Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

BACKGROUND: Alzheimer's disease is intimately tied to amyloid-beta peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein account for a small proportion of AD cases, suggesting that regulation of the associated gene may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" , at -76/-47, from the (...) +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. RESULTS: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 , nm23 nucleoside diphosphate kinase/metastatic inhibitory protein , and specificity protein 1 . These sites crossed a known single nucleotide polymorphism . EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. CONCLUSIONS: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging. (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms of (...) autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (shrink)

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated (...) region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

BACKGROUND: Serotonin transporter promoter genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. METHOD: Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR gene. (...) RESULTS: Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. LIMITATIONS: The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. CONCLUSIONS: 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype. (shrink)

Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

OBJECTIVES: Early-emerging, temperamental differences in fear-related traits may be a heritable vulnerability factor for anxiety disorders. Previous research indicates that the serotonin transporter promoter region polymorphism is a candidate gene for such traits. METHODS: Associations between 5-HTTLPR genotype and indices of fearful child temperament, derived from maternal report and standardized laboratory observations, were examined in a community sample of 95 preschool-aged children. RESULTS: Children with one or more long alleles of the 5-HTTLPR gene were rated as significantly more nervous during (...) standardized laboratory tasks than children who were homozygous for the short alleles. Children homozygous for the short alleles were also rated as significantly shyer, by maternal report, than those with at least one copy of the long allele of the 5-HTTLPR gene. CONCLUSIONS: This study extends the literature linking the short alleles of the serotonin transporter promoter region polymorphism to fear and anxiety-related traits in early childhood and adulthood, and is one of very few studies to examine the molecular genetics of preschoolers' temperament using multiple measures of traits in a normative sample. (shrink)

Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

Amyloid-beta peptide plaque in the brain is the primary diagnostic criterion of Alzheimer's disease . The physiological role of Abeta are poorly understood. We have previously determined an Abeta interacting domain in the promoters of AD-associated genes . This AbetaID interacts in a DNA sequence-specific manner with Abeta. We now demonstrate novel Abeta activity as a possible transcription factor. Herein, we detected Abeta-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma cells treated with FITC conjugated Abeta1-40 (...) localized Abeta to the nucleus in the presence of H2O2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Abeta peptides and/or H2O2. Abeta treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Abeta peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD. (shrink)

This essay explores the aspects of the Aristotelian psuchē that accounts for its contemporary appeal. The poverty of the notion of the mind is discussed. The superiority of the psuchē over the mind is emphasized.

De Marco et al 1 argue that the standard account of medical ‘invasiveness’ (as ‘incision’ or ‘insertion’) fails to capture three aspects of its existing use, namely that invasiveness can come in degrees, often depends on features of alternative medical interventions and can be non-physical. They propose a new schematic account that suggests that medical interventions can possess ‘basic invasiveness’ (which can come in degrees and of which they suggest at least two types: physical and mental), and ‘threshold invasiveness’ which (...) can depend on the alternatives a specific intervention is being compared with. While we agree that the standard account of invasiveness fails to capture existing use and are supportive of their aim, here we express scepticism about the practical utility of De Marco et al ’s revised account. Our scepticism concerns the application of De Marco et al’s revised account in the narrow context of clinician–patient communication and deliberation about medical interventions within clinical practice, which we see as a crucial context for its use. While De Marco et al do not specify the contexts in which their revised account could be used, we assume from their discussion of treatment interventions (e.g. non-invasive prenatal testing, ventilation) and their comparison to ‘more or less invasive’ options, that at least one of the purposes in mind for …. (shrink)

Putative counterexamples to the Principle of Identity of Indiscernibles (PII) are notoriously inconclusive. I establish ground rules for debate in this area, offer a new response to such counterexamples for friends of the PII, but then argue that no response is entirely satisfactory. Finally, I undermine some positive arguments for PII.

