Phylogenetic Studies Research Articles

What constitutes a stigma? A review of isolated pores in raphid diatoms (Bacillariophyceae) and the value of precise terminology

AbstractScanning electron microscopy has revealed variation in the ultrastructure of distinctive isolated pores in or near the central area of raphid diatoms, with different types of pores being restricted to phylogenetic groups. Thus, the widespread use of the term stigma for all such pores not only hides the structural diversity but also obscures the phylogenetic distribution of the different types. This paper provides images of the different types of isolated pores, particularly refining the discrimination of variants within the Cymbellales, and reveals some interesting ecological patterns. Revised definitions of stigmata and stigmoids are proposed, together with the recognition and definition of another type of stigmoid. The restricted distribution of more precisely defined pore types shows the importance of consistent use of terminology and its relevance to phylogenetic studies.

A hairy giant among dwarves: Trichopelma grande, a distinct new species of tarantula from Cuba (Araneae: Theraphosidae)

ABSTRACT Large size, tropical climate, topographic complexity, and millions of years of isolation have turned the Greater Antillean islands into natural laboratories of evolution. Several groups have experienced explosive diversification across these islands, leading to highly diverse and endemic biotas and species experiencing unique adaptations. Here we describe a new tarantula species from the Viñales area, a biodiversity hotspot in western Cuba. Despite being a middle-sized species with large projected setae on the legs, reminiscent of those in arboreal tarantulas, phylogenomic analysis, diagnostic morphological features, and trap-door retreat building behaviour identifies it as the largest known representative of Trichopelma, and the only one with such hirsute legs. We provide mitochondrial barcoding data and a database of ultraconserved elements loci of the holotype of this species, which will help to include it in future phylogenetic studies of Theraphosidae. Given its limited distribution range, and its apparent absence in natural history collections despite its distinct appearance, this species might be scarce, positioning it as a potential conservation concern. http://www.zoobank.org/urn:lsid:zoobank.org:pub:2F9ED7A1-1345-4295-A876-6B617ABF7C75

Progress in molecular systematics of Caprifoliaceae

AbstractCaprifoliaceae sensu APG IV shows a disjunctive distribution between Eurasia and America, and is an excellent study system for exploring the formation of species with an Eurasian–North American disjunct distribution. Due to widespread hybridization and introgression in Caprifoliaceae sensu APG IV as well as morphological convergence and discontinuous distribution of species, the phylogenetic relationships among subfamilies and the systematic positions of some genera have yet to be fully resolved. Therefore, we present an overview of the classification and molecular phylogenetic studies of Caprifoliaceae sensu APG IV in recent years, aiming to provide a reference for the systematic classification of Caprifoliaceae sensu APG IV and to facilitate discussions of problems and directions of systematic studies in the family.

Nuclear phylogenomics of Eperua (Leguminosae) highlights the role of habitat and morphological lability in dispersal and diversification across Amazonia and in the Caatinga-Cerrado ecotone.

Eperua is a genus of Neotropical trees that forms a major component of tropical lowland forests in Amazonia, especially in the Guiana Shield and on white-sand forests. One species occurs in the Cerrado-Caatinga ecotone, and the genus also inhabits riverine and terra firme forests. Species in Eperua exhibit one of two drastically different floral architectures and inflorescence types, each associated with distinct pollinators. Prior phylogenetic studies of Eperua have revealed an unstructured topology concerning floral architectures and inflorescence types. In addition, no investigation has been conducted on how the evolution of these traits and habitat preferences influenced the dispersal and diversification of Eperua. Using target capture sequencing, we inferred the most comprehensive phylogeny for Eperua to date, sampling all 19 known species, five for the first time. We used coalescence, concatenation, and network methods to infer the Eperua phylogeny and investigate sources of incongruence impacting resolution and support. We reconstructed the biogeographic history and ancestral states for the flower architecture, inflorescence type, and habitat preference. Our phylogenomic analyses successfully resolved relationships within Eperua, attributing conflicts between the species tree and concatenated tree to gene tree discordance linked to reticulation events. Biogeographical analyses indicate that Eperua originated and initially diversified in the white-sand forests of the Guiana Shield. A subsequent adaptation to riverine and terra firme forests enabled Eperua to expand into new habitats and regions. Still, its historical preference for white-sand forests probably accounts for its absence in the southern and western parts of Amazonia. Ancestral geographic areas and corolla morphotype reconstructions suggest that speciation in Eperua has occurred in sympatry, likely driven by pollinator shifts mediated by drastic changes in floral architecture.

