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1

Spawforth, A. J. S. "Families at Roman Sparta and Epidaurus: Some Prosopographical Notes." Annual of the British School at Athens 80 (November 1985): 191–258. http://dx.doi.org/10.1017/s0068245400007589.

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The purpose of this article is to correct and expand our understanding of an interrelated group of socially prominent families from Roman Sparta and Epidaurus. Part I publishes an inscription from Sparta, dating to about 240, which attests new members of the Spartan families of the Claudii and the Pomponii: respectively Claudia Tyrannis, a great-granddaughter of the senator Tib. Claudius Brasidas, and C. Pomponius Aristeas qui et Pericles, her husband. At the same time, a revised account is offered of the Claudii and of a further four Spartan families to which they were related: the Memmii, the Voluseni, the Aelii, and the Pompeii. Part II re-examines the evidence for the Epidaurian family of the Statilii. Apart from the new inscription, more recent work on the epigraphic corpora from Sparta and the Asclepieum, the possibility of reinterpreting the older material, and the need to take hitherto neglected documents into account, together seem to justify a fresh treatment of these families. The resulting study, as well as providing up-to-date family histories, includes many corrections on detailed points of local epigraphy, chronology, and prosopography.
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2

Camargo, Carlos Henrique Ferreira, and Hélio Afonso Ghizoni Teive. "Searching for neurological diseases in the Julio-Claudian dynasty of the Roman Empire." Arquivos de Neuro-Psiquiatria 76, no. 1 (January 2018): 53–57. http://dx.doi.org/10.1590/0004-282x20170174.

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ABSTRACT The gens Julia was one of the oldest families in ancient Rome, whose members reached the highest positions of power. They made history because Julius Caesar, perpetual dictator, great-uncle of the first emperor, Augustus, passed his name on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius and Nero. Descriptions of the diseases of these emperors and some of his family members may indicate diagnoses such as epilepsy, dystonia, dementia, encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and sleep disorders. In the historical context of ancient Rome, the possibility of infectious diseases related to the libertine way of life is quite large. However, there is a possibility that some of these diseases occurred from genetic transmission.
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3

Stavek, Jiri. "Trigonometric Functions at a Crossroads." Applied Physics Research 9, no. 3 (May 31, 2017): 40. http://dx.doi.org/10.5539/apr.v9n3p40.

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In the history of physics trigonometric functions played several times a very critical role at crossroads. This time we are at a crossroads with the interpretation of correlation events of entangled particles. In this approach we propose to describe the experimental data of Alice and Bob using not so known trigonometric functions. Claudius Theorem (based on the trigonometric family of Sagitta and Cosagitta) evalutes the probabilistic occurrence of correlated and anticorrelated events. David Theorem (based on the trigonometric family of Hacoversine) describes the probability of the following identical events and gaps between the following identical events. In this trigonometric concept the Team of Alice, Bob, Claudius and David formulated a camouflage legend for Eve – “spooky action at a distance”. Merlin (with unbounded computational ability) should verify the truth of this statement. Trent (a trusted arbitrator, who acts as a neutral third party) should analyze these data and this trigonometric concept. Victor (a verifier) should make his decision which way we should continue in our future research: either through the Niels Bohr avenue or through the Albert Einstein sidewalk.
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4

Rich, J. W. "Drusus and the spolia opima." Classical Quarterly 49, no. 2 (December 1999): 544–55. http://dx.doi.org/10.1093/cq/49.2.544.

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According to Suetonius, Nero Claudius Drusus, the younger of Augustus' two stepsons, was said to have aspired to win spolia opima, that is, spoils taken from an enemy commander killed in battle. The aim of this paper is to consider what substance there may be in this claim and what light it may throw on Augustus’ relationship with the princes of the imperial family.
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5

Retief, Francois P., and Louise C. Cilliers. "Claudius, the handicapped Caesar (41-54 A.D.)." Suid-Afrikaanse Tydskrif vir Natuurwetenskap en Tegnologie 29, no. 2 (January 13, 2010): 39–47. http://dx.doi.org/10.4102/satnt.v29i2.8.

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Claudius, fourth Caesar of the Roman Empire, proved himself an able administrator, but physically and emotionally handicapped from birth. His parents, members of the imperial family, considered him mentally deficient and he was isolated from the general public and put in the care of an uneducated tutor who firmly disciplined the youngster. The historians report that he had a weak constitution caused by frequent illness, and when he appeared in public he was muffled in a protective cloak. To avoid possible embarrassment the ceremony of the toga virilis, at approximately 14 years of age, was a secretive affair held at midnight and devoid of the traditional procession. His grandfather, Augustus Caesar, had some sympathy for the young lad, but did not consider him capable of managing any position of public office appropriate for his age and position. This would also be the approach of the succeeding emperor, Tiberius. Claudius spent the fi rst four decades of his life in relative idleness, isolated from his family and upper class Romans, consorting with the lower classes, playing dice and revelling in excessive eating and drinking. He did, however, also involve himself seriously in a study of the sciences, literature, Greek and history – his role model in the latter being Livy. During his life time he published quite extensively, including dramas, an autobiography, a work in defence of Cicero, histories of Rome, Carthage and Etruria, and a book on dice. His first public office (besides an augurship under Augustus) was at the age of 47 years when the new emperor, Gaius (Caligula) made him a consul for two months. The Knights and a section of Senate now warmed towards Claudius, but Gaius and the majority of aristocratic Romans still despised him as dull-witted. After the assassination of Gaius, the Praetorian Guard in an extraordinary step, proclaimed a protesting Claudius (50 years old) as emperor, and convinced an astounded Senate to endorse this action. In spite of having had no significant preparation for the task, Claudius proved a most sensible and effective manager, improving the effectivity of Senate, putting the legal system on a sound footing, enlarging the borders of the Empire (including the conquest of England), extending citizenship to some of the provincials, foreigners and freedmen. Sensible building programs were initiated as well as the upgrading of roads and communication systems and the ensuring of an efficient food supply to Rome. Grand and regular gladiatorial games and other forms of public entertainment endeared him to the people. But he was also periodically responsible for mismanagement, corruption and brutality; much of this was subsequently blamed on the inordinate influence of people near him, and his trusted freedmen and wives in particular. The last two of his six wives (Messalina and Agrippina) were particularly guilty, and his death of poisoning at the age of 64 years (54 A.D.) was engineered by Agrippina. Through his life Claudius showed evidence of significant physical and psychological/emotional impediments. By many he was considered mentally deficient, but his impressive record as student of literature and history, and his administrative skill as emperor are ample evidence of his intellectual abilities. Physical abnormalities included an ungainly gait due to weakness of his right leg and probably arm. He had a tremor of the limbs and involuntary shaking of the head. He spoke indistinctly in a coarse, stuttering way, his mouth often drooled, his nose tended to run, and he had an uncouth laugh. He was emotionally labile, and when upset the above symptoms worsened and he became prone to irresponsible actions. We suggest that this symptom complex fits in with the diagnosis of cerebral palsy, and probably its extrapyramidal variant, although one-sided weakness suggests an additional component of hemiplegic paresis.
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6

LÓPEZ GÓMEZ, Helena. "Las últimas emperatrices julio-claudias: estudio de sus imágenes públicas." STUDIA ANTIQUA ET ARCHAEOLOGICA 28, no. 2 (2022): 354–84. http://dx.doi.org/10.47743/saa-2022-28-2-7.

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Despite the importance they had in their time, many of the women of the Roman imperial families share a bad image that continues to this day. The pejorative description, present in the accounts of ancient historians, has made these female characters largely unintelligible and it is practically impossible to reach an objective conclusion about their true role in history. The present article aims to offer an analysis of the images of the last empresses of the Julio-Claudian dynasty. We will focus on the wives of Caligula, Claudius and Nero by analyzing the literary evidence we possess about them in order to try to reach a conclusion free of the powerful misogynistic impressions about them that have been provided in the past. To this end, we have taken into account not only the life trajectories of the empresses, but also those of the main men in their lives, the emperors, to try to glimpse if their family relationships could have had some kind of impact on the way women were portrayed by the sources.
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7

Rubel Parvez, Md, and Md Mehedi Hassan. "William Shakespeare’s Hamlet and Eliot’s The Love Song of J. Alfred Prufrock: Procrastinator of ‘To Be or Not To Be’." Shanlax International Journal of English 11, no. 1 (December 1, 2022): 13–22. http://dx.doi.org/10.34293/english.v11i1.5279.

