bluuebunny/crossref_metadata_2025 huggingface dataset:
Group size and modularity interact to shape the spread of infection and information through animal societies
Authors: Evans Julian C , Hodgson David J , Boogert Neeltje J , Silk Matthew J
Published: May 2021

Social interactions between animals can provide many benefits, including the ability to gain useful environmental information through social learning. However, these social contacts can also facilitate the transmission of infectious diseases through a population. Animals engaging in social interactions must therefore face a trade-off between the potential informational benefits and the risk of acquiring disease. In order to understand how this trade-off can influence animal sociality, it is necessary to quantify the effects of different social structures on individuals’ likelihood of acquiring information versus infection Theoretical models have suggested that modular social networks, associated with the formation of groups or sub-groups, can slow spread of infection by trapping it within particular groups. However these social structures will not necessarily impact the spread of information in the same way if its transmission is considered as a “complex contagion”, e.g. through individuals copying the majority (conformist learning). Here we use simulation models to demonstrate that modular networks can promote the spread of information relative to the spread of infection, but only when the network is fragmented and group sizes are small. We show that the difference in transmission between information and disease is maximised for more well-connected social networks when the likelihood of transmission is intermediate. Our results have important implications for understanding the selective pressures operating on the social structure of animal societies, revealing that highly fragmented networks such as those formed in fission-fusion social groups and multilevel societies can be effective in modulating the infection-information trade-off for individuals within them.

Significance statement

Risk of infection is commonly regarded as one of the costs of animal social behaviours, while the potential for acquiring useful information is seen as a benefit. Balancing this risk of infection with the potential to gain useful information is one of the key trade-offs facing animals that engage in social interactions. In order to better understand this trade-off, it is necessary to quantify how different social structures can promote access to useful information while minimising risk of infection. We used simulations of disease and information spread to examine how group sizes and social network fragmentation influences both these transmission processes. Our models find that more subdivided networks slow the spread of disease far more than infection, but only group sizes are small. Our results demonstrate that showing that fragmented social structures can be more effective in balancing the infection-information trade-off for individuals within them.
ACTIVATION LOOP PHOSPHORYLATION OF A NON-RD RECEPTOR KINASE INITIATES PLANT INNATE IMMUNE SIGNALING
Authors: Bender Kyle W. , Couto Daniel , Kadota Yasuhiro , Macho Alberto P. , Sklenar Jan , Bjornson Marta , Petriello Annalise , Farre Maria Font , Schwessinger Benjamin , Ntoukakis Vardis , Stransfeld Lena , Jones Alexandra M.E. , Menke Frank L.H. , Zipfel Cyril
Published: May 2021

Receptor kinases (RKs) play fundamental roles in extracellular sensing to regulate development and stress responses across kingdoms. In plants, leucine-rich repeat receptor kinases (LRR-RKs) function primarily as peptide receptors that regulate myriad aspects of plant development and response to external stimuli. Extensive phosphorylation of LRR-RK cytoplasmic domains is among the earliest detectable responses following ligand perception, and reciprocal transphosphorylation between a receptor and its co-receptor is thought to activate the receptor complex. Originally proposed based on characterization of the brassinosteroid receptor, the prevalence of complex activation via reciprocal transphosphorylation across the plant RK family has not been tested. Using the LRR-RK ELONGATION FACTOR TU RECEPTOR (EFR) as a model RK, we set out to understand the steps critical for activating RK complexes. While the EFR cytoplasmic domain is an active protein kinasein vitroand is phosphorylated in a ligand-dependent mannerin vivo, catalytically deficient EFR variants are functional in anti-bacterial immunity. These results reveal a non-catalytic role for the EFR cytoplasmic domain in triggering immune signaling and indicate that reciprocal transphoshorylation is not a ubiquitous requirement for LRR-RK complex activation. Rather, our analysis of EFR along with a detailed survey of the literature suggests a distinction between LRR-RK complexes with RD- versus non-RD protein kinase domains. Based on newly identified phosphorylation sites that regulate the activation state of the EFR complexin vivo, we propose that LRR-RK complexes containing a non-RD protein kinase may be regulated by phosphorylation-dependent conformational changes of the ligand-binding receptor which could initiate signaling in a feed-forward fashion either allosterically or through driving the dissociation of negative regulators of the complex.
Heritable differences in synaptic zinc-transporter levels drive variation in learned birdsong
Authors: Mets DG. , Mehaffey W. H. , Colquitt B. M. , Brainard M. S.
Published: May 2021

The authors have withdrawn this manuscript. During revision of our manuscript, we carried out several lines of additional experiments and analyses that failed to fully support and reproduce the results previously presented in Figure 4 (regarding potential mechanisms whereby zinc and SLC39all contribute to song tempo). We therefore do not want this result to be cited and are withdrawing our paper while we carry out additional experiments to clarify potential contributions of SLC39all to individual variation in song tempo. We apologize for any inconvenience caused to our readers. Any questions can be addressed to DGM (first/corresponding author) and/or MSB (last/senior author).
The potential of aquatic haematophagous, liquidosomatophagous and macrophagous leeches as a tool for iDNA characterisation
Authors: Lynggaard Christina , Oceguera-Figueroa Alejandro , Kvist Sebastian , Gilbert M Thomas P , Bohmann Kristine
Published: May 2021