Biotransformation of Tetrabromobisphenol A and Its Analogs by Selected Gut Bacteria Strains: Implications for Human Health.

Knowledge of the biotransformation of tetrabromobisphenol A (TBBPA) and its related contaminants by human gut microbiota (GM) remains unexplored. Here, TBBPA and its four analogs were incubated with mixed GM strains, and nine rhamnosylated or debrominated transformation products (TPs) were discovered. Remarkably, rhamnosylation was identified as a common and unique microbial transformation pathway for these contaminants, and six of the seven rhamnosylated TPs were reported for the first time. Additionally, a kinetic transformation study also showed a rapid and strong bioaccumulation of TBBPA and TPs by Clostridium manihotivorum. Genomic analysis and phylogenetic studies identified C1.1_02053 as the gene encoding the C. manihotivorum working rhamnosyltransferase (CmRT), showing elevated gene expression with higher TBBPA exposure. Molecular docking identified five critical amino acid residues in CmRT that catalyze TBBPA rhamnosylation, and molecular dynamics simulations further confirmed the stability of the CmRT-TBBPA complex. Dynamic metabolomics analysis showed microbial growth-dependent disturbing effects in C. manihotivorum upon TBBPA exposure, and key metabolic pathways related to rhamnosyltransferase showed changes closely related to the transformation process. These findings provide insights into the unique transformation of environmental contaminants by the GM and highlight the disturbing effects of exogenous chemicals on the GM, as well as the potential impacts on overall human health.

New insights into the evolution and function of the UMAMIT (USUALLY MULTIPLE ACIDS MOVE IN AND OUT TRANSPORTER) gene family.

UMAMIT proteins have been known as key players in amino acid transport. In Arabidopsis, functions of several UMAMITs have been characterized, but their precise mechanism, evolutionary history and functional divergence remain elusive. In this study, we conducted phylogenetic analysis of the UMAMIT gene family across key species in the evolutionary history of plants, ranging from algae to angiosperms. Our findings indicate that UMAMIT proteins underwent a substantial expansion from algae to angiosperms, accompanied by the stabilization of the EamA (the main domain of UMAMIT) structure. Phylogenetic studies suggest that UMAMITs may have originated from green algae and be divided into four subfamilies. These proteins first diversified in bryophytes and subsequently experienced gene duplication events in seed plants. Subfamily I was potentially associated with amino acid transport in seeds. Regarding subcellular localization, UMAMITs were predominantly localized in the plasma membrane and chloroplasts. However, members from clade 8 in subfamily III exhibited specific localization in the tonoplast. These members may have multiple functions, such as plant disease resistance and root development. Furthermore, our protein structure prediction revealed that the four-helix bundle motif is crucial in controlling the UMAMIT switch for exporting amino acid. We hypothesize that the specific amino acids in the amino acid binding region determine the type of amino acids being transported. Additionally, subfamily II contains genes that are specifically expressed in reproductive organs and roots in angiosperms, suggesting neofunctionalization. Our study highlights the evolutionary complexity of UMAMITs and underscores their crucial role in the adaptation and diversification of seed plants.

Clarifying the phylogenetic placement of Eupoinae Maddison, 2015 (Araneae, Salticidae) with ultra-conserved element data

The subfamily Eupoinae Maddison, 2015 is an enigmatic group of minute leaf-litter-dwelling jumping spiders from Southeast Asia. Although previous molecular phylogenetic studies have suggested that it is one of the basal (non-salticine) lineages within jumping spiders, its exact placement remains unclear. In this study, ultra-conserved element data were collected from major salticid lineages to investigate the phylogenetic relationships of all salticid subfamilies, with a special focus on the placement of Eupoinae. The results provide a well-supported phylogeny for jumping spider subfamilies, and suggest a sister relationship of Eupoinae with Spartaeinae Wanless, 1984, a basal lineage of jumping spiders with relatively high species diversity and morphological and behavioural diversity. With the placement of Eupoinae, we have resolved the relationships of all salticid subfamilies, supplying a robust framework for evolutionary studies of jumping spiders.

