Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.

What one genus of showy moths can say about migration, adaptation, and wing pattern.

The Ornate Moth, Utetheisa ornatrix, has served as a model species in chemical ecology studies for decades. Like in the widely publicized stories of the Monarch and other milkweed butterflies, the Ornate Moth and its relatives are tropical insects colonizing whole continents assisted by their chemical defenses. With the recent advances in genomic techniques and evo-devo research, it is becoming a model for studies in other areas, from wing pattern development to phylogeography, from toxicology to epigenetics. We used a genomic approach to learn about Utetheisa's evolution, detoxification, dispersal abilities, and wing pattern diversity. We present an evolutionary genomic analysis of the worldwide genus Utetheisa, then focusing on U. ornatrix. Our reference genome of U. ornatrix reveals gene duplications in the regions possibly associated with detoxification abilities, which allows them to feed on toxic food plants. Finally, comparative genomic analysis of over 100 U. ornatrix specimens from the museum with apparent differences in wing patterns suggest the potential roles of cortex and lim3 genes in wing pattern formation of Lepidoptera and the utility of museum-preserved collection specimens for wing pattern research.

ECOD domain classification of 48 whole proteomes from AlphaFold Structure Database using DPAM2.

Protein structure prediction has now been deployed widely across several different large protein sets. Large-scale domain annotation of these predictions can aid in the development of biological insights. Using our Evolutionary Classification of Protein Domains (ECOD) from experimental structures as a basis for classification, we describe the detection and cataloging of domains from 48 whole proteomes deposited in the AlphaFold Database. On average, we can provide positive classification (either of domains or other identifiable non-domain regions) for 90% of residues in all proteomes. We classified 746,349 domains from 536,808 proteins comprised of over 226,424,000 amino acid residues. We examine the varying populations of homologous groups in both eukaryotes and bacteria. In addition to containing a higher fraction of disordered regions and unassigned domains, eukaryotes show a higher proportion of repeated proteins, both globular and small repeats. We enumerate those highly populated domains that are shared in both eukaryotes and bacteria, such as the Rossmann domains, TIM barrels, and P-loop domains. Additionally, we compare the sampling of homologous groups from this whole proteome set against our stable ECOD reference and discuss groups that have been enriched by structure predictions. Finally, we discuss the implication of these results for protein target selection for future classification strategies for very large protein sets.

Deep Learning for Subtypes Identification of Pure Seminoma of the Testis.

The most critical step in the clinical diagnosis workflow is the pathological evaluation of each tumor sample. Deep learning is a powerful approach that is widely used to enhance diagnostic accuracy and streamline the diagnosis process. In our previous study using omics data, we identified 2 distinct subtypes of pure seminoma. Seminoma is the most common histological type of testicular germ cell tumors (TGCTs). Here we developed a deep learning decision making tool for the identification of seminoma subtypes using histopathological slides. We used all available slides for pure seminoma samples from The Cancer Genome Atlas (TCGA). The developed model showed an area under the ROC curve of 0.896. Our model not only confirms the presence of 2 distinct subtypes within pure seminoma but also unveils the presence of morphological differences between them that are imperceptible to the human eye.

Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here, we sought to define the roles of PAX1 and newly identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); p=7.07E-11, OR = 1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wild-type. By genetic targeting we found that wild-type Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, the latter suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 or tamoxifen treatment significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a PAX1-COL11a1-MMP3 signaling axis in spinal chondrocytes.

Adolescent idiopathic scoliosis (AIS) is a twisting deformity of the spine that occurs during periods of rapid growth in children worldwide. Children with severe cases of AIS require surgery to stop it from getting worse, presenting a significant financial burden to health systems and families. Although AIS is known to cluster in families, its genetic causes and its inheritance pattern have remained elusive. Additionally, AIS is known to be more prevalent in females, a bias that has not been explained. Advances in techniques to study the genetics underlying diseases have revealed that certain variations that increase the risk of AIS affect cartilage and connective tissue. In humans, one such variation is near a gene called Pax1, and it is female-specific. The extracellular matrix is a network of proteins and other molecules in the space between cells that help connect tissues together, and it is particularly important in cartilage and other connective tissues. One of the main components of the extracellular matrix is collagen. Yu, Kanshour, Ushiki et al. hypothesized that changes in the extracellular matrix could affect the cartilage and connective tissues of the spine, leading to AIS. To show this, the scientists screened over 100,000 individuals and found that AIS is associated with variants in two genes coding for extracellular matrix proteins. One of these variants was found in a gene called Col11a1, which codes for one of the proteins that makes up collagen. To understand the relationship between Pax1 and Col11a1, Yu, Kanshour, Ushiki et al. genetically modified mice so that they would lack the Pax1 gene. In these mice, the activation of Col11a1 was reduced in the mouse spine. They also found that the form of Col11a1 associated with AIS could not suppress the activation of a gene called Mmp3 in mouse cartilage cells as effectively as unmutated Col11a1. Going one step further, the researchers found that lowering the levels of an estrogen receptor altered the activation patterns of Pax1, Col11a1, and Mmp3 in mouse cartilage cells. These findings suggest a possible mechanism for AIS, particularly in females. The findings of Yu, Kanshour, Ushiki et al. highlight that cartilage cells in the spine are particularly relevant in AIS. The results also point to specific molecules within the extracellular matrix as important for maintaining proper alignment in the spine when children are growing rapidly. This information may guide future therapies aimed at maintaining healthy spinal cells in adolescent children, particularly girls.

