RASopathies influences on neuroanatomical variation in children.

BACKGROUND: RASopathies are a group of disorders characterized by pathogenic mutations in the Ras-mitogen-activated protein kinase (Ras/MAPK) signaling pathway. Distinct pathogenic variants in genes encoding proteins in the Ras/MAPK pathway cause Noonan syndrome (NS) and neurofibromatosis type 1 (NF1), which are associated with increased risk for autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD). METHODS: This study examines the effect RASopathies (NS and NF1) has on human neuroanatomy, specifically on surface area (SA), cortical thickness (CT), and subcortical volumes. We compared structural T1-weighted images, using vertex-based analysis for cortical measures and Desikan ROI parcellation for subcortical volumes on children with RASopathies (n=91, mean age = 8.81, SD = 2.12) to sex- and age-matched TD (n=74, mean age=9.07, SD = 1.77). RESULTS: Compared to TD, RASopathies had convergent effects on SA and CT, exhibiting increased SA in the precentral gyrus, decreased SA in occipital regions, and thinner CT in the precentral gyrus. RASopathies exhibit divergent effects on subcortical volumes, with syndrome-specific influences from NS and NF1. Overall children with NS display decreased volumes in striatal and thalamic structures and children with NF1 display increased volumes in the hippocampus, amygdala, and thalamus. CONCLUSIONS: Our study reveals the converging and diverging neuroanatomical effects of RASopathies on human neurodevelopment. The convergence of cortical effects on SA and CT indicates a shared influence of Ras/MAPK hyperactivation on the human brain. Therefore, considering these measures as objective outcome indicators for targeted treatments is imperative.

Immunological and hematological findings as major features in a patient with a new germline pathogenic CBL variant.

Casitas B-lineage lymphoma (CBL) encodes an adaptor protein with E3-ligase activity negatively controlling intracellular signaling downstream of receptor tyrosine kinases. Somatic CBL mutations play a driver role in a variety of cancers, particularly myeloid malignancies, whereas germline defects in the same gene underlie a RASopathy having clinical overlap with Noonan syndrome (NS) and predisposing to juvenile myelomonocytic leukemia and vasculitis. Other features of the disorder include cardiac defects, postnatal growth delay, cryptorchidism, facial dysmorphisms, and predisposition to develop autoimmune disorders. Here we report a novel CBL variant (c.1202G>T; p.Cys401Phe) occurring de novo in a subject with café-au-lait macules, feeding difficulties, mild dysmorphic features, psychomotor delay, autism spectrum disorder, thrombocytopenia, hepatosplenomegaly, and recurrent hypertransaminasemia. The identified variant affects an evolutionarily conserved residue located in the RING finger domain, a known mutational hot spot of both germline and somatic mutations. Functional studies documented enhanced EGF-induced ERK phosphorylation in transiently transfected COS1 cells. The present findings further support the association of pathogenic CBL variants with immunological and hematological manifestations in the context of a presentation with only minor findings reminiscent of NS or a clinically related RASopathy.

Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system.

Imaging reporter genes are indispensable for visualising biological processes in living subjects, particularly in cancer research where they have been used to observe tumour development, cancer cell dissemination, and treatment response. Engineering reporter genes into the germline frequently involves single imaging modality reporters operating over limited spatial scales. To address these limitations, we developed an inducible triple-reporter mouse model (Rosa26LSL - NRL) that integrates reporters for complementary imaging modalities, flfluorescence, bioluminescence and positron emission tomography (PET), along with inducible Cre-lox functionality for precise spatiotemporal control of reporter expression. We demonstrated robust reporter inducibility across various tissues in the Rosa26LSL - NRL mouse, facilitating effective tracking and characterisation of tumours in liver and lung cancer mouse models. We precisely pinpointed tumour location using multimodal whole-body imaging which guided in situ lung microscopy to visualise cell-cell interactions within the tumour microenvironment. The triple-reporter system establishes a robust new platform technology for multi-scale investigation of biological processes within whole animals, enabling tissue-specific and sensitive cell tracking, spanning from the whole-body to cellular scales.

