Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

The combination of plant-expressed cellobiohydrolase and low dosages of cellulases for the hydrolysis of sugar cane bagasse

Background The expression of biomass-degrading enzymes (such as cellobiohydrolases) in transgenic plants has the potential to reduce the costs of biomass saccharification by providing a source of enzymes to supplement commercial cellulase mixtures. Cellobiohydrolases are the main enzymes in commercial cellulase mixtures. In the present study, a cellobiohydrolase was expressed in transgenic corn stover leaf and assessed as an additive for two commercial cellulase mixtures for the saccharification of pretreated sugar cane bagasse obtained by different processes. Results Recombinant cellobiohydrolase in the senescent leaves of transgenic corn was extracted using a simple buffer with no concentration step. The extract significantly enhanced the performance of Celluclast 1.5 L (a commercial cellulase mixture) by up to fourfold on sugar cane bagasse pretreated at the pilot scale using a dilute sulfuric acid steam explosion process compared to the commercial cellulase mixture on its own. Also, the extracts were able to enhance the performance of Cellic CTec2 (a commercial cellulase mixture) up to fourfold on a range of residues from sugar cane bagasse pretreated at the laboratory (using acidified ethylene carbonate/ethylene glycol, 1-butyl-3-methylimidazolium chloride, and ball-milling) and pilot (dilute sodium hydroxide and glycerol/hydrochloric acid steam explosion) scales. We have demonstrated using tap water as a solvent (under conditions that mimic an industrial process) extraction of about 90% recombinant cellobiohydrolase from senescent, transgenic corn stover leaf that had minimal tissue disruption. Conclusions The accumulation of recombinant cellobiohydrolase in senescent, transgenic corn stover leaf is a viable strategy to reduce the saccharification cost associated with the production of fermentable sugars from pretreated biomass. We envisage an industrial-scale process in which transgenic plants provide both fibre and biomass-degrading enzymes for pretreatment and enzymatic hydrolysis, respectively.

The microwell-mesh: A novel device and protocol for the high throughput manufacturing of cartilage microtissues

Microwell platforms are frequently described for the efficient and uniform manufacture of 3-dimensional (3D) multicellular microtissues. Multiple partial or complete medium exchanges can displace microtissues from discrete microwells, and this can result in either the loss of microtissues from culture, or microtissue amalgamation when displaced microtissues fall into common microwells. Herein we describe the first microwell platform that incorporates a mesh to retain microtissues within discrete microwells; the microwell-mesh. We show that bonding a nylon mesh with an appropriate pore size over the microwell openings allows single cells to pass through the mesh into the microwells during the seeding process, but subsequently retains assembled microtissues within discrete microwells. To demonstrate the utility of this platform, we used the microwell-mesh to manufacture hundreds of cartilage microtissues, each formed from 5 × 10(3) bone marrow-derived mesenchymal stem/stromal cells (MSC). The microwell-mesh enabled reliable microtissue retention over 21-day cultures that included multiple full medium exchanges. Cartilage-like matrix formation was more rapid and homogeneous in microtissues than in conventional large diameter control cartilage pellets formed from 2 × 10(5) MSC each. The microwell-mesh platform offers an elegant mechanism to retain microtissues in microwells, and we believe that this improvement will make this platform useful in 3D culture protocols that require multiple medium exchanges, such as those that mimic specific developmental processes or complex sequential drug exposures.

Russell D James and Peter J Wosh (eds)

Public Relations and Marketing for Archives: A How-to-do-it Manual, New York, Neal-Schuman Publishers with the Society of American Archivists, 2011. xiv + 273 pp. ISBN 978-1-5557-0733-0. US$80.00 Public Relations and Marketing for Archives – A How-To-Do-It Manual provides a brief, but broad overview of the key elements of marketing, public relations and stakeholder engagement for archives...

Adding paths to resilience and daily accounts to an already rich field of inquiry: A brief commentary on James Jackson's "Social structure and health disparities"

In absolute terms, there have been improvements in social resources for all racial and ethnic groups in the United States. The rise in education levels among blacks and Hispanics, for instance, suggests a lessening of the gap between classes, beginning in the later part of the 1960’s (Kao & Thompson, 2003). Yet the divide in income and to a lesser extent education between peoples who differ in gender, skin color and ethnic origin continues and in many ways is greater now than ever (Danziger & Gottschalk, 1997); (Gottschalk, 1997). The psychological distance between those high and those low in social-economic status continues unabated and threatens to undermine the capacity of communities to foster the positive architecture of hope, optimism and equal opportunity that holds us together as a nation...

