A global analysis of the determinants of alien geographical range size in birds

Aim Determining the causes of range size variation in the distributions of alien species is important for understanding the spread of invasive species. Factors influencing alien range size have been explored for some species at a regional level, but to date there has been no global analysis of an entire class. Here, we present such an analysis for birds, testing for the effects of introduction event, location and species‐level variables on alien range sizes. Location Global. Methods We used a novel dataset on the global distributions of alien bird species to test for relationships between alien range size and colonization pressure, residence time, extent of the global climatic niche, native range size, body mass and specialization, using a statistical approach based on phylogenetic generalized least squares models. We performed this analysis globally, and for separate biogeographical realms. Results Approximately half of the variation in alien bird range size is explained by colonization pressure in univariate analysis. We identified consistent effects of higher colonization pressure at global and realm levels, as well as support for effects of native range size and residence time. We found less support for effects of body mass, specialization or extent of the global climatic niche on alien range size. Main conclusions Alien bird range sizes are generally small relative to their native range sizes, and many are continuing to expand. Nevertheless, current variation is predictable, most strongly by the event‐level factor of colonization pressure. Whether a species is widespread is a better predictor of alien range size than whether a species could be widespread (estimated by global climatic niche extent), while we also find effects of residence time on alien range size. These relationships may help to identify those alien species that are more likely to spread and hence have greater environmental and economic impacts where they have been introduced.     

Bioavailability of silymarin flavonolignans: drug formulations and biotransformation

Over the past years, great advances have been made on the development of novel delivery systems for bioactive natural compounds, in parallel to their structural modification via chemical, chemo-enzymatic and enzymatic methodologies. These approaches give rise to novel formulations and derivatives that often display advantages over the parental molecule, such as enhanced bioavailability and pharmacological activity, due to improved dissolution and stability. Silymarin components suffer from poor solubility in water and lipid media and their resorption in the intestine is rather limited. Moreover, silybin undergoes intensive Phase II metabolism and is rapidly excreted in bile and urine, leading to low therapeutic efficacy. This work aims to present the current status of available silymarin formulations, and to highlight successful efforts for the biotransformation of its constituent flavonolignans towards the synthesis of novel derivatives. Herein, various pharmaceutical formulations that aim at the bioavailability improvement of these fascinating phytochemicals, i.e., liposomes, phytosomes, self-microemulsifying drug delivery systems, solid dispersions systems, dripping pills, nanosuspensions, floating tablets, and micronization, are reviewed. Silybin (semi)synthetic derivatives prepared by chemical or enzymatic methods, such as fatty acid conjugates, silybin bishemisuccinate, silybin glycosides, silybin sulfates, silybinic acid, and 2,3-dehydrosilybin, are also discussed in detail. Additionally, this work attempts to direct the attention towards the pharmacological implications of optically pure silybin A and silybin B and their biotransformation reactions, both Phase I and II, in relation to bioavailability.     

Insulin stimulation of GLUT4 exocytosis, but not its inhibition of endocytosis, is dependent on RabGAP AS160

Insulin maintains whole body blood glucose homeostasis, in part, by regulating the amount of the GLUT4 glucose transporter on the cell surface of fat and muscle cells. Insulin induces the redistribution of GLUT4 from intracellular compartments to the plasma membrane, by stimulating a large increase in exocytosis and a smaller inhibition of endocytosis. A considerable amount is known about the molecular events of insulin signaling and the complex itinerary of GLUT4 trafficking, but less is known about how insulin signaling is transmitted to GLUT4 trafficking. Here, we show that the AS160 RabGAP, a substrate of Akt, is required for insulin stimulation of GLUT4 exocytosis. A dominant-inhibitory mutant of AS160 blocks insulin stimulation of exocytosis at a step before the fusion of GLUT4-containing vesicles with the plasma membrane. This mutant, however, does not block insulin-induced inhibition of GLUT4 endocytosis. These data support a model in which insulin signaling to the exocytosis machinery (AS160 dependent) is distinct from its signaling to the internalization machinery (AS160 independent).     

