3-Nitrotriazole-based piperazides as potent antitrypanosomal agents

publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved

Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation

publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved

TrpA1 Regulates Thermal Nociception in Drosophila

Pain is a significant medical concern and represents a major unmet clinical need. The ability to perceive and react to tissue-damaging stimuli is essential in order to maintain bodily integrity in the face of environmental danger. To prevent damage the systems that detect noxious stimuli are therefore under strict evolutionary pressure. We developed a high-throughput behavioral method to identify genes contributing to thermal nociception in the fruit fly and have reported a large-scale screen that identified the Ca2+ channel straightjacket (stj) as a conserved regulator of thermal nociception. Here we present the minimal anatomical and neuronal requirements for Drosophila to avoid noxious heat in our novel behavioral paradigm. Bioinformatics analysis of our whole genome data set revealed 23 genes implicated in Ca2+ signaling that are required for noxious heat avoidance. One of these genes, the conserved thermoreceptor TrpA1, was confirmed as a bona fide “pain” gene in both adult and larval fly nociception paradigms. The nociceptive function of TrpA1 required expression within the Drosophila nervous system, specifically within nociceptive multi-dendritic (MD) sensory neurons. Therefore, our analysis identifies the channel TRPA1 as a conserved regulator of nociception

Detection of Neural Activity in the Brains of Japanese Honeybee Workers during the Formation of a “Hot Defensive Bee Ball”

Anti-predator behaviors are essential to survival for most animals. The neural bases of such behaviors, however, remain largely unknown. Although honeybees commonly use their stingers to counterattack predators, the Japanese honeybee (Apis cerana japonica) uses a different strategy to fight against the giant hornet (Vespa mandarinia japonica). Instead of stinging the hornet, Japanese honeybees form a “hot defensive bee ball” by surrounding the hornet en masse, killing it with heat. The European honeybee (A. mellifera ligustica), on the other hand, does not exhibit this behavior, and their colonies are often destroyed by a hornet attack. In the present study, we attempted to analyze the neural basis of this behavior by mapping the active brain regions of Japanese honeybee workers during the formation of a hot defensive bee ball. First, we identified an A. cerana homolog (Acks = Apis cerana kakusei) of kakusei, an immediate early gene that we previously identified from A. mellifera, and showed that Acks has characteristics similar to kakusei and can be used to visualize active brain regions in A. cerana. Using Acks as a neural activity marker, we demonstrated that neural activity in the mushroom bodies, especially in Class II Kenyon cells, one subtype of mushroom body intrinsic neurons, and a restricted area between the dorsal lobes and the optic lobes was increased in the brains of Japanese honeybee workers involved in the formation of a hot defensive bee ball. In addition, workers exposed to 46°C heat also exhibited Acks expression patterns similar to those observed in the brains of workers involved in the formation of a hot defensive bee ball, suggesting that the neural activity observed in the brains of workers involved in the hot defensive bee ball mainly reflects thermal stimuli processing

A Climate Change Vulnerability Assessment of California's At-Risk Birds

Conservationists must develop new strategies and adapt existing tools to address the consequences of anthropogenic climate change. To support statewide climate change adaptation, we developed a framework for assessing climate change vulnerability of California's at-risk birds and integrating it into the existing California Bird Species of Special Concern list. We defined climate vulnerability as the amount of evidence that climate change will negatively impact a population. We quantified climate vulnerability by scoring sensitivity (intrinsic characteristics of an organism that make it vulnerable) and exposure (the magnitude of climate change expected) for each taxon. Using the combined sensitivity and exposure scores as an index, we ranked 358 avian taxa, and classified 128 as vulnerable to climate change. Birds associated with wetlands had the largest representation on the list relative to other habitat groups. Of the 29 state or federally listed taxa, 21 were also classified as climate vulnerable, further raising their conservation concern. Integrating climate vulnerability and California's Bird Species of Special Concern list resulted in the addition of five taxa and an increase in priority rank for ten. Our process illustrates a simple, immediate action that can be taken to inform climate change adaptation strategies for wildlife

Rapid characterisation of vegetation structure to predict refugia and climate change impacts across a global biodiversity hotspot

Identification of refugia is an increasingly important adaptation strategy in conservation planning under rapid anthropogenic climate change. Granite outcrops (GOs) provide extraordinary diversity, including a wide range of taxa, vegetation types and habitats in the Southwest Australian Floristic Region (SWAFR). However, poor characterization of GOs limits the capacity of conservation planning for refugia under climate change. A novel means for the rapid identification of potential refugia is presented, based on the assessment of local-scale environment and vegetation structure in a wider region. This approach was tested on GOs across the SWAFR. Airborne discrete return Light Detection And Ranging (LiDAR) data and Red Green and Blue (RGB) imagery were acquired. Vertical vegetation profiles were used to derive 54 structural classes. Structural vegetation types were described in three areas for supervised classification of a further 13 GOs across the region.Habitat descriptions based on 494 vegetation plots on and around these GOs were used to quantify relationships between environmental variables, ground cover and canopy height. The vegetation surrounding GOs is strongly related to structural vegetation types (Kappa = 0.8) and to its spatial context. Water gaining sites around GOs are characterized by taller and denser vegetation in all areas. The strong relationship between rainfall, soil-depth, and vegetation structure (R2 of 0.8–0.9) allowed comparisons of vegetation structure between current and future climate. Significant shifts in vegetation structural types were predicted and mapped for future climates. Water gaining areas below granite outcrops were identified as important putative refugia. A reduction in rainfall may be offset by the occurrence of deeper soil elsewhere on the outcrop. However, climate change interactions with fire and water table declines may render our conclusions conservative. The LiDAR-based mapping approach presented enables the integration of site-based biotic assessment with structural vegetation types for the rapid delineation and prioritization of key refugia

Testing the Water–Energy Theory on American Palms (Arecaceae) Using Geographically Weighted Regression

Water and energy have emerged as the best contemporary environmental correlates of broad-scale species richness patterns. A corollary hypothesis of water–energy dynamics theory is that the influence of water decreases and the influence of energy increases with absolute latitude. We report the first use of geographically weighted regression for testing this hypothesis on a continuous species richness gradient that is entirely located within the tropics and subtropics. The dataset was divided into northern and southern hemispheric portions to test whether predictor shifts are more pronounced in the less oceanic northern hemisphere. American palms (Arecaceae, n = 547 spp.), whose species richness and distributions are known to respond strongly to water and energy, were used as a model group. The ability of water and energy to explain palm species richness was quantified locally at different spatial scales and regressed on latitude. Clear latitudinal trends in agreement with water–energy dynamics theory were found, but the results did not differ qualitatively between hemispheres. Strong inherent spatial autocorrelation in local modeling results and collinearity of water and energy variables were identified as important methodological challenges. We overcame these problems by using simultaneous autoregressive models and variation partitioning. Our results show that the ability of water and energy to explain species richness changes not only across large climatic gradients spanning tropical to temperate or arctic zones but also within megathermal climates, at least for strictly tropical taxa such as palms. This finding suggests that the predictor shifts are related to gradual latitudinal changes in ambient energy (related to solar flux input) rather than to abrupt transitions at specific latitudes, such as the occurrence of frost

Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses