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1.
Nucleic Acids Res ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31598706

RESUMO

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of interfaces to genomic data across the tree of life, including reference genome sequence, gene models, transcriptional data, genetic variation and comparative analysis. Data may be accessed via our website, online tools platform and programmatic interfaces, with updates made four times per year (in synchrony with Ensembl). Here, we provide an overview of Ensembl Genomes, with a focus on recent developments. These include the continued growth, more robust and reproducible sets of orthologues and paralogues, and enriched views of gene expression and gene function in plants. Finally, we report on our continued deeper integration with the Ensembl project, which forms a key part of our future strategy for dealing with the increasing quantity of available genome-scale data across the tree of life.

2.
J Phys Chem B ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31539255

RESUMO

Low-temperature persistent and transient hole-burning (HB) spectra are presented for the triple hydrogen-bonded L131LH + M160LH + M197FH mutant of Rhodobacter sphaeroides. These spectra expose the heterogeneous nature of the P-, B-, and H-bands, consistent with a distribution of electron transfer (ET) times and excitation energy transfer (EET) rates. Transient P+QA- holes are observed for fast (tens of picoseconds or faster) ET times and reveal strong coupling to phonons and marker mode(s), while the persistent holes are bleached in a fraction of reaction centers with long-lived excited states characterized by much weaker electron-phonon coupling. Exposed differences in electron-phonon coupling strength, as well as a different coupling to the marker mode(s), appear to affect the ET times. Both resonantly and nonresonantly burned persistent HB spectra show weak blue- (∼150 cm-1) and large, red-shifted (∼300 cm-1) antiholes of the P band. Slower EET times from the H- and B-bands to the special pair dimer provide new insight on the influence of hydrogen bonds on mutation-induced heterogeneity.

3.
Genome Biol ; 20(1): 187, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477173

RESUMO

BACKGROUND: Tsetse flies (Glossina sp.) are the vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse flies are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood-specific diet by both sexes, and obligate bacterial symbiosis. This work describes the comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans, G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes), and Fusca (G. brevipalpis) which represent different habitats, host preferences, and vectorial capacity. RESULTS: Genomic analyses validate established evolutionary relationships and sub-genera. Syntenic analysis of Glossina relative to Drosophila melanogaster shows reduced structural conservation across the sex-linked X chromosome. Sex-linked scaffolds show increased rates of female-specific gene expression and lower evolutionary rates relative to autosome associated genes. Tsetse-specific genes are enriched in protease, odorant-binding, and helicase activities. Lactation-associated genes are conserved across all Glossina species while male seminal proteins are rapidly evolving. Olfactory and gustatory genes are reduced across the genus relative to other insects. Vision-associated Rhodopsin genes show conservation of motion detection/tracking functions and variance in the Rhodopsin detecting colors in the blue wavelength ranges. CONCLUSIONS: Expanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control. They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies.

4.
Assessment ; : 1073191119875789, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31538813

RESUMO

Suicide is the second leading cause of death among American Indian and Alaska Native youth, and within the Alaska Native youth subpopulation, the leading cause of death. In response to this public health crisis, American Indian and Alaska Native communities have created strategies to protect their young people by building resilience using localized Indigenous well-being frameworks and cultural strengths. These approaches to suicide prevention emphasize promotion of protective factors over risk reduction. A measure of culturally based protective factors from suicide risk has potential to assess outcomes from these strengths-based, culturally grounded suicide prevention efforts, and can potentially address several substantive concerns regarding direct assessment of suicide risk. We report on the Reasons for Life (RFL) scale, a measure of protective factors from suicide, testing psychometric properties including internal structure with 302 rural Alaska Native Yup'ik youth. Confirmatory factor analyses revealed the RFL is best described through three distinct first-order factors organized under one higher second-order factor. Item response theory analyses identified 11 satisfactorily functioning items. The RFL correlates with other measures of more general protective factors. Implications of these findings are described, including generalizability to other American Indian and Alaska Native, other Indigenous, and other culturally distinct suicide disparities groups.

