bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling the roles of inter- and intraspecific variation on leaf trait distributions across the eastern United States
Authors: Marconi Sergio , Weinstein Benjamin G. , Lichstein Jeremy W. , Bohlman Stephanie A. , Singh Aditya , White Ethan P. 
Published: April 2021

AbstractFunctional traits are influenced by phylogenetic constraints and environmental conditions, but previous large-scale studies modeled traits either as species weighted averages or directly from the environment, precluding analyses of the relative contributions of inter- and intraspecific variation across regions. We developed a joint model integrating phylogenetic and environmental information to understand and predict the distribution of eight leaf traits across the eastern USA. This model explained 68% of trait variation, outperforming both species-only and environment-only models, with variance attributable to species alone (23%), the environment alone (13%), and their combined effects (25%). The importance of the two drivers varied by trait. Predictions for the eastern USA produced accurate estimates of intraspecific variation and deviated from both species-only and environment-only models. Predictions revealed that intraspecific variation holds information across scales, affects relationships in the leaf economic spectrum and is key for interpreting trait distributions and ecosystem processes within and across ecoregions.
Teacher Perceptions of Using Robots to Teach Neuroscience in Secondary School
Authors: de Freitas Claudio C. S. , Hanzlick-Burton Camden , Nestorovic Miroslav , DeBoer Jennifer , Gage Gregory J. , Harris Christopher A. 
Published: April 2021

AbstractThe use of robots to help teachers to engage students in STEM subjects has been increasing in recent years, and much progress has been made in K12 schools to incorporate robots in the pedagogy. Recent studies indicate that robots can play a significant role to engage students in neuroscience subjects, but little is known about teachers’ perceptions of using robots to teach neuroscience. In this paper, we present a study based on a survey questionnaire conducted with 84 teachers across multiple high schools in the United States to understand their perceptions about the usefulness of using robots to teach neuroscience. To situate teachers with an example of how robots can be used in neuroscience classrooms, we describe an educational tool called the SpikerBot. Our preliminary results indicate that there is an opportunity for neuroscience-oriented robots in secondary education, provided sufficient on-boarding and training videos.
A repertoire of foraging decision variables in the mouse brain
Authors: Cazettes Fanny , Mazzucato Luca , Murakami Masayoshi , Morais Joao P. , Renart Alfonso , Mainen Zachary F. 
Published: April 2021

ABSTRACTIn any given situation, the environment can be parsed in different ways to define useful decision variables (DVs) for any task, but the way in which this manifold of potential decision strategies is processed to shape behavioral policies is not known. We recorded neural ensembles in the frontal cortex of mice performing a foraging task admitting multiple DVs. Methods developed to uncover the currently employed DV revealed the use of multiple strategies and latent changes in strategy within sessions. Optogenetic manipulations showed that the secondary motor cortex (M2) is needed for mice to use the different DVs in the task. Surprisingly, we found that, regardless of the DV best explaining the behavior of each mouse, M2 activity reflected a full basis set of computations spanning a repertoire of DVs extending beyond those useful for the present task. This form of multiplexing may confer considerable advantages for learning and adaptive behavior.
Acetylated α-tubulin residue K394 regulates microtubule stability to shape the growth of axon terminals
Authors: Saunders Harriet A. J. , Johnson-Schlitz Dena M. , Jenkins Brian V. , Volkert Peter J. , Yang Sihui Z. , Wildonger Jill 
Published: April 2021

AbstractMicrotubules are essential to neuron shape and function. Therefore, the stability of the microtubule cytoskeleton must be carefully regulated. Acetylation of tubulin has the potential to directly tune microtubule stability, and proteomic studies have identified several acetylation sites in α-tubulin. This includes the highly conserved residue lysine 394 (K394), which is located at the αβ-tubulin dimer interface. Using a fly model, we show that α-tubulin K394 is acetylated in the nervous system and is an essential residue. We found that an acetylation-blocking mutation in endogenous α-tubulin, K394R, perturbs the synaptic morphogenesis of motoneurons by reducing microtubule stability. Intriguingly, the K394R mutation has opposite effects on the growth of two functionally and morphologically distinct motoneurons, revealing neuron-type-specific responses when microtubule stability is altered. Eliminating the deacetylase HDAC6 increases K394 acetylation, and the over-expression of HDAC6 reduces microtubule stability similar to the K394 mutant. Thus, our findings implicate α-tubulin K394 and its acetylation in the regulation of microtubule stability and suggest that HDAC6 regulates K394 acetylation during synaptic morphogenesis.
Regulation of neurogenesis and gliogenesis by the matricellular protein CCN2 in the mouse retina
Authors: Mohiuddin Golam , Lopez Genesis , Sinon Jose , Hartnett M. Elizabeth , Bulakhova Anastasiia , Chaqour Brahim 
Published: April 2021

