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Background: Inference of population structure is crucial for studies of human evolutionary history and genome-wide association studies. While several genomic regions have been reported to distort population structure analysis of European populations, no systematic analysis has been performed on non-European continental groups and with the latest human genome assembly. Methods: Using the 1000 Genomes Project high coverage whole-genome sequencing data from four major continental groups (Europe, East Asia, South Asia, and Africa), we developed a statistical framework and systematically detected genomic regions with unusual contributions to the inference of population structure for each of the continental groups. Results: We identified and characterized 27 unusual genomic regions mapped to GRCh38, including 13 regions around centromeres, 2 with chromosomal inversions, 8 under natural selection, and 4 with unknown causes. Excluding these regions would result in a more interpretable population structure inferred by principal components analysis and ADMIXTURE analysis. Conclusions: Unusual genomic patterns in certain regions can distort the inference of population structure. Our compiled list of these unusual regions will be useful for many population-genetic studies, including those from non-European populations. [ABSTRACT FROM AUTHOR]

Multiplexed PCR amplicon sequencing (AmpSeq) is an increasingly popular application for cost‐effective monitoring of threatened species and managed wildlife populations, and shows strong potential for the genomic epidemiology of infectious disease. AmpSeq data from infectious microbes can inform disease control in multiple ways, such as by measuring drug resistance marker prevalence, distinguishing imported from local cases, and determining the effectiveness of therapeutics. We describe the design and comparative evaluation of two new AmpSeq assays for Plasmodium falciparum malaria parasites: a four‐locus panel ("4CAST") composed of highly diverse antigens, and a 129‐locus panel ("AMPLseq") composed of drug resistance markers, highly diverse loci for inferring relatedness, and a locus to detect Plasmodium vivax co‐infection. We explore the performance of each panel in various public health use cases with in silico simulations as well as empirical experiments. The 4CAST panel appears highly suitable for evaluating the number of distinct parasite strains within samples (complexity of infection), showing strong performance across a wide range of parasitaemia levels without a DNA pre‐amplification step. For relatedness inference, the larger AMPLseq panel performs similarly to two existing panels of comparable size, despite differences in the data and approach used for designing each panel. Finally, we describe an R package (paneljudge) that facilitates the design and comparative evaluation of genetic panels for relatedness estimation, and we provide general guidance on the design and implementation of AmpSeq panels for the genomic epidemiology of infectious disease. [ABSTRACT FROM AUTHOR]

The neglected but highly prevalent Plasmodium vivax in South-east Asia and South America poses a great challenge, with regards to long-term in-vitro culturing and heavily limited functional assays. Such visible challenges as well as narrowed progress in development of experimental research tools hinders development of new drugs and vaccines. The leading vaccine candidate antigen Plasmodium vivax Duffy Binding Protein (PvDBP), is essential for reticulocyte invasion by binding to its cognate receptor, the Duffy Antigen Receptor for Chemokines (DARC), on the host's reticulocyte surface. Despite its highly polymorphic nature, the amino-terminal cysteine-rich region II of PvDBP (PvDBPII) has been considered as an attractive target for vaccine-mediated immunity and has successfully completed the clinical trial Phase 1. Although this molecule is an attractive vaccine candidate against vivax malaria, there is still a question on its viability due to recent findings, suggesting that there are still some aspects which needs to be looked into further. The highly polymorphic nature of PvDBPII and strain-specific immunity due to PvDBPII allelic variation in Bc epitopes may complicate vaccine efficacy. Emergence of various blood-stage antigens, such as PvRBP, PvEBP and supposedly many more might stand in the way of attaining full protection from PvDBPII. As a result, there is an urgent need to assess and re-assess various caveats connected to PvDBP, which might help in designing a long-term promising vaccine for P. vivax malaria. This review mainly deals with a bunch of rising concerns for validation of DBPII as a vaccine candidate antigen for P. vivax malaria. [ABSTRACT FROM AUTHOR]

Background: Human babesiosis, caused by parasites of the genus Babesia, is an emerging and re-emerging tick-borne disease that is mainly transmitted by tick bites and infected blood transfusion. Babesia duncani has caused majority of human babesiosis in Canada; however, limited data are available to correlate its genomic information and biological features. Results: We generated a B. duncani reference genome using Oxford Nanopore Technology (ONT) and Illumina sequencing technology and uncovered its biological features and phylogenetic relationship with other Apicomplexa parasites. Phylogenetic analyses revealed that B. duncani form a clade distinct from B. microti, Babesia spp. infective to bovine and ovine species, and Theileria spp. infective to bovines. We identified the largest species-specific gene family that could be applied as diagnostic markers for this pathogen. In addition, two gene families show signals of significant expansion and several genes that present signatures of positive selection in B. duncani, suggesting their possible roles in the capability of this parasite to infect humans or tick vectors. Conclusions: Using ONT sequencing and Illumina sequencing technologies, we provide the first B. duncani reference genome and confirm that B. duncani forms a phylogenetically distinct clade from other Piroplasm parasites. Comparative genomic analyses show that two gene families are significantly expanded in B. duncani and may play important roles in host cell invasion and virulence of B. duncani. Our study provides basic information for further exploring B. duncani features, such as host-parasite and tick-parasite interactions. [ABSTRACT FROM AUTHOR]

The pain relief formula "Ya Pa Som Kho-Khlan (YPSKK)" or "ยาผสมโคคลาน" in Thai is officially recorded in the Natural List of Essential Medicines (NLEM) of Thailand. The main component is Mallotus repandus (Willd.) Müll. Arg.; however, Anamirta cocculus (L.) Wight & Arn and Croton caudatus Gleiseler share the same common name: "Kho-Khlan". Confused usage of A. cocculus or C. caudatus can have effects via toxicity or unsuccessful treatment. This study aimed to combine a high-performance thin-layer chromatography (HPTLC) technique and DNA barcoding coupled with high-resolution melting (Bar-HRM) to differentiate M. repandus from the other two species. The M. repandus extract exhibited a distinct HPTLC profile that could be used to differentiate it from the others. DNA barcodes of the rbcL, matK, ITS and psbA-trnH intergenic spacer regions of all the plants were established to assist HPTLC analysis. The rbcL region was selected for Bar-HRM analysis. PCR amplification was performed to obtain 102 bp amplicons encompassing nine polymorphic nucleotides. The amplicons were subjected to HRM analysis to obtain melting curve profiles. The melting temperatures (Tm) of authentic A. cocculus (A), C. caudatus (C) and M. repandus (M) were separated at 82.03±0.09°C, 80.93±0.04°C and 80.05±0.07°C, respectively. The protocol was applied to test crude drugs (CD1-6). The HPTLC profiles of CD2-6 showed distinct bands of M. repandus, while CD1 showed unclear band results. The Bar-HRM method was applied to assist the HPTLC and indicated that CD1 was C. caudatus. While ambiguous melting curves from the laboratory-made formulae were obtained, HPTLC analysis helped reveal distinct patterns for the identification of the plant species. The combination of HPTLC and Bar-HRM analysis could be a tool for confirming the identities of plant species sharing the same name, especially for those whose sources are multiple and difficult to identify by either chemical or DNA techniques. [ABSTRACT FROM AUTHOR]

In the age of big data an important question is how to ensure we make the most out of the resources we generate. In this review, we discuss the major methods used in Apicomplexan and Kinetoplastid research to produce big datasets and advance our understanding of Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma and Leishmania biology. We debate the benefits and limitations of the current technologies, and propose future advancements that may be key to improving our use of these techniques. Finally, we consider the difficulties the field faces when trying to make the most of the abundance of data that has already been, and will continue to be, generated. [ABSTRACT FROM AUTHOR]

The Relict Dace is a small cyprinid and the only species in its genus, Relictus. It is naturally distributed in four drainage basins of central Nevada ‐ Butte Valley, Ruby Valley, Steptoe Valley, and Goshute Valley. The species has experienced periods of isolation and connection within these four basins since the late Pliocene, with the last 100 years characterized by anthropogenic disturbance. To better inform conservation actions, we investigated range‐wide and intra‐basin genetic structure and diversity and conducted Fst outlier tests using RAD‐sequencing. We found high levels of genetic structure and four main lineages on a broad scale corresponding primarily to geography, and on a very fine scale (<1 km) within drainage basins. Signatures of selection in the form of outlier loci were documented in multiple locations across the range. Our results provide baseline data for conservation efforts and highlight the degree of fine‐scale genetic structuring that may be present in fishes of the Great Basin that are now restricted to small, isolated habitats—particularly wetland complexes. We caution against assuming that geographic distance is a proxy for genetic similarity in Great Basin fishes, encourage thorough genetic sampling, and note that broad‐scale genetic surveys can overlook fine‐scale genetic structure. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infections remain a significant public health concern worldwide. Over the years, sophisticated sequencing technologies such as next-generation sequencing (NGS) have emerged and been utilized to monitor the spread of HIV drug resistance (HIVDR), identify HIV drug resistance mutations, and characterize transmission dynamics. Similar applications also apply to the Hepatitis C virus (HCV), another bloodborne viral pathogen with significant intra-host genetic diversity. Several advantages to using NGS over conventional Sanger sequencing include increased data throughput, scalability, cost-effectiveness when batched sample testing is performed, and sensitivity for quantitative detection of minority resistant variants. However, NGS alone may fail to detect genomes from pathogens present in low copy numbers. As with all sequencing platforms, the primary determinant in achieving quality sequencing data is the quality and quantity of the initial template input. Samples containing degraded RNA/DNA and/or low copy number have been a consistent sequencing challenge. To overcome this limitation probe capture enrichment is a method that has recently been employed to target, enrich, and sequence the genome of a pathogen present in low copies, and for compromised specimens that contain poor quality nucleic acids. It involves the hybridization of sequence-specific DNA or RNA probes to a target sequence, which is followed by an enrichment step via PCR to increase the number of copies of the targeted sequences after which the samples are subjected to NGS procedures. This method has been performed on pathogens such as bacteria, fungus, and viruses and allows for the sequencing of complete genomes, with high coverage. Post NGS, data analysis can be performed through various bioinformatics pipelines which can provide information on genetic diversity, genotype, virulence, and drug resistance. This article reviews how probe capture enrichment helps to increase the likelihood of sequencing HIV and HCV samples that contain low viral loads and/or are compromised. [ABSTRACT FROM AUTHOR]

Background: Artemisinin-based combination therapies (ACTs) are the global mainstay treatment of uncomplicated Plasmodium falciparum infections. Pf MDR1 and Pf CRT are two transmembrane transporters, associated with sensitivity to several antimalarials, found in the parasite food vacuole. Herein, we explore if their relatedness extends to overlapping patterns of gene transcriptional activity before and during ACT administration. Methods: In a clinical trial performed in Tanzania, we explored the pfmdr1 and pfcrt transcription levels from 48 patients with uncomplicated P. falciparum malaria infections who underwent treatment with artemether-lumefantrine (AL). Samples analyzed were collected before treatment initiation and during the first 24 h of treatment. The frequency of Pf MDR1 N86Y and Pf CRT K76T was determined through PCR-RFLP or direct amplicon sequencing. Gene expression was analyzed by real-time quantitative PCR. Results: A wide range of pre-treatment expression levels was observed for both genes, approximately 10-fold for pfcrt and 50-fold for pfmdr1. In addition, a significant positive correlation demonstrates pfmdr1 and pfcrt co-expression. After AL treatment initiation, pfmdr1 and pfcrt maintained the positive co-expression correlation, with mild downregulation throughout the 24 h post-treatment. Additionally, a trend was observed for Pf MDR1 N86 alleles and higher expression before treatment initiation. Conclusion: pfmdr1 and pfcrt showed significant co-expression patterns in vivo , which were generally maintained during ACT treatment. This observation points to relevant related roles in the normal parasite physiology, which seem essential to be maintained when the parasite is exposed to drug stress. In addition, keeping the simultaneous expression of both transporters might be advantageous for responding to the drug action. [ABSTRACT FROM AUTHOR]

Introduction: Rapid, sensitive, and specific laboratory assays are critical for the diagnosis and management of central nervous system (CNS) infections. The purpose of this study is to explore the intellectual landscape of research investigating methods for the detection of pathogens in patients with CNS infections and to identify the development trends and research frontier in this field. Methods: A bibliometric study is conducted by analyzing literature retrieved from the Web of Science (WoS) Core Collection Database for the years 2000 to 2021. CiteSpace software is used for bibliometric analysis and network visualization, including co-citation analysis of references, co-occurrence analysis of keywords, and cooperation network analysis of authors, institutions, and countries/regions. Results: A total of 2,282 publications are eventually screened, with an upward trend in the number of publications per year. The majority of papers are attributed to the disciplines of MICROBIOLOGY, INFECTIOUS DISEASES, IMMUNOLOGY, NEUROSCIENCES & NEUROLOGY, and VIROLOGY. The co-citation analysis of references shows that recent research has focused on the largest cluster "metagenomic next-generation sequencing"; the results of the analysis of the highest-cited publications and the citation burst of publications reveal that there is a strong interest stimulated in metagenomic next-generation sequencing. The co-occurrence analysis of keywords indicates that "infection", "pathogen", "diagnosis", "gene", "virus", "polymerase chain reaction", "cerebrospinal fluid", "epidemiology", and "metagenomic next-generation sequencing" are the main research priorities in the field of pathogen detection for CNS infections, and the keyword with the highest strength of burst is "metagenomic next-generation sequencing". Collaborative network analysis reveals that the USA, the Centers for Disease Control and Prevention of USA, and XIN WANG and JENNIFER DIEN BARD are the most influential country, institution, and researchers, respectively. Conclusions: Exploring more advanced laboratory assays to improve the diagnostic accuracy of pathogens is essential for CNS infection research. Metagenomic next-generation sequencing is emerging as a novel useful unbiased approach for diagnosing infectious diseases of the CNS. [ABSTRACT FROM AUTHOR]

This article examines the works of Christopher Wordsworth (1807–85), who has hitherto been neglected as an important and intriguing figure in the history of travel writing on Greece. His texts, which invite readers to 'view' the country from mountain-tops and to imagine its caves and quarries filled with ancient figures, highlight the importance of landscape as a frame for studying classical reception. Wordsworth 'received' ancient Greece through its visible, modern landscape in three ways: through a sense of the landscape as a container for memory, through the use of specific landscapes as springboard for 'flights of fancy' enabling a vivid engagement with the classical past, and as a tool for better interpreting and understanding the history and literature of the ancient Mediterranean. Christopher Wordsworth constructed a vision of ancient Greece for his readers through his description of the nineteenth-century landscape. As such he offers an important reminder to consider the role played by the embodied experience of space and place in analysing acts of classical reception. [ABSTRACT FROM AUTHOR]

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by a computational drug repurposing analysis. Cross-ancestry polygenic risk scores showed better performance of association in independent samples than single-ancestry polygenic risk scores. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. This study advances our knowledge of the genetic etiology of PAU, and these findings may bring possible clinical applicability of genetics insights-together with neuroscience, biology and data science-closer., (© 2023. The Author(s).)

In classical archaeology the spatial aspects of deathscapes and associated funerary phenomena are often taken at face value. Beginning from a relational understanding of space, this article examines the necropoleis of middle Hellenistic to late Roman Sagalassos (second century BC to fifth century AD) within the wider context of the city. To facilitate this methodologically, four spatial aspects are investigated for the Hellenistic, Roman Imperial and late Roman periods: the relations between the spaces of the living and dead, landscaping practices, visibility and accessibility. These four aspects offer insight into the funerary and non-funerary relations from which the necropoleis emerged, developed, expanded and eventually disappeared. A whole range of funerary phenomena are included, ranging from cinerary urns, rectangular and vase-shaped ostothekai, aediculae, naiskoi, arcosolia and sarcophagi to larger sepulchral structures like temple tombs. In addition to being compared with urban developments, the observed patterns are further evaluated within the larger framework of Asia Minor. Ultimately, the enunciated archaeological patterns facilitate multicausal answers to where the Sagalassians placed their dead, if and how this changed and became more varied, and why these developments occurred in particular (re)configurations of time-space. [ABSTRACT FROM AUTHOR]

A standard competing risks set-up requires both time to event and cause of failure to be fully observable for all subjects. However, in application, the cause of failure may not always be observable, thus impeding the risk assessment. In some extreme cases, none of the causes of failure is observable. In the case of a recurrent episode of Plasmodium vivax malaria following treatment, the patient may have suffered a relapse from a previous infection or acquired a new infection from a mosquito bite. In this case, the time to relapse cannot be modeled when a competing risk, a new infection, is present. The efficacy of a treatment for preventing relapse from a previous infection may be underestimated when the true cause of infection cannot be classified. In this paper, we developed a novel method for classifying the latent cause of failure under a competing risks set-up, which uses not only time to event information but also transition likelihoods between covariates at the baseline and at the time of event occurrence. Our classifier shows superior performance under various scenarios in simulation experiments. The method was applied to Plasmodium vivax infection data to classify recurrent infections of malaria. [ABSTRACT FROM AUTHOR]

