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Community-based models have become increasingly prominent in prevention, and have special relevance for suicide prevention in circumpolar Indigenous communities. It follows that outcomes from circumpolar suicide prevention programs might be more completely understood at the community level. We present here a methodology for analysis at this level. This paper seeks to understand a cultural prevention program for rural Yup'ik youth in Alaska targeting suicide and co-occurring alcohol abuse as a community development process through changes at the community level.
Study Design
Quasi-experimental design with assessment at pre- and post-intervention or at 4 time points. The community development process for this project began in October 2004. The first program baseline assessment began in November 2006, prior to prevention activities with youth and parents, and the post-intervention assessment concluded in March 2008.
Five key informants pre- and post-intervention completed a community readiness assessment, which is a structured procedure assessing a community's awareness of suicide as an issue and its organizational readiness for prevention programming. Forty-three adult caregivers or sponsors of youth in the prevention program completed an assessment of behaviours that contributed to community protective factors from youth suicide and alcohol abuse at 4 time points before, during and after the intervention. The 54 youth who participated in the prevention program completed an assessment of community protective factors, also at 4 time points before, during and after the intervention. The community protective factors from suicide that were assessed included safety, enforcement of alcohol prohibitions, role models, support and opportunities for youth.
Community readiness for the prevention efforts increased to new developmental stages of readiness post-intervention, and a trend in the data suggested community protective factors increased in the amount of protective behaviours performed by adults (slope estimate=0.0162, 95% CI-0.0028–0.0351, d=.55) and in the perceptions of youth (slope estimate=0.0148, 95% CI-0.0004–0.0291, d=.45), in a dose response relationship to the number of prevention program sessions attended by adults and youth.
Using data from a feasibility study, this paper demonstrates the feasibility and potential utility of methodological approaches that use community-level variables beyond individual level outcomes in circumpolar suicide prevention research.
PMCID: PMC2875412  PMID: 19705659
Suicide; suicide prevention; Alaska Native; community readiness assessment; community-based participatory research
2.  Resuscitation of Preterm Neonates With Limited Versus High Oxygen Strategy 
Pediatrics  2013;132(6):e1488-e1496.
To determine whether a limited oxygen strategy (LOX) versus a high oxygen strategy (HOX) during delivery room resuscitation decreases oxidative stress in preterm neonates.
A randomized trial of neonates of 24 to 34 weeks’ gestational age (GA) who received resuscitation was performed. LOX neonates received room air as the initial resuscitation gas, and fraction of inspired oxygen (Fio2) was adjusted by 10% every 30 seconds to achieve target preductal oxygen saturations (Spo2) as described by the 2010 Neonatal Resuscitation Program guidelines. HOX neonates received 100% O2 as initial resuscitation gas, and Fio2 was adjusted by 10% to keep preductal Spo2 at 85% to 94%. Total hydroperoxide (TH), biological antioxidant potential (BAP), and the oxidative balance ratio (BAP/TH) were analyzed in cord blood and the first hour of life. Secondary outcomes included delivery room interventions, respiratory support on NICU admission, and short-term morbidities.
Forty-four LOX (GA: 30 ± 3 weeks; birth weight: 1678 ± 634 g) and 44 HOX (GA: 30 ± 3 weeks; birth weight: 1463 ± 606 g) neonates were included. LOX decreased integrated excess oxygen (∑Fio2 × time [min]) in the delivery room compared with HOX (401 ± 151 vs 662 ± 249; P < .01). At 1 hour of life, BAP/TH was 60% higher for LOX versus HOX neonates (13 [9–16] vs 8 [6–9]) µM/U.CARR, P < .01). LOX decreased ventilator days (3 [0–64] vs 8 [0–96]; P < .05) and reduced the incidence of bronchopulmonary dysplasia (7% vs 25%; P < .05).
LOX is feasible and results in less oxygen exposure, lower oxidative stress, and decreased respiratory morbidities and thus is a reasonable alternative for resuscitation of preterm neonates in the delivery room.
PMCID: PMC3838529  PMID: 24218465
newborn; oxidative stress; oxygen; preterm; resuscitation
3.  Non-coding RNA gene families in the genomes of anopheline mosquitoes 
BMC Genomics  2014;15(1):1038.
