422 research outputs found
Ingo Plag, Word-Formation in English (2
No full text1. General observations Ingo Plag is Professor of English Linguistics at Heinrich-Heine-Universität Düsseldorf. He has published articles in specialized journals like Linguistics, Language or English Language and Linguistics and in works like the Yearbook of Morphology [2001], Word-Formation: An International Handbook of the Languages of Europe [2016] or Word Knowledge and Word Usage: A Cross-Disciplinary Guide to the Mental Lexicon [2017]. He is the author of Morphological Productivity: Stru..
Roles of bHLH Transcription Factors Neurod1, Neurod2 and Neurod6 in Cerebral Cortex Development and Commissure Formation.
No full textBasische Helix-Loop-Helix (bHLH)-Proteine bilden eine diverse Gruppe evolutionär gut konservierter Transkriptionsfaktoren. Viele transaktivierende bHLH-Proteine werden zelltyp- oder gewebespezifisch exprimiert und fungieren als wichtige Schlüsselregulatoren zellulärer Determinations- und Differenzierungsprozesse. Die eng verwandten neuronalen bHLH-Gene Neurod1, Neurod2 und Neurod6 werden in differenzierenden Pyramidenneuronen des sich entwickelnden zerebralen Kortex exprimiert und stehen schon lange im Verdacht, deren Reifung zu steuern. In der Vergangenheit wurde jedes der drei Gene in Mäusen inaktiviert. Untersuchungen an den einfach-defizienten Tieren konnten jedoch keine wichtigen Funktionen in embryonalen Pyramidenneuronen identifizieren. Da die Aminosäuresequenzen und die Expressionsmuster der Faktoren sehr ähnlich sind, wurde angenommen, dass sie sich redundante Funktionalität teilen. Um dies zu überprüfen, habe ich Neurod2/6-doppel-defiziente Tiere gezüchtet und unter besonderer Berücksichtigung der Differenzierung von Pyramidenneuronen und der Konnektivität des zerebralen Kortex analysiert: Die Experimente zeigen, dass Neurod2 und Neurod6 tatsächlich mehrere bisher unbekannte gemeinsame Funktionen haben, wobei jeder Faktor für den Verlust des jeweils anderen kompensieren kann. Zumindest eines der beiden Gene ist notwendig für (1) die Kontrolle der radialen Migration eines Teils der Pyramidenneurone, (2) die frühe Regionalisierung des zerebralen Kortex und (3) die Bildung kortikaler Projektionen vom Neokortex zum Striatum, zum Thalamus und zur kontralateralen Hemisphäre. Callosale Axone bilden in Neurod2/6-doppel-defizienten Mäusen Faserbündel die tangential in den medialen Kortex einwachsen, aber noch vor Erreichen des ipsilateralen Cingulums und vor dem Kontakt mit der Mittellinie stoppen und defaszikulieren. Es resultiert eine neue Variante der callosalen Agenesie, die nahelegt, dass es bisher nicht identifizierte Wachstumssignale im medialen Kortex gibt. Die Expression von Neurod1, welche sich normalerweise auf die Subventrikularzone beschränkt, persistiert in radial migrierenden Pyramidenneuronen der Intermediärzone und der Kortikalplatte von Neurod2/6-doppel-defizienten Mäusen. Diese ektopische Neurod1-Expression kann dort den Verlust von Neurod2 und Neurod6 kompensieren. In einem weiteren Schritt habe ich konditionale Neurod1/2/6-tripel-defiziente Mäuse gezüchtet. In diesen Tieren wird das Neurod1-Gen durch selektive genetische Rekombination in all jenen Zellen, die über Neurod6-Promoteraktivität verfügen, irreversibel entfernt: Wie erwartet, teilt sich Neurod1 weitere gemeinsame Funktionen mit Neurod2 und Neurod6. Zumindest eines der drei Gene ist notwendig für die Differenzierung hippokampaler Pyramidenzellen und die Hemmung des programmierten Zelltods der unreifen Neuronen des Cornu Ammonis. Während die gemeinsame Inaktivierung von Neurod1/2/6 zur Aplasie des Hippocampus führt, überlebt ein Großteil der neokortikalen Pyramidenzellen. Die terminale neuronale Differenzierung ist jedoch auch im Neokortex gestört und die neokortikale Konnektivität sehr stark reduziert. Diese Arbeit zeigt, dass die Transkriptionsfaktoren der NeuroD-Familie gemeinsam die Differenzierung, das Überleben, die Migration und das axonale Wachstum von pyramidalen Neuronen des sich entwickelnden zerebralen Kortex steuern. Während der Embryonalentwicklung ergeben sich folgende, teils überschneidende Funktionen der NeuroD-Gene: Die Differenzierung und das Überleben von hippocampalen Körnerzellen ist abhängig von Neurod1. Die frühen Schritte der Differenzierung von hippocampalen Pyramidenneuronen und deren Überleben sind eine Funktion von wahlweise Neurod1, Neurod2 oder Neurod6. Spätere neuronale Differenzierungsschritte, die Regionalisierung des Neokortex und das gezielte Wachstum wichtiger neokortikaler Faserzüge basieren auf Funktionen von Neurod2 oder Neurod6, aber nicht von Neurod1. Der postnatale Umbau des somatosensorischen Kortex und die funktionale Integration thalamischer Afferenzen wurden bereits als strikt Neurod2-abhängig beschrieben.Basic helix-loop-helix (bHLH) proteins constitute a diverse group of evolutionary