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For readers unfamiliar with Polish poetry and who thirst for the sacramental, this book is a huge find. A far cry from American Puritanically based poetry--The Oxford Book of American [...]

Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders (1). Substantial risk for schizophrenia is conferred by large (>500-kilobase) CNVs at several loci, including microdeletions at 1q21.1 (ref. 2), 3q29 (ref. 3), 15q13.3 (ref. 2) and22q11.2 (ref. 4) and microduplication at 16p11.2 (ref. 5). However, these CNVs collectively account for a small fraction (2-4%) of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene vipr2. vipr2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs., A majority of the rare CNVs that have been implicated in schizophrenia involve large (>500 kb) genomic regions where local segmental duplication architecture promotes frequent and nearly identical re-arrangements by [...]

Recent claims about the convergence in methodology between 'high politics' and the 'new political history' remain unclear. The first part of this review examines two deeply entrenched misunderstandings of key works of high politics from the 1960s and 1970s, namely that they proposed elitist arguments about the 'closed' nature of the political world, and reductive arguments about the irrelevance of 'ideas' to political behaviour. The second part traces the intellectual ancestry of Maurice Cowling's thinking about politics, and places it within an interpretative tradition of social science. The formative influences of R. G. Collingwood and Michael Oakeshott are examined, and Mark Bevir's Logic of the history of ideas is used to highlight how Cowling's approach can be aligned with ' new political history'. doi: 10.1017/S0018246X10000129

A genome-wide association study (GWAS) mapping of methylation quantitative trait loci for all the CpG sites of genes in adult human cerebellum samples is undertaken to analyze the genetic control of individual differences in gene-specific methylation in human brain. Results reveal that DNA methylation is substantially correlated with gene expression, demonstrating that DNA methylation is a heritable continuous quantitatively variable attribute in the human brain.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.anbehav.2009.12.022 Byline: John M. Marzluff (a), Jeff Walls (a), Heather N. Cornell (a), John C. Withey (a), David P. Craig (b) Abstract: While many domestic and laboratory animals recognize familiar humans, such ability in wild animals is only anecdotally known. Here we demonstrate experimentally that a cognitively advanced, social bird, the American crow, Corvus brachyrhynchos, quickly and accurately learns to recognize the face of a dangerous person and continues to do so for at least 2.7 years. We exposed wild crows to a novel 'dangerous face' by wearing a unique face mask as we trapped, banded and released 7-15 birds at five sites near Seattle, WA, U.S.A. After trapping, crows consistently used harsh vocalizations to scold and mob people of different sizes, ages, genders and walking gaits who wore the dangerous mask, even when they were in crowds. In contrast, prior to trapping, few crows scolded people who wore the dangerous mask. Furthermore, after trapping, few crows scolded trappers who wore no mask or who wore a mask that had not been worn during trapping. In a fully crossed, balanced experiment in which each site had a unique trapping (dangerous) mask and five neutral masks, crows scolded and mobbed a mask more when it was the dangerous mask at that site than when it was a neutral mask at another site. When simultaneously presented with a person in the dangerous mask and a person in the neutral mask, crows typically ignored the neutral mask and followed and scolded the person wearing the dangerous mask. Risky, aggressive scolding by crows was sensitive to variable costs across study sites; aggression was less where people persecuted crows most. We suggest that conditioned and observational learning of specific threats may allow local bird behaviours to include aversions to individual people. Author Affiliation: (a) College of the Environment, University of Washington, Seattle, WA, U.S.A. (b) Department of Biology, Willamette University, Salem, OR, U.S.A. Article History: Received 24 July 2009; Revised 28 September 2009; Accepted 10 December 2009 Article Note: (miscellaneous) MS. number: A09-00496