5.
Am J Community Psychol ; 64(1-2): 146-158, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365138

RESUMO

Many Indigenous communities are concerned with substance use (SU) problems and eager to advance effective solutions for their prevention and treatment. Yet these communities also are concerned about the perpetuation of colonizing, disorder-focused, stigmatizing approaches to mental health, and social narratives related to SU problems. Foundational principles of community psychology-ecological perspectives, empowerment, sociocultural competence, community inclusion and partnership, and reflective practice-provide useful frameworks for informing ethical community-based research pertaining to SU problems conducted with and by Indigenous communities. These principles are explored and extended for Indigenous community contexts through themes generated from seven collaborative studies focused on understanding, preventing, and treating SU problems. These studies are generated from research teams working with Indigenous communities across the United States and Canada-inclusive of urban, rural, and reservation/reserve populations as well as adult and youth participants. Shared themes indicate that Indigenous SU research reflects community psychology principles, as an outgrowth of research agendas and processes that are increasingly guided by Indigenous communities. At the same time, this research challenges these principles in important ways pertaining to Indigenous-settler relations and Indigenous-specific considerations. We discuss these challenges and recommend greater synergy between community psychology and Indigenous research.

6.
Genetics ; 213(2): 555-566, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31444245

RESUMO

In larval zebrafish, melanocyte stem cells (MSCs) are quiescent, but can be recruited to regenerate the larval pigment pattern following melanocyte ablation. Through pharmacological experiments, we found that inhibition of γ-aminobutyric acid (GABA)-A receptor function, specifically the GABA-A ρ subtype, induces excessive melanocyte production in larval zebrafish. Conversely, pharmacological activation of GABA-A inhibited melanocyte regeneration. We used clustered regularly interspaced short palindromic repeats/Cas9 to generate two mutant alleles of gabrr1, a subtype of GABA-A receptors. Both alleles exhibited robust melanocyte overproduction, while conditional overexpression of gabrr1 inhibited larval melanocyte regeneration. Our data suggest that gabrr1 signaling is necessary to maintain MSC quiescence and sufficient to reduce, but not eliminate, melanocyte regeneration in larval zebrafish.

7.
Am J Community Psychol ; 64(1-2): 34-45, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31343758

RESUMO

This retrospective analysis of a long-term community-based participatory research (CBPR) process spans over two decades of work with Alaska Native communities. A call to action from Alaska Native leadership to create more effective strategies to prevent and treat youth suicide and alcohol misuse risk initiated a response from university researchers. This CBPR process transformed into a collaborative effort to indigenously drive and develop solutions through research. The People Awakening project started our team on this translational and transformational pathway through community intervention science in the Central Yup'ik region of Alaska. We examine more deeply the major episodes and their successes and struggles in maintaining a long-term research relationship between university researchers and members of Yup'ik Alaska Native communities. We explore ways that our CBPR relationship has involved negotiation and engagement with power and praxis, to deepen and focus attention to knowledge systems and relational elements. This paper examines these deeper, transformative elements of our CBPR relationship that spans histories, cultures, and systems. Our discussion shares vignettes from academic and community perspectives to describe process in a unique collaboration, reaching to sometimes touch upon rare ground in emotions, tensions, and triumphs over the course of a dozen grants and twice as many years. We conclude by noting how there are points where, in a long-term CBPR relationship, transition out of emergence into coalescing and transformation can occur.

8.
Prev Sci ; 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31152330

RESUMO

This concluding article to the Supplemental Issue on Promoting Health Equity through Rigorous, Culturally Informed Intervention Science: Innovations with Indigenous Populations in the United States draws themes and conclusions from the innovative practices implemented by the National Institutes of Health Intervention Research to Improve Native American Health (IRINAH) consortium. The IRINAH work highlights promising practices for advancing the diverse and underrepresented perspectives essential to develop and test culturally appropriate, effective health interventions in American Indian, Alaska Native, and Native Hawaiian settings. Four emergent themes appear through the IRINAH work. First, community-based participatory research (CBPR) has provided projects an intersectional worldview for bridging cultures and informing an ethics of local control. Second, culture is fundamental as a central organizing principle in IRINAH research and intervention implementation. Third, crucial demands for sustainability of interventions in Indigenous intervention science require a rethinking of the intervention development process. Finally, tensions persist in Indigenous health research, even as significant strides are made in the field. These themes collectively inform an ethical and rigorous Indigenous intervention science. Collectively, they suggest a roadmap for advancing Indigenous perspectives and self-determination in health intervention research. IRINAH studies are leading innovation in intervention science by advancing applications of CBPR in intervention science, promoting new directions in small populations health research, and demonstrating value of participatory team science.

