Designing conformational control of human tissue transglutaminase

Understanding the mechanisms of enzymes is crucial for our understanding of their role in biology and for designing methods to perturb or harness their activities for medical treatments, industrial processes, or biological engineering. One aspect of enzymes that makes them difficult to fully understand is that they are in constant motion, and these motions and the conformations adopted throughout these transitions often play a role in their function.

Traditionally, it has been difficult to isolate a protein in a particular conformation to determine what role each form plays in the reaction or biology of that enzyme. A new technology, computational protein design, makes the isolation of various conformations possible, and therefore is an extremely powerful tool in enabling a fuller understanding of the role a protein conformation plays in various biological processes.

One such protein that undergoes large structural shifts during different activities is human type II transglutaminase (TG2). TG2 is an enzyme that exists in two dramatically different conformational states: (1) an open, extended form, which is adopted upon the binding of calcium, and (2) a closed, compact form, which is adopted upon the binding of GTP or GDP. TG2 possess two separate active sites, each with a radically different activity. This open, calcium-bound form of TG2 is believed to act as a transglutaminse, where it catalyzes the formation of an isopeptide bond between the sidechain of a peptide-bound glutamine and a primary amine. The closed, GTP-bound conformation is believed to act as a GTPase. TG2 is also implicated in a variety of biological and pathological processes.

To better understand the effects of TG2’s conformations on its activities and pathological processes, we set out to design variants of TG2 isolated in either the closed or open conformations. We were able to design open-locked and closed-biased TG2 variants, and use these designs to unseat the current understanding of the activities and their concurrent conformations of TG2 and explore each conformation’s role in celiac disease models. This work also enabled us to help explain older confusing results in regards to this enzyme and its activities. The new model for TG2 activity has immense implications for our understanding of its functional capabilities in various environments, and for our ability to understand which conformations need to be inhibited in the design of new drugs for diseases in which TG2’s activities are believed to elicit pathological effects.

Silenced angels: an obscure Saint Theresa in George Eliots Middlemarch

A presente dissertação objetiva a comparação proposta no Prelúdio do romance Middlemarch por sua autora George Eliot entre a protagonista da obra, Dorothea Brooke, e a figura histórica Teresa dÁvila. A partir de tal estudo, busca-se compreender de que modo a situação específica da mulher na Era Vitoriana é articulada no romance de modo a espelhar a crise ontológica e epistemológica do próprio ser humano diante das transformações consolidadas com o Iluminismo e as revoluções liberais do século XVIII que culminariam na morte de Deus. Dorothea mostra-se uma cristã tão fervorosa quanto a Teresa quinhentista, mas faltam-lhe certezas e a resolução para concretizar as reformas sociais que defende, pois ela encarna o mito de feminilidade oitocentista batizado de Anjo do Lar ideal de sujeição feminina à ordem falocêntrica cujas funções são a proteção e difusão da moralidade burguesa e a substituição de elementos cristãos no universo do sagrado a uma sociedade cada vez mais materialista e insegura de valores absolutos. As aflições de Dorothea representam as aflições da mulher vitoriana, mas o momento crítico desta mulher reflete, em Middlemarch, uma crise muito maior do Ocidente, que teve início com a Era da Razão

Experiments on preservation and weathering of net twines

Koura (1963) reporting the results of the comparative studies on different preservation methods of cotton twines stated that "by the difference of rotting in the different waters, not ever one method may be the most economical one". The observations were simultaneously made at Alexandria in Egypt in the sub-tropical region and Cuxhaven in the estuary of the River Elbe in the temperate zone. The course of weathering and effect of immersion in water of man-made fibres have also been mentioned in this communication. Subsequently work on similar lines were extended to Cochin in the tropical region with Cuxhaven and Hamburg as the other places of observation and the results of these studies are presented in this paper.

Taxonomic study of coenocytic green algae commonly growing on the coast of Karachi

Twelve commonly occurring coenocytic and siphonaceous species of marine benthic algae, i.e., Bryopsis pennatta Lamouroux, Caulerpa chemnitzia (Esper) Lamouroux, Ca. faridii Nizamuddin, Ca. manorensis Nizamuddin, Ca. racemosa (Forsskal) J. Agardh, Ca. taxifolia. (Vahl) C. Agardh, Chaetomorpha antennina (Bory de Saint-Vincent) Kutzing, Cladophora uncinella Harvey, Codium decorticatum (Woodward) Howe, Co. flabellatum Nizamuddin, Co. iyengarii Borgesen, and Valoniopsis pachynema (Martens) Borgesen, belonging to four different orders of the class Bryopsidophyceae, division Chlorophyta, were collected from the intertidal region of different coastal areas near Karachi (Pakistan) and investigated taxonomically. Codium decorticatum is a new report from this region and Co. decorticatum, Co. flabellatum and Co. iyengarii are described for the first time from the coast of Pakistan.

