bluuebunny/crossref_metadata_2025_split huggingface dataset:
The limited spatial scale of dispersal in soil arthropods revealed with whole-community haplotype-level metabarcoding
Authors: Arribas P , Andújar C , Salces-Castellano A , Emerson BC , Vogler AP 
Published: June 2020

ABSTRACTSoil mesofauna communities are hyperdiverse and critical for ecosystem functioning. However, our knowledge on spatial structure and underlying processes of community assembly for soil arthropods is scarce, hampered by limited empirical data on species diversity and turnover. We implement a high-throughput-sequencing approach to generate comparative data for thousands of arthropods at three hierarchical levels: genetic, species and supra-specific lineages. A joint analysis of the spatial arrangement across these levels can reveal the predominant processes driving the variation in biological assemblages at the local scale. This multi-hierarchical approach was performed using haplotype-level-COI metabarcoding of entire communities of mites, springtails and beetles from three Iberian mountain regions. Tens of thousands of specimens were extracted from deep and superficial soil layers and produced comparative phylogeographic data for >1000 co-distributed species and nearly 3000 haplotypes. Local assemblages were highly distinctive between grasslands and forests, and within each of them showed strong spatial structures and high endemicity at the scale of a few kilometres or less. The local distance-decay patterns were self-similar for the haplotypes and higher hierarchical entities, and this fractal structure was very similar in all three regions, pointing to a significant role of dispersal limitation driving the local-scale community assembly. Our results from whole-community metabarcoding provide unprecedented insight into how dispersal limitations constrain mesofauna community structure within local spatial settings over evolutionary timescales. If generalized across wider areas, the high turnover and endemicity in the soil locally may indicate extremely high richness globally, challenging our current estimations of total arthropod-diversity on Earth.
Physicochemical characterization, toxicity andin vivobiodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin
Authors: Torgersen Maria Lyngaas , Judge Peter J. , Juarez Juan F. Bada , Pandya Abhilash D. , Fusser Markus , Davies Charlie W. , Maciejewska Matylda K. , Yin Daniel J. , Mælandsmo Gunhild M. , Skotland Tore , Watts Anthony , Sandvig Kirsten 
Published: June 2020

AbstractMany promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and thein vivoexcretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.
Modified Hypoxia Inducible Factor expression in CD8+ T cells increases anti-tumor efficacy
Authors: Veliça Pedro , Cunha Pedro Pacheco , Vojnovic Nikola , Foskolou Iosifina Petrina , Bargiela David , Gojkovic Milos , Rundqvist Helene , Johnson Randall Scott 
Published: June 2020

AbstractAdoptive transfer of anti-tumor cytotoxic T cells is a novel form of cancer immunotherapy, and a key challenge is to ensure the survival and function of the transferred T cells. Immune cell survival requires adaptation to different micro-environments, and particularly to the hypoxic milieu of solid tumors. The HIF transcription factors are an essential aspect of this adaptation, and we undertook experiments to define structural determinants of HIF that would potentiate anti-tumor efficacy in cytotoxic T cells. We created retroviral vectors to deliver ectopic expression of HIF-1ɑ and HIF-2ɑ in mouse CD8+ T cells, together or individually, and with or without sensitivity to their oxygen-dependent inhibitors Von Hippel-Lindau (VHL) and Factor Inhibiting HIF (FIH). We found that HIF-2ɑ, but not HIF-1ɑ, drives broad transcriptional changes in CD8+ T cells, resulting in increased cytotoxic differentiation and cytolytic function against tumor targets. We further found that a specific mutation replacing the hydroxyl group acceptor site for FIH in the HIF-2ɑ isoform gives rise to the most effective anti-tumor T cells after adoptive transfer in vivo. Lastly, we show that co-delivering an FIH-insensitive form of HIF-2ɑ with an anti-CD19 chimeric antigen receptor greatly enhances cytolytic function of human CD8+ T cells against lymphoma cells. These experiments provide a means to increase the anti-tumor efficacy of therapeutic CD8+ T cells via ectopic expression of the HIF transcription factor.Graphical abstract
GENis, an open-source multi-tier forensic DNA information system
Authors: Chernomoretz Ariel , Balparda Manuel , Grutta Laura La , Calabrese Andres , Martinez Gustavo , Escobar Maria Soledad , Sibilla Gustavo 
Published: June 2020

