Polarization-dependence of anomalous scattering in brominated DNA and RNA molecules, and importance of crystal orientation in single- and multiple-wavelength anomalous diffraction phasing

In this paper the anisotropy of anomalous scattering at the Br K-absorption edge in brominated nucleotides is investigated, and it is shown that this effect can give rise to a marked directional dependence of the anomalous signal strength in X-ray diffraction data. This implies that choosing the correct orientation for crystals of such molecules can be a crucial determinant of success or failure when using single- and multiple-wavelength anomalous diffraction (SAD or MAD) methods to solve their structure. In particular, polarized absorption spectra on an oriented crystal of a brominated DNA molecule were measured, and were used to determine the orientation that yields a maximum anomalous signal in the diffraction data. Out of several SAD data sets, only those collected at or near that optimal orientation allowed interpretable electron density maps to be obtained. The findings of this study have implications for instrumental choices in experimental stations at synchrotron beamlines, as well as for the development of data collection strategy programs

Rural-urban migration in Iganna: a study of the changing relations of production in an agricultural community in northwestern Yorubaland

This thesis focuses on rural-urban migration in Iganna, an ancient Yoruba kingdom located fifty miles west of 0yo in Nigeria. The fieldwork on which this thesis is based took place in Iganna and partly in Ibadan and Lagos between April 1974 and October 1975. The central hypothesis which is put forward in the thesis is that the present-day rural exodus to the urban centres (especially by young people) cannot adequately be accounted for in terms of a 'quest for money' explanation, or, more generally, in terms of formal maximisation theories. The root of this problem, it is argued, lies in the radical changes in the relations of production within the traditional kin-based household units since the inclusion of farm produce in long-distance trade, with the result that farmers become increasingly dependent on/indebted to the middle traders (these are usually their womenfolk) and the hired labourers (these are men from outside Yorubaland). Inherent in this quantitative expansion of commercial farming is a qualitative decrease in social solidarity in the more traditional Yoruba rural communities. The first part of the thesis examines the present-day migration phenomenon as it presents itself in Iganna. While the town has been drained of large numbers of its young people who have been emigrating to the cities since the 1950s, immigration into the area has taken place by Yoruba farmers from other towns, by Fulani pastoralists and by farm labourers from outside Yorubaland. Interviews and questionnaire results concerning the reasons for emigration reveal that most people hold the opinion that there is no money in farming, while emigration to the cities holds the promise of a better and more affluent life. Research into the occupations and living conditions of the people concerned, however, did not fully support such explanations. In the cities the majority of the Iganna migrants live in relative poverty, while in Iganna there are farmers, albeit mainly non-native, who realise good money returns in cash-cropping; although it is true that the majority of the Iganna farmers are chronically hard-up for money. In the second part of the thesis the system of agricultural production in Iganna is examined with why it is unrewarding. A model of the traditional system of agricultural production is presented which explains how farmer- householders used to exert control both over the allocation of their produce and over their dependent co-producers. An analysis is made of the modern changes in agricultural production which were triggered off by the inclusion of farm produce in the external trade with the distant urban markets. In the new system of production farmers no longer depend on their chiefs as patrons and creditors. Instead, their womenfolk who have now become the middle traders in farm produce provide them with credit. Farmers can no longer obtain the assistance of their own household dependants, especially sons and debt-labourers, in order to increase their production. Instead they have to pay for the services of migrant labourers. Hence farmers tend to find themselves socially at the loser's end of the modern system of production, even when they make profits. While the traditional town environment in Iganna tends to disguise these reversed relations of production, it also inhibits farmers from modernising their system of production. At the some time Government policies and initiatives with regard to agriculture have usually proved to be inadequate in coming to grips with the real conditions in which agricultural production is caught in the rural areas. Hence the discrepancies between present-day agricultural production and the rapid social changes in most other domains tend to become more pronounced as time goes on, thus precipitating the large-scale emigration from the rural towns like Iganna to the cities

