bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stepwise maturation of the peptidyl transferase region of human mitoribosomes
Authors: Lenarčič Tea , Jaskolowski Mateusz , Leibundgut Marc , Scaiola Alain , Schönhut Tanja , Saurer Martin , Lee Richard , Rackham Oliver , Filipovska Aleksandra , Ban Nenad 
Published: March 2021

AbstractMitochondrial ribosomes are specialized for the synthesis of membrane proteins responsible for oxidative phosphorylation. Mammalian mitoribosomes diverged considerably from the ancestral bacterial ribosomes and feature dramatically reduced ribosomal RNAs. Structural basis of the mammalian mitochondrial ribosome assembly is currently not understood. Here we present eight distinct assembly intermediates of the human large mitoribosomal subunit involving 7 assembly factors. We discover that NSUN4-MTERF4 dimer plays a critical role in the process by stabilizing the 16S rRNA in a conformation that exposes the functionally important regions of rRNA for modification by MRM2 methyltransferase and quality control interactions with a conserved mitochondrial GTPase MTG2 that contacts the sarcin ricin loop and the immature active site. The successive action of these factors leads to the formation of the peptidyl transferase active site of the mitoribosome and the folding of the surrounding rRNA regions responsible for interactions with tRNAs and the small ribosomal subunit.
Effect of malaria parasite shape on its alignment at erythrocyte membrane
Authors: Dasanna Anil K. , Hillringhaus Sebastian , Gompper Gerhard , Fedosov Dmitry A. 
Published: March 2021

AbstractDuring the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasite’s apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically un-favorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasite’s shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, spherical parasite aligns faster than any other investigated shapes. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes, but is more robust with respect to different adhesion interactions and RBC membrane rigidities.
Plasticity of maternal environment dependent expression-QTLs of tomato seeds
Authors: Sterken Mark G. , Nijveen Harm , van Zanten Martijn , Jiménez-Gómez Jose M. , Geshnizjani Nafiseh , Willems Leo A. J. , Rienstra Juriaan , Hilhorst Henk W. M. , Ligterink Wilco , Snoek Basten L. 
Published: March 2021

AbstractSeeds are essential for plant reproduction, survival, and dispersal. Germination ability and successful establishment of young seedlings strongly depends on seed quality and on environmental factors such as nutrient availability. In tomato (Solanum lycopersicum) and many other species, seed quality and seedling establishment characteristics are determined by genetic variation, as well as the maternal environment in which the seeds develop and mature. The genetic contribution to variation in seed and seedling quality traits and environmental responsiveness can be estimated at transcriptome level in the dry seed by mapping genomic loci that affect gene expression (expression QTLs) in contrasting maternal environments.In this study, we applied RNA-sequencing to measure gene expression of seeds of a tomato RIL population derived from a cross betweenS. lycopersicum(cv. Moneymaker) andS. pimpinellifolium(G1.1554). The seeds matured on plants cultivated under different nutritional environments; i.e. on high phosphorus or low nitrogen. The obtained SNPs were subsequently used to construct a high-density genetic map. We show how the genetic landscape of plasticity in gene regulation in dry seeds is affected by the maternal nutrient environment. The combined information on natural genetic variation mediating (variation in) responsiveness to the environment may contribute to knowledge-based breeding programs aiming to develop crop cultivars that are resilient to stressful environments.
Intrinsic Degradation of the Type-II Antitoxin ParD fromPseudomonas aeruginosa
Authors: Snead Kevin J. , Bourne Christina R. 
Published: March 2021

AbstractType-II Toxin Antitoxin (TA) systems are regulated by differential half-lives of the resulting non-secreted proteins, such that the neutralizing antitoxin undergoes continual degradation and replenishment to maintain neutralization of its cognate toxin. Antitoxin proteins are widely reported as labile, including upon purification andin vitrostorage. During the course of studies on a ParDE TA system we noted a prevalentin vitrodegradation of the ParD antitoxin. In efforts to combat this for practical use in assays, we characterized parameters impacting the degradation as well as the resulting products. These revealed a mechanism likely mediated by a serine or metal-dependent protease. Using Direct Infusion Mass Spectrometry, the cleavage products were identified as an essentially intact DNA binding region of the antitoxin and with the toxin binding domain completely removed. No other species were identified in the solution, such as a contaminant that may mediate such cleavage. Therefore, while our studies revealed viable strategies to mitigate thein vitrodegradation they did not identify any protease, leaving open the possibility of a potential auto-catalytic proteolytic activity of the antitoxin proteins.
Competitive SNP-LAMP probes for rapid and robust single-nucleotide polymorphism detection
Authors: Hyman Leland B. , Christopher Clare R. , Romero Philip A. 
Published: March 2021

