High levels of congenital transmission of Toxoplasma gondii in a commercial sheep flock

Our current understanding of congenital transmission of Toxoplasma gondii from ewe to lamb dictates that infection frequently results in abortion and the death of the developing foetus, that the birth of live infected lambs occurs rarely and that the cat is the predominant source of infection in ewes. Using direct polymerase chain reaction detection of T. gondii, we report high levels of congenital transmission occurring in a commercially managed sheep flock. We sampled foetal-derived placental tissue and tissues from aborted lambs and showed that congenital transmission was detected in these tissues from 61% of all pregnancies. Where pregnancies resulted in the death of one or more lambs, T. gondii was detected in the lamb tissue for all but one of 18 (94%) pregnancies. Of the successful pregnancies resulting in the birth of live lambs we were able to detect T. gondii in foetal-derived placental tissue from 37 of 70 (42%) pregnancies. These results show that congenital transmission is occurring in a high percentage of lambings including normal healthy lambings, at this farm, suggesting that this route of transmission from generation to generation may be much more significant than that reported previously. These results may have implications for sheep husbandry and future epidemiological studies of T. gondii.     

Small Molecule-facilitated Degradation of ANO1 Protein: A NEW TARGETING APPROACH FOR ANTICANCER THERAPEUTICS

ANO1, a calcium-activated chloride channel, is highly expressed and amplified in human cancers and is a critical survival factor in these cancers. The ANO1 inhibitor CaCC_inh-A01 decreases proliferation of ANO1-amplified cell lines; however, the mechanism of action remains elusive. We explored the mechanism behind the inhibitory effect of CaCC_inh-A01 on cell proliferation using a combined experimental and in silico approach. We show that inhibition of ANO1 function is not sufficient to diminish proliferation of ANO1-dependent cancer cells. We report that CaCC_inh-A01 reduces ANO1 protein levels by facilitating endoplasmic reticulum-associated, proteasomal turnover of ANO1. Washout of CaCC_inh-A01 rescued ANO1 protein levels and resumed cell proliferation. Proliferation of newly derived CaCC_inh-A01-resistant cell pools was not affected by CaCC_inh-A01 as compared with the parental cells. Consistently, CaCC_inh-A01 failed to reduce ANO1 protein levels in these cells, whereas ANO1 currents were still inhibited by CaCC_inh-A01, indicating that CaCC_inh-A01 inhibits cell proliferation by reducing ANO1 protein levels. Furthermore, we employed in silico methods to elucidate novel biological functions of ANO1 inhibitors. Specifically, we derived a pharmacophore model to describe inhibitors capable of promoting ANO1 degradation and report new inhibitors of ANO1-dependent cell proliferation. In summary, our data demonstrate that inhibition of the channel activity of ANO1 is not sufficient to inhibit ANO1-dependent cell proliferation, indicating that the role of ANO1 in cancer only partially depends on its function as a channel. Our results provide an impetus for gaining a deeper understanding of ANO1 modulation in cells and introduce a new targeting approach for antitumor therapy in ANO1-amplified cancers.     

Wading through the swamp: what does tropical peatland restoration mean to national‐level stakeholders in Indonesia?

Ecological restoration is considered to play an important role in mitigating climate change, protecting biodiversity, and preventing environmental degradation. Yet, there are often multiple perspectives on what outcomes restoration should be aiming to achieve, and how we should get to that point. In this study we interview a range of policymakers, academics, and non‐governmental organization (NGO) representatives to explore the range of perspectives on the restoration of Indonesia's tropical peatlands—key global ecosystems that have undergone large‐scale degradation. Thematic analysis suggests that participants agreed about the importance of restoration, but had differing opinions on how effective restoration activities to date have been and what a restored peatland landscape should look like. These results exemplify how ecological restoration can mean different things to different people, but also highlight important areas of consensus for moving forward with peatland restoration strategies.     

Changing estuaries and impacts on juvenile salmon: A systematic review

Estuaries are productive ecosystems providing important habitat for a diversity of species, yet they also experience intense levels of anthropogenic development. To inform decision‐making, it is essential to understand the pathways of impacts of particular human activities, especially those that affect species such as salmon, which have high ecological, social‐cultural and economic values. Salmon systems provide an opportunity to build from the substantial body of research on responses to estuary developments and take stock of what is known. We conducted a systematic English‐language literature review on the responses of juvenile salmon to anthropogenic activities in estuaries and nearshore areas asking: what has been studied, where are the major knowledge gaps and how do stressors affect salmon? We found a substantial body of research (n = 167 studies; 1,369 comparative tests) to help understand responses of juvenile salmon to 24 activities and their 14 stressors. Across studies, 82% of the research was conducted in the eastern Pacific (Oregon and Washington, USA and British Columbia, Canada) showing a limited geographical scope. Using a semiquantitative approach to summarize the literature, including a weight‐of‐evidence metric, we found a range of results from low to moderate–high confidence in the consequences of the stressors. For example, we found moderate–high confidence in the negative impacts of pollutants and sea lice and moderate confidence in negative impacts from connectivity loss and changes in flow. Our results suggest that overall, multiple anthropogenic activities cause negative impacts across ecological scales. However, our results also reveal knowledge gaps resulting from minimal research on particular species (e.g. sockeye salmon), regions (e.g. Atlantic) or stressors (e.g. entrainment) that would be expedient areas for future research. With estuaries acting as a nexus of biological and societal importance and hotspots of ongoing development, the insights gained here can contribute to informed decision‐making.     