This paper engages with intersectional feminist theory to explore how Vitruvius's story about the Carian queen Artemisia II in Book 2 of De Architectura illuminates first-century B.C.E. Roman attitudes of hostility towards non-Roman women in spaces of political power—especially given what would have been the recent defeat of the Egyptian queen Cleopatra VII. The paper has two goals: first, I argue that first-century B.C.E. accounts of queen ship configure Artemisia and Cleopatra as raced and gendered embodiments of opposition to the idealized image of Roman imperial masculinity. Second, I demonstrate how race-oriented feminist frameworks can productively bear on historical analyses and classical studies. [ABSTRACT FROM AUTHOR]

Was Cybele brought to Rome to expel Hannibal, as Cicero and Livy suggest, or was she brought to re-establish Rome's Trojan heritage, as Ovid and Herodian propose? Did her sacred stone come from Pessinus, Pergamum, or Mt Ida? In answering these questions this article argues, on the basis of a re-examination of the testimonies of Ovid and Herodian, that the Magna Mater did not come to drive out Hannibal but rather to reaffirm Rome's Trojan ancestry, and that Pergamum and Mt Ida are likely the origin of her sacred stone. In addition the article introduces a passage from Timotheus of Miletus, which locates the goddess in Ilium itself. This new literary evidence emphasizes the connection between the Magna Mater and Troy. By addressing these two questions fresh light will be shed on the Trojan background to the Magna Mater's Roman advent. [ABSTRACT FROM AUTHOR]

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This article, the last of four, summarizes the results of a decade of work on the sculptures of the Temple of Ares, and supersedes some of the tentative conclusions advanced earlier in the series. It assesses the original Periklean project (especially its possible genesis as a response to the plague of 430-426 b.c.) and the Augustan modifications to it after the temple's transfer from Pallene to the Agora ca. 15 b.c. A chronological appendix charts the temple's prehistory from the 8th century b.c. through the Persian sack of 480; its history from ca. 430 through its destruction in late antiquity; and finally its recovery from the Greek excavations of 1891 to the present. [ABSTRACT FROM AUTHOR]

When focusing on Augustus as a commander in chief, a strategist, and a field commander - and especially the formative years of the civil war(s) -, there are numerous potential approaches. We know that he fought battles, campaigns, and wars. Sometimes he did well, sometimes less so. Traditionally, Augustus has not been viewed as a good general, but he was, or so this article claims, an excellent commander. We shall here discuss the actual fighting only when it has a direct bearing on what might be termed the 'command structure', in this case during the triumvirate and beyond, and its formulation of strategy. Rather, the main question is as follows: how did the learning curve followed by Young Caesar on his rise to power create a new, shared command structure as part of a monarchical system, with Augustus as commander in chief? If we look at political initiative in warfare and military campaigns, rather than just considering warfare from a tactical point of view, then leadership is always a learning curve. This is accordingly a question of how we, as scholars, approach ancient warfare, strategy, and the relationships between commanders: for example, the 'high command' or commander in chief in one theatre and the field commander in the other. This is thus an article on how we, as scholars, approach Roman military history in general. [ABSTRACT FROM AUTHOR]

Copyright of Romanitas: Revista de Estudos Greco-Latinas is the property of Universidade Federal do Espirito Santo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Early in Tiberius' reign, the Tiber flooded the city of Rome. Asinius Gallus proposed that it be treated as a prodigy and the Sibylline Books consulted, but Tiberius rejected his request. This paper examines Gallus' proposal and Tiberius' response. It argues that, contrary to the views of many scholars, Gallus was not attempting to undermine the new emperor but rather to support him. Through this incident, the paper explores prodigy reports in the early Roman Empire, as well as the relationship between Gallus and Tiberius. [ABSTRACT FROM AUTHOR]

Background: The UN's Sustainable Development Goals are devoted to eradicate a range of infectious diseases to achieve global well-being. These efforts require monitoring disease transmission at a level that differentiates between pathogen variants at the genetic/molecular level. In fact, the advantages of genetic (molecular) measures like multiplicity of infection (MOI) over traditional metrics, e.g., R0, are being increasingly recognized. MOI refers to the presence of multiple pathogen variants within an infection due to multiple infective contacts. Maximum-likelihood (ML) methods have been proposed to derive MOI and pathogen-lineage frequencies from molecular data. However, these methods are biased. Methods and findings: Based on a single molecular marker, we derive a bias-corrected ML estimator for MOI and pathogen-lineage frequencies. We further improve these estimators by heuristical adjustments that compensate shortcomings in the derivation of the bias correction, which implicitly assumes that data lies in the interior of the observational space. The finite sample properties of the different variants of the bias-corrected estimators are investigated by a systematic simulation study. In particular, we investigate the performance of the estimator in terms of bias, variance, and robustness against model violations. The corrections successfully remove bias except for extreme parameters that likely yield uninformative data, which cannot sustain accurate parameter estimation. Heuristic adjustments further improve the bias correction, particularly for small sample sizes. The bias corrections also reduce the estimators' variances, which coincide with the Cramér-Rao lower bound. The estimators are reasonably robust against model violations. Conclusions: Applying bias corrections can substantially improve the quality of MOI estimates, particularly in areas of low as well as areas of high transmission—in both cases estimates tend to be biased. The bias-corrected estimators are (almost) unbiased and their variance coincides with the Cramér-Rao lower bound, suggesting that no further improvements are possible unless additional information is provided. Additional information can be obtained by combining data from several molecular markers, or by including information that allows stratifying the data into heterogeneous groups. [ABSTRACT FROM AUTHOR]

