Multicellular Research Articles

The extraterrestrial hypothesis: an epistemological case for removing the taboo

The extraterrestrial hypothesis (ETH), the hypothesis that an extraterrestrial civilization (ETC) is active on Earth today, is taboo in academia, but the assumptions behind this taboo are faulty. Advances in biology have rendered the notion that complex life is rare in our Galaxy improbable. The objection that no ETC would come to Earth to hide from us does not consider all possible alien motives or means. For an advanced ETC, the convergent instrumental goals of all rational agents – self-preservation and the acquisition of resources – would support the objectives of removing existential threats and gathering strategic and non-strategic information. It could advance these objectives by proactively gathering information about and from inhabited planets, concealing itself while doing so, and terminating potential rivals before they become imminently dangerous. Other hypotheses of ETC behavior, including the zoo/interdict hypothesis and the dark forest hypothesis also undercut the claim that the ETH is highly improbable, and the ETH overturns none of our well-tested scientific knowledge. It follows that evidence offered in its support need not be extraordinary. The fact that most reports of unidentified anomalous phenomena (UAP) have natural or human explanations does not count against the ETH. Inference to the best explanation offers a way to find evidence for the hypothesis and some evidence exists, some of it taking the form of reliable witness reports. The most plausible alternative explanation for some UAP declines in probability over time. A hypothesis that does not contradict well-established facts or theories, is not highly improbable for other reasons, and explains otherwise unexplained evidence is a rational hypothesis. Since the ETH meets this test, it should be evaluated alongside other possibilities when the case-specific evidence warrants it.

Mackinawite partial oxidation to green rust produces a large, abiotic uranium isotope fractionation

Low-oxygen settings and transition zones between strictly anoxic and oxic conditions may have characterised large expanses of Precambrian continental margins, where oxygen-breathing, complex life emerged and diversified. Accurate reconstructions of oxygen levels in such conditions are therefore required, but current geochemical proxies fail in identifying transitional redox conditions. Uranium isotopes are an emerging palaeoredox proxy, as large isotope fractionations are recorded during the reduction of uranium into anoxic sediments. Their potential application to transitional conditions is, however, unclear, because the redox regulating mineralogy of such environments and the associated isotope fractionations are poorly constrained. Here, we explore the mineralogical transformations occurring during the partial oxidation of mackinawite. We show that green rust, a key mineral of Precambrian oceans, forms as a by-product of mackinawite oxidation, along with uraninite and polysulphide. We also demonstrate that this mechanism records a large abiotic uranium isotope fractionation during its reaction with aqueous iron sulphide.

Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy.

The autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are the two major intracellular proteolytic systems that mediate protein turnover in eukaryotes. Although a crosstalk exists between these two systems, it is still unclear how UPS and ALP interact in vivo. Here, we investigated how impaired function of the proteasome-associated deubiquitinating enzyme (DUB) Uchl5/UBH-4 affects autophagy in human cells and in a multicellular organism. We show that downregulation of Uchl5 by siRNA reduces autophagy by partially blocking the fusion of autophagosomes with the lysosomes in HeLa cells, which is similar to a previously reported role of the proteasome-associated DUB Usp14 on autophagy. However, exposure of Caenorhabditis elegans to ubh-4 or usp-14 RNAi, or to their pharmacological inhibitors, results in diverse effects on numbers of autophagosomes and autolysosomes, without blocking the lysosomal fusion, in the intestine, hypodermal seam cells and the pharynx. Our results reveal that impairment of Uchl5/UBH-4 and Usp14 affects autophagy in a tissue context manner. A deeper insight into the interplay between UPS and ALP in various tissues in vivo has the potential to promote development of therapeutic approaches for disorders associated with proteostasis dysfunction.

