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BACKGROUND: The real-world effectiveness of exposure-based therapies for youth depends on the willingness and ability of young people to tolerate confronting their fears, which can be experienced as highly aversive and create problems with treatment engagement and acceptance. Recently, neuroscientific research on the nonconscious basis of fear has been translated into novel exposure interventions that bypass conscious processing of feared stimuli and that thus do not cause phobic youth to experience distress. We present a review of these unconscious exposure interventions. METHODS: A PRISMA-based search yielded 20 controlled experiments based on three paradigms that tested if fear-related responses could be reduced without conscious awareness in highly phobic, transition-age youth: 14 randomized controlled trials (RCTs), 5 fMRI studies (1 was also an RCT), 4 psychophysiological studies (3 were also RCTs), and 1 ERP study. We conducted meta-analyses of outcomes where feasible. RESULTS: Unconscious exposure interventions significantly (1) reduced avoidance behavior (range of Cohen's d = 0.51-0.95) and self-reported fear (d = 0.45-1.25) during in vivo exposure to the feared situation; (2) reduced neurobiological indicators of fear (d = 0.54-0.62) and concomitant physiological arousal (d = 0.55-0.64); (3) activated neural systems supporting fear regulation more strongly than visible exposure to the same stimuli (d = 1.2-1.5); (4) activated regions supporting fear regulation that mediated the reduction of avoidance behavior (d = 0.70); (5) evoked ERPs suggesting encoding of extinction memories (d = 2.13); and (6) had these effects without inducing autonomic arousal or subjective fear. CONCLUSIONS: Unconscious exposure interventions significantly reduce a variety of symptomatic behaviors with mostly moderate effect sizes in transition-age youth with specific phobias. fMRI and physiological findings establish a neurophysiological basis for this efficacy, and suggest it occurs through extinction learning. Unconscious exposure was well tolerated, entirely unassociated with drop out, and is highly scalable for clinical practice. However, a number of limitations must be addressed to assess potential clinical impacts, including combining unconscious exposure with exposure therapy to boost treatment acceptance and efficacy.
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Melanotic (Ml) is a mutation in chickens that extends black (eumelanin) pigmentation in normally brown or red (pheomelanin) areas, thus affecting multiple within-feather patterns [J. W. Moore, J. R. Smyth Jr, J. Hered. 62, 215-219 (1971)]. In the present study, linkage mapping using a back-cross between Dark Cornish (Ml/Ml) and Partridge Plymouth Rock (ml+/ml+ ) chickens assigned Ml to an 820-kb region on chromosome 1. Identity-by-descent mapping, via whole-genome sequencing and diagnostic tests using a diverse set of chickens, refined the localization to the genomic region harboring GJA5 encoding gap-junction protein 5 (alias connexin 40) previously associated with pigmentation patterns in zebrafish. An insertion/deletion polymorphism located in the vicinity of the GJA5 promoter region was identified as the candidate causal mutation. Four different GJA5 transcripts were found to be expressed in feather follicles and at least two showed differential expression between genotypes. The results showed that Melanotic constitutes a cis-acting regulatory mutation affecting GJA5 expression. A recent study established the melanocortin-1 receptor (MC1R) locus and the interaction between the MC1R receptor and its antagonist agouti-signaling protein as the primary mechanism underlying variation in within-feather pigmentation patterns in chickens. The present study advances understanding the mechanisms underlying variation in plumage color in birds because it demonstrates that the activity of connexin 40/GJA5 can modulate the periodic pigmentation patterns within individual feathers.
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Proteína Agouti Sinalizadora/genética , Galinhas/genética , Conexinas/genética , Plumas/fisiologia , Pigmentação/genética , Receptor Tipo 1 de Melanocortina/genética , Animais , Mutação INDEL/genética , Queratinócitos/metabolismo , Melaninas/genética , Regiões Promotoras Genéticas/genética , Proteína alfa-5 de Junções ComunicantesRESUMO
Madole & Harden's assertion that the effects derived from within-family genome-wide association studies (GWASs) and from randomized controlled trials (RCTs) are equivalent is misleading. GWASs are substantially more "non-unitary, non-uniform, and non-explanatory" than RCTs. While the within-family GWAS bring us closer to identifying genetic causes, whether it will change behavioral genetics into a causal science is an open question.
