Membrane-bound state of the colicin E1 channel domain as an extended two-dimensional helical array

Atomic level structures have been determined for the soluble forms of several colicins and toxins, but the structural changes that occur after membrane binding have not been well characterized. Changes occurring in the transition from the soluble to membrane-bound state of the C-terminal 190-residue channel polypeptide of colicin E1 (P190) bound to anionic membranes are described. In the membrane-bound state, the α-helical content increases from 60–64% to 80–90%, with a concomitant increase in the average length of the helical segments from 12 to 16 or 17 residues, close to the length required to span the membrane bilayer in the open channel state. The average distance between helical segments is increased and interhelix interactions are weakened, as shown by a major loss of tertiary structure interactions, decreased efficiency of fluorescence resonance energy transfer from an energy donor on helix V of P190 to an acceptor on helix IX, and decreased resonance energy transfer at higher temperatures, not observed in soluble P190, implying freedom of motion of helical segments. Weaker interactions are also shown by a calorimetric thermal transition of low cooperativity, and the extended nature of the helical array is shown by a 3- to 4-fold increase in the average area subtended per molecule to 4,200 Å2 on the membrane surface. The latter, with analysis of the heat capacity changes, implies the absence of a developed hydrophobic core in the membrane-bound P190. The membrane interfacial layer thus serves to promote formation of a highly helical extended two-dimensional flexible net. The properties of the membrane-bound state of the colicin channel domain (i.e., hydrophobic anchor, lengthened and loosely coupled α-helices, and close association with the membrane interfacial layer) are plausible structural features for the state that is a prerequisite for voltage gating, formation of transmembrane helices, and channel opening.

Establishment and persistence of photoperiodic memory in hamsters

Long summer days unequivocally stimulate, and short winter days inhibit reproduction in Siberian hamsters. By contrast, intermediate-duration day lengths (12.5–14 h long) either accelerate reproductive development or initiate regression of the reproductive apparatus. Which of these outcomes transpires depends on an animal's photoperiodic history, suggesting that hamsters must encode a representation of prior photoperiods. The duration of nocturnal melatonin secretion is the endocrine representation of day length, but nothing is known about how long it takes to establish photoperiodic histories or how long they endure. Hamsters exposed for 2 or more weeks to long summer day lengths acquired a long-day photoperiodic history that determined subsequent reproductive responses to intermediate-duration day lengths and melatonin signals. The memory for long-day lengths persisted in pinealectomized hamsters for 6.5 weeks, faded significantly after 13 weeks, and was functionally absent after 20 weeks. These findings indicate that hamsters are influenced only by relatively recent day lengths and melatonin signals and ignore earlier ones that might cause them to misinterpret the salience of current day lengths.

RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage

The effect of neoplastic transformation on the response to genotoxic stress is of significant clinical interest. In this study, we offer genetic evidence that the apoptotic response of neoplastically transformed cells to DNA damage requires RhoB, a member of the Rho family of actin cytoskeletal regulators. Targeted deletion of the rhoB gene did not affect cell cycle arrest in either normal or transformed cells after exposure to doxorubicin or gamma irradiation, but rendered transformed cells resistant to apoptosis. This effect was specific insofar as rhoB deletion did not affect apoptotic susceptibility to agents that do not damage DNA. However, rhoB deletion also affected apoptotic susceptibility to Taxol, an agent that disrupts microtubule dynamics. We have demonstrated that RhoB alteration mediates the proapoptotic and antineoplastic effects of farnesyltransferase inhibitors, and we show here that RhoB alteration is also crucial for farnesyltransferase inhibitors to sensitize neoplastic cells to DNA damage-induced cell death. We found RhoB to be an important determinant of long-term survival in vitro and tumor response in vivo after gamma irradiation. Our findings identify a pivotal role for RhoB in the apoptotic response of neoplastic cells to DNA damage at a novel regulatory point that may involve the actin cytoskeleton.

Influencia de la madre sobre la vocación y profesión de los hijos /

Mode of access: Internet.

