bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dram1 confers resistance toSalmonellainfection
Authors: Masud Samrah , Zhang Rui , Prajsnar Tomasz K. , Meijer Annemarie H. 
Published: March 2021

AbstractDram1 is a stress and infection inducible autophagy modulator that functions downstream of transcription factors p53 and NFκB. Using a zebrafish embryo infection model, we have previously shown that Dram1 provides protection against the intracellular pathogenMycobacterium marinumby promoting the p62-dependent xenophagy of bacteria that have escaped into the cytosol. However, the possible interplay between Dram1 and other anti-bacterial autophagic mechanisms remains unknown. Recently, LC3-associated phagocytosis (LAP) has emerged as an important host defense mechanism that requires components of the autophagy machinery and targets bacteria directly in phagosomes. Our previous work established LAP as the main autophagic mechanism by which macrophages restrict growth ofSalmonellaTyphimurium in a systemically infected zebrafish host. We therefore employed this infection model to investigate the possible role of Dram1 in LAP. Morpholino knockdown or CRISPR/Cas9-mediated mutation of Dram1 led to reduced host survival and increased bacterial burden duringS. Typhimurium infections. In contrast, overexpression ofdram1by mRNA injection curtailedSalmonellareplication and reduced mortality of the infected host. During the early response to infection, GFP-Lc3 levels in transgenic zebrafish larvae correlated with thedram1expression level, showing over two-fold reduction of GFP-Lc3-Salmonellaassociation indram1knockdown or mutant embryos and an approximately 30% increase bydram1overexpression. Since LAP is known to require the activity of the phagosomal NADPH oxidase, we used aSalmonellabiosensor strain to detect bacterial exposure to reactive oxygen species (ROS) and found that the ROS response was largely abolished in the absence ofdram1. Together, these results demonstrate the host protective role of Dram1 duringS. Typhimurium infection and suggest a functional link between Dram1 and the induction of LAP.
Mechanosensory input during circuit formation shapes Drosophila motor behavior through Patterned Spontaneous Network Activity
Authors: Carreira-Rosario Arnaldo , York Ryan A. , Choi Minseung , Doe Chris Q. , Clandinin Thomas R. 
Published: March 2021

SummaryNeural activity sculpts circuit wiring in many animals. In vertebrates, patterned spontaneous network activity (PaSNA) generates sensory maps and establishes local circuits1–3. However, it remains unclear how PaSNA might shape neuronal circuits and behavior in invertebrates. Previous work in the developingDrosophilaembryo discovered spontaneous muscle activity that did not require synaptic transmission, and hence was myogenic, preceding PaSNA4–6. These studies, however, monitored muscle movement, not neural activity, and were therefore unable to observe how myogenic activity might relate to subsequent neural network engagement. Here we use calcium imaging to directly record neural activity and characterize the emergence of PaSNA. We demonstrate that the spatiotemporal properties of PaSNA are highly stereotyped across embryos, arguing for genetic programming. Consistent with previous observations, we observe neural activity well before it becomes patterned, initially emerging during the myogenic stage. Remarkably, inhibition of mechanosensory input as well as inhibition of muscle contractions results in premature and excessive PaSNA, demonstrating that muscle movement serves as a brake on this process. Finally, using an optogenetic strategy to selectively disrupt mechanosensory inputs during PaSNA, followed by quantitative modeling of larval behavior, we demonstrate that mechanosensory modulation during development is required for proper larval foraging. This work thus provides a foundation for using theDrosophilaembryo to study the role of PaSNA in circuit formation, provides mechanistic insight into how PaSNA is entrained by motor activity, and demonstrates that spontaneous network activity is essential for locomotor behavior. These studies argue that sensory feedback during the earliest stages of circuit formation can sculpt locomotor behaviors through innate motor learning.HighlightsPaSNA in theDrosophilaembryonic CNS is spatiotemporally stereotypedMechanosensory neurons negatively modulate PaSNAEmbryonic PaSNA is required for larval locomotor behavior
The Geometry of Concept Learning
Authors: Sorscher Ben , Ganguli Surya , Sompolinsky Haim 
Published: March 2021

