bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perturbation of mitochondrial Ca2+ homeostasis activates cross-compartmental proteostatic response in Arabidopsis
Authors: Zhang Xiaoyan , Ma Chongyang , Bao Xinyue , Zhang Shenyu , Zayed Omar , Zhang Zhengjing , Tang Kai , Xie Shaojun , Wang Yunsheng , Zhang Dayong , Xu Huawei , Jia Huifang , Wang Xinying , Lei Qianyan , Wang Xiaocui , Zhang Junli , Dinesh-Kumar Savithramma P , Song Chun-Peng , Zhu Jian-Kang , Zhu Xiaohong 
Published: October 2022

AbstractMitochondrial Ca2+ (mtCa2+) homeostasis is essential to mitochondrial functions. However, how mtCa2+ homeostasis is achieved and the consequences of impaired mtCa2+ homeostasis in plants is poorly understood. Here, we demonstrate a critical role for mitochondrial Ca2+ uniporter (MCU) in the control of mtCa2+ uptake for mtCa2+ homeostasis in planta by characterizing MCU mutants and overexpressed plants. Impaired MCU-controlled mtCa2+ homeostasis (iMUCH) in gain-of-function and loss-of-function MCU plants causes the misregulation of mitochondrial gene expression that triggers mitonuclear protein imbalance. Transcriptome integrated with proteomics analysis reveal activation of multiple compartmental UPR gene expression and decrease of cytosolic translation with selective repression of ribosome and RNA modification protein synthesis upon iMUCH. Intriguingly, TOR signalling is not involved in cytosolic translational response to iMUCH, but the reduction of eIFα phosphorylation is evident under iMUCH induced mitochondrial stress. Thus, our study unveils the essential functions of MCU proteins for mtCa2+ homeostasis, and the involvement of MCU-controlled mtCa2+ homeostasis in mitochondrial stress dependent regulation of protein synthesis for cellular proteostasis that is connected to plant growth and stress resistance.
Epigenetic aging waves: Artificial intelligence detects clustering of switch points in DNA methylation rate in defined sex-dependent age periods
Authors: Segev Elad , Shahal Tamar , Konstantinovsky Thomas , Marcus Yonit , Shefer Gabi , Ebenstein Yuval , Pasmanik-Chor Metsada , Stern Naftali 
Published: October 2022

AbstractBackgroundAging is linked to hypermethylation of CpG sites on promoters and enhancers, along with loss of methylation in intergenic zones. That such changes are not necessarily a continuous process is exemplified by the extensive changes in DNA methylation during development with another significant time of change during adolescence. However, the relation between age and DNA methylation during adult life has not been systematically evaluated. In particular, potential changes in methylation trends in the same CpGs over the years that may occur with aging remain largely unexplored.MethodsHere we set out to determine the average trends by age of the CpG sites represented in the Illumina 450 platform, based on data from 2143 subjects of the age range of 20 to 80 years, compiled from 24 different cohorts. Using several mathematical procedures, we initially separated stationary probes from probes whose methylation changes with age. Among the latter, representing ∼20% of the probes, we then focused on the identification of CpG sites with switch points, i.e., a point where a stable trend of change in the age-averaged methylation is replaced by another linear trend.ResultsUsing several mathematical modeling steps, we generated a machine learning model that identified 5175 CpG sites with switch points in age-related changes in the trend of methylation over the years. Switch points reflect acceleration, deceleration or change of direction of the alteration of methylation with age. The 5175 switch points were limited to 2813 genes in three waves, 80% of which were identical in men and women. A medium-size wave was seen in the early forties, succeeded by a dominant wave as of the late fifties, lasting up to 8 years each. Waves appeared∼4-5 years earlier in men. No switch points were detected on CpGs mapped to the X chromosome.ConclusionIn non-stationary CpG sites, concomitant switch points in age related changes in methylations can be seen in a defined group of sites and genes, which cluster in 3 age- and sex-specific waves.
High-throughput cell spheroid production and assembly analysis by microfluidics and deep learning
Authors: Trossbach Martin , Åkerlund Emma , Langer Krzysztof , Seashore-Ludlow Brinton , Joensson Haakan N. 
Published: October 2022

Abstract3D cell culture models are an important tool in translational research but have been out of reach for high-throughput screening due to complexity, requirement of large cell numbers and inadequate standardization. Here, we present a high-throughput workflow to produce and characterize the formation of miniaturized spheroids using deep learning. We train a convolutional neural network (CNN) for cell ensemble morphology classification, benchmark it against more conventional image analysis, and characterize spheroid assembly determining optimal surfactant concentrations and incubation times for spheroid production for three cell lines with different spheroid formation properties. Notably, this format is compatible with large-scale spheroid production and screening. The presented workflow and CNN offer a template for large scale minispheroid production and analysis and can be extended and re-trained to characterize morphological responses in spheroids to additives, culture conditions and large drug libraries.
Inflammation drives age-induced loss of tissue resident macrophages
Authors: Adé Kémy , Coronilla Javier Saenz , Obino Dorian , Weinberger Tobias , Kaiser Caroline , Mella Sébastien , Chen Cheng , Katsimpardi Lida , Werts Catherine , Li Han , Dardenne Pascal , Lallemand Yvan , Gomez Perdiguero Elisa 
Published: October 2022

AbstractLow-grade chronic systemic inflammation, or inflammageing, is a hallmark of ageing and a risk factor for both morbidity and mortality in elderly people. Resident macrophages are tissue homeostasis sentinels that are embedded in their tissue of residence since embryonic development, thus been exposed to cumulative tissue insults throughout life. Therefore, resident macrophages, among other immune cells, emerge as potential key contributors to age-associated tissue dysfunction. Contrary to what is currently postulated, we demonstrate here that the pool of embryo-derived resident macrophages exhibits an age-dependent depletion in liver, and other solid organs and that they are not replaced by Hematopoietic Stem Cell (HSCs)-derived monocytes throughout life. Further, we demonstrate that gradual, cumulative inflammation during ageing induces this specific loss of tissue resident macrophages. Preserving a “youthful” density of resident macrophages attenuates classical hallmarks of liver age-associated dysfunction.SummaryThe pool of embryo-derived resident macrophages dwindles with age in most tissues, without compensation from Hematopoietic Stem Cell (HSC)-derived cells. This loss is not due to impaired self-renewal in old tissues but rather to increased cell death, which is driven by sustained inflammation. Attenuating inflammation sensing during ageing prevents age-induce macrophage loss and improves hallmarks of liver ageing.
On the origins of phenotypic parallelism in benthic and limnetic stickleback
Authors: Dean Laura L. , Magalhaes Isabel Santos , D’Agostino Daniele , Hohenlohe Paul , MacColl Andrew D. C. 
Published: October 2022

AbstractRapid evolution of similar phenotypes in similar environments, giving rise toin situparallel adaptation, is an important hallmark of ecological speciation. However, what appears to bein situadaptation can also arise by dispersal of divergent lineages from elsewhere. We test whether two contrasting phenotypes repeatedly evolved in parallel, or have a single origin, in an archetypal example of ecological adaptive radiation: benthic-limnetic three-spined stickleback (Gasterosteus aculeatus) across species-pair and solitary lakes in British Columbia. We identify two genomic clusters across freshwater populations, which differ in benthic-limnetic divergent phenotypic traits and separate benthic from limnetic individuals in species pair lakes. Phylogenetic reconstruction and niche evolution modelling both suggest a single evolutionary origin for each of these clusters. We detected strong phylogenetic signal in benthic-limnetic divergent traits, suggesting they are ancestrally retained. Accounting for ancestral state retention, we identify local adaptation of body armour due to the presence of an intraguild predator, the sculpin (Cottus asper) and environmental effects of lake depth and pH on body size. Taken together, our results imply a predominant role for retention of ancestral characteristics in driving trait distribution, with further selection imposed on some traits by environmental factors.
Validation of the linear regression method to evaluate population accuracy and bias of predictions for non-linear models
Authors: Yu Haipeng , Fernando Rohan L , Dekkers Jack CM 
Published: October 2022

AbstractBackgroundThe linear regression method (LR) was proposed to estimate population bias and accuracy of predictions, while addressing the limitations of commonly used cross-validation methods. The validity and behavior of the LR method have been provided and studied for linear model predictions but not for non-linear models. The objectives of this study were to 1) provide a mathematical proof for the validity of the LR method when predictions are based on conditional mean, 2) explore the behavior of the LR method in estimating bias and accuracy of predictions when the model fitted is different from the true model, and 3) provide guidelines on how to appropriately partition the data into training and validation such that the LR method can identify presence of bias and accuracy in predictions.ResultsWe present a mathematical proof for the validity of the LR method to estimate bias and accuracy of predictions based on the conditional mean, including for non-linear models. Using simulated data, we show that the LR method can accurately detect bias and estimate accuracy of predictions when an incorrect model is fitted when the data is partitioned such that the values of relevant predictor variables differ in the training and validation sets. But the LR method fails when the data are not partitioned in that manner.ConclusionsThe LR method was proven to be a valid method to evaluate the population bias and accuracy of predictions based on the conditional mean, regardless of whether it is a linear or non-linear function of the data. The ability of the LR method to detect bias and estimate accuracy of predictions when the model fitted is incorrect depends on how the data are partitioned. To appropriately test the predictive ability of a model using the LR method, the values of the relevant predictor variables need to be different between the training and validation sets.
Machine learning on large-scale proteomics data identifies tissue- and cell type-specific proteins
Authors: Claeys Tine , Menu Maxime , Bouwmeester Robbin , Gevaert Kris , Martens Lennart 
Published: October 2022

