Ecological effects of invasive European bird cherry (Prunus padus) on salmonid food webs in Anchorage, Alaska streams

Thesis (M.S.) University of Alaska Fairbanks, 2011Invasive species are a concern worldwide as they can displace native species, reduce biodiversity, and disrupt ecological processes. European bird cherry (Prunus padus) (EBC) is an invasive ornamental tree that is rapidly spreading and possibly displacing native trees along streams in parts of urban Alaska. The objectives of this study were to: 1) map the current distribution of EBC along two Anchorage streams, Campbell and Chester creeks, and 2) determine the effects of EBC on selected ecological processes linked to stream salmon food webs. Data from the 2009 and 2010 field seasons showed: EBC was widely distributed along Campbell and Chester creeks; EBC leaf litter in streams broke down rapidly and supported similar shredder communities to native tree species; and EBC foliage supported significantly less terrestrial invertebrate biomass relative to native deciduous tree species, and contributed significantly less terrestrial invertebrate biomass to streams compared to mixed native vegetation, but riparian EBC did not appear to affect the amount of terrestrial invertebrate prey ingested by juvenile coho salmon (Oncorhynchus kisutch). Although ecological processes did not seem to be dramatically affected by EBC presence, lowered prey abundance as measured in this study may have long-term consequences for stream-rearing fishes as EBC continues to spread over time.US Fish and Wildlife Service, USDA Forest Service, Alaska EPSCoR, Institute of Arctic Biology, and the Department of Biology and Wildlife at UAFIntroduction. Influence of riparian vegetation on stream salmonid food webs ; Riparian vegetation type can affecdt invertebrate prey for stream salmonids ; Effects of invasive riparian plants on stream food webs ; Potential effects of European bird cherry on salmonid food webs -- ch. 1. The abundance and distribution of invasive Prunus spp. in riparian forests along streams in Anchorage, Alaska -- ch. 2. Leaf litter processing is similar between native plants and invasive European bird cherry in urban Alaskan streams -- ch. 3. Invasive European bird cherry disrupts stream-riparian linkages: influence on terrestrial invertebrate prey subsidies for juvenile coho salmon -- Conclusion

Evaluating the Ecological Trade-Offs of Riparian Thinning for Stream Ecosystems in Second-Growth Redwood Forests of Northern California

Riparian forests provide a myriad of ecosystem functions for adjacent streams and rivers, and due to these linkages, changes in riparian forest conditions can have direct implications for stream ecosystems. Resource managers in the coast redwood forests (Sequoia sempervirens) of northern California (USA) are actively thinning second-growth stands to accelerate the recovery of old-growth redwood forest conditions. These restoration thinning treatments have focused on upland forests to date due to contemporary riparian protections, but now attention is shifting towards second-growth forests in riparian zones recovering from previous timber harvests. As a result, resource managers across the Pacific Northwest are interested in exploring whether thinning second-growth riparian forests may have benefits to address multiple management objectives for riparian and stream ecosystems. However, complex ecological trade-offs may emerge to riparian thinning between potential increases in stream temperature that can exceed the thermal tolerance of cold-water adapted species and possible increases in aquatic productivity. In this dissertation I evaluated the influences of riparian thinning on stream ecosystems by examining the effects of thinning on: 1) riparian shade, light, and reach-scale stream temperature responses; 2) how local responses in stream temperature propagated downstream at a watershed extent; 3) light-mediated trophic pathways supporting the food webs of top predators - coastal giant salamander (Dicamptodon tenebrosus) and coastal cutthroat trout (Oncorhynchus clarkii); and 4) how these potential changes in thermal and trophic resources interacted to influence the growth and energetics of coastal cutthroat trout that occupied the study watersheds. Using a unique watershed-scale field experiment following a before-after-control-impact design, I evaluated the effects of riparian thinning by experimentally manipulating riparian canopy conditions and tracking stream responses before and after treatment. Key findings that emerged from this work include: 1) thinning treatments decreased shade and light to the stream, but the magnitude of these changes ranged widely depending on the intensity of treatments; 2) stream temperatures increased locally with thinning under more-intensive treatments, but did not change under less-intensive treatments; 3) local responses in stream temperature often propagated downstream, but the spatial extent of those responses depended on the local magnitude of increase; 4) increases in light associated with thinning had limited influence on trophic pathways supporting stream food webs and food web responses were largely confined to lower trophic levels; 5) growth and energetics of coastal cutthroat trout often varied more seasonally and due to body size than due to thinning treatments. Bioenergetics models estimated that cutthroat trout growth potential could increase with thinning primarily due to increases in consumption highlighting the importance of trophic processes supporting these stream fish. However, the effects of thinning on thermal and trophic processes supporting growth potential for cutthroat trout varied seasonally, where trophic processes were more influential both in spring and overwinter whereas thermal processes had greater influence in summer. Collectively, results from this series of studies highlight that managers need to consider both thermal and food web processes when thinking about the implications of riparian forest management like thinning on stream ecosystems. Moreover, these results illustrate the value of process-based approaches that tease apart underlying mechanisms. An understanding of processes is especially powerful when analyses are combined with year-round studies that capture seasonal variation and watershed-scale analyses that capture spatial patterns across broader spatial extents. Combined, as in this dissertation, such results contribute a more holistic understanding of aquatic responses to riparian thinning that have direct implications for resource managers considering restoration strategies for riparian forests in the redwoods of northern California, but may also apply to other forested watersheds under similar conditions

