bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locomotor compromises maintain group cohesion in baboon troops on the move
Authors: Harel Roi , Loftus J. Carter , Crofoot Margaret C. 
Published: October 2020

AbstractWhen members of a group differ in locomotor capacity, coordinating collective movement poses a challenge: some individuals may have to move faster (or slower) than their preferred speed to remain together. Such compromises have energetic repercussions yet research in collective behavior has largely neglected locomotor consensus costs. Here we integrate high-resolution tracking of wild baboon locomotion and movement with simulations to demonstrate that size-based variation in locomotor capacity poses an obstacle to collective movement. While all baboons modulate their gait and move-pause dynamics during collective movement, the costs of maintaining cohesion are disproportionately borne by smaller group members. Although consensus costs are not distributed equally, all group-mates do make locomotor compromises, suggesting a shared decision-making process drives the pace of collective movement in this highly despotic species. These results highlight the importance of considering how social dynamics and locomotor capacity interact to shape the movement ecology of group-living species.
CASB: A concanavalin A-based sample barcoding strategy for single-cell sequencing
Authors: Fang Liang , Li Guipeng , Zhu Qionghua , Cui Huanhuan , Li Yunfei , Sun Zhiyuan , Liang Weizheng , Wei Wencheng , Hu Yuhui , Chen Wei 
Published: October 2020

AbstractSample multiplexing facilitates single cell sequencing by reducing costs, revealing subtle difference between similar samples, and identifying artifacts such as cell doublets. However, universal and cost-effective strategies are rather limited. Here, we reported a Concanavalin A-based Sample Barcoding strategy (CASB), which could be followed by both single-cell mRNA and ATAC (assay for transposase accessible chromatin) sequencing techniques. The method involves minimal sample processing, thereby preserving intact transcriptomic or epigenomic patterns. We demonstrated its high labeling efficiency, high accuracy in assigning cells/nuclei to samples regardless of cell type and genetic background, as well as high sensitivity in detecting doublets by two applications: 1) CASB followed by scRNA-seq to track the transcriptomic dynamics of a cancer cell line perturbed by multiple drugs, which revealed compound-specific heterogeneous response; 2) CASB together with both snATAC-seq and scRNA-seq to illustrate the IFN-γ-mediated dynamic changes on epigenome and transcriptome profile, which identified the transcription factor underlying heterogeneous IFN-γ response.
RTP801 REGULATES MOTOR CORTEX SYNAPTIC TRANSMISSION AND LEARNING
Authors: Pérez-Sisqués L , Martín-Flores N , Masana M , Solana J , Llobet A , Romaní-Aumedes J , Canal M , Campoy G , García-García E. , Sánchez-Fernández N , Fernández-García S , Gilbert JP , Rodríguez MJ , Man H-Y , Feinstein E , Williamson D , Soto D , Gasull X , Alberch J , Malagelada C 
Published: October 2020

ABSTRACTRTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death inin vitroandin vivomodels of Parkinson’s and Huntington’s diseases and is up regulated in compromised neurons in human postmortem brains of both neurodegenerative disorders. Indeed, in both Parkinson’s and Huntington’s disease mouse models, RTP801 knockdown alleviates motor-learning deficits.Here, we investigated the physiological role of RTP801 in neuronal plasticity. RTP801 is found in rat, mouse and human synapses. The absence of RTP801 enhanced excitatory synaptic transmission in both neuronal cultures and brain slices from RTP801 knock-out (KO) mice. Indeed, RTP801 KO mice showed improved motor learning, which correlated with lower spine density but increased basal filopodia and mushroom spines in the motor cortex layer V. This paralleled with higher levels of synaptosomal GluA1 and TrkB receptors in homogenates derived from KO mice motor cortex, proteins that are associated with synaptic strengthening. Altogether, these results indicate that RTP801 has an important role modulating neuronal plasticity in motor learning.
Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites
Authors: Borschiwer Marina , Bothe Melissa , Kibar Gözde , Fuchs Alisa , Schöne Stefanie , Prekovic Stefan , Peralta Isabel Mayayo , Chung Ho-Ryun , Zwart Wilbert , Helsen Christine , Claessens Frank , Meijsing Sebastiaan H. 
Published: October 2020