AbstractCellular communication network (CCN) 2 is an extracellular matrix protein with cell type- and context-dependent functions. Using a combination of mouse genetics and omic approaches, we show that CCN2 is expressed in early embryonic retinal progenitor cells (RPCs) and becomes restricted to fully differentiated Müller glial cells (MGCs) thereafter. Germline deletion of CCN2 in mice decreases BrdU labeling, reduces RPC pool, and impairs the competency of remaining RPCs to generate early and late born retinal cell types. Retinal hypocellularity and microphthalmia ensue. The transcriptomic changes associated with CCN2 inactivation include reduced marker and transcriptional regulator genes of retinal ganglion cells, photoreceptors and MGCs. Yap (Yes-associated protein), a singular node for transcriptional regulation of growth and differentiation genes, is also a target of CCN2 signals. In an organotypic model ofex vivocultured embryonic retinas, CCN2 and YAP immunoreactivity signals overlap. Lentivirus-mediated YAP expression in CCN2-deficient retinal explants increases the number of differentiating Sox9-positive MGCs. Taken together, our data indicate that CCN2 controls the proliferative and differentiation potentials of RPCs ultimately endowing, a subpopulation thereof, with Müller glial cell fate.Summary statementA CCN2-YAP regulatory axis controls retinal progenitor cell growth and lineage commitment to neuronal and glial cell fates.
Mechanisms that ensure speed and fidelity in eukaryotic translation termination
Authors: Lawson Michael R. , Lessen Laura N. , Wang Jinfan , Prabhakar Arjun , Corsepius Nicholas C. , Green Rachel , Puglisi Joseph D. 
Published: April 2021

AbstractTranslation termination, which liberates a nascent polypeptide from the ribosome specifically at stop codons, must occur accurately and rapidly. We established single-molecule fluorescence assays to track the dynamics of ribosomes and two requisite release factors (eRF1 and eRF3) throughout termination using anin vitro-reconstituted yeast translation system. We found that the two eukaryotic release factors bind together to recognize stop codons rapidly and elicit termination via a tightly regulated, multi-step process that resembles tRNA selection during translation elongation. Because the release factors are conserved from yeast to humans, the molecular events that underlie yeast translation termination are likely broadly fundamental to eukaryotic protein synthesis.One Sentence SummaryDirect visualization of eukaryotic translation reveals the dynamics of termination at stop codons.
Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations inVRK1
Authors: Bos Rémi , Rihan Khalil , El-Bazzal Lara , Bernard-Marissal Nathalie , Quintana Patrice , Jabbour Rosette , Mégarbané André , Bartoli Marc , Brocard Frédéric , Delague Valérie 
Published: April 2021

SummaryWe recently described new pathogenic variants inVRK1, in patients affected with distal Hereditary Motor Neuropathy associated with upper motor neurons signs. Specifically, we provided evidences that hiPSC-derived Motor Neurons (hiPSC-MN) from these patients display Cajal bodies (CBs) disassembly and defects in neurite outgrowth and branching.We here focused on the Axonal Initial Segment (AIS) and the related firing properties of hiPSC-MNs from these patients. We found that the patient’s Action Potential (AP) was smaller in amplitude, larger in duration, and displayed a more depolarized threshold while the firing patterns were not altered. These alterations were accompanied by a decrease in the AIS length measured in patients’ hiPSC-MNs. These data indicate that mutations in VRK1 impact the AP waveform and the AIS organization in MNs and may ultimately lead to the related motor neuron disease.HighlightshiPSC-MNs are functional and sustain firing patterns, typical of spinal MNshiPSC-MNs from patients with VRK1 mutations have altered Action PotentialAxonal Initial Segment is shorter in hiPSC-MNs from patients with mutated VRK1hiPSC-MNs are a useful platform to study Motor Inherited Peripheral NeuropathieseTOC BlurbIn human spinal Motor Neurons derived from induced Pluripotent Stem Cells from patients with VRK1 -related distal Hereditary Motor Neuropathy, Bos, Rihan et al. show that the mutations inVRK1affect the electrical properties of these neurons: they display defects in the initiation of the Action Potential due to a shortening of the Axonal Initial Segment.
Chemical Editing of Proteoglycan Architecture
Authors: O’Leary Timothy , Critcher Meg , Stephenson Tesia N. , Yang Xueyi , Bartfield Noah H. , Hawkins Richard , Huang Mia L. 
Published: April 2021