Only a small fraction of the mosquito species of the genus Anopheles are able to transmit malaria, one of the biggest killer diseases of poverty, which is mostly prevalent in the tropics. This diversity has genetic, yet unknown, causes. In a further attempt to contribute to the elucidation of these variances, the international “Anopheles Genomes Cluster Consortium” project (a.k.a. “16 Anopheles genomes project”) was established, aiming at a comprehensive genomic analysis of several anopheline species, most of which are malaria vectors. In the frame of the international consortium carrying out this project our team studied the genes encoding families of non-coding RNAs (ncRNAs), concentrating on four classes: microRNA (miRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), and in particular small nucleolar RNA (snoRNA) and, finally, transfer RNA (tRNA).
Our analysis was carried out using, exclusively, computational approaches, and evaluating both the primary NGS reads as well as the respective genome assemblies produced by the consortium and stored in VectorBase; moreover, the results of RNAseq surveys in cases in which these were available and meaningful were also accessed in order to obtain supplementary data, as were “pre-genomic era” sequence data stored in nucleic acid databases. The investigation included the identification and analysis, in most species studied, of ncRNA genes belonging to several families, as well as the analysis of the evolutionary relations of some of those genes in cross-comparisons to other members of the genus Anopheles.
Our study led to the identification of members of these gene families in the majority of twenty different anopheline taxa. A set of tools for the study of the evolution and molecular biology of important disease vectors has, thus, been obtained.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1038) contains supplementary material, which is available to authorized users.
PMCID: PMC4300560  PMID: 25432596
Anopheles; Genome evolution; microRNA; ncRNA; Ribosomal genes; Small nuclear RNA; Small nucleolar RNA; tRNA; Whole Genome Sequencing
4.  Systemic delivery of rAAV6-microdystrophin preserves muscle function and extends lifespan in a murine model of severe muscular dystrophy 
Nature medicine  2006;12(7):787-789.
Mice carrying mutations in both the dystrophin and utrophin genes die prematurely as a consequence of severe muscular dystrophy. Here, we demonstrate that intravascular administration of recombinant adeno-associated viral (rAAV) vectors carrying a microdystrophin gene restores dystrophin expression in the striated musculature of these animals, considerably reducing skeletal muscle pathology and extending lifespan. These findings suggest rAAV vector-mediated systemic gene transfer may be useful for treatment of serious neuromuscular disorders such as Duchenne muscular dystrophy (DMD).
PMCID: PMC4244883  PMID: 16819550
5.  “Where I Have to Learn the Ways How to Live:” Youth Resilience in a Yup’ik Village in Alaska 
Transcultural psychiatry  2014;51(5):713-734.
What is it like to grow-up Yup’ik and come-of-age today in a traditional hunting-gathering community setting located in a remote region of Alaska? Current research describes a contemporary experience often laden with trauma and crisis. Youth in Yup’ik communities today face threats to their very survival as they encounter, early on, things that their ancestors never faced – including alcohol-related deaths, violence in many forms, and high rates of suicide among their young peers. Yet all is not despair for the youth growing up in these remote indigenous communities. Many youth grow-up to become skilled hunters, strong leaders, and able parents. This paper reports findings from the Alaskan Yup’ik site of the Circumpolar Indigenous Pathways to Adulthood (CIPA) study. The goal of this study is to identify strengths and resilience in youth living in a Yup’ik community in southwest Alaska. Interviews were conducted with 25 youth age 11–18, currently residing in a southwest Alaska community. Qualitative analysis revealed important connections between local stressors, community-level protective resources, and youth-driven, solution-focused strategies for overcoming hardship and learning the ‘ways how to live.’ Findings from this study contribute critical information on indigenous youth protection and resilience, including community and cultural resilience processes beyond the individual level, and enhance our understanding of the types of resources that can lead to improved outcomes for Alaska Native youth.
PMCID: PMC4163516  PMID: 24823691
Alaska Native; indigenous; youth; social change; resilience
6.  The Roles of Four Conserved Basic Amino Acids in a Ferredoxin-Dependent Cyanobacterial Nitrate Reductase 
Biochemistry  2013;52(25):4343-4353.
