bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shark conservation risks associated with the use of shark liver oil in SARS-CoV-2 vaccine development
Authors: Macdonald Catherine , Soll Joshua 
Published: October 2020

AbstractThe COVID-19 pandemic may create new demand for wildlife-generated products for human health, including a shark-derived ingredient used in some vaccines. Adjuvants are a vaccine component that increases efficacy, and some adjuvants contain squalene, a natural compound derived from shark liver oil which is found most abundantly in deep-sea sharks. In recent decades, there has been growing conservation concern associated with the sustainability of many shark fisheries. The need for a potentially massive number of adjuvant-containing SARS-CoV-2 vaccines may increase global demand for shark-derived squalene, with possible consequences for shark conservation, especially of vulnerable and understudied deep-sea species. A shift to non-animal-derived sources of squalene, which are similar in cost and identical in effectiveness, or an emphasis on increasing traceability and sustainability of shark-derived squalene from existing well-managed fisheries, could better support conservation and public health goals.
Impact of a tarsonemid prey mite and its fungal diet on the reproductive performance of a predatory mite
Authors: Vangansbeke Dominiek , Duarte Marcus V. A. , Merckx Jonas , Benavente Alfredo , Magowski Wojciech L. , França Soraya C. , Bolckmans Karel , Wäckers Felix 
Published: October 2020

AbstractPhytoseiid predatory mites are the most important group of biocontrol agents currently implemented in protected cultivations worldwide. The possibility to produce these predators at high densities on factitious prey mites is a crucial factor for their success. Commonly used factitious prey mites comprise mainly species belonging to the cohort of Astigmatina. In the present study, we investigated the potential of tarsonemid prey mites as a food source for the spider mite predatorNeoseiulus californicus(McGregor) (Acari: Phytoseiidae). The oviposition ofN. californicuson mixed stages ofTarsonemus fusariiCooreman (Acari: Tarsonemidae) was similar to that on its natural prey, the two-spotted spider miteTetranychus urticaeKoch (Acari: Tetranychidae). As most tarsonemids are specialized fungus-feeders, we tested the effect of different fungal species on the growth ofT. fusarii. Subsequently, we analysed the impact on the fungal growing medium on the oviposition ofN. californicus. The fungal growing medium ofT. fusariihad a significant effect on the reproductive output of the predatory mite, having a negative effect. WhenT. fusariiwas separated from the rearing medium, these detrimental effects were not observed. The present study shows the potential of using tarsonemid prey mites in the production of predatory mites.
Convergence of peptidergic and non-peptidergic protein markers in the human dorsal root ganglion and spinal dorsal horn
Authors: Shiers Stephanie , Sankaranarayanan Ishwarya , Jeevakumar Vivek , Cervantes Anna , Reese Jeffrey C. , Price Theodore J. 
Published: October 2020

AbstractPeripheral sensory neurons are characterized by their size, molecular profiles, and physiological responses to specific stimuli. In mouse, the peptidergic and non-peptidergic subsets of nociceptors are distinct and innervate different lamina of the spinal dorsal horn. The unique molecular signature and neuroanatomical organization of these neurons supports a labeled line theory for certain types of nociceptive stimuli. However, long standing evidence supports the polymodal nature of nociceptors in many species. We have recently shown that the peptidergic marker, CGRP, and the non-peptidergic marker, P2X3R, show largely overlapping expression at the mRNA level in human dorsal root ganglion (DRG). Herein, our aim was to assess the protein distribution of nociceptor markers, including their central projections, in the human DRG and spinal cord. Using DRGs obtained from organ donors, we observed that CGRP and P2X3R were co-expressed by approximately 33% of human DRG neurons and TrpV1 was expressed in ~60% of human DRG neurons. In the dorsal spinal cord, CGRP, P2X3R, TrpV1 and Nav1.7 protein stained the entirety of lamina II, with only P2XR3 showing a gradient of expression. This was confirmed by measuring the size of the substantia gelatinosa using Hematoxylin and Eosin staining of adjacent sections. Our findings are consistent with the known polymodal nature of most primate nociceptors and indicate that the central projection patterns of nociceptors are different between mice and humans. Elucidating how human nociceptors connect to subsets of dorsal horn neurons will be important for understanding the physiological consequences of these species differences.
Simple muscle-lever systems are not so simple: The need for dynamic analyses to predict lever mechanics that maximize speed
Authors: Osgood A. C. , Sutton G.P. , Cox S. M. 
Published: October 2020