Leeches play important roles in food webs due to their abundance, diversity and feeding habits. Studies using invertebrate-derived DNA (iDNA) extracted from leech gut contents to target vertebrate DNA have focused on the Indo-Pacific region and mainly leveraged the leech family Haemadipsidae, composed of haematophagous terrestrial leeches, while the aquatic haematophagous, liquidosomatophagous and macrophagous counterparts have largely been disregarded. While there is general knowledge regarding the taxonomic groups that leeches prefer to feed on, detailed taxonomic resolution is still missing and therefore, their potential use for monitoring animals is not known. In this study, 116 non-haemadipsid leeches belonging to 12 species and spanning the three feeding habits were collected in Mexico and Canada. We used DNA metabarcoding to investigate their diet and assess their potential use for vertebrate monitoring. We detected vertebrate taxa from five orders including fish, turtles and birds in the diet of the aquatic haematophagous leeches; eight invertebrate orders of annelids, arthropods and molluscs in the liquidosomatophagous leeches; and ten orders of invertebrates belonging to Arthropoda and Annelida, as well as one vertebrate and one parasitic nematode, in the macrophagous leeches. These results show the potential use of iDNA from the gut content of aquatic haematophagous leeches for retrieving vertebrate taxa, and from macrophagous and liquidosomatophagous counterparts for invertebrates. Our study provides information about the dietary range of the freshwater leeches and the non-haemadipsid terrestrial leech and proof-of-concept for the use of non-haemadipsid leeches for animal monitoring, expanding our knowledge of the use of iDNA from leech gut contents to North America.
The interplay of spatial scale and landscape transformation moderates the abundance and intraspecific variation in the ecomorphological traits of a phyllostomid bat
Authors: Ramírez-Mejía Andrés F. , Urbina-Cardona J. Nicolás , Sánchez Francisco
Published: May 2021

Land-use intensification imposes selective pressures that systematically change the frequency of wild population phenotypes. Growing evidence is biased towards the comparison of populations from discrete categories of land uses, ignoring the role of landscape emerging properties on the phenotype selection of wild fauna. Across the largest urban-rural gradient of the Colombian Orinoquia, we measured ecomorphological traits of 216 individuals of the Flat-faced Fruit-eating BatArtibeus planirostris, to evaluate the scale of effect at which landscape transformation better predicts changes in phenotype and abundance of an urban-tolerant species. Forest percentage at 1.25 km was the main predictor affecting abundance, wing aspect ratio, and body mass of this phyllostomid; but the direction of the effect differed between abundance and ecomorphological traits. Although landscape factors explained changes in the forearm length at all spatial scales, the effect was sex-dependent and the most important predictor was forest percentage at 0.5 km. Our results indicate that landscape elements and spatial scale interact to shape ecomorphological traits and the abundance ofA. planirostris. Interestingly, the scale of effect was congruent among all biological responses. A pattern that likely arises since species’ abundance can reflect the variation on phenotype under different environmental filters across landscape scenarios.
Symbiont-conferred immunity interacts with the effects of parasitoid genotype and intraguild predation to shape pea aphid immunity in a clone-specific fashion
Authors: Purkiss Samuel Alexander , Khudr Mouhammad Shadi , Aguinaga Oscar Enrique , Hager Reinmar
Published: May 2021

Host-parasite interactions represent complex co-evolving systems in which genetic variation within a species can significantly affect selective pressure on traits in the other (for example via inter-species indirect genetic effects). While often viewed as a two-species interaction between host and parasite species, some systems are more complex due to the involvement of symbionts in the host that influence its immunity, enemies of the host, and the parasite through intraguild predation. However, it remains unclear what the joint effects of intraguild predation, defensive endosymbiosis, within-species genetic variation and indirect genetic effects on host immunity are. We have addressed this question in an important agricultural pest system, the pea aphidAcyrthosiphon pisum, which shows significant intraspecific variability in immunity to the parasitoid waspAphidius ervidue to immunity conferring endosymbiotic bacteria. In a complex experiment involving a quantitative genetic design of the parasitoid, two ecologically different aphid lineages and the aphid lionChrysoperla carneaas an intraguild predator, we demonstrate that aphid immunity is affected by intraspecific genetic variation in the parasitoid and the aphid, as well as by associated differences in the defensive endosymbiont communities. Using 16s rRNA sequencing, we identified secondary symbionts that differed between the lineages. We further show that aphid lineages differ in their altruistic behaviour once parasitised whereby infested aphids move away from the clonal colony to facilitate predation. The outcome of these complex between-species interactions not only shape important host-parasite systems but have also implications for understanding the evolution of multitrophic interactions, and aphid biocontrol.
Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome
Authors: Mattis Joanna , Somarowthu Ala , Goff Kevin M. , Yom Jina , Sotuyo Nathaniel P. , McGarry Laura M. , Feng Huijie , Kaneko Keisuke , Goldberg Ethan M.
Published: May 2021