The roles of four conserved basic amino acids in the reaction catalyzed by the ferredoxin-dependent nitrate reductase from the cyanobacterium Synechococcus sp. PCC 7942 have been investigated using site-directed mutagenesis in combination with measurements of steady-state kinetics, substrate-binding affinities and spectroscopic properties of the enzyme’s two prosthetic groups. Replacement of either Lys58 or Arg70 by glutamine leads to a complete loss of activity, with both the physiological electron donor, reduced ferredoxin and with a non-physiological electron donor, reduced methyl viologen. More conservative, charge-maintaining K58R and R70K variants were also completely inactive. Replacement of Lys130 by glutamine produced a variant that retained 26% of the wild-type activity with methyl viologen as the electron donor and 22% of the wild-type activity with ferredoxin as the electron donor, while replacement by arginine produces a variant that retains a significantly higher percentage of the wild-type activity with both electron donors. In contrast, replacement of Arg146 by glutamine had minimal effect on the activity of the enzyme. These results, along with substrate-binding and spectroscopic measurements, are discussed in terms of an in silico structural model for the enzyme.
PMCID: PMC3741069  PMID: 23692082
7.  Heparin-binding correlates with increased efficiency of AAV1- and AAV6-mediated transduction of striated muscle, but negatively impacts CNS transduction 
Gene therapy  2012;20(5):497-503.
Gene delivery vectors derived from adeno-associated virus (AAV) have great potential as therapeutic agents. rAAV1 and rAAV6, efficiently target striated muscle, but the mechanisms that determine their tropism remain unclear. It is known that AAV6, but not AAV1, interacts with heparin-sulfate proteoglycans (HSPG). HSPGs are not primary receptors for AAV6, but heparin interactions may affect tissue tropism and transduction. To investigate these possibilities, we generated rAAV1 and rAAV6 capsids that do or do not bind heparin. We evaluated the transduction profile of these vectors in vivo across multiple routes of administration, and found that heparin binding capability influences tissue transduction in striated muscle and neuronal tissues. Heparin-binding capsids transduce striated muscle more efficiently than non-binding capsids, via both intramuscular and intravenous injection. However, rAAV6 achieved greater muscle transduction than the heparin-binding rAAV1 variant, suggesting that there are additional factors that influence differences in transduction efficiency between AAV1 and AAV6. Interestingly, the opposite trend was found when vectors were delivered via intracranial injection. Non-binding vectors achieved robust and widespread gene expression, whereas transduction via heparin-binding serotypes was substantially reduced. These data indicate that heparin-binding capability is an important determinant of transduction that should be considered in the design of rAAV-mediated gene therapies.
PMCID: PMC4004370  PMID: 22855092
Heparin; AAV; AAV6; AAV1; muscle transduction; CNS transduction
8.  Children’s Coping in the Context of Disasters and Terrorism 
Journal of loss & trauma  2013;`9(1):78-97.
Disasters and terrorism present significant and often overwhelming challenges for children and families worldwide. Individual, family, and social factors influence disaster reactions and the diverse ways in which children cope. This article links conceptualizations of stress and coping to empirical knowledge of children’s disaster reactions, identifies limitations in our current understanding, and suggests areas for future study of disaster coping. Coping strategies, developmental trajectories influencing coping, and the interplay between parent and child coping represent critical areas for advancing the field and for informing programs and services that benefit children’s preparedness and foster resilience in the face of mass trauma.
PMCID: PMC3969033  PMID: 24683315
child development; coping; disasters; resilience; stress; terrorism
9.  Mobile phone-based asthma self-management aid for adolescents (mASMAA): a feasibility study 
Adolescents report high asthma-related morbidity that can be prevented by adequate self-management of the disease. Therefore, there is a need for a developmentally appropriate strategy to promote effective asthma self-management. Mobile phone-based technology is portable, commonly accessible, and well received by adolescents. The purpose of this study was to develop and evaluate the feasibility and acceptability of a comprehensive mobile phone-based asthma self-management aid for adolescents (mASMAA) that was designed to facilitate symptom monitoring, treatment adherence, and adolescent–parent partnership. The system used state-of-the-art natural language-understanding technology that allowed teens to use unconstrained English in their texts, and to self-initiate interactions with the system.
