bluuebunny/crossref_metadata_2025 huggingface dataset:
Attenuation of blast waves from an intense explosion in dusty gases: a case study
Authors: Chadha Meera
Published: October 2022

An intense explosion in dusty gas is analyzed considering the Beirut ammonium nitrate explosion of 2020 as a case study. The data available from various sources for the Beirut explosion are used to determine the energy released and the possible reduction in damage radius if there were additional dust particles in the atmosphere. The relationship derived in our previous article (
Proc. R. Soc. A
476
, 2020) between the blast radius and the time of arrival of the shock seems quite accurate, and here the energy released by the explosion and the mass of trinitrotoluene (TNT) equivalent based on energy considerations and blast damage are estimated for dusty gases. These estimates depend on

Γ

, the ratio of specific heats of the dusty gas mixture. The hydrostatic overpressure and dynamic pressure are calculated from previous results by using the data available. The variation of the three dust parameters in the atmosphere, i.e. (i) mass concentration of dust particles

(

k
p

)

, (ii) specific heat ratio

(
β
)

, and (iii) density ratio

(
G
)
,

gives the estimated TNT equivalence as

≈

0.1 kt to 2.5 kt up to a distance of 500 m. Enhanced decay and reduced pressure is evident for dusty gases with appropriate dust parameters.
Humans trade off whole-body energy cost to avoid overburdening muscles while walking
Authors: McDonald Kirsty A. , Cusumano Joseph P. , Hieronymi Andrew , Rubenson Jonas
Published: October 2022

Metabolic cost minimization is thought to underscore the neural control of locomotion. Yet, avoiding high muscle activation, a cause of fatigue, often outperforms energy minimization in computational predictions of human gait. Discerning the relative importance of these criteria in human walking has proved elusive, in part, because they have not been empirically decoupled. Here, we explicitly decouple whole-body metabolic cost and ‘fatigue-like' muscle activation costs (estimated from electromyography) by pitting them against one another using two distinct gait tasks. When experiencing these competing costs, participants (
n
= 10) chose the task that avoided overburdening muscles (fatigue avoidance) at the expense of higher metabolic power (
p
< 0.05). Muscle volume-normalized activation more closely models energy use and was also minimized by the participants' decision (
p
< 0.05), demonstrating that muscle activation was, at best, an inaccurate signal for metabolic energy. Energy minimization was only observed when there was no adverse effect on muscle activation costs. By decoupling whole-body metabolic and muscle activation costs, we provide among the first empirical evidence of humans embracing non-energetic optimality in favour of a clearly defined neuromuscular objective. This finding indicates that local muscle fatigue and effort may well be key factors dictating human walking behaviour and its evolution.
The evolution of marsupial social organization
Authors: Qiu J. , Olivier C. A. , Jaeggi A. V. , Schradin C.
Published: October 2022

It is generally believed that marsupials are more primitive than placentals mammals and mainly solitary living, representing the ancestral form of social organization of all mammals. However, field studies have observed pair and group-living in marsupial species, but no comparative study about their social evolution was ever done. Here, we describe the results of primary literature research on marsupial social organization which indicates that most species can live in pairs or groups and many show intra-specific variation in social organization. Using Bayesian phylogenetic mixed-effects models with a weak phylogenetic signal of 0.18, we found that solitary living was the most likely ancestral form (35% posterior probability), but had high uncertainty, and the combined probability of a partly sociable marsupial ancestor (65%) should not be overlooked. For Australian marsupials, group-living species were less likely to be found in tropical rainforest, and species with a variable social organization were associated with low and unpredictable precipitation representing deserts. Our results suggest that modern marsupials are more sociable than previously believed and that there is no strong support that their ancestral state was strictly solitary living, such that the assumption of a solitary ancestral state of all mammals may also need reconsideration.
‘Selfish herders’ finish last in mobile animal groups
Authors: Sankey Daniel W. E.
Published: October 2022

Predation is a powerful selective pressure and probably a driver of why many animal species live in groups. One key explanation for the evolution of sociality is the ‘selfish herd' model, which describes how individuals who stay close to others effectively put neighbours between themselves and a predator to survive incoming attacks. This model is often illustrated with reference to herds of ungulates, schools of fish or flocks of birds. Yet in nature, when a predator strikes, herds are often found fleeing cohesively in the same direction, not jostling for position in the centre of the group. This paper highlights a critical assumption of the original model, namely that prey do not move in response to position of their predator. In this model, I relax this assumption and find that individuals who adopt ‘selfish herd' behaviour are often more likely to be captured, because they end up at the back of a fleeing herd. By contrast, individuals that adopt a rule of ‘neighbour to neighbour alignment' are able to avoid rearmost positions in a moving herd. Alignment is more successful than selfish herding across much of the parameter space, which may explain why highly aligned fleeing behaviour is commonly observed in nature.
Tree-ring evidence of ecological stress memory
Authors: Mu Yumei , Lyu Lixin , Li Yan , Fang Ouya
Published: October 2022

