14002416
Strong and weak male mutation bias at different sites in the primate genomes: insights from the human-chimpanzee comparison.
Male mutation bias is a higher mutation rate in males than in females thought to result from the greater number of germ line cell divisions in males. If errors in DNA replication cause most mutations, then the magnitude of male mutation bias, measured as the male-to-female mutation rate ratio (alpha), should reflect the relative excess of male versus female germ line cell divisions. Evolutionary rates averaged among all sites in a sequence and compared between mammalian sex chromosomes were shown to be indeed higher in males than in females. However, it is presently unknown whether individual classes of substitutions exhibit such bias. To address this issue, we investigated male mutation bias separately at non-CpG and CpG sites using human-chimpanzee whole-genome alignments. We observed strong male mutation bias at non-CpG sites: alpha in the X-autosome comparison was approximately 6-7, which was similar to the male-to-female ratio in the number of germ line cell divisions. In contrast, mutations at CpG sites exhibited weak male mutation bias: alpha in the X-autosome comparison was only approximately 2-3. This is consistent with the methylation-induced and replication-independent mechanism of CpG transitions, which constitute the majority of mutations at CpG sites. Interestingly, our study also indicated weak male mutation bias for transversions at CpG sites, implying a spontaneous mechanism largely not associated with replication. Male mutation bias was equally strong at CpG and non-CpG sites located within unmethylated "CpG islands," suggesting the replication-dependent origin of these mutations. Thus, we found that the strength of male mutation bias is nonuniform in the primate genomes. Importantly, we discovered that male mutation bias depends on the proportion of CpG sites in the loci compared. This might explain the differences in the magnitude of primate male mutation bias observed among studies.
13468480
ESPERR: learning strong and weak signals in genomic sequence alignments to identify functional elements.
Genomic sequence signals - such as base composition, presence of particular motifs, or evolutionary constraint - have been used effectively to identify functional elements. However, approaches based only on specific signals known to correlate with function can be quite limiting. When training data are available, application of computational learning algorithms to multispecies alignments has the potential to capture broader and more informative sequence and evolutionary patterns that better characterize a class of elements. However, effective exploitation of patterns in multispecies alignments is impeded by the vast number of possible alignment columns and by a limited understanding of which particular strings of columns may characterize a given class. We have developed a computational method, called ESPERR (evolutionary and sequence pattern extraction through reduced representations), which uses training examples to learn encodings of multispecies alignments into reduced forms tailored for the prediction of chosen classes of functional elements. ESPERR produces a greatly improved Regulatory Potential score, which can discriminate regulatory regions from neutral sites with excellent accuracy ( approximately 94%). This score captures strong signals (GC content and conservation), as well as subtler signals (with small contributions from many different alignment patterns) that characterize the regulatory elements in our training set. ESPERR is also effective for predicting other classes of functional elements, as we show for DNaseI hypersensitive sites and highly conserved regions with developmental enhancer activity. Our software, training data, and genome-wide predictions are available from our Web site (http://www.bx.psu.edu/projects/esperr).
28296194
Retrovirus Genome Replication: Priming Specificities of Plus-Strand DNA Synthesis
SUMMARY The retroviral reverse transcriptase is a multifunctional protein. Not only does it contain both RNA- and DNA-directed DNA synthesis activities but also it contains an endonuclease activity necessary for the integration of viral RNA and a RNase H. This latter activity can reduce to oligoribonucleotides viral RNA that has been reverse transcribed into minus-strand DNA. However, during avian retrovirus genome replication it does this in a highly specific manner so as to generate a specific 12-base primer for plus-strand DNA synthesis. Even though many other oligoribonucleotides are also made there is an efficient selection of the specific primer followed by its efficient utilization in plus-strand DNA synthesis, and subsequent removal. We have used a reconstructed system to gain an understanding of the factors that contribute towards these observed specificities.
24886138
Comparison and characteristics of motor vehicle accident (MVA) and non-MVA driving fears.
Prior research has revealed the diagnostic complexity among people who report driving fears. However, the focus on survivors of motor vehicle accidents (MVAs) and diagnostic samples may have inadvertently led to a relative neglect of the broader driving-fearful population. No studies could be located that compared MVA survivors with those who had not experienced an MVA. The aim of the present study was to address these deficits by comparing the characteristics of MVA and non-MVA driving-fearfuls and also exploring a range of characteristics associated with driving fears. One hundred and ninety media-recruited driving-fearfuls completed a questionnaire that assessed severity of anxiety and avoidance associated with a variety of driving situations. It was found that fear levels were similar to samples of driving phobics and MVA victims. There were no significant differences between MVA and non-MVA respondents on various measures of fear severity. In addition, the sample rated a high level of anxiety when driving with someone who criticizes their driving. Implications of the findings are discussed, along with suggestions for assessment and treatment of those with driving-related fears.
12985098
A note on the incorporation of amino acids by hamster embryo cells in monolayer culture.
42040828
The Station Community Mental Health Centre Inc: nurturing and empowering.
INTRODUCTION
Consumer-driven community mental health services play an important role in rehabilitation, recovery, and advocacy in rural and remote Australia. The origins of services often lie in the need to provide options for people with mental illness and their carers when there is a lack of on-the-ground support. This article adds to the information about the strengths and limitations of consumer-driven mental health services by presenting the findings of an evaluation of The Station Inc. in rural South Australia. This consumer-driven mental health service provides a safe and supportive environment, social connections, and activities for its members (those with a lived experience of mental illness). Using a realist evaluation approach, the evaluation identified the contextual factors and the program mechanisms that produce positive outcomes for members.


