bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilization demands of walking modulate the vestibular contributions to gait
Authors: Magnani Rina M. , Bruijn Sjoerd M. , van Dieën Jaap H. , Forbes Patrick A.
Published: October 2020

Stable walking relies critically on motor responses to signals of head motion provided by the vestibular system, which are phase-dependent and modulated differently within each muscle. It is unclear, however, whether these vestibular contributions also vary according to the stability of the walking task. Here we investigate how vestibular signals influence muscles relevant for gait stability (medial gastrocnemius, gluteus medius and erector spinae) – as well as their net effect on ground reaction forces – while humans walked normally, with mediolateral stabilization, wide and narrow steps. We estimated local dynamic stability of trunk kinematics together with coherence of electrical vestibular stimulation (EVS) with muscle activity and mediolateral ground reaction forces. Walking with external stabilization increased local dynamic stability and decreased coherence between EVS and all muscles/forces compared to normal walking. Wide-base walking also decreased vestibulomotor coherence, though local dynamic stability did not differ. Conversely, narrow-base walking increased local dynamic stability, but produced muscle-specific increases and decreases in coherence that resulted in a net increase in vestibulomotor coherence with ground reaction forces. Overall, our results show that while vestibular contributions may vary with gait stability, they more critically depend on the stabilization demands (i.e. control effort) needed to maintain a stable walking pattern.
EEG-based decoding and recognition of imagined music
Authors: Tibo Marthe , Geirnaert Simon , Bertrand Alexander
Published: October 2020

The authors have withdrawn their manuscript because they discovered an error in the analysis code after publication of the preprint, which turns out to have a major impact on the main results in the paper. The results on the imagination data become non-significant after correcting for the mistake. Significant results on the perception data are preserved, although the classification results are worse than what is reported.

Therefore, the authors do not wish this work to be cited as a reference.

If you have any questions, please contact the last author.
The PEDtracker: an automatic staging approach forDrosophila melanogasterlarvae
Authors: Schumann Isabell , Triphan Tilman
Published: October 2020

The post-embryonal development of arthropod species, including crustaceans and insects, is characterized by ecdysis or molting. This process defines growth stages and is controlled by a conserved neuroendocrine system. Each molting event is divided in several critical time points, such as pre-molt, molt and post-molt, and leaves the animals in a temporarily highly vulnerable state while their cuticle is re-hardening. The molting events occur in an immediate ecdysis sequence within a specific time window during the development. Each sub-stage takes only a short amount of time, which is generally in the order of minutes. To find these relatively short behavioral events, one needs to follow the entire post-embryonal development over several days. As the manual detection of the ecdysis sequence is time consuming and error prone, we designed a monitoring system to facilitate the continuous observation of the post-embryonal development of the fruit flyDrosophila melanogaster. Under constant environmental conditions we are able to observe the life cycle from the embryonic state to the adult, which takes about ten days in this species. Specific processing algorithms developed and implemented in Fiji and R allow us to determine unique behavioral events on an individual level – including egg hatching, ecdysis and pupation. In addition, we measured growth rates and activity patterns for individual larvae. Our newly created RPackage PEDtracker can predict critical developmental events and thus offers the possibility to perform automated screens that identify changes in various aspects of larval development. In conclusion, the PEDtracker system presented in this study represents the basis for automated real-time staging and analysis not only for the arthropod development.
Positive but variable effects of crop diversification on biodiversity and ecosystem services
Authors: Beillouin D. , Ben-Ari T. , Malézieux E. , Seufert V. , Makowski D.
Published: October 2020

Ecological theory suggests that biodiversity has a positive and stabilizing effect on the delivery of ecosystem services. Yet, the impacts of increasing the diversity of cultivated crop species or varieties in agroecosystems are still under scrutiny. The empirical evidence available is scattered in scope, agronomic and geographical contexts and impacts on ecosystem services may depend on the type of diversification strategy used. To robustly assess the effects of crop diversification in agroecosystems, we compiled the results of 95 meta-analyses integrating 5,156 experiments conducted over 84 experimental years and representing more than 54,500 paired observations on 120 crop species in 85 countries. Overall, our synthesis of experimental data from across the globe shows that crop diversification enhances not only crop production (median effect +14%), but also the associated biodiversity (+24%, i.e. the biodiversity of non-cultivated plants and animals), and several supporting and regulating ecosystem services including water quality (+51%), pest and disease control (+63%) and soil quality (+11%). However, there was substantial variability in the results for each individual ecosystem service between different diversification strategies like agroforestry, intercropping, cover-crops, crop rotation or variety mixtures. Agroforestry is particularly effective in delivering multiple ecosystem services, i.e. water use and quality, pest and diseases regulation, associated biodiversity, long-term soil productivity and quality. Variety mixtures, instead, provide the lowest benefits, while the other strategies show intermediate results. Our results highlight that while increasing the diversity of cultivated crop species or varieties in agroecosystems represents a very promising strategy for more sustainable land management, contributing to enhanced yields, enhanced biodiversity and ecosystem services, some crop diversification strategies are more effective than others in supporting key ecosystem services.
Competition Between Public Resources Promotes Cooperation
Authors: Salahshour Mohammad
Published: October 2020