Materials and methods
mASMAA was developed based on an existing natural dialogue system that supports broad coverage of everyday natural conversation in English. Fifteen adolescent–parent dyads participated in a 2-week trial that involved adolescents’ daily scheduled and unscheduled interactions with mASMAA and parents responding to daily reports on adolescents’ asthma condition automatically generated by mASMAA. Subsequently, four focus groups were conducted to systematically obtain user feedback on the system. Frequency data on the daily usage of mASMAA over the 2-week period were tabulated, and content analysis was conducted for focus group interview data.
Response rates for daily text messages were 81%–97% in adolescents. The average number of self-initiated messages to mASMAA was 19 per adolescent. Symptoms were the most common topic of teen-initiated messages. Participants concurred that use of mASMAA improved awareness of symptoms and triggers, promoted treatment adherence and sense of control, and facilitated adolescent–parent partnerships.
This study demonstrates the utility and user acceptability of mASMAA as a potential asthma self-management tool in a selective group of adolescents. Further research is needed to replicate the findings in a large group of adolescents from sociodemographically diverse backgrounds to validate the findings.
PMCID: PMC3891581  PMID: 24470755
asthma; self-management; text messaging; adolescents
10.  Assessing the State of Substitution Models Describing Noncoding RNA Evolution 
Genome Biology and Evolution  2014;6(1):65-75.
Phylogenetic inference is widely used to investigate the relationships between homologous sequences. RNA molecules have played a key role in these studies because they are present throughout life and tend to evolve slowly. Phylogenetic inference has been shown to be dependent on the substitution model used. A wide range of models have been developed to describe RNA evolution, either with 16 states describing all possible canonical base pairs or with 7 states where the 10 mismatched nucleotides are reduced to a single state. Formal model selection has become a standard practice for choosing an inferential model and works well for comparing models of a specific type, such as comparisons within nucleotide models or within amino acid models. Model selection cannot function across different sized state spaces because the likelihoods are conditioned on different data. Here, we introduce statistical state-space projection methods that allow the direct comparison of likelihoods between nucleotide models and 7-state and 16-state RNA models. To demonstrate the general applicability of our new methods, we extract 287 RNA families from genomic alignments and perform model selection. We find that in 281/287 families, RNA models are selected in preference to nucleotide models, with simple 7-state RNA models selected for more conserved families with shorter stems and more complex 16-state RNA models selected for more divergent families with longer stems. Other factors, such as the function of the RNA molecule or the GC-content, have limited impact on model selection. Our models and model selection methods are freely available in the open-source PHASE 3.0 software.
PMCID: PMC3914692  PMID: 24391153
RNA; phylogenetics; substitution model; hypothesis tests; model selection
11.  Identification of the type II cytochrome c maturation pathway in anammox bacteria by comparative genomics 
BMC Microbiology  2013;13:265.
Anaerobic ammonium oxidizing (anammox) bacteria may contribute up to 50% to the global nitrogen production, and are, thus, key players of the global nitrogen cycle. The molecular mechanism of anammox was recently elucidated and is suggested to proceed through a branched respiratory chain. This chain involves an exceptionally high number of c-type cytochrome proteins which are localized within the anammoxosome, a unique subcellular organelle. During transport into the organelle the c-type cytochrome apoproteins need to be post-translationally processed so that heme groups become covalently attached to them, resulting in mature c-type cytochrome proteins.
In this study, a comparative genome analysis was performed to identify the cytochrome c maturation system employed by anammox bacteria. Our results show that all available anammox genome assemblies contain a complete type II cytochrome c maturation system.
Our working model suggests that this machinery is localized at the anammoxosome membrane which is assumed to be the locus of anammox catabolism. These findings will stimulate further studies in dissecting the molecular and cellular basis of cytochrome c biogenesis in anammox bacteria.
PMCID: PMC4222556  PMID: 24267221
Cytochrome c biogenesis; Anaerobic ammonium oxidizing bacteria; ccs; CcsA; CcsB; CcsX; DsbD; CcdA
12.  High-density Two-Dimensional Small Polaron Gas in a Delta-Doped Mott Insulator 
Scientific Reports  2013;3:3284.
