Nesfatin-1 is a regulator of inflammation with implications during obesity and metabolic syndrome.

Nesfatin-1, derived from the nucleobindin 2 (NUCB2) precursor, is a potent anorexigenic peptide that was discovered in 2006. Since its identification in the hypothalamus, it has been shown to have wide ranging actions within and outside of the central nervous system. One of these actions is the regulation of inflammation, which could potentially be exploited therapeutically in the context of obesity-associated inflammation in adipose tissue. Here, we review recent advances in our knowledge about the ability of nesfatin-1 to control inflammation by regulating NFκB signaling, which likely attenuates pro-inflammatory cytokine production and inhibits apoptosis.

Regulation of ATR-dependent DNA damage response by nitric oxide.

We have shown that nitric oxide limits ataxia-telangiectasia mutated signaling by inhibiting mitochondrial oxidative metabolism in a ß-cell selective manner. In this study, we examined the actions of nitric oxide on a second DNA damage response transducer kinase, ataxia-telangiectasia and Rad3-related protein (ATR). In ß-cells and non-ß-cells, nitric oxide activates ATR signaling by inhibiting ribonucleotide reductase; however, when produced at inducible nitric oxide synthase-derived (low micromolar) levels, nitric oxide impairs ATR signaling in a ß-cell selective manner. The inhibitory actions of nitric oxide are associated with impaired mitochondrial oxidative metabolism and lack of glycolytic compensation that result in a decrease in ß-cell ATP. Like nitric oxide, inhibitors of mitochondrial respiration reduce ATP levels and limit ATR signaling in a ß-cell selective manner. When non-ß-cells are forced to utilize mitochondrial oxidative metabolism for ATP generation, their response is more like ß-cells, as nitric oxide and inhibitors of mitochondrial respiration attenuate ATR signaling. These studies support a dual role for nitric oxide in regulating ATR signaling. Nitric oxide activates ATR in all cell types examined by inhibiting ribonucleotide reductase, and in a ß-cell selective manner, inducible nitric oxide synthase-derived levels of nitric oxide limit ATR signaling by attenuating mitochondrial oxidative metabolism and depleting ATP.

Inhibition of oxidative metabolism by nitric oxide restricts EMCV replication selectively in pancreatic beta-cells.

Environmental factors, such as viral infection, are proposed to play a role in the initiation of autoimmune diabetes. In response to encephalomyocarditis virus (EMCV) infection, resident islet macrophages release the pro-inflammatory cytokine IL-1ß, to levels that are sufficient to stimulate inducible nitric oxide synthase (iNOS) expression and production of micromolar levels of the free radical nitric oxide in neighboring ß-cells. We have recently shown that nitric oxide inhibits EMCV replication and EMCV-mediated ß-cell lysis and that this protection is associated with an inhibition of mitochondrial oxidative metabolism. Here we show that the protective actions of nitric oxide against EMCV infection are selective for ß-cells and associated with the metabolic coupling of glycolysis and mitochondrial oxidation that is necessary for insulin secretion. Inhibitors of mitochondrial respiration attenuate EMCV replication in ß-cells, and this inhibition is associated with a decrease in ATP levels. In mouse embryonic fibroblasts (MEFs), inhibition of mitochondrial metabolism does not modify EMCV replication or decrease ATP levels. Like most cell types, MEFs have the capacity to uncouple the glycolytic utilization of glucose from mitochondrial respiration, allowing for the maintenance of ATP levels under conditions of impaired mitochondrial respiration. It is only when MEFs are forced to use mitochondrial oxidative metabolism for ATP generation that mitochondrial inhibitors attenuate viral replication. In a ß-cell selective manner, these findings indicate that nitric oxide targets the same metabolic pathways necessary for glucose stimulated insulin secretion for protection from viral lysis.

Inhibition of mitochondrial oxidative metabolism attenuates EMCV replication and protects ß-cells from virally mediated lysis.

