bluuebunny/crossref_metadata_2025_split huggingface dataset:
VAE-Sim: a novel molecular similarity measure based on a variational autoencoder
Authors: Samanta Soumitra , O’Hagan Steve , Swainston Neil , Roberts Timothy J. , Kell Douglas B. 
Published: June 2020

AbstractMolecular similarity is an elusive but core ‘unsupervised’ cheminformatics concept, yet different ‘fingerprint’ encodings of molecular structures return very different similarity values even when using the same similarity metric. Each encoding may be of value when applied to other problems with objective or target functions, implying thata priorinone is ‘better’ than the others, nor than encoding-free metrics such as maximum common substructure (MCSS). We here introduce a novel approach to molecular similarity, in the form of a variational autoencoder (VAE). This learns the joint distribution p(z|x) where z is a latent vector and x are the (same) input/output data. It takes the form of a ‘bowtie’-shaped artificial neural network. In the middle is a ‘bottleneck layer’ or latent vector in which inputs are transformed into, and represented as, a vector of numbers (encoding), with a reverse process (decoding) seeking to return the SMILES string that was the input. We train a VAE on over 6 million druglike molecules and natural products (including over one million in the final holdout set). The VAE vector distances provide a rapid and novel metric for molecular similarity that is both easily and rapidly calculated. We describe the method and its application to a typical similarity problem in cheminformatics.
Comparative genomics provides an operational classification system and reveals early emergence and biased spatio-temporal distribution of SARS-CoV-2
Authors: Chiara Matteo , Horner David S. , Gissi Carmela , Pesole Graziano 
Published: June 2020

AbstractEffective systems for the analysis of molecular data are of fundamental importance for real-time monitoring of the spread of infectious diseases and the study of pathogen evolution. While the Nextstrain and GISAID portals offer widely used systems for the classification of SARS-CoV-2 genomes, both present relevant limitations. Here we propose a highly reproducible method for the systematic classification of SARS-CoV-2 viral types. To demonstrate the validity of our approach, we conduct an extensive comparative genomic analysis of more than 20,000 SARS-CoV-2 genomes. Our classification system delineates 12 clusters and 4 super-clusters in SARS-CoV-2, with a highly biased spatio-temporal distribution worldwide, and provides important observations concerning the evolutionary processes associated with the emergence of novel viral types. Based on the estimates of SARS-CoV-2 evolutionary rate and genetic distances of genomes of the early pandemic phase, we infer that SARS-CoV-2 could have been circulating in humans since August-November 2019. The observed pattern of genomic variability is remarkably similar between all clusters and super-clusters, being UTRs and the s2m element, a highly conserved secondary structure element, the most variable genomic regions. While several polymorphic sites that are specific to one or more clusters were predicted to be under positive or negative selection, overall, our analyses also suggest that the emergence of novel genome types is unlikely to be driven by widespread convergent evolution and independent fixation of advantageous substitutions. While, in the absence of rigorous experimental validation, several questions concerning the evolutionary processes and the phenotypic characteristics (increased/decreased virulence) remain open, we believe that the approach outlined in this study can be of relevance for the tracking and functional characterization of different types of SARS-CoV-2 genomes.
Ambient light and mimicry as drivers of wing transparency in Lepidoptera
Authors: Arias Mónica , Barbut Jérôme , Rougerie Rodolphe , Dutry Manon , Kohler Mireia , Laulan Baptiste , Paillard Caroline , Berthier Serge , Andraud Christine , Elias Marianne , Gomez Doris 
Published: June 2020

