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.

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.

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.

Heterotopias of mental health care: The role of space in experiences of distress, madness and mental health service use.

The change from an institutional to community care model of mental health services can be seen as a fundamental spatial change in the lives of service users (Payne, 1999; Symonds & Kelly, 1998; Wolch & Philo, 2000). It has been argued that little attention has been paid to the experience of the specific sites of mental health care, due to a utopic (idealised and placeless) idea of ‘community’ present in ‘community care’ (Symonds, 1998). This project hence explored the role of space in service users’ experiences, both of mental health care, and community living. Seventeen ‘spatial interviews’ with service users, utilising participatory mapping techniques (Gould & White, 1974; Herlihy & Knapp, 2003; Pain & Francis, 2003), plus seven, already published first person narratives of distress (Hornstein, 2009), were analysed using thematic analysis (Braun & Clarke, 2006). Mental health service sites are argued to have been described as heterotopias (Foucault, 1986a) of a ‘control society’ (Deleuze, 1992), dominated by observation and the administration of risk (Rose, 1998a), which can in turn be seen to make visible (Hetherington, 2011) to service users a passive and stigmatised subject position (Scheff, 1974; 1999). Such visible positioning can be seen to ‘modulate’ (Deleuze, 1992) participants’ experiences in mainstream space. The management of space has hence been argued to be a central issue in the production and management of distress and madness in the community, both in terms of a differential experience of spaces as ‘concordant’ or ‘discordant’ with distress, and with movement through space being described as a key mediator of experiences of distress. It is argued that this consideration of space has profound implications for the ‘social inclusion’ agenda (Spandler, 2007; Wallcraft, 2001).

An Address of members of the House of Representatives of the Congress of the United States, to their constituents, on the subject of the war with Great Britain. --

Signed by George Sullivan and thirty-three other Federalist members.

Garden of the Chapman Park Hotel, Wilshire Boulevard, Los Angeles, 1935

Garden of the Chapman Park Hotel, Wilshire Boulevard between Mariposa and Alexandria Avenues, Los Angeles, 1935. Formerly named the Alexandria Hotel, it was built in 1906 and enlarged in 1909. The Santa Ysabel Land Company, controlled by Charles C. Chapman and his son, Stanley Chapman, purchased the hotel in 1930. It housed the United States women for the 1932 Olympics in Los Angeles.

Alexandria Daily Gazette, 9 September 1812 (vol. 12, no. 3744) - Newspaper

Volumes of interest were published in 1812 with articles about the War of 1812. Issue for Sept. 9, 1812 includes a proclamation by Major General Isaac Brock.

Methods of generating carrier-envelope-phase stabilized, intense, few-cycle laser pulses

Ultrafast laser pulses have become an integral part of the toolbox of countless laboratories doing physics, chemistry, and biological research. The work presented here is motivated by a section in the ever-growing, interdisciplinary research towards understanding the fundamental workings of light-matter interactions. Specifically, attosecond pulses can be useful tools to obtain the desired insight. However access to, and the utility of, such pulses is dependent on the generation of intense, few-cycle, carrier-envelope-phase stabilized laser pulses. The presented work can be thought of as a sort of roadmap towards the latter. From the oscillator which provides the broadband seed to amplification methods, the integral pieces necessary for the generation of attosecond pulses are discussed. A range of topics from the fundamentals to design challenges is presented, outfitting the way towards the practical implementation of an intense few-cycle carrier-envelope-phase stabilized laser source.

O culto a Serápis e a coexistência helénico-egípcia na Alexandria ptolomaica

O estabelecimento do culto ao deus Serápis na antiga cidade cosmopolita de Alexandria, capital dos Ptolomeus, em torno de uma imagem única e híbrida, respondeu à necessidade de harmonização intercultural dos dois mais importantes agrupamentos populacionais de Alexandria (os autóctones egípcios e os imigrantes greco-macedónios) e constituiu um factor de superação de anteriores e antigas antíteses e diferenças que os opunham, desenvolvidas com a ocupação grega do Egipto, e que eram,na viragem do séc. IV a.C., um dos maiores problemas e desafios colocados ao novo poder político, geneticamente oriundo da Macedónia, mas residente no Egipto.