AbstractUnderstanding the neural basis of the remarkable human cognitive capacity to learn novel concepts from just one or a few sensory experiences constitutes a fundamental problem. We propose a simple, biologically plausible, mathematically tractable, and computationally powerful neural mechanism for few-shot learning of naturalistic concepts. We posit that the concepts that can be learnt from few examples are defined by tightly circumscribed manifolds in the neural firing rate space of higher order sensory areas. We further posit that a single plastic downstream readout neuron learns to discriminate new concepts based on few examples using a simple plasticity rule. We demonstrate the computational power of our proposal by showing it can achieve high few-shot learning accuracy on natural visual concepts using both macaque inferotemporal cortex representations and deep neural network models of these representations, and can even learn novel visual concepts specified only through linguistic descriptors. Moreover, we develop a mathematical theory of few-shot learning that links neurophysiology to behavior by delineating several fundamental and measurable geometric properties of high-dimensional neural representations that can accurately predict the few-shot learning performance of naturalistic concepts across all our numerical simulations. We discuss testable predictions of our theory for psychophysics and neurophysiological experiments.
Effect of Aqueous Extract of Antiaris Africana Stem Bark on Phagocytic Activities of Human Neutrophil Ex-Vivo
Authors: Bello Ibrahim O. , Adedeji Adebayo L. 
Published: March 2021

ABSTRACTThe immune system is one of the most complex biological systems in the body. During infection, the immune system is under attack by a large number of viruses, bacteria, fungi and parasites. Immune response firstly involves, recognition of the pathogen or foreign object and secondly, a reaction to eliminate it. Aqueous extract ofAntiaris africanais used to study their immune modulator activity. This plant has its various parts used in folk medicines. The mechanism of action has not been fully elucidated. Therefore, this research work studies the effect of aqueous extract ofAntiaris Africanastem bark on phagocytic activities of neutrophil isolated from apparently healthy individual using a non-subjective commercial colourimetric assay kit obtained from Cell-Biolab Inc., USA. The purity and viability of isolated neutrophils were >90% and >95% respectively. The extract enhances neutrophil phagocytosis at 1.0, 5.0, 10.0, 15.0, 20.0 and 25 μg/ml by 2.5%, 11.6%, 18.4%, 24.4%, 31.2% and 38.2% respectively, compared to the control (100%). Hence, it was observed that neutrophil phagocytosis increases with increased extract concentrations. It can be concluded from the study that enhancement of phagocytosis may be the possible mechanism of action of the plant as an immune modulator.
Predicting potentially permissive substitutions that improve the fitness of A(H1N1)pdm09 viruses bearing the H275Y NA substitution
Authors: Farrukee Rubaiyea , Gunalan Vithiagaran , Maurer-Stroh Sebastian , Reading Patrick C. , Hurt Aeron C. 
Published: March 2021

AbstractOseltamivir-resistant influenza viruses arise due to amino-acid mutations in key residues, but these changes often reduce their replicative and transmission fitness. Widespread oseltamivir-resistance has not yet been observed in A(H1N1)pdm09 viruses. However, it is known that permissive mutations in the neuraminidase (NA) of former seasonal A(H1N1) viruses from 2007-2009 buffered the detrimental effect of the NA H275Y mutation, resulting in fit oseltamivir-resistant viruses that circulated widely. This study explored two approaches to predict permissive mutations that may enable a fit H275Y A(H1N1)pdm09 variant to arise.A computational approach used phylogenetic andin silicoprotein stability analyses to predict potentially permissive mutations, which were then evaluated byin vitroNA enzyme activity and expression analysis, followed byin vitroreplication. The second approach involved the generation of a virus library which encompassed all possible individual 2.9 × 104codon mutations in the NA whilst keeping H275Y fixed. To select for variant viruses with the greatest fitness, the virus library was serially passaged in ferrets (via contact and aerosol transmission) and resultant viruses were deep sequenced.The computational approach predicted three NA permissive mutations, and even though they only offset thein vitroimpact of H275Y on NA enzyme expression by 10%, they could restore replication fitness of the H275Y variant in A549 cells. In our experimental approach, a diverse virus library (97% of 8911 possible single amino-acid substitutions were sampled) was successfully transmitted through ferrets, and sequence analysis of resulting virus pools in nasal washes identified three mutations that improved virus transmissibility. Of these, one NA mutation, I188T, has been increasing in frequency since 2017 and is now present in 90% of all circulating A(H1N1)pdm09 viruses.Overall, this study provides valuable insights into the evolution of the influenza NA protein and identified several mutations that may potentially facilitate the emergence of a fit H275Y A(H1N1)pdm09 variant.
Kupeantha yabassi(Coffeeae- Rubiaceae), a new Critically Endangered shrub species of the Ebo Forest area, Littoral Region, Cameroon
Authors: Alvarez-Aguirre Maria G. , Cheek Martin , Sonké Bonaventure 
Published: March 2021

