Migrating Whooping Cranes avoid wind-energy infrastructure when selecting stopover habitat.

Electricity generation from renewable-energy sources has increased dramatically worldwide in recent decades. Risks associated with wind-energy infrastructure are not well understood for endangered Whooping Cranes (Grus americana) or other vulnerable Crane populations. From 2010 to 2016, we monitored 57 Whooping Cranes with remote-telemetry devices in the United States Great Plains to determine potential changes in migration distribution (i.e., avoidance) caused by presence of wind-energy infrastructure. During our study, the number of wind towers tripled in the Whooping Crane migration corridor and quadrupled in the corridor's center. Median distance of Whooping Crane locations from nearest wind tower was 52.1 km, and 99% of locations were >4.3 km from wind towers. A habitat selection analysis revealed that Whooping Cranes used areas ≤5.0 km (95% confidence interval [CI] 4.8-5.4) from towers less than expected (i.e., zone of influence) and that Whooping Cranes were 20 times (95% CI 14-64) more likely to use areas outside compared to adjacent to towers. Eighty percent of Whooping Crane locations and 20% of wind towers were located in areas with the highest relative probability of Whooping Crane use based on our model, which comprised 20% of the study area. Whooping Cranes selected for these places, whereas developers constructed wind infrastructure at random relative to desirable Whooping Crane habitat. As of early 2020, 4.6% of the study area and 5.0% of the highest-selected Whooping Crane habitat were within the collective zone of influence. The affected area equates to habitat loss ascribed to wind-energy infrastructure; losses from other disturbances have not been quantified. Continued growth of the Whooping Crane population during this period of wind infrastructure construction suggests no immediate population-level consequences. Chronic or lag effects of habitat loss are unknown but possible for long-lived species. Preferentially constructing future wind infrastructure outside of the migration corridor or inside of the corridor at sites with low probability of Whooping Crane use would allow for continued wind-energy development in the Great Plains with minimal additional risk to highly selected habitat that supports recovery of this endangered species.

Are whooping cranes destined for extinction? Climate change imperils recruitment and population growth.

Identifying climatic drivers of an animal population's vital rates and locating where they operate steers conservation efforts to optimize species recovery. The population growth of endangered whooping cranes (Grus americana) hinges on juvenile recruitment. Therefore, we identify climatic drivers (solar activity [sunspots] and weather) of whooping crane recruitment throughout the species' life cycle (breeding, migration, wintering). Our method uses a repeated cross-validated absolute shrinkage and selection operator approach to identify drivers of recruitment. We model effects of climate change on those drivers to predict whooping crane population growth given alternative scenarios of climate change and solar activity. Years with fewer sunspots indicated greater recruitment. Increased precipitation during autumn migration signified less recruitment. On the breeding grounds, fewer days below freezing during winter and more precipitation during breeding suggested less recruitment. We predicted whooping crane recruitment and population growth may fall below long-term averages during all solar cycles when atmospheric CO2 concentration increases, as expected, to 500 ppm by 2050. Species recovery during a typical solar cycle with 500 ppm may require eight times longer than conditions without climate change and the chance of population decline increases to 31%. Although this whooping crane population is growing and may appear secure, long-term threats imposed by climate change and increased solar activity may jeopardize its persistence. Weather on the breeding grounds likely affects recruitment through hydrological processes and predation risk, whereas precipitation during autumn migration may influence juvenile mortality. Mitigating threats or abating climate change should occur within ≈30 years or this wild population of whooping cranes may begin declining.

Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors.

Mutations in succinate dehydrogenase (SDH) are associated with tumor development and neurodegenerative diseases. Only in tumors, loss of SDH activity is accompanied with the loss of complex I activity. Yet, it remains unknown whether the metabolic phenotype of SDH mutant tumors is driven by loss of complex I function, and whether this contributes to the peculiarity of tumor development versus neurodegeneration. We addressed this question by decoupling loss of SDH and complex I activity in cancer cells and neurons. We found that sole loss of SDH activity was not sufficient to recapitulate the metabolic phenotype of SDH mutant tumors, because it failed to decrease mitochondrial respiration and to activate reductive glutamine metabolism. These metabolic phenotypes were only induced upon the additional loss of complex I activity. Thus, we show that complex I function defines the metabolic differences between SDH mutation associated tumors and neurodegenerative diseases, which could open novel therapeutic options against both diseases.

Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis.

Cellular proliferation depends on refilling the tricarboxylic acid (TCA) cycle to support biomass production (anaplerosis). The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC) and glutamine conversion to α-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo 13C tracer analysis. We discovered that lung metastases have higher PC-dependent anaplerosis compared to primary breast cancers. Based on in vitro analysis and a mathematical model for the determination of compartment-specific metabolite concentrations, we found that mitochondrial pyruvate concentrations can promote PC-dependent anaplerosis via enzyme kinetics. In conclusion, we show that breast cancer cells proliferating as lung metastases activate PC-dependent anaplerosis in response to the lung microenvironment.