El capital y el trabajo ¿son armónicos ó antagonistas? : Discurso leído en el acto de recibir la investidura de doctor ... /

Tesis de la Universidad Central (Madrid), Facultad de Derecho, leída el 24-10-1861.

Local government and taxation /

Includes bibliographical references.

The American Catholic quarterly review.

Ceased publication.

English music (1604 to 1904) being the lectures given at the Music Loan Exhibition of the Worshipful Company of Musicians, held at Fishmongers' Hall, London Bridge, June-July, 1904.

The evolution of the pianoforte, by T.L. Southgate.- Our English songs, by W.H. Cummings.- The early English viols and their music, by H. Watson.- Madrigals, rounds, catches, glees, and part-songs, by E.M. Lee.- The recorder, flute, fife, and piccolo, by J. Finn.- Music in England in the year 1604, by Sir F. Bridge.- Our dances of bygone days, by A.S. Rose.- Masques and early operas, by A.H.D. Prendergast.- English opera after Purcell, by F.J. Sawyer.- Our cathedral composers and their works, by G.F. Huntley.- The single and double reed instruments, by D.J. Blaikley.- The water-organ of the ancients and the organ of to-day, by F.W. Galpin.- The regal and its successors: the harmonica, by T.L. Southgate.- The violin family and its music, by W.W. Cobbett.- The brass wind instruments, by J.E. Borland.- Some notes on early printed music, by A.H. Littleton.- Music of the country-side, by Sir E. Clarke.

Spontaneous and UV radiation-induced multiple metastatic melanomas in Cdk4(R24C/R24C)/TPras mice

Human melanoma susceptibility is often characterized by germ-line inactivating CDKN2A (INK4A/ARF) mutations, or mutations that activate CDK4 by preventing its binding to and inhibition by INK4A. We have previously shown that a single neonatal UV radiation (UVR) dose delivered to mice that carry melanocyte-specific activation of Hras (TPras) increases melanoma penetrance from 0% to 57%. Here, we report that activated Cdk4 cooperates with activated Hras to enhance susceptibility to melanoma in mice. Whereas UVR treatment failed to induce melanomas in Cdk4(R24C/R24C) mice, it greatly increased the penetrance and decreased the age of onset of melanoma development in Cdk4(R24C/R24C)/TPras animals compared with TPras alone. This increased penetrance was dependent on the threshold of Cdk4 activation as Cdk4(R24C/+)/TPras animals did not show an increase in UVR-induced melanoma penetrance compared with TPras alone. In addition, Cdk4(R24C/R24C)/TPras mice invariably developed multiple lesions, which occurred rarely in TPras mice. These results indicate that germ-line defects abrogating the pRb pathway may enhance UVR-induced melanoma. TPras and Cdk4(R24C/R24C)/TPras tumors were comparable histopathologically but the latter were larger and more aggressive and cultured cells derived from such melanomas were also larger and had higher levels of nuclear atypia. Moreover, the melanomas in Cdk4(R24C/R24C)/TPras mice, but not in TPras mice, readily metastasized to regional lymph nodes. Thus, it seems that in the mouse, Hras activation initiates UVR-induced melanoma development whereas the cell cycle defect introduced by mutant Cdk4 contributes to tumor progression, producing more aggressive, metastatic tumors.

Corporate boards and incentives: empirical evidence from the UK in 1935

We investigate boardroom governance using UK historical data for 1935. We demonstrate that there is a negative relationship between risk and incentives in this year. Prior research has produced anomalous results (Prendergast, 2002). Second, we show that average (median) board ownership of ordinary shares is about 7.95% (2.88%). Heuristically this figure is less than previously reported estimates for the US also using 1935 data. Finally, we show the phenomenon of multiple board membership. UK directors in 1935 hold many directorships – sometimes exceeding 10 concurrent memberships.