Phylogeography of Two Enigmatic Sulphur Butterflies, Colias mongola Alphéraky, 1897 and Colias tamerlana Staudinger, 1897 (Lepidoptera, Pieridae), with Relations to Wolbachia Infection.

The genus Colias Fabricius, 1807 includes numerous taxa and forms with uncertain status and taxonomic position. Among such taxa are Colias mongola Alphéraky, 1897 and Colias tamerlana Staudinger, 1897, interpreted in the literature either as conspecific forms, as subspecies of different but morphologically somewhat similar Colias species or as distinct species-level taxa. Based on mitochondrial and nuclear DNA markers, we reconstructed a phylogeographic pattern of the taxa in question. We recover and include in our analysis DNA barcodes of the century-old type specimens, the lectotype of C. tamerlana deposited in the Natural History Museum (Museum für Naturkunde), Berlin, Germany (ZMHU) and the paralectotype of C. tamerlana and the lectotype of C. mongola deposited in the Zoological Institute, Russian Academy of Sciences, St. Petersburg, Russia (ZISP). Our analysis grouped all specimens within four (HP_I-HP_IV) deeply divergent but geographically poorly structured clades which did not support nonconspecifity of C. mongola-C. tamerlana. We also show that all studied females of the widely distributed haplogroup HP_II were infected with a single Wolbachia strain belonging to the supergroup B, while the males of this haplogroup, as well as all other investigated specimens of both sexes, were not infected. Our data highlight the relevance of large-scale sampling dataset analysis and the need for testing for Wolbachia infection to avoid erroneous phylogenetic reconstructions and species misidentification.

ZNF692 organizes a hub specialized in 40S ribosomal subunit maturation enhancing translation in rapidly proliferating cells.

Increased nucleolar size and activity correlate with aberrant ribosome biogenesis and enhanced translation in cancer cells. One of the first and rate-limiting steps in translation is the interaction of the 40S small ribosome subunit with mRNAs. Here, we report the identification of the zinc finger protein 692 (ZNF692), a MYC-induced nucleolar scaffold that coordinates the final steps in the biogenesis of the small ribosome subunit. ZNF692 forms a hub containing the exosome complex and ribosome biogenesis factors specialized in the final steps of 18S rRNA processing and 40S ribosome maturation in the granular component of the nucleolus. Highly proliferative cells are more reliant on ZNF692 than normal cells; thus, we conclude that effective production of small ribosome subunits is critical for translation efficiency in cancer cells.

Pathogenic mutation hotspots in protein kinase domain structure.

Control of eukaryotic cellular function is heavily reliant on the phosphorylation of proteins at specific amino acid residues, such as serine, threonine, tyrosine, and histidine. Protein kinases that are responsible for this process comprise one of the largest families of evolutionarily related proteins. Dysregulation of protein kinase signaling pathways is a frequent cause of a large variety of human diseases including cancer, autoimmune, neurodegenerative, and cardiovascular disorders. In this study, we mapped all pathogenic mutations in 497 human protein kinase domains from the ClinVar database to the reference structure of Aurora kinase A (AURKA) and grouped them by the relevance to the disease type. Our study revealed that the majority of mutation hotspots associated with cancer are situated within the catalytic and activation loops of the kinase domain, whereas non-cancer-related hotspots tend to be located outside of these regions. Additionally, we identified a hotspot at residue R371 of the AURKA structure that has the highest number of exclusively non-cancer-related pathogenic mutations (21) and has not been previously discussed.

Taxonomic notes on Neotropical Hesperiidae (Lepidoptera).