AbstractHere we argue that quasi-static analyses are insufficient to predict the speed of an organism from its skeletal mechanics alone (i.e. lever arm mechanics). Using a musculoskeletal numerical model we specifically demonstrate that 1) a single lever morphology can produce a range of output velocities, and 2) a single output velocity can be produced by a drastically different set of lever morphologies. These two sets of simulations quantitatively demonstrate that it is incorrect to assume a one-to-one relationship between lever arm morphology and organism maximum velocity. We then use a statistical analysis to quantify what parameters are determining output velocity, and find that muscle physiology, geometry, and limb mass are all extremely important. Lastly we argue that the functional output of a simple lever is dependent on the dynamic interaction of two opposing factors: those decreasing velocity at low mechanical advantage (low torque and muscle work) and those decreasing velocity at high mechanical advantage (muscle force-velocity effects). These dynamic effects are not accounted for in static analyses and are inconsistent with a force-velocity tradeoff in lever systems. Therefore, we advocate for a dynamic, integrative approach that takes these factors into account when analyzing changes in skeletal levers.
Alzheimer’s pathology is associated with dedifferentiation of functional memory networks in aging
Authors: Cassady Kaitlin E. , Adams Jenna N. , Chen Xi , Maass Anne , Harrison Theresa M. , Landau Susan , Baker Suzanne , Jagust William 
Published: October 2020

AbstractIn presymptomatic Alzheimer’s disease (AD), beta-amyloid plaques (Aβ) and tau tangles accumulate in distinct spatiotemporal patterns within the brain, tracking closely with episodic memory decline. Here, we tested whether age-related changes in the segregation of the brain’s functional episodic memory networks - anterior-temporal (AT) and posterior-medial (PM) networks - are associated with the accumulation of Aβ, tau and memory decline using fMRI and PET. We found that AT and PM networks were less segregated in older than younger adults and this reduced specialization was associated with more tau and Aβ in the same regions. The effect of network dedifferentiation on memory depended on the amount of Aβ and tau, with low segregation and pathology associated with better performance at baseline and low segregation and high pathology related to worse performance over time. This pattern suggests a compensation phase followed by a degenerative phase in the early, preclinical phase of AD.
Loss of IL-10 signaling promotes IL-22 dependent host defenses against acuteClostridioides difficileinfection
Authors: Cribas Emily S. , Denny Joshua E. , Maslanka Jeffrey R. , Abt Michael C. 
Published: October 2020

AbstractInfection with the bacterial pathogenClostridioides difficilecauses severe damage to the intestinal epithelium that elicits a robust inflammatory response. Markers of intestinal inflammation accurately predict clinical disease severity. However, determining the extent to which host-derived proinflammatory mediators drive pathogenesis versus promote host protective mechanisms remains elusive. In this report, we employedIl10-/-mice as a model of spontaneous colitis to examine the impact of constitutive intestinal immune activation, independent of infection, onC. difficiledisease pathogenesis. UponC. difficilechallenge,Il10-/-mice exhibited significantly decreased morbidity and mortality compared to littermateIl10heterozygote (Il10HET) control mice, despite a comparableC. difficileburden, innate immune response, and microbiota composition following infection. Similarly, antibody-mediated blockade of IL-10 signaling in wild-type C57BL/6 mice conveyed a survival advantage if initiated three weeks prior to infection. In contrast, no advantage was observed if blockade was initiated on the day of infection, suggesting that constitutive activation of inflammatory defense pathways prior to infection mediated host protection. IL-22, a cytokine critical in mounting a protective response againstC. difficileinfection, was elevated in the intestine of uninfected, antibiotic-treatedIl10-/-mice, and genetic ablation of the IL-22 signaling pathway inIl10-/-mice negated the survival advantage followingC. difficilechallenge. Collectively, these data demonstrate that constitutive loss of IL-10 signaling, via genetic ablation or antibody blockade, enhances IL-22 dependent host defense mechanisms to limitC. difficilepathogenesis.
Cross-reactive anti-hemagglutinin (HA) IgG responses are shaped by previous long-interval monovalent H5 vaccination and highly correlated with HA antigenic distance
Authors: Wang Jiong , Li Dongmei , Perry Sheldon , Hilchey Shannon P. , Wiltse Alexander , Treanor John J. , Sangster Mark Y. , Zand Martin S. 
Published: October 2020