Background: Mosquito-borne diseases have a devastating impact on human civilization. A few species of Anopheles mosquitoes are responsible for malaria transmission, and while there has been a reduction in malaria-related deaths worldwide, growing insecticide resistance is a cause for concern. Aedes mosquitoes are known vectors of viral infections, including dengue, yellow fever, chikungunya, and Zika. Aminoacyl-tRNA synthetases (aaRSs) are key players in protein synthesis and are potent anti-infective drug targets. The structure–function activity relationship of aaRSs in mosquitoes (in particular, Anopheles and Aedes spp.) remains unexplored. Methods: We employed computational techniques to identify aaRSs from five different mosquito species (Anopheles culicifacies, Anopheles stephensi, Anopheles gambiae, Anopheles minimus, and Aedes aegypti). The VectorBase database (https://vectorbase.org/vectorbase/app) and web-based tools were utilized to predict the subcellular localizations (TargetP-2.0, UniProt, DeepLoc-1.0), physicochemical characteristics (ProtParam), and domain arrangements (PfAM, InterPro) of the aaRSs. Structural models for prolyl (PRS)-, and phenylalanyl (FRS)-tRNA synthetases—were generated using the I-TASSER and Phyre protein modeling servers. Results: Among the vector species, a total of 37 (An. gambiae), 37 (An. culicifacies), 37 (An. stephensi), 37 (An. minimus), and 35 (Ae. aegypti) different aaRSs were characterized within their respective mosquito genomes. Sequence identity amongst the aaRSs from the four Anopheles spp. was > 80% and in Ae. aegypti was > 50%. Conclusions: Structural analysis of two important aminoacyl-tRNA synthetases [prolyl (PRS) and phenylanalyl (FRS)] of Anopheles spp. suggests structural and sequence similarity with potential antimalarial inhibitor [halofuginone (HF) and bicyclic azetidine (BRD1369)] binding sites. This suggests the potential for repurposing of these inhibitors against the studied Anopheles spp. and Ae. aegypti. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Fisheries & Aquatic Sciences is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article analyses the power dynamics that Ovid stages in the Metamorphoses as interplay of rhetoric, monumental art, and poetry. It argues that (1) the transformations of gods can be read as a metaphor of rhetoric subjecting the audience to the speaker's will; (2) that the products of the transformations of humans can be regarded as notional monuments to divine power; (3) that, for Ovid, all successful ideological constructs are based on a similar combination of rhetorical manipulation and "monumentalization"; (4) that, at the same time, Ovid casts metamorphosis as a product of the ability of the human imagination to recognize a human presence behind every non-human object, including the "monuments" constructed by superhuman powers; (5) that Ovid conceives of the "re-humanizing" effect of poetry as a function of its ability to make the audience recognize themselves in it; and (6) that the immortality that Ovid attributes to his own text is a function of his writing producing a similar effect on the readers. [ABSTRACT FROM AUTHOR]

Low‐coverage whole genome sequencing (lcWGS) has emerged as a powerful and cost‐effective approach for population genomic studies in both model and nonmodel species. However, with read depths too low to confidently call individual genotypes, lcWGS requires specialized analysis tools that explicitly account for genotype uncertainty. A growing number of such tools have become available, but it can be difficult to get an overview of what types of analyses can be performed reliably with lcWGS data, and how the distribution of sequencing effort between the number of samples analysed and per‐sample sequencing depths affects inference accuracy. In this introductory guide to lcWGS, we first illustrate how the per‐sample cost for lcWGS is now comparable to RAD‐seq and Pool‐seq in many systems. We then provide an overview of software packages that explicitly account for genotype uncertainty in different types of population genomic inference. Next, we use both simulated and empirical data to assess the accuracy of allele frequency, genetic diversity, and linkage disequilibrium estimation, detection of population structure, and selection scans under different sequencing strategies. Our results show that spreading a given amount of sequencing effort across more samples with lower depth per sample consistently improves the accuracy of most types of inference, with a few notable exceptions. Finally, we assess the potential for using imputation to bolster inference from lcWGS data in nonmodel species, and discuss current limitations and future perspectives for lcWGS‐based population genomics research. With this overview, we hope to make lcWGS more approachable and stimulate its broader adoption. [ABSTRACT FROM AUTHOR]

Numerous studies have found evidence that GWAS loci experience negative selection, which increases in intensity with the effect size of identified variants. However, there is also accumulating evidence that this selection is not entirely mediated by the focal trait and contains a substantial pleiotropic component. Understanding how selective constraint shapes phenotypic variation requires advancing models capable of balancing these and other components of selection, as well as empirical analyses capable of inferring this balance and how it is generated by the underlying biology. We first review the classic theory connecting phenotypic selection to selection at individual loci as well as approaches and findings from recent analyses of negative selection in GWAS data. We then discuss geometric theories of pleiotropic selection with the potential to guide future modeling efforts. Recent findings revealing the nature of pleiotropic genetic variation provide clues to which genetic relationships are important and should be incorporated into analyses of selection, while findings that effect sizes vary between populations indicate that GWAS measurements could be misleading if effect sizes have also changed throughout human history. [ABSTRACT FROM AUTHOR]

Background. Malaria parasites reproduce asexually, leading to the production of large numbers of genetically identical parasites, here termed a clonal line or clone. Infected hosts may harbor one or more clones, and the number of clones in a host is termed multiplicity of infection (MOI). Understanding the distribution of parasite clones among hosts can shed light on the processes shaping this distribution and is important for modeling MOI. Here, I determine whether the distribution of clones of the lizard malaria parasite Plasmodium mexicanum differ significantly from statistical distributions commonly used to model MOI and logical extensions of these models. Methods. The number of clones per infection was assessed using four microsatellite loci with the maximum number of alleles at any one locus used as a simple estimate of MOI for each infection. I fit statistical models (Poisson, negative binomial, zero-inflated models) to data from four individual sites to determine a best fit model. I also simulated the number of alleles per locus using an unbiased estimate of MOI to determine whether the simple (but potentially biased) method I used to estimate MOI influenced model fit. Results. The distribution of clones among hosts at individual sites differed significantly from traditional Poisson and negative binomial distributions, but not from zero- inflated modifications of these distributions. A consistent excess of two-clone infections and shortage of one-clone infections relative to all fit distributions was also observed. Any bias introduced by the simple method for estimating of MOI did not appear to qualitatively alter the results. Conclusions. The statistical distributions used to model MOI are typically zero- truncated; truncating the Poisson or zero-inflated Poisson yield the same distribution, so the reasonable fit of the zero-inflated Poisson to the data suggests that the use of the zero-truncated Poisson in modeling is adequate. The improved fit of zero-inflated distributions relative to standard distributions may suggest that only a portion of the host population is located in areas suitable for transmission even at small sites (<1 ha). Collective transmission of clones and premunition may also contribute to deviations from standard distributions. [ABSTRACT FROM AUTHOR]

