Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for disease, is ...poorly understood. Here, we perform comprehensive lipidomics to create a lipid network map during ZIKV infection. We find that ZIKV significantly alters host lipid composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic expression of ZIKV NS4B protein results in similar changes, demonstrating a role for NS4B in modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, including human neural progenitor cells, blocks ZIKV infection. Additionally, the sphingolipid ceramide redistributes to ZIKV replication sites, and increasing ceramide levels by multiple pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV infection.
Determination of the molecular structures of petroporphyrins has been crucial to understand the diagenetic pathways and maturation of petroleum. However, these studies have been hampered by their ...structural complexity and the challenges associated with their isolation. In comparison to the skeletal macrocyclic structures, much less is known about the substitutions, which are more sensitive to the maturation and diagenesis pathways. While these isolated vanadyl petroporphyrins largely consist of etioporphyrin and deoxophylloerythroetioporphyrin as expected, surprisingly, we find evidence that one or a few β hydrogens are present in petroporphyrins of low carbon numbers using a combination of ultraviolet–visible spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry, and non-contact atomic force microscopy. Petroporphyrins with β hydrogens were not anticipated on the basis of their biological precursors. The data support dealkylation under catagenesis but not transalkylation or random alkylation of the β and meso positions, despite the fact that more complex porphyrin structures are formed.
Understanding how kill rates vary among seasons is required to understand predation by vertebrate species living in temperate climates. Unfortunately, kill rates are only rarely estimated during ...summer.
For several wolf packs in Yellowstone National Park, we used pairs of collared wolves living in the same pack and the double-count method to estimate the probability of attendance (PA) for an individual wolf at a carcass. PA quantifies an important aspect of social foraging behavior (i.e., the cohesiveness of foraging). We used PA to estimate summer kill rates for packs containing GPS-collared wolves between 2004 and 2009. Estimated rates of daily prey acquisition (edible biomass per wolf) decreased from 8.4±0.9 kg (mean ± SE) in May to 4.1±0.4 kg in July. Failure to account for PA would have resulted in underestimating kill rate by 32%. PA was 0.72±0.05 for large ungulate prey and 0.46±0.04 for small ungulate prey. To assess seasonal differences in social foraging behavior, we also evaluated PA during winter for VHF-collared wolves between 1997 and 2009. During winter, PA was 0.95±0.01. PA was not influenced by prey size but was influenced by wolf age and pack size.
Our results demonstrate that seasonal patterns in the foraging behavior of social carnivores have important implications for understanding their social behavior and estimating kill rates. Synthesizing our findings with previous insights suggests that there is important seasonal variation in how and why social carnivores live in groups. Our findings are also important for applications of GPS collars to estimate kill rates. Specifically, because the factors affecting the PA of social carnivores likely differ between seasons, kill rates estimated through GPS collars should account for seasonal differences in social foraging behavior.
The impact of physiological stress on lipid metabolism, the metabolome, and systemic responses was examined in chickens. To incite a stress response, birds were continuously administered ...corticosterone (CORT) in their drinking water at three doses (0 mg/L, 10 mg/L, and 30 mg/L), and they were sampled 1, 5, and 12 days after commencement of CORT administration. Corticosterone administration to birds differentially regulated lipogenesis genes (i.e. FAS, ACC, ME, and SREBF1), and histopathological examination indicated lipid deposition in hepatocytes. In addition, CORT affected water-soluble metabolite profiles in the liver, as well as in kidney tissue and breast muscle; thirteen unique metabolites were distinguished in CORT-treated birds and this was consistent with the dysregulation of lipid metabolism due to physiological stress. Acute phase responses (APRs) were also altered by CORT, and in particular, expression of SAA1 was decreased and expression of CP was increased. Furthermore, CORT administration caused lymphoid depletion in the bursa of Fabricius and elevated IL6 and TGFβ2 mRNA expression after 5 and 12 days of CORT administration. Collectively, incitement of physiological stress via administration of CORT in chickens modulated host metabolism and systemic responses, which indicated that energy potentials are diverted from muscle anabolism during periods of stress.
We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on ...the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.