AbstractProteoglycans are heterogeneous macromolecular glycoconjugates that orchestrate many important cellular processes. While much attention has focused on the poly-sulfated glycosaminoglycan chains that decorate proteoglycans, other important elements of proteoglycan architecture, such as their core proteins and cell surface localization, have garnered less emphasis. Hence, comprehensive structure-function relationships that consider the replete proteoglycan architecture as glycoconjugates are limited. Here, we present a comprehensive approach to study proteoglycan structure and biology by fabricating defined semi-synthetic modular proteoglycans that can be tailored for cell surface display. To do so, we integrate amber codon reassignment in the expression of sequence-fined proteoglycan core proteins, metabolic oligosaccharide engineering to produce functionalizable glycosaminoglycans, and bioorthogonal click chemistry to covalently tether the two components. These materials permit the methodical dissection of the parameters required for optimal binding and function of various proteoglycan-binding proteins, and they can be modularly displayed on the surface of any living cell. We demonstrate that these sophisticated materials can recapitulate the functions of native proteoglycans in mouse embryonic stem cell differentiation and cancer cell spreading, while permitting the identification of the most important contributing elements of proteoglycan architecture toward function. This technology platform will confer structural resolution toward the investigation of proteoglycan structure-function relationships in cell biology.
METLIN Neutral Loss Database Enhances Similarity Analysis
Authors: Aisporna Aries , Benton H. Paul , Galano Jean Marie , Giera Martin , Siuzdak Gary 
Published: April 2021

AbstractTandem mass spectrometry (MS2) data is an effective resource for the identification of known molecules and the putative identification of novel, previously uncharacterized molecules (unknowns). Yet, MS2data alone is limited in characterizing structurally closely related molecules with different masses. Neutral loss data is key in retrieving this structural similarity. To facilitate unknown identification and complement METLIN’s MS2fragment ion data for characterizing structurally related molecules, we have created the METLIN neutral loss database (https://metlin-nl.scripps.edu).
Molecular diagnosis of new isolate of tomato yellow leaf curl virus in Iraq
Authors: Alabde Ali , Alisawi Osamah , Fadhal Fadhal Al 
Published: April 2021

AbstractTomato yield and quality in Iraq have been threatened by a variable range of infections caused by tomato yellow leaf curl virus. In previous studies, the TYLCV isolates were partially characterized using molecular tests for small fragments not the entire length of the virus. Sample of TYLCV-infected tomato has applied in this study to diagnose complete sequence of TYLCV isolate. Three sets of primers that belong to three well-identified strains in Iraq were used in a PCR technique and interestingly the results were negative. A new Iraqi isolate has been characterized as a first novel Iraqi isolate detected ever using next generation (NGS) and bioinformatics techniques. The NGS platform has produced about 78,232,062 paired reads of the TYLCV-infected tomato var. Oula F1. The complete raw reads of the infected variety have been analyzed using RepeatExplorer pipeline and Map to reference. The full sequence of TYLCV was reconstructed and extracted to consist of 2770 nt and then deposited in Genbank under accession numberMT583814. Copy numbers and genome proportion of this sequence have been calculated that were 3523 and 0,086% respectively. Phylogenetic analyses of full nucleotide sequences confirmed close relationship to Iranian isolate (TYLCV-Kahnooj) than other published viruses. Additionally, a and β DNA satellites have not discovered in the TYLCV-infected sample.
Dissection of the ATPase active site of McdA reveals the sequential steps essential for carboxysome distribution
Authors: Hakim Pusparanee , Vecchiarelli Anthony G. 
Published: April 2021

