bluuebunny/crossref_metadata_2025_split huggingface dataset:
The locus of recognition memory signals in human cortex depends on the complexity of the memory representations
Authors: Sanders D. Merika W. , Cowell Rosemary A. 
Published: June 2021

AbstractAccording to a “Swiss Army Knife” model of the brain, cognitive functions such as episodic memory and face perception map onto distinct neural substrates. In contrast, representational accounts propose that each brain region is best explained not by which specialized function it performs, but by the type of information it represents with its neural firing. In a functional MRI study, we asked whether the neural signals supporting recognition memory fall mandatorily within the medial temporal lobes (MTL), traditionally thought the seat of declarative memory, or whether these signals shift within cortex according to the content of the memory. Participants studied objects and scenes that were unique conjunctions of pre-defined visual features. Next, we tested recognition memory in a task that required mnemonic discrimination of both simple features and complex conjunctions. Feature memory signals were strongest in posterior visual regions, declining with anterior progression towards the MTL, while conjunction memory signals followed the opposite pattern. Moreover, feature memory signals correlated with feature memory discrimination performance most strongly in posterior visual regions, whereas conjunction memory signals correlated with conjunction memory discrimination most strongly in anterior sites. Thus, recognition memory signals shifted with changes in memory content, in line with representational accounts.
Disentangling top-down drivers of mortality underlying diel population dynamics ofProchlorococcusin the North Pacific Subtropical Gyre
Authors: Beckett Stephen J. , Demory David , Coenen Ashley R. , Casey John R. , Dugenne Mathilde , Follett Christopher L. , Connell Paige , Carlson Michael C.G. , Hu Sarah K. , Wilson Samuel T. , Muratore Daniel , Rodriguez-Gonzalez Rogelio A. , Peng Shengyun , Becker Kevin W. , Mende Daniel R. , Armbrust E. Virginia , Caron David A. , Lindell Debbie , White Angelicque E. , Ribalet François , Weitz Joshua S. 
Published: June 2021

AbstractPhotosynthesis fuels primary production at the base of marine food webs. Yet, in many surface ocean ecosystems, diel-driven primary production is tightly coupled to daily loss. This tight coupling raises the question: which top-down drivers predominate in maintaining persistently stable picocyanobacterial populations over longer time scales? Motivated by high-frequency surface water measurements taken in the North Pacific Subtropical Gyre (NPSG), we developed multitrophic models to investigate bottom-up and top-down mechanisms underlying the balanced control ofProchlorococcuspopulations. We find that incorporating photosynthetic growth with viral- and predator-induced mortality is sufficient to recapitulate daily oscillations ofProchlorococcusabundances with baseline community abundances. In doing so, we infer that grazers function as the primary top-down factor despite high standing viral particle densities while identifying the potential for light-dependent viral traits and non-canonical loss factors to shape the structure and function of marine microbial communities.
Rapid homeostatic modulation of transsynaptic nanocolumn rings
Authors: Muttathukunnel Paola , Frei Patrick , Perry Sarah , Dickman Dion , Müller Martin 
Published: June 2021

