bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling cytosolic delivery of endosomal escape peptides with a quantitative endosomal escape assay (SLEEQ)
Authors: Teo Serena L.Y. , Rennick Joshua J. , Yuen Daniel , Al-Wassiti Hareth , Johnston Angus P.R. , Pouton Colin W. 
Published: August 2020

AbstractEndosomal escape is an essential requirement but a major obstacle to efficient delivery of therapeutic peptides, proteins and nucleic acids. Current understanding of endosomal escape mechanisms remains limited due to significant number of conflicting reports, which are compounded by low sensitivity and indirect assays. To resolve this, we developed a highly sensitive Split Luciferase Endosomal Escape Quantification (SLEEQ) assay to probe mechanisms of cytosolic delivery. We applied SLEEQ to evaluate the endosomal escape of a range of widely studied putative endosomal escape peptides (EEPs). We demonstrated that positively-charged EEPs enhanced cytosolic delivery as a result of increased non-specific cell membrane association, rather than increased endosomal escape efficiency. These findings transform our current understanding of how EEPs increase cytosolic delivery. SLEEQ is a powerful tool that addresses fundamental questions in intracellular drug delivery and will significantly improve the way materials are engineered to increase therapeutic delivery to the cytosol.
Identification of Chlorophyll a-b Binding Protein AB96 as a novel TGFβ1 binding agent
Authors: Lynham Steven , Freile Fabio Grundland , Puri Natasha M , O’Reilly Nicola , Mitchell Graham H , Wells Timothy N.C. , Willcox Merlin , Beatson Richard 
Published: August 2020

AbstractThe discovery of compounds and proteins from plants has greatly contributed to modern medicine, especially in malaria where both quinine and artemisinin have been the cornerstone of therapeutics. Here we describe the first known plant-derived cytokine binding agent. Chlorophyll a-b binding protein AB96, present to varying levels in the leaves of all chlorophyll-containing plants, binds to active TGFβ1. Active TGFβ1 contributes to the pathology of many infectious and neoplastic diseases and therefore, by inhibiting these processes, chlorophyll a-b binding protein opens up new approaches with therapeutic potential.
Neuronal death in pneumococcal meningitis is triggered by pneumolysin and pilus-1 interactions with β-actin
Authors: Tabusi Mahebali , Thorsdottir Sigrun , Lysandrou Maria , Narciso Ana Rita , Minoia Melania , Henriques-Normark Birgitta , Iovino Federico 
Published: August 2020

AbstractNeuronal damage is a major consequence of bacterial meningitis, but little is known about mechanisms that lead to neuronal death.Streptococcus pneumoniae(pneumococcus) is a leading cause of bacterial meningitis and many survivors develop neurological sequelae after the acute infection has resolved, possibly due to neuronal damage. Here, we studied mechanisms for pneumococcal interactions with neurons. Using human primary neurons and co-immunoprecipitation assays, we showed that pneumococci interact with the cytoskeleton protein β-actin through the pilus-1 adhesin RrgA and the cytotoxin pneumolysin (Ply), thereby promoting adhesion and uptake into neurons and neuronal death. Using our bacteremia-derived meningitis mouse model, we observed that RrgA- and Ply-expressing pneumococci co-localize with neuronal β-actin. We found that pneumococcal-infected neurons show increased intracellular Ca2+ levels depending on RrgA and mainly Ply which likely cause actin cytoskeleton disassembly leading to neuronal damage. Finally, neuronal death caused by pneumococcal infection could be inhibited using antibody against β-actin.
Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord
Authors: Danesin Cathy , Darche-Gabinaud Romain , Escalas Nathalie , Bouguetoch Vanessa , Cochard Philippe , Oustah Amir Al , Ohayon David , Glise Bruno , Soula Cathy 
Published: August 2020

