bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving outside the lab: markerless motion capture accurately quantifies sagittal plane kinematics during the vertical jump
Authors: Drazan John F , Phillips William T , Seethapathi Nidhi , Hullfish Todd J , Baxter Josh R
Published: March 2021

Markerless motion capture using deep learning approaches have potential to revolutionize the field of biomechanics by allowing researchers to collect data outside of the laboratory environment, yet there remain questions regarding the accuracy and ease of use of these approaches. The purpose of this study was to apply a markerless motion capture approach to extract lower limb angles in the sagittal plane during the vertical jump and to evaluate agreement between the custom trained model and gold stand motion capture. We performed this study using a large open source data set (N=84) that included synchronized commercial video and gold standard motion capture. We split these data into a training set for model development (n=69) and test set to evaluate capture performance relative to gold standard motion capture using coefficient of multiple correlations (CMC) (n=15). We found very strong agreement between the custom trained markerless approach and marker-based motion capture within the test set across the entire movement (CMC>0.991, RMSE<3.22°), with at least strong CMC values across all trials for the hip (0.853 ± 0.23), knee (0.963 ± 0.471), and ankle (0.970 ± 0.055). The strong agreement between markerless and marker-based motion capture provides evidence that markerless motion capture is a viable tool to extend data collection to outside of the laboratory. As biomechanical research struggles with representative sampling practices, markerless motion capture has potential to transform biomechanical research away from traditional laboratory settings into venues convenient to populations that are under sampled without sacrificing measurement fidelity.
Decoding the Information Structure Underlying the Neural Representation of Concepts
Authors: Fernandino Leonardo , Tong Jia-Qing , Conant Lisa L. , Humphries Colin J. , Binder Jeffrey R.
Published: March 2021

The nature of the representational code underlying conceptual knowledge remains a major unsolved problem in cognitive neuroscience. We assessed the extent to which different representational systems contribute to the instantiation of lexical concepts in high-level, heteromodal cortical areas previously associated with semantic cognition. We found that lexical semantic information can be reliably decoded from a wide range of heteromodal cortical areas in frontal, parietal, and temporal cortex. In most of these areas, we found a striking advantage for experience-based representational structures (i.e., encoding information about sensory-motor, affective, and other features of phenomenal experience), with little evidence for independent taxonomic or distributional organization. These results were found independently for object and event concepts. Our findings indicate that concept representations in heteromodal cortex are based, at least in part, on experiential information. They also reveal that, in most heteromodal areas, event concepts have more heterogeneous representations (i.e., they are more easily decodable) than object concepts, and that other areas beyond the traditional “semantic hubs” contribute to semantic cognition, particularly the posterior cingulate gyrus and the precuneus.
Buffering Updates Enables Efficient Dynamic de Bruijn Graphs
Authors: Alanko Jarno , Alipanahi Bahar , Settle Jonathen , Boucher Christina , Gagie Travis
Published: March 2021

Motivation

The de Bruijn graph has become a ubiquitous graph model for biological data ever since its initial introduction in the late 1990s. It has been used for a variety of purposes including genome assembly (Zerbino and Birney, 2008; Bankevich et al., 2012; Peng et al., 2012), variant detection (Alipanahi et al., 2020b; Iqbal et al., 2012), and storage of assembled genomes (Chikhi et al., 2016). For this reason, there have been over a dozen methods for building and representing the de Bruijn graph and its variants in a space and time efficient manner.

Results

With the exception of a few data structures (Muggli et al., 2019; Holley and Melsted, 2020; Crawford et al., 2018), compressed and compact de Bruijn graphs do not allow for the graph to be efficiently updated, meaning that data can be be added or deleted. The most recent compressed dynamic de Bruijn graph (Alipanahi et al., 2020a), relies on dynamic bit vectors which are slow in theory and practice. To address this shortcoming, we present a compressed dynamic de Bruijn graph that removes the necessity of dynamic bit vectors by buffering data that should be added or removed from the graph. We implement our method, which we refer to as BufBOSS, and compare its performance to Bifrost, DynamicBOSS, and FDBG. Our experiments demonstrate that BufBOSS achieves attractive trade-offs compared to other tools in terms of time, memory and disk, and has the best deletion performance by an order of magnitude.

Contact

alanko.jarno@gmail.com
Enhancing Drug-Drug Interaction Prediction Using Deep Attention Neural Networks
Authors: Liu Shichao , Zhang Yang , Cui Yuxin , Qiu Yang , Deng Yifan , Zhang Wen , Zhang Zhongfei
Published: March 2021