ABSTRACTCarboxysomes, the most prevalent and well-studied anabolic bacterial microcompartment, play a central role in efficient carbon fixation by cyanobacteria and proteobacteria. In previous studies, we identified the two-component system called McdAB that spatially distributes carboxysomes across the bacterial nucleoid. McdA, a ParA-like ATPase, forms a dynamic oscillating gradient on the nucleoid in response to carboxysome-localized McdB. As McdB stimulates McdA ATPase activity, McdA is removed from the nucleoid in the vicinity of carboxysomes, propelling these proteinaceous cargos toward regions of highest McdA concentration via a Brownian-ratchet mechanism. However, how the ATPase cycle of McdA governs itsin vivodynamics and carboxysome positioning remains unresolved. Here, by strategically introducing amino acid substitutions in the ATP-binding region of McdA, we sequentially trap McdA at specific steps in its ATP cycle. We map out critical events in the ATPase cycle of McdA that allows the protein to bind ATP, dimerize, change its conformation into a DNA-binding state, interact with McdB-bound carboxysomes, hydrolyze ATP and release from the nucleoid. We also find that McdA is a member of a previously unstudied subset of ParA family ATPases, harboring unique interactions with ATP and the nucleoid for trafficking their cognate intracellular cargos.
Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A
Authors: Lepelley Alice , Mina Erika Della , Van Nieuwenhove Erika , Waumans Lise , Fraitag Sylvie , Rice Gillian I , Dhir Ashish , Frémond Marie-Louise , Rodero Mathieu P , Seabra Luis , Carter Edwin , Bodemer Christine , Buhas Daniela , Callewaert Bert , de Lonlay Pascale , De Somer Lien , Dyment David A , Faes Fran , Grove Lucy , Holden Simon , Hully Marie , Kurian Manju A , McMillan Hugh J , Suetens Kristin , Tyynismaa Henna , Chhun Stephanie , Wai Timothy , Wouters Carine , Bader-Meunier Brigitte , Crow Yanick J 
Published: April 2021

AbstractMitochondrial DNA (mtDNA) has been suggested to drive immune system activation, but the induction of interferon signaling by mtDNA has not been demonstrated in a Mendelian mitochondrial disease. We initially ascertained two patients, one with a purely neurological phenotype, and one with features suggestive of systemic sclerosis in a syndromic context, and found them both to demonstrate enhanced interferon-stimulated gene (ISG) expression in blood. We determined each to harbor a previously described de novo dominant-negative heterozygous mutation in ATAD3A, encoding ATPase family AAA domain-containing protein 3A (ATAD3A). We identified five further patients with mutations in ATAD3A, and recorded up-regulated ISG expression and interferon alpha protein in four of them. Knockdown of ATAD3A in THP-1 cells resulted in increased interferon signaling, mediated by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Enhanced interferon signaling was abrogated in THP-1 cells and patient fibroblasts depleted of mtDNA. Thus, mutations in the mitochondrial membrane protein ATAD3A define a novel type I interferonopathy.SummaryDominant-negative mutations in ATAD3A, a ubiquitously expressed mitochondrial protein, cause mitochondrial DNA-dependent up-regulation of type I interferon signaling in the context of neurological disease and autoimmunity, thereby defining a novel type I interferonopathy.
A new High-Throughput-Screening-assay for Photoantimicrobials Based on EUCAST Revealed Photoantimicrobials in Cortinariaceae
Authors: Fiala Johannes , Schöbel Harald , Vrabl Pamela , Dietrich Dorothea , Hammerle Fabian , Altmann Desirée Josefine , Stärz Ronald , Peintner Ursula , Siewert Bianka 
Published: April 2021

AbstractA spark of light might unravel antimicrobial activity of colored compounds, which otherwise would have been classified as inactive. While many mushrooms contain such colorful pigments but lack antimicrobial activity, we wondered if a controlled irradiation is needed to unleash their effect. To explore such photoantimicrobial actions in the Kingdom Fungi, an efficient high-throughput-screening (HTS) assay is needed. Here we report on the establishment of a reliable photoantimicrobial assay based on the EUCAST recommendations, which was validated with known photosensitzers (i.e., curcumin, phenalenone, rose bengal, an hypericum extract, and methylene blue). Furthermore, an improved LED-irradiation setup enabling with only 24 LEDs a homogenous irradiation of a 96-well plate is presented. The established HTS-assay was utilized to screen six colorfulCortinariusextracts unrevealingC. xanthophyllusandC. rufo-olivaceusas promising sources for new photoantimicrobials.
Neural mechanisms of distributed value representations and learning strategies
Authors: Farashahi Shiva , Soltani Alireza 
Published: April 2021

