bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma
Authors: Chiasseu Marius , Cueva Vargas Jorge L. , Destroismaisons Laurie , Vande Velde Christine , Leclerc Nicole , Di Polo Adriana 
Published: May 2016

Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by the selective death of retinal ganglion cells (RGCs). Ocular hypertension is the most significant known risk factor for developing the disease, but the mechanism by which elevated pressure damages RGCs is currently unknown. The axonal-enriched microtubule-associated protein tau is a key mediator of neurotoxicity in Alzheimer's disease and other tauopathies. Using a well characterizedin vivorat glaucoma model, we show an age-related increase in endogenous retinal tau that was markedly exacerbated by ocular hypertension. Early alterations in tau phosphorylation, characterized by epitope-dependent hyperphosphorylation and hypophosphorylation, correlated with the appearance of tau oligomers in glaucomatous retinas. Our data demonstrate the mislocalization of tau in the somatodendritic compartment of RGCs subjected to high intraocular pressure. In contrast, tau was depleted from RGC axons in the optic nerve of glaucomatous eyes. Importantly, intraocular administration of short interfering RNA against tau effectively reduced retinal tau accumulation and promoted robust survival of RGC somas and axons, supporting a critical role for tau alterations in ocular hypertension-induced neuronal damage. Our study reveals that glaucoma displays signature pathological features of tauopathies, including tau accumulation, altered phosphorylation, and missorting; and identifies tau as a novel target to counter RGC neurodegeneration in glaucoma and prevalent optic neuropathies.SIGNIFICANCE STATEMENTIn this study, we investigated the role of tau in retinal ganglion cell (RGC) damage in glaucoma. We demonstrate that high intraocular pressure leads to a rapid increase in endogenous retinal tau with altered phosphorylation profile and the formation of tau oligomers. Tau accumulation was primarily observed in RGC dendrites, while tau in RGC axons within the optic nerve was depleted. Attenuation of endogenous retinal tau using a targeted siRNA led to striking protection of RGC somas and axons from hypertension-induced damage. Our study identifies novel and substantial alterations of endogenous tau protein in glaucoma, including abnormal subcellular distribution, an altered phosphorylation profile, and neurotoxicity.
Optogenetic Interrogation of Functional Synapse Formation by Corticospinal Tract Axons in the Injured Spinal Cord
Authors: Jayaprakash Naveen , Wang Zimei , Hoeynck Brian , Krueger Nicholas , Kramer Audra , Balle Eric , Wheeler Daniel S. , Wheeler Robert A. , Blackmore Murray G. 
Published: May 2016

To restore function after injury to the CNS, axons must be stimulated to extend into denervated territory and, critically, must form functional synapses with appropriate targets. We showed previously that forced overexpression of the transcription factor Sox11 increases axon growth by corticospinal tract (CST) neurons after spinal injury. However, behavioral outcomes were not improved, raising the question of whether the newly sprouted axons are able to form functional synapses. Here we developed an optogenetic strategy, paired with single-unit extracellular recordings, to assess the ability of Sox11-stimulated CST axons to functionally integrate in the circuitry of the cervical spinal cord. Initial time course experiments established the expression and function of virally expressed Channelrhodopsin (ChR2) in CST cell bodies and in axon terminals in cervical spinal cord. Pyramidotomies were performed in adult mice to deprive the left side of the spinal cord of CST input, and the right CST was treated with adeno-associated virus (AAV)–Sox11 or AAV–EBFP control, along with AAV–ChR2. As expected, Sox11 treatment caused robust midline crossing of CST axons into previously denervated left spinal cord. Clear postsynaptic responses resulted from optogenetic activation of CST terminals, demonstrating the ability of Sox11-stimulated axons to form functional synapses. Mapping of the distribution of CST-evoked spinal activity revealed overall similarity between intact and newly innervated spinal tissue. These data demonstrate the formation of functional synapses by Sox11-stimulated CST axons without significant behavioral benefit, suggesting that new synapses may be mistargeted or otherwise impaired in the ability to coordinate functional output.SIGNIFICANCE STATEMENTAs continued progress is made in promoting the regeneration of CNS axons, questions of synaptic integration are increasingly prominent. Demonstrating direct synaptic integration by regenerated axons and distinguishing its function from indirect relay circuits and target field plasticity have presented technical challenges. Here we force the overexpression of Sox11 to stimulate the growth of corticospinal tract axons in the cervical spinal cord and then use specific optogenetic activation to assess their ability to directly drive postsynaptic activity in spinal cord neurons. By confirming successful synaptic integration, these data illustrate a novel optogenetic-based strategy to monitor and optimize functional reconnection by newly sprouted axons in the injured CNS.
Chemogenomics and orthology‐based design of antibiotic combination therapies
Authors: Chandrasekaran Sriram , Cokol‐Cakmak Melike , Sahin Nil , Yilancioglu Kaan , Kazan Hilal , Collins James J , Cokol Murat 
Published: May 2016