This article argues that Virgil's First Eclogue naturalises the power discourse of the future Augustan Principate. Throughout the poem, Virgil not only presents the iuvenis as a libertas-restoring benefactor who is treated as a god by his beneficiaries, but even imagines his elevated status as crucial to maintaining social cohesion and civic stability, and idealises the beneficiaries' dependence on his efficacious authority. The poem thus produces the grammar of the discourse of authoritarianism, subtly articulating what will eventually become the central tenets of Augustan ideology. I suggest that it is precisely this process of naturalisation which has led readers since antiquity to identify the iuvenis of Virgil's First Eclogue as the future Augustus. However, in this paper I am interested in transcending this question of individual identification to focus instead on how Virgil's poetic anonymisation is no simple pastoral obfuscation, but rather does the hard graft of 'soft launching' a new political system. [ABSTRACT FROM AUTHOR]

This article offers an account of Roman imperial cameos as an archaeological category, and argues that the production of large high-quality cameos was more restricted in time than currently allowed; that the controversial dates and subjects of individual cameos need to be set in the wider sequence of the main examples; and that early imperial praise poetry sits in relationship to court cameos in a way that can be usefully investigated around their shared concern to understand the particular character of imperial divinity. An Appendix gives details of forty-one examples illustrated and discussed. [ABSTRACT FROM AUTHOR]

A major objective of evolutionary biology is to understand the processes by which organisms have adapted to various environments, and to predict the response of organisms to new or future conditions. The availability of large genomic and environmental data sets provides an opportunity to address those questions, and the R package LEA has been introduced to facilitate population and ecological genomic analyses in this context. By using latent factor models, the program computes ancestry coefficients from population genetic data and performs genotype–environment association analyses with correction for unobserved confounding variables. In this study, we present new functionalities of LEA, which include imputation of missing genotypes, fast algorithms for latent factor mixed models using multivariate predictors for genotype–environment association studies, population differentiation tests for admixed or continuous populations, and estimation of genetic offset based on climate models. The new functionalities are implemented in version 3.1 and higher releases of the package. Using simulated and real data sets, our study provides evaluations and examples of applications, outlining important practical considerations when analysing ecological genomic data in R. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is a routinely measured blood biomarker for inflammation. Elevated levels of circulating CRP are associated with response to infection, risk for a number of complex common diseases, and psychosocial stress. The objective of this study was to compare the contributions of genetic ancestry, socioenvironmental factors, and inflammation-related health conditions to ethnic differences in C-reactive protein levels. We used multivariable regression to compare CRP blood serum levels between Black and White ethnic groups from the United Kingdom Biobank (UKBB) prospective cohort study. CRP serum levels are significantly associated with ethnicity in an age and sex adjusted model. Study participants who identify as Black have higher average CRP than those who identify as White, CRP increases with age, and females have higher average CRP than males. Ethnicity and sex show a significant interaction effect on CRP. Black females have higher average CRP levels than White females, whereas White males have higher average CRP than Black males. Significant associations between CRP, ethnicity, and genetic ancestry are almost completely attenuated in a fully adjusted model that includes socioenvironmental factors and inflammation-related health conditions. BMI, smoking, and socioeconomic deprivation all have high relative effects on CRP. These results indicate that socioenvironmental factors contribute more to CRP ethnic differences than genetics. Differences in CRP are associated with ethnic disparities for a number of chronic diseases, including type 2 diabetes, essential hypertension, sarcoidosis, and lupus erythematosus. Our results indicate that ethnic differences in CRP are linked to both socioenvironmental factors and numerous ethnic health disparities. [ABSTRACT FROM AUTHOR]

The purpose of this article is to explore how Ovid shapes his story of Salmacis and Hermaphroditus (Met. 4.285–388) through a series of allusions to some passages of the Aeneid and the Georgics. Indeed, in the story in question, the transforming of gender roles features as a metaphor for Ovid's processes of aemulatio. The construction of Salmacis as a dominant female relates to the poetic "brotherhood" of Ovid and Vergil, for Ovid creates his character by readapting some aspects of his epic model within a reversal of traditional gender patterns. [ABSTRACT FROM AUTHOR]

The post‐glacial colonization of Gander Lake in Newfoundland, Canada, by Arctic Charr (Salvelinus alpinus) provides the opportunity to study the genomic basis of adaptation to extreme deep‐water environments. Colonization of deep‐water (>50 m) habitats often requires extensive adaptation to cope with novel environmental challenges from high hydrostatic pressure, low temperature, and low light, but the genomic mechanisms underlying evolution in these environments are rarely known. Here, we compare genomic divergence between a deep‐water morph adapted to depths of up to 288 m and a larger, piscivorous pelagic morph occupying shallower depths. Using both a SNP array and resequencing of whole nuclear and mitochondrial genomes, we find clear genetic divergence (FST = 0.11–0.15) between deep and shallow water morphs, despite an absence of morph divergence across the mitochondrial genome. Outlier analyses identified many diverged genomic regions containing genes enriched for processes such as gene expression and DNA repair, cardiac function, and membrane transport. Detection of putative copy number variants (CNVs) uncovered 385 genes with CNVs distinct to piscivorous morphs, and 275 genes with CNVs distinct to deep‐water morphs, enriched for processes associated with synapse assembly. Demographic analyses identified evidence for recent and local morph divergence, and ongoing reductions in diversity consistent with postglacial colonization. Together, these results show that Arctic Charr morph divergence has occurred through genome‐wide differentiation and elevated divergence of genes underlying multiple cellular and physiological processes, providing insight into the genomic basis of adaptation in a deep‐water habitat following postglacial recolonization. [ABSTRACT FROM AUTHOR]