ABSTRACTSulf2a belongs to the Sulf family of extracellular sulfatases which selectively remove 6-O-sulfate groups from heparan sulfates, a critical regulation level for their role in modulating the activity of signalling molecules. Data presented here define Sulf2a as a novel player in the control of Sonic Hedgehog (Shh)-mediated cell type specification during spinal cord development. We show that Sulf2a depletion in zebrafish results in overproduction of V3 interneurons at the expense of motor neurons and also impedes generation of oligodendrocyte precursor cells (OPCs), three cell types that depend on Shh for their generation. We provide evidence that Sulf2a, expressed in a spatially restricted progenitor domain, acts by maintaining the correct patterning and specification of ventral progenitors. More specifically, Sulf2a prevents Olig2 progenitors to activate high-threshold Shh response and, thereby, to adopt a V3 interneuron fate, thus ensuring proper production of motor neurons and OPCs. We propose a model in which Sulf2a reduces Shh signalling levels in responding cells by decreasing their sensitivity to the morphogen factor. More generally, our work, revealing that, in contrast to its paralog Sulf1, Sulf2a regulates neural fate specification in Shh target cells, provides direct evidence of non-redundant functions of Sulfs in the developing spinal cord.
CK2 Phosphorylation is required for Regulation of Syntaxin 1A activity in Ca2+-triggered release in neuroendocrine cells
Authors: Barak-Broner Noa , Singer-Lahat Dafna , Chikvashvili Dodo , Lotan Ilana 
Published: August 2020

AbstractThe polybasic juxtamembrane region (5RK) of the plasma membrane neuronal SNARE, syntaxin1A (Syx), was shown by us to act as a fusion clamp in PC12 cells, making release dependent on stimulation by Ca2+. By using a Syx-based FRET probe, we demonstrated that 5RK is absolutely required for a depolarization-induced Ca+2-dependent, close-to-open transition (CDO) of Syx that involves the vesicular SNARE synaptobrevin2 and occurs concomitantly with Ca2+-triggered release. Here, we investigated the mechanism underlying the 5RK requirement, and identified phosphorylation of Syx at Ser-14 (S14) by protein kinase CK2 as a crucial molecular determinant. Following biochemical verification that both endogenous Syx and CSYS are constitutively S14 phosphorylated in PC12 cells, dynamic FRET analysis of phospho-null and phospho-mimetic mutants of CSYS and the use of a CK2 inhibitor revealed that it is the S14 phosphorylation that confers the 5RK requirement. Concomitant amperometric analysis of catecholamine release revealed that the phospho-null mutants do not support release, spontaneous and evoked. Collectively, these results identify a functionally important CK2 phosphorylation site in Syx that is required for 5RK-regulation of CDO and for concomitant Ca2+-triggered release.Summary statementMany phospho-proteins participate in vesicle exocytosis. We show that a recently identified structural transition of syntaxin1A that accompanies Ca2+-regulated exocytosis in neuroendocrine cells is controlled by CK2 phosphorylation of syntaxin1A.
Segmentation boosting with compensation methods in optical coherence tomography angiography images
Authors: Lee Yih-Cherng , Ding Jian-Jiun , Yeung Ling , Lee Tay-Wey , Chang Chia-Jung , Lin Yu-Tze , Chang Ronald Y. 
Published: August 2020

AbstractOptical coherence tomography angiography is a noninvasive imaging modality to establish the diagnosis of retinal vascular diseases. However, angiography images are significantly interfered if patients jitter or blink. In this study, a novel retinal image analysis method to accurately detect blood vessels and compensate the effect of interference was proposed. We call this the patch U-Net compensation (PUC) system, which is based on the famous U-Net. Several techniques, including a better training mechanism, direction criteria, area criteria, gap criteria, and probability map criteria, have been proposed to improve its accuracy. Simulations show that the proposed PUC achieves much better performance than state-of-art methods.
Primary carbohydrate metabolism genes participate in heat stress memory at the shoot apical meristem ofArabidopsis thaliana
Authors: Olas Justyna Jadwiga , Apelt Federico , Annunziata Maria Grazia , Richard Sarah Isabel , Gupta Saurabh , Kragler Friedrich , Balazadeh Salma , Mueller-Roeber Bernd 
Published: August 2020

AbstractAlthough we have a good understanding of the development of shoot apical meristems (SAM) in higher plants, and the function of the stem cells (SCs) embedded in the SAM, there is surprisingly little known of its molecular responses to abiotic stresses. Here, we show that the SAM ofArabidopsis thalianasenses heat stress (HS) and retains an autonomous molecular memory of a previous non-lethal HS, allowing the SAM to regain growth after exposure to an otherwise lethal HS several days later. Using RNA-seq, we identified genes participating in establishing a SAM-specific HS memory. The genes includeHEAT SHOCK TRANSCRIPTION FACTORs(HSFs), of whichHSFA2is essential, but not sufficient, for full HS memory in the SAM, the SC regulatorsCLAVATA1(CLV1) andCLV3, and several primary carbohydrate metabolism genes, includingFRUCTOSE-BISPHOSPHATE ALDOLASE 6(FBA6). We found that expression ofFBA6during HS at the SAM complements that ofFBA8in the same organ. Furthermore, we show that sugar availability at the SAM is essential for survival at high-temperature HS. Collectively, plants have evolved a sophisticated protection mechanism to maintain SCs and, hence, their capacity to re-initiate shoot growth after stress release.
Genetic evidence indicates new distribution record of endangered Kashmir musk deer (Moschus cupreus) with range expansion in Uttarakhand, India
Authors: Kumar Ajit , Singh Bhim , Sahoo Subhashree , Gautam Kumudani Bala , Gupta Sandeep Kumar 
Published: August 2020