AbstractCombination antibiotic therapies are being increasingly used in the clinic to enhance potency and counter drug resistance. However, the large search space of candidate drugs and dosage regimes makes the identification of effective combinations highly challenging. Here, we present a computational approach called INDIGO, which uses chemogenomics data to predict antibiotic combinations that interact synergistically or antagonistically in inhibiting bacterial growth. INDIGO quantifies the influence of individual chemical–genetic interactions on synergy and antagonism and significantly outperforms existing approaches based on experimental evaluation of novel predictions in Escherichia coli. Our analysis revealed a core set of genes and pathways (e.g. central metabolism) that are predictive of antibiotic interactions. By identifying the interactions that are associated with orthologous genes, we successfully estimated drug‐interaction outcomes in the bacterial pathogens Mycobacterium tuberculosis and Staphylococcus aureus, using the E. coli INDIGO model. INDIGO thus enables the discovery of effective combination therapies in less‐studied pathogens by leveraging chemogenomics data in model organisms.
Will climate change increase the risk of plant invasions into mountains?
Authors: Petitpierre Blaise , McDougall Keith , Seipel Tim , Broennimann Olivier , Guisan Antoine , Kueffer Christoph 
Published: May 2016

AbstractMountain ecosystems have been less adversely affected by invasions of nonnative plants than most other ecosystems, partially because most invasive plants in the lowlands are limited by climate and cannot grow under harsher high‐elevation conditions. However, with ongoing climate change, invasive species may rapidly move upwards and threaten mid‐, and then high‐elevation mountain ecosystems. We evaluated this threat by modeling the current and future habitat suitability for 48 invasive plant species in Switzerland and New South Wales, Australia. Both regions had contrasting climate interactions with elevation, resulting in possible different responses of species distributions to climate change. Using a species distribution modeling approach that combines data from two spatial scales, we built high‐resolution species distribution models (≤250 m) that account for the global climatic niche of species and also finer variables depicting local climate and disturbances. We found that different environmental drivers limit the elevation range of invasive species in each of the two regions, leading to region‐specific species responses to climate change. The optimal suitability for plant invaders is predicted to markedly shift from the lowland to the montane or subalpine zone in Switzerland, whereas the upward shift is far less pronounced in New South Wales where montane and subalpine elevations are already suitable. The results suggest that species most likely to invade high elevations in Switzerland will be cold‐tolerant, whereas species with an affinity to moist soils are most likely to invade higher elevations in Australia. Other plant traits were only marginally associated with elevation limits. These results demonstrate that a more systematic consideration of future distributions of invasive species is required in conservation plans of not yet invaded mountainous ecosystems.
Conservation vs. livelihoods: spatial management of non‐timber forest product harvests in a two‐dimensional model
Authors: Robinson Brian E. 
Published: May 2016

