bluuebunny/crossref_metadata_2025_split huggingface dataset:
Musculotendon Parameters in Lower Limb Models: Simplifications, Uncertainties, and Muscle Force Estimation Sensitivity
Authors: Chen Ziyu , Franklin David W. 
Published: November 2022

AbstractObjectiveMusculotendon parameters are key factors in the Hill-type muscle contraction dynamics, determining the muscle force estimation accuracy of a musculoskeletal model. Their values are mostly derived from muscle architecture datasets, whose emergence has been a major impetus for model development. However, it is often not clear if such parameter update indeed improves simulation accuracy. Our goal is to explain to model users in which way and how accurate these parameters are derived, and to what extent errors in parameter values might influence force estimation.MethodsWe examine in detail the derivation of musculotendon parameters in six muscle architecture datasets and four prominent OpenSim models of the lower limb, and then identify simplifications which could add uncertainties to the derived parameter values. Finally, we analyze the sensitivity of muscle force estimation to these parameters both numerically and analytically.ResultsNine typical simplifications in parameter derivation are identified. Partial derivatives of the Hill-type contraction dynamics are derived. Tendon slack length is determined as the musculotendon parameter that muscle force estimation is most sensitive to, whereas pennation angle is the least impactful.ConclusionAnatomical measurements alone are not enough to calibrate musculotendon parameters, and the improvement on muscle force estimation accuracy will be limited if the source muscle architecture datasets are the only main update.SignificanceModel users may check if a dataset or model is free of concerning factors for their research or application requirements. The derived partial derivatives may be used as gradients for musculotendon parameter calibration. For model development, we demonstrate that it is more promising to focus on other model parameters or components and seek alternative strategies to further increase simulation accuracy.
Identification of key residues of the DNA glycosylase OGG1 controlling efficient DNA scanning and recruitment to oxidized bases in living cells
Authors: D’Augustin Ostiane , Gaudon Virginie , Siberchicot Capucine , Smith Rebecca , Chapuis Catherine , Depagne Jordane , Veaute Xavier , Busso Didier , Di Guilmi Anne-Marie , Castaing Bertrand , Radicella J. Pablo , Campalans Anna , Huet Sébastien 
Published: November 2022

ABSTRACTThe DNA-glycosylase OGG1 oversees the detection and clearance of the 7,8-dihydro-8-oxoguanine (8-oxoG), which is the most frequent form of oxidized base in the genome. This lesion is deeply buried within the double-helix and its detection requires careful inspection of the bases by OGG1 via a mechanism that remains only partially understood. By analyzing OGG1 dynamics in the nucleus of living human cells, we demonstrate that the glycosylase constantly scans the DNA by rapidly alternating between diffusion within the nucleoplasm and short transits on the DNA. This scanning process, that we find to be tightly regulated by the conserved residue G245, is crucial for the rapid recruitment of OGG1 at oxidative lesions induced by laser micro-irradiation. Furthermore, we show that residues Y203, N149 and N150, while being all involved in early stages of 8-oxoG probing by OGG1 based on previous structural data, differentially regulate the scanning of the DNA and recruitment to oxidative lesions.
Molecular Machines Stimulate Intercellular Calcium Waves and Cause Muscle Contraction
Authors: Beckham Jacob L. , van Venrooy Alexis R. , Kim Soonyoung , Li Gang , Li Bowen , Duret Guillaume , Arnold Dallin , Zhao Xuan , Santos Ana L. , Chaudhry Gautam , Robinson Jacob T. , Tour James M. 
Published: November 2022