Viral infection is one environmental factor that may contribute to the initiation of pancreatic ß-cell destruction during the development of autoimmune diabetes. Picornaviruses, such as encephalomyocarditis virus (EMCV), induce a pro-inflammatory response in islets leading to local production of cytokines, such as IL-1, by resident islet leukocytes. Furthermore, IL-1 is known to stimulate ß-cell expression of iNOS and production of the free radical nitric oxide. The purpose of this study was to determine whether nitric oxide contributes to the ß-cell response to viral infection. We show that nitric oxide protects ß-cells against virally mediated lysis by limiting EMCV replication. This protection requires low micromolar, or iNOS-derived, levels of nitric oxide. At these concentrations nitric oxide inhibits the Krebs enzyme aconitase and complex IV of the electron transport chain. Like nitric oxide, pharmacological inhibition of mitochondrial oxidative metabolism attenuates EMCV-mediated ß-cell lysis by inhibiting viral replication. These findings provide novel evidence that cytokine signaling in ß-cells functions to limit viral replication and subsequent ß-cell lysis by attenuating mitochondrial oxidative metabolism in a nitric oxide-dependent manner.

The location of sensing determines the pancreatic ß-cell response to the viral mimetic dsRNA.

Viral infection is an environmental trigger that has been suggested to initiate pancreatic ß-cell damage, leading to the development of autoimmune diabetes. Viruses potently activate the immune system and can damage ß cells by either directly infecting them or stimulating the production of secondary effector molecules (such as proinflammatory cytokines) during bystander activation. However, how and where ß cells recognize viruses is unclear, and the antiviral responses that are initiated following virus recognition are incompletely understood. In this study, we show that the ß-cell response to dsRNA, a viral replication intermediate known to activate antiviral responses, is determined by the cellular location of sensing (intracellular versus extracellular) and differs from the cellular response to cytokine treatment. Using biochemical and immunological methods, we show that ß cells selectively respond to intracellular dsRNA by expressing type I interferons (IFNs) and inducing apoptosis, but that they do not respond to extracellular dsRNA. These responses differ from the activities of cytokines on ß cells, which are mediated by inducible nitric oxide synthase expression and ß-cell production of nitric oxide. These findings provide evidence that the antiviral activities of type I IFN production and apoptosis are elicited in ß cells via the recognition of intracellular viral replication intermediates and that ß cells lack the capacity to respond to extracellular viral intermediates known to activate innate immune responses.

CCR5 is a required signaling receptor for macrophage expression of inflammatory genes in response to viral double-stranded RNA.

Double-stranded (ds) RNA, both synthetic and produced during virus replication, rapidly stimulates MAPK and NF-κB signaling that results in expression of the inflammatory genes inducible nitric oxide synthase, cyclooxygenase 2, and IL-1ß by macrophages. Using biochemical and genetic approaches, we have identified the chemokine ligand-binding C-C chemokine receptor type 5 (CCR5) as a cell surface signaling receptor required for macrophage expression of inflammatory genes in response to dsRNA. Activation of macrophages by synthetic dsRNA does not require known dsRNA receptors, as poly(inosinic:cytidylic) acid [poly(I:C)] activates signaling pathways leading to expression of inflammatory genes to similar levels in wild-type and Toll-like receptor 3- or melanoma differentiation antigen 5-deficient macrophages. In contrast, macrophage activation in response to poly(I:C) is attenuated in macrophages isolated from mice lacking CCR5. These findings support a role for CCR5 as a cell surface signaling receptor that participates in activation of inflammatory genes in macrophages in response to the viral dsRNA mimetic poly(inosinic:cytidylic) acid by pathways that are distinct from classical dsRNA receptor-mediated responses.

The first documented interaction between a long-tailed weasel (Mustela frenata) and a plains spotted skunk (Spilogale interrupta) carcass.

A novel interaction between a long-tailed weasel (Mustela frenata) and a plains spotted skunk (Spilogale interrupta) carcass is detailed. In November 2020, a farmer in Edmunds County in north-central South Dakota sent in a video recording of a long-tailed weasel with a spotted skunk carcass. Location of the event, carcass condition, and recorded behavior of the long-tailed weasel offer probable, but unconfirmed, evidence that the spotted skunk was killed by the long-tailed weasel.

