Movement drives population dynamics of one of the most mobile ungulates on Earth: Insights from a mechanistic model.

Long-distance movements are hypothesized to positively influence population size and stability of mobile species. We tested this hypothesis with a novel modeling approach in which moving herbivores interact with the environment created by a dynamic global vegetation model using highly mobile Mongolian gazelles in the eastern Mongolian grasslands as a case study. Gazelle population dynamics were modeled from 1901 to 2018 under two scenarios, one allowing free movement and one restricting movement. Gazelles were 2.2 times more abundant when they could move freely and were extirpated in 71% of the study area when mobility was restricted. Mobility resulted in greater population increases during times of abundant forage and smaller population decreases during drought. Reduced thermoregulatory costs associated with climate change, combined with an increase in vegetation biomass, increased gazelle abundance. Since high abundances often resulted in overgrazing and, thus, extirpation when movement was restricted, mobility had an important role in maintaining higher densities. The novel modeling approach shows how accounting for not just herbivore but also plant ecophysiology can improve our understanding of the population dynamics of highly mobile herbivores, in particular when examining the effects of habitat and climate change. Since the model simulates herbivores based on general physiological mechanisms that apply across large herbivores and the vegetation model can be applied globally, it is possible to adapt the model to other large-herbivore systems.

Body size and digestive system shape resource selection by ungulates: A cross-taxa test of the forage maturation hypothesis.

The forage maturation hypothesis (FMH) states that energy intake for ungulates is maximised when forage biomass is at intermediate levels. Nevertheless, metabolic allometry and different digestive systems suggest that resource selection should vary across ungulate species. By combining GPS relocations with remotely sensed data on forage characteristics and surface water, we quantified the effect of body size and digestive system in determining movements of 30 populations of hindgut fermenters (equids) and ruminants across biomes. Selection for intermediate forage biomass was negatively related to body size, regardless of digestive system. Selection for proximity to surface water was stronger for equids relative to ruminants, regardless of body size. To be more generalisable, we suggest that the FMH explicitly incorporate contingencies in body size and digestive system, with small-bodied ruminants selecting more strongly for potential energy intake, and hindgut fermenters selecting more strongly for surface water.

ERO1-PDI Redox Signaling in Health and Disease.

Significance: Protein disulfide isomerase (PDI) and endoplasmic reticulum oxidoreductase 1 (ERO1) are crucial for oxidative protein folding in the endoplasmic reticulum (ER). These enzymes are frequently overexpressed and secreted, and they contribute to the pathology of neurodegenerative, cardiovascular, and metabolic diseases. Recent Advances: Tissue-specific knockout mouse models and pharmacologic inhibitors have been developed to advance our understanding of the cell-specific functions of PDI and ERO1. In addition to their roles in protecting cells from the unfolded protein response and oxidative stress, recent studies have revealed that PDI and ERO1 also function outside of the cells. Critical Issues: Despite the well-known contributions of PDI and ERO1 to specific disease pathology, the detailed molecular and cellular mechanisms underlying these activities remain to be elucidated. Further, although PDI and ERO1 inhibitors have been identified, the results from previous studies require careful evaluation, as many of these agents are not selective and may have significant cytotoxicity. Future Directions: The functions of PDI and ERO1 in the ER have been extensively studied. Additional studies will be required to define their functions outside the ER.

Resource selection of a nomadic ungulate in a dynamic landscape.

Nomadic movements are often a consequence of unpredictable resource dynamics. However, how nomadic ungulates select dynamic resources is still understudied. Here we examined resource selection of nomadic Mongolian gazelles (Procapra gutturosa) in the Eastern Steppe of Mongolia. We used daily GPS locations of 33 gazelles tracked up to 3.5 years. We examined selection for forage during the growing season using the Normalized Difference Vegetation Index (NDVI). In winter we examined selection for snow cover which mediates access to forage and drinking water. We studied selection at the population level using resource selection functions (RSFs) as well as on the individual level using step-selection functions (SSFs) at varying spatio-temporal scales from 1 to 10 days. Results from the population and the individual level analyses differed. At the population level we found selection for higher than average NDVI during the growing season. This may indicate selection for areas with more forage cover within the arid steppe landscape. In winter, gazelles selected for intermediate snow cover, which may indicate preference for areas which offer some snow for hydration but not so much as to hinder movement. At the individual level, in both seasons and across scales, we were not able to detect selection in the majority of individuals, but selection was similar to that seen in the RSFs for those individuals showing selection. Difficulty in finding selection with SSFs may indicate that Mongolian gazelles are using a random search strategy to find forage in a landscape with large, homogeneous areas of vegetation. The combination of random searches and landscape characteristics could therefore obscure results at the fine scale of SSFs. The significant results on the broader scale used for the population level RSF highlight that, although individuals show uncoordinated movement trajectories, they ultimately select for similar vegetation and snow cover.