Drug-drug interactions are one of the main concerns in drug discovery. Accurate prediction of drug-drug interactions plays a key role in increasing the efficiency of drug research and safety when multiple drugs are c o-prescribed. With various data sources that describe the relationships and properties between drugs, the comprehensive approach that integrates multiple data sources would be considerably effective in making high-accuracy prediction. In this paper, we propose a Deep Attention Neural Network based Drug-Drug Interaction prediction framework, abbreviated as DANN-DDI, to predict unobserved drug-drug interactions. First, we construct multiple drug feature networks and learn drug representations from these networks using the graph embedding method; then, we concatenate the learned drug embeddings and design an attention neural network to learn representations of drug-drug pairs; finally, we adopt a deep neural network to accurately predict drug-drug interactions. The experimental results demonstrate that our model DANN-DDI has improved prediction performance compared with state-of-the-art methods. Moreover, the proposed model can predict novel drug-drug interactions and drug-drug interaction-associated events.
Florigen governs shoot regeneration
Authors: Kutsher Yaarit , Fisler Michal , Faigenboim Adi , Reuveni Moshe
Published: March 2021

It is widely known that during the reproductive stage (flowering), plants do not root well. Most protocols of shoot regeneration in plants utilize juvenile tissue. Adding these two realities together encouraged us to studied the role of florigen in shoot regeneration. Mature tobacco tissue that expresses the endogenous tobacco florigen mRNA regenerates poorly, while juvenile tissue that does not express the florigen regenerates shoots well. Inhibition of Nitric Oxide (NO) synthesis reduced shoot regeneration as well as promoted flowering and increased tobacco florigen level. In contrast, the addition of NO (by way of NO donor) to the tissue increased regeneration, delayed flowering, reduced tobacco florigen mRNA. Ectopic expression of florigen genes in tobacco or tomato decreased regeneration capacity significantly. Overexpression pearPcFT2gene increased regeneration capacity. During regeneration, florigen mRNA was not changed. We conclude that florigen presence in mature tobacco leaves reduces roots and shoots regeneration and is the possible reason for the age-related decrease in regeneration capacity.
Targeting CISH enhances natural cytotoxicity receptor signaling and reduces NK cell exhaustion to improve solid tumor immunity
Authors: Bernard P-L. , Delconte R. B. , Pastor S. , Laletin V. , Costa Da Silva C. , Goubard A. , Josselin E. , Castellano R. , Krug A. , Vernerey J. , Devillier R. , Olive D. , Verhoeyen E. , Vivier E. , Huntington N. D. , Nunès J. A. , Guittard G.
Published: March 2021

Cytokine inducible SH2-containing protein (CISH) is a natural killer (NK) cell negative regulator of cytokine signaling pathway. To further understand CISH functions in NK cells, we developed a conditionalCish-deficient mouse model in NK cells (Cishfl/flNcr1Ki/+). We detected no developmental or homeostatic difference in NK cells.

However, global gene expression ofCishfl/flNcr1Ki/+NK cells compared toCish+/+Ncr1Ki/+NK cells revealed upregulation of pathways and genes associated with NK cell cycling and activation. We show that CISH does not only regulate interleukin-15 (IL-15) signaling pathways but also natural cytotoxicity receptors (NCR) pathways. Indeed, CISH protein expression level increases upon NCR triggering. PrimedCishfl/flNcr1Ki/+NK cells display increased activation upon NCR stimulation.Cishfl/flNcr1Ki/+NK cells display lower activation thresholds andCishfl/flNcr1Ki/+mice are more resistant to tumor metastasis. Remarkably, we found thatCishfl/flNcr1Ki/+mice were also more resistant to primary breast cancer growth in addition to superior control of spontaneous tumor metastasis. CISH deletion favors NK cell accumulation to the primary tumor, optimizes NK cell killing properties and decreases TIGIT immune checkpoint receptor expression, limiting NK cell exhaustion. Finally, we argue that specifically enhancing NK cell function is sufficient to boost anti-tumor response to both primary and secondary tumor models. Using CRISPRi, we then targetedCISHin human NK-92 or primary NK cells. According to the results in our mouse model, CISH deletion favors NCR signaling and anti-tumor functions in human NK cells. Our results validate CISH as an emerging therapeutic target to enhance NK cell immunotherapy.
Loss of glutamate transportereaat2aleads to aberrant neuronal excitability, recurrent epileptic seizures and hypoactivity
Authors: Hotz Adriana L. , Jamali Ahmed , Rieser Nicolas N. , Niklaus Stephanie , Aydin Ecem , Myren-Svelstad Sverre , Lalla Laetitia , Jurisch-Yaksi Nathalie , Yaksi Emre , Neuhauss Stephan C.F.
Published: March 2021

Astroglial excitatory amino acid transporter 2 (EAAT2, GLT-1, SLC1A2) regulates the duration and extent of neuronal excitation by removing glutamate from the synaptic cleft. Hence, an impairment in EAAT2 function could lead to an imbalanced neural network excitability. Here, we investigated the functional alterations of neuronal and astroglial networks associated with the loss of function in the astroglia predominanteaat2agene in zebrafish. We observed thateaat2a-/-mutant zebrafish larvae display recurrent spontaneous and light-induced seizures in neurons and astroglia, which coincide with an abrupt increase in extracellular glutamate levels. In stark contrast to this hyperexcitability, basal neuronal and astroglial activity was surprisingly reduced ineaat2a-/-mutant animals, which manifested in decreased overall locomotion. Our results reveal an essential and mechanistic contribution of EAAT2a in balancing brain excitability, and its direct link to epileptic seizures.
Differential detection ofTomato mosaic virus(ToMV) andTomato brown rugose fruit virus(ToBRFV) using CRISPR-Cas12
Authors: Alon Dan , Hak Hagit , Bornstein Menachem , Pines Gur , Spiegelman Ziv
Published: March 2021