ABSTRACTAvian H5 influenza is an emerging influenza strain with the potential for human pandemic spread. One unresolved issue in pandemic vaccine preparedness is to what extent a vaccine recall response depends on the interval between the priming and boosting vaccinations. In this study, we analyzed the anti-H5 HA IgG responses to an H5 A/Indonesia/5/2005 boosting vaccination in three cohorts: (1) a short interval boosting cohort that received a prime and boost 28 days apart, (2) a long-interval boosting cohort that received an H5 A/Vietnam/203/2004 priming vaccination 5 years before boosting, and (3) a double long-boost cohort that received single doses of all three vaccines separated by 5-6 year intervals. Anti-HA IgG levels were measured using a multiple-plex assay against 21 H5 and 16 seasonal strains covering both influenza phylogenetic groups. We used the antigentic distance between the vaccine strain and each HA in the assay panel to de1ne the antibody response landscape. Both single and double long-interval boosting with the H5 variant vaccine elicited a broad antibody response to all H5 subtype strains, and double boosting resulted in sustained, vaccine-speci1c, anti-HA IgG levels over a six month period. Antibody-mediated immune responses were shaped by prior H5 exposure history, and the magnitude of both vaccine speci1c and cross-reactive anti-H5 HA IgG responses was highly correlated with the relative antigenic distance between the measured and the vaccine HAs. We conclude that the relative antibody landscape method can be used to quantify the phenomenon of antigenic imprinting on human influenza vaccine immune responses.IMPORTANCEA signi1cant obstacle to development of a universal influenza vaccine is understanding the relationship between multidimensional host humoral immunity, prior antigen exposure, and viral antigenicity. In this study, we used a multiplexed antibody assay to measure antibody cross-reactivities against antigenically similar H5 influenza virus strains. This work uses a novel method, relative antibody landscapes, to analyze the relationship between immune response and antigenic distance between the target H5 vaccine HA and other HAs in the assay after a boosting vaccination. This method improves analysis of immune responses by relating antigen exposure history to the influenza vaccination antibody response. This study also revealed that multiple vaccine boosting over several years can generate high levels of long-lasting cross-reactive antibodies against the priming H5 strains vaccine that subjects received, suggesting the HA imprinting mechanism(s) have a strong influence in the adult antibody response to H5 MIV vaccination.
Poor protection of amphibian evolutionary history reveals opportunities for global protected areas
Authors: Upton Jasmin , Gray Claudia L. , Tapley Benjamin , Murray Kris A. , Gumbs Rikki 
Published: October 2020

AbstractAs habitat loss is a major driver of amphibian population declines, protected areas (PAs) can play a crucial role in amphibian conservation. Documenting how well the global PA network captures the evolutionary history of amphibians can inform conservation prioritisation and action. We conducted a phylogenetic gap analysis to assess the extent to which amphibian phylogenetic diversity (PD) is unprotected by the PA network and compared this to other terrestrial vertebrate groups. 78% of amphibian species and 64% of global amphibian PD remains unprotected, which is higher than corresponding figures for squamates, mammals and birds. Amongst amphibians, salamanders were the least well protected, with 78% of PD unprotected, compared with 64% for caecilians and 63% for frogs. We identify areas that offer the greatest opportunity to capture unprotected amphibian evolutionary history. We could capture an additional 29.4% of amphibian PD, representing 40 billion years of evolutionary history, by protecting an additional 1.9% of global amphibian distributions (1.74% of global land area) and increasing the restrictions in 0.6% of amphibian distributions to match the management objectives of PAs in IUCN categories I or II. Importantly, we found that the spatial distribution of unprotected PD was correlated across all groups, indicating that expanding the PA network to conserve amphibian PD can secure imperilled vertebrate diversity more generally.
Neuroprotective pentapeptide, CN-105, improves outcomes in translational models of intracerebral hemorrhage
Authors: Wang Haichen , Faw Timothy D. , Lin Yufeng , Huang Shan , Venkatraman Talaignair N. , Cantillana Viviana , Lascola Christopher D. , James Michael L. , Laskowitz Daniel T. 
Published: October 2020