well-conserved transcription factors. Many transactivating bHLH proteins follow cell type- or tissue-specific expression patterns and act as key regulators of cellular determination and differentiation processes. The closely related neuronal bHLH genes Neurod1, Neurod2 and Neurod6 are expressed by differentiating pyramidal neurons in the developing cerebral cortex and have long been suspected to regulate the maturation of these cells. Each of the three genes was genetically inactivated in mice, but studies of single-deficient animals failed to identify important functions in embryonic pyramidal neurons. Considering high sequence similarity and overlapping expression patterns, most authors suggested functional redundancy amongst the NeuroD-family. To test this, I bred transgenic mice lacking the two most similarly expressed NeuroD genes, Neurod2/6; and analyzed cerebral cortex development with an emphasis on pyramidal neuron identity and neocortical connectivity. Neurod2 and Neurod6 indeed share several hitherto unknown functions and compensate for each other’s loss. At least one of the two genes is necessary for: (1) the control of radial migration in a subset of pyramidal neurons; (2) area determination in the neocortex; and (3) the formation of fiber tracts connecting the neocortex to the striatum, to the thalamus, and to the contralateral hemisphere. In Neurod2/6 double-deficient mice, callosal axons form fasciculated fiber bundles that grow tangentially into the medial neocortex, but stall and defasciculate before reaching the ipsilateral cingulum or any midline associated structure. This new variant of callosal agenesis implies the presence of a not yet identified axon guidance mechanism in the medial neocortex. Neocortical Neurod1 expression, which is normally restricted to the subventricular zone, persists in the intermediate zone and cortical plate of Neurod2/6 double-deficient embryos. Ectopically upregulated Neurod1 can provide redundant functionality to compensate for the loss of Neurod2/6. I went further and bred conditional Neurod1/2/6 triple-deficient mice, in which the Neurod1 gene is specifically inactivated in cells with Neurod6-promoter activity. As hypothesized, Neurod1 shares additional functions with Neurod2 and Neurod6. At least one of the three genes is necessary for hippocampal pyramidal neuron differentiation and the prevention of developmental cell death in the medial cortex. While the simultaneous inactivation of Neurod1/2/6 results in the complete loss of archicortical pyramidal neurons, many neocortical pyramidal cells survive, migrate radially and settle in the cortical plate. However, terminal pyramidal neuron differentiation is incomplete and neocortical connectivity is dramatically reduced in the triple-deficient mice. Taken together, this work shows that NeuroD-family transcription factors cooperatively regulate pyramidal neuron differentiation, survival, migration, specification and axon growth in the developing cerebral cortex. The partly overlapping functions of Neurod1/2/6 during embryonic cortex development might be summarized as follows: Hippocampal granule cell differentiation and survival depend essentially on Neurod1. 1 Early aspects of hippocampal pyramidal neuron differentiation and survival depend on functionality shared by Neurod1, Neurod2 and Neurod6. Later aspects of neocortical pyramidal neuron differentiation, cortical arealization and the guidance of major neocortical axon tracts depend on redundant functionality of Neurod2 and Neurod6, but not Neurod1. Postnatally, the remodeling of the somatosensory cortex in response to functional integration of thalamocortical afferents and the maturation of the hippocampal mossy fiber pathway depend specifically on Neurod2. Adult functions are largely unknown, although Neurod6 has recently been associated with the development of obsessive-compulsive disorder, schizophrenia and Alzheimer’s disease.2016-04-2
Remarks on Early Medieval legal charters — The legend of “dux Ingo” and his “carta sine litteris”
No full textEnea Silvio Piccolomini in his work entitled
De Europa
written in 1458, tells an interesting story defined as a legend in terms of genre about a duke called Ingo, who lived during the reign of Charlemagne. This narrative claims that in 790
dux gentis
Ingo held a feast for the inhabitants of his province where food was served to the peasants allowed to appear before him in golden and silver bowls, while to the dignitaries standing further away from him in bowls made of clay. The researchers’ attention is deservedly raised by the query how come that this parabolical story with biblical tone was included in Enea Silvio’s work; if it had been borrowed who the
auctor
might have been he borrowed it from. The answer seems to be very simple: from the
Conversio Bagoariorum et Carantanorum
