bluuebunny/crossref_metadata_2025 huggingface dataset:
On the problems of not accounting for measurement- and sampling uncertainty in ecological and environmental models
Authors: Damgaard Christian
Published: March 2020

In many applied cases of ecological and environmental modelling, there is a sizeable variation among the measured variables due to measurement- and sampling error. Such measurement- and sampling error among the independent variables may lead to regression dilution and biased prediction intervals in traditional empirical modelling. It is possible to avoid these shortcomings by subsampling and hierarchical modelling, but this is still not a common practice. Here, it is recommended to model the measurement- and sampling errors by integrating the stochastic modelling of the errors into hierarchical ecological and environmental models.
Explainable Transformer Models for Functional Genomics in Prokaryotes
Authors: Clauwaert Jim , Menschaert Gerben , Waegeman Willem
Published: March 2020

The effectiveness of deep learning methods can be largely attributed to the automated extraction of relevant features from raw data. In the field of functional genomics, this generally comprises the automatic selection of relevant nucleotide motifs from DNA sequences. To benefit from automated learning methods, new strategies are required that unveil the decision-making process of trained models. In this paper, we present several methods that can be used to gather insights on biological processes that drive any genome annotation task. This work builds upon a transformer-based neural network framework designed for prokaryotic genome annotation purposes. We find that the majority of sub-units (attention heads) of the model are specialized towards identifying DNA binding sites. Working with a neural network trained to detect transcription start sites in E. coli, we successfully characterize both locations and consensus sequences of transcription factor binding sites, including both well-known and potentially novel elements involved in the initiation of the transcription process.
gauseR: Simple methods for fitting Lotka-Volterra models describing Gause’s “Struggle for Existence”
Authors: Mühlbauer Lina K. , Schulze Maximilienne , Harpole W. Stanley , Clark Adam T.
Published: March 2020

The ecological models of Alfred J. Lotka and Vito Volterra have had an enormous impact on ecology over the past century. Some of the earliest – and clearest – experimental tests of these models were famously conducted by Georgy Gause in the 1930’s. Although well known, the data from these experiments are not widely available, and are often difficult to analyze using standard statistical and computational tools. Here, we introduce thegauseRpackage, a collection of tools for fitting Lotka-Volterra models to time series data of one or more species. The package includes several methods for parameter estimation and optimization, and includes 42 datasets from Gause’s species interaction experiments and related work. Additionally, we include with this paper a short blog post discussing the historical importance of these data and models, and an R vignette with a walk-through introducing the package methods. The package is available for download at github.com/adamtclark/gauseR. To demonstrate the package, we apply it to several classic experimental studies from Gause, as well as two other well-known datasets on multi-trophic dynamics on Isle Royale, and in spatially structured mite populations. In almost all cases, models fit observations closely, and fitted parameter values make ecological sense. Taken together, we hope that the methods, data, and analyses that we present here provide a simple and user-friendly way to interact with complex ecological data. We are optimistic that these methods will be especially useful to students and educators who are studying ecological dynamics, as well as researchers who would like a fast tool for basic analyses.
An osmolality/ salinity-responsive enhancer 1 (OSRE1) in intron 1 promotes salinity induction of tilapia glutamine synthetase
Authors: Kim Chanhee , Kültz Dietmar
Published: March 2020

Euryhaline tilapia (Oreochromis mossambicus) are fish that tolerate a wide salinity range from fresh water to >3x seawater. Even though the physiological effector mechanisms of osmoregulation that maintain plasma homeostasis in fresh water and seawater fish are well known, the corresponding molecular mechanisms that control switching between hyper- (fresh water) and hypo-osmoregulation (seawater) remain mostly elusive. In this study we show that hyperosmotic induction ofglutamine synthetaserepresents a prominent part of this switch. Proteomics analysis of theO. mossambicusOmB cell line revealed that glutamine synthetase is transcriptionally regulated by hyperosmolality. Therefore, the 5’ regulatory sequence ofO. mossambicus glutamine synthetasewas investigated. Using an enhancer trapping assay, we discovered a novel osmosensitive mechanism by which intron 1 positively mediatesglutamine synthetasetranscription. Intron 1 includes a single, functional copy of an osmoresponsive element, osmolality/salinity-responsive enhancer 1 (OSRE1). Unlike for conventional enhancers, the hyperosmotic induction ofglutamine synthetaseby intron 1 is position dependent. But irrespective of intron 1 position, OSRE1 deletion from intron 1 abolishes hyperosmotic enhancer activity. These findings indicate that proper intron 1 positioning and the presence of an OSRE1 in intron 1 are required for precise enhancement of hyperosmoticglutamine synthetaseexpression.
Causal evidence for a cerebellar role in prefrontal-hippocampal interaction in spatial working memory decision-making
Authors: Liu Yu , McAfee Samuel S. , Van Der Heijden Meike E. , Dhamala Mukesh , Sillitoe Roy V. , Heck Detlef H.
Published: March 2020