This article challenges the idea, presented by both ancient and modern writers, that the armies of the Middle Republic were governed by a clearly articulated ideology of discipline. I contend that the notion of an all-encompassing system of military discipline is a fiction created by a variety of interconnected and historically-constructed intellectual genealogies by examining the two most important sources for the discipline of Middle Republican army, Polybius and Livy, and the reception of their ideas in post-Renaissance Europe. [ABSTRACT FROM AUTHOR]

Plasmodium vivax, a major contributor to the malaria burden in India, has the broadest geographic distribution and shows higher genetic diversity than P. falciparum. Here, we investigated the genetic diversity of two leading P. vivax vaccine candidate antigens, at three geographically diverse malaria-endemic regions in India. Pvama1 and Pvmsp119 partial coding sequences were generated from one hundred P. vivax isolates in India (Chennai n = 28, Nadiad n = 50 and Rourkela n = 22) and ~1100 published sequences from Asia, South America, North America, and Oceania regions included. These data were used to assess the genetic diversity and potential for vaccine candidacy of both antigens on a global scale. A total of 44 single nucleotide polymorphism (SNPs) were identified among 100 Indian Pvama1 sequences, including 10 synonymous and 34 nonsynonymous mutations. Nucleotide diversity was higher in Rourkela and Nadiad as compared to Chennai. Nucleotide diversity measures showed a strong balancing selection in Indian and global population for domain I of Pvama1, which suggests that it is a dominant target of the protective immune response. In contrast, the Pvmsp119 region showed highly conserved sequences in India and across the Oceania, South America, North America and Asia, demonstrating low genetic diversity in the global population when compared to Pvama1. Results suggest the possibility of including Pvmsp119 in a multivalent vaccine formulation against P. vivax infections. However, the high genetic diversity seen in Pvama1 would be more challenging for vaccine development. Author summary: Plasmodium vivax is the dominant malaria species in several countries, and a safe and effective vaccine against the species is needed if progress is to be made towards malaria control and elimination. The P. vivax Apical Membrane Antigen 1 (AMA1) ectodomain and the C-terminal region (19 kDa) of the Merozoite Surface Protein 1 (MSP1) are important malaria vaccine antigens. However, antigenic diversity remains a critical factor for acquisition of immunity and also a major barrier for development of an effective vaccine. Here, investigations on the genetic diversity of two blood stage vaccine candidate antigens, Merozoite surface protein 119 and Apical membrane antigen 1, of P. vivax from three malaria endemic regions of the India was attempted and compared with global population. High genetic variation was observed in Pvama1 domain I, which has been reported as a dominant target of host immune response. In contrast, Pvmsp119 showed highly conserved sequences from three geographically diverse populations of India and globally, which further suggests Pvmsp119 as an extremely conserved protein. Collectively, the diversity data generated in this study provides a baseline data towards development of a broadly efficacious Pvama1 and Pvmsp119 based vaccine. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated an inverse association between parathyroid hormone (PTH) and the risk of osteoarthritis (OA). However, it remains unknown whether such association reflects causality. We aimed to apply a Mendelian randomization (MR) approach to investigate the causal association between PTH and OA. Materials and Methods: We performed a two-sample MR analysis using summary statistics from 13 cohorts (PTH, N = 29,155) and a recent genome-wide association study meta-analysis (OA, N = 455,221) by the UK Biobank and Arthritis Research UK OA Genetics (arcOGEN). MR analyses were carried out mainly using the inverse-variance-weighted method. Sensitivity analyses were performed to test the robustness of the associations using the weighted median method, the MR–Egger method, and "leave-one-out" analysis. Analyses were performed again to test whether the associations remained statistically significant after excluding any outlier variants that were detected using the MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) test. Results: Five single-nucleotide polymorphisms (SNPs) were selected as instrumental variables at the genome-wide significance threshold (p < 5 × 10–8). The causal effect between PTH and OA was genetically predicted using the inverse-variance-weighted method (odds ratio = 0.67, 95% confidence interval: 0.50–0.90; p = 0.008). This result was borne out using the weighted median method (odds ratio = 0.73, 95% confidence interval: 0.60–0.90; p = 0.004). The causality remained robust after discarding the outlier variants as well as SNPs associated with confounding factors. Conclusion: MR analysis supported a potential causative relationship between decreased serum circulating PTH and a higher risk of hip and knee OA. [ABSTRACT FROM AUTHOR]

Although 'squatters' have been identified in excavated contexts globally, it is unclear what this term actually means. In most archaeological publications, it seems to refer to the occupants of abandoned or destroyed buildings, especially those of the elite. 'Squatting', however, carries additional negative connotations which have been under-interrogated in the field. In this study, I explore the treatment of squatters in Anglophone archaeological writing, drawing upon two chronologically and geographically distinct examples: the Aegean Bronze Age and Late Roman North Africa. I argue that, in general, 'squatters' are identified uncritically and used as an index of cultural decline, with little consideration of the squatters--or reoccupants--themselves. Because 'legitimacy' of occupation is difficult to ascertain in archaeological contexts, I argue that this term is of little use in describing ancient reoccupation levels, particularly where they are distinguished only by their relative poverty. I suggest instead that an agency-centered assessment of impoverished architectural contexts is required. [ABSTRACT FROM AUTHOR]

