First-time-in-human study and prediction of early bactericidal activity for GSK3036656, a potent leucyl-tRNA synthetase inhibitor for tuberculosis treatment

This first-time-in-human (FTIH) study evaluated the safety, tolerability, pharmacokinetics, and food effect of single and repeat oral doses of GSK3036656, a leucyl-tRNA synthetase inhibitor. In part A, GSK3036656 single doses of 5 mg (fed and fasted), 15 mg, and 25 mg and placebo were administered. In part B, repeat doses of 5 and 15 mg and placebo were administered for 14 days once daily. GSK3036656 showed dose-proportional increase following single-dose administration and after dosing for 14 days. The maximum concentration of drug in serum (Cmax) and area under the concentration-time curve from 0 h to the end of the dosing period (AUC0–τ) showed accumulation with repeated administration of approximately 2- to 3-fold. Pharmacokinetic parameters were not altered in the presence of food. Unchanged GSK3036656 was the only drug-related component detected in plasma and accounted for approximately 90% of drug-related material in urine. Based on total drug-related material detected in urine, the minimum absorbed doses after single (25 mg) and repeat (15 mg) dosing were 50 and 78%, respectively. Unchanged GSK3036656 represented at least 44% and 71% of the 25- and 15-mg doses, respectively. Clinical trial simulations were performed to guide dose escalation during the FTIH study and to predict the GSK3036656 dose range that produces the highest possible early bactericidal activity (EBA0–14) in the prospective phase II trial, with consideration of the predefined exposure limit. GSK3036656 was well tolerated after single and multiple doses, with no reports of serious adverse events. (This study has been registered at ClinicalTrials.gov under identifier NCT03075410.

Changes in the Geographic Distribution of the Diana Fritillary (Speyeria diana: Nymphalidae) under Forecasted Predictions of Climate Change

Climate change is predicted to alter the geographic distribution of a wide variety of taxa, including butterfly species. Research has focused primarily on high latitude species in North America, with no known studies examining responses of taxa in the southeastern United States. The Diana fritillary (Speyeria diana) has experienced a recent range retraction in that region, disappearing from lowland sites and now persisting in two phylogenetically distinct high elevation populations. These findings are consistent with the predicted effects of a warming climate on numerous taxa, including other butterfly species in North America and Europe. We used ecological niche modeling to predict future changes to the distribution of S. diana under several climate models. To evaluate how climate change might influence the geographic distribution of this butterfly, we developed ecological niche models using Maxent. We used two global circulation models, the community climate system model (CCSM) and the model for interdisciplinary research on climate (MIROC), under low and high emissions scenarios to predict the future distribution of S. diana. Models were evaluated using the receiver operating characteristics area under curve (AUC) test and the true skill statistics (TSS) (mean AUC = 0.91 ± 0.0028 SE, TSS = 0.87 ± 0.0032 SE for representative concentration pathway (RCP) = 4.5; and mean AUC = 0.87 ± 0.0031 SE, TSS = 0.84 ± 0.0032 SE for RCP = 8.5), which both indicate that the models we produced were significantly better than random (0.5). The four modeled climate scenarios resulted in an average loss of 91% of suitable habitat for S. diana by 2050. Populations in the southern Appalachian Mountains were predicted to suffer the most severe fragmentation and reduction in suitable habitat, threatening an important source of genetic diversity for the species. The geographic and genetic isolation of populations in the west suggest that those populations are equally as vulnerable to decline in the future, warranting ongoing conservation of those populations as well. Our results suggest that the Diana fritillary is under threat of decline by 2050 across its entire distribution from climate change, and is likely to be negatively affected by other human-induced factors as well

Contribution of inbreeding to extinction risk in threatened species

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Walking with Giants: Mitigating human-elephant conflict in Myanmar

Myanmar has experienced dramatic declines in its wild elephant populations over the last seven decades, dropping from as many as 10,000 wild elephants to as few as 2,000 today. The main reasons for this loss is the live capture of wild elephants for use in logging operations, and significant habitat loss and the ensuing human-elephant conflict. We are investigating the causes for human-elephant conflict (HEC) and possible mitigation methods in rural areas outside of the former capital city Yangon. We have conducted over 300 interview surveys with village residents to determine the levels and types of HEC experienced and conservation attitudes towards the wild elephant population. We have also captured and attached satellite-GPS collars to four wild male elephants to monitor their movements and behavior before, during, and after HEC. The results from our initial interview surveys demonstrate that most households experience HEC, with 38% of farmers losing over half their crops annually to elephant crop raiding. However, a majority of the interviewees favored elephant conservation (88%). We will use these results to work with the Myanmar government to focus HEC management strategies and provide recommendations to combat HEC as the development of Myanmar continues to progress

Effects of illegal grazing and invasive Lantana camara on Asian elephant habitat use

