Risk-taking in free-living spotted hyenas is associated with anthropogenic disturbance,predicts survivorship,and is consistent across experimental contexts

Anthropogenic disturbance can have important influences on the fitness and behaviors of wild animals, including their boldness when exposed to risky conditions. We presented spotted hyenas (Crocuta crocuta) from two populations, each exposed to a different level of human activity, with a life-size model hyena representing an intruder from another clan. The high-disturbance population lived adjacent to human settlements, and the low-disturbance population inhabited a relatively undisturbed part of the same national park in Kenya. The mock intruder was presented to individual hyenas to assess their reactions to an alien hyena, and to determine whether their reactions varied with their exposure to anthropogenic activity. We found that human disturbance was indeed associated with hyena risk-taking behavior in response to the model intruder. Hyenas tested in the low-disturbance area exhibited more risk-taking behaviors by approaching the mock intruder more closely, and spending more time near it, than did their counterparts living in high-disturbance areas. Hyenas that spent less time in close proximity to the model had greater survivorship than those that spent more time in close proximity to it, regardless of disturbance level. Furthermore, the individual differences in risk-taking measured here were consistent with those obtained previously from the same animals using a different set of experimental manipulations. However, the experimentally induced behaviors were not consistent with naturally occurring risk-taking behaviors in proximity to lions; this suggests that risk-taking behaviors are consistent within individuals across experimental contexts, but that exposure to lions elicits different responses. Although our results are consistent with those from earlier tests of anthropogenic disturbance and boldness in spotted hyenas and other predators, they differ from results obtained from birds and small mammals, which are generally found to be bolder in areas characterized by human disturbance.     

Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice

A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity.     

Tumor necrosis factor is critical to control tuberculosis infection

Tumor necrosis factor (TNF) is critical and non-redundant to control Mycobacterium tuberculosis infection and cannot be replaced by other proinflammatory cytokines. Overproduction of TNF may cause immunopathology, while TNF neutralization reactivates latent and chronic, controlled infection, which is relevant for the use of neutralizing TNF therapies in patients with rheumatoid arthritis.     

Biological warfare in the garden pond: tadpoles suppress the growth of mosquito larvae

Abstract. 1. Although tadpoles and mosquito larvae may compete for scarce resources in natural freshwater systems, the mechanisms involved in such competition remain largely unstudied.
2. Replicated artificial ponds were set up to examine the role of pathogenic interference (water-borne growth inhibitors) in two tadpole–mosquito systems from south-eastern Australia. One system comprised taxa that are commonly sympatric in freshwater ponds (tadpoles of Limnodynastes peronii and larvae of Culex quinquefasciatus ) while the other comprised species that co-occur in brackish water ponds (tadpoles of Crinia signifera and larvae of Ochlerotatus australis ).
3. Water that had previously contained tadpoles suppressed the rates of survival and pupation of mosquito larvae in both systems. Fungicide reduced or eliminated this effect, suggesting that the growth inhibitors may be fungal organisms (possibly the yeast Rhodotorula glutinis ) from tadpole faeces. Fungicide also enhanced growth rates of tadpoles.
4. These results suggest that interference competition between tadpoles and mosquito larvae is mediated by other organisms in some ecological systems.     

Pond attributes influence competitive interactions between tadpoles and mosquito larvae

Abstract Tadpoles and mosquito larvae often coexist in natural freshwater bodies. We studied competitive interactions between: (i) tadpoles of the striped marsh frog (Limnodynastes peronii) and larvae of the mosquito Culex quinquefasciatus; and (ii) tadpoles of the common eastern froglet (Crinia signifera) and larvae of the mosquito Aedes australis. These two sets of taxa occur in natural water bodies in the Sydney region. Laboratory trials revealed competition between mosquito larvae and tadpoles in both systems. For example, mosquitoes displayed reduced rates of survival, growth and development, and smaller size at metamorphosis, when they were raised with tadpoles. The intensity of competitive suppression was influenced by attributes such as pond size (and hence, larval density), the location of food (on the water surface vs the substrate), and the extent of opportunities for direct physical interactions between the two competing organisms. These effects differed between the two study systems, suggesting that the mechanisms of suppression also differed. Limnodynastes peronii tadpoles suppressed C. quinquefasciatus even when the two types of organisms were separated by a physical partition, suggesting that chemical or microbiological cues may be responsible. Pond attributes also affected the impact of C. signifera tadpoles on Aedes larvae, but (unlike the Limnodynastes–Culex system) these effects disappeared when densities were lowered or when the tadpoles and mosquito larvae were physically separated. Thus, direct physical interactions may suppress mosquitoes in the Crinia–Aedes system. Our results suggest that tadpoles suppress the viability of larval mosquitoes by multiple pathways.     

