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932 results on '"Horsthemke, Bernhard"'

1. Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation

Author

Godfrey, Laura K., Forster, Jan, Liffers, Sven-Thorsten, Schröder, Christopher, Köster, Johannes, Henschel, Leonie, Ludwig, Kerstin U., Lähnemann, David, Trajkovic-Arsic, Marija, Behrens, Diana, Scarpa, Aldo, Lawlor, Rita T., Witzke, Kathrin E., Sitek, Barbara, Johnsen, Steven A., Rahmann, Sven, Horsthemke, Bernhard, Zeschnigk, Michael, and Siveke, Jens T.

Published
2024
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2. Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X

Author

Leitão, Elsa, Schröder, Christopher, Parenti, Ilaria, Dalle, Carine, Rastetter, Agnès, Kühnel, Theresa, Kuechler, Alma, Kaya, Sabine, Gérard, Bénédicte, Schaefer, Elise, Nava, Caroline, Drouot, Nathalie, Engel, Camille, Piard, Juliette, Duban-Bedu, Bénédicte, Villard, Laurent, Stegmann, Alexander PA, Vanhoutte, Els K, Verdonschot, Job AJ, Kaiser, Frank J, Tran Mau-Them, Frédéric, Scala, Marcello, Striano, Pasquale, Frints, Suzanna GM, Argilli, Emanuela, Sherr, Elliott H, Elder, Fikret, Buratti, Julien, Keren, Boris, Mignot, Cyril, Héron, Delphine, Mandel, Jean-Louis, Gecz, Jozef, Kalscheuer, Vera M, Horsthemke, Bernhard, Piton, Amélie, and Depienne, Christel

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Brain Disorders, Mental Health, Intellectual and Developmental Disabilities (IDD), Biotechnology, Autism, Human Genome, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Mental health, Humans, Chromosomes, Human, X, Genes, X-Linked, Intellectual Disability, Autism Spectrum Disorder, Databases, Genetic
Abstract

Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression, and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using machine learning classifiers trained to distinguish disease-associated from dispensable genes, we classify 247 genes, including 115 of the 127, as having high probability of being disease-associated. We provide evidence of an excess of variants in predicted genes in existing databases. Finally, we report damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism spectrum disorders. This study predicts large-scale gene-disease associations that could be used for prioritization of X-linked pathogenic variants.

Published
2022

4. The Genetics and Epigenetics of Anticipatory Adaptation

Author

Horsthemke, Bernhard, Dillmann, Rüdiger, Series Editor, Nakamura, Yoshihiko, Series Editor, Schaal, Stefan, Series Editor, Vernon, David, Series Editor, Bülthoff, Heinrich H., Advisory Editor, Inaba, Masayuki, Advisory Editor, Kelso, J.A. Scott, Advisory Editor, Khatib, Oussama, Advisory Editor, Kuniyoshi, Yasuo, Advisory Editor, Okuno, Hiroshi G., Advisory Editor, Ritter, Helge, Advisory Editor, Sandini, Giulio, Advisory Editor, Siciliano, Bruno, Advisory Editor, Steedman, Mark, Advisory Editor, Takanishi, Atsuo, Advisory Editor, and Nadin, Mihai, editor

Published
2022
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13. Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis

Author

Beckmann, Denise, Römer-Hillmann, Anja, Krause, Annika, Hansen, Uwe, Wehmeyer, Corinna, Intemann, Johanna, de Gorter, David J. J., Dankbar, Berno, Hillen, Jan, Heitzmann, Marianne, Begemann, Isabell, Galic, Milos, Weinhage, Toni, Foell, Dirk, Ai, Rizi, Kremerskothen, Joachim, Kiener, Hans P., Müller, Sylvia, Kamradt, Thomas, Schröder, Christopher, Leitão, Elsa, Horsthemke, Bernhard, Rosenstiel, Philip, Nordström, Karl, Gasparoni, Gilles, Gasparoni, Nina, Walter, Jörn, Li, Na, Yang, Xinyi, Chung, Ho-Ryun, Pavenstädt, Hermann, Lindemann, Nico, Schnittler, Hans J., Wang, Wei, Firestein, Gary S., Pap, Thomas, and Korb-Pap, Adelheid

Published
2021
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17. The adult phenotype of Schaaf-Yang syndrome

Author

Marbach, Felix, Elgizouli, Magdeldin, Rech, Megan, Beygo, Jasmin, Erger, Florian, Velmans, Clara, Stumpel, Constance T. R. M., Stegmann, Alexander P. A., Beck-Wödl, Stefanie, Gillessen-Kaesbach, Gabriele, Horsthemke, Bernhard, Schaaf, Christian P., and Kuechler, Alma

Published
2020
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20. Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment

Author

Lechner, Lara, primary, Opitz, Robert, additional, Silver, Matt J., additional, Krabusch, Philipp M., additional, Prentice, Andrew M., additional, Field, Martha S., additional, Stachelscheid, Harald, additional, Leitão, Elsa, additional, Schröder, Christopher, additional, Fernandez Vallone, Valeria, additional, Horsthemke, Bernhard, additional, Jöckel, Karl-Heinz, additional, Schmidt, Börge, additional, Nöthen, Markus M., additional, Hoffmann, Per, additional, Herms, Stefan, additional, Kleyn, Patrick W., additional, Megges, Matthias, additional, Blume-Peytavi, Ulrike, additional, Weiss, Katja, additional, Mai, Knut, additional, Blankenstein, Oliver, additional, Obermayer, Benedikt, additional, Wiegand, Susanna, additional, and Kühnen, Peter, additional

Published
2023
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23. Additional file 2 of Whole-genome methylation analysis of testicular germ cells from cryptozoospermic men points to recurrent and functionally relevant DNA methylation changes

Author

Di Persio, Sara, Leitão, Elsa, Wöste, Marius, Tekath, Tobias, Cremers, Jann-Frederik, Dugas, Martin, Li, Xiaolin, zu Hörste, Gerd Meyer, Kliesch, Sabine, Laurentino, Sandra, Neuhaus, Nina, and Horsthemke, Bernhard

Abstract

Additional file 2. Fig. S1: Screening for somatic DNA contamination of the testicular germ cell (TGC) samples. Dotplots representing the mean methylation levels of MEST and H19 (left) and XIST and DDX4 (right) measured by deep bisulfite sequencing in 24 normal controls (CTR, teal) and 10 cryptozoospermic (CZ, purple) testicular germ cell (TGC) samples. Fig. S2: DNA methylation levels in imprinting control regions. A) Methylation levels of the 50 ICRs in the CTR and CZ samples. * Not imprinted according to this data, ** Possible polymorphism. B) Box plots showing the distribution of methylation levels of the 34 oocyte DMRs in the four CTR (teal) and four CZ testicular germ cell samples (purple). C) Comparison of the distributions of the average methylation levels of the 34 oocyte DMRs in the human embryonic stem cells (ESC, n = 2), the SSEA+ spermatogonial stem cells from Guo et al. [29] (SSC, n = 2), the primordial germ cells isolated from 7–19-week-old embryos datasets from Guo et al. [6] (PGC, n = 8) and the CTR and CZ testicular germ cell samples (TGC, n = 8, black). D) Comparison of the distribution of the methylation levels of the 34 oocyte DMRs in the eight primordial germ cells samples isolated from 7–19-week-old embryos [6]. Values can be found in Additional file 1: Table S5. Box plots elements are defined as follows: center line: median; box limits: upper and lower quartiles; whiskers: 1.5× interquartile range; points: outliers. Fig. S3: Global comparison of methylomes of control testicular germ cells and control sperm. A) Box plots showing the distribution of global methylation values in control testicular germ cells (CTR, n = 4, Additional file 1: Table S4) and sperm normal control samples (SP, n = 5, [16]). Statistical analysis showed difference between the two groups (Mann-Whitney U test). Box plots elements are defined as follows: center line: median; box limits: upper and lower quartiles; whiskers: 1.5× interquartile range; points: outliers. B) Violin plots showing the distribution of the mean methylation values for various genomic features in control testicular germ cells (CTR, n = 4) and sperm normal control samples (SP, n = 5, [16]). Promoters were defined as the 2,000 bp region around TSSs. GeneHancer regions refer to the DoubleElite regulatory elements. Repeats refer to elements from RepeatMasker. C) PCA