Dravet syndrome (DS) is a neurodevelopmental disorder defined by treatment-resistant epilepsy, autism spectrum disorder, and sudden death, due to pathogenic variants inSCN1Aencoding the Nav1.1 sodium channel subunit. Convergent data suggest hippocampal dentate gyrus (DG) pathology. We found that optogenetic stimulation of entorhinal cortex was ictogenic in DS (Scn1a+/-) but not wild-type mice in vivo. Two-photon calcium imaging in brain slice demonstrated profound impairment in filtering of perforant path input by DG in young adultScn1a+/-mice due to enhanced excitatory input to granule cells. Excitability of parvalbumin interneurons (PV-INs) was near-normal and selective activation of PV-INs rescued circuit impairments. This demonstrates developmental reorganization of hippocampal circuitry that can be modulated by recruitment of functional PV-INs, suggesting potential therapeutic approaches towards seizure modulation. The identified circuit abnormality mirrors that seen in models of chronic temporal lobe epilepsy, suggesting convergent mechanisms linking genetic and acquired causes of temporal lobe-onset seizures.
Convergence of proprioceptive and visual feedback on neurons in primary motor cortex
Authors: Cross Kevin P. , Cook Douglas J. , Scott Stephen H.
Published: May 2021

An important aspect of motor function is our ability to rapidly generate goal-directed corrections for disturbances to the limb or behavioural goal. Primary motor cortex (M1) is a key region involved in feedback processing, yet we know little about how different sources of feedback are processed by M1. We examined feedback-related activity in M1 to compare how different sources (visual versus proprioceptive) and types of information (limb versus goal) are represented. We found sensory feedback had a broad influence on M1 activity with ∼73% of neurons responding to at least one of the feedback sources. Information was also organized such that limb and goal feedback targeted the same neurons and evoked similar responses at the single-neuron and population levels indicating a strong convergence of feedback sources in M1.
Modeling in yeast how rDNA introns slow growth and increase desiccation tolerance in lichens
Authors: Armaleo Daniele , Chiou Lilly
Published: May 2021

We define a molecular connection between ribosome biogenesis and desiccation tolerance in lichens, widespread symbioses between specialized fungi (mycobionts) and unicellular phototrophs. Our experiments test whether the introns present in the nuclear ribosomal DNA of lichen mycobionts contribute to their anhydrobiosis. Self-splicing introns are found in the rDNA of several eukaryotic microorganisms, but most introns populating lichen rDNA are unable to self-splice, being either degenerate group I introns lacking the sequences needed for catalysis, or spliceosomal introns ectopically present in rDNA. Although all introns are eventually removed from rRNA by the splicing machinery of the mycobiont, Northern analysis of its RNA indicates that they are not removed quickly during rRNA transcription but are still present in early post-transcriptional processing and ribosome assembly stages, suggesting that delayed splicing interferes with ribosome assembly. To study the phenotypic repercussions of lichen introns in a model system, we used CRISPR to introduce a spliceosomal intron from the rDNA of the lichen fungusCladonia grayiinto all nuclear rDNA copies of the yeastSaccharomyces cerevisiae, which lacks rDNA introns. Three intron-bearing yeast mutants were constructed with the intron inserted either in the 18S rRNA genes, the 25S rRNA genes, or in both. The mutants removed the introns correctly but had half the rDNA genes of the wildtype strain, grew 4.4 to 6 times slower, and were 40 to 1700 times more desiccation tolerant depending on intron position and number. Intracellular trehalose, a disaccharide implicated in desiccation tolerance, was detected, but at low concentration. Overall, our data suggest that the constitutive interference of the intron splicing machinery with ribosome assembly and the consequent lowering of the cytoplasmic concentration of ribosomes and proteins are the primary causes of slow growth and increased desiccation tolerance in the yeast mutants. The relevance of these findings for slow growth and desiccation tolerance in lichens is discussed.
Mechanisms Underlying WNT-mediated Priming of Human Embryonic Stem Cells
Authors: Yoney Anna , Bai Lu , Brivanlou Ali H. , Siggia Eric D.
Published: May 2021

Embryogenesis is guided by a limited set of signaling pathways dynamically expressed in different places. How a context dependent signaling response is generated has been a central question of developmental biology, which can now be addressed within vitromodels of human embryos that are derived from embryonic stem cells (hESCs) called gastruloids. Our previous work demonstrated that during early self-organization of gastruloids, cells chronicle signaling hierarchy. Only cells that have been exposed (primed) by WNT signaling can respond to subsequent Activin exposure and differentiate to mesendodermal (ME) fates. Here, we show that WNT priming does not alter SMAD2 binding nor its chromatin opening, but rather, acts by inducing the expression of the SMAD2 co-factor, EOMES. Expression of EOMES is sufficient to replace WNT upstream of Activin-mediated ME differentiation, thus unveiling the mechanistic basis for priming and cellular memory in early development.
Time-reversal symmetric component of the flagellar beat enhances the translational and rotational velocities of isolated Chlamydomonas flagella
Authors: Gholami A. , Ahmad R. , Bae A. , Pumir A. , Bodenschatz E.
Published: May 2021

