The cholangiocyte primary cilium in health and disease

Cholangiocytes, like most cells, express primary cilia extending from their membranes. These organelles function as antennae which detect stimuli from bile and transmit the information into cells regulating several signaling pathways involved in secretion, proliferation and apoptosis. The ability of primary cilia to detect different signals is provided by ciliary associated proteins which are expressed in its membrane. Defects in the structure and/or function of these organelles lead to cholangiociliopathies that result in cholangiocyte hyperproliferation, altered fluid secretion and absorption. Since primary cilia dysfunction has been observed in several epithelial tumors, including cholangiocarcinoma (CCA), primary cilia have been proposed as tumor suppressor organelles. In addition, the loss of cilia is associated with dysregulation of several molecular pathways resulting in CCA development and progression. Thus, restoration of the primary cilia may be a potential therapeutic approach for several ciliopathies and CCA.     

Patterns and drivers of aquatic invertebrate diversity across an arid biome

Managing and restoring faunal diversity across large areas requires an understanding of the roles of connectivity and dispersal in driving community patterns. We sought to determine the influence of connectivity, water regime, water source, geographical location, and dispersal traits on patterns of aquatic invertebrate diversity across a continent‐wide arid biome. We compiled data on freshwater invertebrate assemblages from sites spanning the breadth of arid Australia. Univariate analyses (analysis of variance and rarefaction) revealed that alpha and gamma diversity across sites decreased as latitude increased. Multivariate analyses (ordination and analysis of similarity) revealed that community composition had considerable fidelity to geographic regions. Hydrological connectivity was strongly associated with riverine community composition although water rarely flowed (often less than annually). Hydrologically isolated sites (springs and rockholes) supported communities that were markedly dissimilar to hydrologically connected sites, and to each other. We investigated the influence of dispersal on diversity patterns by examining distance decay relationships for each of four dispersal trait groups (obligate aquatic and passive, weak, and strong aerial dispersers) on the basis of geodesic (shortest path) distances between pairs of sites and Mantel tests. We did not detect clear differences between dispersal traits and distance decay relationships at the continental scale, even for the two groups with the lowest dispersal ability (obligate aquatics and passive dispersers). Our results suggest that the loss of hydrological connectivity from water developments in arid lands (for example, the impoundment of intermittent rivers) is likely to affect macroinvertebrates. However, the exact flow mechanisms underlying such changes remain to be determined.     

The large‐scale drivers of population declines in a long‐distance migratory shorebird

Migratory species can travel tens of thousands of kilometers each year, spending different parts of their annual cycle in geographically distinct locations. Understanding the drivers of population change is vital for conserving migratory species, yet the challenge of collecting data over entire geographic ranges has hindered attempts to identify the processes leading to observed population changes. Here, we use remotely sensed environmental data and bird count data to investigate the factors driving variability in abundance in two subspecies of a long‐distance migratory shorebird, the bar‐tailed godwit Limosa lapponica. We compiled a spatially and temporally explicit dataset of three environmental variables to identify the conditions experienced by each subspecies in each stage of their annual cycle (breeding, non‐breeding and staging). We used a Bayesian N‐mixture model to analyze 18 years of monthly count data from 21 sites across Australia and New Zealand in relation to the remote sensing data. We found that the abundance of one subspecies L. l. menzbieri in their non‐breeding range was related to climate conditions in breeding grounds, and detected sustained population declines between 1995 and 2012 in both subspecies (L. l. menzbieri, –6.7% and L. l. baueri, –2.1% year^–1). To investigate the possible causes of the declines, we quantified changes in habitat extent at 22 migratory staging sites in the Yellow Sea, East Asia, over a 25‐year period and found –1.7% and –1.2% year^–1 loss of habitat at staging sites used by L. l. menzbieri and L. l baueri, respectively. Our results highlight the need to identify environmental and anthropogenic drivers of population change across all stages of migration to allow the formulation of effective conservation strategies across entire migratory ranges.     

