bluuebunny/crossref_metadata_2025_split huggingface dataset:
An experimental assessment of the distribution of environmental DNA along the water column
Authors: Agostinis André O. , Dal Pont Giorgi , Borio Alexandre , Horodesky Aline , da Silva Bertão Ana Paula , Mäder Netto Otto Samuel , Zanin Thiago Luis , Ostrensky Antonio , Pie Marcio R. 
Published: December 2020

AbstractThe study of environmental DNA (eDNA) is increasingly becoming a valuable tool to survey and monitor aquatic communities. However, there are important gaps in our understanding of the dynamics governing the distribution of eDNA under natural conditions. In this report we carry out controlled experiments to assess the extent and timing of eDNA distribution along the water column. A sample of known eDNA concentration was placed at the bottom of a 5-m high tube (20 cm in diameter and total volume of 160 L), and water samples were obtained at different depths over an 8 h-period. The presence of the target eDNA was assessed by qPCR analysis. This sampling protocol allowed for assessing the timescale for the diffusion of eDNA while minimizing the influence of turbulence. We demonstrate that, after a time-period of as little as 30 min, the eDNA had spread across the entire container. The implications of these results for eDNA sampling protocols in the field are discussed.
β-cell SENP1 facilitates responsiveness to incretins and limits oral glucose intolerance in high fat fed mice
Authors: Lin Haopeng , Smith Nancy , Spigelman Aliya F , Suzuki Kunimasa , Ferdaoussi Mourad , Jin Yaxing , Bautista Austin , Wang Ying Wayne , Fox Jocelyn E. Manning , Buteau Jean , MacDonald Patrick E 
Published: December 2020

AbstractSUMOylation reduces oxidative stress and preserves islet mass; but this happens at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzymesentrin-specificprotease1(SENP1) in glycemia following metabolic stress, we put pancreas/gut-specific SENP1 knockout mice (pSENP1-KO) on an 8-10-week high fat diet (HFD). Male pSENP1-KO mice were more glucose intolerant following HFD than littermate controls, but this was only obvious in response to oral glucose, and a similar but milder phenotype was observed in females. Plasma incretin responses were identical, and glucose-dependent insulinotropic polypeptide (GIP) was equally upregulated after HFD, in pSENP1-KO and - WT littermates. Islet mass was not different, but insulin secretion and β-cell exocytotic responses to Exendin4 (Ex4) and GIP were impaired in islets lacking SENP1. Glucagon secretion from pSENP1-KO islets was also reduced, consistent with the expected SENP1 knockout in all islet cells, so we generated β-cell–specific SENP1 knockout mice (βSENP1-KO). These phenocopied the pSENP1-KO mice with selective impairment in oral glucose tolerance following HFD, preserved islet mass expansion, and impaired β-cell exocytosis and insulin secretion to Ex4 and GIP. Thus, β-cell SENP1 limits glucose intolerance following HFD by ensuring a robust facilitation of insulin secretion by incretins such as GIP.
wQFM: Statistically Consistent Genome-scale Species Tree Estimation from Weighted Quartets
Authors: Mahbub Mahim , Wahab Zahin , Reaz Rezwana , Rahman M. Saifur , Bayzid Md. Shamsuzzoha 
Published: December 2020

