bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of a temperature-sensitive prophage on the evolution of virulence in an opportunistic bacterial pathogen
Authors: Bruneaux Matthieu , Ashrafi Roghaieh , Kronholm Ilkka , Laanto Elina , Örmälä-Odegrip Anni-Maria , Galarza Juan A. , Zihan Chen , Sumathi Mruthyunjay Kubendran , Ketola Tarmo 
Published: November 2019

AbstractViruses are key actors of ecosystems and have major impacts on global biogeochemical cycles. Prophages deserve particular attention as they are ubiquitous in bacterial genomes and can enter a lytic cycle when triggered by environmental conditions. We explored how temperature affects the interactions between prophages and other biological levels by using an opportunistic pathogen, the bacterium Serratia marcescens, that harbours several prophages and that had undergone an evolution experiment under several temperature regimes. We found that the release of one of the prophages was temperature-sensitive and malleable to evolutionary changes. We further discovered that the virulence of the bacterium in an insect model also evolved and was positively correlated with phage release rates. We determined through analysis of genetic and epigenetic data that changes in the outer cell wall structure possibly explain this phenomenon. We hypothezise that the temperature-dependent phage release rate acted as a selection pressure on S. marcescens and that it resulted in modified bacterial virulence in the insect host. Our study system illustrates how viruses can mediate the influence of abiotic environmental changes to other biological levels and thus be involved in ecosystem feedback loops.
Amplitude and timescale of metacommunity trait-lag response to climate change
Authors: Norberg Jon , Moor Helen 
Published: November 2019

Climate change is altering the structure and functioning of communities1. Trait-based approaches are powerful predictive tools that allow consideration of changes in structure and functioning simultaneously2, 3. The realised biomass-weighted trait distribution of a community rests on the ecophysiology of individuals, but integrates local species interactions and spatial dynamics that feed back to ecosystem functioning. Consider a response trait that determines species performance (e.g. growth rate) as a function of an environmental variable (e.g. temperature). The change in this response trait’s distribution following directional environmental change integrates all factors contributing to the community’s response and directly reflects the community’s response capacity3.Here we introduce the average regional community trait-lag (TLMC) as a novel measure of whole-metacommunity response to warming. We show that functional compensation (shifts in resident species relative abundances) confers initial response capacity to communities by reducing and delaying the initial development of a trait-lag. Metacommunity adaptive capacity in the long-term, however, was dependent on dispersal and species tracking of their climate niche by incremental traversal of the landscape. With increasing inter-patch distances, network properties of the functional connectivity network became increasingly more important, and may guide prioritisation of habitat for conservation.
Axonal mitochondria across species adjust in diameter depending on thickness of surrounding myelin
Authors: Ineichen Benjamin V , Zhu Keying , Carlström Karl E 
Published: November 2019

AbstractIn the central nervous system (CNS), axons and its surrounding myelin sheaths, generated by oligodendrocytes, greatly depend on each other, where oligodendrocytes provide axons with both trophic and metabolic support. Across spices, assessment of the axon-myelin ultrastructure is the key-approach to visualize de- and re-myelination of axons. However, this assessment omits to provide information on axonal homeostasis or how axon-myelin influence one another. Since mitochondria may adjust in size thus mirroring the intracellular physiological and metabolic status we applied this to myelinated axons in the CNS. We herein show that a large axonal mitochondria diameter correlates with thinner surrounding myelin sheaths across different CNS tracts and species, including human. We also show that the relation between axonal mitochondria diameter and surrounding myelin thickness is a valuable measurement to verify advanced remyelination in two commonly used experimental demyelinating models, namely the cuprizone and the lysolecithin (LPC) model. Lastly, we show that axonal mitochondria adjust in diameter in response to the thickness of the axonal surrounding myelin whereas the opposite adaption was absent. In summary, the link between axonal mitochondria diameter and surrounding myelin thickness provide insight on the axon-myelin relation both during homeostasis and pathological conditions. This link is also translational applicable and can thus contribute to a better understanding on how to study remyelination using experimental models.
Construction of light-activated neurotrophin receptors using the improved Light-Induced Dimerizer (iLID)
Authors: Hope Jen M. , Liu Aofei , Calvin Ghawayne J. , Cui Bianxiao 
Published: November 2019

