bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidimensional trophic niche revealed by complementary approaches: gut content, digestive enzymes, fatty acids and stable isotopes in soil fauna
Authors: Potapov Anton M. , Pollierer Melanie M. , Salmon Sandrine , Šustr Vladimír , Chen Ting-Wen 
Published: May 2020

AbstractThe trophic niche of an organism is tightly related to its role in the ecosystem and to interactions with other species. Thousands of species of soil animals feed on detritus and co-exist with apparently low specialisation in food resource use. Trophic niche differentiation may explain species coexistence in such a cryptic environment. However, most of the existing studies provide only few and isolated evidence on food resources, thus simplifying the multidimensional nature of the trophic niches available in soil.Focusing on one of the most diverse soil taxa – springtails (Collembola) – we aimed to reveal the additional value of information provided by four complementary methods: visual gut content-, digestive enzyme-, fatty acid- and stable isotope analyses, and to demonstrate the multidimensional nature of trophic niches.From 40 studies, we compiled fifteen key trophic niche parameters for 125 species, each analysed with at least one method. Focusing on interspecific variability, we explored correlations of trophic niche parameters and described variation of these parameters in different Collembola species, taxonomic groups and life forms.Correlation between trophic niche parameters of different methods was weak in 45 out of 64 pairwise comparisons, reflecting the complementarity of the multidimensional trophic niche approach. Gut content and fatty acids provided comparable information on fungivory and plant feeding in Collembola. Information provided by digestive enzymes differed from that gained by the other methods, suggesting its high additional value. Stable isotopes were mainly related to plant versus microbial feeding. Many parameters were affected by taxonomic affiliation but not life form. Furthermore, we showed evidence of bacterial feeding, which may be more common in Collembola than usually assumed.Different methods reveal different feeding dimensions, together drawing a comprehensive picture of the trophic niche in taxa with diverse feeding habits. Food web studies will benefit from simultaneously applying several joint approaches, allowing to trace trophic complexity. Future studies on the multidimensional trophic niche may improve understanding of food-web functioning and help to explain species coexistence in cryptic environments such as soil.
Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array
Authors: Jiman Ahmad A. , Ratze David C. , Welle Elissa J. , Patel Paras R. , Richie Julianna M. , Bottorff Elizabeth C. , Seymour John P. , Chestek Cynthia A. , Bruns Tim M. 
Published: May 2020

AbstractAutonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8-9 μm in diameter, 150-250 μm in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1-91.7 μV and signal-to-noise ratios of 2.0-8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7-4.4 m/sec) and efferent (0.7-8.8 m/sec) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.
AFTERHYPERPOLARIZATION AMPLITUDE IN CA1 PYRAMIDAL CELLS OF AGED LONG-EVANS RATS CHARACTERIZED FOR INDIVIDUAL DIFFERENCES
Authors: Severin Daniel , Gallagher Michela , Kirkwood Alfredo 
Published: May 2020

ABSTRACTAltered neural excitability is considered a prominent contributing factor to cognitive decline during aging. A clear example is the excess neural activity observed in several temporal lobe structures of cognitively impaired older individuals in rodents and humans. At a cellular level, aging-related changes in mechanisms regulating intrinsic excitability have been well examined in pyramidal cells of the CA1 hippocampal subfield. Studies in the inbred Fisher 344 rat strain document an age-related increase in the slow afterhyperpolarization (AHP) that normally occurs after a burst of action potentials, and serves to reduce subsequent firing. We evaluated the status of the AHP in the outbred Long-Evans rat, a well-established model for studing individual differences in neurocognitive aging. In contrast to the findings reported in the Fisher 344 rats, in the Long-Evan rats we detected a selective reduction in AHP in cognitively impaired aged individuals. We discuss plausible scenarios to account for these differences and also discuss possible implications of these differences.
Dopaminergic neuromodulation of spike timing dependent plasticity in mature adult rodent and human cortical neurons
Authors: Louth Emma Louise , Jørgensen Rasmus Langelund , Korshøj Anders Rosendal , Sørensen Jens Christian Hedemann , Capogna Marco 
Published: May 2020