Brief Report: Does Gender Matter in Intervention for ASD? Examining the Impact of the PEERS® Social Skills Intervention on Social Behavior Among Females with ASD

A paucity of research has been conducted to examine the effect of social skills intervention on females with ASD. Females with ASD may have more difficulty developing meaningful friendships than males, as the social climate can be more complex (Archer, Coyne, Personality and Social Psychology Review 9(3):212–230, 2005). This study examined whether treatment response among females differed from males. One hundred and seventy-seven adolescents and young adults with ASD (N = 177) participated in this study. When analyzed by group, no significant differences by gender emerged: PEERS® knowledge (TASSK/TYASSK, p = .494), direct interactions (QSQ, p = .762), or social responsiveness (SRS, p = .689; SSIS-RS, p = .482). Thus, females and males with ASD respond similarly to the PEERS® intervention

Changes in Depressive Symptoms Among Adolescents with ASD Completing the PEERS® Social Skills Intervention

Depression is a common concern among people with autism spectrum disorder (ASD) and is often associated with social skills and relationship challenges. The present data, from a randomized controlled trial, examined the effect of PEERS® on self-reported depressive symptoms via the Children’s Depression Inventory (CDI) among 49 adolescents with ASD. Findings revealed that many CDI subscale scores declined (p’s \u3c 0.05) and were related to direct social contact on the Quality of Socialization Questionnaire at posttest (p’s \u3c 0.05). Exploratory analyses uncovered that suicidality was less evident following PEERS®. Findings support the notion that social functioning and depression may be intimately intertwined in ASD; therefore, bolstering social skills in ASD may positively influence other domains of functioning, including mental health

A novel gamma-N-methylaminobutyrate demethylating oxidase involved in catabolism of the tobacco alkaloid nicotine by Arthrobacter nicotinovorans pAO1

Nicotine catabolism, linked in Arthrobacter nicotinovorans to the presence of the megaplasmid pAO1, leads to the formation of gamma-N-methylaminobutyrate from the pyrrolidine ring of the alkaloid. Until now the metabolic fate of gamma-N-methylaminobutyrate has been unknown. pAO1 carries a cluster of ORFs with similarity to sarcosine and dimethylglycine dehydrogenases and oxidases, to the bifunctional enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase and to formyltetrahydrofolate deformylase. We cloned and expressed the gene carrying the sarcosine dehydrogenase-like ORF and showed, by enzyme activity, spectrophotometric methods and identification of the reaction product as gamma-aminobutyrate, that the predicted 89 395 Da flavoprotein is a demethylating gamma-N-methylaminobutyrate oxidase. Site-directed mutagenesis identified His67 as the site of covalent attachment of FAD and confirmed Trp66 as essential for FAD binding, for enzyme activity and for the spectral properties of the wild-type enzyme. A K-m of 140 mum and a k(cat) of 800 s(-1) was determined when gamma-N-methylaminobutyrate was used as the substrate. Sarcosine was also turned over by the enzyme, but at a rate 200-fold slower than gamma-N-methylaminobutyrate. This novel enzyme activity revealed that the first step in channelling the gamma-N-methylaminobutyrate generated from nicotine into the cell metabolism proceeds by its oxidative demethylation

Examining the Links Between Challenging Behaviors in Youth with ASD and Parental Stress, Mental Health, and Involvement: Applying an Adaptation of the Family Stress Model to Families of Youth with ASD

Raising a child with autism spectrum disorder (ASD) poses unique challenges that may impact parents’ mental health and parenting experiences. The current study analyzed self-report data from 77 parents of youth with ASD. A serial multiple mediation model revealed that parenting stress (SIPA) and parental mental health (BAI and BDI-II) appears to be impacted by challenging adolescent behaviors (SSIS-PBs) and, in turn, affect parental involvement (PRQ), controlling for social skills (SSIS-SSs). Further, the study explored the malleability of parents’ mental health over the course of a social skills intervention, and provides modest evidence that parent depressive symptoms decline across intervention. This study illustrates the importance of considering the entire family system in research on youth with ASD

