bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly contiguous assemblies of 101 drosophilid genomes
Authors: Kim Bernard Y. , Wang Jeremy R. , Miller Danny E. , Barmina Olga , Delaney Emily , Thompson Ammon , Comeault Aaron A. , Peede David , D’Agostino Emmanuel R. R. , Pelaez Julianne , Aguilar Jessica M. , Haji Diler , Matsunaga Teruyuki , Armstrong Ellie E. , Zych Molly , Ogawa Yoshitaka , Stamenković-Radak Marina , Jelić Mihailo , Savić Veselinović Marija , Tanasković Marija , Erić Pavle , Gao Jian-jun , Katoh Takehiro K. , Toda Masanori J. , Watabe Hideaki , Watada Masayoshi , Davis Jeremy S. , Moyle Leonie C. , Manoli Giulia , Bertolini Enrico , Košťál Vladimír , Hawley R. Scott , Takahashi Aya , Jones Corbin D. , Price Donald K. , Whiteman Noah , Kopp Artyom , Matute Daniel R. , Petrov Dmitri A. 
Published: December 2020

ABSTRACTOver 100 years of studies inDrosophila melanogasterand related species in the genusDrosophilahave facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long read sequencing allow high quality genome assemblies for tens or even hundreds of species to be generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of high-quality assemblies for 101 lines of 95 drosophilid species encompassing 14 species groups and 35 sub-groups with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. These assemblies, along with detailed wet lab protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution within this key group.
Distinguishing the behavioral potencies of α-pyrrolidino-phenone cathinone stimulants
Authors: Taffe Michael A. , Nguyen Jacques D. , Vandewater Sophia A. , Grant Yanabel , Dickerson Tobin J. 
Published: December 2020

AbstractThe α-pyrrolidino-phenone cathinone stimulants first came to widespread attention because of bizarre behavior consequent to the use of α-pyrrolidinopentiophenone (α-PVP, “flakka”) reported in the popular press. As with other designer drugs, diversification of cathiones has been driven by desireable subjective effects, but also by attempts to stay ahead of legal controls of specific molecules. The α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopropiophenone (α-PPP) compounds have been relatively under-investigated relative to α-PVP and provide a key opportunity to also investigate structure-activity relationships, i.e., how the extension of the alpha carbon chain may affect potency or efficacy. Male and female rats were used to contrast the effects of α-PHP and α-PPP with those of α-PVP in altering wheel activity and effects on spontaneous locomotion and body temperature were assessed in female rats. The α-PHP and α-PVP compounds (5, 10 mg/kg, i.p.) suppressed wheel activity in female and male rats, whereas α-PPP was only effective in female rats. Inhalation of α-PHP or α-PVP by female rats suppressed wheel activity for an abbreviated duration, compared with the injection route. Spontaneous activity was increased in a dose-dependent manner by all three compounds in female rats, and a small decrements in body temperature were observed after the highest dose of all three compounds. These data show that all three of the α-pyrrolidino-phenone cathinones exhibit significant stimulant-like activity in both male and female rats. Differences were minor and were mostly in potency and the duration of activity. Abuse liability is therefore likely to be equivalent for all three pyrrolidino-phenones.
Genomic diversity analysis of SARS-CoV-2 genomes in Rwanda
Authors: Nzungize Lambert , Ndishimye Pacifique , Zakham Fathiah 
Published: December 2020

AbstractCOVID-19 (Coronavirus disease 2019) is an emerging pneumonia-like respiratory disease of humans and is recently spreading across the globe.ObjectiveTo analyze the genome sequence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) isolated from Rwanda with other viral strains from African countries.MethodsWe downloaded 75 genomes sequences of clinical SARS-CoV-2 from the GISAID (global initiative on sharing all influenza data) database and we comprehensively analyzed these SARS-CoV-2 genomes sequences alongside with Wuhan SARS-CoV-2 sequences as the reference strains.ResultsWe analyzed 75 genomes sequences of SARS-CoV-2 isolated in different African countries including 10 samples of SARS-CoV-2 isolated in Rwanda between July and August 2020. The phylogenetic analysis of the genome sequence of SARS-CoV-2 revealed a strong identity with reference strains between 90-95%. We identified a missense mutation in four proteins including orf1ab polyprotein, NSP2, 2’-O-ribose methyltransferase and orf1a polyprotein. The most common changes in the base are C > T. We also found that all clinically SARS-CoV-2 isolated from Rwanda had genomes belonging to clade G and lineage B.1.ConclusionsTracking the genetic evolution of SARS-CoV-2 over time is important to understand viral evolution pathogenesis. These findings may help to implement public health measures in curbing COVID-19 in Rwanda.
CD137-stimulated cytotoxic T lymphocytes exert superior tumour control due to an enhanced antimitotic effect on tumour cells
Authors: Beck Richard J , Weigelin Bettina , Beltman Joost B 
Published: December 2020