AbstractReceptor tyrosine kinases (RTKs) play crucial roles in human health, and their misregulation is implicated in disorders ranging from neurodegenerative disorders to cancers. The highly conserved mechanism of activation of RTKs makes them especially appealing candidates for control via optogenetic dimerization methods. This work offers a strategy for using the improved Light-Induced Dimer (iLID) system with a constructed tandem-dimer of its binding partner nano (tdnano) to build light-activatable versions of RTKs. In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive. Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK. We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano. We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells. By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination, allowing us to confidently probe the impact of context on signaling outcome.
A user guide to environmental protistology: primers, metabarcoding, sequencing, and analyses
Authors: Geisen Stefan , Vaulot Daniel , Mahé Frédéric , Lara Enrique , de Vargas Colomban , Bass David 
Published: November 2019

AbstractProtists – all eukaryotes besides fungi, animals, and plants - represent a major part of the taxonomic and functional diversity of eukaryotic life on the planet and drive many ecosystem processes. However, knowledge of protist communities and their diversity lags behind that of most other groups of organisms, largely due to methodological constraints. While protist communities differ markedly between habitats and biomes, they can be studied in very similar ways. Here we provide a guide to current molecular approaches used for studying protist diversity, with a particular focus on amplicon-based high-throughput sequencing (metabarcoding). We highlight that the choice of suitable primers artificially alters community profiles observed in metabarcoding studies. While there are no true ‘universal’ primers to target all protist taxa as a whole, we identify some primer combinations with a wide taxonomic coverage and provide detailed information on their properties. Although environmental protistan ecological research will probably shift towards PCR-free metagenomics or/and transcriptomic approaches in a near future, metabarcoding will remain the method of choice for in-depth community analyses and taxon inventories in biodiversity surveys and ecological studies, due its great cost-efficiency, sensitivity, and throughput. In this paper we provide a guide for scientists from a broad range of disciplines to implement protists in their ecological analyses.
Quantitative Phenotyping of Vascular Damage Caused by Fusarium Wilt Disease in Cowpea
Authors: Ndeve Arsenio D. , Roberts Philip A. 
Published: November 2019

ABSTRACTAssessment of the severity of Fusarium wilt disease in cowpea and other crops relies mainly on visual rating scales which are prone to errors, which can compromise the reproducibility of the data. Furthermore, the rating scales require considerable practical training and routine experience for reliable assessment. Two objective metrics, stem vascular discoloration length (%VDL) and number of Fusarium necrotic vessels (NFNV), for quantitative measurement of vascular damage incited by Fusarium oxysporum f. sp. tracheiphilum race 4 (Fot4) of cowpea, were compared and their utility as a measure of disease severity and potential usefulness in other crop pathosystems is proposed. The metrics were tested in seven F2 populations and one F2:3 population, segregating for wilt response, and inoculated with race Fot4 at the seedling stage. %VDL and NFNV were highly correlated with plant wilting for all populations (r = 0.51 – 0.93 and 0.52 – 0.94, respectively). Furthermore, the relationships between the variables were linear in all populations (R2 = 0.81 to 0.87 and 0.71 to 0.91), indicating that they can provide accurate and reliable measurement of severity of Fusarium wilt disease. Also, %VDL and NFNV were strongly correlated (r = 0.88 - 0.97) and demonstrated a linear relationship (R2 = 0.69 – 0.94). Analysis of goodness-of-fit in two F2 populations revealed that errors in measurement of vascular discoloration length can result in higher segregation distortion when compared to enumeration of necrotic vessels. However, both metrics were highly effective in accounting for the severity of vascular damage caused by Fusarium wilt disease.
Into the deep (sequence) of the foot-and-mouth disease virus gene pool: bottlenecks and adaptation during infection in naïve and vaccinated cattle
Authors: Fish Ian , Stenfeldt Carolina , Palinski Rachel M. , Pauszek Steven J. , Arzt Jonathan 
Published: November 2019