AbstractKashmir musk deer, KMD (Moschus cupreus) is one the most threatened species reported from the Himalayan region of Kashmir, Pakistan and Afghanistan. A comprehensive and reliable distribution range of musk deer is still lacking. Recently, a molecular study confirmed the presence of KMD in Mustang in Nepal, west of Annapurna Himalayas. Here, we investigated the phylogenetic relationship of musk deer from Jammu and Kashmir (J&K), Kedarnath Wildlife Sanctuary (KWLS), and Nanda Devi Biosphere Reserve (NDBR), Uttarakhand region, India based on mitochondrial control region. The Bayesian phylogenetic analysis indicated a close genetic relationship between samples from J&K, KWLS and NDBR with identified lineages of KMD from Nepal with high posterior probabilities (PP∼100). It confirmed that the musk deer lineage from the Uttarakhand region of KWLS (1025-3662 m) and NDBR (1800-7817 m) to be of KMD (M. cupreus) and hence a distinct Evolutionary Significant Unit (ESU). Besides, as per the IUCN database, the Western Himalayan region also holds the population ofM. leucogasterandM. chrysogaster. Hence, we suggest extensive sampling for proper identification and validation of the geographic limits of musk deer species. We report for the first time the existence of KMD from the Uttarakhand region that we recommend to be updated in the IUCN database. It will assist in the effective conservation and management of this enigmatic endangered species.
Specialized terminology limits the reach of new scientific knowledge
Authors: Martínez Alejandro , Mammola Stefano 
Published: August 2020

AbstractWords are the building blocks of science. As our understanding of the world progresses, scientific disciplines naturally enrich their specialized vocabulary (jargon). However, in the era of interdisciplinarity, the use of jargon may hinder effective communication amongst scientists that do not share a common linguistic background. The question of how jargon limits the transmission of scientific knowledge has long been debated, but rarely addressed quantitatively. We explored the relationship between the use of jargon and citations using 21,486 articles focusing on cave research, a multidisciplinary field particularly prone to terminological specialization and where linguistic disagreement among peers is frequent. We demonstrate that the use of jargon in the title and abstract significantly reduces the number of citations a paper receives. Given that these elements are the hook to readers, we urge scientists to restrict jargon to sections of the paper where its use is unavoidable.
Effects of fine-scale population structure on the distribution of heterozygosity in a long-term study ofAntirrhinum majus
Authors: Surendranadh Parvathy , Arathoon Louise , Baskett Carina A. , Field David L. , Pickup Melinda , Barton Nicholas H. 
Published: August 2020

AbstractMany studies have quantified the distribution of heterozygosity and relatedness in natural populations, but surprisingly few have examined the demographic processes driving these patterns. In this study we take a novel approach by studying how population structure affects both pairwise identity and the distribution of heterozygosity in a natural population of a self-incompatible plantAntirrhinum majus. We look at a measure of the variance in heterozygosity within a population, identity disequilibrium (g2), together with FSTusing a panel of 91 SNPs in 22,353 individuals collected over 11 years. We find that pairwise relatedness (FST) declines rapidly over short spatial scales, and the excess variance in heterozygosity between individuals (g2) reflects significant variation in inbreeding. Additionally, we detect an excess of individuals with around half the average heterozygosity, indicating that some are due to selfing or matings between close relatives. We use two types of simulation to ask whether variation in heterozygosity is consistent with fine-scale spatial population structure. First, by simulating offspring using parents drawn from a range of spatial scales, we show that the known pollen dispersal kernel explainsg2. Second, we simulate a 1000-generation pedigree using the known dispersal and spatial distribution and find that the resultingg2is consistent with that observed from the field data. In contrast, a simulated population with uniform density underestimatesg2, indicating that heterogeneous density promotes identity disequilibrium. Our study shows that heterogeneous density and leptokurtic dispersal can together explain the distribution of heterozygosity. Furthermore, our study highlights the limitations of making theoretical predictions from simulations that only assume simple density and dispersal distributions.
Patterning the embryonic pulmonary mesenchyme
Authors: Goodwin Katharine , Jaslove Jacob M. , Tao Hirotaka , Zhu Min , Hopyan Sevan , Nelson Celeste M. 
Published: August 2020