Microtubule inner proteins of Plasmodium are essential for transmission of malaria parasites

Microtubule inner proteins (MIPs) are microtubule-associated proteins that bind to tubulin from the luminal side. MIPs can be found in axonemes to stabilize flagellar beat or within cytoplasmic microtubules. Plasmodium spp. are the causative agents of malaria that feature different parasite forms across a complex life cycle with both unique and divergent microtubule-based arrays. Here, we investigate four MIPs in a rodent malaria parasite for their role in transmission to and from the mosquito. We show by single and double gene deletions that SPM1 and TrxL1, MIPs associated with subpellicular microtubules, are dispensable for transmission from the vertebrate host to the mosquito and back. In contrast, FAP20 and FAP52, MIPs associated with the axonemes of gametes, are essential for transmission to mosquitoes but only if both genes are deleted. In the absence of both FAP20 and FAP52, the B-tubule of the axoneme partly detaches from the A-tubule, resulting in the deficiency of axonemal beating and hence gamete formation and egress. Our data suggest that a high level of redundancy ensures microtubule stability in the transmissive stages of Plasmodium, which is important for parasite transmission.

N-Cadherin based adhesion and Rac1 activity regulate tension polarization in the actin cortex.

Tension-adhesion interplay is a crucial mechanism in multicellular organisms that determines the tension differential among internal and external interfaces, which in turn, mediates tissue surface tension and cell sorting, morphogenesis and remodeling, and cancer progression. Cadherins are widely believed to be involved, yet key aspects of the process are neither well characterized nor quantified. This study demonstrates the critical role of N-cadherin in driving tension polarization throughout the actin cortical network. N-cadherin regulates both tension increase at the cell-medium (external) interface and decrease at the cell-cell (internal) interface, and their quantitative magnitudes, both absolute and relative, strongly depend on the surface density of N-cadherin. Furthermore, the strength of tension polarization also increases with respect to the number of cell-cell interfaces for cells within a multicellular cluster. The cadherin-actin contractility linkage is mediated by Rac1, which serves as a molecular switch to trigger cortex remodeling and contraction via myosin II. Inhibition of Rac1 activity decreases tension polarization and leads to reduced coherence in both small clusters and spheroids. These results provide a pathway to reconcile opposing theories for tissue surface tension generation and perspectives in cancer treatment.

Biosilica 3D Micromorphology of Geodiidae Sponge Spicules Is Patterned by F-Actin.

Demosponges (phylum Porifera) are among the first multicellular organisms on the planet and represent a unique archive of biosilica-based skeletal structures with species-specific microstructures called spicules. With more than 80 morphotypes, this class of sponges is recognized as a unique source of amorphous silica with superficial ornamentation patterned by organic phases. In this study, we investigated spicules of selected representatives of the family Geodiidae (order Tetractinellida), to identify F-actin-containing axial filaments within these 3D skeletal microconstructs defined as oxyspherasters and sterrasters. Their desilicification using 10% HF leads to isolation of multifilamentous, radially oriented organic matrices, which resemble the shape and size of the original spicules. Our data show that highly specific indicators of F-actin such as iFluorTM 594-Phalloidin, iFluorTM 488-Phalloidin, as well as iFluorTM 350-Phalloidin unambiguously confirm its localization within demineralized oxyspherasters and sterrasters of 11 diverse demosponges species belonging to the subfamily Geodiinae (genera Geodia, Rhabdastrella) and the subfamily Erylinae (genera Caminella, Caminus, Erylus, Pachymatisma). Well-defined periodicity in Geodia cydonium sterrasters actin filaments has been observed using atomic force microscopy (AFM) for the first time. The findings of F-actin as a possible pattern driver in spicules of geodiids brings additional light to our knowledge of spiculogenesis in this group. However, no specific actin structures were found between the geodiid subfamilies or genera thereby suggesting a common actin process, present already at the emergence of the family (~170 million years ago).

Establishment of the complete life cycle of Calicophoron daubneyi under experimental conditions.