AbstractFoot-and-mouth disease virus (FMDV), like many RNA viruses, infects hosts as a population of closely related viruses referred to as a quasispecies. The behavior of this quasispecies has not been described in detail over the full course of infection in a natural host species. In this study, virus samples taken from vaccinated and non-vaccinated cattle up to 35 days post experimental infection with FMDV A24-Cruzeiro were analyzed by deep-sequencing. Vaccination induced significant differences compared to viruses from non-vaccinated cattle. in virus substitution rates, entropy, and evidence for adaptation. Genomic variation detected during early infection was found to reflect the diversity inherited from the source virus (inoculum), whereas by 12 days post infection (dpi) dominant viruses were defined by newly acquired mutations. In most serially sampled cattle, mutations conferring recognized fitness gain occurred within numerous genetic backgrounds, often associated with selective sweeps. Persistent infections always included multiple FMDV subpopulations, suggesting independently maintained foci of infection within the nasopharyngeal mucosa. Although vaccination prevented disease, subclinical infection in this group was associated with very early bottlenecks which subsequently reduced the diversity within the virus population. This implies an added consequence of vaccination in the control of foot-and-mouth disease. Viruses sampled from both animal cohorts contained putative antigenic escape mutations. However, these mutations occurred during later stages of infection, at which time transmission between animals is less likely to occur.ImportancePreparedness and control of foot-and-mouth disease virus have substantial, yet distinct implications in endemic and free regions. Viral evolution and emergence of novel strains are of critical concern in both settings. The factors that contribute to the asymptomatic carrier state, a common form of long-term FMDV infection in cattle and other species, are important but not well-understood. This experimental study of foot-and-mouth disease virus in cattle explored the evolution of the pathogen through detailed sampling and analytical methods in both vaccinated and non-vaccinated hosts. Significant differences were identified between the viruses subclinically infecting vaccinated animals and those causing clinical disease in the non-vaccinated cohort. These results can benefit vaccination programs and contribute to the understanding of persistent infection of cattle.
Intramembrane protease RHBDL4 cleaves oligosaccharyltransferase subunits to target them for ER-associated degradation
Authors: Knopf Julia D. , Landscheidt Nina , Pegg Cassandra L. , Schulz Benjamin L. , Kühnle Nathalie , Chao Chao-Wei , Huck Simon , Lemberg Marius K. 
Published: November 2019

AbstractThe Endoplasmic Reticulum (ER)-resident intramembrane rhomboid protease RHBDL4 generates metastable protein fragments and together with the ER-associated degradation (ERAD) machinery provides a clearance mechanism for aberrant and surplus proteins. However, the endogenous substrate spectrum and with that the role of RHBDL4 in physiological ERAD is mainly unknown. Here, we use a substrate trapping approach in combination with quantitative proteomics to identify physiological RHBDL4 substrates. This revealed oligosacharyltransferase (OST) complex subunits such as the catalytic active subunit STT3A as substrates for the RHBDL4-dependent ERAD pathway. RHBDL4-catalyzed cleavage inactivates OST subunits by triggering dislocation into the cytoplasm and subsequent proteasomal degradation. Thereby, RHBDL4 controls the abundance and activity of OST, suggesting a novel link between the ERAD machinery and glycosylation tuning.
Balancing Selection atHLA-GModulates Fetal Survival, Preeclampsia and Human Birth Sex Ratio
Authors: Wedenoja S. , Yoshihara M. , Teder H. , Sariola H. , Gissler M. , Katayama S. , Wedenoja J. , Häkkinen I.M. , Ezer S. , Linder N. , Lundin J. , Skoog T. , Sahlin E. , Iwarsson E. , Pettersson K. , Kajantie E. , Mokkonen M. , Heinonen S. , Laivuori H. , Krjutškov K. , Kere J. 
Published: November 2019

