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opencc-by-4.0Dec 2023View details →

Cross-reactive CD8+ T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs)

Background: We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP). Method: A library of >100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers. Homologous peptides were selected from the Cancer Antigenic Peptide Database, as well as Bacteroidetes/Firmicutes-derived peptides. They were incubated with CD8+ T cells from the peripheral blood of HLA-A*02:01 healthy individuals (n=10) and cancer patients (n=16). T cell recognition was identified using tetramer-staining analysis. Cytotoxicity assay was performed using as target cells TAP-deficient T2 cells loaded with MoA or the paired TuA. Results: A total of 66 unique pMHC recognized by CD8+ T cells across all groups were identified. Of these, 21 epitopes from microbiota were identified as novel immunological targets. Reactivity against selected TAAs was observed for both HS and CP. pMHC tetramer staining confirmed CD8+ T cell populations cross-reacting with CTA SSX2 and paired microbiota epitopes. Moreover, PBMCs activated with the MoA where shown to release IFNγ as well as to exert cytotoxic activity against cells presenting the paired TuA. Conclusions: Several predicted microbiota-derived MoAs are recognized by T cells in HS and CP. Reactivity against TAAs was observed also in HS, primed by the homologous bacterial antigens. CD8+ T cells cross-reacting with MAGE-A1 and paired microbiota epitopes were identified in three subjects. Therefore, the microbiota can elicit an extensive repertoire of natural memory T cells to TAAs, possibly able to control tumor growth (“natural anti-cancer vaccination”). In addition, non-self MoAs can be included in preventive/therapeutic off-the-shelf cancer vaccines with more potent anti-tumor efficacy than those based on TAAs.

opencc-by-4.0Mar 2022View details →

Homologous Missense Constraint scores

For all missense variants with HMC scores: 1. If one missense variant could be mapped to the multiple Pfam domains, we report the worst HMC scores (smallest, more likely to be deleterious) since it's the worst scenario.    2. The genomic positions are provided with genome build in both hg19 and hg38.

opencc-by-4.0Jun 2020View details →

Diffraction images of a crystal of the F-BAR domain of PSTPIP1 (Proline-serine-threonine phosphatase-interacting protein 1) bound to the C-terminal homology (CTH) segment of the phosphatase LYP (PTPN22) (PDB entry 7AAM)

Diffraction images of a crystal of the F-BAR domain of human PSTPIP1 (residues 1-289, Uniprot reference O43586-1) in complex with the CTH of LYP (residues 787-807, Uniprot Q9Y2R2-1). Data were collected on a single crystal at the beamline i03 of the Diamond Light Source synchrotron (Didcot, UK) using radiation of 0.99987 Å wavelength and a PILATUS3 6M detector. The dataset consists of 3 groups, each containing of 1800 images (0.1 degree oscillation per image), collected at three different positions of the same crystal. Crystal belongs to the space group P2(1)2(1)2(1) with unit cell dimensions a=48.0 Å, b=72.0 Å, c=205.0 Å. The asymmetric unit contains an homodimer of the F-BAR domain bound to a LYP-CTH (~53% solvent content), which is the biological complex. Diffraction data was notably anisotropic. The lowest resolution limit was 4.05 Å in the direction b* and the highest limits were 2.11 Å and 2.10 in the directions a* and c*, respectively.   The structure derived form these data is published in: Manso, J.A., Marcos, T., Ruiz-Martín, V. Casas J, Alcón P, Sánchez Crespo M, Bayón Y, de Pereda JM, Alonso A PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders. Cell. Mol. Life Sci. 79, 131 (2022). <a href="https://doi.org/10.1007/s00018-022-04173-w">https://doi.org/10.1007/s00018-022-04173-w</a> The structure is available at the PDB under the code 7AAM: <a href="https://www.ebi.ac.uk/pdbe/entry/pdb/7aam">https://www.ebi.ac.uk/pdbe/entry/pdb/7aam</a>

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Molecular and electrophysiological features of GABAergic neurons in the dentate gyrus reveal limited homology with cortical interneurons

