bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain activity during reciprocal social interaction investigated using conversational robots as control condition
Authors: Rauchbauer Birgit , Nazarian Bruno , Bourhis Morgane , Ochs Magalie , Prévot Laurent , Chaminade Thierry
Published: March 2019

We present a novel functional magnetic resonance imaging paradigm for second-person neuroscience. The paradigm compares a human social interaction (human–human interaction, HHI) to an interaction with a conversational robot (human–robot interaction, HRI). The social interaction consists of 1 min blocks of live bidirectional discussion between the scanned participant and the human or robot agent. A final sample of 21 participants is included in the corpus comprising physiological (blood oxygen level-dependent, respiration and peripheral blood flow) and behavioural (recorded speech from all interlocutors, eye tracking from the scanned participant, face recording of the human and robot agents) data. Here, we present the first analysis of this corpus, contrasting neural activity between HHI and HRI. We hypothesized that independently of differences in behaviour between interactions with the human and robot agent, neural markers of mentalizing (temporoparietal junction (TPJ) and medial prefrontal cortex) and social motivation (hypothalamus and amygdala) would only be active in HHI. Results confirmed significantly increased response associated with HHI in the TPJ, hypothalamus and amygdala, but not in the medial prefrontal cortex. Future analysis of this corpus will include fine-grained characterization of verbal and non-verbal behaviours recorded during the interaction to investigate their neural correlates.

This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction'.
A neurocognitive investigation of the impact of socializing with a robot on empathy for pain
Authors: Cross Emily S. , Riddoch Katie A. , Pratts Jaydan , Titone Simon , Chaudhury Bishakha , Hortensius Ruud
Published: March 2019

To what extent can humans form social relationships with robots? In the present study, we combined functional neuroimaging with a robot socializing intervention to probe the flexibility of empathy, a core component of social relationships, towards robots. Twenty-six individuals underwent identical fMRI sessions before and after being issued a social robot to take home and interact with over the course of a week. While undergoing fMRI, participants observed videos of a human actor or a robot experiencing pain or pleasure in response to electrical stimulation. Repetition suppression of activity in the pain network, a collection of brain regions associated with empathy and emotional responding, was measured to test whether socializing with a social robot leads to greater overlap in neural mechanisms when observing human and robotic agents experiencing pain or pleasure. In contrast to our hypothesis, functional region-of-interest analyses revealed no change in neural overlap for agents after the socializing intervention. Similarly, no increase in activation when observing a robot experiencing pain emerged post-socializing. Whole-brain analysis showed that, before the socializing intervention, superior parietal and early visual regions are sensitive to novel agents, while after socializing, medial temporal regions show agent sensitivity. A region of the inferior parietal lobule was sensitive to novel emotions, but only during the pre-socializing scan session. Together, these findings suggest that a short socialization intervention with a social robot does not lead to discernible differences in empathy towards the robot, as measured by behavioural or brain responses. We discuss the extent to which long-term socialization with robots might shape social cognitive processes and ultimately our relationships with these machines.

This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction’.
Brain stimulation to left prefrontal cortex modulates attentional orienting to gaze cues
Authors: Wiese Eva , Abubshait Abdulaziz , Azarian Bobby , Blumberg Eric J.
Published: March 2019

In social interactions, we rely on non-verbal cues like gaze direction to understand the behaviour of others. How we react to these cues is determined by the degree to which we believe that they originate from an entity with a mind capable of having internal states and showing intentional behaviour, a process calledmind perception. While prior work has established a set of neural regions linked to mind perception, research has just begun to examine how mind perception affects social-cognitive mechanisms like gaze processing on a neuronal level. In the current experiment, participants performed a social attention task (i.e. attentional orienting to gaze cues) with either a human or a robot agent (i.e. manipulation of mind perception) while transcranial direct current stimulation (tDCS) was applied to prefrontal and temporo-parietal brain areas. The results show that temporo-parietal stimulation did not modulate mechanisms of social attention, neither in response to the human nor in response to the robot agent, whereas prefrontal stimulation enhanced attentional orienting in response to human gaze cues and attenuated attentional orienting in response to robot gaze cues. The findings suggest that mind perception modulates low-level mechanisms of social cognition via prefrontal structures, and that a certain degree of mind perception is essential in order for prefrontal stimulation to affect mechanisms of social attention.

This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction’.
Immediate and deferred epigenomic signature of neuronal activation
Authors: Fernandez-Albert Jordi , Lipinski Michal , Lopez-Cascales María T. , Rowley M. Jordan , Martin-Gonzalez Ana M. , del Blanco Beatriz , Corces Victor G. , Barco Angel
Published: March 2019

Activity-driven transcription plays an important role in many brain processes, including those underlying memory and epilepsy. Here, we combine the genetic tagging of neuronal nuclei and ribosomes with various sequencing-based techniques to investigate the transcriptional and chromatin changes occurring at hippocampal excitatory neurons upon synchronous activation during status epilepticus and sparse activation during novel context exploration. The transcriptional burst, which affects both nucleus-resident non-coding RNAs and numerous protein-coding genes involved in neuroplasticity, is associated with a dramatic increase in chromatin accessibility of activity-regulated genes and enhancers,de novobinding of activity-regulated transcription factors, augmented promoter-enhancer interactions, and the formation of gene loops that bring together the TSS and TTS of strongly induced genes to sustain the fast re-loading of RNAPII complexes. Remarkably, some chromatin occupancy changes and interactions remain long after neuronal activation and may underlie the changes in neuronal responsiveness and circuit connectivity observed in these neuroplasticity paradigms.
Synergetic effect of non-complementary 5’ AT-rich sequences on the development of a multiplex TaqMan real-time PCR for specific and robust detection of Clavibacter michiganensis and C. michiganensis subsp. nebraskensis
Authors: Larrea-Sarmiento Adriana , Alvarez Anne M. , Stack James P. , Arif Mohammad
Published: March 2019

Clavibacter is an agriculturally important genus comprising a single species, Clavibacter michiganensis, and multiple subspecies, including, C. michiganensis subsp. nebraskensis which causes Goss’s wilt/blight of corn and accounts for high yield losses - listed among the five most significant diseases of corn in the United States of America. Our research objective was to develop a robust and rapid multiplex TaqMan real-time PCR (qPCR) to detect C. michiganensis in general and C. michiganensis subsp. nebraskensis with enhanced reliability and accuracy by adding non-complementary AT sequences to the 5’ end of the forward and reverse primers. Comparative genomic analyses were performed to identify unique and conserved gene regions for primer and probe design. The unique genomic regions, ABC transporter ATP-binding protein CDS/ABC-transporter permease and MFS transporter were determined for specific detection of C. michiganensis and C. m. subsp. nebraskensis, respectively. The AT-rich sequences at the 5’ position of the primers enhanced the reaction efficiency and sensitivity of rapid qPCR cycling; the reliability, accuracy and high efficiency of the developed assay was confirmed after testing with 59 strains from inclusivity and exclusivity panels – no false positives or false negatives were detected. The assays were also validated through naturally and artificially infected corn plant samples; all samples were detected for C. michiganensis and C. m. subsp. nebraskensis with 100% accuracy. The assay with 5’ AT-rich sequences detected up to 10- and 100-fg of C. michiganensis and C. michiganensis subsp. nebraskensis genome targets, respectively. No adverse effect was observed when sensitivity assays were spiked with host genomic DNA. Addition of 5’ AT rich sequences enhanced the qPCR reaction efficiency from 0.82 (M = -3.83) and 0.91 (M = -3.54) to 1.04 (with optimum slope value; M = -3.23) for both C. michiganensis and C. michiganensis subsp. nebraskensis, respectively; a increase of 10-fold sensitivity was also obtained with C. michiganensis primer set. The methodology proposed here can be used to optimize the reaction efficiency and to harmonize the diagnostic protocols which have prodigious applications in routine diagnostics, biosecurity and microbial forensics.
CUX1 and IκBζ mediate the synergistic inflammatory response to TNF and IL-17A in stromal fibroblasts
Authors: Slowikowski Kamil , Nguyen Hung N. , Noss Erika H. , Simmons Daimon P. , Mizoguchi Fumitaka , Watts Gerald F.M. , Gurish Michael F. , Brenner Michael B. , Raychaudhuri Soumya
Published: March 2019

The role of stromal fibroblasts in chronic inflammation is unfolding. In rheumatoid arthritis (RA), leukocyte-derived cytokines tumor necrosis factor (TNF) and IL-17A work together, activating fibroblasts to become a dominant source of the hallmark cytokine IL-6. However, IL-17A alone has minimal effect on fibroblasts. To identify key mediators of the synergistic response to TNF and IL-17A in human synovial fibroblasts, we performed time series, dose response, and gene silencing transcriptomics experiments. Here we show that in combination with TNF, IL-17A selectively induces a specific set of genes mediated by factors including CUX1 and IκBζ. In the promoters of CXCL1, CXCL2, and CXCL3, we found a putative CUX1-NF-κB binding motif not found elsewhere in the genome. CUX1 and NF-κB p65 mediate transcription of these genes independent of LIFR, STAT3, STAT4, and ELF3. Transcription of NFKBIZ, encoding the atypical IκB factor IκBζ, is IL-17A dose-dependent, and IκBζ only mediates the transcriptional response to TNF and IL-17A, but not to TNF alone. In fibroblasts, IL-17A response depends on CUX1 and IκBζ to engage the NF-κB complex to produce chemoattractants for neutrophil and monocyte recruitment.
The life of P.I. Transitions to Independence in Academia
Authors: Acton Sophie E. , Bell Andrew , Toseland Christopher P. , Twelvetrees Alison
Published: March 2019

The data in this report summarises the responses gathered from 365 principal investigators of academic laboratories, who started their independent positions in the UK within the last 6 years up to 2018. We find that too many new investigators express frustration and poor optimism for the future. These data also reveal, that many of these individuals lack the support required to make a successful transition to independence and that simple measures could be put in place by both funders and universities in order to better support these early career researchers. We use these data to make both recommendations of good practice and for changes to policies that would make significant improvements to those currently finding independence challenging. We find that some new investigators face significant obstacles when building momentum and hiring a research team. In particular, access to PhD students. We also find some important areas such as starting salaries where significant gender differences persist, which cannot be explained by seniority. Our data also underlines the importance of support networks, within and outside the department, and the positive influence of good mentorship through this difficult career stage.
Convergent loss of an EDS1/PAD4 signalling pathway in several plant lineages predicts new components of plant immunity and drought response
Authors: Baggs EL , Thanki AS , O’Grady R , Schudoma C , Haerty W , Krasileva KV
Published: March 2019

Plant innate immunity relies on NLR receptors that recognize pathogen derived molecules and activate downstream signalling pathways. We analyzed the variation in copy number of NLR genes across flowering plants, and identified a number of species with a low number of NLRs relative to sister species. Two distinct lineages, one monocot (Lentibulariaceae) and one dicot (Alismatales) encapsulate four species with particularly few NLR genes. In these lineages, loss of NLRs coincided with loss of the well-known downstream immune signalling complex (EDS1-PAD4). When we expanded our analysis across the whole proteomes, we were able to identify other characterized immune genes absent only in Lentibulariaceae and Alismatales. Additionally, we identified a small subset of genes with unknown function convergently lost in all four species. We predicted that some of these genes may have a role in plant immunity. Gene expression analyses confirmed that a group of these genes was differentially expressed under pathogen infection. Another subset of these genes was differentially expressed upon drought providing further evidence of a link between the drought and plant immunity.
Effects of a rifampicin pre-treatment on linezolid pharmacokinetics
Authors: Okazaki Fumiyasu , Tsuji Yasuhiro , Seto Yoshihiro , Ogami Chika , Yamamoto Yoshihiro , To Hideto
Published: March 2019

Linezolid is an oxazolidinone antibiotic that effectively treats methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Since rifampicin induces other antibiotic effects, it is combined with linezolid in therapeutic regimes. However, linezolid blood concentrations are reduced by this combination, which increases the risk of the emergence of antibiotic-resistant bacteria. We herein demonstrated that the combination of linezolid with rifampicin inhibited its absorption and promoted its elimination, but not through microsomal enzymes. Our results indicate that the combination of linezolid with rifampicin reduces linezolid blood concentrations via metabolic enzymes.
Deriving Accurate Lipid Classification based on Molecular Formula
Authors: Mitchell Joshua M. , Moseley Hunter N.B.
Published: March 2019

Introduction

Although Fourier-transform mass spectrometry has substantially improved our ability to detect lipids and other metabolites; the untargeted and accurate assignment of detected metabolites remains an unsolved problem in metabolomics. New assignment methods such as our SMIRFE algorithm can assign elemental molecular formula to observed spectral features in an untargeted manner without orthogonal information from tandem MS or chromatography. However, for many lipidomics applications, it is necessary to know at least the lipid category or class that is associated with a detected spectral feature in order to derive biochemical interpretation.

Objectives

Our goal is to develop a method for robustly classifying elemental molecular formula assignments into lipid categories for application to SMIRFE-generated assignments.

Results

Using machine learning, we developed a method that can predict lipid category and class from SMIRFE molecular formula assignments. Our methods achieve high accuracy (>90%) and precision (>83%) for all eight of the lipid categories in the LIPIDMAPS database. Model performance was evaluated using sets of theoretical, data-derived, and artifactual molecular formulas. Our models were generalizable, applicable to real-world datasets, and very discriminating with most molecular formulas classified to the “not lipid” category. Lipid categories with the highest classification propensities were glycerophospholipids and sphingolipids, matching the highest category prevalence in LIPIDMAPS.

Conclusions

Our methods enable the lipid classification of untargeted molecular formula assignments generated by SMIRFE without orthogonal information, facilitating biochemical interpretation of highly untargeted lipidomics experiments. However, this lipid classification appears insufficient for validating single-spectrum assignments, but could be useful in cross-spectrum assignment validation.
Inferring neural signalling directionality from undirected structural connectomes
Authors: Seguin Caio , Razi Adeel , Zalesky Andrew
Published: March 2019