AbstractThe glucocorticoid (GR) and androgen (AR) receptors execute unique functionsin vivo, yet have nearly identical DNA binding specificities. To identify mechanisms that facilitate functional diversification among these transcription factor paralogs, we studied AR and GR in an equivalent cellular context. Analysis of chromatin and sequence features suggest that divergent binding, and corresponding gene regulation, are driven by different abilities of AR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the results of subtle differences in DNA binding preference between AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differs significantly, indicating a role for the sequence environment in selectively guiding AR and GR to distinct binding sites. The comparison of binding sites that are shared between AR and GR shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, we find that shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications. Genomic deletion of shared binding sites demonstrates their contribution to directing receptor-specific gene regulation. Together, these data suggest that differences in genomic occupancy as well as divergence in the events that occur downstream of receptor binding direct functional diversification among transcription factor paralogs.
High-Resolution Single-Molecule FRET via DNA eXchange (FRET X)
Authors: Filius Mike , Kim Sung Hyun , Severins Ivo , Joo Chirlmin 
Published: October 2020

ABSTRACTSingle-molecule FRET is a versatile tool to study nucleic acids and proteins at the nanometer scale. However, currently, only a couple of FRET pairs can be reliably measured on a single object. The limited number of available FRET pair fluorophores and complicated data analysis makes it challenging to apply single-molecule FRET for structural analysis of biomolecules. Currently, only a couple of FRET pairs can be reliably measured on a single object. Here we present an approach that allows for the determination of multiple distances between FRET pairs in a single object. We use programmable, transient binding between short DNA strands to resolve the FRET efficiency of multiple fluorophore pairs. By allowing only a single FRET pair to be formed at a time, we can determine the FRET efficiency and pair distance with sub-nanometer resolution. We determine the distance between other pairs by sequentially exchanging DNA strands. We name this multiplexing approach FRET X for FRET via DNA eXchange. We envision that our FRET X technology will be a tool for the high-resolution structural analysis of biomolecules and other nano-structures.
Preventing neutrophil from oxygen exposure allows their basal state maintenance
Authors: Injarabian Louise , Gianetto Quentin Giai , Witko-Sarsat Véronique , Marteyn Benoit S 
Published: October 2020

AbstractNeutrophils are the most abundant circulating white blood cells and are central players of the innate immune response. During their lifecycle, neutrophils mainly evolve under low oxygen conditions (0.1 - 4% O2) to which they are well adapted. Neutrophils are atypical cells since they are mainly glycolytic, and highly susceptible to oxygen-exposure, which induces their activation and death, through mechanisms which remain currently elusive. Nevertheless, nearly all studies conducted on neutrophils are carried out under atmospheric oxygen (21%), corresponding to hyperoxic conditions. Here we investigated the impact of hyperoxia during neutrophil purification and culture on neutrophil viability, activation and cytosolic protein content. Neutrophil hyper-activation (CD62L shedding) is induced during culture under hyperoxic conditions (24h), compared to neutrophils cultured under anoxic conditions. In addition, we show that maintaining neutrophils in autologous plasma is the most suitable strategy to maintain their basal state.Our results show that manipulating neutrophils under hyperoxic conditions leads to the loss of ~100 cytosolic proteins during purification, while it does not lead to an immediate impact on neutrophils activation (CD11bhigh, CD54high, CD62Llow) or viability (DAPI+). We identified two clusters of proteins belonging to the cholesterol metabolism and to the complement and coagulation cascade pathways, which are highly susceptible to neutrophil oxygen-exposure during their purification.In conclusion, preserving neutrophil from oxygen-exposure during their manipulation – purification and culture- is recommended to avoid their experimental activation and for preserving a large set of cytosolic proteins from alteration.
Hypoxia pathway proteins regulate the synthesis and release of epinephrine in the mouse adrenal gland
Authors: Watts Deepika , Bechmann Nicole , Meneses Ana , Poutakidou Ioanna K. , Kaden Denise , Conrad Catleen , Krüger Anja , Stein Johanna , El-Armouche Ali , Chavakis Triantafyllos , Eisenhofer Graeme , Peitzsch Mirko , Wielockx Ben 
Published: October 2020

