-
Proceedings of the National Academy of... Sep 2023Cell size and cell count are adaptively regulated and intimately linked to growth and function. Yet, despite their widespread relevance, the relation between cell size...
Cell size and cell count are adaptively regulated and intimately linked to growth and function. Yet, despite their widespread relevance, the relation between cell size and count has never been formally examined over the whole human body. Here, we compile a comprehensive dataset of cell size and count over all major cell types, with data drawn from >1,500 published sources. We consider the body of a representative male (70 kg), which allows further estimates of a female (60 kg) and 10-y-old child (32 kg). We build a hierarchical interface for the cellular organization of the body, giving easy access to data, methods, and sources (https://humancelltreemap.mis.mpg.de/). In total, we estimate total body counts of ≈36 trillion cells in the male, ≈28 trillion in the female, and ≈17 trillion in the child. These data reveal a surprising inverse relation between cell size and count, implying a trade-off between these variables, such that all cells within a given logarithmic size class contribute an equal fraction to the body's total cellular biomass. We also find that the coefficient of variation is approximately independent of mean cell size, implying the existence of cell-size regulation across cell types. Our data serve to establish a holistic quantitative framework for the cells of the human body, and highlight large-scale patterns in cell biology.
Topics: Child; Humans; Female; Male; Cell Count; Biomass; Cell Size; Correlation of Data
PubMed: 37722043
DOI: 10.1073/pnas.2303077120 -
Science Translational Medicine Jan 2024Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how... (Review)
Review
Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.
Topics: Humans; Prospective Studies; UK Biobank; Biological Specimen Banks; Research Design; Data Analysis
PubMed: 38198570
DOI: 10.1126/scitranslmed.adf4428 -
MBio Oct 2023Recent reports showing that human cancers have a distinctive microbiome have led to a flurry of papers describing microbial signatures of different cancer types. Many of...
Recent reports showing that human cancers have a distinctive microbiome have led to a flurry of papers describing microbial signatures of different cancer types. Many of these reports are based on flawed data that, upon re-analysis, completely overturns the original findings. The re-analysis conducted here shows that most of the microbes originally reported as associated with cancer were not present at all in the samples. The original report of a cancer microbiome and more than a dozen follow-up studies are, therefore, likely to be invalid.
Topics: Humans; Computational Biology; Metagenomics; Microbiota; Neoplasms; Data Analysis
PubMed: 37811944
DOI: 10.1128/mbio.01607-23 -
Physical Biology Jul 2023Mitochondria serve a wide range of functions within cells, most notably via their production of ATP. Although their morphology is commonly described as bean-like,... (Review)
Review
Mitochondria serve a wide range of functions within cells, most notably via their production of ATP. Although their morphology is commonly described as bean-like, mitochondria often form interconnected networks within cells that exhibit dynamic restructuring through a variety of physical changes. Further, though relationships between form and function in biology are well established, the extant toolkit for understanding mitochondrial morphology is limited. Here, we emphasize new and established methods for quantitatively describing mitochondrial networks, ranging from unweighted graph-theoretic representations to multi-scale approaches from applied topology, in particular persistent homology. We also show fundamental relationships between mitochondrial networks, mathematics, and physics, using ideas of graph planarity and statistical mechanics to better understand the full possible morphological space of mitochondrial network structures. Lastly, we provide suggestions for how examination of mitochondrial network form through the language of mathematics can inform biological understanding, and vice versa.
Topics: Mathematics; Lens, Crystalline; Mitochondria; Physics
PubMed: 37290456
DOI: 10.1088/1478-3975/acdcdb -
Cognitive Psychology Nov 2023Mathematical expressions consist of recursive combinations of numbers, variables, and operators. According to theoretical linguists, the syntactic mechanisms of natural... (Review)
Review
Mathematical expressions consist of recursive combinations of numbers, variables, and operators. According to theoretical linguists, the syntactic mechanisms of natural language also provide a basis for mathematics. To date, however, no theoretically rigorous investigation has been conducted to support such arguments. Therefore, this study uses a methodology based on theoretical linguistics to analyze the syntactic properties of mathematical expressions. Through a review of recent behavioral and neuroimaging studies on mathematical syntax, we report several inconsistencies with theoretical linguistics, such as the use of ternary structures. To address these, we propose that a syntactic category called Applicative plays a central role in analyzing mathematical expressions with seemingly ternary structures by combining binary structures. Besides basic arithmetic expressions, we also examine algebraic equations and complex expressions such as integral and differential calculi. This study is the first attempt at building a comprehensive framework for analyzing the syntactic structures of mathematical expressions.
Topics: Humans; Language; Linguistics; Mathematics
PubMed: 37748253
DOI: 10.1016/j.cogpsych.2023.101606 -
Molecular & Cellular Proteomics : MCP Sep 2023Data-independent acquisition (DIA) mass spectrometry-based proteomics generates reproducible proteome data. The complex processing of the DIA data has led to the...
Data-independent acquisition (DIA) mass spectrometry-based proteomics generates reproducible proteome data. The complex processing of the DIA data has led to the development of multiple data analysis tools. In this study, we assessed the performance of five tools (OpenSWATH, EncyclopeDIA, Skyline, DIA-NN, and Spectronaut) using six DIA datasets obtained from TripleTOF, Orbitrap, and TimsTOF Pro instruments. By comparing identification and quantification metrics and examining shared and unique cross-tool identifications, we evaluated both library-based and library-free approaches. Our findings indicate that library-free approaches outperformed library-based methods when the spectral library had limited comprehensiveness. However, our results also suggest that constructing a comprehensive library still offers benefits for most DIA analyses. This study provides comprehensive guidance for DIA data analysis tools, benefiting both experienced and novice users of DIA-mass spectrometry technology.
