bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid induction of antigen-specific CD4+T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination
Authors: Painter Mark M. , Mathew Divij , Goel Rishi R. , Apostolidis Sokratis A. , Pattekar Ajinkya , Kuthuru Oliva , Baxter Amy E. , Herati Ramin S. , Oldridge Derek A. , Gouma Sigrid , Hicks Philip , Dysinger Sarah , Lundgreen Kendall A. , Kuri-Cervantes Leticia , Adamski Sharon , Hicks Amanda , Korte Scott , Giles Josephine R. , Weirick Madison E. , McAllister Christopher M. , Dougherty Jeanette , Long Sherea , D’Andrea Kurt , Hamilton Jacob T. , Betts Michael R. , Bates Paul , Hensley Scott E. , Grifoni Alba , Weiskopf Daniela , Sette Alessandro , Greenplate Allison R. , Wherry E. John 
Published: April 2021

SummaryThe SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses in healthy individuals following mRNA vaccination. Vaccination induced rapid near-maximal antigen-specific CD4+T cell responses in all subjects after the first vaccine dose. CD8+T cell responses developed gradually after the first and second dose and were variable. Vaccine-induced T cells had central memory characteristics and included both Tfh and Th1 subsets, similar to natural infection. Th1 and Tfh responses following the first dose predicted post-boost CD8+T cell and neutralizing antibody levels, respectively. Integrated analysis of 26 antigen-specific T cell and humoral responses revealed coordinated features of the immune response to vaccination. Lastly, whereas booster vaccination improved CD4+and CD8+T cell responses in SARS-CoV-2 naïve subjects, the second vaccine dose had little effect on T cell responses in SARS-CoV-2 recovered individuals. Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4+T cells.Graphical Abstract
Glycowork: A Python package for glycan data science and machine learning
Authors: Thomès Luc , Burkholz Rebekka , Bojar Daniel 
Published: April 2021

AbstractAs a biological sequence, glycans occur in every domain of life and comprise monosaccharides that are chained together to form oligo- or polysaccharides. While glycans are crucial for most biological processes, existing analysis modalities make it difficult for researchers with limited computational background to include information from these diverse and nonlinear sequences into standard workflows. Here, we present glycowork, an open-source Python package that was designed for the processing and analysis of glycan data by end users, with a strong focus on glycan-related data science and machine learning. Glycowork includes numerous functions to, for instance, automatically annotate glycan motifs and analyze their distributions via heatmaps and statistical enrichment. We also provide visualization methods, routines to interact with stored databases, trained machine learning models, and learned glycan representations. We envision that glycowork can extract further insights from any glycan dataset and demonstrate this with several workflows that analyze glycan motifs in various biological contexts. Glycowork can be freely accessed athttps://github.com/BojarLab/glycowork/.
Co-option of the Limb Patterning Program in Cephalopod Lens Development
Authors: Neal Stephanie , McCulloch Kyle J. , Napoli Francesca , Daly Christina M. , Coleman James H. , Koenig Kristen M. 
Published: April 2021

AbstractAcross the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Here we identify the co-option of the canonical bilaterian limb pattering program redeployed during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factorsSP6-9/sp1, Dlx/dll, Pbx/exd, Meis/hth, and aPrdlhomolog in the squidDoryteuthis pealeii, similar to expression required inDrosophilalimb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate this co-option. These results suggest that the limb network does not exclusively pattern appendage outgrowth but is performing a more universal developmental function: radial patterning.
A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes
Authors: Grancharova Tanya , Gerbin Kaytlyn A. , Rosenberg Alexander B. , Roco Charles M. , Arakaki Joy , DeLizzo Colette , Dinh Stephanie Q. , Donovan-Maiye Rory , Hirano Matthew , Nelson Angelique , Tang Joyce , Theriot Julie A. , Yan Calysta , Menon Vilas , Palecek Sean P. , Seelig Georg , Gunawardane Ruwanthi N. 
Published: April 2021