ABSTRACTThe adrenal gland and its hormones regulate numerous fundamental biological processes; however, the impact of hypoxia signalling on its function remains scarcely understood. Here, we reveal that deficiency of HIF (Hypoxia Inducible Factors) prolyl hydroxylase domain protein-2 (PHD2) in the adrenal medulla of mice results in HIF2α-mediated reduction in phenylethanolamine N-methyltransferase (PNMT) expression, and consequent reduction in epinephrine synthesis. Concomitant loss of PHD2 in renal erythropoietin (EPO) producing cells stimulated HIF2α-driven EPO overproduction, excessive RBC formation (erythrocytosis) and systemic hypoglycaemia. Using mouse lines displaying only EPO-induced erythrocytosis or anaemia, we show that hypo- or hyperglycaemia is necessary and sufficient to respectively enhance or reduce exocytosis of epinephrine from the adrenal gland. Based on these results, we propose that the PHD2-HIF2α axis in the adrenal medulla and beyond regulates both synthesis and release of catecholamines, especially epinephrine. Our findings are also of great significance in view of the small molecule PHD inhibitors being tested in phase III global clinical development trials for use in renal anaemia patients.
Indirect Vibration of the Upper Limbs Alters Transmission Along Spinal but not Corticospinal Pathways
Authors: Barss Trevor S. , Collins David F. , Miller Dylan , Pujari Amit N. 
Published: October 2020

AbstractThe aim of this study was to investigate whether indirect upper limb vibration (ULV) modulates transmission along spinal and corticospinal pathways that control the human forearm. All measures were assessed under CONTROL (no vibration) and ULV (30 Hz; 0.4 mm displacement) conditions while participants maintained a small contraction of the right flexor carpi radialis (FCR) muscle. To assess spinal pathways, Hoffmann reflexes (H-reflexes) elicited by stimulation of the median nerve were recorded from FCR with motor response (M-wave) amplitudes matched between conditions. An H-reflex conditioning paradigm was also used to assess changes in presynaptic inhibition by stimulating the superficial radial (SR) nerve (5 pulses at 300Hz) 37 ms prior to median nerve stimulation. Cutaneous reflexes in FCR elicited by stimulation of the SR nerve at the wrist were also recorded. To assess corticospinal pathways, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation of the contralateral motor cortex were recorded from the right FCR and biceps brachii (BB). ULV significantly reduced H-reflex amplitude by 15.7% for both conditioned and unconditioned reflexes (24.0±15.7 vs 18.4±11.2 % Mmax;p<0.05). Middle latency cutaneous reflexes were also significantly reduced by 20.0% from CONTROL (−1.50 ± 2.1 % Mmax) to ULV (−1.73 ± 2.2 % Mmax;p<0.05). There was no significant effect of ULV on MEP amplitude (p>0.05). Therefore, ULV inhibits cutaneous and H-reflex transmission without influencing corticospinal excitability of the forearm flexors suggesting increased presynaptic inhibition of afferent transmission as a likely mechanism. A general increase in inhibition of spinal pathways with ULV may have important implications for improving rehabilitation for individuals with spasticity (SCI, stroke, MS, etc).
Pesticide-induced Alterations to Phytoplankton Abundance and Community Structure Alter Ecosystem Respiration: Implications for the Carbon Cycle?
Authors: Rumschlag Samantha L. , Casamatta Dale A. , Mahon Michael B. , Hoverman Jason T. , Raffel Thomas R. , Carrick Hunter J. , Hudson Peter J. , Rohr Jason R. 
Published: October 2020