9.
Am J Public Health ; 109(5): 668-670, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30969819
10.
Sci Total Environ ; 668: 1232-1241, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31018463

RESUMO

Wave farms, i.e., arrays of wave energy converters (WECs), have been proposed to fulfil the dual function of carbon-free energy generation and coastal protection. The objective of this work is to investigate, for the first time, how the coastal protection performance against flooding is affected by WEC geometry. This is done by means of a case study with WaveCat WECs (floating, overtopping WECs) deployed off the Playa Granada beach (Spain). To this end, two models of WaveCat WECs with different geometries are tested in a laboratory tank at a 1:30 scale under low-, mid- and high-energy sea states representative of the wave conditions of Playa Granada. The geometries differed in the angle between the twin hulls (wedge angle) of WaveCat: 30° and 60°. The reflection and transmission coefficients thus obtained are used in a coupled numerical modelling approach, combining wave and coastal processes models (SWAN and XBeach-G, respectively). We find that WECs with an angle of 60° provide more (less) protection for long (short) wave periods in terms of reductions in wave height and run-up on the beach. As for the flooded dry beach areas, they are generally smaller for WECs with 60°, with only some exceptions under mild conditions. Thus, considering that beach inundation usually occurs under high-energy, storm conditions, we conclude that the wave farm composed by WECs with a wedge angle of 60° is more efficient against coastal flooding.

11.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-30828437

RESUMO

Innovations are expanding the capabilities of experimental investigations of the structural properties of membrane proteins. Traditionally, three-dimensional structures have been determined by measuring x-ray diffraction using protein crystals with a size of least 100 µm. For membrane proteins, achieving crystals suitable for these measurements has been a significant challenge. The availabilities of micro-focus x-ray beams and the new instrumentation of x-ray free-electron lasers have opened up the possibility of using submicrometer-sized crystals. In addition, advances in cryo-electron microscopy have expanded the use of this technique for studies of protein crystals as well as studies of individual proteins as single particles. Together, these approaches provide unprecedented opportunities for the exploration of structural properties of membrane proteins, including dynamical changes during protein function.

12.
Cultur Divers Ethnic Minor Psychol ; 25(1): 44-54, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30714766

RESUMO

OBJECTIVES: The foundational role culture and Indigenous knowledge (IK) occupy within community intervention in American Indian and Alaska Native (AIAN) communities is explored. To do this, we define community or complex interventions, then critically examine ways culture is translated into health interventions addressing AIAN disparities in existing programs and research initiatives. We then describe an Indigenous intervention based in the cultural logic of its contexts, as developed by Alaska Native communities. Yup'ik coauthors and knowledge keepers provided their critical and theoretical perspectives and understandings to the overall narrative, constructing from their IK system an argument that culture is prevention. CONCLUSIONS: The intervention, the Qungasvik (phonetic: koo ngaz vik; "tools for life") intervention, is organized and delivered through a Yup'ik Alaska Native process the communities term qasgiq (phonetic: kuz gik; "communal house"). We describe a theory of change framework built around the qasgiq model and explore ways this Indigenous intervention mobilizes aspects of traditional Yup'ik cultural logic to deliver strengths-based interventions for Yup'ik youth. This framework encompasses both an IK theory-driven intervention implementation schema and an IK approach to knowledge production. This intervention and its framework provide a set of recommendations to guide researchers and Indigenous communities who seek to create Indigenously informed and locally sustainable strategies for the promotion of health and well-being. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Comportamento do Adolescente/psicologia , Nativos do Alasca/psicologia , Alcoolismo/prevenção & controle , Pesquisa Participativa Baseada na Comunidade/métodos , Suicídio/prevenção & controle , Adolescente , Comportamento do Adolescente/etnologia , Desenvolvimento do Adolescente , Alcoolismo/etnologia , Feminino , Humanos , Fatores de Proteção , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Suicídio/etnologia , Tradução
13.
Mol Ther ; 27(3): 623-635, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30718090