Neural information flow is inherently directional. To date, investigation of directional communication in the human structural connectome has been precluded by the inability of non-invasive neuroimaging methods to resolve axonal directionality. Here, we demonstrate that decentralized measures of network communication, applied to the undirected topology and geometry of brain networks, can predict putative directions of large-scale neural signalling. We propose the concept of send-receive communication asymmetry to characterize cortical regions as senders, receivers or neutral, based on differences between their incoming and outgoing communication efficiencies. Our results reveal a send-receive cortical hierarchy that recapitulates established organizational gradients differentiating sensory-motor and multimodal areas. We find that send-receive asymmetries are significantly associated with the directionality of effective connectivity derived from spectral dynamic causal modeling. Finally, using fruit fly, mouse and macaque connectomes, we provide further evidence suggesting that directionality of neural signalling is significantly encoded in the undirected architecture of nervous systems.
Affordable and robust phenotyping framework to analyse root system architecture of soil-grown plants
Authors: Bontpart Thibaut , Concha Cristobal , Giuffrida Valerio , Robertson Ingrid , Admkie Kassahun , Degefu Tulu , Girma Nigusie , Tesfaye Kassahun , Haileselassie Teklehaimanot , Fikre Asnake , Fetene Masresha , Tsaftaris Sotirios A. , Doerner Peter
Published: March 2019

The analysis of root system growth, root phenotyping, is important to inform efforts to enhance plant resource acquisition from soils. However, root phenotyping remains challenging due to soil opacity and requires systems that optimize root visibility and image acquisition. Previously reported systems require costly and bespoke materials not available in most countries, where breeders need tools to select varieties best adapted to local soils and field conditions. Here, we present an affordable soil-based growth container (rhizobox) and imaging system to phenotype root development in greenhouses or shelters. All components of the system are made from commodity components, locally available worldwide to facilitate the adoption of this affordable technology in low-income countries. The rhizobox is large enough (~6000 cm2visible soil) to not restrict vertical root system growth for at least seven weeks after sowing, yet light enough (~21 kg) to be routinely moved manually. Support structures and an imaging station, with five cameras covering the whole soil surface, complement the rhizoboxes. Images are acquiredviathe Phenotiki sensor interface, collected, stitched and analysed. Root system architecture (RSA) parameters are quantified without intervention. RSA of a dicot (chickpea,Cicer arietinumL.) and a monocot (barley,Hordeum vulgareL.) species, which exhibit contrasting root systems, were analysed. The affordable system is relevant for efforts in Ethiopia and elsewhere to enhance yields and climate resilience of chickpea and other crops for improved food security.

Significance Statement

An affordable system to characterize root system architecture of soil-grown plants was developed. Using commodity components, this will enable local efforts world-wide to breed for enhanced root systems.
Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording
Authors: Obaid Abdulmalik , Hanna Mina-Elraheb , Wu Yu-Wei , Kollo Mihaly , Racz Romeo , Angle Matthew R , Müller Jan , Brackbill Nora , Wray William , Franke Felix , Chichilnisky E.J. , Hierlemann Andreas , Ding Jun B , Schaefer Andreas T , Melosh Nicholas A
Published: March 2019

Multi-channel electrical recordings of neural activity in the brain is an increasingly powerful method revealing new aspects of neural communication, computation, and prosthetics. However, while planar silicon-based CMOS devices in conventional electronics scale rapidly, neural interface devices have not kept pace. Here, we present a new strategy to interface silicon-based chips with three-dimensional microwire arrays, providing the link between rapidly-developing electronics and high density neural interfaces. The system consists of a bundle of microwires mated to large-scale microelectrode arrays, such as camera chips. This system has excellent recording performance, demonstrated via single unit and local-field potential recordings in isolated retina and in the motor cortex or striatum of awake moving mice. The modular design enables a variety of microwire types and sizes to be integrated with different types of pixel arrays, connecting the rapid progress of commercial multiplexing, digitisation and data acquisition hardware together with a three-dimensional neural interface.
Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug
Authors: Sanderson Lisa , da Silva Marcelo , Sekhar Gayathri N. , Brown Rachel C. , Burrell-Saward Hollie , Fidanboylu Mehmet , Liu Bo , Dailey Lea Ann , Dreiss Cécile A. , Lorenz Chris , Christie Mark , Persaud Shanta J. , Yardley Vanessa , Croft Simon L , Valero Margarita , Thomas Sarah A.
Published: March 2019

Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10-100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations. To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluationin vitro, quantified pentamidine CNS delivery of a sub-set of formulationsin vitroandin vivo, and progressed one pentamidine-Pluronic formulation for further evaluation using anin vivosingle dose brain penetration study. Screening pentamidine against 40 CNS targets did not reveal any major neurotoxicity concerns, however, pentamidine had a high affinity for the imidazoline2receptor. The reduction in insulin secretion in MIN6 β-cells by pentamidine maybe secondary to pentamidine-mediated activation of β-cell imidazoline receptors and impairment of cell viability. Pluronic F68 (0.01%w/v)-pentamidine formulation had a similar inhibitory effect on insulin secretion as pentamidine alone and an additive trypanocidal effectin vitro. However, all Pluronics tested (P85, P105 and F68) did not significantly enhance brain exposure of pentamidine. These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.
Identification of DNA motifs that regulate DNA methylation
Authors: Wang Mengchi , Zhang Kai , Ngo Vu , Liu Chengyu , Fan Shicai , Whitaker John W , Chen Yue , Ai Rizi , Chen Zhao , Wang Jun , Zheng Lina , Wang Wei
Published: March 2019

DNA methylation is an important epigenetic mark but how its locus-specificity is decided in relation to DNA sequence is not fully understood. Here, we have analyzed 34 diverse whole-genome bisulfite sequencing datasets in human and identified 313 motifs, including 92 and 221 associated with methylation (methylation motifs, MMs) and unmethylation (unmethylation motifs, UMs), respectively. The functionality of these motifs is supported by multiple lines of evidences. First, the methylation levels at the MM and UM motifs are respectively higher and lower than the genomic background. Second, these motifs are enriched at the binding sites of methylation modifying enzymes including DNMT3A and TET1, indicating their possible roles of recruiting these enzymes. Third, these motifs significantly overlap with SNPs associated with gene expression and those with DNA methylation. Fourth, disruption of these motifs by SNPs is associated with significantly altered methylation level of the CpGs in the neighbor regions. Furthermore, these motifs together with somatic SNPs are predictive of cancer subtypes and patient survival. We revealed some of these motifs were also associated with histone modifications, suggesting possible interplay between the two types of epigenetic modifications. We also found some motifs form feed forward loops to contribute to DNA methylation dynamics.
Optimized Mucosal MVA Prime/ Soluble gp120 Boost Vaccination Regimen Induces Similar Antibody Responses as an Intramuscular Regimen
Authors: Jones Dorothy I. , Pollara Justin J. , Johnson-Weaver Brandi T. , LaBranche Celia C. , Montefiori David C. , Pickup David J. , Permar Sallie R. , Abraham Soman N. , Maddaloni Massimo , Pascual David W. , Staats Herman F.
Published: March 2019

The benefits of mucosal vaccines over injected vaccines are difficult to ascertain since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if mucosal vaccination using a modified vaccinia Ankara expressing HIV-1 gp120 (MVA-g120) prime and HIV-1 gp120 protein boost could be optimized to induce serum antibody responses similar to those induced by an intramuscularly (IM) administered MVA prime/gp120 boost to allow comparison of an IM immunization regimen to a mucosal vaccination regimen for their ability to protect against a low dose rectal SHIV challenge while inducing similar serum anti-HIV-1 antibody responses. A 3-fold higher antigen dose was required for intranasal (IN) immunization with gp120 to induce serum anti-gp120 IgG responses not significantly different than those induced by IM immunization. Gp120 fused to the Adenovirus type 2 fiber binding domain (gp120-Ad2F), a mucosal targeting ligand, exhibited enhanced IN immunogenicity when compared to gp120 alone. MVA-gp120 was more immunogenic after IN delivery than gastric or rectal delivery, although serum antibodies induced by IN immunization were lower than those induced by intramuscular immunization. Using these optimized vaccines, an IN MVA-gp120 prime, combined IM (gp120) and IN (gp120-Ad2F) boost regimen (IN/IM+IN) induced serum anti-gp120 antibody titers similar to those induced by the intramuscular prime/boost regimen (IM/IM) in rabbits and non-human primates. Despite the induction of similar systemic anti-HIV-1 antibody responses, neither the IM/IM nor the IN/IM+IN regimen induced elevated anti-HIV-1 mucosal IgA responses nor protected against a repeated low-dose rectal SHIV challenge. These results demonstrate that immunization regimens utilizing the IN route are able to induce serum antigen-specific antibody responses similar to those induced by systemic immunization

IMPORTANCE

Mucosal vaccination is proposed as a method of immunization able to induce protection against mucosal pathogens that is superior to protection provided by parenteral immunization. However, mucosal vaccination often induces serum antigen-specific immune responses of lower magnitude than those induced by parenteral immunization, making the comparison of mucosal and parenteral immunization difficult. We identified vaccine parameters that allowed an immunization regimen consisting of an IN prime followed with boosters administered by both IN and IM routes to induce serum antibody responses similar to those induced by IM prime/boost vaccination. Additional studies are needed to determine the potential benefit of mucosal immunization for HIV-1 and other mucosally-transmitted pathogens.
Vertical niche definition of test-bearing protists (Rhizaria) into the twilight zone revealed by in situ imaging
Authors: Biard Tristan , Ohman Mark D.
Published: March 2019