Spatial working memory (SWM) is a cognitive skill supporting survival-relevant behaviors, such as optimizing foraging behavior by remembering recent routes and visited sites. It is known that SWM decision-making in rodents requires the medial prefrontal cortex (mPFC) and dorsal hippocampus. The decision process in SWM tasks carries a specific electrophysiological signature of a brief, decision-related increase in neuronal communication in the form of an increase in the coherence of neuronal theta oscillations (4-12 Hz) between the mPFC and dorsal hippocampus, a finding we replicated here during spontaneous exploration of a plus maze in freely moving mice. We further evaluated SWM decision-related coherence changes within frequency bands above theta. Decision-related coherence increases occurred in seven frequency bands between 4 and 200 Hz and decision-outcome related differences in coherence modulation occurred within the beta and gamma frequency bands and in higher frequency oscillations up to 130 Hz. With recent evidence that Purkinje cells in the cerebellar lobulus simplex (LS) represent information about the phase and phase differences of gamma oscillations in the mPFC and dorsal hippocampus, we hypothesized that LS might be involved in the modulation of mPFC-hippocampal gamma coherence. We show that optical stimulation of LS significantly impairs SWM performance and decision-related mPFC-dCA1 coherence modulation, providing causal evidence for an involvement of cerebellar LS in SWM decision making at the behavioral and neuronal level. Our findings suggest that the cerebellum might contribute to SWM decision-making by optimizing the decision-related modulation of mPFC-dCA1 coherence.
Niche Partitioning Between Coastal and Offshore Shelf Waters Results in Differential Expression of Alkane and PAH Catabolic Pathways
Authors: Doyle Shawn M. , Lin Genmei , Morales-McDevitt Maya , Wade Terry L. , Quigg Antonietta , Sylvan Jason B.
Published: March 2020

Marine oil spills can impact both coastal and offshore marine environments, but little information is available on how the microbial response to oil and dispersants might differ between these biomes. Here we describe the compositional and functional response of microbial communities to different concentrations of oil and chemically dispersed oil in coastal and offshore surface waters from the Texas-Louisiana continental shelf. Using a combination of analytical chemistry, 16S rRNA amplicon, and metatranscriptomic sequencing, we provide a broad, comparative overview of the ecological response of hydrocarbon degrading bacteria and their expression of hydrocarbon degrading genes in marine surface waters over time between two oceanic biomes. We found evidence for the existence of different ecotypes of several commonly described hydrocarbon degrading bacterial taxa which behaved differentially in coastal and offshore shelf waters despite being exposed to similar concentrations of oil, dispersants, and nutrients. This resulted in the differential expression of catabolic pathways for n-alkanes and polycyclic aromatic hydrocarbons (PAH)—the two major categories of compounds found in crude oil—with preferential expression of n-alkane degradation genes in coastal waters while offshore microbial communities trended more towards the expression of PAH degradation genes. This was unexpected as it contrasts with the generally held view that n-alkanes, being more labile, are attacked before the more refractory PAHs. Collectively, our results provide new insights into the existence and potential consequences of niche partitioning of hydrocarbon degrading taxa between neighboring marine environments.

IMPORTANCE

In the wake of the Deepwater Horizon oil spill, the taxonomic response of marine microbial communities to oil and dispersants has been extensively studied. However, relatively few studies on the functional response of these microbial communities have been reported, especially in a longitudinal fashion. Moreover, despite the fact that marine oil spills typically impact thousands of square kilometers of both coastal and offshore marine environments, little information is available on how the microbial response to oil and dispersants might differ between these biomes. The results of this study help fill this critical knowledge gap and provide valuable insight into how oil spill response efforts, such as chemically dispersing oil, may have differing effects in neighboring coastal and offshore marine environments.
Enhancer and promoter usage in the normal and failed human heart
Authors: Gacita Anthony M. , Dellefave-Castillo Lisa , Page Patrick G. T. , Barefield David Y. , Waserstrom J. Andrew , Puckelwartz Megan J. , Nobrega Marcelo A. , McNally Elizabeth M
Published: March 2020

The failed heart is characterized by re-expression of a fetal gene program, which contributes to adaptation and maladaptation in heart failure. To define genomewide enhancer and promoter use in heart failure, Cap Analysis of Gene Expression (CAGE-seq) was applied to healthy and failed human left ventricles to define short RNAs associated with both promoters and enhancers. Integration of CAGE-seq data with RNA sequencing identified a combined ∼17,000 promoters and ∼1,500 enhancers active in healthy and failed human left ventricles. Comparing promoter usage between healthy and failed hearts highlighted promoter shifts which altered amino-terminal protein sequences. Comparing enhancer usage between healthy and failed hearts revealed a majority of differentially utilized heart failure enhancers were intronic and primarily localized within the first intron, identifying this position as a common feature associated with tissue-specific gene expression changes in the heart. This dataset defines the dynamic genomic regulatory landscape underlying heart failure and serves as an important resource for understanding genetic contributions to cardiac dysfunction.
Evidence of Antibody Repertoire Functional Convergence through Public Baseline and Shared Response Structures
Authors: Raybould Matthew I. J. , Marks Claire , Kovaltsuk Aleksandr , Lewis Alan P. , Shi Jiye , Deane Charlotte M.
Published: March 2020