Comparison between PCR-RFLP and sequencing techniques in the analysis of Paracoccidioides spp. biodiversity: limitations and insights into species and variant differentiation.

The study of Paracoccidioides spp. faces significant challenges due to limitations inherent in the molecular biology techniques employed. Recently, new species were described whose geographical and genetic distributions were investigated. The phylogenetic studies have revealed that genotypes originally thought to be exclusive in specific regions from South American countries are now being found in other areas of the continent. This finding indicates a broader geographic distribution of these genotypes than previously recognized. To evaluate two molecular biology techniques employed to identify genotypes of Paracoccidioides spp. strains from a Brazilian culture collection previously identified only by mycological methods. DNA samples from 35 Paracoccidioides spp. strains maintained in a Brazilian culture collection were subjected to amplification and enzymatic digestion with PCR-RFLP of tub1 gene, followed by sequencing of gp43 Exon 2 loci. Strains with species identification discrepancies had their tub1 sequences determined to verify possible nucleotide mutations. The genotypic characterization of Paracoccidioides spp. using PCR-RFLP of the tub1 gene identified 22 isolates as P. brasiliensis sensu stricto, two as P. americana, four as P. restrepiensis, and eight as P. lutzii. Sequencing of the gp43 Exon 2 loci revealed discrepancies in the identification of four P. venezuelensis isolates, previously characterized as P. brasiliensis sensu stricto by PCR-RFLP of tub1. The sequencing of tub1 from P. brasiliensis sensu stricto and P. venezuelensis isolates revealed nucleotide differences in the pyrimidine class (C and T) in their sequences, specifically at the position 176bp. These molecular tools were able to establish the genetic diversity within the Paracoccidioides genus, crucial for taxonomy and epidemiology studies. The finding of presence of P. venezuelensis in Brazil, previously thought to be exclusive to Venezuela, highlights genetic connections and evolutionary divergences within the genus. While the PCR-RFLP of tub1technique showed limitations in identifying P. venezuelensis, sequencing of the gp43 Exon 2 loci was able to accurately identify this genotype. Thus, our findings contribute to the understanding of the molecular epidemiology of PCM and emphasize the need for precise species characterization in mycological research.

Unsupervised learning analysis on the proteomes of Zika virus

Background The Zika virus (ZIKV), which is transmitted by mosquito vectors to nonhuman primates and humans, causes devastating outbreaks in the poorest tropical regions of the world. Molecular epidemiology, supported by clustering phylogenetic gold standard studies using sequence data, has provided valuable information for tracking and controlling the spread of ZIKV. Unsupervised learning (UL), a form of machine learning algorithm, can be applied on the datasets without the need of known information for training. Methods In this work, unsupervised Random Forest (URF), followed by the application of dimensional reduction algorithms such as principal component analysis (PCA), Uniform Manifold Approximation and Projection (UMAP), t-distributed stochastic neighbor embedding (t-SNE), and autoencoders were used to uncover hidden patterns from polymorphic amino acid sites extracted on the proteome ZIKV multi-alignments, without the need of an underlying evolutionary model. Results The four UL algorithms revealed specific host and geographical clustering patterns for ZIKV. Among the four dimensionality reduction (DR) algorithms, the performance was better for UMAP. The four algorithms allowed the identification of imported viruses for specific geographical clusters. The UL dimension coordinates showed a significant correlation with phylogenetic tree branch lengths and significant phylogenetic dependence in Abouheif’s Cmean and Pagel’s Lambda tests (p value < 0.01) that showed comparable performance with the phylogenetic method. This analytical strategy was generalizable to an external large dengue type 2 dataset. Conclusion These UL algorithms could be practical evolutionary analytical techniques to track the dispersal of viral pathogens.