SummaryA new species to science of evergreen forest shrub,Kupeantha yabassi(Coffeeae - Rubiaceae), is described, illustrated, mapped, and compared morphologically with the closely similar speciesK. pentamera. Restricted so far to a single site in evergreen lowland forest near the Ebo Forest, Yabassi, Littoral Region, Cameroon, this species is Critically Endangered using the IUCN 2012 standard due to habitat clearance driven mainly by agriculture, adding to the growing list of threatened species resulting from anthropogenic pressure on Cameroon forests. A revised key to the six species ofKupeanthais presented. Two distinct geographical and ecological species groupings within the genus are identified and discussed. Notes are given on other narrowly endemic and threatened species in the Ebo forest area, a threatened centre of diversity important for conservation in Littoral Region.
The E3 ubiquitin ligase RNF216/TRIAD3 is a central regulator of the hypothalamic-pituitary-gonadal axis
Authors: George Arlene J. , Hoffiz Yarely C. , Ware Christopher , Dong Bin , Fang Ning , Hrabovszky Erik , Mabb Angela M. 
Published: March 2021

SummaryRNF216/TRIAD3 is an E3 ligase that ubiquitinates substrates in the nervous system. Recessive mutations inRNF216/TRIAD3cause Gordon Holmes syndrome (GHS), where hypogonadotropic hypogonadism is a core phenotype. However, the functions of RNF216/TRIAD3 within the neuroendocrine system are not well-understood. Here, we used the CRISPR-Cas9 system to knock outRnf216/Triad3in GT1-7 cells, a GnRH immortalized cell line derived from mouse hypothalamus.Rnf216/Triad3knockout cells had decreased steady stateGnrhand reduced calcium transient frequency. To address functions of RNF216/TRIAD3in vivo, we generated aRnf216/Triad3constitutive knockout (KO) mouse. KO mice of both sexes showed reductions in GnRH and soma size. Furthermore, KO mice exhibited sex-specific phenotypes with males showing gonadal impairment and derangements in gonadotropin release compared to KO females, which only had irregular estrous cyclicity. Our work shows that dysfunction of RNF216/TRIAD3 affects the HPG axis in a sex-dependent manner, implicating sex-specific therapeutic interventions for GHS.HighlightsRnf216/Triad3controlsGnrhand intrinsic hypothalamic cell activityRnf216/Triad3knockout male mice have greater reproductive impairments than femalesRnf216/Triad3controls the HPG axis at multiple levels
Minimal clustering and species delimitation based on multi-locus alignments vs SNPs: the case of theSeriphium plumosumL. complex (Gnaphalieae: Asteraceae)
Authors: Shaik Zaynab , Bergh Nicola G , Oxelman Bengt , Verboom G Anthony 
Published: March 2021

