Functional recycling of C2 domains throughout evolution: A comparative study of synaptotagmin, protein kinase C and phospholipase C by sequence, structural and modelling approaches

The C2 domain is one of the most frequent and widely distributed calcium-binding motifs. Its structure comprises an eight-stranded beta-sandwich with two structural types as if the result of a circular permutation. Combining sequence, structural and modelling information, we have explored, at different levels of granularity, the functional characteristics of several families of C2 domains. At the coarsest level,the similarity correlates with key structural determinants of the C2 domain fold and, at the finest level, with the domain architecture of the proteins containing them, highlighting the functional diversity between the various subfamilies. The functional diversity appears as different conserved surface patches throughout this common fold. In some cases, these patches are related to substrate-binding sites whereas in others they correspond to interfaces of presumably permanent interaction between other domains within the same polypeptide chain. For those related to substrate-binding sites, the predictions overlap with biochemical data in addition to providing some novel observations. For those acting as protein-protein interfaces' our modelling analysis suggests that slight variations between families are a result of not only complementary adaptations in the interfaces involved but also different domain architecture. In the light of the sequence and structural genomic projects, the work presented here shows that modelling approaches along with careful sub-typing of protein families will be a powerful combination for a broader coverage in proteomics. (C) 2003 Elsevier Ltd. All rights reserved.

Phosphatidylinositol 3-kinase C2 alpha is essential for ATP-dependent priming of neurosecretory granule exocytosis

Neurotransmitter release and hormonal secretion are highly regulated processes culminating in the calcium-dependent fusion of secretory vesicles with the plasma membrane. Here, we have identified a role for phosphatidylinositol 3-kinase C2 alpha (PI3K-C2 alpha) and its main catalytic product, PtdIns3P, in regulated exocytosis. In neuroendocrine cells, PI3K-C2 alpha is present on a subpopulation of mature secretory granules. Impairment of PI3K-C2 alpha function specifically inhibits the ATP-dependent priming phase of exocytosis. Overexpression of wild-type PI3K-C2 alpha enhanced secretion, whereas transfection of PC12 cells with a catalytically inactive PI3K-C2 alpha mutant or a 2xFYVE domain sequestering PtdIns3P abolished secretion. Based on these results, we propose that production of PtdIns3P by PI3K-C2 alpha is required for acquisition of fusion competence in neurosecretion.

Колекция от цифрови обекти за Балканската война (1912 –1913)

Доклад, поместен в сборника на Националната конференция "Образованието в информационното общество", Пловдив, май, 2012 г.

Expression of Bf/C2 Gene(S) in the Japanese Medaka Fish

Complement factor B and C2 are two central serine proteases of the alternative and classical complement pathways, respectively, that serve as the catalytic subunits of the C3 convertase. Research has been completed using a female Japanese medaka fish, (Oryzias latipes), and other teleost and elasmobrach species in order to isolate eDNA clones and perform linkage analysis of the Bf/C2 gene(s). To further analyze the evolution of the complement system in teleosts, different tissues than the ones from previous studies of medaka fish were analyzed for the constitutive gene expression of factor B and C2. Bf/C2 sequences were amplified by reverse transcription-polymerase chain reaction with primers corresponding to the common amino acid sequences shared by mammalian Bf and C2. Agarose gel electrophoresis was used to visualize sample bands and to calculate the concentration of gene expression of the Bf/C2 gene(s) in each tissue. All five tissue types, kidney, liver, muscle, testis, and spleen from a male medaka fish demonstrated Bf/C2 gene(s) expression, confirming that the messages of Bf/C2 gene(s) are distributed throughout the medaka fish. Tissues of the spleen, liver, and kidney contained the highest concentrations of expression of Bf/C2 gene( s ), while tissues of the muscle and testis contained the lowest concentrations. This research also determined that RT-PCR allowed for more sensitive analysis of gene expression than other molecular biology techniques such as Northern blotting analysis.

Lincoln Institute Board of Curators Meeting Minutes, 1913 to May 1921

Board of Curators Meeting Minutes for Lincoln Institute (later Lincoln University) from 1913 to May, 1921.