The complex life cycle of the rumen fluke Calicophoron daubneyi is similar to that of the liver fluke Fasciola hepatica. Interestingly, C. daubneyi and F. hepatica share the same intermediate host, Galba truncatula. However, in contrast to its relative, experimental production of metacercariae is a major challenge for C. daubneyi, hampering a detailed analysis of its life cycle, especially in the definitive host. G. truncatula snails collected from natural habitats were bred in glass Petri dishes and fed dried organic lettuce leaves. C. daubneyi eggs were obtained from feces of naturally infected cattle and incubated until miracidia were hatching. Subsequently, these miracidia were allowed to infect snails, which were kept under specific laboratory conditions to monitor the shedding of metacercariae. In total, 177 G. truncatula snails were exposed to C. daubneyi miracidia during eleven snail infection trials. Sixty-eight of these snails survived for longer than 30 days post-infection (p.i.). From day 35 p.i., seven snails from five trials started shedding an average number of 106 metacercariae (range: 38-186) per snail. Three ewe lambs (aged 7-10 months) were inoculated orally with 150 metacercariae each. A different batch of metacercariae (obtained from three different snail trials) was used for each lamb. Another two lambs served as controls. All animals were regularly examined clinically, hematologically and coproscopically, using sedimentation techniques for the detection of trematode eggs. Low numbers of C. daubneyi eggs were detected in fecal samples of two of the three inoculated lambs on day 86 post-inoculation (yielding ≤ 2 epg), but only one lamb continued to shed eggs (up to 6 epg) until the end of the experiment (day 104 post-inoculation). None of the animals showed any abnormal clinical findings or blood parameters throughout the course of the study. Production of C. daubneyi metacercariae under laboratory conditions is reported, followed by experimental infection of the definitive host, thus completing the full life cycle of this parasite under experimental conditions. However, neither the survival rate of the snails nor the amount of metacercariae produced were comparable to previously published experiments using F. hepatica, necessitating further optimization of the laboratory protocols. Nevertheless, the results can serve as a starting point for more in-depth studies of this increasingly important trematode.

Considerations for Domestication of Novel Strains of Filamentous Fungi.

Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.

GlucoGenes®, a database of genes and proteins associated with glucose metabolism disorders, its description and applications in bioinformatics research

Data on the genetics and molecular biology of diabetes are accumulating rapidly. This poses the challenge of creating research tools for a rapid search for, structuring and analysis of information in this field. We have developed a web resource, GlucoGenes®, which includes a database and an Internet portal of genes and proteins associated with high glucose (hyperglycemia), low glucose (hypoglycemia), and both metabolic disorders. The data were collected using text mining of the publications indexed in PubMed and PubMed Central and analysis of gene networks associated with hyperglycemia, hypoglycemia and glucose variability performed with ANDSystems, a bioinformatics tool. GlucoGenes® is freely available at: https://glucogenes.sysbio.ru/genes/main. GlucoGenes® enables users to access and download information about genes and proteins associated with the risk of hyperglycemia and hypoglycemia, molecular regulators with hyperglycemic and antihyperglycemic activity, genes up-regulated by high glucose and/or low glucose, genes down-regulated by high glucose and/or low glucose, and molecules otherwise associated with the glucose metabolism disorders. With GlucoGenes®, an evolutionary analysis of genes associated with glucose metabolism disorders was performed. The results of the analysis revealed a significant increase (up to 40 %) in the proportion of genes with phylostratigraphic age index (PAI) values corresponding to the time of origin of multicellular organisms. Analysis of sequence conservation using the divergence index (DI) showed that most of the corresponding genes are highly conserved (DI < 0.6) or conservative (DI < 1). When analyzing single nucleotide polymorphism (SNP) in the proximal regions of promoters affecting the affinity of the TATA-binding protein, 181 SNP markers were found in the GlucoGenes® database, which can reduce (45 SNP markers) or increase (136 SNP markers) the expression of 52 genes. We believe that this resource will be a useful tool for further research in the field of molecular biology of diabetes.