Plants experiencing stress could develop the ability to reshape their response toward present stress based on past stress experience, called ‘ecological stress memory’ (ESM), which is important for plant acclimation to repeated stresses. Although ESM has been largely reported, it remains unclear whether ESM could improve tree resistance to recurrent stress in subsequent decades. Here, we explore it from a tree-ring network of 1491 trees from 50 long-living juniper forests on the Tibetan Plateau. Through comparing performances of tree radial growth in past sequential growth stresses, we found that trees could obtain ESM under antecedent stresses and elevate resistance to subsequent stress after several years or even decades. Such positive effects of ESM are associated with post-stress recovery. Trees with slow recovery trajectories after antecedent stress show significantly improved resistance to subsequent stress, while trees with extremely fast post-stress recovery showed decreased resistance to subsequent stress. These results imply that temporary depressive tree radial growth after antecedent stress might be a trigger of long storage of ESM. Incorporating positive effects of ESM and relationship between ESM activation and post-stress recovery into future Earth system models could advance our capacity to predict forest dynamics and forest ecosystem stabilization under future stress conditions.
Acinetobacter amyesii sp. nov., widespread in the soil and water environment and animals
Authors: Nemec Alexandr , Radolfová-Křížová Lenka , Maixnerová Martina , Nemec Matěj , Shestivska Violetta , Španělová Petra , Kyselková Martina , Wilharm Gottfried , Higgins Paul G.
Published: October 2022

We studied a novel taxon of the genus

Acinetobacter

, which comprised six strains collected in Czechia, Germany, Indonesia and Turkey between 2015 and 2021. The organisms were isolated from environmental soil, water samples and cow faeces. Their genome sizes varied between 3.3 and 3.5 Mb, with a G+C content of 40.4–40.8 mol%. Based on genus-wide core genome analysis, the taxon formed a distinct clade, with

Acinetobacter gandensis

being the phylogenetically closest related species. The intrataxon genomic average nucleotide identity based on blast (ANIb) and digital DNA–DNA hybridization (dDDH) values reached 95.3–97.4% and 62.5–77.8 %, respectively, whereas its ANIb/dDDH values against the known

Acinetobacter

type strains were ≤82.7 %/≤25.7 %. Cluster analysis of whole-cell MALDI-TOF mass spectra corroborated the distinctness and cohesiveness of the taxon. The novel strains were non-glucose-oxidizing, non-haemolytic and non-proteolytic, growing at up to 37–41 °C but not at 44 °C and utilizing 8–10 of the 36 carbon sources tested. Growth on glutarate, tricarballylate and at 37 °C combined with the inability to assimilate 4-aminobutyrate and d-malate differentiated them from all validly named

Acinetobacter

species. The inspection of genome sequences in the NCBI database revealed the existence of numerous strains conspecific with this group, which were collected from pig faeces and environmental samples in China. We conclude that the taxon represents an ecologically and geographically widespread species, for which we propose the name Acinetobacter amyesii sp. nov., with ANC 5579T (= CCM 9242T=CCUG 76274T=CNCTC 8134T) as the type strain.
MAW - The Reproducible Metabolome Annotation Workflow for Untargeted Tandem Mass Spectrometry
Authors: Zulfiqar Mahnoor , Gadelha Luiz , Steinbeck Christoph , Sorokina Maria , Peters Kristian
Published: October 2022

Mapping the chemical space of compounds to chemical structures remains a challenge in metabolomics. Despite the advancements in untargeted liquid chromatography-mass spectrometry (LC-MS) to achieve a high-throughput profile of metabolites from complex biological resources, only a small fraction of these metabolites can be annotated with confidence. Many novel computational methods and tools have been developed to enable chemical structure annotation to known and unknown compounds such asin silicogenerated spectra and molecular networking. Here, we present an automated and reproducibleMetabolomeAnnotationWorkflow (MAW) for untargeted metabolomics data to further facilitate and automate the complex annotation by combining tandem mass spectrometry (MS2) input data pre-processing, spectral and compound database matching with computational classification, andin silicoannotation. MAW takes the LC-MS2spectra as input and generates a list of putative candidates from spectral and compound databases. The databases are integrated via the R package Spectra and the metabolite annotation tool SIRIUS as part of the R segment of the workflow (MAW-R). The final candidate selection is performed using the cheminformatics tool RDKit in the Python segment (MAW-Py). Furthermore, each feature is assigned a chemical structure and can be imported to a chemical structure similarity network. MAW is following the FAIR (Findable, Accessible, Interoperable, Reusable) principles and has been made available as the docker images, maw-r and mawpy. The source code and documentation are available on GitHub (https://github.com/zmahnoor14/MAW). The performance of MAW is evaluated on two case studies. MAW can improve candidate ranking by integrating spectral databases with annotation tools like SIRIUS which contributes to an efficient candidate selection procedure. The results from MAW are also reproducible and traceable, compliant with the FAIR guidelines. Taken together, MAW could greatly facilitate automated metabolite characterization in diverse fields such as clinical metabolomics and natural product discovery.
Small hand-designed convolutional neural networks outperform transfer learning in automated cell shape detection in confluent tissues
Authors: Combe L. , Durande M. , Delanoë-Ayari H. , Cochet-Escartin O.
Published: October 2022

Mechanical cues such as stresses and strains are now recognized as essential regulators in many biological processes such as cell division, gene expression or morphogenesis. Studying the interplay between these mechanical cues and biological responses requires experimental tools to measure these cues. In the context of large scale tissues, this can be achieved by segmenting individual cells to extract their shapes and deformations which in turn inform on their mechanical environment. Historically, this has been done by segmentation methods which are well known to be time consuming and error prone. In this context however, one doesn’t necessarily require a cell-level description and a coarse grained approach can be more efficient while using tools different than segmentation.