AbstractUsing data from 183 public human data sets from PRIDE, a machine learning model was trained to identify tissue and cell-type specific protein patterns. PRIDE projects were searched with ionbot and tissue/cell type annotation was manually added. Data from physiological samples were used to train a Random Forest model on protein abundances to classify samples into tissues and cell types. Subsequently, a one-vs-all classification and feature importance were used to analyse the most discriminating protein abundances per class. Based on protein abundance alone, the model was able to predict tissues with 98% accuracy, and cell types with 99% accuracy. The F-scores describe a clear view on tissue-specific proteins and tissue-specific protein expression patterns. In-depth feature analysis shows slight confusion between physiologically similar tissues, demonstrating the capacity of the algorithm to detect biologically relevant patterns. These results can in turn inform downstream uses, from identification of the tissue of origin of proteins in complex samples such as liquid biopsies, to studying the proteome of tissue-like samples such as organoids and cell lines.
Selective accumulation of matrix proteins inside of peroxisomal subdomains
Authors: Ast Julia , Bäcker Nils , Martorana Domenica , Renicke Christian , Stehlik Thorsten , Heimerl Thomas , Taxis Christof , Bange Gert , Bölker Michael , Sandrock Björn , Schink Kay Oliver , Freitag Johannes 
Published: October 2022

AbstractFormation of specialized reaction spaces prevents interference between distinct cellular pathways. Peroxisomes are cellular compartments involved in a large diversity of metabolic processes. How peroxisomes differentiate into subpopulations and by which mechanism intraorganellar domains are formed remains largely elusive. Here, we report on enzymes from the fungusUstilago maydis, which accumulate inside of peroxisomal subdomains. We describe a short peptide motif (Thr-Ile-Ile-Val) sufficient to trigger focal localization. Mining for proteins with similar motifs uncovered several peroxisomal matrix proteins that accumulate in intraorganellar foci. These foci are enriched in the enzyme urate oxidase – a typical constituent of the paracrystalline core of peroxisomes. Upon peroxisome proliferation uneven distribution of focal structures results in the formation of peroxisome subpopulations with different protein content. The underlying principle of subdomain formation is evolutionary conserved in mammalian peroxisomes and formation of similar foci was also observed inside of mitochondria. We propose that peroxisomal proteins show an individual propensity to self-assemble. This formation of protein aggregates appears to be a ubiquitous driving force to spatially organize the peroxisomal proteome.
Misuse of Historical Data to Determine Past Distribution Range and Migratory Patterns of the Patagonian Huemul Misleads Conservation Targets
Authors: Corti Paulo , Díaz Norma I. 
Published: October 2022

ABSTRACTHistorical information is widely used to understand mammals’ distribution dynamics and drivers, and it has been worldwide acknowledged by conservation programmes. Although these records have some limitations such as spatial and temporal accuracy, non-standardized sampling, geographical imprecisions, and levels of bias, they can fulfil a useful function to set reference conditions, priorities, and conservation goals. In the case of huemul (Hippocamelus bisulcus), an endemic cervid of shrubby and forested habitats from the Andes Mountains of southern Argentina and Chile, some reports suggest its historical presence in the steppe biome. This led Flueck et al. (2022) to assume that the past distribution of the huemul extended as far as the Atlantic coast and even in Tierra del Fuego, proposing that the altitudinal migratory tradition has been broken. Here, we carried out a qualitative and quantitative analysis of the written sources used by the authors to support their assumptions. We conclude that there are errors, uncertainties, and questionable interpretations on the use of historical data that do not add more value, instead, add mostly confusion with the misleading potential of conservation efforts on huemul.
On the reliability of wearable technology: A tutorial on measuring heart rate and heart rate variability in the wild
Authors: Dudarev Veronica , Barral Oswald , Zhang Chuxuan , Davis Guy , Enns James T. 
Published: October 2022

AbstractWearable sensors are quickly making their way into psychophysiological research, as they allow collecting longitudinal and ecologically valid data. The present tutorial considers fidelity of physiological measurement with wearable sensors, focusing on reliability. We elaborate why ensuring reliability for wearables is important and offer statistical tools for assessing wearable reliability for between participants and within-participant designs. The framework offered here is illustrated using several brands of commercially available heart rate sensors. Our hope is that by systematically quantifying measurement reliability, researchers will be able to make informed choices about specific wearable devices and measurement procedures that meet their research goals.
Cytoophidia maintain the integrity of Drosophila follicle epithelium
Authors: Wang Qiao-Qi , You Dong-Dong , Liu Ji-Long 
Published: October 2022