Mitochondrial Genome Analysis of Babesia ovis (Apicomplexa: Babesiidae) Endemic in Sheep in Türkiye

This study presents the first comprehensive analysis of the mitochondrial genome of Babesia ovis, a significant pathogen in ovine babesiosis in Türkiye. The B. ovis mitochondrial genome is a linear monomeric molecule of 6015 bp with an A + T content of 70.5%, featuring terminal inverted repeats (TIRs) at both ends. It encodes three essential proteins (Cox1, Cox3, and Cob) and six fragments of large subunit rRNA genes. Comparative analysis revealed high sequence identity with Babesia sp. Xinjiang (87.5%) and Babesia sp. Dunhuang (87.5%), suggesting a close evolutionary relationship. The study highlights the conservation of mitochondrial gene content across Babesia and Theileria species, emphasizing their utility in phylogenetic studies. The findings also suggest that TIR variability plays a role in mitochondrial genome size differences, influencing species-specific adaptations. This research provides valuable insights into the evolution and functional adaptations of B. ovis and underscores the potential of mitochondrial genomic data in enhancing diagnostic and therapeutic strategies for babesiosis. Further exploration of mitochondrial genomes in Babesia species is essential for understanding their biology and developing effective control measures.

Genetic characterization of influenza B virus and oseltamivir resistance in pediatric patients with acute respiratory infections: a cross-sectional study.

Influenza virus neuraminidase inhibitors (NAIs) drug usage can result in NAI resistance, especially in children and individuals with weakened immune systems. The aim of the present study was to identify NAI-resistant variants of IBV and to introduce probable novel mutations, phylogenetic study, and its epitope mapping based on NA gene in patients from Shiraz, Iran. A cross-sectional study was conducted between 2017 and 2018 on symptomatic children. A real-time PCR was run for IBV screening. Then, making use of direct sequencing, amplified 1401 bases of NA gene and phylogenetic tree reconstructed. Epitopes were predicted using ABCpred server. From among a total of 235 specimens, 9.7% were identified with IBV infection. Of them, sequence of NA gene for 17 isolates were analyzed. Phylogenetic analysis showed that 15 isolates belonged to Yamagata clade 3 Wisconsin/01-like subclade and 2 were related to Victoria clade 1 Brisbane/60-like subclade (Vic-1A-2). NA gene sequence analysis showed a total of 52 substitutions in which 27 were for BVic and 37 were for BYam isolates and 19 were novel substitutions. Only one substitution (S198N) was found in NA active site and T49M, I120V, N198S, N219K, S295R, D320K N340D, E358K, D384G, and D463N were found as probable resistance variants to NAIs. Epitope mapping showed some major differences in our isolates NA gene. Present study was one of the rare comprehensive studies conducted in Shiraz/Iran on IBV resistant associated variants to NAIs. We reported 11.7% mutation in NA active site and some probable NAIs resistant mutations. Epitope mapping confirmed major changes in NA gene which needs broader studies to confirm.

Generation of genomic resources and phylogenetic contributions in Oxalis from desert fog oases in Peru

AbstractSeveral species in the genus Oxalis occupy Peruvian fog oases (Lomas) with a significant habitat‐adapted and endemic diversity. Acknowledging this aspect, the genus Oxalis is a conceivable group for evolutionary and biogeographic hypothesis testing; however, molecular resources for the genus still need improvement. We conducted a genome skimming approach to assemble new plastomes from 18 accessions (six species) of Oxalis collected in Lomas locations in Peru. These complete plastomes of Oxalis species (several reported for the first time) present a highly conserved composition. Our phylogenetic results were congruent with previous section‐based backbone phylogenies of Oxalis; however, a closer look at the phylogeny of sect. Carnosae revealed nonmonophyletic arrangements involving Oxalis megalorrhiza and Oxalis bulbocastanum individuals. We also propose a set of three hypervariable plastid regions as potential molecular markers. Likewise, an array of primers for nuclear simple sequence repeat markers based on the most widely distributed species, O. megalorrhiza, were listed and evaluated for their transferability to the other species under examination. These new genomic resources represent a significant development for future population, phylogenetic, and biogeographic studies in Oxalis.

Seven mitochondrial genomes of tribe Hylurgini (Coleoptera: Curculionidae: Scolytinae) in Eurasia and their phylogenetic analysis.

