bluuebunny/crossref_metadata_2025_split huggingface dataset:
Top-down and bottom-up controls on soil carbon and nitrogen cycling with repeated burning across four ecosystems
Authors: Pellegrini Adam F. A. , Hobbie Sarah E. , Reich Peter B. , Jumpponen Ari , Brookshire E. N. Jack , Caprio Anthony C. , Coetsee Corli , Jackson Robert B. 
Published: March 2019

AbstractFires shape the biogeochemistry and functioning of many ecosystems, but fire frequencies are changing across large areas of the globe. Frequent fires can change soil carbon (C) and nitrogen (N) storage through both “top-down” pathways, by altering inputs through shifting plant composition and biomass, and “bottom-up” ones, by altering losses through decomposition and turnover of soil organic matter. However, the relative importance of these different pathways and the degree to which they regulate ecosystem responses to decades of changing fire frequencies is uncertain. Here, we sampled soils and plant communities in four North American and African sites spanning tropical savanna, temperate coniferous savanna, temperate broadleaf savanna, and temperate coniferous forest that each contained multiple plots repeatedly burned for 33-61 years and nearby plots that were protected from fire over the same period. The sites varied markedly in temperature, precipitation, species composition, fire history and soil chemistry; thus they represent a broad test for the generality of fire impacts on biogeochemical cycling. For all four sites, bulk soil C and N by were 25-180% higher in unburned vs. frequently burned plots, with greater soil losses occurring in areas with greater declines in tree cover and biomass inputs into soils. Fire reduced the activity of soil extracellular enzymes that hydrolyze labile C and N from soil organic matter by two- to ten-fold, whereas tree cover was the predominant control on the oxidation of recalcitrant C compounds. C-acquisition enzyme activity tended to decline with decreasing soil N, suggesting that N losses may contribute to limited decomposition, buffering systems against increased losses of soil C with fire. In conclusion, variability in how fire alters soil C and N across ecosystems can be explained partly by fire-driven changes in tree cover and biomass, but the slower turnover of organic matter we observed may offset some of the reduction of C inputs from plants after fire.
Exon-mediated activation of transcription starts
Authors: Fiszbein Ana , Krick Keegan S. , Burge Christopher B. 
Published: March 2019

SummaryThe processing of transcripts from mammalian genes often occurs near in time and space to their transcription. Here we describe a phenomenon we call exon-mediated activation of transcription starts (EMATS) that affects thousands of mammalian genes in which the splicing of internal exons impacts the spectrum of promoters used and expression level of the host gene. We observed that evolutionary gain of new internal exons is associated with gain of new TSSs nearby and increased gene expression. Inhibiting exon splicing reduced transcription from nearby promoters. Conversely, creation of new splice sites and enable splicing of new exons activated transcription from cryptic promoters. The strongest effects were associated with weak promoters located proximal and upstream of efficiently spliced exons. Together, our findings support a model in which splicing factors recruit transcription machinery locally to influence TSS choice, and identify exon gain, loss and regulatory change as major contributors to the evolution of alternative promoters and altered gene expression in mammals.
The DNA Methylome of Inflammatory Bowel Disease (IBD) reflects intrinsic and extrinsic factors in intestinal epithelial cells
Authors: Agliata Iolanda , Fernandez-Jimenez Nora , Goldsmith Chloe , Marie Julien C. , Bilbao Jose Ramon , Dante Robert , Hernandez-Vargas Hector 
Published: March 2019