AbstractCurrent predictions of the effects of synthetic chemicals on freshwater ecosystems are hampered by the sheer number of chemical contaminants entering aquatic systems, the diversity of organisms inhabiting these systems, and uncertainties about how contaminants alter ecosystem metabolism. We conducted a mesocosm experiment that elucidated the responses of ponds composed of phytoplankton and zooplankton to standardized concentrations of 12 pesticides, nested within four pesticide classes and two pesticide types. We show that the effects of the pesticides on algae were consistent within herbicides and insecticides and responses of over 70 phytoplankton species and genera were consistent within broad taxonomic groups. Insecticides generated top-down effects on phytoplankton community composition and abundance, which were associated with persistent increases in ecosystem respiration. Herbicides reduced phytoplankton abundance, which was associated with decreases in primary productivity and ecosystem respiration. These results suggest that widespread pesticide use could have underexplored implications for the global carbon cycle. While these effects on ecosystem respiration were mediated through complex effects on communities, taxonomic groups of organisms responded similarly to pesticide types, suggesting opportunities to simplify ecological risk assessment.
Reservoir host community and vector density predict human tick-borne diseases across the United States
Authors: Mahon Michael B. , Rohr Jason R. 
Published: October 2020

AbstractIn the United States, tick-borne disease cases have tripled since the 1990s and cost upwards of 10 billion USD annually. Tick density and densities and diversity of non-human mammalian reservoir hosts are hypothesized to drive tick-borne disease dynamics and are targets for interventions. Here, we relate human prevalence of four tick-borne diseases (Lyme disease, monocytic ehrlichiosis, granulocytic anaplasmosis, and babesiosis) to tick and reservoir host community data collected by the U.S. National Ecological Observatory Network (NEON) across the contiguous U.S. We show that human disease prevalence is correlated positively with tick and reservoir host densities and negatively with mammalian diversity for Lyme disease and ehrlichiosis, but positively for anaplasmosis and babesiosis. Our results suggest that the efficacy of tick-borne disease interventions depends on tick and host densities and host diversity. Thus, policymakers and disease managers should consider these ecological contexts before implementing preventative measures.SignificanceTick-borne disease incidence has increased in the United States over the last three decades. Because life-long symptoms can occur if reactive antibiotics are not administered soon after the tick bite, prevention is imperative. Yet, control of tick-borne zoonoses has been largely unsuccessful, at least partly because of a limited understanding of the ecological complexities of these diseases, especially non-Lyme disease tick-borne zoonoses. We use continental-scale data to quantify the relationships among four tick-borne diseases and tick and reservoir host communities, revealing that disease incidence is driven by a combination of tick densities and reservoir host densities and diversity. Thus, the efficacy of tick-borne disease interventions is likely dependent on these ecological contexts.
Hypoxia Drives Dihydropyrimidine Dehydrogenase Expression in Macrophages and Confers Chemoresistance in Colorectal Cancer
Authors: Malier Marie , Court Magali , Gharzeddine Khaldoun , Laverierre Marie-Hélène , Marsili Sabrina , Thomas Fabienne , Decaens Thomas , Roth Gael , Millet Arnaud 
Published: October 2020

AbstractColon adenocarcinoma is characterized by an infiltration of tumor-associated macrophages (TAMs). TAMs are associated with a chemoresistance to 5-Fluorouracil (5-FU), but the mechanisms involved are still poorly understood. In the present study, we found that macrophages specifically overexpress dihydropyrimidine dehydrogenase (DPD) in hypoxia, leading to a macrophage-induced chemoresistance to 5-FU by inactivation of the drug. Macrophage DPD expression in hypoxia is translationally controlled by the cap-dependent protein synthesis complex eIF4FHypoxic, which includes HIF-2α. We discovered that TAMs constitute the main contributors to DPD activity in human colorectal primary or secondary tumors where cancer cells do not express significant levels of DPD. Together, these findings shed light on the role of TAMs in forming chemoresistance in colorectal cancers and offer the identification of new therapeutic targets. Additionally, we report that, contrary to what is found in humans, macrophages in mice do not express DPD.
The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder
Authors: Weibel Catherine , James Jennifer E , Willis Sara M , Nelson Paul G , Masel Joanna 
Published: October 2020