AbstractSynapses in the cerebral cortex constantly change and this dynamic property regulated by the action of neuromodulators such as dopamine (DA), is essential for reward learning and memory. DA modulates spike-timing-dependent plasticity (STDP), a cellular model of learning and memory, in juvenile rodent cortical neurons. However, it is unknown whether this neuromodulation also occurs at excitatory synapses of cortical neurons in mature adult mice or in humans. Cortical layer V pyramidal neurons were recorded with whole cell patch clamp electrophysiology and an extracellular stimulating electrode was used to induce STDP. DA was either bath-applied or optogenetically released in slices from mice. Classical STDP induction protocols triggered non-Hebbian excitatory synaptic depression in the mouse or no plasticity at human cortical synapses. DA reverted long term synaptic depression to baseline in mouse or elicited long term synaptic potentiation in human cortical synapses. Furthermore, when DA was applied during a STDP protocol it depressed presynaptic inhibition in the mouse but not in the human cortex. Thus, DA modulates excitatory synaptic plasticity differently in humanversusmouse cortex. The data strengthens the importance of DA in gating cognition in humans, and may inform on therapeutic interventions to recover brain function from diseases.
Lipopolysaccharide stimulation of RAW264.7 cells is a model for identifying novel clients of Hsc70
Authors: Rakus John F. , Kegley Nicholas R. , Ashley Alex J. , Parsons Michael A. , Takeuchi Megumi 
Published: May 2020

AbstractHeat shock cognate protein 71 kDa (Hsc70, Hspa8, Hspa10, Hsp73) is a member of the heat shock protein 70 kDa family of molecular chaperones. These chaperones function to aid the correct folding of client proteins using an ATP-dependent mechanism. Though Hsc70 is accepted to be a constitutively expressed protein, it has a well-documented function in modulating the induction of the pro-inflammatory cytokine TNFα by the LPS/TLR4 pathway. In this work we attempt to identify protein clients of Hsc70 to gain insight into those which may be responsible for this regulatory effect. RAW264.7 cells were cultured in the absence or presence of 1 μg/mL LPS for 0 to 24 hours. Herein we describe of a large number of newly-categorized Hsc70 clients using immunoprecipitation and nanoLC-MS/MS and we validate several novel Hsc70/client interactions using co-immunoprecipitation. After performing immunoprecipitation using a commercially available antibody, eluted fractions were proteolytically digested either immediately after immunoprecipitation or after separation by SDS-PAGE and sequence analyzed using nanoLC-MS/MS with a Q-Exactive Plus triple-quadrupole/orbitrap mass spectrometer. Using these methods, 292 total unique protein hits were identified with high confidence; 34 of which were only detected in LPS-treated cells.
Phylogenomics ofBrosimumSw. (Moraceae) and allied genera, including a revised subgeneric system
Authors: Gardner Elliot M. , Audi Lauren , Zhang Qian , Sauquet Hervé , Monro Alexandre K. , Zerega Nyree J.C. 
Published: May 2020