The beating of cilia and flagella is essential to perform many important biological functions, including generating fluid flows on the cell surface or propulsion of micro-organisms. In this work, we analyze the motion of isolated and demembranated flagella from green algaeChlamydomonas reinhardtii, which act as ATP-driven micro-swimmers. The waveform of theChlamydomonasbeating flagella has an asymmetric waveform that is known to involve the superposition of a static component, corresponding to a fixed, intrinsic curvature, and a dynamic wave component traveling in the base-to-tip direction at the fundamental beat frequency, plus higher harmonics. Here, we demonstrate that these modes are not sufficient to reproduce the observed flagella waveforms. We find that two extra modes play an essential role to describe the motion: first, a time-symmetric mode, which corresponds to a global oscillation of the axonemal curvature, and second, a secondary tip-to-base wave component at the fundamental frequency that propagates opposite to the dominant base-to-tip wave, albeit with a smaller amplitude. Although the time-symmetric mode cannot, by itself, contribute to propulsion (scallop theorem), it does enhance the translational and rotational velocities of the flagellum by approximately a factor of 2. This mode highlights a long-range coupled on/off activity of force-generating dynein motors and can provide further insight into the underling biology of the ciliary beat.
RNA splicing programs define tissue compartments and cell types at single cell resolution
Authors: Olivieri Julia Eve , Dehghannasiri Roozbeh , Wang Peter , Jang SoRi , de Morree Antoine , Tan Serena Y. , Ming Jingsi , Wu Angela Ruohao , Consortium Tabula Sapiens , Quake Stephen R. , Krasnow Mark A. , Salzman Julia
Published: May 2021

More than 95% of human genes are alternatively spliced. Yet, the extent splicing is regulated at single-cell resolution has remained controversial due to both available data and methods to interpret it. We apply the SpliZ, a new statistical approach that is agnostic to transcript annotation, to detect cell-type-specific regulated splicing in > 110K carefully annotated single cells from 12 human tissues. Using 10x data for discovery, 9.1% of genes with computable SpliZ scores are cell-type specifically spliced. These results are validated with RNA FISH, single cell PCR, and in high throughput with Smart-seq2. Regulated splicing is found in ubiquitously expressed genes such as actin light chain subunitMYL6and ribosomal proteinRPS24, which has an epithelial-specific microexon. 13% of the statistically most variable splice sites in cell-type specifically regulated genes are also most variable in mouse lemur or mouse. SpliZ analysis further reveals 170 genes with regulated splicing during sperm development using, 10 of which are conserved in mouse and mouse lemur. The statistical properties of the SpliZ allow model-based identification of subpopulations within otherwise indistinguishable cells based on gene expression, illustrated by subpopulations of classical monocytes with stereotyped splicing, including an un-annotated exon, inSAT1, a Diamine acetyltransferase. Together, this unsupervised and annotation-free analysis of differential splicing in ultra high throughput droplet-based sequencing of human cells across multiple organs establishes splicing is regulated cell-type-specifically independent of gene expression.
The ASC inflammasome adapter controls the extent of peripheral protein aggregate deposition in inflammation-associated amyloidosis
Authors: Losa Marco , Emmenegger Marc , De Rossi Pierre , Schürch Patrick M , Serdiuk Tetiana , Pengo Niccolò , Capron Danaëlle , Bieli Dimitri , Rupp Niels J , Carta Manfredi C , Frontzek Karl J , Lysenko Veronika , Reimann Regina R , Lakkaraju Asvin KK , Nuvolone Mario , Westermark Gunilla T , Nilsson K. Peter R. , Polymenidou Magdalini , Theocharides Alexandre P. A. , Hornemann Simone , Picotti Paola , Aguzzi Adriano
Published: May 2021

ASC-containing inflammasomes form specks, extracellular aggregates which enhance the aggregation of Aβ amyloid in Alzheimer’s disease. This raises the question whether ASC participates to additional aggregation proteinopathies. Here we show that ASC controls the extent of inflammation-associated AA amyloidosis, a systemic disease caused by the aggregation of the acute-phase reactant serum amyloid A (SAA). Using superresolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis. Purified recombinant ASC specks accelerated SAA fibril formationin vitro. Mass spectrometry after limited proteolysis showed that ASC interacts with SAA via its pyrin domain. In a murine model of inflammation-associated AA amyloidosis, splenic AA amyloid load was conspicuously decreased inPycardtm1Vmd/tm1Vmdmice which lack ASC. This reduction was not a consequence of enhanced amyloid phagocytosis, as SAA stimulation increased phagocytic activity inPycard+/+, but not inPycard-/-macrophages. Treatment with anti-ASC antibodies decreased the amyloid loads in wild-type mice suffering from AA amyloidosis. The prevalence of natural anti-ASC IgG (-logEC50≥ 2) in 19,334 hospital patients was <0.01%, suggesting that anti-ASC antibody treatment modalities would not be confounded by natural autoimmunity. Higher anti-ASC titers did not correlate with any specific disease, suggesting that anti-ASC immunotherapy may be well-tolerated. These findings expand the role played by ASC to extraneural proteinopathies of humans and experimental animals and suggest that anti-ASC immunotherapy may contribute to resolving such diseases.
Structural and evolutionary analysis unveil functional adaptations in the promiscuous behavior of serum albumins
Authors: Rueda Ana Julia Velez , Benítez Guillermo Ignacio , Sommese Leandro Matías , Ardanaz Sebastián M. , Borucki Estefanía L. , Palopoli Nicolas , Iglesias Luis E , Parisi Gustavo
Published: May 2021