SummaryRobust neural information transfer relies on a delicate molecular nano-architecture of chemical synapses. Neurotransmitter release is controlled by a specific arrangement of proteins within presynaptic active zones. How the specific presynaptic molecular architecture relates to postsynaptic organization, and how synaptic nano-architecture is transsynaptically regulated to achieve stable synaptic transmission remains enigmatic. Using time-gated stimulated emission depletion (gSTED) microscopy at the Drosophila neuromuscular junction, we here find that presynaptic nano-rings formed by the active-zone scaffold Bruchpilot (Brp) precisely align with postsynaptic glutamate receptor (GluR) rings. Individual rings harbor ~5 transsynaptically-aligned Brp-GluR ‘nanocolumns’. Intriguingly, acute GluR impairment rapidly triggers the formation of new transsynaptic nanocolumns on the minute time scale during homeostatic plasticity. We reveal distinct phases of structural transsynaptic homeostatic plasticity, with postsynaptic reorganization preceding presynaptic modulation. Finally, the auxiliary GluR subunit Neto-β promotes structural and functional homeostatic plasticity. Thus, transsynaptic nanocolumns arrange in stereotypic rings that are rapidly modulated during homeostatic plasticity to stabilize synaptic efficacy.One Sentence SummaryRapid changes of transsynaptic nanocolumn rings during homeostatic plasticity.
Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro
Authors: Panchariya Love , Khan Wajahat Ali , Kuila Shobhan , Sonkar Kirtishila , Sahoo Sibasis , Ghoshal Archita , Kumar Ankit , Verma Dileep Kumar , Hasan Abdul , Das Shubhashis , Thakur Jitendra K , Halder Rajkumar , Sunil Sujatha , Arockiasamy Arulandu 
Published: June 2021

AbstractZinc deficiency is linked to poor prognosis in COVID-19 patients while clinical trials with Zinc demonstrate better clinical outcome. The molecular target and mechanistic details of anti-coronaviral activity of Zinc remain obscure. We show that ionic Zinc not only inhibits SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication. We present the first crystal structure of Mpro-Zn2+ complex at 1.9 Å and provide the structural basis of viral replication inhibition. We show that Zn2+ coordinates with the catalytic dyad at the enzyme active site along with two previously unknown water molecules in a tetrahedral geometry to form a stable inhibited Mpro-Zn2+ complex. Further, natural ionophore quercetin increases the anti-viral potency of Zn2+. As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn2+ mediated inhibition of Mpro may have wider implications.
Emergent properties of coupled bistable switches
Authors: Hari Kishore , Harlapur Pradyumna , Gopalan Aditi , Ullanat Varun , Duddu Atchuta Srinivas , Jolly Mohit Kumar 
Published: June 2021

AbstractUnderstanding the dynamical hallmarks of network motifs is one of the fundamental aspects of systems biology. Positive feedback loops constituting one or two nodes – self-activation, toggle switch, and double activation loops – are commonly observed motifs in regulatory networks underlying cell-fate decision systems. Their individual dynamics are well-studied; they are capable of exhibiting bistability. However, studies across various biological systems suggest that such positive feedback loops are interconnected with one another, and design principles of coupled bistable motifs remain unclear. We wanted to ask what happens to bistability or multistability traits and the phenotypic space (collection of phenotypes exhibited by a system) due to the couplings. In this study, we explore a set of such interactions using discrete and continuous simulation methods. Our results suggest that couplings that do not connect the bistable switches in a way that contradicts the connections within individual bistable switches lead to a steady state space that is strictly a subset of the set of possible combinations of steady states of bistable switches. Furthermore, adding direct and indirect self-activations to these coupled networks can increase the frequency of multistability. Thus, our observations reveal specific dynamical traits exhibited by various coupled bistable motifs.
Nucleus accumbens D1-receptors regulate and focus transitions to reward-seeking action
Authors: Grima LL , Panayi MC , Haermson O , Syed E , Manohar SG , Husain M , Walton ME 
Published: June 2021

AbstractWhile it is well established that dopamine transmission is integral in mediating the influence of reward expectations on reward-seeking actions, the precise causal role of dopamine transmission in moment-to-moment cue-driven behavioural control remains contentious. This is a particular issue in situations where it is necessary to refrain from responding to achieve a beneficial outcome. To examine this, we manipulated dopamine transmission pharmacologically as rats performed a Go/No-Go task that required them to either make or withhold action to gain either a small or large reward. Stimulation of D1Rs, both globally and locally in the nucleus accumbens core (NAcC) region consistently disrupted No-Go performance, potentiating inappropriate responses that clustered strongly just after cue presentation. D1R blockade did not, however, improve rats’ ability to withhold responses, but instead primarily disrupted performance on Go trials. While global D1R blockade caused a general reduction of invigoration of reward seeking actions, intra-NAcC administration of the D1R antagonist by contrast increased the likelihood that Go trial performance was in an “unfocused” state. Such a state was characterised, both on and off drug, by a reduction in the precision and speed of responding even though the appropriate action sequence was often executed. These findings suggests that the balance of activity at NAcC D1Rs plays a key role in enabling the rapid activation of a focused, reward-seeking state to enable animals to efficiently and accurately achieve their goal.
Musculoskeletal modelling of sprawling and parasagittal forelimbs provides insight into synapsid postural transition
Authors: Brocklehurst Robert J. , Fahn-Lai Philip , Regnault Sophie , Pierce Stephanie E. 
Published: June 2021