AbstractAbnormal DNA methylation has been described in human inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD). As other complex diseases, IBD results from the balance between genetic predisposition and environmental exposures. As such, DNA methylation may be placed as an effector of both, genetic susceptibility variants and/or environmental signals such as cytokine exposure. We attempted to discern between these two non-excluding possibilities by performing a meta-analysis of DNA methylation data in intestinal epithelial cells of IBD and control samples. We identified abnormal DNA methylation at different levels: deviation from mean methylation signals at site and region levels, and differential variability. A fraction of such changes are associated with genetic polymorphisms linked to IBD susceptibility. In addition, by comparing with another intestinal inflammatory condition (i.e. celiac disease) we propose that aberrant DNA methylation can also be the result of unspecific processes such as chronic inflammation. Our characterization suggests that IBD methylomes combine intrinsic and extrinsic responses in intestinal epithelial cells, and could point to knowledge-based biomarkers of IBD detection and progression.Graphical AbstractConceptual representation of the study. Using a meta-analysis strategy we identified differentially methylated positions or regions (DMP/DMR) in IBD. Our assumption is that gene expression changes (IBD phenotype) take place downstream of DNA methylation. In turn, abnormal DNA methylation can be explained by a direct effect of inflammatory cytokines (“signaling”) and/or the result of a genetic polymorphism (SNP). SNP-DMP associations are called methylation quantitative trait loci (mQTL).
Zebrafish (Danio rerio) behavioral laterality predicts increased short-term avoidance memory but not stress-reactivity responses
Authors: Fontana Barbara D. , Cleal Madeleine , Clay James M. , Parker Matthew O. 
Published: March 2019

AbstractOnce considered a uniquely human attribute, behavioral laterality has proven to be ubiquitous among non□human animals, being frequently associated with different neurophenotypes in rodents and fish species. Zebrafish (Danio rerio) are a versatile vertebrate model system that has been widely used in translational neuropsychiatric research due their highly conserved genetic homology, well characterized physiological and extensive behavioral repertoire. Although the spontaneous left- and right-bias responses and associated behavioral domains (e.g. stress reactivity, aggression and learning) have previously been observed in other teleost species, no information regarding how spontaneous motor left-right bias responses of zebrafish predicts other behavioral domains has been described. Thus, we aimed to investigate the existence and incidence of natural left-right bias of adult zebrafish in the Y-maze test and explore any relationship of biasedness on the performance of different behavioral domains. This included learning about threat-cues in the fear conditioning test and locomotion and anxiety-related behavior in the novel tank diving test. In conclusion, we showed for the first time that zebrafish exhibit a natural manifestation of motor behavioral lateralization which can influence aversive learning responses. Although laterality did not change locomotion or anxiety-related behaviors, we found that biased animals had an altered exploration pattern in the Y-maze, making them easily discernable from their unbiased counterparts, and increased learning associated to fear cues.
A stimuli-responsive, pentapeptide, nanofiber hydrogel for tissue engineering
Authors: Tang James D. , Mura Cameron , Lampe Kyle J. 
Published: March 2019

ABSTRACTShort peptides are uniquely versatile building blocks for self-assembly. Supramolecular peptide assemblies can be used to construct functional hydrogel biomaterials—an attractive approach for neural tissue engineering. Here, we report a new class of short, five-residue peptides that form hydrogels with nanofiber structures. Using rheology and spectroscopy, we describe how sequence variations, pH, and peptide concentration alter the mechanical properties of our pentapeptide hydrogels. We find that this class of seven unmodified peptides forms robust hydrogels from 0.2–20 kPa at low weight percent (less than 3 wt. %) in cell culture media, and undergoes shear-thinning and rapid self-healing. The peptides self-assemble into long fibrils with sequence-dependent fibrillar morphologies. These fibrils exhibit a unique twisted ribbon shape, as visualized by TEM and Cryo-EM imaging, with diameters in the low tens of nanometers and periodicities similar to amyloid fibrils. Experimental gelation behavior corroborates our molecular dynamics simulations, which demonstrate peptide assembly behavior, an increase in β-sheet content, and patterns of variation in solvent accessibility. Our Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels are syringe-injectable and support cytocompatible encapsulation of oligodendrocyte progenitor cells (OPCs), as well as their proliferation and three-dimensional process extension. Furthermore, RAPID gels protect OPCs from mechanical membrane disruption and acute loss of viability when ejected from a syringe needle, highlighting the protective capability of the hydrogel as potential cell carriers for trans-plantation therapies. The tunable mechanical and structural properties of these supramolecular assemblies are shown to be permissive to cell expansion and remodeling, making this hydrogel system suitable as an injectable material for cell delivery and tissue engineering applications.
Developmental Recovery of Impaired Multisensory Processing in Autism and the Cost of Switching Sensory Modality
Authors: Crosse Michael J. , Foxe John J. , Molholm Sophie 
Published: March 2019