Promiscuous activities have been related to the capacity to catalyze reactions different from those a protein has evolved to sustain. From this evolutionary perspective, we rethought the serum albumins promiscuous behavior. We found that the cross aldol condensation of acetone and p-formylbenzonitrile is a promiscuous reaction conserved in humans and other mammals. Structural and evolutionary analysis indicates that the involved residues could have evolved for a still unknown biological function. Our results could contribute to better characterize the serum albumin family and raise questions about the evolution of protein promiscuity and function.
Seroepidemiological survey on pigs and cattle for novel K88 (F4)-like colonization factor detected in human enterotoxigenicEscherichia coli
Authors: Tanimoto Yoshihiko , Inoue Miyoko , Komatsu Kana , Odani Atsuyuki , Wada Takayuki , Kage-Nakadai Eriko , Nishikawa Yoshikazu
Published: May 2021

EnterotoxigenicEscherichia coli(ETEC) strains that express various fimbrial or nonfimbrial colonization factors and enterotoxins are critical causes of diarrheal diseases. Human ETEC serotype O169:H41 (O169) has been a representative of epidemic ETEC worldwide; the organism shows massive adherence to HEp-2 cells similar to enteroaggregativeE. coli. Previously, we determined the complete sequence of the unstable virulence plasmid, pEntYN10. The plasmid included a unique set of genes encoding a novel colonization factor (CF) resembling K88 (F4) of porcine ETEC, in addition to CS6, a well-known representative CF of human ETEC, and another novel CF similar to CS8 (CFA/III) of human ETEC. To determine whether the K88-like CF (after this, K88O169) allows the organisms to infect domestic animals like the original K88-harboring strains that can cause diarrhea in piglets, samples were tested for antibodies against recombinant proteins of possible paralogous adhesins, FaeG1 and FaeG2, from K88O169and the FaeG of typical K88 (F4). The seroepidemiological study using recombinant antigens (two paralogs FaeG1 and FaeG2 from K88O169) showed reactivity of porcine (18.0%) and bovine (17.1%) sera to K88O169FaeG1 and/or FaeG2 antigens on indirect ELISA tests. These results suggest thatE. coliwith K88O169adhesin can infect various hosts, including pigs and cattle. This is the first report of domestic animals having antibodies to K88O169of human ETEC. Although human ETEC had been thought to be distinguished from those of domestic animals based on colonization factors, zoonotic strains may conceal themselves among human ETEC organisms. The concept of One Health should be adopted to intervene in ETEC infections among animals and humans.
Ventilation-induced epithelial injury drives biological onset of lung traumain vitroand is mitigated with anti-inflammatory therapeutics
Authors: Nof Eliram , Artzy-Schnirman Arbel , Bhardwaj Saurabh , Sabatan Hadas , Waisman Dan , Hochwald Ori , Gruber Maayan , Borenstein-Levin Liron , Sznitman Josué
Published: May 2021

Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite maintenance of blood homeostasis. Thebiotraumahypothesis advances that mechanical forces from invasive ventilation trigger immunological factors that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here we show that flow-induced stresses under mechanical ventilation can injure the bronchial epithelium of ventilatedin vitroupper airway models and directly modulate inflammatory cytokine secretion associated with pulmonary injury. We identify site-specific susceptibility to epithelial erosion in airways from jet-flow impaction and measure an increase in cell apoptosis and modulated secretions of cytokines IL-6, 8 and 10. We find that prophylactic pharmacological treatment with anti-inflammatory therapeutics reduces apoptosis and pro-inflammatory signaling during ventilation. Our 3Din vitroairway platform points to a previously overlooked origin of lung injury and showcases translational opportunities in preclinical pulmonary research towards protective therapies and improved protocols for patient care.
Phenomics data processing: A plot-level model for repeated measurements to extract the timing of key stages and quantities at defined time points
Authors: Roth Lukas , Rodríguez-Álvarez María Xosé , van Eeuwijk Fred , Piepho Hans-Peter , Hund Andreas
Published: May 2021

Decision-making in breeding increasingly depends on the ability to capture and predict crop responses to changing environmental factors. Advances in crop modeling as well as high-throughput field phenotyping (HTFP) hold promise to provide such insights. Processing HTFP data is an interdisciplinary task that requires broad knowledge on experimental design, measurement techniques, feature extraction, dynamic trait modeling, and prediction of genotypic values using statistical models. To get an overview of sources of variation in HTFP, we develop a general plot-level model for repeated measurements. Based on this model, we propose a seamless step-wise procedure that allows for carry on of estimated means and variances from stage to stage. The process builds on the extraction of three intermediate trait categories; (1) timing of key stages, (2) quantities at defined time points or periods, and (3) dose-response curves. In a first stage, these intermediate traits are extracted from low-level traits’ time series (e.g., canopy height) using P-splines and the quarter of maximum elongation rate method (QMER), as well as final height percentiles. In a second and third stage, extracted traits are further processed using a stage-wise linear mixed model analysis. Using a wheat canopy growth simulation to generate canopy height time series, we demonstrate the suitability of the stage-wise process for traits of the first two above-mentioned categories. Results indicate that, for the first stage, the P-spline/QMER method was more robust than the percentile method. In the subsequent two-stage linear mixed model processing, weighting the second and third stage with error variance estimates from the previous stages improved the root mean squared error. We conclude that processing phenomics data in stages represents a feasible approach if estimated means and variances are carried forward from one processing stage to the next. P-splines in combination with the QMER method are suitable tools to extract timing of key stages and quantities at defined time points from HTFP data.

