bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pairwise sequence similarity mapping with PaSiMap: reclassification of immunoglobulin domains from titin as case study
Authors: Su Kathy , Mayans Olga , Diederichs Kay , Fleming Jennifer R. 
Published: May 2022

ABSTRACTSequence comparison is critical for the functional assignment of newly identified protein genes. As uncharacterised protein sequences accumulate, there is an increasing need for sensitive tools for their classification. Here, we present a novel multidimensional scaling pipeline, PaSiMap, which creates a map of pairwise sequence similarities. Uniquely, PaSiMap distinguishes between unique and shared features, allowing for a distinct view of protein-sequence relationships. We demonstrate PaSiMap’s efficiency in detecting sequence groups and outliers using titin’s 169 immunoglobulin (Ig) domains. We show that Ig domain similarity is hierarchical, being firstly determined by chain location, then by the loop features of the Ig fold and, finally, by super-repeat position. The existence of a previously unidentified domain repeat in the distal, constitutive I-band is revealed. Prototypic Igs, plus notable outliers, are identified and thereby domain classification improved. This re-classification can now guide future molecular research. In summary, we demonstrate that PaSiMap is a sensitive tool for the classification of protein sequences, which adds a new perspective in the understanding of inter-protein relationships. PaSiMap is applicable to any biological system defined by a linear sequence, including nucleotides.
Asymmetric Signaling Across the Hierarchy of Cytoarchitecture within the Human Connectome
Authors: Parkes Linden , Kim Jason Z , Stiso Jennifer , Calkins Monica E , Cieslak Matthew , Gur Raquel E , Gur Ruben C , Moore Tyler M , Ouellet Mathieu , Roalf David R , Shinohara Russell T , Wolf Daniel H , Satterthwaite Theodore D , Bassett Dani S 
Published: May 2022

AbstractCortical variations in cytoarchitecture form a sensory-fugal axis that systematically shapes regional profiles of extrinsic connectivity. Additionally, this axis is thought to guide signal propagation and integration across the cortical hierarchy. While human neuroimaging work has shown that this axis constrains local properties of the human connectome, it remains unclear whether it also shapes the asymmetric signaling that arises from higher-order connectome topology. Here, we used network control theory to examine the amount of energy required to propagate dynamics across the sensory-fugal axis. Our results revealed an asymmetry in this energy indicating that bottom-up transitions were easier to complete compared to top-down transitions. Supporting analyses demonstrated that this asymmetry was underpinned by a connectome topology that is wired to support efficient bottom-up signaling. Finally, we found that this asymmetry correlated with changes in intrinsic neuronal timescales and lessened throughout youth. Our results show that cortical variation in cytoarchitecture may guide the formation of macroscopic connectome topology.
Accurate Identification of Extrachromosomal Circular DNA from Long-read Sequences
Authors: Wanchai Visanu , Jenjaroenpun Piroon , Leangapichart Thongpan , Arrey Gerard , Burnham Charles M , Tümmle Maria C , Delgado-Calle Jesus , Regenberg Birgitte , Nookaew Intawat 
Published: May 2022

ABSTRACTExtrachromosomal circular DNA (eccDNA) of chromosomal origin is found in a range of eukaryotic species and cell type including cancer where eccDNA with oncogenes appear to drive tumorigenesis. Most studies of eccDNA employ short-read sequencing to identify for their identification. However, short-read sequencing cannot resolve the complexity of genomic repeats, which can lead to missing eccDNA identification. An alternative is the long-read sequencing technologies that can potentially be used to construct complete eccDNA. We present a software suite,Construction-basedRolling-circle amplification for eccDNA SequenceIdentification andLocation (CReSIL) 2.0, to identify and characterize eccDNA from long-read sequences. CReSIL’s performance in the identification of eccDNA, with a minimum F1 score of 0.98, is superior to the other bioinformatic tools based on simulated data. CReSIL provides many useful features for genomic annotation, which can used to infer eccDNA function and Circos visualization for eccDNA architecture investigation. We demonstrated CReSIL’s capability in many of the long-read sequencing datasets. This includes datasets enriched for eccDNA as well as whole genome datasets from many cells that contained large eccDNA. CReSIL suite software will be a versatile tool to deeply investigate eccDNA in biological samples.
C-terminal determinants for RNA binding motif 7 protein stability and RNA recognition
Authors: Sobeh Amr M. , Eichhorn Catherine D. 
Published: May 2022

AbstractThe 7SK ribonucleoprotein (RNP) is a critical regulator of eukaryotic transcription. Recently, RNA binding motif 7 (RBM7), which contains an RNA recognition motif (RRM), was reported to associate with 7SK RNA and core 7SK RNP protein components in response to DNA damage. However, little is known about the mode of RBM7-7SK RNA recognition. Here, we recombinantly expressed and purified RBM7 RRM constructs and found that constructs containing extended C-termini have increased solubility and stability compared to shorter constructs. To identify potential RBM7-7SK RNA binding sites, we analyzed deposited data from in cellulo crosslinking experiments and found that RBM7 crosslinks specifically to the distal region of 7SK stem-loop 3 (SL3). Electrophoretic mobility shift assays and NMR chemical shift perturbation experiments showed weak binding to 7SK SL3 constructs in vitro. Together, these results provide new insights into RBM7 RRM folding and recognition of 7SK RNA.Graphical abstractHighlightsExtending the RBM7 RRM C-terminus improves protein expression and solubilityThe RBM7 RRM interacts weakly with 7SK stem-loop 3 single-stranded RNASolution state NMR dynamics measurements support presence of additional β4’ strand
Species identification of early colonial bone artefacts excavated from Pyrmont, Australia, by mass spectrometric identification of collagen peptides
Authors: Multari Dylan H. , Sullivan Geraldine J. , Hartley Mary , Power Ronika K. , Haynes Paul A. 
Published: May 2022

AbstractZooarchaeology by Mass Spectrometry (ZooMS) is a rapidly developing and increasingly utilised peptide mass fingerprinting (PMF) technique that analyses Collagen 1A1 and 1A2 marker peptides for the genus- or species-level identification of fragmentary bones in the archaeological record. Traditionally, this analysis is performed using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-ToF-MS) to identify characteristic m/z values of known marker peptides. Here we present data on the application of a modified ZooMS approach, using nanoflow liquid chromatography - tandem mass spectrometry proteomics, to the analysis of a collection of six early colonial Australian (early to mid-19th Century CE) worked bone artefacts, believed to be mostly knife handles, excavated from a site in Pyrmont, Sydney, Australia in 2017. We were successfully able to identify characteristic marker peptides for bovine COL1A1 and COL1A2 in all six bone artefacts.
Comparative Transcriptome Analysis of Hypocotyls During the Developmental Transition of C3cotyledons to C4Leaves inHalimocnemis mollissimaBunge
Authors: Zolfaghar Mahdis , Rutten Twan , Ghaffari Mohammad Reza , Banaei-Moghaddam Ali Mohammad 
Published: May 2022

AbstractIdentification of signaling pathways that control C4photosynthesis development is essential for introducing the C4pathway into C3crops. Species with dual photosynthesis in their life cycle are interesting models to study such regulatory mechanisms. The species used hereHalimocnemis mollissimaBunge, belonging to the Caroxyleae tribe, displays C3photosynthesis in its cotyledons and a NAD-ME subtype of C4photosynthesis in the First leaves (FLs) onwards. We explored the long-distance signaling pathways that are probably implicated in the shoot-root coordination associated with the manifestation of the C4traits, including efficient resource usage by comparing the mRNA content of hypocotyls before and after the C4first leave’s formation. Histological examination showed the presence of C3anatomy in cotyledons and C4anatomy in the FLs. Our transcriptome analyses verified the performance of the NAD-ME subtype of C4in FLs and revealed differential transcript abundance of several potential mobile regulators and their associated receptors or transporters in two developmentally different hypocotyls ofH. mollissimaBunge. These differentially expressed genes (DEGs) belong to diverse functional groups, including various transcription factor (TF) families, phytohormones metabolism, and signaling peptides, part of which could be related to hypocotyl development. Our findings support the higher nitrogen and water use efficiency associated with C4photosynthetic and provide insights into the coordinated above- and under-ground tissue communication during the developmental transition of C3to C4photosynthesis in this species.
Application and comparison of lyophilisation protocols to enhance stable long-term storage of filovirus pseudotypes for use in antibody neutralisation tests
Authors: Neto Martin Mayora , Wright Edward , Temperton Nigel , Soema Peter , ten Have Rimko , Ploemen Ivo , Scott Simon 
Published: May 2022

ABSTRACTFiloviruses encompass highly pathogenic viruses placing sporadic public health burden on countries affected. Efforts for improved diagnostics and surveillance are needed considering the recent Ebola outbreaks in Africa. The need for high containment facilities can be circumvented by the use of pseudotype viruses (PV), which can be handled in low containment, for tropism, drug screening, vaccine immunogenicity and serosurveillance studies.In this study we assessed stability and functionality after long-term storage of lyophilised filovirus pseudotypes for use in neutralisation assays. Lyophilised Ebola and Marburg PVs retained production titres for at least two years when stored at +4°C or less. Lyophilised Ebola PVs performed similarly to non-lyophilised PVs in neutralisation assays after reconstitution. When stored at high temperatures (+37°C), lyophilised PVs did not retain titres after one-month storage, however, when lyophilised using pilot scale facilities EBOV PVs retained titres and performed well in neutralisation assays after one-month storage at 37°C suggesting removing residual moisture might be crucial for avoiding cold-chain transportation. Lyophilisation could allow reagents to be transported more efficiently as well as reducing costs for a future serological kit.
Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens
Authors: Wang Zijun , Muecksch Frauke , Muenn Friederike , Cho Alice , Zong Shuai , Raspe Raphael , Ramos Victor , Johnson Brianna , Tanfous Tarek Ben , DaSilva Justin , Bednarski Eva , Guzman-Cardozo Camila , Turroja Martina , Millard Katrina G. , Tober-Lau Pinkus , Hillus David , Yao Kai-Hui , Shimeliovich Irina , Dizon Juan , Kaczynska Anna , Jankovic Mila , Gazumyan Anna , Oliveira Thiago Y. , Caskey Marina , Bieniasz Paul D. , Hatziioannou Theodora , Kurth Florian , Sander Leif Erik , Nussenzweig Michel C. , Gaebler Christian 
Published: May 2022

AbstractThe SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID- 19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.
VAP-A intrinsically disordered regions enable versatile tethering at membrane contact sites
Authors: Subra Mélody , Dezi Manuela , Bigay Joëlle , Lacas-Gervais Sandra , Di Cicco Aurélie , Dias Araújo Ana Rita , Abélanet Sophie , Fleuriot Lucile , Debayle Delphine , Gautier Romain , Patel Amanda , Roussi Fanny , Antonny Bruno , Lévy Daniel , Mesmin Bruno 
Published: May 2022

SUMMARYMembrane contact sites (MCSs) between organelles are heterogeneous in shape, composition and dynamics. Despite this diversity, VAP proteins act as receptors for multiple FFAT motif-containing proteins and drive the formation of most MCSs involving the endoplasmic reticulum (ER). Although the VAP‒FFAT interaction is well characterized, no model explains how VAP adapts to its partners in various MCSs. We report here that VAP-A localization to different MCSs depends on its intrinsically disordered regions (IDRs). We show that VAP-A interaction with PTPIP51 and VPS13A at ER‒mitochondria MCS conditions mitochondria fusion by promoting lipid transfer and cardiolipin buildup. VAP-A also enables lipid exchange at ER‒Golgi MCS by interacting with OSBP and CERT. However, removing IDRs from VAP-A restricts its distribution and function to ER‒ mitochondria MCS, at the expense of ER‒Golgi MCS. Our data suggest that IDRs of VAP-A do not modulate its preference towards specific partners, but adjust its geometry to the constraints linked to different MCS organization and lifetime. Thus, VAP-A conformational flexibility mediated by its IDRs ensures membrane tethering plasticity and efficiency.
Doublecortin-like kinase 1 (DCLK1) Facilitates Dendritic Spine Growth of Pyramidal Neurons in Mouse Prefrontal Cortex
Authors: Murphy Kelsey E. , Zhang Erin Y. , Wyatt Elliott V. , Sperringer Justin E. , Duncan Bryce W. , Maness Patricia F. 
Published: May 2022

AbstractThe L1 cell adhesion molecule NrCAM (Neuron-glia related cell adhesion molecule) functions as a co-receptor for secreted class 3 Semaphorins to prune subpopulations of dendritic spines on apical dendrites of pyramidal neurons in the developing mouse neocortex. The developing spine cytoskeleton is enriched in actin filaments but a small number of microtubules have been shown to enter the spine apparently trafficking vesicles to the membrane. Doublecortin-like kinase 1 (DCLK1) is a member of the Doublecortin (DCX) family of microtubule-binding proteins with serine/threonine kinase activity. To determine if DCLK1 plays a role in spine remodeling, we generated a tamoxifen-inducible mouse line (Nex1Cre-ERT2: DCLK1flox/flox : RCE) to delete microtubule binding isoforms of DCLK1 from pyramidal neurons during postnatal stages of spine development. Homozygous DCLK1 conditional mutant mice exhibited decreased spine density on apical dendrites of pyramidal neurons in the prefrontal cortex (layer 2/3). Mature mushroom spines were selectively decreased upon DCLK1 deletion but dendritic arborization was unaltered. Mutagenesis and binding studies revealed that DCLK1 bound NrCAM at the conserved FIGQY1231 motif in the NrCAM cytoplasmic domain, a known interaction site for the actin-spectrin adaptor Ankyrin. These findings demonstrate that DCLK1 facilitates spine growth and maturation on cortical pyramidal neurons in the mouse prefrontal cortex potentially through microtubule and NrCAM interactions.
PleistoDist: A toolbox for visualising and quantifying the effects of Pleistocene sea-level change on island archipelagos
Authors: Tan David J.X. , Gyllenhaal Ethan F. , Andersen Michael J. 
Published: May 2022

AbstractPleistocene sea-level change played a significant role in the evolution and assembly of island biotas. The formation of land bridges between islands during Quaternary glacial maxima, when sea levels were up to 120 metres below present-day sea levels, often facilitated historical dispersal and gene flow between islands that are today geographically disconnected.Despite this, relatively few studies have attempted to quantify the effects of Pleistocene sea-level change on the evolution of island species assemblages.Here we present PleistoDist, an R package that allows users to visualise and quantify the effects of Pleistocene sea-level change on islands over time, and test multiple temporally explicit hypotheses of inter-island dispersal and community assembly.Re-analysing published datasets, we demonstrate how using PleistoDist to account for historical sea-level change can provide greater explanatory power when analysing extant island communities, and show how population genetic simulations can be used to generate spatiotemporally explicit neutral expectations of population genetic structure across island archipelagos.
Flexing the principal gradient of the cerebral cortex to suit changing semantic task demands
Authors: Gao Zhiyao , Zheng Li , Krieger-Redwood Katya , Halai Ajay , Margulies Daniel S. , Smallwood Jonathan , Jefferies Elizabeth 
Published: May 2022

AbstractUnderstanding how thought emerges from the topographical structure of the cerebral cortex is a primary goal of cognitive neuroscience. Recent work has revealed a principal gradient of intrinsic connectivity capturing the separation of sensory-motor cortex from transmodal regions of the default mode network (DMN); this is thought to facilitate memory-guided cognition. However, studies have not explored how this dimension of connectivity changes when conceptual retrieval is controlled to suit the context. We used gradient decomposition of informational connectivity in a semantic association task to establish how the similarity in connectivity across brain regions changes during familiar and more original patterns of retrieval. Multivoxel activation patterns at opposite ends of the principal gradient were more divergent when participants retrieved stronger associations; therefore, when long-term semantic information is sufficient for ongoing cognition, regions supporting heteromodal memory are functionally separated from sensory-motor experience. In contrast, when less related concepts were linked, this dimension of connectivity was reduced in strength as semantic control regions separated from the DMN to generate more flexible and original responses. We also observed fewer dimensions within the neural response towards the apex of the principal gradient when strong associations were retrieved, reflecting less complex or varied neural coding across trials and participants. In this way, the principal gradient explains how semantic cognition is organised in the human cerebral cortex: the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared.Significance statementA central task in neuroscience is to understand how cognition emerges from the topographical structure of cerebral cortex. We used fMRI during a semantic task to assess informational connectivity as participants retrieved stereotypical or more unusual associations. The principal gradient of variation in informational connectivity captured the separation of heteromodal memory regions from unimodal cortex. This separation was reduced when weaker associations were retrieved; these trials also produced higher-dimensional neural responses in heteromodal regions. We conclude that the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared, while more complex and diverse cognition can be generated as this separation in connectivity is reduced.
pH-responsive self-assembled compartments as tuneable model protocellular membrane systems
Authors: Sarkar Susovan , Dagar Shikha , Lahiri Kushan , Rajamani Sudha 
Published: May 2022

AbstractPrebiotically plausible single-chain amphiphiles are enticing as model protocellular compartments to study the emergence of cellular life owing to their self-assembling properties. Here, we investigated the self-assembly behaviour of mono-N-dodecyl phosphate (DDP) and mixed systems of DDP with dodecyl 1-dodecanol (DOH) at varying pH conditions. Membranes composed of DDP showed pH-responsive vesicle formation in a wide range of pH with a low critical bilayer concentration (CBC). Further, the addition of DOH to DDP membrane system enhanced vesicle formation and stability in alkaline pH regimes. We also compared the high-temperature behaviour of DDP and DDP-DOH membranes with conventional fatty acid membranes. Both, DDP and DDP:DOH mixed membranes possess packing that is similar to decanoic acid membrane. However, the micropolarity of these systems are similar to phospholipid membranes. Finally, the pH-dependent modulation of different phospholipid membranes doped with DDP was also demonstrated to engineer tuneable membranes with potential translational implications.
Intrinsic RNA targeting constrains the utility of CRISPR-Cas13 systems
Authors: Li Zexu , Li Zihan , Cheng Xiaolong , Wang Xiaofeng , Ma Shixin , Wang Shengnan , Lu Zhiyan , Zhang Han , Zhao Wenchang , Chen Zhisong , Yao Yingjia , Chao Lumen , Li Wei , Fei Teng 
Published: May 2022

SUMMARYCRISPR-Cas13 systems have been adapted as versatile toolkits for RNA-related applications. Here we systematically evaluate the performance of several popular Cas13 family effectors (Cas13a, Cas13b and Cas13d) under lentiviral vectors and reveal surprisingly differential defects and characteristics of these systems. Using RNA immunoprecipitation sequencing, transcriptome profiling, biochemistry analysis, high-throughput CRISPR-Cas13 screening and machine learning approaches, we determine that each Cas13 system has its intrinsic RNA targets in mammalian cells. Viral process-related host genes can be targeted by Cas13 and affect production of fertile lentiviral particles, thereby restricting the utility of lentiviral Cas13 systems. Multiple RNase activities of Cas13 are involved in endogenous RNA targeting. Unlike target-induced nonspecific collateral effect, intrinsic RNA cleavage can be specific, target-independent and dynamically tuned by varied states of Cas13 nucleases. Our work provides guidance on appropriate use of lentiviral Cas13 systems and further raises cautions about intrinsic RNA targeting during Cas13-based basic and therapeutic applications.
Activity-based CRISPR Scanning Uncovers Allostery in DNA Methylation Maintenance Machinery
Authors: Ngan Kevin C. , Hoenig Samuel M. , Gosavi Pallavi M. , Tanner David A. , Lue Nicholas Z. , Garcia Emma M. , Lee Ceejay , Liau Brian B. 
Published: May 2022

AbstractAllostery enables dynamic control of protein function. A paradigmatic example is the tightly orchestrated process of DNA methylation maintenance. Despite their fundamental importance, systematic identification of allosteric sites remains highly challenging. Here we perform CRISPR scanning on the essential maintenance methylation machinery—DNMT1 and its partner UHRF1—with the activity-based inhibitor decitabine to uncover allosteric mechanisms regulating DNMT1. Through computational analyses, we identify putative mutational hotspots in DNMT1 distal from the active site that encompass mutations spanning a multi-domain autoinhibitory interface and the uncharacterized BAH2 domain. We biochemically characterize these mutations as gain-of-function mutations that increase DNMT1 activity. Extrapolating our analysis to UHRF1, we discern putative gain-of-function mutations in multiple domains, including key residues across the autoinhibitory TTD–PBR interface. Collectively, our findings highlight the utility of activity-based CRISPR scanning for nominating candidate allosteric sites, even beyond the direct drug target.