AbstractChildren with autism spectrum disorder (ASD) are often impaired in their ability to cope with and process multisensory information, which may contribute to some of the social and communicative deficits that are prevalent in this population. Amelioration of such deficits in adolescence has been observed for ecologically-relevant stimuli such as speech. However, it is not yet known if this recovery generalizes to the processing of nonsocial stimuli such as more basic beeps and flashes, typically used in cognitive neuroscience research. We hypothesize that engagement of different neural processes and lack of environmental exposure to such artificial stimuli leads to protracted developmental trajectories in both neurotypical (NT) individuals and individuals with ASD, thus delaying the age at which we observe this “catch up”. Here, we test this hypothesis using a bisensory detection task by measuring human response times to randomly presented auditory, visual and audiovisual stimuli. By measuring the behavioral gain afforded by an audiovisual signal, we show that the multisensory deficit previously reported in children with ASD recovers in adulthood by the mid-twenties. In addition, we examine the effects of switching between sensory modalities and show that teenagers with ASD incur less of a behavioral cost than their NT peers. Computational modelling reveals that multisensory information interacts according to different rules in children and adults, and that sensory evidence is weighted differently too. In ASD, weighting of sensory information and allocation of attention during multisensory processing differs to that of NT individuals. Based on our findings, we propose a theoretical framework of multisensory development in NT and ASD individuals.
Structural basis of the differential binding of engineered knottins 2.5F and 2.5D to integrins αVβ3 and α5β1
Authors: Van Agthoven Johannes F. , Shams Hengameh , Cochran Frank V. , Alonso José L. , Kintzing James R. , Garakani Kiavash , Xiong Jian-Ping , Mofrad Mohammad R. K. , Cochran Jennifer R. , Arnaout M. Amin 
Published: March 2019

AbstractIntegrins αVβ3 and α5β1 play critical roles in tumor survival, invasion, metastasis, and angiogenesis and are validated targets for cancer therapy and molecular imaging. Increasing evidence suggests that targeting both integrins simultaneously with antagonists is more effective in cancer therapy because of concerns about resistance and paradoxical promotion of tumor growth with use of agents highly selective for a single integrin. Engineered Arg-Gly-Asp (RGD)-containing 3.5 kDa cysteine-knot proteins (knottins 2.5F and 2.5D) are attractive drug candidates due to their exceptional structural stability and high affinity binding to certain integrins. 2.5F binds both αVβ3 and α5β1, whereas 2.5D is αVβ3-selective. To elucidate the structural basis of integrin selection, we determined the structures of 2.5F and 2.5D both as apo-proteins and in complex with αVβ3. These data, combined with MD simulations and mutational studies, revealed a critical role of two αVβ3-specific residues in the vicinity of the metal ion dependent adhesion site (MIDAS) in promoting an αVβ3-induced fit of 2.5D. In contrast, conformational selection accounted for the specificity of 2.5F to both integrins. These data provide new insights into the structural basis of integrin-ligand binding specificity, and could help in development of integrin-targeted therapeutics.
Body-map proto-organization in newborn macaques
Authors: Arcaro Michael J. , Schade Peter F. , Livingstone Margaret S. 
Published: March 2019