AbstractIntercellular calcium waves (ICW) are complex signaling phenomena that control many essential biological activities, including smooth muscle contraction, vesicle secretion, gene expression, and changes in neuronal excitability. Accordingly, the remote stimulation of ICW may result in versatile new biomodulation and therapeutic strategies. Here, we demonstrate that light-activated molecular machines (MM), molecules that rotate and perform mechanical work on the molecular scale, can remotely stimulate ICW. Live-cell calcium tracking and pharmacological experiments reveal that MM-induced ICW are driven by the activation of inositol triphosphate (IP3) mediated signaling pathways by unidirectional, fast-rotating MM. We then demonstrated that MM-induced ICW can be used to control muscle contractionin vitroin cardiomyocytes and animal behaviorin vivoinHydra vulgaris. Consequentially, this work demonstrates a new strategy for the direct control of cell signaling and downstream biological function using molecular-scale devices.
SYRINGAE: A web-based application forPseudomonas syringaeisolate characterization
Authors: Fautt Chad , Couradeau Estelle , Hockett Kevin L. 
Published: November 2022

AbstractThePseudomonas syringaespecies complex (PSSC) is a diverse group of plant pathogens with a collective host range encompassing almost every food crop grown throughout the world. As a threat to global food security, rapid detection and characterization of epidemic and emerging pathogenic lineages is essential. However, phylogenetic identification and prediction of virulence is often complicated by an unclarified taxonomy and the diversity of virulence factor repertoires carried by PSSC isolates. To address these issues, we have built SYRINGAE (www.syringae.org), a web-based phylogenetic placement and functional inference pipeline for PSSC. SYRINGAE contains a comprehensive phylogeny of 2,161 quality-checked genome assemblies annotated with 120 virulence genes. From this dataset, naïve Baye classification models trained from life identification numbers (LINs) and common marker gene sequences can be used for accurate identification of isolates. SYRINGAE efficiently articulates taxonomical and functional data generated over the last several decades on PSSC and constitutes a unique tool tailored towards the rapid characterization of PSSC emerging strains of concern.
A peptide-centric quantitative proteomics dataset for the phenotypic assessment of Alzheimer’s disease
Authors: Merrihew Gennifer E. , Park Jea , Plubell Deanna , Searle Brian C. , Keene C. Dirk , Larson Eric B. , Bateman Randall , Perrin Richard J. , Chhatwal Jasmeer P. , Farlow Martin R. , McLean Catriona A. , Ghetti Bernardino , Newell Kathy L. , Frosch Matthew P. , Montine Thomas J. , MacCoss Michael J. 
Published: November 2022

AbstractAlzheimer’s disease (AD) is a looming public health disaster with limited interventions. Alzheimer’s is a complex disease that can present with or without causative mutations and can be accompanied by a range of age-related comorbidities. This diverse presentation makes it difficult to study molecular changes specific to AD. To better understand the molecular signatures of disease we constructed a unique human brain sample cohort inclusive of autosomal dominant AD dementia (ADD), sporadic ADD, and those without dementia but with high AD histopathologic burden, and cognitively normal individuals with no/minimal AD histopathologic burden. All samples are clinically well characterized, and brain tissue was preserved postmortem by rapid autopsy. Samples from four brain regions were processed and analyzed by data-independent acquisition LC-MS/MS. Here we present a high-quality quantitative dataset at the peptide and protein level for each brain region. Multiple internal and external control strategies were included in this experiment to ensure data quality. All data are deposited in the ProteomeXchange repositories and available from each step of our processing.
How bumblebees coordinate path integration and body orientation at the start of their first learning flight
Authors: Collett TS , Robert T , Frasnelli E , Philippides A. , de Ibarra N Hempel 
Published: November 2022

AbstractThe start of a bumblebee’s first learning flight from its nest provides an opportunity to examine the bee’s learning behaviour on its initial view of the nest’s unfamiliar surroundings. Bumblebees like many other ants, bees and wasps learn views of their nest surroundings while facing their nest. A bumblebee’s first fixation of the nest is a coordinated manoeuvre in which the insect faces the nest with its body oriented towards a particular visual feature within its surroundings. The manoeuvre’s utility is that during return flights after foraging bees, when close to the nest, adopt the same preferred body-orientation (Hempel de Ibarra et al., 2009; Robert et al., 2018). A translational scan oriented orthogonally to the bee’s body-orientation helps the bee reach the preferred conjunction of nest-fixation and body-orientation.How does a bee, unacquainted with its surroundings, know when it is facing its nest? The details of nest-fixation argue that, like desert ants (Fleischmann et al., 2018), the bee relies on path integration. Path integration gives bees continuously updated information about the current direction of their nest and enables them to fixate the nest when the body points in the appropriate direction. We relate the three components of the coordinated manoeuvre to events in the central complex, noting that nest fixation is in egocentric coordinates, whereas body orientation and flight direction within the visual surroundings of the nest are in geocentric coordinates.
Subcytoplasmic location of translation controls protein output
Authors: Horste Ellen L. , Fansler Mervin M. , Cai Ting , Chen Xiuzhen , Mitschka Sibylle , Zhen Gang , Lee Flora C. Y. , Ule Jernej , Mayr Christine 
Published: November 2022