ABSTRACTWe applied species delimitation methods based on the Multi-Species Coalescent (MSC) model to 500+ loci derived from genotyping-by-sequencing on the South AfricanSeriphium plumosum(Asteraceae) species complex. The loci were represented either as multiple sequence alignments or single nucleotide polymorphisms (SNPs), and analysed by the STACEY and Bayes Factor Delimitation (BFD)/SNAPP methods, respectively. Both methods supported species taxonomies where virtually all of the 32 sampled individuals, each representing its own geographical population, were identified as separate species. Computational efforts required to achieve adequate mixing of MCMC chains were considerable, and the species/minimal cluster trees identified similar strongly supported clades in replicate runs. The resolution was, however, higher in the STACEY trees than in the SNAPP trees, which is consistent with the higher information content of full sequences. The computational efficiency, measured as effective sample sizes of likelihood and posterior estimates per time unit, was consistently higher for STACEY. A random subset of 56 alignments had similar resolution to the 524-locus SNP data set. The STRUCTURE-like sparse Non-negative Matrix Factorisation (sNMF) method was applied to six individuals from each of 48 geographical populations and 28023 SNPs. Significantly fewer (13) clusters were identified as optimal by this analysis compared to the MSC methods. The sNMF clusters correspond closely to clades consistently supported by MSC methods, and showed evidence of admixture, especially in the western Cape Floristic Region. We discuss the significance of these findings, and conclude that it is important toa prioriconsider the kind of species one wants to identify when using genome-scale data, the assumptions behind the parametric models applied, and the potential consequences of model violations may have.
Identification of biomarkers and candidate regulators for multiple myeloma under the knockout of AURKA
Authors: Gu Hanming , Wang Wei , Yuan Gongsheng 
Published: March 2021

AbstractMultiple myeloma (MM) is a plasma cell malignancy that is characterized by the overabundance of monoclonal paraprotein. Aurora kinase A (AURKA) was upregulated in patients with high-risk MM. AURKA inhibitors were used to inhibit MM cell proliferation by inducing cell apoptosis and injury. In our study, we aim to identify biological processes and pathways of MM cells under the knockout of AURKA (AURKA KO) by using a bioinformatics method to elucidate their potential pathogenesis. The gene expression profiles of the GSE163589 dataset were originally produced by using the high-throughput BGISEQ-500 (Homo sapiens). The biological categories and pathways were analyzed by the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), Gene Ontology (GO), and Reactom enrichment. KEGG and GO results indicated the biological pathways related to the immune responses and cancer activities were mostly affected in the development of MM with AURKA KO. Moreover, we identified several genes including GNG5, UBE2D1, and BUB1B were involved in the regulation of cancer genesis. We further predicted novel regulators that had the ability to affect the progression of MM with AURKA KO based on the L1000fwd analysis. Therefore, this study provides further insights into the mechanism of MM under AURKA inhibitor treatments.
The effects of experimental floral resource removal on plant-pollinator interactions
Authors: Bain Justin A. , Dickson Rachel G. , Gruver Andrea M. , CaraDonna Paul J. 
Published: March 2021

AbstractPollination is essential for ecosystem functioning, yet our understanding of the empirical consequences of species loss for plant-pollinator interactions remains limited. It is hypothesized that the loss of abundant and generalized (well-connected) species from a pollination network will have a large effect on the remaining species and their interactions. However, to date, relatively few studies have experimentally removed species from their natural setting to address this hypothesis. We investigated the consequences of losing an abundant, well-linked species from a series of plant-pollinator networks by experimentally removing the flowers ofHelianthella quinquenervis(Asteraceae) from half of a series of 10 paired plots (15 m diameter) within a subalpine ecosystem. We then asked how the localized loss of this species influenced pollinator visitation patterns, floral visitor composition, and interaction network structure. The experimental removal ofHelianthellaflowers led to an overall decline in plot-level pollinator visitation rates and shifts in pollinator composition. Species-level responses to floral removal differed between the two other abundant, co-flowering plants in our experiment:Potentilla pulcherrimareceived higher visitation rates, whereasErigeron speciosusvisitation rates did not change. Experimental floral removal altered the structural properties of the localized plant-pollinator networks such that they were more specialized, less nested, and less robust to further species loss. Such changes to interaction structure were consistently driven more by species turnover than by interaction rewiring. Our findings suggest that the local loss of an abundant, well-linked, generalist plant can bring about diverse responses within pollination networks, including potential competitive and facilitative effects for individual species, changes to network structure that may render them more sensitive to future change, but also numerous changes to interactions that may also suggest flexibility in response to species loss.
A Hierarchy of Biomolecular Proportional-Integral-Derivative Feedback Controllers for Robust Perfect Adaptation and Dynamic Performance
Authors: Filo Maurice , Kumar Sant , Khammash Mustafa 
Published: March 2021

