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Keturakis, Saulius. "THE PHOTOS BY “THE MOLE”, OR IN SEARCH OF THE WAY TO THE OTHER / FOTOGRAFUOJANTIS „KURMIS“, ARBA KELIO LINK KITO PAIEŠKOSE." CREATIVITY STUDIES 5, no. 1 (June 28, 2012): 22–31. http://dx.doi.org/10.3846/20297475.2011.645890.
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The title of the paper is not associated with the exotic show of a circus with the trained, capable of making the photos mole, but with the movie by Dalia Survilaitė The Mole, which is narrating the story of the poet, musician and blind from the birth photographer Remigijus Audiejaitis, who was tragically killed in the fire. The paper discusses the seemingly oxymoronic phenomena – the intention of the blind to express his experience by media, which he could experience himself only by using the ekphrasis device – by retelling the visual by words – or by using more complicated techniques of figurative meaning, when through photography the experience of smell or touch is expressed. In the paper the paradoxical figure of the blind photographer is interpreted by using the idea of William J. Thomas Mitchell about qualifying the relationships between the word and the image not only as impossible (in the meaning of Gotthold Ephraim Lessing's Laokoon, oder Über die Grenzen der Malerei und Poesie), but as the act of communication and range of the experience of the Other. The concepts of intertextuality and intermediality and the criticism related with the concepts helps to explore the theoretical basis of understanding the phenomenon. Santrauka Straipsnio pavadinimas susijęs su Dalios Survilaitės filmu Kurmis, kuriame pasakojama tragiškai žuvusio fotografo Remigijaus Audiejaičio, aklo nuo gimimo ir, anot jo paties, niekada neturėjusio jokio supratimo apie erdvę ir spalvą, istorija. Straipsnyje analizuojama ši oksimoroniška situacija, kai fotografijos – vizualios medijos – patirtis pačiam menininkui yra prieinama tik naudojantis ekfrastinėmis technikomis. Paradoksali aklojo fotografo figūra aptariama trijuose teoriniuose kontekstuose, siekiant išsiaiškinti jos galimybes nebūti paliktai tik kaip keistenybei, o būti paaiškintai remiantis teorinėmis įžvalgomis, susijusiomis su žodžio ir vaizdo sąveikos (Gottholdas Ephraimas Lessingas) analize, intertekstualumo bei intermedialumo tyrinėjimais (Michailas Bachtinas, Julia Kristeva, Rolandas Barthesas) ir Williamo J. Thomaso Mitchello ekfrazės kaip komunikacijos su kitu idėjomis. Straipsnyje aptariant išskirtinį Audiejaičio atvejį parodytas komunikacijos aspekto stiprėjimas žodžio ir vaizdo sąveikos teorijose, taip pat intertekstualumo bei intermedialumo tyrinėjimuose. Remiantis Mitchellu, daroma išvada, kad aklumas nėra atimantis galimybę komunikuoti su vizualiuoju kitu, nes ekfrazėje dalyvaujančios kalbos kontūras, jos juslėmis patiriamas medžiagiškumas gali būti suvokiamas kaip vizualumo pavidalas, per kurį vyksta komunikacija.
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Subotin-Golubovic, Tatjana. "Octoechos: A model and inspiration for Serbian medieval hymnographer." Muzikologija, no. 11 (2011): 53–61. http://dx.doi.org/10.2298/muz1111053s.
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Octoechos is not merely a musical manual in everyday use during the service in Orthodox Church, but also a comprehensive anthology of church poetry. It contains poetical works of great Byzantine poets, such as John of Damascus, Joseph the Hymnographer, Andrew of Crete. The use of Octoechos during the service is strictly regulated by Typicon. After accepting the Orthodox rite, the Slavs were acquainted with Octoechos which has undoubtedly made a great impression on the attentive audiences present at the service. Octoechos has also influenced the work of medieval Serbian hymnographers all of whom were, as it is well known, pious men. The influence of the poetics typical of hymns of the Octoechos has already been present in the Akoluthia to St. Simeon written by St. Sava. In the hymnographical work of Theodosius this influence is even more present, especially in his Canons on the eight modes (echoi) that follow the pattern of the supplicatory canons of the Octoechos. Ephraim, who was the Serbian patriarch in two turns (1375-1379, 1389-1392), wrote his church hymns and prayers following those of the Octoechos. Ephraim composed his stichera dedicated to Christ and Theotokos following the regular change of tones of the Octoechos. The spirit of Octoechos has also marked the work of the last Serbian anonymous hymnographers who wrote Akoluthia to the Translation of the holy relics of Saint Apostle Luke to Serbia and the Paraklisis to St. Luke (mid 15th century).
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Pryce, Rhys, Kristopher Azarm, Ilona Rissanen, Karl Harlos, Thomas A. Bowden, and Benhur Lee. "A key region of molecular specificity orchestrates unique ephrin-B1 utilization by Cedar virus." Life Science Alliance 3, no. 1 (December 20, 2019): e201900578. http://dx.doi.org/10.26508/lsa.201900578.
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The emergent zoonotic henipaviruses, Hendra, and Nipah are responsible for frequent and fatal disease outbreaks in domestic animals and humans. Specificity of henipavirus attachment glycoproteins (G) for highly species-conserved ephrin ligands underpins their broad host range and is associated with systemic and neurological disease pathologies. Here, we demonstrate that Cedar virus (CedV)—a related henipavirus that is ostensibly nonpathogenic—possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry. Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition. The structural and functional insights presented uncover diversity within the known henipavirus receptor repertoire and suggest that only modest structural changes may be required to modulate receptor specificities within this group of lethal human pathogens.
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Kimelman, Reuven. "Abraham Joshua Heschel's Theology of Judaism and the Rewriting of Jewish Intellectual History." Journal of Jewish Thought and Philosophy 17, no. 2 (2009): 207–38. http://dx.doi.org/10.1163/105369909x12506863090512.
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AbstractAbraham Joshua Heschel's oeuvre deals with the continuum of Jewish religious consciousness from the biblical and rabbinic periods through the kabbalistic and Hasidic ones with regard to God's concern for humanity. The goal of this study is to show how such a “Nachmanidean” reading has partially displaced the discontinuous “Maimonidean” reading promoted by Yehezkel Kaufman, Ephraim Urbach, and Gershom Scholem. The result is that Heschel's understanding of the development of Jewish theologizing is more influential now than it was during his lifetime. This study traces the growth of that development and explores how Heschel became the scholar-theologian who most succeeded in bridging the gap between scholarship and constructive theology.
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Forse, Garry Jason, Maria Loressa Uson, Fariborz Nasertorabi, Anand Kolatkar, Ilaria Lamberto, Elena Bianca Pasquale, and Peter Kuhn. "Distinctive Structure of the EphA3/Ephrin-A5 Complex Reveals a Dual Mode of Eph Receptor Interaction for Ephrin-A5." PLOS ONE 10, no. 5 (May 20, 2015): e0127081. http://dx.doi.org/10.1371/journal.pone.0127081.
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Zyskina, Esther. "From Ally to Enemy: the Ottoman Empire in Publicistic Works by Ephraim Deinard." Tirosh. Jewish, Slavic & Oriental Studies 18 (2018): 77–92. http://dx.doi.org/10.31168/2658-3380.2018.18.2.2.
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The paper considers is the transformation of the image of the Ottoman Empire in the publicistic texts by Ephraim Deinard, outstand ing Jewish writer and journalist of the turn of the 19th and 20th centu ries. The research was based on two Deinard’s works, “Atidot Israel” (“The Future of Israel”, 1892) and “Tzion be’ad mi?” (“Zion for Whom?”, 1918), which deal with a variety of topics, including Deinard’s opinion on the Ottoman Empire. In particular, the radical change of his position from the statements in “Atidot Israel” to those in “Tzion be’ad mi?” is observed. Deinard discusses the following three aspects, each case being a vivid example of this controversy: 1. The Ottoman government’s attitude towards Jews and the pros pects of the collaboration of the Jewish community with the government; 2. The economic situation in the Ottoman Empire and its foreign policy; 3. The culture and cultural policy in the Ottoman Empire. Deinard’s interest in Turkey was initially caused by his Zionist views, as the Land of Israel was part of the Ottoman Empire. Later, after World War I and especially after the Balfour Declaration in 1917, the Zionists placed their expectations on Britain, while Turkey, after losing the war and the territory so important for Jews, could no more be praised by Dei nard. In addition, Deinard had lived in the USA for more than 30 years by 1918, and it is merely logical that his publicistic works were aimed against the USA’s enemy in World War I. This shift looks especially interesting when looked at through the context of the history of the Russian Jewish Enlightenment. A very simi lar process occurred in the ideology of the Russian maskilim in the 19th century. Throughout the 19th century, they believed that the Jews should be integrated in the Russian society and viewed the Russian government as their ally. The Russian authorities, correspondingly, tried to assimilate the Jews and to make them an integral part of the society. However, af ter the pogroms of 1880s, the authorities’ attitude towards Jews changed dramatically, and so did that of the maskilim towards the government. Laws regarding Jews were tightened and became openly anti-Semitic, and the maskilim started to criticize the state instead of hoping for col laboration with it. Deinard’s works used for this research date to a later period. More over, the aforementioned events influenced his positive attitude towards the Ottoman Empire: concerning the status of Jews in the both countries, Deinard opposed Turkey to Russia. Eventually, however, Turkey took the same place for Deinard as Russia did for his predecessors, the maskilim. His hopes for collaboration with the state were just as replaced by disap pointment and criticism. To conclude, the above similarity may suggest that the shift in Dein ard’s views might have correlated with the change in the ideology of the Russian maskilim.
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Yuan, Junfa, Glenn Marsh, Dimple Khetawat, Christopher C. Broder, Lin-Fa Wang, and Zhengli Shi. "Mutations in the G–H loop region of ephrin-B2 can enhance Nipah virus binding and infection." Journal of General Virology 92, no. 9 (September 1, 2011): 2142–52. http://dx.doi.org/10.1099/vir.0.033787-0.