CRISPR/Cas12-based detection is a novel approach for efficient, sequence-specific identification of viruses. Here we adopt the use of CRISPR/Cas12a to identify theTomato brown rugose fruit virus(ToBRFV), a new and emergingTobamoviruscausing substantial damage to the global tomato industry. Specific guide RNAs (gRNAs) were designed to detect either ToBRFV or the closely relatedTomato mosaic virus(ToMV). This technology enabled the differential detection of ToBRFV and ToMV. Sensitivity assays revealed that viruses can be detected from 15-30 ng of RT-PCR product, and that specific detection could be achieved from a mix of ToMV and ToBRFV. In addition, we show that this method enabled the identification of ToBRFV in samples collected from commercial greenhouses. These results demonstrate a new method for species-specific detection of plant viruses. This could provide a platform for the development of efficient and user-friendly ways to distinguish between closely related strains and resistance-breaking pathogens.
Parasitic wasps do not lack lipogenesis
Authors: Ruther Joachim , Prager Lorena , Pokorny Tamara
Published: March 2021

Fatty acids are crucial primary metabolites for virtually any creature on earth. Therefore, most organisms do not rely exclusively on nutritional supply with fatty acids but have the ability to synthesize fatty acids and triacylglycerides de novo from carbohydrates, a process called lipogenesis. The ubiquity of lipogenesis has been questioned by a series of studies reporting that many parasitic wasps (parasitoids) do not accumulate lipid mass despite having unlimited access to sugar. This has been interpreted as an evolutionary metabolic trait loss in parasitoids. Here, we demonstrate de novo biosynthesis of fatty acids from13C-labeled α-D-glucose in eleven species of parasitoids from six families. We furthermore show with the model organismNasonia vitripennisthat lipogenesis occurs even when lipid reserves are still intact, but relative13C-incorporation rates increase in females with widely depleted fat reserves. Therefore, we conclude that the presumed “lack of lipogenesis” in parasitoids needs to be re-evaluated.
Dietary habits of free-ranging banded langur (Presbytis femoralis) in a secondary-human modified forest in Johor, Malaysia
Authors: Najmuddin Mohd Faudzir , Haris Hidayah , Norazlimi Noratiqah , Ruslin Farhani , Matsuda Ikki , Md-Zain Badrul Munir , Abdul-Latiff Muhammad Abu Bakar
Published: March 2021

Banded langurs,Presbytis femoralis, are distributed in southern Peninsular Malaysia, i.e., Johor and its borders including Singapore. It has been estimated that there are only < 250 mature individuals ofP. femoralisin Malaysia and Singapore, and it is currently assessed as Critically Endangered. The dietary information ofP. femoralisand even other closely related species has rarely been reported. This study, therefore, aimed to describe their dietary habits and discuss interaction between their feeding behaviour and its surrounding. This study was conducted from February to November 2018, with 15 sampling days each month. We collected a total of 186 sighting hours, using a scan sampling method with 10-min intervals, on a five-langur focal group. We have identified 29 species with 47 items consumed by the banded langur, mostly young leaves (51 %) followed by fruits (45 %), and flowers (3.8 %). The study group spent slightly more time consuming non-cultivated plants but relied on cultivated plants for the fruits. Over 75% of fruit feeding involved consuming cultivar plants; in most cases (73%), they ate only the pulp, not the seeds. Since the cultivated plants was planted in human settlement, there is an urgent need to implement conservation measures to untangle the human-langur conflicts for instance, reforestation of a buffer region using non-cultivated plants. There is a potential for building upon our new findings with more detailed investigations, such as more extensive ecological factors influencing the dietary adaptation which would be necessary to support conservation efforts and management decisions of this species.
A millennium of increasing ecosystem diversity until the mid-20thcentury
Authors: Martins Inês S. , Dornelas Maria , Vellend Mark , Thomas Chris D.
Published: March 2021

Land-use change is widely regarded as a simplifying and homogenising force in nature. In contrast, analysing global land-use reconstructions from the 10thto 20thcenturies, we found progressive increases in the number, evenness, and diversity of ecosystems (including human-modified land-use types) across the globe. Ecosystem diversity increased more rapidly after ∼1700CE, then slowed or partially reversed (depending on the metric) following the mid-20thcentury acceleration of human impacts. Differentiation also generally increased across space, with homogenization only evident in the presence-absence analysis of ecosystem types at the global scale. Our results suggest that human land-use changes have primarily driven increases in ecosystem diversity over the last millennium.
Fitness costs and benefits of gene expression plasticity in rice under drought
Authors: Groen Simon C. , Hamann Elena , Ćalić Irina , Cochran Colleen , Konshok Rachel , Purugganan Michael D. , Franks Steven J.
Published: March 2021