Novel amide and imidazole compounds as potent hematopoietic prostaglandin D2 synthase inhibitors.

In seeking novel and potent small molecule hematopoietic prostaglandin D2 synthase (H-PGDS) inhibitors as potential therapies for PGD2-mediated diseases and conditions, we explored a series comprising multiple aryl/heteroaryl rings attached in a linear arrangement. Each compound incorporates an amide or imidazole "linker" between the pyrimidine or pyridine "core" ring and the "tail" ring system. We synthesized and screened twenty analogs by fluorescence polarization binding assay, thermal shift assay, glutathione S-transferase inhibition assay, and a cell-based assay measuring suppression of LPS-induced PGD2 stimulation. Amide analogs show ten-fold greater shift in the thermal shift assay in the presence of glutathione (GSH) versus the same assay run in the absence of GSH. The imidazole analogs did not produce a significant change in thermal shift between the two assay conditions, suggesting a possible stabilization effect of the amide linker in the synthase-GSH-inhibitor complex. Imidazole analog 23, (KMN-010034) demonstrates superior potency across the in vitro assays and good in vitro metabolic stability in both human and guinea pig liver microsomes.

Hidden treasure of the Gobi: understanding how water limits range use of khulan in the Mongolian Gobi.

Most large herbivores in arid landscapes need to drink which constrains their movements and makes them vulnerable to disturbance. Asiatic wild ass or khulan (Equus hemionus) were widespread and abundant throughout the arid landscapes of Central Asia and Mongolia, but have undergone dramatic population declines and range constrictions; denying khulan access to water is believed to have played a major role. Mongolia's South Gobi Region now houses the world largest remaining khulan population, but is undergoing rapid land use changes. Khulan water use is poorly understood, largely due to the difficulty of mapping waterpoints used by khulan throughout their exceptionally large ranges, prone to high variations in precipitation. We used the special movement path characteristics of GPS tagged khulan to show us where water is located. We identified 367 waterpoints, 53 of which were of population importance, characterized the seasonal and circadian use, and identified snow cover as the most important variable predicting khulan visits during the non-growing season, and vegetation greenness during the growing season. Our results provide a data layer to help guide a regional khulan conservation strategy, allow predictions for other part of the global khulan range, and illustrates the overall importance of waterpoints for dryland herbivores.

Author Correction: Longest terrestrial migrations and movements around the world.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Longest terrestrial migrations and movements around the world.

Long-distance terrestrial migrations are imperiled globally. We determined both round-trip migration distances (straight-line measurements between migratory end points) and total annual movement (sum of the distances between successive relocations over a year) for a suite of large mammals that had potential for long-distance movements to test which species displayed the longest of both. We found that caribou likely do exhibit the longest terrestrial migrations on the planet, but, over the course of a year, gray wolves move the most. Our results were consistent with the trophic-level based hypothesis that predators would move more than their prey. Herbivores in low productivity environments moved more than herbivores in more productive habitats. We also found that larger members of the same guild moved less than smaller members, supporting the 'gastro-centric' hypothesis. A better understanding of migration and movements of large mammals should aid in their conservation by helping delineate conservation area boundaries and determine priority corridors for protection to preserve connectivity. The magnitude of the migrations and movements we documented should also provide guidance on the scale of conservation efforts required and assist conservation planning across agency and even national boundaries.

Border Security Fencing and Wildlife: The End of the Transboundary Paradigm in Eurasia?

The ongoing refugee crisis in Europe has seen many countries rush to construct border security fencing to divert or control the flow of people. This follows a trend of border fence construction across Eurasia during the post-9/11 era. This development has gone largely unnoticed by conservation biologists during an era in which, ironically, transboundary cooperation has emerged as a conservation paradigm. These fences represent a major threat to wildlife because they can cause mortality, obstruct access to seasonally important resources, and reduce effective population size. We summarise the extent of the issue and propose concrete mitigation measures.

From fine-scale foraging to home ranges: a semivariance approach to identifying movement modes across spatiotemporal scales.