Parasitofauna of Dolly Varden Salvelinus malma complex in Kamchatka

Systematized information on the species composition of parasites of S. malma complex in the water bodies of Kamchatka based on own and literature data is provided. Presented taxonomic list of parasites gives information about localization, distribution, host range, findings with indication of water body, malmoid form, infestation indices and authors of findings for each species. The parasitofauna of Dolly Varden in Kamchatka includes 65 species from 3 kingdoms, 10 types, 15 classes, 25 orders and 42 families. The most diverse taxa are trematodes (16 species), nematodes (10), myxosporidia (10), cestodes (8) and acanthocephalans (7). The basis of the parasitofauna of Dolly Varden in Kamchatka is formed by freshwater species (47), species with a complex life cycle (50), using fish as definitive hosts (38), having Holarctic and circumpolar distribution (29), being a part of the Arctic freshwater and Pacific piedmont faunal complexes (33), specific to fish of the genus Salvelinus, family Salmonidae and the order Salmoniformes (39). The high species and ecological diversity of Dolly Varden parasites is due to its ubiquitous distribution in the region and its complex population structure, including several ecotypes and forms that differ in life strategy, diet, and habitats.

Geological Complexity: Bridging Cosmic Evolution and the Evolution of Life

Earth occupies a unique position in Big History as a bridge between cosmic evolution and the rise of complex life. While discussions often emphasize monumental events like the Big Bang or the rise of civilizations, the intermediate phase of planetary formation and life’s emergence reveals the intricate interplay of cosmic, geological, and biological processes. Earth’s development—from the chaotic dynamics of the early solar system, including the Moon-forming collision, to the establishment of a protective magnetic field and diverse energy gradients—created the conditions necessary for life to arise and co-evolve with the planet’s systems. This co-evolution is evident in feedback loops such as carbon sequestration, atmospheric oxygenation, and life-driven erosion processes, which shaped Earth’s environment over billions of years. Despite challenges like Snowball Earth events, asteroid impacts, and mass extinctions, the planet’s systems maintained a delicate balance of habitability, with life itself playing an active regulatory role as suggested by the Gaia hypothesis. Understanding Earth’s improbable trajectory highlights the rarity of life-bearing planets, the fragility of planetary systems, and the profound interconnectedness of cosmic and biological evolution. As human activity increasingly disrupts Earth’s delicate balance, this perspective provides valuable insights into planetary sustainability and informs the search for life on other worlds.

Ultra-deep sequencing of somatic mutations induced by a maize transposon.

Cells accumulate mutations throughout development, contributing to cancer, aging, and evolution. Quantitative data on the abundance of de novo mutations within plants or animals are limited, as new mutations are often rare within a tissue and fall below the limits of current sequencing depths and error rates. Here, we show that mutations induced by the maize Mutator (Mu) transposon can be reliably quantified down to a detection limit of 1 part in 12,000. We measured the abundance of millions of de novo Mu insertions across four tissue types. Within a tissue, the distribution of de novo Mu allele frequencies was highly reproducible between plants, showing that, despite the stochastic nature of mutation, repeated statistical patterns of mutation abundance emerge. In contrast, there were significant differences in the allele frequency distribution between tissues. At the extremes, root was dominated by a small number of highly abundant de novo insertions, while endosperm was characterized by thousands of insertions at low allele frequencies. Finally, we used the measured pollen allele frequencies to reinterpret a classic genetic experiment, showing that evidence for late Mu activity in pollen are better explained by cell division statistics. These results provide insight into the complexity of mutation accumulation in multicellular organisms and a system to interrogate the factors that shape mutation abundance.

Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.

In multicellular organisms, Wnt proteins govern stem and progenitor cell renewal and differentiation to regulate embryonic development, adult tissue homeostasis and tissue regeneration. Defects in canonical Wnt signalling, which is transduced intracellularly by β-catenin, have been associated with developmental disorders, degenerative diseases and cancers. Although a simple model describing Wnt-β-catenin signalling is widely used to introduce this pathway and has largely remained unchanged over the past 30 years, in this Review we discuss recent studies that have provided important new insights into the mechanisms of Wnt production, receptor activation and intracellular signalling that advance our understanding of the molecular mechanisms that underlie this important cell-cell communication system. In addition, we review the recent development of molecules capable of activating the Wnt-β-catenin pathway with selectivity in vitro and in vivo that is enabling new lines of study to pave the way for the development of Wnt therapies for the treatment of human diseases.

