bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous aerosol and intra-muscular immunization with influenza vaccine induces powerful protective local T cell and systemic Ab immune responses in pigs
Authors: Martini Veronica , Paudyal Basu , Chrun Tiphany , McNee Adam , Edmans Matthew , Maze Emmanuel , Clark Beckie , Nunez Alejandro , Dolton Garry , Sewell Andrew , Beverley Peter , MacLoughlin Ronan , Townsend Alain , Tchilian Elma 
Published: September 2020

AbstractA vaccine providing both powerful antibody and cross-reactive T cell immune responses against influenza viruses would be beneficial for both humans and pigs. Here we evaluated intramuscular (IM), aerosol (Aer) and simultaneous immunization (SIM) by both routes in pigs, using the single cycle candidate influenza vaccine S-FLU. After prime and boost immunization pigs were challenged with H1N1pdm09 virus. IM immunized pigs generated high titer of neutralizing antibodies but poor T cell responses, while Aer induced powerful respiratory tract T cell responses, but a low titer of antibodies. SIM pigs combined high antibody titers and strong local T cell responses. SIM pigs showed the most complete suppression of virus shedding and the greatest improvement in pathology. We conclude that SIM regimes for immunization against respiratory pathogens warrant further study.
Computational 4D-OCM for label-free imaging of collective cell invasion and force-mediated deformations in collagen
Authors: Mulligan Jeffrey A. , Ling Lu , Fischbach Claudia , Adie Steven G. 
Published: September 2020

AbstractTraction force microscopy (TFM) is an important family of techniques used to measure and study the role of cellular traction forces (CTFs) associated with many biological processes. However, current standard TFM methods rely on imaging techniques that do not provide the experimental capabilities necessary to study CTFs within 3D collective and dynamic systems embedded within optically scattering media. Traction force optical coherence microscopy (TF-OCM) was developed to address these needs, but has only been demonstrated for the study of isolated cells embedded within optically clear media. Here, we present computational 4D-OCM methods that enable the study of dynamic invasion behavior of large tumor spheroids embedded in collagen. Our multi-day, time-lapse imaging data provided detailed visualizations of evolving spheroid morphology, collagen degradation, and collagen deformation, all using label-free scattering contrast. These capabilities, which provided insights into how stromal cells affect cancer progression, significantly expand access to critical data about biophysical interactions of cells with their environment, and lay the foundation for future efforts toward volumetric, time-lapse reconstructions of collective CTFs with TF-OCM.
Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences
Authors: Karasik Agnes , Jones Grant D. , DePass Andrew V. , Guydosh Nicholas R. 
Published: September 2020

SUMMARYRibonuclease L (RNase L) is activated as part of the innate immune response and plays an important role in the clearance of viral infections. When activated, it endonucleolytically cleaves both viral and host RNAs, leading to a global reduction in protein synthesis. However, it remains unknown how widespread RNA decay, and consequent changes in the translatome, promote the elimination of viruses. To study how this altered transcriptome is translated, we assayed the global distribution of ribosomes in RNase L activated human cells with ribosome profiling. We found that RNase L activation leads to a substantial increase in the fraction of translating ribosomes in ORFs internal to coding sequences (iORFs) and ORFs within 5’ and 3’ UTRs (uORFs and dORFs). Translation of these alternative ORFs was dependent on RNase L’s cleavage activity, suggesting that mRNA decay fragments are translated to produce short peptides that may be important for antiviral activity.
Molecular basis for SARS-CoV-2 spike affinity for human ACE2 receptor
Authors: Delgado Julián M. , Duro Nalvi , Rogers David M. , Tkatchenko Alexandre , Pandit Sagar A. , Varma Sameer 
Published: September 2020

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused substantially more infections, deaths, and economic disruptions than the 2002-2003 SARS-CoV. The key to understanding SARS-CoV-2’s higher infectivity may lie in its host receptor recognition mechanism. This is because experiments show that the human ACE2 protein, which serves as the primary receptor for both CoVs, binds to CoV-2’s spike protein 5-20 fold stronger than SARS-CoV’s spike protein. The molecular basis for this difference in binding affinity, however, remains unexplained and, in fact, a comparison of X-ray structures leads to an opposite proposition. To gain insight, we use all-atom molecular dynamics simulations. Free energy calculations indicate that CoV-2’s higher affinity is due primarily to differences in specific spike residues that are local to the spike-ACE2 interface, although there are allosteric effects in binding. Comparative analysis of equilibrium simulations reveals that while both CoV and CoV-2 spike-ACE2 complexes have similar interfacial topologies, CoV-2’s spike protein engages in greater numbers, combinatorics and probabilities of hydrogen bonds and salt bridges with ACE2. We attribute CoV-2’s higher affinity to these differences in polar contacts, and these findings also highlight the importance of thermal structural fluctuations in spike-ACE2 complexation. We anticipate that these findings will also inform the design of spike-ACE2 peptide blockers that, like in the cases of HIV and Influenza, can serve as antivirals.
Microbial colonization induces histone acetylation critical for inherited gut-germline-neural signaling
Authors: Hong Chunlan , Lalsiamthara Jonathan , Ren Jie , Sang Yu , Aballay Alejandro 
Published: September 2020

