E3 ubiquitin ligase CBLB regulates innate immune responses and bacterial dissemination during nontuberculous mycobacteria infection.

Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens causing pulmonary infection to fatal disseminated disease. NTM infections are steadily increasing in children and adults, and immune-compromised individuals are at a greater risk of fatal infections. The NTM disease's adverse pathology and resistance to antibiotics have further worsened the therapeutic measures. Innate immune regulators are potential targets for therapeutics to NTM, especially in a T cell-suppressed population, and many ubiquitin ligases modulate pathogenesis and innate immunity during infections, including mycobacterial infections. Here, we investigated the role of an E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (CBLB), in immunocompromised mouse models of NTM infection. We found that CBLB is essential to prevent bacterial growth and dissemination. Cblb deficiency debilitated natural killer cells, inflammatory monocytes, and macrophages in vivo. However, Cblb deficiency in macrophages did not wane its ability to inhibit bacterial growth or production of reactive oxygen species or interferon γ production by natural killer cells in vitro. CBLB restricted NTM growth and dissemination by promoting early granuloma formation in vivo. Our study shows that CBLB bolsters innate immune responses and helps prevent the dissemination of NTM during compromised T cell immunity.

Metabolically active angiosperms survive passage through the digestive tract of a large-bodied waterbird.

Avian vectors, such as ducks, swans and geese, are important dispersers of plant propagules. Until recently, it was thought that small vegetative propagules were reliant on adherence to vectors and are unlikely to survive passage through the avian digestive tract. Here, we conclusively demonstrate that metabolically active angiosperms can survive passage through the digestive tract of a large-bodied waterbird. In addition, we show that extended periods of air exposure for up to 7 days does not inhibit the survival of plantlets embedded in faecal matter. Following air exposure, plantlets (n = 3000) were recovered from 75 faecal samples of mute swans, Cygnus olor, with the survival of 203 plantlets. The number of recovered and surviving plantlets did not significantly differ among durations of air exposure. For recovered plantlets, the long-term viability and clonal reproduction of two duckweed species, Lemna minor and L. gibba, were confirmed following greater than eight months of growth. These data further amplify the key role of waterbirds as vectors for aquatic plant dispersal and demonstrate the internal transport (i.e. endozoochory) of metabolically active plantlets. These data suggest dispersal of vegetative plant propagules by avian vectors is likely to be a common occurrence, underpinning connectivity, range expansion and invasions of some aquatic plants.

Ingestion of anthropogenic debris by migratory barnacle geese Branta leucopsis on a remote north-eastern Atlantic island.

Although seabirds are frequently used as sentinel species for anthropogenic pollution, the extent and impacts of synthetic debris ingestion remains poorly studied for many water bird species. Here, we assess ingestion of synthetic particles (≥0.5 mm) by barnacle geese, Branta leucopsis, wintering on a remote island. Faecal samples were collected over a period of four wintering seasons. In total, 71 individual samples were assessed, with 79% of samples displaying at least one debris particle (maximum lengths 0.5-5 mm) from anthropogenic sources. The recovered synthetic debris were identified as micro-fibres (n = 166) and micro-fragments (n = 165). The number of synthetic particles detected per sample was generally low at 4.7 ± 0.9, 43 (mean ± SE, maximum): micro-fibres 2.3 ± 0.3, 10; micro-fragments 2.3 ± 0.8, 40. Particle numbers detected per gram of faecal sample differed amongst wintering seasons. Our results suggest that non-marine water birds can frequently ingest low quantities of synthetic particles in remote coastal habitats.

Memory and adaptive behavior in population dynamics: anti-predator behavior as a case study.

Memory allows organisms to forecast the future on the basis of experience, and thus, in some form, is important for the development of flexible adaptive behavior by animal communities. To model memory, we use the concept of hysteresis, which mathematically is described by the Preisach operator. As a case study, we consider anti-predator adaptation in the classic Lotka-Volterra predator-prey model. Despite its simplicity, the model allows us to naturally incorporate essential features of an adaptive system and memory. Our analysis and simulations show that a system with memory can have a continuum of equilibrium states with non-trivial stability properties. The main factor that determines the actual equilibrium state to which a trajectory converges is the maximal number achieved by the population of predator along this trajectory.

Adaptive behaviour and multiple equilibrium states in a predator-prey model.