Genomic sequencing (or morphology when indicated) and analysis of Hesperiidae that includes a number of primary type specimens reveals inconsistencies between the phylogenetic trees and the current classification that are resolved here. The following taxonomic changes are proposed. Oeonus Godman, 1900, stat. nov. is a subgenus of Oxynthes Godman, 1900. Decinea lydora (Plötz, 1882), stat. rev. is a valid species, not a synonym of Lindra neroides (Herrich-Schäffer, 1869), comb. nov. The following are: species-level taxa, not subspecies: Cabirus junta Evans, 1952, stat. nov. and Cabirus purda Evans, 1952, stat. nov. (not Cabirus procas (Cramer, 1777)), Orthos hyalinus (E. Bell, 1930), stat. rest. and Orthos minka Evans, 1955, stat. nov. (not Orthos orthos (Godman, 1900)), Eprius obrepta (Kivirikko, 1936), stat. rest. (not Eprius veleda (Godman, 1901)), Corra catargyra (C. Felder & R. Felder, 1867), stat. rest. and Corra conka (Evans, 1955), stat. nov. (not Corra coryna (Hewitson, 1866)), Cymaenes macintyrei Hayward, 1939, stat. rest. (not Cymaenes tripunctata (Latreille, [1824])), Duroca lenta (Evans, 1955), stat. rest. (not Duroca duroca Plötz, 1882), Oarisma (Copaeodes) favor (Evans, 1955), stat. nov. (not Oarisma (Copaeodes) jean (Evans, 1955)), Panoquina eugeon (Godman & Salvin, 1896), stat. rest., Panoquina calna Evans, 1955, stat. nov. and Panoquina albistriga O. Mielke, 1980, stat. nov. (not Panoquina panoquinoides (Skinner, 1891)); subspecies-level taxa, not species: Carystus elvira rufoventris Austin & O. Mielke, 2007, stat. nov.; junior subjective synonyms: Bungalotis gagarini O. Mielke, 1967, syn. nov. of Bungalotis corentinus (Plötz, 1882), Salantoia dinka (Evans, 1952), syn. nov. of Adina adrastor (Mabille and Boullet, 1912), Lindra brasus ackeryi O. Mielke, 1978, stat. nov. of Lindra neroides neroides (Herrich-Schäffer, 1869) (but Lindra brasus (O. Mielke, 1968) is still a valid species), Vidius felus O. Mielke, 1968, syn. nov. of Vidius dagon (Evans, 1955), comb. nov., and Cobalopsis dorpa de Jong, 1983, syn. nov. of Vidius catocala (Herrich-Schäffer, 1869), comb. nov.; new genus-species combinations: Oxynthes (Oxynthes) egma (Evans, 1955), comb. nov. (not Oeonus Godman, 1900), Lindra neroides (Herrich-Schäffer, 1869), comb. nov. (not Decinea Evans, 1955), Mucia rusta (Evans, 1955), comb. nov. (not Psoralis Mabille, 1904), Rhomba mirnae (Siewert, Nakamura & O. Mielke, 2014), comb. nov. (not Alychna Grishin, 2019), Eprius planus (Weeks, 1901), comb. nov. and Eprius penna (Evans, 1955), comb. nov. (changed based on morphology) (not Mnasicles Godman, 1901), Lattus minor (O. Mielke, 1967), comb. nov. (not Eutocus Godman, 1901), Panca fiedleri (Carneiro, O. Mielke & Casagrande, 2015), comb. nov., Eutocus rogan (Evans, 1955), comb. nov. (changed based on morphology and cytochrome c oxidase subunit I (COI) DNA barcode) and Eutocus brasilia (Carneiro, O. Mielke & Casagrande, 2015), comb. nov. (not Ginungagapus Carneiro, O. Mielke & Casagrande, 2015), Eutocus fosca (Evans, 1955), comb. nov. (not Artines Godman, 1901), Rectava cascatona (O. Mielke, 1992), comb. nov. (not Papias Godman, 1900), Lurida zama (Hayward, 1939), comb. nov. and Vehilius campestris (O. Mielke, 1980), comb. nov. (not Cymaenes Scudder, 1872), Corra xanthus (O. Mielke, 1989), comb. nov., Cymaenes catarinae (O. Mielke, 1989), comb. nov., Vehilius spitzi (O. Mielke, 1967), comb. nov., Vehilius tinta (Evans, 1955), comb. nov. (not Vidius Evans, 1955), Cymaenes incomptus (Hayward, 1934), comb. nov. and Vehilius tanta (Evans, 1955), comb. nov. (not Nastra Evans, 1955), Vidius catocala (Herrich-Schäffer, 1869), comb. nov. Vidius cocalus (Hayward, 1939), comb. nov., Vidius dagon (Evans, 1955), and Vidius obscurior (Hayward, 1934), comb. nov. (not Cobalopsis Godman, 1900), Duroca caraca (O. Mielke, 1992), comb. nov. (not Lerema Scudder, 1872), and Cantha eteocla (Plötz, 1882), comb. nov. and Cantha buriti (O. Mielke, 1968), comb. nov. (not Phlebodes Hübner, [1819]); and new species-subspecies combinations: Lindra neroides huxleyi O. Mielke, 1978, comb. nov. (not Lindra brasus (O. Mielke, 1968)), Corra conka argentus (H. Freeman, 1969), stat. nov. (not Corra coryna (Hewitson, 1866)), Panoquina eugeon minima de Jong, 1983, comb. nov. (not Panoquina panoquinoides (Skinner, 1891)). The following neotype and lectotypes are designated to ensure nomenclatural identity and stability: neotype of Cobalus neroides Herrich-Schäffer, 1869 and lectotypes of Cobalus catocala Herrich-Schäffer, 1869 and Lerema elgina Schaus, 1902.

Lessons from the genomic analysis of Hesperiidae (Lepidoptera) holotypes in the MIZA collection (Maracay, Venezuela).

Genomic sequencing and analysis of holotypes from the MIZA collection (Maracay, Venezuela) and their comparison with other species and their type specimens advances our understanding of their taxonomy. Jemadia demarmelsi Orellana, [2010] is confirmed as a species-level taxon and its female is genetically verified. The following are species-level taxa, not subspecies: Amenis pedro O. Mielke & Casagrande, 2022, stat. nov. (not Amenis pionia (Hewitson, 1857)) and Jemasonia sosia (Mabille, 1878), stat. rest. (not Jemasonia hewitsonii (Mabille, 1878)). Amenis ponina rogeri Orellana, [2010], stat. nov. and Jemasonia pater ortizi (Orellana, [2010]), stat. nov. are subspecies, not species. Jemadia pseudognetus imitator (Mabille, 1891), comb. nov. (not Jemadia hospita (Butler, 1877)) and Damas cervelina Orellana & Costa, 2019, comb. nov. (not Megaleas Godman, 1901) are new combinations.

Pan-cancer structurome reveals overrepresentation of beta sandwiches and underrepresentation of alpha helical domains.