Genome-wide gene expression changes in response to environmental variability have been widely documented, but we lack detailed and comprehensive understanding of the interplay between this form of phenotypic plasticity and natural selection. Selection on expression plasticity may be limited by environment-specific costs, and plasticity may in turn affect selection on baseline expression levels. Here, we address this fundamental issue by measuring selection on drought-induced plasticity of leaf transcripts in field-grown rice populations. Selection disfavored switching off housekeeping genes under drought. This stress-induced dysregulation did not constrain selection on baseline transcript levels, suggesting compensatory evolution may be possible. Selection rarely acted strongly on individual transcripts but worked polygenically on gradual (continuous) plasticity of co-expressed gene modules regulating photosynthesis via known drought-responsive transcription factors. Finally, selection was tied to inefficient gene architectural features and metabolic costs of expression. Our study provides a genome-wide view of costs and benefits of gene expression plasticity.
Population differences in the length and early-life dynamics of telomeres among European pied flycatchers
Authors: Kärkkäinen Tiia , Laaksonen Toni , Burgess Malcolm , Cantarero Alejandro , Martínez-Padilla Jesús , Potti Jaime , Moreno Juan , Thomson Robert L. , Tilgar Vallo , Stier Antoine
Published: March 2021

Telomere length and shortening rate are increasingly used as biomarkers for long-term costs in ecological and evolutionary studies because of their relationships with survival and fitness. Both early-life conditions and growth, and later-life stressors can create variation in telomere shortening rate. Studies on between- population telomere length and dynamics are scarce, despite the expectation that populations exposed to varying environmental constraints would present divergent telomere length patterns. The pied flycatcher (Ficedula hypoleuca) is a passerine bird breeding across Eurasia (from Spain to western Siberia) and migrating through the Iberian Peninsula to spend the non-breeding period in sub-Saharan Africa. Thus, different populations show marked differences in migration distance. We studied the large-scale variation of telomere length and early-life dynamics in the pied flycatcher by comparing six European populations across a north- south gradient (Finland, Estonia, England, and Spain) predicting negative effect of migration distance on adult telomere length, and of nestling growth on nestling telomere dynamics. There were clear population differences in telomere length, with English birds from mid-latitudes having the longest telomeres. Telomere length did not thus show consistent latitudinal variation and was not linearly linked to differences in migration distance. Early-life telomere shortening rate tended to vary between populations. Fast growth was associated with shorter telomeres in the early life, but faster nestling growth affected telomeres more negatively in northern than southern populations. While the sources of between-population differences in telomere-related biology remain to be more intensively studied, our study illustrates the need to expand telomere studies at the between-population level.
Micrometer-resolution reconstruction and analysis of whole mouse brain vasculature by synchrotron-based phase-contrast tomographic microscopy
Authors: Miettinen Arttu , Zippo Antonio G. , Patera Alessandra , Bonnin Anne , Shahmoradian Sarah H. , Biella Gabriele E. M. , Stampanoni Marco
Published: March 2021

Nervous tissue metabolism is mainly supported by the dense thread of blood vessels which mainly provides fast supplies of oxygen and glucose. Recently, the supplying role of the brain vascular system has been examined in major neurological conditions such as the Alzheimer’s and Parkinson’s diseases. However, to date, fast and reliable methods for the fine level microstructural extraction of whole brain vascular systems are still unavailable. We present a methodological framework suitable for reconstruction of the whole mouse brain cerebral microvasculature by X-ray tomography with the unprecedented pixel size of 0.65 μm. Our measurements suggest that the resolving power of the technique is better than in many previous studies, and therefore it allows for a refinement of current measurements of blood vessel properties. Relevant insights emerged from analyses characterizing the regional morphology and topology of blood vessels. Specifically, vascular diameter and density appeared non-homogeneously distributed among the brain regions suggesting preferential sites for high-demanding metabolic requirements. Also, topological features such as the vessel branching points were non-uniformly distributed among the brain districts indicating that specific architectural schemes are required to serve the distinct functional specialization of the nervous tissue. In conclusion, here we propose a combination of experimental and computational method for efficient and fast investigations of the vascular system of entire organs with submicrometric precision.
Single-cell transcriptome profiling simulation reveals the impact of sequencing parameters and algorithms on clustering
Authors: Liu Yunhe , Shi Bisheng , Wu Aoshen , Peng Xueqing , Yuan Zhenghong , Liu Gang , Liu Lei
Published: March 2021