Seed size,number and strategies in annual plants: a comparative functional analysis and synthesis

Background and AimsPlants depend fundamentally on establishment from seed. However, protocols in trait-based ecology currently estimate seed size but not seed number. This can be rectified. For annuals, seed number should simply be a positive function of vegetative biomass and a negative function of seed size.MethodsUsing published values of comparative seed number as the ‘gold standard’ and a large functional database, comparative seed yield and number per plant and per m² were predicted by multiple regression. Subsequently, ecological variation in each was explored for English and Spanish habitats, newly calculated C-S-R strategies and changed abundance in the British flora.Key ResultsAs predicted, comparative seed mass yield per plant was consistently a positive function of plant size and competitive ability, and largely independent of seed size. Regressions estimating comparative seed number included, additionally, seed size as a negative function. Relationships differed numerically between regions, habitats and C-S-R strategies. Moreover, some species differed in life history over their geographical range. Comparative seed yield per m² was positively correlated with FAO crop yield, and increasing British annuals produced numerous seeds. Nevertheless, predicted values must be viewed as comparative rather than absolute: they varied according to the ‘gold standard’ predictor used. Moreover, regressions estimating comparative seed yield per m² achieved low precision.ConclusionsFor the first time, estimates of comparative seed yield and number for >800 annuals and their predictor equations have been produced and the ecological importance of these regenerative traits has been illustrated. ‘Regenerative trait-based ecology’ remains in its infancy, with work needed on determinate vs. indeterminate flowering (‘bet-hedging’), C-S-R methodologies, phylogeny, comparative seed yield per m² and changing life history. Nevertheless, this has been a positive start and readers are invited to use estimates for >800 annuals, in the Supplementary data, to help advance ‘regenerative trait-based ecology’ to the next level.     

Foraging interactions between Wandering Albatrosses Diomedea exulans breeding on Marion Island and long-line fisheries in the southern Indian Ocean

Wandering Albatrosses Diomedea exulans are frequently killed when they attempt to scavenge baited hooks deployed by long-line fishing vessels. We studied the foraging ecology of Wandering Albatrosses breeding on Marion Island in order to assess the scale of interactions with known long-line fishing fleets. During incubation and late chick-rearing, birds foraged further away from the island, in warmer waters, and showed high spatial overlap with areas of intense tuna Thunnus spp. long-line fishing. During early chick-rearing, birds made shorter foraging trips and showed higher spatial overlap with the local Patagonian Toothfish Dissostichus eleginoides long-line fishery. Tracks of birds returning with offal from the Toothfish fishery showed a strong association with positions at which Toothfish long-lines were set and most diet samples taken during this stage contained fishery-related items. Independent of these seasonal differences, females foraged further from the islands and in warmer waters than males. Consequently, female distribution overlapped more with tuna long-line fisheries, whereas males interacted more with the Toothfish long-line fishery. These factors could lead to differences in the survival probabilities of males and females. Non-breeding birds foraged in warmer waters and showed the highest spatial overlap with tuna long-line fishing areas. The foraging distribution of Marion Island birds showed most spatial overlap with birds from the neighbouring Crozet Islands during the late chick-rearing and non-breeding periods. These areas of foraging overlap also coincided with areas of intense tuna long-line fishing south of Africa. As the population trends of Wandering Albatrosses at these two localities are very similar, it is possible that incidental mortality during the periods when these two populations show the highest spatial overlap could be driving these trends.     

A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration.

We have produced yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 and YAC72) huntingtin (htt) in a developmental and tissue-specific manner identical to that observed in Huntington's disease (HD). YAC46 and YAC72 mice show early electrophysiological abnormalities, indicating cytoplasmic dysfunction prior to observed nuclear inclusions or neurodegeneration. By 12 months of age, YAC72 mice have a selective degeneration of medium spiny neurons in the lateral striatum associated with the translocation of N-terminal htt fragments to the nucleus. Neurodegeneration can be present in the absence of macro- or microaggregates, clearly showing that aggregates are not essential to initiation of neuronal death. These mice demonstrate that initial neuronal cytoplasmic toxicity is followed by cleavage of htt, nuclear translocation of htt N-terminal fragments, and selective neurodegeneration.