Copy of bill of costs for Lewis Gomes' denization

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Copy of letter from Jacques Judah Lyons to Sir Moses Montefiore enclosing bill of exchange for Palestinian Jews

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Modelling multiple disulphide loop containing polypeptides by random conformation generation. The test cases of α-conotoxin GI and edothelin I

A general procedure for arriving at 3-D models of disulphiderich olypeptide systems based on the covalent cross-link constraints has been developed. The procedure, which has been coded as a computer program, RANMOD, assigns a large number of random, permitted backbone conformations to the polypeptide and identifies stereochemically acceptable structures as plausible models based on strainless disulphide bridge modelling. Disulphide bond modelling is performed using the procedure MODIP developed earlier, in connection with the choice of suitable sites where disulphide bonds could be engineered in proteins (Sowdhamini,R., Srinivasan,N., Shoichet,B., Santi,D.V., Ramakrishnan,C. and Balaram,P. (1989) Protein Engng, 3, 95-103). The method RANMOD has been tested on small disulphide loops and the structures compared against preferred backbone conformations derived from an analysis of putative disulphide subdatabase and model calculations. RANMOD has been applied to disulphiderich peptides and found to give rise to several stereochemically acceptable structures. The results obtained on the modelling of two test cases, a-conotoxin GI and endothelin I, are presented. Available NMR data suggest that such small systems exhibit conformational heterogeneity in solution. Hence, this approach for obtaining several distinct models is particularly attractive for the study of conformational excursions.

O trafico da escravatura, e o Bill de Lord Palmerston

Ex-secretário de Estado dos Negócios Estrangeiros de Portugal, o autor analisa as medidas tomadas por Portugal e Inglaterra em relação à abolição do tráfico de escravos. O Parlamento britânico adotou, em 1840, uma lei proposta por Lord Palmerston, autorizando os navios de guerra britânicos a "capturar, em todos os mares, as embarcações que, com bandeira portuguesa, se empreguem ou sejam suspeitas de empregar-se no tráfico da escravatura. O visconde de Sá da Bandeira, que havia negociado com o governo inglês vários acordos e projetos de tratados, escreveu um livro sobre o assunto, onde há informações históricas importantes não só a respeito da escravidão nas colônias portuguesas como nas inglesas, nas dinamarquesas, francesas, espanholas e nos Estados Unidos

Przyszłość amerykańskiej potęgi

W artykule autor analizuje percepcję potęgi amerykańskiej. Nie zgadza się z założeniem innych badaczy, iż nastąpi upadek siły Stanów Zjednoczonych. Nawet gdyby do tego doszło, USA nadal będą „Primus Inter Pares” wśród innych członków Wielkiej Szachownicy. Przygląda się On uważnie wadom i zaletom polityki tego mocarstwa. Dzieli potęgę imperium na trzy płaszczyzny: segment siły militarnej, potencjał ekonomiczny oraz soft power. Jego zdaniem tylko rozsądne użycie odpowiedniego zasobu siły „miękkiej” lub „twardej” prowadzi do smart power, czyli rozważnej polityki. Na tym właśnie powinno się opierać amerykańskie mocarstwo, a nie na nadużywaniu siły. USA powinny określić swoją rolę na arenie międzynarodowej, nie bać się „nadwyrężenia imperialnego” oraz stać się prawdziwym przywódcą a nie tylko hegemonem. Takie właśnie postępowanie, polegające na właściwym użyciu swojej potęgi doprowadzi do wzajemnej kooperacji, jak również wzrostu bezpieczeństwa międzynarodowego.

