A branching process with coalescence to model random phylogenetic networks

We introduce a biologically natural, mathematically tractable model of random phylogenetic network to describe evolution in the presence of hybridization. One of the features of this model is that the hybridization rate of the lineages correlates negatively with their phylogenetic distance. We give formulas / characterizations for quantities of biological interest that make them straightforward to compute in practice. We show that the appropriately rescaled network, seen as a metric space, converges to the Brownian continuum random tree, and that the uniformly rooted network has a local weak limit, which we describe explicitly

Synthèse en solution et en phase solide de petits carbocyles et étude de la formation de macrocycles à quatorze membres par réaction au palladium et au cuivre

La synthèse en solution et son application à la synthèse sur support solide sont présentées pour: (1) La réaction d'alkylation du connecteur malonate, (2) L'étude de la formation de cycles carbonés à cinq, six et sept membres avec deux connecteurs, le malonate et le phénylacétate, (3) L'étude de la formation de macrocycles à quatorze membres par cyclisation de type iodure aromatique--étain (type Stille) et de type étain--étain (type Piers)

Experimental silicification of the extremophilic Archaea Pyrococcus abyssi and Methanocaldococcus jannaschii: applications in the search for evidence of life in early Earth and extraterrestrial rocks

International audienceHydrothermal activity was common on the early Earth and associated micro-organisms would most likely have included thermophilic to hyperthermophilic species. 3.5–3.3 billion-year-old, hydrothermally influenced rocks contain silicified microbial mats and colonies that must have been bathed in warm to hot hydrothermal emanations. Could they represent thermophilic or hyperthermophilic micro-organisms and if so, how were they preserved? We present the results of an experiment to silicify anaerobic, hyperthermophilic micro-organisms from the Archaea Domain Pyrococcus abyssi and Methanocaldococcus jannaschii, that could have lived on the early Earth. The micro-organisms were placed in a silica-saturated medium for periods up to 1 year. Pyrococcus abyssi cells were fossilized but the M. jannaschii cells lysed naturally after the exponential growth phase, apart from a few cells and cell remains, and were not silicified although their extracellular polymeric substances were. In this first simulated fossilization of archaeal strains, our results suggest that differences between species have a strong influence on the potential for different micro-organisms to be preserved by fossilization and that those found in the fossil record represent probably only a part of the original diversity. Our results have important consequences for biosignatures in hydrothermal or hydrothermally influenced deposits on Earth, as well as on early Mars, as environmental conditions were similar on the young terrestrial planets and traces of early Martian life may have been similarly preserved as silicified microfossils

Examination of Urinary Pesticide Concentrations, Protective Behaviors, and Risk Perceptions Among Latino and Latina Farmworkers in Southwestern Idaho

Introduction: Studies have documented high levels of pesticide exposure among men farmworkers; however, few have examined exposures or the experiences of women farmworkers. Data gaps also exist regarding farmworkers’ perceived risk and control related to pesticides, information that is critical to develop protective interventions. Objective: We aimed to compare urinary pesticide biomarker concentrations between Latino and Latina farmworkers and examine associations with occupational characteristics, risk perceptions, perceived control, and protective behaviors. Methods: We enrolled a convenience sample of 62 farmworkers (30 men and 32 women) during the pesticide spray season from April–July 2022 in southwestern Idaho. Participants were asked to complete two visits within a seven-day period; at each visit, we collected a urine sample and administered a questionnaire assessing demographic and occupational information. Urine samples were composited and analyzed for 17 biomarkers of herbicides and of organophosphate (OP) and pyrethroid insecticides. Results: Ten pesticide biomarkers (TCPy, MDA, PNP, 3-PBA, 4-F-3-PBA, cis- and trans-DCCA, 2,4-D, Glyphosate, AMPA) were detected in \u3e80% of samples. Men and women had similar urinary biomarker concentrations (p = 0.19–0.94); however, women worked significantly fewer hours than men (p = 0.01), wore similar or greater levels of Personal Protective Equipment (PPE), and were slightly more likely to report having experienced an Acute Pesticide Poisoning (26% of women vs. 14% of men; p = 0.25). We observed inconsistencies in risk perceptions, perceived control, and protective behaviors among men. Discussion: Our study is one the first to examine pesticide exposure and risk perceptions among a cohort of farmworkers balanced on gender. Taken with previous findings, our results suggest that factors such as job tasks, biological susceptibility, or access to trainings and protective equipment might uniquely impact women farmworkers’ exposure and/or vulnerability to pesticides. Women represent an increasing proportion of the agricultural workforce, and larger studies are needed to disentangle these findings

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

A branching process with coalescence to model random phylogenetic networks

We introduce a biologically natural, mathematically tractable model of random phylogenetic network to describe evolution in the presence of hybridization. One of the features of this model is that the hybridization rate of the lineages correlates negatively with their phylogenetic distance. We give formulas / characterizations for quantities of biological interest that make them straightforward to compute in practice. We show that the appropriately rescaled network, seen as a metric space, converges to the Brownian continuum random tree, and that the uniformly rooted network has a local weak limit, which we describe explicitly

The Moran forest

Starting from any graph on {1,. .. , n}, consider the Markov chain where at each time-step a uniformly chosen vertex is disconnected from all of its neighbors and reconnected to another uniformly chosen vertex. This Markov chain has a stationary distribution whose support is the set of non-empty forests on {1,. .. , n}. The random forest corresponding to this stationary distribution has interesting connections with the uniform rooted labeled tree and the uniform attachment tree. We fully characterize its degree distribution , the distribution of its number of trees, and the limit distribution of the size of a tree sampled uniformly. We also show that the size of the largest tree is asymptotically α log n, where α = (1 − log(e − 1)) −1 ≈ 2.18, and that the degree of the most connected vertex is asymptotically log n/ log log n