Copper and manganese forms in Lake Edku sediments, Alexandria, Egypt

Lake Edku is one of the Nile Delta lakes. It is subjected to contaminations by several anthropogenic materials such as trace elements and other wastes. The distribution of the different chemical forms of copper and manganese has been studied using sequential extraction techniques. Chemical analysis of the sediments shows that CaCO sub(3) ranged from 3.7% to 9.6% and organic matter from 3.06% to 8.11%. The results indicate that the distribution of manganese among the six chemical forms in the sediments of the lake obeys the following order: Mn-residual>Mn-carbonate>Mn-moderately reducible>Mn-organic form>Mn-exchangeable > Mn-easily reducible fraction. Also, the data revealed that more than 50% of the total manganese was found in the residual form, while the remainder was distributed among the other forms. In contrast, more than 70% of the total copper content was associated with the five chemical forms (exchangeable, carbonate, easily and moderately reducible and organic forms). Generally, the enrichment of manganese in the residual form revealed the important role in building up of clay minerals, while the distribution of copper among the different forms reflects an important role in biological and biochemical processes.

Dinoflagellate "brown tides" in Alexandria, Egypt waters during 1997-1998

Charles Darwin the research ship undertook an Oceanographic Cruise in 1986, CD 86/17 of the North Arabian Sea. Sediment cores were collected between 15° and 25°N. In this study sediment cores collected from deep Indus and Oman basins (CD 1715, CD 1730, CD 1738) have been analyzed for mineralogy, water content and porosity. In general, the cores are mainly composed of clay to silt sized terrigenous and biogenic constituents. Quartz, chlorite and illite are the common minerals of Arabian Sea sediments. Porosity determined by water content of sediments has been correlated with quartz/chlorite and quartz/illite peak ratios to show a relationship between mineral composition and physical properties.

Saint Martin's biological survey report, Bangladesh: fauna and flora checklist

This report presents an overview of the land-based biodiversity of the St Martin's Island, based on field visits during October 2014 and from historical data.

Report on Saint Martin's Island ecosystem boundary, Bangladesh: final report

This report seeks to strengthen national capacity on managing Marine Protected Area (MPAs) in Bangladesh. St Martin's Island was used as the pilot ecosystem boundary delineation.

Life of St. Vincent of Paul, founder of the Congregation of the Mission and of the Sisters of Charity / M. Collet... ; translated from the French by a Catholic clergyman.

http://www.archive.org/details/lifeofstvincento00colluoft

The day-breaking, if not the sun-rising of the Gospell with the Indians in New-England.

University of California Libraries

The Whitby life of Gregory the Great: exegesis and hagiography

The eight-century Whitby Vita Gregorii is one of the earliest examples of Anglo-Saxon hagiography, and is the earliest surviving life of Gregory the Great (590-604). The work has proved itself an anomaly in subject matter, style and approach, not least because of the writer’s apparently arbitrary insertion of an account of the retrieval of the relics of the Anglo-Saxon King Edwin (d.633). There has, however, been relatively little research on the document to date, the most recent concentrating on elements in the Gregorian material in the work. The present thesis adapts a methodology which identifies patristic exegetical themes and techniques in the Vita. That is not only in material originating from the pen of Gregory himself, which is freely quoted and cited by the writer, but also in the narrative episodes concerning the Pope. It also identifies related exegetical themes underlying the narrative of the Anglo-Saxon material in the document, and this suggests that the work is of much greater coherence then has previously been thought. In the course of the thesis some of the Vita Gregorii’s major patristic themes are compared with Bede and other insular writers in the presentation of topics that have been of considerable interest to insular historians in recent years. That is themes including: the conversion and salvation of the English people; the ideal pastor; monastic influence on formation of Episcopal spiritual authority; relations between king and bishop. The thesis also includes a re-evaluation of the possible historical context and purpose of the work, and demonstrates the value of a proper understanding of the Vita’s spiritual nature in order to achieve this. Finally the research is supported by a new structural analysis of the entire Vita Gregorii as an artefact formed within literary traditions.