The recent progress in the prediction of protein structures marked a historical milestone. AlphaFold predicted 200 million protein models with an accuracy comparable to experimental methods. Protein structures are widely used to understand evolution and to identify potential drug targets for the treatment of various diseases, including cancer. Thus, these recently predicted structures might convey previously unavailable information about cancer biology. Evolutionary classification of protein domains is challenging and different approaches exist. Recently our team presented a classification of domains from human protein models released by AlphaFold. Here we evaluated the pan-cancer structurome, domains from over and under expressed proteins in 21 cancer types, using the broadest levels of the ECOD classification: the architecture (A-groups) and possible homology (X-groups) levels. Our analysis reveals that AlphaFold has greatly increased the three-dimensional structural landscape for proteins that are differentially expressed in these 21 cancer types. We show that beta sandwich domains are significantly overrepresented and alpha helical domains are significantly underrepresented in the majority of cancer types. Our data suggest that the prevalence of the beta sandwiches is due to the high levels of immunoglobulins and immunoglobulin-like domains that arise during tumor development-related inflammation. On the other hand, proteins with exclusively alpha domains are important elements of homeostasis, apoptosis and transmembrane transport. Therefore cancer cells tend to reduce representation of these proteins to promote successful oncogeneses.

Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than five-fold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here we sought to define the roles of PAX1 and newly-identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); P=7.07e-11, OR=1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc (IVD)-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wildtype. By genetic targeting we found that wildtype Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, this suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2, or tamoxifen treatment, significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a Pax1-Col11a1-Mmp3 signaling axis in spinal chondrocytes.

Classification of domains in predicted structures of the human proteome.

Recent advances in protein structure prediction have generated accurate structures of previously uncharacterized human proteins. Identifying domains in these predicted structures and classifying them into an evolutionary hierarchy can reveal biological insights. Here, we describe the detection and classification of domains from the human proteome. Our classification indicates that only 62% of residues are located in globular domains. We further classify these globular domains and observe that the majority (65%) can be classified among known folds by sequence, with a smaller fraction (33%) requiring structural data to refine the domain boundaries and/or to support their homology. A relatively small number (966 domains) cannot be confidently assigned using our automatic pipelines, thus demanding manual inspection. We classify 47,576 domains, of which only 23% have been included in experimental structures. A portion (6.3%) of these classified globular domains lack sequence-based annotation in InterPro. A quarter (23%) have not been structurally modeled by homology, and they contain 2,540 known disease-causing single amino acid variations whose pathogenesis can now be inferred using AF models. A comparison of classified domains from a series of model organisms revealed expansions of several immune response-related domains in humans and a depletion of olfactory receptors. Finally, we use this classification to expand well-known protein families of biological significance. These classifications are presented on the ECOD website (http://prodata.swmed.edu/ecod/index_human.php).

Additional taxonomic refinements suggested by genomic analysis of butterflies.

Comparative analyses of genomic data reveal further insights into the phylogeny and taxonomic classification of butterflies presented here. As a result, 2 new subgenera and 2 new species of Hesperiidae are described: Borna Grishin, subgen. n. (type species Godmania borincona Watson, 1937) and Lilla Grishin, subgen. n. (type species Choranthus lilliae Bell, 1931) of Choranthus Scudder, 1872, Cecropterus (Murgaria) markwalkeri Grishin, sp. n. (type locality in Mexico: Sonora), and Hedone yunga Grishin, sp. n. (type locality in Bolivia: Yungas, La Paz). The lectotype is designated for Aethilla toxeus Plötz, 1882. The type locality of Dion uza (Hewitson, 1877) is likely in southern Brazil. A number of taxonomic changes are proposed. The following taxa are subgenera, not genera: Plebulina Nabokov, 1945 of Icaricia Nabokov, 1945; Sinia Forster, 1940 of Glaucopsyche Scudder, 1872; Pseudophilotes Beuret, 1958 of Palaeophilotes Forster, 1938; and Agraulis Boisduval & Le Conte, [1835] of Dione Hübner, [1819]. Asbolis Mabille, 1904 is a subgenus of Choranthus Scudder, 1872 rather than its synonym. The following are species, not subspecies or synonyms: Glaucopsyche algirica (Heyne, 1895) (not Glaucopsyche melanops (Boisduval, 1829)), Chlosyne flavula (W. Barnes & McDunnough, 1918) (not Chlosyne palla (Boisduval, 1852)), Cercyonis hypoleuca Hawks & J. Emmel, 1998 (not Cercyonis sthenele (Boisduval, 1852)), Cecropterus coyote (Skinner, 1892) and Cecropterus nigrociliata (Mabille & Boullet, 1912) (not Aethilla toxeus Plötz, 1882), Aguna malia Evans, 1952 (not Aguna megaeles (Mabille, 1888)), Polygonus arizonensis (Skinner, 1911), Polygonus histrio Röber, 1925, Polygonus pallida Röber, 1925, and Polygonus hagar Evans, 1952 (not Polygonus leo (Gmelin, [1790])), Viola kuma (Bell, 1942), comb. nov. (not Pachyneuria helena (Hayward, 1939)), Tamela maura (Snellen, 1886) (not Tamela othonias (Hewitson, 1878)), Tamela diocles (Moore, [1866]) (not Tamela nigrita (Latreille, [1824])), Vinius phellus (Mabille, 1883) (not Vinius exilis (Plötz, 1883)), Vinius sophistes (Dyar, 1918) (not Vinius tryhana (Kaye, 1914)), and Rhinthon andricus (Mabille, 1895) and Rhinthon aqua (Evans, 1955) (not Rhinthon braesia (Hewitson, 1867)). The following are new and revised species-subspecies combinations: Cercyonis sthenele damei W. Barnes & Benjamin, 1926 (not Cercyonis meadii (W. H. Edwards, 1872)) and Chlosyne flavula blackmorei Pelham, 2008 and Chlosyne flavula calydon (W. Holland, 1931) (not Chlosyne palla). The following are valid subspecies resurrected from synonymy in new and reinstated species-subspecies combinations: Chlosyne palla pola (Boisduval, 1869) (not Chlosyne gabbii gabbii (Behr, 1863)) and Cercyonis meadii mexicana R. Chermock, 1949 (not Cercyonis sthenele damei W. Barnes & Benjamin, 1926, comb. rev.). The following are new junior subjective synonyms: Aethilla toxeus Plötz, 1882 of Cecropterus albociliatus (Mabille, 1877) and Viola dagamba Steinhauser, 1989 of Viola kuma (Bell, 1942), comb. nov., stat. rest. Leucochitonea janice Ehrmann, 1907 is a junior subjective synonym of Heliopetes alana (Reakirt, 1868) and not of Heliopetes petrus (Hübner, [1819]). The holotype of Hermeuptychia sinuosa Grishin, 2021 is illustrated after being spread.