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Nipah virus (NiV) and Hendra virus (HeV) are zoonotic paramyxoviruses classified in the genus Henipavirus of the family Paramyxoviridae. The entry of henipaviruses occurs through a pH-independent membrane-fusion mechanism mediated by the cooperation of the viral attachment (G) and fusion (F) envelope glycoproteins following virion binding to susceptible host cells. Virus attachment is mediated by the interaction of the G glycoprotein with ephrin-B2 or ephrin-B3, which were identified as the functional receptors of henipavirus. Several residues of the G glycoprotein that are important for receptor binding have been determined through mutagenesis and structural analyses; however, similar approaches have not been carried out for the viral receptor ephrin-B2. Here, an alanine-scanning mutagenesis analysis was performed to identify residues of ephrin-B2 which are critical for NiV binding and entry by using an NiV-F- and -G-glycoprotein pseudotyped lentivirus assay. Results indicated that the G–H loop of ephrin-B2 was indeed critical for the interaction between ephrin-B2 and NiV-G. Unexpectedly, however, some alanine-substitution mutants located in the G–H loop enhanced the infectivity of the NiV pseudotypes, in particular an L124A mutation enhanced entry >30-fold. Further analysis of the L124A ephrin-B2 mutant demonstrated that an increased binding affinity of the mutant receptor with NiV-G was responsible for the enhanced infectivity of both pseudovirus and infectious virus. In addition, cell lines that were stably expressing the L124A mutant receptor were able to support NiV infection more efficiently than the wild-type molecule, potentially providing a new target-cell platform for viral isolation or virus-entry inhibitor screening and discovery.
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Gong, Jingyi, Roman Körner, Louise Gaitanos, and Rüdiger Klein. "Exosomes mediate cell contact–independent ephrin-Eph signaling during axon guidance." Journal of Cell Biology 214, no. 1 (June 27, 2016): 35–44. http://dx.doi.org/10.1083/jcb.201601085.
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The cellular release of membranous vesicles known as extracellular vesicles (EVs) or exosomes represents a novel mode of intercellular communication. Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands have very important roles in such biologically diverse processes as neuronal development, plasticity, and pathological diseases. Until now, it was thought that ephrin-Eph signaling requires direct cell contact. Although the biological functions of ephrin-Eph signaling are well understood, our mechanistic understanding remains modest. Here we report the release of EVs containing Ephs and ephrins by different cell types, a process requiring endosomal sorting complex required for transport (ESCRT) activity and regulated by neuronal activity. Treatment of cells with purified EphB2+ EVs induces ephrinB1 reverse signaling and causes neuronal axon repulsion. These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2+ EVs in neural development and synapse physiology.
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Levy, Shimon. "‘How Are the Mighty Fallen’: Aspects of Contemporary Israeli Theatre." New Theatre Quarterly 6, no. 24 (November 1990): 382–94. http://dx.doi.org/10.1017/s0266464x00004966.
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Even at its most political, contemporary Israeli theatre tends to be self-referential – nowhere more so, suggests Shimon Levy, than in the theatre festivals held at Acre, where year by year over the past decade the plays selected seem to have reflected, more than coincidentally, the preoccupations of the nation, with its haunted past, its militaristic present, and a future full of uncertain or resented accommodations with neighbours for so long perceived as enemies. But Shimon Levy, who teaches in the Theatre Department at Tel Aviv University, also notes two exceptions in a generally gloomy theatrical scene: the exuberant entertainment Yanti Parazi – ‘a metaphor for the yearning for this screwed-up Holy Land’ – and a long-unperformed play on the ‘difficult’ subject of the West Bank occupation, Ephraim Returns to the Army, with its schitzoid title-character ‘deconstructing’ the conflicting elements of Israeli hopes and beliefs, for audiences not presumed to share the play's own progressive but unsentimentalized sympathies.
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Welch, Paul D. "Ancient monuments of the Mississippi Valley by E.G. Squier & E.H. Davis: the first classic of US archaeology." Antiquity 72, no. 278 (December 1998): 921–27. http://dx.doi.org/10.1017/s0003598x00087597.
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The two most important 19th-century books on archaeology in the United States both dealt with earthworks. The earlier of these two, Ancient monuments of the Mississippi Valley by Ephraim G. Squier & Edwin H. Davis, was the first volume published by the fledgling Smithsonian Institution, and is 150 years old this year. It presented, with lavish illustrations, information about hundreds of earthworks. Its principal argument was that the mounds had been built by an American race distinct from the historically known indigenes, no less and perhaps considerably more than 1000 years ago. This volume in no small measure catalysed the development of archaeology in the United States. Without Squier & Davis’ extensive documentation of the vast number, size, complexity and variety of earthworks, the later book might never have been commissioned or might have been conceived in far less ambitious terms.
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Bowden, Thomas A., Max Crispin, David J. Harvey, E. Yvonne Jones, and David I. Stuart. "Dimeric Architecture of the Hendra Virus Attachment Glycoprotein: Evidence for a Conserved Mode of Assembly." Journal of Virology 84, no. 12 (April 7, 2010): 6208–17. http://dx.doi.org/10.1128/jvi.00317-10.
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ABSTRACT Hendra virus is a negative-sense single-stranded RNA virus within the Paramyxoviridae family which, together with Nipah virus, forms the Henipavirus genus. Infection with bat-borne Hendra virus leads to a disease with high mortality rates in humans. We determined the crystal structure of the unliganded six-bladed β-propeller domain and compared it to the previously reported structure of Hendra virus attachment glycoprotein (HeV-G) in complex with its cellular receptor, ephrin-B2. As observed for the related unliganded Nipah virus structure, there is plasticity in the Glu579-Pro590 and Lys236-Ala245 ephrin-binding loops prior to receptor engagement. These data reveal that henipaviral attachment glycoproteins undergo common structural transitions upon receptor binding and further define the structural template for antihenipaviral drug design. Our analysis also provides experimental evidence for a dimeric arrangement of HeV-G that exhibits striking similarity to those observed in crystal structures of related paramyxovirus receptor-binding glycoproteins. The biological relevance of this dimer is further supported by the positional analysis of glycosylation sites from across the paramyxoviruses. In HeV-G, the sites lie away from the putative dimer interface and remain accessible to α-mannosidase processing on oligomerization. We therefore propose that the overall mode of dimer assembly is conserved for all paramyxoviruses; however, while the geometry of dimerization is rather closely similar for those viruses that bind flexible glycan receptors, significant (up to 60°) and different reconfigurations of the subunit packing (associated with a significant decrease in the size of the dimer interface) have accompanied the independent switching to high-affinity protein receptor binding in Hendra and measles viruses.
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Lazarova, P., Q. Wu, G. Kvalheim, Z. Suo, K. W. Haakenstad, K. Metodiev, and J. M. Nesland. "Growth Factor Receptors in Hematopoietic Stem Cells: EPH Family Expression in CD34+ and CD133+ Cell Populations from Mobilized Peripheral Blood." International Journal of Immunopathology and Pharmacology 19, no. 1 (January 2006): 205873920601900. http://dx.doi.org/10.1177/205873920601900105.
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Cell-surface antigen expression of hematopoietic stem cells has a crucial role in characterizing cell subpopulation with distinct functional properties. The Eph receptors are the largest receptor tyrosine kinase family being involved in processes like vascular remodelling during development and physiological and pathological angiogenesis. Some Eph/Ephrin members are expressed in hematopoietic cells. The ability to isolate purified cell populations co-expressing CD34 and CD133 antigens as most commonly used markers for identification of hematopoietic progenitors has provided the opportunity to identify their surface-receptor profile. As positively expressed CD34 and CD133 cells take place not only in hematopoietic but also in endothelial differentiation, we aimed to define the Eph/Ephrin characteristic of these cells and relate these findings to new therapy strategies. Positive selections of CD34 and CD133 cells from PBPC in lymphoma patients were performed using magnetic beads and AutoMACS (Miltenyi Biotec) device. The purity of isolated cells was tested by flow cytometry. Immunocytochemistry was used to assess the Eph/Ephrin expression profile of positively selected samples. Our study revealed that all samples (10 from CD34+ and 8 from CD133+ cells) expressed one or more of Eph/Ephrin antigens in different proportions. All CD34 + cell samples, and 6 of 8 in the CD133+ cell fraction were strongly immunoreactive for EphA2. EphB2 was strongly expressed in all CD133+ cases, but 50% of the CD34 positive group lacked or weakly expressed this receptor. EphB4 was negative in 9 of 10 CD34+ cases and in all CD133 +cells. Thus, we have shown the surface marker profile of positively selected CD34 and CD133 cells in leukapheresis samples from lymphoma patients with regard to Eph/Ephrin receptors and discussed their biological clinical potential.
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Matsui, Toshimitsu, Hiroshi Matsuoka, Akira Tamekane, Ryuichi Inoue, Manabu Shimoyama, Atsushi Okamura, Hiroya Obama, Meghan L. Kelly, and Masaru Nakamoto. "Cell Adhesion and Migration Regulated by EphB6 Expressed on Human Hematopoietic Progenitors." Blood 106, no. 11 (November 16, 2005): 1386. http://dx.doi.org/10.1182/blood.v106.11.1386.1386.