AbstractTransparency reduces prey detectability by predators. While transparent aquatic species hold higher transparency levels as the light availability of their habitat increases, less is known about such variation in terrestrial species. Lepidoptera species exhibiting transparent wings display various levels of transparency. Using two complementary approaches, we explore how the evolution of different transparency degrees relates to habitat openness, activity rhythm and mimicry syndrome (bee/wasp versus dead-leaf mimic). First, by exposing artificial moth-like prey to wild avian predators in a range of habitat openness, we show that survival is lower in more open habitats. We also found that less transparent morphs are more attacked than more transparent ones, regardless of habitat openness degree. Second, by analysing the evolution of wing features and ecological traits in 107 clearwing species, we found that diurnal species transmit more light than nocturnal species under certain conditions (when considering only forewings, at smaller clearwing surfaces and at larger wing lengths) and that species flying in open habitats and exhibiting large percentages of clearwing surface transmit slightly more light than those flying in closed habitats, although this is reversed at smaller percentages of clearwing surfaces. Additionally, bee/wasp mimics are more often diurnal and have higher and less variable light transmittances than dead-leaf mimics, which are more often nocturnal. Flying during the day, in open habitats and mimicking insects with transparent wings seem to promote high light transmittance under certain circumstances. Activity rhythm, habitat openness and species interactions play a crucial role in determining transparency design on land.
Impact of a rapid decline in malaria transmission on antimalarial IgG subclasses and avidity
Authors: Ssewanyana Isaac , Rek John , Rodriguez Isabel , Wu Lindsey , Arinaitwe Emmanuel , Nankabirwa Joaniter I , Beeson James G , Mayanja-Kizza Harriet , Rosenthal Philip J , Dorsey Grant , Kamya Moses , Drakeley Chris , Greenhouse Bryan , K.A.Tetteh Kevin 
Published: June 2020

AbstractUnderstanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response.Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18P. falciparumblood stage antigens in samples from 160 Ugandans collected at 2 time points during high malaria transmission and 2 time points following a dramatic reduction in transmission.Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age.Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.
Estimation of the SNP mutation rate in two vegetatively propagating species of duckweed
Authors: Sandler George , Bartkowska Magdalena , Agrawal Aneil F. , Wright Stephen I. 
Published: June 2020

AbstractMutation rate estimates for vegetatively reproducing organisms are rare, despite their frequent occurrence across the tree of life. Here we report mutation rate estimates in two vegetatively reproducing duckweed species,Lemna minorandSpirodela polyrhiza. We use a modified approach to estimating mutation rates by taking into account the reduction in mutation detection power that occurs when new individuals are produced from multiple cell lineages. We estimate an extremely low per generation mutation rate in both species of duckweed and note that allelic coverage atde novomutation sites is very skewed. We also find no substantial difference in mutation rate between mutation accumulation lines propagated under benign conditions and those grown under salt stress. Finally, we discuss the implications of interpreting mutation rate estimates in vegetatively propagating organisms.
Population dynamics with spatial structure and an Allee effect
Authors: Surendran Anudeep , Plank Michael , Simpson Matthew 
Published: June 2020

AbstractAllee effects describe populations in which long-term survival is only possible if the population density is above some threshold level. A simple mathematical model of an Allee effect is one where initial densities below the threshold lead to population extinction, whereas initial densities above the threshold eventually asymptote to some positive carrying capacity density. Mean field models of population dynamics neglect spatial structure that can arise through short-range interactions, such as short-range competition and dispersal. The influence of such non mean-field effects has not been studied in the presence of an Allee effect. To address this we develop an individual-based model (IBM) that incorporates both short-range interactions and an Allee effect. To explore the role of spatial structure we derive a mathematically tractable continuum approximation of the IBM in terms of the dynamics of spatial moments. In the limit of long-range interactions where the mean-field approximation holds, our modelling framework accurately recovers the mean-field Allee threshold. We show that the Allee threshold is sensitive to spatial structure that mean-field models neglect. For example, we show that there are cases where the mean-field model predicts extinction but the population actually survives and vice versa. Through simulations we show that our new spatial moment dynamics model accurately captures the modified Allee threshold in the presence of spatial structure.
Population genomic and historical analysis reveals a global invasion by bridgehead processes inMimulus guttatus
Authors: Vallejo-Marín Mario , Friedman Jannice , Twyford Alex D. , Lepais Olivier , Ickert-Bond Stefanie M. , Streisfeld Matthew A. , Yant Levi , van Kleunen Mark , Rotter Michael C. , Puzey Joshua R. 
Published: June 2020