SummaryThe cytoplasm is highly compartmentalized, but the extent and consequences of subcytopIasmic mRNA localization in non-polarized cells are largely unknown. We determined mRNA enrichment in TIS granules (TGs) and the rough endopIasmic reticuIum (ER) through particle sorting and isolated cytosolic mRNAs by digitonin extraction. When focusing on non-membrane protein-encoding mRNAs, we observed that 52% have a biased transcript distribution across these compartments. Compartment enrichment is determined by a combinatorial code based on mRNA length, exon length, and 3′UTR-bound RNA-binding proteins. Compartment-biased mRNAs differ in the functional classes of their encoded proteins: TG-enriched mRNAs encode low-abundance proteins with strong enrichment of transcription factors, whereas ER-enriched mRNAs encode large and highly expressed proteins. Compartment localization is an important determinant of mRNA and protein abundance, which is supported by reporter experiments showing that redirecting cytosolic mRNAs to the ER increases their protein expression. In summary, the cytoplasm is functionally compartmentaIized by local translation environments.
Regulatory fine-tuning and horizontal gene transfer stabilize mobile colistin resistance
Authors: Ogunlana Lois , Shaw Liam , Kaur Divjot , Jangir Pramod , Walsh Timothy , Uphoff Stephan , MacLean R.C. 
Published: November 2022

AbstractAntibiotic resistance tends to carry fitness costs, making it difficult to understand how resistance can be stably maintained in pathogen populations over the long-term. Here, we investigate this problem in the context ofmcr-1, a fitness-costly gene that confers resistance to the ‘last-resort’ antibiotic, colistin. Here we show that regulatory evolution has fine-tuned the expression ofmcr-1, allowingE. colito reduce the cost ofmcr-1while simultaneously increasing colistin resistance. Conjugative plasmids have transferred low cost/high resistancemcr-1alleles across an incredible diversity ofE. colistrains, further stabilizingmcr-1at the species level. Crucially, regulatory mutations were associated with increasedmcr-1stability in pig farms following a ban on the use of colistin as a growth promoter that decreased colistin consumption by 90%. Our study shows how the rapid evolution and horizontal transmission of resistance genes can combine to stabilize resistance and reduce the efficiency of interventions aimed at reducing AMR by limiting antibiotic consumption.
Accurate Mutation Effect Prediction using RoseTTAFold
Authors: Mansoor Sanaa , Baek Minkyung , Juergens David , Watson Joseph L. , Baker David 
Published: November 2022

AbstractPredicting the effects of mutations on protein function is an outstanding challenge. Here we assess the performance of the deep learning based RoseTTAFold structure prediction and design method for unsupervised mutation effect prediction. Using RoseTTAFold in inference mode, without any additional training, we obtain state of the art accuracy on predicting mutation effects for a set of diverse protein families. Thus, although the architecture of RoseTTAFold was developed to address the protein structure prediction problem, during model training RoseTTAFold acquired an understanding of the mutational landscapes of proteins comparable to that of large recently developed language models. The ability to reason over structure as well as sequence could enable even more precise mutation effect predictions following supervised training.
Autophagy is required to prevent early pro-inflammatory responses and neutrophil recruitment duringMycobacterium tuberculosisinfection without affecting pathogen replication in macrophages
Authors: Kinsella Rachel L. , Kimmey Jacqueline M. , Smirnov Asya , Woodson Reilly , Gaggioli Margaret R. , Chavez Sthefany M. , Kreamalmeyer Darren , Stallings Christina L. 
Published: November 2022