AbstractWe present a phylogenomic study ofBrosimumand the allied generaTrymatococcusandHelianthostylis, with near-complete taxon sampling. Distributed from Mexico and the Greater Antilles to the Amazon, this clade contains the underutilized crop ramón (bread nut) (Brosimum alicastrum) as well as other species valued for timber or medicinal uses. Target enrichment for 333 genes produced a well-resolved phylogenetic tree and showed thatTrymatoccocusandHelianthostylisare nested withinBrosimum. We present a revised subgeneric classification ofBrosimumbased on phylogenetic and morphological considerations, including the reduction ofTrymatococcusandHelianthostylisto subgenera. The monophyletic subgenera can be diagnosed based on stipule, pistillode, and cotyledon synapomorphies. Divergence date estimates suggest a Miocene origin forBrosimum, and ancestral area reconstruction indicated that all four subgenera originated and initially diversified in Amazonia before dispersing into other parts of South and Central America.ResumenPresentamos un estudio filogenómico del géneroBrosimumy sus aliados,TrymatococcusyHelianthostylis, y que incluye prácticamente todas las especies descritas. Su distribución va desde México y las Antillas Mayores hasta el Amazonas y comprende especies como el ramón (B. alicastrum), un cultivo infrautilizado, y otras especies empleadas como madera o en medicina. La secuenciación masiva dirigida de 333 marcadores nucleares de copia única permitió la reconstrucción de una filogenia bien resuelta, en la que se demuestra queTrymatococcusyHelianthostylisestán anidados enBrosimum. Presentamos, por lo tanto, una clasificación revisada a nivel de especies, teniendo en cuenta los resultados moleculares y las características morfológicas, y dondeTrymatococcusyHelianthostylispasan a ser subgéneros deBrosimum. Estos subgéneros monofiléticos pueden ser identificados por caracteres de las estípulas y de los pistilodios.
Astrocytes close a critical period of motor circuit plasticity
Authors: Ackerman Sarah D. , Perez-Catalan Nelson A. , Freeman Marc R. , Doe Chris Q. 
Published: May 2020

AbstractCritical periods – brief intervals where neural circuits can be modified by sensory input – are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders, including schizophrenia and autism; however, the mechanisms that ensure timely critical period closure remain unknown. Here, we define the extent of a critical period in the developingDrosophilamotor circuit, and identify astrocytes as essential for proper critical period termination. During the critical period, decreased activity produces larger motor dendrites with fewer inhibitory inputs; conversely, increased motor neuron activity produces smaller motor dendrites with fewer excitatory inputs. Importantly, activity has little effect on dendrite morphology after critical period closure. Astrocytes invade the neuropil just prior to critical period closure, and astrocyte ablation prolongs the critical period. Finally, we use a genetic screen to identify astrocyte-motor neuron signaling pathways that close the critical period, including Neuroligin-Neurexin signaling. Reduced signaling destabilizes dendritic microtubules, increases dendrite dynamicity, and impairs locomotor behavior, underscoring the importance of critical period closure. Previous work defines astroglia as regulators of plasticity at individual synapses; here, we show that astrocytes also regulate large-scale structural plasticity to motor dendrite, and thus, circuit architecture to ensure proper locomotor behavior.
Quantitativein vivobioluminescence imaging of orthotopic patient-derived glioblastoma xenografts
Authors: Koessinger Anna L. , Koessinger Dominik , Stevenson Katrina , Cloix Catherine , Mitchell Louise , Chalmers Anthony J. , Norman Jim C. , Tait Stephen W.G 
Published: May 2020

AbstractDespite extensive research, little progress has been made in glioblastoma therapy, owing in part to a lack of adequate preclinicalin vivomodels to study this disease. To mitigate this, primary patient-derived cell lines, which maintain their specific stem-like phenotypes, have replaced established glioblastoma cell lines. However, due to heterogenous tumour growth inherent in glioblastoma, the use of primary cells for orthotopicin vivostudies often requires large experimental group sizes. Therefore, when using intracranial patient-derived xenograft (PDX) approaches, it is advantageous to deploy imaging techniques to monitor tumour growth and allow stratification of mice. Here we show that stable expression of near-infrared fluorescent protein (iRFP) in patient-derived glioblastoma cells enables rapid direct non-invasive monitoring of tumour development without compromising tumour stemness or tumorigenicity. Moreover, as this approach does not depend on the use of agents like luciferin, which can cause variability due to changing bioavailability, it can be used for quantitative longitudinal monitoring of tumour growth. Notably, we show that this technique also allows quantitative assessment of tumour burden in highly invasive models spreading throughout the brain. Thus, iRFP transduction of primary patient-derived glioblastoma cells is a reliable, cost- and time-effective way to monitor heterogenous orthotopic PDX growth.
Hsp70 chaperone blocks α-synuclein oligomer formation via a novel engagement mechanism
Authors: Tao Jiahui , Berthet Amandine , Citron Rose , Stanley Robert , Gestwicki Jason , Agard David A. , McConlogue Lisa 
Published: May 2020