Despite of scRNA-seq analytic algorithms developed, their performance for cell clustering cannot be quantified due to the unknown “true” clusters. Referencing the transcriptomic heterogeneity of cell clusters, a “true” mRNA number matrix of cell individuals was defined as ground truth. Based on the matrix and real data generation procedure, a simulation program (SSCRNA) for raw data was developed. Subsequently, the consistence between simulated data and real data was evaluated. Furthermore, the impact of sequencing depth, and algorithms for analyses on cluster accuracy was quantified. As a result, the simulation result is highly consistent with that of the real data. It is found that mis-classification rate can be attributed to multiple reasons on current scRNA platforms, and clustering accuracy is not only sensitive to sequencing depth increasement, but can also be reflected by the position of the cluster on TSNE plot. Among the clustering algorithms, Gaussian normalization method is more appropriate for current workflows. In the clustering algorithms, k-means&louvain clustering method performs better in dimension reduced data than full data, while k-means clustering method is stable under both situations. In conclusion, the scRNA simulation algorithm developed restores the real data generation process, discovered impact of parameters on mis-clustering, compared the normalization/clustering algorithms and provided novel insight into scRNA analyses.
Bloom syndrome helicase contributes to germ line development and longevity in zebrafish
Authors: Annus Tamás , Müller Dalma , Jezsó Bálint , Ullaga György , Harami Gábor M. , Orbán László , Kovács Mihály , Varga Máté
Published: March 2021

RecQ helicases - also known as the ‘guardians of the genome’ - play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis and shortened life expectancy brought on by genomic instability. We show that zebrafishblmmutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlikefancgenes andrad51, however,blmappears to effect its function independent oftp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility.
Climate Change Controls Phosphorus Transport from the Watershed into Lake Kinneret (Israel)
Authors: Gophen Moshe
Published: March 2021

Part of the Kinneret watershed, the Hula Valley, was modified from wetlands – shallow lake for agricultural cultivation. Enhancement of nutrient fluxes into Lake Kinneret was predicted. Therefore, a reclamation project was implemented and eco-tourism partly replaced agriculture. Since the mid-1980s, regional climate change has been documented. Statistical evaluation of long-term records of TP (Total Phosphorus) concentrations in headwaters and potential resources in the Hula Valley was carried out to identify efficient management design targets. Significant correlation between major headwater river discharge and TP concentration was indicated, whilst the impact of external fertilizer loads and 50,000 winter migratory cranes was probably negligible. Nevertheless, confirmed severe bdamage to agricultural crops carried out by cranes led to their maximal deportation and optimization of their feeding policy. Consequently, the continuation of the present management is recommended.
Integration of plant carbohydrate dynamics by Fourier polynomials
Authors: Seydel Charlotte , Biener Julia , Brodsky Vladimir , Eberlein Svenja , Nägele Thomas
Published: March 2021

Quantification of system dynamics is a central aim of mathematical modelling in biology. Defining experimentally supported functional relationships between molecular entities by mathematical terms enables the application of computational routines to simulate and analyse the underlying molecular system. In many fields of natural sciences and engineering, trigonometric functions are applied to describe oscillatory processes. As biochemical oscillations occur in many aspects of biochemistry and biophysics, Fourier analysis of metabolic functions promises to quantify, describe and analyse metabolism and its reaction towards environmental fluctuations. Here, Fourier polynomials were developed from experimental time-series data and combined with block diagram simulation of plant metabolism to study heat shock response of photosynthetic CO2assimilation and carbohydrate metabolism. Findings suggest that increased capacities of starch biosynthesis stabilize photosynthetic CO2assimilation under transient heat exposure. Among soluble sugars, fructose concentrations were observed to fluctuate least under heat exposure which might be the consequence of high respiration rates under elevated temperature. Finally, Col-0 and two mutants ofArabidopsis thalianawith deficiencies in starch and sucrose metabolism were discriminated by fundamental frequencies of Fourier polynomials across different experiments. This suggests balance modelling based on Fourier polynomials as a suitable approach for mathematical analysis of dynamic plant-environment interactions.

Highlight

A balance equation model is developed to quantify effects of transient heat exposure on plant carbon assimilation. The model is based on Fourier polynomials for quantitative assessment of system dynamics.
Electrochemical measurements reveal reactive oxygen species in stress granules
Authors: Hu Keke , Relton Emily , Locker Nicolas , Phan Nhu T. N. , Ewing Andrew G.
Published: March 2021

Stress granules (SGs) are membraneless organelles that assemble in the cytoplasm to organize cellular contents and promote rapid adaptation during stress. To understand how SGs contribute to physiological functions, we used electrochemical measurements to detect electroactive species in SGs. With amperometry, we discovered that reactive oxygen species (ROS) are encapsulated inside arseniteinduced SGs, and H2O2is the main species. The release kinetics of H2O2from single SGs and the number of H2O2molecules were quantified. The discovery that SGs contain ROS implicates them as communicators of the cellular stresses rather than a simple end-point. This may explain how SGs regulate cellular metabolism and stress responses. This may also help better understand their cytoprotective functions in pathological conditions associated with SGs such as neurodegenerative diseases, cancers and viral infections.
P-sort: an open-source software for cerebellar neurophysiology
Authors: Sedaghat-Nejad Ehsan , Fakharian Mohammad Amin , Pi Jay , Hage Paul , Kojima Yoshiko , Soetedjo Robi , Ohmae Shogo , Medina Javier F , Shadmehr Reza
Published: March 2021