AbstractSingle-nucleotide polymorphisms (SNPs) are the most common source of genetic variation between individuals and have implications in human disease, pathogen drug resistance, and agriculture. SNPs are typically detected using DNA sequencing, which requires advanced sample preparation and instrumentation, and thus cannot be deployed for on-site testing or in low-resource settings. In this work we have developed a simple and robust assay to rapidly detect SNPs in nucleic acid samples. Our approach combines LAMP-based target amplification with fluorescent probes to detect SNPs with high specificity in a one-pot reaction format. A competitive “sink” strand preferentially binds to off-target products and shifts the free energy landscape to favor specific activation by SNP products. We demonstrated the broad utility and reliability of our SNP-LAMP method by detecting three distinct SNPs across the human genome. We also designed an assay to rapidly detect highly transmissible SARS-CoV-2 variants. This work demonstrates that competitive SNP-LAMP is a powerful and universal method that could be applied in point-of-care settings to detect any target SNP with high specificity and sensitivity.
Complex Computation from Developmental Priors
Authors: Barabási Dániel L. , Beynon Taliesin , Katona Ádám 
Published: March 2021

AbstractArtificial Intelligence (AI) research has provided key insights into the mechanics of learning complex tasks. However, AI models have long overlooked innateness: how strong pressures for survival lead to the encoding of complex behaviors in the nascent wiring of a brain. Although innate neural solutions have inspired AI approaches from layered architectures to ConvNets, the underlying neuroevolutionary search for novel heuristics has not been successfully systematized. In this manuscript, we examine how neurodevelopmental principles can inform the discovery of computational heuristics. We begin by considering the weight matrix of a neural network to be emergent from well-studied rules of neuronal compatibility. Rather than updating the network’s weights directly, we improve task fitness by updating the neurons’ wiring rules, thereby mirroring evolutionary selection on brain development. We find that the resulting framework can not only achieve high performance on standard machine learning tasks, but does so with a fraction of the full network’s parameters. Further, when we condition neuronal identity on biologically-plausible spatial constraints, we discover representations that resemble visual filters and are capable of learning transfer. Finally, we show that developmentally-inspired techniques have higher and more stable performance on metalearning tasks than the standard models they encode. In summary, by introducing realistic developmental considerations into machine learning frameworks, we not only capture the emergence of innate behaviors, but also define a discovery process for structures that promote complex computations.
The Digital 3D-Atlas MAKER (DAMAKER): a dynamic and expandable digital 3D-tool for monitoring the temporal changes in tissue growth during hindbrain morphogenesis
Authors: Blanc Matthias , Udina Frederic , Pujades Cristina 
Published: March 2021

ABSTRACTReconstruction of prototypic three-dimensional (3D) atlases at the scale of whole tissues or organs requires specific methods to be developed. We have established a digital 3D-atlas maker (DAMAKER) and built a digital 3D-temporal atlas to monitor the changes in the growth of the tissue and neuronal differentiation domain in the zebrafish hindbrain. DAMAKER integrates spatial and temporal data from cell populations, neuronal differentiation and brain morphogenesis, throughin vivoimaging techniques paired with image analyses and segmentation tools. First, we generated a 3D-reference from several imaged hindbrains and segmented them using a trainable tool; these were aligned using rigid registration, revealing distribution of neuronal differentiation growth patterns along the axes. Second, we quantified the dynamic growth of the neuronal differentiation domain vs. the progenitor domain, and byin vivoneuronal birthdating experiments we generated a digital 3D-temporal map of the neuronal growth in the whole hindbrain, revealing the spatiotemporal dynamics of neuronal differentiation upon morphogenesis. Last, we applied it to glutamatergic and GABAergic neurons, as proof-of-concept that the digital 3D-temporal map could be used as a proxy to infer neuronal birthdate. As this protocol uses open-access tools and algorithms, it can be shared for standardized, accessible, tissue-wide cell population atlas construction.
Epigenetic models predict age and aging in plains zebras and other equids
Authors: Larison Brenda , Pinho Gabriela M. , Hagani Amin , Zoller Joseph A. , Li Caesar Z. , Finno Carrie J. , Farrell Colin , Kaelin Christopher B. , Barsh Gregory S. , Wooding Bernard , Robeck Todd R. , Maddox Dewey , Pellegrini Matteo , Horvath Steve 
Published: March 2021