ABSTRACTCTP synthase (CTPS) forms a filamentous structure termed the cytoophidium in all three domains of life. The female reproductive system of Drosophila is an excellent model for studying the physiological function of cytoophidia. Here, we use CTPSH355A, a point mutation that destroys the cytoophidium-forming ability of CTPS, to explore the in vivo function of cytoophidia. In CTPSH355A egg chambers, we observe the ingression and increased heterogeneity of follicle cells. In addition, we find that the cytoophidium-forming ability of CTPS, rather than the protein level, is the cause of the defects observed in CTPSH355A mutants. To sum up, our data indicate that cytoophidia play an important role in maintaining the integrity of follicle epithelium.
Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in obesity
Authors: Hall Liam G , Czeczor Juliane K. , Connor Timothy , Botella Javier , De Jong Kirstie A. , Renton Mark C. , Genders Amanda J. , Venardos Kylie , Martin Sheree D. , Bond Simon T. , Aston-Mourney Kathryn , Howlett Kirsten F. , Campbell James A , Collier Greg R. , Walder Ken R. , McKenzie Matthew , Ziemann Mark , McGee Sean L. 
Published: October 2022

ABSTRACTThere are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. While some common aetiological mechanisms are known, the role of amyloid beta 42 (Aβ42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Aβ42, which is increased from adipose tissue of obese mice and is associated with higher plasma Aβ42. Increasing circulating Aβ42levels in non-obese mice had no effect on systemic glucose homeostasis but had obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. These effects on cardiac function were not observed when circulating levels of the closely related Aβ40isoform were increased. Administration of an Aβ neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Aβ neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Aβ42impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Aβ42inhibited mitochondrial function. These data reveal a role for systemic Aβ42in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.
Spatial cell fate manipulation of human pluripotent stem cells by controlling the microenvironment using photocurable hydrogel
Authors: Wang Zhe , Numada Akira , Wagai Fumi , Oda Yusuke , Ohgushi Masatoshi , Maki Koichiro , Adachi Taiji , Eiraku Mototsugu 
Published: October 2022

AbstractHuman pluripotent stem cells (hPSCs) dynamically respond to their chemical and physical microenvironment, dictating their behavior. However, conventional in vitro studies predominantly employ plastic culture wares, which offer a simplified representation of the in vivo microenvironment. Emerging evidence underscores the pivotal role of mechanical and topological cues in hPSC differentiation and maintenance. In this study, we cultured hPSCs on hydrogel substrates with spatially controlled stiffness.The use of culture substrates that enable precise manipulation of spatial mechanical properties holds promise for better mimicking in vivo conditions and advancing tissue engineering techniques. We designed a photocurable polyethylene glycol–polyvinyl alcohol (PVA-PEG) hydrogel, allowing for spatial control of surface stiffness and geometry at a micrometer scale. This versatile hydrogel can be functionalized with various extracellular matrix (ECM) proteins. Laminin 511-functionalized PVA-PEG gel effectively supports the growth and differentiation of hPSCs.Moreover, by spatially modulating the stiffness of the patterned gel, we achieved spatially selective cell differentiation, resulting in the generation of intricate, patterned structures.Summary statementA new hydrogel substrate enables spatial control of surface stiffness at the micrometer level, enabling local differentiation of hPSC and facilitating complex pattern formation.
Foot form and function: Variable and versatile, yet sufficiently related to predict one from the other
Authors: Schuster Robert W. , Cresswell Andrew , Kelly Luke A. 
Published: October 2022

AbstractThe modern human foot is a complex structure thought to play an important role in our ability to walk and run efficiently. Comparisons of our feet to those of our evolutionary ancestors and closest living relatives have linked the shape of several foot components (e.g., the longitudinal and transverse arches, size of the heel and length of the toes) to specific mechanical functions. But since foot shape varies widely across the modern human population, this study aimed to investigate how closely foot shape, deformation and joint mechanics during various locomotor tasks are actually linked. And whether the latter can be accurately predicted based entirely on the former two. A statistical shape-function model (SFM) was constructed by performing a principal component analysis on 100 participants’ three-dimensional foot scans, and joint angles and moments captured during level, uphill, and downhill walking and running. This SFM revealed that the main sources of variation were the longitudinal and transverse arches, relative foot proportions and toe shape along with their associated joint mechanics. However, each of these only accounted for a small proportion of the overall variation in foot shape, deformation and joint mechanics, most likely due to the high structural complexity and variability of the foot. Nevertheless, a leave-one-out analysis showed that the SFM can be used to accurately predict the joint angles and moments of a new foot based only on its shape. These results have implications and potential applicability across numerous fields, such as evolutionary anthropology, podiatry, orthopaedics and footwear design.