AbstractGENis is an open source multi-tier information system developed to run a forensic DNA database at local, regional and national levels.1It was conceived as a highly customizable system, enforcing several security policies including: data encryption, double factor identification, structure of user’s roles and permissions, system-wide secure log auditing, non-repudiation protocols and a blockchain-based option to reinforce genetic profile’s integrity. GENis is able to perform genetic profile queries of autosomal STR’s and its design follows ENFSI2and ISFG3standards and recommendations. In this work, we present a summary of GENis architecture, the implemented matching rule definitions, and the Bayesian framework used to provide statistical significance of cold hits, that includes a new strategy to identify common contributors in mixture pairs.
Impacts of landscape-scale windthrow and subsequent, variable reforestation on bird communities in Central Europe
Authors: Kamp Johannes , Trappe Johanna , Dübbers Luca , Funke Stephanie 
Published: June 2020

AbstractWith climate change, the area affected by and the intensity of forest disturbances such as windthrow, insect outbreaks and fire will be increasing. Post-disturbance forest management will be varied, and it is difficult to predict how much natural succession will be allowed in comparison to reforestation. Both, disturbance and reforestation will affect forest biodiversity globally, but potential shifts in species distribution, abundance and community composition are poorly understood.We studied the response of breeding bird communities to windthrow and different reforestation strategies in one of Central Europe’s largest contiguous windthrow areas created by storm Kyrill in 2007. A decade after the disturbance, we compared bird species diversity, population densities and community composition on plots in replanted beech, replanted conifers and secondary succession (all salvage-logged after the storm), with undisturbed old Norway sprucePicea abiesas a control, in the setting of a natural experiment.Of the stands blown down, 95% were Norway Spruce. Reforestation strategies varied, with Spruce and non-native conifers planted on twice the area that was replanted with European BeechFagus sylvestris. Large areas were still dominated by successional tree species a decade after the storm, especially birch, mirroring recommendations of sub-national forestry agencies to include secondary succession in future forest development. Birds responded strongly to windthrow, with a pronounced community turnover. Species associated with high conifer stands reached significantly lower densities on sample plots in disturbed areas. Replanted areas were characterized by mostly ubiquitous bird species. Areas dominated by secondary succession, especially birchBetula spp., were characterized by high densities of long-distance migrants (often species of conservation concern) and shrubland species, among them several indicator species.Our results suggest that an increase of forest disturbance across Central Europe will lead to a pronounced reorganisation of biodiversity. Strategies that allow more secondary succession, and avoid replanting allochthonous tree species are likely to benefit populations of depleted bird species, even at salvage-logged and cleared disturbance sites.
Multimodal small-molecule screening for human prion protein binders
Authors: Reidenbach Andrew G , Mesleh Michael F , Casalena Dominick , Vallabh Sonia M , Dahlin Jayme L , Leed Alison J , Chan Alix I , Usanov Dmitry L , Yehl Jenna B , Lemke Christopher T , Campbell Arthur J , Shah Rishi N , Shrestha Om K , Sacher Joshua R , Rangel Victor L , Moroco Jamie A , Sathappa Murugappan , Nonato Maria Cristina , Nguyen Kong T , Wright S Kirk , Liu David R , Wagner Florence F , Kaushik Virendar K , Auld Douglas S , Schreiber Stuart L , Minikel Eric Vallabh 
Published: June 2020

ABSTRACTPrion disease is a rapidly progressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), and there are currently no therapeutic options. PrP ligands could theoretically antagonize prion formation by protecting the native protein from misfolding or by targeting it for degradation, but no validated small-molecule binders have been discovered to date. We deployed a variety of screening methods in an effort to discover binders of PrP, including19F-observed and saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, differential scanning fluorimetry (DSF), DNA-encoded library selection, andin silicoscreening. A single benzimidazole compound was confirmed in concentration-response, but affinity was very weak (Kd> 1 mM), and it could not be advanced further. The exceptionally low hit rate observed here suggests that PrP is a difficult target for small-molecule binders. While orthogonal binder discovery methods could yield high affinity compounds, non-small-molecule modalities may offer independent paths forward against prion disease.
Tissue-autonomous phenylpropanoid production is essential for establishment of root barriers
Authors: Andersen Tonni Grube , Molina David , Kilian Joachim , Franke Rochus , Ragni Laura , Geldner Niko 
Published: June 2020