AbstractSeveral immunotherapeutic strategies for the treatment of cancer are under development. Two prominent strategies are adoptive cell transfer (ACT) of cytotoxic T lymphocytes (CTLs) and modulation of CTL function with immune checkpoint inhibitors or with costimulatory antibodies. Despite some success with these approaches, there remains a lack of detailed and quantitative descriptions of the events following CTL transfer and the impact of immunomodulation.Here, we have applied ordinary differential equation models to two photon imaging data derived from a B16F10 murine melanoma. Models were parameterised with data from two different treatment conditions: either ACT-only, or ACT with intratumoural costimulation using a CD137 targeted antibody. Model dynamics and best fitting parameters were compared, in order to assess the mode of action of the CTLs and examine how the CD137 antibody influenced their activities.We found that the cytolytic activity of the transferred CTLs was minimal without CD137 costimulation, and that the CD137 targeted antibody did not enhance the per-capita killing ability of the transferred CTLs. Instead, the results of our modelling study suggest that an antiproliferative effect of CTLs exerted upon the tumour likely accounted for the majority of the reduction in tumour growth after CTL transfer. We found that CD137 most likely improved tumour control via enhancement of this antiproliferative effect, as well as prolonging the period in which CTLs were inside the tumour, leading to a sustained duration of their antitumour effects following CD137 stimulation.SignificanceCTLs play an important role in controlling tumours, and improved understanding of how they accomplish this will benefit immunotherapeutic cancer treatment strategies. Stimulation of CTLs by targeting their CD137 receptor is a strategy currently under investigation for enhancing responses against tumours, yet so far only limited quantitative knowledge regarding the effects of such stimulation upon CTLs has been obtained. Here, we develop mathematical models to describe dynamicin vivotwo-photon imaging of tumour infiltrating CTLs, to characterise differences in their function either in the presence or absence of a CD137 agonist antibody. We showed that an increased antiproliferative effect and a more sustained presence of CTLs within the tumour were the most significant effects associated with anti-CD137 treatment.
Scaling of Internal Organs duringDrosophilaEmbryonic Development
Authors: Tiwari P. , Rengarajan H. , Saunders T. E. 
Published: December 2020

AbstractMany species show a diverse range of sizes; for example, domestic dogs have large variation in body mass. Yet, the internal structure of the organism remains similar,i.e. the system scales to organism size.Drosophila melanogasterhas been a powerful model system for exploring scaling mechanisms. In the early embryo, gene expression boundaries scale very precisely to embryo length. Later in development, the adult wings grow with remarkable symmetry and scale well with animal size. Yet, our knowledge of whether internal organs initially scale to embryo size remains largely unknown. Here, we utilise artificially smallDrosophilaembryos to explore how three critical internal organs – the heart, hindgut and ventral nerve cord (VNC) – adapt to changes in embryo morphology. We find that the heart scales precisely with embryo length. Intriguingly, reduction in cardiac cell length, rather than number, appears to be important in controlling heart length. The hindgut – which is the first chiral organ to form – displays scaling with embryo size under large-scale changes in the artificially smaller embryos but shows few hallmarks of scaling within wild-type size variation. Finally, the VNC only displays weak scaling behaviour; even large changes in embryo geometry result in only small shifts in VNC length. This suggests that the VNC may have an intrinsic minimal length, which is largely independent of embryo length. Overall, our work shows that internal organs can adapt to embryo size changes inDrosophila. but the extent to which they scale varies significantly between organs.
Reassessing associations between white matter and behaviour with multimodal microstructural imaging
Authors: Lazari Alberto , Salvan Piergiorgio , Cottaar Michiel , Papp Daniel , van der Werf Olof Jens , Johnstone Ainslie , Sanders Zeena-Britt , Sampaio-Baptista Cassandra , Eichert Nicole , Miyamoto Kentaro , Winkler Anderson , Callaghan Martina F. , Nichols Thomas E. , Stagg Charlotte J , Rushworth Matthew , Verhagen Lennart , Johansen-Berg Heidi 
Published: December 2020