The Rhizaria is a super-group of ameoboid protists with ubiquitous distributions, from the euphotic zone to the twilight zone and beyond. While rhizarians have been recently described as important contributors to both silica and carbon fluxes, we lack the most basic information about their ecological preferences. Here, using the in situ imaging (Underwater Vision Profiler 5), we characterize the vertical ecological niches of different test-bearing rhizarian taxa in the southernCalifornia Current Ecosystem. We define three vertical layers between 0-500 m occupied, respectively, by 1) surface dwelling and mostly symbiont-bearing rhizarians (Acantharia and Collodaria), 2) flux-feeding phaeodarians in the lower epipelagic (100-200 m), and 3) Foraminifera and Phaeodaria populations adjacent to the Oxygen Minimum Zone. We then use Generalized Additive Models to analyze the response of each rhizarian category to a suite of environmental variables. The models explain between 13 and 93% of the total variance observed for the different groups. While temperature and the depth of the deep chlorophyll maximum, appear as the main factors influencing populations in the upper 200 m, silicic acid concentration is the most important variable related to the abundance of mesopelagic phaeodarians. The relative importance of biotic interactions (e.g., predation, parasitism) is still to be considered, in order to fully incorporate the dynamics of test-bearing pelagic rhizarians in ecological and biogeochemical models.
High-speed multifocal plane fluorescence microscopy for three-dimensional visualisation of beating flagella
Authors: Wheeler Richard J.
Published: March 2019

Analysis of flagellum beating in three dimensions is important for understanding how cells can undergo complex flagellum-driven motility and the ability to use fluorescence microscopy for such three-dimensional analysis would be extremely powerful. Trypanosoma and Leishmania are unicellular parasites which undergo complex cell movements in three dimensions as they swim and would particularly benefit from such an analysis. Here, high-speed multifocal plane fluorescence microscopy, a technique in which a light path multi-splitter is used to visualise 4 focal planes simultaneously, was used to reconstruct the flagellum beating of Trypanosoma brucei and Leishmania mexicana in three dimensions. It was possible to use either an organic fluorescent stain or a genetically-encoded fluorescence fusion protein to visualise flagellum and cell movement in three dimensions at a 200 Hz frame rate. This high-speed multifocal plane fluorescence microscopy approach was used to address two open questions regarding Trypanosoma and Leishmania swimming: To quantify the planarity of the L. mexicana flagellum beat and analyse the nature of flagellum beating during T. brucei ‘tumbling’.
Genome-wide sequencing uncovers cryptic diversity and mito-nuclear discordance in theOctopus vulgarisspecies complex
Authors: Amor Michael D. , Doyle Stephen R. , Norman Mark D. , Roura Alvaro , Hall Nathan E. , Robinson Andrew J. , Leite Tatiana S. , Strugnell Jan M.
Published: March 2019

Many marine species once considered to be cosmopolitan are now recognised as cryptic species complexes. Mitochondrial markers are ubiquitously used to address phylogeographic questions, and have been used to identify some cryptic species complexes; however, their efficacy in inference of evolutionary processes in the nuclear genome has not been thoroughly investigated. We used double digest restriction site-associated DNA sequencing (ddRADseq) markers to quantify species boundaries in the widely distributed and high value common octopus,Octopus vulgaris, comparing genome-wide phylogenetic signal to that obtained from mitochondrial markers. Phylogenetic analyses, genome-wide concordance and species tree estimation based on 604 genome-wide ddRADseq loci revealed six species within theO. vulgarisgroup. Divergence time estimates suggested modern-day species evolved over the last 2.5 ma, during a period of global cooling. Importantly, our study identified significant phylogenetic discordance between mitochondrial and nuclear markers; genome-wide nuclear loci supportedO. vulgarissensu stricto and Type III (South Africa) as distinct species, which mtDNA failed to recognise. Our finding of conflicting phylogenetic signal between mitochondrial and nuclear markers has broad implications for many taxa. Improved phylogenetic resolution ofO. vulgarishas significant implications for appropriate management of the group and will allow greater accuracy in global fisheries catch statistics.
Universal trends of post-duplication evolution revealed by the genomes of 13Parameciumspecies sharing an ancestral whole-genome duplication
Authors: Gout Jean-Francois , Johri Parul , Arnaiz Olivier , Doak Thomas G. , Bhullar Simran , Couloux Arnaud , Guérin Fréderic , Malinsky Sophie , Sperling Linda , Labadie Karine , Meyer Eric , Duharcourt Sandra , Lynch Michael
Published: March 2019

Whole-Genome Duplications (WGDs) have shaped the gene repertoire of many eukaryotic lineages. The redundancy created by WGDs typically results in a phase of massive gene loss. However, some WGD-derived paralogs are maintained over long evolutionary periods and the relative contributions of different selective pressures to their maintenance is still debated. Previous studies have revealed a history of three successive WGDs in the lineage of the ciliateParamecium tetraureliaand two of its sister species from theP. aureliacomplex. Here, we report the genome sequence and analysis of 10 additionalP. aureliaspecies and one additional outgroup, allowing us to track post-WGD evolution in 13 species that share a common ancestral WGD. We found similar biases in gene retention compatible with dosage constraints playing a major role opposing post-WGD gene loss across all 13 species. Interestingly we found that post-WGD gene loss was slower inParameciumthan in other species having experienced genome duplication, suggesting that the selective pressures against post-WGD gene loss are especially strong inParamecium. We also report a lack of recent segmental duplications inParamecium, which we interpret as additional evidence for strong selective pressures against individual genes dosage changes. Finally, we hope that this exceptional dataset of 13 species sharing an ancestral WGD and two closely related outgroup species will be a useful resource for future studies and will help establishParameciumas a major model organism in the study of post-WGD evolution.
Metabolic constraints drive self-organization of specialized cell groups
Authors: Varahan Sriram , Walvekar Adhish , Sinha Vaibhhav , Krishna Sandeep , Laxman Sunil
Published: March 2019