generated for 1,350,244 CpG loci where all samples show methylation values. Only loci with minimum coverage of five in all samples and minimum mapping quality of 10 are considered. ESC, embryonic stem cells; SSC, spermatogonial stem cells [29]; PGC, primordial germ cells [6][5]; TGC, control testicular germ cells; SP, sperm [16]. Fig. S4: Global comparison of methylomes from control and cryptozoospermic testicular germ cells. A) Box plots showing the distribution of the global methylation values in control testicular germ cells (CTR) and cryptozoospermic testicular germ cells (CZ) (Additional file 1: Table S4). Statistical analysis showed no difference between the two groups (Mann-Whitney U test). Box plots elements are defined as follows: center line: median; box limits: upper and lower quartiles; whiskers: 1.5× interquartile range; points: outliers. B) Violin plots showing the distribution of the mean methylation values for various genomic features in control testicular germ cells (CTR, n = 4) and cryptozoospermic testicular germ cells (CZ, n = 4). Promoters were defined as the 2000 bp region around TSSs. GeneHancer regions refer to the DoubleElite regulatory elements. Repeats refer to elements from RepeatMasker. C) Distribution of the number (left) and total genomic size (right) of unmethylated (UMR) and low-methylated regions (LMR) obtained by segmenting CTR (teal, n = 4) and CZ methylomes (purple, n = 4) with MethylSeekR. Statistical analysis showed no difference between the two groups (Mann-Whitney U test). Fig. S5: Differentially methylation regions. A) Flow chart of the discovery of differentially methylated regions (DMRs) between the testicular germ cells from controls and cryptozoospermic men. DMRs were identified with camel, metilene and bsmooth requiring coverage of at least 4 CpGs, with at least 30% difference in methylation, minimum coverage of 5 reads and a maximum q-value of 0.05. Filters on the ranges of methylation values in CTR and CZ groups were further applied. B) Scatter plots showing the relation between the range of methylation values within the CTR and the CZ group for each DMR. DMRs are shown as black dots (included) or white dots (excluded) according to filters on the range of methylation values. Left: no range filters applied. Right: CTR and CZ ranges < 0.3. Numbers of considered DMRs are shown above. C) Cluster analyses of the methylation values of the 1,329 DMRs considered without range filters applied. CTR testicular germ cell samples in teal, CZ samples in purple. Arrows indicate a CZ sample clustering together with the CTR group. D) Number of DMRs from the 271 set that overlap specific functional genomic regions. Fig. S6: scRNA seq analysis. A) UMAP plot showing the integrated CTR-CZ germ cell dataset. The cells are colour-coded according to their knot group identity. Knot group 1 includes cells from undifferentiated spermatogonia to pachytene spermatocytes; Knot group 2 includes cells from pachytene spermatocytes to meiotic divisions; Knot group 3 includes cells from meiotic divisions to late spermatids. B) Schematic representation summarizing the results of the tradeSeq and MAST differential expression analyses. Red colour indicates significant down-regulation of a gene, whereas green indicates significant up-regulation. Fig. S7: IGV browser snapshots of WGBS data from control (CTR) and cryptozoospermic (CZ) testicular germ cells showing CTR-CZ DMRs associated with differentially expressed genes. Each DMR is shown as a red region either spanning the entire width (top panels) or with the surrounding genomic regions (lower panels). Only a subset of reads is shown for each sample. Methylated CpGs are shown in red and unmethylated CpGs in blue