Is it time for a precision health approach to the management of newborn hyperbilirubinemia?

Newborn hyperbilirubinemia during the first two weeks of life is one of most common problems requiring management decisions by a pediatrician. However, high bilirubin levels in the circulation have been associated with neurologic injury under a variety of conditions encountered in the newborn infant, such as hemolysis. The risk for developing dangerous hyperbilirubinemia is multifactorial and is determined by a complex set of factors related to a newborn infant's genetic capacities as well as intra- and extrauterine exposures. To this end, a precision health approach based on the integration of prenatal genetic and postnatal diagnostic measures might improve the management of neonatal hyperbilirubinemia.

Vascular health years after a hypertensive disorder of pregnancy: The EPOCH study.

BACKGROUND: Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum. METHODS: Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound. RESULTS: Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P = .034), higher calculated ASCVD risk (0.6 vs 0.4, P = .02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P = .0004; diastolic: 75.2 vs 69.8 mm Hg, P = .0004), and higher augmentation index values (7.7 vs 2.3, P = .03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P = .29) or reactive hyperemia index (2.1 vs 2.1, P = .93), nor in pulse wave amplitude (416 vs 326, P = .11), carotid elastic modulus (445 vs 426, P = .36), or carotid beta stiffness (2.8 vs 2.8, P = .86). CONCLUSION: Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis.

New CMS Nursing Home Ownership Data: Major Gaps And Discrepancies.

Nursing home ownership has become increasingly complicated, partly because of the growth of facilities owned by institutional investors such as private equity (PE) firms and real estate investment trusts (REITs). Although the ownership transparency and accountability of nursing homes have historically been poor, the Biden administration's nursing home reform plans released in 2022 included a series of data releases on ownership. However, our evaluation of the newly released data identified several gaps: One-third of PE and fewer than one-fifth of REIT investments identified in the proprietary Irving Levin Associates and S&P Capital IQ investment data were present in Centers for Medicare and Medicaid Services (CMS) publicly available ownership data. Similarly, we obtained different results when searching for the ten top common owners of nursing homes using CMS data and facility survey reports of chain ownership. Finally, ownership percentages were missing in the CMS data for 82.40 percent of owners in the top ten chains and 55.21 percent of owners across all US facilities. Although the new data represent an important step forward, we highlight additional steps to ensure that the data are timely, accurate, and responsive. Transparent ownership data are fundamental to understanding the adequacy of public payments to provide patient care, enable policy makers to make timely decisions, and evaluate nursing home quality.

Identifying therapeutic candidates for endometriosis through a transcriptomics-based drug repositioning approach.

Existing medical treatments for endometriosis-related pain are often ineffective, underscoring the need for new therapeutic strategies. In this study, we applied a computational drug repurposing pipeline to stratified and unstratified disease signatures based on endometrial gene expression data to identify potential therapeutics from existing drugs, based on expression reversal. Of 3,131 unique genes differentially expressed by at least one of six endometriosis signatures, only 308 (9.8%) were in common; however, 221 out of 299 drugs identified, (73.9%) were shared. We selected fenoprofen, an uncommonly prescribed NSAID that was the top therapeutic candidate for further investigation. When testing fenoprofen in an established rat model of endometriosis, fenoprofen successfully alleviated endometriosis-associated vaginal hyperalgesia, a surrogate marker for endometriosis-related pain. These findings validate fenoprofen as a therapeutic that could be utilized more frequently for endometriosis and suggest the utility of the aforementioned computational drug repurposing approach for endometriosis.

A rapidly time-varying equatorial jet in Jupiter's deep interior.