Increased extracellular pressure stimulates [[beta].sub.1]-integrin-dependent cancer cell adhesion. We asked whether pressure-induced adhesion is mediated by changes in [[beta].sub.1]-integrin binding affinity or avidity and whether these changes are phosphorylation dependent. We evaluated integrin affinity and clustering in human SW620 colon cancer cells by measuring differences in binding between soluble Arg-Gly-Asp (RGD)-Fc ligands and RGD-Fc-F[(ab').sub.2] multimeric complexes under ambient and 15-mmHg increased pressures. Phosphorylation of [[beta].sub.1]-integrin S785 and T788/9 residues in SW620 and primary malignant colonocytes was assessed in parallel. We further used GD25-[[beta].sub.1]-integrin-null murine fibroblasts stably transfected with either wild-type [[beta].sub.1A]-integrin, S785A, TT788/9AA, or T788D mutants to investigate the role of [[beta].sub.1]-integrin site-specific phosphorylation. SW620 binding of RGD-Fc-F[(ab').sub.2] multimeric complexes, but not soluble RGD-Fc ligands, was sensitive to integrin clustering. RGD-Fc ligand binding was significantly increased under elevated pressure, suggesting that pressure modulates [[beta].sub.1]-integrin affinity. Pressure stimulated both [[beta].sub.1]-integrin S785 and T788/9 phosphorylation. GD25-[[beta].sub.1A]-integrin wild-type and S785A cells displayed an increase in adhesion to fibronectin under elevated pressure, an effect absent in [[beta].sub.1]-integrin-null and TT788/9AA cells. T788D substitution significantly elevated basal cell adhesion but displayed no further increase under pressure. These results suggest pressure-induced cell adhesion is mediated by [[beta].sub.1]-integrin T788/9 phosphorylation-dependent changes in integrin binding affinity. adhesion; mechanotransduction; metastasis

Noninvasive analysis of metabolism at the single cell level will have many applications in evaluating cellular physiology. One clinically relevant application would be to determine the metabolic activities of embryos produced through assisted reproduction. There is increasing evidence that embryos with greater developmental capacity have distinct metabolic profiles. One of the standard techniques for evaluating embryonic metabolism has been to evaluate consumption and production of several key energetic substrates (glucose, pyruvate, and lactate) using microfluorometric enzymatic assays. These assays are performed manually using constriction pipets, which greatly limits the utility of this system. Through multilayer soft-lithography, we have designed a microfluidic device that can perform these assays in an automated fashion. Following manual loading of samples and enzyme cocktail reagents, this system performs sample and enzyme cocktail aliquotting, mixing of reagents, data acquisition, and data analysis without operator intervention. Optimization of design and operating regimens has resulted in the ability to perform serial measurements of glucose, pyruvate, and lactate in triplicate with submicroliter sample volumes within 5 min. The current architecture allows for automated analysis of 10 samples and intermittent calibration over a 3 h period. Standard curves generated for each metabolite have correlation coefficients that routinely exceed 0.99. With the use of a standard epifluorescent microscope and CCD camera, linearity is obtained with metabolite concentrations in the low micromolar range (low femtomoles of total analyte). This system is inherently flexible, being easily adapted for any NAD(P)H-based assay and scaled up in terms of sample ports. Open source JAVA-based software allows for simple alterations in routine algorithms. Furthermore, this device can be used as a standalone device in which media samples are loaded or be integrated into microfluidic culture systems for in line, real time metabolic evaluation. With the improved throughput and flexibility of this system, many barriers to evaluating metabolism of embryos and single cells are eliminated. As a proof of principle, metabolic activities of single murine embryos were evaluated using this device.