GABAergic interneurons tend to diversify into similar classes across telencephalic regions. However, it remains unclear whether the electrophysiological and molecular properties commonly used to define these classes are discriminant in the hilus of the dentate gyrus. Here, using patch-clamp combined with single cell RT-PCR, we compare the relevance of commonly used electrophysiological and molecular features for the clustering of GABAergic interneurons sampled from the mouse hilus and primary sensory cortex. While unsupervised clustering groups cortical interneurons into well-established classes, it fails to provide a convincing partition of hilar interneurons. Statistical analysis based on resampling indicates that hilar and cortical GABAergic interneurons share limited homology. While our results do not invalidate the use of classical molecular marker in the hilus, they indicate that classes of hilar interneurons defined by the expression of molecular markers do not exhibit strongly discriminating electrophysiological properties.

opencc-zeroJun 2022View details →

opencc-by-4.0May 2024View details →

Structural Homology of Epitope Pair Candidates for Molecular Mimicry Trigger of Type 1 Diabetes Mellitus

Background: Molecular mimicry, where foreign and self-peptides contain similar epitopes, can induce autoimmune responses. Identifying potential molecular mimics and studying their properties is key to understanding the onset of autoimmune diseases such as type 1 diabetes mellitus (T1DM). Previous work identified pairs of infectious epitopes (EINF) and T1DM epitopes (ET1D) that demonstrated sequence homology; however, structural homology was not considered. Correlating sequence homology with structural properties is important for streamlining translational investigation of potential molecular mimics. Therefore, the purpose of this work is to compare sequence homology with structural homology by calculating the structures and electrostatic potential surfaces of the epitope pairs identified in previous work from our laboratory.   Results:  For each epitope pair the root mean square deviation (RMSD) was calculated between their predicted structures and their electrostatic potentials were compared. Structures were predicted using the AlphaFold software program. Of the 52 epitope pairs considered here only 10 do not exhibit any matching (i.e. less than 3 residues overlap). When considering all residues the RMSD ranges from 0.33 Å to 11.66 Å with an average of 2.68 Å. Twenty-two pairs (42%) have RMSD of less than 1.5 Å and 30 (58%) less than 3 Å. Even some of the matching pairs show some electrostatic similarities that need to be considered. In general there is good agreement between the folding predicted for the isolated EINF and ET1D epitopes and the folding of the corresponding amino acid sequence in the parent antigen, but in some cases there are deviation that need to be considered, even when the RMDS is small.  Conclusions: Despite differences, most of the EINF/ET1D pairs selected by sequence homology show similar structural and electrostatic distributions, indicating that the EINF may bind to the same protein targets, the major histocompatibility complex molecules, for T1DM, leading to molecular mimicry onset of the disease. These findings suggest that searching for epitope pairs using sequence homology, a much less computationally demanding approach, leads to strong candidates for molecular mimicry that should be considered for further study. Still structure and full docking calculations will be necessary to advance the in-silico molecular mimicry predictions.  Here we presnt the following files: ·         Fasta files of all epitopes studied. ·         Alphafold calculated Structures of all epitopes. ·         Antigen structures. ·         Epitope pair structure comparison and their electrostatics.

opencc-by-4.0Dec 2022View details →

Fig. 1 in Echinoderm model systems, homology, and phylogenetic inference: comment and reply to Paul (2021)

Fig. 1. Tree comparison between two phylogenetic inference methods with bootstrap support at the nodes. A. Phylogenetic hypothesis from Paul (2021) inferred via maximum parsimony. B. Phylogenetic hypothesis inferred via maximum likelihood.

opencc-by-4.0Jun 2016View details →

Pleckstrin Homology domain Interacting Protein (PHIP); A Target Enabling Package

SGC Oxford has expressed, purified and crystallized the second bromodomain of PHIP as part of the probe programme. Fragment screening and X-ray crystallography identified binders, some of which optimised to uM affinity. However, molecules with probe properties were not obtained. Consequently it has been decided to put the information generated into the public domain.

opencc-by-4.0Nov 2018View details →

Persistent Homology for Characterization of Fracture Patterns in Rocks

The data sets are for fracture characterizations of serpentinite by persistent homology.

