ABCC Subfamily Vacuolar Transporters are Involved in Pb (Lead) Detoxification in Saccharomyces cerevisiae

The present work has as objective to contribute for the elucidation of the mechanism associated with Pb detoxification, using the yeast Saccharomyces cerevisiae as a model organism. The deletion of GTT1 or GTT2 genes, coding for functional glutathione transferases (GST) enzymes in S. cerevisiae, caused an increased susceptibility to high Pb concentrations (500-1000 μmol L(-1)). These results suggest that the formation of glutathione-Pb conjugate (GS-Pb), dependent of GSTs, is important in Pb detoxification. The involvement of ATP-binding cassette (ABC) vacuolar transporters, belonging to class C subfamily (ABCC) in vacuolar compartmentalization of Pb, was evaluated. For this purpose, mutant strains disrupted in YCF1, VMR1, YBT1 or BPT 1 genes were used. All mutants tested, without vacuolar ABCC transporters, presented an increased sensitivity to 500-1000 μmol L(-1) Pb comparative to wild-type strain. Taken together, the obtained results suggest that Pb detoxification, by vacuolar compartmentalization, can occur as a result of the concerted action of GSTs and vacuolar ABCC transporters. Pb is conjugated with glutathione, catalysed by glutathione transferases and followed to the transport of GS-Pb conjugate to the vacuole by ABCC transporters.

A formação e o desenvolvimento de arranjos cooperativos sob a ótica da imersão social e da economia dos custos de transação: um estrudo de caso na Coopercam e na Unipesca

The current study analyzes the birth and development of two strategic alliances established between shrimp producers in Rio Grande do Norte: the Unipesca and the Coopercam. To achieve this aim, two approaches which, at first sight, could be considered contradictory were used: the Transactional Costs Economy and Embeddedness. The first approach is fundamentally based in the studies of Williamson (1985; 1991; 1996; 1999; 2000; 2002). Embededness, on the other hand, went through the review of a series of authors, such as Burt (1992), Granovetter (1973; 1985), Uzzi (1997), Gulati (1994; 1995; 1997; 1998; 1999; 2000), Nielsen (2005), Ring (2002), Ring and Van de Ven (1994), Zafirovski (2002), among others. To analyze the birth and development of the cooperatives in this study, Gulati s work (1998) was used. This study shows the steps to be studied for a better comprehension of an alliance: the decision of starting an alliance and the choice of the partners, the decision about the governance structure, the evolution of the alliance and the development of the companies which established this partnership. To carry this study out, a study case accordingly to Yin s proposal (2001) was adopted. Semi-structured interviews with pre-defined plots were conducted in two phases: in the beginning of 2006 and in the beginning of 2007. The subjects from the research were, in 2006, representative members of the main associations and corporations, besides the shrimp producers from the state, when the context of the activity was set. In the second phase, in 2007, representative members from the two cooperatives that were listed above were interviewed the president from Coopercam and the marketing manager from Unipesca. Besides these two members, directors from two important organizations in each of these cooperatives were also interviewed, giving out the necessary information for the research. Secondary data was also collected from the Brazilian Association of Crab producers website, as well as from news from important newspapers in RN, such as Tribuna do Norte. The primary data was analyzed in terms of quality, accordingly to the documental analysis technique. Thus, through the data that was collected, it can be concluded that the reasons that motivated the companies to cooperate can be explained in terms of the transactional costs economy. However, the choice of partners is more connected to aspects approached by the social embededness. When aspects related to development and evolution were analyzed, it could be seen that both aspects from TCE and Embededness were vital to explain the development of the cooperatives mentioned

Regolazione dell'attivita dei trasportatori MXR nel mitilo (Mytilus galloprovincialis)

