bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical modeling of genetic pest management through female-specific lethality: Is one locus better than two?
Authors: Vella Michael R. , Gould Fred , Lloyd Alun L. 
Published: April 2020

AbstractMany novel genetic approaches are under development to combat insect pests. One genetic strategy aims to suppress or locally eliminate a species through large, repeated releases of genetically engineered strains that render female offspring unviable under field conditions. Strains with this female-killing (FK) characteristic have been developed either with all of the molecular components in a single construct or with the components in two constructs inserted at independently assorting loci. Strains with two constructs are typically considered to be only of value as research tools and for producing solely male offspring in rearing factories which are subsequently sterilized by radiation before release. A concern with the two-construct strains is that once released, the two constructs would become separated and therefore non-functional. The only FK strains that have been released in the field without sterilization are single-construct strains. Here, we use a population genetics model with density dependence to evaluate the relative effectiveness of female killing approaches based on single- and two-construct arrangements. We find that, in general, the single-construct arrangement results in slightly faster population suppression, but the two-construct arrangement can eventually cause stronger suppression and cause local elimination with a smaller release size. Based on our results, there is no a priori reason that males carrying two independently segregating constructs need to be sterilized prior to release. In some cases, a fertile release would be more efficient for population suppression.
WD 40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance inDeinococcus radiodurans
Authors: Sharma Dhirendra Kumar , Bihani Subhash C. , Misra Hari S , Rajpurohit Yogendra S. 
Published: April 2020

SummaryRqkA, a DNA damage responsive Serine / Threonine kinase is characterized for its role in DNA repair and cell division inD. radiodurans. It has a unique combination of a kinase domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 domain is comprised of eight β propeller repeats held together via “tryptophan-docking motifs” and forming a typical ‘velcro’ closure structure. RqkA mutants lacking the WD40 region (hereafter referred to as WD mutant) could not complement RqkA loss in γ radiation resistance inD. radioduransand lacked γ radiation mediated activation of kinase activityin vivo. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogateE. colicells. Further, unlike wild type enzyme, the kinase activity of its WD40 mutants was not stimulated by Pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ interaction and stimulation of its kinase activity. Together, results highlighted the importance of the WD40 domain in the regulation of RqkA kinase signaling functionsin vivoand thus the role of WD40 domain in the regulation of any STPK is the first time demonstrated in bacteria.ImportanceThis study highlights the importance of the WD40 domain in activity regulation and signaling activity of bacterial serine/ threonine kinase for the first time in the bacterial response to gamma radiation and DNA damage.
Capsid Proteins are Necessary for Replication of a Parvovirus
Authors: Labadie Thomas , Garcia Deborah , Mutuel Doriane , Ogliastro Mylène , Cambray Guillaume 
Published: April 2020

AbstractDespite tight genetic compression, viral genomes are often organized in functional gene clusters, a modular structure that might favor their evolvability. This has greatly facilitated biotechnological developments, such as the recombinant Adeno-Associated Virus (AAV) systems for gene therapy. Following this lead, we endeavored to engineer the related insect parvovirusJunonia coeniadensovirus (JcDV) to create addressable vectors for insect pest biocontrol. To enable safer manipulation of capsid mutants, we translocated the non-structural (ns) gene cluster outside the viral genome. To our dismay, this yielded a virtually non-replicable clone. We linked the replication defect to an unexpected modularity breach, asnstranslocation truncated the overlapping 3’ UTR of the capsid transcript (vp). We found that nativevp3’UTR is necessary to high VP production, but that decreased expression do not adversely impact the expression of NS proteins, which are known replication effectors. As nonsensevpmutations recapitulate the replication defect, VP proteins appear directly implicated in the replication process. Our findings suggest intricate replication-encapsidation couplings that favor maintenance of genetic integrity. We discuss possible connections with an intriguing cis-packaging phenomenon previously observed in parvoviruses, whereby capsids preferentially package the genome from which they were expressed.ImportanceDensoviruses could be used as biological control agents to manage insect pests. Such applications require in depth biological understanding and associated molecular tools. However, the genomes of these viruses remain hard to manipulate due too poorly tractable secondary structures at their extremities. We devised a construction strategy that enable precise and efficient molecular modifications. Using this approach, we endeavored to create a split clone of theJunonia coeniadensovirus (JcDV) that can be used to safely study the impact of capsid mutations on host specificity. Our original construct proved to be non-functional. Fixing this defect led us to uncover that capsid proteins and their correct expression are essential for continued rolling-hairpin replication. This points to an intriguing link between replication and packaging, which might be shared with related viruses. This serendipitous discovery illustrates the power of synthetic biology approaches to advance our knowledge of biological systems.
Similar gut bacterial microbiota in two fruit-feeding moth pests collected from different host species and locations
Authors: Gong Qiang , Cao Li-Jun , Chen Jin-Cui , Gong Ya-Jun , Pu De-Qiang , Huang Qiong , Hoffmann Ary Anthony , Wei Shu-Jun 
Published: April 2020