This book is the first complete survey and critical appraisal of the large body of research that has appeared during approximately the last decade concerning the analysis of knowing. Robert K. Shope pays special attention to the social aspects of knowing and proposes a new formulation of the fundamental structure of the Gettier problem. Originally published in 1983. The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University (...) Press. These editions preserve the original texts of these important books while presenting them in durable paperback and hardcover editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905. (shrink)

Philosophy of religion has been the object of penetrating critiques concerning its continued near-complete blindness to all but a single religion. The need for philosophy of religion to open up so as to include more than merely occasional and tokenistic treatments of ‘Other’ religions is clearly evident from the slew of recently published titles concerned with diversifying the field. In this light, a book such as Victoria Harrison’s Eastern Philosophy of Religion should surely come as a welcome addition. And yet, (...) unfortunately, this book turns out to be a case study in how not to diversify philosophy of religion in the twenty-first century. (shrink)

Provider claims to conscientious objection have generated a great deal of heated debate in recent years. However, the conflicts that arise when providers make claims to the "conscience" are only a subset of the more fundamental challenges that arise in health care practice when patients and providers come into conflict. In this piece, the author provides an account of patient-provider conflict from within the moral tradition of St. Thomas Aquinas. He argues that the practice of health care providers should be (...) understood as a form of practical reasoning and that this practical reasoning must necessarily incorporate both "moral" and "professional" commitments. In order to understand how the practical reasoning of provider should account for the needs and commitments of the patient and vice versa, he explores the account of dependence provided by Alasdair MacIntyre in his book Dependent Rational Animals. MacIntyre argues that St. Thomas’ account of practical reasoning should be extended and adapted to account for the embodied vulnerability of all humans. In light of this insight, providers must view patients not only as the subjects of their moral reflection but also as fellow humans upon whom the provider depends for feedback on the effectiveness and relevance of her practical reasoning. The author argues that this account precludes responsive providers from adopting either moral or professional conclusions on the appropriateness of interventions outside the individual circumstances that arise in particular situations. The adoption of this orientation toward patients will neither eradicate provider-patient conflict nor compel providers to perform interventions to which they object. But this account does require that providers attend meaningfully to the suffering of patients and seek feedback on whether their intervention has effectively addressed that suffering. (shrink)

On the basis of the archival materials, first identified by the authors, and the published historical sources that have not yet come to the attention of historians of science, this article reconstructs the biography of Johann Christian Weltzien (1767–1829), doctor of medicine and surgery. In 1785, Weltzien became a court physician. In 1799, in the retinue of Grand Duke Konstantin Pavlovich, he participated in Italian and Swiss military campaigns. After that, Weltzien was assigned to the Сourt of Grand Duke Konstantin (...) Pavlovich of Russia and stayed at his court until 1810. He started his charitable activities in the Medico-Philanthropic Committee. From May 1810 to the middle of 1825, Weltzien was a physician at the Imperial Page Corps. It turned out that around the same time, in 1804–1825, he was a member of the Medical Council. Furthermore, as there were two medical councils under two ministries at the time, in 1811–1822, he was a member of both. Since 1825, Weltzien lived on his estate in Somel, now Vaiatu Manor in Estonia, and died in St. Petersburg. Weltzien’s work as a provincial physician prompted him to write a book on medical police, which was published in 1785. It has been established that this remained his only book on the topic. The article shows that Weltzien became one of the first ideologists of state care for public health in the Russian Empire. Weltzien’s ideas, expressed over 200 years ago, regarding the state having mechanisms to impact public health and the importance of not excluding it from solving health problems have not lost their significance even today. (shrink)

This research focused on one of the messages in the Lord’s Prayer, particularly Matthew 6:12 about prayer for forgiveness and forgiveness to others in order to suggest a concept revision for the sake of a rather normative modern Arabic audience. In the Smith-Van Dyck version, asking God for forgiveness serves as the basis for forgiving sinners by using the present and future form of the verb نغفر كما (as we will forgive). This translation is in contrast to 1881 Jesuit Arabic (...) Bible, which used the past tense غفرنا كما and أعفينا فقد (as we have forgiven) as written in the Greek Bible as ὀφειλήματα ‘debts’ by referring to the debt metaphor. This study examined the Arabic translation of Matthew 6:12 in the perspective of Nida and Taber’s semantic adjustments. In light of the research findings, it was clear that the semantic adjustment and grammatical adjustment in the translation did not run on the grammatical structure of the Arabic language. The translation into Arabic also did not comply with the original source of the text, but it was accentuated by the interpretation of ‘debts’ into ‘sins’. Contribution: In conclusion, this fact can be seen from the choice of the word ‘نغفر’ and the use of the future tense ( fi’l muḍār’i ) as opposed to the source text that uses the past tense ( fi’l māḍy ). (shrink)

