MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

a festival at the interstices of value systems

This chapter puts observations made in previous parts of this book into perspective, as it highlights the diversity of positionalities in internal relations in the context of the organization of an Iranian cultural festival. As agents that appeared in previous chapters come to interact with the young and unexperienced organizer, Behruz, during fundraising activities and at the festival itself, it becomes clear that their exchanges are driven by multiple, partly compatible, partly competing strategies of capital creation deriving from individual or collective politics of value within a large variety of local and transnational social fields

One-pot enzymatic synthesis of the Gal alpha 1-->3Gal beta 1-->4GlcNAc sequence with in situ UDP-Gal regeneration.

The trisaccharide Gal alpha 1-->3Gal beta 1-->4GlcNAc beta 1-->O-(CH2)8COOCH3 was enzymatically synthesized, with in situ UDP-Gal regeneration. By combination in one pot of only four enzymes, namely, sucrose synthase, UDP-Glc 4'-epimerase, UDP-Gal:GlcNAc beta 4-galactosyltransferase and UDP-Gal:Gal beta 1-->4GlcNAc alpha 3-galactosyltransferase, Gal alpha 1-->3Gal beta 1-->4GlcNAc beta 1-->O-(CH2)8COOCH3 was formed in a 2.2 mumol ml-1 yield starting from the acceptor GlcNAc beta 1-->O-(CH2)8COOCH3. This is an efficient and convenient method for the synthesis of the Gal alpha 1-->3Gal beta 1-->4GlcNAc epitope which pays an important role in various biological and immunological processes

Dermatologia e gestação Dermatology and pregnancy

Neste estudo conduz-se uma revisão bibliográfica da literatura sobre dermatologia e gravidez abrangendo o período de 1962 a 2003. O banco de dados do Medline foi consultado com referência ao mesmo período. Não se incluiu a colestase intra-hepática da gravidez por não ser ela uma dermatose primária; contudo deve ser feito o diagnóstico diferencial entre suas manifestações na pele e as dermatoses específicas da gravidez. Este apanhado engloba as características clínicas e o prognóstico das alterações fisiológicas da pele durante a gravidez, as dermatoses influenciadas pela gravidez e as dermatoses específicas da gravidez. Ao final apresenta-se uma discussão sobre drogas e gravidez.<br>This study is a literature review on dermatology and pregnancy from 1962 to 2003, based on Medline database search. Intrahepatic cholestasis of pregnancy was not included because it is not a primary dermatosis; however, its secondary skin lesions must be differentiated from specific dermatoses of pregnancy. This overview comprises clinical features and prognosis of the physiologic skin changes that occur during pregnancy; dermatoses influenced by pregnancy and the specific dermatoses of pregnancy. A discussion on drugs and pregnancy is presented at the end of this review

Cultural Challenges for L2 Communication Among Persian Migrants in Australia

This chapter addresses some of the challenges that Iranian migrants encounter in their L2 oral communication in Australia, and how they deal with them. The challenges addressed in this chapter include speakers&rsquo; reconstruction of identity, power dynamics, and critical thinking. Persian concepts such as zaher (appearance) and baten (inner self) (Beeman in Int J Sociol Lang 148: 31&ndash;57, 1986) as well as nationalistic attitude via concepts like ta&rsquo;sob/ghairat &lsquo;emotional prejudice&rsquo; that influence the above challenges are discussed. These concepts are analyzed in light of Bourdieu&rsquo;s (Language and Symbolic Power. Harvard University Press, Cambridge, MA, 1991) linguistic capital and Foucault&rsquo;s notion of power (1994), by employing Fairclough&rsquo;s (Essential Works of Foucault 1954&ndash;1984. Vol. 3, Power. Penguin, London, pp. 1&ndash;89, 2013) critical discourse analysis (CDA) approach which posits that linguistic choices exhibit cultural and political overtones, which entangled with power dynamics can either enable L2 communicators, or hamper their performance. The data analyzed come from 12 Iranian male-female migrants&rsquo; interview sessions about their lived experiences, including their settlement, migrant English classes, and workplace, in Australia. Results have revealed that many participants wished they had the expressive power in L2 to boast about Iran&rsquo;s glorious past and Persian Empire. The data have further revealed the participant&rsquo;s general agreeability to Australians&rsquo; open-mindedness that helped them build on their critical thinking in the new context