Heterointerfaces in complex oxide systems open new arenas in which to test models of strongly correlated material, explore the role of dimensionality in metal-insulator-transitions (MITs) and small polaron formation. Close to the quantum critical point Mott MITs depend on band filling controlled by random disordered substitutional doping. Delta-doped Mott insulators are potentially free of random disorder and introduce a new arena in which to explore the effect of electron correlations and dimensionality. Epitaxial films of the prototypical Mott insulator GdTiO3 are delta-doped by substituting a single (GdO)+1 plane with a monolayer of charge neutral SrO to produce a two-dimensional system with high planar doping density. Unlike metallic SrTiO3 quantum wells in GdTiO3 the single SrO delta-doped layer exhibits thermally activated DC and optical conductivity that agree in a quantitative manner with predictions of small polaron transport but with an extremely high two-dimensional density of polarons, ~7 × 1014 cm−2.
PMCID: PMC3836037  PMID: 24257578
13.  Ensembl Genomes 2013: scaling up access to genome-wide data 
Nucleic Acids Research  2013;42(Database issue):D546-D552.
Ensembl Genomes ( is an integrating resource for genome-scale data from non-vertebrate species. The project exploits and extends technologies for genome annotation, analysis and dissemination, developed in the context of the vertebrate-focused Ensembl project, and provides a complementary set of resources for non-vertebrate species through a consistent set of programmatic and interactive interfaces. These provide access to data including reference sequence, gene models, transcriptional data, polymorphisms and comparative analysis. This article provides an update to the previous publications about the resource, with a focus on recent developments. These include the addition of important new genomes (and related data sets) including crop plants, vectors of human disease and eukaryotic pathogens. In addition, the resource has scaled up its representation of bacterial genomes, and now includes the genomes of over 9000 bacteria. Specific extensions to the web and programmatic interfaces have been developed to support users in navigating these large data sets. Looking forward, analytic tools to allow targeted selection of data for visualization and download are likely to become increasingly important in future as the number of available genomes increases within all domains of life, and some of the challenges faced in representing bacterial data are likely to become commonplace for eukaryotes in future.
PMCID: PMC3965094  PMID: 24163254
14.  Umyuangcaryaraq “Reflecting”: Multidimensional Assessment of Reflective Processes on the Consequences of Alcohol Use among Rural Yup’ik Alaska Native Youth 
Concerns in some settings regarding the accuracy and ethics of employing direct questions about alcohol use suggest need for alternative assessment approaches with youth. Umyuangcaryaraq is a Yup’ik Alaska Native word meaning “Reflecting.” The Reflective Processes Scale is a youth measure tapping awareness and thinking over potential negative consequences of alcohol misuse as a protective factor that includes cultural elements often shared by many other Alaska Native and American Indian cultures. A bifactor model of the scale items with three content factors provided excellent fit to observed data. Item response theory analysis suggested a binary response format as optimal. Evidence of convergent and discriminant validity is presented.
PMCID: PMC3476469  PMID: 22931081
American Indian and Alaska Native; adolescents; alcohol; alcohol expectancies
15.  Patterns of Protective Factors in an Intervention for the Prevention of Suicide and Alcohol Abuse with Yup’ik Alaska Native Youth 
Community-based participatory research (CBPR) with American Indian and Alaska Native communities creates distinct interventions, complicating cross-setting comparisons. In this study, coding CBPR intervention activities from three communities for protective factors and latent class analysis identified five patterns of exposure to protective factors: Internal, External, Limits on alcohol, Community and family, and Low probabilities of all protective factors. Patterns differed significantly by community and youth age. Standardizing protective factors by the functions an intervention serves instead of its form or components can assist in refining CBPR interventions and evaluating effects in culturally distinct settings.
PMCID: PMC3506184  PMID: 22931082
16.  Reinterpretation of the electron density at the site of the eighth bacteriochlorophyll in the FMO protein from Pelodictyon phaeum 
Photosynthesis research  2012;112(1):71-74.