AbstractProportional-Integral-Derivative (PID) feedback controllers have been the most widely used controllers in industry for almost a century due to their good performance, simplicity, and ease of tuning. Motivated by their success in various engineering disciplines, PID controllers recently found their way into synthetic biology, where the design of feedback molecular control systems has been identified as an important goal. In this paper, we consider the mathematical realization of PID controllers via biomolecular interactions. We propose an array of topologies that offer a compromise between simplicity and high performance. We first demonstrate that different Proportional-Integral (PI) controllers exhibit different capabilities for enhancing the dynamics and reducing variance (cell-to-cell variability). Next, we introduce several derivative controllers that are realized based on incoherent feedforward loops acting in a feedback configuration. Alternatively, we show that differentiators can be realized by placing molecular integrators in a negative feedback loop—an arrangement that can then be augmented by PI components to yield PID feedback controllers. We demonstrate that the derivative component can be exploited for enhancing system stability, dramatically increasing the molecular control system’s dynamic performance, and for reducing the noise effect on the output of interest. The PID controller features are established through various deterministic and stochastic analyses as well as numerical simulations. Finally, we provide an experimental demonstration using a recently developed hybrid setup, the cyberloop, where the controller is implementedin silicoto control a biological genetic circuitin vivo. The large array of novel biomolecular PID controllers introduced here forms a basis for the design and construction of advanced high-performance biomolecular control systems that robustly regulate the dynamics of living systems.
MAAPER: model-based analysis of alternative polyadenylation using 3’ end-linked reads
Authors: Li Wei Vivian , Zheng Dinghai , Wang Ruijia , Tian Bin 
Published: March 2021

AbstractMost eukaryotic genes harbor multiple cleavage and polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms. APA regulation has been implicated in a diverse array of physiological and pathological conditions. While RNA sequencing tools that generate reads containing the PAS, namedonSitereads, have been instrumental in identifying PASs, they have not been widely used. By contrast, a growing number of methods generate reads that are close to the PAS, namednearSitereads, including the 3’ end counting strategy commonly used in single cell analysis. How these nearSite reads can be used for APA analysis, however, is poorly studied. Here, we present a computational method, named model-based analysis of alternative polyadenylation using 3’ end-linked reads (MAAPER), to examine APA using nearSite reads. MAAPER uses a probabilistic model to predict PASs for nearSite reads with high accuracy and sensitivity, and examines different types of APA events, including those in 3’UTRs and introns, with robust statistics. We show MAAPER’s accuracy with data from both bulk and single cell RNA samples and its applicability in unpaired or paired experimental designs. Our result also highlights the importance of using well annotated PASs for nearSite read analysis.
Drosophilaprimary microRNA-8 encodes a microRNA encoded peptide acting in parallel ofmiR-8
Authors: Montigny Audrey , Tavormina Patrizia , Duboe Carine , San Clémente Hélène , Aguilar Marielle , Valenti Philippe , Lauressergues Dominique , Combier Jean-Philippe , Plaza Serge 
Published: March 2021

SummaryBackgroundRecent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs, some of them producing functional small peptides via the translation of short ORFs. It now appears that any kind of RNA presumably has a potential to encode small peptides. Accordingly, our team recently discovered that plant primary transcripts of microRNAs (pri-miRNAs) produce small regulatory peptides (miPEPs) involved in auto-regulatory feedback loops enhancing their cognate microRNA expression which in turn controls plant development. Here we investigate whether this regulatory feedback loop is present inDrosophila melanogaster.ResultsWe perform a survey of ribosome profiling data and reveal that many pri-miRNAs exhibit ribosome translation marks. Focusing on miR-8, we show thatpri-miR-8can produce a miPEP-8. Functional assays performed in Drosophila reveal that miPEP-8 affects development when overexpressed or knocked down. Combining genetic and molecular approaches as well as genome-wide transcriptomic analyses, we show thatmiR-8expression is independent of miPEP-8 activity and that miPEP-8 acts in parallel tomiR-8to regulate the expression of hundreds of genes.ConclusionTaken together, these results reveal that severalDrosophila pri-miRNAsexhibit translation potential. Contrasting with the mechanism described in plants, these data shed light on the function of yet un-describedpri-microRNAencoded peptides inDrosophilaand their regulatory potential on genome expression.