L’elevato consumo e il limitato tasso di rimozione dei farmaci favoriscono l’entrata di questi composti, biologicamente attivi, nell’ambiente acquatico. Essendo continuamente aggiunti, più velocemente di quanto si degradino, tali sostanze diventano pseudo-persistenti nell’ambiente, e gli organismi acquatici possono risultarne esposti a lungo termine. Per limitare gli effetti avversi di ambienti inquinanti, gli organismi più resistenti hanno sviluppato vari meccanismi di protezione cellulare, fra cui il sistema denominato Multixenobiotic resistance (MXR). Tale meccanismo agisce da sistema di detossificazione attraverso l’azione di specifici trasportatori transmembrana quali la P-glicoproteina (Pgp) e la Multidrug Resistance-associated Protein (MRP). Questi, codificati rispettivamente dai prodotti genici ABCB e ABCC, favorendo l’efflusso attivo di composti tossici, prevengono il loro accumulo cellulare e, dunque, i loro potenziali effetti dannosi. Tuttavia, alcune sostanze possono influenzare questo delicato meccanismo, esponendo gli organismi acquatici agli effetti tossici degli inquinanti. In questo lavoro di Tesi è stato condotto uno studio sperimentale in vitro volto a determinare i possibili effetti dell’antidepressivo fluoxetina (FX), dell’antiepilettico carbamazepina (CBZ) e del β-bloccante propranololo (PROP) sul meccanismo MXR, in emociti di Mytilus galloprovincialis. In particolare si è valutata l’azione di questi farmaci sulla funzionalità dei trasportatori e/o sulla modulazione trascrizionale. I risultati ottenuti hanno dimostrato l’importante effetto del PROP, della CBZ e della FX sul sistema MXR. In particolare, il PROP e la CBZ alterano tale sistema, agendo, principalmente, sui livelli di espressione del prodotto genico ABCB, nonostante influenzino anche i livelli di ABCC. La FX, invece, non porta ad alterazioni dell’attività MXR totale, sebbene induca variazioni sui livelli di espressione di ABCB. In conclusione, le analisi dei profili trascrizionali dimostrano che la proteina predominante nell’efflusso di tali contaminanti negli emociti di M. galloprovincialis è la P-glicoproteina e che le variazioni dell’attività MXR osservate in questa Tesi sono il risultato combinato dell’azione dei farmaci analizzati come modulatori trascrizionali e come substrati da parte dei trasportatori MXR.

MS 073 Guide to the William C. Moloney MD papers; 1952-1954

William C. Moloney MD kept a personal journal, with photographs, for much of his two years in Japan with the Atomic Bomb Casualty Commission. In January of 1986, Dr.Moloney donated his journal, correspondence and diary pages to the Harris County Medical Archive. He died in 1998 at the age of 91. His first contribution was a set of ten reprints representing his work with the ABCC from 1952 to 1954. Dr.Moloney's journal is a fine document, one which will be of great use to historians. It is an important record of personal impressions, thoughts and details of events. The journal gives new insights into the work of the ABCC and into the people who participated in that work. Dr. Moloney wrote in his journal from April 1952 to February 1954. The Korean War was on and there was a great deal of military activity in southern Japan. The collection is open for research. The collection consists of a handwritten journal, loose calendar or notebook pages and some reprints. The journal is in generally fair condition. The paper is slightly acidic and the binding is loose. There are numerous photos glued onto the pages. The collection encompasses the years 1952-1954 and is 0.25 cubic feet (1 box).

MS 066 Guide to the Howard B. Hamilton, MD, papers; 1945-1997

The Howard B. Hamilton, MD, papers, MS 66, includes material from 1945-1997 related to the Atomic Bomb Casualty Commission (ABCC) and the Radiation Effects Research Foundation (RERF). Hamilton was the Chief of Clinical Laboratories for the Atomic Bomb Casualty Commission from 1956 until its dissolution in 1975. He served in the same capacity for the Radiation Effects Research Foundation, which succeeded the ABCC, until 1984. This collection encompasses this period of time in Dr. Hamilton's career, as well as his related scholarly work after his retirement from RERF. Dr. Hamilton donated his collection of letters, reprints, newspaper articles, photographs, memos, and ephemera to the John P. McGovern Historical Collections and Research Center between 1985 and 2002. The collection is in good condition and consists of 3.75 cubic feet (10 boxes).