AbstractMotivationSpecies tree estimation from genes sampled from throughout the whole genome is complicated due to thegene tree-species tree discordance. Incomplete lineage sorting (ILS) is one of the most frequent causes for this discordance, where alleles can coexist in populations for periods that may span several speciation events. Quartet-based summary methods for estimating species trees from a collection of gene trees are becoming popular due to their high accuracy and statistical guarantee under ILS. Generating quartets with appropriate weights, where weights correspond to the relative importance of quartets, and subsequently amalgamating the weighted quartets to infer a single coherent species tree allows for a statistically consistent way of estimating species trees. However, handling weighted quartets is challenging.ResultsWe propose wQFM, a highly accurate method for species tree estimation from multi-locus data, by extending the quartet FM (QFM) algorithm to a weighted setting. wQFM was assessed on a collection of simulated and real biological datasets, including the avian phylogenomic dataset which is one of the largest phylogenomic datasets to date. We compared wQFM with wQMC, which is the best alternate method for weighted quartet amalgamation, and with ASTRAL, which is one of the most accurate and widely used coalescent-based species tree estimation methods. Our results suggest that wQFM matches or improves upon the accuracy of wQMC and ASTRAL.AvailabilitywQFM is available in open source form athttps://github.com/Mahim1997/wQFM-2020.
A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation
Authors: Milosevic Luka , Kalia Suneil K , Hodaie Mojgan , Lozano Andres M , Popovic Milos R , Hutchison William D , Lankarany Milad 
Published: December 2020

AbstractWith the growing interest in the expansion of deep brain stimulation indications, we aimed to provide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on human neuronal activity. Experimentally, we demonstrated microstimulation-evoked excitatory neuronal responses in the ventral intermediate nucleus and reticular thalamus, and inhibitory responses in the subthalamic nucleus and substantia nigra pars reticulata; hypothesized to be the result of simultaneous activations of convergent afferent inputs. Higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression; hypothesized to be mediated by synaptic depression. These experimental findings were reproduced by a computational framework in which relative distributions of convergent excitatory/inhibitory afferents were embedded within a model of short-term synaptic plasticity for the prediction of site-specific and frequency-dependent responses to extracellular stimulation. This theoretical framework may aid in the design of physiologically-informed stimulation paradigms in existing or prospective deep brain stimulation indications.
Strain- and age-dependent features of the nigro-striatal circuit in three common laboratory mouse strains, C57BL/6J, A/J, and DBA/2J -Implications for Parkinson’s disease modeling
Authors: Thomas Mélanie H. , Karout Mona , Rodriguez Beatriz Pardo , Gui Yujuan , Jaeger Christian , Michelucci Alessandro , Kollmus Heike , Schughart Klaus , Coowar Djalil , Balling Rudi , Mittelbronn Michel , Sinkkonen Lasse , Garcia Pierre , Buttini Manuel 
Published: December 2020

AbstractMouse models have been instrumental in understanding genetic determinants of aging and its crucial role in neurodegenerative diseases. However, few studies have analyzed the evolution of the mouse brain over time at baseline. Furthermore, mouse brain studies are commonly conducted on the C57BL/6 strain, limiting the analysis to a specific genetic background. In Parkinson’s disease, the gradual demise of nigral dopaminergic neurons mainly contributes to the motor symptoms. Interestingly, a decline of the dopaminergic neuron function and integrity is also a characteristic of physiological aging in some species. Age-related nigro-striatal features have never been studied in mice of different genetic backgrounds. In this study, we analyze the morphological features in the striatum of three common mouse strains, C57BL/6J, A/J, and DBA/2J at 3-, 9- and 15 months of age. By measuring dopaminergic markers, we uncover age-related changes that differ between strains and evolve dynamically over time. Overall, our results highlight the importance of considering background strain and age when studying the murine nigro-striatal circuit in health and disease.HighlightsStudy of the integrity of the nigro-striatal circuit in C57BL/6J, A/J, and DBA/2J at different agesAge related evolution of essential features of nigral dopaminergic neurons differ between strainsConsider background strain and age is crutial to study the nigrostriatal circuit in health and disease
Freely behaving mice can brake and turn during optogenetic stimulation of the Mesencephalic Locomotor Region
Authors: van der Zouwen Cornelis Immanuel , Boutin Joël , Fougère Maxime , Flaive Aurélie , Vivancos Mélanie , Santuz Alessandro , Akay Turgay , Sarret Philippe , Ryczko Dimitri 
Published: December 2020