AbstractSmooth muscle guides morphogenesis of several epithelia during organogenesis, including the mammalian airways. However, it remains unclear how airway smooth muscle differentiation is spatiotemporally patterned and whether it originates from distinct mesenchymal progenitors. Using single-cell RNA-sequencing of embryonic mouse lungs, we show that the pulmonary mesenchyme contains a continuum of cell identities, but no distinct progenitors. Transcriptional variability correlates with sub-epithelial and sub-mesothelial mesenchymal compartments that are regulated by Wnt signaling. Live-imaging and tension-sensors reveal compartment-specific migratory behaviors and cortical forces, and show that sub-epithelial mesenchyme contributes to airway smooth muscle. Cytoskeletal and Wnt signaling pathways are activated early in reconstructed differentiation trajectories. Consistently, Wnt activation stimulates the earliest stages of smooth muscle differentiation and induces local accumulation of mesenchymal F-actin, which influences epithelial morphology. Our single-cell approach uncovers the principles of pulmonary mesenchymal patterning during branching morphogenesis and identifies a morphogenetically active mesenchymal layer that sculpts the airway epithelium.
Defining the RBPome of T helper cells to study higher order post-transcriptional gene regulation
Authors: Hoefig Kai P. , Reim Alexander , Gallus Christian , Wong Elaine H. , Behrens Gesine , Conrad Christine , Xu Meng , Ito-Kureha Taku , Defourny Kyra , Geerlof Arie , Mautner Josef , Hauck Stefanie M. , Baumjohann Dirk , Feederle Regina , Mann Matthias , Wierer Michael , Glasmacher Elke , Heissmeyer Vigo 
Published: August 2020

AbstractPost-transcriptional gene regulation is complex, dynamic and ensures proper T cell function. The targeted transcripts can simultaneously respond to various factors as evident forIcos, an mRNA regulated by several RNA binding proteins (RBPs), including Roquin. However, fundamental information about the entire RBPome involved in post-transcriptional gene regulation in T cells is lacking. Here, we applied global RNA interactome capture (RNA-IC) and orthogonal organic phase separation (OOPS) to human and mouse primary T cells and identified the core T cell RBPome. This defined 798 mouse and 801 human proteins as RBPs, unexpectedly containing signaling proteins like Stat1, Stat4 and Vav1. Based on the vicinity to Roquin-1 in proximity labeling experiments, we selected ∼50 RBPs for testing coregulation of Roquin targets. Induced expression of these candidate RBPs in wildtype and Roquin-deficient T cells unraveled several Roquin-independent contributions, but also revealed Celf1 as a new Roquin-1-dependent and target-specific coregulator ofIcos.One sentence statementWe provide an atlas of RNA-binding proteins in human and mouse T helper cells as a resource for studying higher order post-transcriptional gene regulation.
Dynamics of transcriptional programs and chromatin accessibility in mouse spermatogonial cells from early postnatal to adult life
Authors: Lazar-Contes Irina , Arzate-Mejia Rodrigo G. , Tanwar Deepak K. , Steg Leonard C. , Uzel Kerem , Feudjio Olivier Ulrich , Crespo Marion , Germain Pierre-Luc , Mansuy Isabelle M. 
Published: August 2020