Planetary magnetic fields provide a window into the otherwise largely inaccessible dynamics of a planet's deep interior. In particular, interaction between fluid flow in electrically conducting interior regions and the magnetic field there gives rise to observable secular variation (time dependency) of the externally observed magnetic field. Secular variation of Jupiter's field has recently been revealed1-3 and been shown to arise, in part, from an axisymmetric, equatorial jet2. Whether this jet is time dependent has not previously been addressed, yet it is of critical importance for understanding the dynamics of the planet's interior. If steady, it would probably be a manifestation of deep dynamo convective flow (and jets are anticipated as part of that flow4-9) but if time dependent on a timescale much shorter than the convective turnover timescale of several hundred years, it would probably have a different origin. Here we show that the jet has a wavelike fluctuation with a period of roughly 4 years, strongly suggestive of the presence of a torsional oscillation10 (a cylindrically symmetric oscillating flow about the rotation axis) or a localized Alfvén wave in Jupiter's metallic hydrogen interior. This opens a pathway towards revealing otherwise hidden aspects of the magnetic field within the metallic hydrogen region and hence constraining the dynamo that generates Jupiter's magnetic field.

Corrigendum: Advances and potential of omics studies for understanding the development of food allergy.

[This corrects the article DOI: 10.3389/falgy.2023.1149008.].

Reassessing acquired neonatal intestinal diseases using unsupervised machine learning.

BACKGROUND: Acquired neonatal intestinal diseases have an array of overlapping presentations and are often labeled under the dichotomous classification of necrotizing enterocolitis (which is poorly defined) or spontaneous intestinal perforation, hindering more precise diagnosis and research. The objective of this study was to take a fresh look at neonatal intestinal disease classification using unsupervised machine learning. METHODS: Patients admitted to the University of Florida Shands Neonatal Intensive Care Unit January 2013-September 2019 diagnosed with an intestinal injury, or had imaging findings of portal venous gas, pneumatosis, abdominal free air, or had an abdominal drain placed or exploratory laparotomy during admission were included. Congenital gastroschisis, omphalocele, intestinal atresia, malrotation were excluded. Data was collected via retrospective chart review with subsequent hierarchal, unsupervised clustering analysis. RESULTS: Five clusters of intestinal injury were identified: Cluster 1 deemed the "Low Mortality" cluster, Cluster 2 deemed the "Mature with Inflammation" cluster, Cluster 3 deemed the "Immature with High Mortality" cluster, Cluster 4 deemed the "Late Injury at Full Feeds" cluster, and Cluster 5 deemed the "Late Injury with High Rate of Intestinal Necrosis" cluster. CONCLUSION: Unsupervised machine learning can be used to cluster acquired neonatal intestinal injuries. Future study with larger multicenter datasets is needed to further refine and classify types of intestinal diseases. IMPACT: Unsupervised machine learning can be used to cluster types of acquired neonatal intestinal injury. Five major clusters of acquired neonatal intestinal injury are described, each with unique features. The clusters herein described deserve future, multicenter study to determine more specific early biomarkers and tailored therapeutic interventions to improve outcomes of often devastating neonatal acquired intestinal injuries.

Integrating evidence and causal mapping of factors that influence medication decision-making by pregnant women at risk of hypertensive disorder: protocol for a scoping review.