Highlights

General plot-level model for repeated high-throughput field phenotyping measurements

Extraction of three main intermediate trait categories for dynamic modeling

Seamless processing approach that integrates temporal and spatial modeling

Phenomics data processing cheatsheet
Effects of short-term plasticity in early olfactory information processing inDrosophila
Authors: Liu Yuxuan , Li Qianyi , Tang Chao , Qin Shanshan , Tu Yuhai
Published: May 2021

InDrosophila, olfactory information received by the olfactory receptor neurons (ORNs) is first processed by an incoherent feed forward neural circuit in the antennal lobe (AL) that consists of ORNs (input), the inhibitory local neurons (LNs), and projection neurons (PNs). This “early” olfactory information process has two important characteristics. First, response of a PN to its cognate ORN is normalized by the overall activity of other ORNs, a phenomenon termed “divisive normalization”. Second, PNs respond strongly to the onset of ORN activities, but they adapt to prolonged or continuously increasing inputs. Despite the importance of these characteristics for learning and memory, their underlying mechanism remains not fully understood. Here, we develop a circuit model for describing the ORN-LN-PN dynamics by including key features of neuron-neuron interactions, in particular short-term plasticity (STP) and presynaptic inhibition (PI). Our model shows that STP is critical in shaping PN’s steady-state response properties. By fitting our model to experimental data quantitatively, we found that strong and balanced short-term facilitation (STF) and short-term depression (STD) in STP is crucial for the observed nonlinear divisive normalization inDrosophila. By comparing our model with the observed adaptive response to time-varying signals quantitatively, we find that both STP and PI contribute to the highly adaptive response with the latter being the dominant factor for a better fit with experimental data. Our model not only helps reveal the mechanisms underlying two main characteristics of the early olfactory process, it can also be used to predict the PN responses to arbitrary time-dependent signals and to infer microscopic properties of the circuit (such as the strengths of STF and STD) from the measured input-output relation.
Fine-scale spatial genetic structure across the species range reflects recent colonization of high elevation habitats in silver fir (Abies albaMill.)
Authors: Major Enikő I. , Höhn Mária , Avanzi Camilla , Fady Bruno , Heer Katrin , Opgenoorth Lars , Piotti Andrea , Popescu Flaviu , Postolache Dragos , Vendramin Giovanni G. , Csilléry Katalin
Published: May 2021

Variation in genetic diversity across species ranges has long been recognized as highly informative for assessing populations’ resilience and adaptive potential. The spatial distribution of genetic diversity, referred to as fine-scale spatial genetic structure (FSGS), also carries information about recent demographic changes, yet it has rarely been connected to range scale processes. We studied eight silver fir (Abies albaMill.)population pairs (sites), growing at high and low elevations, representative of the main genetic lineages of the species. A total of 1368 adult trees and 540 seedlings were genotyped using 137 and 116 single nucleotide polymorphisms (SNPs), respectively. Sites revealed a clear east-west isolation-by-distance pattern consistent with the post-glacial colonization history of the species. Genetic differentiation among sites (FCT=0.148) was an order of magnitude greater than between elevations within sites (FSC=0.031), nevertheless high elevation populations consistently exhibited a stronger FSGS. Structural equation modeling revealed that elevation and, to a lesser extent, post-glacial colonization history, but not climatic and habitat variables, were the best predictors of FGSG across populations. These results may suggest that high elevation habitats have been colonized more recently across the species range. Additionally, paternity analysis revealed a high reproductive skew among adults and a stronger FSGS in seedlings than in adults, suggesting that FSGS may conserve the signature of demographic changes for several generations. Our results emphasize that spatial patterns of genetic diversity within populations provide complementary information about demographic history and could be used for defining conservation priorities.
Aminoglycoside antibiotics inhibit phage infection by blocking an early step of the phage infection cycle
Authors: Kever Larissa , Hardy Aël , Luthe Tom , Hünnefeld Max , Gätgens Cornelia , Milke Lars , Wiechert Johanna , Wittmann Johannes , Moraru Cristina , Marienhagen Jan , Frunzke Julia
Published: May 2021