ABSTRACTFive of the seven extant wild species of the genusEquusare species of significant conservation concern. Effective conservation and management of such threatened wildlife populations depends on the ability to estimate demographic trends and population viability and therefore requires accurate assessment of age structure. However, reliably aging wildlife is challenging as many methods are highly invasive, inaccurate, or both. Epigenetic aging models, which estimate individual age with high accuracy based on genomic methylation patterns, are promising developments in this regard. Importantly, epigenetic aging models developed for one species can potentially predict age with high accuracy in sister taxa. Using blood and biopsy samples from known age plains zebras (Equus quagga), we developed epigenetic clocks (ECs) to predict chronological age, and epigenetic pacemaker (EPM) models to predict biological age. We tested the ability of our blood-based EC to predict ages of Grevy’s zebras, Somali asses and domestic horses, from blood samples. Because our samples came from a population with a complex pedigree, we also leveraged information from a previous sequencing effort to measure the association between levels of inbreeding (F and ROH) and the age acceleration as measured by DNA methylation. The resulting models describe the trajectory of epigenetic aging in plains zebras and accurately predict the ages of plains zebras and other equids. We found moderate support for a slight acceleration of aging with increased inbreeding.
Transcriptional activity and epigenetic regulation of transposable elements in the symbiotic fungusRhizophagus irregularis
Authors: Dallaire A , Manley BF , Wilkens M , Bista I , Quan C , Evangelisti E , Bradshaw CR , Ramakrishna NB , Schornack S , Butter F , Paszkowski U , Miska EA 
Published: March 2021

AbstractArbuscular mycorrhizal (AM) fungi form mutualistic relationships with most land plant species and have long been considered as ancient asexuals. Long-term clonal evolution would be remarkable for a eukaryotic lineage and suggests the importance of alternative mechanisms to promote genetic variability facilitating adaptation. Here, we assessed the potential of transposable elements (TEs) for generating genomic diversity. The dynamic expression of TEs duringRhizophagus irregularisspore development suggests ongoing TE activity. We findMutator-likeelements located near genes belonging to highly expanded gene families. Characterising the epigenomic status ofR. irregularisprovides evidence of DNA methylation and small RNA production occurring at TE loci. Our results support a potential role for TEs in shaping the genome, and roles for DNA methylation and small RNA-mediated silencing in regulating TEs. A well-controlled balance between TE activity and repression may therefore contribute to genome evolution in AM fungi.
Ghost lineages highly influence the interpretation of introgression tests
Authors: Tricou Théo , Tannier Eric , de Vienne Damien M. 
Published: March 2021

AbstractMost species are extinct; those that are not are often unknown. Sequenced and sampled species are often a minority of known ones. Past evolutionary events involving horizontal gene flow, such as horizontal gene transfer, hybridization, introgression and admixture, are therefore likely to involve “ghosts”,i.e. extinct, unknown or unsampled lineages. The existence of these ghost lineages is widely acknowledged, but their possible impact on the detection of gene flow and on the identification of the species involved is largely overlooked. It is generally considered as a possible source of error that, with reasonable approximation, can be ignored. We explore the possible influence of absent species on an evolutionary study by quantifying the effect of ghost lineages on introgression as detected by the popular D-statistic method. We show from simulated data that under certain frequently encountered conditions, the donors and recipients of horizontal gene flow can be wrongly identified if ghost lineages are not taken into account. In particular, having a distant outgroup, which is usually recommended, leads to an increase in the error probability and to false interpretations in most cases. We conclude that introgression from ghost lineages should be systematically considered as an alternative possible, even probable, scenario.
Combined Nanopore and Single-Molecule Real-Time Sequencing Survey of Human Betaherpesvirus 5 Transcriptome
Authors: Kakuk Balázs , Tombácz Dóra , Balázs Zsolt , Moldován Norbert , Csabai Zsolt , Torma Gábor , Megyeri Klára , Snyder Michael , Boldogkői Zsolt 
Published: March 2021