As cooperation incurs a cost to the cooperator for others to benefit, its evolution seems to contradict natural selection. How evolution has resolved this obstacle, has been among the most intensely studied questions in the evolutionary theory in recent decades. Here, by showing that competition between public resources provides a simple mechanism for cooperation to flourish, we uncover a novel road to the evolution of cooperation. Such a mechanism can be at work in many biological or social contexts where individuals can form different groups or join different institutions to perform a collective action task, or when they can choose between different collective actions, with different profitability. As a simple evolutionary model suggests, in such a context, defectors tend to join the highest quality resource. This allows cooperators to survive and out-compete defectors by sheltering in a lower quality resource. Cooperation level is maximized however, when the qualities of the two highest quality resources are similar, and thus, they can perform the most competitively to attract individuals.
Nonlinear post-selection inference for genome-wide association studies
Authors: Slim Lotfi , Chatelain Clément , Azencott Chloé-Agathe
Published: October 2020

To address the lack of statistical power and interpretability of genome-wide association studies (GWAS), gene-level analyses combine the p-values of individual single nucleotide polymorphisms (SNPs) into gene statistics. However, using all SNPs mapped to a gene, including those with low association scores, can mask the association signal of a gene.

We therefore propose a new two-step strategy, consisting in first selecting the SNPs most associated with the phenotype within a given gene, before testing their joint effect on the phenotype. The recently proposed kernelPSI framework for kernel-based post-selection inference makes it possible to model non-linear relationships between features, as well as to obtain valid p-values that account for the selection step.

In this paper, we show how we adapted kernelPSI to the setting of quantitative GWAS, using kernels to model epistatic interactions between neighboring SNPs, and post-selection inference to determine the joint effect of selected blocks of SNPs on a phenotype. We illustrate this tool on the study of two continuous phenotypes from the UKBiobank.

We show that kernelPSI can be successfully used to study GWAS data and detect genes associated with a phenotype through the signal carried by the most strongly associated regions of these genes. In particular, we show that kernelPSI enjoys more statistical power than other gene-based GWAS tools, such as SKAT or MAGMA.

kernelPSI is an effective tool to combine SNP-based and gene-based analyses of GWAS data, and can be used successfully to improve both statistical performance and interpretability of GWAS.
The CoREST Repressor Complex Mediates Phenotype Switching and Therapy Resistance in Melanoma
Authors: Wu Muzhou , Hanly Ailish , Gibson Frederick , Kuang Kevin , Kalin Jay , Nocco Sarah , Collard Marianne , Cole Matthew , Xiao Amy , Agus Filisia , Labadorf Adam , Cole Philip A , Alani Rhoda M.
Published: October 2020

Virtually all patients with BRAF-mutant melanoma develop resistance to MAPK inhibitors largely through non-mutational events1,2. Although the epigenetic landscape has been shown to be altered in therapy-resistant melanomas and other cancers3,4, a specific targetable epigenetic mechanism regulating treatment resistance has not been validated to date. Here we evaluate the CoREST repressor complex and the novel inhibitor, corin5, within the context of melanoma phenotype plasticity and therapeutic resistance in order to define epigenetic mechanisms underlying these processes. We find that CoREST is a critical mediator of the major distinct melanoma phenotypes and that corin treatment of melanoma cells leads to phenotype reprogramming. We further demonstrate that treatment of BRAF inhibitor (BRAFi)-resistant melanomas with corin leads to resensitization of tumor cells to BRAFi. Among the transcriptional targets of CoREST in melanoma are the dual-specificity phosphatases (DUSPs). DUSP1 is shown to be consistently downregulated in BRAFi-resistant melanomas which can be reversed by corin treatment, thereby leading to downstream inhibition of p38 MAPK activity and resensitization of resistant cells to targeted BRAFi therapies. These findings identify the CoREST repressor complex as a central mediator of melanoma phenotype plasticity and resistance to targeted therapy and suggest that CoREST inhibitors may prove beneficial to patients with BRAF-mutant melanomas who have acquired BRAFi-resistance.
A time-lagged association between the gut microbiome, nestling weight and nestling survival in wild great tits
Authors: Davidson Gabrielle L. , Somers Shane E. , Wiley Niamh , Johnson Crystal N. , Reichert Michael S. , Ross R. Paul , Stanton Catherine , Quinn John L.
Published: October 2020

Natal body mass is a key predictor of viability and fitness in many animals. While variation in body mass and therefore juvenile viability may be explained by genetic and environmental factors, emerging evidence points to the gut microbiota as an important factor influencing host health. The gut microbiota is known to change during development, but it remains unclear whether the microbiome predicts fitness, and if it does, at which developmental stage it affects fitness traits.