Do ancoradouro à sala de espera: as obras de melhoramento do porto e a construção de uma Natal moderna (1893-1913)

Through the nineteenth century, it was constant in the discourse of the local norte-rio-grandenses (Natal city, Brazil) administrators, the appeal for subsidy to the central government for the works of the port of Natal upgrade. The port in the capital, the main route of the Rio Grande do Norte communication, because of the limitations attached to it, as the dunes surrounding the city spreading sand in the riverbed, and several reefs located along the coast, did not allow the entry in his berth larger ships. These difficulties brought major problems the province, who could not hold the flow of production coming from the inside, resulting in the north of Rio Grande political scene, questioning the centrality of Christmas position in the province. Only Republican scheme had been approved credit by the federal government for the improvement works of the port. The port became the Republican political discourse Potiguar one of the main promises to bring "progress" the Potiguar land, being placed as a central issue of which depend on the "future" of the state. The objective of this study is to analyse the emergence of a new port concept in speeches and interventions of the local ruling groups in the early twentieth century. We analyse the emergence of a modern notion of port, marked by the organizing effort, rationalization and regulation of port activities by the state, and the new relationship assumed by the harbour front to the city resulting from this new perception. The port has become for local leaders to groups of capital "waiting room", requiring change of the composition of urban space for integrating the port to the city. The Port of Natal became endowed with a pedagogical function, incorporating the urban fabric, codes, values and practices considered by local managers as modern and civilized. This new city space, considered a "waiting room", caused conflicts between the local ruling groups and influential figures in the Potiguar political field, which sought to encourage with the process of organizing the harbour front undesirable regarded figures in the city views as an impediment to the image of progress and modernity that the dominant groups intended to expose the port.

Shakespeare and the Birmingham Repertory Theatre 1913-1929

It is well known that the Birmingham Repertory Theatre launched the careers of some of the greatest twentieth-century Shakespearian actors including Laurence Olivier and Ralph Richardson. What is not so well known is that the Rep legend was based on a radical commitment to the innovative staging of Shakespeare which dates back to the earliest years of the century. By the 1920s this had initiated a profound shift in Shakespeare performance values which continues to inform modern production. In telling the story of Rep Shakespeare and the directors, designers and actors who contributed to the company's world-wide reputation, this book sets the work of the first purpose-built British repertory theatre in the context of the major aesthetic and organisational changes which were to transform twentieth-century theatre as a whole.

”Buffalo Bill and his Wild West Show”. William F. ”Buffalo Bill” Codyn ja hänen Villin lännen show’nsa julkisuuskuva yhdysvaltalaisessa aikalaislehdistössä vuosina 1883 ̶ 1913.

Tässä tutkielmassa tutkin yhdysvaltalaisen aikalaislehdistön lukijoilleen välittämää julkisuuskuvaa Buffalo Billistä ja hänen Villin lännen show’staan sen toiminnan aikana 1883 ̶ 1913. Primääriaineistona käytän The New York Timesiä, mutta lisäksi hyödynnän myös pienempiä paikallislehtiä täydentämään kuvaa. William F. ”Buffalo Bill” Cody on yksi Villin lännen tunnetuimmista hahmoista ja hänen suurin saavutuksensa oli sen legendojen tekeminen tutuksi maailmanlaajuiselle yleisölle. Villin lännen show’n ohjelma koostui viidestä pääteemasta: ratsastustaidoista, ampumataidoista, eläinnäytöksistä, näytelmistä sekä tasankointiaanien ja valkoisten välisistä konflikteista. Tutkitulla ajanjaksolla aikalaislehdistön kuvaukset osoittautuivat hyvin myönteisiksi show’ta kohtaan ja kilpailijoista huolimatta se oli The New York Timesin mukaan ”the only and original Wild West”. Show’ta mainostettiin koko perheelle sopivana ja sen esityksissä vieraili vuosien aikana miljoonia katsojia. Ohjelman kantavana ideana oli kuitenkin väkivallan välttämättömyys lännen valloittamisessa. Samalla show’hun kuuluneet intiaanit esiteltiin areenalla ja lehdistössä hyvin stereotyyppisinä vihollisina, maalattuina ja verenhimoisina. Lehdistö, joka välitti lukijoilleen varsin intensiivisiä kuvauksia tapahtumista showareenalla, huolestui esityksien vaikutuksista lapsiin ja nuoriin. Buffalo Billin yhteistyökumppanit rakensivat hänelle sankarillisen imagon viihderomaanien ja show’n avulla. Riitaisan avioeroprosessin myötä ennen niin hyvä julkisuuskuva lehdistössä alkoi murentua, kun naisseikkailut ja muut salaisuudet tulivat päivänvaloon. Suurista tuloista huolimatta Buffalo Billillä oli vaikeuksia hallita talouttaan anteliaisuutensa ja huonojen sijoituksien vuoksi. Iän karttuessa ja terveyden heikentyessä hänen roolinsa show’ssa väheni, minkä seurauksena myös median kiinnostus alkoi hiipua. Villin lännen show ajautui konkurssiin vuonna 1913, mutta sitä ennen se kiersi lukuisat kaupungit Pohjois-Amerikassa ja Euroopassa. Aikalaislehdistön mukaan Buffalo Bill ja show olivat tehneet suuren vaikutuksen Yhdysvaltojen entiseen siirtomaaisäntään Britanniaan ja seuraava askel on vertailla näiden kahden maan lehdistön suhtautumista esitykseen.