The Fenna-Matthews-Olson antenna protein from the green bacterium Pelodictyon phaeum mediates the energy transfer from a peripheral antenna complex to the membrane-bound reaction center. The three-dimensional structure of this protein has been previously modeled using X-ray diffraction to a resolution limit of 2.0 Å, with Rwork and Rfree values of 16.6% and 19.9% respectively (Larson et al. (2011) Photosyn Res 107: 139–150). This model shows the protein as consisting of β-sheets surrounding several bacteriochlorophyll cofactors. While most of the model clearly matches the electron density maps, in this paper we re-examine the electron density for a specific feature, namely the eighth bacteriochlorophyll a cofactor. This electron density is now interpreted as arising primarily from the end of an otherwise disordered polyethylene glycol molecule. Additional electron density is present but the density is weak and cannot be unambiguously assigned. The new model has Rwork and Rfree values of 16.2% and 19.0%, respectively.
PMCID: PMC3732665  PMID: 22457093
Energy transfer; light harvesting complex; three dimensional structure; green bacteria
17.  Divergence of Erv1-Associated Mitochondrial Import and Export Pathways in Trypanosomes and Anaerobic Protists 
Eukaryotic Cell  2013;12(2):343-355.
In yeast (Saccharomyces cerevisiae) and animals, the sulfhydryl oxidase Erv1 functions with Mia40 in the import and oxidative folding of numerous cysteine-rich proteins in the mitochondrial intermembrane space (IMS). Erv1 is also required for Fe-S cluster assembly in the cytosol, which uses at least one mitochondrially derived precursor. Here, we characterize an essential Erv1 orthologue from the protist Trypanosoma brucei (TbERV1), which naturally lacks a Mia40 homolog. We report kinetic parameters for physiologically relevant oxidants cytochrome c and O2, unexpectedly find O2 and cytochrome c are reduced simultaneously, and demonstrate that efficient reduction of O2 by TbERV1 is not dependent upon a simple O2 channel defined by conserved histidine and tyrosine residues. Massive mitochondrial swelling following TbERV1 RNA interference (RNAi) provides evidence that trypanosome Erv1 functions in IMS protein import despite the natural absence of the key player in the yeast and animal import pathways, Mia40. This suggests significant evolutionary divergence from a recently established paradigm in mitochondrial cell biology. Phylogenomic profiling of genes also points to a conserved role for TbERV1 in cytosolic Fe-S cluster assembly. Conversely, loss of genes implicated in precursor delivery for cytosolic Fe-S assembly in Entamoeba, Trichomonas, and Giardia suggests fundamental differences in intracellular trafficking pathways for activated iron or sulfur species in anaerobic versus aerobic eukaryotes.
PMCID: PMC3571301  PMID: 23264646
18.  Seeking balance between the past and the present: Vietnamese refugee parenting practices and adolescent well-being 
This qualitative study examines the resources that Vietnamese refugee parents use in raising their adolescent youth in exile and how they, and their adolescents, regard their experiences of different parenting styles. The study is based on 55 semi-structured interviews and several focus groups performed with a small sample of Vietnamese refugee parents and their adolescent children. Three main themes from the interviews were identified: the role of the extended family and siblings in bringing up children; language acquisition and cultural continuity and, finally, religion and social support. Our findings suggest extended kin are involved in the raising of adolescent children, providing additional family ties and support. Parents regarded Vietnamese language acquisition by their youth as facilitating both communication with extended kin and cultural transmission. Several parents stressed the importance of religious community to socialising and creating a sense of belonging for their youth. Vietnamese refugee parents seek a balance between Vietnamese values and their close extended family social networks, and the opportunities in Norway to develop autonomy in pursuit of educational and economic goals. Together these parenting practices constituted a mobilization of resources in support of their youth. These findings may have important implications for future research on resiliency and the role of these strategies as protective factors mediating mental health outcomes. They may also have implications for treatment, in terms of the types of resources treatment can access and for prevention strategies that maximize key cultural resources for Vietnamese refugee youth.