AbstractBackgroundIntracerebral hemorrhage (ICH) is a devastating form of cerebrovascular disease for which there are no approved pharmacological interventions that improve outcomes. Apolipoprotein E (apoE) has emerged as a promising therapeutic target given its neuroprotective properties and ability to modify neuroinflammatory responses. We developed a 5-amino acid peptide, CN-105, that mimics the polar face of the apoE helical domain involved in receptor interactions, readily crosses the blood-brain barrier, and improves outcomes in well-established preclinical ICH models. In the current study, we investigated the therapeutic potential of CN-105 in translational ICH models that account for hypertensive comorbidity, sex, species, and age.MethodsIn three separate experiments, we delivered three intravenous doses of CN-105 (up to 0.20 mg/kg) or vehicle to hypertensive male BPH/2J mice, spontaneously hypertensive female rats, or 11-month old male mice within 24-hours of ICH. Neuropathological and neurobehavioral outcomes were determined over 3, 7, and 9 days, respectively.ResultsIn spontaneously hypertensive male mice, there was a significant dose-dependent effect of CN-105 on vestibulomotor function at 0.05 and 0.20 mg/kg doses (p < 0.05; 95% CI: 0.91 – 153.70 and p < 0.001; 95% CI: 49.54 – 205.62), while 0.20 mg/kg also improved neuroseverity scores (p < 0.05; 95% CI: 0.27 – 11.00) and reduced ipsilateral brain edema (p < 0.05; 95% CI:−0.037 –−0.001). In spontaneously hypertensive female rats, CN-105 (0.05 mg/kg) had a significant effect on vestibulomotor function (p < 0.01; η2= 0.093) and neuroseverity scores (p < 0.05; η2= 0.083), and reduced contralateral edema expansion (p < 0.01; 95% CI:−1.41 –−0.39). In 11-month old male mice, CN-105 had a significant effect on vestibulomotor function (p < 0.001; η2= 0.111) but not neuroseverity scores (p > 0.05; η2= 0.034).ConclusionsAcute treatment with CN-105 improves outcomes in translational ICH models independent of sex, species, age, or hypertensive comorbidity.
Single-cell joint detection of chromatin occupancy and transcriptome enables higher-dimensional epigenomic reconstructions
Authors: Xiong Haiqing , Luo Yingjie , Wang Qianhao , Yu Xianhong , He Aibin 
Published: October 2020

SUMMARYDeciphering mechanisms in cell fate decisions requires single-cell holistic reconstructions of multi-dimensional epigenome in transcriptional regulation. Here we develop CoTECH, a combinatorial barcoding method allowing for high-throughput single-cell joint detection of chromatin occupancy and transcriptome. First, we used CoTECH to examine bivalent histone marks (H3K4me3 and H3K27me3) with transcription from naïve to primed mouse embryonic stem cells. Concurrent bivalent marks in pseudo-single cells linked via transcriptome were computationally derived, resolving pseudotemporal bivalency trajectories and disentangling a context-specific interplay between H3K4me3/H3K27me3 and transcription level. Next, CoTECH with H3K27ac, an active enhancer marker, revealed the regulatory basis of endothelial-to-hematopoietic transition in two waves of hematopoietic cells and distinctive enhancer-gene linking schemes guiding hemogenic endothelial cell (HEC) emergence, indicating a unique epigenetic control of transcriptional regulation for hematopoietic stem cell priming. Together, CoTECH provides an efficient framework for single-cell co-assay of chromatin occupancy and transcription, thus, enabling higher-dimensional epigenomic reconstructions.
Genome sequencing sheds light on the contribution of structural variants toBrassica oleraceadiversification
Authors: Guo Ning , Wang Shenyun , Gao Lei , Liu Yongming , Duan Mengmeng , Wang Guixiang , Li Jingjing , Yang Meng , Zong Mei , Han Shuo , Pei Yanzheng , Borm Theo , Sun Honghe , Miao Liming , Liu Di , Yu Fangwei , Zhang Wei , Ji Heliang , Zhu Chaohui , Xu Yong , Bonnema Guusje , Li Jianbin , Fei Zhangjun , Liu Fan 
Published: October 2020