METHOD
The evaluation was conducted as participatory action research with The Station members, volunteers, management committee members, and staff involved in all phases of the research process. Because of the complexity of The Station's functioning a realist evaluation using qualitative data was conducted to identify how the program worked, for whom, and in what circumstances. Twenty-five in-depth interviews were conducted with participants who were randomly selected from within the groups identified above. Interviews focused on The Station's role in assisting recovery from mental illness, the limitations and strengths of the program, and relationships with the mental health system. The Station's goals, policies and procedures, and the role of stakeholders were analysed in order to identify any links among these contextual factors, program mechanisms, and program outcomes. Qualitative data were entered into descriptive categories in N6 software (QSR; www.qsr.international.com). Data from the stakeholder analysis were entered into Microsoft Excel. Using an iterative approach to include the three data sets, a model was developed that identified important contextual factors that linked with two groups of program mechanisms that produced positive outcomes for members.


RESULTS
Program mechanisms are categorised by descriptive themes referred to as 'nurturing' and 'empowering'. Nurturing' is experienced as feeling of belonging and being accepted 'as one is' and 'empowerment' mechanisms engender a belief in oneself. Respondents identified features of The Station's program, policies, atmosphere, connections and networks, stakeholder relationships, and staff and volunteers that are nurturing and empowering. Five key contextual factors enable the program mechanisms to work. The Station's coordinators ensure that nurturing and empowerment processes are highlighted through careful facilitation. The governance arrangements, policies, and administrative systems at The Station are well developed but flexibly implemented so that they support the nurturing and empowerment processes. Support and legitimacy for the program is obtained from the mental health system at state and local levels. The Station obtains resources and connections to its rural community through key stakeholders and a peak organisation One Voice Network acts as an advocate.


CONCLUSIONS
Information about the benefits and limitations of consumer-driven mental health services in rural and remote Australia is in short supply. Increasing the available information about the contribution these services make may result in services being legitimised, understood, and resourced within mental health systems thus making the services sustainable. The benefits of consumer-driven services are that they provide flexibility and adaptation, an ability to capture the energy and passion of rural communities to improve the wellbeing of community members, and they overcome the power differential that exists between professionals and 'patients' or 'clients'.
30994161
Sex differences, assortative mating, and cultural transmission effects on adolescent delinquency: a twin family study.
The twin study literature contains inconsistencies regarding both the estimates of genetic, shared, and nonshared environmental influence on delinquency and sex differences in the etiological influences on delinquency. Additionally, little is known about assortative mating and cultural transmission effects on delinquency. The present study was aimed at examining the etiology of delinquency in adolescence and examining assortative mating and transmission effects. To this end, we applied the social homogamy structural equation model to self-reported delinquency data from 486 families with 17-year-old male and female twins. We expected stronger shared environmental influences on delinquency among girls than boys and stronger environmental than genetic effects on adolescent delinquency in general. The results indicated nonsignificant sex differences in the estimates of genetic and environmental influences on delinquency. The best-fitting model suggested that 18 %, 56 %, and 26% of the variance in delinquency among both boys and girls is associated with additive genetic, nonshared environmental, and shared environmental factors, respectively. This finding was consistent with our expectation that environmental factors play an important role in adolescent delinquency. Parental cultural effects accounted for a small part of the transmission of delinquency within families while assortative mating was, in part, accounted for by cultural and social background factors. Future work should focus on identifying important environmental factors related to delinquency.