There is evidence that multiple stable equilibrium states are possible in real-life ecological systems. Phenomenological mathematical models which exhibit such properties can be constructed rather straightforwardly. For instance, for a predator-prey system this result can be achieved through the use of non-monotonic functional response for the predator. However, while formal formulation of such a model is not a problem, the biological justification for such functional responses and models is usually inconclusive. In this note, we explore a conjecture that a multitude of equilibrium states can be caused by an adaptation of animal behaviour to changes of environmental conditions. In order to verify this hypothesis, we consider a simple predator-prey model, which is a straightforward extension of the classic Lotka-Volterra predator-prey model. In this model, we made an intuitively transparent assumption that the prey can change a mode of behaviour in response to the pressure of predation, choosing either "safe" of "risky" (or "business as usual") behaviour. In order to avoid a situation where one of the modes gives an absolute advantage, we introduce the concept of the "cost of a policy" into the model. A simple conceptual two-dimensional predator-prey model, which is minimal with this property, and is not relying on odd functional responses, higher dimensionality or behaviour change for the predator, exhibits two stable co-existing equilibrium states with basins of attraction separated by a separatrix of a saddle point.

Chaos in a seasonally perturbed SIR model: avian influenza in a seabird colony as a paradigm.

Seasonality is a complex force in nature that affects multiple processes in wild animal populations. In particular, seasonal variations in demographic processes may considerably affect the persistence of a pathogen in these populations. Furthermore, it has been long observed in computer simulations that under seasonal perturbations, a host-pathogen system can exhibit complex dynamics, including the transition to chaos, as the magnitude of the seasonal perturbation increases. In this paper, we develop a seasonally perturbed Susceptible-Infected-Recovered model of avian influenza in a seabird colony. Numerical simulations of the model give rise to chaotic recurrent epidemics for parameters that reflect the ecology of avian influenza in a seabird population, thereby providing a case study for chaos in a host- pathogen system. We give a computer-assisted exposition of the existence of chaos in the model using methods that are based on the concept of topological hyperbolicity. Our approach elucidates the geometry of the chaos in the phase space of the model, thereby offering a mechanism for the persistence of the infection. Finally, the methods described in this paper may be immediately extended to other infections and hosts, including humans.

Intrapopulational distribution of Meiogymnophallus minutus (Digenea, Gymnophallidae) infections in its first and second intermediate host.

Host size and age are generally assumed to play a pivotal role in digenean trematode infection patterns, accounting for much of the variation found within intermediate host populations. However, knowledge is based on a limited number of studied host-parasite systems. We investigated the shell length class distribution of Meiogymnophallus minutus infections within populations of the first intermediate host Scrobicularia plana and second intermediate host Cerastoderma edule. Infections occurred very early in the life of the two intermediate hosts. Both prevalence and intensity of infections increased with host shell length and displayed extremely high values amongst large individuals. Whilst metacercarial infection patterns in juvenile C. edule could be best explained by differences in host shell length, in adult cockles, the effect of host age on infection levels prevailed. The microsporidian hyperparasite Unikaryon legeri, occurring in the metacercarial stage of M. minutus, was particularly abundant in aged cockles, strongly influencing infection patterns of the gymnophallid. Our results are consistent with the intrapopulational distribution reported from other digenean trematode parasites. The relative influence of both host size and age and the underlying mechanisms as well as the impact of hyperparasitism on M. minutus infection patterns are discussed.

Aminoguanidine reduces cisplatin ototoxicity.

Cisplatin is known to cause high-frequency neurosensory hearing loss. While reactive oxygen species have been shown to play a role, reactive nitrogen species have been implicated, but not proven to be involved, in cisplatin ototoxicity. The purpose of the present study was to investigate the role of nitric oxide (*NO) in cisplatin ototoxicity by administering aminoguanidine (AG), a relatively specific inhibitor of inducible nitric oxide synthase (iNOS), in conjunction with cisplatin. Rats were injected with cisplatin, AG, or both. Auditory brainstem evoked responses (ABR) were measured before and 3 days after cisplatin administration. The cochlear tissue was then assayed for *NO and malondialdehyde. Cisplatin alone caused significant ABR threshold shifts at all stimuli tested, whereas AG alone caused no shifts. There was a significant reduction in threshold shift for clicks and 16 kHz tone bursts (but not 32 kHz) when AG was given with cisplatin. The malondialdehyde concentration (but not the *NO concentration) in the AG/cisplatin group was significantly lower than that of the cisplatin group. This suggests that AG reduces cisplatin ototoxicity by directly scavenging hydroxyl radicals. The iNOS pathway may play a role in the generation of free radicals and hearing loss resulting from cisplatin administration, but this conclusion was not supported by our data.