AbstractHumans are transforming species ranges worldwide. While artificial translocations trigger biological invasions with negative effects on biodiversity, invasions provide exceptional opportunities to generate ecological and evolutionary hypotheses. Unfortunately, imperfect historical records and exceedingly complex demographic histories present challenges for the reconstruction of invasion histories. Here we combine historical records, extensive worldwide and genome-wide sampling, and demographic analyses to investigate the global invasion of yellow monkeyflowers (Mimulus guttatus) from North America to Europe and the Southwest Pacific. By sampling 521 plants from 158 native and introduced populations genotyped at >44,000 loci, we determined that invasive North AmericanM. guttatuswas first likely introduced to the British Isles from the Aleutian Islands (Alaska), followed by rapid admixture from multiple parts of the native range. Populations in the British Isles then appear to have served as a bridgehead for vanguard invasions worldwide into the rest of Europe, New Zealand and eastern North America. Our results emphasise the highly admixed nature of introducedM. guttatusand demonstrate the potential of introduced populations to serve as sources of secondary admixture, producing novel hybrids. Unravelling the history of biological invasions provides a starting point to understand how invasive populations adapt to novel environments.
Different effects of phytohormones on Fusarium head blight and Fusarium root rot resistance inBrachypodium distachyon
Authors: Haidoulis J F. , Nicholson P. 
Published: June 2020

AbstractFusarium graminearumis a devastating pathogen of small grain cereals causing both Fusarium head blight (FHB) and Fusarium root rot (FRR). Exogenous application of phytohormones has been shown to affect FHB resistance. In contrast to FHB, FRR remains poorly characterised and it is unknown whether phytohormones play similar roles in FHB and FRR. In this present study,B. distachyonfloral tissues at mid-anthesis and root tissues from seedlings were exogenously treated with several phytohormones before inoculation withF. graminearum. The canonical defence-associated phytohormones had differing effects on FHB and FRR. Salicylic acid (SA) significantly increased susceptibility to FRR but not to FHB while jasmonic acid (JA) and ethylene increased resistance to FRR but increased susceptibility to FHB. Additionally, the growth-associated phytohormones auxin and cytokinin significantly increased resistance and susceptibility, respectively, to both diseases. This study is the first to compare phytohormone effects between FHB and FRR in the same host.HighlightThe tissue-dependent effects of defence phytohormones and tissue-independent effects of development phytohormones onF. graminearum-induced Fusarium head blight and Fusarium root rot diseases in the model cerealBrachypodium distachyon.
BBB pathophysiology independent delivery of siRNA in traumatic brain injury
Authors: Li Wen , Qiu Jianhua , Li Xiang-Ling , Aday Sezin , Zhang Jingdong , Conley Grace , Xu Jun , Langer Robert , Mannix Rebekah , Karp Jeffrey M. , Joshi Nitin 
Published: June 2020

AbstractSmall interfering RNA (siRNA) represents a powerful strategy to mitigate the long-term sequelae of traumatic brain injury (TBI). However, poor permeability of siRNA across the blood brain barrier (BBB) poses a major hurdle. One approach to overcome this challenge involves treatment administration while the BBB is physically breached post-injury. However, this approach is only applicable to a subset of injuries with substantial BBB breach and can lead to variable therapeutic response due to the heterogeneity of physical breaching of BBB in TBI. Moreover, since physical breaching of BBB is transient, this approach offers a limited window for therapeutic intervention, which is not ideal as repeated dosing beyond the transient window of physically breached BBB might be required. Herein, we report a nanoparticle platform for BBB pathophysiology-independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density, which maximized the active transport of nanoparticles across BBB. Intravenous injection of engineered nanoparticles, within or outside the window of physically breached BBB in TBI mice resulted in 3-fold higher brain accumulation compared to conventional PEGylated nanoparticles and demonstrated up to 50% gene silencing. To our knowledge, this is the first reported example of BBB pathophysiology-independent drug delivery in TBI, and the first time combined modulation of surface chemistry and coating density has been shown to tune BBB penetration of nanoparticles. Taken together, our approach offers a clinically relevant approach to develop siRNA therapeutics for preventing long-term effects of TBI and deserves further exploration.
Monoterpenes alter TAR1-driven physiology inDrosophilaspecies
Authors: Finetti Luca , Tiedemann Lasse , Zhang Xiaoying , Civolani Stefano , Bernacchia Giovanni , Roeder Thomas 
Published: June 2020