Overview,opportunities and outlook for Australian spiny lobster fisheries

Australia’s lobster fisheries are relatively small in volume (9500t) compared with global production (289,000t), but are the country’s most valuable in terms of both overall production and value of export (2014 Gross Value of Production of $610 million AUD). Further, they support commercial, recreational and indigenous fishers along most of the continent’s coastline. Here we review similarities and key differences between these lobster fisheries, based on biological characteristics, fishery data collection, assessment and management methods, and supply chain considerations. A diverse range of palinurid lobsters occur in Australia, but only three genera, distributed across eight different management jurisdictions, support significant fisheries. Catches of western rock lobster Panulirus cygnus dominate landings (61%), followed by southern rock lobster Jasus edwardsii, tropical lobster Panulirus ornatus and the eastern rock lobster Sagmariasus verreauxi. Large-scale environmental influences such as climate change are impacting on these fisheries in similar or different ways forcing new management and raising the need for greater resilience in current supply chains. Although these are separate fisheries, the integrated nature of the dominant Chinese export markets suggests potentially important economic and market-related interactions. Our overview highlights the critical role of continued monitoring of recruitment pulses, in combination with robust harvest strategies, to ensure that harvests respond adequately and fisheries achieve biological and economic sustainability. Approaches that also include socio-cultural considerations (triple bottom line) are important given many fisheries include indigenous Australians. Our integrated analysis of Australian lobster fisheries highlights differences and similarities with spiny lobster fisheries worldwide and lessons from opportunities, including adapting to new free trade agreements, enhancing the reputation of wild lobsters as a whole, sharing expertise, and better alignment of supply and demand.     

A net ecosystem carbon budget for snow dominated forested headwater catchments: linking water and carbon fluxes to critical zone carbon storage

Climate-driven changes in carbon (C) cycling of forested ecosystems have the potential to alter long-term C sequestration and the global C balance. Prior studies have shown that C uptake and partitioning in response to hydrologic variation are system specific, suggesting that a comprehensive assessment is required for distinct ecosystems. Many sub-humid montane forest ecosystems in the US are projected to experience increased water limitation over the next decades and existing water-limited forests can be used as a model for how changes in the hydrologic cycle will impact such ecosystems more broadly. Toward that goal we monitored precipitation, net ecosystem exchange and lateral soil and stream C fluxes in three semi-arid to sub-humid montane forest catchments for several years (WY 2009–2013) to investigate how the amount and timing of water delivery affect C stores and fluxes. The key control on aqueous and gaseous C fluxes was the distribution of water between winter and summer precipitation, affecting ecosystem C uptake versus heterotrophic respiration. We furthermore assessed C stores in soil and above- and below-ground biomass to assess how spatial patterns in water availability influence C stores. Topographically-driven patterns in catchment wetness correlated with modeled soil C stores, reflecting both long-term trends in local C uptake as well as lateral redistribution of C leached from upslope organic soil horizons to convergent landscape positions. The results suggest that changes in the seasonality of precipitation from winter snow to summer rain will influence both the amount and the spatial distribution of soil C stores.     

Honest error,precaution or alertness advertisement? Reactions to vertebrate pseudopredators in red‐nosed cuxiús (Chiropotes albinasus), a high‐canopy neotropical primate

Predation on primates is considered to have far‐reaching effects on the foraging and social ecology of a species. Primate species display a variety of responses to predator proximity and attack, ranging from active physical defense and mobbing, to flight and concealment. Warning calls are often given, and potentially threatening animals may be tracked, either actively or with head movements. Such behaviors take time that could be used for other activities. Accordingly, there should be strong selection to respond only to those species that represent a genuine threat. However, primates give defense‐based behaviors to non‐predator species. We tested the hypotheses that responses to pseudopredators are (i) precautionary calls made by individuals following the Dinner/Life Principle, or (ii) represent the ontogeny of species recognition. Of the species that ellicted a response from the cuxiús, 80% resembled a primate predator; 95% of the encounters that elicited a response from the cuxiús occurred when the distance between the pseudopredator and cuxiús was ≤20 m. In regard to the frequency of responses to pseudopredators, we found no difference between adults and juveniles (47.6% and 52.4%, respectively) and no differences between adult males and adult females (60% and 40% of the responses, respectively). However, reactions to pseudopredators were of shorter duration ( ± standard error (SE): 42.2 ± 15.9 s) than were reactions to actual predator species ( ± SE: 1,024.3 ± 329.1 s). There were only three instances where alarm calls were made to species that did not resemble predators, and 66.7% (N = 2) were made by adult cuxiús and only 33.3% (N = 1) were made by a juvenile cuxiú. Therefore, we found partial support for the Dinner/Life Principle hypothesis, but no support for the ontogeny hypothesis. Examination of such responses to pseudopredators in other primate and non‐primate species may help understand the evolution of such behaviors.     