Factors influencing autumn-winter movements of midcontinent Mallards and consequences for harvest and habitat management.

Annual phenology and distributions of migratory wildlife have been noticeably influenced by climate change, leading to concerns about sustainable populations. Recent studies exploring conditions influencing autumn migration departure have provided conflicting insights regarding factors influencing the movements of Mallards (Anas platyrhynchos), a popular game species. We determined factors affecting timing and magnitude of long-distance movements of 97 juvenile Mallards during autumn-winter across the midcontinent of North America marked with implanted transmitters in North and South Dakota, 2018-2019. Factors influencing variation in movement timing, along with direction and magnitudes, depended on type of movement (i.e., regional [25-310 km], initial migration, or subsequent migration movements [>310 km]). Photoperiod influenced probability of initiating all movements, although the effect was most influential for regional movements. Minimum temperature most influenced initial migration events (probability of movement increased 29% for each 1°C decrease); favorable winds also increased likelihood of initial migration events. Probability of subsequent migration events increased 80% for each 1 cm increase in depth of snow. Subsequent migration movements also were 2.0 times more likely to occur on weekend days, indicating disturbance from humans may influence movements. Migration distances increased 166 km for each 1°C reduction in minimum temperature. We also observed markedly different autumn-winter distributions of marked birds between years. Median locations during autumn-winter 2018-2019 were ~250 km farther north and ~300 km farther west during mid-December-January compared to the same time in 2019-2020. Concurrently, harvest rates for marked females and males were 10% and 26% during autumn-winter 2018-2019 and 26% and 31% during autumn-winter 2019-2020. Climate-related changes may result in increasingly variable autumn-winter distributions, with implications for wildlife recreationalists, conservation planners, and harvest managers.

The effect of weather on the decision to migrate from stopover sites by autumn-migrating ducks.

BACKGROUND: Previous investigations of autumn-migrating ducks have reported weak connections between weather conditions and the decision to migrate from stopover sites. We leveraged relatively new weather surveillance radar technology to remotely detect departures of discrete groups of various species of migratory dabbling ducks (Anatidae) in autumn to more directly assess the effect of specific weather conditions on departure from discrete stopover sites. METHODS: Using radar data collected over fifteen years (1995-2009), we documented a consistent phenomenon where a single, identifiable group departed from our study area on 30% of days during the autumn study period, and no ducks departed on the other days. We gathered weather variables from nearby stations and used them to develop competing models to explain temporal patterns of departure versus non-departure to better understand the potential mechanisms associated with binomial patterns of departures. RESULTS: The best approximating model of departure probability was our integrated model, which included variables accounting for wind aloft direction favorable for departure (i.e., tailwind), absence of precipitation, and a partially or completely clear sky. The integrated model accounted for all model weight in the candidate set and explained 55% of the variation in departure probability. Estimated probability of departure was 0.76 after parameterizing the best model with favorable conditions for all covariates. CONCLUSIONS: Our results contrasted those of previous studies of autumn duck migration as a small set of simplistic, extrinsic conditions substantially influenced departure decision.

Indirect risk effects reduce feeding efficiency of ducks during spring.

Indirect risk effects of predators on prey behavior can have more of an impact on prey populations than direct consumptive effects. Predation risk can elicit more vigilance behavior in prey, reducing the amount of time available for other activities, such as foraging, which could potentially reduce foraging efficiency. Understanding the conditions associated with predation risk and the specific effects predation risk have on prey behavior is important because it has direct influences on the profitability of food items found under various conditions and states of the forager. The goals of this study were to assess how ducks perceived predation risk in various habitat types and how strongly perceived risk versus energetic demand affected foraging behavior. We manipulated food abundance in different wetland types in Illinois, USA to reduce confounding between food abundance and vegetation structure. We conducted focal-animal behavioral samples on five duck species in treatment and control plots and used generalized linear mixed-effects models to compare the effects of vegetation structure versus other factors on the intensity with which ducks fed and the duration of feeding stints. Mallards fed more intensively and, along with blue-winged teal, used longer feeding stints in open habitats, consistent with the hypothesis that limited visibility was perceived to have a greater predation risk than unlimited visibility. The species temporally nearest to nesting, wood ducks, were willing to take more risks for a greater food reward, consistent with an increase in a marginal value of energy as they approached nesting. Our results indicate that some duck species value energy differently based on the surrounding vegetation structure and density. Furthermore, increases in the marginal value of energy can be more influential than perceived risk in shaping foraging behavior patterns. Based on these findings, we conclude that the value of various food items is not solely determined by energy contained in the item but by conditions in which it is found and the state of the forager.