PMCID: PMC3375913  PMID: 22711948
Vietnamese; Refugees; Parenting; Well-being; Resilience; Qualitative method
19.  The Cellular and Molecular Carcinogenic Effects of Radon Exposure: A Review 
Radon-222 is a naturally occurring radioactive gas that is responsible for approximately half of the human annual background radiation exposure globally. Chronic exposure to radon and its decay products is estimated to be the second leading cause of lung cancer behind smoking, and links to other forms of neoplasms have been postulated. Ionizing radiation emitted during the radioactive decay of radon and its progeny can induce a variety of cytogenetic effects that can be biologically damaging and result in an increased risk of carcinogenesis. Suggested effects produced as a result of alpha particle exposure from radon include mutations, chromosome aberrations, generation of reactive oxygen species, modification of the cell cycle, up or down regulation of cytokines and the increased production of proteins associated with cell-cycle regulation and carcinogenesis. A number of potential biomarkers of exposure, including translocations at codon 249 of TP53 in addition to HPRT mutations, have been suggested although, in conclusion, the evidence for such hotspots is insufficient. There is also substantial evidence of bystander effects, which may provide complications when calculating risk estimates as a result of exposure, particularly at low doses where cellular responses often appear to deviate from the linear, no-threshold hypothesis. At low doses, effects may also be dependent on cellular conditions as opposed to dose. The cellular and molecular carcinogenic effects of radon exposure have been observed to be both numerous and complex and the elevated chronic exposure of man may therefore pose a significant public health risk that may extend beyond the association with lung carcinogenesis.
PMCID: PMC3742230  PMID: 23880854
radon; carcinogenesis; cytogenetics; DNA damage; alpha particles; bystander effect; chromosome aberrations; micronuclei; linear; no-threshold; hormesis
20.  Multicultural Mastery Scale for Youth: Multidimensional Assessment of Culturally Mediated Coping Strategies 
Psychological Assessment  2011;24(2):313-327.
Self-mastery refers to problem-focused coping facilitated through personal agency. Communal mastery describes problem solving through an interwoven social network. This study investigates an adaptation of self- and communal mastery measures for youth. Given the important distinction between family and peers in the lives of youth, these adaptation efforts produced Mastery-Family and Mastery-Friends subscales, along with a Mastery-Self subscale. We tested these measures for psychometric properties and internal structure with 284 12 to 18-year-old predominately Yup’ik Eskimo Alaska Native adolescents from rural, remote communities — a non-Western culturally distinct group hypothesized to display higher levels of collectivism and communal mastery. Results demonstrate a subset of items adapted for youth function satisfactorily, a three-response alternative format provided meaningful information, and the subscale’s underlying structure is best described through three distinct first-order factors organized under one higher order mastery factor.
PMCID: PMC3394699  PMID: 21928912
American Indian and Alaska Native; mastery; self-efficacy; communal mastery; coping
21.  Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts 
Annals of Human Genetics  2012;76(3):221-236.
Orofacial clefts are common birth defects with strong evidence for both genetic and environmental causal factors. Candidate-gene studies combined with exposures known to influence the outcome provide a highly targeted approach to detecting GxE interactions. We developed a new statistical approach that combines the case-control and offspring-parent triad designs into a “hybrid design” to search for GxE interactions among 334 autosomal cleft candidate genes and maternal first-trimester exposure to smoking, alcohol, coffee, folic acid supplements, dietary folate, and vitamin A. The study population comprised 425 case-parent triads of isolated clefts and 562 control-parent triads derived from a nationwide study of orofacial clefts in Norway (1996-2001). A full maximum-likelihood model was used in combination with a Wald test statistic to screen for statistically significant GxE interaction between strata of exposed and unexposed mothers. In addition, we performed pathway-based analyses on 28 detoxification genes and 21 genes involved in folic acid metabolism. With the possible exception of the T-box 4 gene (TBX4) and dietary folate interaction in isolated CPO, there was little evidence overall of GxE interaction in our data. This study is the largest to date aimed at detecting interactions between orofacial clefts candidate genes and well-established risk exposures.
PMCID: PMC3334353  PMID: 22497478
Birth defects; orofacial cleft; cleft lip; cleft palate; genetic epidemiology
22.  “Oh No, We are Just Getting to Know You”: The Relationship in Research with Children and Youth in Indigenous Communities 
We describe important elements in the process of engagement with tribal communities in research with children and youth and their families. We believe it helpful to understand the research relationship with tribal communities through the lens of kinship relations. This calls for re-examination of the nature of research and researcher, with important implications for the research process, design and organization, recovery from errors, and dissemination of results. Implications include a re-examination of some of our canons of research methods and research ethics, along with a willingness to address new challenges, to share control of the research process, and to be open to new conceptual perspectives, including alternative research strategies. Its repercussions hold promise for a deepening of the research relationship, and the role of researcher in the community.