ABSTRACTThe immune response toMycobacterium tuberculosisinfection determines tuberculosis disease outcomes, yet we have an incomplete understanding of what immune factors contribute to a protective immune response. Neutrophilic inflammation has been associated with poor disease prognosis in humans and in animal models duringM. tuberculosisinfection and, therefore, must be tightly regulated. ATG5 is an essential autophagy protein that is required in innate immune cells to control neutrophil-dominated inflammation and promote survival duringM. tuberculosisinfection, however, the mechanistic basis for how ATG5 regulates neutrophil recruitment is unknown. To interrogate what innate immune cells require ATG5 to control neutrophil recruitment duringM. tuberculosisinfection, we used different mouse strains that conditionally deleteAtg5in specific cell types. We found that ATG5 is required in CD11c+cells (lung macrophages and dendritic cells) to control the production of proinflammatory cytokines and chemokines duringM. tuberculosisinfection, which would otherwise promote neutrophil recruitment. This role for ATG5 is autophagy-dependent, but independent of mitophagy, LC3-associated phagocytosis, and inflammasome activation, which are the most well-characterized ways that autophagy proteins regulate inflammation. In addition to the increase in proinflammatory cytokine production duringM. tuberculosisinfection, loss of ATG5 in innate immune cells also results in an early induction of TH17 responses. Despite prior publishedin vitrocell culture experiments supporting a role for autophagy in controllingM. tuberculosisreplication in macrophages, loss of autophagy does not affectM. tuberculosisburden in macrophagesin vivoand, therefore, the effects of autophagy on inflammatory responses occur without changes in pathogen numbers. These findings reveal new roles for autophagy proteins in lung resident macrophages and dendritic cells that are required to suppress inflammatory responses that are associated with poor control ofM. tuberculosisinfection.
Consistent individual positions within roosts in Spix’s disc-winged bats
Authors: Giacomini Giada , Chaves-Ramírez Silvia , Hernández-Pinsón H. Andrés , Barrantes José Pablo , Chaverri Gloriana 
Published: November 2022

ABSTRACTIndividuals within both moving and stationary groups arrange themselves in a predictable manner; for example, some individuals are consistently found at the front of the group or in the periphery and others in the center. Each position may be associated with various costs, such as greater exposure to predators, and benefits, such as preferential access to food. In social bats, we would expect a similar consistent arrangement for groups at roost-sites, which is where these mammals spend the largest portion of their lives. Here we study the relative position of individuals within a roost-site and establish if sex, age, and vocal behavior are associated with a given position. We focus on the highly cohesive and mobile social groups found in Spix’s disc-winged bats (Thyroptera tricolor) given this species’ use of a tubular roosting structure that forces individuals to be arranged linearly within its internal space. We obtained high scores for linearity measures, particularly for the top and bottom positions, indicating that bats position themselves in a predictable way despite constant roost-switching. We also found that sex and age were associated with the use of certain positions within the roost; for example, males and subadults tend to occupy the top part (near the roost’s entrance) more often than expected by chance. Our results demonstrate, for the first time, that bats are capable of maintaining a consistent and predictable position within their roosts despite having to relocate daily, and that there is a link between individual traits and position preferences.
Higher-order epistasis shapes natural variation in germ stem cell niche activity
Authors: Fausett Sarah R , Sandjak Asma , Billard Bénédicte , Braendle Christian 
Published: November 2022