The antibody repertoires of different individuals ought to exhibit significant functional commonality, given that most pathogens trigger a successful immune response in most people. Sequence-based approaches have so far offered little evidence for this phenomenon. For example, a recent study estimated the number of shared (‘public’) antibody clonotypes in circulating baseline repertoires to be around 0.02% across ten unrelated individuals. However, to engage the same epitope, antibodies only require a similar binding site structure and the presence of key paratope interactions, which can occur even when their sequences are dissimilar. Here, we investigate functional convergence in human antibody repertoires by comparing the anti-body structures they contain. We first structurally profile base-line antibody diversity (using snapshots from 41 unrelated individuals), predicting all modellable distinct structures within each repertoire. This analysis uncovers a high (much greater than random) degree of structural commonality. For instance, around 3% of distinct structures are common to the ten most diverse individual samples (‘Public Baseline’ structures). Our approach is the first computational method to provide support for the long-assumed levels of baseline repertoire functional commonality. We then apply the same structural profiling approach to repertoire snapshots from three individuals before and after flu vaccination, detecting a convergent structural drift indicative of recognising similar epitopes (‘Public Response’ structures). Antibody Model Libraries derived from Public Baseline and Public Response structures represent a powerful geometric basis set of low-immunogenicity candidates exploitable for general or target-focused therapeutic antibody screening.
Same same but different: Cluster architecture variation in five ‘Pinot Noir’ clonal selection lines correlates with differential expression of three transcription factors and further growth related genes
Authors: Richter Robert , Rossmann Susanne , Gabriel Doreen , Töpfer Reinhard , Theres Klaus , Zyprian Eva
Published: March 2020

Grapevine (Vitis viniferaL.) is an economically important crop that needs to comply with high quality standards for fruit, juice and wine production. Intense plant protection is required to avoid losses caused by fungal infections. Grapevine cultivars with loose cluster architecture enable to reduce protective chemical treatments due to their enhanced resilience against fungal infections such asBotrytis cinereainduced grey mold. A recent study identified transcription factor geneVvGRF4as determinant of inflorescence structure in exemplary samples of loose and compact quasi-isogenic ‘Pinot Noir’ clones. Here, we extended the analysis to 12 differently clustered ‘Pinot Noir’ clones originating from five different clonal selection programs. Differential gene expression of these clones was studied in three different locations over three seasons in demonstrative vineyards. Two phenotypically contrasting clones were grown at all three locations and served for standardization of downstream analyses. Differential gene expression data were correlated to the phenotypic variation of cluster architecture sub-traits. A consistent differential gene expression ofVvGRF4in relation to loose clusters was verified over the different environments and in the extended set of ‘Pinot Noir’ clones. In addition, 14 more genes with consistent expression differences between loosely and compactly clustered clones independent from season and location were identified. These genes show annotations related to cellular growth, cell wall extension, cell division and auxin metabolism. They include two more transcription factor genes.
A novel framework for modeling the evolution of cross-scale ecological assembly
Authors: Gallinat Amanda S. , Pearse William D.
Published: March 2020

Community assembly can be driven by species’ responses to environmental gradients, and interactions within (e.g., competition) and across (e.g., herbivory) clades. These ecological dynamics are mediated by species’ traits, which are in turn shaped by past evolution. As such, identifying the drivers of species assembly is made difficult by the differing temporal and spatial scales of ecological and evolutionary dynamics. Two recent advances have emerged to address the cross-scale challenge of modeling species assembly: phylogenetic generalized linear mixed modeling (PGLMM) and earth observation networks (EONs). PGLMM integrates through time by modeling the evolution of trait-based community assembly, while EONs synthesize across space by placing standardized site-level species occurrence data within their regional context. Here we describe a framework for combining these tools to investigate the drivers of species assembly, and so address three outstanding questions: (1) Does evolution adapt or constrain regional-scale environmental responses? (2) Do evolved responses to past competition minimize or enhance present-day competition? (3) Are species’ cross-clade associations evolutionarily constrained? We provide a conceptual overview of how PGLMM and EONs can be synthesized to answer these questions, and provide exemplar Bayesian PGLMM code. Finally, we describe the capacity of these tools to aid in conservation and natural resource management, including predicting future colonization by rare and invasive species, vulnerable mutualisms, and pest and pathogen outbreaks.
Changes in group size during resource shifts reveal drivers of sociality across the tree of life
Authors: Kao Albert B. , Hund Amanda K. , Santos Fernando P. , Young Jean-Gabriel , Bhat Deepak , Garland Joshua , Oomen Rebekah A. , McCreery Helen F.
Published: March 2020

From biofilms to whale pods, organisms have repeatedly converged on sociality as a strategy to improve individual fitness. Yet, it remains challenging to identify the most important drivers—and by extension, the evolutionary mechanisms—of sociality for particular species. Here, we present a conceptual framework, literature review, and model demonstrating that the direction and magnitude of the response of group size to sudden resource shifts provides a strong indication of the underlying drivers of sociality. We catalog six functionally distinct mechanisms related to the acquisition of resources, and we model these mechanisms’ effects on the survival of individuals foraging in groups. We find that whether, and to what degree, optimal group size increases, decreases, or remains constant when resource abundance declines depends strongly on the dominant mechanism. Existing empirical data support our model predictions, and we demonstrate how our framework can be used to predict the dominant social benefit for particular species. Together, our framework and results show that a single easily measurable characteristic, namely, group size under different resource abundances, can illuminate the potential drivers of sociality across the tree of life.
Diffusion property and functional connectivity of superior longitudinal fasciculus underpin human metacognition
Authors: Zheng Yunxuan , Wang Danni , Ye Qun , Zou Futing , Li Yao , Kwok Sze Chai
Published: March 2020

Metacognition as the capacity of monitoring one’s own cognition operates across domains. Here, we addressed whether metacognition in different cognitive domains rely on common or distinct neural substrates with combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) techniques. After acquiring DTI and resting-state fMRI data, we asked participants to perform a temporal-order memory task and a perceptual discrimination task, followed by trial-specific confidence judgments. DTI analysis revealed that the structural integrity (indexed by fractional anisotropy) in the anterior portion of right superior longitudinal fasciculus (SLF) was associated with both perceptual and mnemonic metacognitive abilities. Using perturbed mnemonic metacognitive scores produced by inhibiting the precuneus using TMS, the mnemonic metacognition scores did not correlate with individuals’ SLF structural integrity anymore, revealing the relevance of this tract in memory metacognition. In order to further verify the involvement of several cortical regions connected by SLF, we took the TMS-targeted precuneus region as a seed in a functional connectivity analysis and found the functional connectivity between precuneus and two SLF-connected regions (inferior parietal cortex and precentral gyrus) differentially mediated mnemonic but not perceptual metacognition performance. These results illustrate the importance of SLF and a putative white-matter grey-matter circuitry that supports human metacognition.
Gene expression profiling of Tea (Camellia sinensisL.) in response to biotic stress using microarrays
Authors: Ashokraj S. , Raj E. Edwin , Chandrashekara K.N. , Govindaraj R. , Blessia T. Femlin , Radhakrishnan B.
Published: March 2020

The blister blight (BB) and grey blight (GB) diseases are the major biotic stresses, which affecting the plant health, yield and quality of tea. The study aims to understand the gene response of tea plants against destructing foliar diseases in terms of differential gene expression and their pathways through microarray analysis aid by MapMan®software. The results of expression profile analysis showed that 235 in BB and 258 for GB genes were differentially expressed (at P<0.05) which involving in gene regulatory function as biotic stress response. Similarly, 76 and 86 differentially expressed genes involving in cellular response during BB and GB diseases, respectively. However, 28 in BB and 9 in GB differentially expressed (P<0.01) genes were putatively involved in biotic stress response. The study also identified differentially expressed 75 transcription factors (TFs) belongs to 23 TFs superfamily act as either transcriptional activators or repressors. The study helps to understand the differential gene expression pattern and its cellular, molecular and biological mechanisms of tea plants of two different diseases based on microarray analysis. Further studies using biotechnological tools on the stress-responsive genes in the germplasm may enable us for development of disease resistance.
Development of non-destructive methods to estimate functional traits and field evaluation in tea plantations using a smartphone
Authors: Raj Esack Edwin , Kumar Rajagobal Raj , Shanmugam Ashokraj , Radhakrishnan Balakrishnan
Published: March 2020

Smartphones are equipped with various types of sensors which make them a promising tool to assist diverse digital farming tasks because of their mobility, cost, accessibility, and computing power allow us to perform real-time practical applications. This paper presents the utilization of various non-destructive methods of nutrient and disease classification techniques using smartphone collected images, processed through various image segmentation algorithms. Bothin vivoandin vitroestimations shows comparable results with both chlorophyll and nitrogen contents of a crop shoot. Moreover, the correlation between SPAD measured values and nitrogen of crop shoot showed a significant linear association (R2=0.7309), revealing the potency ofin vivoobservation for prediction of actual chlorophyll content in tea crop. SPAD values and yield have a strong linear relationship (R2=0.7103), in which SPAD-meter performed better detection at very low values. The study concluded that the proposed techniques could be used for automatic detection as well as classification of foliar diseases and nutrients in tea.
Phosphatidylinositol 3-phosphate and Hsp70 protectPlasmodium falciparumfrom heat-induced cell death
Authors: Lu Kuan-Yi , Pasaje Charisse Flerida A. , Srivastava Tamanna , Loiselle David R. , Niles Jacquin C. , Derbyshire Emily R.
Published: March 2020