The Hylurgini tribe (Coleoptera: Curculionidae: Scolytinae) comprises commercially significant bark beetles, including invasive species within the genera Dendroctonus and Hylurgus. These invasive species coexist with native Tomicus species of Hylurgini and cooperatively infest host trees in China. However, we lack sufficient mitochondrial genome data of Hylurgini to conduct phylogenetic studies, clarify the phylogenetic relationships of the above species, and improve the understanding of niche divergence and common hazards. Here, we sequenced and analyzed the mitochondrial genomes of seven Hylurgini species, including Dendroctonus valens, Hylurgus ligniperda, Hylurgus micklitzi, Tomicus piniperda, Tomicus brevipilosus, Tomicus minor and Tomicus yunnanensis. All sequenced mitochondrial genomes ranged from 15,339 bp to 17,545 bp in length, and their AT contents ranged from 73.24% to 78.81%. The structure of the seven mitochondrial genomes was consistent with that of ancestral insects. Based on 13 protein-coding genes from the reported mitochondrial genomes of 29 species of bark beetles, we constructed phylogenetic trees using maximum likelihood and Bayesian inference methods. The topology of the two phylogenetic trees was almost consistent. The findings elucidated the taxonomy classification of Hylurgini and the evolutionary connections of its sister taxa within the Scolytinae. This study offers insights for examining the evolutionary connections between invasive and native bark beetles, as well as the molecular identification and detection of newly invading species.

Identification, characterization, and sensitivity to phytochemicals of a novel Curvularia species associated with leaf spot disease on Curcuma kwangsiensis

A leaf spot disease affecting Curcuma kwangsiensis (Zingiberaceae) has been observed in Qinzhou City, Guangxi Province. Infected leaves exhibit yellow-brown spots that progressively expand and eventually lead to leaf death. Curvularia isolates were obtained from the diseased leaves with tissue isolation and single spore purification methods. To accurately identify these isolates, we analyzed their morphological characteristics and phylogenetic relationships using combinations of ITS, GAPDH, and EF-1α gene sequences. Phylogenetic analysis showed that the investigated strains formed a distinct clade separate from other recognized Curvularia species. Furthermore, the strains exhibited differences in conidiophore size and conidia shape/size. Based on phylogenetic studies, morphology, and pathogenicity tests, the pathogen was identified as a new species named Curvularia qinzhouensis. Optimal conditions for mycelial growth were observed at 30 °C and pH 8. The sensitivity of the pathogen to various phytochemicals was also examined. Honokiol, thymol, and citral demonstrated effective antifungal effects, with EC50 values of 6.72 ± 1.75, 25.74 ± 4.30, and 54.24 ± 4.69 µg/ml, respectively. The present investigation provides the first report of leaf spot disease on C. kwangsiensis caused by C. qinzhouensis, and valuable insights for the prevention and control of this disease.

The complete mitochondrial genome of Cylicocyclus ultrajectinus (Ihle, 1920)

In this study, the mitochondrial genome of Cylicocyclus ultrajectinus (Ihle, 1920) was sequenced for the first time using next-generation sequencing technology, and its compositional characteristics, structure, and phylogenetic relationship with other strongylid nematodes were analyzed by biological software. The results showed that these sequences contained 12 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 2 non-coding regions, all exhibiting a significant AT bias. Phylogenetic studies showed that C. ultrajectinus formed a distinct branch form other Cylicocyclus nematodes. This study contributes to the mitochondrial genome database of Strongylidae, laying a foundation for genetic variation, molecular classification, and evolutionary studies of strongylid nematodes.

Dealing with dissention in the ranks: A phylogenetic study of Odontadenieae (Apocynaceae)

Dealing with dissention in the ranks: A phylogenetic study of Odontadenieae (Apocynaceae)

A phylogenetic study of South-Western Tibetic

Abstract This study performs primary data collection, transcription, and cognate coding for eight South West Tibetic languages (Lowa, Gyalsumdo, Nubri, Tsum, Yohlmo, Kagate, Jirel, and Sherpa). This includes partial cognate coding, which analyses linguistic relations at the morpheme level. Prior resources and inferences are leveraged to conduct a Bayesian phylogenetic analysis. This helps estimate the extent to which the historical relationships between the languages represent a tree-like structure. We argue that small-scale projects like this are critical to wider attempts to reconstruct the cultural evolutionary history of Sino-Tibetan and other families.