PMCID: PMC3275908  PMID: 22327297
American Indian; Alaska Native; community based participatory research; tribal participatory research; youth; children
23.  Parents and Children Only? Acculturation and the Influence of Extended Family Members among Vietnamese Refugees 
The nuclear family is often the point of departure in much of the existing acculturation research on refugee youth and children of refugees. The influence of other extended family members appears to receive less attention in understanding acculturation processes and intergenerational perspectives. This qualitative study explores the influence of extended family members upon a small sample of Vietnamese refugee parents and their adolescents while they undergo acculturation through their long-term resettlement process in Norway. With repeated interviews over a time span of 3 years, we identified situations and processes in family life in which extended kin become particularly activated and influential. Vietnamese refugee families in Norway keep close contact with extended kin even in the face of geographical distance to kin remaining in Vietnam, or globally dispersed. Aunts, uncles, and cousins are experienced as significant persons in the lives of many adolescents. Additionally, birth order of parents can often influence relationship dynamics among siblings and siblings children. Extended kin surfaced as especially important and influential at critical stages and crisis situations in family life. Extended family, and in particular, parental siblings play important roles in the acculturation experience and family functioning of Vietnamese refugee families in Norway. This has important implications for the study of Vietnamese and other refugee and immigrant families in acculturation research.
PMCID: PMC3478776  PMID: 24510190
Acculturation; Extended Family; Vietnamese; Refugees; Qualitative Methods; Mental Health
24.  Disseminating research in rural Yup'ik communities: challenges and ethical considerations in moving from discovery to intervention development 
International Journal of Circumpolar Health  2013;72:10.3402/ijch.v72i0.20958.
The native people of Alaska have experienced historical trauma and rapid changes in culture and lifestyle patterns. As a consequence, these populations shoulder a disproportionately high burden of psychological stress. The Yup'ik Experiences of Stress and Coping project originated from rural Yup'ik communities’ concerns about stress and its effects on health. It aimed to understand the stressful experiences that affect Yup'ik communities, to identify coping strategies used to deal with these stressors and to inform culturally responsive interventions.
Here, we examine the process of moving from research (gaining understanding) to disseminating project findings to translation into intervention priorities. We highlight the importance of community participation and discuss challenges encountered, strategies to address these challenges and ethical considerations for responsible intervention research with indigenous communities that reflect their unique historical and current socio-cultural realities.
Community-wide presentations and discussions of research findings on stress and coping were followed by smaller Community Planning Group meetings. During these meetings, community members contextualized project findings and discussed implications for interventions. This process placed priority on community expertise in interpreting findings and translating results and community priorities into grant applications focused on intervention development and evaluation.
Challenges included translation between English and Yup'ik, funding limitations and uncertainties, and the long timelines involved in moving from formative research to intervention in the face of urgent and evolving community needs. The lack of congruence between institutional and community worldviews in the intervention research enterprise highlights the need for “principled cultural sensitivity”.
Cultural sensitivity requires sharing results that have practical value, communicating openly, planning for sustainability and incorporating indigenous knowledge and expertise through a community-guided process. Our research findings will inform continued work within our partnership as we co-develop culturally based strategies for multilevel community interventions to address stress.
PMCID: PMC3753057  PMID: 23984272
Alaska Native; stress; coping; reporting research results; community-based participatory research (CBPR); research ethics
25.  Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin 
The Journal of Cell Biology  2012;197(7):997-1008.
Smad3/Akt/mTOR/S6K/S6RP signaling plays a critical role in follistatin-mediated muscle growth that operates independently of myostatin-driven mechanisms.
Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2. Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling. Expression of constitutively active Smad3 not only markedly prevented skeletal muscle growth induced by follistatin but also potently suppressed follistatin-induced Akt/mTOR/S6K signaling. Importantly, the regulation of Smad3- and mTOR-dependent events by follistatin occurred independently of overexpression or knockout of myostatin, a key repressor of muscle development that can regulate Smad3 and mTOR signaling and that is itself inhibited by follistatin. These findings identify a critical role of Smad3/Akt/mTOR/S6K/S6RP signaling in follistatin-mediated muscle growth that operates independently of myostatin-driven mechanisms.
PMCID: PMC3384410  PMID: 22711699

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