AbstractThe gut-neural axis plays a critical role in the control of several physiological processes, including the communication of signals from the microbiome to the nervous system, which affects learning, memory, and behavior. However, the pathways involved in gut-neural signaling of gut-governed behaviors remain unclear. We found that the intestinal distension caused by the bacteriumPseudomonas aeruginosainduces histone H4 Lys8 acetylation (H4K8ac) in the germline ofCaenorhabditis elegans, which is required for both a bacterial aversion behavior and its transmission to the next generation. We show that induction of H4K8ac in the germline is essential for bacterial aversion and that a 14-3-3 chaperone protein family member, PAR-5, is required for H4K8ac. Our findings highlight a role for H4K8ac in the germline not only in the intergenerational transmission of pathogen avoidance but also in the transmission of pathogenic cues that travel through the gut-neural axis to control the aversive behavior.
Arabidopsis thalianazinc accumulation in leaf trichomes is correlated with zinc concentration in leaves
Authors: Ricachenevsky Felipe K. , Punshon Tracy , Salt David E. , Fett Janette P. , Guerinot Mary Lou 
Published: September 2020

AbstractZinc (Zn) is a key micronutrient. In humans, Zn deficiency is a common nutritional disorder, and most people acquire dietary Zn from eating plants. In plants, Zn deficiency can decrease plant growth and yield. Understanding Zn homeostasis in plants can improve agriculture and human health. While root Zn transporters in plat model species have been characterized in detail, comparatively little is known about shoot processes controlling Zn concentrations and spatial distribution. Previous work showed that Zn hyperaccumulator species such asArabidopsis halleriaccumulate Zn and other metals in leaf trichomes. The model speciesArabidopsis thalianais a non-accumulating plant, and to date there is no systematic study regarding Zn accumulation inA. thalianatrichomes. Here, we used Synchrotron X-Ray Fluorescence mapping to show that Zn accumulates at the base of trichomes ofA. thaliana, as had seen previously for hyperaccumulators. Using transgenic and natural accessions ofA. thalianathat vary in bulk leaf Zn concentration, we demonstrated that higher leaf Zn increases total Zn found at the base of trichome cells. Furthermore, our data suggests that Zn accumulates in the trichome apoplast, likely associated with the cell wall. Our data indicates that Zn accumulation in trichomes is a function of the Zn status of the plant, and provides the basis for future studies on a genetically tractable plant species aiming at understanding the molecular steps involved in Zn spatial distribution in leaves.
Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk
Authors: Vazquez Juan Manuel , Lynch Vincent J. 
Published: September 2020

AbstractThe risk of developing cancer is correlated with body size and lifespan within species. Between species, however, there is no correlation between cancer and either body size or lifespan, indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Elephants and their relatives (Proboscideans) are a particularly interesting lineage for the exploration of mechanisms underlying the evolution of augmented cancer resistance because they evolved large bodies recently within a clade of smaller bodied species (Afrotherians). Here, we explore the contribution of gene duplication to body size and cancer risk in Afrotherians. Unexpectedly, we found that tumor suppresxssor duplication was pervasive in Afrotherian genomes, rather than restricted to Proboscideans. Proboscideans, however, have duplicates in unique pathways that may underlie some aspects of their remarkable anti-cancer cell biology. These data suggest that duplication of tumor suppressor genes facilitated the evolution of increased body size by compensating for decreasing intrinsic cancer risk.
Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours
Authors: Thomas Catherine S. , Mohammadkhani Aida , Rana Madiha , Qiao Min , Baimel Corey , Borgland Stephanie L. 
Published: September 2020

ABSTRACTReward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic (LH) orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin. Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (oxR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LH orexin/dynorphin-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LH orexin/dynorphin inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and conditioned place preference, and increases the food cue-directed orientation in a Pavlovian conditioning procedure. LH orexin/dynorphin potentiation of NAc dopamine release and real time place preference was blocked by an oxR1, but not KOR antagonist. Thus, rewarding effects associated with optical stimulation of LH orexin/dynorphin inputs in the VTA are predominantly driven by orexin rather than dynorphin.
Switch-1 Instability at the Active Site Decouples ATP Hydrolysis from Force Generation in Myosin II
Authors: Walker Benjamin C. , Walczak Claire E. , Cochran Jared C. 
Published: September 2020