Iatrogenic tumor cell implantation within surgical wounds can compromise curative cancer surgery. Adhesion of cancer cells, in particular colon cancer cells, is stimulated by exposure to increased extracellular pressure through a cytoskeleton-dependent signaling mechanism requiring FAK, Src, Akt, and paxillin. Mechanical stimuli during tumor resection may therefore negatively impact patient outcome. We hypothesized that perioperative administration of colchicine, which prevents microtubule polymerization, could disrupt pressure-stimulated tumor cell adhesion to surgical wounds and enhance tumor-free survival. Ex vivo treatment of Co26 and Co51 colon cancer cells with colchicine inhibited pressure-stimulated cell adhesion to murine surgical wounds and blocked pressure-induced FAK and Akt phosphorylation. Surgical wound contamination with pressure-activated Co26 and Co51 cells significantly reduced tumor-free survival compared with contamination with tumor cells under ambient pressure. Mice treated with pressure-activated Co26 and Co51 cells from tumors preoperatively treated with colchicine in vivo displayed reduced surgical site implantation and significantly increased tumor-free survival compared with mice exposed to pressure-activated cells from tumors not pretreated with colchicine. Our data suggest that pressure activation of malignant cells promotes tumor development and impairs tumor-free survival and that perioperative colchicine administration or similar interventions may inhibit this effect., Introduction Viable tumor cells can frequently be recovered from the peritoneal cavity and from the portal and systemic venous circulation during colon cancer resections (1), (2). The presence of free [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.anbehav.2007.11.009 Byline: Jacquelyn Grace, David P. Craig Abstract: Laterality or the preferential use of one or the other side of the body is associated with differential brain activity and increased specialization of brain function. Right or left biases are widespread among vertebrates and have been documented among some birds. Bill load holding or the delivery of whole prey in a bird's beak is common among terns (Charadriiformes) and many other birds. We recorded more than 2000 Caspian tern, Hydroprogne caspia, chick-feeding events for analysis of lateralization of prey within the bills of adult birds, size and shape of prey items delivered to chicks in relation to chick age, and the development of prey-handling skills among chicks. No initial lateralization of prey head position was found as adults flew into the colony, but head position of successful feeds was found to be significantly lateralized with a bias to the right side. Adults switched prey orientation significantly more often from left to right than from right to left without dropping the prey item, suggesting an adult bias. Adults appeared to adjust the length but not the shape of prey delivered according to chick age. Ability of chicks to manipulate prey items increased with age. Lateralization was most obvious in the first week of a tern's life, and adults modified their delivery behaviour to respond to these changes. Bill load-holding birds are excellent subjects to study lateralization of feeding behaviour in the wild and they may allow integration of lateralization with developmental changes. Author Affiliation: Willamette University, U.S.A. Article History: Received 2 August 2007; Revised 6 September 2007; Accepted 5 November 2007 Article Note: (miscellaneous) MS. number: A10835

The cause of hypothalamic hamartoma (HH) pathogenesis in sporadic cases is investigated. The chromosomal abnormalities within the GLI3 locus are associated with HH pathogenesis in sporadic, nonsyndromic patients with HH and intractable epilepsy.

Physical forces including pressure, strain, and shear can be converted into intracellular signals that regulate diverse aspects of cell biology. Exposure to increased extracellular pressure stimulates colon cancer cell adhesion by a [[beta].sub.1]-integrin-dependent mechanism that requires an intact cytoskeleton and activation of focal adhesion kinase (FAK) and Src. [alpha]-Actinin facilitates focal adhesion formation and physically links integrin-associated focal adhesion complexes with the cytoskeleton. We therefore hypothesized that [alpha]-actinin may be necessary for the mechanical response pathway that mediates pressure-stimulated cell adhesion. We reduced [alpha]-actinin-1 and [alpha]-actinin-4 expression with isoform-specific small interfering (si)RNA. Silencing of [alpha]-actinin-1, but not [alpha]-actinin-4, blocked pressure-stimulated cell adhesion in human SW620, HT-29, and Caco-2 colon cancer cell lines. Cell exposure to increased extracellular pressure stimulated [alpha]-actinin-1 tyrosine phosphorylation and [alpha]-actinin-1 interaction with FAK and/or Src, and enhanced FAK phosphorylation at residues Y397 and Y576. The requirement for [alpha]-actinin-1 phosphorylation in the pressure response was investigated by expressing the [alpha]-actinin-1 tyrosine phosphorylation mutant Y 12F in the colon cancer cells. Expression of Y12F blocked pressure-mediated adhesion and inhibited the pressure-induced association of [alpha]-actinin-1 with FAK and Src, as well as FAK activation. Furthermore, siRNA-mediated reduction of [alpha]-actinin-1 eliminated the pressure-induced association of [alpha]-actinin-1 and Src with [[beta].sub.1]-integrin receptor, as well as FAK-Src complex formation. These results suggest that [alpha]-actinin-1 phosphorylation at Y12 plays a crucial role in pressure-activated cell adhesion and mechanotransduction by facilitating Src recruitment to [[beta].sub.1]-integrin, and consequently the association of FAK with Src, to enhance FAK phosphorylation. mechanical signaling; pressure; cancer