AbstractThe sprawling–parasagittal postural shift was a major transition during synapsid evolution and is considered key to mammalian ecological diversity. Despite a good fossil record, debate remains over when the shift to parasagittal posture occurred, primarily due to limited comparative biomechanical data on extant species. Here, we built forelimb musculoskeletal models of three extant taxa that bracket the sprawling–parasagittal transition: a tegu lizard, an echidna, and an opossum. We measured shoulder joint range of motion (ROM) about all three degrees of rotational freedom and characterized shoulder muscle moment arms (MMAs) across the entire pose space. Our results show that both the opossum and the tegu had high shoulder joint ROM, and both were substantially higher than the echidna. However, the opossum occupied a distinct region of pose space characterized by high humeral retraction angles. There are clear interspecific differences in MMAs related to posture, with the sprawling tegu and echidna emphasizing humeral depression, and the parasagittal opossum emphasizing humeral elevation. There are also notable differences between our sprawling taxa, with the echidna possessing much greater moment arms for humeral pronation than the tegu. We demonstrate clear functional variation between locomotor grades and use these data to hypothesize major shifts in forelimb function and posture along the mammalian stem.
Evolutionary History Impacts Phyllosphere Community Assembly on Forage Grasses
Authors: Bechtold Emily K. , Nüsslein Klaus 
Published: June 2021

ABSTRACTBenefits leaf bacterial communities provide to plant hosts are reduced by external stress. Understanding how plant hosts impact phyllosphere community assembly, how microbes influence plant traits, and how this interaction changes under stress will advance our insight into the evolutionary relationship between plants and their microbial communities. We investigated phyllosphere community assembly change over time, between host species, and under drought stress on three native temperate grasses and three non-native tropical grasses. By growing them together, effects of host geography and differences in environmental variables were eliminated allowing us to test evolutionary history on community assembly. We found evidence of phylosymbiosis which increased significantly under drought stress, indicating phyllosphere communities and their response to stress relate to grass species phylogeny. We also show native temperate grasses displayed stronger cophylogenetic relationships between grass hosts and their microbial communities and had increased selection by host species over time compared to non-native tropical hosts. Interestingly, the functional marker genenifH, though differentially present on all host species was not susceptible to drought. The evidence of shared evolutionary history, presence of functionally important bacteria, and responses to drought suggest that microbial communities are important plant traits that coevolve alongside their plant hosts.
Fire and forest loss in the Dominican Republic during the 21st Century
Authors: Martínez-Batlle José-Ramón 
Published: June 2021