AbstractAreas of high biodiversity often coincide with communities living in extreme poverty. As a livelihood support, these communities often harvest wild products from the environment. But harvest activities can have negative impacts on fragile and globally important ecosystems. This paper examines trade‐offs in ecological protection and community welfare from the harvest of wild products. With a novel model and empirical evidence, I show that management of harvest activity does not always resolve these trade‐offs. In a model of continuous harvests in a two‐dimensional landscape, managed harvest activity improves welfare, but is uniformly bad for other ecosystem services that are sensitive to the presence (as opposed to the intensity) of human activity. Empirical results from a unique dataset of mushroom harvesters in Yunnan, China suggest more experienced, poorer, and more vulnerable individuals tend to rely on more distant harvests. Thus, policies that limit the extent of forest travel, such as protected areas, may protect fragile ecosystems but can have a disproportionately negative effect on those most vulnerable.
Evolutionary patterns and physicochemical properties explain macroinvertebrate sensitivity to heavy metals
Authors: Malaj Egina , Guénard Guillaume , Schäfer Ralf B. , von der Ohe Peter C. 
Published: May 2016

AbstractEcological risk assessment depends strongly on species sensitivity data. Typically, sensitivity data are based on laboratory toxicity bioassays, which for practical constraints cannot be exhaustively performed for all species and chemicals available. Bilinear models integrating phylogenetic information of species and physicochemical properties of compounds allow to predict species sensitivity to chemicals. Combining the molecular information (DNA sequences) of 31 invertebrate species with the physicochemical properties of six bivalent metals, we built bilinear models that explained 70–80% of the variability in species sensitivity to heavy metals. Phylogeny was the most important component of the bilinear models, as it explained the major part of the explained variance (>40%). Predicted values from bilinear modeling were in agreement with experimental values (>50%); therefore, this approach is a good starting point to build statistical models which can potentially predict heavy metal toxicity for untested invertebrate species based on empirical values for similar species. Despite their good performance, development of the presented bilinear models would benefit from improved phylogenetic and toxicological datasets. Our analysis is an example for linking evolutionary biology with applied ecotoxicology. Its future applications may encompass other stress factors or traits influencing the survival of aquatic organisms in polluted environments.
Assessing the umbrella value of a range‐wide conservation network for jaguars (Panthera onca)
Authors: Thornton Daniel , Zeller Kathy , Rondinini Carlo , Boitani Luigi , Crooks Kevin , Burdett Christopher , Rabinowitz Alan , Quigley Howard 
Published: May 2016

AbstractUmbrella species are employed as conservation short‐cuts for the design of reserves or reserve networks. However, empirical data on the effectiveness of umbrellas is equivocal, which has prevented more widespread application of this conservation strategy. We perform a novel, large‐scale evaluation of umbrella species by assessing the potential umbrella value of a jaguar (Panthera onca) conservation network (consisting of viable populations and corridors) that extends from Mexico to Argentina. Using species richness, habitat quality, and fragmentation indices of ~1500 co‐occurring mammal species, we show that jaguar populations and corridors overlap a substantial amount and percentage of high‐quality habitat for co‐occurring mammals and that the jaguar network performs better than random networks in protecting high‐quality, interior habitat. Significantly, the effectiveness of the jaguar network as an umbrella would not have been noticeable had we focused on species richness as our sole metric of umbrella utility. Substantial inter‐order variability existed, indicating the need for complementary conservation strategies for certain groups of mammals. We offer several reasons for the positive result we document, including the large spatial scale of our analysis and our focus on multiple metrics of umbrella effectiveness. Taken together, our results demonstrate that a regional, single‐species conservation strategy can serve as an effective umbrella for the larger community and should help conserve viable populations and connectivity for a suite of co‐occurring mammals. Current and future range‐wide planning exercises for other large predators may therefore have important umbrella benefits.
Tracking wild sockeye salmon smolts to the ocean reveals distinct regions of nocturnal movement and high mortality
Authors: Clark Timothy D. , Furey Nathan B. , Rechisky Erin L. , Gale Marika K. , Jeffries Ken M. , Porter Aswea D. , Casselman Matthew T. , Lotto Andrew G. , Patterson David A. , Cooke Steven J. , Farrell Anthony P. , Welch David W. , Hinch Scott G. 
Published: May 2016