AbstractSeveral studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2*).Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone.To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40 to 200 may be required to detect such joint multimodal effects, depending on the task being considered.These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WM’s relationship with behaviour, suggesting that variable biological effects may be shaping their interaction.HighlightsPre-registered testing of microstructural imaging across modalities (FA, MT, R1, R2*) to test WM-behaviour relationships.Partial support for FA-behaviour relationships hypothesised based on previous literature.Multimodal approaches can help detect WM-behaviour relationships that are not detected with FA alone.Sample sizes of 40 to 200 may be needed to detect myelin-behaviour relationships in joint multimodal analyses.Variable biological effects may be shaping WM-behaviour relationships.
Predicting which genes will respond to perturbations of a TF: TF-independent properties of genes are major determinants of their responsiveness
Authors: Kang Yiming , Brent Michael R. 
Published: December 2020

ABSTRACTBackgroundThe ability to predict which genes will respond to perturbation of a TF’s activity serves as a benchmark for our systems-level understanding of transcriptional regulatory networks. In previous work, machine learning models have been trained to predict static gene expressionlevelsin a given sample by using data from the same or similar conditions, including data on TF binding locations, histone marks, or DNA sequence. We report on a different challenge – training machine learning models that can predict which genes will respond to perturbation of a TFwithout using any data from the perturbed cells.ResultsExisting TF location data (ChIP-Seq) from human K562 cells have no detectable utility for predicting which genes will respond to perturbation of the TF, but data obtained by newer methods in yeast cells are useful. TF-independent features of genes, including their pre-perturbation expression level and expression variation, are very useful for predicting responses to TF perturbations. This shows that some genes are poised to respond to TF perturbations and others are resistant, shedding significant light on why it has been so difficult to predict responses from binding locations. Certain histone marks (HMs), including H3K4me1 and H3K4me3, have some predictive power, especially when downstream of the transcription start site. In human, the predictive power of HMs is much less than that of gene expression level and variation. Code is available athttps://github.com/yiming-kang/TFPertRespExplainer.ConclusionsSequence-based or epigenetic properties of genes strongly influence their tendency to respond to direct TF perturbations, partially explaining the oft-noted difficulty of predicting responsiveness from TF binding location data. These molecular features are largely reflected in and summarized by the gene’s expression level and expression variation.
Unsupervised logic-based mechanism inference for network-driven biological processes
Authors: Prugger Martina , Einkemmer Lukas , Beik Samantha P. , Harris Leonard A. , Lopez Carlos F. 
Published: December 2020

AbstractModern analytical techniques enable researchers to collect data about cellular states, before and after perturbations. These states can be characterized using analytical techniques, but the inference of regulatory interactions that explain and predict changes in these states remains a challenge. Here we present a generalizable unsupervised approach to generate parameter-free, logic-based mechanistic hypotheses of cellular processes, described by multiple discrete states. Our algorithm employs a Hamming-distance based approach to formulate, test, and identify, the best mechanism that links two states. Our approach comprises two steps. First, a model with no prior knowledge except for the mapping between initial and attractor states is built. Second, we employ biological constraints to improve model fidelity. Our algorithm automatically recovers the relevant dynamics for the explored models and recapitulates all aspects of the original models biochemical species concentration dynamics. We then conclude by placing our results in the context of ongoing work in the field and discuss how our approach could be used to infer mechanisms of signaling, gene-regulatory, and any other input-output processes describable by logic-based mechanisms.
Shoot-root interaction in control of camalexin exudation in Arabidopsis
Authors: Koprivova Anna , Volz Vanessa , Kopriva Stanislav 
Published: December 2020

AbstractPlants exude secondary metabolites from the roots to shape the composition and function of their microbiome. Many of these compounds are known for their anti-microbial activity and are part of the plant immunity, such as the indole-derived phytoalexin camalexin. Here we studied the dynamics of camalexin synthesis and exudation upon induction ofArabidopsis thalianawith a plant growth promotion bacteriaPseudomonas sp. CH267 or a bacterial pathogenBurkholderia glumaePG1. We show that while the camalexin accumulation and exudation is more rapidly but transiently induced upon interaction with the growth promoting strain, the pathogen induces a higher and more stable camalexin levels. The concentration of camalexin in shoots, roots and exudates is well correlated, triggering a question on the origin of the exuded camalexin. By combination of experiments with cut shoots and roots and grafting of wild type plant with mutants in camalexin synthesis we showed that while camalexin can be produced and released by both organs, in intact plant the exuded camalexin originates in the shoots. We show that camalexin synthesis in response toB. glumaePG1 is dependent on cooperation of four CYP71 genes and a loss of function of any of them reduces camalexin synthesis. In conclusion, camalexin synthesis seems to be controlled on a whole plant level and coordinated between shoots and roots.
ViralRecall – A Flexible Command-Line Tool for the Detection of Giant Virus Signatures in ‘Omic Data
Authors: Aylward Frank O. , Moniruzzaman Mohammad 
Published: December 2020