INTRODUCTION: In 2018, the American College of Obstetricians and Gynecologists recommended low-dose aspirin to prevent the onset of pre-eclampsia among women who were at high risk. Factors influencing women's acceptance of this recommendation span multiple sectors and levels. Understanding how these factors interact will help stakeholders design effective population-level intervention strategies. Our study aims to identify and map relationships among factors influencing the medication decisions of pregnant women at risk of hypertensive disorders. METHODS AND ANALYSIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines will be followed for this review. A research librarian developed a comprehensive search strategy to retrieve published and unpublished English studies after 1 January 1980, involving factors that influence pregnant women's uptake and adherence to medication for gestational hypertensive disorders. This literature includes perceptions, patterns, acceptance, refusal, tendencies, probability and service utilisation. We will search PubMed, Embase, Web of Science and CINAHL. Reference lists of the selected papers will be searched manually to identify more relevant studies. A two-stage independent screening, consisting of title and abstract screening, followed by full-text screening, will be conducted by two independent reviewers to identify eligible articles. Extracted data will be recorded in a customised variable extraction form and input into a Microsoft Access database. The PRISMA-ScR will be used to guide the presentation of the results, which will be presented in a table and causal map to demonstrate the relationships between extracted variables and medication uptake and adherence. A conceptual simulation model will be formulated to validate the logic of the relationships between variables and identify knowledge gaps. Lastly, experts and stakeholders will be invited to critique and comment on the results. ETHICS AND DISSEMINATION: This study does not require ethical approval. The full review results will be presented at a relevant conference and submitted to a peer-reviewed scientific journal for publication.

Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth.

Preterm birth affects ~10% of pregnancies in the US. Despite familial associations, identifying at-risk genetic loci has been challenging. We built deep learning and graphical models to score mutational effects at base resolution via integrating the pregnant myometrial epigenome and large-scale patient genomes with spontaneous preterm birth (sPTB) from European and African American cohorts. We uncovered previously unidentified sPTB genes that are involved in myometrial muscle relaxation and inflammatory responses and that are regulated by the progesterone receptor near labor onset. We studied genomic variants in these genes in our recruited pregnant women administered progestin prophylaxis. We observed that mutation burden in these genes was predictive of responses to progestin treatment for preterm birth. To advance therapeutic development, we screened ~4000 compounds, identified candidate molecules that affect our identified genes, and experimentally validated their therapeutic effects on regulating labor. Together, our integrative approach revealed the druggable genome in preterm birth and provided a generalizable framework for studying complex diseases.

Discovery of sparse, reliable omic biomarkers with Stabl.

Adoption of high-content omic technologies in clinical studies, coupled with computational methods, has yielded an abundance of candidate biomarkers. However, translating such findings into bona fide clinical biomarkers remains challenging. To facilitate this process, we introduce Stabl, a general machine learning method that identifies a sparse, reliable set of biomarkers by integrating noise injection and a data-driven signal-to-noise threshold into multivariable predictive modeling. Evaluation of Stabl on synthetic datasets and five independent clinical studies demonstrates improved biomarker sparsity and reliability compared to commonly used sparsity-promoting regularization methods while maintaining predictive performance; it distills datasets containing 1,400-35,000 features down to 4-34 candidate biomarkers. Stabl extends to multi-omic integration tasks, enabling biological interpretation of complex predictive models, as it hones in on a shortlist of proteomic, metabolomic and cytometric events predicting labor onset, microbial biomarkers of pre-term birth and a pre-operative immune signature of post-surgical infections. Stabl is available at https://github.com/gregbellan/Stabl .

C-di-AMP accumulation disrupts glutathione metabolism and inhibits virulence program expression in Listeria monocytogenes.