AbstractNumerous gut microbes are associated with insects, but their composition remains largely unknown for many insect groups, along with factors influencing their composition. Here, we compared gut bacterial microbiota of two co-occurring agricultural pests, the peach fruit moth (PFM) and the oriental fruit moth (OFM), collected from different orchards and host plant species. Gut microbiota of both species was mainly composed of bacteria from Proteobacteria, followed by Firmicutes. The two species shared bacteria from the generaPseudomonas,Gluconobacter,Acetobacter, andPantoea, although endosymbioticWolbachiawas the most abundant genus in PFM andLactobacilluswas the most abundant in OFM. PFM tended to have lower diversity and richness of gut microbiota than OFM; however, only some of the comparisons were statistically significant. Orchards can influence gut microbiota in terms of richness, particularly for PFM, but not so much for diversity parameters. Functional prediction of gut microbiota showed that the top pathways are amino acid metabolism, translation, and membrane transport in both species, but their abundance varied between the two moth species. These results show that two fruit moths share many features of gut microbiota, and the bacterial species are relatively stable within moth species even when they use different host plants. Our study suggests that fruit-feeding behavior may play a role in shaping gut microbiota of the two fruit moths, which may provide microbial targets for pest control.ImportanceUnderstanding the associated microbes with insects can point to new targets for pest control. Here we compared bacterial community in the gut of two co-occurring agricultural pests, the peach fruit moth (PFM) and the oriental fruit moth (OFM), collected from different orchards and host plant species. We found that the bacterial generaPseudomonas,Gluconobacter,Acetobacter, andPantoeaare abundant and shared in two moths. The composition of the bacterial species is relatively stable within moth species even when they use different host plants, indicating that the gut microbiota community in the PFM and OFM is likely to be related to their fruit-feeding behavior. The findings have implications for developing novel pest control approaches by targeting gut microbes associated with the two moths.
The impact of early social distancing at COVID-19 Outbreak in the largest Metropolitan Area of Brazil
Authors: Ganem Fabiana , Mendes Fabio Macedo , de Oliveira Silvano Barbosa , Porto Victor Bertollo Gomes , de Araújo Wildo Navegantes , Nakaya Helder I. , Diaz-Quijano Fredi A. , Croda Julio 
Published: April 2020

AbstractWe calculated the impact of early social distancing on the COVID-19 transmission in the São Paulo metropolitan area and forecasted the ICU beds needed to cope the epidemic demand by using an age-stratified SEIR model. Within 60 days, these measures would avoid 89,133 deaths.
Unsupervised learning predicts human perception and misperception of gloss
Authors: Storrs Katherine R. , Anderson Barton L. , Fleming Roland W. 
Published: April 2020