Asynchronous food-web pathways could buffer the response of Serengeti predators to El Niño Southern Oscillation.

Understanding how entire ecosystems maintain stability in the face of climatic and human disturbance is one of the most fundamental challenges in ecology. Theory suggests that a crucial factor determining the degree of ecosystem stability is simply the degree of synchrony with which different species in ecological food webs respond to environmental stochasticity. Ecosystems in which all food-web pathways are affected similarly by external disturbance should amplify variability in top carnivore abundance over time due to population interactions, whereas ecosystems in which a large fraction of pathways are nonresponsive or even inversely responsive to external disturbance will have more constant levels of abundance at upper trophic levels. To test the mechanism underlying this hypothesis, we used over half a century of demographic data for multiple species in the Serengeti (Tanzania) ecosystem to measure the degree of synchrony to variation imposed by an external environmental driver, the El Niño Southern Oscillation (ENSO). ENSO effects were mediated largely via changes in dry-season vs. wet-season rainfall and consequent changes in vegetation availability, propagating via bottom-up effects to higher levels of the Serengeti food web to influence herbivores, predators and parasites. Some species in the Serengeti food web responded to the influence of ENSO in opposite ways, whereas other species were insensitive to variation in ENSO. Although far from conclusive, our results suggest that a diffuse mixture of herbivore responses could help buffer top carnivores, such as Serengeti lions, from variability in climate. Future global climate changes that favor some pathways over others, however, could alter the effectiveness of such processes in the future.

Predictability of anthrax infection in the Serengeti, Tanzania.

Anthrax is endemic throughout Africa, causing considerable livestock and wildlife losses and severe, sometimes fatal, infection in humans. Predicting the risk of infection is therefore important for public health, wildlife conservation and livestock economies. However, because of the intermittent and variable nature of anthrax outbreaks, associated environmental and climatic conditions, and diversity of species affected, the ecology of this multihost pathogen is poorly understood.We explored records of anthrax from the Serengeti ecosystem in north-west Tanzania where the disease has been documented in humans, domestic animals and a range of wildlife. Using spatial and temporal case-detection and seroprevalence data from wild and domestic animals, we investigated spatial, environmental, climatic and species-specific associations in exposure and disease.Anthrax was detected annually in numerous species, but large outbreaks were spatially localized, mostly affecting a few focal herbivores.Soil alkalinity and cumulative weather extremes were identified as useful spatial and temporal predictors of exposure and infection risk, and for triggering the onset of large outbreaks.Interacting ecological and behavioural factors, specifically functional groups and spatiotemporal overlap, helped to explain the variable patterns of infection and exposure among species.Synthesis and applications. Our results shed light on ecological drivers of anthrax infection and suggest that soil alkalinity and prolonged droughts or rains are useful predictors of disease occurrence that could guide risk-based surveillance. These insights should inform strategies for managing anthrax including prophylactic livestock vaccination, timing of public health warnings and antibiotic provision in high-risk areas. However, this research highlights the need for greater surveillance (environmental, serological and case-detection-orientated) to determine the mechanisms underlying anthrax dynamics.

A disease-mediated trophic cascade in the Serengeti and its implications for ecosystem C.

Tree cover is a fundamental structural characteristic and driver of ecosystem processes in terrestrial ecosystems, and trees are a major global carbon (C) sink. Fire and herbivores have been hypothesized to play dominant roles in regulating trees in African savannas, but the evidence for this is conflicting. Moving up a trophic scale, the factors that regulate fire occurrence and herbivores, such as disease and predation, are poorly understood for any given ecosystem. We used a Bayesian state-space model to show that the wildebeest population eruption that followed disease (rinderpest) eradication in the Serengeti ecosystem of East Africa led to a widespread reduction in the extent of fire and an ongoing recovery of the tree population. This supports the hypothesis that disease has played a key role in the regulation of this ecosystem. We then link our state-space model with theoretical and empirical results quantifying the effects of grazing and fire on soil carbon to predict that this cascade may have led to important shifts in the size of pools of C stored in soil and biomass. Our results suggest that the dynamics of herbivores and fire are tightly coupled at landscape scales, that fire exerts clear top-down effects on tree density, and that disease outbreaks in dominant herbivores can lead to complex trophic cascades in savanna ecosystems. We propose that the long-term status of the Serengeti and other intensely grazed savannas as sources or sinks for C may be fundamentally linked to the control of disease outbreaks and poaching.

Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients.

BACKGROUND: Human herpesvirus-6 (HHV-6), Epstein-Barr virus and parvovirus B19 have been suggested as etiological agents of chronic fatigue syndrome but none of these viruses is consistently detected in all patients. However, active viral infections may be localized in specific tissues, and, therefore, are not easily detectable. The aim of this study was to investigate the presence of HHV-6, HHV-7, EBV and parvovirus B19 in the gastro-intestinal tract of CFS patients. PATIENTS AND METHODS: Using real-time PCR, viral DNA loads were quantified in gastro-intestinal biopsies of 48 CFS patients and 35 controls. RESULTS: High loads of HHV-7 DNA were detected in most CFS and control biopsies. EBV and HHV-6 were detected in 15-30% of all biopsies. Parvovirus B19 DNA was detected in 40% of the patients versus less than 15% of the controls. CONCLUSION: Parvovirus B19 may be involved in the pathogenesis of CFS, at least for a subset of patients. The gastro-intestinal tract appears as an important reservoir of infection for several potentially pathogenic viruses.

Lower frequency of IL-17F sequence variant (His161Arg) in chronic fatigue syndrome patients.

Chronic fatigue syndrome (CFS) is characterized by immune dysfunctions including chronic immune activation, inflammation, and alteration of cytokine profiles. T helper 17 (Th17) cells belong to a recently identified subset of T helper cells, with crucial regulatory function in inflammatory and autoimmune processes. Th17 cells are implicated in allergic inflammation, intestinal diseases, central nervous system inflammation, disorders that may all contribute to the pathophysiology of CFS. IL-17F is one of the pro-inflammatory cytokines secreted by Th17 cells. We investigated the association between CFS and the frequency of rs763780, a C/T genetic polymorphism leading to His161Arg substitution in the IL-17F protein. The His161Arg variant (C allele) antagonizes the pro-inflammatory effects of the wild-type IL-17F. A significantly lower frequency of the C allele was observed in the CFS population, suggesting that the His161Arg variant may confer protection against the disease. These results suggest a role of Th17 cells in the pathogenesis of CFS.

Inorganic nitrogen availability after severe stand-replacing fire in the Greater Yellowstone ecosystem.

Understanding ecosystem processes as they relate to wildfire and vegetation dynamics is of growing importance as fire frequency and extent increase throughout the western United States. However, the effects of severe, stand-replacing wildfires are poorly understood. We studied inorganic nitrogen pools and mineralization rates after stand-replacing wildfires in the Greater Yellowstone Ecosystem, Wyoming. After fires that burned in summer 2000, soil ammonium concentration peaked in 2001 (33 mg NH(4)-N x kg(soil)(-1)); soil nitrate increased subsequently (2.7 mg NO(3)-N.kg(soil)(-1) in 2003) but was still low. However, annual net ammonification rates were largely negative from 2001 to 2004, indicating ammonium depletion. Thus, although net nitrification rates were positive, annual net nitrogen mineralization (net ammonification plus net nitrification) remained low. Aboveground net primary production (ANPP) increased from 0.25 to 1.6 Mg x ha(-1) x yr(-1) from 2001 to 2004, but variation in ANPP among stands was not related to net nitrogen mineralization rates. Across a broader temporal gradient (stand age zero to >250 yr), negative rates of net annual ammonification were especially pronounced in the first postfire year. Laboratory incubations using (15)N isotope pool dilution revealed that gross production of ammonium was reduced and ammonium consumption greatly exceeded gross production during the initial postfire years. Our results suggest a microbial nitrogen sink for several years after severe, stand-replacing fire, confirming earlier hypotheses about postdisturbance succession and nutrient cycling in cold, fire-dominated coniferous forests. Postfire forests in Yellowstone seem to be highly conservative for nitrogen, and microbial immobilization of ammonium plays a key role during early succession.

Synthesis of N-acyl homoserine lactone analogues reveals strong activators of SdiA, the Salmonella enterica serovar Typhimurium LuxR homologue.