Beyond hope: Rhetorics of mobility, possibility, and literacy

When writing teachers enter the classroom, they often bring with them a deep faith in the power of literacy to rectify social inequalities and improve their students’ social and economic standing. It is this faith—this hope for change—that draws some writing teachers to locations of social and economic hardship. I am interested in how teachers and theorists construct their own narratives of social mobility, possibility, and literacy. My dissertation analyzes the production and expression of beliefs about literacy in the narratives of a diverse group of writing teachers and theorists, from those beginning their careers to those who are published and widely read. The central questions guiding this study are: How do teachers’ and theorists’ narratives of becoming literate intersect with literacy theories? and How do such literacy narratives intersect with beliefs in the power of literacy to improve individuals’ lives socially, economically, and personally? I contend that the professional literature needs to address more fully how teachers’ and theorists’ personal histories with literacy shape what they see as possible (and desirable) for students, especially those from marginalized communities. A central focus of the dissertation is on how teachers and theorists attempt to resolve a paradox they are likely to encounter in narratives about literacy. On one hand, they are immersed in a popular culture that cherishes narrative links between literacy and economic advancement (and, further, between such advancement and a “good life”). On the other hand, in professional discourse and in teacher preparation courses, they are likely to encounter narratives that complicate an assumed causal relationship between literacy and economic progress. Understanding, through literacy narratives, how teachers and theorists chart a practical path through or around this paradox can be beneficial to literacy education in three ways. First, it can offer direction in professional development and teacher education, addressing how teachers negotiate the boundaries between personal experience, theory, and pedagogy. Second, it can help teachers create spaces wherein students can explore the impact of paradoxical views about the role of literacy on their own lives. Finally, it can offer direction in public policy discourse, extending awareness of what we want—and need—from English language arts education in the twenty-first century. To explore these issues, I draw on case studies and ethnographic observation as well as narrative inquiry into teachers’ and theorists’ published literacy narratives. I situate my findings within three interrelated frames: 1) the narratives of new teachers, 2) the published works of literacy educators and theorists, and 3) my own literacy narrative. My first chapter, “Beyond Hope,” explores the tenuous connections between hope and critique in literacy studies and provides a methodological overview of the study. I argue that scholarship must move beyond a singular focus on either hope or critique in order to identify the transformative potential of literacy in particular circumstances. Analyzing literacy narratives provides a way of locating a critically informed sense of possibility. My second chapter, “Making Teachers, Making Literacy,” explores the intersection between teachers’ lives and the theories they study, based on qualitative analysis of a preservice course for secondary education English teachers. I examine how these preservice English teachers understood literacy, how their narratives of becoming literate and teaching English connected—and did not connect—with theoretical and pedagogical positions, and how these stories might inform their future work as practitioners. Centering primarily on preservice teachers who resisted Nancie Atwell’s pedagogy of possibility because they found it too good to be true, this research concentrates on moments of disjuncture, as expressed in class discussion and in one-on-one interviews, when literacy theories failed to align with aspiring teachers’ understandings of their own experiences and also with what they imagined as possible in disadvantaged educational settings. In my third and fourth chapters, I analyze the narratives of celebrated teachers and theorists who put forth an agenda that emphasizes possibilities through literacy, examining how they negotiate the relationship between their own literacy stories and literacy theories. Specifically, I investigate the narratives of three proponents of critical literacy: Mike Rose, Paulo Freire, and Myles Horton, all highly respected literacy teachers whose working-class backgrounds influenced their commitment to teaching in disenfranchised communities. In chapter 3, “Reading Lives on the Boundary,” I demonstrate how Mike Rose’s 1989 autobiographical text, Lives on the Boundary, juxtaposes rhetorics of mobility with critiques of such possibility. Through an analysis of work published in professional journals, I offer a reception history of Rose’s narrative, focusing specifically on how teachers have negotiated the tension between hope and critique. I follow this analysis with three case studies, drawn from a larger sampling, that inquire into the personal connections that writing teachers make with Lives on the Boundary. The teachers in this study, who provided written responses and participated in audio-recorded follow-up interviews, were asked to compare Rose’s story to their own stories, considering how their personal literacy histories influenced their teaching. My findings illustrate how a group of teachers and theorists have projected their own assessments of what literacy and higher education can and cannot accomplish onto this influential text. In my fourth chapter, “Horton and Freire’s Road as Literacy Narrative,” I concentrate on Myles Horton and Paulo Freire’s 1990 collaborative spoken book, We Make the Road by Walking. Central to my analysis are the educators’ stories about their formative years, including their own primary and secondary education experiences. I argue that We Make the Road by Walking demonstrates how theories of literacy cannot be divorced from personal histories. I begin by examining the spoken book as a literacy narrative that fuses personal and theoretical knowledge, focusing specifically on its authors’ ideas on theory. Drawing on Bakhtin’s notion of the chronotope—the intersection of time and space within narrative—I then explore the literacy narratives emerging from the production process of the book, in a video production about Horton and Freire’s meeting, and ultimately in the two men’s reflections on their childhood years (Dialogic). Interspersed with these accounts is archival material on the book’s editorial production that illustrates the value of increased dialogue between personal history and theories of literacy. My fifth chapter is both a reflective analysis and a qualitative study of my work at a men’s medium-high security prison in Illinois, where I conducted research and served as the instructor of an upper-level writing course, “Writing for a Change,” in the spring of 2009. Entitled “Doing Time with Literacy Narratives,” this chapter explores the complex ways in which literacy and incarceration are configured in students’ narratives as well as my own. With and against students’ stories, I juxtapose my own experiences with literacy, particularly in relation to being the son of an imprisoned father. In exploring the intersections between such stories, I demonstrate how literacy narratives can function as a heuristic for exploring beliefs about literacy between teachers and students both inside and outside of the prison-industrial complex. My conclusion pulls together the various themes that emerged in the three frames, from the making of new teachers to the published literacy narratives of teachers and theorists to my own literacy narrative. Writing teachers encounter considerable pressure to align their curricula with one or another theory of literacy, which has the effect of negating the authority of knowledge about literacy gleaned from experience as readers and writers. My dissertation contends that there is much to be gained by finding ways of articulating theories of literacy that encompass teachers’ knowledge of reading and writing as expressed in personal narratives of literacy. While powerful cultural rhetorics of upward social mobility often neutralize the critical potential of teachers’ own narratives of literacy—potential that has been documented by scholars in writing studies and allied disciplines—this is not always the case. The chapters in this dissertation offer evidence that hopeful and critical positions on the transformational possibilities of literacy are not mutually exclusive.