We collected data on two traits associated with fitness in wild nestling great tits (Parus major): weight and survival to fledging. We characterised the gut microbiome using 16S rRNA sequencing from nestling faeces and investigated temporal associations between the gut microbiome and fitness traits across development at day 8 (D8) and day 15 (D15) post-hatching. We also explored whether particular microbial taxa were ‘indicator species’ that reflected whether nestlings survived or not.

There was no link between mass and microbial diversity on D8 or D15. However, we detected a time-lagged relationship where weight at D15 was negatively associated with the microbial diversity at D8, controlling for weight at D8, therefore reflectingrelativeweight gain over the intervening period.

Indicator species analysis revealed that specificity values were high and fidelity values were low, suggesting that indicator taxa were primarily detected within either the survived or not survived groups, but not always detected in birds that either survived or died. Therefore these indicator taxa may be sufficient, but not necessary for determining either survival or mortality, perhaps owing to functional overlap in microbiota.

We highlight that measuring microbiome-fitness relationships at just one time point may be misleading, especially early in life. Instead, microbial-host fitness effects may be best investigated longitudinally to detect critical development windows for key microbiota and host traits associated with neonatal weight. Our findings should inform future hypothesis testing to pinpoint which features of the gut microbial community impact on host fitness, and when during development this occurs. Such confirmatory research will shed light on population level processes and could have the potential to support conservation.
Probing universal protein dynamics using residue-level Gibbs free energy
Authors: Smit Jochem H. , Krishnamurthy Srinath , Srinivasu Bindu Y. , Parakra Rinky , Karamanou Spyridoula , Economou Anastassios
Published: October 2020

Hydrogen Deuterium Exchange Mass Spectrometry is a powerful monitor of protein intrinsic dynamics, yet the interpretation, visualization and cross-comparison of HDX-MS datasets is challenging. Here we present PyHDX, an open-source python package and web server, that batch-extracts the universal quantity Gibbs free energy at residue level over multiple protein conditions and homologues. ΔGvalues relate to protein normal modes and together provide a universal measure of protein flexibility.

Availability

PyHDX source code is released under the MIT license and can be accessed onGitHub.
The DOE JGI Metagenome Workflow
Authors: Clum Alicia , Huntemann Marcel , Bushnell Brian , Foster Brian , Foster Bryce , Roux Simon , Hajek Patrick P. , Varghese Neha , Mukherjee Supratim , Reddy T.B.K. , Daum Chris , Yoshinaga Yuko , Seshadri Rekha , Kyrpides Nikos C , Eloe-Fadrosh Emiley A. , Chen I-Min A. , Copeland Alex , Ivanova Natalia N.
Published: October 2020

The DOE JGI Metagenome Workflow performs metagenome data processing, including assembly, structural, functional, and taxonomic annotation, and binning of metagenomic datasets that are subsequently included into theIntegrated Microbial Genomes and Microbiomes(IMG/M) comparative analysis system (I. Chen, K. Chu, K. Palaniappan, M. Pillay, A. Ratner, J. Huang, M. Huntemann, N. Varghese, J. White, R. Seshadri, et al, Nucleic Acids Rsearch, 2019) and provided for download via the Joint Genome Institute (JGI) Data Portal (https://genome.jgi.doe.gov/portal/). This workflow scales to run on thousands of metagenome samples per year, which can vary by the complexity of microbial communities and sequencing depth. Here we describe the different tools, databases, and parameters used at different steps of the workflow, to help with interpretation of metagenome data available in IMG and to enable researchers to apply this workflow to their own data. We use 20 publicly available sediment metagenomes to illustrate the computing requirements for the different steps and highlight the typical results of data processing. The workflow modules for read filtering and metagenome assembly are available as a Workflow Description Language (WDL) file (https://code.jgi.doe.gov/BFoster/jgi_meta_wdl.git). The workflow modules for annotation and binning are provided as a service to the user community athttps://img.jgi.doe.gov/submitand require filling out the project and associated metadata descriptions in Genomes OnLine Database (GOLD) (S. Mukherjee, D. Stamatis, J. Bertsch, G. Ovchinnikova, H. Katta, A. Mojica, I Chen, and N. Kyrpides, and T. Reddy, Nucleic Acids Research, 2018).

