Using molecular phylogeny has accelerated the discovery of peptidic ligands targeted to ion channels and receptors. One clade of venomous cone snails, Asprella, appears to be significantly enriched in conantokins, antagonists of N-Methyl D-Asparate receptors (NMDARs). Here, we describe the characterization of two novel conantokins from Conus rolani, including conantokin conRl-B that has shown an unprecedented selectivity for blocking NMDARs that contain NR2B subunits. ConRl-B shares only some sequence similarity to the most studied NR2B-selective conantokin, conG. The divergence between conRl-B and conG in the second inter-Gla loop was used to design analogs for structure-activity studies; the presence of Pro10 was found to be key to the high potency of conRl-B for NR2B, whereas the ε-amino group of Lys8 contributed to discrimination in blocking NR2B- and NR2A-containing NMDARs. In contrast to previous findings from Tyr5 substitutions in other conantokins, conRl-B [L5Y] showed potencies on the four NR2 NMDA receptor subtypes that were similar to those of the native conRl-B. When delivered into the brain, conRl-B was active in suppressing seizures in the model of epilepsy in mice, consistent with NR2B-containing NMDA receptors being potential targets for antiepileptic drugs. Circular dichroism experiments confirmed that the helical conformation of conRl-B is stabilized by divalent metal ions. Given the clinical applications of NMDA antagonists, conRl-B provides a potentially important pharmacological tool for understanding the differential roles of NMDA receptor subtypes in the nervous system. This work shows the effectiveness of coupling molecular phylogeny, chemical synthesis and pharmacology for discovering new bioactive natural products.

Mast cell tumors represent the most common malignant skin tumor in the dog. This review outlines the incidence, etiology and clinical signs of mast cell tumors. Diagnostic tests, staging and treatments are also discussed.

Abstract:Periosteal osteosarcoma is an uncommon primary malignant bone tumor in dogs and humans. This type of tumor is one of the four variants of osteosarcoma. The main feature is a superficial lesion without evidence of bone marrow involvement. The treatment usually performed is limb amputation. There is insufficient data on long-term disease-free time, surgical resection or local recurrence in dogs. The present review aims to gather information on periosteal osteosarcoma in dogs

This paper brings advances in weather data collection and modeling, and developments in socioeconomic climate microsimulations to bear on the analysis of the implications of climate change (CC) in the design of public policies to combat food insecurity. It uses new downscaled predictions of future climate in 2050, derived from three Earth System Models calibrated with a new historical weather station dataset for Peru. This climate data is used in a three-stage socioeconomic microsimulation model that includes climate risk, and deals with the endogeneity of incomes and simultaneity of expected food consumption and its variability. We estimate the impact of CC on agricultural yields, and find results consistent and fully bounded within what the global simulations literature has found, with yields falling up to 13% in some regions. However, we show that these drops (and increases) in yields translate to much smaller changes in food consumption, and also surprisingly, to very minor impacts on vulnerability to food insecurity. The document explores what explains this surprising result, showing that in addition to characteristics that are specific to Peru, there are household and market mediating mechanisms that are available in all countries, which explain how changes in yields, and corresponding farm incomes have a reduced impact in vulnerability to food insecurity. Finally, in light of these findings, we explore which policies might have greater impact in reducing food insecurity in contexts of hunger prevalence.

Osteosarcoma is the most commonly reported bone tumor in dogs, typically affecting the axial and appendicular skeleton. Involvement of the paranasal sinuses and the nasal cavity is extremely rare. This report describes a 6-year-old, female, cross-breed dog presented with signs of 90 days duration and diagnosed with a mass located in the right nasal cavity. Radiography, rhinoscopy, and computed tomography findings suggested the presence of an intranasal tumor. Osteosarcoma in the nasal cavity was diagnosed based on histopathological examination and clinical and imaging findings. Survival time was 12 months from diagnosis.