AbstractBackgroundStimulation of the Mesencephalic Locomotor Region (MLR) is increasingly considered as a target to improve locomotor function in Parkinson’s disease, spinal cord injury and stroke. A key function of the MLR is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented.Objective/hypothesisWe investigated whether freely behaving mice could brake or turn based on environmental cues during MLR stimulation.MethodsWe stimulated the cuneiform nucleus in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites.ResultsOptogenetic stimulation of the MLR evoked locomotion and increasing laser power increased locomotor speed. Gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. Mice could brake and make sharp turns (∼90⁰) when approaching a corner during MLR stimulation in an open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. In a reporter mouse, many Vglut2-ZsGreen neurons were immunopositive for glutamate in the MLR. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short latency spiking in MLR neurons.ConclusionMLR glutamatergic neurons are a relevant target to improve locomotor activity without impeding the ability to brake and turn when approaching an obstacle, thus ensuring smooth and adaptable navigation.Highlights-Mice brake and turn when approaching the arena’s corner during MLR-evoked locomotion-Speed decrease is scaled to speed before the turn during MLR-evoked locomotion-Turn angle is scaled to turn speed during MLR-evoked locomotion-Gait and limb kinematics are similar during spontaneous and MLR-evoked locomotion
The transcriptional landscape ofArabidopsis thalianapattern-triggered immunity
Authors: Bjornson Marta , Pimprikar Priya , Nürnberger Thorsten , Zipfel Cyril 
Published: December 2020

AbstractPlants initiate immunity upon recognition of a wide array of self and non-self molecular patterns. Whether plants tune their immune outputs to patterns of different biological origins or of different biochemical nature remains mostly unclear. Here, we performed a detailed early time-series transcriptomics analysis inArabidopsis thaliana, revealing that the response to diverse patterns is remarkably congruent. Early transcriptional reprogramming is dominated by a plant general stress response (GSR), which is essential for pattern-induced immunity. The definition of ‘core immunity response’ genes common and specific to pattern response in addition revealed the function of previously uncharacterized GLUTAMATE RECEPTOR-LIKE calcium-permeable channels in immunity. This study thus illustrates general and unique properties of early immune transcriptional reprogramming and uncovered important components of plant immunity.One Sentence SummaryTime-resolved transcriptomics reveals new properties of pattern-triggered immunity and function of calcium-permeable channels.
Towards Inferring Nanopore Sequencing Ionic Currents from Nucleotide Chemical Structures
Authors: Ding Hongxu , Anastopoulos Ioannis , Bailey Andrew D. , Stuart Joshua , Paten Benedict 
Published: December 2020

ABSTRACTThe characteristic ionic currents of nucleotide kmers are commonly used in analyzing nanopore sequencing readouts. We present a graph convolutional network-based deep learning framework for predicting kmer characteristic ionic currents from corresponding chemical structures. We show such a framework can generalize the chemical information of the 5-methyl group from thymine to cytosine by correctly predicting 5-methylcytosine-containing DNA 6mers, thus shedding light on thede novodetection of nucleotide modifications.
Recruited macrophages that colonise the post-inflammatory peritoneal niche convert into functionally divergent resident cells
Authors: Louwe P. A. , Gomez L. Badiola , Webster H. , Perona-Wright G. , Bain C. C. , Forbes S. J. , Jenkins S. J. 
Published: December 2020