RESUMO

Gene therapies using adeno-associated viral (AAV) vectors have advanced into clinical trials for several diseases, including Duchenne muscular dystrophy (DMD). A limitation of AAV is the carrying capacity (∼5 kb) available for genes and regulatory cassettes (RCs). These size constraints are problematic for the 2.2-Mb dystrophin gene. We previously designed a variety of miniaturized micro-dystrophins (µDys) that displayed significant, albeit incomplete, function in striated muscles. To develop µDys proteins with improved performance, we explored structural modifications of the dystrophin central rod domain. Eight µDys variants were studied that carried unique combinations of between four and six of the 24 spectrin-like repeats present in the full-length protein, as well as various hinge domains. Expression of µDys was regulated by a strong but compact muscle-restricted RC (CK8e) or by the ubiquitously active cytomegalovirus (CMV) RC. Vectors were evaluated by intramuscular injection and systemic delivery to dystrophic mdx4cv mice, followed by analysis of skeletal muscle pathophysiology. Two µDys designs were identified that led to increased force generation compared with previous µDys while also localizing neuronal nitric oxide synthase to the sarcolemma. An AAV vector expressing the smaller of these (µDys5) from the CK8e RC is currently being evaluated in a DMD clinical trial.

15.
PLoS One ; 13(12): e0210043, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30589902

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0204284.].

16.
Nucleic Acids Res ; 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30407521

RESUMO

The Ensembl project (https://www.ensembl.org) makes key genomic data sets available to the entire scientific community without restrictions. Ensembl seeks to be a fundamental resource driving scientific progress by creating, maintaining and updating reference genome annotation and comparative genomics resources. This year we describe our new and expanded gene, variant and comparative annotation capabilities, which led to a 50% increase in the number of vertebrate genomes we support. We have also doubled the number of available human variants and added regulatory regions for many mouse cell types and developmental stages. Our data sets and tools are available via the Ensembl website as well as a through a RESTful webservice, Perl application programming interface and as data files for download.

17.
J Virol ; 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30429350

RESUMO

The vast majority of people already have pre-existing immune responses to influenza viruses from one or more subtypes. However, almost all preclinical studies evaluate new influenza vaccine candidates in immunologically naïve animals. Recently, our group demonstrated that priming naive ferrets with broadly reactive H1 COBRA HA based vaccines boosted pre-existing antibodies induced by wild-type H1N1 virus infections. These H1 COBRA HA antigens induced antibodies with HAI activity against multiple antigenically different H1N1 viral variants. In this study, ferrets, preimmune to historical H3N2 viruses, were vaccinated with virus-like particle (VLP) vaccines expressing either an HA from a wild-type H3 influenza virus or a COBRA H3 HA antigen (T6, T7, T10, or T11). The elicited antisera had the ability to neutralize virus infection against a panel of viruses representing vaccine strains selected by the World Health Organization (WHO), or a set of viral variants that co-circulated during the same time period. Preimmune animals vaccinated with H3 COBRA T10 HA antigen elicited sera with higher HAI antibody titers than antisera elicited by VLP vaccines with wild-type HA VLPs in preimmune ferrets. However, while the T11 COBRA vaccine did not elicit HAI activity, the elicited antibodies did neutralize antigenically distinct H3N2 influenza viruses. Overall, H3 COBRA-based HA vaccines were able to neutralize both historical H3 and comtemporary, as well as future H3N2 viruses with higher titers than vaccines with wild-type H3 HA antigens. This is the first report demonstrating the effectiveness of a broadly reactive H3N3 vaccine in a preimmune ferret model.IMPORTANCE Following influenza virus exposure, the host generates neutralizing anti-hemagglutinin antibodies against that specific infecting influenza strain. These antibodies can also neutralize some, but not all, co-circulating strains. The goal of next generation influenza vaccines, such as HA head-based COBRA, is to stimulate broadly protective neutralizing antibodies against all strains circulating within a subtype, in particular those that persist over multiple influenza seasons, without requiring an update to the vaccine. To mimic the human condition, COBRA HA virus-like particle vaccines were tested in ferrets that were previously exposed to historical H3N2 influenza viruses. In this model, these vaccines elicited broadly protective antibodies that neutralized co-circulating H3N2 influenza viruses isolated over a 20-year period. This is the first study to show the effectiveness of H3N3 COBRA HA vaccines in a host with pre-existing immunity to influenza.