Protected areas provide some of the last refuges for Asian elephants in the wild. Managing these areas for elephants will be critical for elephant conservation. Scientists know little about elephant habitat use in Asia and how invasive species or livestock grazing influence habitat use. We studied these issues in two protected areas in Sri Lanka, Udawalawe National Park and Hurulu Eco-Park. These areas contain some of Sri Lanka's largest remaining grasslands. These grasslands are threatened by the invasive and toxic shrub, Lantana camara, and are used for illegal livestock grazing. To measure habitat use by elephants and livestock, we conducted dung surveys along over 50 km of transects stratified across grassland, scrub, and forest. We surveyed 159 vegetation plots along these transects to assess plant composition, and mapped habitat types based on satellite images. We used mixed-effect models to determine the relative importance of habitats, livestock presence, and plant associations for elephant use. Elephant presence was greatest in scrub and grassland habitats, positively associated with both livestock presence and short graminoids, and unaffected by L. camara, which was widespread but at low densities. Given the importance of these areas to elephants, we recommend a precautionary management approach that focuses on curbing both illegal grazing and the spread of L. camara

Insect-Mediated Dispersal of the Rhizobacterium Pseudomonas chlororaphis

The southern corn rootworm, Diabrotica undecimpunctata subsp. howardi, a common and mobile insect pest, was shown to transmit the rhizobacte-rium Pseudomonas chlororaphis strain L11 between corn plants. Strain L11 has been genetically modified to contain the lacZY genes from Escherichia coli. It can reach high densities on roots and invade the roots and move into the foliage. D. undecimpunctata subsp. howardi became infested with L11 as larvae while feeding on roots of seed-inoculated corn and retained the bacteria through pupation, molting to the adult stage, and emergence from the soil. Bacterial densities on or in the insects increased 100-fold after they fed again as adults on L11-infested foliage. Adults retained the bacteria for at least 2 weeks after last exposure and could transmit L11 to new plants. The likelihood of transmission decreased with time since last exposure to L11, but increased with time spent on the new plants. This research demonstrates that rhizobacteria can escape the rhizosphere by moving in or onto foliage, where they can then be acquired and transmitted by insects. This transmission route may be common among naturally occurring rhizobacteria and facilitate the dispersal of both beneficial and harmful soilborne microorganisms

A Rearing Method for Argynnis (Speyeria) diana (Lepidoptera: Nymphalidae) That Avoids Larval Diapause

We describe a rearing protocol that allowed us to raise the threatened butterfly, Argynnis diana (Nymphalidae), while bypassing the first instar overwintering diapause. We compared the survival of offspring reared under this protocol from field-collected A. diana females from North Carolina, Georgia, and Tennessee. Larvae were reared in the lab on three phylogenetically distinct species of Southern Appalachian violets (Viola sororia, V. pubescens, and V. pedata). We assessed larval survival in A. diana to the last instar, pupation, and adulthood. Males reared in captivity emerged significantly earlier than females. An ANOVA revealed no evidence of host plant preference by A. diana toward three native violet species. We suggest that restoration of A. diana habitat which promotes a wide array of larval and adult host plants, is urgently needed to conserve this imperiled species into the future

Identification of gas-phase pyrolysis products in a prescribed fire: First detections using infrared spectroscopy for naphthalene, methyl nitrite, allene, acrolein and acetaldehyde

Volatile organic compounds (VOCs) are emitted from many sources, including wildland fire. VOCs have received heightened emphasis due to such gases\u27 influential role in the atmosphere, as well as possible health effects. We have used extractive infrared (IR) spectroscopy on recent prescribed burns in longleaf pine stands and herein report the first detection of five compounds using this technique. The newly reported IR detections include naphthalene, methyl nitrite, allene, acrolein and acetaldehyde. We discuss the approaches used for detection, particularly the software methods needed to fit the analyte and multiple (interfering) spectral components within the selected spectral micro-window(s). We also discuss the method\u27s detection limits and related parameters such as spectral resolution

Una storia di Stato? Leggi memoriali, religione civile, conflitto

In the southern Bago Yoma mountain range in Myanmar, Asian elephants are being killed at a disturbing rate. This emerging crisis was identified initially through a telemetry study when 7 of 19 of collared elephants were poached within a year of being fitted with a satellite-GPS collar. Subsequent follow up of ground teams confirmed the human caused death or disappearance of at least 19 elephants, including the seven collared individuals, within a 35 km2 area in less than two years. The carcasses of 40 additional elephants were found in areas located across south-central Myanmar once systematic surveys began by our team and collaborators. In addition to the extreme rate of loss, this study documents the targeting of elephants for their skin instead of the more common ivory, an increasing trend in Myanmar. Intensive research programs focused on other conservation problems identified this issue and are now encouraging local authorities to prioritize anti-poaching efforts and improve conservation policies within the country. Myanmar represents one of the last remaining countries in Asia with substantial wildlands suitable for elephants. Increasing rates of human-elephant conflict and poaching events in this country pose a dire threat to the global population