Motivation Principal component analysis (PCA) is a commonly used tool in genetics to capture and visualize population structure. Due to technological advances in sequencing, such as the widely used non-invasive prenatal test, massive datasets of ultra-low coverage sequencing are being generated. These datasets are characterized by having a large amount of missing genotype information. Results We present EMU, a method for inferring population structure in the presence of rampant non-random missingness. We show through simulations that several commonly used PCA methods cannot handle missing data arisen from various sources, which leads to biased results as individuals are projected into the PC space based on their amount of missingness. In terms of accuracy, EMU outperforms an existing method that also accommodates missingness while being competitively fast. We further tested EMU on around 100K individuals of the Phase 1 dataset of the Chinese Millionome Project, that were shallowly sequenced to around 0.08×. From this data we are able to capture the population structure of the Han Chinese and to reproduce previous analysis in a matter of CPU hours instead of CPU years. EMU's capability to accurately infer population structure in the presence of missingness will be of increasing importance with the rising number of large-scale genetic datasets. Availability and implementation EMU is written in Python and is freely available at https://github.com/rosemeis/emu. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Detecting genetic regions under selection in structured populations is of great importance in ecology, evolutionary biology and breeding programmes. We recently proposed EigenGWAS, an unsupervised genomic scanning approach that is similar to FST but does not require grouping information of the population, for detection of genomic regions under selection. The original EigenGWAS is designed for the random mating population, and here we extend its use to inbred populations. We also show in theory and simulation that eigenvalues, the previous corrector for genetic drift in EigenGWAS, are overcorrected for genetic drift, and the genomic inflation factor is a better option for this adjustment. Applying the updated algorithm, we introduce the new EigenGWAS online platform with highly efficient core implementation. Our online computational tool accepts plink data in a standard binary format that can be easily converted from the original sequencing data, provides the users with graphical results via the R‐Shiny user‐friendly interface. We applied the proposed method and tool to various data sets, and biologically interpretable results as well as caveats that may lead to an unsatisfactory outcome are given. The EigenGWAS online platform is available at www.eigengwas.com, and can be localized and scaled up via R (recommended) or docker. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have been widely adopted in studies of human complex traits and diseases. Results: This review surveys areas of active research: quantifying and partitioning trait heritability, fine mapping functional variants and integrative analysis, genetic risk prediction of phenotypes, and the analysis of sequencing studies that have identified millions of rare variants. Current challenges and opportunities are highlighted. Conclusion: GWAS have fundamentally transformed the field of human complex trait genetics. Novel statistical and computational methods have expanded the scope of GWAS and have provided valuable insights on the genetic architecture underlying complex phenotypes. [ABSTRACT FROM AUTHOR]

This study offers a theoretical context for reading political education literature. Comparing the two classical cultural exemplars (Latin/Greek) we build our working framework upon the firm distinction between Republican and Democratic ideals and we suggest that the current political culture is shaped into the Republican mold. Setting these findings as our conceptual framework, we scrutinize the 2018's democratic education proposal of the Council of Europe, which although represents modern Republican states, it rather employs concepts—participation, living-together, ethical competencies—extracted from the Democratic exemplar. Finally, we assess the effectiveness of our framework and the coherence of the CoE's text. [ABSTRACT FROM AUTHOR]

Sarah Auburn and co-authors discuss the unique biology and epidemiology of P. vivax and current evidence on conventional and new approaches to surveillance. [ABSTRACT FROM AUTHOR]

There are research questions whose answers require record linkage of multiple databases that may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run large-scale analyses in a high-performance computing (HPC) environment. Here, we report a successful record linkage genomewide association (GWA) study on expenditure for total health, mental health, primary and hospital care, and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and single nucleotide polymorphism (SNP)-based heritability. The total heritability of expenditure ranged between 29.4% (SE 0.8) and 37.5% (SE 0.8), but GWA analyses did not identify SNPs or genes that were genomewide significantly associated with health care expenditure. SNP-based heritability was between 0.0% (SE 3.5) and 5.4% (SE 4.0) and was different from zero for mental health care and primary care expenditure. We conclude that successfully linking genotype data to administrative health care expenditure data from Statistics Netherlands is feasible and demonstrates a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analyzing linked data in large scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify genetic variants associated with NAS through a genome-wide association study (GWAS) and estimate a Polygenic Risk Score (PRS) model for NAS., Methods: A prospective case-control study included 476 in utero opioid-exposed term neonates. A GWAS of 1000 genomes-imputed genotypes was performed to identify variants associated with need for pharmacotherapy for NAS. PRS models for estimating genetic predisposition were generated via a nested cross-validation approach using 382 neonates of European ancestry. PRS predictive ability, discrimination, and calibration were assessed., Results: Cross-ancestry GWAS identified one intergenic locus on chromosome 7 downstream of SNX13 exhibiting genome-wide association with need for pharmacotherapy. PRS models derived from the GWAS for a subset of the European ancestry neonates reliably discriminated between need for pharmacotherapy using cis variant effect sizes within validation sets of European and African American ancestry neonates. PRS were less effective when applying variant effect sizes across datasets and in calibration analyses., Conclusions: GWAS has the potential to identify genetic loci associated with need for pharmacotherapy for NAS and enable development of clinically predictive PRS models. Larger GWAS with additional ancestries are needed to confirm the observed SNX13 association and the accuracy of PRS in NAS risk prediction models., Impact: Genetic associations appear to be important in neonatal abstinence syndrome. This is the first genome-wide association in neonates with neonatal abstinence syndrome. Polygenic risk scores can be developed examining single-nucleotide polymorphisms across the entire genome. Polygenic risk scores were higher in neonates receiving pharmacotherapy for treatment of their neonatal abstinence syndrome. Future studies with larger cohorts are needed to better delineate these genetic associations., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)