Phosphatidylinositol 3-phosphate (PI(3)P) levels inPlasmodium falciparumcorrelate with tolerance to cellular stresses caused by artemisinin, a first-line malaria treatment, and environmental factors. However, the functional role of PI(3)P in thePlasmodiumstress response and a possible mechanism of protection were unknown. Here, we used multiple chemical probes including PI3K inhibitors and known antimalarial drugs to examine the importance of PI(3)P under thermal conditions that recapitulate malaria fever. Live cell microscopy using both chemical and genetic reporters revealed that PI(3)P stabilizes the acidic and proteolytic digestive vacuole (DV) under heat stress. We demonstrate that heat-induced DV destabilization in PI(3)P-deficientP. falciparumprecedes cell death and is reversible after withdrawal of the stress condition and the PI3K inhibitor. These phenotypes are not observed with an inactive structural analog of the PI3K inhibitor. A chemoproteomic and biochemical approach identified PfHsp70-1 as a parasite PI(3)P-binding protein. Targeting PfHsp70-1 with a small molecule inhibitor phenocopied PI(3)P-deficient parasites under heat shock. Furthermore, tunable knockdown of PfHsp70-1 showed that PfHsp70-1 downregulation causes DV destabilization and hypersensitizes parasites to heat shock and PI3K inhibitors. Our findings underscore a mechanistic link between PI(3)P and PfHsp70-1, and present a novel PI(3)P function in stabilizing the DV compartment during heat stress.
Testing the pathogenic potential ofCryphonectria parasiticaand related species on three common European Fagaceae
Authors: Dennert Francesca , Rigling Daniel , Meyer Joana B. , Schefer Christopher , Augustiny Eva , Prospero Simone
Published: March 2020

Invasions by non-native pathogens represent a major threat to managed and natural ecosystems worldwide. Although necessary for adopting preventive strategies, the identification of invasive species before they are introduced is particularly difficult. Indeed, most pathogenic species that have become established in the last decades were first described only after they became invasive. To prevent further biological invasions, not only the early identification of potential new invasive plant pathogens is crucial, but also the assessment of their potential host range. In this study, we determined the pathogenicity and the saprotrophic ability of threeCryphonectriaspecies towards three potential hosts in the family Fagaceae. For this, seedlings and dormant stems of European chestnut (Castanea sativa), pedunculate oak (Quercus robur) and European beech (Fagus sylvatica) were inoculated with different genotypes ofC. parasitica(Asian species, invasive in Europe),C. naterciae(European species), andC. japonica(Asian species, not present in Europe). Lesion growth was measured and mortality assessed for four months. The highest damage was caused byC. parasiticaon European chestnut, whileC. japonicaandC. naterciaeinduced significantly smaller lesions on this host species. All threeCryphonectriaspecies did not grow saprophytically onF. sylvaticaandQ. robur, but successfully colonized dormant stems ofC. sativa. In the context of biological invasions, our study shows that the AsianC. japonicamost likely represents a much less severe threat thanC. parasiticafor the tested European host species. Nonetheless, the ability ofC. naterciaeandC. japonicato saprotrophically colonize fresh chestnut wood may suggest that they could become established in chestnut forests and eventually infect weakened chestnut trees or other hosts not tested in this study.
Cell-free protein synthesis enables one-pot cascade biotransformation in an aqueous-organic biphasic system
Authors: Liu Wan-Qiu , Wu Changzhu , Jewett Michael C. , Li Jian
Published: March 2020

Biocatalytic cascade reactions have become increasingly important and useful for chemical synthesis. However, biocatalysts are often incompatible with organic solvents, which prohibits many cascade reactions involving nonpolar substrates. In this work, we used cell-free protein synthesis (CFPS) to express enzymes in an aqueous-organic biphasic system for the construction of an artificial enzymatic pathway. CFPS-expressed enzymes without purification performed efficiently to convert styrene (below 20 mM) to (S)-1-phenyl-1,2-ethanediol (two steps in one pot) with 100% conversion. In addition, our CFPS system showed great tolerance to different organic solvents and, importantly, the entire biocatalytic system can be consistently scaled up without reduction of the substrate conversion rate. We therefore anticipate that our cell-free approach will make possible cost-effective, high-yielding synthesis of valuable chemicals.
CYCA3;4 Is a Post-Prophase Target of the APC/CCCS52A2E3-Ligase Controlling Formative Cell Divisions in Arabidopsis
Authors: Willems Alex , Heyman Jefri , Eekhout Thomas , Achon Ignacio , Pedroza-Garcia Jose Antonio , Zhu Tingting , Li Lei , Vercauteren Ilse , Van den Daele Hilde , van de Cotte Brigitte , De Smet Ive , De Veylder Lieven
Published: March 2020

The Anaphase Promoting Complex/Cyclosome (APC/C) controls unidirectional progression through the cell cycle by marking key cell cycle proteins for proteasomal turnover. Its activity is temporally regulated by the docking of different activating subunits, known in plants as CDC20 and CCS52. Despite the importance of the APC/C during cell proliferation, the number of identified targets in the plant cell cycle is limited. Here, we used the growth and meristem phenotypes of Arabidopsis CCS52A2-deficient plants in a suppressor mutagenesis screen to identify APC/CCCS52A2substrates or regulators, resulting in the identification of a mutant cyclinCYCA3;4allele. CYCA3;4 deficiency partially rescues the earlyccs52a2-1phenotypes, whereas increased CYCA3;4 levels enhances them. Furthermore, whereas CYCA3;4 proteins are promptly broken down after prophase in wild-type plants, they remain present in later stages of mitosis inccs52a2-1mutant plants, marking them as APC/CCCS52A2substrates. Strikingly,CYCA3;4overexpression results in aberrant root meristem and stomatal divisions, mimicking phenotypes of plants with reduced RBR1 activity. Correspondingly, RBR1 hyperphosphorylation was observed in CYCA3;4-overproducing plants. Our data thus demonstrate that an inability to timely destroy CYCA3;4 attributes to disorganized formative divisions, likely in part caused by the inactivation of RBR1.