AbstractMyosin active site elements (i.e. switch-1) bind both ATP and a divalent metal to coordinate ATP hydrolysis. ATP hydrolysis at the active site is linked via allosteric communication to the actin polymer binding site and lever arm movement, thus coupling the free energy of ATP hydrolysis to force generation. How active site motifs are functionally linked to actin binding and the power stroke is still poorly understood. We hypothesize that destabilizing switch-1 movement at the active site will negatively affect the tight coupling of ATP hydrolysis to force production. Using a metal-switch system, we tested the effect of interfering with switch-1 coordination of the divalent metal cofactor on force generation. We found that while ATPase activity increased, motility was inhibited. Our results demonstrate that a single atom change that affects the switch-1 interaction with the divalent metal directly regulates actin binding and force generation. Even slight modification of the switch-1 divalent metal coordination can decouple ATP hydrolysis from motility. Switch-1 movement is therefore critical for both structural communication with the actin binding site, as well as coupling the energy of ATP hydrolysis to force generation.
Evolution of Boldness and Exploratory Behavior in Giant Mice from Gough Island
Authors: Stratton Jered A. , Nolte Mark J. , Payseur Bret A. 
Published: September 2020

AbstractIsland populations are hallmarks of extreme phenotypic evolution. Radical changes in resource availability and predation risk accompanying island colonization drive changes in behavior, which Darwin likened to tameness in domesticated animals. Although many examples of animal boldness are found on islands, the heritability of observed behaviors, a requirement for evolution, remains largely unknown. To fill this gap, we profiled anxiety and exploration in island and mainland inbred strains of house mice raised in a common laboratory environment. The island strain was descended from mice on Gough Island, the largest wild house mice on record. Experiments utilizing open environments across two ages showed that Gough Island mice are bolder and more exploratory, even when a shelter is provided. Concurrently, Gough Island mice retain an avoidance response to predator urine. F1 offspring from crosses between these two strains behave more similarly to the mainland strain for most traits, suggesting recessive mutations contributed to behavioral evolution on the island. Our results provide a rare example of novel, inherited behaviors in an island population and demonstrate that behavioral evolution can be specific to different forms of perceived danger. Our discoveries pave the way for a genetic understanding of how island populations evolve unusual behaviors.
A reduction in voluntary physical activity during pregnancy in mice is mediated by prolactin
Authors: Ladyman S.R. , Carter K.M. , Aung Z. Khant , Grattan D. R. 
Published: September 2020

AbstractAs part of the maternal adaptations to pregnancy, mice show a rapid, profound reduction in voluntary running wheel activity (RWA) as soon as pregnancy is achieved. Here, we evaluate the hypothesis that prolactin, one of the first hormones to change secretion pattern following mating, is involved in driving this suppression of physical activity levels during pregnancy. We show that prolactin can acutely suppress RWA in virgin female mice, and that conditional deletion of prolactin receptors (Prlr) from either all forebrain neurons or from GABA neurons prevented the early pregnancy-induced suppression of RWA. Deletion of Prlr specifically from the medial preoptic area, a brain region associated with multiple homeostatic and behavioural roles including parental behaviour, completely abolished the early pregnancy-induced suppression of RWA. Our data demonstrate a key role for prolactin in suppressing voluntary physical activity during early pregnancy, highlighting a novel biological basis for reduced physical activity in pregnancy.
Deep-sea mussels from a hybrid zone on the Mid-Atlantic Ridge host genetically indistinguishable symbionts
Authors: Ücker Merle , Ansorge Rebecca , Sato Yui , Sayavedra Lizbeth , Breusing Corinna , Dubilier Nicole 
Published: September 2020

AbstractThe composition and diversity of animal microbiomes is shaped by a variety of factors, many of them interacting, such as host traits, the environment, and biogeography. Hybrid zones, in which the ranges of two host species meet and hybrids are found, provide natural experiments for determining the drivers of microbiome communities, but have not been well studied in marine environments. Here, we analysed the composition of the symbiont community in two deep-sea,Bathymodiolusmussel species along their known distribution range at hydrothermal vents on the Mid-Atlantic Ridge, with a focus on the hybrid zone where they interbreed. In-depth metagenomic analyses of the sulphur-oxidising symbionts of 30 mussels from the hybrid zone, at a resolution of single nucleotide polymorphism analyses of ∼2500 orthologous genes, revealed that parental and hybrid mussels have genetically indistinguishable symbionts. While host genetics does not appear to affect symbiont composition in these mussels, geographic location of the mussels on the Mid-Atlantic Ridge explained 45 % of symbiont genetic variability based on redundancy analyses. We hypothesize that geographic structuring of the free-living symbiont population plays a major role in driving the composition of the microbiome in these deep-sea mussels.
Temporal trait plasticity and neighborhood crowding predict the growth of tropical trees
Authors: Asefa Mengesha , Song Xiaoyang , Cao Min , Lasky Jesse R. , Yang Jie 
Published: September 2020