Thirteen new species of butterflies (Lepidoptera: Hesperiidae) from Texas.

Analyses of whole genomic shotgun datasets, COI barcodes, morphology, and historical literature suggest that the following 13 butterfly species from the family Hesperiidae (Lepidoptera: Papilionoidea) in Texas, USA are distinct from their closest named relatives and therefore are described as new (type localities are given in parenthesis): Spicauda atelis Grishin, new species (Hidalgo Co., Mission), Urbanus (Urbanus) rickardi Grishin, new species (Hidalgo Co., nr. Madero), Urbanus (Urbanus) oplerorum Grishin, new species (Hidalgo Co., Mission/Madero), Telegonus tsongae Grishin, new species (Starr Co., Roma), Autochton caballo Grishin, new species (Hidalgo Co., 6 mi W of Hidalgo), Epargyreus fractigutta Grishin, new species (Hidalgo Co., McAllen), Aguna mcguirei Grishin, new species (Cameron Co., Brownsville), Polygonus pardus Grishin, new species (Hidalgo Co., McAllen), Arteurotia artistella Grishin, new species (Hidalgo Co., Mission), Heliopetes elonmuski Grishin, new species (Cameron Co., Boca Chica), Hesperia balcones Grishin, new species (Travis Co., Volente), Troyus fabulosus Grishin, new species (Hidalgo Co., Peñitas), and Lerema ochrius Grishin, new species (Hidalgo Co., nr. Relampago). Most of these species are known in the US almost exclusively from the Lower Rio Grande Valley in Texas. Nine of the holotypes were collected in 1971-1975, a banner period for butterfly species newly recorded from the Rio Grande Valley of Texas; five of them collected by William W. McGuire, and one by Nadine M. McGuire. At the time, these new species have been recorded under the names of their close relatives. A Neotype is designated for Papilio fulminator Sepp, [1841] (Suriname). Lectotypes are designated for Goniurus teleus Hübner, 1821 (unknown, likely in South America), Goniloba azul Reakirt, [1867] (Mexico: Veracruz) and Eudamus misitra Plötz, 1881 (Mexico). Several taxonomic changes are proposed. The following taxa are species (not subspecies): Spicauda zalanthus (Plötz, 1880), reinstated status (not Spicauda teleus (Hübner, 1821)), Telegonus fulminator (Sepp, [1841]), reinstated status (not Telegonus fulgerator (Walch, 1775), Telegonus misitra (Plötz, 1881), reinstated status (not Telegonus azul (Reakirt, [1867])), Autochton reducta (Mabille and Boullet, 1919), new status (not Autochton potrillo (Lucas, 1857)), Epargyreus gaumeri Godman and Salvin, 1893, reinstated status (not Epargyreus clavicornis (Herrich-Schäffer, 1869)), and Polygonus punctus E. Bell and W. Comstock, 1948, new status (not Polygonus savigny (Latreille, [1824])). Urbanus ehakernae Burns, 2014 and Epargyreus socus chota Evans, 1952 are junior subjective synonyms of Urbanus alva Evans, 1952 and Epargyreus clavicornis (Herrich-Schäffer, 1869), respectively, and Epargyreus gaumeri tenda Evans, 1955, new combination is not a subspecies of E. clavicornis.

DPAM: A domain parser for AlphaFold models.

The recent breakthroughs in structure prediction, where methods such as AlphaFold demonstrated near-atomic accuracy, herald a paradigm shift in structural biology. The 200 million high-accuracy models released in the AlphaFold Database are expected to guide protein science in the coming decades. Partitioning these AlphaFold models into domains and assigning them to an evolutionary hierarchy provide an efficient way to gain functional insights into proteins. However, classifying such a large number of predicted structures challenges the infrastructure of current structure classifications, including our Evolutionary Classification of protein Domains (ECOD). Better computational tools are urgently needed to parse and classify domains from AlphaFold models automatically. Here we present a Domain Parser for AlphaFold Models (DPAM) that can automatically recognize globular domains from these models based on inter-residue distances in 3D structures, predicted aligned errors, and ECOD domains found by sequence (HHsuite) and structural (Dali) similarity searches. Based on a benchmark of 18,759 AlphaFold models, we demonstrate that DPAM can recognize 98.8% of domains and assign correct boundaries for 87.5%, significantly outperforming structure-based domain parsers and homology-based domain assignment using ECOD domains found by HHsuite or Dali. Application of DPAM to the massive AlphaFold models will enable efficient classification of domains, providing evolutionary contexts and facilitating functional studies.