The aging of attentional and emotional functions has been extensively studied but relatively independently. Therefore, the relationships between aging and the interactions of attentional and emotional processes remain elusive. This study aimed to determine how age affected the interactions between attentional and emotional processes during adulthood. One-hundred forty adults aged 18–79 performed the emotional variant of the Attention Network Test, which probed alerting, orienting, and executive control in the presence and absence of threatening faces. During this task, contexts with varying (...) levels of task preparatory processes were created to modulate the effect of threatening faces on attention, and functional near-infrared spectroscopy (fNIRS) was used to examine the neural underpinnings of the behavioural effects. The behavioural results showed that aging was associated with a significant decline in alerting efficiency, and there was a statistical trend for age-related deficits in executive control. Despite these age differences, age did not significantly moderate the interactions among attentional networks or between attention and emotion. Additionally, the fNIRS results showed that decreased frontal cortex functioning might underlie the age-related decline in executive control. Therefore, while aging has varying effects on different attentional networks, the interactions of attentional and emotional processes remain relatively unaffected by age. (shrink)

Gaze cueing effect (GCE) refers to attention orienting towards the gazed-at location, characterised by faster responses to gazed-at than non-gazed-at stimuli. A previous study investigated the effects of affective priming on GCE and reported that threatening primes enhanced GCE. However, it remains unknown whether the threat or heightened arousal potentiated GCE. We investigated how highly arousing threatening and positive primes, compared to low arousing neutral primes modulate GCE. After a brief exposure to an affective prime (pictures of threat or erotica) (...) or a neutral prime, participants detected an asterisk validly or invalidly cued by the gaze direction of a neutral face. The results showed that the threatening primes diminished the magnitude of GCE. The highly arousing positive primes did not have an effect on GCE. Further analyses showed that, as compared to neutral priming, the reaction times after threatening primes were shortened on invalid trials. This finding was interpreted to suggest that the threatening primes enhanced goal-directed target detection and attenuated attention orienting by irrelevant gaze cues via improving executive control. In sum, the present findings indicate that threat priming modulates GCE, not because of heightened arousal but because of the threat. (shrink)

Bipolar affective disorder (BPAD) can be a devastating disorder for both sufferers and their relatives. In addition to the variety of distressing and severe affective symptoms, the consequences of illness onset may be equally debilitating, particularly as the illness may commonly present in early adulthood. As such, the developmental trajectory between late adolescence and early adulthood is commonly interrupted. Relationships with family, friends and partners may deteriorate, employment or studies may be interrupted, and criminal histories may be acquired. In turn, (...) such events worsen stress, reduce self-esteem, and may make the recovery process more difficult.... (shrink)

Considerable attention has been paid in recent years to Catullus 63. A number of salient features have been discussed: the psychological study of emotions; the use of animal imagery; the theme of marriage and love. There have also been some helpful studies on smaller, though important, aspects of the poem such as its use of ring composition or Catullus′ inventive treatment of the challenging Galliambic metre. But little work has been done on the literary background of poem 63 apart from (...) the question of whether or not Catullus was following an Alexandrian model. I shall suggest that the basic narrative of the poem, and the way in which Catullus has handled it, have literary antecedents which have influenced the poet. The final product, however, still remains a very original piece of work. (shrink)

Considerable attention has been paid in recent years to Catullus 63. A number of salient features have been discussed: the psychological study of emotions; the use of animal imagery; the theme of marriage and love. There have also been some helpful studies on smaller, though important, aspects of the poem such as its use of ring composition or Catullus′ inventive treatment of the challenging Galliambic metre. But little work has been done on the literary background of poem 63 apart from (...) the question of whether or not Catullus was following an Alexandrian model. I shall suggest that the basic narrative of the poem, and the way in which Catullus has handled it, have literary antecedents which have influenced the poet. The final product, however, still remains a very original piece of work. (shrink)