drafted regarding the lawsuit proceeded against Methodius. In the case narrated in the
Conversio
Ingo sent a charter or much rather a parchment without any writing, or letters on it
(carta sine litteris)
, which provided his legate with sufficient authenticity to demand obedience from the people.In this study-after having compared the two narratives and outlined the place of De Europa in Enea Silvio Piccolomini’s oeuvre and the circumstances of the drafting and tendencies of the Conversio Bagoariorum et Carantanorum-the author attempts to answer the following questions. To what extent can duke Ingo, mentioned by Enea Silvio and not questioned in the literature for long centuries, be considered a real historical person? Does the Conversio refer to Ingo as a duke, and if it does, what is his existence as a duke and introduction in the literature as a duke owing to? What could the meaning of carta sine litteris referred to in Conversio have been, and why did Enea Silvio not take this item over although he could have put it forward as a further proof of Ingo’s dignity? To what literary prefigurations can the description of the feast held by Ingo be traced back to, and what role did it play in the Conversio? Regarding the borrowing of the Ingo story by Enea Silvio, what possible intermediary writing and author can be reckoned with
Author response image 1. Assessment of apoptosis using propidium iodide.
No full textBeyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons. Conversely, genetic elimination of oxytocin receptors increases the expression of protein components of excitatory synapses and excitatory synaptic transmission in vitro. In vivo, oxytocin-receptor-deficient hippocampal pyramidal neurons develop more complex dendrites, which leads to increased spine number and reduced γ-oscillations. These results indicate that oxytocin controls the development of hippocampal excitatory neurons and contributes to the maintenance of a physiological excitation/inhibition balance, whose disruption can cause neurobehavioral disturbances.</jats:p
Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation
No full textThe pyramidal neurons of the mammalian neocortex form two major types of long-range connections-corticocortical and cortico-subcortical. The transcription factors Satb2 and Ctip2 are critical regulators of neuronal cell fate that control interhemispheric versus corticofugal connections respectively. Here, we investigate the axon guidance molecules downstream of Satb2 and Ctip2 that establish these connections. We show that the expression of two Netrin1 receptors-DCC and Unc5C is under direct negative regulation by Satb2 and Ctip2, respectively. Further, we show that the Netrin1-Unc5C/DCC interaction is involved in controlling the interhemispherical projection in a subset of early born, deep layer callosal neurons
Correction: Discovering the opposite shore: How did hominins cross sea straits?
No full textThe ORCID iDs are missing for the second, fifth, and sixth authors. Please see the authors’ respective ORCID iDs here:
Author Christine Hertler’s ORCID iD is: 0000-0002-8252-9674 (https://orcid.org/0000-0002-8252-9674).
Author Jan Ole Berndt’s ORCID iD is: 0000-0001-7241-3291 (https://orcid.org/0000-0001-7241-3291).
Author Ingo J. Timm’s ORCID iD is: 0000-0002-3369-813X (https://orcid.org/0000-0002-3369-813X)
Authorship as cultural performance: new perspectives in authorship studies
No full textThis article proposes a performative model of authorship, based on the historical alternation between predominantly 'weak' and 'strong' author concepts and related practices of writing, publication and reading. Based on this model, we give a brief overview of the historical development of such author concepts in English literature from the Middle Ages to the twentieth century. We argue for a more holistic approach to authorship within a cultural topography, comprising social contexts, technological and media factors, and other cultural developments, such as the distinction between privacy and the public sphere
Assistance in medical insurance (on the example of InsCo "Ingo Ukraine")
No full textУ роботі розглядаються теоретичні аспекти розвитку медичного
страхування в Україні; особливостей врегулювання збитків у медичному страхуванні. Проаналізовано систему медичного ассистансу на прикладі ПраТ «Інго Україна»; проведена оцінка системи врегулювання збитків на підприємстві. Запропоновано напрями розвитку маркетингу у медичному страхуванні
України; шляхи вдосконалення системи врегулювання збитків.The work deals with the theoretical aspects development of medical
insurance in Ukraine; peculiarities of the settlement of losses in medical insurance. Author analysis a system of medical assistances with example on InsCo "Ingo Ukraine"; An estimation of the system of claims settlement at the company is carried out
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