Neotype designation for Papilio fulgerator Walch, 1775 (Hesperiidae: Eudaminae).

The discovery that a skipper butterfly Telegonus fulgerator (Walch, 1775), previously placed in the genus Astraptes Hübner, [1819], is a complex of many similar-looking species-level taxa with different COI barcodes, caterpillar foodplants and body patterns, and subtle differences in adult phenotypes raised a question about which species is the original T. fulgerator. To answer this question, being unable to locate its holotype, we designate the neotype of Papilio fulgerator Walch, 1775, a female specimen from Suriname in the Zoological State Collection, Munich, Germany. This neotype will form the foundation for a comprehensive revision of the T. fulgerator complex based on genomic sequencing and analysis augmented with phenotypic considerations.

Integrated Molecular Analysis Reveals 2 Distinct Subtypes of Pure Seminoma of the Testis.

Objective: Testicular germ cell tumors (TGCT) are the most common solid malignancy in adolescent and young men, with a rising incidence over the past 20 years. Overall, TGCTs are second in terms of the average life years lost per person dying of cancer, and clinical therapeutics without adverse long-term side effects are lacking. Platinum-based regimens for TGCTs have heterogeneous outcomes even within the same histotype that frequently leads to under- and over-treatment. Understanding of molecular differences that lead to diverse outcomes of TGCT patients may improve current treatment approaches. Seminoma is the most common subtype of TGCTs, which can either be pure or present in combination with other histotypes. Methods: Here we conducted a computational study of 64 pure seminoma samples from The Cancer Genome Atlas, applied consensus clustering approach to their transcriptomic data and revealed 2 clinically relevant seminoma subtypes: seminoma subtype 1 and 2. Results: Our analysis identified significant differences in pluripotency stage, activity of double stranded DNA breaks repair mechanisms, rates of loss of heterozygosity, and expression of lncRNA responsible for cisplatin resistance between the subtypes. Seminoma subtype 1 is characterized by higher pluripotency state, while subtype 2 showed attributes of reprograming into non-seminomatous TGCT. The seminoma subtypes we identified may provide a molecular underpinning for variable responses to chemotherapy and radiation. Conclusion: Translating our findings into clinical care may help improve risk stratification of seminoma, decrease overtreatment rates, and increase long-term quality of life for TGCT survivors.

Taxonomic discoveries enabled by genomic analysis of butterflies.