Published
2023
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24. Epigenetics

Author

Horsthemke, Bernhard, Speicher, Michael R., editor, Motulsky, Arno G., editor, and Antonarakis, Stylianos E., editor

Published
2010
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26. Leveraging Cross-Species Transcription Factor Binding Site Patterns: From Diabetes Risk Loci to Disease Mechanisms

Author

Voight, Benjamin F., Scott, Laura J., Steinthorsdottir, Valgerdur, Morris, Andrew P., Dina, Christian, Welch, Ryan P., Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S., Thorleifsson, Gudmar, McCulloch, Laura J., Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J., Raychaudhuri, Soumya, McCarroll, Steve A., Langenberg, Claudia, Hofmann, Oliver M., Dupuis, Josée, Qi, Lu, Segrè, Ayellet V., van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J., Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L., Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P., Charpentier, Guillaume, Chines, Peter S., Cornelis, Marilyn, Couper, David J., Crawford, Gabe, Doney, Alex S.F., Elliott, Katherine S., Elliott, Amanda L., Erdos, Michael R., Fox, Caroline S., Franklin, Christopher S., Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J., Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U., Johnson, Paul R.V., Jørgensen, Torben, Kao, Wen H.L., Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M., Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, Midthjell, Kristian, Morken, Mario A., Narisu, Narisu, Nilsson, Peter, Owen, Katharine R., Payne, Felicity, Perry, John R.B., Petersen, Ann-Kristin, Platou, Carl, Proença, Christine, Prokopenko, Inga, Rathmann, Wolfgang, Rayner, N. William, Robertson, Neil R., Rocheleau, Ghislain, Roden, Michael, Sampson, Michael J., Saxena, Richa, Shields, Beverley M., Shrader, Peter, Sigurdsson, Gunnar, Sparsø, Thomas, Strassburger, Klaus, Stringham, Heather M., Sun, Qi, Swift, Amy J., Thorand, Barbara, Tichet, Jean, Tuomi, Tiinamaija, van Dam, Rob M., van Haeften, Timon W., van Herpt, Thijs, van Vliet-Ostaptchouk, Jana V., Walters, G. Bragi, Weedon, Michael N., Wijmenga, Cisca, Witteman, Jacqueline, Bergman, Richard N., Cauchi, Stephane, Collins, Francis S., Gloyn, Anna L., Gyllensten, Ulf, Hansen, Torben, Hide, Winston A., Hitman, Graham A., Hofman, Albert, Hunter, David J., Hveem, Kristian, Laakso, Markku, Mohlke, Karen L., Morris, Andrew D., Palmer, Colin N.A., Pramstaller, Peter P., Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D., Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Wareham, Nicholas J., Watanabe, Richard M., Abecasis, Goncalo R., Boehm, Bernhard O., Campbell, Harry, Daly, Mark J., Hattersley, Andrew T., Hu, Frank B., Meigs, James B., Pankow, James S., Pedersen, Oluf, Wichmann, H.-Erich, Barroso, Inês, Florez, Jose C., Frayling, Timothy M., Groop, Leif, Sladek, Rob, Thorsteinsdottir, Unnur, Wilson, James F., Illig, Thomas, Froguel, Philippe, van Duijn, Cornelia M., Stefansson, Kari, Altshuler, David, Boehnke, Michael, McCarthy, Mark I., Claussnitzer, Melina, Dankel, Simon N., Klocke, Bernward, Glunk, Viktoria, Berulava, Tea, Lee, Heekyoung, Oskolkov, Nikolay, Fadista, Joao, Ehlers, Kerstin, Wahl, Simone, Hoffmann, Christoph, Qian, Kun, Rönn, Tina, Riess, Helene, Müller-Nurasyid, Martina, Bretschneider, Nancy, Schroeder, Timm, Skurk, Thomas, Horsthemke, Bernhard, Spieler, Derek, Klingenspor, Martin, Seifert, Martin, Kern, Michael J., Mejhert, Niklas, Dahlman, Ingrid, Hansson, Ola, Hauck, Stefanie M., Blüher, Matthias, Arner, Peter, Suhre, Karsten, Hsu, Yi-Hsiang, Mellgren, Gunnar, Hauner, Hans, and Laumen, Helmut

Published
2014
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28. Korrelationen zwischen BMI-assoziierten genetischen Varianten und zirkulären RNAs (#19)

Author

Rajcsanyi, Luisa S, additional, Diebels, Inga, additional, Pastoors, Lydia, additional, Kanber, Deniz, additional, Peters, Triinu, additional, Volckmar, Anna-Lena, additional, Zheng, Yiran, additional, Grosse, Martin, additional, Dieterich, Christoph, additional, Hebebrand, Johannes, additional, Kaiser, Frank J, additional, Horsthemke, Bernhard, additional, and Hinney, Anke, additional

Published
2022
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29. Retinoblastom

Author

Lohmann, Dietmar R., Horsthemke, Bernhard, Bornfeld, Norbert, Aguzzi, Adriano, editor, Bielka, Heinz, editor, Herrmann, Falko, editor, Holsboer, Florian, editor, Kaufmann, Stefan H. E., editor, Scriba, Peter C., editor, Stock, Günter, editor, Hausen, Harald zur, editor, Ganten, Detlev, editor, Ruckpaul, Klaus, editor, Hahn, Stephan A., editor, and Schmiegel, Wolff, editor

Published
2001
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37. Epigenetic plasticity via adaptive DNA hypermethylation and clonal expansion underlie resistance to oncogenic pathway inhibition in pancreatic cancer

Author

Godfrey, Laura K., primary, Forster, Jan, additional, Liffers, Sven-Thorsten, additional, Schröder, Christopher, additional, Köster, Johannes, additional, Henschel, Leonie, additional, Ludwig, Kerstin U., additional, Trajkovic-Arsic, Marija, additional, Behrens, Diana, additional, Scarpa, Aldo, additional, Lawlor, Rita T., additional, Witzke, Kathrin E., additional, Sitek, Barbara, additional, Johnsen, Steven A., additional, Rahmann, Sven, additional, Horsthemke, Bernhard, additional, Zeschnigk, Michael, additional, and Siveke, Jens T., additional

Published
2022
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38. Microdissection and Molecular Analysis of Proximal 15q

Author

Buiting, Karin, Greger, Valerie, Hörstmann, Ingrid, Lüdecke, Hermann-Josef, Senger, Gabriele, Claussen, Uwe, Brownstein, Bernhard H., Schlessinger, David, Knoll, Joan H. M., Lalande, Marc, Zabel, Bernhard, Horsthemke, Bernhard, and Cassidy, Suzanne B., editor