AbstractFew estimates of migration rates or descriptions of behavior or survival exist for wild populations of out‐migrating Pacific salmon smolts from natal freshwater rearing areas to the ocean. Using acoustic transmitters and fixed receiver arrays across four years (2010–2013), we tracked the migration of >1850 wild sockeye salmon (Oncorhynchus nerka) smolts from Chilko Lake, British Columbia, to the coastal Pacific Ocean (>1000 km distance). Cumulative survival to the ocean ranged 3–10% among years, although this may be slightly underestimated due to technical limitations at the final receiver array. Distinct spatial patterns in both behavior and survival were observed through all years. In small, clear, upper‐river reaches, downstream migration largely occurred at night at speeds up to 50 km/d and coincided with poor survival. Among years, only 57–78% of smolts survived the first 80 km. Parallel laboratory experiments revealed excellent short‐term survival and unhindered swimming performance of dummy‐tagged smolts, suggesting that predators rather than tagging effects were responsible for the initial high mortality of acoustic‐tagged smolts. Migration speeds increased in the Fraser River mainstem (~220 km/d in some years), diel movement patterns ceased, and smolt survival generally exceeded 90% in this segment. Marine movement rates and survival were variable across years, with among‐year segment‐specific survival being the most variable and lowest (19–61%) during the final (and longest, 240 km) marine migration segment. Osmoregulatory preparedness was not expected to influence marine survival, as smolts could maintain normal levels of plasma chloride when experimentally exposed to saltwater (30 ppt) immediately upon commencing their migration from Chilko Lake. Transportation of smolts downstream generally increased survival to the farthest marine array. The act of tagging may have affected smolts in the marine environment in some years as dummy‐tagged fish had poorer survival than control fish when transitioned to saltwater in laboratory‐based experiments. Current fisheries models for forecasting the number of adult sockeye returning to spawn have been inaccurate in recent years and generally do not incorporate juvenile or smolt survival information. Our results highlight significant potential for early migration conditions to influence adult recruitment.
Projected wetland densities under climate change: habitat loss but little geographic shift in conservation strategy
Authors: Sofaer Helen R. , Skagen Susan K. , Barsugli Joseph J. , Rashford Benjamin S. , Reese Gordon C. , Hoeting Jennifer A. , Wood Andrew W. , Noon Barry R. 
Published: May 2016

AbstractClimate change poses major challenges for conservation and management because it alters the area, quality, and spatial distribution of habitat for natural populations. To assess species’ vulnerability to climate change and target ongoing conservation investments, researchers and managers often consider the effects of projected changes in climate and land use on future habitat availability and quality and the uncertainty associated with these projections. Here, we draw on tools from hydrology and climate science to project the impact of climate change on the density of wetlands in the Prairie Pothole Region of the USA, a critical area for breeding waterfowl and other wetland‐dependent species. We evaluate the potential for a trade‐off in the value of conservation investments under current and future climatic conditions and consider the joint effects of climate and land use. We use an integrated set of hydrological and climatological projections that provide physically based measures of water balance under historical and projected future climatic conditions. In addition, we use historical projections derived from ten general circulation models (GCMs) as a baseline from which to assess climate change impacts, rather than historical climate data. This method isolates the impact of greenhouse gas emissions and ensures that modeling errors are incorporated into the baseline rather than attributed to climate change. Our work shows that, on average, densities of wetlands (here defined as wetland basins holding water) are projected to decline across the U.S. Prairie Pothole Region, but thatGCMs differ in both the magnitude and the direction of projected impacts. However, we found little evidence for a shift in the locations expected to provide the highest wetland densities under current vs. projected climatic conditions. This result was robust to the inclusion of projected changes in land use under climate change. We suggest that targeting conservation towards wetland complexes containing both small and relatively large wetland basins, which is an ongoing conservation strategy, may also act to hedge against uncertainty in the effects of climate change.
Interaction of ecological and angler processes: experimental stocking in an open access, spatially structured fishery
Authors: Mee Jonathan A. , Post John R. , Ward Hillary , Wilson Kyle L. , Newton Eric , Cantin Ariane 
Published: May 2016