SummaryNatural quantitative variation in developmental processes must be driven by allelic variation. Yet, the genotype-phenotype relationships underlying developmental system variation are understudied due to their inherent complexity. Taking advantage of the simpleCaenorhabditis elegansgermline stem cell system, we characterized natural differences in the germ stem cell niche activity of two distinct wild isolates—measured as differences in germline progenitor zone (PZ) size. Through quantitative trait locus (QTL) analysis, we detected multiple candidate causal loci, including two large-effect QTL on chromosomes II and V. Resolving the chromosome V QTL, we show that the isolate with a smaller PZ exhibits a unique 148 bp deletion in the promoter region of the Notch ligand,lag-2, a central signal promoting germ stem cell fate and proliferation. As predicted, introducing this deletion into the isolate with a large PZ resulted in a smaller PZ. Unexpectedly, re-introducing the deleted ancestral sequence in the isolate with a smaller PZ further reduced PZ size. Using allelic replacement lines, we show that these contradictory phenotypic effects are due to epistatic interactions among thelag-2promoter, the chromosome II QTL, and additional loci in the genome. Although thelag-2deletion appeared to explain natural variation in germ stem cell niche activity, its effects across multiple genetic backgrounds were unpredictable due to higher-order epistasis. Studying the genetic architecture of quantitative developmental systems without taking into account its natural variation may be misleading, emphasizing the need for a better integration of developmental and quantitative genetics.
Oral Feeding of Nanoplastics reduces Brain function of Mice by Inducing Intestinal IL-1β-producing Macrophages
Authors: Yang Qianyu , Dai Huaxing , Cheng Ying , Wang Beilei , Xu Jialu , Zhang Yue , Chen Yitong , Xu Fang , Ma Qingle , Fei Ziying , Lin Fang , Wang Chao 
Published: November 2022

AbstractBackground and AimsNanoplastics (NPs) as contaminants in food and water have drawn an increasing public attention. However, little is known about how NPs shape the gut immune landscape after entering the body. The objective of the study was to explore indirect effects caused by the interaction of NPs with the mammalian gut and whole immune system after entering the body.MethodsIn this study, we fabricated NPs (∼500 nm) and microplastics (MPs) (∼2 μm) and aimed to evaluate their in vivo effects by feeding them in mice. The mechanism was then investigated by various technology including single-cell RNA sequencing of gut and brain tissue.ResultsThe results suggested that NPs showed a better ability to induce gut macrophage activation than did MPs. In addition, NPs triggered gut interleukin 1 beta (IL-1β)-producing macrophage reprogramming via inducing lysosomal damage after phagocytosis. More importantly, IL-1β released from the intestine could affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlated with a decline in cognitive and short-term memory in NPs-fed miceConclusionsThus, this study provides new insight into the mechanism of action of the gut-brain axis and delineates the way NPs reduce brain function, highlights the importance to fix the plastic pollution problem worldwide.
Key supply chain strategies for post-COVID-19 recovery: evidence from an Indian smart furniture industry
Authors: Sachan Sandeep , Kumar Vimal , Vardhan Sachit , Mittal Ankesh , Verma Pratima , Bag Surajit 
Published: November 2022

PurposeSmart furniture is an essential part of research that has been designed to best complement easy and safe human interaction. The purpose of smart furniture is to save the space of the house and make the products unique, awesome and safe, functional, strong and also make it works better so the people can live better with it. This research aims to explore the key supply chain strategies implemented by the Indian smart furniture industry to reduce the impact of a post-COVID-19 pandemic.Design/methodology/approachThis work utilized a case study and conducted semi-structured interviews with the top leadership of the smart furniture manufacturing industry to explore key supply chain strategies to reduce the influence of the post-COVID-19 pandemic. Additionally, key supply chain strategies have been analyzed using a multi-criteria decision-making technique known as grey relational analysis (GRA) to determine their ranking significance in the smart furniture industry.FindingsThe results of this study discovered that “Inventory-Categorization” is essential in ensuring business continuity during the COVID-19 pandemic and helps reduce the amount of stock they have on hand. It enhanced the opportunity for employees to properly focus on their work and an opportunity for better work-life balance. The results of the study can also help supply chain stakeholders in their establishment of critical strategies.Research limitations/implicationsThe implications of this research work help the Indian furniture industry to make supply chain investment decisions that benefit the organization to sustain itself.Originality/valueThis is the first study to explore key supply chain strategies for the post-COVID-19 era. This work will assist managers and practitioners in helping the organization decide which supply chain strategies are more critical to the betterment of the organization.