How phenotypically distinct states in isogenic cell populations appear and stably co-exist remains an unresolved question. We find that within a clonal yeast colony developing in low glucose, cells arrange into metabolically disparate cell groups. Using this system, we model and experimentally identify metabolic constraints sufficient to drive such assembly. Beginning in a gluconeogenic state, cells in a contrary state, exhibiting high pentose phosphate pathway activity, spontaneously appear and proliferate, in a spatially constrained manner. The gluconeogenic cells in the developing colony produce a resource, which we identify as trehalose. At threshold concentrations of trehalose, cells in the new metabolic state emerge and proliferate. A self-organized system establishes, where cells in this new state are sustained by trehalose consumption, which thereby restrains other cells in the trehalose producing, gluconeogenic state. Our work suggests simple physico-chemical principles that determine how isogenic cells spontaneously self-organize into structured assemblies in complimentary, specialized states.
A systematic review of MERS-CoV (Middle East Respiratory Syndrome Coronavirus) seroprevalence and viral RNA prevalence in dromedary camels: implications for animal vaccination
Authors: Dighe Amy , Jombart Thibaut , Van Kerkhove Maria D. , Ferguson Neil
Published: March 2019

Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We systematically reviewed the published literature reporting seroprevalence and/or prevalence of active MERS-CoV infection in dromedary populations from both cross-sectional and longitudinal studies, including 60 studies in our qualitative syntheses. MERS-CoV seroprevalence increased with age up to 80-100% in adult dromedaries supporting geographically wide spread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design.
Medication-related osteonecrosis of the jaws after tooth extraction in senescent female mice treated with zoledronic acid: microtomographic, histological and immunohistochemical characterization
Authors: Biguetti Claudia Cristina , De Oliva André Hergesel , Healy Kent , Mahmoud Ramez Hassan , Custódio Isabela Do Carmo , Constantino Dulce Helena , Ervolino Edilson , Duarte Marco Antonio Hungaro , Fakhouri Walid D. , Matsumoto Mariza Akemi
Published: March 2019

Treatment with cumulative dosages of zoledronic acid (ZA) in elderly patients is a risk factor for the development of medication-related osteonecrosis of the jaws (MRONJ), mainly related to surgical triggers such as tooth extraction. However, animal models for the investigation and understanding of MRONJ pathophysiology in senescent and postmenopausal stages remains to be developed and characterized. The aim of this study was to analyze MRONJ development in senescent female mice treated with cumulative dosages of ZA. For this purpose, twenty 129/Sv female mice, 64 weeks old, were treated with 0.9% saline solution as Control group (n=10), and with ZA at 250µg/Kg (n=10), once a week, starting 4 weeks before the upper right incisor extraction and until the end of the experimental time points (7 days and 21 days). At 7 and 21 days, specimens were harvested for microCT, histological, birefringence and immunohistochemical analysis. Clinically, an incomplete epithelialization was observed in ZA group at 7 days and a delayed bone matrix mineralization and collagen maturation at 7 and 21 days compared to the controls. Controls revealed sockets filled with mature bone at 21 days as observed by microCT and birefringence, while ZA group presented delayed bone deposition at 7 and 21 days, as well increased leukocyte infiltration and blood clot at 7 days, and increased bone sequestrum and empty osteocyte lacunae at 21 days (p<0.05). Also, ZA group presented decreased quantity TGFb+ and Runx-2+ cells at 7 days, and decreased quantity of TRAP+ osteoclasts compared to the control at 21 days (p<0.05). Togheter, these data demonstrate the usefulness of this model to understanding the pathophysiology of MRONJ.
Trait plasticity of intensive pasture species due to growth in mixture across seasons and nutrient addition levels
Authors: Mason Norman W.H. , Lambie Suzanne , Waugh Deanne , Orwin Kate , Carmona Carlos P. , Mudge Paul
Published: March 2019

Questions

How do the traits of pastoral species respond to growth in mixture, nitrogen addition and season? What are the impacts of trait plasticity on community aggregate trait values?

Study site

A large-scale field experiment on intensively managed dairy pastures in New Zealand.

Methods

We measured traits linked to rate of return on investment in leaves – leaf nitrogen content (leaf N) and specific leaf area (SLA) – and biomass investment in leaf area – leaf area ratio (LAR). We collected trait data for 5 pasture species (one grass, two forbs, and two N2-fixing legumes) grown in monoculture or a five-species mixture across three levels of nitrogen (N) addition in four seasons. For each species in each season we tested for significant effects of growth in mixture, N addition, and their interaction. We calculated community-weighted mean (CWM) values in mixture plots using traits collected either from mixtures or monocultures. We tested for significant mixture and N addition effects on CWM, and for significant interactions between mixture and N addition.