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This paper will explore the procrastination of the protagonists of William Shakespeare’s “Hamlet” and T.S Eliot’s “The Love Song of J. Alfred Prufrock”. Both protagonists of Hamlet &The Love Song Of J. Alfred Prufrock were in procrastination, The protagonist of “Hamlet” play is Hamlet who was informed supernaturally that his uncle Claudius killed his father and he was planning to take the revenge but was procrastinating to kill King Claudius. This thesis paper also demonstrates the conspiracy of the palace of Hamlet’s royal family. This play had a tragedy in the end. On the other hand, the protagonist of “The Love Song of J. Alfred Prufrock” is Prufrock who fell in love with a young lady but he was also procrastinating to expose his feeling to that lady as he was old also a bald spot on his head. That is why he was afraid to express his feeling to that woman if he gets rejected. This paper also contains critical analysis; feminist elements, compare and contrasts of these two texts.
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8

Mancini, Willian, and Fábio Faversani. "Laudationes et Iniuriae: debate sobre um aspecto da construção da imagem do governante em Sêneca." Nuntius Antiquus 6 (December 31, 2010): 28. http://dx.doi.org/10.17851/1983-3636.6.0.28-40.

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<p class="MsoNormal" style="margin: 0cm 0cm 0pt; text-align: justify; line-height: normal; mso-layout-grid-align: none;"><span style="font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA; mso-ansi-language: EN-US;" lang="EN-US">ABSTRACT: The article aims to understand specific aspects of the </span><span style="font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA; mso-ansi-language: EN-US;" lang="EN-US">relations between emperors and aristocrats, especially regarding the </span><span style="font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA; mso-ansi-language: EN-US;" lang="EN-US">role of clemency in the making of these relationships. The authors </span><span style="font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA; mso-ansi-language: EN-US;" lang="EN-US">analyse this issue in the context of the principates of Claudius and </span><span style="font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA; mso-ansi-language: EN-US;" lang="EN-US">Nero in three works of Seneca (</span><em><span style="font-family: 'Aldine401BT-ItalicA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-ItalicA; mso-ansi-language: EN-US;" lang="EN-US">De consolatione ad Polybium, </span></em><em><span style="font-family: 'Aldine401BT-ItalicA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-ItalicA;">Apolococintosis, De clementia</span></em><span style="font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA;">).</span></p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; text-align: justify; line-height: normal; mso-layout-grid-align: none;"> </p><p class="MsoNormal" style="margin: 0cm 0cm 0pt; text-align: justify; line-height: normal; mso-layout-grid-align: none;"><span style="font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA; mso-ansi-language: EN-US;" lang="EN-US">KEYWORDS: Seneca; Claudius; Nero; clemency; Roman empire; </span><span style="line-height: 115%; font-family: 'Aldine401BT-RomanA','serif'; font-size: 10pt; mso-bidi-font-family: Aldine401BT-RomanA; mso-ansi-language: EN-US;" lang="EN-US">aristocracy.</span></p>
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9

Flower, Harriet I. "The Tradition of the Spolia Opima: M. Claudius Marcellus and Augustus." Classical Antiquity 19, no. 1 (April 1, 2000): 34–64. http://dx.doi.org/10.2307/25011111.

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This paper aims to reexamine how traditions about the spolia opima developed with special emphasis on two crucial phases of their evolution, the time of Marcus Claudius Marcellus' dedication in 222 BC and the early years of Augustus' principate, following the restoration of the temple of Jupiter Feretrius on the Capitol. In particular, I will argue that Marcellus invented the spolia opima, that his feat shaped the entire tradition about such dedications, and that this tradition was later enhanced and "reinvented" by Augustus, probably following upon renewed interest under Julius Caesar. Through an evaluation of the surviving evidence about the three canonical dedicators (Romulus, A. Cornelius Cossus, and Marcellus) the possibility is explored that the spolia opima, rather than being an archaic ritual dating back to the regal period, represent a tradition invented (and reinvented) by specific individuals at certain well-defined moments in Roman history. Augustus himself, beginning while he was still a child, was influenced by traditions about the career and achievements of M. Claudius Marcellus. Augustus' interest in Marcellus helps to explain his special focus on the spolia opima as a significant and hallowed Roman tradition. Consequently, in the late first century B.C., spolia opima were associated both with old-fashioned "republican" aspirations and also with the iconography and self-definition of the new ruling family. In this context other leading Romans of the age considered dedicating such spolia, notably M. Licinius Crassus, grandson of the triumvir, and the elder Drusus, brother of Tiberius. In addition, Virgil included the spolia opima as a recurring theme in the second half of the Aeneid. The poem reaches its climax when Aeneas kills his rival Italian leader Turnus in a duel which would have entitled him to dedicate spolia opima.
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10

Sumi, Geoffrey S. "Nero and Britannicus in the pompa circensis: The Circus Procession as Dynastic Ceremony in the Court of Claudius." Klio 102, no. 2 (November 26, 2020): 617–64. http://dx.doi.org/10.1515/klio-2019-1008.

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SummaryAs part of the events marking Nero’s assumption of the toga virilis in 51 CE, he along with Britannicus led the circus procession (pompa circensis) in advance of games in the Circus Maximus. The aim of this paper is to reconstruct this pompa circensis, both in its processional elements and route through the city. The presence of potential successors along with images of the deified and honored dead of the imperial family shows how this ceremony evolved and expanded in the Principate to become a dynastic ceremony. The route of the newly modified pompa circensis, marked by monuments built by or dedicated to members of the imperial family, also had become increasingly dynastic. An essential element of the pompa circensis was the participation of the senate and equestrian order as well as the urban plebs, an act of performed consensus fully realized when the procession ended in the Circus Maximus. This circus procession, as reconstructed here, has further implications for the larger question of the imperial succession under Claudius.
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11

Dircksen, M. "Tacitus se uitbeelding van Agrippina Minor." Literator 20, no. 1 (April 26, 1999): 119–40. http://dx.doi.org/10.4102/lit.v20i1.455.

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Tacitus’ portrayal of Agrippina MinorAncient historiography has more in common with the historical novel than with modem historiography. The Annals of Tacitus should be seen as an artistic, narrative text which demands active participation by the reader in the process of interpretation. A narratological analysis of Tacitus' description of the life and death of Agrippina, mother of the emperor Nero, reveals a serious ethical reflection on the atrocities committed by the imperial family. Agrippina is characterised as an exceptionally strongwilled woman who had an immense influence on the Roman Empire while she was the wife of the emperor Claudius and mother of his successor, Nero. On the other hand, her typically female character traits are accentuated from which the reader has to infer that it was precisely the fact that she was a woman which made her authoritative position intolerable.
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Pająkowska‑Bouallegui, Anna. "Eusebia, Elena e l’imperatore romano Giuliano l’Apostata." Studia Historica Gedanensia 14 (December 21, 2023): 34–49. http://dx.doi.org/10.4467/23916001hg.23.004.18805.

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Eusebia, Helena, and the Emperor Julian the Apostate The Emperor Flavius Claudius Julianus, known to posterity as the Apostate, is an extraordinary figure in the history of the Roman Empire. And although he was Caesar for only five years (355–360), and Emperor for less than two years (361–363), he became famous as a wise and just ruler, a good commander, a brave soldier, and an efficient administrator. He was also a great lover of ancient culture and a talented writer. He left behind many official letters and literary works. His writings provide valuable information both about the Roman state in the fourth century and about himself and his family. He was also one of the best educated Roman rulers, well versed in Greek and Latin literature, philosophy, and history. Two exceptional women played a particularly important role in the life of Julian the Apostate: his wife Helena and Eusebia, the wife of Emperor Constantius II, his cousin. Both were endowed with many good qualities, which are mentioned not only by Julian the Apostate himself in his writings, but also by other ancient authors, including the historians Ammianus Marcellinus, Eutropius, Zosimos, the rhetorician Libanius, and historians of the Church Socrates Scholasticus and Hermias Sozomen. Both Eusebia and Helena are very interesting figures. But, while about Eusebia there is a great deal of information in various sources, about Helena there are only brief mentions. Nevertheless, both of these empresses are worth closer attention. In my article, written in Italian, I present a picture of the virtues of Helena and Eusebia, as contained in the writings of the Emperor Julian the Apostate himself, as well as other ancient authors.
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13

Hommes, Margriet van Eikema, and Emilie Froment. "'Een doek van geene beteekenis' De nachtelijke samenzwering van Claudius Civilis in het Schakerbos van Govert Flinck en Jürgen Ovens technisch onderzocht." Oud Holland - Quarterly for Dutch Art History 124, no. 2-3 (2011): 141–70. http://dx.doi.org/10.1163/187501711798264193.