The advent of machine learning and deep neural networks has revolutionized the field of image analysis in recent years, including in biomedical research. With the democratization of these techniques, more and more researchers are trying to apply them to their own biological systems. In this paper, we tackle a problem of cell shape measurement thanks to a large annotated dataset. We develop simple CNNs which we thoroughly optimize in terms of architecture and complexity to question construction rules usually applied. We find that increasing the complexity of the networks rapidly no longer yields improvements in performance and that the number of kernels in each convolutional layer is the most important parameter to achieve good results. In addition, we compare our step-by-step approach with transfer learning and find that our simple, optimized CNNs give better predictions, are faster in training and analysis and don’t require more technical knowledge to be implemented. Overall, we offer a rational roadmap to develop optimized models and argue that we should limit the complexity of such models. We conclude by illustrating this strategy on a similar problem and dataset.
CoRegNet: Unraveling Gene Co-regulation Networks from Public RNA-Seq Repositories Using a Beta-Binomial Statistical Model
Authors: Wang Jiasheng , Wan Ying-Wooi , Al-Ouran Rami , Huang Meichen , Liu Zhandong
Published: October 2022

Millions of RNA sequencing samples have been deposited into public databases, providing a rich resource for biological research. These datasets encompass tens of thousands of experiments and offer comprehensive insights into human cellular regulation. However, a major challenge is how to integrate these experiments that acquired at different conditions. We propose a new statistical tool based on beta-binomial distributions that can construct robust gene co-regulation network (CoRegNet) across tens of thousands of experiments. Our analysis of over 12,000 experiments involving human tissues and cells shows that CoRegNet significantly outperforms existing gene co-expression-based methods. Although the majority of the genes are linearly co-regulated, we did discover an interesting set of genes that are non-linearly co-regulated; half of the time they change in the same direction and the other half they change in the opposite direction. Additionally, we identified a set of gene pairs that follows the Simpson’s paradox. By utilizing public domain data, CoRegNet offers a powerful approach for identifying functionally related gene pairs, thereby revealing new biological insights.
Phasic locus coeruleus activity enhances trace fear conditioning by increasing dopamine release in the hippocampus
Authors: Wilmot Jacob H. , Diniz Cassiano R.A.F. , Crestani Ana P. , Puhger Kyle , Roshgadol Jacob , Tian Lin , Wiltgen Brian J.
Published: October 2022

Locus coeruleus (LC) projections to the hippocampus play a critical role in learning and memory. However, the precise timing of LC-hippocampus communication during learning and which LC-derived neurotransmitters are important for memory formation in the hippocampus are currently unknown. Although the LC is typically thought to modulate neural activity via the release of norepinephrine, several recent studies have suggested that it may also release dopamine into the hippocampus and other cortical regions. In some cases, it appears that dopamine release from LC into the hippocampus may be more important for memory than norepinephrine. Here, we extend these data by characterizing the phasic responses of the LC and its projections to the dorsal hippocampus during trace fear conditioning. We find that the LC and its projections to the hippocampus respond to task-relevant stimuli and that amplifying these responses with optogenetic stimulation can enhance long-term memory formation. We also demonstrate that LC activity increases both norepinephrine and dopamine content in the dorsal hippocampus and that the timing of hippocampal dopamine release during trace fear conditioning is similar to the timing of LC activity. Finally, we show that hippocampal dopamine is important for trace fear memory formation, while norepinephrine is not.
HALO: Hierarchical Causal Modeling for Single Cell Multi-Omics Data
Authors: Mao Haiyi , Jia Minxue , Di Marissa , Valenzi Eleanor , Cai Xiaoyu Tracy , Singh Harinder , Lafyatis Robert , Zhang Kun , Benos Panagiotis
Published: October 2022