AbstractReflectance, lighting, and geometry combine in complex ways to create images. How do we disentangle these to perceive individual properties, like surface glossiness? We suggest that brains disentangle properties by learning to model statistical structure in proximal images. To test this, we trained unsupervised generative neural networks on renderings of glossy surfaces and compared their representations with human gloss judgments. The networks spontaneously cluster images according to distal properties such as reflectance and illumination, despite receiving no explicit information about them. Intriguingly, the resulting representations also predict the specific patterns of ‘successes’ and ‘errors’ in human perception. Linearly decoding specular reflectance from the model’s internal code predicts human gloss perception better than ground truth, supervised networks, or control models, and predicts, on an image-by-image basis, illusions of gloss perception caused by interactions between material, shape, and lighting. Unsupervised learning may underlie many perceptual dimensions in vision, and beyond.
Unsupervised protein embeddings outperform hand-crafted sequence and structure features at predicting molecular function
Authors: Villegas-Morcillo Amelia , Makrodimitris Stavros , van Ham Roeland C.H.J. , Gomez Angel M. , Sanchez Victoria , Reinders Marcel J.T. 
Published: April 2020

AbstractMotivationProtein function prediction is a difficult bioinformatics problem. Many recent methods use deep neural networks to learn complex sequence representations and predict function from these. Deep supervised models require a lot of labeled training data which are not available for this task. However, a very large amount of protein sequences without functional labels is available.ResultsWe applied an existing deep sequence model that had been pre-trained in an unsupervised setting on the supervised task of protein function prediction. We found that this complex feature representation is effective for this task, outperforming hand-crafted features such as one-hot encoding of amino acids,k-mer counts, secondary structure and backbone angles. Also, it partly negates the need for deep prediction models, as a two-layer perceptron was enough to achieve state-of-the-art performance in the third Critical Assessment of Functional Annotation benchmark. We also show that combining this sequence representation with protein 3D structure information does not lead to performance improvement, hinting that three-dimensional structure is also potentially learned during the unsupervised pre-training.AvailabilityImplementations of all used models can be found athttps://github.com/stamakro/GCN-for-Structure-and-Function.Contactameliavm@ugr.esSupplementary informationSupplementary data are available online.
Lamin B2 follows lamin A/C- mediated nuclear mechanics and cancer cell invasion efficacy
Authors: Vortmeyer-Krause Marina , Lindert Mariska te , Riet Joost te , Boekhorst Veronika te , Marke Rene , Perera Ramanil , Isermann Philipp , van Oorschot Tom , Zwerger Monika , Yang Fengwei , Svoreň Martin , Madzvamuse Anotida , Lammerding Jan , Friedl Peter , Wolf Katarina 
Published: April 2020

AbstractInterstitial tumor cell invasion depends upon complex mechanochemical adaptation of both cell body and the rigid nucleus in response to extracellular tissue topologies. Nuclear mechanics during cell migration through confined environments is controlled by A-type lamins, however, the contribution of B-type lamins to the deformability of the nucleus remains unclear. Using systematic expression regulation of different lamin isoforms, we applied multi-parameter wet-lab and in silico analysis to test their impact on nuclear mechanics, shape regulation, and cancer cell migration. Modulation of lamin A/C and B2 but not B1 isoforms controlled nuclear deformation and viscoelasticity, whereby lamin B2 generally followed lamin A/C-mediated effects. Cell migration rates were altered by 5 to 9-fold in dense collagen environments and synthetic devices, with accelerated rates after lamin downregulation and reverse effects after lamin upregulation, with migration rates strongly depending on nuclear shape change. These findings implicate cooperation of lamin B2 with lamin A/C in regulating nuclear mechanics for shape adaptation and migration efficacy.SummaryNuclear deformability during cancer cell invasion and metastasis is critically regulated by lamin A. Here, researchers showed that lamin B2 also contributes to nuclear mechanics, implicating cooperating lamin networks regulating nuclear integrity, migration efficacy, and metastatic tumor progression.
Targeting c-Myc with a novel Peptide Nuclear Delivery Device
Authors: Ting Trinda Anne , Chaumet Alexandre , Bard Frederic 
Published: April 2020