Understanding animal movement is a key challenge in ecology and conservation biology. Relocation data often represent a complex mixture of different movement behaviors, and reliably decomposing this mix into its component parts is an unresolved problem in movement ecology. Traditional approaches, such as composite random walk models, require that the timescales characterizing the movement are all similar to the usually arbitrary data-sampling rate. Movement behaviors such as long-distance searching and fine-scale foraging, however, are often intermixed but operate on vastly different spatial and temporal scales. An approach that integrates the full sweep of movement behaviors across scales is currently lacking. Here we show how the semivariance function (SVF) of a stochastic movement process can both identify multiple movement modes and solve the sampling rate problem. We express a broad range of continuous-space, continuous-time stochastic movement models in terms of their SVFs, connect them to relocation data via variogram regression, and compare them using standard model selection techniques. We illustrate our approach using Mongolian gazelle relocation data and show that gazelle movement is characterized by ballistic foraging movements on a 6-h timescale, fast diffusive searching with a 10-week timescale, and asymptotic diffusion over longer timescales.

Optimizing the search for resources by sharing information: Mongolian gazelles as a case study.

We investigate the relationship between communication and search efficiency in a biological context by proposing a model of Brownian searchers with long-range pairwise interactions. After a general study of the properties of the model, we show an application to the particular case of acoustic communication among Mongolian gazelles, for which data are available, searching for good habitat areas. Using Monte Carlo simulations and density equations, our results point out that the search is optimal (i.e., the mean first hitting time among searchers is minimum) at intermediate scales of communication, showing that both an excess and a lack of information may worsen it.

Discovery of an Oral Potent Selective Inhibitor of Hematopoietic Prostaglandin D Synthase (HPGDS).

Hematopoietic prostaglandin D synthase (HPGDS) is primarly expressed in mast cells, antigen-presenting cells, and Th-2 cells. HPGDS converts PGH2 into PGD2, a mediator thought to play a pivotal role in airway allergy and inflammatory processes. In this letter, we report the discovery of an orally potent and selective inhibitor of HPGDS that reduces the antigen-induced response in allergic sheep.

Mobile larynx in Mongolian gazelle: Retraction of the larynx during rutting barks in male Mongolian gazelle (Procapra gutturosa Pallas, 1777).

This study provides the first evidence of pronounced temporary laryngeal descent in a bovid species. An elaborate acoustic display is prominent in male courtship behavior of polygynous Mongolian gazelle. During rut, rounding up of females is accompanied by continuous head-up barking by dominant males. Throughout the rut their evolutionarily enlarged larynx descends to a low mid-neck resting position. In the course of each bark the larynx is additionally retracted toward the sternum by 30% of the resting vocal tract length. A geometric model of active larynx movements was constructed by combining results of video documentation, dissection, skeletonization, and behavioral observation. The considerable distance between resting position and maximal laryngeal descent suggests a backward tilting of the hyoid apparatus and an extension of the thyrohyoid connection during the retraction phase. Return to the resting position is effected by strap muscles and by the elastic recoil of the pharynx and the thyrohyoid connection. An intrapharyngeal inflation of the peculiar palatinal pharyngeal pouch of adult males is inferred from a short-time expansion of the ventral neck region rostral to the laryngeal prominence. The neck of adult dominant males is accentuated by long gray guard hairs during the rut. The passive swinging of the heavy larynx of adult males during locomotion gives the impression of a handicap imposed on rutting males. Apparently, this disadvantage becomes outweighed by the profits for reproductive success.

Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship.

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a novel agonist of the alpha7 neuronal nicotinic acetylcholine receptor (alpha7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective alpha7 nAChR agonist with an excellent in vitro profile. The compound is characterized by rapid brain penetration and high oral bioavailability in rat and demonstrates in vivo efficacy in auditory sensory gating and, in an in vivo model to assess cognitive performance, novel object recognition.

Exposure of Mongolian gazelles (Procapra gutturosa) to foot and mouth disease virus.

Foot and mouth disease is a highly contagious acute viral disease that affects most ruminant and porcine species. During 2001, 33 serum samples were collected from Mongolian gazelles (Procapra gutturosa) in the Eastern Steppe of Mongolia. Samples were tested for antibodies to seven subtypes of foot-and-mouth-disease virus (FMDV). Antibodies were detected in 67% of the animals, and serologic results indicated exposure to FMDV-O. This virus was present in domestic animal populations in Mongolia from 2000 to 2002, and it is likely that the antibodies to FMDV detected in these gazelles resulted from spillover of virus from domestic animal sources.