Niezamknięte księgi – o księgach cechowych na Pomorzu Zachodnim

Niniejsze badanie koncentruje się na księgach powstałych w wyniku działalności organizacji cechowych na Pomorzu Zachodnim. Jest to specyficzny rodzaj zabytków, w których odzwierciedla się życie zarówno zawodowe, jak i społeczne oraz towarzyskie korporacji. Pisane były niejednokrotnie przez kolejne pokolenia, obejmują nawet kilka stuleci, przez co stanowią cenne źródło historyczne. Księgi dzieliły się na urzędowe, obejmujące całokształt działalności (Amtsbuch), oraz wyspecjalizowane – księgi protokołów (Protokollbuch), księgi mistrzów, czeladników i uczniów (Meister-, Gesellen- i Lehrjungenbuch), księgi rachunkowe (Rechnungsbuch) i księgi normatywne. Tekst ukazuje znaczną różnorodność kwestii poruszanych w poszczególnych rodzajach ksiąg, a także ich formę zewnętrzną. Podstawę do badań stanowią obiekty przechowywane w Archiwum Państwowym w Szczecinie. Daleko posunięte podobieństwo w funkcjonowaniu cechów poza granicami Pomorza pozwala na przeniesienie wniosków również na inne organizacje cechowe.

Filmy dla muzyki. Egar Varèse i Bill Viola

Anno Mungen focuses on “films made for music” and on the rare phenomenon of ‘music depicted by picture’ (S. Kracauer). The narration about historical metamorphoses of varied forms of coexistence between music and picture is accompanied by a reflection on the laws of audiovisual perception. The main examples are discussed, these concentrating on the artistic ideas of Walt Disney’s animated film Fantasia and – first of all – on Edgard Varèse’s bold ideal of spatial music, attained post mortem in Bill Viola’s Déserts (1994). After a detailed analysis of Viola’s film the author admits that the movie pictures deduced from music are able to render the latter its own substantial visual power.

Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes.

-Transgenic mouse models have been developed to manipulate beta-adrenergic receptor (betaAR) signal transduction. Although several of these models have altered betaAR subtypes, the specific functional sequelae of betaAR stimulation in murine heart, particularly those of beta2-adrenergic receptor (beta2AR) stimulation, have not been characterized. In the present study, we investigated effects of beta2AR stimulation on contraction, [Ca2+]i transient, and L-type Ca2+ currents (ICa) in single ventricular myocytes isolated from transgenic mice overexpressing human beta2AR (TG4 mice) and wild-type (WT) littermates. Baseline contractility of TG4 heart cells was increased by 3-fold relative to WT controls as a result of the presence of spontaneous beta2AR activation. In contrast, beta2AR stimulation by zinterol or isoproterenol plus a selective beta1-adrenergic receptor (beta1AR) antagonist CGP 20712A failed to enhance the contractility in TG4 myocytes, and more surprisingly, beta2AR stimulation was also ineffective in increasing contractility in WT myocytes. Pertussis toxin (PTX) treatment fully rescued the ICa, [Ca2+]i, and contractile responses to beta2AR agonists in both WT and TG4 cells. The PTX-rescued murine cardiac beta2AR response is mediated by cAMP-dependent mechanisms, because it was totally blocked by the inhibitory cAMP analog Rp-cAMPS. These results suggest that PTX-sensitive G proteins are responsible for the unresponsiveness of mouse heart to agonist-induced beta2AR stimulation. This was further corroborated by an increased incorporation of the photoreactive GTP analog [gamma-32P]GTP azidoanilide into alpha subunits of Gi2 and Gi3 after beta2AR stimulation by zinterol or isoproterenol plus the beta1AR blocker CGP 20712A. This effect to activate Gi proteins was abolished by a selective beta2AR blocker ICI 118,551 or by PTX treatment. Thus, we conclude that (1) beta2ARs in murine cardiac myocytes couple to concurrent Gs and Gi signaling, resulting in null inotropic response, unless the Gi signaling is inhibited; (2) as a special case, the lack of cardiac contractile response to beta2AR agonists in TG4 mice is not due to a saturation of cell contractility or of the cAMP signaling cascade but rather to an activation of beta2AR-coupled Gi proteins; and (3) spontaneous beta2AR activation may differ from agonist-stimulated beta2AR signaling.

beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi.