AbstractForest loss is an environmental issue that threatens ecosystems in the Dominican Republic (the DR). Although shifting agriculture by slash-and-burn methods is thought to be the main driver of forest loss in the DR, empirical evidence of this relationship is still lacking. Since remotely sensed data on fire occurrence is a suitable proxy for estimating the spread of shifting agriculture, here I explore the association between forest loss and fire during the first 18 years of the 21st Century using zonal statistics and spatial autoregressive models on different spatio-temporal layouts. First, I found that both forest loss and fire were spatially autocorrelated and statistically associated with each other at a country scale over the study period, particularly in the western and central part of the DR. However, no statistical association between forest loss and fire was found in the eastern portion, a region that hosts a large international tourism hub. Second, deforestation and fire showed a joint cyclical variation pattern of approximately four years up to 2013, and from 2014 onwards deforestation alone followed a worrying upward trend, while at the same time fire activity declined significantly. Third, I found no significant differences in forest loss patterns between the deforested area of small (<1 ha) and large (>1 ha) clearings of forest. I propose these findings hold potential to inform land management policies that help reduce forest loss, particularly in protected areas, mountain areas, and the vicinity of tourism hubs.
MyoD-Cre driven alterations in K-Ras and p53 lead to a mouse model with histological and molecular characteristics of human rhabdomyosarcoma with direct translational applications
Authors: Nakahata Kengo , Simons Brian W. , Pozzo Enrico , Shuck Ryan , Kurenbekova Lyazat , Coarfa Cristian , Patel Tajhal D. , Yustein Jason T. 
Published: June 2021

AbstractRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, with overall long-term survival rates of about 65-70%. Thus, additional molecular insights and representative models are critical for further identifying and evaluating new treatment modalities. Using MyoD-Cre mediated introduction of mutant K-RasG12D and perturbations in p53 we have developed a novel genetically engineered mouse model (GEMM) for RMS. Specifically, we directly crossed mice expressing MyoD promoter-regulated Cre-recombinase with germline p53Flox or Lox-Stop-Lox (LSL) knock-in alleles expressing oncogenic p53R172H and/or K-RasG12D mutants. The anatomic sites of primary RMS development observed in these mice recapitulated human disease, with the most frequent sites of tumor growth seen in the head, neck, extremities, and abdomen.We have confirmed RMS histology and diagnosis through hematoxylin and eosin (H&E) staining, as well as positive immunohistochemistry (IHC) staining for desmin, myogenin, and phosphotungstic acid hematoxylin (PTAH). We established cell lines from several of the GEMM tumors with the ability to engraft and develop tumors in immunocompetent mice with similar histological and staining features as the primary tumors. Furthermore, injection of syngeneic RMS lines via tail vein had high metastatic potential to the lungs. Transcriptomic analyses of p53R172H/K-RasG12D GEMM-derived tumors showed evidence of high molecular homology with human RMS. Specifically, we noted alterations in gene ontologies including immune response, metabolism and mRNA processing. Finally, pre-clinical use of these murine RMS lines demonstrated similar therapeutic responsiveness to relevant chemotherapy and targeted therapies as human cell line models.Summary StatementWe have developed a new conditional genetically engineered mouse model of rhabdomyosarcoma (RMS) with homologous molecular signature to human RMS that provides valuable pre-clinical models for evaluating novel therapies.
Getting more out of FLAG-Tag co-immunoprecipitation mass spectrometry experiments using FAIMS
Authors: Ang Ching-Seng , Sacharz Joanna , Leeming Michael G. , Nie Shuai , Varshney Swati , Scott Nichollas E. , Williamson Nicholas A. 
Published: June 2021

AbstractCo-immunoprecipitation of proteins coupled to mass spectrometry is critical for the understanding of protein interaction networks. In instances where a suitable antibody is not available, it is common to graft synthetic tags onto target protein sequences and allowing the use of commercially available antibodies for affinity purification. A common approach is through FLAG-Tag co-immunoprecipitation. To allow the selective elution of protein complexes, competitive displacement using a large molar excess of the tag peptides is often carried out. Yet, this creates downstream challenges for the mass spectrometry analysis due to the presence of large quantities of these peptides. Here, we demonstrate that Field Asymmetric Ion Mobility Spectrometry (FAIMS), a gas phase ion separation device prior to mass spectrometry analysis can be applied to FLAG-Tag co-immunoprecipitation experiment to increase the depth of protein coverage. By excluding these abundant tag peptides, we were able to observe deeper coverage of interacting proteins and as a result, deeper biological insights, without the need for additional sample handling or altering sample preparation protocols.
Commonly used Hardy-Weinberg equilibrium filtering schemes impact population structure inferences using RADseq data
Authors: Pearman William S. , Urban Lara , Alexander Alana 
Published: June 2021