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AbstractBecause of its extreme darkness, The nocturnal conspiracy of Claudius Civilis by Govert Flinck (16151660) and Jürgen Ovens (1623-1678) holds an isolated position within the decoration program with the Batavian revolt in the galleries of Amsterdam's former Town Hall. Of course the canvas depicts a nocturnal scene with light from only the fire and the moon, but in this painting the darkness dominates virtually everything. The rough, rather sketchy execution, whereby large parts of the canvas are left unpainted is also peculiar. Because of this appearance, some art historians have thought it an outrage that this 'painting with no value' should have replaced Rembrandt's masterpiece with the same subject. However, Flinck and Ovens – both pupils of Rembrandt – were painters of the first rank and there is nothing in the oeuvre of either master that is reminiscent of this rather unbalanced gallery painting. The question is therefore: to what does this piece owe its inaccessible appearance? This, of course, also relates to the manufacture-process and function of the canvas. Archival records and historical texts contain many relevant details on the paintings' genesis but have so far mainly given rise to confusion. The technical investigation, carried out during the 2007-2009 conservation campaign of the Batavian series, now demonstrates that the painting's extreme appearance traces back to both its peculiar genesis that is wholly different from that of the other gallery paintings and to its unfortunate conservation history. It was found that the piece was never intended to be a permanent decoration: the canvas is the one surviving remnant of a series of temporary festive decorations that Flinck had produced in the summer of 1659 in honour of the visit of Amalia van Solms and the Orange family to the Town Hall. Because of the painting's temporary nature, Flinck has modified his usual working procedures. Rather than taking sturdy, durable linen he chose a thin, fine canvas; and instead of applying to his canvas a reliable ground layer he painted on it directly. Flinck elected for fast-drying water-based paint (gum arabic) and worked with an extremely modest palette: he coloured his canvas with a thinned brown paint and on this base modelled his figures with only black contours and beige highlights. The original idea was that Flinck's temporary works would be replaced by permanent decorations from his hand, consisting of twelve paintings. But because of his untimely death in 1660, the commission was divided between Jordaens, Lievens and Rembrandt. Rembrandt's painting, to replace Flinck's work with the nocturnal conspiracy, was almost immediately removed, probably in the summer of 1662. When the Bishop of Cologne visited Amsterdam shortly afterwards, this empty space needed to be filled in a hurry and Flinck's old decoration was retrieved from storage. Jürgen Ovens was commissioned to 'work up [= finish] a sketch by Govert Flinck into a complete ordonnance'. Once again we seem to be dealing with a temporary decoration, for the modest sum of 48 guilders was all that Ovens was paid. The painter only did what was absolutely essential – after applying an isolating glue layer, he just added a few lines and touches of colour in oil paint here and there, all just enough to clarify Flinck's image, which was by then probably somewhat battered. The planned replacement of the Flinck/Ovens' canvas by a permanent painting never materialized; oppressed by a shortage of finance, the city governors decided in 1664 to postpone for five years all commissions or purchases of paintings for the Town Hall. This is why Flinck's canvas, dressed up a little by Ovens, has remained in the gallery to this day. Obviously, this painting, produced for a strictly temporary purpose, was never intended to have such a long 'life'. An ungrounded canvas painted with water-based paint is highly fragile and discolours as the fabric ages. But quite apart from this discolouration the dark and empty impression that the painting conveys today, is mainly due to earlier treatments by those who had no understanding of its unique characteristics. As archival records show, in the eighteenth century the canvas was lined twice using glue; a treatment that involved the use of considerable amounts of water. In addition, over the centuries the painting has been varnished several times and in the 1960's it was given a wax-resin lining. It is because these treatments, each of which is totally unsuitable for a water-based canvas, that the painting has acquired its present patchy and dark orange-brown appearance. Since nothing can be done to remedy the consequences of the lack of understanding of previous centuries - one cannot return to the painting's original appearance - the aim of the recent restoration was to achieve a balance between the aspects of the painting that stem from its unusual manufacture-process and the qualities that are the consequence of its conservation history.
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Agócs, Nándor. "Savariából jöttek." Belvedere Meridionale 31, no. 1 (2019): 100–128. http://dx.doi.org/10.14232/belv.2019.1.7.

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Around one hundred inscriptions were recovered outside Pannonia mentioning people originating from Savaria. It is quite an abundant source group considsering there are currently 247 inscriptions that were recovered on Savarian territory. The presence of Savarians is attested earliest in the twin legions, the legio I Adiutrix and the legio II Adiutrix. These two legions recruited mainly from cities founded by Emperor Claudius and were transferred in Flavian times to Germania and Britannia respectively. Soldiers who were subsequently transferred to the cohors XIII urbana (and plausibly to the cohors X urbana) as a grant, likely merited their awards in these provinces. After the 1st century AD no Pannonian recruits are known in the cohortes urbanae. In the Flavian era, possibly from AD 71 onwards, Savarian citizens enlisted to the legio XV Apollinaris stationed at that time in Carnuntum. The unit was led east in AD 113 with the last group of Savarian conscripts. At the end of the 1st century AD several Savarians lived in Rome, who served in the newly established ranks of the equites singulares Augusti. By Emperor Hadrian’s reign the latest several Savarians are attested amongst the officers of the cohortes praetoriae. From the second half of the 2nd century AD we find a handful of Savarians amongst legionary centurions and equestrian military officers as well. Part of the Savarian recruits certainly enlisted in the legiones Adiutrices during the course of the 2nd century AD. It was most likely a result of the campaigns of these legions that Savarians are attested in Africa and from the ascension of Emperor Septimius Severus, in Rome. In the Severus era numerous Savarians are attested in the ranks of the cohortes praetoriae and the legio II Parthica, yet their numbers decline amongst the equites singulares. The Savarians who are the subject of this study are mostly descendants of the veterans who established Savaria, themselves being soldiers as well. The majority of civilians leaving Pannonia where following their recruited family member.
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Salmin, Anton K. "HISTORICAL AND ETHNOGRAPHIC IDENTITY OF THE CHUVASH." Vestnik Chuvashskogo universiteta, no. 4 (December 25, 2020): 139–46. http://dx.doi.org/10.47026/1810-1909-2020-4-139-146.

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The article deals with some issues of the ethnicity’s self-preservation in the space-time coordinates of history. Attention is paid to those significant milestones when an ethnic group and its leaders had to make fateful decisions. The author assumes that the concepts of «historical identity» and «ethnic identity» are closely related to the terms «ethnicity» and «ethnic self-awareness». According to the author, ethnic identity implies the connection of one’s «Ego» and «WE» with one’s history, traditions and language. The article provides a brief analysis to clarify the connection between the history of an ethnic group and its identity. It is emphasized that a person is prone to know the history of his family, birthplace, his nationality, and he is interested in the features of the ethnic group of which he considers himself a part. He wants to get an answer to the questions: who were the historical neighbors, what transformations took place over the past 20 centuries in the history of his ancestors, who they were originally, whether all these components can be reconstructed. For example, the article points out incompatibility of the ethnonym «Bulgar» with the ethnonym «the Sabirs – the Sapirs – the Savirs – the Suvars – the Suvash – the Chuvash» from the etymological point of view. In addition, neither the Bulgars nor the Savirs ever lived in the Asian part of Eurasia. The Sabirs were first mentioned and recorded by Claudius Ptolemy in the Caucasus in the second century. At the very least, we have no facts or other historical and philological grounds to identify the Chuvash as the historical heirs of the Bulgars. The article highly evaluates the historical role and the «female power» of the Savir ruler Boa (rix), as well as calculates the number of the Savir tribe as of the VI century. The Savirs were extremely competent in technical terms when besieging and destroying fortresses. Their ramming tools were popular with both the Persians and the Byzantines. The novelty of the research consists in a concise but systematic analysis of the historical identity of the Chuvash people from ancient times to the present day.
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Angelow, Susanne, Robert Ahlstrom, and Alan S. L. Yu. "Biology of claudins." American Journal of Physiology-Renal Physiology 295, no. 4 (October 2008): F867—F876. http://dx.doi.org/10.1152/ajprenal.90264.2008.

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Claudins are a family of tight junction membrane proteins that regulate paracellular permeability of epithelia, likely by forming the lining of the paracellular pore. Claudins are expressed throughout the renal tubule, and mutations in two claudin genes are now known to cause familial hypercalciuric hypomagnesemia with nephrocalcinosis. In this review, we discuss recent advances in our understanding of the physiological role of various claudins in normal kidney function, and in understanding the fundamental biology of claudins, including the molecular basis for selectivity of permeation, claudin interactions in tight junction formation, and regulation of claudins by protein kinases and other intracellular signals.
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Singh, Amar B., Ashok Sharma, and Punita Dhawan. "Claudin Family of Proteins and Cancer: An Overview." Journal of Oncology 2010 (2010): 1–11. http://dx.doi.org/10.1155/2010/541957.