Plant controls on Late Quaternary whole ecosystem structure and function

Plants and animals influence biomass production and nutrient cycling in terrestrial ecosystems; however, their relative importance remains unclear. We assessed the extent to which mega‐herbivore species controlled plant community composition and nutrient cycling, relative to other factors during and after the Late Quaternary extinction event in Britain and Ireland, when two‐thirds of the region's mega‐herbivore species went extinct. Warmer temperatures, plant–soil and plant–plant interactions, and reduced burning contributed to the expansion of woody plants and declining nitrogen availability in our five study ecosystems. Shrub biomass was consistently one of the strongest predictors of ecosystem change, equalling or exceeding the effects of other biotic and abiotic factors. In contrast, there was relatively little evidence for mega‐herbivore control on plant community composition and nitrogen availability. The ability of plants to determine the fate of terrestrial ecosystems during periods of global environmental change may therefore be greater than previously thought.     

Multi-angle light scattering as a process analytical technology measuring real-time molecular weight for downstream process control

For many protein therapeutics including monoclonal antibodies, aggregate removal process can be complex and challenging. We evaluated two different process analytical technology (PAT) applications that couple a purification unit performing preparative hydrophobic interaction chromatography (HIC) to a multi-angle light scattering (MALS) system. Using first principle measurements, the MALS detector calculates weight-average molar mass, M_w and can control aggregate levels in purification. The first application uses an in-line MALS to send start/stop fractionation trigger signals directly to the purification unit when preset M_w criteria are met or unmet. This occurs in real-time and eliminates the need for analysis after purification. The second application uses on-line ultra-high performance size-exclusion liquid chromatography to sample from the purification stream, separating the mAb species and confirming their M_w using a µMALS detector. The percent dimer (1.5%) determined by the on-line method is in agreement with the data from the in-line application (M_w increase of approximately 2750 Da). The novel HIC-MALS systems demonstrated here can be used as a powerful tool for real-time aggregate monitoring and control during biologics purification enabling future real time release of biotherapeutics.     

EVIDENCE FOR GENETIC DIFFERENTIATION BETWEEN CHOKE-INDUCING AND ASYMPTOMATIC STRAINS OF THE EPICHLOË GRASS ENDOPHYTE FROM BRACHYPODIUM SYLVATICUM

Life cycle and breeding system variation in Epichloë grass endophytes (choke disease) is tightly linked to the degree of stroma formation. It is not known whether this variation results from differences in host resistance, fungal virulence, or environmental conditions. We found genetic differentiation between 173 asymptomatic (NS) and 93 stromata-forming (S) Epichloë strains isolated from one grass species, Brachypodium sylvaticum, based on 13 presumed allozyme loci, of which six were variable. The fungal strains originated from 10 sites in Switzerland, three sites of which were represented by both NS and S subpopulations. In total, 19 allozyme genotypes, that were nonrandomly distributed among S and NS were detected. Genetic variation measured as G_ST between S and NS strains isolated from the same site ranged from 0.73 to 0.98. Clonality, measured as linkage disequilibrium at one site, was significant in the NS subpopulation (P ? 0.001), but not in the S subpopulation (P = 0.21), implying asexual reproduction by NS strains as well as successful horizontal transmission of S strains. Since all seeds are usually infected vegetatively, horizontal transmission implies the occurrence of multiple host infections. Altogether, these results provide indirect evidence that NS and S strains do not belong to one panmictic population and that differentiation patterns of stroma formation found in nature are due to genetic differences among fungi in associations with their host plants. We discuss the direction of evolution of disease expression in this system. The distribution of genetic variability suggests that the asymptomatic strains were derived from stromata-forming populations.