PGF2alpha-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN.

Prostaglandin F2alpha (PGF2alpha) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2alpha-induced VSMC hypertrophy we examined the ability of the PGF2alpha analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6k), glycogen synthase kinase-3beta (GSK-3beta), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt, mTOR, GSK-3beta, PTEN and ERK1/2 but not JNK phosphorylation. Whereas inhibition of phosphatidylinositol 3-kinase (PI3K) by LY-294002 blocked fluprostenol-induced changes in total protein content, pre-treatment with rapamycin or with the MEK1/2 inhibitor U0126 did not. Taken together, these findings suggest that fluprostenol-induced changes in A7r5 hypertrophy involve mTOR translocation and occur through PI3K-dependent mechanisms.

Analogical priming via semantic relations.

Research on semantic memory has often tacitly treated semantic relations as simple conduits for spreading activation between associated object concepts, rather than as integral components of semantic organization. Yet conceptual relations, and the role bindings they impose on the objects they relate, are central to such cognitive tasks as discourse comprehension, inference, problem solving, and analogical reasoning. The present study addresses the question of whether semantic relations and their bindings can influence access to semantic memory. The experiments investigated whether, and under what conditions, presenting a prime pair of words linked by 1 of 10 common semantic relations would facilitate processing of a target pair of words linked by the same relation. No effect was observed when participants merely read the prime; however, relational priming was observed under instructions to note and use the semantic relations. Participants were faster at making a lexical decision or naming a word on a related pair of target words when that pair was primed with an analogously related pair of words than when the prime pair consisted of either two unrelated words or two words linked by some other relation. This evidence of analogical priming suggests that under an appropriate strategic set, lexical decisions and naming latencies can be influenced by a process akin to analogical mapping.

Periodicity in alpha-helix lengths and C-capping preferences.

We surveyed 299 high resolution, non-homologous protein crystal structures for alpha-helix lengths and capping preferences. We find that helices show a preference to have close to an integral number of turns. Helices can be usefully subdivided into either "favoured length" with 6, 7, 10, 11, 13, 14, 17, 18, 21, 22, 24, 25, 28, 29 or 31 residues, or "disfavoured length" with 8, 9, 12, 15, 16, 19, 20, 23, 26, 27 or 30 residues. Favoured length helices have their N and C-caps on the same side of the helix so they can lie on the protein surface. There is no significant difference in amino acid preferences at the N terminus between favoured and disfavoured length helices. At the C terminus, favoured length helices prefer non-polar side-chains at C4 and polar amino acid residues at C2, while disfavoured length helices prefer non-polar amino acid residues at C2. There are strong periodic trends in the likelihood of terminating a helix with a Schellman or alphaL C-capping motif. These can be rationalised by the preference for a non-polar side-chain at C3 with these motifs, favouring placing C3 on the buried side of the helix. We suggest that algorithms aiming to predict helices or C-capping in proteins should include a weight for the helix length.

Role of a telencephalic nucleus in the delayed song learning of socially isolated zebra finches.

Male zebra finches normally learn their song from adult models during a restricted period of juvenile development. If song models are not available then, juveniles develop an isolate song which can be modified in adulthood. In this report we investigate the features of juvenile experience that underly the timing of song learning. Juvenile males raised in soundproof chambers or in visual isolation from conspecifics developed stable isolate song. However, whereas visual isolate song notes were similar to those of colony-reared males, soundproof chamber isolates included many phonologically abnormal notes in their songs. Despite having stable isolate songs, both groups copied new notes from tutors presented to them in adulthood (2.7 notes per bird for soundproof chamber isolates, 4.4 notes per bird for visual isolates). Old notes were often modified or eliminated. We infer that social interactions with live tutors are normally important for closing the sensitive period for song learning. Lesions of a forebrain nucleus (IMAN) had previously been shown to disrupt juvenile song learning, but not maintenance of adult song for up to 5 weeks after surgery. In this study, colony-reared adult males given bilateral lesions of IMAN retained all their song notes for up to 4-7.5 months after lesioning. However, similar lesions blocked all song note acquisition in adulthood by both visual and soundproof chamber isolates. Other work has shown that intact hearing is necessary for the maintenance of adult zebra finch song. We infer that auditory pathways used for song maintenance and acquisition differ: IMAN is necessary for auditorily guided song acquisition--whether by juveniles or adults--but not for adult auditorily guided song maintenance.

Epidermotropic neuroendocrine carcinoma. Immunohistochemical differentiation from simulators, including malignant melanoma.

Epidermotropic neuroendocrine carcinoma (NEC) is rare. Based on such a case in an 88-year-old woman with a facial NEC showing epidermotropism with a pagetoid growth pattern, we asked whether several similar tumors involving the epidermis could be easily differentiated by immunohistochemical methods. We constructed a panel of control cases (2 each) for NEC, clear cell Bowen's disease (CCBD), Paget's disease (PD), superficial basal cell carcinoma (SBCC), cutaneous T-cell lymphoma (CTTL), and superficial spreading malignant melanoma (SSMM) to compare with our patient. A panel of antibodies including epithelial membrane antigen (EMA), neuron specific enolase (NSE), AE1/3 cytokeratin (CK), carcinoembryonic antigen (CEA), leukocyte common antigen (LCA), S-100, and HMB-45 were applied. Cutaneous NEC controls and our patient's tumor were strongly positive for EMA and NSE and had paranuclear dot-like cytoplasmic positivity for CK. CCBD was moderate to strong for CK. PD was strong for CEA. SBCC was essentially negative for all. CTLL was strong for LCA. SSMM was strong for S-100 and HMB-45. Controls were either negative or weak for the antibodies not mentioned. We conclude that this antibody panel can reliably differentiate these epidermotropic or juxtaepidermal tumors in diagnostic dermatopathology and should be applied to lesions requiring separation beyond H & E capabilities, especially with superficial shave biopsies showing small cell "Pagetoid" growth patterns.

Medical and public health aspects of boxing.

In recent years, an extensive medical literature has accumulated regarding the health hazards associated with boxing. As the evidence that boxing produces irreversible brain damage in boxers has become more compelling, physicians have begun to consider the larger issue of whether the sport is acceptable in its present form. This has resulted in a number of proclamations concerning boxing by various representatives of the medical community, which have both added information to and fueled the public debate over boxing. This article seeks to review the relevant medical literature concerning the health effects of boxing; to look at the contributions made in the last few years by the medical community to the public debate over boxing; and to suggest ways in which the objectives of the medical professional concerning boxing can best be achieved.