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Tight junctions are the apical cell-cell adhesion that regulate paracellular permeability and are critical for epithelial cell polarity. Molecular architecture of tight junction has been studied extensively, which has confirmed that claudin family of proteins is integral component of tight junction. Loss of cell-cell adhesion is central to the cellular transformation and acquisition of metastatic potential; however, the role of claudin family of proteins play in a series of pathophysiological events, including human carcinoma development, is only now beginning to be understood. Several claudin mouse knockout models have been generated and the diversity of phenotypes observed clearly demonstrates their important roles in the maintenance of tissue integrity in various organs and suggest that claudins also participate in cellular contexts other than tight junctions. The mechanisms of claudin regulation and their exact roles in normal physiology and disease are being elucidated, but much work remains to be done. In this review, we have discussed the conceptual framework concerning claudins and their potential implication in cancer. We predict that next several years will likely witness a boom in our understanding of the potential role of claudins in the regulation of tumorigenesis, which may, in turn, provide new approaches for the targeted therapy.
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Will, Constanze, Michael Fromm, and Dominik Müller. "Claudin Tight Junction Proteins: Novel Aspects in Paracellular Transport." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 28, no. 6 (November 2008): 577–84. http://dx.doi.org/10.1177/089686080802800605.

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Claudins are essential components of the intercellular tight junction and major determinants of paracellular solute fluxes across epithelia and endothelia. Many members of this family display a distinct charge or size specificity, whereas others render the epithelium impermeable to transport. Due to intercellular localization, claudin-mediated transport processes are passive and driven by an electrochemical gradient. In epithelial tissues, claudins exhibit a temporal–spatial expression pattern corresponding with regional and local solute transport profiles. Whereas paracellular transport mechanisms in organs such as intestine and kidney have been extensively investigated, little is known about the molecular mechanisms determining solute transport in the peritoneum, and thus the determinants of peritoneal dialysis. Given the ubiquitous expression of claudins in endothelia and epithelia, it is predictable that claudins also contribute to pore formation and determination in the peritoneum, and that they are involved in solute flux. Therefore, we review the basic characteristics of claudin family members and their function as exemplified in renal tubular transport and give an outlook to what extent claudin family members might be of importance for solute reabsorption across the peritoneal membrane.
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Cox, Kristin E., Shanglei Liu, Robert M. Hoffman, Surinder K. Batra, Punita Dhawan, and Michael Bouvet. "The Expression of the Claudin Family of Proteins in Colorectal Cancer." Biomolecules 14, no. 3 (February 24, 2024): 272. http://dx.doi.org/10.3390/biom14030272.

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Claudins (CLDN1–CLDN24) are a family of tight junction proteins whose dysregulation has been implicated in tumorigeneses of many cancer types. In colorectal cancer (CRC), CLDN1, CLDN2, CLDN4, and CLDN18 have been shown to either be upregulated or aberrantly expressed. In the normal colon, CLDN1 and CLDN3–7 are expressed. Although a few claudins, such as CLDN6 and CLDN7, are expressed in CRC their levels are reduced compared to the normal colon. The present review outlines the expression profiles of claudin proteins in CRC and those that are potential biomarkers for prognostication.
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Muto, Shigeaki. "Physiological roles of claudins in kidney tubule paracellular transport." American Journal of Physiology-Renal Physiology 312, no. 1 (January 1, 2017): F9—F24. http://dx.doi.org/10.1152/ajprenal.00204.2016.

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The paracellular pathways in renal tubular epithelia such as the proximal tubules, which reabsorb the largest fraction of filtered solutes and water and are leaky epithelia, are important routes for transepithelial transport of solutes and water. Movement occurs passively via an extracellular route through the tight junction between cells. The characteristics of paracellular transport vary among different nephron segments with leaky or tighter epithelia. Claudins expressed at tight junctions form pores and barriers for paracellular transport. Claudins are from a multigene family, comprising at least 27 members in mammals. Multiple claudins are expressed at tight junctions of individual nephron segments in a nephron segment-specific manner. Over the last decade, there have been advances in our understanding of the structure and functions of claudins. This paper is a review of our current knowledge of claudins, with special emphasis on their physiological roles in proximal tubule paracellular solute and water transport.
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Van Itallie, Christina M., and James Melvin Anderson. "The Molecular Physiology of Tight Junction Pores." Physiology 19, no. 6 (December 2004): 331–38. http://dx.doi.org/10.1152/physiol.00027.2004.

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Tight junctions form selective barriers that regulate paracellular transport across epithelia. A large family of tetraspanning cell-cell adhesion proteins called claudins create the barrier and regulate electrical resistance, size, and ionic charge selectivity. Study of inherited human claudin diseases and the outcome of the genetic manupulation of claudins in mice, Drosophila, and Caenorhabditis elegans are furthering our understanding of paracellular physiology.
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22

Hana, Caroline, Nyein Nyein Thaw Dar, Michael Galo Venegas, and Michel Vulfovich. "Claudins in Cancer: A Current and Future Therapeutic Target." International Journal of Molecular Sciences 25, no. 9 (April 24, 2024): 4634. http://dx.doi.org/10.3390/ijms25094634.

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Claudins are a family of 27 proteins that have an important role in the formation of tight junctions. They also have an important function in ion exchange, cell mobility, and the epithelial-to-mesenchymal transition, the latter being very important in cancer invasion and metastasis. Therapeutic targeting of claudins has been investigated to improve cancer outcomes. Recent evidence shows improved outcomes when combining monoclonal antibodies against claudin 18.2 with chemotherapy for patients with gastroesophageal junction cancer. Currently, chimeric antigen receptor T-cells targeting claudin 18 are under investigation. In this review, we will discuss the major functions of claudins, their distribution in the normal as well as cancerous tissues, and their effect in cancer metastasis, with a special focus on the therapeutic targeting of claudins to improve cancer outcomes.
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23

Furuse, Mikio, Hiroyuki Sasaki, and Shoichiro Tsukita. "Manner of Interaction of Heterogeneous Claudin Species within and between Tight Junction Strands." Journal of Cell Biology 147, no. 4 (November 15, 1999): 891–903. http://dx.doi.org/10.1083/jcb.147.4.891.

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In tight junctions (TJs), TJ strands are associated laterally with those of adjacent cells to form paired strands to eliminate the extracellular space. Claudin-1 and -2, integral membrane proteins of TJs, reconstitute paired TJ strands when transfected into L fibroblasts. Claudins comprise a multigene family and more than two distinct claudins are coexpressed in single cells, raising the questions of whether heterogeneous claudins form heteromeric TJ strands and whether claudins interact between each of the paired strands in a heterophilic manner. To answer these questions, we cotransfected two of claudin-1, -2, and -3 into L cells, and detected their coconcentration at cell–cell borders as elaborate networks. Immunoreplica EM confirmed that distinct claudins were coincorporated into individual TJ strands. Next, two L transfectants singly expressing claudin-1, -2, or -3 were cocultured and we found that claudin-3 strands laterally associated with claudin-1 and -2 strands to form paired strands, whereas claudin-1 strands did not interact with claudin-2 strands. We concluded that distinct species of claudins can interact within and between TJ strands, except in some combinations. This mode of assembly of claudins could increase the diversity of the structure and functions of TJ strands.
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Tanaka, Hiroo, Yasuko Yamamoto, Hiroka Kashihara, Yuji Yamazaki, Kazutoshi Tani, Yoshinori Fujiyoshi, Katsuhiko Mineta, Kosei Takeuchi, Atsushi Tamura, and Sachiko Tsukita. "Claudin-21 Has a Paracellular Channel Role at Tight Junctions." Molecular and Cellular Biology 36, no. 6 (January 4, 2016): 954–64. http://dx.doi.org/10.1128/mcb.00758-15.

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Claudin protein family members, of which there are at least 27 in humans and mice, polymerize to form tight junctions (TJs) between epithelial cells, in a tissue- and developmental stage-specific manner. Claudins have a paracellular barrier function. In addition, certain claudins function as paracellular channels for small ions and/or solutes by forming selective pores at the TJs, although the specific claudins involved and their functional mechanisms are still in question. Here we show for the first time that claudin-21, which is more highly expressed in the embryonic than the postnatal stages, acts as a paracellular channel for small cations, such as Na+, similar to the typical channel-type claudins claudin-2 and -15. Claudin-21 also allows the paracellular passage of larger solutes. Our findings suggest that claudin-21-based TJs allow the passage of small and larger solutes by both paracellular channel-based and some additional mechanisms.
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25

Ogbu, Chinemerem P., Sourav Roy, and Alex J. Vecchio. "Disruption of Claudin-Made Tight Junction Barriers by Clostridium perfringens Enterotoxin: Insights from Structural Biology." Cells 11, no. 5 (March 5, 2022): 903. http://dx.doi.org/10.3390/cells11050903.