The comparative genomics of butterflies yields additional insights into their phylogeny and classification that are compiled here. As a result, 3 genera, 5 subgenera, 5 species, and 3 subspecies are proposed as new, i.e., in Hesperiidae: Antina Grishin, gen. n. (type species Antigonus minor O. Mielke, 1980), Pompe Grishin and Lamas, gen. n. (type species Lerema postpuncta Draudt, 1923), and Curva Grishin, gen. n. (type species Moeris hyagnis Godman, 1900); in Lycaenidae: Fussia Grishin, subgen. n. (type species Polyommatus standfussi Grum-Grshimailo, 1891) and Pava Grishin, subgen. n. (type species Thecla panava Westwood, 1852); in Hesperiidae: Monoca Grishin, subgen. n. (type species Tagiades monophthalma Plötz, 1884), Putuma Grishin, subgen. n. (type species Tisias putumayo Constantino and Salazar, 2013), and Rayia Grishin, subgen. n. (type species Mastor perigenes Godman, 1900); Cissia wahala Grishin, sp. n. (Nymphalidae; type locality in Mexico: Oaxaca); in Hesperiidae: Hedone mira Grishin and Lamas, sp. n. (type locality in Peru: Apurímac), Vidius pompeoides Grishin, sp. n. (type locality in Brazil: Amazonas), Parphorus hermieri Grishin, sp. n. (Hesperiidae; type locality in Brazil: Rondônia), and Zenis par Grishin, sp. n. (Hesperiidae; type locality in Peru: Cuzco); in Pieridae: Glutophrissa drusilla noroesta Grishin, ssp. n. (type locality in USA: Texas, Cameron Co.) and Pieris marginalis siblanca Grishin, ssp. n. (type locality in USA: New Mexico, Lincoln Co.), and Argynnis cybele neomexicana Grishin, ssp. n. (Nymphalidae; type locality in USA: New Mexico, Sandoval Co.). Acidalia leto valesinoides-alba Reuss, [1926] and Acidalia nokomis valesinoides-alba Reuss, [1926] are unavailable names. Neotypes are designated for Mylothris margarita Hübner, [1825] (type locality in Brazil) and Papilio coras Cramer, 1775 (type locality becomes USA: Pennsylvania, Montgomery Co., Flourtown). Mylothris margarita Hübner, [1825] becomes a junior objective synonym of Pieris ilaire Godart, 1819, currently a junior subjective synonym of Glutophrissa drusilla (Cramer, 1777). Lectotypes are designated for Hesperia ceramica Plötz, 1886 (type locality in Indonesia: Seram Island), Pamphila trebius Mabille, 1891 (type locality Colombia: Bogota), Methionopsis modestus Godman, 1901 and Papias microsema Godman, 1900 (type locality in Mexico: Tabasco), Hesperia fusca Grote & Robinson, 1867 (type locality in USA: Georgia), Goniloba corusca Herrich-Schäffer, 1869, and Goniloba devanes Herrich-Schäffer, 1869; the type localities of the last two species, together with Pamphila stigma Skinner, 1896 and Carystus (Argon) lota (Hewitson, 1877), are deduced to be in South America. Type locality of Junonia pacoma Grishin, 2020 is in Sinaloa, not Sonora (Mexico). Abdomen is excluded from the holotype of Staphylus ascalon (Staudinger, 1876). Furthermore, a number of taxonomic changes are proposed. Alciphronia Koçak, 1992 is treated as a subgenus, not a synonym of Heodes Dalman, 1816. The following genera are treated as subgenera: Lafron Grishin, 2020 of Lycaena [Fabricius], 1807, Aremfoxia Real, 1971 of Epityches D'Almeida, 1938, Placidina D'Almeida, 1928 of Pagyris Boisduval, 1870, and Methionopsis Godman, 1901 of Mnasinous Godman, 1900. Polites (Polites) coras (Cramer, 1775) is not a nomen dubium but a valid species. The following are species-level taxa (not subspecies or synonyms of taxa given in parenthesis): Lycaena pseudophlaeas (Lucas, 1866) and Lycaena hypophlaeas (Boisduval, 1852) (not Lycaena phlaeas (Linnaeus, 1761), Satyrium dryope (W. H. Edwards, 1870) (not Satyrium sylvinus (Boisduval, 1852)), Apodemia cleis (W. H. Edwards, 1882) (not Apodemia zela (Butler, 1870)), Epityches thyridiana (Haensch, 1909), comb. nov. (not Epityches ferra Haensch, 1909, comb. nov.), Argynnis bischoffii W. H. Edwards, 1870 (not Argynnis mormonia Boisduval, 1869), Argynnis leto Behr, 1862 (not Argynnis cybele (Fabricius, 1775)), Boloria myrina (Cramer, 1777) (not Boloria selene ([Denis & Schiffermüller], 1775)), Phyciodes jalapeno J. Scott, 1998 (not Phyciodes phaon (W. H. Edwards, 1864)), Phyciodes incognitus Gatrelle, 2004 and Phyciodes diminutor J. Scott, 1998 (not Phyciodes cocyta (Cramer, 1777)), Phyciodes orantain J. Scott, 1998 (not Phyciodes tharos (Drury, 1773)), Phyciodes anasazi J. Scott, 1994 (not Phyciodes batesii (Reakirt, [1866])), Cercyonis silvestris (W. H. Edwards, 1861) (not Cercyonis sthenele (Boisduval, 1852)), Paramacera allyni L. Miller, 1972 and Paramacera rubrosuffusa L. Miller, 1972 (not Paramacera xicaque (Reakirt, [1867])), Cissia cheneyorum (R. Chermock, 1949), Cissia pseudocleophes (L. Miller, 1976), and Cissia anabelae (L. Miller, 1976) (not Cissia rubricata (W. H. Edwards, 1871)), Tarsoctenus gaudialis (Hewitson, 1876) (not Tarsoctenus corytus (Cramer, 1777)), Nisoniades inca (Lindsey, 1925) (not Nisoniades mimas (Cramer, 1775), Xenophanes ruatanensis Godman & Salvin, 1895 (not Xenophanes tryxus (Stoll, 1780)), Lotongus shigeoi Treadaway & Nuyda, 1994, Lotongus balta Evans, 1949, Lotongus zalates (Mabille, 1893), and Lotongus taprobanus (Plötz, 1885) (not Lotongus calathus (Hewitson, 1876)), Oxynthes martius (Mabille, 1889) (not Oxynthes corusca (Herrich-Schäffer, 1869)), Notamblyscirtes durango J. Scott, 2017 (not Notamblyscirtes simius W. H. Edwards, 1881), Hedone praeceps Scudder, 1872, Hedone catilina (Plötz, 1886), and Hedone calla (Evans, 1955) (not Hedone vibex (Geyer, 1832)), Atalopedes huron (W. H. Edwards, 1863) (not Atalopedes campestris (Boisduval, 1852)), Papias microsema Godman, 1900 (not Mnasinous phaeomelas (Hübner, [1829]), comb. nov.), Papias unicolor (Hayward, 