Analysis of electrophysiological data from Purkinje cells (P-cells) of the cerebellum presents challenges for spike detection. Complex spikes have waveforms that vary significantly from one event to the next, raising the problem of misidentification. Even when complex spikes are detected correctly, the simple spikes may belong to a different P-cell, raising the danger of misattribution. Here, we analyzed data from over 300 P-cells in marmosets, macaques, and mice, using an open-source, semi-automated software called P-sort that addresses the spike identification and attribution problems. Like other sorting software, P-sort relies on nonlinear dimensionality reduction to cluster spikes. However, it also uses the statistical relationship between simple and complex spikes to merge seemingly disparate clusters, or split a single cluster. In comparison with expert manual curation, occasionally P-sort identified significantly more complex spikes, as well as prevented misattribution of clusters. Three existing automatic sorters performed less well, particularly for identification of complex spikes. To improve development of analysis tools for the cerebellum, we provide labeled data for 313 recording sessions, as well as statistical characteristics of waveforms and firing patterns.
Sacsin cotranslational degradation causes autosomal recessive spastic ataxia of Charlevoix-Saguenay
Authors: Longo Fabiana , De Ritis Daniele , Miluzio Annarita , Fraticelli Davide , Baets Jonathan , Scarlato Marina , Santorelli Filippo M. , Biffo Stefano , Maltecca Francesca
Published: March 2021

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is caused by more than 200 different mutations in theSACSgene encoding sacsin, a huge multimodular protein of unknown function. ARSACS phenotypic spectrum is highly variable. Previous studies correlated the nature and position ofSACSmutations with age of onset or disease severity, though the effects on protein stability were not considered.

In this study, we explain mechanistically the lack of genotype-phenotype correlation in ARSACS, with important consequences for disease diagnosis and treatment.

We found that sacsin is almost absent in ARSACS fibroblasts, regardless of the nature of the mutation. We did not detect sacsin in patients with truncating mutations, while we found it strikingly reduced or absent also in compound heterozygotes carrying diverse missense mutations. We excludedSACSmRNA decay, defective translation, or faster post-translational degradation as causes of protein reduction. Conversely, we demonstrated that nascent mutant sacsin protein undergoes preemptive cotranslational degradation, emerging as a novel cause of a human disease. Based on these findings, sacsin levels should be included in the diagnostic algorithm for ARSACS.
Signal complexity indicators of health status in clinical-EEG
Authors: Shen Kelly , McFadden Alison , McIntosh Anthony R.
Published: March 2021

Brain signal variability changes across the lifespan in both health and disease, likely reflecting changes in information processing capacity related to development, aging and neurological disorders. While signal complexity, and multiscale entropy (MSE) in particular, has been proposed as a biomarker for neurological disorders, most observations of altered signal complexity have come from studies comparing patients with few to no comorbidities against healthy controls. In this study, we examined whether MSE of brain signals was distinguishable across individuals in a large and heterogeneous set of clinical-EEG data. Using a multivariate analysis, we found unique timescale-dependent differences in MSE across various neurological disorders. We also found MSE to differentiate individuals with non-brain comorbidities, suggesting that MSE is sensitive to brain signal changes brought about by metabolic and other non-brain disorders. Such changes were not detectable in the spectral power density of brain signals. Our findings suggest that brain signal complexity may offer complementary information to spectral power about an individual’s health status and is a promising avenue for clinical biomarker development.
Male rat sexual behavior: insights from inter-copulatory intervals
Authors: Huijgens Patty T. , Guarraci Fay A. , Olivier Jocelien D.A. , Snoeren Eelke M.S.
Published: March 2021

The assessment of sexual behavior in male rats with the aim of unraveling underlying neurobiological mechanisms has in the recent decades been reduced to the annotation of mounts, intromissions and ejaculations. To provide a better understanding of the structure and patterns of copulation, it is necessary to extend and tailor the analysis to the natural organization of male rat copulation. This will lead to better formulation of hypotheses about neurobiological underpinnings of behavior. Mounts and intromissions are naturally organized in mount bouts consisting of one or more copulatory behaviors and are interspersed with time outs. We hypothesized that time outs and the post-ejaculatory interval (inter-copulatory intervals) are related and possibly under the control of a common copulatory inhibition mechanism that is the result of penile sensory stimulation. To test this hypothesis, we analyzed sexual behavior in male rats of three different cohorts from three different laboratories. Results showed that the post-ejaculatory interval and mean time out duration are strongly correlated in all cohorts analyzed. In addition, we showed that individual time out duration is at least partially predicted by the sum of sensory stimulation of copulatory components in the preceding mount bout, with more penile stimulation associated with longer time outs. These findings suggest that both time out and post-ejaculatory interval duration may be determined by the magnitude of sensory stimulation, which inhibits copulation. Whether the same neural pathways are involved in the central orchestration of both time outs and the post-ejaculatory interval should be subject to future studies.
DeepCob: Precise and high-throughput analysis of maize cob geometry using deep learning with an application in genebank phenomics
Authors: Kienbaum Lydia , Abondano Miguel Correa , Blas Raul , Schmid Karl
Published: March 2021