TLR2 stimulation drives human naive and effector regulatory T cells into a Th17-like phenotype with reduced suppressive function

Naturally occurring CD4(+)CD25(+)FOXP3(+) regulatory T cells suppress the activity of pathogenic T cells and prevent development of autoimmune responses. There is growing evidence that TLRs are involved in modulating regulatory T cell (Treg) functions both directly and indirectly. Specifically, TLR2 stimulation has been shown to reduce the suppressive function of Tregs by mechanisms that are incompletely understood. The developmental pathways of Tregs and Th17 cells are considered divergent and mutually inhibitory, and IL-17 secretion has been reported to be associated with reduced Treg function. We hypothesized that TLR2 stimulation may reduce the suppressive function of Tregs by regulating the balance between Treg and Th17 phenotype and function. We examined the effect of different TLR2 ligands on the suppressive functions of Tregs and found that activation of TLR1/2 heterodimers reduces the suppressive activity of CD4(+)CD25(hi)FOXP3(low)CD45RA(+) (naive) and CD4(+)CD25(hi)FOXP3(hi)CD45RA(-) (memory or effector) Treg subpopulations on CD4(+)CD25(-)FOXP3(-)CD45RA(+) responder T cell proliferation while at the same time enhancing the secretion of IL-6 and IL-17, increasing RORC, and decreasing FOXP3 expression. Neutralization of IL-6 or IL-17 abrogated Pam3Cys-mediated reduction of Treg suppressive function. We also found that, in agreement with recent observations in mouse T cells, TLR2 stimulation can promote Th17 differentiation of human T helper precursors. We conclude that TLR2 stimulation, in combination with TCR activation and costimulation, promotes the differentiation of distinct subsets of human naive and memory/effector Tregs into a Th17-like phenotype and their expansion. Such TLR-induced mechanism of regulation of Treg function could enhance microbial clearance and increase the risk of autoimmune reactions.     

Opposing functions for retromer and Rab11 in extracellular vesicle traffic at presynaptic terminals

Neuronal extracellular vesicles (EVs) play important roles in intercellular communication and pathogenic protein propagation in neurological disease. However, it remains unclear how cargoes are selectively packaged into neuronal EVs. Here, we show that loss of the endosomal retromer complex leads to accumulation of EV cargoes including amyloid precursor protein (APP), synaptotagmin-4 (Syt4), and neuroglian (Nrg) at Drosophila motor neuron presynaptic terminals, resulting in increased release of these cargoes in EVs. By systematically exploring known retromer-dependent trafficking mechanisms, we show that EV regulation is separable from several previously identified roles of neuronal retromer. Conversely, mutations in rab11 and rab4, regulators of endosome-plasma membrane recycling, cause reduced EV cargo levels, and rab11 suppresses cargo accumulation in retromer mutants. Thus, EV traffic reflects a balance between Rab4/Rab11 recycling and retromer-dependent removal from EV precursor compartments. Our data shed light on previous studies implicating Rab11 and retromer in competing pathways in Alzheimer’s disease, and suggest that misregulated EV traffic may be an underlying defect.     

Structural determinants of calmodulin binding to the intracellular C-terminal domain of the metabotropic glutamate receptor 7A

Calmodulin (CaM) binds in a Ca2+-dependent manner to the intracellular C-terminal domains of most group III metabotropic glutamate receptors (mGluRs). Here we combined mutational and biophysical approaches to define the structural basis of CaM binding to mGluR 7A. Ca2+/CaM was found to interact with mGluR 7A primarily via its C-lobe at a 1:1 CaM:C-tail stoichiometry. Pulldown experiments with mutant CaM and mGluR 7A C-tail constructs and high resolution NMR with peptides corresponding to the CaM binding region of mGluR 7A allowed us to define hydrophobic and ionic interactions required for Ca2+/CaM binding and identified a 1-8-14 CaM-binding motif. The Ca2+/CaM.mGluR 7A peptide complex displays a classical wraparound structure that closely resembles that formed by Ca2+/CaM upon binding to smooth muscle myosin light chain kinase. Our data provide insight into how Ca2+/CaM regulates group III mGluR signaling via competition with intracellular proteins for receptor-binding sites.     

Population structure and phylogeography of the Gentoo Penguin (Pygoscelis papua) across the Scotia Arc