1938) and Papias monus Bell, 1942 (not Papias phainis Godman, 1900), Nastra leuconoides (Lindsey, 1925) (not Nastra leucone (Godman, 1900)), Nastra fusca (Grote & Robinson, 1867) (not Nastra lherminier (Latreille, [1824])), Zenis hemizona (Dyar, 1918) and Zenis janka Evans, 1955 (not Zenis jebus (Plötz, 1882)), Carystus (Argon) argus Möschler, 1879 (not Carystus (Argon) lota Hewitson, 1877), and Lycas devanes (Herrich-Schäffer, 1869) (not Lycas argentea (Hewitson, 1866)). Borbo impar ceramica (Plötz, 1886), comb. nov. is not a synonym of Pelopidas agna larika (Pagenstecher, 1884) but a valid subspecies. Parnassius smintheus behrii W. H. Edwards, 1870 and Cercyonis silvestris incognita J. Emmel, T. Emmel & Mattoon, 2012 are subspecies, not species. The following are junior subjective synonyms: Shijimiaeoides Beuret, 1958 of Glaucopsyche Scudder, 1872, Micropsyche Mattoni, 1981 of Turanana Bethune-Baker, 1916, Cyclyrius Butler, 1897 of Leptotes Scudder, 1876, Mesenopsis Godman & Salvin, 1886 of Xynias Hewitson, 1874, Carystus tetragraphus Mabille, 1891 of Lotongus calathus parthenope (Plötz, 1886), Parnara bipunctata Elwes & J. Edwards, 1897 of Borbo impar ceramica (Plötz, 1886), Hesperia peckius W. Kirby, 1837 of Polites (Polites) coras (Cramer, 1775), and Lerodea neamathla Skinner & R. Williams, 1923 of Nastra fusca (Grote & Robinson, 1867). The following transfers are proposed: of species between genera (i.e., revised genus-species combinations): Nervia niveostriga (Trimen, 1864) (not Kedestes Watson, 1893), Leona lota Evans, 1937 (not Lennia Grishin, 2022), Leona pruna (Evans, 1937) and Leona reali (Berger, 1962) (not Pteroteinon Watson, 1893), Mnasinous phaeomelas (Hübner, [1829]) (not Papias Godman, 1900), Saturnus jaguar (Steinhauser, 2008) (not Parphorus Godman, 1900), Parphorus harpe (Steinhauser, 2008) (not Saturnus Evans, 1955), Parphorus kadeni (Evans, 1955) (not Lento Evans, 1955), and Calpodes chocoensis (Salazar & Constantino, 2013) (not Megaleas Godman, 1901); of subspecies between species (i.e., revised species-subspecies combinations): Melitaea sterope W. H. Edwards, 1870 of Chlosyne palla (Boisduval, 1852) (not Chlosyne acastus (W. H. Edwards, 1874)) and Panoquina ocola distipuncta Johnson & Matusik, 1988 of Panoquina lucas (Fabricius, 1793); and junior subjective synonym transferred between species: Rhinthon zaba Strand, 1921 of Conga chydaea (A. Butler, 1877), not Cynea cynea (Hewitson, 1876), Pamphila stigma Skinner, 1896 of Hedone catilina (Plötz, 1886), not Hedone praeceps Scudder, 1872, and Pamphila ortygia Möschler, 1883 of Panoquina hecebolus (Scudder, 1872), not Panoquina ocola (W. H. Edwards, 1863). Proposed taxonomic changes result in additional revised species-subspecies combinations: Lycaena pseudophlaeas abbottii (Holland, 1892), Satyrium dryope putnami (Hy. Edwards, 1877), Satyrium dryope megapallidum Austin, 1998, Satyrium dryope itys (W. H. Edwards, 1882), Satyrium dryope desertorum (F. Grinnell, 1917), Argynnis bischoffi opis W. H. Edwards, 1874, Argynnis bischoffi washingtonia W. Barnes & McDunnough, 1913, Argynnis bischoffi erinna W. H. Edwards, 1883, Argynnis bischoffi kimimela Marrone, Spomer & J. Scott, 2008, Argynnis bischoffi eurynome W. H. Edwards, 1872, Argynnis bischoffi artonis W. H. Edwards, 1881, Argynnis bischoffi luski W. Barnes & McDunnough, 1913, Argynnis leto letona (dos Passos & Grey, 1945), Argynnis leto pugetensis (F. Chermock & Frechin, 1947), Argynnis leto eileenae (J. Emmel, T. Emmel & Mattoon, 1998), Boloria myrina nebraskensis (W. Holland, 1928), Boloria myrina sabulocollis Kohler, 1977, Boloria myrina tollandensis (W. Barnes & Benjamin, 1925), Boloria myrina albequina (W. Holland, 1928), Boloria myrina atrocostalis (Huard, 1927), Boloria myrina terraenovae (W. Holland, 1928), Phyciodes anasazi apsaalooke J. Scott, 1994, Polites coras surllano J. Scott, 2006, and Curva darienensis (Gaviria, Siewert, Mielke & Casagrande, 2018). Specimen curated as the holotype of Acidalia leto valesinoides-alba Reuss, [1926] is Argynnis leto letona (dos Passos & Grey, 1945) (not A. leto leto Behr, 1862) from USA: Utah, Provo. A synonymic list of available genus-group names for Lycaeninae [Leach],[1815] is given. Unless stated otherwise, all subgenera, species, subspecies and synonyms of mentioned genera and species are transferred with their parent taxa, and others remain as previously classified.

Genomic analysis reveals a new genus of Firetip skippers (Lepidoptera: Hesperiidae: Pyrrhopyginae).

We obtained whole genome shotgun sequence reads for a number of Firetip skippers (subfamily Pyrrhopyginae), including all known species from the genera Yanguna Watson, 1893 and Gunayan Mielke, 2002 and representative species of Pyrrhopyge Hübner, [1819]. Phylogenetic analysis of their protein-coding regions unexpectedly revealed that Yanguna tetricus Bell, 1931 was not monophyletic with the other species of Yanguna (type species Pyrrhopyga spatiosa Hewitson, 1870). Instead, Y. tetricus formed a phylogenetic lineage as ancient as other three genera in its clade (Pyrrhopyge, Yanguna and Gunayan) that rapidly diversified from their ancestor. Therefore a new genus, Guyanna Grishin, gen. n. (type species Yanguna tetricus), is proposed for this lineage. The specimen that we sequenced was the Y. tetricus holotype in the Natural History Museum, London, leaving no doubt that we are dealing with this species. Genomic sequencing and comparison of specimens from museum collections offers a powerful strategy to reveal unforeseen phylogenetic relationships, and sequencing of primary types ensures that the conclusions are accurate in terms of nomenclature.