AbstractLearning appropriate representations of the reward environment is extremely challenging in the real world where there are many options to learn about and these options have many attributes or features. Despite existence of alternative solutions for this challenge, neural mechanisms underlying emergence and adoption of value representations and learning strategies remain unknown. To address this, we measured learning and choice during a novel multi-dimensional probabilistic learning task in humans and trained recurrent neural networks (RNNs) to capture our experimental observations. We found that participants estimate stimulus-outcome associations by learning and combining estimates of reward probabilities associated with the informative feature followed by those of informative conjunctions. Through analyzing representations, connectivity, and lesioning of the RNNs, we demonstrate this mixed learning strategy relies on a distributed neural code and distinct contributions of inhibitory and excitatory neurons. Together, our results reveal neural mechanisms underlying emergence of complex learning strategies in naturalistic settings.
New insights from 33,813 publicly available metagenome-assembled-genomes (MAGs) assembled from the rumen microbiome
Authors: Watson Mick 
Published: April 2021

AbstractRecent rumen microbiome metagenomics papers1,2have published hundreds of metagenome-assembled genomes (MAGs), comparing them to 4,941 MAGs published by Stewartet al3in order to define novelty. However, there are many more publicly available MAGs from ruminants. In this paper, for the first time, all available resources are combined, catalogued and de-replicated to define putative species-level bins. As well as providing new insights into the constitution of the rumen microbiome, including an updated estimate of the number of microbial species in the rumen, this work demonstrates that a lack of community-adopted standards for the release and annotation of MAGs hinders progress in microbial ecology and metagenomics.
Inability to switch from ARID1A-BAF to ARID1B-BAF impairs exit from pluripotency and commitment towards neural crest formation inARID1B-related neurodevelopmental disorders
Authors: Pagliaroli Luca , Porazzi Patrizia , Curtis Alyxandra T. , Scopa Chiara , Mikkers Harald M.M. , Freund Christian , Daxinger Lucia , Deliard Sandra , Welsh Sarah A. , Offley Sarah , Ott Connor A. , Calabretta Bruno , Brugmann Samantha A. , Santen Gijs W.E. , Trizzino Marco 
Published: April 2021

AbstractThe BAF complex modulates chromatin accessibility. Specific BAF configurations have functional consequences, and subunit switches are essential for cell differentiation.ARID1Band its paralogARID1Aencode for mutually exclusive BAF subunits.De novo ARID1Bhaploinsufficient mutations cause a neurodevelopmental disorder spectrum, including Coffin-Siris syndrome, which is characterized by neurological and craniofacial features. Here, we reprogrammedARID1B+/-Coffin-Siris patient-derived skin fibroblasts into iPSCs and modeled cranial neural crest cell (CNCC) formation. We discovered that ARID1B is active only during the first stage of this process, coinciding with neuroectoderm specification, where it is part of a lineage-specific BAF configuration (ARID1B-BAF), which includes SMARCA4 and nine additional subunits. ARID1B-BAF acts as a gatekeeper, ensuring exit from pluripotency and lineage commitment, by attenuatingNANOG, SOX2and thousands of enhancers directly regulated by these two pluripotency factors at the iPSC stage.In iPSCs, these enhancers are maintained active by an ARID1A-containing BAF. At the onset of differentiation, cells transition from ARID1A-BAF to ARID1B-BAF, eliciting attenuation of the NANOG/SOX2 networks, and triggering pluripotency exit. Coffin-Siris patient cells fail to perform the ARID1A/ARID1B switch and maintain ARID1A-BAF at pluripotency enhancers throughout all stages of CNCC formation. This leads to a persistent and aberrant SOX2 and NANOG activity, which impairs CNCC formation. In fact, despite showing the typical neural crest signature (TFAP2A+, SOX9+),ARID1B-haploinsufficient CNCCs are also NANOG/OCT4-positive, in stark contrast with theARID1B-wt CNCCs, which are NANOG/OCT4-negative.These findings suggest a connection betweenARID1Bmutations, neuroectoderm formation, and a pathogenic mechanism for Coffin-Siris syndrome.