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Claudins are a family of integral membrane proteins that enable epithelial cell/cell interactions by localizing to and driving the formation of tight junctions. Via claudin self-assembly within the membranes of adjoining cells, their extracellular domains interact, forming barriers to the paracellular transport of small molecules and ions. The bacterium Clostridium perfringens causes prevalent gastrointestinal disorders in mammals by employing an enterotoxin (CpE) that targets claudins. CpE binds to claudins at or near tight junctions in the gut and disrupts their barrier function, potentially by disabling their assembly or via cell signaling means—the mechanism(s) remain unclear. CpE ultimately destroys claudin-expressing cells through the formation of a cytotoxic membrane-penetrating β-barrel pore. Structures obtained by X-ray crystallography of CpE, claudins, and claudins in complex with CpE fragments have provided the structural bases of claudin and CpE functions, revealing potential mechanisms for the CpE-mediated disruption of claudin-made tight junctions. This review highlights current progress in this space—what has been discovered and what remains unknown—toward efforts to elucidate the molecular mechanism of CpE disruption of tight junction barriers. It further underscores the key insights obtained through structure that are being applied to develop CpE-based therapeutics that combat claudin-overexpressing cancers or modulate tight junction barriers.
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26

Capaldo, Christopher T. "Claudin Barriers on the Brink: How Conflicting Tissue and Cellular Priorities Drive IBD Pathogenesis." International Journal of Molecular Sciences 24, no. 10 (May 10, 2023): 8562. http://dx.doi.org/10.3390/ijms24108562.

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Inflammatory bowel diseases (IBDs) are characterized by acute or chronic recurring inflammation of the intestinal mucosa, often with increasing severity over time. Life-long morbidities and diminishing quality of life for IBD patients compel a search for a better understanding of the molecular contributors to disease progression. One unifying feature of IBDs is the failure of the gut to form an effective barrier, a core role for intercellular complexes called tight junctions. In this review, the claudin family of tight junction proteins are discussed as they are a fundamental component of intestinal barriers. Importantly, claudin expression and/or protein localization is altered in IBD, leading to the supposition that intestinal barrier dysfunction exacerbates immune hyperactivity and disease. Claudins are a large family of transmembrane structural proteins that constrain the passage of ions, water, or substances between cells. However, growing evidence suggests non-canonical claudin functions during mucosal homeostasis and healing after injury. Therefore, whether claudins participate in adaptive or pathological IBD responses remains an open question. By reviewing current studies, the possibility is assessed that with claudins, a jack-of-all-trades is master of none. Potentially, a robust claudin barrier and wound restitution involve conflicting biophysical phenomena, exposing barrier vulnerabilities and a tissue-wide frailty during healing in IBD.
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Colegio, Oscar R., Christina M. Van Itallie, Heather J. McCrea, Christoph Rahner, and James Melvin Anderson. "Claudins create charge-selective channels in the paracellular pathway between epithelial cells." American Journal of Physiology-Cell Physiology 283, no. 1 (July 1, 2002): C142—C147. http://dx.doi.org/10.1152/ajpcell.00038.2002.

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Epithelia separate tissue spaces by regulating the passage of ions, solutes, and water through both the transcellular and paracellular pathways. Paracellular permeability is defined by intercellular tight junctions, which vary widely among tissues with respect to solute flux, electrical resistance, and ionic charge selectivity. To test the hypothesis that members of the claudin family of tight junction proteins create charge selectivity, we assessed the effect of reversing the charge of selected extracellular amino acids in two claudins using site-directed mutagenesis. Claudins were expressed in cultured Madin-Darby canine kidney cell monolayers under an inducible promoter, and clones were compared with and without induction for transmonolayer electrical resistance and dilution potentials. Expression and localization of claudins were determined by immunoblotting, immunofluorescence microscopy, and freeze-fracture electron microscopy. We observed that substituting a negative for a positive charge at position 65 in the first extracellular domain of claudin-4 increased paracellular Na+ permeability. Conversely, substituting positive for negative charges at three positions in the first extracellular domain of claudin-15, singly and in combination, reversed paracellular charge selectivity from a preference for Na+ to Cl−. These results support a model where claudins create charge-selective channels in the paracellular space.
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28

Ahn, C., D. Lee, and E. B. Jeung. "216 HORMONAL REGULATION OF CLAUDIN-4 TIGHT JUNCTION MOLECULE IN MOUSE PLACENTA." Reproduction, Fertility and Development 27, no. 1 (2015): 198. http://dx.doi.org/10.1071/rdv27n1ab216.

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Tight junctions (TJ) are composed of a branching network of sealing strands. TJ regulate paracellular conductance and ionic selectivity. TJ components include the peripheral protein ZO-1, junctional adhesion molecules (JAM) and the integral proteins such as occludin and claudin. Claudins are a family of proteins that are the most important components in the tight junctions. The established paracellular transport barriers that control transportation of molecules within intercellular space. The present study focused on the expression of claudin, suggesting as major working molecules in the paracellular transport system. To study the regulation and roles of claudin family, we examined expression of mouse placental claudin family. Fifteen pregnant C57/BL6 mice were used in this study and TJ proteins including Claudin-1 to Claudin-24 expressions by real-time RT–PCR and Western blotting. The mice were divided into 3 groups depending on the gestational day (on Days 12, 16, and 20 of gestation).The localization of TJ proteins were examined by immunohistochemistry. After we identified the fluctuation of claudin expression during pregnancy, we assumed that the hormones are one regulator for claudin family. Therefore, we performed an in vivo study with hormone receptor antagonists (ICI 182, 780, and RU-486) for examining hormonal effect on claudin expression in the placenta. Forty-nine mice were divided into 7 groups. The changes of claudin expression were examined with real-time RT-PCR and Western blotting. In the transcription levels, Claudin-1, claudin-2, claudin-4, and Claudin-5 expression levels were relatively high compared to others in the claudin family in all periods of the pregnancy. The claudin-4 expression, which reduces permeability of ions, increased over a period of time. However, caludin-5 expression that is the responsive protein for a decrease in paracellular conductance, were decreased. Claudin-1 and -4 have been known as responsive genes for a decrease in paracellular conductance. On the other hand, claudin 2 and 5 have been known as increasing paracellular conductance. In addition, immunohistochemistry was performed to identify their localization for inferring permeability in placenta. In summary, we analysed the claudin expressions and presented possible important claudins among its family. Furthermore, their localization was also examined in the mouse placenta. In addition, the regulation of critically expressed claudins by pregnancy-associated hormones, E2 and P4, was examined. These results may provide functional and structural roles of claudins and their involvement in the maternal-fetal interaction and in the transportation of placental materials.
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29

Robertson, Susan L., James G. Smedley, and Bruce A. McClane. "Identification of a Claudin-4 Residue Important for Mediating the Host Cell Binding and Action of Clostridium perfringens Enterotoxin." Infection and Immunity 78, no. 1 (November 2, 2009): 505–17. http://dx.doi.org/10.1128/iai.00778-09.

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ABSTRACT The 24-member claudin protein family plays a key role in maintaining the normal structure and function of epithelial tight junctions. Previous studies with fibroblast transfectants and naturally sensitive Caco-2 cells have also implicated certain claudins (e.g., Claudin-4) as receptors for Clostridium perfringens enterotoxin (CPE). The present study first provided evidence that the second extracellular loop (ECL-2) of claudins is specifically important for mediating the host cell binding and cytotoxicity of native CPE. Rat fibroblast transfectants expressing a Claudin-4 chimera, where the natural ECL-2 was replaced by ECL-2 from Claudin-2, exhibited no CPE-induced cytotoxicity. Conversely, CPE bound to, and killed, CPE-treated transfectants expressing a Claudin-2 chimera with a substituted ECL-2 from Claudin-4. Site-directed mutagenesis was then used to alter an ECL-2 residue that invariably aligns as N in claudins known to bind native CPE but as D or S in claudins that cannot bind CPE. Transfectants expressing a Claudin-4N149D mutant lost the ability to bind or respond to CPE, while transfectants expressing a Claudin-1 mutant with the corresponding ECL-2 residue changed from D to N acquired CPE binding and sensitivity. Identifying carriage of this N residue in ECL-2 as being important for native CPE binding helps to explain why only certain claudins can serve as CPE receptors. Finally, preincubating CPE with soluble recombinant Claudin-4, or Claudin-4 fragments containing ECL-2 specifically blocked the cytotoxicity on Caco-2 cells. This result opens the possibility of using receptor claudins as therapeutic decoys to ameliorate CPE-mediated intestinal disease.
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30

Anderson, James Melvin. "Molecular Structure of Tight Junctions and Their Role in Epithelial Transport." Physiology 16, no. 3 (June 2001): 126–30. http://dx.doi.org/10.1152/physiologyonline.2001.16.3.126.