Climate change, fisheries' pressure on penguin prey, and direct human disturbance of wildlife have all been implicated in causing large shifts in the abundance and distribution of penguins in the Southern Ocean. Without mark‐recapture studies, understanding how colonies form and, by extension, how ranges shift is challenging. Genetic studies, particularly focused on newly established colonies, provide a snapshot of colonization and can reveal the extent to which shifts in abundance and occupancy result from changes in demographic rates (e.g., reproduction and survival) or migration among suitable patches of habitat. Here, we describe the population structure of a colonial seabird breeding across a large latitudinal range in the Southern Ocean. Using multilocus microsatellite genotype data from 510 Gentoo penguin (Pygoscelis papua) individuals from 14 colonies along the Scotia Arc and Antarctic Peninsula, together with mitochondrial DNA data, we find strong genetic differentiation between colonies north and south of the Polar Front, that coincides geographically with the taxonomic boundary separating the subspecies P. p. papua and P. p. ellsworthii. Using a discrete Bayesian phylogeographic approach, we show that southern Gentoos expanded from a possible glacial refuge in the center of their current range, colonizing regions to the north and south through rare, long‐distance dispersal. Our findings show that this dispersal is important for new colony foundation and range expansion in a seabird species that ordinarily exhibits high levels of natal philopatry, though persistent oceanographic features serve as barriers to movement.     

Community Attitudes and Practices of Urban Residents Regarding Predation by Pet Cats on Wildlife: An International Comparison

International differences in practices and attitudes regarding pet cats'' interactions with wildlife were assessed by surveying citizens from at least two cities in Australia, New Zealand, the UK, the USA, China and Japan. Predictions tested were: (i) cat owners would agree less than non-cat owners that cats might threaten wildlife, (ii) cat owners value wildlife less than non-cat owners, (iii) cat owners are less accepting of cat legislation/restrictions than non-owners, and (iv) respondents from regions with high endemic biodiversity (Australia, New Zealand, China and the USA state of Hawaii) would be most concerned about pet cats threatening wildlife. Everywhere non-owners were more likely than owners to agree that pet cats killing wildlife were a problem in cities, towns and rural areas. Agreement amongst non-owners was highest in Australia (95%) and New Zealand (78%) and lowest in the UK (38%). Irrespective of ownership, over 85% of respondents from all countries except China (65%) valued wildlife in cities, towns and rural areas. Non-owners advocated cat legislation more strongly than owners except in Japan. Australian non-owners were the most supportive (88%), followed by Chinese non-owners (80%) and Japanese owners (79.5%). The UK was least supportive (non-owners 43%, owners 25%). Many Australian (62%), New Zealand (51%) and Chinese owners (42%) agreed that pet cats killing wildlife in cities, towns and rural areas was a problem, while Hawaiian owners were similar to the mainland USA (20%). Thus high endemic biodiversity might contribute to attitudes in some, but not all, countries. Husbandry practices varied internationally, with predation highest where fewer cats were confined. Although the risk of wildlife population declines caused by pet cats justifies precautionary action, campaigns based on wildlife protection are unlikely to succeed outside Australia or New Zealand. Restrictions on roaming protect wildlife and benefit cat welfare, so welfare is a better rationale.     

Nest trampling and ground nesting birds: Quantifying temporal and spatial overlap between cattle activity and breeding redshank

Conservation grazing for breeding birds needs to balance the positive effects on vegetation structure and negative effects of nest trampling. In the UK, populations of Common redshank Tringa totanus breeding on saltmarshes declined by >50% between 1985 and 2011. These declines have been linked to changes in grazing management. The highest breeding densities of redshank on saltmarshes are found in lightly grazed areas. Conservation initiatives have encouraged low‐intensity grazing at <1 cattle/ha, but even these levels of grazing can result in high levels of nest trampling. If livestock distribution is not spatially or temporally homogenous but concentrated where and when redshank breed, rates of nest trampling may be much higher than expected based on livestock density alone. By GPS tracking cattle on saltmarshes and monitoring trampling of dummy nests, this study quantified (i) the spatial and temporal distribution of cattle in relation to the distribution of redshank nesting habitats and (ii) trampling rates of dummy nests. The distribution of livestock was highly variable depending on both time in the season and the saltmarsh under study, with cattle using between 3% and 42% of the saltmarsh extent and spending most their time on higher elevation habitat within 500 m of the sea wall, but moving further onto the saltmarsh as the season progressed. Breeding redshank also nest on these higher elevation zones, and this breeding coincides with the early period of grazing. Probability of nest trampling was correlated to livestock density and was up to six times higher in the areas where redshank breed. This overlap in both space and time of the habitat use of cattle and redshank means that the trampling probability of a nest can be much higher than would be expected based on standard measures of cattle density. Synthesis and applications: Because saltmarsh grazing is required to maintain a favorable vegetation structure for redshank breeding, grazing management should aim to keep livestock away from redshank nesting habitat between mid‐April and mid‐July when nests are active, through delaying the onset of grazing or introducing a rotational grazing system.