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Abstract Normal human hematopoietic progenitors as well as leukemia/lymphoma cells express kinase-defective EphB6 receptors. The only unique high affinity ligand for EphB6 among eight known mammalian ephrins, ephrins-B2 is expressed not only on hematopoietic malignancies, but also on mesenchymal stem cells. However, the biological functions of the receptor and its ligand in hematopoietic cells are largely unknown. In the present study, we showed that the interaction between EphB6 and ephrinB2 could initiate forward as well as reverse signaling in vitro. Both pre-clustered and unclustered ligands could trigger the signal transduction, but pre-clustered ones more rapidly down-regulated the signaling. We also examined the EphB6/ephrinB2 function in cell adhesion and migration. Figure Figure HEK-EphB6 cells placed in the upper chamber of a Transwell apparatus, in which the lower side of filter was coated with different concentrations of ephrin-B2-Fc or Fc, were allowed to migrate to the lower side at 37°C overnight. Vector-transfected cells were used as controls. The cells that had migrated to the lower side of filter were stained, photographed. A BSA-coated filter is shown as a control. EphB6 exerted biphasic effects in response to different concentrations of the ephrin-B2. EphB6 promoted cell adhesion and migration when stimulated with low concentrations of ephrin-B2, whereas it induced repulsion and inhibited migration upon stimulation with high concentrations of ephrin-B2. A truncated EphB6 receptor lacking the cytoplasmic domain showed monophasic positive effects on cell adhesion and migration, indicating that the cytoplasmic domain is essential for the negative effects. We further explored the signal transduction of the biphasic effects. Figure Figure The Src family kinase, Fyn was co-immunoprecipitated with anti-EphB6 antibody in the absence or presence of ephrin-B2 stimulation. High concentrations of ephrin-B2 induced tyrosine phosphorylation of EphB6 through a Src family kinase activity. These results indicate that EphB6 can both positively and negatively regulate cell adhesion and migration, and suggest that tyrosine phosphorylation of the kinase-defective EphB6 receptor by a Src family kinase acts as the molecular switch for the functional transition. Thus, EphB6 expressed on hematopoietic cells may play an important role in the regulation of cell homing to hematopoietic tissues as well as leukemia cell infiltration.
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Taylor, Gwen M., Gregory M. Cooper, Joseph E. Losee, Mark P. Mooney, and James Gilbert. "Molecular Analysis of Ephrin A4 and Ephrin B1 in a Rabbit Model of Craniosynostosis." Cleft Palate-Craniofacial Journal 55, no. 7 (February 22, 2018): 1020–25. http://dx.doi.org/10.1597/16-135.
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Craniosynostosis (CS) has a prevalence of approximately 1 in every 2000 live births and is characterized by the premature fusion of one or more cranial sutures. Failure to maintain the cell lineage boundary at the coronal suture is thought to be involved in the pathology of some forms of CS. The Ephrin family of receptor tyrosine kinases consists of membrane-bound receptors and ligands that control cell patterning and the formation of developmental boundaries. Mutations in the ephrin A4 (EFNA4) and ephrin B1 (EFNB1) ligands have been linked to nonsyndromic CS and craniofrontonasal syndrome, respectively, in patient samples. We have previously described a colony of rabbits with a heritable pattern of coronal suture synostosis, although the genetic basis for synostosis within this model remains unknown. The present study was performed to determine if EFNA4 or EFNB1 could be the loci of the causal mutation in this unique animal model. Sequencing of EFNA4 and EFNB1 was performed using templates obtained from wild-type (n = 4) and craniosynostotic (n = 4) rabbits. No structural coding errors were identified in either gene. A single-nucleotide transversion was identified in one wild-type rabbit within the third intron of EFNA4. These data indicate that the causal locus for heritable CS in this rabbit model is not located within the structural coding regions of either EFNA4 or EFNB1.
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Kujawa, Sheryl A., and Brother Philip Armstrong. "A More Perfect Legacy: A Portrait of Brother Ephrem O'Dwyer, C. S. C., 1888-1978." History of Education Quarterly 36, no. 4 (1996): 542. http://dx.doi.org/10.2307/369808.
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Lieber, Laura. "Portraits of Righteousness: Noah in Early Christian and Jewish Hymnography." Zeitschrift für Religions- und Geistesgeschichte 61, no. 4 (2009): 332–55. http://dx.doi.org/10.1163/157007309789346461.
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AbstractThe transformation of Noah into a Christian ideal in the writings of Aphrahat and Ephrem (4th century), with the resulting denigration of Noah in much rabbinic exegesis, is well documented. The purpose of this essay is to examine the characterization of Noah in the liturgical (as opposed to the scholarly) setting. Four groups of works are examined: the Hebrew Avodah poems and the hymns of Ephrem the Syrian (4th century); and the kontakia of Romanos the Melodist and the liturgical poems of the Jewish poet Yannai (6th century). These sources reveal that the individual poets felt great freedom to shape the character of Noah in distinctive ways, engaging with the various traditions of interpretation evident in the prose sources but using them in individualized ways. The resulting picture of Noah, when these poetic sources are brought to bear on the discussion, is much less predictable and more dynamic than might be assumed from study of the more“academic” prose sources alone.
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Prévost, Nicolas, Donna S. Woulfe, Massimiliano Tognolini, Takako Tanaka, Wenying Jian, Ryan R. Fortna, Hong Jiang, and Lawrence F. Brass. "Signaling by ephrinB1 and Eph kinases in platelets promotes Rap1 activation, platelet adhesion, and aggregation via effector pathways that do not require phosphorylation of ephrinB1." Blood 103, no. 4 (February 15, 2004): 1348–55. http://dx.doi.org/10.1182/blood-2003-06-1781.
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Abstract We have previously shown that platelets express 2 receptor tyrosine kinases, EphA4 and EphB1, and the Eph kinase ligand, ephrinB1, and proposed that transcellular Eph/ephrin interactions made possible by the onset of platelet aggregation promote the further growth and stability of the hemostatic plug. The present study examines how this might occur. The results show that clustering of either ephrinB1 or EphA4 causes platelets to adhere to immobilized fibrinogen via αIIbβ3. Adhesion occurs more slowly than with adenosine diphosphate (ADP) and requires phosphatidylinositol 3 (PI3)–kinase and protein kinase C activity but not ephrinB1 phosphorylation. By itself, Eph and ephrin signaling is insufficient to cause aggregation or the binding of soluble fibrinogen, but it can potentiate aggregation initiated by a Ca++ ionophore or by agonists for thrombin and thromboxane receptors. It also enhances Rap1 activation without requiring ADP secretion, ephrinB1 phosphorylation, or the activation of PI3-kinase and Src. From this we conclude that (1) Eph/ephrin signaling enhances the ability of platelet agonists to cause aggregation provided that those agonists can increase cytosolic Ca++; (2) this is accomplished in part by activating Rap1; and (3) these effects require oligomerization of ephrinB1 but not phosphotyrosine-based interactions with the ephrinB1 cytoplasmic domain.
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Bell, Daniel M. "Trump as Mirror for the Church: Death and Despair, Hope and Resurrection of the Church." Religions 11, no. 3 (February 27, 2020): 107. http://dx.doi.org/10.3390/rel11030107.
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The election of Donald Trump inaugurated a wave of anxiety-bordering-on-despair among various peoples hoping for another, better world. This paper considers whether Trump deserves such acclaim in the sense that Trump is at best a symptom or cipher that can be approached by heeding Martin Luther’s observation that our politicians reflect who we are. To make this argument first I draw upon the work of Andrew Bacevich to suggest a certain continuity rather than apocalyptic break in recent American politics. Then I ask what the production of such politicians and politics says about American Christianity, which is far more frightening than the fleeting ascendancy of a mere Trump. In particular, using the National Study of Youth and Religion I suggest that the church in America suffers from a widespread failure of formation in the faith. What are we to make of this failure? Whence cometh hope? Building on Ephraim Radner’s interrogation of the divided church and on Jonathan Lear’s exploration of radical hope in the wake of cultural devastation, I will suggest both a theologically appropriate despair and also a hope for emergent forms and practices of faith capable of resisting the darkness of these times.
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Torabi, Katayoun. "Asceticism in Old English and Syriac Soul and Body Narratives." Humanities 9, no. 3 (August 31, 2020): 100. http://dx.doi.org/10.3390/h9030100.
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A great deal of scholarship on Old English soul-body poetry centers on whether or not the presence of dualist elements in the poems are unorthodox in their implication that the body, as a material object, is not only wicked but seems to possess more agency in the world than the soul. I argue that the Old English soul-body poetry is not heterodox or dualist, but is best understood, as Allen J. Frantzen suggests, within the “context of penitential practice.” The seemingly unorthodox elements are resolved when read against the backdrop of pre-Conquest English monastic reform culture, which was very much concerned with penance, asceticism, death, and judgment. Focusing especially on two anonymous 10th-century Old English poems, Soul and Body I in the Vercelli Book and Soul and Body II in the Exeter Book, I argue that that both body and soul bear equal responsibility in achieving salvation and that the work of salvation must be performed before death, a position that was reinforced in early English monastic literature that was inspired, at least in part, by Eastern ascetics such as fourth-century Syrian hymnologist and theologian, St. Ephraim.
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Vaidya, Ashish, Anna Pniak, Greg Lemke, and Arthur Brown. "EphA3 Null Mutants Do Not Demonstrate Motor Axon Guidance Defects." Molecular and Cellular Biology 23, no. 22 (November 15, 2003): 8092–98. http://dx.doi.org/10.1128/mcb.23.22.8092-8098.2003.
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ABSTRACT Motor axon projections are topographically ordered. Medial motor column axons project to axial muscles, whereas lateral motor column axons project to limb muscles and, along the rostrocaudal axis of the animal, the more rostral motor neuron pools project to more rostral muscle targets. We have shown that EphA3 is specifically expressed in the developing medial motor column and have postulated that EphA3 might be responsible for directing their axons to axial muscle targets. This hypothesis was supported by our demonstration that EphA3 can direct retinal ganglion cell axon targeting and by studies of ephrin-A5−/− mutants that show that EphA receptor signaling controls the topographic innervation of the acromiotrapezius. To test the role of EphA3 in motor axon guidance, we generated an EphA3 null mutant. Retrograde labeling studies in EphA3−/− embryos and adults indicate that, contrary to our predictions, EphA3 is not necessary to direct motor axons to axial muscle targets. Our results also demonstrate that ephrin A5's ability to direct topographic innervation of the acromiotrapezius must be mediated through EphA receptors other than, or in addition to, EphA3.
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Panin, Leonid G. "A. S. Pushkin’s Poem The Hermit Fathers and the Immaculate Wives... (Linguostylistic Analysis of a Poem and Its Source)." Philology 19, no. 9 (2020): 74–86. http://dx.doi.org/10.25205/1818-7919-2020-19-9-74-86.