Characterization of p53 family homologs in evolutionary remote branches of Holozoa

Supplementary materials to article: Characterization of p53 family homologs in evolutionary remote branches of Holozoa The p53 family of transcription factors plays key roles in development, genome stability, senescence and tumor development, and p53 is the most important tumor suppressor protein in humans. Although intensively investigated for many years, its initial evolutionary history is not yet fully elucidated. Using bioinformatic and structure prediction methods on current databases containing newly-sequenced genomes and transcriptomes, we present a detailed characterization of p53 family homologs in remote members of the Holozoa group, in the unicellular clades Filasterea, Ichthyosporea and Corallochytrea. Moreover, we show that these newly characterized homologous sequences contain domains that can form structures with high similarity to the human p53 family DNA-binding domain, and some also show similarities to the oligomerization and SAM domains. The presence of these remote homologs demonstrates an ancient origin of the p53 protein family.

FIG. 26. Melanoblossiinae Roewer, 1933 in Cheliceral Morphology in Solifugae (Arachnida): Primary Homology, Terminology, and Character Survey

FIG. 26. Melanoblossiinae Roewer, 1933, Melanoblossia sp., 3 (NMNW 13396), chelicera (A) and setiform flagellar complex (B, C), prolateral views. Abbreviations: FD, fixed finger, distal tooth; FM, fixed finger, medial tooth; FP, fixed finger, proximal tooth; FSM, fixed finger, submedial tooth; MM, movable finger, medial tooth; MP, movable finger, proximal tooth; mpd, movable finger prodorsal setae; mpm, movable finger promedial setae; mpv, movable finger proventral setae; MSM, movable finger, submedial tooth; pic, prolateral interdigital condyle; pvd, proventral distal setae; pvsd, proventral subdistal setae; RFM, retrofondal medial tooth; sfc, setiform flagellar complex; STF, subterminal flange.

FIG. 24. Solpugidae Leach, 1815 in Cheliceral Morphology in Solifugae (Arachnida): Primary Homology, Terminology, and Character Survey

FIG. 24. Solpugidae Leach, 1815, chelicerae and cheliceral fixed fingers, prolateral views (A–D), indicating stridulatory organs (A, D), bulbous base of flagellum, prolateral view (E), and apex of flagellar shaft, prolateral view (F). A, B. Solpugiba lineata (C.L. Koch, 1842), 3 (NMNW 13814), shaft distorted during processing for scanning electron microscopy. Inset: closeup of mucron organ (mo). C. Zeriassa cuneicornis (Purcell, 1899), 3 (NMNW 13883). D, E. Zeria sericea (Pocock, 1897), 3 (NMNW 13800). F. Metasolpuga picta (Kraepelin, 1899), 3, Namibia: Gobabeb. Arrows indicate suture in bulbous base (B, C, E) and shaft (F). Abbreviations: FD, fixed finger, distal tooth; FGP, flagellar groove process; FM, fixed finger, medial tooth; FP, fixed finger, proximal tooth; FSD, fixed finger, subdistal tooth; FSM, fixed finger, submedial teeth; MD, movable finger, distal tooth; MM, movable finger, medial tooth; mo, mucron organ; MP, movable finger, proximal tooth; MSM, movable finger, submedial tooth; pvd, proventral distal setae.

FIG. 13. Solpugidae Leach, 1815 in Cheliceral Morphology in Solifugae (Arachnida): Primary Homology, Terminology, and Character Survey

FIG. 13. Solpugidae Leach, 1815, Solpugiba lineata (C.L. Koch, 1842), 3 (NMNW 13814), cheliceral movable finger, prolateral view, illustrating dorsodistally directed prodorsal (mpd) setae, distally directed promedian (mpm) setae, and ventrodistally directed proventral (mpv) setae (A); closeup of distal setal area illustrating long apical mpd seta (arrow) and modified distal mpv setae (B); and closeup of socket of modified subapical mpv seta with distally directed insertion (C). Additional abbreviations: MD, movable finger, distal tooth; MP, movable finger, proximal tooth; MSD, movable finger, subdistal tooth.