18.
Prev Sci ; 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30443847

RESUMO

Research in indigenous communities is at the forefront of innovation currently influencing several new perspectives in engaged intervention science. This is innovation born of necessity, involving efforts to create health equity complicated by a history of distrust of research. Immense diversity across indigenous cultures, accompanied by variation in associated explanatory models, health beliefs, and health behaviors, along with divergent structural inequities add further complexity to this challenge. The aim of this Supplemental Issue on Promoting Health Equity through Rigorous, Culturally Informed Intervention Science: Innovations with Indigenous Populations in the United States is to highlight the promising new approaches and perspectives implemented by a group of engaged researchers and their community partners, as they seek to move intervention research forward within indigenous communities. Case studies presented are from projects led by members of the National Institutes of Health Intervention Research to Improve Native American Health (IRINAH) consortioum, investigators who conduct health promotion and disease prevention research among American Indians, Alaska Natives, and Native Hawaiians. The promising practices profiled include new strategies in (a) community partnerships, engagement, and capacity building; (b) integration of indigenous and academic perspectives; (c) alignment of interventions with indigenous cultural values and practices; and (d) implementation and evaluation of multilevel interventions responsive to complex cultural contexts. The IRINAH projects illustrate the evolution of an intervention science responsive to the needs, realities, and promise of indigenous communities, with application to health research among other culturally distinct health inequity groups.

19.
Prev Sci ; 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30397737

RESUMO

Given the paucity of empirically based health promotion interventions designed by and for American Indian, Alaska Native, and Native Hawaiian (i.e., Native) communities, researchers and partnering communities have had to rely on the adaptation of evidence-based interventions (EBIs) designed for non-Native populations, a decidedly sub-optimal approach. Native communities have called for development of Indigenous health promotion programs in which their cultural worldviews and protocols are prioritized in the design, development, testing, and implementation. There is limited information regarding how Native communities and scholars have successfully collaborated to design and implement culturally based prevention efforts "from the ground up." Drawing on five diverse community-based Native health intervention studies, we describe strategies for designing and implementing culturally grounded models of health promotion developed in partnership with Native communities. Additionally, we highlight indigenist worldviews and protocols that undergird Native health interventions with an emphasis on the incorporation of (1) original instructions, (2) relational restoration, (3) narrative-[em]bodied transformation, and (4) indigenist community-based participatory research (ICBPR) processes. Finally, we demonstrate how culturally grounded interventions can improve population health when they prioritize local Indigenous knowledge and health-positive messages for individual to multi-level community interventions.

20.
J Phys Chem B ; 122(44): 10097-10107, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30351114

RESUMO

Energetics, protein dynamics, and electronic coupling are the key factors in controlling both electron and energy transfer in photosynthetic bacterial reaction centers (RCs). Here, we examine the rates and mechanistic pathways of the P+HA- radical-pair charge recombination, triplet state formation, and subsequent triplet energy transfer from the triplet state of the bacteriochlorophyll dimer (P) to the carotenoid in a series of mutant RCs (L131LH + M160LH (D1), L131LH + M197FH (D2), and L131LH + M160LH + M197FH (T1)) of Rhodobacter sphaeroides. In these mutants, the electronic structure of P is perturbed and the P/P+ midpoint potential is systematically increased due to addition of hydrogen bonds between P and the introduced residues. High-resolution, broad-band, transient absorption spectroscopy on the femtosecond to microsecond timescale shows that the charge recombination rate increases and the triplet energy transfer rate decreases in these mutants relative to the wild type (WT). The increase of the charge recombination rate is correlated to the increase in the energy level of P+HA- and the increase in the P/P+ midpoint potential. On the other hand, the decrease in rate of triplet energy transfer in the mutants can be explained in terms of a lower energy of 3P and a shift in the electron spin density distribution in the bacteriochlorophylls of P. The triplet energy-transfer rate follows the order of WT > L131LH + M197FH > L131LH + M160LH > L131LH + M160LH + M197FH, both at room temperature and at 77 K. A pronounced temperature dependence of the rate is observed for all of the RC samples. The activation energy associated to this process is increased in the mutants relative to WT, consistent with a lower 3P energy due to the addition of hydrogen bonds between P and the introduced residues.

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