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The following article presents a linguistic and stylistic analysis of A. S. Pushkin’s poem The hermit Fathers and the immaculate wives... in comparison with the Greek text of the prayer of St. Ephrem the Syrian and its Church Slavonic translation, which was the source of the Poet’s poem. The similarities of the text content and the existing differences are shown. The outstanding role of Pushkin’s text, which essentially performs the ‘transliterating’ function of transmitting Church Slavonic literature to the system of Russian verbal culture, is acknowledged. For Alexander Pushkin, the Church Slavonic language was very important as a source (or one of the sources) of formation of the Russian literary language. The poet introduced many Church Slavonic words into Russian literary speech, for which he was often criticized. Indeed, from the point of view of a native speaker of an exquisite literary language, many lexical introductions of Church Slavonisms to the text of Eugene Onegin were a stylistic challenge. Russian lexical field was regularly expanded by the poet by the means of the Church Slavonic dictionary. This is clearly confirmed by works where the Church Slavonic words fit the theme logically, without causing complaints from adherents of literary norms, but also serve the purpose of lexical enrichment of the Russian language. The analyzed poem is among such works. A comparison of the two texts (the Church Slavonic translation of the prayer of St. Ephrem the Syrian and the poem of Alexander Pushkin) shows a very important difference between them. There is humility as the highest Christian virtue and Evangelical hope in Ephrem the Syrian’s work. And there is Evangelical love as a goal and the most cherished, necessary value for a person who has fallen, but lives in hope, in A. S. Pushkin. Each of these ascetics (St. Ephrem the Syrian and Alexander Pushkin) has his own vision of the outcome of earthly life. For all its signs of Lenten prayer, the poet’s requests have a different sound. More general, more generalized. The text goes beyond the category of calendar-timed (within the Church year) prayers, it pushes the boundaries of its use. This is its further development, its further life. And this is quite natural. Having left the liturgical, prayerful, more secluded and more strict sphere for the sphere of literature (resp. in the sphere of public perception and worldview, addressed to contemporaries who are not always aware of the significance of the presence of God in their lives), the text has already changed, it has spread out. A shift in internal emphasis changes its content. It is a fundamentally independent work.
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Panin, Leonid G. "A. S. Pushkin’s Poem The Hermit Fathers and the Immaculate Wives... (Linguostylistic Analysis of a Poem and Its Source)." Philology 19, no. 9 (2020): 74–86. http://dx.doi.org/10.25205/1818-7919-2020-19-9-74-86.
Full textAbstract:
The following article presents a linguistic and stylistic analysis of A. S. Pushkin’s poem The hermit Fathers and the immaculate wives... in comparison with the Greek text of the prayer of St. Ephrem the Syrian and its Church Slavonic translation, which was the source of the Poet’s poem. The similarities of the text content and the existing differences are shown. The outstanding role of Pushkin’s text, which essentially performs the ‘transliterating’ function of transmitting Church Slavonic literature to the system of Russian verbal culture, is acknowledged. For Alexander Pushkin, the Church Slavonic language was very important as a source (or one of the sources) of formation of the Russian literary language. The poet introduced many Church Slavonic words into Russian literary speech, for which he was often criticized. Indeed, from the point of view of a native speaker of an exquisite literary language, many lexical introductions of Church Slavonisms to the text of Eugene Onegin were a stylistic challenge. Russian lexical field was regularly expanded by the poet by the means of the Church Slavonic dictionary. This is clearly confirmed by works where the Church Slavonic words fit the theme logically, without causing complaints from adherents of literary norms, but also serve the purpose of lexical enrichment of the Russian language. The analyzed poem is among such works. A comparison of the two texts (the Church Slavonic translation of the prayer of St. Ephrem the Syrian and the poem of Alexander Pushkin) shows a very important difference between them. There is humility as the highest Christian virtue and Evangelical hope in Ephrem the Syrian’s work. And there is Evangelical love as a goal and the most cherished, necessary value for a person who has fallen, but lives in hope, in A. S. Pushkin. Each of these ascetics (St. Ephrem the Syrian and Alexander Pushkin) has his own vision of the outcome of earthly life. For all its signs of Lenten prayer, the poet’s requests have a different sound. More general, more generalized. The text goes beyond the category of calendar-timed (within the Church year) prayers, it pushes the boundaries of its use. This is its further development, its further life. And this is quite natural. Having left the liturgical, prayerful, more secluded and more strict sphere for the sphere of literature (resp. in the sphere of public perception and worldview, addressed to contemporaries who are not always aware of the significance of the presence of God in their lives), the text has already changed, it has spread out. A shift in internal emphasis changes its content. It is a fundamentally independent work.
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Ebrahim, Abdul Shukkur, Zeyad Hailat, Sudeshna Bandyopadhyay, Daniel Neill, and Mustapha Kandouz. "The Value of EphB2 Receptor and Cognate Ephrin Ligands in Prognostic and Predictive Assessments of Human Breast Cancer." International Journal of Molecular Sciences 22, no. 15 (July 28, 2021): 8098. http://dx.doi.org/10.3390/ijms22158098.
Full textAbstract:
Cell–cell communication proteins Eph and ephrin constitute the largest family of receptor tyrosine kinases (RTKs). They are distinguished by the fact that both receptors and ligands are membrane-bound, and both can drive intracellular signaling in their respective cells. Ever since these RTKs have been found to be involved in cancer development, strategies to target them therapeutically have been actively pursued. However, before this goal can be rationally achieved, the contributions of either Eph receptors or their ephrin ligands to cancer development and progression should be scrutinized in depth. To assess the clinical pertinence of this concern, we performed a systematic review and meta-analysis of the prognostic/predictive value of EphB2 and its multiple cognate ephrin ligands in breast cancer. We found that EphB2 has prognostic value, as indicated by the association of higher EphB2 expression levels with lower distant metastasis-free survival (DMFS), and the association of lower EphB2 expression levels with poorer relapse-free survival (RFS). We also found that higher EphB2 expression could be a prognostic factor for distant metastasis, specifically in the luminal subtypes of breast cancer. EFNB2 showed a marked correlation between higher expression levels and shorter DMFS. EFNA5 or EFNB1 overexpression is correlated with longer RFS. Increased EFNB1 expression is correlated with longer OS in lymph node (LN)-negative patients and the luminal B subtype. Higher levels of EFNB2 or EFNA5 are significantly correlated with shorter RFS, regardless of LN status. However, while this correlation with shorter RFS is true for EFNB2 in all subtypes except basal, it is also true for EFNA5 in all subtypes except HER2+. The analysis also points to possible predictive value for EphB2. In systemically treated patients who have undergone either endocrine therapy or chemotherapy, we found that higher expression of EphB2 is correlated with better rates of RFS. Bearing in mind the limitations inherent to any mRNA-based profiling method, we complemented our analysis with an immunohistochemical assessment of expression levels of both the EphB2 receptor and cognate ephrin ligands. We found that the latter are significantly more expressed in cancers than in normal tissues, and even more so in invasive and metastatic samples than in ductal carcinoma in situ (DCIS). Finally, in an in vitro cellular model of breast cancer progression, based on H-Ras-transformation of the MCF10A benign mammary cell line, we observed dramatic increases in the mRNA expression of EphB2 receptor and EFNB1 and EFNB2 ligands in transformed and invasive cells in comparison with their benign counterparts. Taken together, these data show the clinical validity of a model whereby EphB2, along with its cognate ephrin ligands, have dual anti- and pro-tumor progression effects. In so doing, they reinforce the necessity of further biological investigations into Ephs and ephrins, prior to using them in targeted therapies.
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Mui, Stina H., Robert Hindges, Dennis D. M. O’Leary, Greg Lemke, and Stefano Bertuzzi. "The homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of the eye." Development 129, no. 3 (February 1, 2002): 797–804. http://dx.doi.org/10.1242/dev.129.3.797.
Full textAbstract:
The vertebrate retina is highly ordered along both its dorsoventral (DV) and nasotemporal (NT) axes, and this order is topographically maintained in its axonal connections to the superior colliculus of the midbrain. Although the graded axon guidance cues that mediate the topographic mapping of retinocollicular connections are increasingly well understood, the transcriptional regulators that set the DV and NT gradients of these cues are not. We now provide genetic evidence that Vax2, a homeodomain protein expressed in the ventral retina, is one such regulator. We demonstrate that in Vax2 mutant mice, retinocollicular projections from the ventral temporal retina are dorsalized relative to wild type. Remarkably, however, this dorsalization becomes systematically less severe in progressively more nasal regions of the ventral retina. Vax2 mutants also exhibit flattened DV and NT gradients of the EphA5, EphB2, EphB3, ephrin-B1 and ephrin-B2 axon guidance cues. Together, these data identify Vax2 as a fundamental regulator of axial polarization in the mammalian retina.
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Riches, John. "Lessing as Editor of Reimarus." Expository Times 129, no. 6 (December 5, 2017): 265–70. http://dx.doi.org/10.1177/0014524617745797.
Full textAbstract:
Gotthold Ephraim Lessing’s publication of Fragments of an Unknown Wolfenbüttel Author in the 1770s unleashed a storm of debate and controversy, which ended with censor stepping in and forbidding further contributions. The Fragmentenstreit, the ‘Battle of the Fragments’, as it came to be known, was a critical point in the development of German theology. For Schweitzer, as is made clear by the full title of his survey of historical Jesus studies ( The Quest of the Historical Jesus: A Critical Study of its Progress from Reimarus to Wrede), the publication of the fragment ‘On the purpose of Jesus and his disciples’ marks the true beginnings of an historical engagement with the Gospel stories about Jesus. For Lessing, Reimarus’ text certainly raised questions about the interpretative methods and categories which are most properly applied to the Gospels; it also raised issues about the relationship between reason and revelation, the place of the Bible, the canon, in the development of Christian faith, and indeed of the very nature of faith itself. We will look briefly at some of these questions. There is, too, a much wider and more demanding question: what influence did this debate have on the subsequent history of German theology which, in the 150 years which followed, saw the rise of both liberal and more confessionally oriented theologies, the prominence of figures like Schleiermacher, Hegel, Ritschl, Barth, and Bultmann? We can offer no more than a few pointers to the beginnings of such developments.