Results

SLA and LAR for all non-N2-fixers were significantly higher in spring, summer or autumn, and never significantly lower in mixture than in monoculture. All three non-N2-fixers experienced higher leaf N in mixture during summer, but two species had significantly lower leaf N in either winter or autumn. Mixture effects on CWM values for all three traits were negative in winter and positive in either spring or summer.

Conclusions

The direction of trait plasticity effects on community level trait means was highly seasonally dependent.
Development of a model estimating root length density from root impacts on a soil profile in pearl millet (Pennisetum glaucum(L.) R. Br). Application to measure root system response to water stress in field conditions
Authors: Faye A. , Sine B. , Chopart J.L. , Grondin A. , Lucas M. , Diedhiou A. , Gantet P. , Cournac L. , Min D. , Audebert A. , Kane A. , Laplaze L.
Published: March 2019

Pearl millet, unlike other cereals, is able to withstand dry and hot conditions and plays an important role for food security in arid and semi-arid areas of Africa and India. However, low soil fertility and drought constrain pearl millet yield. One of the main targets to address these constraints through agricultural practices or breeding is root system architecture. In this study, in order to easily phenotype the root system in field conditions, we developed a model to predict root length density (RLD) of pearl millet plants from root intersection densities (RID) counted on a trench profile in field conditions. We identified root orientation as an important parameter to improve the relationship between RID and RLD. Root orientation was notably found to differ between thick roots (more anisotropic with depth) and fine roots (isotropic at all depths). We used our model to study pearl millet root system response to drought and showed that pearl millet reorients its root growth toward deeper soil layers that retain more water in these conditions. Overall, this model opens ways for the characterization of the impact of environmental factors and management practices on pearl millet root system development.
Coexpression patterns define epigenetic regulators associated with neurological dysfunction
Authors: Boukas Leandros , Havrilla James M. , Hickey Peter F. , Quinlan Aaron R. , Bjornsson Hans T. , Hansen Kasper D.
Published: March 2019

Coding variants in epigenetic regulators are emerging as causes of neurological dysfunction and cancer. However, a comprehensive effort to identify disease candidates within the human epigenetic machinery (EM) has not been performed; it is unclear whether features exist that distinguish between variation-intolerant and variation-tolerant EM genes, and between EM genes associated with neurological dysfunction versus cancer. Here, we rigorously define 295 genes with a direct role in epigenetic regulation (writers, erasers, remodelers, readers). Systematic exploration of these genes reveals that although individual enzymatic functions are always mutually exclusive, readers often also exhibit enzymatic activity (dual-function EM genes). We find that the majority of EM genes are very intolerant to loss-of-function variation, even when compared to the dosage sensitive transcription factors, and we identify 102 novel EM disease candidates. We show that this variation intolerance is driven by the protein domains encoding the epigenetic function, suggesting that disease is caused by a perturbed chromatin state. We then describe a large subset of EM genes that are coexpressed within multiple tissues. This subset is almost exclusively populated by extremely variation-intolerant genes and shows enrichment for dual-function EM genes. It is also highly enriched for genes associated with neurological dysfunction, even when accounting for dosage sensitivity, but not for cancer-associated EM genes. Finally, we show that regulatory regions near epigenetic regulators are genetically important for common neurological traits. These findings prioritize novel disease candidate EM genes and suggest that this coexpression plays a functional role in normal neurological homeostasis.
Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
Authors: Benayoun Bérénice A. , Pollina Elizabeth A. , Singh Param Priya , Mahmoudi Salah , Harel Itamar , Casey Kerriann M. , Dulken Ben W. , Kundaje Anshul , Brunet Anne
Published: March 2019

Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice—yielding 143 high-quality data sets. We focused on chromatin marks linked to gene expression regulation and cell identity: histone H3 trimethylation at lysine 4 (H3K4me3), a mark enriched at promoters, and histone H3 acetylation at lysine 27 (H3K27ac), a mark enriched at active enhancers. Epigenomic and transcriptomic landscapes could easily distinguish between ages, and machine-learning analysis showed that specific epigenomic states could predict transcriptional changes during aging. Analysis of data sets from all tissues identified recurrent age-related chromatin and transcriptional changes in key processes, including the up-regulation of immune system response pathways such as the interferon response. The up-regulation of the interferon response pathway with age was accompanied by increased transcription and chromatin remodeling at specific endogenous retroviral sequences. Pathways misregulated during mouse aging across tissues, notably innate immune pathways, were also misregulated with aging in other vertebrate species—African turquoise killifish, rat, and humans—indicating common signatures of age across species. To date, our data set represents the largest multitissue epigenomic and transcriptomic data set for vertebrate aging. This resource identifies chromatin and transcriptional states that are characteristic of young tissues, which could be leveraged to restore aspects of youthful functionality to old tissues.