Though open chromatin may promote active transcription, gene expression responses may not be directly coordinated with changes in chromatin accessibility. Most existing methods for single-cell multi-omics data focus only on learning stationary and shared information among these modalities, overlooking modality-specific information delineating cellular states and dynamics resulting from causal relations among modalities. To account for this, the epigenome and transcriptome relationship can be characterized in relation to time as “coupled” (changing dependently) or “decoupled” (changing independently). We propose the framework HALO, which adopts a causal approach to model these temporal causal relations on two levels. On the representation level, HALO factorizes these two modalities into both coupled and decoupled latent representations, identifying the dynamic interplay between chromatin accessibility and transcription through temporal modulations in the latent space. On the individual gene level, HALO matches gene-peak pairs and characterizes changing dynamics between gene expression and local peaks with time. HALO reveals bipotency in a subset of AT2 cells that exhibit different decisions in lineage specification between systemic sclerosis (SSc) and normal conditions. We demonstrate that using coupled and decoupled information, HALO discovers analogous biological functions between modalities, distinguishes epigenetic factors for lineage specification, and identifies temporalcis-regulation interactions relevant to cellular differentiation and complex human diseases.
Oral Delivery of Kidney Targeting Nanotherapeutics for Polycystic Kidney Disease
Authors: Huang Yi , Wang Jonathan , Chin Deborah , Mancino Valeria , Pham Jessica , Li Hui , Jiang Kairui , Ram Aparna , Poon Christopher , Ho Pei-Yin , Gyarmati Georgina , Peti-Peterdi János , Hallows Kenneth R. , Chung Eun Ji
Published: October 2022

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. Although a variety of candidate drugs have been found to modulate cystogenesis in animal studies, results from clinical trials have often been unfavorable due to low renal bioavailability and drug-induced side effects. To mitigate this, nanoparticles can be designed to deliver drugs directly to the target organ to increase effective dose while limiting off-target side effects. Unfortunately, there are no kidney-targeted nanomedicines clinically available, and most of the existing FDA-approved nanoparticles require intravenous administration which is not suitable for ADPKD that require lifelong therapy. To address this, we developed an oral drug delivery system using chitosan nanoparticles (CS-NP) that were loaded with peptide amphiphile micelles carrying metformin (met), an ADPKD drug candidate (CS-KM-met). We previously showed that CS-NP can shield met in the gastrointestinal tract; thus, we hypothesized that CS-NP could also enhance bioavailability of kidney-targeting micelles (KMs) upon oral administration. Specifically, we measured the loading capacity of KM-met in CS-NP, evaluated the stability of CS-KM-met under acidic conditions that mimic the gastric environment, and measuredin vitrotherapeutic effects. Upon oral administration in C57BL/6J mice, CS-KM-met showed significantly greater bioavailability and accumulation in the kidneys as compared to KM-met without CS-NP or free met for up to 24 hours. As such, CS-KM-met showed enhanced therapeutic efficacyin vivoupon oral administration in PKD mice (Pkd1fl/fl; Pax8-rtTA; Tet-O-Cre) compared to KM-met only. Herein, we demonstrate the potential of an oral delivery nanoformulation for the treatment of chronic kidney diseases such as ADPKD for the first time.
A ten-year community reporting database reveals rising coyote boldness and associated human concern in Edmonton, Canada
Authors: Farr Jonathan J. , Pruden Matthew J. , Glover Robin , Murray Maureen H. , Sugden Scott A. , Harshaw Howard W. , Cassady St. Clair Colleen
Published: October 2022

In cities throughout North America, sightings of coyotes (Canis latrans) have become common. Reports of human-coyote conflict are also rising, as is the public demand for proactive management to prevent negative human-coyote interactions. Effective and proactive management can be informed by the direct observations of community members, who can report their interactions with coyotes and describe the location, time, and context that led to their interactions. To assess the predictors of human-coyote conflict, we used a web-based reporting system to collect 9,134 community-supplied reports of coyotes in Edmonton, Canada, between January 2012 and December 2021. We used a standardized ordinal ranking system to score each report on two indicators of human-coyote conflict: coyote boldness, based on the reported coyote behaviour, and human perceptions about coyotes, determined from the emotions expressed by reporters. We assigned greater conflict scores to behaviours where coyotes followed, approached, charged or contacted pets or people, and to perceptions where reporters expressed fear, worry, concern, discomfort or alarm. Using ordered logistic regression and chi-square tests, we compared conflict scores for each response variable to spatial, temporal and contextual covariates. Our analysis showed that coyotes were bolder in less developed open areas and during the pup rearing season, but human perceptions were most negative in residential areas and during the dispersal season. Reports that mentioned dogs or cats were more likely to describe bolder coyote behaviour, and those that mentioned pets or children had more negative perceptions about coyotes. Coyote boldness and human perceptions both indicated rising human-coyote conflict in Edmonton over the 10 years of reporting.
Development of a clot-adhesive coating to improve the performance of thrombectomy devices
Authors: Skarbek Charles , Anagnostakou Vaia , Propocio Emanuele , Epshtein Mark , Raskett Christopher M. , Romagnoli Romeo , Iviglia Giorgio , Morra Marco , Antonucci Marta , Nicoletti Antonino , Caligiuri Giuseppina , Gounis Matthew J.
Published: October 2022

Background

The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices.

Objective

Evaluate the potential of DNA reacting surface toaid the retention of the main clot as well as of its small fragments within the thrombectomy deviceand improve the potential of MT procedures.

Methods

Device-suitable alloy experimental samples were coated with 15 different compounds and contacted with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus flowing blood elements,in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests aiming to studying clot retrieval and distal emboli release, concomitant with contact aspiration, using an M1 occlusion model.