IMPORTANCE

The DOE JGI Metagenome Workflow is designed for processing metagenomic datasets starting from Illumina fastq files. It performs data pre-processing, error correction, assembly, structural and functional annotation, and binning. The results of processing are provided in several standard formats, such as fasta and gff and can be used for subsequent integration into the Integrated Microbial Genome (IMG) system where they can be compared to a comprehensive set of publicly available metagenomes. As of 7/30/2020 7,155 JGI metagenomes have been processed by the JGI Metagenome Workflow.
Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype
Authors: Bahcecioglu Gokhan , Yue Xiaoshan , Howe Erin , Guldner Ian , Stack M. Sharon , Nakshatri Harikrishna , Zhang Siyuan , Zorlutuna Pinar
Published: October 2020

Age is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. Here, we show for the first time that the aging breast ECM is sufficient to drive normal mammary epithelial cells (KTB21) to a more invasive and cancer-like phenotype, while promoting motility and invasiveness in MDA-MB-231 cells. E-cadherin membrane localization was lost in KTB21 cells cultured on the decellularized breast matrix from aged mice. Cell motility, cell invasion, and inflammatory cytokine and cancer-related protein production were increased significantly on the aged matrix, and many genes related to invasion were upregulated. Strikingly, we showed using single cell RNA sequencing that the aged matrix led to enrichment of a subpopulation of KTB21 cells that highly expressed epithelial-mesenchymal transition (EMT) and invasion-related genes. Lysyl oxidase (LOX) knockdown reverted the aged matrix-induced changes to the young levels;LOXsiRNA treatment prevented the loss of E-cadherin membrane localization, and reduced cell motility, cell invasion, and cytokine and cancer-related protein production. Finally, we showed that the biophysical, mechanical and biochemical properties of the breast ECM were altered dramatically upon aging. Analyzing these factors and studying the differential response of the epithelial cells to young and aged ECMs could lead to identification of new targets for cancer treatment and could pave the way for the discovery of new therapeutic options.
Genome-wide SNP genotyping of DNA pools identifies untapped landraces and genomic regions that could enrich the maize breeding pool
Authors: Arca Mariangela , Gouesnard Brigitte , Mary-Huard Tristan , Le Paslier Marie-Christine , Bauland Cyril , Combes Valérie , Madur Delphine , Charcosset Alain , Nicolas Stéphane D.
Published: October 2020

Maize landraces preserved in genebanks have a large genetic diversity that is still poorly characterized and underexploited in modern breeding programs. Here, we genotyped DNA pools from 156 American and European landraces with a 50K SNP Illumina array to study the effect of both human selection and environmental adaptation on the genome-wide diversity of maize landraces. Genomic diversity of landraces varied strongly in different parts of the genome and with geographic origin. We detected selective footprints between landraces of different geographic origin in genes involved in the starch pathway (Su1, Waxy1), flowering time (Zcn8, Vgt3, ZmCCT9) and tolerance to abiotic and biotic stress (ZmASR, NACanddkggenes). Landrace diversity was compared to that of (i) 327 inbred lines representing American and European diversity (“CK lines) and (ii) 103 new lines derived directly from landraces (“DH-SSD lines”). We observed limited diversity loss or selective sweep between landraces and CK lines, except in peri-centromeric regions. However, analysis of modified Roger’s distance between landraces and the CK lines showed that most landraces were not closely related to CK lines. Assignment of CK lines to landraces using supervised analysis showed that only a few landraces, such as Reid’s Yellow Dent, Lancaster Surecrop and Lacaune, strongly contributed to modern European and American breeding pools. Haplotype diversity of CK lines was more enriched by DH-SSD lines that derived from the landraces with no related lines and the lowest contribution to CK lines. Our approach opens an avenue for the identification of promising landraces for pre-breeding.

SIGNIFICANCE STATEMENTS

Maize landraces are a valuable source of genetic diversity for addressing the challenges of climate change and the requirements of low input agriculture as they have been long selected to be well adapted to local agro-climatic conditions and human uses. However, they are underutilized in modern breeding programs because they are poorly characterized, genetically heterogeneous and exhibit poor agronomic performance compared to elite hybrid material. In this study, we developed a high-throughput approach to identify landraces that could potentially enlarge the genetic diversity of modern breeding pools. We genotyped DNA pools from landraces using 50K array technology, which is widely used by breeders to characterize the genetic diversity of inbred lines. To identify landraces that could enrich the modern maize germplasm, we estimated their contribution to inbred lines using supervised analysis and a new measurement of genetic distance.
Evolution of anticipatory effects mediated by epigenetic changes
Authors: Kronholm Ilkka
Published: October 2020

Anticipatory effects mediated by epigenetic changes occur when parents modify the phenotype of their offspring by making epigenetic changes in their gametes guided by information from an environmental cue. To investigate when do anticipatory effects mediated by epigenetic changes evolve in a fluctuating environment, I use an individual based simulation model with explicit genetic architecture. The model allows for the population to respond to environmental changes by evolving plasticity, bet-hedging, or by tracking the environment with genetic adaptation, in addition to the evolution of anticipatory effects. The results show that anticipatory effects evolve when the environmental cue provides reliable information about the environment and the environment changes at intermediate rates, provided that fitness costs of anticipatory effects are rather low. Moreover, evolution of anticipatory effects is quite robust to different genetic architectures when reliability of the environmental cue is high. Anticipatory effects always give smaller fitness benefits than within generation plasticity, suggesting a possible reason for generally small observed anticipatory effects in empirical studies.
Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy
Authors: Verweij Marieke , Hansen Scott G. , Iyer Ravi , John Nessy , Malouli Daniel , Morrow David , Scholz Isabel , Womack Jennie , Abdulhaqq Shaheed , Gilbride Roxanne M. , Hughes Colette M. , Ventura Abigail B. , Ford Julia C. , Selseth Andrea N. , Oswald Kelli , Shoemaker Rebecca , Berkemeier Brian , Bosche William J. , Hull Michael , Shao Jason , Sacha Jonah B. , Axthelm Michael K. , Edlefsen Paul T. , Lifson Jeffrey D. , Picker Louis J. , Früh Klaus
Published: October 2020

Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8+T cells that recognize peptide epitopes presented by major histocompatibility complex (MHC)-II and MHC-E molecules, instead of MHC-Ia, and are uniquely able to mediate stringent control and subsequent clearance of highly pathogenic SIV in ∼50% of vaccinated rhesus macaques (RMs). We show that the MHC-E ligand VMAPRTLLL (VL9), encoded by the Rh67 gene (or its HCMV UL40 counterpart) is required for recognition of RhCMV-infected fibroblasts by MHC-E-restricted CD8+T cells via its ability to promote intracellular MHC-E transport. Moreover, deletion of Rh67 from 68-1 RhCMV/SIV vectors, or mutation of its embedded VL9 ligand, abrogated induction of MHC-E-restricted CD8+T cell responses, leaving responses that exclusively target MHC-II-restricted epitopes. These MHC-II-presented CD8+T cell responses, though comparable in response magnitude and functional differentiation to responses arising from the efficacious 68-1 vector, did not protect RMs against SIV challenge, indicating that Rh67/UL40-enabled direct priming of MHC-E-targeted CD8+T cells is a crucial element of RhCMV/SIV vaccine efficacy.

One Sentence Summary

A cytomegalovirus protein (Rh67/UL40) that upregulates MHC-E expression on RhCMV/SIV-vector infected cells is required for induction of MHC-E-restricted CD8+T cells and for protection against SIV.
Circulating Clonally Expanded T Cells Reflect Functions of Tumor Infiltrating T Cells
Authors: Lucca Liliana , Axisa Pierre-Paul , Lu Benjamin , Harnett Brian , Jessel Shlomit , Zhang Le , Raddassi Khadir , Zhang Lin , Olino Kelly , Clune James , Singer Meromit , Kluger Harriet M. , Hafler David A.
Published: October 2020

Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed from matched tumor and blood from patients with metastatic melanoma at the single cell level. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by T cells present only in tumor. Finally, genes associated with a high degree of blood-tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs, identified by TCRs shared with T cells in tumors, have unique transcriptional expression patterns that may have utility for the interrogation of T cell function in cancer immunotherapy.

Combining transcriptomic and TCRαβ repertoire analysis of circulating and tumor-infiltrating CD8 T cells from patients with metastatic melanoma, we identify a blood-based population with effector properties that reflect those of clonally related tumor-resident T cells.
The maize Aliphatic Suberin Feruloyl Transferase genes affect leaf water movement but are dispensable for bundle sheath CO2concentration
Authors: Mertz Rachel A. , Ellsworth Patrick , Ellsworth Patricia , Tausta S. Lori , von Caemmerer Susanne , Berg R. Howard , Nelson Timothy , Carpita Nicholas C. , Brutnell Thomas P. , Cousins Asaph B.
Published: October 2020

C4grasses often outperform C3species under hot, arid conditions due to superior water and nitrogen use efficiencies and lower rates of photorespiration. A method of concentrating CO2around the site of carbon fixation in the bundle sheath (BS) is required to realize these gains. In NADP-malic enzyme (NADP-ME)-type C4grasses such as maize, suberin deposition in the BS cell wall is hypothesized to act as a diffusion barrier to CO2escape and O2entry from surrounding mesophyll cells. Suberin is a heteropolyester comprised of acyl-lipid-derived aliphatic and phenylpropanoid-derived aromatic components. To disrupt BS suberization, we mutated two paralogously duplicated, unlinked maize orthologues of Arabidopsis thalianaALIPHATIC SUBERIN FERULOYL TRANSFERASE, ZmAsft1andZmAsft2, using closely linkedDissociationtransposons. Loss-of-function double mutants revealed a 97% reduction in suberin-specific omega-hydroxy fatty acids without a stoichiometric decrease in ferulic acid. However, BS suberin lamellae were deficient in electron opaque material, and cohesion between the suberin lamellae and polysaccharide cell walls was attenuated in double mutants. There were no other morphological phenotypes under ambient conditions. Furthermore, there was no significant effect on net CO2assimilation at any intercellular CO2concentration, and no effect on13C isotope discrimination relative to wild type. Thus,ZmAsftexpression is not required to establish a functional CO2concentrating mechanism in in maize. Double mutant leaves exhibit elevated cell wall elasticity, transpirational, and stomatal conductance relative to WT. Thus, theZmAsftgenes are dispensable for gas exchange barrier function but may be involved in regulation of leaf water movement.

