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1.  SUICIDE PREVENTION AS A COMMUNITY DEVELOPMENT PROCESS: UNDERSTANDING CIRCUMPOLAR YOUTH SUICIDE PREVENTION THROUGH COMMUNITY LEVEL OUTCOMES 
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.  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.
doi:10.1080/15325024.2013.791797
PMCID: PMC3969033
child development; coping; disasters; resilience; stress; terrorism
3.  Mobile phone-based asthma self-management aid for adolescents (mASMAA): a feasibility study 
Purpose
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.
Results
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.
Conclusion
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.
doi:10.2147/PPA.S53504
PMCID: PMC3891581  PMID: 24470755
asthma; self-management; text messaging; adolescents
4.  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.
doi:10.1093/gbe/evt206
PMCID: PMC3914692  PMID: 24391153
RNA; phylogenetics; substitution model; hypothesis tests; model selection
5.  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.
doi:10.1038/srep03284
PMCID: PMC3836037  PMID: 24257578
6.  Ensembl Genomes 2013: scaling up access to genome-wide data 
Nucleic Acids Research  2013;42(D1):D546-D552.
Ensembl Genomes (http://www.ensemblgenomes.org) 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.
doi:10.1093/nar/gkt979
PMCID: PMC3965094  PMID: 24163254
7.  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.
doi:10.3109/00952990.2012.702169
PMCID: PMC3476469  PMID: 22931081
American Indian and Alaska Native; adolescents; alcohol; alcohol expectancies
8.  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.
doi:10.3109/00952990.2012.704460
PMCID: PMC3506184  PMID: 22931082
9.  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.
doi:10.1007/s11120-012-9735-8
PMCID: PMC3732665  PMID: 22457093
Energy transfer; light harvesting complex; three dimensional structure; green bacteria
10.  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.
doi:10.1128/EC.00304-12
PMCID: PMC3571301  PMID: 23264646
11.  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.
doi:10.1016/j.ijintrel.2012.03.004
PMCID: PMC3375913  PMID: 22711948
Vietnamese; Refugees; Parenting; Well-being; Resilience; Qualitative method
12.  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.
doi:10.3390/ijms140714024
PMCID: PMC3742230  PMID: 23880854
radon; carcinogenesis; cytogenetics; DNA damage; alpha particles; bystander effect; chromosome aberrations; micronuclei; linear; no-threshold; hormesis
13.  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.
doi:10.1037/a0025505
PMCID: PMC3394699  PMID: 21928912
American Indian and Alaska Native; mastery; self-efficacy; communal mastery; coping
14.  The Brief Family Relationship Scale: A Brief Measure of the Relationship Dimension in Family Functioning 
Assessment  2011;10.1177/1073191111425856.
The Relationship dimension of the Family Environment Scale (FES; Moos & Moos, 1994), which consists of the Cohesion, Expressiveness, and Conflict subscales, measures a person's perception of the quality of their family relationship functioning. This study investigates an adaptation of the Relationship dimension of the FES for Alaska Native youth. We tested the adapted measure, the Brief Family Relationship Scale (BFRS), for psychometric properties and internal structure with 284 12 to18 year-old predominately Yup'ik Eskimo Alaska Native adolescents from rural, remote communities. This non-Western cultural group is hypothesized to display higher levels of collectivism traditionally organized around an extended kinship family structure. Results demonstrate a subset of the adapted items 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 factor. Convergent and discriminant validity of the BFRS was assessed through correlational analysis.
doi:10.1177/1073191111425856
PMCID: PMC3292682  PMID: 22084400
Alaska Native; cohesion; expressiveness; conflict; family relationships; family climate
15.  Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts 
Annals of Human Genetics  2012;76(3):221-236.
Summary
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.
doi:10.1111/j.1469-1809.2012.00707.x
PMCID: PMC3334353  PMID: 22497478
Birth defects; orofacial cleft; cleft lip; cleft palate; genetic epidemiology
16.  “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.
doi:10.1111/j.1750-8606.2011.00199.x
PMCID: PMC3275908  PMID: 22327297
American Indian; Alaska Native; community based participatory research; tribal participatory research; youth; children
17.  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.
doi:10.1016/j.ijintrel.2011.03.005
PMCID: PMC3478776  PMID: 24510190
Acculturation; Extended Family; Vietnamese; Refugees; Qualitative Methods; Mental Health
18.  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.
Background
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.
Objectives
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.
Design
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.