AbstractThe population sex ratio is thought to be maintained through balancing selection on rare phenotypes. However, empirical evidence for genetic influence has thus far proven elusive. We combined 1000 Genomes data and large cohorts to study human sex ratios. We found underrepresentation of male offspring in preeclampsia, a serious pregnancy disorder with uncertain pathogenesis. Genetic variation of fetalhuman leukocyte antigen G(HLA-G), regulating maternal anti-fetal immune responses, was found to be under balancing selection. Sex-linked downregulation ofHLA-Gand upregulation ofinterferon alpha-1(IFNA1) expression contribute to loss of fetal immunotolerance in preeclampsia and suggest hydroxychloroquine as a treatment option. Our findings indicate that an evolutionary trade-off between fetal immunotolerance and protection against infections promotes genetic diversity inHLA-G, thereby maintaining human sex ratios.One Sentence SummaryFetalHLA-Gmodulates human sex ratio.
Selective facilitation of egocentric mental transformations under short-term microgravity
Authors: Meirhaeghe Nicolas , Bayet Virginie , Paubel Pierre-Vincent , Mélan Claudine 
Published: November 2019

ABSTRACTUnderstanding the impact of microgravity on human cognitive performance is crucial to guarantee the safety and success of future long-term manned missions. The effects of weightlessness on key mental processes such as spatial abilities are in particular not fully characterized. In this study, we examine the influence of microgravity on perspective-taking abilities—a type of mental operation especially relevant in the context of collaborative teamwork between ‘free-floating’ astronauts. Twelve subjects performed a cooperative task in virtual-reality under both normal and short-term microgravity conditions during a parabolic flight. The task involved various degrees of mental transformations, and required subjects to perform actions instructed by a fellow astronaut aboard a virtual spacecraft. The experimental design allowed us to control for nuisance variables, training effects, and non-gravity related factors of parabolic flights. Overall, our results indicated that microgravity has a facilitatory effect on perspective-taking abilities. Notably, this facilitation was selective to conditions requiring subjects to rotate their perspective around their line of sight, i.e., for mental rotations in the frontal plane. Moreover, microgravity affected subjects differently depending on their visual field dependence, as determined via a classic rod-and-frame test. Specifically, improvement in performance was more pronounced in field-independent subjects. Together, these results shed light on a long standing debate about the impact of microgravity on egocentric mental imagery, and have direct operational consequences for future long-term missions.
Alternative splicing in neuroblastoma generates RNA-fusion transcripts and is associated with vulnerability to spliceosome inhibitors
Authors: Shi Yao , Rraklli Vilma , Maxymovitz Eva , Li Shuijie , Westerlund Isabelle , Bedoya-Reina Oscar C. , Yuan Juan , Bullova Petra , Juhlin C. Christofer , Stenman Adam , Larsson Catharina , Kogner Per , O’Sullivan Maureen J. , Schlisio Susanne , Holmberg Johan 
Published: November 2019

AbstractThe paucity of recurrent mutations has hampered efforts to understand and treat neuroblastoma. Alternative splicing and splicing-dependent RNA-fusions represent mechanisms able to increase the gene product repertoire but their role in neuroblastoma remains largely unexplored. Through analysis of RNA-sequenced neuroblastoma we here show that elevated expression of splicing factors is a strong predictor of poor clinical outcome. Furthermore, we identified >900 primarily intrachromosomal fusions containing canonical splicing sites. Fusions included transcripts from well-known oncogenes, were enriched for proximal genes and in chromosomal regions commonly gained or lost in neuroblastoma. As a proof-of-principle that these fusions can generate altered gene products, we characterized a ZNF451-BAG2 fusion, generating a truncated BAG2-protein which inhibited retinoic acid-induced differentiation. Spliceosome inhibition impeded neuroblastoma fusion expression, induced apoptosis and inhibited xenograft tumor growth. Our findings elucidate a splicing-dependent mechanism producing altered gene products in neuroblastoma and suggest that the spliceosome is a tractable therapeutical target.
Identification of a novel missense variant in SLC45A2 associated with dilute snowdrop phenotype in Gypsy horses
Authors: Bisbee D. , Carpenter M. L. , Hoefs-Martin K. , Brooks S. A. , Lafayette C. 
Published: November 2019