AbstractOver-expression and aggregation of α-synuclein (ASyn) are linked to the onset and pathology of Parkinson’s disease and related synucleinopathies. Elevated levels of the stress induced chaperone, Hsp70, protects against ASyn misfolding and ASyn-driven neurodegeneration in cell and animal models, yet there is minimal mechanistic understanding of this important protective pathway. It is generally assumed that Hsp70 binds to ASyn using its canonical and promiscuous substrate-binding cleft to limit aggregation. Here we report that this activity is due to a novel and unexpected mode of Hsp70 action, involving neither ATP nor the typical substrate-binding cleft. We use novel ASyn oligomerization assays to show that Hsp70 directly blocks ASyn oligomerization, an early event in ASyn misfolding. Using truncations, mutations and inhibitors, we confirmed that Hsp70 interacts with ASyn via an as yet unidentified, non-canonical interaction site in the C-terminal domain. Finally, a biological role for a non-canonical interaction was observed in H4 neuroglioma cells. Together, these findings suggest that new chemical approaches will be required to target Hsp70-ASyn interaction in synucleinopathies. Such approaches are likely to be more specific than targeting Hsp70 canonical actions. Additionally, these results raise the question of whether other misfolded proteins might also engage via the same non-canonical mechanism.
intern: Integrated Toolkit for Extensible and Reproducible Neuroscience
Authors: Matelsky Jordan , Rodriguez Luis , Xenes Daniel , Gion Timothy , Hider Robert , Wester Brock , Gray-Roncal William 
Published: May 2020

AbstractAs neuroscience datasets continue to grow in size, the complexity of data analyses can require a detailed understanding and implementation of systems computer science for storage, access, processing, and sharing. Currently, several general data standards (e.g., Zarr, HDF5, precompute, tensorstore) and purpose-built ecosystems (e.g., BossDB, CloudVolume, DVID, and Knossos) exist. Each of these systems has advantages and limitations and is most appropriate for different use cases. Using datasets that don’t fit into RAM in this heterogeneous environment is challenging, and significant barriers exist to leverage underlying research investments. In this manuscript, we outline our perspective for how to approach this challenge through the use of community provided, standardized interfaces that unify various computational backends and abstract computer science challenges from the scientist. We introduce desirable design patterns and our reference implementation called intern.
Machine Learning Identifies Novel Candidates for Drug Repurposing in Alzheimer’s Disease
Authors: Rodriguez Steve , Hug Clemens , Todorov Petar , Moret Nienke , Boswell Sarah A. , Evans Kyle , Zhou George , Johnson Nathan T. , Hyman Brad , Sorger Peter K. , Albers Mark W. , Sokolov Artem 
Published: May 2020

AbstractClinical trials of novel therapeutics for Alzheimer’s Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. Repurposing can yield a useful therapeutic and also accelerate proof of concept studies that ultimately lead to a new molecular entity. We present a novel machine learning framework, DRIAD (DrugRepurposing InAD), that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in lists of gene names. DRIAD was validated on gene lists known to be associated with AD from other studies and subsequently applied to evaluate lists of genes arising from perturbations in differentiated human neural cell cultures by 80 FDA-approved and clinically tested drugs, producing a ranked list of possible repurposing candidates. Top-scoring drugs were inspected for common trends among their nominal molecular targets and their “off-targets”, revealing a high prevalence of kinases from the Janus (JAK), Unc-51-like (ULK) and NIMA-related (NEK) families. These kinase families are known to modulate pathways related to innate immune signaling, autophagy, and microtubule formation and function, suggesting possible disease-modifying mechanisms of action. We propose that the DRIAD method can be used to nominate drugs that, after additional validation and identification of relevant pharmacodynamic biomarker(s), could be evaluated in a clinical trial.
Linking Anthocyanin Diversity, Hue, And Genetics In Purple Corn
Authors: Chatham Laura A. , Juvik John A. 
Published: May 2020