Results
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”.
Conclusions
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.
doi:10.3402/ijch.v72i0.20958
PMCID: PMC3753057  PMID: 23984272
Alaska Native; stress; coping; reporting research results; community-based participatory research (CBPR); research ethics
19.  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.
doi:10.1083/jcb.201109091
PMCID: PMC3384410  PMID: 22711699
20.  Suicide and alcohol related disorders in the U.S. Arctic: boosting research to address a primary determinant of health disparities 
Objectives
To review the existing epidemiological literature on suicide and alcohol related disorders and their social determinants in the U.S. Arctic, as it relates to U.S. government research and evaluation efforts, and to offer recommendations to boost research capacity in the U.S. Arctic and collaborations across the circumpolar arctic as part of global health initiatives. Study design: Synthetic literature review.
Methods
Published literature, federal and state reports on suicide and alcohol-related disorders, federal databases on research and program evaluation in the U.S Arctic were reviewed, with a focus on epidemiological trends over the past 50 years.
Results
Suicide and alcohol-related disorders play a significant role in health disparities t in the U.S. Arctic, with evidence of a disturbing prevalence trend over the past 50 years. Important variations exist in suicide rates across different regions of Alaska with different majority populations of Alaska Native cultural groups, and in selected key instances, within these regions, with immense implications for guiding effective prevention efforts. Consequences of alcohol abuse are severe and particularly significant in their impact upon Alaska Native people. Health related conditions associated with alcohol abuse are among leading causes of mortality.
Conclusions
Recommendations to boost research capacity in behavioural health in the U.S. Arctic are offered; specifically on strategies and methods of inquiry and analysis, distinctions between populations and communities in rural circumpolar contexts, future epidemiological and implementation research.
PMCID: PMC3249490  PMID: 22067096
Arctic; Alaska; Alaska Native; suicide; alcohol; U.S. Arctic research and research infrastructure
21.  Impact of Life Stage and Duration of Exposure on Arsenic-Induced Proliferative Lesions and Neoplasia in C3H Mice 
Toxicology  2009;262(2):106-113.
Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumors in mice exposed to 85 ppm (∼8 mg/kg) inorganic arsenic during gestation. To further characterize age susceptibility to arsenic carcinogenesis we administered 85 ppm inorganic arsenic in drinking water to C3H mice during gestation, prior to pubescence and post-pubescence to compare proliferative lesion and tumor outcomes over a one-year exposure period. Inorganic arsenic significantly increased the incidence of hyperplasia in urinary bladder (48%) and oviduct (36%) in female mice exposed prior to pubescence (beginning on postnatal day 21 and extending through one year) compared to control mice (19 and 5%, respectively). Arsenic also increased the incidence of hyperplasia in urinary bladder (28%) of female mice continuously exposed to arsenic (beginning on gestation day 8 and extending though one year) compared to gestation only exposed mice (0%). In contrast, inorganic arsenic significantly decreased the incidence of tumors in liver (0%) and adrenal glands (0%) of male mice continuously exposed from gestation through one year, as compared to levels in control (30 and 65%, respectively) and gestation only (33 and 55%, respectively) exposed mice. Together, these results suggest that continuous inorganic arsenic exposure at 85 ppm from gestation through one year increases the incidence and severity of urogenital proliferative lesions in female mice and decreases the incidence of liver and adrenal tumors in male mice. The paradoxical nature of these effects may be related to altered lipid metabolism, the effective dose in each target organ, and/or the shorter one-year observational period.
doi:10.1016/j.tox.2009.05.003
PMCID: PMC3496158  PMID: 19450653
arsenic; carcinogenesis; life-stage; age susceptibility; urinary bladder; C3H mice
22.  Assessment of Awareness of Connectedness as a Culturally-based Protective Factor for Alaska Native Youth 
Research with Native Americans has identified connectedness as a culturally-based protective factor against substance abuse and suicide. Connectedness refers to the interrelated welfare of the individual, one’s family, one’s community, and the natural environment. We developed an 18-item quantitative assessment of awareness of connectedness and tested it with 284 Alaska Native youth. Evaluation with confirmatory factor analysis and item response theory identified a 12-item subset that functions satisfactorily in a second-order, four-factor model. The proposed Awareness of Connectedness Scale displays good convergent and discriminant validity and correlates positively with hypothesized protective factors such as reasons for living and communal mastery. The measure has utility in the study of culture-specific protective factors and as an outcomes measure for behavioral health programs with Native American youth.