Riparian defoliation by the invasive green alder sawfly influences terrestrial prey subsidies to salmon streams

Invasive species in riparian forests are unique as their effects can transcend ecosystem boundaries via stream-riparian linkages. The green alder sawfly (Monsoma pulveratum) is an invasive wasp whose larvae are defoliating riparian thin-leaf alder (Alnus tenuifolia) stands across southcentral Alaska. To test the hypothesis that riparian defoliation by this invasive sawfly negatively affects the flow of terrestrial prey resources to stream fishes, we sampled terrestrial invertebrates on riparian alder foliage, their subsidies to streams and their consumption by juvenile coho salmon (Oncorhynchus kisutch). Invasive sawflies altered the composition of terrestrial invertebrates on riparian alder foliage and as terrestrial prey subsidies to streams. Community analyses supported these findings revealing that invasive sawflies shifted the community structure of terrestrial invertebrates between seasons and levels of energy flow (riparian foliage, streams and fish). Invasive sawfly biomass peaked mid-summer, altering the timing and magnitude of terrestrial prey subsidies to streams. Contrary to our hypothesis, invasive sawflies had no effect on the biomass of native taxa on riparian alder foliage, as terrestrial prey subsidies, or in juvenile coho salmon diets. Juvenile coho salmon consumed invasive sawflies when most abundant, but relied more on other prey types selecting against sawflies relative to their availability. Although we did not find effects of invasive sawflies extending to juvenile coho salmon in this study, these results could change as the distribution of invasive sawflies expands or as defoliation intensifies. Nevertheless, riparian defoliation by these invasive sawflies is likely having other ecological effects that merits further investigation

Iron accumulation induces oxidative stress, while depressing inflammatory polarization in human iPSC-derived microglia

Iron accumulation in microglia has been observed in Alzheimer’s disease and other neurodegenerative disorders and is thought to contribute to disease progression through various mechanisms, including neuroinflammation. To study this interaction, we treated human induced pluripotent stem cell-derived microglia (iPSC-MG) with iron, in combination with inflammatory stimuli such as interferon gamma (IFN-γ) and amyloid β. Both IFN-γ and iron treatment increased labile iron levels, but only iron treatment led to a consistent increase of ferritin levels, reflecting long-term iron storage. Therefore, in iPSC-MG, ferritin appeared to be regulated by iron revels rather than inflammation. Further investigation showed that while IFN-γ induced pro-inflammatory activation, iron treatment dampened both classic pro- and anti-inflammatory activation on a transcriptomic level. Notably, iron-loaded microglia showed strong upregulation of cellular stress response pathways, the NRF2 pathway, and other oxidative stress pathways. Functionally, iPSC-MG exhibited altered phagocytosis and impaired mitochondrial metabolism following iron treatment. Collectively, these data suggest that in MG, in contrast to current hypotheses, iron treatment does not result in pro-inflammatory activation, but rather dampens it and induces oxidative stress

A modelling framework for the prediction of the herd-level probability of infection from longitudinal data