AbstractThe effectiveness of selection varies among species. It is often estimated by means of an “effective population size” based on neutral polymorphism, but this is confounded in complex ways with demography. The strength of codon bias more directly pertains to how well adaptation at many sites can be maintained in the face of deleterious mutations, but past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS) that corrects for both confounders. Unlike previous metrics, CAIS yields the expected relationship with adult vertebrate body mass. As an example of the use of CAIS, we ask whether protein domains evolve lower intrinsic structural disorder (ISD) when present in more exquisitely adapted species, as expected given that ISD is higher in eukaryotic proteomes than prokaryotic proteomes. Using phylogenetically corrected linear models, we find, contrary to expectations, that the ISD of a given protein domain evolves to be higher when in well-adapted species. This effect is stronger in young protein domains but is also present in ancient domains.
Quantifying the subjective cost of self-control in humans
Authors: Raio Candace M. , Glimcher Paul W. 
Published: October 2020

ABSTRACTSince Odysseus committed to resisting the Sirens, mechanisms to limit self-control failure have been a central feature of human behavior. Psychologists have long argued that the use of self-control is an effortful process and, more recently, that its failure arises when the cognitive costs of self-control outweigh its perceived benefits. In a similar way, economists have argued that sophisticated choosers can adopt “pre-commitment strategies” that tie the hands of their future selves in order to reduce these costs. Yet, we still lack an empirical tool to quantify and demonstrate the cost of self-control. Here, we develop and validate a novel economic decision-making task toquantify the subjective cost of self-controlby determining the monetary cost a person is willing to incur in order to eliminate the need for self-control. We find that humans will pay to avoid having to exert self-control in a way that scales with increasing levels of temptation and that these costs are modulated both by motivational incentives and stress exposure. Our psychophysical approach allows us to index moment-to-moment self-control costs at the within-subject level, validating important theoretical work across multiple disciplines and opening new avenues of self-control research in healthy and clinical populations.
Gut Fungi Possess a Conserved Toxin Immunity Gene of Bacterial Origin
Authors: Rizvi Syed M. , Zhang Chengxin , Freddolino Peter L. , Zhang Yang 
Published: October 2020

AbstractProkaryotes and some unicellular eukaryotes routinely overcome evolutionary pressures with the help of horizontally acquired genes. In contrast, it is unusual for multicellular eukaryotes to adapt through horizontal gene transfer (HGT). Recent studies identified several cases of adaptive acquisition in the gut-dwelling multicellular fungal phylumNeocallimastigomycota. Here, we add to these cases the acquisition of a putative bacterial toxin immunity gene, PoNi, by an ancient common ancestor of four extantNeocallimastigomycotagenera through HGT from an extracellularRuminococcusbacterium. The PoNi homologs in these fungal genera share extraordinarily high (>70%) amino acid sequence identity with their bacterial donor xenolog, providing definitive evidence of HGT as opposed to lineage-specific gene retention. Furthermore, PoNi genes are nested on native sections of chromosomal DNA in multiple fungal genomes and are also found in polyadenylated fungal transcriptomes, confirming that these genes are authentic fungal genomic regions rather than sequencing artifacts from bacterial contamination. The HGT event, which is estimated to have occurred at least 66 (±10) million years ago in the gut of a Cretaceous mammal, gave the fungi a putative toxin immunity protein (PoNi) which likely helps them survive toxin-mediated attacks by bacterial competitors in the mammalian gut microbiome.SignificanceAdaptation via horizontal gene transfer (HGT) is uncommon in multicellular eukaryotes. Here, we report anotherbona fidecase of adaptive evolution involving the horizontal transfer of a bacterial toxin immunity gene from extracellularRuminococcusbacteria to gut-dwelling multicellular fungi. The acquired gene may help the fungi compete against bacterial neighbors in the gut.