A genomewide case control association study is carried out to identify the specific genetic variants associated with sporadic amyotrophic lateral sclerosis (ALS). Results concluded that variants of the uncharacterized gene, FLJ10986 may confer susceptibility to sporadic ALS.

A hypothesis that additional genetic loci might be involved in conferring risk of progressive supranuclear palsy (PSP) that could be identified through a pooling-based genomewide association study of >500,000 SNPs is presented. Ranking all SNPs by their probe-intensity difference between cohorts identifies candidate SNPs with large differences in alleic frequency.

The development and validation of experimental methods, study designs and analysis software are reported for pooling-based genomewide association (GWA) studies. The results of theoretical calculations and their experimental validation suggest that pooling-based genomewide association studies are a logical first step for determining whether major genetic associations exist in diseases with high heritability.

Objective: This study examines the impact of a social norms intervention to reduce alcohol misuse among student-athletes. The intervention was designed to reduce harmful misperceptions of peer norms and, in turn, reduce personal risk. Method: A comprehensive set of interventions communicating accurate local norms regarding alcohol use targeted student-athletes at an undergraduate college. An anonymous survey of all student-athletes was conducted annually for 3 years (2001: n = 414, 86% response; 2002: n = 373, 85% response; and 2003: n = 353, 79% response). A pre/post comparison of student-athletes was conducted separately for new and ongoing athletes at each time point to isolate any general time period effects from intervention effects. A cross-sectional analysis of student-athletes with varying degrees of program exposure was also performed. Results: The intervention substantially reduced misperceptions of frequent alcohol consumption and high-quantity social drinking as the norm among student-athlete peers. During this same time period, frequent personal consumption, high-quantity consumption, high estimated peak blood alcohol concentrations during social drinking, and negative consequences all declined by 30% or more among ongoing student-athletes after program exposure. In contrast, no significant differences across time were seen for new student-athletes each year with low program exposure. Among student-athletes with the highest level of program exposure, indications of personal misuse were at least 50% less likely on each measure when compared with student-athletes with the lowest level of program exposure. Conclusions: This social norms intervention was highly effective in reducing alcohol misuse in this high-risk collegiate subpopulation by intensively delivering data-based messages about actual peer norms through multiple communication venues., THERE CAN BE LITTLE DOUBT that heavy alcohol consumption on college campuses and its many negative effects constitute one of the most persistent and challenging problems facing most institutions of [...]

Current models of analogical reasoning assume that representations of source examples and target problems occur in an amodal format--that is, a representation whose construction and processing are independent of activity in the perceptual and motor cortices of the brain. We examined the possible use of kinesthetic information--perceptual structures associated with the sensation of space and force--in the representation of source examples and target problems. Participants who recreated a source story while acting out the key elements were more likely to access the story when later working on the target problem than were participants who only verbally recreated the story or who verbally recreated it as well as sketched it. We argue that enactment made kinesthetic and spatial features more salient in participants' source story representations and that this aided performance. These results suggest that current models of analogical reasoning might be improved by including perceptual information as part of their representational schemes.

Taranaki Gothic is arguably the most important narrative archetype in New Zealand cultural production and political economy. The basic Taranaki Gothic pattern--innocent, fast rising excitement, peaking early, seeing itself threatened, unravelling as wider realities tell, crashing and burning at the end--resonates widely through national experience and sensibility. It's discernable in crucial identity narrative experiences--Gallipoli, Flanders, Phar Lap, national development by import substitution, Think Big, the '87 sharemarket crash, the America's Cup--and in thematic obsessions of cultural production: innocence hypostatized or violated by trauma, slapstick adventure going wrong, apparently dissociated elements and protagonists coming together quick with explosive consequence. When cultural and political economic Taranaki Gothic moments run into each other, there's a standard repertoire of formal outcomes: the overwrought, the understated, the faux naive, quirky, frenzied, grotesque, and doctrinaire. This, the essay argues, is a predictable experience for a small, distanced political and cultural economy in the semi-periphery of modern capitalism. But while the basic Taranaki Gothic narrative has remained archetypal, it has been differently engaged, and perversely instantiated, in different phases of New Zealand political-economic-cultural production.