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Classen, Albrecht. "Religious Toleration as a Subject for World Education? Past and Present Perspectives for Students the World Over Based on Literary-Historical Material." Current Research Journal of Social Sciences and Humanities 4, no. 1 (June 25, 2021): 17–26. http://dx.doi.org/10.12944/crjssh.4.1.03.
Full textAbstract:
This study reexamines the meaning of education in global terms as the foundation of all open and democratic societies both in the past and the present. Literary studies create useful mirrors taking the learner into the past where parallel cases of human problems and conflicts existed. The learning experience then allows the individual to carry the new insights back to the own presence and to apply them to current situations. This process can and must be applied particularly to the principle of tolerance, one of the highest ideals in all of education. In order to illustrate this concept, this study examines Boccaccio’s Decameron and Gotthold Ephraim Lessing’s Nathan the Wise as model cases for global education leading to a more peaceful and mutually respectful world. With all due respect for religion, hating and murdering other people for religious reasons betrays the very principles of that religion whatever denomination or creed it might be. Ignorance and lack of education make it possible for fanatics or zelots to whip the masses into violent actions against those who adhere to another faith. One of the major tasks by educators is to introduce rationality, mutual respect, honor, and dignity, which is all possible through an intensive study of well-chosen literary texts for class discussions addressing world religions.
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Spalding, Thomas. "A More Perfect Legacy: A Portrait of Brother Ephrem O'Dwyer, C.S.C., 1888-1978 by Brother Philip Armstrong, C.S.C." Catholic Historical Review 83, no. 1 (1997): 147–48. http://dx.doi.org/10.1353/cat.1997.0113.
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Schaupp, Andreas, Ola Sabet, Irina Dudanova, Marion Ponserre, Philippe Bastiaens, and Rüdiger Klein. "The composition of EphB2 clusters determines the strength in the cellular repulsion response." Journal of Cell Biology 204, no. 3 (January 27, 2014): 409–22. http://dx.doi.org/10.1083/jcb.201305037.
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Trans interactions of erythropoietin-producing human hepatocellular (Eph) receptors with their membrane-bound ephrin ligands generate higher-order clusters that can form extended signaling arrays. The functional relevance of the cluster size for repulsive signaling is not understood. We used chemical dimerizers and fluorescence anisotropy to generate and visualize specific EphB2 cluster species in living cells. We find that cell collapse responses are induced by small-sized EphB2 clusters, suggesting that extended EphB2 arrays are dispensable and that EphB2 activation follows an ON–OFF switch with EphB2 dimers being inactive and trimers and tetramers being fully functional. Moreover, the strength of the collapse response is determined by the abundance of multimers over dimers within a cluster population: the more dimers are present, the weaker the response. Finally, we show that the C-terminal modules of EphB2 have negative regulatory effects on ephrin-induced clustering. These results shed new light on the mechanism and regulation of EphB2 activation and provide a model on how Eph signaling translates into graded cellular responses.
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Imondi, Ralph, and Zaven Kaprielian. "Commissural axon pathfinding on the contralateral side of the floor plate: a role for B-class ephrins in specifying the dorsoventral position of longitudinally projecting commissural axons." Development 128, no. 23 (December 1, 2001): 4859–71. http://dx.doi.org/10.1242/dev.128.23.4859.
Full textAbstract:
In both invertebrate and lower vertebrate species, decussated commissural axons travel away from the midline and assume positions within distinct longitudinal tracts. We demonstrate that in the developing chick and mouse spinal cord, most dorsally situated commissural neuron populations extend axons across the ventral midline and through the ventral white matter along an arcuate trajectory on the contralateral side of the floor plate. Within the dorsal (chick) and intermediate (mouse) marginal zone, commissural axons turn at a conserved boundary of transmembrane ephrin expression, adjacent to which they form a discrete ascending fiber tract. In vitro perturbation of endogenous EphB-ephrinB interactions results in the failure of commissural axons to turn at the appropriate dorsoventral position on the contralateral side of the spinal cord; consequently, axons inappropriately invade more dorsal regions of B-class ephrin expression in the dorsal spinal cord. Taken together, these observations suggest that B-class ephrins act locally during a late phase of commissural axon pathfinding to specify the dorsoventral position at which decussated commissural axons turn into the longitudinal axis.
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Schulte, D., and C. L. Cepko. "Two homeobox genes define the domain of EphA3 expression in the developing chick retina." Development 127, no. 23 (December 1, 2000): 5033–45. http://dx.doi.org/10.1242/dev.127.23.5033.
Full textAbstract:
Graded expression of the Eph receptor EphA3 in the retina and its two ligands, ephrin A2 and ephrin A5 in the optic tectum, the primary target of retinal axons, have been implicated in the formation of the retinotectal projection map. Two homeobox containing genes, SOHo1 and GH6, are expressed in a nasal-high, temporal-low pattern during early retinal development, and thus in opposing gradients to EphA3. Retroviral misexpression of SOHo1 or GH6 completely and specifically repressed EphA3 expression in the neural retina, but not in other parts of the central nervous system, such as the optic tectum. Under these conditions, some temporal ganglion cell axons overshot their expected termination zones in the rostral optic tectum, terminating aberrantly at more posterior locations. However, the majority of ganglion cell axons mapped to the appropriate rostrocaudal locations, although they formed somewhat more diffuse termination zones. These findings indicate that other mechanisms, in addition to differential EphA3 expression in the neural retina, are required for retinal ganglion axons to map to the appropriate rostrocaudal locations in the optic tectum. They further suggest that the control of topographic specificity along the retinal nasal-temporal axis is split into several independent pathways already at a very early time in development.
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Ramirez-Garcia, M. A., O. F. Chacon-Camacho, C. Leyva-Hernandez, A. Cardenas-Conejo, and J. C. Zenteno. "A NovelDe Novo EFNB1Gene Mutation in a Mexican Patient with Craniofrontonasal Syndrome." Case Reports in Genetics 2013 (2013): 1–4. http://dx.doi.org/10.1155/2013/349725.
Full textAbstract:
Craniofrontonasal syndrome (CNFS) is an X-linked disorder caused by mutations in theEFNB1gene in which, paradoxically, heterozygous females are more severely affected than hemizygous males. In this paper, the clinical and molecular studies of a female subject with CFNS are described. A novelde novoc.473T>C (p.M158T) mutation in exon 3 ofEFNB1was demonstrated in this patient. The M158 residue of the Ephrin-B1 protein is highly conserved between species. Our results expand the mutational spectrum exposed by CNFS.
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Neill, Thomas, Simone Buraschi, Atul Goyal, Catherine Sharpe, Elizabeth Natkanski, Liliana Schaefer, Andrea Morrione, and Renato V. Iozzo. "EphA2 is a functional receptor for the growth factor progranulin." Journal of Cell Biology 215, no. 5 (November 30, 2016): 687–703. http://dx.doi.org/10.1083/jcb.201603079.
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Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. Furthermore, we found an autoregulatory mechanism of progranulin whereby a feed-forward loop occurred in an EphA2-dependent manner that was independent of the endocytic receptor sortilin. The discovery of a functional signaling receptor for progranulin offers a new avenue for understanding the underlying mode of action of progranulin in cancer progression, tumor angiogenesis, and perhaps neurodegenerative diseases.
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Quist, Sven R., Maximilian Eckardt, André Kriesche, and Harald P. Gollnick. "Expression of Potential Dermal Progenitor Cell Markers in the Tumour and Stroma of Skin Adnexal Malignant and Benign Tumours." Stem Cells International 2019 (April 1, 2019): 1–10. http://dx.doi.org/10.1155/2019/9320701.
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Stem cells are multipotent cells that maintain the skin epidermis including skin appendages such as hair follicle, sebaceous glands, and sweat glands. There is evidence that reciprocal signalling between the epidermis and the dermis plays an important role in skin development, homeostasis, wound repair, and skin cancer. The origin of skin cancer that derive from skin appendages is still controversial, including basal cell carcinoma and even more of rare tumours such as sebaceous carcinomas and whether those tumours originate from resident tissue stem cells. To investigate whether markers reported to label dermal progenitor cells are preserved in the tumour including the tumour stroma of skin adnexal tumours, we tested 45 human basal cell carcinomas, including superficial, nodular, adenoid, infiltrating, and sclerosing types, and further 38 human tumours of skin appendages including 13 sebaceous adenomas and carcinomas, 20 eccrine sweat gland tumours, and 5 pilomatricomas, syringomas, and hair follicle tumours for the expression of the potential dermal and epidermal cell markers CRABP1, Nestin, and Ephrin B2 and compared these findings with healthy, age-related human epidermis. We detected that CRABP1, Nestin, and Ephrin B2 are expressed in the intratumoural stroma as well as the tumour invasive front of skin tumours of appendages and BCCs.
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Crawford, Matthew R. "Resolving Genealogical Ambiguity: Eusebius and (ps-)Ephrem on Luke 1.36." Aramaic Studies 14, no. 2 (2016): 83–97. http://dx.doi.org/10.1163/17455227-01402005.
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The earliest formal New Testament commentary in Syriac is the so-called Commentary on the Diatessaron attributed to Ephrem. This commentary is thoroughly at home in the world of Syriac Christianity, as seen not least in the fact that it focuses on Tatian’s idiosyncratic gospel version. Nevertheless, portions of the commentary also exhibit awareness of exegetical traditions shared with contemporary Greek authors. This paper focuses on one of the more striking of these parallels, namely, (ps-)Ephrem’s treatment of Mary’s Davidic lineage and relation to Elizabeth her ‘kinswoman’. Eusebius of Caesarea had taken up this issue in his Gospel Problems and Solutions, and the author of the Syriac commentary argues for the same three points evident in Eusebius’ treatment. Hence, the Syriac commentator has likely been directly or indirectly influenced by Eusebius’ formulation of this tradition, although specifying the manner of this transmission of ideas is impossible.