AbstractMonoterpenes are molecules with insecticide properties whose mechanism of action is however not completely elucidated. Furthermore, they seem to be able to modulate the monoaminergic system and several behavioural aspects in insects. In particular, tyramine (TA) and octopamine (OA) and their associated receptors orchestrate physiological processes such as feeding, locomotion and metabolism. Here we show that monoterpenes not only act as biopesticides inDrosophilaspecies but can cause complex behavioural alterations that require a functional type 1 tyramine receptors (TAR1s). Variations in metabolic traits as well as locomotory activity were evaluated in bothDrosophila suzukiiandDrosophila melanogasterafter treatment with three monoterpenes. A TAR1−/−D. melanogasterstrain was used to better understand the relationships between the receptor and monoterpenes-related behavioural changes. Immunohistochemistry analysis revealed that, in theD. melanogasterbrain, TAR1 appeared to be expressed in areas controlling metabolism. In comparison to theD. melanogasterwild type, the TAR−/−flies showed a phenotype characterized by higher triglyceride levels and food intake as well as lower locomotory activity. The monoterpenes, tested at sublethal concentrations, were able to induce a downregulation of the TAR1 coding gene in bothDrosophilaspecies. Furthermore, monoterpenes also altered the behaviour inD. suzukiiandD. melanogasterwild types 24 h after a continuous monoterpene exposure. Interestingly, they were ineffective in modifying the physiological performances of TAR1−/−flies. In conclusion, it appears that monoterpenes not only act as biopesticides forDrosophilabut they can also interfere with its behaviour and metabolism in a TAR1-dependent fashion.
G9a/GLP-Sensitivity of H3K9me2 Demarcates Two Types of Genomic Compartments
Authors: Yan Zixiang , Ji Luzhang , Huo Xiangru , Wang Qianfeng , Zhang Yuwen , Wen Bo 
Published: June 2020

AbstractIn the nucleus, chromatin is folded into hierarchical architecture that is tightly linked to various nuclear functions. However, the underlying molecular mechanisms that confer these architectures remain incompletely understood. Here, we investigated the functional roles of H3 lysine 9 dimethylation (H3K9me2), one of the abundant histone modifications, in three-dimensional (3D) genome organization. Unlike mouse embryonic stem cells (mESCs), inhibition of methyltransferases G9a and GLP in differentiated cells eliminated H3K9me2 predominantly at A-type (active) genomic compartments, and the level of residual H3K9me2 modification was strongly associated with genomic compartments in differentiated cells. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes led to the decreased chromatin-nuclear lamina interactions mainly at G9a/GLP sensitive regions (GSRs), the increased degree of genomic compartmentalization, and the up-regulation of hundreds of genes that were associated with alterations of the 3D chromatin. Collectively, our data demonstrated essential roles of H3K9me2 in 3D genome organization.
Nrl is dispensable for specification of rod photoreceptors in adult zebrafish contrasting a deeply conserved requirement earlier in ontogeny
Authors: Oel A. Phillip , Neil Gavin J. , Dong Emily M. , Balay Spencer D. , Collett Keon , Allison W. Ted 
Published: June 2020