A Chlamydia trachomatis strain with a chemically generated amino acid substitution (P370L) in the cthtrA gene shows reduced elementary body production

Background Chlamydia (C.) trachomatis is the most prevalent bacterial sexually transmitted infection worldwide and the leading cause of preventable blindness. Genetic approaches to investigate C. trachomatis have been only recently developed due to the organism’s intracellular developmental cycle. HtrA is a critical stress response serine protease and chaperone for many bacteria and in C. trachomatis has been previously shown to be important for heat stress and the replicative phase of development using a chemical inhibitor of the CtHtrA activity. In this study, chemically-induced SNVs in the cthtrA gene that resulted in amino acid substitutions (A240V, G475E, and P370L) were identified and characterized. Methods SNVs were initially biochemically characterized in vitro using recombinant protein techniques to confirm a functional impact on proteolysis. The C. trachomatis strains containing the SNVs with marked reductions in proteolysis were investigated in cell culture to identify phenotypes that could be linked to CtHtrA function. Results The strain harboring the SNV with the most marked impact on proteolysis (cthtrAP370L) was detected to have a significant reduction in the production of infectious elementary bodies. Conclusions This provides genetic evidence that CtHtrA is critical for the C. trachomatis developmental cycle.

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Rationality, governmentality, natio(norm)ality: Shaping social science, scientific objects, and the invisible

The discipline of education in Anglophone-dominant contexts has always grappled with a kind of status anxiety relative to other disciplines. This is in part due to the ways in which evidence has been thought about in the theoretico-experimental sciences relative to the ethico-redemptive ones. By examining that which was considered to fall to the side of science, even of social science, this paper complexifies contemporary debates over educational science and research, including debates over evidence-based education or assumed divisions between the quantitative/qualitative and empirical/conceptual. It reapproaches historical vagaries in discourses of vision that underscore the arbitrariness of approaches to social scientific research and its objects. A less-considered set of spatializations and regionalisms in social scientific conceptions of rationality especially are exposed through a close reading of the Harvard University philosopher William James' more marginalized texts.

Canon and Beyond : Edvard Fazer and the Imperial Russian Ballet 1908 - 1910

The study explores the first appearances of Russian ballet dancers on the stages of northern Europe in 1908 1910, particularly the performances organized by a Finnish impresario, Edvard Fazer, in Helsinki, Stockholm, Copenhagen and Berlin. The company, which consisted of dancers from the Imperial Theatres of St. Petersburg, travelled under the name The Imperial Russian Ballet of St. Petersburg. The Imperial Russian Ballet gave more than seventy performances altogether during its tours of Finland, Sweden, Denmark and central Europe. The synchronic approach of the study covers the various cities as well as genres and thus stretches the rather rigid geographical and genre boundaries of dance historiography. The study also explores the role of the canon in dance history, revealing some of the diversity which underlies the standard canonical interpretation of early twentieth-century Russian ballet by bringing in source material from the archives of northern Europe. Issues like the central position of written documentation, the importance of geographical centres, the emphasis on novelty and reformers and the short and narrow scholarly tradition have affected the formation of the dance history canon in the west, often imposing limits on the historians and narrowing the scope of research. The analysis of the tours concentrates on four themes: virtuosity, character dancing, the idea of the expressive body, and the controversy over ballet and new dance. The debate concerning the old and new within ballet is also touched upon. These issues are discussed in connection with each city, but are stressed differently depending on the local art scene. In Copenhagen, the strong local canon based on August Bournonville s works influenced the Danish criticism of Russian ballet. In Helsinki, Stockholm and Berlin, the lack of a solid local canon made critics and audiences more open to new influences, and ballet was discussed in a much broader cultural context than that provided by the local ballet tradition. The contemporary interest in the more natural, expressive human body, emerging both in theatre and dance, was an international trend that also influenced the way ballet was discussed. Character dancing, now at low ebb, played a central role in the success of the Imperial Russian Ballet, not only because of its exoticism but also because it was considered to echo the kind of performing body represented by new dance forms. By exploring this genre and its dancers, the thesis brings to light artists who are less known in the current dance history canon, but who made considerable careers in their own time.

Stenotaphrum secundatum, Buffalo Grass 'Sir James'

Spontaneous mutation: discovered in February 2001 as a superior plant growing among “Common” buffalo grass growing on the breeder’s property at Saltash in the Hunter Valley (NSW). The selected material has smaller (finer) leaves and showed better growth and colour than the parent variety with minimal inputs (water, fertiliser) under stressful climatic conditions. Subsequently, it also showed better leaf colour retention than the parent variety during winter. A vegetative plug taken from the original plant has now undergone four subsequent vegetative divisions to expand the original material for performance trials in NSW and Queensland without showing any discernible off types. Main selection criteria: winter colour retention, small leaves, low fertiliser requirement. Propagation: vegetative. Breeder: Brent Redman, Maitland North, NSW. PBR Certificate Number 2715, Application Number 2002/283, granted 18 March 2005.