Competition between apex predators can alter the strength of top‐down forcing, yet we know little about the behavioral mechanisms that drive competition in multipredator ecosystems. Interactions ...between predators can be synergistic (facilitative) or antagonistic (inhibitive), both of which are widespread in nature, vary in strength between species and across space and time, and affect predation patterns and predator–prey dynamics. Recent research has suggested that gray wolf (Canis lupus) kill rates decrease where they are sympatric with brown bears (Ursus arctos), however, the mechanisms behind this pattern remain unknown. We used data from two long‐term research projects in Scandinavia (Europe) and Yellowstone National Park (North America) to test the role of interference and exploitation competition from bears on wolf predatory behavior, where altered wolf handling and search time of prey in the presence of bears are indicative of interference and exploitation competition, respectively. Our results suggest the mechanisms driving competition between bears and wolves were dependent on the season and study system. During spring in Scandinavia, interference competition was the primary mechanism driving decreased kill rates for wolves sympatric with bears; handling time increased, but search time did not. In summer, however, when both bear and wolf predation focused on neonate moose, the behavioral mechanism switched to exploitation competition; search time increased, but handling time did not. Alternartively, interference competition did affect wolf predation dynamics in Yellowstone during summer, where wolves prey more evenly on neonate and adult ungulates. Here, bear presence at a carcass increased the amount of time wolves spent at carcasses of all sizes and wolf handling time for small prey, but decreased handling time for the largest prey. Wolves facilitate scavenging opportunities for bears, however, bears alter wolf predatory behavior via multiple pathways and are primarily antagonistic to wolves. Our study helps to clarify the behavioral mechanisms driving competition between apex predators, illustrating how interspecific interactions can manifest into population‐level predation patterns.
While the functional response of predators is commonly measured, recent work has revealed that the age and sex composition of prey killed is often a better predictor of prey population dynamics ...because the reproductive value of adult females is usually higher than that of males or juveniles.
Climate is often an important mediating factor in determining the composition of predator kills, but we currently lack a mechanistic understanding of how the multiple facets of climate interact with prey abundance and demography to influence the composition of predator kills.
Over 20 winters, we monitored 17 wolf packs in Yellowstone National Park and recorded the sex, age and nutritional condition of kills of their dominant prey—elk—in both early and late winter periods when elk are in relatively good and relatively poor condition, respectively.
Nutritional condition (as indicated by per cent marrow fat) of wolf‐killed elk varied markedly with summer plant productivity, snow water equivalent (SWE) and winter period. Moreover, marrow was poorer for wolf‐killed bulls and especially for calves than it was for cows.
Wolf prey composition was influenced by a complex set of climatic and endogenous variables. In early winter, poor plant growth in either year t or t − 1, or relatively low elk abundance, increased the odds of wolves killing bulls relative to cows. Calves were most likely to get killed when elk abundance was high and when the forage productivity they experienced in utero was poor. In late winter, low SWE and a relatively large elk population increased the odds of wolves killing calves relative to cows, whereas low SWE and poor vegetation productivity 1 year prior together increased the likelihood of wolves killing a bull instead of a cow.
Since climate has a strong influence on whether wolves prey on cows (who, depending on their age, are the key reproductive components of the population) or lower reproductive value of calves and bulls, our results suggest that climate can drive wolf predation to be more or less additive from year to year.
The impacts of large carnivores on their prey are importantly impacted by the composition of the prey killed. Here the authors show that climate and elk population size interact in important ways to determine when wolves kill cows, bulls or calves.
Trophic interactions are a fundamental topic in ecology, but we know little about how competition between apex predators affects predation, the mechanism driving top-down forcing in ecosystems. We ...used long-term datasets from Scandinavia (Europe) and Yellowstone National Park (North America) to evaluate how grey wolf (Canis lupus) kill rate was affected by a sympatric apex predator, the brown bear (Ursus arctos). We used kill interval (i.e. the number of days between consecutive ungulate kills) as a proxy of kill rate. Although brown bears can monopolize wolf kills, we found no support in either study system for the common assumption that they cause wolves to kill more often. On the contrary, our results showed the opposite effect. In Scandinavia, wolf packs sympatric with brown bears killed less often than allopatric packs during both spring (after bear den emergence) and summer. Similarly, the presence of bears at wolf-killed ungulates was associated with wolves killing less often during summer in Yellowstone. The consistency in results between the two systems suggests that brown bear presence actually reduces wolf kill rate. Our results suggest that the influence of predation on lower trophic levels may depend on the composition of predator communities.
PDF