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Liu, Hua, Jinju Wang, Yusen Chen, Yanfang Chen, Xiaotang Ma, Ji C. Bihl, and Yi Yang. "NPC-EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR-210 Downstream Nox2 and VEGFR2 Pathways." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/9397631.
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We have demonstrated that neural progenitor cells (NPCs) protect endothelial cells (ECs) from oxidative stress. Since exosomes (EXs) can convey the benefit of parent cells through their carried microRNAs (miRs) and miR-210 is ubiquitously expressed with versatile functions, we investigated the role of miR-210 in the effects of NPC-EXs on oxidative stress and dysfunction in ECs. NPCs were transfected with control and miR-210 scramble/inhibitor/mimic to generate NPC-EXscon, NPC-EXssc, NPC-EXsanti-miR-210, and NPC-EXsmiR-210. The effects of various NPC-EXs on angiotensin II- (Ang II-) induced reactive oxygen species (ROS) overproduction, apoptosis, and dysfunction, as well as dysregulation of Nox2, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 in ECs were evaluated. Results showed (1) Ang II-induced ROS overproduction, increase in apoptosis, and decrease in tube formation ability, accompanied with Nox2 upregulation and reduction of p-VEGFR2/VEGFR2 in ECs. (2) Compared to NPC-EXscon or NPC-EXssc, NPC-EXsanti-miR-210 were less whereas NPC-EXsmiR-210 were more effective on attenuating these detrimental effects induced by Ang II in ECs. (3) These effects of NPC-EXsanti-miR-210 and NPC-EXsmiR-210 were associated with the changes of miR-210, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 ratio in ECs. Altogether, the protective effects of NPC-EXs on Ang II-induced endothelial injury through miR-210 which controls Nox2/ROS and VEGF/VEGFR2 signals were studied.
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DeBuysscher, Blair L., Dana P. Scott, Rebecca Rosenke, Victoria Wahl, Heinz Feldmann, and Joseph Prescott. "Nipah Virus Efficiently Replicates in Human Smooth Muscle Cells without Cytopathic Effect." Cells 10, no. 6 (May 25, 2021): 1319. http://dx.doi.org/10.3390/cells10061319.
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Nipah virus (NiV) is a highly pathogenic zoonotic virus with a broad species tropism, originating in pteropid bats. Human outbreaks of NiV disease occur almost annually, often with high case-fatality rates. The specific events that lead to pathogenesis are not well defined, but the disease has both respiratory and encephalitic components, with relapsing encephalitis occurring in some cases more than a year after initial infection. Several cell types are targets of NiV, dictated by the expression of the ephrin-B2/3 ligand on the cell’s outer membrane, which interact with the NiV surface proteins. Vascular endothelial cells (ECs) are major targets of infection. Cytopathic effects (CPE), characterized by syncytia formation and cell death, and an ensuing vasculitis, are a major feature of the disease. Smooth muscle cells (SMCs) of the tunica media that line small blood vessels are infected in humans and animal models of NiV disease, although pathology or histologic changes associated with antigen-positive SMCs have not been reported. To gain an understanding of the possible contributions that SMCs might have in the development of NiV disease, we investigated the susceptibility and potential cytopathogenic changes of human SMCs to NiV infection in vitro. SMCs were permissive for NiV infection and resulted in high titers and prolonged NiV production, despite a lack of cytopathogenicity, and in the absence of detectable ephrin-B2/3. These results indicate that SMC might be important contributors to disease by producing progeny NiV during an infection, without suffering cytopathogenic consequences.
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Kamoun, Walid, Elden Swindell, Christine Pien, Lia Luus, Jason Cain, Minh Pham, Irawati Kandela, et al. "Targeting EphA2 in Bladder Cancer Using a Novel Antibody-Directed Nanotherapeutic." Pharmaceutics 12, no. 10 (October 20, 2020): 996. http://dx.doi.org/10.3390/pharmaceutics12100996.
Full textAbstract:
Ephrin receptor A2 (EphA2) is a member of the Ephrin/Eph receptor cell-to-cell signaling family of molecules, and it plays a key role in cell proliferation, differentiation, and migration. EphA2 is overexpressed in a broad range of cancers, and its expression is in many cases associated with poor prognosis. We recently developed a novel EphA2-targeting antibody-directed nanotherapeutic encapsulating a labile prodrug of docetaxel (EphA2-ILs-DTXp) for the treatment of EphA2-expressing malignancies. Here, we characterized the expression of EphA2 in bladder cancer using immunohistochemistry in 177 human bladder cancer samples and determined the preclinical efficacy of EphA2-ILs-DTXp in four EphA2-positive patient-derived xenograft (PDX) models of the disease, either as a monotherapy, or in combination with gemcitabine. EphA2 expression was detected in 80–100% of bladder cancer samples and correlated with shorter patient survival. EphA2 was found to be expressed in tumor cells and/or tumor-associated blood vessels in both primary and metastatic lesions with a concordance rate of approximately 90%. The EphA2-targeted antibody-directed nanotherapeutic EphA2-ILs-DTXp controlled tumor growth, mediated greater regression, and was more active than free docetaxel at equitoxic dosing in all four EphA2-positive bladder cancer PDX models. Combination of EphA2-ILs-DTXp and gemcitabine in one PDX model led to improved tumor growth control compared to monotherapies or the combination of free docetaxel and gemcitabine. These data demonstrating the prevalence of EphA2 in bladder cancers and efficacy of EphA2-ILs-DTXp in PDX models support the clinical exploration of EphA2 targeting in bladder cancer.
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Taylor, Harriet B., Anaïs Khuong, Zhonglin Wu, Qiling Xu, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R. Taylor, and David G. Wilkinson. "Cell segregation and border sharpening by Eph receptor–ephrin-mediated heterotypic repulsion." Journal of The Royal Society Interface 14, no. 132 (July 2017): 20170338. http://dx.doi.org/10.1098/rsif.2017.0338.
Full textAbstract:
Eph receptor and ephrin signalling has a major role in cell segregation and border formation, and may act through regulation of cell adhesion, repulsion or tension. To elucidate roles of cell repulsion and adhesion, we combined experiments in cell culture assays with quantitations of cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing cells, and this is disrupted by knockdown of N-cadherin. Measurements of contact inhibition of locomotion reveal that EphB2-, kiEphB2- and ephrinB1-expressing cells have strong heterotypic and weak homotypic repulsion. EphB2 cells have a transient increase in migration after heterotypic activation, which underlies a shift in the EphB2–ephrinB1 border but is not required for segregation or border sharpening. Simulations with the measured values of cell behaviour reveal that heterotypic repulsion can account for cell segregation and border sharpening, and is more efficient than decreased heterotypic adhesion. By suppressing homotypic repulsion, N-cadherin creates a sufficient difference between heterotypic and homotypic repulsion, and enables homotypic cohesion, both of which are required to sharpen borders.
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Maretzky, Thorsten, Steven Swendeman, Elin Mogollon, Gisela Weskamp, Umut Sahin, Karina Reiss, and Carl P. Blobel. "Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays." Biochemical Journal 474, no. 9 (April 13, 2017): 1467–79. http://dx.doi.org/10.1042/bcj20170075.
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ADAM9 (A Disintegrin And Metalloprotease 9) is a membrane-anchored metalloproteinase that has been implicated in pathological retinal neovascularization and in tumor progression. ADAM9 has constitutive catalytic activity in both biochemical and cell-based assays and can cleave several membrane proteins, including epidermal growth factor and Ephrin receptor B4; yet little is currently known about the catalytic properties of ADAM9 and its post-translational regulation and inhibitor profile in cell-based assays. To address this question, we monitored processing of the membrane-anchored Ephrin receptor B4 (EphB4) by co-expressing ADAM9, with the catalytically inactive ADAM9 E > A mutant serving as a negative control. We found that ADAM9-dependent shedding of EphB4 was not stimulated by three commonly employed activators of ADAM-dependent ectodomain shedding: phorbol esters, pervanadate or calcium ionophores. With respect to the inhibitor profile, we found that ADAM9 was inhibited by the hydroxamate-based metalloprotease inhibitors marimastat, TAPI-2, BB94, GM6001 and GW280264X, and by 10 nM of the tissue inhibitor of metalloproteinases (TIMP)-3, but not by up to 20 nM of TIMP-1 or -2. Additionally, we screened a non-hydroxamate small-molecule library for novel ADAM9 inhibitors and identified four compounds that selectively inhibited ADAM9-dependent proteolysis over ADAM10- or ADAM17-dependent processing. Taken together, the present study provides new information about the molecular fingerprint of ADAM9 in cell-based assays by showing that it is not stimulated by strong activators of ectodomain shedding and by defining a characteristic inhibitor profile. The identification of novel non-hydroxamate inhibitors of ADAM9 could provide the basis for designing more selective compounds that block the contribution of ADAM9 to pathological neovascularization and cancer.
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Smołucha, Grzegorz, Artur Gurgul, Igor Jasielczuk, Aldona Kawęcka, and Anna Miksza-Cybulska. "A genome-wide association study for prolificacy in three Polish sheep breeds." Journal of Applied Genetics 62, no. 2 (February 20, 2021): 323–26. http://dx.doi.org/10.1007/s13353-021-00615-6.
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AbstractReproductive traits (especially litter size) are usually characterized by low heritability, and thus, phenotypic selection is often ineffective and slow. In order to improve fertility characteristics such as ovulation rate and litter size, it seems more effective to select breeding animals based on their genotype. The aim of the study was to use genome-wide association study (GWAS) in three sheep breeds to identify the genetic variants affecting the litter size in sheep. The study allowed us to identify one genome-wide significant SNP (rs402032081—located in ephrin type-A receptor 6, EPHA6) showing an association with litter size in Polish Mountain Sheep. We suggest that the EPHA6 gene can be a candidate gene for prolificacy trait in selected breeds of sheep; however, it needs further functional data for validation.
