2,790 research outputs found
Person to Person in Ecuador
While still in the midst of their study abroad experiences, students at Linfield College write reflective essays. Their essays address issues of cultural similarity and difference, compare lifestyles, mores, norms, and habits between their host countries and home, and examine changes in perceptions about their host countries and the United States. In this essay, Hannah Greider describes her observations during her study abroad program at the Universidad San Francisco de Quito in Ecuador
The Importance of Unions in Contemporary Times
This article examines the importance of unions in contemporary times. Our research focuses on United Auto Workers Local 72, a union representing workers at a factory in Kenosha, Wisconsin, during several plant closings. Using qualitative data collected over a span of more than 20 years, we examine the role of the local union in helping the workers respond to the plant closing in ways that would produce the most beneficial results for them. We trace stories of the workers’ and union’s resistance, cooperation, and pride in their work. The workers’ continued commitment to quality and their strong work ethic seemed to be key factors in persuading the company to keep some work on the site and, later, to add more. These tactics were successful through several changes in ownership and economic cycles until the Great Recession of 2008, at which point the work destined for the plant in Kenosha was finally sent to Mexico, yet most of the workers affected by the original plant closing in 1988 were eventually able to come back to work and to retire with full pensions from the company. Our evidence suggests the roles that unions may continue to play in this age of globalization
Tetrahymena telomerase catalyzes nucleolytic cleavage and nonprocessive elongation
Telomerase is a ribonucleoprotein enzyme that adds telomeric repeats to chromosomes, maintaining telomere length and stabilizing chromosome ends. In vitro, telomerase from the ciliate Tetrahymena elongates single-stranded, guanosine-rich DNA primers by adding repeats of the Tetrahymena telomeric sequence, dT2G4. We have identified two activities of Tetrahymena telomerase in addition to the previously described processive elongation reaction: a 3'-5' nucleolytic cleavage of primer or product DNA and a nonprocessive mode of elongation. The nucleolytic cleavage activity removed residues not conforming to the telomeric repeat sequence from a primer 3' end, eliminating mismatch between DNA primer and RNA template sequences. Template-matched residues were also cleaved from primer or product DNA. Specific primer lengths, sequences, and concentrations stimulated cleavage and processive or nonprocessive elongation differentially. These newly identified activities suggest that telomerase may catalyze a range of telomere synthesis and repair functions and suggest mechanistic similarities between telomerase and RNA polymerase enzymes. On the basis of our results, we propose a model for telomerase primer binding, cleavage, and elongation
Boundary elements of the Tetrahymena telomerase RNA template and alignment domains
Telomerase is a DNA polymerase fundamental to the replication and maintenance of telomere sequences at chromosome ends. The RNA component of telomerase is essential for the synthesis of telomere repeats. In vitro, the template domain (5'-CAACCCCAA-3') of the Tetrahymena telomerase RNA dictates the addition of Tetrahymena-specific telomere repeats d(TTGGGG)n, onto the 3' end of G-rich or telomeric substrates that are base-paired with the template and alignment regions of the RNA. Using a reconstituted in vitro system, we determined that altering the sequence of the alignment and template domains affects processivity of telomerase without abolishing telomerase activity. These results suggest that alternative template/alignment regions may be functional. In the ciliate telomerase RNAs, there is a conserved sequence 5'-(CU)GUCA-3', located two residues upstream of the template domain. The location and sequence of this conserved domain defined the 5' boundary of the template region. These data provide insights into the regulation of telomere synthesis by telomerase
Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer
Telomeric dysfunction is linked to colorectal cancer (CRC) initiation. However, the relationship of normal tissue and tumor telomere lengths with CRC progression, molecular features and prognosis is unclear. Here, we measured relative telomere length (RTL) by real-time quantitative PCR in 90 adenomas (aRTL), 419 stage I-IV CRCs (cRTL) and adjacent normal mucosa (nRTL). Age-adjusted RTL was analyzed against germline variants in telomere biology genes, chromosome instability (CIN), microsatellite instability (MSI), CpG island methylator phenotype (CIMP), TP53, KRAS, BRAF mutations and clinical outcomes. In 509 adenoma or CRC patients, nRTL decreased with advancing age. Female gender, proximal location and the TERT rs2736100 G allele were independently associated with longer age-adjusted nRTL. Adenomas and carcinomas exhibited telomere shortening in 79% and 67% and lengthening in 7% and 15% of cases. Age-adjusted nRTL and cRTL were independently associated with tumor stage, decreasing from adenoma to stage III and leveling out or increasing from stage III to IV, respectively. Cancer MSI, CIMP, TP53, KRAS and BRAF status were not related to nRTL or cRTL. Near-tetraploid CRCs exhibited significantly longer cRTLs than CIN- and aneuploidy CRCs, while cRTL was significantly shorter in CRCs with larger numbers of chromosome breaks. Age-adjusted nRTL, cRTL or cRTL:nRTL ratios were not associated with disease-free or overall survival in stage II/III CRC. Taken together, our data show that both normal mucosa and tumor RTL are independently associated with CRC progression, and highlight divergent associations of CRC telomere length with tumor CIN profiles
Multiple Tumor Suppressor Pathways Negatively Regulate Telomerase
AbstractTelomerase expression is repressed in most somatic cells but is observed in stem cells and a high percentage of human cancers and has been hypothesized to contribute to tumorigenesis and maintenance of stem cell states. To explore telomerase regulation, we employed a general genetic screen to identify negative regulators of hTERT. We discovered three tumor suppressor/oncogene pathways involved in hTERT repression. One, the Mad1/c-Myc pathway, had been previously implicated in hTERT regulation. The second, SIP1, a transcriptional target of the TGF-β pathway, mediates the TGF-β regulated repression of hTERT. The third, the tumor suppressor Menin, is a direct repressor of hTERT. Depleting Menin immortalizes primary human fibroblasts and causes a transformation phenotype when coupled with expression of SV40 Large and Small T antigen and oncogenic ras. These studies suggest that multiple tumor suppressor/oncogene pathways coordinately repress hTERT expression and imply that telomerase is reactivated in human tumors through oncogenic mutations
Law in other contexts: stand bravely brothers! a report from the law wars
This essay argues against the two pillars of current research on law and globalisation, from the perspective of legal theory and political philosophy: first, the distinction between ‘well-ordered’ and ‘not so well-ordered’ societies; second, the sociological model of the subject as pacified, fearful and isolated (to sum up, in harmony). It is argued that mainstream legal theory and political philosophy merely reflects the actual rules of the game of competition, dispute and conflict. In contrast, this essay takes sides with the anthropological and philosophical tradition that conceives the subject as antagonistic and in state of lack, profoundly concerned with the other, whom she imitates and whose standpoint she must be able to share if she is to make sense of the world. Furthermore, it is argued that transitivity or imitation lies at the very origin of conflict and dispute; lack and antagonism remain thus at the core of society, in spite of the surface appearance of harmony that characterises post-modern societies. Because of this, any general theory of law and society that wishes to be relevant at the time of globalisation must make the experience of antagonism and violence, motivated by imitation and envy, and its containment, its object of study. To do this, it must abandon the dualist conception of subjects and societies expressed in the distinction between ‘well-ordered’ (more violent) and ‘not-so-well-ordered’ (less violent) societies that has informed its investigation to this day, in order to declare in the most general terms a critique of violence from the standpoint of the victim, as of a piece with its demand for global social and political justice. Description from publisher website at: http://journals.cambridge.org/action/displayIssue?jid=IJC&volumeId=4&issueId=02&iid=243936
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