AbstractWe performed a comprehensive analysis of the transcriptional changes within and across cell populations during human induced pluripotent stem cell (hiPSC) differentiation to cardiomyocytes. Using the single cell RNA-seq combinatorial barcoding method SPLiT-seq, we sequenced >20,000 single cells from 55 independent samples representing two differentiation protocols and multiple hiPSC lines. Samples included experimental replicates ranging from undifferentiated hiPSCs to mixed populations of cells at D90 post-differentiation. As expected, differentiated cell populations clustered by time point, with differential expression analysis revealing markers of cardiomyocyte differentiation and maturation changing from D12 to D90. We next performed a complementary cluster-independent sparse regression analysis to identify and rank genes that best assigned cells to differentiation time points. The two highest ranked genes between D12 and D24 (MYH7andMYH6) resulted in an accuracy of 0.84, and the three highest ranked genes between D24 and D90 (A2M, H19, IGF2) resulted in an accuracy of 0.94, revealing that low dimensional gene features can identify differentiation or maturation stages in differentiating cardiomyocytes. Expression levels of select genes were validated using RNA FISH. Finally, we interrogated differences in differentiation population composition and cardiac gene expression resulting from two differentiation protocols, experimental replicates, and three hiPSC lines in the WTC-11 background to identify sources of variation across these experimental variables.
Exploring the genomic diversity and antimicrobial susceptibility ofBifidobacterium pseudocatenulatumin the Vietnamese population to aid probiotic design
Authors: The Hao Chung , Ngoc Minh Chau Nguyen , Thi Hong Chau Tran , Thi Nguyen To Nguyen , Pike Lindsay J. , Zellmer Caroline , Duc Trung Pham , Tran Tuan-Anh , Thanh Tuyen Ha , Van Minh Pham , Thwaites Guy E. , Rabaa Maia A. , Hall Lindsay J. , Baker Stephen 
Published: April 2021

AbstractBifidobacterium pseudocatenulatumis a member of the human gut microbiota, and has previously been used as a probiotic to improve gut integrity and reduce inflammatory responses. We showed previously thatB. pseudocatenulatumwas significantly depleted during dysenteric diarrhea, suggesting the organism may aid in recovery from diarrhea. Here, in order to investigate its probiotic potential, we aimed to assess the genomic diversity and predicted metabolic profiles ofB. pseudocatenulatumfound colonizing the gut of healthy Vietnamese adults and children. We found that the population ofB. pseudocatenulatumfrom each individual was distinct and highly diverse, with intra-clonal variation attributed to gain or loss of carbohydrate utilizing enzymes. TheB. pseudocatenulatumgenomes were enriched with glycosyl hydrolases that target plant-based non-digestible carbohydrates (GH13, GH43), but not host-derived glycans. Notably, the exopolysaccharide biosynthesis region from organisms isolated from healthy children showed greater genetic diversity, and was subject to a high degree of genetic modification. Antimicrobial susceptibility testing revealed that the VietnameseB. pseudocatenulatumwere uniformly susceptible to beta-lactams, but exhibited variable resistance to azithromycin, tetracycline, ciprofloxacin and metronidazole. The genomic presence ofermXandtetvariants conferred resistance against azithromycin and tetracycline, respectively; ciprofloxacin resistance was associated with mutation(s) in the quinolone resistance determining region (GyrA, S115 and/or D119). Our work provides the first detailed genomic and antimicrobial resistance characterization ofB. pseudocatenulatumfound in the Vietnamese population, which could inform the next phase of rational probiotic design.ImportanceBifidobacterium pseudocatenulatumis a probiotic candidate with potential applications in several health conditions, but its efficacy is largely strain-dependent and associated with distinct genomic and biochemical features. However, most commercial probiotics have been developed by Western institutions, which may not have ideal efficacy when administered in developing countries. This study taps into the underexplored diversity of the organism in Vietnam, and provides more understanding to its lifestyles and antimicrobial susceptibility. These data are key for selecting an optimal probiotic candidate, from our established collection, for downstream investigations and validation. Thus, our work represents a model in identifying and characterizing bespoke probiotics from an indigenous population in a developing setting.
Structuring time: The hippocampus constructs sequence memories that generalize temporal relations across experiences
Authors: Bellmund Jacob L. S. , Deuker Lorena , Montijn Nicole D. , Doeller Christian F. 
Published: April 2021

AbstractThe hippocampal-entorhinal region supports memory for episodic details, such as temporal relations of sequential events, and mnemonic constructions combining experiences for inferential reasoning. However, it is unclear whether hippocampal event memories reflect temporal relations derived from mnemonic constructions, event order, or elapsing time, and whether these sequence representations generalize temporal relations across similar sequences. Here, participants mnemonically constructed times of events from multiple sequences using infrequent cues and their experience of passing time. After learning, event representations in the anterior hippocampus reflected temporal relations based on constructed times. Temporal relations were generalized across sequences, revealing distinct representational formats for events from the same or different sequences. Structural knowledge about time patterns, abstracted from different sequences, biased the construction of specific event times. These findings demonstrate that mnemonic construction and the generalization of relational knowledge combine in the hippocampus, consistent with the simulation of scenarios from episodic details and structural knowledge.
Molecular reconstruction of recurrent evolutionary switching in olfactory receptor specificity
Authors: Prieto-Godino Lucia L. , Schmidt Hayden R. , Benton Richard 
Published: April 2021