SUMMARYSLC45A2 mutations are responsible for several dilution phenotypes in horses, including cream, pearl, and sunshine. We sequenced the SLC45A2 gene in a horse that possessed a diluted coat color but tested negative for any known dilution genotypes. We identified a novel homozygous missense mutation in ECA21: SLC45A2:c.305G>A; p.(Arg102Gln) which we have named snowdrop (Csno). The snowdrop dilution is autosomal recessive and dilutes both red and black pigment in the homozygous state, creating a phenotype similar to homozygous cream. We also identified this mutation in the heterozygous state in several relatives, including the sire and dam of the affected horse, where it has no visible effect on phenotype. Based on these data, the snowdrop variant produces a recessive dilution similar to cream, and its discovery confirms that multiple SLC45A2 alleles cause dilute phenotypes in horses.
An electrostatic-interaction-based mechanism triggering misfolding of prion proteins from cellular isoform to scrapie isoform
Authors: Li J. , Ma X. , Guo S. , Hou C. , Shi L. , Ye L. , Yang L. , Zheng B. , He X. 
Published: November 2019

AbstractUnderstanding how prion proteins refold from a cellular isoform (PrPC) to a disease-causing isoform (PrPSc) has been among the “ultimate challenges” in molecular biology, biophysics, pathology, and immunology. Conformational changes of prion proteins from PrPC to PrPSc involve the unfolding of a short α-helix that overshadows the challenge. Considering the mechanisms of electrostatic attraction, thermal disturbance, hydrogen ion concentration, hydrophobic interaction, and the shielding effect of water molecules, this study reveals an electrostatic-interaction-based mechanism by means of which prion proteins refold in an aqueous environment. The electrostatic-interaction-induced protein unfolding mechanism causes a hydrophobic polypeptide segment to dangle out over the conglobate main body of the prion protein, thereby allowing the first triangular hydrophobic rung formation via hydrophobic interaction. A molecular model of PrPSc is proposed that allows the β-solenoid with a triangular hydrophobic core.Statement of SignificanceWe present three main results that would revolutionize the understanding of pathology of prion diseases. First, the prion protein refolding (from cellular isoform to scrapie isoform) derives from the unfolding of the shortest α-helix of PrPC, which provides a long polypeptide segment full of hydrophobic residues dangling out over the conglobate main body of the prion protein, thereby allowing formation of the first triangular hydrophobic rung via hydrophobic interaction. Second, polyanions-induced increasing in local concentration of hydrogen ion (i.e., the PH increase) undermines the shielding effect of water molecules, thereby allowing escape of the arginine side chains from the hydration shell, destabilizing the shortest α-helix and initiating the refolding of PrPC. Third, a β-solenoid structural model for PrPSc with a triangular hydrophobic core is proposed.
ETV7 limits antiviral gene expression and control of SARS-CoV-2 and influenza viruses
Authors: Froggatt Heather M. , Harding Alfred T. , Heaton Brook E. , Heaton Nicholas S. 
Published: November 2019

AbstractThe type I interferon (IFN) response is an important component of the innate immune response to viral infection. Precise control of interferon responses is critical; insufficient levels of interferon-stimulated genes (ISGs) can lead to a failure to restrict viral spread while excessive ISG activation can result in interferon-related pathologies. While both positive and negative regulatory factors control the magnitude and duration of IFN signaling, it is also appreciated that a number of ISGs regulate aspects of the interferon response themselves. However, the mechanisms underlying these ISG regulatory networks remain incompletely defined. In this study, we performed a CRISPR activation screen to identify new regulators of the type I IFN response. We identified ETS variant transcription factor 7 (ETV7), a strongly induced ISG, as a protein that acts as a negative regulator of the type I IFN response; however, ETV7 did not uniformly suppress ISG transcription. Instead, ETV7 preferentially targeted a subset of known antiviral ISGs. Further, we showed the subset of ETV7-modulated ISGs was particularly important for IFN-mediated control of some viruses including influenza viruses and SARS-CoV-2. Together, our data assign a function for ETV7 as an IFN response regulator and also identify ETV7 as a therapeutic target to increase innate responses and potentiate the efficacy of interferon-based antiviral therapies.One Sentence SummaryETV7 is an interferon-induced, repressive transcription factor that negatively regulates antiviral interferon-stimulated genes essential for controlling influenza virus and SARS-CoV-2 infections.