Abstract The prospect of government agencies, local government and community groups working together holds a number of promises. In Waitakere City, collaborative activity in social sectors is based on a [...]

We examined nesting distribution and demography of the Pacific Coast population of Caspian Terns (Sterna caspia) using breeding records and band recoveries spanning two decades since the first population assessment. Since 1980, population size has more than doubled to about 12 900 pairs, yet the proportion of the population nesting at inland (18%) versus coastal sites (82%) has remained constant. Although the breeding range of the Pacific Coast population has expanded northward into Alaska and farther south in Mexico, there was no net latitudinal shift in the distribution of breeding pairs or new colonies. The distribution of breeding birds among areas changed dramatically, however, with 69% of breeding terns now nesting in Oregon (primarily in the Columbia River estuary) versus 4% during the late 1970s. During the past 20 years, there has continued to be a greater proportion of Caspian Terns breeding at anthropogenic sites compared to natural sites. Estimated annual survival rates for hatch-year and after-third-year birds during 1981-1998 were greater than during 1955-1980, consistent with the higher rate of population increase in recent decades. Fecundity required to maintain a stable population ([lambda] = 1) was estimated at 0.32-0.74 fledglings [pair.sup.-1] depending on band recovery probabilities for sub-adults. Caspian Terns readily moved among breeding sites and rapidly colonized new areas; however, a greater concentration of breeding Caspian Terns among fewer colonies in response to anthropogenic factors is an important conservation concern for this species. Key words: anthropogenic effects, Caspian Tern, population size, range expansion, redistribution, Sterna caspia, survival rates.

We have identified a lethal phenotype characterized by sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males [Online Mendelian Inheritance in Man (OMIM) accession no. 608800]. Twenty-one affected individuals with this autosomal recessive syndrome were ascertained in nine separate sibships among the Old Order Amish. High-density single-nucleotide polymorphism (SNP) genotyping arrays containing 11,555 single-nucleotide polymorphisms evenly distributed across the human genome were used to map the disease locus. A genomewide autozygosity scan localized the disease gene to a 3.6-Mb interval on chromosome 6q22.1-q22.31. This interval contained 27 genes, including two testis-specific Y-like genes (TSPYL and TSPYL4) of unknown function. Sequence analysis of the TSPYL gene in affected individuals identified a homozygous frame-shift mutation (457_458insG) at codon 153, resulting in truncation of translation at codon 169. Truncation leads to loss of a peptide domain with strong homology to the nucleosome assembly protein family. GFP-fusion expression constructs were constructed and illustrated loss of nuclear localization of truncated TSPYL, suggesting loss of a nuclear localization patch in addition to loss of the nucleosome assembly domain. These results shed light on the pathogenesis of a disorder of sexual differentiation and brainstem-mediated sudden death, as well as give insight into a mechanism of transcriptional regulation.

John Milbank appropriates John Ruskin as part of his 'Augustinian' tradition. Milbank's selective reading, however, omits Ruskin's fixed hierarchies as well as his acknowledgment of conflict in economic life. Neither of these ideas fits the social aesthetics of harmony and difference that Milbank claims is unique to Christian theology. While Milbank's strictly theoretical portrait of theology gains critical force from Ruskin's robust account of social practices and just exchange, Milbank lacks effective historical and institutional responses to the problems in Ruskin's corpus. This deficiency undermines Milbank's dichotomy between theology and secular reason. KEY WORDS: aesthetics, capitalism, charity, Milbank, John Ruskin, secular reason, social practices

