Phylogeny of Geomydoecus and Thomomydoecus pocket gopher lice (phthiraptera, trichodectidae) inferred from cladistic analysis of adult and first instar morphology

The phylogeny for all 122 species and subspecies of chewing lice of the genera Geomydoecus and Thomomydoecus (Phthiraptera: Trichodectidae) hosted by pocket gophers (Rodentia: Geomyidae) is estimated by a cladistic analysis of fifty-eight morphological characters obtained from adults and first instars. The data set has considerable homoplasy, but still contains phylogenetic information. The phylogeny obtained is moderately resolved and, with some notable exceptions, supports the species complexes proposed by Hellenthal and Price over the the last two decades. The subgenera G. (Thaelerius) and T. (Thomomydoecus) are both shown to be monophyletic, but the monophly of subgenus T. (Jamespattonius) could not be confirmed, perhaps due to the lack of first-instar data for one of its component species. The nominate subgenus of Geomydoecus may be monophyletic, but our cladogram was insufficiently resolved to corroborate this. Mapping the pocket gopher hosts onto the phylogeny reveals a consistent pattern of louse clades being restricted to particular genera or subgenera of gophers, but the history of the host-parasite association appears complex and will require considerable effort to resolve

Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome

Telomere maintenance by telomerase activation or alternative lengthening of telomeres (ALT) is a major determinant of poor outcome in neuroblastoma. Here, we screen for ALT in primary and relapsed neuroblastomas (n = 760) and characterize its features using multi-omics profiling. ALT-positive tumors are molecularly distinct from other neuroblastoma subtypes and enriched in a population-based clinical sequencing study cohort for relapsed cases. They display reduced ATRX/DAXX complex abundance, due to either ATRX mutations (55%) or low protein expression. The heterochromatic histone mark H3K9me3 recognized by ATRX is enriched at the telomeres of ALT-positive tumors. Notably, we find a high frequency of telomeric repeat loci with a neuroblastoma ALT-specific hotspot on chr1q42.2 and loss of the adjacent chromosomal segment forming a neo-telomere. ALT-positive neuroblastomas proliferate slowly, which is reflected by a protracted clinical course of disease. Nevertheless, children with an ALT-positive neuroblastoma have dismal outcome

MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

Aberrant expression of MYC transcription factor family members predicts poor clinical outcome in many human cancers. Oncogenic MYC profoundly alters metabolism and mediates an antioxidant response to maintain redox balance. Here we show that MYCN induces massive lipid peroxidation on depletion of cysteine, the rate-limiting amino acid for glutathione (GSH) biosynthesis, and sensitizes cells to ferroptosis, an oxidative, non-apoptotic and iron-dependent type of cell death. The high cysteine demand of MYCN-amplified childhood neuroblastoma is met by uptake and transsulfuration. When uptake is limited, cysteine usage for protein synthesis is maintained at the expense of GSH triggering ferroptosis and potentially contributing to spontaneous tumor regression in low-risk neuroblastomas. Pharmacological inhibition of both cystine uptake and transsulfuration combined with GPX4 inactivation resulted in tumor remission in an orthotopic MYCN-amplified neuroblastoma model. These findings provide a proof of concept of combining multiple ferroptosis targets as a promising therapeutic strategy for aggressive MYCN-amplified tumors

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Nematode lungworms of two species of anuran amphibians: Evidence for co-adaptation

Genetic studies have indicated that some parasite species formerly thought to be generalists are complexes of morphologically similar species, each appearing to specialize on different host species. Studies on such species are needed to obtain ecological and parasitological data to address whether there are fitness costs in parasitizing atypical host species. We examined whether lungworms from two anuran host species, Lithobates sylvaticus and Lithobates pipiens, differed in measures of infection success in L. pipiens recipient hosts. We also determined if the worms from the two host species were sources of genetically resolvable species of morphologically similar nematodes. Sequences of internal transcribed spacer and lsrDNA regions of adult lungworms from each host species indicated that worms from L. sylvaticus matched Rhabdias bakeri, whereas worms from L. pipiens matched Rhabdias ranae. Our work suggested that these morphologically similar species are distant non-sibling taxa. We infected male and female metamorphs experimentally with lungworm larvae of the two species. We observed higher penetration, higher prevalence and higher mean abundance of adult worms in lungs of male and female metamorphs exposed to R. ranae larvae than in lungs of metamorphs exposed to R. bakeri larvae. Furthermore, metamorphs exposed to R. ranae larvae carried larger adult female worms in their lungs. Some variation in infection measures depended on host sex, but only for one parasite species considered. Overall, the differential establishment and reproductive potential of R. ranae and R. bakeri in L. pipiens suggests co-adaptation

Similar yet different: co-analysis of the genetic diversity and structure of an invasive nematode parasite and its invasive mammalian host

Animal parasitic nematodes can cause serious diseases and their emergence in new areas can be an issue of major concern for biodiversity conservation and human health. Their ability to adapt to new environments and hosts is likely to be affected by their degree of genetic diversity, with gene flow between distinct populations counteracting genetic drift and increasing effective population size. The raccoon roundworm (Baylisascaris procyonis), a gastrointestinal parasite of the raccoon (Procyon lotor), has increased its global geographic range after being translocated with its host. The raccoon has been introduced multiple times to Germany, but not all its populations are infected with the parasite. While fewer introduced individuals may have led to reduced diversity in the parasite, admixture between different founder populations may have counteracted genetic drift and bottlenecks. Here, we analyse the population genetic structure of the roundworm and its raccoon host at the intersection of distinct raccoon populations infected with B. procyonis. We found evidence for two parasite clusters resulting from independent introductions. Both clusters exhibited an extremely low genetic diversity, suggesting small founding populations subjected to inbreeding and genetic drift with no, or very limited, genetic influx from population admixture. Comparison of the population genetic structures of both host and parasite suggested that the parasite spread to an uninfected raccoon founder population. On the other hand, an almost perfect match between cluster boundaries also suggested that the population genetic structure of B. procyonis has remained stable since its introduction, mirroring that of its raccoon host

Phylogeny of Cephalobina (Nematoda): Molecular evidence for recurrent evolution of probolae and incongruence with traditional classifications

Nematodes of the suborder Cephalobina include an ecologically and morphologically diverse array of species that range from soil-dwelling microbivores to parasites of vertebrates and invertebrates. Despite a long history of study, certain of these microbivores (Cephaloboidea) present some of the most intractable problems in nematode systematics; the lack of an evolutionary framework for these taxa has prevented the identification of natural groups and inhibited understanding of soil biodiversity and nematode ecology. Phylogenetic analyses of ribosomal (LSU) sequence data from 53 taxa revealed strong support for monophyly of taxa representing the Cephaloboidea, but do not support the monophyly of most genera within this superfamily. Historically these genera have primarily been recognized based on variation in labial morphology, but molecular phylogenies show the same general labial (probolae) morphotype often results from recurrent similarity, a result consistent with the phenotypic plasticity of probolae previously observed for some species in ecological time. Phylogenetic analyses of LSU rDNA also recovered strong support for some other groups of cephalobs, including taxa representing most (but not all) Panagrolaimoidea. In addition to revealing homoplasy of probolae, molecular trees also imply other unexpected patterns of character evolution or polarity, including recurrent similarity of offset spermatheca presence, and representation of complex probolae as the ancestral condition within Cephaloboidea. For Cephalobidae, molecular trees do not support traditional genera as natural groups, but it remains untested if deconstructing probolae morphotypes or other structural features into finer component characters may reveal homologies that help delimit evolutionary lineage

Factor Analysis via Components Analysis

factor loadings, factor scores, component loadings, component scores,