ABSTRACTTopographic sensory maps are a prominent feature of the adult primate brain. Here, we asked whether topographic representations of the environment are fundamental to early development. Using fMRI, we find that the newborn somato-motor system, spanning frontoparietal cortex and subcortex, comprises multiple topographic body representations. The organization of these large-scale body maps was indistinguishable from those in adults and already exhibited features stereotypical of adult maps. Finer-scale differentiation of individual fingers increased over the first two years, suggesting that topographic representations are refined during early development. Last, we found that somato-motor representations were unchanged in two visually impaired monkeys who relied entirely on touch for interacting with their environment, demonstrating that massive shifts in early sensory experience in an otherwise anatomically intact brain are not sufficient for driving cross-modal plasticity. We propose that a topographic scaffolding is present at birth that both directs and constrains experience-driven modifications throughout sensory systems.
TGF-β family ligands exhibit distinct signaling dynamics that are driven by receptor localization
Authors: Miller Daniel S. J. , Schmierer Bernhard , Hill Caroline S. 
Published: March 2019

AbstractGrowth factor-induced signal transduction pathways are tightly regulated at multiple points intracellularly, but how cells monitor levels of extracellular ligand and translate this information into appropriate downstream responses remains unclear. Understanding signaling dynamics is thus a key challenge in determining how cells respond to external cues. Here, we demonstrate that different TGF-β family ligands, namely Activin A and BMP4, signal with distinct dynamics, which differ profoundly from those of TGF-β itself. The distinct signaling dynamics are driven by differences in the localization and internalization of receptors for each ligand, which in turn determine the capability of cells to monitor levels of extracellular ligand. Using mathematical modeling, we demonstrate that the distinct receptor behaviors and signaling dynamics observed may be primarily driven by differences in ligand-receptor affinity. Furthermore, our results provide a clear rationale for the different mechanisms of pathway regulation foundin vivofor each of these growth factors.
Supercharged Assembly: A Broad-Spectrum Mechanism of Action for Drugs that Undermine Controlled HIV-1 Viral Capsid Formation
Authors: Pak Alexander J. , Grime John M. A. , Yu Alvin , Voth Gregory A. 
Published: March 2019

AbstractThe early and late stages of human immunodeficiency virus (HIV) replication are orchestrated by the capsid (CA) protein, which self-assembles into a conical protein shell during viral maturation. Small molecule drugs known as capsid inhibitors (CIs) impede the highly-regulated activity of CA. Intriguingly, a few CIs, such as PF-3450074 (PF74) and GS-CA1, exhibit effects at multiple stages of the viral lifecycle at effective concentrations in the pM to nM regimes, while the majority of CIs target a single stage of the viral lifecycle and are effective at nM to µM concentrations. In this work, we use coarse-grained (CG) molecular dynamics simulations to elucidate the molecular mechanisms that enable CIs to have such curious broad-spectrum activity. Our quantitatively analyzed findings show that CIs can have a profound impact on the hierarchical self-assembly of CA by perturbing the population of small CA oligomers. The self-assembly process is accelerated by the emergence of alternative assembly pathways that favor the rapid incorporation of CA pentamers, and leads to increased structural pleomorphism of mature capsids. Two relevant phenotypes are observed: (1) eccentric capsid formation that may fail to encase the viral genome and (2) rapid disassembly of the capsid, which express at late and early stages of infection, respectively. Finally, our study emphasizes the importance of adopting a dynamical perspective on inhibitory mechanisms and provides a basis for the design of future therapeutics that are effective at low stoichiometric ratios of drug to protein.
Avant-garde: An automated data-driven DIA data curation tool
Authors: Jacome Alvaro Sebastian Vaca , Peckner Ryan , Shulman Nicholas , Krug Karsten , DeRuff Katherine C. , Officer Adam , MacLean Brendan , MacCoss Michael J. , Carr Steven A. , Jaffe Jacob D. 
Published: March 2019