Background

Maize cobs are an important component of crop yield that exhibit a high diversity in size, shape and color in native landraces and modern varieties. Various phenotyping approaches were developed to measure maize cob parameters in a high throughput fashion. More recently, deep learning methods like convolutional neural networks (CNN) became available and were shown to be highly useful for high-throughput plant phenotyping. We aimed at comparing classical image segmentation with deep learning methods for maize cob image segmentation and phenotyping using a large image dataset of native maize landrace diversity from Peru.

Results

Comparison of three image analysis methods showed that a Mask R-CNN trained on a diverse set of maize cob images was highly superior to classical image analysis using the Felzenszwalb algorithm and a Window-based CNN due to its robustness to image quality and object segmentation accuracy (r= 0.99). We integrated Mask R-CNN into a high-throughput pipeline to segment both maize cobs and rulers in images and perform an automated quantitative analysis of eight phenotypic traits, including diameter, length, ellipticity, asymmetry, aspect ratio and average RGB values for cob color. Statistical analysis identified key training parameters for efficient iterative model updating. We also show that a small number of 10-20 images is sufficient to update the initial Mask R-CNN model to process new types of cob images. To demonstrate an application of the pipeline we analyzed phenotypic variation in 19,867 maize cobs extracted from 3,449 images of 2,484 accessions from the maize genebank of Peru to identify phenotypically homogeneous and heterogeneous genebank accessions using multivariate clustering.

Conclusions

Single Mask R-CNN model and associated analysis pipeline are widely applicable tools for maize cob phenotyping in contexts like genebank phenomics or plant breeding.
The long-term effects of genomic selection: Response to selection, additive genetic variance and genetic architecture
Authors: Wientjes Yvonne C.J. , Bijma Piter , Calus Mario P.L. , Zwaan Bas J. , Vitezica Zulma G. , van den Heuvel Joost
Published: March 2021

Genomic selection has revolutionized genetic improvement in animals and plants, but little is known of its long term effects. Here we investigate the long-term effects of genomic selection on the change in the genetic architecture of traits over generations. We defined the genetic architecture as the subset, allele frequencies and statistical additive effects of causal loci. We simulated a livestock population under 50 generations of phenotypic, pedigree, or genomic selection for a single trait, controlled by either only additive, additive and dominance, or additive, dominance and epistatic effects. The simulated epistasis was based on yeast data. The observed change in genetic architecture over generations was similar for genomic and pedigree selection, and slightly smaller for phenotypic selection. Short-term response was highest with genomic selection, while long-term response was highest with phenotypic selection, especially when non-additive effects were present. This was mainly because the loss in genetic variance and in segregating loci was much greater with genomic selection. Compared to pedigree selection, genomic selection lost a similar amount of the genetic variance but maintained more segregating loci, which on average had lower minor allele frequencies. For all selection methods, the presence of epistasis limited the changes in allele frequency and the fixation of causal loci, and substantially changed the statistical additive effects over generations. Our results show that non-additive effects can have a substantial impact on the change in genetic architecture. Therefore, non-additive effects can substantially impact the accuracy and future genetic gain of genomic selection.
HIV-1 Vpr Induces Degradation of Nucleolar Protein CCDC137 as a Consequence of Cell Cycle Arrest
Authors: Martins Laura , DePaula-Silva Ana Beatriz , Planelles Vicente
Published: March 2021

Expression of HIV-1 accessory proteins Vif and Vpr results in G2/M cell cycle arrest by hijacking the host ubiquitin-proteasome system. Vif directs cell cycle arrest by targeting protein phosphatase 2, regulatory subunit B alpha (PP2AB56) for degradation. However, the ubiquitination target(s) of Vpr that is directly responsible for G2/M arrest has remained elusive. Recently, Vpr directed degradation of nucleolar protein coiled-coil domain containing 137 (CCDC137), also known as retinoic acid resistance factor (RaRF), has been implicated as the proximal event leading to G2/M cell cycle arrest. In this study we aimed to further investigate this finding. We confirm that CCDC137 is targeted for degradation in the presence of Vpr with a requirement for the CUL4ADDB1.DCAF1E3 ligase complex. However, degradation of CCDC137 is a general consequence, rather than a trigger, of G2/M arrest. Thus, whether induced by Vpr expression or pharmacologically via CDK1 inhibition, G2/M blockade results in degradation of CCDC137. Furthermore, siRNA-mediated depletion of CCDC137 failed to induce G2/M arrest.
VASP mediated actin dynamics activate and recruit a filopodia myosin
Authors: Arthur Ashley L. , Crawford Amy , Houdusse Anne , Titus Margaret A.
Published: March 2021