Topics: Mass Spectrometry; Proteomics; Proteome; Gene Library; Data Analysis
PubMed: 37481071
DOI: 10.1016/j.mcpro.2023.100623 -
Neuroscience and Biobehavioral Reviews Mar 2024Numerical abilities are complex cognitive skills essential for dealing with requirements of the modern world. Although the brain structures and functions underlying... (Review)
Review
Numerical abilities are complex cognitive skills essential for dealing with requirements of the modern world. Although the brain structures and functions underlying numerical cognition in different species have long been appreciated, genetic and molecular techniques have more recently expanded the knowledge about the mechanisms underlying numerical learning. In this review, we discuss the status of the research related to the neurobiological bases of numerical abilities. We consider how genetic factors have been associated with mathematical capacities and how these link to the current knowledge of brain regions underlying these capacities in human and non-human animals. We further discuss the extent to which significant variations in the levels of specific neurotransmitters may be used as potential markers of individual performance and learning difficulties and take into consideration the therapeutic potential of brain stimulation methods to modulate learning and improve interventional outcomes. The implications of this research for formulating a more comprehensive view of the neural basis of mathematical learning are discussed.
Topics: Humans; Learning; Cognition; Brain; Mathematics; Neurobiology
PubMed: 38220032
DOI: 10.1016/j.neubiorev.2024.105545 -
Journal of Experimental Child Psychology Feb 2024The associations between parental mathematics anxiety and attitudes and children's mathematics attainment in early primary school were explored. Initially, parents of...
The associations between parental mathematics anxiety and attitudes and children's mathematics attainment in early primary school were explored. Initially, parents of preschool children (M = 3;11 [years;months]) completed a questionnaire indexing parental mathematics anxiety and attitudes and the frequency of preschool home number experiences. The children completed mathematics assessments in their first year (n = 231, M = 5;2) and second year (n = 119, M = 6;3) of schooling and a mathematics anxiety questionnaire in their third year of schooling (n = 119, M = 6;7). A questionnaire indexing the frequency of primary school home number experiences was completed by 119 of the parents in their children's second year of schooling (M = 6;0). All indices of parental mathematics anxiety and attitudes predicted children's mathematics attainment in their first school year. These associations were independent of parental mathematics attainment and were not mediated by the frequency of preschool home number experiences. Furthermore, the positive association between preschool home number experiences and children's mathematics attainment was not weaker in the context of high parental mathematics anxiety or negative parental mathematics attitudes. One index of parental mathematics attitudes predicted children's mathematics attainment in their second school year, but this association was not significant when prior attainment was controlled. There was a stronger association between maternal mathematics anxiety and girls' attainment versus boys' attainment. Parental mathematics anxiety did not predict children's mathematics anxiety. The findings suggest that children whose parents have high mathematics anxiety or negative mathematics attitudes are more likely to have lower mathematics attainment in their first year of school. However, the mechanism underpinning this association is not yet established.
Topics: Male; Female; Humans; Child, Preschool; Child; Parents; Educational Status; Attitude; Mathematics; Anxiety
PubMed: 37783015
DOI: 10.1016/j.jecp.2023.105779 -
Nature Communications Sep 2023Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for...
Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for full-length transcriptome analysis. We present an integrated computational toolkit named TAGET for Iso-seq full-length transcript data analyses, including transcript alignment, annotation, gene fusion detection, and quantification analyses such as differential expression gene analysis and differential isoform usage analysis. We evaluate the performance of TAGET using a public Iso-seq dataset and newly sequenced Iso-seq datasets from tumor patients. TAGET gives significantly more precise novel splice site prediction and enables more accurate novel isoform and gene fusion discoveries, as validated by experimental validations and comparisons with RNA-seq data. We identify and experimentally validate a differential isoform usage gene ECM1, and further show that its isoform ECM1b may be a tumor-suppressor in laryngocarcinoma. Our results demonstrate that TAGET provides a valuable computational toolkit and can be applied to many full-length transcriptome studies.
Topics: Humans; Data Analysis; Gene Expression Profiling; Gene Fusion; RNA-Seq; Transcriptome; Extracellular Matrix Proteins
PubMed: 37741817
DOI: 10.1038/s41467-023-41649-0 -
Current Biology : CB Dec 2023Cellular responses to environmental changes are often highly heterogeneous and exhibit seemingly random dynamics. The astonishing insight of chaos theory is that such...
Cellular responses to environmental changes are often highly heterogeneous and exhibit seemingly random dynamics. The astonishing insight of chaos theory is that such unpredictable patterns can, in principle, arise without the need for any random processes, i.e., purely deterministically without noise. However, while chaos is well understood in mathematics and physics, its role in cell biology remains unclear because the complexity and noisiness of biological systems make testing difficult. Here, we show that chaos explains the heterogeneous response of Escherichia coli cells to oxidative stress. We developed a theoretical model of the gene expression dynamics and demonstrate that chaotic behavior arises from rapid molecular feedbacks that are coupled with cell growth dynamics and cell-cell interactions. Based on theoretical predictions, we then designed single-cell experiments to show we can shift gene expression from periodic oscillations to chaos on demand. Our work suggests that chaotic gene regulation can be employed by cell populations to generate strong and variable responses to changing environments.
Topics: Nonlinear Dynamics; Models, Theoretical
PubMed: 38029757
DOI: 10.1016/j.cub.2023.11.002