AbstractReduced representation sequencing (RRS) is a widely used method to assay the diversity of genetic loci across the genome of an organism. The dominant class of RRS approaches assay loci associated with restriction sites within the genome (restriction site associated DNA sequencing, or RADseq). RADseq is frequently applied to non-model organisms since it enables population genetic studies without relying on well-characterized reference genomes. However, RADseq requires the use of many bioinformatic filters to ensure the quality of genotyping calls. These filters can have direct impacts on population genetic inference, and therefore require careful consideration. One widely used filtering approach is the removal of loci which do not conform to expectations of Hardy-Weinberg equilibrium (HWE). Despite being widely used, we show that this filtering approach is rarely described in sufficient detail to enable replication. Furthermore, through analyses of in silico and empirical datasets we show that some of the most widely used HWE filtering approaches dramatically impact inference of population structure. In particular, the removal of loci exhibiting departures from HWE after pooling across samples significantly reduces the degree of inferred population structure within a dataset (despite this approach being widely used). Based on these results, we provide recommendations for best practice regarding the implementation of HWE filtering for RADseq datasets.
Spatial dynamics of feedback and feedforward regulation in cell lineages
Authors: Uhl Peter , Lowengrub John , Komarova Natalia , Wodarz Dominik 
Published: June 2021

AbstractFeedback mechanisms within cell lineages are thought to be important for maintaining tissue homeostasis. Mathematical models that assume well-mixed cell populations, together with experimental data, have suggested that negative feedback from differentiated cells on the stem cell self-renewal probability can maintain a stable equilibrium and hence homeostasis. Cell lineage dynamics, however, are characterized by spatial structure, which can lead to different properties. Here, we investigate these dynamics using spatially explicit computational models, including cell division, differentiation, death, and migration / diffusion processes. According to these models, the negative feedback loop on stem cell self-renewal fails to maintain homeostasis, both under the assumption of strong spatial restrictions and fast migration / diffusion. Although homeostasis cannot be maintained, this feedback can regulate cell density and promote the formation of spatial structures in the model. Tissue homeostasis, however, can be achieved if spatially restricted negative feedback on self-renewal is combined with an experimentally documented spatial feedforward loop in which stem cells regulate the fate of transit amplifying cells. This indicates that the dynamics of feedback regulation in tissue cell lineages are more complex than previously thought, and that combinations of spatially explicit control mechanisms are likely instrumental.
A 3D transcriptomics atlas of the mouse olfactory mucosa
Authors: Segura Mayra L. Ruiz Tejada , Moussa Eman Abou , Garabello Elisa , Nakahara Thiago S. , Makhlouf Melanie , Mathew Lisa S. , Valle Filippo , Huang Susie S.Y. , Mainland Joel D. , Caselle Michele , Osella Matteo , Lorenz Stephan , Reisert Johannes , Logan Darren W. , Malnic Bettina , Scialdone Antonio , Saraiva Luis R. 
Published: June 2021

ABSTRACTThe sense of smell helps us navigate the environment, but its molecular architecture and underlying logic remain unknown. The spatial location of odorant receptor genes (Olfrs) in the nose is widely thought to be independent of the structural diversity of the odorants they detect. Using spatial transcriptomics, we created a genome-wide 3D atlas of the mouse olfactory mucosa (OM). Topographic maps of genes differentially expressed in space reveal that bothOlfrsand non-Olfrsare distributed in a continuous and overlapping fashion over five broad zones in the OM. The spatial locations ofOlfrscorrelate with the mucus solubility of the odorants they recognize, providing direct evidence for the chromatographic theory of olfaction. This resource resolved the molecular architecture of the mouse OM, and will inform future studies on mechanisms underlyingOlfrgene choice, axonal pathfinding, patterning of the nervous system, and basic logic for the peripheral representation of smell.