Foraging ecology of fall-migrating shorebirds in the Illinois River valley.

Populations of many shorebird species appear to be declining in North America, and food resources at stopover habitats may limit migratory bird populations. We investigated body condition of, and foraging habitat and diet selection by 4 species of shorebirds in the central Illinois River valley during fall migrations 2007 and 2008 (Killdeer [Charadrius vociferus], Least Sandpiper [Calidris minutilla], Pectoral Sandpiper [Calidris melanotos], and Lesser Yellowlegs [Tringa flavipes]). All species except Killdeer were in good to excellent condition, based on size-corrected body mass and fat scores. Shorebird diets were dominated by invertebrate taxa from Orders Diptera and Coleoptera. Additionally, Isopoda, Hemiptera, Hirudinea, Nematoda, and Cyprinodontiformes contribution to diets varied by shorebird species and year. We evaluated diet and foraging habitat selection by comparing aggregate percent dry mass of food items in shorebird diets and core samples from foraging substrates. Invertebrate abundances at shorebird collection sites and random sites were generally similar, indicating that birds did not select foraging patches within wetlands based on invertebrate abundance. Conversely, we found considerable evidence for selection of some diet items within particular foraging sites, and consistent avoidance of Oligochaeta. We suspect the diet selectivity we observed was a function of overall invertebrate biomass (51.2 ± 4.4 [SE] kg/ha; dry mass) at our study sites, which was greater than estimates reported in most other food selection studies. Diet selectivity in shorebirds may follow tenants of optimal foraging theory; that is, at low food abundances shorebirds forage opportunistically, with the likelihood of selectivity increasing as food availability increases. Nonetheless, relationships between the abundance, availability, and consumption of Oligochaetes for and by waterbirds should be the focus of future research, because estimates of foraging carrying capacity would need to be revised downward if Oligochaetes are truly avoided or unavailable for consumption.

Multi-stage sampling for large scale natural resources surveys: a case study of rice and waterfowl.

Large-scale sample surveys to estimate abundance and distribution of organisms and their habitats are increasingly important in ecological studies. Multi-stage sampling (MSS) is especially suited to large-scale surveys because of the natural clustering of resources. To illustrate an application, we: (1) designed a stratified MSS to estimate late autumn abundance (kg/ha) of rice seeds in harvested fields as food for waterfowl wintering in the Mississippi Alluvial Valley (MAV); (2) investigated options for improving the MSS design; and (3) compared statistical and cost efficiency of MSS to simulated simple random sampling (SRS). During 2000-2002, we sampled 25-35 landowners per year, 1 or 2 fields per landowner per year, and measured seed mass in 10 soil cores collected within each field. Analysis of variance components and costs for each stage of the survey design indicated that collecting 10 soil cores per field was near the optimum of 11-15, whereas sampling >1 field per landowner provided few benefits because data from fields within landowners were highly correlated. Coefficients of variation (CV) of annual estimates of rice abundance ranged from 0.23 to 0.31 and were limited by variation among landowners and the number of landowners sampled. Design effects representing the statistical efficiency of MSS relative to SRS ranged from 3.2 to 9.0, and simulations indicated SRS would cost, on average, 1.4 times more than MSS because clustering of sample units in MSS decreased travel costs. We recommend MSS as a potential sampling strategy for large-scale natural resource surveys and specifically for future surveys of the availability of rice as food for waterfowl in the MAV and similar areas.