bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streptococcus pneumoniae,S. pyogenes, andS. agalactiaemembrane phospholipid remodeling in response to human serum
Authors: Joyce Luke. R. , Guan Ziqiang , Palmer Kelli L. 
Published: January 2021

AbstractStreptococcus pneumoniae,S. pyogenes(Group AStreptococcus; GAS), andS. agalactiae(Group BStreptococcus; GBS) are major etiological agents of diseases in humans. The cellular membrane, a crucial site in host-pathogen interactions, is poorly characterized in streptococci. Moreover, little is known about whether or how environmental conditions influence their lipid compositions. Using normal phase liquid chromatography coupled with electrospray ionization mass spectrometry, we characterized the phospholipids and glycolipids ofS. pneumoniae, GAS, and GBS in routine undefined laboratory medium, streptococcal defined medium, and, in order to mimic the host environment, defined medium supplemented with human serum. In human serum-supplemented medium, all three streptococcal species synthesize phosphatidylcholine (PC), a zwitterionic phospholipid commonly found in eukaryotes but relatively rare in bacteria. We previously reported thatS. pneumoniaeutilizes the glycerophosphocholine (GPC) biosynthetic pathway to synthesize PC. Through substrate tracing experiments, we confirm that GAS and GBS scavenge lysoPC, a major metabolite in human serum, thereby using an abbreviated GPC pathway for PC biosynthesis. Furthermore, we found that plasmanyl-PC is uniquely present in the GBS membrane during growth with human serum, suggesting GBS possesses unusual membrane biochemical or biophysical properties. In summary, we report cellular lipid remodeling by the major pathogenic streptococci in response to metabolites present in human serum.
Adaptations and responses of the common dandelion to low atmospheric pressure in high altitude environments
Authors: Arce Carla C. M. , Bont Zoe , Machado Ricardo A. R. , Cristaldo Paulo F. , Erb Matthias 
Published: January 2021

AbstractAtmospheric pressure is an important, yet understudied factor that may shape plant ecology and evolution. By growing plants under controlled conditions at different experimental stations in the Swiss alps, we evaluated the impact of ecologically realistic atmospheric pressures between 660 and 950 hPa on the growth and defence of different dandelion populations. Low atmospheric pressure was associated with reduced root growth and defensive sesquiterpene lactone production. Defense suppression only occurred in populations originating from lower altitudes. Populations from higher altitudes constitutively produced less sesquiterpene lactones and did not suffer from suppression under low atmospheric pressure. We conclude that atmospheric pressure modulates root growth and defence traits, and that evolutionary history shapes plant phenotypic responses to atmospheric pressure. Our findings have important implications for our understanding of altitudinal gradients and the future use of plants as a source of food and bioactive metabolites in extraterrestrial habitats.
Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce robust immune responses in mice
Authors: Spencer Alexandra J , McKay Paul F , Belij-Rammerstorfer Sandra , Ulaszewska Marta , Bissett Cameron D , Hu Kai , Samnuan Karnyart , Blakney Anna K. , Wright Daniel , Sharpe Hannah R , Gilbride Ciaran , Truby Adam , Allen Elizabeth R , Gilbert Sarah C , Shattock Robin J , Lambe Teresa 
Published: January 2021

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.
Novel regulators of PrPCbiosynthesis revealed by genome-wide RNA interference
Authors: Heinzer Daniel , Avar Merve , Pease Daniel Patrick , Dhingra Ashutosh , Yin Jiang-An , Schaper Elke , Doğançay Berre , Emmenegger Marc , Spinelli Anna , Maggi Kevin , Chincisan Andra , Mead Simon , Hornemann Simone , Heutink Peter , Aguzzi Adriano 
Published: January 2021

AbstractThe cellular prion protein PrPCis necessary for prion replication, and its reduction greatly increases life expectancy in animal models of prion infection. Hence the factors controlling the levels of PrPCmay represent therapeutic targets against human prion diseases. Here we performed an arrayed whole-transcriptome RNA interference screen to identify modulators of PrPCexpression. We cultured human U251-MG glioblastoma cells in the presence of 64’752 unique siRNAs targeting 21’584 annotated human genes, and measured PrPCusing a one-pot fluorescence-resonance energy transfer immunoassay in 51’128 individual microplate wells. This screen yielded 743 candidate regulators of PrPC. When downregulated, 563 of these candidates reduced and 180 enhanced PrPCexpression. Recursive candidate attrition through multiple secondary screens yielded 54 novel regulators of PrPC, 9 of which were confirmed by CRISPR interference as robust regulators of PrPCbiosynthesis and degradation. The phenotypes of 6 of the 9 candidates were inverted in response to transcriptional activation using CRISPRa. The RNA-binding post-transcriptional repressor Pumilio-1 was identified as a potent limiter of PrPCexpression through the degradation ofPRNPmRNA. Because of its hypothesis-free design, this comprehensive genetic-perturbation screen delivers an unbiased landscape of the genes regulating PrPClevels in cells, most of which were unanticipated, and some of which may be amenable to pharmacological targeting in the context of antiprion therapies.
Contribution of climate models and APSIM phenological parameters to uncertainties in spring wheat simulations: application of SUFI-2 algorithm in northeast Australia
Authors: Collins Brian , Najeeb Ullah , Luo Qunying , Tan Daniel K.Y. 
Published: January 2021