One-sentence Summary

Double mutants of two paralogously duplicated maize Aliphatic Suberin Feruloyl Transferase (ZmAsft) genes exhibit reduced aliphatic suberin content, cell wall cohesion defects, and elevated leaf transpiration, but no changes in CO2 assimilation relative to wild type.
Ontogenetic Oxycodone Exposure Affects Early-Life Communicative Behaviors, Sensorimotor Reflexes, and Weight Trajectory in Mice
Authors: Minakova Elena , Sarafinovska Simona , Mikati Marwa O. , Barclay Kia , McCullough Katherine B. , Dougherty Joseph D. , Al-Hasani Ream , Maloney Susan E.
Published: October 2020

Nation-wide, opioid misuse among pregnant women has risen 4-fold from 1999 to 2014, with commensurate increase in neonates hospitalized for Neonatal Abstinence Syndrome (NAS). NAS occurs when a fetus exposed to opioidsin uterogoes into rapid withdrawal after birth. NAS treatment via continued postnatal opioid exposure has been suggested to worsen neurodevelopmental outcomes. We developed a novel model to characterize the impact ofin uteroand postnatal oxycodone (Oxy) exposure on early behavior and development. Via subcutaneous pump implanted before breeding, C57BL/6J dams were infused with oxycodone at 10 mg/kg/day from conception through pup-weaning. At birth,in uterooxy-exposed pups were either cross-fostered (paired with non-oxy exposed dams) to model opioid abstinence (short-oxy) or reared by their biological dams still receiving Oxy to model continued postnatal opioid exposure (long-oxy). Offspring from vehicle-exposed dams served as cross-fostered (short-veh) or biologically-reared (long-veh) controls. Short-oxy exposure resulted in sex-dependent weight reductions and altered spectrotemporal features of isolation-induced ultrasonic vocalization (USV). Meanwhile, long-oxy pups exhibited reduced weight and sex-differential delays in righting reflex. Specifically, long-oxy female offspring exhibited increased latency to righting reflex. Long-oxy pups also showed decreases in number of USV calls, and changes to spectrotemporal USV features. Overall, ontogenetic Oxy exposure was associated with impaired attainment of gross and sensorimotor milestones, as well as alterations in communication and affective behaviors, indicating a need for therapeutic interventions. The model developed here will enable studies of withdrawal physiology and opioid-mediated mechanisms underlying these neurodevelopmental deficits.
Flexible analysis of animal behavior via time-resolved manifold embedding
Authors: York Ryan A. , Carreira-Rosario Arnaldo , Giocomo Lisa M. , Clandinin Thomas R.
Published: October 2020

Uncovering relationships between neural activity and behavior represents a critical challenge, one that would benefit from facile tools that can capture complex structures within large datasets. Here we demonstrate a generalizable strategy for capturing such structures across diverse behaviors: Time-REsolved BehavioraL Embedding (TREBLE). Using data from synthetic trajectories, adult and larvalDrosophila, and mice we show how TREBLE captures both continuous and discrete behavioral dynamics, can uncover variation across individuals, detect the effects of optogenetic perturbation in unbiased fashion, and reveal structure in pose estimation data. By applying TREBLE to moving mice, and medial entorhinal cortex (MEC) recordings, we show that nearly all MEC neurons encode information relevant to specific movement patterns, expanding our understanding of how navigation is related to the execution of locomotion. Thus, TREBLE provides a flexible framework for describing the structure of complex behaviors and their relationships to neural activity.
Macrophage metallothioneins participate in the antileishmanial activity of antimonials
Authors: Vargas Deninson Alejandro , Gregory David J. , Koren Roni Nitzan , Zilberstein Dan , Belew Ashton Trey , El-Sayed Najib M. , Gómez María Adelaida
Published: October 2020

SYNOPSIS

Background

Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of pentavalent antimonials for treatment of American cutaneous leishmaniasis (CL) are critical for drug efficacy.

Objectives

In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to drug-dependent elimination of intracellularLeishmania.

Methods

Transcriptomes of primary macrophages from CL patients (n=6), exposed ex vivo toLeishmaniainfection and SbVwere generated. Candidate genes were selected and validated using short harping RNA interference (shRNA) in THP-1 cells.

Results

Strong induction of metallothionein (MT) genes was observed uponLeishmaniainfection and exposure to SbV, with 7 MT genes (MT1 and MT2 family members) appearing within the top 20 up-regulated genes. Tandem knockdown (KD) of MT2-A and MT1-E, 1F, and 1X in THP-1 cells was achieved using a pan-MT shRNA., Intracellular parasite survival after SbVexposure was unaffected in tandem-KD cells, and this was a consequence of strong transcriptional upregulation of MTs by infection and SbV, overcoming the KD effect. Gene silencing of the metal transcription factor-1 (MTF-1) abrogated expression of MT1 and MT2-A genes. Upon exposure to SbV, intracellular survival ofLeishmaniain MTF-1KDcells was significantly enhanced (p ≤ 0.05).