AbstractGiant viruses are widespread in the biosphere and play important roles in biogeochemical cycling and host genome evolution. Also known as Nucleo-Cytoplasmic Large DNA Viruses (NCLDV), these eukaryotic viruses harbor the largest and most complex viral genomes known. Recent studies have shown that NCLDV are frequently abundant in metagenomic datasets, and that sequences derived from these viruses can also be found endogenized in diverse eukaryotic genomes. The accurate detection of sequences derived from NCLDV is therefore of great importance, but this task is challenging owing to both the high level of sequence divergence between NCLDV families and the extraordinarily high diversity of genes encoded in their genomes, including some encoding for metabolic or translation-related functions that are typically found only in cellular lineages. Here we present ViralRecall, a bioinformatic tool for the identification of NCLDV signatures in ‘omic data. This tool leverages a library of Giant Virus Orthologous Groups (GVOGs) to identify sequences that bear signatures of NCLDV. We demonstrate that this tool can effectively identify NCLDV sequences with high sensitivity and specificity. Moreover, we show that it can be useful both for removing contaminating sequences in metagenome-assembled viral genomes as well as the identification of eukaryotic genomic loci that derived from NCLDV. ViralRecall is written in Python 3.5 and is freely available on GitHub:https://github.com/faylward/viralrecall.
DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling
Authors: Aghayeva Ulkar , Bhattacharya Abhishek , Sural Surojit , Jaeger Eliza , Churgin Matthew , Fang-Yen Christopher , Hobert Oliver 
Published: December 2020

ABSTRACTMany cell types display the remarkable ability to alter their cellular phenotype in response to specific external or internal signals. Such phenotypic plasticity is apparent in the nematodeC. eleganswhen adverse environmental conditions trigger entry into the dauer diapause stage. This entry is accompanied by structural, molecular and functional remodeling of a number of distinct tissue types of the animal, including its nervous system. The transcription factor effectors of three different hormonal signaling systems, the insulin-responsive DAF-16/FoxO transcription factor, the TGFβ-responsive DAF-3/SMAD transcription factor and the steroid nuclear hormone receptor, DAF-12/VDR, a homolog of the vitamin D receptor, were previously shown to be required for entering the dauer arrest stage, but their cellular and temporal focus of action for the underlying cellular remodeling processes remained incompletely understood. Through the generation of conditional alleles that allowed us to spatially and temporally control gene activity, we show here that all three transcription factors are not only required to initiate tissue remodeling upon entry into the dauer stage, as shown before, but are also continuously required to maintain the remodeled state. We show that DAF-3/SMAD is required in sensory neurons to promote and then maintain animal-wide tissue remodeling events. In contrast, DAF-16/FoxO or DAF-12/VDR act cell autonomously to control anatomical, molecular and behavioral remodeling events in specific cell types. Intriguingly, we also uncover non-cell autonomous function of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling, indicating the presence of several insulin-dependent inter-organ signaling axes. Our findings provide novel perspectives on how hormonal systems control tissue remodeling.
Zfp36l1 and Zfp36l2 balances proliferation and differentiation in the developing retina
Authors: Wu Fuguo , Kaczynski Tadeusz , Matheson Louise S. , Liu Tao , Wang Jie , Turner Martin , Mu Xiuqian 
Published: December 2020

AbstractBoth transcriptional and post-transcriptional regulation of gene expression play significant roles in diverse biological processes, but little is known about how post-transcriptional regulation impacts retinal development. Here we report our study of the function of two members of the TTP (tristetraprolin) mRNA binding protein family, Zfp36l1 and Zfp36l2, in the developing retina. TTP proteins are highly conserved CCCH zinc finger proteins, which carry out their functions by promoting target mRNA decay and modulating translation. We found that Zfp36l1 and Zfp36l2 were expressed in retinal progenitor cells (RPCs) during development and Müller glial cells and photoreceptors in the mature retina. Our analysis of the mutant retinas showed that, whereas the single knockout retinas were largely normal, the double knockout (DKO) retina showed decreased RPC proliferation and increased differentiation of multiple retinal cell types. RNA-seq analysis confirmed the imbalance of proliferation and differentiation in the DKO retina. Gene ontology and in silico target gene analysis indicates that Zfp36l1 and Zfp36l2 exert their function by directly regulating multiple classes of proteins, including components of multiple signaling pathways such as the sonic hedgehog pathway and the Notch pathway, cell cycle regulators, and most interestingly transcription factors directly involved in retinal differentiation. These results reveal a new tier of gene regulation controlling retinal development.