AbstractBiologics such as peptides and antibodies are a well-established class of therapeutics. However, their intracellular delivery remains problematic. In particular, methods to efficiently inhibit intra-nuclear targets are lacking. We previously described that Pseudomonas Exotoxin A reaches the nucleoplasm via the endosomes-to-nucleus trafficking pathway. Here, we show that a non-toxic truncated form of PE can be coupled to peptides and efficiently reach the nucleoplasm. It can be used as a Peptide Nuclear Delivery Device (PNDD) to deliver polypeptidic cargos as large as Glutathione-S-transferase (GST) to the nucleus. PNDD1 is a fusion of PNDD to the c-myc inhibitor peptide H1. PNDD1 is able to inhibit c-Myc dependent transcription at nanomolar concentration. In contrast, H1 fused to various cell-penetrating peptides are active only in the micromolar range. PNDD1 attenuates cell proliferation and induces cell death in various tumor cell lines. In particular, several patient-derived Diffuse Large B-Cell Lymphomas cell lines die after exposure to PNDD1, while normal B-cells survive. Altogether, our data indicate that PNDD is a powerful tool to bring active cargo to the nucleus and PNDD1 could be the basis of a new therapy against lymphoma.
Disseminating cells in human oral tumours acquire an EMT cancer stem cell state that is predictive of metastasis
Authors: Youssef Gehad , Gammon Luke , Ambler Leah , Lunetto Sophia , Scemama Alice , Cottom Hannah , Piper Kim , Mackenzie Ian C. , Philpott Michael P. , Biddle Adrian 
Published: April 2020

AbstractCancer stem cells (CSCs) undergo epithelial-mesenchymal transition (EMT) to drive metastatic dissemination in experimental cancer models. However, tumour cells undergoing EMT have not been observed disseminating into the tissue surrounding human tumour specimens, leaving the relevance to human cancer uncertain. We have previously identified both EpCAM and CD24 as markers of EMT CSCs with enhanced plasticity. This afforded the opportunity to investigate whether retention of EpCAM and CD24 alongside upregulation of the EMT marker Vimentin can identify disseminating EMT CSCs in human tumours. Examining disseminating tumour cells in over 12,000 imaging fields from 84 human oral cancer specimens, we see a significant enrichment of single EpCAM, CD24 and Vimentin co-stained cells disseminating beyond the tumour body in metastatic specimens. Through training an artificial neural network, these predict metastasis with high accuracy (cross-validated accuracy of 87-89%). In this study, we have observed single disseminating EMT CSCs in human oral cancer specimens, and these are highly predictive of metastatic disease.
Distribution of disease-causing germline mutations in coiled-coils suggests essential role of their N-terminal region
Authors: Kalman Zsofia E. , Mészáros Bálint , Gáspári Zoltán , Dobson Laszlo 
Published: April 2020

AbstractNext-generation sequencing resulted in the identification of a huge number of naturally occurring variations in human proteins. The correct interpretation of the functional effects of these variations necessitates the understanding of how they modulate protein structure. Coiled-coils are α-helical structures responsible for a diverse range of functions, but most importantly, they facilitate the structural organization of macromolecular scaffoldsviaoligomerization. In this study, we analyzed a comprehensive set of disease-associated germline mutations in coiled-coil structures. Our results highlight the essential role of residues near the N-terminal part of coiled-coil regions, possibly critical for superhelix assembly and folding in some cases. We also show that coiled-coils of different oligomerization states exhibit characteristically distinct patterns of disease-causing mutations. Our study provides structural and functional explanations on how disease emerges through the mutation of these structural motifs.
Gain and Loss of Function mutations in biological chemical reaction networks: a mathematical model with application to colorectal cancer cells
Authors: Sommariva Sara , Caviglia Giacomo , Piana Michele 
Published: April 2020

