Regulation of the IGK Locus and B Cell Development

Allelic exclusion coupled to lineage and stage specific regulation ensure the Igκ locus undergoes RAG mediated V-J recombination only at the small pre-BII stage of lymphocyte development. These mechanisms also ensure the final antigen receptor is monospecific and allow self-specific receptors to be recognised and altered at later stages of development. Allelic exclusion is controlled by mechanism involving either epigenetic based allele selection early in development or probabilistic activation of a single allele at the small pre-BII stage. Current models favour the probabilistic model based on an elegant GFP reporter system. We present a reappraisal of this models based on an absence of the originally detected probabilistic activation. We find the absence to be explained in part by an aberrant splice event generated by developmentally regulated Igκ germline promoter usage. The activity of the promoter was investigated using in-vitro models of critical events during the B cell development but their role remains elusive. Intense investigation for the last 20 years has determined that chromatic regulation underpins the stage and lineage specification of rearrangement. The protein factors responsible for this regulation remain unknown. Using transgene reporters of cis-acting sequences and in-vitro model systems of B cell development, we find an involvement for members of the zinc finger family of Ikaros transcription factors, IRF4 and LEF1. We determined a bipartite role for Ikaros whereby its activity could both suppress rearrangement prior to pre-BCR signalling and promote rearrangement thereafter, possibly through an IRF4 based mechanism. Finally we present evidence for a role for Ikaros protein in later stages of B cell development. We find modulation of Ikaros activity directly influences the ability of cells to differentiate to the plasma cell fate. We used a transgenic model to allow genome-wide mapping of the transcriptional events regulated by Ikaros and find multiple small modulations of factors and pathways

The Ungrudging Indian: The Political Economy of Salt in India, c. 1878–1947

This article investigates the long background to Mohandas K. Gandhi’s choice of salt as a symbol of protest against British colonial rule. Arguably the largest of all the colonial monopolies in India, the salt tax had the smallest effect on the lives of Indians when compared with other forms of deprivation and inequality. How was the salt monopoly different from other kinds of extractive colonialism? Why did salt never become part of the lexicon of protest against British rule until 1930? The article discusses the operation of the salt monopoly, its impact on consumption and health, the criticism it provoked, and the growth of support in the 1920s for protection for the domestic salt industry.Peer Reviewe

Kinetics of substrate oxidation and hydrogen peroxide production by Mycoplasma mycoides subsp. mycoides Large Colony (LC) type and Mycoplasma mycoides subsp. capri

Mycoplasma mycoides subsp. mycoides Large Colony (LC) type is a pathogen of goats causing contagious agalactia and respiratory disease, found on all continents where small ruminants are kept. It shares close genetic characteristics with M. mycoides subsp. capri. Substrate oxidation by 22 strains of M. mycoides subsp. mycoides LC from nine countries was compared with that of eight strains of M. mycoides subsp. capri from five countries. There was considerable similarity in the substrates used, but substrate saturation coefficients (Ks) varied for different substrates. Substrate utilization patterns and Ks values did not (1) significantly differentiate the LC strains from each other, (2) show any correlation with geographical origin, or (3) distinguish the LC strains from the capri strains. These results support previous studies justifying the reclassification of these subspecies as a single species

HOMETOWN: A Cultural Analysis of a Small Southern Town

In recognition of the fact that in American Society distinctions are made on the basis of race, we are concerned with social organization within the Negro community. In any society where distinctions are made on a racial basis, where the races are segregated, and one is ascribed an inferior status, the kind of social organization that evolves in the segregated community will be characterized by accommodation to the larger society. In the many research monographs on the Negro in the South this theme predominates.2 Up to now, no analysis of the Negro community in the Southwest, specifically in Texas, has been made. It is quite possible that there is so much similarity between the social organization in the Negro community in Texas and those communities in the South which have been more thoroughly investigated that such a study is unnecessary. However, only empirical evidence can establish the assumption as a fact. It was for this reason that the present study was undertaken. The present study is based upon the following hypotheses: 1. That in any society at a particular time the institutional structure is subject to analysis and description. 2. That basically the institutional structure of social organization within any community is similar to that of all other communities within the larger society. Those differences that do exist are a response to geographical, economic, or racial factors, and are differences of degree rather than differences of kind. 3. That social organization in the Negro Community is similar to social organization of the larger community, subject only to those conditions of race which give him an inferior status. The method employed will be descriptive primarily, although statistical data will be relied upon from time to time to support the thesis. 2Sutherland, Robert, Color, Class, and Personality

VRML Virtual Worlds - An Alternative to the Desktop Metaphor for GUI's?

Metaphors are commonly used by software developers in the creation of GUI's. This paper looks at the use of multi-user VRML to create virtual metaphors, developing a conceptual design tool that can be used intuitively with little or no training

MEMS 411: Rowing Force Plate

The Rowing Force Plate is a device that is designed to measure a rower’s forceover time so that they can understand how hard they are rowing. Most rowingaids communicate the speed at which someone is rowing, which is variant on waterspeed, wind speed, and other inconsistent environmental and situational factors.Force, however, can be consistently measured and is a better indicator of effort arower is exerting. Other products that measure force do exist, but use complex andexpensive technology, unlike our design.After brainstorming and analyzing multiple possible designs, we concluded to usefour force sensors under the existing shoes in the boat would be the most feasibledesign. These force sensors would be connected to an Arduino (a microcontroller),which would then display data to a screen for the rower to read while rowing. Thisdesign was chosen over other concepts because of its high expected accuracy, lowweight, and fairly easy integration with existing systems.We set three performance goals of measuring force at time point, accuratelymeasuring force, and making the device strong in tension for safety purposes. Theinitial prototype was able to measure force at time points and be strong in tension,but could not measure force accurately. This was due to electronic issues withold load cells measuring force and integrating with the circuit. With new loadcells, we were able to meet our prototype performance goals, and were even able tosuccessfully use the device in a real boat on the water

Enhancing cultural competence: Trans-Atlantic experiences of European and Canadian nursing students

This paper describes the enhancement of cultural competence through trans-Atlantic rural community experiences of European and Canadian nursing students using critical incident technique (CIT) as the students' reflective writing method. The data generated from 48 students' recordings about 134 critical incidents over a 2-year project were analysed by qualitative content analysis. Five main learning categories were identified as: cross-cultural ethical issues; cultural and social differences; health-care inequalities; population health concerns; and personal and professional awareness. Four emergent cultural perspectives for the health sector that became apparent from the reflections were: health promotion realm; sensitivity to social and cultural aspects of people's lives; channels between the health sector and society; cultural language and stories of local people. CIT was successfully used to foster European and Canadian undergraduate students' cultural reflections resulting in considerations and suggestions for future endeavours to enhance cultural competence in nursing education

The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

Bootstrapping Trust with Partial and Subjective Observability

Assessment of trust and reputation typically relies on prior experiences of a trustee agent, which may not exist, e.g. especially in highly dynamic environments. In these cases stereotypes can be used, where traits of trustees can be used as an indicator of their behaviour during interactions. Communicating observations of traits to witnesses who are unable to observe them is difficult, however, when the traits are interpreted subjectively. In this paper we propose a mechanism for learning translations between such subjective observations, evaluating it in a simulated marketplace