AbstractOlfactory receptor repertoires exhibit remarkable functional diversity, but how these proteins have evolved is poorly understood. Through analysis of extant and ancestrally-reconstructed drosophilid olfactory receptors from the Ionotropic Receptor (IR) family, we investigated evolution of two organic acid-sensing receptors, IR75a and IR75b. Despite their low amino acid identity, we identify a common “hotspot” in their ligand-binding pocket that has a major effect on changing the specificity of both IRs, as well as at least two distinct functional transitions in IR75a during evolution. Ligand-docking into IR models predicts that the hotspot does not contact odor molecules, suggesting that this residue indirectly influences ligand/receptor interactions. Moreover, we show that odor specificity is refined by changes in additional, receptor-specific sites, including those outside the ligand-binding pocket. Our work reveals how a core, common determinant of ligand-tuning acts within epistatic and allosteric networks of substitutions to lead to functional evolution of olfactory receptors.
Differential impact of acute and chronic stress on CA1 spatial coding and gamma oscillations
Authors: Tomar Anupratap , Polygalov Denis , McHugh Thomas 
Published: April 2021

AbstractChronic and acute stress differentially affect behaviour, as well as the structural integrity of the hippocampus, a key brain region involved in cognition and memory. However, it remains unclear if and how the facilitatory effects of acute stress on hippocampal information coding are disrupted as the stress becomes chronic. To examine this, we compared the impact of acute and chronic stress on neural activity in the CA1 subregion of male mice subjected to a chronic immobilization stress paradigm. We observed that following first exposure to stress (acute stress), the spatial information encoded in the hippocampus sharpened and the neurons became increasingly tuned to the underlying theta oscillation in the local field potential (LFP). However, following repeated exposure to same stress (chronic stress), spatial tuning was poorer and the power of both the slow-gamma (30-50 Hz) and fast-gamma (55-90 Hz) oscillations, which correlate with excitatory inputs into the region, decreased. These results support the idea that acute and chronic stress differentially affect neural computations carried out by hippocampal circuits and suggest that acute stress may improve cognitive processing.
In silico DNA codon optimization of the variant antigen-encoding genes of diverse strains of Nipah virus
Authors: Gupta Aeshna , Gangotia Disha , Vasdev Kavita , Mani Indra 
Published: April 2021

AbstractDue to an increase in human and wildlife interaction, more and more zoonotic diseases are emerging. A prime example of this is the emergence of the Nipah virus (NiV). Due to high rate of mortality specifically in India and Bangladesh, there is an urgent need for accelerated research for NiV involving the development of vaccines or drugs. The genome of NiV consists of six genes (N, P, M, F, G and L) encoding yielding nucleoprotein, phosphoprotein, matrix, fusion, glycoprotein and large RNA polymerase. We have used these six genes for in silico assessment of DNA codon optimization inEscherichia coli. It was observed that the codon adaptation index (CAI) and GC content of the genes in optimized DNA were enhanced significantly as compared to wild-type strain. On an average, CAI and GC content of N gene in optimized DNA was enhanced by 2.3 (135.1%) and 1.2(9.9 %) fold respectively, while in P/V/C it was increased by 2.0 (98.3 %) and 1.1(7.8%) fold respectively. Further, the CAI and GC content in optimized DNA of M gene and F gene was enhanced by 2.0(99.0%) and 1.1(7.2%) fold respectively for gene M and 2.4(142.5 %), 1.2(15.4%) fold respectively for gene F. Gene G showed an increase of 2.1(114.8 %) fold for CAI, 1.1(11.2%) fold for GC content and gene L showed an increase of 2.4(143.7%) fold for CAI, 1.2(17.2%) fold for GC content. Our result demonstrates that the optimized genes could be useful for better expression in host without any truncated proteins and also useful for protein folding and function.
After-hyperpolarization promotes the firing of mitral cells through a voltage dependent modification of action potential threshold
Authors: Nicolas Fourcaud-Trocmé , Mickaël Zbili , Patricia Duchamp-Viret , Nicola Kuczewski 
Published: April 2021

AbstractIn the olfactory bulb (OB), mitral cells (MCs) display a spontaneous firing that is characterized by bursts of action potentials intermixed with silent periods. Burst firing frequency and duration are heterogeneous among MCs and increase with membrane depolarization. By using patch clamp recording on rat slices, we dissected out the intrinsic properties responsible of this activity. We showed that the threshold of action potential (AP) generation dynamically changes as a function of the trajectory of the membrane potential; becoming more negative when the membrane was hyperpolarized and having a recovering rate, inversely proportional to the membrane repolarization rate. Such variations appeared to be produced by changes in the inactivation state of voltage dependent Na+channels. Thus, the modification AP threshold favours the initiation of the burst following hyperpolarizing event such as negative membrane oscillations or inhibitory transmission. After the first AP, the following afterhyperpolarization (AHP) brought the threshold just below the membrane resting potential or within membrane oscillations and, as a consequence, the threshold was exceeded during the fast repolarization component of the AHP. In this way the fast AHP acts as a regenerative mechanism that sustains the firing. Bursts were stopped by the development of a slow repolarization component of the AHP. The AHP characteristics appeared as determining the bursting properties; AHP with larger amplitudes and faster repolarizations being associated with longer and higher frequency bursts. Thus, the increase of bursts length and frequency upon membrane depolarization would be attributable to the modifications of the AHP and of Na+channels inactivation.
Locomotion induced by medial septal glutamatergic neurons is linked to intrinsically generated persistent firing
Authors: Korvasová Karolína , Ludwig Felix , Kaneko Hiroshi , Sosulina Liudmila , Tetzlaff Tom , Remy Stefan , Mikulovic Sanja 
Published: April 2021

AbstractMedial septal glutamatergic neurons are active during theta oscillations and locomotor activity. Prolonged optogenetic activation of medial septal glutamatergic neurons drives theta oscillations and locomotion for extended periods of time outlasting the stimulus duration. However, the cellular and circuit mechanisms supporting the maintenance of both theta oscillations and locomotion remain elusive. Specifically, it remains unclear whether the presence of theta oscillations is a necessary prerequisite for locomotion, and whether neuronal activity within the medial septum underlies its persistence. Here we show that a persistent theta oscillation can be induced by a brief transient activation of glutamatergic neurons. Moreover, persistent locomotion is initiated even if the theta oscillation is abolished by blocking synaptic transmission in the medial septum. We observe persistent spiking of medial septal neurons that outlasts the stimulus for several seconds, both in vivo and in vitro. This persistent activity is driven by intrinsic excitability of glutamatergic neurons.
Identifying Oscillatory Hyperconnectivity and Hypoconnectivity Networks in Major Depression Using Coupled Tensor Decomposition
Authors: Liu Wenya. , Wang Xiulin. , Xu Jing. , Chang Yi. , Hämäläinen Timo. , Cong Fengyu. 
Published: April 2021

AbstractPrevious researches demonstrate that major depression disorder (MDD) is associated with widespread network dysconnectivity, and the dynamics of functional connectivity networks are important to delineate the neural mechanisms of MDD. Cortical electroencephalography (EEG) oscillations act as coordinators to connect different brain regions, and various assemblies of oscillations can form different networks to support different cognitive tasks. Studies have demonstrated that the dysconnectivity of EEG oscillatory networks is related with MDD. In this study, we investigated the oscillatory hyperconnectivity and hypoconnectivity networks in MDD under a naturalistic and continuous stimuli condition of music listening. With the assumption that the healthy group and the MDD group share similar brain topology from the same stimuli and also retain individual brain topology for group differences, we applied the coupled nonnegative tensor decomposition algorithm on two adjacency tensors with the dimension of time × frequency × connectivity × subject, and imposed double-coupled constraints on spatial and spectral modes. The music-induced oscillatory networks were identified by a correlation analysis approach based on the permutation test between extracted temporal factors and musical features. We obtained three hyperconnectivity networks from the individual features of MDD and three hypoconnectivity networks from common features. The results demonstrated that the dysfunction of oscillation-modulated networks could affect the involvement in music perception for MDD patients. Those oscillatory dysconnectivity networks may provide promising references to reveal the pathoconnectomics of MDD and potential biomarkers for the diagnosis of MDD.
Rich and lazy learning of task representations in brains and neural networks
Authors: Flesch Timo , Juechems Keno , Dumbalska Tsvetomira , Saxe Andrew , Summerfield Christopher 
Published: April 2021

AbstractHow do neural populations code for multiple, potentially conflicting tasks? Here, we used computational simulations involving neural networks to define “lazy” and “rich” coding solutions to this multitasking problem, which trade off learning speed for robustness. During lazy learning the input dimensionality is expanded by random projections to the network hidden layer, whereas in rich learning hidden units acquire structured representations that privilege relevant over irrelevant features. For context-dependent decision-making, one rich solution is to project task representations onto low-dimensional and orthogonal manifolds. Using behavioural testing and neuroimaging in humans, and analysis of neural signals from macaque prefrontal cortex, we report evidence for neural coding patterns in biological brains whose dimensionality and neural geometry are consistent with the rich learning regime.