From physics to metaphysics: philosophy and style in the critical writings of T. S. Eliot (1913-1935)

This thesis considers Eliot's critical writing from the late 1910s till the mid-1930s, in the light of his PhD thesis - Knowledge and Experience in the Philosophy of F. H. Bradley - and a range of unpublished material: T S. Eliot's Philosophical Essays and Notes (1913- 4) in the Hayward Bequest (King's College, Cambridge University); T. S. Eliot's Family Papers in the T. S. Eliot Collection at the Houghton Library (Harvard University); and items from the Harvard University Archives at the Pusey Library. 'Me thesis offers a comprehensive view of Eliot's critical development throughout this important period. It starts by considering The Sacred Wood's ambivalence towards the metaphysical philosophy of F. H. Bradley and Eliot's apparent adoption of a scientific method, under the influence of Bertrand Russell. It will be argued that Eliot uses rhetorical strategies which simultaneously subvert the method he is propounding, and which set the tone for an assessment of his criticism throughout the 1920s. His indecision, in this period, about the label 'Metaphysical' for some poets of the seventeenth century, reveals the persistence of the philosophical thought he apparently rejects in 1916, when he chooses not to pursue a career in philosophy in Harvard. This rhetorical tactic achieves its fulfilment in Dante (1929), where Eliot finds a model in the medieval allegorical method and 'philosophical' poetry. Allegory is also examined in connection with the evaluation of Eliot's critical writings themselves to determine, for instance, the figurative dimension of his early scientific vocabulary and uncover metaphysical residues he had explicitly disowned but would later embrace. Finally, it is suggested that, the hermeneutics of allegory are historical and it is used here to test the relationship between Eliot's early and later critical writings, that is the early physics and the later metaphysics.

Charges against members of the House and lobby activities of the National association of manufacturers of the United States and others. Hearings before the Select Committee of the House of Representatives appointed under House resolution 198, Sixty-third Congress, first session, July 12 to [Sept. 19] 1913.

Mode of access: Internet.

On the temperature dependence of the rate coefficient of formation of C2+ from C + CH+

[EN] We carry out quasi-classical trajectory caculations for theC + CH+ → C2+ + H reaction on an ad hoc computed high-level ab initio potential energy surface. Thermal rate coefficients at the temperatures of relevance in cold interstellar clouds are derived and compared with the assumed, temperature-independent estimates publicly available in kinetic databases KIDA and UDfA. For a temperature of 10 K the database value overestimates by a factor of two the one obtained by us (thus improperly enhancing the destruction route of CH+ in astrochemical kinetic models) which is seen to double in the temperature range 5–300 K with a sharp increase in the first 50 K. The computed values are fitted via the popular Arrhenius–Kooij formula and best-fitting parameters α = 1:32 X 10-9 cm3s-1, β = 0:10 and γ = 2:19 K to be included in the online mentioned databases are provided. Further investigation shows that the temperature dependence of the thermal rate coefficient better conforms to the recently proposed so-called ‘deformed Arrhenius’ law by Aquilanti and Mundim.