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The crime drop in New York City has produced a whole academic literature that is unable to explain the decline. This article argues that this literature has ignored the simplest explanation of all: a simultaneous increase in the supply, and decrease in demand for illegal drugs led to a drop in the price of illegal drugs, which in turn led to a drop in crime. We use ethnography to document the drop in demand, secondary literature to document the increase in supply, and econometric analysis to illustrate Granger causality between drug prices and crime rates. While crime dropped across the nation and internationally, our article is focused on New York City.  相似文献   

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The Epstein-Barr virus (EBV)-coded nuclear antigen (EBNA) 1, a latent cycle protein endogenously expressed in EBV-transformed B lymphoblastoid cell lines (LCLs), is reported to be processed for CD4(+) T cell recognition by an intracellular route involving antigen delivery to the endosome/lyosome (MHC class II loading) compartment via macroautophagy. In contrast we find that, in the same cell type, two other virus-coded nuclear proteins of the latent cycle, EBNA2 and EBNA3C, are processed by a different route that is unaffected by autophagy inhibition. This involves the intercellular transfer of an antigenic moiety, detectable in cell-free culture supernatants, and its uptake and processing as exogenous antigen by neighboring cells. The process is cumulative and leads over several days of LCL culture to high levels of CD4+ T cell epitope display. The presentation of certain EBV lytic cycle proteins to CD4+ T cells has also recently been found to involve a similar intercellular antigen transfer. It becomes important to know why, even in the same cell type, some antigens but not others appear to access the MHC class II presentation pathway by autophagy.  相似文献   

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In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins.  相似文献   

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Besides the implication of ascorbate and glutathione in the defence against oxidative stress, these two compounds are involved in plant growth and cell cycle control. Ascorbate metabolism is closely linked to the development of embryos and seedlings. Furthermore, ascorbate stimulates cell cycle activity in competent cells, while the oxidised form, dehydroascorbate, blocks normal cell cycle progression. Several possible mechanisms have been proposed to explain the effect of these compounds. The links between glutathione and the cell cycle are less clear. It has long been assumed that both compounds are closely linked by way of the Halliwell–Asada cycle. Any hypothesis concerning the pathways by which ascorbate or glutathione influence cell division, should take this connection into account. However, other mechanisms have been proposed for ascorbate-mediated cell cycle control, e.g. via the thioredoxin pathway.  相似文献   

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Saksela K  Permi P 《FEBS letters》2012,586(17):2609-2614
An increasing number of SH3 domain-ligand interactions continue to be described that involve the conserved peptide-binding surface of SH3, but structurally deviate substantially from canonical docking of consensus motif-containing SH3 ligands. Indeed, it appears that that the relative frequency and importance of these types of interactions may have been underestimated. Instead of atypical, we propose referring to such peptides as type I or II (depending on the binding orientation) non-consensus ligands. Here we discuss the structural basis of non-consensus SH3 ligand binding and the dominant role of the SH3 domain specificity zone in selective target recognition, and review some of the best-characterized examples of such interactions.  相似文献   

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Biallelic germline mutations of MUTYH—a gene encoding a base excision repair protein—are associated with an increased susceptibility of colorectal cancer. Whether monoallelic MUTYH mutations also increase cancer risk is not yet clear, although there is some evidence suggesting a slight increase of risk. As the MUTYH protein interacts with the mismatch repair (MMR) system, we hypothesised that the combination of a monoallelic MUTYH mutation with an MMR gene mutation increases cancer risk. We therefore investigated the prevalence of monoallelic MUTYH mutations in carriers of a germline MMR mutation: 40 carriers of a truncating mutation (group I) and 36 of a missense mutation (group II). These patients had been diagnosed with either colorectal or endometrial cancer. We compared their MUTYH mutation frequencies with those observed in a group of 134 Dutch colorectal and endometrial cancer patients without an MMR gene mutation (0.7%) and those reported for Caucasian controls (1.5%). In group I one monoallelic MUTYH mutation was found (2.5%). In group II five monoallelic germline MUTYH mutations were found (14%), four of them in MSH6 missense mutation carriers (20%). Of all patients with an MMR gene mutation, only those with a missense mutation showed a significantly higher frequency of (monoallelic) MUTYH mutations than the Dutch cancer patients without MMR gene mutations (P=0.002) and the published controls (P=0.001). These results warrant further study to test the hypothesis of mutations in MMR genes (in particular MSH6) and MUTYH acting together to increase cancer risk.  相似文献   

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Situated at the intersection of anthropological work on illness narratives and research on the anthropology of autism, this paper is a close reading of an autobiographical narrative recounted by Peter, a young man diagnosed with Asperger’s Syndrome, a type of autism spectrum disorder (ASD). Responding to Solomon’s (2010a:252) call for phenomenologically grounded accounts of “the subjective, sensory, and perceptual experiences of autism … based on personal narratives and practices of being and self-awareness,” this paper calls into question key assumptions in the clinical and popular literature about ASD relating to theory of mind, empathy, capacity for metaphorical thinking, and ASD as a life-long condition.  相似文献   

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This article examines the relationship between whiteness and communication through analysing how white business community members acknowledge their own, usually invisible, white identity. Discourse analysis of interactions in a Texas organization shows how white members construct white identity as intersecting with Texan, masculine, age and professional identity categories. Members mark the overt construction of white identity as a dispreferred action through using disclaimers, formulations, pauses, humour and non-racial terms. Analysis of minority business member talk illustrates how minorities orient to white members’ talk as exclusive towards minorities because they do not overtly and directly discuss race and because they orient to regional identity in a way that ignores racial diversity among Texans. Thus while white members attempt to acknowledge their raced position in the Texas business community, their communicative actions repeatedly index white identities and reproduce the hegemonic position of white, male, Texan professional identities in this community.  相似文献   

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The first few words of the title of this symposium are “Anchoring Biodiversity Information”. In order to properly anchor anything for a long-lasting future, a solid foundation needs to have been laid. For the zoological portion of biodiversity information, that firm foundation is best exemplified in the works of Charles Davies Sherborn. This man, like others of his ilk, was intimately focused on indexing names. This incredible focus was a life-long passion for him and culminated in his 9500-page Index Animalium of over 400,000 names of animals. This Index represents not only one of the most prodigious efforts in publication by a single man and the single most important reference to names in zoology, but a permanent legacy to the efforts of an indexer that proved to be an inspiration to many.  相似文献   

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Darwin’s Cirripedia project was an exacting exercise in systematics, as well as an encrypted study of evolution in action. Darwin had a long-standing interest and expertise in marine invertebrates and their sexual arrangements. The surprising and revealing sexual differentiation he would uncover amongst barnacles represented an important step in his understanding of the origins of sexual reproduction. But it would prove difficult to reconcile these findings with his later theorizing. Moreover, the road to discovery was hardly straightforward. Darwin was both helped and hindered by the tacit expectations generated by his transformist theorizing, and had to overcome culturally-embedded assumptions about gender and reproductive roles. Significant observational backtracking was required to correct several oversights and misapprehensions, none more so than those relating to the chronically misunderstood “Mr. Arthrobalanus.” With careful attention to chronology, this paper highlights some curious and overlooked aspects of Darwin’s epic project.  相似文献   

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When, in the 1980s, Alzheimer's disease became a disease of major public concern, 'personhood' also became an important, related topic of discussion. Those in caring professions (psychology, social work, etc.) and caregiver groups advocated for the 'person within' who was getting lost in a forgetful body and in a reductionist biomedical system. This essay aims to critically approach the dualism of this kind of argument by focusing on the moral positioning of claims such as personhood or biomedical reductionism.  相似文献   

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