AbstractIn mammals, spermatogonial cells (SPGs) are undifferentiated male germ cells in testis that are quiescent until birth and then self-renew and differentiate to produce spermatogenic cells and functional sperm from early postnatal life throughout adulthood. The transcriptome of SPGs is highly dynamic and timely regulated during postnatal development. We examined if such dynamics involves changes in chromatin organization by profiling the transcriptome and chromatin accessibility of SPGs from early postnatal stages to adulthood in mice using deep RNA-seq, ATAC-seq and computational deconvolution analyses. By integrating transcriptomic and epigenomic features, we show that SPGs undergo massive chromatin remodeling during postnatal development that partially correlates with distinct gene expression profiles and transcription factors (TF) motif enrichment. We identify genomic regions with significantly different chromatin accessibility in adult SPGs that are marked by histone modifications associated with enhancers and promoters. Some of the regions with increased accessibility correspond to transposable element subtypes enriched in multiple TFs motifs and close to differentially expressed genes. Our results underscore the dynamics of chromatin organization in developing germ cells and complement existing datasets on SPGs by providing maps of the regulatory genome at high resolution from the same cell populations at early postnatal, late postnatal and adult stages collected from single individuals.
An evolutionary model identifies the main selective pressures for the evolution of genome-replication profiles
Authors: Droghetti Rossana , Agier Nicolas , Fischer Gilles , Gherardi Marco , Lagomarsino Marco Cosentino 
Published: August 2020

AbstractRecent results comparing the temporal program of genome replication of yeast species belonging to theLachanceaclade support the scenario that the evolution of replication timing program could be mainly driven by correlated acquisition and loss events of active replication origins. Using these results as a benchmark, we develop an evolutionary model defined as birth-death process for replication origins, and use it to identify the selective pressures that shape the replication timing profiles. Comparing different evolutionary models with data, we find that replication origin birth and death events are mainly driven by two evolutionary pressures, the first imposes that events leading to higher double-stall probability of replication forks are penalized, while the second makes less efficient origins more prone to evolutionary loss. This analysis provides an empirically grounded predictive framework for quantitative evolutionary studies of the replication timing program.
Colony expansions underlie the evolution of army ant mass raiding
Authors: Chandra Vikram , Gal Asaf , Kronauer Daniel J. C. 
Published: August 2020

ABSTRACTCollective behavior emerges from local interactions between group members, and natural selection can fine-tune these interactions to achieve different collective outcomes. However, at least in principle, collective behavior can also evolve via changes in group-level parameters. Here, we show that army ant mass raiding, an iconic collective behavior in which many thousands of ants spontaneously leave the nest to go hunting, has evolved from group raiding, in which a scout directs a much smaller group of ants to a specific target. We describe the structure of group raids in the clonal raider ant, a close relative of army ants. We find that the coarse structure of group raids and mass raids is highly conserved, and that army ants and their relatives likely follow similar behavioral rules, despite the fact that their raids differ strikingly in overall appearance. By experimentally increasing colony size in the clonal raider ant, we show that mass raiding gradually emerges from group raiding without altering individual behavioral rules. This suggests a simple mechanism for the evolution of army ant mass raids, and more generally that scaling effects may provide an alternative mechanism for evolutionary transitions in complex collective behavior.
Soft X-ray induced radiation damage in thin freeze-dried brain samples studied by FTIR microscopy
Authors: Surowka Artur D. , Gianoncelli A. , Birarda G. , Sala S. , Cefarin N. , Matruglio A. , Szczerbowska-Boruchowska M. , Ziomber-Lisiak A. , Vaccari L. 
Published: August 2020

In order to push the spatial resolution limits to the nanoscale, synchrotron-based soft X-ray microscopy (XRM) experiments require higher radiation doses to be delivered to materials. Nevertheless, the associated radiation damage impacts on the integrity of delicate biological samples. Herein, the extent of soft X-ray radiation damage in popular thin freeze-dried brain tissue samples mounted onto Si3N4 membranes, as highlighted by Fourier transform infrared microscopy (FTIR), is reported. The freeze-dried tissue samples were found to be affected by general degradation of the vibrational architecture, though these effects were weaker than those observed in paraffin-embedded and hydrated systems reported in the literature. In addition, weak, reversible and specific features of the tissue–Si3N4 interaction could be identified for the first time upon routine soft X-ray exposures, further highlighting the complex interplay between the biological sample, its preparation protocol and X-ray probe.
TlPO3and its comparison with isotypic RbPO3and CsPO3
Authors: Weil Matthias 
Published: August 2020

The crystal structure of thallium(I)catena-polyphosphate, TlPO3, contains a polyphosphate chain extending parallel to [010] with a repeating unit of two phosphate tetrahedra. The TlIatom is located in-between the polyphosphate chains and is bonded by oxygen atoms in a distorted [6 + 1] coordination in the form of a monocapped prism, with the longest Tl—O bond to the bridging O atom of the polyphosphate chain. A quantitative structural comparison with isotypic RbPO3and CsPO3reveals that the usually pronounced stereoactivity of the 6s2lone pair at the TlIatom is not apparent in the case of TlPO3.