Filopodia are thin, actin-based structures that cells use to interact with their environments. Filopodia initiation requires a suite of conserved proteins but the mechanism remains poorly understood. The actin polymerase VASP and a MyTH-FERM (MF) myosin, DdMyo7 in amoeba, are essential for filopodia initiation. DdMyo7 is localized to dynamic regions of the actin-rich cortex. Analysis of VASP mutants and treatment of cells with anti-actin drugs shows that myosin recruitment and activation inDictyosteliumrequires localized VASP-dependent actin polymerization. Targeting of DdMyo7 to the cortex alone is not sufficient for filopodia initiation; VASP activity is also required. The actin regulator locally produces a cortical actin network that activates myosin and together they shape the actin network to promote extension of parallel bundles of actin during filopodia formation. This work reveals how filopodia initiation requires close collaboration between an actin binding protein, the state of the actin cytoskeleton and MF myosin activity.
Role of bacterial persistence in spatial population expansion
Authors: Patra Pintu , Klumpp Stefan
Published: March 2021

Bacterial persistence, tolerance to antibiotics via stochastic phenotype switching provides a survival strategy and a fitness advantage in temporally fluctuating environments. Here we study its possible benefit in spatially varying environments using a Fisher wave approach. We study the spatial expansion of a population with stochastic switching between two phenotypes in spatially homogeneous conditions and in the presence of an antibiotic barrier. Our analytical results show that the expansion speed in growth-supporting conditions depends on the fraction of persister cells at the leading edge of the population wave. The leading edge contains a small fraction of persister cells, keeping the effect on the expansion speed minimal. The fraction of persisters increases gradually in the interior of the wave. This persister pool benefits the population when it is stalled by an antibiotic environment. In that case, the presence of persister enables the population to spread deeper into the antibiotic region and to cross an antibiotic region more rapidly. The interplay of population dynamics at the interface separating the two environments and phenotype switching in the antibiotic region results in a optimal switching rate. Overall, our results show that stochastic switching can promote population expansion in the presence of antibiotic barriers or other stressful environments.
The role of vimentin-nuclear interactions in persistent cell motility through confined spaces
Authors: Gupta Sarthak , Patteson Alison E. , Schwarz J. M.
Published: March 2021

The ability of cells to move through small spaces depends on the mechanical properties of the cellular cytoskeleton and on nuclear deformability. In mammalian cells, the cytoskeleton is comprised of three interacting, semi-flexible polymer networks: actin, microtubules, and intermediate filaments (IF). Recent experiments of mouse embryonic fibroblasts with and without vimentin have shown that the IF vimentin plays a role in confined cell motility. We, therefore, develop a minimal model of cells moving through confined geometries that effectively includes all three types of cytoskeletal filaments with a cell consisting of an actomyosin cortex and a deformable cell nucleus and mechanical connections between the two cortices—the outer actomyosin one and the inner nuclear one. By decreasing the amount of vimentin, we find that the cell speed is typically faster for vimentin-null cells as compared to cells with vimentin. Vimentin-null cells also contain more deformed nuclei in confinement. Finally, vimentin affects nucleus positioning within the cell. By positing that as the nucleus position deviates further from the center of mass of the cell, microtubules become more oriented in a particular direction to enhance cell persistence or polarity, we show that vimentin-nulls are more persistent than vimentin-full cells. The enhanced persistence indicates that the vimentin-null cells are more subjugated by the confinement since their internal polarization mechanism that depends on cross-talk of the centrosome with the nucleus and other cytoskeletal connections is diminished. In other words, the vimentin-null cells rely more heavily on external cues. Our modeling results present a quantitative interpretation for recent experiments and have implications for understanding the role of vimentin in the epithelial-mesenchymal transition.
TheArabidopsisERF transcription factor ORA59 coordinates jasmonic acid- and ethylene-responsive gene expression to regulate plant immunity
Authors: Yang Young Nam , Kim Youngsung , Kim Hyeri , Kim Su Jin , Cho Kwang-Moon , Kim Yerin , Lee Dong Sook , Lee Myoung-Hoon , Kim Soo Young , Hong Jong Chan , Kwon Sun Jae , Choi Jungmin , Park Ohkmae K.
Published: March 2021

Jasmonic acid (JA) and ethylene (ET) signaling modulate plant defense against necrotrophic pathogens. These hormone pathways lead to transcriptional reprogramming, which is a major part of plant immunity and requires the roles of transcription factors. ET response factors are responsible for the transcriptional regulation of JA/ET-responsive defense genes, among which ORA59 functions as a key regulator of this process and has been implicated in the JA-ET crosstalk. Here, we identified the ERELEE4 as an ORA59-bindingcis-element, in addition to the well-characterized GCC box, demonstrating that ORA59 regulates JA/ET-responsive genes through direct binding to these elements in the gene promoters. Notably, ORA59 exhibited differential preference for the GCC box and ERELEE4, depending on whether ORA59 activation is achieved by JA and ET, respectively. Our results provide insights into how ORA59 can generate specific patterns of gene expression dynamics through JA and ET hormone pathways.