doi:10.1037/a0025456
PMCID: PMC3193160  PMID: 21988583
American Indian and Alaska Native youth; assessment; indigenous psychology
23.  Navigating International, Interdisciplinary, and Indigenous Collaborative Inquiry: Phase 1 in the Circumpolar Indigenous Pathways to Adulthood Project 
This report describes how multiple community constituents came together to work with university researchers on developing a shared agenda for studying young indigenous people in five international circumpolar communities. The paper focuses on the set up and process of an initial face-to-face methodological planning workshop involving youth and adult community members and academics. Members of Yup'ik, Inupiat, Eveny, Inuit and Sámi communities from Siberia to Norway participated in the workshop and engaged in negotiations to arrive at shared research interests. This was essential since the ultimate goal of the research is translational and transformative, spurring social action in communities. Describing the beginning stage of this project and the underlying participatory methodology offers reader insight into the how the approach engaged community members with varying degrees of sustained interest and practical success. It, therefore, articulates a methodological approach for those interested in doing community-based participatory research in international contexts.
PMCID: PMC3410398  PMID: 22866196
youth; resilience; indigenous; circumpolar; international; community-based participatory research
24.  Drebrin controls neuronal migration through the formation and alignment of the leading process 
Formation of a functional nervous system requires neurons to migrate to the correct place within the developing brain. Tangentially migrating neurons are guided by a leading process which extends towards the target and is followed by the cell body. How environmental cues are coupled to specific cytoskeletal changes to produce and guide leading process growth is unknown. One such cytoskeletal modulator is drebrin, an actin-binding protein known to induce protrusions in many cell types and be important for regulating neuronal morphology.
Using the migration of oculomotor neurons as a model, we have shown that drebrin is necessary for the generation and guidance of the leading process. In the absence of drebrin, leading processes are not formed and cells fail to migrate although axon growth and pathfinding appear grossly unaffected. Conversely, when levels of drebrin are elevated the leading processes turn away from their target and as a result the motor neuron cell bodies move along abnormal paths within the brain. The aberrant trajectories were highly reproducible suggesting that drebrin is required to interpret specific guidance cues. The axons and growth cones of these neurons display morphological changes, particularly increased branching and filopodial number but despite this they extend along normal developmental pathways.
Collectively these results show that drebrin is initially necessary for the formation of a leading process and subsequently for this to respond to navigational signals and grow in the correct direction. Furthermore, we have shown that the actions of drebrin can be segregated within individual motor neurons to direct their migration independently of axon guidance.
doi:10.1016/j.mcn.2012.01.006
PMCID: PMC3356577  PMID: 22306864
OMN, oculomotor nucleus; PCN, precerebellar nuclei; YFP, yellow fluorescent protein; Drebrin; Actin-binding; Migration; Leading process; Oculomotor
25.  Being useful: achieving indigenous youth involvement in a community-based participatory research project in Alaska 
International Journal of Circumpolar Health  2012;71:10.3402/ijch.v71i0.18413.
Objectives
To report on a participatory research process in southwest Alaska focusing on youth involvement as a means to facilitate health promotion. We propose youth-guided community-based participatory research (CBPR) as way to involve young people in health promotion and prevention strategizing as part of translational science practice at the community-level.
Study design
We utilized a CBPR approach that allowed youth to contribute at all stages.
Methods
Implementation of the CBPR approach involved the advancement of three key strategies including: (a) the local steering committee made up of youth, tribal leaders, and elders, (b) youth-researcher partnerships, and (c) youth action-groups to translate findings.
Results
The addition of a local youth-action and translation group to the CBPR process in the southwest Alaska site represents an innovative strategy for disseminating findings to youth from a research project that focuses on youth resilience and wellbeing. This strategy drew from two community-based action activities: (a) being useful by helping elders and (b) being proud of our village.
Conclusions
In our study, youth informed the research process at every stage, but most significantly youth guided the translation and application of the research findings at the community level. Findings from the research project were translated by youth into serviceable action in the community where they live. The research created an experience for youth to spend time engaged in activities that, from their perspectives, are important and contribute to their wellbeing and healthy living. Youth-guided CBPR meant involving youth in the process of not only understanding the research process but living through it as well.
doi:10.3402/ijch.v71i0.18413
PMCID: PMC3367883  PMID: 22584510
Alaska Native; Yup'ik Eskimo; youth-guided; community-based participatory research; youth prevention; translational science

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