Sexual behaviour in early adolescence: a cross-national comparison of Australian and United States youth

Objective: This study used matched samples from schools in the states of Victoria and Washington to compare sexual behaviour in early adolescence. It was hypothesised that the contrasting dominant policy objectives of harm minimisation in Australia and abstinence in the USA would result in state differences for markers of sexual risk, mirroring prior cross-national findings in substance use. Method: A two-stage cluster sampling approach was used to recruit students from the two states. Self-reported sexual behaviour was examined for 1,596 students in annual surveys from Grade 7 in 2002 to Grade 9 in 2004. Prevalence estimates were derived for each measure of sexual behaviour, and comparisons were made between gender groups in each state. Results: State differences were found for girls' first sex, with significantly more girls in Washington than Victoria having had sex by Grade 7. By Grade 9, significantly more girls in Victoria reported sex in the last year and more sexual partners than girls in Washington. A large proportion of Grade 9 students across both states reported inconsistent contraception use. Conclusions: Contradicting the abstinence policy objective, first sex by Grade 7 was more prevalent in Washington than in Victoria. While sexual behaviour was more prevalent in Grade 9 in Victoria, the sexually active showed no clear cross-national differences in markers of risk such as contraception use and pregnancy outcomes. Findings demonstrate few cross-national differences in adolescent sexual behaviour despite the different policy contexts of Victoria and Washington.