AbstractData-Independent Acquisition (DIA) is a technique that promises to comprehensively detect and quantify all peptides above an instrument’s limit of detection. Several software tools to analyze DIA data have been developed in recent years. However, several challenges still remain, like confidently identifying peptides, defining integration boundaries, dealing with interference for selected transitions, and scoring and filtering of peptide signals in order to control false discovery rates. In practice, a visual inspection of the signals is still required, which is impractical with large datasets. Avant-garde is a new tool to refine DIA (and PRM) by removing interfered transitions, adjusting integration boundaries and scoring peaks to control the FDR. Unlike other tools where MS runs are scored independently from each other, Avant-garde uses a novel data-driven scoring strategy. DIA signals are refined by learning from the data itself, using all measurements in all samples together to achieve the best optimization. We evaluated the performances of Avant-garde with a calibrated sample using spiked-in standards in a complex background, a phospho-enriched dataset (Abelin et al, 2016), and two complex hybrid proteome samples for benchmarking DIA software tools. The results clearly showed that Avant-garde is capable of improving the selectivity, accuracy, and reproducibility of the quantification results in very complex biological matrices. We have further shown that it can evaluate the suitability of a peak to be used for quantification reaching the same levels of selectivity, accuracy, and reproducibility obtained with manual validation.
Syndecan-1 facilitates breast cancer metastasis to the brain
Authors: Sayyad Megan R. , Puchalapalli Madhavi , Vergara Natasha G. , Wangensteen Sierra Mosticone , Moore Melvin , Mu Liang , Edwards Chevaunne , Anderson Aubree , Kall Stefanie , Sullivan Megan , Dozmorov Mikhail , Singh Jaime , Idowu Michael O. , Koblinski Jennifer E. 
Published: March 2019

AbstractPurposeAlthough survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis.MethodsTo assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 was silenced.ResultsSilencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that the reduction in brain metastases with Sdc1 knockdown was likely due to reduced breast cancer cell migration across the BBB and adhesion to the perivascular regions of the brain. However, there was no change in attachment to brain endothelial cells or astrocytes. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines, which may influence the BBB.ConclusionsTaken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.
Trait convergence in photosynthetic nutrient‐use efficiency along a 2‐million year dune chronosequence in a global biodiversity hotspot
Authors: Guilherme Pereira Caio , Hayes Patrick E. , O’Sullivan Odhran S. , Weerasinghe Lasantha K. , Clode Peta L. , Atkin Owen K. , Lambers Hans 
Published: March 2019

Abstract

The Jurien Bay dune chronosequence in south‐western Australia’s biodiversity hotspot comprises sites differing in nutrient availability, with phosphorus (P) availability declining strongly with increasing soil age. We have explored the exceptionally high photosynthetic P‐use efficiency (PPUE) of Proteaceae in this region, triggering the question what the PPUE of co‐occurring species in other families might be along the Jurien Bay chronosequence.

We explored how traits associated with PPUE, photosynthetic nitrogen (N)‐use efficiency (PNUE) and leaf respiration might converge along the chronosequence, and whether Proteaceae and non‐Proteaceae species differ in leaf traits associated with nutrient use.

Seven to 10 species were sampled at three sites differing in nutrient availability (ranging from N‐ to P‐limited). Measurements of leaf light‐saturated photosynthesis and dark respiration were integrated with measurements of total N and P concentration in both mature and senesced leaves, and leaf mass per unit area (LMA).

Contrary to what is known for other chronosequences, rates of photosynthesis and respiration did not decrease with increasing soil age and LMA along the Jurien Bay chronosequence. However, they increased when expressed per unit leaf P. Both N and P were used much more efficiently for photosynthesis on nutrient‐poor sites, in both Proteaceae and non‐Proteaceae species. Proteaceae had the fastest rate of photosynthesis per unit leaf P, followed by species that preferentially allocate P to mesophyll cells, rather than epidermal cells.

Synthesis. Our results show that with declining soil P availability, photosynthetic P‐use efficiency of all investigated species from different families increased. Plants growing on the oldest, most nutrient‐impoverished soils exhibited similar rates of CO2 exchange as plants growing on more nutrient‐rich younger soils, and extraordinarily high photosynthetic P‐use efficiency. This indicates convergence in leaf traits related to photosynthetic nutrient use on severely P‐impoverished sites.