AbstractWe used SUFI-2 for the first time to calibrate the phenology module of the APSIM-wheat model for 10 spring wheat cultivars cultivated in northeast Australia (south-eastern Queensland). Calibration resulted in an average RMSE of 5.5 d for developmental stages from stem elongation up to flowering. Projections from 33 climate models under the representative concentration pathway 8.5 were used for simulations at 17 sites. Using adapted sowing times, we simulated significantly shorter crop cycles and grain yield improvements for the period 2036-2065 relative to 1990-2019 for three selected cultivars (Hartog, Scout and Gregory). Photoperiod and vernalisation sensitivities were shown to be the largest and smallest contributors to total uncertainties in the simulated flowering day and grain yield. Uncertainties in climate models had a relatively minor contribution to the total uncertainties in the simulated values of target traits. This contribution significantly increased when climate change impact on the target traits was estimated.
Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM
Authors: Antanasijevic Aleksandar , Sewall Leigh M. , Cottrell Christopher A. , Carnathan Diane G. , Jimenez Luis E. , Ngo Julia T. , Silverman Jennifer B. , Groschel Bettina , Georgeson Erik , Bhiman Jinal , Bastidas Raiza , LaBranche Celia , Allen Joel D. , Copps Jeffrey , Perrett Hailee R. , Rantalainen Kimmo , Cannac Fabien , Yang Yuhe R. , de la Peña Alba Torrents , Rocha Rebeca Froes , Berndsen Zachary T. , Baker David , King Neil P. , Sanders Rogier W. , Moore John P. , Crotty Shane , Crispin Max , Montefiori David C. , Burton Dennis R. , Schief William R. , Silvestri Guido , Ward Andrew B. 
Published: January 2021

In BriefHerein, we evaluated the immunogenicity of several BG505 SOSIP-based HIV Env immunogens in the rhesus macaque animal model using a combination of serology and biophysical approaches. We applied electron cryo-microscopy for high-resolution mapping of elicited polyclonal antibody responses, which provided detailed insights into the binding modes of the most common classes of antibodies elicited by BG505 SOSIP immunogens as well as the critical differences in immunogenicity that can occur as a consequence of engineered stabilizing mutations and partial glycan occupancy at different sites.SummaryEngineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic.Graphical abstract
Coevolution between primates and venomous snakes revealed by α-neurotoxin susceptibility
Authors: Harris Richard J. , Nekaris K. Anne-Isola , Fry Bryan G. 
Published: January 2021

AbstractEvidence suggests venomous snakes and primates have evolved certain traits in response to a coevolutionary arms-race. In both clades, evolved traits include an increase in brain size and enhanced vision. Lineage specific traits include in primates an inherent fear of snakes, while cobras have evolved defensive toxins, hooding, aposematism and venom spitting. To strengthen the claims of coevolution between venomous snakes and primates, more evidence of coevolved traits is needed to highlight the importance of this arms-race. We report a significantly reduced susceptibility of snake venom α-neurotoxins toward the α-1 nicotinic acetylcholine receptor orthosteric site within the catarrhine primates. This trait is particularly amplified within the clade Homininae. This relationship is supported by post-synaptic neurotoxic symptoms of envenoming relative to prey species being much lower humans due to weak binding of α-neurotoxins to human nicotinic receptors. Catarrhines are sympatric with many species of large, diurnal, neurotoxically venomous snakes and as such are likely to have had a long history of interaction with them. Conversely, the Lemuriformes and Platyrrhini are highly susceptible to binding of α-neurotoxins, which is consistent with them occupying geographical locations either devoid of venomous snakes or areas with neurotoxic snakes that are small, fossorial, and nocturnal. These data are consistent with the snake detection theory in that they follow a similar pattern of evolved traits within specific primate clades that are sympatric with venomous snakes. These results add new strong evidence in support of snakes and primates coevolving through arms-races that shaped selection pressures for both lineages.Significance StatementWe have discovered a pattern of primate susceptibility towards α-neurotoxins that supports the theory of a coevolutionary arms-race between venomous snakes and primates.
Structure of Ycf1p reveals the transmembrane domain TMD0 and the regulatory R region of ABCC transporters
Authors: Bickers Sarah C. , Benlekbir Samir , Rubinstein John L. , Kanelis Voula 
Published: January 2021