FIG. 5 in Cheliceral Morphology in Solifugae (Arachnida): Primary Homology, Terminology, and Character Survey

FIG. 5. Solifugae, chelicerae, retrolateral (A, B, D, G, I) and dorsal (C, E, F) views, and fixed finger, retrolateral view (H), measurements, ratios, and landmarks. A–C. Landmarks used to measure cheliceral length (CL), including (A) fixed finger apex to cheliceropeltidial condyle (Muma, 1951; Brookhart and Cushing, 2004); (B) fixed finger apex to anterolateral propeltidial lobe anterior margin, in direct line (i) or parallel to longitudinal axis (ii) of chelicera; and (C) fixed finger apex to propeltidium anterior margin. D. CL/CH ratio (CloudsleyThompson, 1961). E. CL/CW* ratio (asterisk indicates use of CW as defined in present contribution). F. A/ CP index (Brookhart and Muma, 1981, 1987; Muma and Brookhart, 1988). G. Fixed and movable (ventral) finger lengths from retrolateral interdigital condyle (ric) center to (applicable) finger apex. H. FN ratio (FNL/ FNH), i.e., fondal notch L/W or FN ratio sensu Brookhart and Muma (1981, 1987) and Muma and Brookhart (1988), and FL/FW ratio sensu Brookhart and Cushing (2004); and FNH/FFH ratio (FW/FFW) sensu Brookhart and Cushing (2004), based on finger to notch ratio (FF/FN) of Brookhart and Muma (1987), with numerator and denominator switched. I. CH/FFH ratio. Abbreviations: CH, cheliceral height; CL, cheliceral length; CP, chelicera-propeltidium length; CW, cheliceral height; FFH, fixed finger height; FFL, fixed finger length; FN, fondal notch; FNH, fondal notch height; FNL, fondal notch length; MFL, movable finger length; ric, retrolateral interdigital condyle.

FIG. 23. Lipophaginae Wharton, 1981 in Cheliceral Morphology in Solifugae (Arachnida): Primary Homology, Terminology, and Character Survey

FIG. 23. Lipophaginae Wharton, 1981, Bdellophaga angulata Wharton, 1981, 3 (NMNW 11601), chelicera, prolateral view (A) and flagellar complex setae, retrolateral (B) and prolateral (C) views, indicating stridulatory apparatus and type B sfc. Abbreviations: MM, movable finger, medial tooth; MP, movable finger, proximal tooth; MSM, movable finger, submedial tooth; pic, prolateral interdigital condyle; pvd, proventral distal setae (plumose); pvsd, proventral subdistal setae; sfc, setiform flagellar complex.

FIG. 1. Galeodidae Sundevall, 1833 in Cheliceral Morphology in Solifugae (Arachnida): Primary Homology, Terminology, and Character Survey

FIG. 1. Galeodidae Sundevall, 1833 (A, B), Rhagodidae Pocock, 1897 (C, D), Hexisopodidae Pocock, 1897 (E, F), Solpugidae Leach, 1815 (G, H), Daesiidae Kraepelin, 1899 (I, J), Gylippinae Roewer, 1933 (K), Eremobatidae Kraepelin, 1899 (L), Ammotrechidae Roewer, 1934 (M), and Mummuciidae Roewer, 1934 (N), habitus in life. A, B Galeodes caspius fuscus Birula, 1890, Kazakhstan, ♀ (A) and 3 (B). C. Rhagodes sp., ♀, Kenya. D. Rhagodes sp., ♀, India. E. Hexisopus sp., ♀, Namibia. F. Chelypus sp., 3, Namibia. G. Metasopuga picta (Kraepelin, 1899), 3, Namibia. H. Zeria sericea (Pocock, 1897), 3, Namibia. I. Hemiblossia sp., ♀, Namibia. J. Blossia sp., 3, Namibia. K. Gyllipus (Paragylippus) monoceros Werner, 1905, 3, Turkey. L. Eremocosta striata (Putnam 1883), ♀, U.S.A. M. Nothopuga cuyana Maury, 1976, 3, Argentina, N. Gaucha sp. ♀, Brazil.

FIG. 7. Eremobatidae Kraepelin, 1899 in Cheliceral Morphology in Solifugae (Arachnida): Primary Homology, Terminology, and Character Survey