AbstractBrassica oleraceaincludes several morphologically diverse, economically important vegetable crops. Here we present high-quality chromosome-scale genome assemblies for twoB. oleraceamorphotypes, cauliflower and cabbage. Direct comparison of these two assemblies identifies ~120 K high-confidence structural variants (SVs). Population analysis of 271B. oleraceaaccessions using these SVs clearly separates different morphotypes, suggesting the association of SVs withB. oleraceaintraspecific divergence. Genes affected by SVs selected between cauliflower and cabbage are enriched with functions related to response to stress and stimulus and meristem and flower development. Furthermore, genes affected by selected SVs and involved in the switch from vegetative to generative growth that defines curd initiation, inflorescence meristem proliferation for curd formation, maintenance and enlargement, are identified, providing insights into the regulatory network of curd development. This study reveals the important roles of SVs in diversification of different morphotypes ofB. oleracea, and the newly assembled genomes and the SVs provide rich resources for future research and breeding.
Persistence of plant-mediated microbial soil legacy effects in soil and inside roots
Authors: Hannula S. Emilia , Heinen Robin , Huberty Martine , Steinauer Katja , De Long Jonathan R. , Jongen Renske , Bezemer T. Martijn 
Published: October 2020

AbstractPlant-soil feedbacks are shaped by microbial legacies previous plants leave in the soil. We tested the persistence of such soil legacies after subsequent colonization by the same or other plant species, and whether the microbiome created by the previous plant explains current plant growth. Legacies of previous plants were detectable in soil fungal communities several months after their removal while concomitantly the effect of the current plant amplified in time. Remarkably, bacterial legacies faded away rapidly in the soil and bacterial communities were selected strongly by plant currently growing in the soil. Both fungal and bacterial legacies wrought by the previous plant were conserved inside the root endophytic compartment of the current plant and these endophytes affected significantly the plant growth. Hence, microbial soil legacies present at the time of plant establishment play a vital role in shaping plant growth even as the composition gradually changes in the soil after subsequent plant colonization, as they are taken up as endophytes in the plant. This suggests that plant-soil feedbacks may be partly mediated by a relatively stable endophytic community acquired in early ontogeny while the effects of previous plants detected on soil microbiomes vary between organisms studied. We further show that plants growing in their own soils harbor different endophytic microbiomes than plants growing in soils with legacy of other plants and that especially grasses are sensitive to species specific fungal pathogens while all plant species have less endophyticStreptomyceteswhen growing in their own soil. In conclusion, we show that soil legacies wrought by previous plants can remain present in the soils and inside the roots for months, even when subsequent plants colonize the soil and that these legacies also substantially modulate the plant growth.
Improving the sensitivity of differential-expression analyses for under-powered RNA-seq experiments
Authors: Kalinka Alex T. 
Published: October 2020

AbstractHigh-throughput studies, in which thousands of hypothesis tests are conducted simultaneously, can be under-powered when effect sizes are small and there are few replicates. Here, I describe an approach to estimate the FDR for a given experiment such that the ground truth is known. A decision boundary between true and false positive calls can then be learned from the data itself along the axes of fold change and expression level. By excluding hits that fall into the false positive space, the FDR of any given method can be controlled providing a means to employ less conservative methods for detecting differential expression without incurring the usual loss of precision. I show that coupling this approach with a feature-selection method - an elastic-net logistic regression - can increase sensitivity 10-fold above what is achievable with the prevailing methods of the day. An R package implementing these methods is available athttps://github.com/alextkalinka/delboy.