Published
1992
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39. A variant allele of Growth Factor Independence 1 (GFI1) is associated with acute myeloid leukemia

Author

Khandanpour, Cyrus, Thiede, Christian, Valk, Peter J.M., Sharif-Askari, Ehssan, Nückel, Holger, Lohmann, Dietmar, Horsthemke, Bernhard, Siffert, Winfried, Neubauer, Andreas, Grzeschik, Karl-Heinz, Bloomfield, Clara D., Marcucci, Guido, Maharry, Kati, Slovak, Marilyn L., van der Reijden, Bert A., Jansen, Joop H., Schackert, Hans K., Afshar, Khashayar, Schnittger, Susanne, Peeters, Justine K., Kroschinsky, Frank, Ehninger, Gerhard, Lowenberg, Bob, Dührsen, Ulrich, and Möröy, Tarik

Published
2010
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40. Systematic analysis and prediction of genes associated with disorders on chromosome X

Author

Leitão, Elsa, primary, Schröder, Christopher, additional, Parenti, Ilaria, additional, Dalle, Carine, additional, Rastetter, Agnès, additional, Kühnel, Theresa, additional, Kuechler, Alma, additional, Kaya, Sabine, additional, Gérard, Bénédicte, additional, Schaefer, Elise, additional, Nava, Caroline, additional, Drouot, Nathalie, additional, Engel, Camille, additional, Piard, Juliette, additional, Duban-Bedu, Bénédicte, additional, Villard, Laurent, additional, Stegmann, Alexander P.A., additional, Vanhoutte, Els K., additional, Verdonshot, Job A.J, additional, Kaiser, Frank J., additional, Mau-Them, Frédéric Tran, additional, Scala, Marcello, additional, Striano, Pasquale, additional, Frints, Suzanna G.M., additional, Argilli, Emanuela, additional, Sherr, Elliott H., additional, Elder, Fikret, additional, Buratti, Julien, additional, Keren, Boris, additional, Mignot, Cyril, additional, Héron, Delphine, additional, Mandel, Jean-Louis, additional, Gecz, Jozef, additional, Kalscheuer, Vera M., additional, Horsthemke, Bernhard, additional, Piton, Amélie, additional, and Depienne, Christel, additional

Published
2022
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43. The Diagnostic Journey of a Patient with Prader–Willi-Like Syndrome and a Unique Homozygous SNURF-SNRPN Variant

Author

Pellikaan, Karlijn, Woerden, Geeske M. van, Kleinendorst, Lotte, Rosenberg, Anna G. W., Horsthemke, Bernhard, Grosser, Christian, Zutven, Laura J. C. M. van, Rossum, Elisabeth F. C. van, Lely, Aart J. van der, Resnick, James L., Brüggenwirth, Hennie T., Haelst, Mieke M. van, and Graaff, Laura C. G. de

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, brain, genetic variation, nutritional and metabolic diseases, genetics, prader–willi syndrome, nervous system diseases, genomic imprinting
Abstract

Prader–Willi syndrome (PWS) is a rare genetic condition characterized by hypotonia, intellectual disability, and hypothalamic dysfunction, causing pituitary hormone deficiencies and hyperphagia, ultimately leading to obesity. PWS is most often caused by the loss of expression of a cluster of genes on chromosome 15q11.2-13. Patients with Prader–Willi-like syndrome (PWLS) display features of the PWS phenotype without a classical PWS genetic defect. We describe a 46-year-old patient with PWLS, including hypotonia, intellectual disability, hyperphagia, and pituitary hormone deficiencies. Routine genetic tests for PWS were normal, but a homozygous missense variant NM_003097.3(SNRPN):c.193C&gt, T, p.(Arg65Trp) was identified. Single nucleotide polymorphism array showed several large regions of homozygosity, caused by high-grade consanguinity between the parents. Our functional analysis, the ‘Pipeline for Rapid in silico, in vivo, in vitro Screening of Mutations’ (PRiSM) screen, showed that overexpression of SNRPN-p.Arg65Trp had a dominant negative effect, strongly suggesting pathogenicity. However, it could not be confirmed that the variant was responsible for the phenotype of the patient. In conclusion, we present a unique homozygous missense variant in SNURF-SNRPN in a patient with PWLS. We describe the diagnostic trajectory of this patient and the possible contributors to her phenotype in light of the current literature on the genotype–phenotype relationship in PWS.

Published
2021
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