ONE-SENTENCE SUMMARY

Timely post-prophase breakdown of the Arabidopsis cyclin CYCA3;4 by the Anaphase Promoting Complex/Cyclosome is essential for meristem organization and development.
Two groups ofArabidopsisreceptor kinases preferentially regulate the growth of intraspecies pollen tubes in the female reproductive tract
Authors: Lee Hyun Kyung , Goring Daphne R.
Published: March 2020

In flowering plants, continuous cell-cell communication between the compatible male pollen grain/growing pollen tube and the female pistil is required for successful sexual reproduction. InArabidopsis thaliana, the later stages of this dialogue are mediated by several peptide ligands and receptor kinases that guide pollen tubes to the ovules for the release of sperm cells. Despite a detailed understanding of these processes, a key gap remains on the nature of the regulators that function at the earlier stages. Here, we report on two groups ofA. thalianareceptor kinases, theLRR-VIII-2 RKsubclass and theSERKs, that function in the female reproductive tract to regulate the compatible pollen grains and early pollen tube growth, both essential steps for the downstream processes leading to fertilization. MultipleA. thaliana LRR-VIII-2 RKandSERKknockout mutant combinations were created, and several phenotypes were observed such as reduced wild-type pollen hydration and reduced pollen tube travel distances. As these mutant pistils displayed a wild-type morphology, the observed altered responses of the wild-type pollen are proposed to result from the loss of these receptor kinases leading to an impaired pollen-pistil dialogue at these early stages. Furthermore, using pollen from related Brassicaceae species, we also discovered that these receptor kinases are required in the female reproductive tract to establish a reproductive barrier to interspecies pollen. Thus, we propose that theLRR-VIII-2 RKs and theSERKs play a dual role in the preferential selection and promotion of intraspecies pollen over interspecies pollen.
Sox2 controls neural stem cell self-renewal through a Fos-centered gene regulatory network
Authors: Pagin Miriam , Pernebrink Mattias , Giubbolini Simone , Barone Cristiana , Sambruni Gaia , Zhu Yanfen , Chiara Matteo , Ottolenghi Sergio , Pavesi Giulio , Wei Chia-Lin , Cantù Claudio , Nicolis Silvia K.
Published: March 2020

The Sox2 transcription factor is necessary for the long-term self-renewal of neural stem cells (NSC). Its mechanism of action is still poorly defined. To identify molecules regulated by Sox2, and acting in mouse NSC maintenance, we transduced, into Sox2-deleted NSC, genes whose expression is strongly downregulated following Sox2 loss (Fos, Jun, Egr2), individually or in combination. Fos alone rescued long-term proliferation, as shown by in vitro cell growth and clonal analysis. Further, pharmacological inhibition of the FOS/JUN AP1 complex binding to its targets, decreased cell proliferation and expression of the putative target Suppressor of cytokine signaling 3 (Socs3). Additionally, Fos requirement for efficient long-term proliferation was demonstrated by the reduction of NSC clones capable of long-term expansion following CRISPR/Cas9-mediated Fos inactivation. Previous work showed that the Socs3 gene is strongly downregulated following Sox2 deletion, and its reexpression by lentiviral transduction rescues long-term NSC proliferation. Fos appears to be an upstream regulator of Socs3, possibly together with Jun and Egr2; indeed, Sox2 reexpression in Sox2-deleted NSC progressively activates both Fos and Socs3 expression; in turn, Fos transduction activates Socs3 expression. Based on available SOX2 ChIPseq and ChIA-PET data, we propose a model whereby Sox2 is a direct activator of both Socs3 and Fos, as well as possibly Jun and Egr2; further, we provide direct evidence for FOS and JUN binding onSocs3promoter, suggesting direct transcriptional regulation. These results provide the basis for developing a model of a network of interactions, regulating critical effectors of NSC proliferation and long-term maintenance.

Significance statement

Proliferation and maintenance of NSC are essential during normal brain development, and, postnatally, for the maintenance of hippocampal function and memory until advanced age. Little is known about the molecular mechanisms that maintain the critical aspects of NSC biology (quiescence and proliferation) in postnatal age. Our work provides a methodology, transduction of genes deregulated following Sox2 deletion, that allows to test many candidate genes for their ability to sustain NSC proliferation. In principle, this may have interesting implications for identifying targets for pharmacological manipulations.