Insufficient access to harm reduction measures in prisons in 5 countries (PRIDE Europe): a shared European public health concern

Background: Prisoners constitute a high-risk population, particularly for infectious diseases. The aim of this study was to estimate the level of infectious risk in the prisons of five different European countries by measuring to what extent the prison system adheres to WHO/UNODC recommendations. Methods: Following the methodology used in a previous French survey, a postal/electronic questionnaire was sent to all prisons in Austria, Belgium, Denmark and Italy to collect data on the availability of several recommended HIV-HCV prevention interventions and HBV vaccination for prisoners. A score was built to compare adherence to WHO/UNODC recommendations (considered a proxy of environmental infectious risk) in those 4 countries. It ranged from 0 (no adherence) to 12 (full adherence). A second score (0 to 9) was built to include data from a previous French survey, thereby creating a 5-country comparison. Results: A majority of prisons answered in Austria (100 %), France (66 %) and Denmark (58 %), half in Belgium (50 %) and few in Italy (17 %), representing 100, 74, 89, 47 and 23 % coverage of the prison populations, respectively. Availability of prevention measures was low, with median adherence scores ranging from 3.5 to 4.5 at the national level. These results were confirmed when using the second score which included France in the inter-country comparison. Overall, the adherence score was inversely associated with prison overpopulation rates (p = 0.08). Conclusions: Using a score of adherence to WHO/UNODC recommendations, the estimated environmental infectious risk remains extremely high in the prisons of the 5 European countries assessed. Public health strategies should be adjusted to comply with the principle of equivalence of care and prevention with the general community

Increasing Burden of Complex Multimorbidity Across Gradients of Cognitive Impairment

Introduction: This study evaluates the burden of multimorbidity (MM) across gradients of cognitive impairment (CI). Methods: Using data from the 2010 Health and Retirement Study, we identified individuals with no CI, mild CI, and moderate/ severe CI. In addition, we adopted an expansive definition of complex MM by accounting for the occurrence and co-occurrence of chronic conditions, functional limitations, and geriatric syndromes. Results: In a sample of 18 913 participants (weighted n = 87.5 million), 1.93% and 1.84% presented with mild and moderate/severe CI, respectively. The prevalence of most conditions constituting complex MM increased markedly across the spectrum of CI. Further, the percentage of individuals presenting with 10 or more conditions was 19.9%, 39.3%, and 71.3% among those with no CI, mild CI, and moderate/severe CI, respectively. Discussion: Greater CI is strongly associated with increased burden of complex MM. Detailed characterization of MM across CI gradients will help identify opportunities for health care improvement

Dual chaperone role of the c-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin

Throughout evolution, one of the most ancient forms of aggression between cells or organisms has been the production of proteins or peptides affecting the permeability of the target cell membrane. This class of virulence factors includes the largest family of bacterial toxins, the pore-forming toxins (PFTs). PFTs are bistable structures that can exist in a soluble and a transmembrane state. It is unclear what drives biosynthetic folding towards the soluble state, a requirement that is essential to protect the PFT-producing cell. Here we have investigated the folding of aerolysin, produced by the human pathogen Aeromonas hydrophila, and more specifically the role of the C-terminal propeptide (CTP). By combining the predictive power of computational techniques with experimental validation using both structural and functional approaches, we show that the CTP prevents aggregation during biosynthetic folding. We identified specific residues that mediate binding of the CTP to the toxin. We show that the CTP is crucial for the control of the aerolysin activity, since it protects individual subunits from aggregation within the bacterium and later controls assembly of the quaternary pore-forming complex at the surface of the target host cell. The CTP is the first example of a C-terminal chain-linked chaperone with dual function