International audienceThe collective control programmes (CPs) that exist for many infectious diseases of farm animals rely on the application of diagnostic testing at regular time intervals for the identification of infected animals or herds. The diversity of these CPs complicates the trade of animals between regions or countries because the definition of freedom from infection differs from one CP to another. In this paper, we describe a statistical model for the prediction of herd-level probabilities of infection from longitudinal data collected as part of CPs against infectious diseases of cattle. The model was applied to data collected as part of a CP against bovine viral diarrhoea virus (BVDV) infection in Loire-Atlantique, France. The model represents infection as a herd latent status with a monthly dynamics. This latent status determines test results through test sensitivity and test specificity. The probability of becoming status positive between consecutive months is modelled as a function of risk factors (when available) using logistic regression. Modelling is performed in a Bayesian framework, using either Stan or JAGS. Prior distributions need to be provided for the sensitivities and specificities of the different tests used, for the probability of remaining status positive between months as well as for the probability of becoming positive between months. When risk factors are available, prior distributions need to be provided for the coefficients of the logistic regression, replacing the prior for the probability of becoming positive. From these prior distributions and from the longitudinal data, the model returns posterior probability distributions for being status positive for all herds on the current month. Data from the previous months are used for parameter estimation. The impact of using different prior distributions and model implementations on parameter estimation was evaluated. The main advantage of this model is its ability to predict a probability of being status positive in a month from inputs that can vary in terms of nature of test, frequency of testing and risk factor availability/presence. The main challenge in applying the model to the BVDV CP data was in identifying prior distributions, especially for test characteristics, that corresponded to the latent status of interest, i.e. herds with at least one persistently infected (PI) animal. The model is available on Github as an R package (https://github.com/AurMad/STOCfree) and can be used to carry out output-based evaluation of disease CPs

Amyloid beta accumulations and enhanced neuronal differentiation in cerebral organoids of Dutch-type cerebral amyloid angiopathy patients

IntroductionADutch-type cerebral amyloid angiopathy (D-CAA) is a hereditary brain disorder caused by a point mutation in the amyloid precursor protein (APP) gene. The mutation is located within the amyloid beta (Aβ) domain of APP and leads to Aβ peptide accumulation in and around the cerebral vasculature. There lack of disease models to study the cellular and molecular pathological mechanisms of D-CAA together with the absence of a disease phenotype in vitro in overexpression cell models, as well as the limited availability of D-CAA animal models indicates the need for a D-CAA patient-derived model.MethodsWe generated cerebral organoids from four D-CAA patients and four controls, cultured them up to 110 days and performed immunofluorescent and targeted gene expression analyses at two time points (D52 and D110).ResultsD-CAA cerebral organoids exhibited Aβ accumulations, showed enhanced neuronal and astrocytic gene expression and TGFβ pathway de-regulation.ConclusionsThese results illustrate the potential of cerebral organoids as in vitro disease model of D-CAA that can be used to understand disease mechanisms of D-CAA and can serve as therapeutic intervention platform for various Aβ-related disorders

Delivery of oligonucleotide-based therapeutics : challenges and opportunities

Funding Information: This work was supported by funding from Cooperation of Science and Technology (COST) Action CA17103 (networking grant to V.A-G). V.A-G holds a Miguel Servet Fellowship from the ISCIII [grant reference CPII17/00004] that is part-funded by the European Regional Development Fund (ERDF/FEDER) and also acknowledges funding from Ikerbasque (Basque Foundation for Science). S.M.H is funded by the Medical Research Council and Muscular Dystrophy UK. A.A-R receives funding from amongst others the Duchenne Parent Project, Spieren voor Spieren, the Prinses Beatrix Spierfonds, Duchenne UK and through Horizon2020 project BIND. A.G and R.W.J.C are supported by several foundations including the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Stichting Blinden-Penning, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Oogfonds Nederland, Stichting Macula Degeneratie Fonds, and Stichting Retina Nederland Fonds (who contributed through UitZicht 2015-31 and 2018-21), together with the Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting tot Verbetering van het Lot der Blinden, Stichting voor Ooglijders, and Stichting Dowilvo; as well as the Foundation Fighting Blindness USA, grant no. PPA-0517-0717-RAD. R.A.M.B is supported by Hersenstichting Nederland Grant DR-2018-00253. G.G. is supported by Ministry of Research and Innovation in Romania/National Program 31N/2016/PN 16.22.02.05. S.A is supported by Project PTDC/BBB-BMD/6301/2014 (Funda??o para a Ci?ncia e a Tecnologia?MCTES, Portugal). L.R.D. is supported by Fundaci?n Ram?n Areces Grant XVII CN and Spanish Ministry of Science and Innovation (MICINN, grant PID2019-105344RB-I00). T.L is supported by Estonian Research Council grant PSG226. S.K is supported by the Friedrich-Baur-Stiftung. C.F is funded by The Danish Council for Independent Research, Technology and Production Sciences (grant number DFF-4184-00422). W.vRM is supported by ZonMw Programme Translational Research 2 [Project number 446002002], Campaign Team Huntington and AFM Telethon [Project number 20577]. S.E.B is supported by the H2020 projects B-SMART, Grant number 721058, and REFINE, Grant number 761104. A.T.G is supported by the Institut National de la sant? et la recherche m?dicale (INSERM) and the Association Monegasque contre les myopathies (AMM). L.E. is founded by the Association Monegasque contre les myopathies (AMM). Publisher Copyright: © 2021 The Authors. Published under the terms of the CC BY 4.0 licenseNucleic acid-based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid-based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid-based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide-based therapeutics.publishersversionPeer reviewe