Results

Binding properties of samples coated with all compounds were increased for DNA (≈ 3-fold) and decreased (≈ 5-fold) for blood elements, essentially platelet, as compared to the bare alloy samples,in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced secondary embolism during experimental recanalization of occluded artery 3D model by thrombectomy procedures.

Conclusion

Our results suggest that device coating with DNA-binding compounds can considerably improve the outcome of MT procedures in stroke patients.

What is already known on this topic –New mechanical thrombectomy device are being improved on the conformation and shape to increase the interaction clot on the physical point of view. However, none interact specifically with the structure or composition of the clot.

What this study adds –The design of a chemical surface modification of the device opens the way for a specific targeting tool to increase the interaction with the clot on the molecular level.

How this study might affect research, practice or policy –This new surface modification, which can be applied to all commercially available mechanical thrombectomy devices, leads to a decrease in secondary embolization which cannot and is not monitored during the procedure and responsible for new territory damage.
Efficient minimizer orders for large values ofkusing minimum decycling sets
Authors: Pellow David , Pu Lianrong , Ekim Baris , Kotlar Lior , Berger Bonnie , Shamir Ron , Orenstein Yaron
Published: October 2022

Minimizers are ubiquitously used in data structures and algorithms for efficient searching, mapping, and indexing of high-throughput DNA sequencing data. Minimizer schemes select a minimumk-mer in everyL-long sub-sequence of the target sequence, where minimality is with respect to a predefinedk-mer order. Commonly used minimizer orders select morek-mers than necessary and therefore provide limited improvement in runtime and memory usage of downstream analysis tasks. The recently introduced universalk-mer hitting sets produce minimizer orders with fewer selectedk-mers. Unfortunately, generating compact universalk-mer hitting sets is currently infeasible fork> 13, and thus cannot help in the many applications that require minimizer orders for largerk.

Here, we close the gap of efficient minimizer orders for large values ofkby introducingdecycling-set-based minimizer orders, new orders based on minimum decycling sets. We show that in practice these new minimizer orders select a number ofk-mers comparable to that of minimizer orders based on universalk-mer hitting sets, and can also scale up to largerk. Furthermore, we developed a method that computes the minimizers in a sequence on the fly without keeping thek-mers of a decycling set in memory. This enables the use of these minimizer orders for any value ofk. We expect the new orders to improve the runtime and memory usage of algorithms and data structures in high-throughput DNA sequencing analysis.
High-resolution methylome analysis in the clonalPopulus nigracv. ‘Italica’ reveals environmentally sensitive hotspots and drought-responsive TE superfamilies
Authors: Peña-Ponton C. , Diez-Rodriguez B. , Perez-Bello P. , Becker C. , McIntyre L.M. , Van der Putten W. , De Paoli E. , Heer K. , Opgenoorth L. , Verhoeven KJF.
Published: October 2022

ABSTRACT/SUMMARY

DNA methylation is environment-sensitive and can mediate plant stress responses. In long-lived trees, changing environments might cumulatively shape the methylome landscape over their lifetime. However, because high-resolution methylome studies usually focus on single environments, it remains unclear to what extent the methylation responses are generic or stress-specific, and how this relates to their long-term stability.

Here, we studied the methylome plasticity of a single poplar genotype,Populus nigracv. ‘Italica’. Adult poplar trees with diverse environmental histories were clonally propagated, and the ramets exposed to experimental cold, heat, drought, herbivory, rust infection and salicylic acid treatments. Then, we identified and compared stress-induced vs. naturally occurring DNA methylation changes using whole genome bisulfite sequencing data.

Methylation changes mainly targeted transposable elements and when occurring in CG/CHG contexts, the same regions were often affected by multiple stresses, indicating a generic response. Drought triggered a unique CHH hypermethylation response in transposable elements, affecting entire superfamilies and often occurring near drought-responsive genes. Stress-induced methylation variation in CG/CHG contexts showed striking overlap with methylation differences observed between trees from distinct geographical locations.

Altogether, our results indicate that generic methylome stress responses can persist as epialleles in nature while some environments trigger more transient but large and specific responses, with possible functional consequences.
Spatio-temporal modeling of high-throughput multi-spectral aerial images improves agronomic trait genomic prediction in hybrid maize
Authors: Morales Nicolas , Anche Mahlet T. , Kaczmar Nicholas S. , Lepak Nicholas , Ni Pengzun , Romay Maria Cinta , Santantonio Nicholas , Buckler Edward S. , Gore Michael A. , Mueller Lukas A. , Robbins Kelly R.
Published: October 2022