ABSTRACTLong-read sequencing (LRS), a powerful novel approach, is able to read full-length transcripts and confers a major advantage over the earlier gold standard short-read sequencing in the efficiency of identifying for example polycistronic transcripts and transcript isoforms, including transcript length- and splice variants. In this work, we profile the human cytomegalovirus transcriptome using two third-generation LRS platforms: the Sequel from Pacific BioSciences, and MinION from Oxford Nanopore Technologies. We carried out both cDNA and direct RNA sequencing, and applied the LoRTIA software, developed in our laboratory, for the transcript annotations. This study identified a large number of novel transcript variants, including splice isoforms and transcript start and end site isoforms, as well as putative mRNAs with truncated in-frame ORFs (located within the larger ORFs of the canonical mRNAs), which potentially encode N-terminally truncated polypeptides. Our work also disclosed a highly complex meshwork of transcriptional read-throughs and overlaps.
Exploiting synergistic interactions ofMedicago sativaL. andParaburkholderia tropicafor enhanced biodegradation of diesel fuel hydrocarbons
Authors: Eze Michael O. , Thiel Volker , Hose Grant C. , George Simon C. , Daniel Rolf 
Published: March 2021

AbstractThe biotechnological application of microorganisms for rhizoremediation of contaminated sites requires the development of plant-microbe symbionts capable of plant growth promotion and hydrocarbon degradation. Studies focusing on microbial consortia are often difficult to reproduce, thereby necessitating the need for culturable single bacterial species for biotechnological applications. Through genomic analyses and plant growth experiments, we examined the synergistic interactions ofMedicago sativaL. andParaburkholderia tropicafor enhanced remediation of diesel fuel-contaminated soils. Comparative genomics revealed strong potential ofP. tropicafor plant growth-promotion, chemotaxis and motility, root nodulation and colonization, and diesel fuel degradation. Plant growth experiments confirmed thatP. tropicathrived in the contaminated soils and effectively enhancedM. sativagrowth. Geochemical analysis showed that theM. sativa+P. tropicatreatment resulted in an efficient degradation of diesel fuel hydrocarbons within two months, offering great prospects for enhanced biodegradation of organic pollutants.
Part 1: robust adaptive control of quadrotor with disturbance observer
Authors: Ahmed Nigar , Raza Abid , Khan Rameez 
Published: March 2021

PurposeThe aim of this paper is to design a nonlinear disturbance observer-based control (DOBC) method obtained by patching a control method developed using a robust adaptive technique and a DO.Design/methodology/approachFor designing a DOBC, initially a class of nonlinear system is considered with an external disturbance. First, a DO is designed to estimate the external disturbances. This estimate is combined with the controller to reject the disturbances and obtain the desired control objective. For designing a controller, the robust sliding mode control theory is used. Furthermore, instead of using a constant switching gain, an adaptive gain tuning criterion is designed using Lyapunov candidate function. To investigate the stability and effectiveness of the developed DOBC, stability analysis and simulation study are presented.FindingsThe major findings of this paper include the criteria of designing the robust adaptive control parameters and investigating the disturbance rejection when robust adaptive control based DOBC is developed.Practical implicationsIn practice, the flight of quadrotor is affected by different kind of external disturbances, thus leading to the change in dynamics. Hence, it is necessary to design DOBCs based on robust adaptive controllers such that the quadrotor model adapts to the change in dynamics, as well as nullify the effect of disturbances.Originality/valueDesigning DOBCs based on robust control method is a common practice; however, the robust adaptive control method is rarely developed. This paper contributes in the domain of DOBC based on robust adaptive control methods such that the behavior of controller varies with the change in dynamics occurring due to external disturbances.
Food safety at home: Serbian students
Authors: Radulovic Ana , Marklinder Ingela , Mirkovic Milica , Miocinovic Jelena , Jankovic Soja Svjetlana 
Published: March 2021

PurposeStrengthening awareness and education to address food safety problem is of importance. The purpose of this study is to investigate food safety knowledge and opinion among Serbian students and the efficiency of education on their self-reported behaviour as consumers.Design/methodology/approachA questionnaire on the attitudes and self-reported behaviour of students was completed by 414 students at the Faculty of Agriculture, University of Belgrade, Serbia. The questions covered hand hygiene; cross-contamination; conditions of food cooling; and knowledge of risky food. Students were divided into two groups: students in their first and second year of study (1–2 YoS) who had not attended any subjects related to food safety during their education; students in the third and fourth years of the Food Technology Program (3–4 YoS) who had completed one or more courses concerning food safety during their education.FindingsOverall, there were significant differences in the opinions of 1–2 YoS students and 3–4 YoS students on most issues. It was noted that male students are at higher risk when it comes to food handling. Considering the significant impact of education as evidenced by the opinions of 3–4 YoS students, it can be concluded that education is effective in raising awareness and changing behaviour among young people.Originality/valueThe study identified how education affects students' opinion and food handling. Moreover, it highlighted the areas of deficiency in students' food safety behaviour, knowledge and attitudes. Limited research has been conducted on food safety knowledge among students.