A bi-kinase module sensitizes and potentiates plant immune signaling.

Systemic signaling is an essential hallmark of multicellular life. Pathogen encounter occurs locally but triggers organ-scale and organismic immune responses. In plants, elicitor perception provokes systemically expanding Ca2+ and H2O2 signals conferring immunity. Here, we identify a Ca2+ sensing bi-kinase module as becoming super-activated through mutual phosphorylation and as imposing synergistically enhanced NADPH oxidase activation. A combined two-layer bi-kinase/substrate phospho-code allows for sensitized signaling initiation already by near-resting elevations of Ca2+ concentration. Subsequently, it facilitates further signal wave proliferation with minimal Ca2+ amplitude requirement, triggering protective defense responses throughout the plant. Our study reveals how plants build and perpetuate trans-cellular immune signal proliferation while avoiding disturbance of ongoing cellular signaling along the path of response dissemination.

Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.

SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole. During colony differentiation, an almost infinite number of ecological and physiological population-forming forces are at work, creating complex, intricate colony structures with divergent functions. Understanding the assembly and dynamics of such populations requires resolving individual cells or cell groups within such macroscopic structures. Addressing how each cell contributes to the collective action requires pushing the resolution boundaries of key technologies that will be presented in this review. In particular, single-cell techniques provide powerful tools for studying bacterial multicellularity with unprecedented spatial and temporal resolution. These advancements include novel microscopic techniques, mass spectrometry imaging, flow cytometry, spatial transcriptomics, single-bacteria RNA sequencing, and the integration of spatiotemporal transcriptomics with microscopy, alongside advanced microfluidic cultivation systems. This review encourages exploring the synergistic potential of the new technologies in the study of bacterial multicellularity, with a particular focus on individuals in differentiated bacterial biofilms (colonies). It highlights how resolving population structures at the single-cell level and understanding their respective functions can elucidate the overarching functions of bacterial multicellular populations.

Programmed Cell Death Tunes Periodontitis.

To review current knowledge of the various processes of programmed cell death and their roles in immunoregulation in periodontitis. Relevant literature in the PubMed, Medline, and Scopus databases was searched, and a narrative review was performed. Programmed cell death and the regulation of its various pathways implicated in periodontal infection were reviewed. Multicellular organisms dispose of unnecessary or damaged cells via programmed cell death. Programmed cell death lies at the core of the balance of cell death and survival in pathological progress and infection. Periodontitis is a complex infectious disease involving virulence factors of periodontal pathogens and tightly regulated immune responses of the host. Different types of programmed cell death can play opposite roles in periodontitis or exert their action combinatorially. The coordinated system of various programmed cell death pathways and the extensive crosstalk among them play a fundamental role in the pathophysiology of periodontitis. Illuminating the precise roles and mechanisms of programmed cell death in periodontitis could open up novel therapeutic approaches.

A Primer on Proteomic Characterization of Intercellular Communication in a Virus Microenvironment.

Intercellular communication is fundamental to multicellular life and a core determinant of outcomes during viral infection, where the common goals of virus and host for persistence and replication are generally at odds. Hosts rely on encoded innate and adaptive immune responses to detect and clear viral pathogens, while viruses can exploit or disrupt these pathways and other intercellular communication processes to enhance their spread and promote pathogenesis. While virus-induced signaling can result in systemic changes to the host, striking alterations are observed within the cellular microenvironment directly surrounding a site of infection, termed the virus microenvironment (VME). Mechanisms employed by viruses to condition their VMEs are emerging and are critical for understanding the biology and pathologies of viral infections. Recent advances in experimental approaches, including proteomic methods, have enabled study of the VME in unprecedented detail. In this review article, we provide a primer on proteomic approaches used to study how viral infections alter intercellular communication, highlighting the ways in which these approaches have been implemented and the exciting biology they have uncovered. First, we consider the different molecules secreted by an infected cell, including proteins, either soluble or contained within extracellular vesicles, and metabolites. We further discuss the modalities of interactions facilitated by alteration at the cell surface of infected cells, including immunopeptide presentation and interactions with the extracellular matrix. Finally, we review spatial profiling approaches that have allowed distinguishing how specific subpopulations of cells within a VME respond to infection and alter their protein composition, discussing valuable insights these methods have offered.