Conclusions

MTs are potent scavengers of heavy metals, and central elements of the mammalian cell machinery for xenobiotic detoxification. Results from this study highlight the participation of macrophage MTs in Sb-dependent parasite killing, revealing novel strategies for host-targeted optimization of antileishmanial drugs.
Astrocytes close the critical period for visual plasticity
Authors: Ribot Jérôme , Breton Rachel , Calvo Charles-Félix , Moulard Julien , Ezan Pascal , Zapata Jonathan , Samama Kevin , Bemelmans Alexis-Pierre , Sabatet Valentin , Dingli Florent , Loew Damarys , Milleret Chantal , Billuart Pierre , Dallérac Glenn , Rouach Nathalie
Published: October 2020

Summary paragraph

Brain postnatal development is characterized by critical periods of experience-dependent remodeling1,2. Termination of these periods of intense plasticity is associated with settling of neuronal circuits, allowing for efficient information processing3. Failure to end critical periods thus results in neurodevelopmental disorders4,5. Yet, the cellular processes defining the timing of these developmental periods remain unclear. Here we show in the mouse visual cortex that astrocytes control the closure of the critical period. We uncover a novel underlying pathway involving regulation of the extracellular matrix that allows interneurons maturation via an unconventional astroglial connexin signaling. We find that timing of the critical period closure is controlled by a marked developmental upregulation of the astroglial protein connexin 30 that inhibits expression of the matrix degrading enzyme MMP9 through the RhoA-GTPase signaling pathway. Our results thus demonstrate that astrocytes not only influence activity and plasticity of single synapses, but are also key elements in the experience-dependent wiring of brain developing circuits. This work, by revealing that astrocytes promote the maturation of inhibitory circuits, hence provide a new cellular target to alleviate malfunctions associated to impaired closure of critical periods.
Biological traits of seabirds predict extinction risk and vulnerability to anthropogenic threats
Authors: Richards Cerren , Cooke Robert S. C. , Bates Amanda E.
Published: October 2020

Aim

Here we aim to: 1) test whether globally-threatened vs non-threatened seabirds are separated in trait space; 2) quantify the redundancy and uniqueness of species trait combinations per IUCN Red List Category; and 3) identify traits that render species vulnerable to anthropogenic threats.

Location

Global

Time period

Contemporary

Major taxa studied

Seabirds

Methods

We compile and impute eight traits that relate to species’ vulnerabilities and ecosystem functioning across 341 seabird species. Using these traits, we build a mixed data PCA of species’ trait space. We further quantify trait redundancy with a unique trait combinations (UTCs) approach. Finally, we employ a similarity of percentages analysis (SIMPER) to identify which traits explain the greatest difference between threat groups.

Results

We find seabirds segregate in trait space based on threat status, indicating anthropogenic impacts are selectively removing large, long-lived, pelagic surface feeders with narrow habitat breadths. We further find that globally threatened species have higher trait redundancy, while non-threatened species have relatively unique ecological strategies and limited redundancy. Finally, we find that species with narrow habitat breadths, fast reproductive speeds, and omnivorous diets are more likely to be threatened by habitat-modifying processes (e.g., pollution and natural system modifications); whereas pelagic specialists with slow reproductive speeds and omnivorous diets are vulnerable to threats that directly impact survival and fecundity (e.g., invasive species and biological resource use).

Main conclusions

Our results suggest both globally threatened and non-threatened species contribute unique ecological strategies. Consequently, conserving both threat groups, but with contrasting approaches may avoid potential changes in ecosystem functioning and stability.
Precision as a metric for acoustic survey design using occupancy or spatial capture-recapture
Authors: Juodakis Julius , Castro Isabel , Marsland Stephen
Published: October 2020

Passive acoustic surveys provide a convenient and cost-effective way to monitor animal populations. Methods for conducting and analysing such surveys, especially for performing automated call recognition from sound recordings, are undergoing rapid development. However, no standard metric exists to evaluate the proposed changes. Furthermore, most metrics that are currently used are specific to a single stage of the survey workflow, and therefore may not reflect the overall effects of a design choice.

Here, we attempt to define and evaluate the effectiveness of surveys conducted in two common frameworks of population inference – occupancy modelling and spatially explicit capture-recapture (SCR). Specifically, we investigate precision (standard error of the final estimate) as a possible metric of survey performance, but we show that it does not lead to generally optimal designs in occupancy modelling. In contrast, precision of the SCR density estimate can be optimised with fewer experiment-specific parameters. We illustrate these issues using simulations.

We further demonstrate how SCR precision can be used to evaluate design choices on a field survey of little spotted kiwi (Apteryx owenii). We show that precision correctly measures tradeoffs involving sampling effort. As a case study, we compare automated call recognition software with human annotations. The proposed metric captured the tradeoff between missed calls (8% loss of precision when using the software) and faster data through-put (60% gain), while common metrics based on per-second agreement failed to identify optimal improvements and could be inflated by deleting data.