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Tight junctions create a paracellular barrier with physiological properties that differ among epithelia. Among these differences are electrical resistance and discrimination for solute size and charge. Emerging evidence suggests that a large family of transmembrane proteins called the claudins create these variable properties.
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31

Günzel, Dorothee, and Alan S. L. Yu. "Claudins and the Modulation of Tight Junction Permeability." Physiological Reviews 93, no. 2 (April 2013): 525–69. http://dx.doi.org/10.1152/physrev.00019.2012.

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Claudins are tight junction membrane proteins that are expressed in epithelia and endothelia and form paracellular barriers and pores that determine tight junction permeability. This review summarizes our current knowledge of this large protein family and discusses recent advances in our understanding of their structure and physiological functions.
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32

Perez-Hernandez, Daniel, Lorena Suarez-Artiles, Mattson S. O. Jones, and Gunnar Dittmar. "Using PrISMa to reveal the interactome of the human claudins family." STAR Protocols 4, no. 4 (December 2023): 102549. http://dx.doi.org/10.1016/j.xpro.2023.102549.

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33

Yamazaki, Yuji, Reitaro Tokumasu, Hiroshi Kimura, and Sachiko Tsukita. "Role of claudin species–specific dynamics in reconstitution and remodeling of the zonula occludens." Molecular Biology of the Cell 22, no. 9 (May 2011): 1495–504. http://dx.doi.org/10.1091/mbc.e10-12-1003.

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Tight-junction strands, which are organized into the beltlike cell–cell adhesive structure called the zonula occludens (TJ), create the paracellular permselective barrier in epithelial cells. The TJ is constructed on the basis of the zonula adherens (AJ) by polymerized claudins in a process mediated by ZO-1/2, but whether the 24 individual claudin family members play different roles at the TJ is unclear. Here we established a cell system for examining the polymerization of individual claudins in the presence of ZO-1/2 using an epithelial-like cell line, SF7, which lacked endogenous TJs and expressed no claudin but claudin-12 in immunofluorescence and real-time PCR assays. In stable SF7-derived lines, exogenous claudin-7, -14, or -19, but no other claudins, individually reconstituted TJs, each with a distinct TJ-strand pattern, as revealed by freeze-fracture analyses. Fluorescence recovery after photobleaching (FRAP) analyses of the claudin dynamics in these and other epithelial cells suggested that slow FRAP-recovery dynamics of claudins play a critical role in regulating their polymerization around AJs, which are loosely coupled with ZO-1/2, to form TJs. Furthermore, the distinct claudin stabilities in different cell types may help to understand how TJs regulate paracellular permeability by altering the paracellular flux and the paracellular ion permeability.
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34

Khan, Niamat, and Abdul R. Asif. "Transcriptional Regulators of Claudins in Epithelial Tight Junctions." Mediators of Inflammation 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/219843.

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Human gastrointestinal tract is covered by a monolayer of specialized epithelial cells that constitute a protective barrier surface to external toxic and infectious agents along with metabolic and digestive functions. Intercellular junctions, among epithelial cells, such as desmosomes, adherens, gap, and tight junctions (TJs), not only provide mechanical integrity but also limit movement of molecules across the monolayer. TJ is a complex structure composed of approximately 35 different proteins that interact with each other at the apical side of two adjacent epithelial cells. Claudin family proteins are important members of TJ with so far 24 known isoforms in different species. Claudins are structural proteins of TJ that help to control the paracellular movement by forming fence and barrier across the epithelial monolayer. Altered function of claudins is implicated in different form of cancers, inflammatory bowel diseases (IBDs), and leaky diarrhea. Based on their significant role in the molecular architecture of TJ, diversity, and disease association, further understanding about claudin family proteins and their genetic/epigenetic regulators is indispensable.
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35

Daugherty, Brandy L., Madalina Mateescu, Anand S. Patel, Kelly Wade, Shioko Kimura, Linda W. Gonzales, Susan Guttentag, Philip L. Ballard, and Michael Koval. "Developmental regulation of claudin localization by fetal alveolar epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 287, no. 6 (December 2004): L1266—L1273. http://dx.doi.org/10.1152/ajplung.00423.2003.

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Tight junction proteins in the claudin family regulate epithelial barrier function. We examined claudin expression by human fetal lung (HFL) alveolar epithelial cells cultured in medium containing dexamethasone, 8-bromo-cAMP, and isobutylmethylxanthanine (DCI), which promotes alveolar epithelial cell differentiation to a type II phenotype. At the protein level, HFL cells expressed claudin-1, claudin-3, claudin-4, claudin-5, claudin-7, and claudin-18, where levels of expression varied with culture conditions. DCI-treated differentiated HFL cells cultured on permeable supports formed tight transepithelial barriers, with transepithelial resistance (TER) >1,700 ohm/cm2. In contrast, HFL cells cultured in control medium without DCI did not form tight barriers (TER <250 ohm/cm2). Consistent with this difference in barrier function, claudins expressed by HFL cells cultured in DCI medium were tightly localized to the plasma membrane; however, claudins expressed by HFL cells cultured in control medium accumulated in an intracellular compartment and showed discontinuities in claudin plasma membrane localization. In contrast to claudins, localization of other tight junction proteins, zonula occludens (ZO)-1, ZO-2, and occludin, was not sensitive to HFL cell phenotype. Intracellular claudins expressed by undifferentiated HFL cells were localized to a compartment containing early endosome antigen-1, and treatment of HFL cells with the endocytosis inhibitor monodansylcadaverine increased barrier function. This suggests that during differentiation to a type II cell phenotype, fetal alveolar epithelial cells use differential claudin expression and localization to the plasma membrane to help regulate tight junction permeability.
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36

Balkovetz, Daniel F. "Claudins at the gate: determinants of renal epithelial tight junction paracellular permeability." American Journal of Physiology-Renal Physiology 290, no. 3 (March 2006): F572—F579. http://dx.doi.org/10.1152/ajprenal.00135.2005.

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The epithelial tight junction (TJ) is responsible for the control of paracellular transport between epithelial cells (gate function) and the maintenance of apical/basolateral polarity by preventing the diffusion of membrane lipids and/or proteins from one surface domain to another (fence function). Renal tubule epithelia in the mammalian nephron have TJs that determine paracellular transport characteristics. Paracellular transport across renal tubular epithelial TJs (gate function) varies in different segments of the nephron. A large family of recently identified TJ-associated transmembrane proteins named claudins appear to determine the paracellular permeability properties of the TJ. A combination of inherited human diseases, renal epithelial cell culture models, and nephron expression patterns of claudins is providing important clues about how claudin molecules determine the TJ gate function of renal epithelia in different segments of the nephron.
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37

Cardoso Guedes de Souza, Luísa. "Desigualdade de gênero e o equilíbrio entre trabalho e família." Revista Brasileira de Estudos de População 39 (September 12, 2022): 1–6. http://dx.doi.org/10.20947/s0102-3098a0219.

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38

Colegio, Oscar R., Christina Van Itallie, Christoph Rahner, and James Melvin Anderson. "Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture." American Journal of Physiology-Cell Physiology 284, no. 6 (June 1, 2003): C1346—C1354. http://dx.doi.org/10.1152/ajpcell.00547.2002.

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Tight junctions (TJs) regulate paracellular permeability across epithelia and vary widely in their transepithelial electrical resistance (TER) and charge selectivity. The claudin family of transmembrane proteins influences these properties. We previously reported that claudin-4 increased TER ∼300% when expressed in low-resistance Madin-Darby canine kidney (MDCK) II cells and decreased the paracellular permeability for Na+ more than Cl− (Van Itallie C, Rahner C, and Anderson JM. J Clin Invest 107: 1319–1327, 2001). In comparison, we report here that expression of claudin-2 increases TER by only ∼20% and does not change the ionic selectivity of MDCK II cells from their cation-selective background. To test whether the extracellular domains of claudins-4 and -2 determine their unique paracellular properties, we determined the effects of interchanging these domains between claudins-4 and -2. Inducible expression of wild-type claudins and extracellular domain chimeras increased both the number and depth of fibrils, but the characteristic fibril morphologies of claudin-4 or -2 were not altered by switching extracellular domains. Like claudin-4, chimeras expressing the first or both extracellular domains of claudin-4 on claudin-2 increased TER severalfold and profoundly decreased the permeability of Na+ relative to Cl−. In contrast, chimeras expressing the first or both extracellular domains of claudin-2 on claudin-4 increased the TER by only ∼60 and ∼40%, respectively, and only modestly altered charge selectivity. These results support a model in which the claudins create paracellular channels and the first extracellular domain is sufficient to determine both paracellular charge selectivity and TER.
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Van Itallie, Christina M., Alan S. Fanning, and James M. Anderson. "Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins." American Journal of Physiology-Renal Physiology 285, no. 6 (December 2003): F1078—F1084. http://dx.doi.org/10.1152/ajprenal.00116.2003.