ABSTRACTPlants deposit polymeric barriers in their root cell walls to protect against external stress and facilitate selective nutrient uptake. The compounds that make up these barriers originate from the fatty acid- and phenylpropanoid biosynthetic pathways. Although the machinery responsible for production of the barrier constituents is well-char-acterized, our pathway models lack spatiotemporal resolution – especially in roots - and the source tissue is often not clear due to the apoplastic nature of barriers. Insights into how the individual root tissues or cells contribute to forming apoplastic barriers is important for elucidation of their ultrastructure, function and development. Manipulation of the associated biosynthesis is delicate, as mutants often display pleiotropic phenotypes due to the broad role of the underlying metabolites. Here, we address these issues by creating a genetic tool that allows in vivo repression of the phenylpropanoid pathway with both spatial and temporal control. We provide strong evidence that tissue-auton-omous production of phenylpropanoids is essential for establishment of the endodermal Casparian strip. Moreover, we find that in order to maintain deposition and attachment of a coherent suberin matrix to the cell wall, cells require continuous production of aromatic constituents. This process is especially crucial in the suberized endodermis where we find that repression of phenylpropanoid production leads to active removal of suberin.
“A Novel Therapeutic Approach to Corneal Alkaline Burn Model by Targeting Fidgetin-like 2, a Microtubule Regulator”
Authors: Wang Jessie , Dey Abhinav , Kramer Adam , Miao Yuan , Liu Juan , Baker Lisa , Friedman Joel , Nacharaju Parimala , Chuck Roy , Zhang Cheng , Sharp David J. 
Published: June 2020

AbstractPurposeTo determine the efficacy of nanoparticle-encapsulated FL2 siRNA (FL2-NPsi), a novel therapeutic agent targeting the Fidgetin-like 2 (FL2) gene, for the treatment of corneal alkaline chemical injury.MethodsEighty 12-week-old, male Sprague-Dawley rats were divided evenly into 8 treatment groups: prednisolone, empty nanoparticles, control-NPsi (1 μM, 10 μM, 20 μM) and FL2-NPsi (1 μM, 10 μM, 20 μM). An alkaline burn was induced onto the cornea of each rat, which was then treated for 14 days according to group assignment. Clinical (N=10 per group), histopathologic (N=6 per group), and immunohistochemical (N=4 per group) analyses were conducted to assess for wound healing. FL2-NPsi-mediated knockdown of FL2 was confirmed byin vitroqPCR. Toxicity assays were performed to assess for apoptosis (TUNEL assay, N=3 per group) and nerve damage (whole mount immunochemical staining, N=2 per group). Statistical analyses were performed using student’s t-test and ANOVA.ResultsCompared to controls, FL2-NPsi-treated groups demonstrated enhanced corneal wound healing, with the 10 and 20 μM FL2-NPsi-treated groups demonstrating maximum rates of corneal re-epithelialization (p=0.0003 at Day 4 and p<0.0001 at Day 8) as assessed by ImageJ software, enhanced corneal transparency, and improved stromal organization on histology. Immunohistochemical analysis of vascular endothelial cells, macrophages, and neutrophils did not show significant differences between treatment groups. FL2-NPsi was not found to be toxic to nerves or induce apoptosis (p=0.917).ConclusionDose-response studies found both 10 and 20 μM FL2-NPsi to be efficacious in this rat model. FL2-NPsi may offer a novel treatment for corneal alkaline chemical injuries.
Transcriptomic analysis of four cerianthid (Cnidaria, Ceriantharia) venoms
Authors: Klompen Anna M. L. , Macrander Jason , Reitzel Adam M. , Stampar Sérgio N. 
Published: June 2020

AbstractTube anemones, or cerianthids, are a phylogenetically informative group of cnidarians with complex life histories, including a pelagic larval stage and tube-dwelling adult stage, both known to utilize venom in stinging-cell rich tentacles. Cnidarians are an entirely venomous group that utilize their proteinaceous-dominated toxins to capture prey and defend against predators, in addition to several other ecological functions, including intraspecific interactions. At present there are no studies describing the venom for any species within cerianthids. Given their unique development, ecology, and distinct phylogenetic-placement within Cnidaria, our objective is to evaluate the venom-like gene diversity of four species of cerianthids from newly collected transcriptomic data. We identified 525 venom-like genes between all four species. The venom-gene profile for each species was dominated by enzymatic protein and peptide families, which is consistent with previous findings in other cnidarian venoms. However, we found few toxins that are typical of sea anemones and corals, and furthermore, three of the four species express toxin-like genes closely related to potent pore-forming toxins in box jellyfish. Our study is the first to provide a survey of the putative venom composition of cerianthids, and contributes to our general understanding of the diversity of cnidarian toxins.
GardeninA confers neuroprotection against environmental toxin in aDrosophilamodel of Parkinson’s disease
Authors: Maitra Urmila , Harding Thomas , Liang Qiaoli , Ciesla Lukasz 
Published: June 2020