Investigation of genes expression of the JAK/STAT signalling pathway and AMPs in the presence of Borrelia spirochetes in Ixodes ricinus

Multicellular animals need to control the spread of invading pathogens. This is a particular challenge for blood-feeding vectors such as ticks, which ingest large amounts of blood potentially laden with harmful microorganisms. Ticks have a basic innate immune system and protect themselves from infection through innate immune responses involving pathways such as Janus kinase (JAK) or the signalling transducer activator of transcription (STAT). Direct antimicrobial defence occurs through the rapid synthesis of numerous antimicrobial agents including antimicrobial peptides (AMPs). The tick Ixodes ricinus is one of the main vectors of the Lyme disease pathogen, the spirochete Borrelia burgdorferi sensu lato. Data suggest that the JAK/STAT signalling pathway controls the expression of AMPs and regulates the infection of the pathogen in the tick body. The innate immune system during the off-host period keeps the level of spirochete infection in check. Spirochetes may influence the innate immune response in ticks. Therefore, the aim of this study was to analyse the expression of the genes related to the JAK/STAT pathway and selected AMPs in questing ticks in which B. burgorferi s.l. was detected. In the ticks infected with spirochetes, overexpression of genes related to the JAK/STAT signalling pathway was observed in the case of STAM and SOCS genes. AMPs genes such as def1, ric, lzs were overexpressed with different expression patterns. The results obtained suggest that AMPs may be involved in infection management in ticks.

Metal Ion Signaling in Biomedicine.

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species are defined by their genomes, and differences between individuals within a given species directly result from variations in their genetic codes. While genetic alterations can give rise to disease-causing acquisitions of distinct cell identities, it is now well-established that biochemical imbalances within a cell can also lead to cellular dysfunction and diseases. Specifically, nongenetic chemical events orchestrate cell metabolism and transcriptional programs that govern functional cell identity. Thus, imbalances in cell signaling, which broadly defines the conversion of extracellular signals into intracellular biochemical changes, can also contribute to the acquisition of diseased cell states. Metal ions exhibit unique chemical properties that can be exploited by the cell. For instance, metal ions maintain the ionic balance within the cell, coordinate amino acid residues or nucleobases altering folding and function of biomolecules, or directly catalyze specific chemical reactions. Thus, metals are essential cell signaling effectors in normal physiology and disease. Deciphering metal ion signaling is a challenging endeavor that can illuminate pathways to be targeted for therapeutic intervention. Here, we review key cellular processes where metal ions play essential roles and describe how targeting metal ion signaling pathways has been instrumental to dissecting the biochemistry of the cell and how this has led to the development of effective therapeutic strategies.

The Formation of a Waliullahi Public in Eighteenth-Century India

Abstract Shah Waliullah of Delhi, the famous eighteenth-century Naqshbandi, is widely recognized as a major figure in the emergence of Islamic reformist discourse in South Asia, but we still have little sense of the first audiences who engaged with his ideas. This article seeks to further our understanding of the crystallization of this reform-oriented Waliullahi public by recreating the fragmentary biography of his lifelong companion and disciple Nurullah Budhanwi. While he didn't write any books that survive, accounts of Nurullah's life and reports of his oral statements are scattered throughout texts produced by Waliullah's circle, and provide insight into the conflicting intellectual, ethical, and affective responses to Waliullah's thought in his own lifetime. This article demonstrates that Nurullah felt deep concern about what his acceptance of Waliullahi reformist ideas might mean for his material and spiritual life, suggesting that the formation of this new reform-oriented public was a fraught process entailing contestation and negotiation. Nurullah's biography shows us that intellectual histories that rely on discussions of abstract ideas of famous thinkers or the simplistic reconstruction of scholarly networks fail to do justice to the complex life of ideas in the world.