C-di-AMP is an essential second messenger in many bacteria but its levels must be regulated. Unregulated c-di-AMP accumulation attenuates the virulence of many bacterial pathogens, including those that do not require c-di-AMP for growth. However, the mechanisms by which c-di-AMP regulates bacterial pathogenesis remain poorly understood. In Listeria monocytogenes , a mutant lacking both c-di-AMP phosphodiesterases, denoted as the ΔPDE mutant, accumulates a high c-di-AMP level and is significantly attenuated in the mouse model of systemic infection. All key L. monocytogenes virulence genes are transcriptionally upregulated by the master transcription factor PrfA, which is activated by reduced glutathione (GSH) during infection. Our transcriptomic analysis revealed that the ΔPDE mutant is significantly impaired for the expression of virulence genes within the PrfA core regulon. Subsequent quantitative gene expression analyses validated this phenotype both at the basal level and upon PrfA activation by GSH. A constitutively active PrfA * variant, PrfA G145S, which mimics the GSH-bound conformation, restores virulence gene expression in ΔPDE but only partially rescues virulence defect. Through GSH quantification and uptake assays, we found that the ΔPDE strain is significantly depleted for GSH, and that c-di-AMP inhibits GSH uptake. Constitutive expression of gshF (encoding a GSH synthetase) does not restore GSH levels in the ΔPDE strain, suggesting that c-di-AMP inhibits GSH synthesis activity or promotes GSH catabolism. Taken together, our data reveals GSH metabolism as another pathway that is regulated by c-di-AMP. C-di-AMP accumulation depletes cytoplasmic GSH levels within L. monocytogenes that leads to impaired virulence program expression. IMPORTANCE: C-di-AMP regulates both bacterial pathogenesis and interactions with the host. Although c-di-AMP is essential in many bacteria, its accumulation also attenuates the virulence of many bacterial pathogens. Therefore, disrupting c-di-AMP homeostasis is a promising antibacterial treatment strategy, and has inspired several studies that screened for chemical inhibitors of c-di-AMP phosphodiesterases. However, the mechanisms by which c-di-AMP accumulation diminishes bacterial pathogenesis are poorly understood. Such understanding will reveal the molecular function of c-di-AMP, and inform therapeutic development strategies. Here, we identify GSH metabolism as a pathway regulated by c-di-AMP that is pertinent to L. monocytogenes replication in the host. Given the role of GSH as a virulence signal, nutrient, and antioxidant, GSH depletion impairs virulence program expression and likely diminishes host adaptation.

Exogenous butyrate inhibits butyrogenic metabolism and alters virulence phenotypes in Clostridioides difficile.

The gut microbiome engenders colonization resistance against the diarrheal pathogen Clostridioides difficile, but the molecular basis of this colonization resistance is incompletely understood. A prominent class of gut microbiome-produced metabolites important for colonization resistance against C. difficile is short-chain fatty acids (SCFAs). In particular, one SCFA (butyrate) decreases the fitness of C. difficile in vitro and is correlated with C. difficile-inhospitable gut environments, both in mice and in humans. Here, we demonstrate that butyrate-dependent growth inhibition in C. difficile occurs under conditions where C. difficile also produces butyrate as a metabolic end product. Furthermore, we show that exogenous butyrate is internalized into C. difficile cells and is incorporated into intracellular CoA pools where it is metabolized in a reverse (energetically unfavorable) direction to crotonyl-CoA and (S)-3-hydroxybutyryl-CoA and/or 4-hydroxybutyryl-CoA. This internalization of butyrate and reverse metabolic flow of a butyrogenic pathway(s) in C. difficile coincides with alterations in toxin release and sporulation. Together, this work highlights butyrate as a marker of a C. difficile-inhospitable environment to which C. difficile responds by releasing its diarrheagenic toxins and producing environmentally resistant spores necessary for transmission between hosts. These findings provide foundational data for understanding the molecular and genetic basis of how C. difficile growth is inhibited by butyrate and how butyrate alters C. difficile virulence in the face of a highly competitive and dynamic gut environment.IMPORTANCEThe gut microbiome engenders colonization resistance against the diarrheal pathogen Clostridioides difficile, but the molecular basis of this colonization resistance is incompletely understood, which hinders the development of novel therapeutic interventions for C. difficile infection (CDI). We investigated how C. difficile responds to butyrate, an end-product of gut microbiome community metabolism which inhibits C. difficile growth. We show that exogenously produced butyrate is internalized into C. difficile, which inhibits C. difficile growth by interfering with its own butyrate production. This growth inhibition coincides with increased toxin release from C. difficile cells and the production of environmentally resistant spores necessary for transmission between hosts. Future work to disentangle the molecular mechanisms underlying these growth and virulence phenotypes will likely lead to new strategies to restrict C. difficile growth in the gut and minimize its pathogenesis during CDI.