TIP-1 Translocation onto the Cell Plasma Membrane Is a Molecular Biomarker of Tumor Response to Ionizing Radiation

Background

Tumor response to treatment has been generally assessed with anatomic and functional imaging. Recent development of in vivo molecular and cellular imaging showed promise in time-efficient assessment of the therapeutic efficacy of a prescribed regimen. Currently, the in vivo molecular imaging is limited with shortage of biomarkers and probes with sound biological relevance. We have previously shown in tumor-bearing mice that a hexapeptide (HVGGSSV) demonstrated potentials as a molecular imaging probe to distinguish the tumors responding to ionizing radiation (IR) and/or tyrosine kinase inhibitor treatment from those of non-responding tumors.

Methodology/Principal Findings

In this study we have studied biological basis of the HVGGSSV peptide binding within the irradiated tumors by use of tumor-bearing mice and cultured cancer cells. The results indicated that Tax interacting protein 1 (TIP-1, also known as Tax1BP3) is a molecular target that enables the selective binding of the HVGGSSV peptide within irradiated xenograft tumors. Optical imaging and immunohistochemical staining indicated that a TIP-1 specific antibody demonstrated similar biodistribution as the peptide in tumor-bearing mice. The TIP-1 antibody blocked the peptide from binding within irradiated tumors. Studies on both of human and mouse lung cancer cells showed that the intracellular TIP-1 relocated to the plasma membrane surface within the first few hours after exposure to IR and before the onset of treatment associated apoptosis and cell death. TIP-1 relocation onto the cell surface is associated with the reduced proliferation and the enhanced susceptibility to the subsequent IR treatment.

Conclusions/Significance

This study by use of tumor-bearing mice and cultured cancer cells suggested that imaging of the radiation-inducible TIP-1 translocation onto the cancer cell surface may predict the tumor responsiveness to radiation in a time-efficient manner and thus tailor radiotherapy of cancer.     

Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study

Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [¹⁸F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [¹⁸F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [¹⁸F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [¹⁸F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes.     

Adaptive introgression of the beta-globin cluster in two Andean waterfowl

Introgression of beneficial alleles has emerged as an important avenue for genetic adaptation in both plant and animal populations. In vertebrates, adaptation to hypoxic high-altitude environments involves the coordination of multiple molecular and cellular mechanisms, including selection on the hypoxia-inducible factor (HIF) pathway and the blood-O₂ transport protein hemoglobin (Hb). In two Andean duck species, a striking DNA sequence similarity reflecting identity by descent is present across the ~20 kb β-globin cluster including both embryonic (HBE) and adult (HBB) paralogs, though it was yet untested whether this is due to independent parallel evolution or adaptive introgression. In this study, we find that identical amino acid substitutions in the β-globin cluster that increase Hb-O₂ affinity have likely resulted from historical interbreeding between high-altitude populations of two different distantly-related species. We examined the direction of introgression and discovered that the species with a deeper mtDNA divergence that colonized high altitude earlier in history (Anas flavirostris) transferred adaptive genetic variation to the species with a shallower divergence (A. georgica) that likely colonized high altitude more recently possibly following a range shift into a novel environment. As a consequence, the species that received these β-globin variants through hybridization might have adapted to hypoxic conditions in the high-altitude environment more quickly through acquiring beneficial alleles from the standing, hybrid-origin variation, leading to faster evolution.Subject terms: Evolutionary genetics, Evolutionary biology