reveal discrepancies between this literature and the TMH1-2-3 region of each CB1 crystal structure. The chapter also examines crystal packing issues with each X-ray structure and shows that the discrepancies with the experimental literature can be attributed to crystal packing problems that force the N-terminus deep in the binding pocket of the two inactive state structures and force TMH2 to bend at G2.53/S2.54 and invade the binding pocket in the activated state structure. Revision is advisable before these structures are used for structure-based drug discovery

Up and away: ontogenic transference as a pathway for aerial dispersal of microplastics

Microplastics (MPs) are ubiquitous pollutants found in marine, freshwater and terrestrial ecosystems. With so many MPs in aquatic systems it is inevitable that they will be ingested by aquatic organisms, and be transferred up through the food chain. However, to date, no study has considered whether MPs can be transmitted by means of ontogenic transference i.e. between life stages that utilise different habitats. Here, we determine whether fluorescent polystyrene beads could transfer between Culex mosquito life stages and, particularly, could move into the flying adult stage. We show for the first time that MPs can be transferred ontogenically from a feeding (larva) into a non-feeding (pupa) life stage and subsequently into the adult terrestrial life stage. However, transference is dependent on particle size, with smaller 2 µm MPs transferring readily into pupae and adult stages, whilst 15 µm MPs transferred at a significantly reduced rate. Microplastics appear to accumulate in the Malpighian tubule renal excretion system. The transfer of MPs to the adults represents a potential aerial pathway to contamination of new environments. Thus, any organism that feeds on terrestrial life phases of freshwater insects could be impacted by MPs found in aquatic ecosystems

Latent Space Model for Multi-Modal Social Data

With the emergence of social networking services, researchers enjoy the increasing availability of large-scale heterogenous datasets capturing online user interactions and behaviors. Traditional analysis of techno-social systems data has focused mainly on describing either the dynamics of social interactions, or the attributes and behaviors of the users. However, overwhelming empirical evidence suggests that the two dimensions affect one another, and therefore they should be jointly modeled and analyzed in a multi-modal framework. The benefits of such an approach include the ability to build better predictive models, leveraging social network information as well as user behavioral signals. To this purpose, here we propose the Constrained Latent Space Model (CLSM), a generalized framework that combines Mixed Membership Stochastic Blockmodels (MMSB) and Latent Dirichlet Allocation (LDA) incorporating a constraint that forces the latent space to concurrently describe the multiple data modalities. We derive an efficient inference algorithm based on Variational Expectation Maximization that has a computational cost linear in the size of the network, thus making it feasible to analyze massive social datasets. We validate the proposed framework on two problems: prediction of social interactions from user attributes and behaviors, and behavior prediction exploiting network information. We perform experiments with a variety of multi-modal social systems, spanning location-based social networks (Gowalla), social media services (Instagram, Orkut), e-commerce and review sites (Amazon, Ciao), and finally citation networks (Cora). The results indicate significant improvement in prediction accuracy over state of the art methods, and demonstrate the flexibility of the proposed approach for addressing a variety of different learning problems commonly occurring with multi-modal social data.Comment: 12 pages, 7 figures, 2 table

Renal neuroendocrine control of desiccation and cold tolerance by Drosophila suzukii

Background: Neuropeptides are central to the regulation of physiological, and behavioural processes in insects, directly impacting cold and desiccation survival. However, little is known about the control mechanisms governing these responses in D. suzukii. The close phylogenetic relationship of D. suzukii with D. melanogaster allows, through genomic and functional studies, an insight into the mechanisms directing stress tolerance in D. suzukii. Results: Capa, Leucokinin, DH44 and DH31 neuropeptides demonstrate a high level of conservation between D. suzukii and D. melanogaster with respect to peptide sequences, neuronal expression, receptor localisation, and diuretic function in the Malpighian tubules. Despite D. suzukii’s ability to populate cold environments, they proved sensitive to both cold and desiccation. Furthermore, in D. suzukii, Capa acts as a desiccation-and cold stress-responsive gene, while DH44 gene expression is increased only after desiccation exposure, and the LK gene after nonlethal cold stress recovery. Conclusion: This study provides a comparative investigation into stress tolerance mediation by neuroendocrine signalling in two Drosophila species, providing evidence that similar signalling pathways control fluid secretion in the Malpighian tubules. Identifying processes governing specific environmental stresses affecting D. suzukii could lead to the development of targeted integrated management strategies to control insect pest populations