Design randomizations and spatial corrections have increased understanding of genotypic, spatial, and residual effects in field experiments, but precisely measuring spatial heterogeneity in the field remains a challenge. To this end, our study evaluated approaches to improve spatial modeling using high-throughput phenotypes (HTP) via unoccupied aerial vehicle (UAV) imagery. The normalized difference vegetation index (NDVI) was measured by a multi-spectral MicaSense camera and ImageBreed. Contrasting to baseline agronomic trait spatial correction and a baseline multi-trait model, a two-stage approach that quantified NDVI local environmental effects (NLEE) was proposed. Firstly, NLEE were separated from additive genetic effects over the growing season using two-dimensional spline (2DSpl), separable autoregressive (AR1) models, or random regression models (RR). Secondly, the NLEE were leveraged within agronomic trait genomic best linear unbiased prediction (GBLUP) either modeling an empirical covariance for random effects, or by modeling fixed effects as an average of NLEE across time or split among three growth phases. Modeling approaches were tested using simulation data and Genomes-to-Fields (G2F) hybrid maize (Zea maysL.) field experiments in 2015, 2017, 2019, and 2020 for grain yield, grain moisture, and ear height. The two-stage approach improved heritability, model fit, and genotypic effect estimation compared to all baseline models. Electrical conductance and elevation from a 2019 soil survey significantly improved model fit, while 2DSpl NLEE were most correlated to the soil parameters and grain yield 2DSpl effects. Simulation of field effects demonstrated improved specificity for RR models. In summary, NLEE increased experimental accuracy and understanding of field spatio-temporal heterogeneity.
Inhibition of GCN5 decreases skeletal muscle fat metabolism during high fat diet feeding
Authors: Green Alexander E. , Perras Brayden L. , Zhang Hongbo , Katsyuba Elena , Haboush Alaa , Nyarko Kwadjo M. , Pandey Dheeraj K. , Nik-Akhtar Abolfazl , Ryu Dongryeol , Auwerx Johan , Menzies Keir J.
Published: October 2022

Introduction

GCN5 (Kat2a) is a lysine acetyl transferase capable of acetylating and inhibiting PGC-1α activity. As such, it is described as a negative regulator of PGC-1α and subsequently restricts mitochondrial content. However, elimination of GCN5 in skeletal muscle does not increase mitochondrial content or alter lipid metabolism under normal metabolic conditions. GCN5 levels increase with high-fat diet (HFD) feeding in rodents. Additionally, the GCN5 homolog, PCAF, has previously been shown to also acetylate and inhibit PGC-1α and therefore may possibly compensate for loss of GCN5.

Objective

The objective of this study was to examine if with HFD feeding that elimination of GCN5 (Kat2agene) from skeletal muscle would elicit improvements in mitochondrial and metabolic markers.

Methods

Skeletal muscle specific GCN5 knockouts (Gcn5 skm-/-) were fed an HFD. Body composition, cardio-metabolic and physical fitness outcomes were monitored. Additionally, cultured myotubes were treated with a pan-GCN5/PCAF inhibitor and examined for changes in mitochondrial markers.

Results

Elimination of skeletal muscle GCN5 did not alter body composition, tissue masses, energy intake, or energy expenditure measurements of mice fed an HFD. Furthermore, whole body glucose homeostasis and cardiac measurements were not altered. There were few differences in lipid metabolism genes, relatively more glucose oxidation versusGcn5 skm+/+(wildtype) mice, and a reduction inPdk4expression. Exercise capacity and mitochondrial content levels were not altered inGcn5 skm-/-mice. Further, elimination of GCN5 in skeletal muscle increasedKat2b(PCAF) mRNA expression; however, inhibition of GCN5/PCAF bromodomains in cultured myotubes did not increase oxidative metabolism genes and decreased expression of some mitochondrial genes andPdk4mRNA.

Conclusions

Neither elimination of GCN5, nor simultaneous inhibition of GCN5 and its homolog PCAF improved skeletal muscle mitochondrial content under normal or HFD-fed conditions. Despite this, GCN5 may play a role in regulating macronutrient preference by regulatingPdk4content. Thus, HFD/macronutrient excess revealed novel roles of GCN5 in skeletal muscle.

Highlights

– Skeletal muscle specific elimination ofGcn5/Kat2adecreases fat oxidation without 1) preventing high-fat diet induced weight gain, 2) improving whole body glucose handling, or 3) improving skeletal muscle mitochondrial content.

– Inhibition of the GCN5 and PCAF bromodomains andGcn5ablation decreases expression ofPdk4.

– Expression ofKat2bincreases withGcn5elimination in skeletal muscle.

– Inhibition of the GCN5 and PCAF bromodomains do not result in increased skeletal muscle mitochondrial content.
Sex differences in pain: Spinal cord injury in female and male mice elicits behaviors related to neuropathic pain
Authors: Lee Sydney E. , Greenough Emily K. , Oancea Paul , Scheinfeld Ashley R. , Douglas Apsaline M. , Gaudet Andrew D.
Published: October 2022