MS#73 William C. Moloney, M.D., papers; 1952-1954

Dr. Moloney kept a personal journal, with photographs, for much of his two years with the Atomic Bomb Casualty Commission in Japan. Along with other scientists, he studied the biological and medical effects of ionized radiation on the survivors of the Hiroshima and Nagasaki atomic bombings. In January of 1986, Dr. Moloney donated his journal, correspondence and diary pages to the Harris County Medical Archive, whose collections were later incorporated into the Texas Medical Center Library. Dr. Moloney's journal is in relatively good shape containing a mix of handwritten notes and comments, news-clippings, photos, and ephemera. The journal is an important record of personal impressions, thoughts and details of events during a pivotal time in Japan. This 192-pagee journal gives new insights into the work of the ABCC and into the people who participated in that work. The journal covers the period from April 1952 to February 1954. In these documents, Moloney records his struggles with understanding the Japanese culture, his frustration at not being allowed to treat the survivors he studied, and his concerns, fears, hopes and revelations as he dealt with the bombing survivors and their children. The original papers are open for research at the John P. McGovern Historical Collections and Research Center in the TMC Library in Houston.

The Atomic Bomb Casualty Commission in retrospect

For 50 years, the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF), have conducted epidemiological and genetic studies of the survivors of the atomic bombs and of their children. This research program has provided the primary basis for radiation health standards. Both ABCC (1947–1975) and RERF (1975 to date) have been a joint enterprise of the United States (through the National Academy of Sciences) and of Japan. ABCC began in devastated, occupied Japan. Its mission had to be defined and refined. Early research revealed the urgent need for long term study. In 1946, a Directive of President Truman enjoined the National Research Council of the National Academy of Sciences to develop the program. By 1950, ABCC staff exceeded 1,000, and clinical and genetic studies were underway. Budgetary difficulties and other problems almost forced closure in 1953. In 1955, the Francis Report led to a unified epidemiological study. Much progress was made in the next decade, but changing times required founding of a binational nonprofit organization (RERF) with equal participation by Japan and the United States. New programs have been developed and existing ones have been extended in what is the longest continuing health survey ever undertaken.

Simultaneous optimisation of structural topology and material grading using level set method

Peer reviewed

The existence and source of stock return predictability : Evidence from dividend, output and consumption ratios

Date of Acceptance: 13/03/2015

The existence and source of stock return predictability : Evidence from dividend, output and consumption ratios

Date of Acceptance: 13/03/2015

A formação e o desenvolvimento de arranjos cooperativos sob a ótica da imersão social e da economia dos custos de transação: um estrudo de caso na Coopercam e na Unipesca

The current study analyzes the birth and development of two strategic alliances established between shrimp producers in Rio Grande do Norte: the Unipesca and the Coopercam. To achieve this aim, two approaches which, at first sight, could be considered contradictory were used: the Transactional Costs Economy and Embeddedness. The first approach is fundamentally based in the studies of Williamson (1985; 1991; 1996; 1999; 2000; 2002). Embededness, on the other hand, went through the review of a series of authors, such as Burt (1992), Granovetter (1973; 1985), Uzzi (1997), Gulati (1994; 1995; 1997; 1998; 1999; 2000), Nielsen (2005), Ring (2002), Ring and Van de Ven (1994), Zafirovski (2002), among others. To analyze the birth and development of the cooperatives in this study, Gulati s work (1998) was used. This study shows the steps to be studied for a better comprehension of an alliance: the decision of starting an alliance and the choice of the partners, the decision about the governance structure, the evolution of the alliance and the development of the companies which established this partnership. To carry this study out, a study case accordingly to Yin s proposal (2001) was adopted. Semi-structured interviews with pre-defined plots were conducted in two phases: in the beginning of 2006 and in the beginning of 2007. The subjects from the research were, in 2006, representative members of the main associations and corporations, besides the shrimp producers from the state, when the context of the activity was set. In the second phase, in 2007, representative members from the two cooperatives that were listed above were interviewed the president from Coopercam and the marketing manager from Unipesca. Besides these two members, directors from two important organizations in each of these cooperatives were also interviewed, giving out the necessary information for the research. Secondary data was also collected from the Brazilian Association of Crab producers website, as well as from news from important newspapers in RN, such as Tribuna do Norte. The primary data was analyzed in terms of quality, accordingly to the documental analysis technique. Thus, through the data that was collected, it can be concluded that the reasons that motivated the companies to cooperate can be explained in terms of the transactional costs economy. However, the choice of partners is more connected to aspects approached by the social embededness. When aspects related to development and evolution were analyzed, it could be seen that both aspects from TCE and Embededness were vital to explain the development of the cooperatives mentioned