In response to viral predation, bacteria have evolved a wide range of defense mechanisms, which rely mostly on proteins acting at the cellular level. Here, we show that aminoglycosides, a well-known class of antibiotics produced byStreptomyces, are potent inhibitors of phage infection in widely divergent bacterial hosts. We demonstrate that aminoglycosides block an early step of the viral life cycle, prior to genome replication. Phage inhibition was also achieved using supernatants from natural aminoglycoside producers, hinting at a broad physiological significance of the antiviral properties of aminoglycosides. Strikingly, we show that acetylation of the aminoglycoside antibiotic apramycin abolishes its antibacterial effect, but retains its antiviral properties. Altogether, this study expands the knowledge of potential aminoglycoside functions in bacterial communities suggesting that aminoglycosides are not only used by their producers as toxic molecules against their bacterial competitors, but could also provide protection against the threat of phage predation at the community level.
Immunoinformatics approach for a novel multi-epitope vaccine construct against spike protein of human coronaviruses
Authors: Kumar Avinash , Rathi Ekta , Kini Suvarna G
Published: May 2021

Spike (S) proteins are an attractive target as it mediates the binding of the SARS-CoV-2 to the host through ACE-2 receptors. We hypothesize that the screening of S protein sequences of all the HCoVs would result in the identification of potential multi-epitope vaccine candidates capable of conferring immunity against various HCoVs. In the present study, several machine learning-basedin-silicotools were employed to design a broad-spectrum multi-epitope vaccine candidate against S protein of human coronaviruses. To the best of our knowledge, it is one of the first study, where multiple B-cell epitopes and T-cell epitopes (CTL and HTL) were predicted from the S protein sequences of all seven known HCoVs and linked together with an adjuvant to construct a potential broad-spectrum vaccine candidate. Secondary and tertiary structures were predicted, validated and the refined 3D-model was docked with an immune receptor. The vaccine candidate was evaluated for antigenicity, allergenicity, solubility, and its ability to achieve high-level expression in bacterial hosts. Finally, the immune simulation was carried out to evaluate the immune response after three vaccine doses. The designed vaccine is antigenic (with or without the adjuvant), non-allergenic, binds well with TLR-3 receptor and might elicit a diverse and strong immune response.
N-glycosylation of CD24 mediates cell motility but inhibits cell proliferation in colorectal cancer
Authors: Hakami Zaki , Raposo Teresa , Alsulaiman Abdullah , Dalleywater William , Otifi Hassan , Horobin Charlotte , Garrie Karin , Ilyas Mohammad
Published: May 2021

CD24 confers features of stemness and enhances cell motility in colorectal cancer. It contains numerousO-glycosylation sites but just two putativeN-glycosylation sites. The study aimed to mutateN-glycosylation as it thought to be important in mediating many glycoproteins’ function.

Site-directed mutagenesis performed to mutateN-glycosylation sites by converting asparagine residues to glutamine. Each site was mutated individually (CD24N36Qand CD24N52Q) and in combination (CD24N[36,52]Q) and were overexpressed in HCT116 and SW480 cell lines. The effect of the mutant CD24 on cell viability, cell motility and induction of downstream targets was compared to wild-type CD24 and empty vector control (EVC).

Overexpression of the individually mutated clones increased cell motility compared to EVC but was significantly less than that induced by CD24WT. Overexpression of the double mutant clone resulted in near-complete abrogation of cell motility induction. Unexpectedly, the expression of mutant clones (single and double) increased cell viability. Analysis of downstream targets and F-actin staining demonstrated reduced induction of known CD24 targets by mutant vectors and reduced epithelial-mesenchymal transition.

In conclusion, eachN-glycosylation site on CD24 contributes partially to induce motility by CD24, and these are additive. Loss of theN-glycosylation results in an unexpected gain of proliferative function.

Highlights

CD24 is a heavily glycosylated molecule that contains two N-glycosylation sites, and these contribute to the activation of downstream targets and induction of cell motility

Each N-glycosylation site contributes partially, and their effects appear to be additive

The N-glycosylation sites may exert an inhibitory effect on cell proliferation

Much of the CD24 activity is mediated through post-transcriptional effects
Ventral Intermediate Nucleus structural connectivity-derived segmentation: anatomical reliability and variability
Authors: Bertino Salvatore , Basile Gianpaolo Antonio , Bramanti Alessia , Ciurleo Rossella , Tisano Adriana , Anastasi Giuseppe Pio , Milardi Demetrio , Cacciola Alberto
Published: May 2021

The Ventral intermediate nucleus (Vim) of thalamus is the most targeted structure for the treatment of drug-refractory tremors. Since methodological differences across existing studies are remarkable and no gold-standard pipeline is available, in this study, we tested different parcellation pipelines for tractography-derived putative Vim identification.

Thalamic parcellation was performed on a high quality, multi-shell dataset and a downsampled, clinical-like dataset using two different diffusion signal modeling techniques and two different voxel classification criteria, thus implementing a total of four parcellation pipelines. The most reliable pipeline in terms of inter-subject variability has been picked and parcels putatively corresponding to motor thalamic nuclei have been selected by calculating similarity with a histology-based mask of Vim. Then, spatial relations with optimal stimulation points for the treatment of essential tremor have been quantified. Finally, effect of data quality and parcellation pipelines on a volumetric index of connectivity clusters has been assessed.