Due to the flexibility of SCR framework, the approach presented here can be applied to a wide range of different survey designs. As the precision is directly related to the power of detecting temporal trends or other effects in the subsequent inference, this metric evaluates design choices at the application level, and can capture tradeoffs that are missed by stage-specific metrics, thus enabling reliable comparison between different experimental designs and analysis methods.
Sensory experience selectively reorganizes the late component of evoked responses
Authors: Bermudez-Contreras Edgar , Schjetnan Andrea Gomez-Palacio , Luczak Artur , Mohajerani Majid H.
Published: October 2020

In response to sensory stimulation, the cortex exhibits an early transient response followed by a late and slower activation pattern. Recent studies suggest that the early component represents features of the stimulus while the late component is associated with stimulus perception. Although very informative, these studies only focus on the amplitude of the evoked responses to study its relationship with sensory perception. In this work we expand upon the study of how patterns of evoked and spontaneous activity are modified by experience at mesoscale level using voltage and extracellular glutamate transient recordings over widespread regions of mice dorsal neocortex. We find that repeated tactile or auditory stimulation selectively modifies the spatiotemporal patterns of cortical activity, mainly of the late evoked response in anesthetized mice injected with amphetamine and also in awake mice. This modification lasted up to 60 minutes and results not only in an increase in amplitude of the late response after repeated stimulation, but also in an increase in the similarity between the spatiotemporal patterns of the late and the early evoked response patterns in anesthetized mice. This similarity increase occurs only for the evoked responses of the sensory modality that received the repeated stimulation. Thus, this selective long-lasting spatiotemporal modification of the cortical activity patterns might provide evidence that evoked responses are a cortex-wide phenomenon. This work opens new questions about how perception-related cortical activity changes with sensory experience across the cortex.
A Hilbert-based method for processing respiratory timeseries
Authors: Harrison Samuel J. , Bianchi Samuel , Heinzle Jakob , Stephan Klaas Enno , Iglesias Sandra , Kasper Lars
Published: October 2020

In this technical note, we introduce a new method for estimating changes in respiratory volume per unit time (RVT) from respiratory bellows recordings. By using techniques from the electrophysiological literature, in particular the Hilbert transform, we show how we can better characterise breathing rhythms, with the goal of improving physiological noise correction in functional magnetic resonance imaging (fMRI). Specifically, our approach leads to a representation with higher time resolution and better captures atypical breathing events than current peak-based RVT estimators. Finally, we demonstrate that this leads to an increase in the amount of respiration-related variance removed from fMRI data when used as part of a typical preprocessing pipeline.

Our implementation will be publicly available as part of the PhysIO package, which is distributed as part of the open-source TAPAS toolbox (translationalneuromodeling.org/tapas).

Highlights

We introduce a new estimator for respiratory volume per unit time from respiratory recordings.

We demonstrate how this is able to accurately characterise atypical breathing events.

This removes significantly more variance when used as a confound regressor for fMRI data.

Our implementation will be included in PhysIO, released as part of TAPAS:translationalneuromodeling.org/tapas.
Sex-Dependent Age Trajectories of Subcortical Brain Structures: Analysis of Large-Scale Percentile Models and Shape Morphometry
Authors: Ching Christopher R. K. , Abaryan Zvart , Santhalingam Vigneshwaran , Zhu Alyssa H. , Bright Joanna K. , Jahanshad Neda , Thompson Paul M.
Published: October 2020

Modeling of structural brain variation over the lifespan is important to better understand factors contributing to healthy aging and risk for neurological conditions such as Alzheimer’s disease. Even so, we lack normative data on brain morphometry across the adult lifespan in large, well-powered samples. Here, in a large population-based sample of 26,440 adults from the UK Biobank (age: 44-81 yrs.), we created normative percentile charts for MRI-derived subcortical volumes. Next, we investigated associations between these morphometric measures and the strongest known genetic risk factor for late-onset Alzheimer’s disease (APOEgenotype) and mapped the spatial distribution of age-by-sex interactions using computational surface mesh modeling and shape analysis. Vertex-wise shape mapping supplements traditional gross volumetric approaches to reveal finer-grained variations across functionally important brain subcompartments. Normative curves revealed volumetric loss with age, as expected, for all subcortical brain structures except for the lateral ventricles, which expanded with age. Surprisingly, no volumetric associations withAPOEgenotype were detected, despite the very large sample size. Age-related trajectories for volumes differed in women versus men, and surface-based statistical maps revealed the spatial distribution of the age-by-sex interaction. Subcortical volumes declined faster in men than women over the full age range, but after age 60, fewer structures showed sex-dependent trajectories, indicating similar volumetric changes in older men and women. Large-scale statistical modeling of age effects on brain structures may drive new insights into individual differences in brain aging and help to identify factors that promote healthy brain aging and risk for disease.