Various first messengers linked to phospholipase C, including acetylcholine and interleukin 1, regulate the production both of the secreted form of the amyloid protein precursor (APP) and of amyloid a-protein. We have now identified intracellular signals which are responsible for mediating these effects. We show that activation of phospholipase C may affect APP processing by either of two pathways, one involving an increase in protein kinase C and the other an increase in cytoplasmic calcium levels. The effects ofcalcium on APP processing appear to be independent of protein kinase C activation. The observed effects of calcium on APP processing may be of therapeutic utility.Alzheimer disease is characterized by distinct neuropathological lesions, including intracellular neurofibrillary tangles, extracellular parenchymal and cerebrovascular amyloid deposits; and selective cell death that particularly affects cholinergic neurons in the basal forebrain (1). The principal component of parenchymal amyloid plaque cores and cerebrovascular amyloid is the amyloid (3-protein (A(3) (2-4). It has been shown that this -4-kDa protein is produced by various cultured cells (5-7), including transfected cells stably expressing the amyloid protein precursor (APP), from which AB is derived (8)(9)(10)(11)(12)(13)(14).During the past few years, a variety of evidence has emerged indicating that the processing of APP is regulated by signal transduction pathways. Thus, phorbol esters (activators of protein kinase C) and okadaic acid (an inhibitor of protein phosphatases 1 and 2A) increase APP metabolism and secretion (15-18). More recently, it has been shown that first messengers known to activate the phospholipase C/protein kinase C cascade increase the secretion of APP (17,19). It was also shown that the formation of a peptide with properties similar to those of Af was decreased by phorbol esters, by okadaic acid, by direct activators of phospholipase C, and by first messengers that activate phospholipase C (20-22). However, activation of phospholipase C not only activates protein kinase C (through the formation ofdiacylglycerol) but also increases cytoplasmic calcium (through the action of inositol 1,4,5-trisphosphate, IP3). For this reason, we undertook an investigation to determine whether the IP3/calcium limb of this pathway might, like the diacylglycerol/protein kinase C limb, affect APP processing. MATERIALS AND METHODSCell culture conditions and the sources of analytical reagents have been described (17,20 Pulse-chase labeling of cells was carried out on confluent cell monolayers in six-well culture dishes (Corning) with 1 ml of methionine-free Dulbecco's modified Eagle's medium (DMEM) supplemented with 1 mCi (37 MBq) of [35S]methionine/cysteine (EXPRE35S35S; NEN). Metabolic labeling was carried out for 2 hr, followed by a chase period of 2 hr. The chase was initiated by replacing the labeling medium with DMEM containing 0.2 mM unlabeled methionine. Two minutes after the start of the chase, the indicated test compounds ...

The purpose of this empirical study was to present a detailed description and interpretation of what happens in schools to beginning teachers who are prepared to enact reform‐based practices in mathematics and science. The focus was on a select sample of graduates from the Maryland Collaborative for Teacher Preparation [MCTP], a statewide reform‐based undergraduate teacher preparation program funded by the National Science Foundation. Interpretative research methodology was used to conduct a cultural case study of the beginning teachers' first 2 years of practice (first year, N = 5; second year, N = 3). We documented differential experiences and perceptions of the beginning teachers from both inside (emic) and outside (etic) perspectives. Documented discussion centered on an analytical framework suggested elsewhere. Findings were framed in two components: the individual's intentions, needs, and capabilities; and the institutional demands, affordances, and constraints. The major insight was that the beginning teachers' perception of their school culture was a major factor in whether reform‐aligned mathematics and science teaching was regularly implemented by the beginning teachers. In instances where the beginning teachers' perceived that their school cultures offered a lack of support for their intent to implement reform‐based practices the beginning teachers exhibited differing social strategies (resistance, moving on, and exit). Therefore, to sustain reform (and, by extension, to retain beginning mathematics and science teachers), a key implication is to place additional attention on the use of the school culture perspective to improve teacher preparation and induction experiences. © 2004 Wiley Periodicals, Inc. J Res Sci Teach 41: 720–747, 2004

Aging and apolipoprotein E (APOE) isoform are among the most consistent risks for the development of Alzheimer's disease (AD). Metabolic factors that modulate risk have been elusive, though oxidative reactions and their by-products have been implicated in human AD and in transgenic mice with overt histological amyloidosis. We investigated the relationship between the levels of endogenous murine amyloid b (Ab) peptides and the levels of a marker of oxidation in mice that never develop histological amyloidosis [i.e. APOE knockout (KO) mice with or without transgenic human APOE e3 or human APOE e4 alleles]. Aging-, gender-, and APOE-genotypedependent changes were observed for endogenous mouse brain Ab40 and Ab42 peptides. Levels of the oxidized lipid F 2 -isoprostane (F 2 -isoPs) in the brains of the same animals as those used for the Ab analyses revealed aging-and genderdependent changes in APOE KO and in human APOE e4 transgenic KO mice. Human APOE e3 transgenic KO mice did not exhibit aging-or gender-dependent increases in F 2 -isoPs. In general, the changes in the levels of brain F 2 -isoPs in mice according to age, gender, and APOE genotype mirrored the changes in brain Ab levels, which, in turn, paralleled known trends in the risk for human AD. These data indicate that there exists an aging-dependent, APOE-genotype-sensitive rise in murine brain Ab levels despite the apparent inability of the peptide to form histologically detectable amyloid. Human APOE e3, but not human APOE e4, can apparently prevent the aging-dependent rise in murine brain Ab levels, consistent with the relative risk for AD associated with these genotypes. The fidelity of the brain Ab/F 2 -isoP relationship across multiple relevant variables supports the hypothesis that oxidized lipids

This study investigates how two newcomer students, Elena and Martin, identified with and in science within the context of a classroom utilizing a reform-based science curriculum where instruction occurred only in English. Using ethnographic case study methods, we drew from anthropological theories on identity development and sociocultural perspectives on language development to argue that as English language proficiency mediated the newcomers' access to academic content, the viability of the newcomers' authored sciencerelated identities in practice were contingent on the dynamics generated within their small groups. We conceptualized the small groups as microfigured worlds and show how these spaces, in particular the kinds of patterned activities and practices that emerged in relation to the use of language brokering and/or code switching, mediated the kinds of identities in practices that the newcomers were able to author. We end the article by interpreting our results in relation to how Ms. Hall, the teacher, structured her classroom and discuss the relevance of race/ethnicity and gender. We conclude with suggestions about how focusing on group, or peer networks, might inform both theory and practice around how newcomers, and emergent bilinguals more broadly, engage in science.

Explanation as a genre may support children's reasoning and understanding particularly effectively. In this study, 20 fourth graders were given the task of explaining the effects of a pollutant on an ecosystem to third graders. Before writing, they completed a commercially developed science unit, instruction in reading and writing an explanation, and text reading. An analysis of their writings revealed that all children used rhetorical devices to connect with third-grade readers. Sixteen children synthesized text content with personal experiences to compose subexplanations that reported information, gave examples, and presented scenarios and that were logically ordered to enhance reader understanding. Nine of these children explicitly used the scientific model to explain phenomena. Outcomes suggested that writing explanations supported children's reasoning about and understanding of an important scientific model.