AbstractInflammation generally leads to substantial recruitment of monocyte-derived macrophages. What regulates the fate of these cells and to what extent they can assume the identity and function of resident macrophages remains unclear. We compared the normal fate of inflammation-elicited macrophages in the peritoneal cavity with their potential under non-inflamed conditions and in the absence of established resident macrophages. Following mild inflammation, elicited macrophages persisted for at least 5 months but failed to fully assume a GATA6hiresident identity due to the presence of enduring resident cells. In contrast, severe inflammation resulted in ablation of resident macrophages and a protracted phase wherein the cavity was incapable of sustaining a resident phenotype, yet ultimately elicited cells acquired a mature GATA6hiidentity. Elicited macrophages also exhibited divergent features resulting from inflammation-driven alterations to the peritoneal cavity micro-environment and environment-independent features related to origin and time-of-residency. Critically, one environment-dependent feature of inflammation-elicited macrophages irrespective of severity of inflammation was a failure to produce the chemokine CXCL13, which correlated with a progressive loss in accumulation of peritoneal B1 cells post-inflammation. Hence, rather than being predetermined, the fate of inflammation-elicited peritoneal macrophages appears largely regulated by environment, changes in which result in long-term alteration in function of the peritoneal macrophage compartment post-inflammation.
Donor-Specific Plasma Factors Contribute to Aberrant Staining Artifacts with a Commercial Lyophilized Mass Cytometry Antibody Panel
Authors: Geanon Daniel , Lee Brian , Rahman Adeeb H. 
Published: December 2020

AbstractHigh-dimensional mass cytometry (CyTOF) phenotyping allows for the routine measurement of over 40 parameters and is increasingly being utilized across a wide range of studies. However, CyTOF-specific panel design and optimization represent challenges to wider adoption and standardization of immune profiling with CyTOF. To address this, Fluidigm recently commercialized its MaxPar Direct Immune Profiling Assay (MDIPA), which comprises a lyophilized 30-marker antibody panel that is able to identify all major circulating immune cell subsets and offers a streamlined solution for standardized human immune monitoring. However, in the course of applying the MDIPA to characterize large numbers of whole blood samples, we observed several instances of unusual aberrant staining patterns, most notably CD19 expression on non-B cells, which can potentially confound data analysis and lead to erroneous interpretation of results when using this assay. Here, we report that this complex phenomenon is mediated by donor-specific plasma factors that mediate non-specific interactions between specific antibodies in the MDIPA panel. Our findings additionally suggest specific strategies that can be used to mitigate the issue, including the use of PBMCs or lysed/washed whole blood to remove endogenous plasma prior to staining, or blocking specific antibodies in the MDIPA panel.
Synergy between a shallow root system with aDRO1homologue and localized P application improves rice P uptake
Authors: Oo Aung Zaw , Tsujimoto Yasuhiro , Mukai Mana , Nishigaki Tomohiro , Takai Toshiyuki , Uga Yusaku 
Published: December 2020

ABSTRACTThe development of genotypes and fertilizer management practices that facilitate high phosphorus (P) use efficiency is needed given the depleting phosphorus ore deposits and increasing ecological concerns about its excessive use. Root system architecture (RSA) is important in efficiently capturing immobile P in soils, while agronomically, localized P application near the roots is a potential approach to address this issue. However, the interaction between genetic traits of RSA and localized P application has not been examined. Near-isogenic lines (NILs) and their parent of rice (qsor1-NIL,Dro1-NIL, and IR64, with shallow, deep, and intermediate root growth angles (RGA), respectively) were grown in flooded pots in a uniform and P-sufficient condition (Pinco), and with localized P application by dipping seedling roots into P-enriched slurry at transplanting (P-dipping). The P-dipping created an available P hotspot at the soil surface and substantially improved applied P-use efficiency (equivalent biomass at one fifth of application rate of the Pinco). Further, theqsor1-NIL had significantly greater biomass and P uptake than the other genotypes in the P-dipping. Theqsor1-NIL consistently had a greater root biomass and surface area in the 0–3 cm soil layer, despite that there were no genotype differences in total values and that the other genotypes also reduced their RGAs responding to the P hotspot in the P-dipping. The shallow root system ofqsor1-NIL facilitated P uptake from the P hotspot. P-use efficiency in crop production can be further increased by combining genetic traits of RSA and localized P application.
Role of Long-range Allosteric Communication in Determining the Stability and Disassembly of SARS-COV-2 in Complex with ACE2
Authors: Mugnai Mauro L. , Templeton Clark , Elber Ron , Thirumalai D. 
Published: December 2020