Singular Short Range Potentials in the J-Matrix Approach

We use the tools of the J-matrix method to evaluate the S-matrix and then deduce the bound and resonance states energies for singular screened Coulomb potentials, both analytic and piecewise differentiable. The J-matrix approach allows us to absorb the 1/r singularity of the potential in the reference Hamiltonian, which is then handled analytically. The calculation is performed using an infinite square integrable basis that supports a tridiagonal matrix representation for the reference Hamiltonian. The remaining part of the potential, which is bound and regular everywhere, is treated by an efficient numerical scheme in a suitable basis using Gauss quadrature approximation. To exhibit the power of our approach we have considered the most delicate region close to the bound-unbound transition and compared our results favorably with available numerical data.Comment: 14 pages, 5 tables, 2 figure

Mapping an atlas of tissue-specific drosophila melanogaster metabolomes by high resolution mass spectrometry

Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes

Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis

<p>Abstract</p> <p>Background</p> <p>Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear.</p> <p>Presentation of the hypothesis</p> <p>Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis.</p> <p>Testing and implications of the hypothesis</p> <p>Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.</p

Peak strain magnitudes and rates in the tibia exceed greatly those in the skull: An in vivo study in a human subject

Bone mass and architecture are the result of a genetically determined baseline structure, modified by the effect of internal hormonal/biochemical regulators and the effect of mechanical loading. Bone strain is thought to drive a feedback mechanism to regulate bone formation and resorption to maintain an optimal, but not excessive mass and organisation of material at each skeletal location. Because every site in the skeleton has different functions, we have measured bone strains induced by physiological and more unusual activities, at two different sites, the tibia and cranium of a young human male in vivo. During the most vigorous activities, tibial strains were shown to exceed 0.2%, when ground reaction exceeded 5 times body weight. However in the skull the highest strains recorded were during heading a heavy medicine/exercise ball where parietal strains were up to 0.0192%. Interestingly parietal strains during more physiological activities were much lower, often below 0.01%. Strains during biting were not dependent upon bite force, but could be induced by facial contortions of similar appearance without contact between the teeth. Rates of strain change in the two sites were also very different, where peak tibial strain rate exceeded rate in the parietal bone by more than 5 fold. These findings suggest that the skull and tibia are subject to quite different regulatory influences, as strains that would be normal in the human skull would be likely to lead to profound bone loss by disuse in the long bones

Near real-time input to a propagation model for nowcasting of HF communications with aircraft on polar routes

There is a need for improved techniques for nowcasting and forecasting (over several hours) HF propagation at northerly latitudes to support airlines operating over the increasingly popular trans-polar routes. In this paper the assimilation of real-time measurements into a propagation model developed by the authors is described, including ionosonde measurements and Total Electron Content (TEC) measurements to define the main parameters of the ionosphere. The effects of D-region absorption in the polar cap and auroral regions are integrated with the model through satellite measurements of the flux of energetic solar protons (>1 MeV) and the X-ray flux in the 0.1-0.8 nm band, and ground-based magnetometer measurements which form the Kp and Dst indices of geomagnetic activity. The model incorporates various features (e.g. convecting patches of enhanced plasma density) of the polar ionosphere that are, in particular, responsible for off-great circle propagation and lead to propagation at times and frequencies not expected from on-great circle propagation alone. The model development is supported by the collection of HF propagation measurements over several paths within the polar cap, crossing the auroral oval, and along the mid-latitude trough