AbstractWhile maize with anthocyanin-rich pericarp (purple corn) is rising in popularity as a source of natural colorant for foods and beverages, information on color range and stability—factors associated with anthocyanin decorations and compositional profiles—are currently limited. Using the natural anthocyanin diversity present in a purple corn landrace, Apache Red, we generated a population with variable flavonoid profiles—flavonol-anthocyanin condensed forms (0-83%), acylated anthocyanins (2-72%), pelargonidin-derived anthocyanins (5-99%), and C-glycosyl flavone co-pigments up to 1904 µg/g—all of which contributed in part to the absorbance profile, used here as a proxy for hue. This variability offers targets of selection for breeders looking to expand both stability and the available range of colors that can be sourced from purple corn. With genotyping-by-sequencing of this population we mapped these anthocyanin profile traits. Major QTL for anthocyanin type were found near loci previously identified only in aleurone-pigmented maize varieties [Purple aleurone1(Pr1) andAnthocyanin acyltransferase1(Aat1)]. A QTL nearP1(Pericarp color1) was found for both flavone content and flavanol-anthocyanin condensed forms. A significant QTL associated with peonidin-derived anthocyanins near a candidate S-adenosylmethionine-dependent methyltransferase was also identified, warranting further investigation. This population represents the most anthocyanin diverse pericarp-pigmented maize variety characterized to date. Moreover, the candidates identified here will serve as branching points for future research studying the genetic and molecular processes determining anthocyanin profile in pericarp.
A system-view ofB. pertussisbooster vaccine responses in adults primed with whole-cell vs. acellular vaccine in infancy
Authors: da Silva Antunes Ricardo , Pomaznoy Mikhail , Soldevila Ferran , Babor Mariana , Bennett Jason , Tian Yuan , Khalil Natalie , Qian Yu , Mandava Aishwarya , Scheuermann Richard H. , Cortese Mario , Pulendran Bali , Petro Christopher D. , Gilkes Adrienne , Purcell Lisa A. , Sette Alessandro , Peters Bjoern 
Published: May 2020

AbstractWhole-cell inactivated vaccine againstBordetella pertussis(wP) was substituted in many countries by an acellular subunit vaccine (aP) to reduce side effects. Recent epidemiological studies have shown that aP vaccination in infancy induces less durable immunity than wP vaccination. To determine immunological differences associated with aP vs. wP priming, we performed system-level profiling of the immune response in adults primed with aP vs. wP vaccine in infancy following the Tdap booster vaccination as a surrogate to antigen encounterin vivo. Shared immune responses across cohorts were identified, including an increase of the blood monocyte frequency on day 1, and strong antigen-specific IgG response seven days after boost. Comparing aP and wP primed individuals, we found a subset of aP-primed individuals with higher levels of expression for several genes including CCL3 on day 3 and NFKBIA and ICAM1 on day 7 post immunization. These observations were supported by increased CCL3 concentrations in plasma of aP primed individuals. Contrary to the wP individuals, the CCL3-high aP subset presented boosted PT-specific IgE responses. Furthermore, higher antigen specific IgG4 and IgG3 antibodies against specific vaccine antigens at baseline and post boost of aP individuals was observed, suggesting a long term maintained difference in the IgG subtype response. Overall our findings demonstrate that, while broad immune response patterns to Tdap boost overlap between aP and wP primed individuals, a subset of aP primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.