AbstractATP binding cassette (ABC) proteins typically function in active transport of solutes across membranes. The ABC core structure is comprised of two transmembrane domains (TMD1 and TMD2) and two cytosolic nucleotide binding domains (NBD1 and NBD2). Some members of the C-subfamily of ABC (ABCC) proteins, including human multidrug resistance proteins (MRPs), also possess an N-terminal transmembrane domain (TMD0) that contains five transmembrane α-helices and is connected to the ABC core by the L0 linker. While TMD0 was resolved in SUR1, the atypical ABCC protein that is part of the hetero-octameric ATP-sensitive K+ channel, little is known about the structure of TMD0 in monomeric ABC transporters. Here, we present the structure of yeast cadmium factor 1 protein (Ycf1p), a homologue of human MRP1, determined by electron cryomicroscopy (cryo-EM). Comparison of Ycf1p, SUR1, and a structure of MRP1 that showed TMD0 at low resolution demonstrates that TMD0 can adopt different orientations relative to the ABC core, including a 145° rotation between Ycf1p and SUR1. The cryo-EM map also reveals that segments of the regulatory (R) region, which links NBD1 to TMD2 and was poorly resolved in earlier ABCC structures, interacts with the L0 linker, NBD1, and TMD2. These interactions, combined with fluorescence quenching experiments of isolated NBD1 with and without the R region, suggests how post-translational modifications of the R region modulate ABC protein activity. Mapping known mutations from MRP2 and MRP6 onto the Ycf1p structure explains how mutations involving TMD0 and the R region of these proteins lead to disease.Statement of SignificanceThe Ycf1p structure provides an atomic model for the TMD0 domain of ABCC transporters and for two segments of the regulatory (R) region that links NBD1 to TMD2. The orientation of TMD0 in Ycf1p differs from that seen in SUR1, the regulatory ABCC protein in KATP channels, demonstrating flexibility in TMD0/ABC core contacts. The structure suggests how post-translational modifications of the R region modulate ABC protein activity and provides a mechanistic understanding of several diseases that occur due to mutation of human homologues of Ycf1p.
The regulatory landscape of cells in the developing mouse cerebellum
Authors: Sarropoulos Ioannis , Sepp Mari , Frömel Robert , Leiss Kevin , Trost Nils , Leushkin Evgeny , Okonechnikov Konstantin , Joshi Piyush , Kutscher Lena M. , Cardoso-Moreira Margarida , Pfister Stefan M. , Kaessmann Henrik 
Published: January 2021

AbstractOrgan development is orchestrated by cell- and time-specific gene regulatory networks. Here we investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood. By acquiring snATAC-seq profiles for ~90,000 cells spanning eleven stages, we mapped all major cerebellar cell types and identified candidatecis-regulatory elements (CREs). We detected extensive spatiotemporal heterogeneity among progenitor cells and characterized the regulatory programs underlying the differentiation of cerebellar neurons. Although CRE activity is predominantly cell type- and time-specific, periods of greater regulatory change are shared across cell types. There is a universal decrease in CRE conservation and pleiotropy during development and differentiation, but the degree of evolutionary constraint differs between cerebellar cell types. Our work delineates the developmental and evolutionary dynamics of gene regulation in cerebellar cells and provides general insights into mammalian organ development.
Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds
Authors: Haimson Baruch , Meir Oren , Sudakevitz-Merzbach Reut , Elberg Gerard , Friedrich Samantha , Lovell Peter V. , Paixão Sónia , Klein Rüdiger , Mello Claudio V. , Klar Avihu 
Published: January 2021

AbstractFlight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avianephrin-B3gene lacks an enhancer that drives midline expression, and is missing in Galliformes. The morphology and wiring at brachial levels of the chick spinal cord resemble those ofephrin-B3null mice. Importantly, dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level, and is prevented by expression of exogenousephrin-B3at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.TeaserWalking vs flying: Deciphering the organization and evolution of the neuronal network that controls wing flapping in birds.
The evolutionary making of SARS-CoV-2
Authors: Iruegas Ruben , Dosch Julian , Sikora Mateusz , Hummer Gerhard , Covino Roberto , Ebersberger Ingo 
Published: January 2021