AbstractFunctional traits and neighborhood composition have been used to predict tree growth dynamics. Temporal changes in trait values (temporal trait plasticity) is one of the mechanisms for adaptive plastic response to environmental change. However, the consequence of temporal change in trait values and neighborhoods on the growth performance of individuals has rarely been investigated. We, therefore tested the effect of temporal changes in trait values and neighborhood crowding on the growth rate of individuals in a tropical forest using a dataset containing individual level growth and functional trait data forFicusindividuals. We collected trait and size data at two time points (2010 and 2017) for 472 individuals of 15Ficusspecies in Xishuangbanna tropical forest dynamics plot, southwest China. We used linear mixed effect model to predict the effect of temporal trait plasticity and neighborhood crowding on the relative growth rate of individuals using these data. We found significant temporal changes in individuals’ functional traits suggesting a shift in ecological strategies from being functionally acquisitive to conservative. We also found differences in neighborhood crowding between the two census years indicating that the strength of individual interactions might change over time. The temporal changes in trait values and neighborhood crowding were found to predict better the relative growth rate of individuals, compared to static trait or crowding values in the initial and final censuses. We also found major axes of tree functional strategies in a principal component analysis, highlighting potentially adaptive trait differences. Our results in general highlight to consider the temporal dimension of functional traits and biotic interactions, as our result suggest that growth-trait relationships may vary between time points, allowing us to understand the demographic response of species to temporal environmental change.
Feature-specific reaction times reveal a semanticisation of memories over time and with repeated remembering
Authors: Lifanov Julia , Linde-Domingo Juan , Wimber Maria 
Published: September 2020

AbstractMemories are thought to undergo an episodic-to-semantic transformation in the course of their consolidation. We here tested if repeated recall induces a similar semanticization, and if the resulting qualitative changes in memories can be measured using simple feature-specific reaction time probes. Participants studied associations between verbs and object images, and then repeatedly recalled the objects when cued with the verb, immediately and after a two-day delay. Reaction times during immediate recall demonstrated that conceptual features were accessed faster than perceptual features. Consistent with a semanticization process, this perceptual-conceptual gap significantly increased across the delay. A significantly smaller perceptual-conceptual gap was found in the delayed recall data of a control group who repeatedly studied the verb-object pairings on the first day, instead of actively recalling them. Our findings suggest that wake recall and offline consolidation interact to transform memories over time, strengthening meaningful semantic information over perceptual detail.
Canonical goal-selective representations are absent from prefrontal cortex in a spatial working memory task requiring behavioral flexibility
Authors: Böhm Claudia , Lee Albert K. 
Published: September 2020

AbstractThe prefrontal cortex (PFC)’s functions are thought to include working memory, as its activity can reflect information that must be temporarily maintained to realize the current goal. We designed a flexible spatial working memory task that required rats to navigate - after distractions and a delay - to multiple possible goal locations from different starting points and via multiple routes. This made the current goal location the key variable to remember, instead of a particular direction or route to the goal. However, across a broad population of PFC neurons, we found no evidence of current-goal-specific memory in any previously reported form - i.e. differences in the rate, sequence, phase or covariance of firing. This suggests such patterns do not hold working memory in the PFC when information must be employed flexibly. Instead, the PFC grouped locations representing behaviorally equivalent task features together, consistent with a role in encoding long-term knowledge of task structure.
Backcasting for desirable futures in Finnish forest-based firms
Authors: Näyhä Annukka 
Published: September 2020

Purpose
In Finland, new forest-based sector (FBS) businesses are seen as important for the transition to the circular bioeconomy. The purpose of this study is to explore the transition of Finnish FBS companies to new business models. The aim is to understand how FBS companies define their ideal future states and related business models for the year 2030.

Design/methodology/approach
This study uses thematic interviews with managers from various FBS firms and companies from interfacing sectors. In the interviews, the key idea of backcasting was pursued when respondents discussed the desirable future states of their business.

Findings
The effort to achieve growth of the business and the appearance of new products characterize the company-specific desirable future states. In these desirable futures, expanded businesses will be based on strong knowledge. Resource efficiency and collaboration create a strong basis for the desirable future state of the whole FBS to create a sustainable and innovative “Wood Valley.”

Research limitations/implications
The key limitations are that the backcasting process has been conducted only through interviews and a participative approach with stakeholder dialogue is lacking in the process. This means that the desirable futures are created by the FBS companies only.

Originality/value
As a practical contribution, the study shows the future-oriented thinking and goals of FBS firms. As a theoretical contribution, it extends research on sustainable business models and discussions on the novel field of corporate foresight.