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Jaffe, Ian S., Anja K. Jaehne, Eugenia Quackenbush, Micah T. McClain, Geoffrey S. Ginsburg, Christopher W. Woods, Emanuel Rivers, and Ephraim L. Tsalik. "1218. Comparing the Diagnostic Accuracy of Clinician Judgement to a Novel Host Response Diagnostic for Acute Respiratory Illness." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S630. http://dx.doi.org/10.1093/ofid/ofaa439.1403.
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Abstract Background Discriminating bacterial and viral infections remains clinically challenging. The resulting antibacterial misuse contributes to antimicrobial resistance. Host gene expression-based tests are a promising strategy to discriminate of bacterial and viral infections, but their potential clinical utility has not yet been evaluated. Methods A host gene expression biosignature was measured using either qRT-PCR or microarray in 683 ED subjects with suspected infection. Based on chart reviews, we recorded clinical diagnosis as defined both by the provider assessment and by the provider treatment plan. The biosignature, diagnosis, treatment plan, and procalcitonin were compared to clinical adjudication as the reference standard. With this as a baseline, we then calculated average weighted accuracy (AWA) and change in overall net benefit (∆NB), weighting bacterial false negatives four times more seriously than false positives. Results Gene expression correctly classified the three possible disease etiologies (bacterial, viral, or non-infectious) 76.1% of the time, outperforming provider diagnosis, provider treatment, and procalcitonin (Table 1). Overall accuracy was higher in subjects with bacterial infections (n=278, 83.8% accurate) compared to those with viral (n=234, 76.5%) and non-infectious (n=171, 63.2%) etiologies. Due to a strong sensitivity bias to treat bacterial infections at the expense of diagnostic accuracy and specificity, the provider diagnosis was overall more accurate than the corresponding treatment plan (71.4% accuracy vs. 68.1%), resulting in inappropriate antibiotic use in 41.0% of cases where antibiotics were prescribed. The gene expression test had significantly higher AWA for the diagnosis of bacterial infection than both procalcitonin and provider treatment (82.4% vs. 70.3% and 74.4%, respectively; p < 0.0001). Consequently, the host gene expression test had greater net benefit than provider treatment (∆NBbact = 9.9%), provider diagnosis (∆NBbact = 4.4%), and procalcitonin (∆NBbact = 27.1%). Table 1: Summary of provider, procalcitonin, and host gene expression test performance in a cohort of 683 subjects. Conclusion Host gene expression-based tests to distinguish bacterial and viral infection can facilitate more appropriate treatment, leading to improved patient outcomes and mitigating the antibiotic resistance crisis. Disclosures Geoffrey S. Ginsburg, MD PhD, Predigen, Inc (Shareholder, Other Financial or Material Support) Ephraim L. Tsalik, MD, MHS, PhD, Predigen (Shareholder, Other Financial or Material Support, Founder)
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VO, BRADLY Q., A. JOSEPH BLOOM, and SUSAN M. CULICAN. "Phr1 is required for proper retinocollicular targeting of nasal–dorsal retinal ganglion cells." Visual Neuroscience 28, no. 2 (February 16, 2011): 175–81. http://dx.doi.org/10.1017/s0952523810000386.
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AbstractPrecise targeting of retinal projections is required for the normal development of topographic maps in the mammalian primary visual system. During development, retinal axons project to and occupy topographically appropriate positions in the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). Phr1 retinal mutant mice, which display mislocalization of the ipsilateral retinogeniculate projection independent of activity and ephrin-A signaling, were found to have a more global disruption of topographic specificity of retinofugal inputs. The retinocollicular projection lacks local refinement of terminal zones and multiple ectopic termination zones originate from the dorsal–nasal (DN) retinal quadrant. Similarly, in the dLGN, the inputs originating from the contralateral DN retina are poorly refined in the Phr1 mutant. These results show that Phr1 is an essential regulator of retinal ganglion cell projection during both dLGN and SC topographic map development.
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Bodkin, Nicholas, Melissa H. Ross, Ricardo Henao, and Ephraim L. Tsalik. "1216. Benchmarking Published Gene Signatures for Robust Infection Classification." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S629—S630. http://dx.doi.org/10.1093/ofid/ofaa439.1401.
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Abstract Background Host gene expression has emerged as a promising diagnostic strategy to discriminate bacterial and viral infection. Multiple gene signatures of varying size and complexity have been developed in various clinical populations. However, there has been no systematic comparison of these signatures. It is also unclear how these signatures apply to different clinical populations. This meta-analysis examined 19 published signatures, validated in 49 publicly available datasets for a total of 4750 patients. The objectives were to understand how the signatures compared to each other with respect to composition and performance, and to evaluate their performance in different patient subgroups. Methods Signatures were characterized with respect to size, platform, and discovery population. For each of the 19 signatures, we ran leave-one-out cross-validation to generate AUCs for bacterial classification and viral classification. We then applied dataset-specific thresholds to generate accuracies, pooling patients across datasets. Results Signature performance varied significantly with a median AUC across all validation datasets ranging from 0.55 to 0.94 for bacterial classification and 0.79 to 0.96 for viral classification. Signature size varied (1- 341 genes) with smaller signatures generally performing more poorly for both bacterial classification (P < .001) and for viral classification (P = 0.02). Viral infection was easier to diagnose than bacterial infection (85% vs. 80% overall accuracy, respectively; P < .001). Host gene expression classifiers performed more poorly in children < 12-years compared to those older than 12-years for both bacterial infection (77% vs. 83%, respectively; P < .001) and for viral infection (82% vs. 89%, respectively; P < .001). We did not observe differences based on illness severity as defined by ICU care for either bacterial or viral infections. Conclusion We observed significant differences among gene expression signatures for bacterial/viral discrimination, though these were not due to variations in the discovery methods or populations. Signature size directly correlated with test performance, which was generally better for the diagnosis of viral infection and in populations >12-years. Disclosures Ephraim L. Tsalik, MD, MHS, PhD, Predigen (Shareholder, Other Financial or Material Support, Founder)
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Gajdzis, Malgorzata, Stamatios Theocharis, Pawel Gajdzis, Nathalie Cassoux, Sophie Gardrat, Piotr Donizy, Jerzy Klijanienko, and Radoslaw Kaczmarek. "Ephrin Receptors (Eph): EphA1, EphA5, and EphA7 Expression in Uveal Melanoma—Associations with Clinical Parameters and Patient Survival." Life 10, no. 10 (September 30, 2020): 225. http://dx.doi.org/10.3390/life10100225.
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Uveal melanoma is the most common primary intraocular malignancy in adults. The development of distant metastases is associated with a poor prognosis. Ephrine receptors (Eph) are the largest subpopulation of tyrosine kinase receptors. They play an important role in processes related to the formation and progression of cancer. The aim of the study was to evaluate the expression of ephrin receptors EphA1, EphA5, and EphA7 in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. The study included 94 previously untreated patients who underwent enucleation due to uveal melanoma. High expression of EphA1 was positively correlated with a smaller tumor size, less frequent extra-scleral extension, lower mitotic activity, and more frequent vitreous hemorrhage. High expression of EphA5 was associated with less frequent chromosome 3 loss, absence of distant metastases, and more frequent vitreous hemorrhage. High expression of EphA7 was associated with a more frequent primary tumor location in the posterior pole. High EphA5 expression was associated with longer overall survival time. The above findings indicate that high expression of EphA1 and EphA5 can be considered a beneficial prognostic factor in uveal melanoma.
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Kazmyrchuk, Mariia. "ORTHODOX RELIGIOUS TRADITIONS AND HISTORY OF ORTHODOX PILGRIMAGE IN UKRAINE." Journal of Ukrainian History, no. 39 (2019): 72–80. http://dx.doi.org/10.17721/2522-4611.2019.39.10.
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Ukraine has very old Orthodox religious traditions, as well as a long and stormy history of Orthodox pilgrimage. Just like in Spain and Italy, where pilgrimage routes in Santiago de Compostela and Via Francigena are popular today, Ukraine should popularize its own pilgrimage history. Numerous ancient holy places and shrines of Russia, Cossacks period, the Ukrainian lands under the Russian Empire, the Soviet period are waiting for their pilgrims today. Despite the growing interest in religious travel, there is no analysis of Orthodox religious traditions and the history of Orthodox pilgrimage in Ukraine in historiography. Only certain issues of the problem are covered, mainly on the history of religion. Religious journeys has a long tradition. This is not a new phenomenon. Orthodox religious traditions in Ukraine are very old and are associated with the development of the main religion – Orthodoxy. The pilgrimage has been rapidly intensified and has received a legal framework since the days of Kievan Rus and until the present days. Many prominent pilgrims are known in the history of Ukraine. Among of them: the Kiev Grand Duchess Olga the Monk Anthony of Caves, Varlaam Pechersky, Saint Ephraim of the Caves, bishop of Pereyaslav, Vasyl Hryhorovych-Barskyi and others.Since ancient times, Ukrainians can be proud of their immemorial shrines, which attracted many pilgrims. Among them: the saints canonized in Kievan Rus’, the Kiev-Pechersky Monastery and many others. The tradition of Orthodox pilgrimage has become an integral part of the life of the Ukrainian people, despite the numerous obstacles that have arisen in the historical development of Ukraine. The full history of the Orthodox pilgrimage can not be analyzed in one article. There are many more questions that need to be discussed. It is necessary to pay attention to other religions and their traditions of pilgrimage in the history of Ukraine, as they developed in close cooperation with Orthodoxy in the territory of Ukraine.
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Baldyga, Natalya. "Corporeal Eloquence and Sensate Cognition: G. E. Lessing, Acting Theory, and Properly Feeling Bodies in Eighteenth-Century Germany." Theatre Survey 58, no. 2 (April 19, 2017): 162–85. http://dx.doi.org/10.1017/s0040557417000059.