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Tight junctions (TJ) regulate paracellular ionic charge selectivity and conductance across epithelial tissues and cell lines. These properties vary among epithelia, and recent evidence implicates the claudins, a family of TJ transmembrane proteins, as important determinants of both characteristics. To test the hypothesis that each claudin contributes a characteristic charge discrimination to the TJ, we expressed claudins-2, -4, -11, and -15 in both cation-selective Madin-Darby canine kidney (MDCK) II cells and in anion-selective LLC-PK1 cells and examined changes in transepithelial electrical resistance (TER) and paracellular charge selectivity. Regulated expression and localization were verified by immunoblot analysis and immunofluorescence microscopy, respectively. Expression of claudin-4 increased TER in both cell lines, whereas effects of the others on TER were variable. Claudin-4 and -11 decreased paracellular permeability for Na+ in MDCK II cells, whereas neither claudin-2 nor -15 had an effect. Conversely, in LLC-PK1 cells, claudin-2 and -15 increased the permeability for Na+, whereas claudin-4 and -11 were without effect. We conclude that the contribution of each claudin is most easily detectable when it reverses the direction of monolayer charge selectivity. These results are consistent with a model in which exogenous claudins add new charge-selective pores, leading to a physiological phenotype that combines endogenous and exogenous contributions. Additionally, it is possible to rationalize the direction of charge selectivity conferred by the individual claudins on the basis of electrostatic effects of the charged amino acids in their first extracellular loops.
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40

Seker, Murat, Cármen Fernández-Rodríguez, Luis Martínez-Cruz, and Dominik Müller. "Mouse Models of Human Claudin-Associated Disorders: Benefits and Limitations." International Journal of Molecular Sciences 20, no. 21 (November 5, 2019): 5504. http://dx.doi.org/10.3390/ijms20215504.

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In higher organisms, epithelia separate compartments in order to guarantee their proper function. Such structures are able to seal but also to allow substances to pass. Within the paracellular pathway, a supramolecular structure, the tight junction transport is largely controlled by the temporospatial regulation of its major protein family called claudins. Besides the fact that the expression of claudins has been identified in different forms of human diseases like cancer, clearly defined mutations in the corresponding claudin genes have been shown to cause distinct human disorders. Such disorders comprise the skin and its adjacent structures, liver, kidney, the inner ear, and the eye. From the phenotype analysis, it has also become clear that different claudins can cause a complex phenotype when expressed in different organs. To gain deeper insights into the physiology and pathophysiology of claudin-associated disorders, several mouse models have been generated. In order to model human disorders in detail, they have been designed either as full knockouts, knock-downs or knock-ins by a variety of techniques. Here, we review human disorders caused by CLDN mutations and their corresponding mouse models that have been generated thus far and assess their usefulness as a model for the corresponding human disorder.
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41

Bruewer, Matthias, Ann M. Hopkins, Michael E. Hobert, Asma Nusrat, and James L. Madara. "RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and F-actin." American Journal of Physiology-Cell Physiology 287, no. 2 (August 2004): C327—C335. http://dx.doi.org/10.1152/ajpcell.00087.2004.

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Epithelial intercellular junctions regulate cell-cell contact and mucosal barrier function. Both tight junctions (TJs) and adherens junctions (AJs) are regulated in part by their affiliation with the F-actin cytoskeleton. The cytoskeleton in turn is influenced by Rho family small GTPases such as RhoA, Rac1, and Cdc42, all of which constitute eukaryotic targets for several pathogenic organisms. With a tetracycline-repressible system to achieve regulated expression in Madin-Darby canine kidney (MDCK) epithelial cells, we used dominant-negative (DN) and constitutively active (CA) forms of RhoA, Rac1, and Cdc42 as tools to evaluate the precise contribution of each GTPase to epithelial structure and barrier function. All mutant GTPases induced time-dependent disruptions in epithelial gate function and distinct morphological alterations in apical and basal F-actin pools. TJ proteins occludin, ZO-1, claudin-1, claudin-2, and junctional adhesion molecule (JAM)-1 were dramatically redistributed in the presence of CA RhoA or CA Cdc42, whereas only claudins-1 and -2 were redistributed in response to CA Rac1. DN Rac1 expression also induced selective redistribution of claudins-1 and -2 in addition to JAM-1, whereas DN Cdc42 influenced only claudin-2 and DN RhoA had no effect. AJ protein localization was unaffected by any mutant GTPase, but DN Rac1 induced a reduction in E-cadherin detergent solubility. All CA GTPases increased the detergent solubility of claudins-1 and -2, but CA RhoA alone reduced claudin-2 and ZO-1 partitioning to detergent-insoluble membrane rafts. We conclude that Rho family GTPases regulate epithelial intercellular junctions via distinct morphological and biochemical mechanisms and that perturbations in barrier function reflect any imbalance in active/resting GTPase levels rather than simply loss or gain of GTPase activity.
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42

Gamero-Estevez, Andonian, Jean-Claude, Gupta, and Ryan. "Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells." International Journal of Molecular Sciences 20, no. 19 (October 2, 2019): 4889. http://dx.doi.org/10.3390/ijms20194889.

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: Kidney stones affect 10% of the population. Yet, there is relatively little known about how they form or how to prevent and treat them. The claudin family of tight junction proteins has been linked to the formation of kidney stones. The flavonoid quercetin has been shown to prevent kidney stone formation and to modify claudin expression in different models. Here we investigate the effect of quercetin on claudin expression and localization in MDCK II cells, a cation-selective cell line, derived from the proximal tubule. For this study, we focused our analyses on claudin family members that confer different tight junction properties: barrier-sealing (Cldn1, -3, and -7), cation-selective (Cldn2) or anion-selective (Cldn4). Our data revealed that quercetin’s effects on the expression and localization of different claudins over time corresponded with changes in transepithelial resistance, which was measured continuously throughout the treatment. In addition, these effects appear to be independent of PI3K/AKT signaling, one of the pathways that is known to act downstream of quercetin. In conclusion, our data suggest that quercetin’s effects on claudins result in a tighter epithelial barrier, which may reduce the reabsorption of sodium, calcium and water, thereby preventing the formation of a kidney stone.
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43

Konson, Claudia. "The memory to the teacher, Doctor of Medical Sciences, Professor E.V. Frolova." Russian Family Doctor 28, no. 1 (March 31, 2024): 71–73. http://dx.doi.org/10.17816/rfd625455.

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The article is dedicated to the memory of Professor of the Department of Family Medicine, member of the editorial board of the journal “Russian Family Doctor”, Doctor of Medical Sciences, Professor E.V. Frolova, who became a mentor and supervisor for a nurse with higher education, citizen of Israel Claudia Konson.
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44

Naranjo Acosta, Susana M. "Los hijos de Gregoria: Relato de una familia mexicana. Regnar Kristensen y Claudia Adeath." Alteridades 32, no. 63 (May 3, 2022): 141–42. http://dx.doi.org/10.24275/uam/izt/dcsh/alteridades/2022v32n63/naranjo.

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45

Gamba, Gerardo. "Role of WNK kinases in regulating tubular salt and potassium transport and in the development of hypertension." American Journal of Physiology-Renal Physiology 288, no. 2 (February 2005): F245—F252. http://dx.doi.org/10.1152/ajprenal.00311.2004.

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A recently discovered family of protein kinases is responsible for an autosomal-dominant disease known as Gordon's syndrome or pseudohypoaldosteronism type II (PHA-II) that features hyperkalemia and hyperchloremic metabolic acidosis, accompanied by hypertension and hypercalciuria. Four genes have been described in this kinase family, which has been named WNK, due to the absence of a key lysine in kinase subdomain II (with no K kinases). Two of these genes, WNK1 and WNK4 located in human chromosomes 12 and 17, respectively, are responsible for PHA-II. Immunohystochemical analysis revealed that WNK1 and WNK4 are predominantly expressed in the distal convoluted tubule and collecting duct. The physiological studies have shown that WNK4 downregulates the activity of ion transport pathways expressed in these nephron segments, such as the apical thiazide-sensitive Na+-Cl−cotransporter and apical secretory K+channel ROMK, as well as upregulates paracellular chloride transport and phosphorylation of tight junction proteins such as claudins. In addition, WNK4 downregulates other Cl−influx pathways such as the basolateral Na+-K+-2Cl−cotransporter and Cl−/HCO3−exchanger. WNK4 mutations behave as a loss of function for the Na+-Cl−cotransporter and a gain of function when it comes to ROMK and claudins. These dual effects of WNK4 mutations fit with proposed mechanisms for developing electrolyte abnormalities and hypertension in PHA-II and point to WNK4 as a multifunctional regulator of diverse ion transporters.
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46

Markov, Alexander G., Anastasia E. Bikmurzina, Arina A. Fedorova, Ekaterina P. Vinogradova, Natalia M. Kruglova, Igor I. Krivoi, and Salah Amasheh. "Prednisolone Targets Claudins in Mouse Brain Blood Vessels." International Journal of Molecular Sciences 25, no. 1 (December 24, 2023): 276. http://dx.doi.org/10.3390/ijms25010276.