Spinal cord injury (SCI) in humans frequently causes intractable chronic pain. Females are susceptible to worsened pain compared to males, and females may show higher pain prevalence after SCI. Despite this difference in clinical prevalence of SCI pain, few preclinical studies have systematically studied in rodents sex differences in SCI-elicited pain-related behaviors. Here, we leverage data from a large cohort of mice to test whether contusion SCI consistently causes pain symptoms in mice, and to establish whether female (vs. male) mice display heightened hypersensitivity after SCI. Mechanical and heat sensory thresholds were assessed using the von Frey test and Hargreaves test, respectively. In an initial experiment, female mice receiving moderate 60 kDyn SCI or moderate-to-severe 75 kDyn SCI at T9 both exhibited mechanical and heat pain symptoms compared to sham controls. 75 kDyn SCI caused excess motor deficits that confounded defining pain sensitivity at acute times, so the moderate SCI force was used for subsequent experiments. Next, adult female and male C57BL6/J mice received sham surgery or T9 moderate contusion SCI. Comparing female to male mice after SCI, we reveal that mice of both sexes displayed mechanical and heat hypersensitivity compared to sham controls, from acute-to-chronic post-injury times. Females had amplified SCI-elicited hypersensitivity compared to males. Our data suggest that thoracic contusion SCI elicits consistent and persistent pain-associated symptoms, which are more intense in female vs. male mice. These results have important implications for uncovering sex-specific mechanisms and therapeutic targets to ameliorate neuropathic pain after SCI.
Comparative genome analysis ofEnterococcus cecorumreveals intercontinental spread of a lineage of clinical poultry isolates
Authors: Laurentie Jeanne , Loux Valentin , Hennequet-Antier Christelle , Chambellon Emilie , Deschamps Julien , Trotereau Angélina , Furlan Sylviane , Darrigo Claire , Kempf Florent , Lao Julie , Milhes Marine , Roques Céline , Quinquis Benoit , Vandecasteele Céline , Boyer Roxane , Bouchez Olivier , Repoila Francis , Le Guennec Jean , Chiapello Hélène , Briandet Romain , Helloin Emmanuelle , Schouler Catherine , Kempf Isabelle , Serror Pascale
Published: October 2022

Enterococcus cecorumis an emerging pathogen responsible for osteomyelitis, spondylitis, and femoral head necrosis causing animal suffering, mortality, and requiring antimicrobial use in poultry. Paradoxically,E. cecorumis a common inhabitant of the intestinal microbiota of adult chickens. Despite evidence suggesting the existence of clones with pathogenic potential, the genetic and phenotypic relatedness of disease-associated isolates remains little investigated. Here, we sequenced and analyzed the genomes and characterized the phenotypes of more than 100 isolates, the majority of which were collected over the last ten years in 16 French broiler farms. Comparative genomics, genome-wide association study, and measured susceptibility to serum, biofilm forming capacity, and adhesion to chicken type II collagen were used to identify features associated with clinical isolates. We found that none of the tested phenotypes could discriminate origin of the isolates or phylogenetic group. Instead, we found that most clinical isolates are grouped phylogenetically and our analyses selected six genes that discriminate 94% of isolates associated with disease from those that are not. Analysis of the resistome and the mobilome revealed that multidrug-resistant clones ofE. cecorumcluster in few clades and that integrative conjugative elements and genomic islands are the main carriers of antimicrobial resistance. This comprehensive genomic analysis shows that disease-associated clones ofE. cecorumbelong mainly to one phylogenetic clade.

IMPORTANCE

Enterococcus cecorumis an important pathogen in poultry worldwide. It causes a number of locomotor disorders and septicemia, particularly in fast-growing broilers. Animal suffering, antimicrobial use, and associated economic losses require a better understanding of disease-associatedE. cecorumisolates. To address this need, we performed whole genome sequencing and analysis of a large collection of isolates responsible for outbreaks in France. By providing the first dataset on the genetic diversity and resistome ofE. cecorumstrains circulating in France, we pinpoint an epidemic lineage probably also circulating elsewhere and which should be targeted preferentially by preventive strategies in order to reduce the burden ofE. cecorum-related diseases.
Correcting batch effects in large-scale multiomic studies using a reference-material-based ratio method
Authors: Yu Ying , Zhang Naixin , Mai Yuanbang , Chen Qiaochu , Cao Zehui , Chen Qingwang , Liu Yaqing , Ren Luyao , Hou Wanwan , Yang Jingcheng , Hong Huixiao , Xu Joshua , Tong Weida , Shi Leming , Zheng Yuanting
Published: October 2022

Batch effects are notorious technical variations that are common in multiomic data and may result in misleading outcomes. With the era of big data, tackling batch effects in multiomic integration is urgently needed. As part of the Quartet Project for quality control and data integration of multiomic profiling, we comprehensively assess the performances of seven batch-effect correction algorithms (BECAs) for mitigating the negative impact of batch effects in multiomic datasets, including transcriptomics, proteomics, and metabolomics. Performances are evaluated based on accuracy of identifying differentially expressed features, robustness of predictive models, and the ability of accurately clustering cross-batch samples into their biological sample groups. Ratio-based method is more effective and widely applicable than others, especially in cases when batch effects are highly confounded with biological factors of interests. We further provide practical guidelines for the implementation of ratio-based method using universal reference materials profiled with study samples. Our findings show the promise for eliminating batch effects and enhancing data integration in increasingly large-scale, cross-batch multiomic studies.
Neural activity in human eyeblink conditioning: an optically pumped magnetometer-based MEG study
Authors: Lin Chin-Hsuan Sophie , Tierney Tim M , Mellor Stephanie , O’Neill George C , Bestmann Sven , Barnes Gareth R , Miall R Chris
Published: October 2022