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Most know Gotthold Ephraim Lessing (1729–81) for his dramatic theory, specifically that which is found in his periodical the Hamburg Dramaturgy (1767–69), a collection of 101 essays that has since earned Lessing the moniker of “the first dramaturg.” Many are also familiar with Lessing's major plays, Miss Sara Sampson (1755), Minna von Barnhelm (1767), Emilia Galotti (1772), and Nathan the Wise (1779). Fewer, however, may be familiar with his acting theory and his long association with actors, an association that began in his college years and which so disturbed Lessing's father that the respectable pastor lured the wayward student home by falsely claiming that Lessing's mother was ill. During his time as a university student in Leipzig, Lessing translated plays for the troupe of Karoline Neuber (1697–1760) and socialized with the company's actors; over time he would continue to accrue significant firsthand knowledge of actors and the art of acting, not only through his frequent theatregoing but also through the coaching of his own plays. Lessing's familiarity with actors and acting informs both his performance and dramatic theory, including that which one finds in the Hamburg Dramaturgy; in Anglophone studies of Lessing's journal, however, one infrequently sees Lessing's dramatic theory placed in conversation with his acting theory, reception theory, or performance reviews. Due to the short and contentious life of the Hamburg National Theatre, the experimental theatre project to which the Hamburg Dramaturgy was ostensibly attached, historical narratives more often focus on Lessing's strained relations with the actors of the Hamburg acting company. If one views Lessing's writing about performance solely in terms of a frustrated critic's attempts to rein in “unruly” actors, however, one loses sight of how Lessing's acting theory supports his wider ideas about the form and function of theatre and about how the Hamburg Dramaturgy and the Hamburg theatre experiment might function as a force for social change.
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Slape, Christopher I. "EphA3 Is Expressed on Leukemia Stem Cells, and Eph/Ephrin Signalling Features in the Remodelling of the Leukemia Stem Cell Niche." Blood 124, no. 21 (December 6, 2014): 4783. http://dx.doi.org/10.1182/blood.v124.21.4783.4783.
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Abstract EphA3 is a member of the Eph receptor tyrosine kinase family, the largest such family in the human genome. The bi-directional signalling of Eph receptors and their ligands (the ephrins) is responsible for correct migration and positioning of cells during development, as well as adult processes such as angiogenesis and neurogenesis. EphA3 was first discovered as a receptor expressed on the surface of LK63, a B-cell leukemia cell line. It is not expressed on normal human hematopoietic cells, but expression has been noted on the cell surface of leukemic blasts from a high percentage of patients with hematopoietic neoplasia of all lineages. It is particularly commonly expressed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), where it is present in approximately 50% of patients. A therapeutic antibody against EphA3 has been developed and is in Phase II clinical trials for MDS and AML. Consistent with data from human MDS patients, the NUP98-HOXD13 (NHD13) mouse model of MDS spontaneously expresses EphA3 on a percentage of cells from all populations throughout the hematopoietic compartment. The proportion of positive cells varies from mouse to mouse, but the proportion positively correlates with disease severity, indicating a possible causative relationship. Studies crossing the NHD13 transgene onto an EphA3 knockout background are ongoing and will definitively answer this question. Recent studies have demonstrated the alteration (or “remodelling”) of the hematopoietic stem cell (HSC) micro-environment (or “niche”) by malignant hematopoietic cells, and the role that this plays in maintaining the leukemia stem cell (LSC) population. This self-reinforcing niche remodelling is critical to the maintenance of hematopoietic disease, particularly during a course of chemotherapy. These niche changes have also been shown to be sufficient to drive malignancy, and are therefore an attractive target for the design of disruptive therapeutics. EphA3 and other Eph/ephrin family members are expressed on normal mesenchymal stem/stromal cells (MSCs) and other stromal component cells of the HSC niche. EfnA5 (EphrinA5) is the high-affinity ligand for EphA3, and we observed an increased expression of EfnA5 on stromal cells in the NHD13 mice, indicating that the EphA3-EfnA5 interaction in these mice may facilitate LSC maintenance in the LSC niche. More broadly, it appears that Eph/Ephrin signalling may be a component of the remodelling of the niche to favour LSCs over normal HSCs. Possible indirect means by which this remodelling may occur include production of the cytokines CCL3 (decreased in NHD13 mice) or CXCL12 (variably decreased in NHD13 mice, and its receptor CXCR4 is increased on the cell surface of NHD13 HSCs). Imaging studies confirm preferential homing of EphA3-positive LSCs to niche locations, including co-localisation with CXCL12. It is therefore likely that the remodelled stem cell niche maintains stemness and leukemogenicity of the LSCs via interaction of the Eph/ephrin family members abnormally expressed on the LSCs and stromal cells, respectively. Disclosures No relevant conflicts of interest to declare.
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Du, Wei, Lvzhen Huang, Xin Tang, Jiarui Li, and Xiaoxin Li. "Ephrin-A5 Is Involved in Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy." BioMed Research International 2020 (October 10, 2020): 1–10. http://dx.doi.org/10.1155/2020/7161027.
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Retinal neovascularization (RNV) is an important pathological feature of vitreoretinopathy that can lead to severe vision loss. The purpose of this study was to identify the role of ephrin-A5 (Efna5) in RNV and to explore its mechanism. The expression pattern and biological significance of Efna5 were investigated in a mouse model of oxygen-induced retinopathy (OIR). The expression of Efna5 and downstream signaling pathway members was determined by RT-PCR, immunofluorescence, immunohistochemistry, and western blot analyses. shRNA was used to knockdown Efna5 in the retina of the OIR mouse model. Retinal flat mounts were performed to evaluate the impact of Efna5 silencing on the RNV process. We found that the Efna5 was greatly upregulated in the retina of OIR mice. Elevated Efna5 mainly colocalized with the retinal vessels and endothelial cells. We then showed that knockdown of Efna5 in OIR mouse retinas using lentivirus-mediated shRNA markedly decreased the expression of Efna5 and reduced the retinal neovascularization and avascular retina area. We further showed hypoxia stimulation dramatically increased both total and phosphorylation levels of ERK1/2 and the phosphorylation levels of Akt in OIR mice. More importantly, knockdown of Efna5 could inhibit the p-Akt and p-ERK signaling pathways. Our results suggested that Efna5 may regulate the RNV. This study suggests that Efna5 was significantly upregulated in the retina of OIR mice and closely involved in the pathological retinal angiogenesis.
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Underhill, Karen. "Bruno Schulz, E.M. Lilien and the Archaeology of Polish Jewish Modernism." Ruch Literacki 57, no. 6 (December 1, 2016): 655–80. http://dx.doi.org/10.1515/ruch-2017-0093.
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Summary This paper discusses Bruno Schulz’s recently discovered 1937 essay on the Drohobycz-born graphic artist Ephraim Moses Lilien, best known for his iconic Zionist-themed black-and-white graphics in the Secessionist style. Schulz describes in his essay the seminal influence that the encounter with Lilien’s art had on him at the age of thirteen: “There took place in me at that time a kind of internal shift. Lilien effected a powerful fertilization of my internal world, that revealed itself in an early, youthful and clumsy creativity.” As the first known document in which Bruno Schulz openly presents his views on the contemporary political, cultural and spiritual concerns of his Jewish generation in Poland and Eastern Europe, the Lilien article enables a more direct reading of Schulz’s own aesthetic project as an inheritor of the ethos of the fin-de-siècle Jewish Renaissance Movement, and as a contribution to the development of Jewish literary modernisms in Central Europe. The disappearance of the Lilien article from readers′ consciousness for over three quarters of a century - since World War II - and its reemergence today not only represents an exciting next episode in the quest, initially undertaken by Jerzy Ficowski, to recover Schulz’s existing oeuvre. It also offers a fitting metaphor for a larger phenomenon taking place today within the fields of both Polish and Jewish studies, that I have called here the archaeology of Polish Jewish modernism. The discussion proposes an additional paradigm of “national indifference”, adapted from the work of historian Tara Zahra, as a tool for thinking Schulz’s texts as a simultaneously Jewish and Universal writing that resists attachment to political nationalisms, and to the project of nation-state building. More directly than he had done in the Sanatorium stories, Schulz reveals in the Lilien essay a strong commitment to the Jewish/Universal project of Cultural Zionism, inspired by Ahad Ha’am and promoted by prominent Jewish thinkers and spokespeople of the Lemberg/Lwów region, and a deep reticence about and finally rejection of political Zionism. Thus Schulz’s Lilien essay points to, and becomes an apologia for, his own decision to seek a continuation of the religious, mythic and messianic Jewish tradition not in the promise of return to Palestine, but through the medium of the living book, which he calls here “that creation born of the longing of golus”.
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Anderton, Meg, Emma van der Meulen, Melissa J. Blumenthal, and Georgia Schäfer. "The Role of the Eph Receptor Family in Tumorigenesis." Cancers 13, no. 2 (January 8, 2021): 206. http://dx.doi.org/10.3390/cancers13020206.
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The Eph receptor tyrosine kinase family, activated by binding to their cognate ephrin ligands, are important components of signalling pathways involved in animal development. More recently, they have received significant interest due to their involvement in oncogenesis. In most cases, their expression is altered, affecting the likes of cell proliferation and migration. Depending on the context, Eph receptors have the potential to act as both tumour promoters and suppressors in a number of cancers, such as breast cancer, colorectal cancer, lung cancer, prostate cancer, brain cancer and Kaposi’s sarcoma (KS), the latter being intrinsically linked to EphA2 as this is the receptor used for endothelial cell entry by the Kaposi’s sarcoma-associated herpesvirus (KSHV). In addition, EphA2 deregulation is associated with KS, indicating that it has a dual role in this case. Associations between EphA2 sequence variation and KSHV infection/KS progression have been detected, but further work is required to formally establish the links between EphA2 signalling and KS oncogenesis. This review consolidates the available literature of the role of the Eph receptor family, and particularly EphA2, in tumorigenesis, with the aim to develop a better understanding of Eph signalling pathways for potential targeting in novel cancer therapies.