359 research outputs found

    Plea Bargains: What to Do When the Prosecutor Says No

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    A common misconception of the American criminal justice system is the belief that an accused may only be convicted by a jury of his peers after a trial in which his defense lawyer and the prosecutor sharply contest his guilt. In a majority of cases, however, this scenario never occurs. Instead, the prosecution and defense usually make a deal; that is, the defendant agrees to plead guilty and the prosecutor agrees to make concessions in return. One study has estimated that guilty pleas account for ninety percent of all convictions and that most of these pleas are the result of plea bargaining. In short, plea bargaining has become an important part of our criminal justice system. Despite its advantages, plea bargaining is not without its critics. One critic has written that when plea negotiations occur the rule of law is invariably sacrificed to the rule of convenience.” Furthermore, plea bargaining may create a danger that defendants will be deterred from exercising their constitutional rights and, in some cases, may even induce innocent defendants to plead guilty. Other critics maintain that plea bargaining compromises the prosecutor\u27s duty to enforce the law. Nevertheless, courts could not handle the workload if all criminal defendants insisted on a trial. In light of this fact, plea bargaining is a bureaucratic necessity which has become indispensible to the administration of the present criminal justice system. The practice of plea bargaining was expressly sanctioned by the United States Supreme Court in Santobello v. New York. Many issues, however, remain unresolved. This comment will examine the remedies available to a defendant who, having entered a negotiated plea, subsequently alleges that the prosecutor breached his part of the bargain. In this context, the relevant questions that will be examined are: 1) Was there in fact a promise? 2) Was the promise broken? 3) Under what theory may relief be given? and 4) What type of relief is appropriate

    LKB1 and AMPK maintain epithelial cell polarity under energetic stress

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    LKB1 is mutated in both familial and spontaneous tumors, and acts as a master kinase that activates the PAR-1 polarity kinase and the adenosine 5′monophosphate–activated kinase (AMPK). This has led to the hypothesis that LKB1 acts as a tumor suppressor because it is required to maintain cell polarity and growth control through PAR-1 and AMPK, respectively. However, the genetic analysis of LKB1–AMPK signaling in vertebrates has been complicated by the existence of multiple redundant AMPK subunits. We describe the identification of mutations in the single Drosophila melanogaster AMPK catalytic subunit AMPKα. Surprisingly, ampkα mutant epithelial cells lose their polarity and overproliferate under energetic stress. LKB1 is required in vivo for AMPK activation, and lkb1 mutations cause similar energetic stress–dependent phenotypes to ampkα mutations. Furthermore, lkb1 phenotypes are rescued by a phosphomimetic version of AMPKα. Thus, LKB1 signals through AMPK to coordinate epithelial polarity and proliferation with cellular energy status, and this might underlie the tumor suppressor function of LKB1

    Ectopic Expression of Zmiz1 Induces Cutaneous Squamous Cell Malignancies in a Mouse Model of Cancer

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    Cutaneous squamous cell carcinoma (SCC) is the second most common form of cancer in the human population, yet the underlying genetic mechanisms contributing to the disease are not well understood. We recently identified Zmiz1 as a candidate oncogene in nonmelanoma skin cancer through a transposon mutagenesis screen. Here we show that transposon-induced mutations in Zmiz1 drive expression of a truncated transcript that is similar to an alternative endogenous ZMIZ1 transcript found to be overexpressed in human SCCs relative to normal skin. We also describe an original mouse model of invasive keratoacanthoma driven by skin-specific expression of the truncated Zmiz1 transcript. Unlike most mouse models, Zmiz1-induced skin tumors develop rapidly and in the absence of promoting agents such as phorbol esters. In addition, we found that the alternative Zmiz1 isoform has greater protein stability than its full-length counterpart. Finally, we provide evidence that ZMIZ1 is overexpressed in a significant percentage of human breast, ovarian, and colon cancers in addition to human SCCs, suggesting that ZMIZ1 may play a broader role in epithelial cancers

    Functional and Biogenetical Heterogeneity of the Inner Membrane of Rat-Liver Mitochondria

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    Rat liver mitochondria were fragmented by a combined technique of swelling, shrinking, and sonication. Fragments of inner membrane were separated by density gradient centrifugation. They differed in several respects: electronmicroscopic appearance, phospholipid and cytochrome contents, electrophoretic behaviour of proteins and enzymatic activities. Three types of inner membrane fractions were isolated. The first type is characterized by a high activity of metal chelatase, low activities of succinate-cytochrome c reductase and of glycerolphosphate dehydrogenase, as well as by a high phospholipid content and low contents of cytochromes aa3 and b. The second type displays maximal activities of glycerolphosphate dehydrogenase and metal chelatase, but contains relatively little cytochromes and has low succinate-cytochrome c reductase activity. The third type exhibits highest succinate-cytochrome c reductase activity, a high metal chelatase activity and highest cytochrome contents. However, this fraction was low in both glycerolphosphate dehydrogenase activity and phospholipid content. This fraction was also richest in the following enzyme activities: cytochrome oxidase, oligomycin-sensitive ATPase, proline oxidase, 3-hydroxybutyrate dehydrogenase and rotenone-sensitive NADH-cytochrome c reductase. Amino acid incorporation in vitro and in vivo in the presence of cycloheximide occurs predominantly into inner membrane fractions from the second type. These data suggest that the inner membrane is composed of differently organized parts, and that polypeptides synthesized by mitochondrial ribosomes are integrated into specific parts of the inner membrane

    Do Doctors Vote?

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    BACKGROUND: Organizational leaders and scholars have issued calls for the medical profession to refocus its efforts on fulfilling the core tenets of professionalism. A key element of professionalism is participation in community affairs. OBJECTIVE: To measure physician voting rates as an indicator of civic participation. DESIGN: Cross-sectional survey of a subgroup of physicians from a nationally representative household survey of civilian, noninstitutionalized adult citizens. PARTICIPANTS: A total of 350,870 participants in the Current Population Survey (CPS) November Voter Supplement from 1996–2002, including 1,274 physicians and 1,886 lawyers; 414,989 participants in the CPS survey from 1976–1982, including 2,033 health professionals. MEASUREMENTS: Multivariate logistic regression models were used to compare adjusted physician voting rates in the 1996–2002 congressional and presidential elections with those of lawyers and the general population and to compare voting rates of health professionals in 1996–2002 with those in 1976–1992. RESULTS: After multivariate adjustment for characteristics known to be associated with voting rates, physicians were less likely to vote than the general population in 1998 (odds ratio 0.76; 95% confidence interval [CI] 0.59–0.99), 2000 (odds ratio 0.64; 95% CI 0.44–0.93), and 2002 (odds ratio 0.62; 95% CI 0.48–0.80) but not 1996 (odds ratio 0.83; 95% CI 0.59–1.17). Lawyers voted at higher rates than the general population and doctors in all four elections (P < .001). The pooled adjusted odds ratio for physician voting across the four elections was 0.70 (CI 0.61–0.81). No substantial changes in voting rates for health professionals were observed between 1976–1982 and 1996–2002. CONCLUSIONS: Physicians have lower adjusted voting rates than lawyers and the general population, suggesting reduced civic participation

    Oocyte expression with injection of purified T7 RNA polymerase.

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    International audienceThe Xenopus oocyte is a widely used system for protein expression. Investigators have had the choice between two different techniques: injection into the cytoplasm of in vitro transcribed complementary RNA (cRNA) or injection into the nucleus of complementary DNA (cDNA). We report on a third expression technique that is based on the combined injection of cDNA and purified T7 RNA polymerase directly into the cytoplasm of oocytes
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