AbstractParkinson’s disease (PD) is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide, paraquat (PQ) as major contributors to PD etiology in both mammalian and invertebrate models. We have employed a PQ-induced PD model inDrosophilaas an inexpensivein vivoplatform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against PQ-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully detected GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced PD pathogenesis for novel therapeutic intervention.
Honeyweed (Leonurus sibiricus) and Buckwheat (Fagopyrum esculentum) supplemented diet improve growth performance, lipid profile and hematological values of broiler chicks
Authors: Abedin M.T. , Rahman S.T. , Islam M.M. , Hayder S. , Ashraf M.A. , Pelc J. , Sayed M.A. 
Published: June 2020

AbstractThe study was conducted to investigate the combined effects of honeyweed (HW) and buckwheat (BW) supplemented diets on the growth, feed intake, serum lipid profile and blood parameters in broiler chicks. One hundred fifty (150) day old chicks (Cobb-500) were divided into five groupsviz. T1 (Commercial control, CC), T2 (FF+10% BW), T3 (FF+10% BW +5% (w/v) HW powder), T4 (FF+10% BW +10% (w/v) HW powder), T5 (FF+10% BW +15% (w/v) HW powder) in complete randomized design with five (5) replications, each of which contain six (6) birds. The CC feed and the FF with HW and BW supplemented diet fed on broiler for 30 days. At the end of the study, the body weight gain, FCR and mortality rate were calculated. It was found that T3 (FF+10% BW +5% (w/v) HW powder) diet significantly (p <0.05) showed the good FCR, mortality rate and body weight gain. Interestingly, T3 decreased the serum cholesterol, triglycerides (TG), low density lipoprotein (LDL), increased high density lipoprotein (HDL) and improves blood parameters significantly (p < 0.05). Our results suggested that this newly formulated feed T3 (FF+10% BW +5% (w/v) HW powder) could be considered as an alternative natural feed additive to hazardous synthetic antibiotics.
Estimation of sinking velocities using free-falling dynamically scaled models: foraminifera as a test case
Authors: Walker Matthew , Humphries Stuart , Schuech Rudi 
Published: June 2020

AbstractThe velocity of settling particles is an important determinant of distribution in extinct and extant species with passive dispersal mechanisms, such as plants, corals, and phytoplankton. Here we adapt dynamic scaling, borrowed from engineering, to determine settling velocities. Dynamic scaling leverages physical models with relevant dimensionless numbers matched to achieve similar dynamics to the original object. Previous studies have used flumes, wind tunnels, or towed models to examine fluid flows around objects with known velocities. Our novel application uses free-falling models to determine the unknown sinking velocities of planktonic foraminifera – organisms important to our understanding of the Earth’s current and historic climate. Using enlarged 3D printed models of microscopic foraminifera tests, sunk in viscous mineral oil to match their Reynolds numbers and drag coefficients, we predict sinking velocities of real tests in seawater. This method can be applied to study other settling particles such as plankton, spores, or seeds.Summary StatementWe developed a novel method to determine the sinking velocities of biologically important microscale particles using 3D printed scale models.
SLAP2 adaptor binding disrupts c-CBL autoinhibition to activate ubiquitin ligase function
Authors: Wybenga-Groot Leanne E. , Tench Andrea J. , Simpson Craig D. , Germain Jonathan St. , Raught Brian , Moran Michael F. , McGlade C. Jane 
Published: June 2020

AbstractCBL is a RING type E3 ubiquitin ligase that functions as a negative regulator of tyrosine kinase signaling and loss of CBL E3 function is implicated in several forms of leukemia. The Src-like adaptor proteins (SLAP/SLAP2) bind to CBL and are required for CBL-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling. Despite the established role of SLAP/SLAP2 in regulating CBL activity, the nature of the interaction and the mechanisms involved are not known. To understand the molecular basis of the interaction between SLAP/SLAP2 and CBL, we solved the crystal structure of CBL tyrosine kinase binding domain (TKBD) in complex with SLAP2. The carboxy-terminal region of SLAP2 adopts an α-helical structure which binds in a cleft between the 4H, EF-hand, and SH2 domains of the TKBD. This SLAP2 binding site is remote from the canonical TKBD phospho-tyrosine peptide binding site but overlaps with a region important for stabilizing CBL in its autoinhibited conformation. In addition, binding of SLAP2 to CBLin vitroactivates the ubiquitin ligase function of autoinhibited CBL. Disruption of the CBL/SLAP2 interface through mutagenesis demonstrated a role for this protein-protein interaction in regulation of CBL E3 ligase activity in cells. Our results reveal that SLAP2 binding to a regulatory cleft of the TKBD provides an alternative mechanism for activation of CBL ubiquitin ligase function.