AbstractThis paper studies a system of Ordinary Differential Equations modeling a chemical reaction network and derives from it a simulation tool mimicking Loss of Function and Gain of Function mutations found in cancer cells. More specifically, from a theoretical perspective, our approach focuses on the determination of moiety conservation laws for the system and their relation with the corresponding stoichiometric surfaces. Then we show that Loss of Function mutations can be implemented in the model via modification of the initial conditions in the system, while Gain of Function mutations can be implemented by eliminating specific reactions. Finally, the model is utilized to examine in detail the G1-S phase of a colorectal cancer cell.
Decoding transcriptional regulation via a human gene expression predictor
Authors: Wang Yuzhou , Zhang Yu , Gong Jiazhen , Bao Jianqiang , Ma Shisong 
Published: April 2020

ABSTRACTTranscription factors (TF) regulate cellular activities via controlling gene expression, but a predictive model describing how TFs quantitatively modulate human transcriptomes was lacking. We constructed a universal human gene expression predictor and utilized it to decode transcriptional regulation. Using 1613 TFs’ expression, the predictor reconstituted highly accurate transcriptomes for samples derived from a wide range of tissues and conditions. The predictor’s broad applicability indicated it had recapitulated the quantitative relationships between TFs and target genes ubiquitous across tissues. Significant interacting TF-target gene pairs were then extracted from the predictor and enabled downstream inference of TF regulators for diverse pathways involved in development, immunity, metabolism, and stress response. Thus, we present a novel approach to study human transcriptional regulation following the “understanding by modeling” principle.
The histone variant H2A.Z is required to establish normal patterns of H3K27 methylation inNeurospora crassa
Authors: Courtney Abigail J. , Kamei Masayuki , Ferraro Aileen R. , Gai Kexin , He Qun , Honda Shinji , Lewis Zachary A. 
Published: April 2020

ABSTRACTNeurospora crassacontains a minimal Polycomb repression system, which provides rich opportunities to explore Polycomb-mediated repression across eukaryotes and enables genetic studies that can be difficult in plant and animal systems. Polycomb Repressive Complex 2 is a multi-subunit complex that deposits mono-, di-, and tri-methyl groups on lysine 27 of histone H3, and tri-methyl H3K27 is a molecular marker of transcriptionally repressed facultative heterochromatin. In mouse embryonic stem cells and multiple plant species, H2A.Z has been found to be co-localized with H3K27 methylation. H2A.Z is required for normal H3K27 methylation in these experimental systems, though the regulatory mechanisms are not well understood. We report here thatNeurospora crassamutants lacking H2A.Z or SWR-1, the ATP-dependent histone variant exchanger, exhibit a striking reduction in levels of H3K27 methylation. RNA-sequencing revealed downregulation ofeed, encoding a subunit of PRC2, in anhH2Azmutant compared to wild type and overexpression of EED in a ΔhH2Az;Δeedbackground restored most H3K27 methylation. Reducedeedexpression leads to region-specific losses of H3K27 methylation suggesting that EED-dependent mechanisms are critical for normal H3K27 methylation at certain regions in the genome.AUTHOR SUMMARYEukaryotic DNA is packaged with histone proteins to form a DNA-protein complex called chromatin. Inside the nucleus, chromatin can be assembled into a variety of higher-order structures that profoundly impact gene expression. Polycomb Group proteins are important chromatin regulators that control assembly of a highly condensed form of chromatin. The functions of Polycomb Group proteins are critical for maintaining stable gene repression during development of multicellular organisms, and defects in Polycomb proteins are linked to disease. There is significant interest in elucidating the molecular mechanisms that regulate the activities of Polycomb Group proteins and the assembly of transcriptionally repressed chromatin domains. In this study, we used a model fungus to investigate the regulatory relationship between a histone variant, H2A.Z, and a conserved histone modifying enzyme complex, Polycomb Repressive Complex 2 (PRC2). We found that H2A.Z is required for normal expression of a PRC2 component. Mutants that lack H2A.Z have defects in chromatin structure at some parts of the genome, but not others. Identification of PRC2-target domains that are differentially dependent on EED provides insights into the diverse mechanisms that regulate assembly and maintenance of facultative heterochromatin in a simple model system.Data Reference NumbersGSE146611