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Endothelial cells in brain capillaries are crucial for the function of the blood–brain barrier (BBB), and members of the tight junction protein family of claudins are regarded to be primarily responsible for barrier properties. Thus, the analysis of bioactive substances that can affect the BBB’s permeability is of great importance and may be useful for the development of new therapeutic strategies for brain pathologies. In our study, we tested the hypothesis that the application of the glucocorticoid prednisolone affects the murine blood–brain barrier in vivo. Isolated brain tissue of control and prednisolone-injected mice was examined by employing immunoblotting and confocal laser scanning immunofluorescence microscopy, and the physiological and behavioral effects were analyzed. The control tissue samples revealed the expression of barrier-forming tight junction proteins claudin-1, -3, and -5 and of the paracellular cation and water-channel-forming protein claudin-2. Prednisolone administration for 7 days at doses of 70 mg/kg caused physiological and behavioral effects and downregulated claudin-1 and -3 and the channel-forming claudin-2 without altering their localization in cerebral blood vessels. Changes in the expression of these claudins might have effects on the ionic and acid–base balance in brain tissue, suggesting the relevance of our findings for therapeutic options in disorders such as cerebral edema and psychiatric failure.
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47

Kitajiri, Shin-ichiro, and Tatsuya Katsuno. "Tricellular Tight Junctions in the Inner Ear." BioMed Research International 2016 (2016): 1–5. http://dx.doi.org/10.1155/2016/6137541.

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Tight junctions (TJs) are structures that seal the space between the epithelial cell sheets. In the inner ear, the barrier function of TJs is indispensable for the separation of the endolymphatic and perilymphatic spaces, which is essential for the generation and maintenance of the endocochlear potential (EP). TJs are formed by the intercellular binding of membrane proteins, known as claudins, and mutations in these proteins cause deafness in humans and mice. Within the epithelial cell sheet, however, a bound structure is present at the site where the corners of three cells meet (tricellular tight junctions (tTJs)), and the maintenance of the barrier function at this location cannot be explained by the claudins alone. Tricellulin and the angulin family of proteins (angulin-1/LSR, angulin-2/ILDR1, and angulin-3/ILDR2) have been identified as tTJ-associated proteins. Tricellulin and ILDR1 are localized at the tTJ and alterations in these proteins have been reported to be involved in deafness. In this review, we will present the current state of knowledge for tTJs.
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48

Ahn, C., J. S. Lee, and E. B. Jeung. "128 EXPRESSIONS OF MOUSE TIGHT JUNCTION MOLECULES IN PLACENTA – CLAUDINS AND OTHER PARACELLULAR TRANSPORT MOLECULES." Reproduction, Fertility and Development 26, no. 1 (2014): 178. http://dx.doi.org/10.1071/rdv26n1ab128.

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Tight junctions (TJ) are composed of a branching network of sealing strands. Tight junctions regulate paracellular conductance and ionic selectivity. The TJ components include the peripheral protein ZO-1, junctional adhesion molecules (JAM), and integral proteins, such as occludin and claudin. Claudins, a family of proteins, are the most important components in TJ. They establish paracellular transport barriers, which control transportation of molecules within intercellular space. The current study focused on expression of claudin, suggesting claudin as a major working molecule in the paracellular transport system. In order to study the mechanisms and roles of the claudin family, the expression levels of claudin family in various organs should be determined. In this study, we examined expression of the mouse placental claudin family. Pregnant C57/BL6 mice (n = 5) were used in this study, and compared with β-actin, expression of TJ proteins, including Claudin-1 to Claudin-24, JAM-a, Zo-1, and occludin, tricellulin, and MarvelD3 was examined. In the transcription levels, Claudin-1 and -4 proteins were predominantly expressed. Claudin-1 and -4 have been known as a responsive gene for a direct decrease in paracellular conductance by selective reduction of the permeability of Na+ ions. On the other hand, Claudin-2, Claudin-3, Claudin-5, Cludin-11, and Claudin-12 showed ~33% expression compared with Claudin-1. Claudin-6 and Claudin-7 showed ~20% relative expression compared to Claudin 1. Claudin-10a and Claudin-16 were not detectable by real-time RT-PCR under our experimental conditions. Other claudin proteins showed low expression. Because the transcriptional levels of TJ genes were expressed variously, protein levels and their localization in the placenta will be further evaluated by immunostaining and Western blot assay. This study will provide data on expression of TJ genes and their localization in the mouse placenta, which may contribute to assuming the roles of these TJ genes regarding maternal-fetal ion transportation in the placenta.
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49

Li, Jiahua, Susanne Angelow, Anna Linge, Min Zhuo, and Alan S. L. Yu. "Claudin-2 pore function requires an intramolecular disulfide bond between two conserved extracellular cysteines." American Journal of Physiology-Cell Physiology 305, no. 2 (July 15, 2013): C190—C196. http://dx.doi.org/10.1152/ajpcell.00074.2013.

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Claudins constitute a family of tight junction transmembrane proteins whose first extracellular loop (ECL1) determines the paracellular permeability and ion selectivity in epithelia. There are two cysteines in the ECL1 that are conserved among all claudins. We hypothesized that these extracellular cysteines are linked by an intramolecular disulfide bond that is necessary for correct pore folding and function. To test this, we mutated C54 and C64 in claudin-2, either individually or together to alanine or serine, and generated stable Madin-Darby canine kidney (MDCK) I Tet-off cell lines. Immunoblotting showed a higher molecular mass band in the mutants with a single cysteine mutation, consistent with a claudin-2 dimer, suggesting that the two conserved cysteines normally form an intramolecular disulfide bond in wild-type claudin-2. By immunofluorescent staining, the alanine mutants were mislocalized intracellularly, while the serine mutants were expressed at the tight junction. Thus dimerization of both C54A and C64A did not require tight junction expression, suggesting that C54 and C64 are located near an intermolecular interface involved in cis-interaction. The conductance and Na+ permeability of the serine mutants were markedly lower than the wild type, but there was no difference between the single mutants and the double mutant. We conclude that the disulfide bond between the conserved extracellular cysteines in claudin-2 is necessary for pore formation, probably by stabilizing the ECL1 fold, but is not required for correct protein trafficking. We further speculate that this role is generalizable to other claudin family members.
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50

Flores-Benítez, D., A. Ruiz-Cabrera, C. Flores-Maldonado, L. Shoshani, M. Cereijido, and R. G. Contreras. "Control of tight junctional sealing: role of epidermal growth factor." American Journal of Physiology-Renal Physiology 292, no. 2 (February 2007): F828—F836. http://dx.doi.org/10.1152/ajprenal.00369.2006.

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Epithelia can adjust the permeability of their paracellular permeation route to physiological requirements, pathological conditions, and pharmacological challenges. This is reflected by a transepithelial electrical resistance (TER) ranging from a few tenth to several thousands Ω·cm2, depending on the degree of sealing of the tight junction (TJ). The present work is part of an effort to understand the causes and mechanisms underlying these adaptations. We observed that an extract of human urine (hDLU) increases TER in a concentration- and time-dependent manner and is more effective when added from the basolateral side of cultured monolayers of Madin-Darby canine kidney cells than from the apical one. We found that its main TER-increasing component is epidermal growth factor (hEGF), as depletion of this peptide with specific antibodies, or inhibition of its receptor with PD153035, abolishes its effect. Since the permeability of the TJ depends on the expression of several species of membrane proteins, chiefly claudins, we explored whether hDLU can affect five members of the claudin family, the three known members of the ZO family, and occludin. EGF present in hDLU decreases the content of claudins-1 and -2 as well as delocalizes them from the TJ and increases the content of claudin-4. As expected from the fact that the degree of sealing of the TJ must be a physiologically regulated parameter, besides of hEGF, we also found that hDLU appears to contain also other components that decrease TER, claudin-4 and -7, and that seem to act with different kinetics than the TER-increasing ones.
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