Lacewing‐specific Universal Single Copy Orthologs designed towards resolution of backbone phylogeny of Neuropterida

AbstractUniversal Single Copy Orthologs (USCOs), as a set of markers of nearly universal single‐copy genes, show a superiority in phylogenomic inference. Here, we developed a Benchmarking Universal Single Copy Orthologs (BUSCOs) dataset, neuropterida_odb10, tailored for Neuropterida, based on high‐quality genome assemblies and transcriptome data, comprising 5438 BUSCOs. A range of 1524–5328 complete and single‐copy USCOs could be captured from the genome assemblies and transcriptomes of 104 species of Neuropterida. The reconstruction of a higher‐level phylogeny of Neuropterida based on a comprehensive sampling and refined genomic data in reference to neuropterida_odb10 validates the efficiency of this BUSCO dataset for phylogenomic inference. We recovered Psychopsidae as the sister group to Ithonidae, and corroborated the sister group relationship between Sisyridae and Nevrorthidae within Osmyloidea and the sister group relationship between Chrysopidae and Mantispoidea. Furthermore, our findings highlight that focusing on alignments with a higher presence of parsimony‐informative sites, rather than on the total number of alignments, can diminish errors in gene tree estimation, a process notably vulnerable to error when using multispecies coalescent methods. The neuropterida_odb10 BUSCO reference dataset holds promise for phylogenetic studies at various hierarchical levels, as well as for comparative genomics and the exploration of species diversity within Neuropterida.

Phylogenetic Study of Several Parasitic Plant Species Based on The atp-1 Gene Sequence

The distinction between parasitic and non-parasitic plants can be determined by analyzing the atp-1 gene, which plays a vital role in respiration and is known for its high mutation rate. This study analyzed the kinship of parasitic plant subclass species through the construction of a phylogenetic tree based on atp-1 gene sequences. The atp-1 gene sequences of parasitic and non-parasitic plants with a total of 29 species were obtained from NCBI. The sequences were then aligned with ClustalW and analyzed for mutation patterns. Sequences that have been aligned, phylogenetic trees were made with MEGA11 software with the Maximum Likelihood method and analyzed using the iTOL website. The sequences were analyzed for similarity and kinship with Matrix Coefficient and Haplotype Construction. The atp-1 gene proved that parasitic plants (hemiparasites) are furthermore related to non-parasitic plants compared to holoparasite parasitic plants. Besides that, the kinship of parasitic plants can be analyzed by several methods, namely matrix coefficient to measure similarity, DnaSP to analyzing haplotype, and haplotype network to find out detailed information on mutations that occur. Matrix coefficients can also be used to measure specific similarities between species. It was found that the same subclass had high similarities, for example the species Santalum album and Heisteria parvifolia with a genetic distance value of 0.00574. Meanwhile, different subclasses have low similarity, such as Cassytha filiformis and Ombrophytum with a genetic distance value of 0.07871. This study shows that the atp-1 gene is effective in analyzing the kinship between parasitic and non-parasitic plants. Hemiparasites are genetically closer to non-parasitic plants than holoparasites, with higher genetic similarity within the same subclass.

Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites

Plasmodium falciparum malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, P. falciparum requires nutritional iron to support essential metabolic pathways, but the critical mechanisms of iron acquisition and trafficking during RBC infection have remained obscure. Parasites internalize and liberate massive amounts of heme during large-scale digestion of RBC hemoglobin within an acidic food vacuole (FV) but lack a heme oxygenase to release porphyrin-bound iron. Although most FV heme is sequestered into inert hemozoin crystals, prior studies indicate that trace heme escapes biomineralization and is susceptible to nonenzymatic degradation within the oxidizing FV environment to release labile iron. Parasites retain a homolog of divalent metal transporter 1 (DMT1), a known mammalian iron transporter, but its role in P. falciparum iron acquisition has not been tested. Our phylogenetic studies indicate that P. falciparum DMT1 (PfDMT1) retains conserved molecular features critical for metal transport. We localized this protein to the FV membrane and defined its orientation in an export-competent topology. Conditional knockdown of PfDMT1 expression is lethal to parasites, which display broad cellular defects in iron-dependent functions, including impaired apicoplast biogenesis and mitochondrial polarization. Parasites are selectively rescued from partial PfDMT1 knockdown by supplementation with exogenous iron, but not other metals. These results support a cellular paradigm whereby PfDMT1 is the molecular gatekeeper to essential iron acquisition by blood-stage malaria parasites and suggest that therapeutic targeting of PfDMT1 may be a potent antimalarial strategy.