There is a profound lack of electrophysiological data from the cerebellum in humans, as compared to animals, because the pervading perception is that it is difficult to record human cerebellar activity non-invasively using magnetoencephalography (MEG) or electroencephalography (EEG). We used on-scalp MEG based on optically pumped magnetometers (OP-MEG) to detect learning related cerebellar signals in a classical eyeblink conditioning paradigm. In four healthy human adults, we observed unconditioned stimulus-related evoked responses locating in the cerebellum. These evoked responses diminished during the acquisition of conditioned responses, which corresponds with previous observed changes of Purkinje cell activities in animals. We also observed evoked responses immediately before conditioned blinks in 3 out of 4 participants, which were also located in the cerebellum. We discuss the potential nature of these cerebellar evoked responses and future applications of OP-MEG to the studies of human cerebellar physiology.
Next-generation ABACUS biosensors reveal cellular ABA dynamics driving root growth at low aerial humidity
Authors: Rowe James , Grangé-Guermente Mathieu , Exposito-Rodriguez Marino , Wimalasekera Rinukshi , Lenz Martin , Shetty Kartika , Cutler Sean R. , Jones Alexander M.
Published: October 2022

The plant hormone abscisic acid (ABA) accumulates under abiotic stress to recast water relations and development. To overcome a lack of high-resolution, sensitive reporters, we developed ABACUS2s, next-generation FRET biosensors for ABA with high affinity, signal-to-noise ratio and orthogonality, that reveal endogenous ABA patterns in Arabidopsis thaliana. We mapped stress-induced ABA dynamics in high-resolution to reveal the cellular basis for local and systemic ABA functions. At reduced foliar humidity, roots cells accumulated ABA in the elongation zone, the site of phloem transported ABA unloading. Phloem ABA and root ABA signalling were both essential to maintain root growth at low humidity. ABA coordinates a robust system to maintain root growth in response to foliar stresses, enabling plants to maintain foraging of deeper soil for water uptake
DANCE: A Deep Learning Library and Benchmark Platform for Single-Cell Analysis
Authors: Ding Jiayuan , Wen Hongzhi , Tang Wenzhuo , Liu Renming , Li Zhaoheng , Venegas Julian , Su Runze , Molho Dylan , Jin Wei , Zuo Wangyang , Wang Yixin , Yang Robert , Xie Yuying , Tang Jiliang
Published: October 2022

In the realm of single-cell analysis, computational approaches have brought an increasing number of fantastic prospects for innovation and invention. Meanwhile, it also presents enormous hurdles to reproducing the results of these models due to their diversity and complexity. In addition, the lack of gold-standard benchmark datasets, metrics, and implementations prevents systematic evaluations and fair comparisons of available methods. Thus, we introduce the DANCE platform, the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts (e.g., only one command line). In addition, DANCE provides an ecosystem of deep learning architectures and tools for researchers to develop their own models conveniently. The goal of DANCE is to accelerate the development of deep learning models with complete validation and facilitate the overall advancement of single-cell analysis research. DANCE is an open-source python package that welcomes all kinds of contributions. All resources are integrated and available athttps://omicsml.ai/.
Elevated oxidative phosphorylation is critical for immune cell activation by polyethylene wear particles
Authors: Maduka Chima V. , Kuhnert Maxwell M. , Habeeb Oluwatosin M. , Tundo Anthony , Makela Ashley V. , Goodman Stuart B. , Contag Christopher H.
Published: October 2022

Chronic inflammation is a major concern after total joint replacements (TJRs), as it is associated with bone loss, limited bone-implant integration (osseointegration), implant loosening and failure. Inflammation around implants could be directed away from adverse outcomes and toward enhanced osseointegration and improved surgical outcome. Activated macrophages exposed to polyethylene particles play a dominant inflammatory role, and exhibit elevated mitochondrial oxidative phosphorylation (OXPHOS) whose role is unclear. By probing the contribution of the electron transport chain (ETC), we show that increased oxygen consumption does not contribute to bioenergetic (ATP) levels in fibroblasts and primary bone marrow-derived macrophages activated by polyethylene particles. Rather, it generates reactive oxygen species (ROS) at complex I by increasing mitochondrial membrane potential in macrophages. Inhibition of OXPHOS in a dosedependent manner without affecting glycolysis was accomplished by targeting complex I of the ETC using either rotenone or metformin. Metformin decreased mitochondrial ROS and, subsequently, expression of proinflammatory cytokines, including IL-1β, IL-6 and MCP-1 but not TNF-a in macrophages. These results highlight the contribution of mitochondrial bioenergetics to activation of immune cells by polyethylene wear particles, offering new opportunities to modulate macrophage states toward desired clinical outcomes.