AbstractA mechanistic understanding of how SARS-CoV-2 (sarbecovirus, betacoronavirus) infects human cells is emerging, but the evolutionary trajectory that gave rise to this pathogen is poorly understood. Here we scan SARS-CoV-2 protein sequences in-silico for innovations along the evolutionary lineage starting with the last common ancestor of coronaviruses. SARS-CoV-2 substantially differs from viruses outside sarbecovirus both in its set of encoded proteins and in their domain architectures, indicating divergent functional demands. Within sarbecoviruses, sub-domain level profiling using predicted linear epitopes reveals how the primary interface between host cell and virus, the spike, was gradually reshaped. The only epitope that is private to SARS-CoV-2 overlaps with the furin cleavage site, a “switch” that modulates spike’s conformational landscape in response to host-cell interaction. This cleavage site has fundamental relevance for both immune evasion and cell infection, and the apparently ongoing evolutionary fine-tuning of its use by SARS-CoV-2 should be monitored.
Temperature reduces fish dispersal as larvae grow faster to their settlement size
Authors: Raventos Nuria , Torrado Héctor , Arthur Rohan , Alcoverro Teresa , Macpherson Enrique 
Published: January 2021

AbstractAs species struggle to cope with rising ocean temperatures, temperate marine assemblages are facing major reorganization. Many benthic species have a brief but critical period dispersing through the plankton, when they are particularly susceptible to variations in temperature. Impacts of rising temperatures can thus ripple through the population with community‐wide consequences. However, responses are highly species‐specific, making it difficult to discern assemblage‐wide patterns in the life histories of different fish species.Here, we evaluate the responses to temperature in the early life histories of several fish species using otolith reconstructive techniques. We also assess the consequences of future warming scenarios to this assemblage.We sampled recent settlers of nine common species across a temperature gradient in the Mediterranean Sea and obtained environmental data for each individual. Using otolith microstructure, we measured early life traits including pelagic larval duration (PLD), growth rate, settlement size, hatching and settlement dates. We used a GLM framework to examine how environmental variables influenced early life‐history parameters.We show that increasing temperature results in considerable reduction in the dispersal potential of temperate fish. We find a nearly universal, assemblage‐wide decline in pelagic larval duration (PLD) of between 10% and 25%. This was because, with increasing temperature, larvae grew quicker to their settlement size. Settlement size itself was less affected by temperature and appears to be an ontogenetically fixed process.Given current estimates of ocean warming, there could be an assemblage‐wide reduction in larval dispersal of up to 50 km across the Mediterranean, reducing connectivity and potentially isolating populations as waters warm.
Combining conservation status and species distribution models for planning assisted colonisation under climate change
Authors: Casazza Gabriele , Abeli Thomas , Bacchetta Gianluigi , Dagnino Davide , Fenu Giuseppe , Gargano Domenico , Minuto Luigi , Montagnani Chiara , Orsenigo Simone , Peruzzi Lorenzo , Varaldo Lucia , Rossi Graziano 
Published: January 2021

Abstract

Effects of climate change are particularly important in the Mediterranean Biodiversity hotspot where rising temperatures and drought are negatively affecting several plant taxa, including endemic species. Assisted colonisation (AC) represents a useful tool for reducing the effect of climate change on endemic plant species threatened by climate change.

We combined species distribution models (SDMs) for 188 taxa endemic to Italy with the IUCN red listing range loss threshold under criterion A (30%) to define: (a) the number of AC (measured as 2 × 2 km grid cells that should be occupied by new populations, i.e. grid cells = new populations) required to fully compensate for predicted range loss and to halt the decline below the 30% of range loss; (b) The number of cells necessary to compensate for range loss was calculated as the number of currently occupied cells lost under future climate due to unsuitable conditions. We used two representative concentration pathways, +2.6 and +8.5 W/m2, optimistic and pessimistic scenarios respectively. Availability of suitable areas for AC was also assessed within the current species distribution and within protected areas.

Under the optimistic scenario, no taxa would lose more than 30% of their range and AC would not be required. Under the pessimistic scenario, roughly the 90% of taxa showed a cell loss higher than 30%. Eight taxa were predicted to lose >95% of their range. For these species, AC was required from 13 to 16 new populations (=13–16 grid cells) per taxon to cap the range loss at 30%. For currently VU or EN species, an average number of 32–35 AC attempts would be necessary to fully compensate their range loss under a pessimistic scenario. Suitable recipient sites within protected areas falling in their projected range were identified, allowing for short‐distance AC.

Synthesis. Combining species distribution models and red listing thresholds under Criterion A has enabled the strategic planning of multiple species assisted colonisation minimising the effort in terms of new populations to be created and maximising the conservation benefit in terms of range loss compensation.