AbstractThe transcription factor NRL (Neural Retinal Leucine-zipper) has been canonized, appropriately enough, as the master regulator of photoreceptor cell fate in the retina. NRL is necessary and sufficient to specify rod cell fate and to preclude cone cell fate in mice. By engineering zebrafish we tested if NRL function has conserved roles beyond mammals or beyond nocturnal species, i.e. in a vertebrate possessing a greater and more typical diversity of cone sub-types. Here, transgenic expression of a Nrl homolog from zebrafish or mouse was sufficient to convert developing zebrafish cones into rod photoreceptors. Zebrafishnrl-/-mutants lacked rods (and had excess UV-sensitive cones) as young larvae, thus the conservation of Nrl function between mice and zebrafish appears sound. These data inform hypotheses of photoreceptor evolution through the Nocturnal Bottleneck, suggesting that a capacity to favor nocturnal vision is a property ofNRLthat predates the emergence of early mammals. Strikingly, however, rods were abundant in adultnrl-/-null mutant zebrafish. Rods developed in adults despite Nrl protein being undetectable. Therefore a yet-to-be-revealed non-canonical pathway independent ofnrlis able to specify the fate of some rod photoreceptors.Highlights- Nrl is conserved and sufficient to specify rod photoreceptors in zebrafish retina- Nrl is necessary for rod photoreceptors in early ontogeny of zebrafish larvae- Zebrafish Nrl is functionally conserved with mouse and human NRL- Remarkably, Nrl is dispensable for rod specification in adult zebrafish
Vascular smooth muscle-derived TRPV1-expressing progenitors are a new source of cold-induced thermogenic adipocytes
Authors: Shamsi Farnaz , Lynes Matthew D. , Piper Mary , Ho Li-Lun , Huang Tian Lian , Tseng Yu-Hua 
Published: June 2020

AbstractBrown adipose tissue (BAT) functions in energy expenditure in part due its role in thermoregulation. The prominent capacity of BAT to enhance fuel utilization and energy expenditure makes it an attractive target for treating obesity and metabolic disorders. Prolonged cold exposure inducesde novorecruitment of brown adipocytes and activates their thermogenic activity. However, the exact source of cold-induced brown adipocytes is not completely understood. In this study, we sought to investigate the cellular origin of cold-induced brown adipocytes using single-cell RNA sequencing. We identified two distinct types of adipocyte progenitors that contribute tode novorecruitment of brown adipocytes in response to cold challenge. One is the previously known Pdgfra-expressing mesenchymal progenitors and the other is a vascular smooth muscle-derived adipocyte progenitor (VSM-APC) population, which expresses the temperature-sensitive ion channel transient receptor potential cation channel subfamily V member 1 (Trpv1). Using flow cytometry and lineage tracing, we demonstrated that the Trpv1posVSM-APCs were indeed distinct from the Pdgfraposprogenitors and could contribute to brown adipocytes with greater thermogenic potential. Together, these findings illustrate a landscape of thermogenic adipose niche at the single cell resolution and identify a new cellular origin for the development of brown adipocytes.
Fast 3D imaging of giant unilamellar vesicles using reflected light-sheet microscopy with single molecule sensitivity
Authors: Szilagyi Sven A. , Burmeister Moritz , Davis Q. Tyrell , Hermsdorf Gero L. , De Suman , Schäffer Erik , Jannasch Anita 
Published: June 2020

AbstractObservation of highly dynamic processes inside living cells at the single molecule level is key for a quantitative understanding of biological systems. However, imaging of single molecules in living cells usually is limited by the spatial and temporal resolution, photobleaching and the signal-to-background ratio. To overcome these limitations, light-sheet microscopes with thin selective plane illumination have recently been developed. For example, a reflected light-sheet design combines the illumination by a thin light-sheet with a high numerical aperture objective for single-molecule detection. Here, we developed a reflected light-sheet microscope with active optics for fast, high contrast, two-color acquisition ofz-stacks. We demonstrate fast volume scanning by imaging a two-color giant unilamellar vesicle (GUV) hemisphere. In addition, the high signal-to-noise ratio enabled the imaging and tracking of single lipids in the cap of a GUV. In the long term, the enhanced reflected scanning light sheet microscope enables fast 3D scanning of artificial membrane systems and cells with single-molecule sensitivity and thereby will provide quantitative and molecular insight into the operation of cells.