Dicer and miRNA in relation to clinicopathological variables in colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>Dicer is aberrantly expressed in several types of cancers. Applying real-time PCR, we detected the expression of Dicer mRNA in normal mucosa (n = 162), primary colorectal cancer (CRC) (n = 162) and liver metastasis (n = 37), and analysed the relationship between Dicer expression and clinicopathological features. We also correlated the expression of Dicer mRNA to the miRNA expression of miR-141, miR-200a, miR-200b, mir-200c and miR-429 in liver metastases.</p> <p>Methods</p> <p>RT-PCR and qPCR were used to analyse the Dicer expression in normal mucosa, primary tumour and liver metastasis by using the High Capacity cDNA Reverse Transcription Kit and TaqMan™^®Gene Expression assays for <it>Dicer </it>and <it>GAPDH</it>. RT-PCR and qPCR were used to detect miRNA expression in liver metastases by utilizing TaqMan^®MicroRNA Reverse Transcription Kit and TaqMan^®miRNA Assays. Statistical analyses were performed with STATISTICA.</p> <p>Results</p> <p>Dicer expression in rectal cancer (3.146 ± 0.953) was higher than in colon cancer (2.703 ± 1.204, P = 0.018). Furthermore the Dicer expression was increased in primary tumours (3.146 ± 0.952) in comparison to that in normal mucosa from rectal cancer patients (2.816 ± 1.009, P = 0.034) but this is not evident in colon cancer patients. Dicer expression in liver metastases was decreased in comparison to that of either normal mucosa or primary tumour in both colon and rectal cancers (P < 0.05). Patients with a high Dicer expression in normal mucosa had a worse prognosis compared to those with a low Dicer expression, independently of gender, age, tumour site, stage and differentiation (P < 0.001, RR 3.682, 95% CI 1.749 - 7.750). In liver metastases, Dicer was positively related to miR-141 (R = 0.419, P = 0.015).</p> <p>Conclusion</p> <p>Dicer is up-regulated in the early development of rectal cancers. An increased expression of Dicer mRNA in normal mucosa from CRC patients is significantly related to poor survival independently of gender, age, tumour site, stage and differentiation.</p

Virus Capsid Dissolution Studied by Microsecond Molecular Dynamics Simulations

Dissolution of many plant viruses is thought to start with swelling of the capsid caused by calcium removal following infection, but no high-resolution structures of swollen capsids exist. Here we have used microsecond all-atom molecular simulations to describe the dynamics of the capsid of satellite tobacco necrosis virus with and without the 92 structural calcium ions. The capsid expanded 2.5% upon removal of the calcium, in good agreement with experimental estimates. The water permeability of the native capsid was similar to that of a phospholipid membrane, but the permeability increased 10-fold after removing the calcium, predominantly between the 2-fold and 3-fold related subunits. The two calcium binding sites close to the icosahedral 3-fold symmetry axis were pivotal in the expansion and capsid-opening process, while the binding site on the 5-fold axis changed little structurally. These findings suggest that the dissociation of the capsid is initiated at the 3-fold axis