AbstractEffective management of socioecological systems requires an understanding of the complex interactions between people and the environment. In recreational fisheries, which are prime examples of socioecological systems, anglers are analogous to mobile predators in natural predator–prey systems, and individual fisheries in lakes across a region are analogous to a spatially structured landscape of prey patches. Hence, effective management of recreational fisheries across large spatial scales requires an understanding of the dynamic interactions among ecological density dependent processes, landscape‐level characteristics, and angler behaviors. We focused on the stocked component of the open access rainbow trout (Oncorhynchus mykiss) fishery in British Columbia (BC), and we used an experimental approach wherein we manipulated stocking densities in a subset of 34 lakes in which we monitored angler effort, fish abundance, and fish size for up to seven consecutive years. We used an empirically derived relationship between fish abundance and fish size across rainbow trout populations in BC to provide a measure of catch‐based fishing quality that accounts for the size‐abundance trade off in this system. We replicated our experimental manipulation in two regions known to have different angler populations and broad‐scale access costs. We hypothesized that angler effort would respond to variation in stocking density, resulting in spatial heterogeneity in angler effort but homogeneity in catch‐based fishing quality within regions. We found that there is an intermediate stocking density for a given lake or region at which angler effort is maximized (i.e., an optimal stocking density), and that this stocking density depends on latent effort and lake accessibility. Furthermore, we found no clear effect of stocking density on our measure of catch‐based fishing quality, suggesting that angler effort homogenizes catch‐related attributes leading to an eroded relationship between stocking density and catch‐based fishing quality at the timescale of annual surveys. We conclude that declines in fishing quality resulting from understocking (due to declines in catch rate with low fish abundance) and overstocking (due to suppressed growth and limited recruitment at high density) give an optimal stocking rate that depends on accessibility and latent effort.
Addressing potential local adaptation in species distribution models: implications for conservation under climate change
Authors: Hällfors Maria Helena , Liao Jishan , Dzurisin Jason , Grundel Ralph , Hyvärinen Marko , Towle Kevin , Wu Grace C. , Hellmann Jessica J. 
Published: May 2016

AbstractSpecies distribution models (SDMs) have been criticized for involving assumptions that ignore or categorize many ecologically relevant factors such as dispersal ability and biotic interactions. Another potential source of model error is the assumption that species are ecologically uniform in their climatic tolerances across their range. Typically,SDMs treat a species as a single entity, although populations of many species differ due to local adaptation or other genetic differentiation. Not taking local adaptation into account may lead to incorrect range prediction and therefore misplaced conservation efforts. A constraint is that we often do not know the degree to which populations are locally adapted. Lacking experimental evidence, we still can evaluate niche differentiation within a species’ range to promote better conservation decisions. We explore possible conservation implications of making type I or typeIIerrors in this context. For each of two species, we construct three separate MaxEnt models, one considering the species as a single population and two of disjunct populations.Principal componentanalyses and response curves indicate different climate characteristics in the current environments of the populations. Model projections into future climates indicate minimal overlap between areas predicted to be climatically suitable by the whole species vs. population‐based models. We present a workflow for addressing uncertainty surrounding local adaptation inSDMapplication and illustrate the value of conducting population‐based models to compare with whole‐species models. These comparisons might result in more cautious management actions when alternative range outcomes are considered.