Abstract Figure
Temporal context actively shapes EEG signatures of time perception
Authors: Damsma Atser , Schlichting Nadine , van Rijn Hedderik
Published: March 2020

Our subjective perception of time is optimized to temporal regularities in the environment. This is illustrated by the central tendency effect: when estimating a range of intervals, short intervals are overestimated whereas long intervals are underestimated to reduce the overall estimation error. Most models of interval timing ascribe this effect to the weighting of the current interval with previous memory tracesafterthe interval has been perceived. Alternatively, theperceptionof the duration could already be flexibly tuned to its temporal context. We investigated this hypothesis using an interval reproduction task in which human participants (both sexes) reproduced a shorter and longer interval range. As expected, reproductions were biased towards the subjective mean of each presented range. EEG analyses showed that temporal context indeed affected neural dynamics during the perception phase. Specifically, longer previous durations decreased CNV and P2 amplitude and increased beta power. In addition, multivariate pattern analysis showed that it is possible to decode context from the transient EEG signal quickly after both onset and offset of the perception phase. Together, these results suggest that temporal context creates dynamic expectations which actively affect theperceptionof duration.

Significance Statement

The subjective sense of duration does not arise in isolation, but is informed by previous experiences. This is demonstrated by abundant evidence showing that the production of duration estimates is biased towards previously experienced time intervals. However, it is yet unknown whether this temporal context actively affects perception or only asserts its influence in later, post-perceptual stages as proposed by most current formal models of this task. Using an interval reproduction task, we show that EEG signatures flexibly adapt to the temporal context during perceptual encoding. Furthermore, interval history can be decoded from the transient EEG signal even when the current duration was identical. Thus, our results demonstrate that context actively influences perception.
YAP and TAZ promote periosteal osteoblast precursor expansion and differentiation for fracture repair
Authors: Kegelman Christopher D. , Nijsure Madhura P. , Moharrer Yasaman , Pearson Hope B. , Dawahare James H. , Jordan Kelsey M. , Qin Ling , Boerckel Joel D.
Published: March 2020

In response to bone fracture, periosteal progenitor cells proliferate, expand, and differentiate to form cartilage and bone in the fracture callus. These cellular functions require the coordinated activation of multiple transcriptional programs, and the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) regulate osteochondroprogenitor activation during endochondral bone development. However, recent observations raise important distinctions between the signaling mechanisms used to control bone morphogenesis and repair. Here, we tested the hypothesis that YAP and TAZ regulate osteochondroprogenitor activation during endochondral bone fracture healing. Constitutive YAP and/or TAZ deletion from Osterix-expressing cells impaired both cartilage callus formation and subsequent mineralization. However, this could be explained either by direct defects in osteochondroprogenitor differentiation after fracture, or by developmental deficiencies in the progenitor cell pool prior to fracture. Consistent with the second possibility, we found that developmental YAP/TAZ deletion produced long bones with impaired periosteal thickness and cellularity. Therefore, to remove the contributions of developmental history, we next generated adult onset-inducible knockout mice (using Osx1-CretetOff) in which YAP and TAZ were deleted prior to fracture, but after normal development. Adult onset-induced YAP/TAZ deletion had no effect on cartilaginous callus formation, but impaired bone formation at 14 days post-fracture (dpf). Earlier, at 4 dpf, adult onset-induced YAP/TAZ deletion impaired the proliferation and expansion of osteoblast precursor cells located in the shoulder of the callus. Further, activated periosteal cells isolated from this region at 4 dpf exhibited impaired osteogenic differentiationin vitroupon YAP/TAZ deletion. Finally, confirming the effects on osteoblast functionin vivo, adult onset-induced YAP/TAZ deletion impaired bone formation in the callus shoulder at 7 dpf, prior to the initiation of endochondral ossification. Together, these data show that YAP and TAZ promote the expansion and differentiation of periosteal osteoblast precursors to accelerate bone fracture healing.
High-order interdependencies in the aging brain
Authors: Gatica Marilyn , Cofré Rodrigo , Mediano Pedro A.M. , Rosas Fernando E. , Orio Patricio , Diez Ibai , Swinnen S.P. , Cortes Jesus M.
Published: March 2020

Brain interdependencies can be studied either from a structural/anatomical perspective (“structural connectivity”, SC) or by considering statistical interdependencies (“functional connectivity”, FC). Interestingly, while SC is typically pairwise (white-matter fibers start in a certain region and arrive at another), FC is not; however, most FC analyses focus only on pairwise statistics and neglect high-order interactions. A promising tool to study high-order interdependencies is the recently proposedO-Information, which can quantify the intrinsic statistical synergy and redundancy in groups of three or more interacting variables. In this paper we used the O-Information to investigate how high-order statistical interdependencies are affected by age. For this, we analised functional magnetic resonance imaging (fMRI) data at rest obtained from 164 healthy participants, ranging from 10 to 80 years old. Our results show that older subjects (age ranging from 60 to 80 years) exhibit a higher predominance of redundant dependencies than younger subjects; moreover, this effect seems to be pervasive, taking place at all interaction orders. Additionally, we found that these effects are highly heterogeneous across brain regions, and suggest the existence of a “redundancy core” formed by the prefrontal and motor cortices – thus involving functions such as working memory, executive and motor functions. Our methodology to assess high-order interdependencies in fMRI data has unlimited applications. The code to calculate these metrics is freely available.
The giant sequoia genome and proliferation of disease resistance genes
Authors: Scott Alison D. , Zimin Aleksey V. , Puiu Daniela , Workman Rachael , Britton Monica , Zaman Sumaira , Caballero Madison , Read Andrew C. , Bogdanove Adam J. , Burns Emily , Wegrzyn Jill , Timp Winston , Salzberg Steven L. , Neale David B.
Published: March 2020