N-Acyl homoserine lactones (AHLs) are molecules that are synthesized and detected by many gram-negative bacteria to monitor the population density, a phenomenon known as quorum sensing. Salmonella enterica serovar Typhimurium is an exceptional species since it does not synthesize its own AHLs, while it does encode a LuxR homologue, SdiA, which enables this bacterium to detect AHLs that are produced by other species. To obtain more information about the specificity of the ligand binding by SdiA, we synthesized and screened a limited library of AHL analogues. We identified two classes of analogues that are strong activators of SdiA: the N-(3-oxo-acyl)-homocysteine thiolactones (3O-AHTLs) and the N-(3-oxo-acyl)-trans-2-aminocyclohexanols. To our knowledge, this is the first report of compounds (the 3O-AHTLs) that are able to activate a LuxR homologue at concentrations that are lower than the concentrations of the most active AHLs. SdiA responds with greatest sensitivity to AHTLs that have a keto modification at the third carbon atom and an acyl chain that is seven or eight carbon atoms long. The N-(3-oxo-acyl)-trans-2-aminocyclohexanols were found to be less sensitive to deactivation by lactonase and alkaline pH than the 3O-AHTLs and the AHLs are. We also examined the activity of our library with LuxR of Vibrio fischeri and identified three new inhibitors of LuxR. Finally, we performed preliminary binding experiments which suggested that SdiA binds its activators reversibly. These results increase our understanding of the specificity of the SdiA-ligand interaction, which could have uses in the development of anti-quorum-sensing-based antimicrobials.

Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling.

Rhomboids, evolutionarily conserved integral membrane proteases, participate in crucial signaling pathways. Presenilin-associated rhomboid-like (PARL) is an inner mitochondrial membrane rhomboid of unknown function, whose yeast ortholog is involved in mitochondrial fusion. Parl-/- mice display normal intrauterine development but from the fourth postnatal week undergo progressive multisystemic atrophy leading to cachectic death. Atrophy is sustained by increased apoptosis, both in and ex vivo. Parl-/- cells display normal mitochondrial morphology and function but are no longer protected against intrinsic apoptotic death stimuli by the dynamin-related mitochondrial protein OPA1. Parl-/- mitochondria display reduced levels of a soluble, intermembrane space (IMS) form of OPA1, and OPA1 specifically targeted to IMS complements Parl-/- cells, substantiating the importance of PARL in OPA1 processing. Parl-/- mitochondria undergo faster apoptotic cristae remodeling and cytochrome c release. These findings implicate regulated intramembrane proteolysis in controlling apoptosis.

Determinants of woody cover in African savannas.

Savannas are globally important ecosystems of great significance to human economies. In these biomes, which are characterized by the co-dominance of trees and grasses, woody cover is a chief determinant of ecosystem properties. The availability of resources (water, nutrients) and disturbance regimes (fire, herbivory) are thought to be important in regulating woody cover, but perceptions differ on which of these are the primary drivers of savanna structure. Here we show, using data from 854 sites across Africa, that maximum woody cover in savannas receiving a mean annual precipitation (MAP) of less than approximately 650 mm is constrained by, and increases linearly with, MAP. These arid and semi-arid savannas may be considered 'stable' systems in which water constrains woody cover and permits grasses to coexist, while fire, herbivory and soil properties interact to reduce woody cover below the MAP-controlled upper bound. Above a MAP of approximately 650 mm, savannas are 'unstable' systems in which MAP is sufficient for woody canopy closure, and disturbances (fire, herbivory) are required for the coexistence of trees and grass. These results provide insights into the nature of African savannas and suggest that future changes in precipitation may considerably affect their distribution and dynamics.

Chemical synthesis of (S)-4,5-dihydroxy-2,3-pentanedione, a bacterial signal molecule precursor, and validation of its activity in Salmonella typhimurium.

We describe an original, short, and convenient chemical synthesis of enantiopure (S)-4,5-dihydroxy-2,3-pentanedione (DPD), starting from commercial methyl (S)-(-)-2,2-dimethyl-1,3-dioxolane-4-carboxylate. DPD is the precursor of autoinducer (AI)-2, the proposed signal for bacterial interspecies communication. AI-2 is synthesized by many bacterial species in three enzymatic steps. The last step, a LuxS-catalyzed reaction, leads to the formation of DPD, which spontaneously cyclizes into AI-2. AI-2-like activity of the synthesized molecule was ascertained by the Vibrio harveyi bioassay. To further validate the biological activity of synthetic DPD and to explore its potential in studying DPD (AI-2)-mediated signaling, a Salmonella typhimurium luxS mutant was constructed. Expression of the AI-2 regulated lsr operon can be rescued in this luxS mutant by addition of synthetic DPD or genetic complementation. Biofilm formation by S. typhimurium has been reported to be defective in a luxS mutant, and this was confirmed in this study to test DPD for chemical complementation. However, biofilm formation of the luxS mutant cannot be restored by addition of DPD. In contrast, introduction of luxS under control of its own promoter complemented biofilm formation. Further results demonstrated that biofilm formation of the luxS mutant cannot be restored with luxS under control of the strong nptII promoter. This indicates that altering the intrinsic promoter activity of luxS affects Salmonella biofilm formation. Conclusively, we synthesized biologically active DPD. Using this chemical compound in combination with genetic approaches opens new avenues in studying AI-2-mediated signaling.