Large-scale proteomics in the first trimester of pregnancy predict psychopathology and temperament in preschool children: an exploratory study.

BACKGROUND: Understanding the prenatal origins of children's psychopathology is a fundamental goal in developmental and clinical science. Recent research suggests that inflammation during pregnancy can trigger a cascade of fetal programming changes that contribute to vulnerability for the emergence of psychopathology. Most studies, however, have focused on a handful of proinflammatory cytokines and have not explored a range of prenatal biological pathways that may be involved in increasing postnatal risk for emotional and behavioral difficulties. METHODS: Using extreme gradient boosted machine learning models, we explored large-scale proteomics, considering over 1,000 proteins from first trimester blood samples, to predict behavior in early childhood. Mothers reported on their 3- to 5-year-old children's (N = 89, 51% female) temperament (Child Behavior Questionnaire) and psychopathology (Child Behavior Checklist). RESULTS: We found that machine learning models of prenatal proteomics predict 5%-10% of the variance in children's sadness, perceptual sensitivity, attention problems, and emotional reactivity. Enrichment analyses identified immune function, nervous system development, and cell signaling pathways as being particularly important in predicting children's outcomes. CONCLUSIONS: Our findings, though exploratory, suggest processes in early pregnancy that are related to functioning in early childhood. Predictive features included far more proteins than have been considered in prior work. Specifically, proteins implicated in inflammation, in the development of the central nervous system, and in key cell-signaling pathways were enriched in relation to child temperament and psychopathology measures.

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study.

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.

Potential endpoints for assessment of bone health in persons with neurofibromatosis type 1.

Neurofibromatosis type 1 is a genetic syndrome characterized by a wide variety of tumor and non-tumor manifestations. Bone-related issues, such as scoliosis, tibial dysplasia, and low bone mineral density, are a significant source of morbidity for this population with limited treatment options. Some of the challenges to developing such treatments include the lack of consensus regarding the optimal methods to assess bone health in neurofibromatosis type 1 and limited data regarding the natural history of these manifestations. In this review, the Functional Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration: (1) presents the available techniques for measuring overall bone health and metabolism in persons with neurofibromatosis type 1, (2) reviews data for use of each of these measures in the neurofibromatosis type 1 population, and (3) describes the strengths and limitations for each method as they might be used in clinical trials targeting neurofibromatosis type 1 bone manifestations. The Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration supports the development of a prospective, longitudinal natural history study focusing on the bone-related manifestations and relevant biomarkers of neurofibromatosis type 1. In addition, we suggest that the neurofibromatosis type 1 research community consider adding the less burdensome measurements of bone health as exploratory endpoints in ongoing or planned clinical trials for other neurofibromatosis type 1 manifestations to expand knowledge in the field.

Modelling the structure and evolution of cultural information as quasispecies.

We present a novel mode of cultural evolution whereby some forms of transmission may be modelled as quasispecies. The model incorporates the effect of high rates of error in certain forms of communication; while also building on the structural similarities between biological molecules and written language. Firstly, both written language and key biological molecules, such as RNA and proteins, are modular. Within these molecules, structural domains may be recombined, while retaining their function. Likewise, sentences are structured as combinations of clauses, in which each clause contains a domain of information. The clausal structure permits the recombination of information to adopt different meanings, while allowing each unit to retain its identity. Secondly, by virtue of intrinsically-high error rates, we show that some, but not all, aspects of communicated culture information exists as rapidly evolving clouds within the population. These clouds of cultural information behave as quasispecies, which we model with varying mutation rates and suitable selection coefficients. We then integrate these ideas with the application of Shannon Diversity Index to produce a more holistic view of culture that is centred on the evolution of its information. Re-imagining culture, as evolving clouds of information, unifies the mode in which information is stored culturally and biologically, and opens up new avenues of comparative analysis.