We found that the pipeline characterized by higher-order signal modeling and threshold-based voxel classification criteria was the most reliable in terms of inter-subject reliability regardless data quality. The maps putatively corresponding to Vim were those derived by precentral- and dentate nucleus-thalamic connectivity. However, tractography-derived functional targets showed remarkable differences in shape and sizes when compared to a ground truth model based on histochemical staining on seriate sections of human brain. Thalamic voxels connected to contralateral dentate nucleus resulted to be the closest to literature-derived stimulation points for essential tremor but at the same time showing the most remarkable inter-subject variability. Finally, the volume of connectivity parcels resulted to be significantly influenced by data quality and parcellation pipelines. Hence, caution is warranted when performing thalamic connectivity-based segmentation for stereotacting targeting.
Protective pan-ebolavirus combination therapy by two multifunctional human antibodies
Authors: Gilchuk Pavlo , Murin Charles D. , Cross Robert W. , Ilinykh Philipp A. , Huang Kai , Kuzmina Natalia , Borisevich Viktoriya , Agans Krystle N. , Geisbert Joan B. , Carnahan Robert H. , Nargi Rachel S. , Sutton Rachel E , Suryadevara Naveenchandra , Zost Seth J. , Bombardi Robin G. , Bukreyev Alexander , Geisbert Thomas W. , Ward Andrew B. , Crowe James E.
Published: May 2021

Ebolaviruses cause a severe and often fatal illness with the potential for global spread. Monoclonal antibody-based treatments that have become available recently have a narrow therapeutic spectrum and are ineffective against ebolaviruses other than Ebola virus (EBOV), including medically important Bundibugyo (BDBV) and Sudan (SUDV) viruses. Here we report the development of a therapeutic cocktail comprising two broadly neutralizing human antibodies rEBOV-515 and rEBOV-442 that recognize non-overlapping sites on the ebolavirus glycoprotein (GP). Antibodies in the cocktail exhibited synergistic neutralizing activity and resisted viral escape, and they were optimized for their Fc-mediated effector function activities. The cocktail protected non-human primates from ebolavirus disease caused by EBOV, BDBV, or SUDV with high therapeutic effectiveness. High-resolution structures of the cocktail antibodies in complex with GP revealed the molecular determinants for neutralization breadth and potency. This study provides advanced preclinical data to support clinical development of this cocktail for pan-ebolavirus therapy.
The effects of cognitive load on query reformulation: mental demand, temporal demand and frustration
Authors: Na Kyoungsik
Published: May 2021

Purpose

This study explores the effects of cognitive load on the propensity to reformulate queries during information seeking on the web.

Design/methodology/approach

This study employs an experimental design to analyze the effect of manipulations of cognitive load on the propensity for query reformulation between experimental and control groups. In total, three affective components that contribute to cognitive load were manipulated: mental demand, temporal demand and frustration.

Findings

A significant difference in the propensity of query reformulation behavior was found between searchers exposed to cognitive load manipulations and searchers who were not exposed. Those exposed to cognitive load manipulations made half as many search query reformulations as searchers not exposed. Furthermore, the National Aeronautical and Space Administration Task Load Index (NASA-TLX) cognitive load scores of searchers who were exposed to the three cognitive load manipulations were higher than those of searchers who were not exposed indicating that the manipulation was effective. Query reformulation behavior did not differ across task types.

Originality/value

The findings suggest that a dual-task method and NASA-TLX assessment serve as good indicators of cognitive load. Because the findings show that cognitive load hinders a searcher's interaction with information search tools, this study provides empirical support for reducing cognitive load when designing information systems or user interfaces.
Nitrogen dioxide hourly distribution and health risk assessment for winter season in low town of Mohammedia city, Morocco
Authors: El Morabet Rachida , Khan Roohul Abad , Bouhafa Soufiane , Barhazi Larbi
Published: May 2021

Purpose

Air quality and its assessment in urban areas has become a necessity. This is attributed to the increasing air pollution in urban landscape from anthropogenic activities necessary for economic growth and development. This study investigates air quality and potential health risk posed from nitrogen dioxide (NO2) to the residents of low town of Mohammedia city, Morocco.

Design/methodology/approach

The NO2 concentration was measured on an hourly basis for the winter season of the year 2014, 2015 and 2016. The air quality was assessed in terms of Air Quality Index (AQI). Noncarcinogenic risk assessment was done to evaluate possible health risk to the inhabitant of low town from NO2 exposure.

Findings

The maximum concentration reached 85–96 µg/m3 (at 6 p.m., 2014), 96–104 µg/m3 (7–9 p.m., 2015) and 102–117 (8–11 p.m., 2016). The AQI during maximum NO2 levels (peak hours) ranged between 0–50 µg/m3 (good) to 51–100 µg/m3 (unhealthy for sensitive group). The risk quotient (RQ) was calculated for average daily intake and average hourly intake of NO2. RQ was found to be less than 1 (no potential health risk, lifetime and hourly) for all three years. However, increase in RQ value from 0.84 (2014) to 0.98 (2016) indicates increase in potential health risk. Hence, policy and measures should be adopted to reduce the potential health risk.

Originality/value

This study is very first of its kind for the area and hence can serve as reference study for future works. Further studies are required to assess air pollution in other seasons (summer, spring, autumn), impact of climatic condition and parameters on air quality. Also, for direct impact assessment number of cases attributed to air pollution needs to be investigated.