Fibronectin (FN) forms fibrillar networks coupling cells to the extracellular matrix. The formation of FN fibrils, fibrillogenesis, is a tightly regulated process involving the exposure of cryptic binding sites in individual FN type III (FN-III) repeats presumably exposed by mechanical tension. The FN-[III.sub.1] module has been previously proposed to contain such cryptic sites that promote the assembly of extracellular matrix FN fibrils. We have combined NMR and steered molecular dynamics simulations to study the structure and mechanical unfolding pathway of FN-[III.sub.1]. This study finds that FN-[III.sub.1] consists of a [beta]-sandwich structure that unfolds to a mechanically stable intermediate about four times the length of the native folded state. Considering previous experimental findings, our studies provide a structural model by which mechanical stretching of FN-[III.sub.1] may induce fibrillogenesis through this partially unfolded intermediate.

In the last two decades historians have been increasingly interested in the modernization of the monarchy, and the nature of the republican threat. This review evaluates some of this recent literature. The first section argues that while Walter Bagehot's views about ceremony in The English constitution (1867) have influenced historical writing, these approaches do not yield much information about what the monarchy actually meant to people. The second section turns to the political powers of the monarchy, and examines the wide range of views about what the constitutional limits of royal power were. It also shows that even radical writers were often unable to dispel the monarchy from their imaginations. Finally, the review suggests that criticism of the royal family was not necessarily republican, and arose more from concern that particular figures were failing to conform to shared public values. Pure republicans were few, and did not usually focus their energies on the monarchy, but rather on the nature of parliamentary representation and the power of the Lords.

Poverty reduction strategy papers represent both a primary policy device of international development institutions, and an instance of a wider international convergence of public policy around global integration and social inclusion. Charting the emergence of these approaches, this paper argues that this convergence has a number of structural predilections which favor the technical and juridical over the political economic, and a disciplinary framework over a practical contest. Drawing extensively on decentralized governance and poverty reduction programs in Uganda, this paper shows how these predilections obscure power relations and restrict practical and political options, while exacting heavy establishment and compliance costs. Key words--poverty reduction, PRSP, governance, Africa, Uganda

The relocation of Caspian terns to protect juvenile salmonids in the Columbia River region is described and evaluated. The short-term results of relocating terns from Rice Island to East Sand Island has reduced salmonid predation without harming tern breeding populations.

Popular medical knowledge and practice exist in forms that people are able to remember, and that they use to manage their daily lives. This knowledge is fundamentally practical and relates to the patterns of everyday life and the rhythms of the body. The broad 'polythetic' concepts of this knowledge system are typically drawn from both dominant and other medical knowledges, and combined in pragmatic, mnemonic ways that constitute a hybrid system. Such popular medical knowledge is attuned to local, family and cultural patterns of medical and other authority, and to the personal dispositions and environmental contexts of its users. Health promoters and educators who understand these formal, embodied and familiar dimensions of popular knowledge can potentially mimic this knowledge system, making their interventions a sustainable part of everyday family life.

Quail eggs are useful for identifying predators as small as chipmunks. This was found in an examination of the behavior of least chipmunks eating quail eggs in artificial nests in the Colorado Front Range. The birds were found to eat quail eggs by first breaking through the small end of the eggs, since its gape is not wide enough to bite the egg from the side or the large end. These results showed that although the maximum gape size of a predator is smaller than the width of an egg, the animal still cannot be eliminated as a likely predator.

Journalism and mass communication students and professors feel that technological innovations in the mass media will require curricular changes for journalism courses. Q-sorting statements were used to determine four attitudinal types. The Champion of Change are excired about the changes and feel unthreatened by the developments. The Pessimistic Prophet feels there are moral problems connected to technology and that it is destructive to society. The Laid-Back Liberals think the new media will benefit individuals but will have a negative social impact. The Skeptical Optimist believes in technology's potential but is not convinced.

Laboratory studies of the evolution of the outcome of competition, interspecific competitive ability, and character displacement have produced mixed results. Many investigators (e.g., Pimental et al. 1965; Powell and Wistrand [...]