The giant sequoia (Sequoiadendron giganteum) of California are massive, long-lived trees that grow along the U.S. Sierra Nevada mountains. As they grow primarily in isolated groves within a narrow range, conservation of existing trees has been a national goal for over 150 years. Genomic data are limited in giant sequoia, and the assembly and annotation of the first giant sequoia genome has been an important goal to allow marker development for restoration and management. Using Illumina and Oxford Nanopore sequencing combined with Dovetail chromosome conformation capture libraries, 8.125 Gbp of sequence was assembled into eleven chromosome-scale scaffolds. This giant sequoia assembly represents the first genome sequenced in the Cupressaceae family, and lays a foundation for using genomic tools to aid in giant sequoia conservation and management. Beyond conservation and management applications, the giant sequoia assembly is a resource for answering questions about the life history of this enigmatic and robust species. Here we provide an example by taking an inventory of the large and complex family of NLR type disease resistance genes.
Structure of population activity in primary motor cortex for single finger flexion and extension
Authors: Arbuckle Spencer A. , Weiler Jeff , Kirk Eric A. , Rice Charles L. , Schieber Marc , Pruszynski J. Andrew , Ejaz Naveed , Diedrichsen Jörn
Published: March 2020

How is the primary motor cortex (M1) organized to control fine finger movements? We investigated the population activity in M1 for single finger flexion and extension, using 7T functional magnetic resonance imaging (fMRI) in female and male human participants, and compared these results to the neural spiking patterns recorded in two male monkeys performing the identical task. fMRI activity patterns were distinct for movements of different fingers, but quite similar for flexion and extension of the same finger. In contrast, spiking patterns in monkeys were quite distinct for both fingers and directions, similar to what was found for muscular activity patterns. The discrepancy between fMRI and electrophysiological measurements can be explained by two (non-mutually exclusive) characteristics of the organization of finger flexion and extension movements. Given that fMRI reflects predominantly input and recurrent activity, the results can be explained by an architecture in which neural populations that control flexion or extension of the same finger produce distinct outputs, but interact tightly with each other and receive similar inputs. Additionally, neurons tuned to different movement directions for the same finger (or combination of fingers) may cluster closely together, while neurons that control different finger combinations may be more spatially separated. When measuring this organization with fMRI at a coarse spatial scale, the activity patterns for flexion and extension of the same finger would appear very similar. Overall, we suggest that the discrepancy between fMRI and electrophysiological measurements provides new insights into the general organization of fine finger movements in M1.

Significance statement

The primary motor cortex (M1) is important for producing individuated finger movements. Recent evidence shows that movements that commonly co-occur are associated with more similar activity patterns in M1. Flexion and extension of the same finger, which never co-occur, should therefore be associated with distinct representations. However, using carefully controlled experiments and multivariate analyses, we demonstrate that human fMRI activity patterns for flexion or extension of the same finger are highly similar. In contrast, spiking patterns measured in monkey M1 are clearly distinct. This suggests that populations controlling opposite movements of the same finger, while producing distinct outputs, may cluster together and share inputs and local processing. These results provide testable hypotheses about the organization of hand control in M1.
Novel genes required for surface-associated motility inAcinetobacter baumannii
Authors: Blaschke Ulrike , Skiebe Evelyn , Wilharm Gottfried
Published: March 2020

Acinetobacter baumanniiis an opportunistic and increasingly multi-drug resistant human pathogen rated as a critical priority 1 pathogen for the development of new antibiotics by the WHO in 2017. Despite the lack of flagella,A. baumanniican move along wet surfaces in 2 different ways: via twitching motility and surface-associated motility. While twitching motility is known to depend on type IV pili, the mechanism of surface-associated motility is poorly understood. In this study we established a library of 30A. baumanniiATCC 17978 mutants that displayed deficiency in surface-associated motility. By making use of natural competence we also introduced these mutations into strain 29D2 to differentiate strain-specific versus species-specific effects of mutations. Mutated genes were associated with purine/pyrimidine/folate biosynthesis (e.g.purH,purF,purM,purE), alarmone/stress metabolism (e.g. Ap4A hydrolase), RNA modification/regulation (e.g. methionyl-tRNA synthetase), outer membrane proteins (e.g.ompA), and genes involved in natural competence (comEC). All tested mutants originally identified as motility-deficient in strain ATCC 17978 also displayed a motility-deficient phenotype in 29D2. By contrast, further comparative characterization of the mutant sets of both strains regarding pellicle biofilm formation, antibiotic resistance, and virulence in theGalleria mellonellainfection model revealed numerous strain-specific mutant phenotypes. Our studies highlight the need for comparative analyses to characterize gene functions inA. baumanniiand for further studies on the mechanisms underlying surface-associated motility.