AbstractSevere acute respiratory syndrome (SARS) and novel coronavirus disease (COVID-19) are caused by two closely related beta-coronaviruses, SARS-CoV and SARS-CoV-2, respectively. The envelopes surrounding these viruses are decorated with spike proteins, whose receptor binding domains (RBDs) initiate invasion by binding to the human angiotensin-converting enzyme 2 (ACE2). Subtle changes at the interface with ACE2 seem to be responsible for the enhanced affinity for the receptor of the SARS-CoV-2 RBD compared to SARS-CoV RBD. Here, we use Elastic Network Models (ENMs) to study the response of the viral RBDs and ACE2 upon dissassembly of the complexes. We identify a dominant detachment mode, in which the RBD rotates away from the surface of ACE2, while the receptor undergoes a conformational transition which stretches the active-site cleft. Using the Structural Perturbation Method, we determine the network of residues, referred to as the Allostery Wiring Diagram (AWD), which drives the large-scale motion activated by the detachment of the complex. The AWD for SARS-CoV and SARS-CoV-2 are remarkably similar, showing a network that spans the interface of the complex and reaches the active site of ACE2, thus establishing an allosteric connection between RBD binding and receptor catalytic function. Informed in part by the AWD, we used Molecular Dynamics simulations to probe the effect of interfacial mutations in which SARS-CoV-2 residues are replaced by their SARS-CoV counterparts. We focused on a conserved glycine (G502 in SARS-CoV-2, G488 in SARS-CoV) because it belongs to a region that initiates the dissociation of the complex along the dominant detachment mode, and is prominent in the AWD. Molecular Dynamics simulations of SARS-CoV-2 wild-type and G502P mutant show that the affinity for the human receptor of the mutant is drastically diminished. Our results suggest that in addition to residues that are in direct contact with the interface those involved in long range allosteric communication are also a determinant of the stability of the RBD-ACE2 complex.
PKR and the Integrated Stress Response drive immunopathology caused by ADAR1 mutation
Authors: Maurano Megan , Snyder Jessica M. , Connelly Caitlin , Henao-Mejia Jorge , Sidrauski Carmela , Stetson Daniel B. 
Published: December 2020

SummaryMutations inADAR, the gene that encodes the ADAR1 RNA deaminase, cause numerous human diseases, including Aicardi-Goutières Syndrome (AGS). ADAR1 is an essential negative regulator of the RNA sensor MDA5, and loss of ADAR1 function triggers inappropriate activation of MDA5 by self-RNAs. However, the mechanisms of MDA5-dependent disease pathogenesisin vivoremain unknown. Here, we introduce a knockin mouse that models the most commonADARAGS mutation in humans. TheseAdar-mutant mice develop lethal disease that requires MDA5, the RIG-I-like receptor LGP2, type I interferons, and the eIF2α kinase PKR. We show that a small molecule inhibitor of the integrated stress response (ISR) that acts downstream of eIF2α phosphorylation prevents immunopathology and rescues the mice from mortality. These findings place PKR and the ISR as central components of immunopathologyin vivoand identify new therapeutic targets for treatment of human diseases associated with the ADAR1-MDA5 axis.
Efficacy and Cost of High-Frequency IGRT in Elderly Stage III Non-Small-Cell Lung Cancer Patients
Authors: Heilbroner Samuel P , Xanthopoulos Eric P , Buono Donna , Carrier Daniel , Durkee Ben Y , Corradetti Michael , Wang Tony JC , Neugut Alfred I , Hershman Dawn L , Cheng Simon K 
Published: December 2020

ABSTRACTBackgroundHigh-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC).MethodsWe selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods.ResultsOf the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86 – 1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84 – 1.04), or OS (HR 0.95; 95% CI 0.87 – 1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively.ConclusionhfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost.