bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omicron breakthrough infections in vaccinated or previously infected hamsters
Authors: Zhou Jie , Sukhova Ksenia , McKay Paul F. , Kurshan Ashwini , Yau Yeuk , Lechmere Thomas , Brown Jonathan C. , Moshe Maya , Kugasathan Ruthiran , Snell Luke B. , Edgeworth Jonathan D. , Shattock Robin J. , Doores Katie J. , Peacock Thomas P. , Barclay Wendy S. 
Published: May 2022

AbstractThe second and third years of the SARS-CoV-2 pandemic have been marked by the repeated emergence and replacement of ‘variants’ with genetic and phenotypic distance from the ancestral strains, the most recent examples being Delta and Omicron. Here we describe a hamster contact exposure challenge model to assess protection conferred by vaccination or prior infection against re-infection. We found that 2-doses of self-amplifying RNA vaccine based on the ancestral spike ameliorated weight loss following Delta infection and decreased viral loads, but had minimal effect on Omicron/BA.1 infection. Prior infection with ancestral or Alpha variant was partially protective against Omicron/BA.1 infection, whereas all animals previously infected with Delta and exposed to Omicron became infected, although shed less virus. We further tested whether prior infection with Omicron/BA.1 protected from re-infection with Delta or Omicron/BA.2. Omicron/BA.1 was protective against Omicron/BA.2, but not Delta reinfection, again showing Delta and Omicron have a very large antigenic distance. Indeed, cross-neutralisation assays with human antisera from otherwise immunonaïve individuals (unvaccinated and no known prior infection), confirmed a large antigenic distance between Delta and Omicron. Prior vaccination followed by Omicron or Delta breakthrough infection led to a higher degree of cross-reactivity to all tested variants. To conclude, cohorts whose only immune experience of COVID is Omicron/BA.1 infection may be particularly vulnerable to future circulation of Delta or Delta-like derivatives. In contrast, repeated exposure to antigenically distinct spikes, via infection and or vaccination drives a more cross-reactive immune response, both in hamsters and people.One Sentence SummaryInfection with the Delta and Omicron SARS-CoV-2 variants do not provide cross-protective immunity against reinfection with one another in hamsters.
Histone H3K27 methyltransferase EZH2 interacts with MEG3-lncRNA to directly regulate integrin signaling and endothelial cell function
Authors: Dudnakova Tatiana , Dunn-Davies Hywel , Nogara Antonella , Rodor Julie , Thomas Anita , Parish Elisa , Gautier Philippe , Meynert Alison , Madeddu Paolo , Caporali Andrea , Baker Andrew , Tollervey David , Mitić Tijana 
Published: May 2022

SummaryEnhancer of Zeste Homologue 2 (EZH2) modulates gene transcription during endothelial cell (EC) dysfunction, via interaction with non-coding RNAs (ncRNAs). Thus, EZH2 can act as a rheostat in deposition of histone H3K27 trimethylation (H3K27me3) to repress many genes. We profiled EZH2-RNA interactions using formaldehyde/UV assisted cross-linking ligation and sequencing of hybrids (FLASH-seq) in primary human ECs. Transcriptome-wide EZH2-associated ncRNAs and RNA–RNA interactome were obtained. This approach revealed EZH2 directly binding maternally expressed gene (MEG3) and MEG3:MEG3 hybrid structures. By chromatin immunoprecipitation with sequencing (ChIP-seq) following depletion of MEG3, we discovered that MEG3 targets and controls recruitment of EZH2/H3K27me3 onto a regulatory region of integrin subunit alpha 4 (ITGA4). MEG3 knockdown or pharmacological inhibition of EZH2 de-repressed ITGA4, whilst improving endothelial cell function in vitro, and increasing ITGA4 expression in vivo. Our study demonstrates new role for MEG3, as instrumental in epigenetic regulation of EC function by EZH2, through targeting of integrin-dependent signalling.
Geometric morphometric analysis reveals cranial shape divergence and asymmetry in extinct and extant species of big cats (Carnivora: Felidae)
Authors: Noga Aidan , Anyonge William , Powers Amanda K. 
Published: May 2022

AbstractFelidae, a family of the order Carnivora, includes extinct and extant species of cats spread across a wide ecological and geographical landscape. Cats are well-suited for predation due to various physical and behavioral characteristics, such as optimized limb length, skull shape, as well as enhanced hearing and vision. Morphological changes across Felidae species, particularly changes in skull shape, are likely explained by differences in predatory and feeding behaviors. Toward that end, cranial shape was analyzed across six different extant and extinct Felidae species using two-dimensional geometric morphometrics. From the lateral cranial view, we discovered that the cheetah (Acinonyx jubatus) and the North American Sabretooth (Smilodon) had the most significant shape divergence, specifically at the frontal bone and post orbital regions of the skull. Specifically, we found that the Sabretooth had a significantly shorter coronoid process compared to other Felids. We also observed a significant difference in post orbital shape in the cheetah dorsal cranium. Interestingly, we found that both the cheetah and the extinct North American Lion demonstrate significant shape asymmetry in the postorbital region from a ventral view of the skull. Shape divergence and asymmetry in select Felid skulls may arise from decreased genetic diversity. Taken together, we reasoned that morphological changes in skull shape likely evolved to support differences in predatory behavior across Felidae.
Single cell analysis of the dorsal V-SVZ reveals differential quiescence of postnatal pallial and subpallial neural stem cells driven by TGFbeta/BMP-signalling
Authors: Marcy Guillaume , Foucault Louis , Babina Elodie , Texeraud Emeric , Zweifel Stefan , Heinrich Christophe , Hernandez-Vargas Hector , Parras Carlos , Jabaudon Denis , Raineteau Olivier 
Published: May 2022

AbstractThe ventricular-subventricular zone (V-SVZ) is the largest neurogenic region of the postnatal forebrain, containing neural stem cells (NSCs) that emerge from both the embryonic pallium and subpallium. Despite of this dual origin, glutamatergic neurogenesis declines rapidly after birth, while gabaergic neurogenesis persists throughout life. Here, we performed single-cell RNA-sequencing (scRNA-Seq) of the postnatal dorsal V-SVZ for unravelling the mechanisms leading to pallial lineage germinal activity silencing. We identify cell lineage-specific NSCs primed for the generation of neurons or glial cells, as well as a large population of so far uncharacterized quiescent NSCs (qNSC). Pallial qNSCs enter a state of deep quiescence, characterized by persistent TGFbeta/BMP signalling, reduced transcriptional activity and Hopx expression, whilst in contrast, subpallial qNSCs remain transcriptionally primed for activation. Induction of deep pallial quiescence is paralleled by a rapid blockade of glutamatergic neuron production and differentiation. Finally, manipulation of the TGFbeta/BMP receptor Bmpr1a demonstrate its key role in mediating these effects at early postnatal times. Together, our results highlight a central role of TGFbeta/BMP-signalling in synchronizing quiescence induction and blockade of neuronal differentiation to rapidly silence pallial germinal activity after birth.
Structure of nucleosome-bound human PBAF complex
Authors: Wang Li , Yu Jiali , Yu Zishuo , Wang Qianmin , Li Wanjun , Ren Yulei , Chen Zhenguo , He Shuang , Xu Yanhui 
Published: May 2022

AbstractBAF and PBAF are mammalian SWI/SNF family chromatin remodeling complexes that possess multiple histone/DNA-binding subunits and create nucleosome-depleted/free regions for transcription activation. Despite structural studies of nucleosome-bound human BAF and yeast SWI/SNF family complexes, it remains elusive how PBAF-nucleosome complex is organized. Here we determined structure of 13-subunit human PBAF in complex with acetylated nucleosome in ADP-BeF3-bound state. Four PBAF-specific subunits work together with nine BAF/PBAF-shared subunits to generate PBAF-specific modular organization, distinct from that of BAF at various regions. PBAF-nucleosome structure reveals six histone-binding domains and four DNA-binding domains/modules, the majority of which directly bind histone/DNA. This multivalent nucleosome-binding pattern, not observed in previous studies, suggests that PBAF may integrate comprehensive chromatin information to target genomic loci for function. Our study reveals molecular organization of subunits and histone/DNA-binding domains/modules in PBAF-nucleosome complex and provides a framework to understand chromatin targeting of SWI/SNF family complexes.
Ephemeral Resource Availability Makes Wild Guppies More Social
Authors: Snijders Lysanne , Krause Stefan , Tump Alan Novaes , Breuker Michael , Ramnarine Indar W. , Kurvers Ralf , Krause Jens 
Published: May 2022

AbstractResource availability and sociality are tightly coupled. Sociality facilitates resource access in a wide range of animal species. Simultaneously, resource availability may change sociality. However, experimental evidence for resource-driven social changes in the wild, beyond local aggregations at the resource, remains scarce. Moreover, it is largely unclear how potential changes in sociality relate to the social foraging benefits obtained by individual group members. Here, we recorded immediate and prolonged changes in social dynamics following ephemeral food availability in 18 mixed-sex Trinidadian guppies (Poecilia reticulata) groups in natural rainforest pools. Using a counter-balanced within-group design, the social associations within each group was observed before, between and after ephemeral patch availability for two consecutive days. We show that groups increased their time spent socially two-fold following ephemeral food patch, but not control (empty) patch, availability. Groups with stronger foraging motivation, measured as the average proportion of fish feeding, showed a stronger increase in sociality. This resource-induced increase in sociality was still detectable the next day. Increase in the time spent socially by a group also positively correlated with the more frequent arrival at detected food patches for individual members of motivated groups, which, in turn, correlated strongly with individual food consumption. Our study causally demonstrates that changes in ephemeral resource availability can induce rapid, substantial, and prolonged changes in the social dynamics of wild fish and that this change positively correlated with individual foraging success. Further research is needed to investigate whether this social change is a cause or consequence of individual foraging success and why some groups respond more strongly than others.
Recognition of BRAF by CDC37 and Re-Evaluation of the Activation Mechanism for the Class 2 BRAF-L597R Mutant
Authors: Bjorklund Dennis M. , Morgan R. Marc L. , Oberoi Jasmeen , Day Katie L. I. M. , Galliou Panagiota A. , Prodromou Chrisostomos 
Published: May 2022

AbstractThe kinome specific co-chaperone, CDC37 (cell division cycle 37), is responsible for delivering BRAF (B-Rapidly Accelerated Fibrosarcoma) to the Hsp90 (heat shock protein 90) complex, where it is then translocated to the RAS (protooncogene product p21) complex at the plasma membrane for RAS mediated dimerization and subsequent activation. We identify a bipartite interaction between CDC37 and BRAF and delimitate the essential structural elements of CDC37 involved in BRAF recognition. We find an extended and conserved CDC37 motif, 20HPNID---SL--W31, responsible for recognizing the C-lobe of BRAF kinase domain, while the c-terminal domain of CDC37 is responsible for the second of the bipartite interaction with BRAF. We show that dimerization of BRAF, independent of nucleotide binding, can act as a potent signal that prevents CDC37 recognition and discuss the implications of mutations in BRAF and the consequences on signaling in a clinical setting, particularly for class 2 BRAF mutations.
Biomolecular solution X-ray scattering at n2STAR Beamline
Authors: Göcenler Oktay , Yenici Cansu M. , Kahraman Kerem , Büyükdağ Cengizhan , Dağ Çağdaş 
Published: May 2022

AbstractSmall angle X-ray Scattering (SAXS) is a method for determining basic structural characteristics such as size, shape, and surface of particles. SAXS can generate low resolution models of biomolecules faster than any other conventional structural biology tools. SAXS data is mostly collected in synchrotron facilities to obtain the best scattering data possible however home source SAXS devices can also generate valuable data when optimized properly. Here, we examined sample data collection and optimization at home source SAXS beamline in terms of concentration, purity, and the duration of data acquisition. We validated that high concentration, monodisperse and ultra pure protein samples obtained by size exclusion chromatography are necessary for generating viable SAXS data using home source beamline. Longer data collection time does not always generate higher resolutions but at least one hour is required for generating a feasible model from SAXS data. Furthermore, with small optimizations both during data collection and later data analysis SAXS can determine properties such as oligomerization, molecular mass, and overall shape of particles in solution under physiological conditions.
Temporal origin of mouse claustrum and development of its cortical projections
Authors: Hoerder-Suabedissen Anna , Ocana-Santero Gabriel , Draper Thomas H. , Scott Sophie A. , Kimani Jesse G. , Shelton Andrew M. , Butt Simon J.B. , Molnár Zoltán , Packer Adam M. 
Published: May 2022

AbstractThe claustrum is known for its extensive connectivity with many other forebrain regions, but its elongated shape and deep location have made further study difficult. We have sought to understand when mouse claustrum neurons are born, where they are located in developing brains and when they develop their widespread connections to cortex. We established that a well-characterised parvalbumin-plexus, which identifies the claustrum in adults, is only present from postnatal day (P)21. A myeloarchitectonic outline of the claustrum can be derived from a triangular fibre arrangement from P15. A dense patch of Nurr1+ cells is present at its core, and is already evident at birth. BrdU-birthdating of forebrain progenitors reveals that the majority of claustrum neurons are born during a narrow time window centred on embryonic day (E)12.5, which is later than the adjacent subplate and endopiriform nucleus. Retrograde tracing revealed that claustrum projections to anterior cingulate (ACA) and retrosplenial cortex (RSP) follow distinct developmental trajectories. Claustrum-ACA connectivity matures rapidly, and reaches adult-like innervation density by P10, whereas claustrum-RSP innervation emerges later over a protracted time window. This work establishes the timeline of claustrum development, and provides a framework for understanding how the claustrum is built and develops its unique connectivity.
From Data to Theory: Understanding the Role of Naive Learners in Cultural Change
Authors: Chimento Michael , Aplin Lucy M. 
Published: May 2022

AbstractA change to a population’s social network is a change to the substrate of cultural transmission, affecting behavioral diversity and adaptive cultural evolution. While features of network structure such as population size and density have been well studied, less is understood about the influence of social processes such as population turnover— or the repeated replacement of individuals. Experimental data has led to the hypothesis that naive learners can drive cultural evolution by being better samplers, although this hypothesis has only been expressed verbally. We conduct a formal exploration of this hypothesis using a generative model that concurrently simulates its two key ingredients: social transmission and reinforcement learning. We explore how variation in turnover influences changes in the distributions of cultural behaviors over long and short time-scales. We simulate competition between a high and low reward behavior, while varying turnover magnitude and tempo. We find optimal turnover regimes that amplify the production of higher reward behaviors. We also find that these optimal regimes result in a new population composition, where fewer agents which know both behaviors, and more agents know only the high reward behavior. These two effects depend on network size, density, behavioral transmissibility, and characteristics of the learners. Our model provides formal theoretical support for, and predictions about, the hypothesis that naive learners can shape cultural change through their enhanced sampling ability, identified by previous experimental studies. By moving from experimental data to theory, we illuminate an under-discussed generative process arising from an interaction between social dynamics and learning that can lead to changes in cultural behavior.
Septin-Mediated RhoA Activation Engages the Exocyst Complex to Recruit the Cilium Transition Zone
Authors: Safavian Darya , Kim Moshe S. , Xie Hong , Dai Lu , Collins Richard F. , Froese Carol , Nagata Koh-ichi , Trimble William S. 
Published: May 2022

ABSTRACTSeptins are filamentous GTPases that play important, but poorly characterized roles in ciliogenesis. Here, we show that SEPTIN9 regulates RhoA signaling at the base of cilia by binding and activating the RhoA guanine nucleotide exchange factor, ARHGEF18. GTP-RhoA is known to activate the membrane targeting exocyst complex, and suppression of SEPTIN9 causes disruption of ciliogenesis and mislocalization of an exocyst subunit, SEC8. Using basal body-targeted proteins we show that upregulating RhoA signaling at the cilium can rescue ciliary defects and mislocalization of SEC8 caused by global SEPTIN9 depletion. Moreover, we demonstrate that transition zone components, RPGRIP1L and TCTN2 fail to accumulate at the transition zone in cells lacking SEPTIN9 or depleted of the exocyst complex. Thus, SEPTIN9 regulates the recruitment of transition zone proteins on Golgi-derived vesicles by activating the exocyst via RhoA to allow the formation of primary cilia.
Cortical circuits modulate mouse social vocalizations
Authors: Gan-Or Benjamin , London Michael 
Published: May 2022

AbstractVocalizations provide a means of communication with high fidelity and information rate for many species. Male mice emit ultrasonic vocalizations (USVs) during female courtship. Diencephalon and brainstem neural circuits have been shown to control the production of USVs, however, the role of cortical circuits in this process is debatable. We show that male mice produced USVs following intracortical microstimulation (ICMS) in a specific location of their anterior cingulate cortex (ACC). Moreover, ACC Ca2+-imaging showed an increase in Ca2+ dynamics preceding USV initiation. Optogenetically suppressing ACC activity caused mice to emit fewer USVs during courtship. Neuropixel electrophysiological recordings in head-restrained male mice indicated a differential increase in neural activity in response to female social exposure (SE). The firing rate in SE trials where USVs were emitted was significantly higher when compared to SE leading to silence. Taken together, these results indicate that the ACC is a key node in the neuronal circuits controlling USV production.
ExplaiNN: interpretable and transparent neural networks for genomics
Authors: Novakovsky Gherman , Fornes Oriol , Saraswat Manu , Mostafavi Sara , Wasserman Wyeth W. 
Published: May 2022

AbstractSequence-based deep learning models, particularly convolutional neural networks (CNNs), have shown superior performance on a wide range of genomic tasks. A key limitation of these models is the lack of interpretability, slowing down their adoption by the genomics community. Current approaches to model interpretation do not readily reveal how a model makes predictions, can be computationally intensive, and depend on the implemented architecture. Here, we introduce ExplaiNN, an adaptation of neural additive models[1] for genomic tasks wherein predictions are computed as a linear combination of multiple independent CNNs, each consisting of a single convolutional filter and fully connected layers. This approach brings together the expressiveness of CNNs with the interpretability of linear models, providing global (cell state level) as well as local (individual sequence level) biological insights into the data. We use ExplaiNN to predict transcription factor (TF) binding and chromatin accessibility states, demonstrating performance levels comparable to state-of-the-art methods, while providing a transparent view of the model’s predictions in a straightforward manner. Applied tode novomotif discovery, ExplaiNN identifies equivalent motifs to those obtained from specialized algorithms across a range of datasets. Finally, we present ExplaiNN as a plug-and-play platform in which pretrained TF binding models and annotated position weight matrices from reference databases can be easily combined. We expect that ExplaiNN will accelerate the adoption of deep learning by biological domain experts in their daily genomic sequence analyses.
Buforin II-Escherichia coli’s DNA interactome: Detailed biophysical characterization revealed nanoscale complexes likely formed by DNA supercoiling
Authors: Rubio-Olaya Daniela , Cifuentes Javier , Ruiz-Puentes Paola , Castañeda Octavio A. , Reyes Luis H. , Duitama Jorge , Muñoz Carolina , Cruz Juan C. 
Published: May 2022

AbstractAntimicrobial peptides (AMPs) have emerged as exciting alternatives to the alarming increase of multiresistant bacteria due to their high activity against them through mechanisms that are thought to largely avoid resistance in the long term. Buforin II (BUFII) is an antibacterial peptide hypothesized to kill bacteria by crossing their membranes to interact with intracellular molecules and interrupt key processes for survival. In particular, interactions with DNA have been considered crucial for triggering cell death mechanisms. However, such interactions are still unknown, and thus far, no reports are available describing BUFII-DNA complexes. Here, we describe a complete biophysical study of the interaction between BUFII and Escherichia coli gDNA via spectrofluorimetric, spectroscopic, and microscopic techniques, complemented with whole-genome sequencing. The E. coli’s DNA-BUFII interactome was isolated by an in vitro pull-down method aided by BUFII-magnetite nanobioconjugates. Our results demonstrated that DNA-BUFII formed round-shape nanoscale complexes by strong electrostatic interactions, likely occurring nonspecifically throughout the entire bacterial genome. Further sequencing of the isolated DNA fragments corroborated this notion and led to hypothesize that BUFII is possibly responsible for inducing DNA’s supercoiling.Other evidence for this idea was provided by the significant DNA conformational changes observed upon interaction with BUFII. Even though the evidence found fails to describe the complete action mechanism of BUFII in vivo, our findings pave the way to engineer DNA-peptide supramolecular complexes very precisely, which might find application in the field of gene therapy delivery.