Phosphorylation of the beta(2) adrenoreceptor (beta(2)AR) by cAMP-activated protein kinase A (PKA) switches its predominant coupling from stimulatory guanine nucleotide regulatory protein (G(s)) to inhibitory guanine nucleotide regulatory protein (G(i)). beta-Arrestins recruit the cAMP-degrading PDE4 phosphodiesterases to the beta(2)AR, thus controlling PKA activity at the membrane. Here we investigate a role for PDE4 recruitment in regulating G protein switching by the beta(2)AR. In human embryonic kidney 293 cells overexpressing a recombinant beta(2)AR, stimulation with isoprenaline recruits beta-arrestins 1 and 2 as well as both PDE4D3 and PDE4D5 to the receptor and stimulates receptor phosphorylation by PKA. The PKA phosphorylation status of the beta(2)AR is enhanced markedly when cells are treated with the selective PDE4-inhibitor rolipram or when they are transfected with a catalytically inactive PDE4D mutant (PDE4D5-D556A) that competitively inhibits isoprenaline-stimulated recruitment of native PDE4 to the beta(2)AR. Rolipram and PDE4D5-D556A also enhance beta(2)AR-mediated activation of extracellular signal-regulated kinases ERK12. This is consistent with a switch in coupling of the receptor from G(s) to G(i), because the ERK12 activation is sensitive to both inhibitors of PKA (H89) and G(i) (pertussis toxin). In cardiac myocytes, the beta(2)AR also switches from G(s) to G(i) coupling. Treating primary cardiac myocytes with isoprenaline induces recruitment of PDE4D3 and PDE4D5 to membranes and activates ERK12. Rolipram robustly enhances this activation in a manner sensitive to both pertussis toxin and H89. Adenovirus-mediated expression of PDE4D5-D556A also potentiates ERK12 activation. Thus, receptor-stimulated beta-arrestin-mediated recruitment of PDE4 plays a central role in the regulation of G protein switching by the beta(2)AR in a physiological system, the cardiac myocyte.

Direct evidence that Gi-coupled receptor stimulation of mitogen-activated protein kinase is mediated by G beta gamma activation of p21ras.

Stimulation of Gi-coupled receptors leads to the activation of mitogen-activated protein kinases (MAP kinases). In several cell types, this appears to be dependent on the activation of p21ras (Ras). Which G-protein subunit(s) (G alpha or the G beta gamma complex) primarily is responsible for triggering this signaling pathway, however, is unclear. We have demonstrated previously that the carboxyl terminus of the beta-adrenergic receptor kinase, containing its G beta gamma-binding domain, is a cellular G beta gamma antagonist capable of specifically distinguishing G alpha- and G beta gamma-mediated processes. Using this G beta gamma inhibitor, we studied Ras and MAP kinase activation through endogenous Gi-coupled receptors in Rat-1 fibroblasts and through receptors expressed by transiently transfected COS-7 cells. We report here that both Ras and MAP kinase activation in response to lysophosphatidic acid is markedly attenuated in Rat-1 cells stably transfected with a plasmid encoding this G beta gamma antagonist. Likewise in COS-7 cells transfected with plasmids encoding Gi-coupled receptors (alpha 2-adrenergic and M2 muscarinic), the activation of Ras and MAP kinase was significantly reduced in the presence of the coexpressed G beta gamma antagonist. Ras-MAP kinase activation mediated through a Gq-coupled receptor (alpha 1-adrenergic) or the tyrosine kinase epidermal growth factor receptor was unaltered by this G beta gamma antagonist. These results identify G beta gamma as the primary mediator of Ras activation and subsequent signaling via MAP kinase in response to stimulation of Gi-coupled receptors.

Termination of tenancies for tenant default: Law Commission's draft Bill

Reviews key proposals of a draft Bill set out in Command Paper: The Law Commission: Termination of Tenancies for Tenant Default (Cm.6946), aimed at replacing the existing law on forfeiture of tenancies. Summarises the main elements of the proposed termination action by landlords, the events justifying such an action, the time limits for serving default notices, the revised range of court orders available and the considerations influencing which type of order to make. Examines the position of qualifying interest holders and the circumstances in which summary termination notices are prohibited.