FIG. 7. Eremobatidae Kraepelin, 1899 (A, B), Solpugidae Leach, 1815 (C), and Ammotrechidae Roewer, 1934 (D), cheliceral shape modifications and positional comparison of fondal notch and medial notch, prolateral (A) and retrolateral (B–D) views. A. Eremochelis andreasana (Muma, 1962), holotype 3 (AMNH), shallow fondal notch, illustrating proximal position, relative to reduced median series dentition. B. Eremobates bajadae Muma and Brookhart, 1988, 3 (AMNH [LP 5740]), deep fondal notch. C. Solpugema derbiana (Pocock, 1895), 3 (AMNH [LP 7709]), illustrating medial notch situated within median series dentition, distal to FP. D. Branchia angustus Muma, 1951, 3, adapted from Muma (1951: 136, fig. 305), illustrating medial notch situated within median series dentition. Abbreviations: FD, fixed finger, distal tooth; FM, fixed finger, medial tooth; FN, fondal notch; FP, fixed finger, proximal tooth; FSM, fixed finger, submedial tooth; MN, medial notch; MPL, movable finger, prolateral tooth; PFM, profondal medial tooth; PFP, profondal proximal tooth; PFSM, profondal submedial tooth; PFSP, profondal subproximal tooth; RDP, retrodorsal process; RF, retrofondal teeth; RFM, retrofondal medial tooth; RFP, retrofondal proximal tooth; RFSM, retrofondal submedial tooth; RFSP, retrofondal subproximal tooth; VN, ventral notch.

Fig. 11 in Morphological homology, evolution, and proposed nomenclature for bear dentition

Fig. 11. Occlusal views of m2 homologous structures in cave bear (A, B) and giant panda (C, D) lineages. A. Ursavus tedfordi Qiu, Deng, and Wang, 2014 (HMV1453) from Huaigou, Gansu Province, Late Miocene. B. Ursus deningeri von Reichenau, 1904 (NMM1956/909, photo Jan Wagner) from Mosbach 2, Germany, early Middle Pleistocene. C. Ailuropoda wulingshanensis Wang and Lin, 1982 (IVPP V13459.91) from Longgu Cave, Jianshi, Hubei Province. D. Ailurarctos lufengensis Qiu and Qi, 1989 (IVPP V6892) from Lufeng, Yunnan Province, Latest Miocene. A1–D1, photographs; A2–D2, photographs with homologous structures indicated. Not to scale.

Fig. 8 in Morphological homology, evolution, and proposed nomenclature for bear dentition

Fig. 8. Occlusal views of m1 homologous structures in cave bear (A, B) and giant panda (C, D) lineages. A. Ursavus tedfordi Qiu, Deng, and Wang, 2014 (HMV1453) from Huaigou, Gansu Province, Late Miocene. B. Ursus deningeri Von Reichenau, 1904 (NMM1956/907, photo Jan Wagner) from Mosbach 2, Germany, early Middle Pleistocene. C. Ailuropoda wulingshanensis Wang and Lin, 1982 (IVPP V13459.10) from Longgu Cave, Jianshi, Hubei Province. D. Ailurarctos lufengensis Qiu and Qi, 1989 (IVPP V25032) from Lufeng, Yunnan Province, Latest Miocene. A1–D1, photographs; A2–D2, photographs with homologous structures indicated. Not to scale.

Fig. 4 in Morphological homology, evolution, and proposed nomenclature for bear dentition

Fig. 4. Occlusal views of P4 inner lobe structure of Musteloidea and Ursidae, showing the homology of inner lobe cusps. A. Meles leucurus Hodgson, 1847 (IOZ08129), Recent, China. B. Procyon lotor (Linnaeus, 1758) (IVPP OV1551), Recent, zoo specimen. C. Plithocyon teilhardi (Colbert, 1939) (AMNH FM26594) from the Tunggur Formation, Middle Miocene; the dashed line indicates that the protocone is absent in this species. D. Ailurarctos yuanmouensis Zong, 1996 (IVPP RV97001, cast) from Yuanmou, Yunnan Province. Not to scale.

Fig. 5 in Morphological homology, evolution, and proposed nomenclature for bear dentition

Fig. 5. Occlusal views of M1 homologous structures in cave bear (A, B) and giant panda (C, D) lineages. A. Ursavus tedfordi Qiu, Deng, and Wang, 2014 HMV1453) from Huaigou, Gansu Province, Late Miocene. B. Ursus deningeri Von Reichenau, 1904 (NMM1953/119, photo Jan Wagner) from Mosbach 2, Germany, early Middle Pleistocene. C. Ailuropoda melanoleuca (David, 1869) (IVPP V87025.109) from cave deposit of Guangxi Province, Late Pleistocene. D. Ailurarctos lufengensis Qiu and Qi, 1989 (IVPP V6892) from Lufeng, Yunnan Province, Latest Miocene. A1–D1, photographs; A2–D2, photographs with homologous structures indicated. Not to scale.