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Estudo de Associação Genômica Ampla , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
In his 'script theory,' Tomkins first proposed that people unconsciously organize their life experiences in terms of narrative structures he termed "scripts." I use a clinical vignette to illustrate how the psychotherapeutic process of "making the unconscious conscious" involves becoming aware of the maladaptive scripts that people unwittingly live by, and developing them into the "conviction narratives" proposed by the authors.
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Estado de Consciência , Inconsciência , Masculino , HumanosRESUMO
Feathered leg is a trait in domestic chickens that has undergone intense selection by fancy breeders. Previous studies have shown that two major loci controlling feathered leg are located on chromosomes 13 and 15. Here, we present genetic evidence for the identification of candidate causal mutations at these loci. This was accomplished by combining classical linkage mapping using an experimental cross segregating for feathered leg and high-resolution identical-by-descent mapping using whole-genome sequence data from 167 samples of chicken with or without feathered legs. The first predicted causal mutation is a single-base change located 25 kb upstream of the gene for the forelimb-specific transcription factor TBX5 on chromosome 15. The second is a 17.7-kb deletion located â¼200 kb upstream of the gene for the hindlimb-specific transcription factor PITX1 on chromosome 13. These mutations are predicted to activate TBX5 and repress PITX1 expression, respectively. The study reveals a remarkable convergence in the evolution of the feathered-leg phenotype in domestic chickens and domestic pigeons, as this phenotype is caused by noncoding mutations upstream of the same two genes. Furthermore, the PITX1 causal variants are large overlapping deletions, 17.7 kb in chicken and 44 kb in pigeons. The results of the present study are consistent with the previously proposed model for pigeon that feathered leg is caused by reduced PITX1 expression and ectopic expression of TBX5 in hindlimb buds resulting in a shift of limb identity from hindlimb to more forelimb-like identity.
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Galinhas/genética , Plumas/crescimento & desenvolvimento , Fatores de Transcrição Box Pareados/genética , Proteínas com Domínio T/genética , Animais , Galinhas/crescimento & desenvolvimento , Mapeamento Cromossômico , Feminino , Deleção de Genes , Extremidade Inferior , Masculino , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Chickens from lines selected for low (LWS) or high (HWS) body weight (BW) differ in appetite and adiposity. Mechanisms associated with the predisposition to becoming obese are unclear. The objective of the experiment was to evaluate developmental changes in depot-specific adipose tissue during the first 2 wk posthatch. Subcutaneous (SQ), clavicular (CL), and abdominal (AB) depots were collected at hatch (DOH) and days 4 (D4) and 14 (D14) posthatch for histological and mRNA measurements. LWS chicks had decreased SQ fat mass on a BW basis with reduced adipocyte size from DOH to D4 and increased BW and fat mass with unchanged adipocyte size from D4 to D14. HWS chicks increased in BW from DOH to D14 and increased in fat mass in all three depots with enlarged adipocytes in the AB depot from D4 to D14. Meanwhile, CCAAT/enhancer-binding protein-α, neuropeptide Y, peroxisome proliferator-activated receptor-γ, and acyl-CoA dehydrogenase mRNAs differed among depots between lines at different ages. Plasma nonesterified fatty acids were greater in LWS than HWS at D4 and D14. From DOH to D4, LWS chicks mobilized SQ fat and replenished the reservoir through hyperplasia, whereas HWS chicks were dependent on hyperplasia and hypertrophy to maintain adipocyte size and depot mass. From D4 to D14, adipose tissue catabolism and adipogenesis slowed. Whereas LWS fat depots and adipocyte sizes remained stable, HWS chicks rapidly accumulated fat in CL and AB depots. Chicks predisposed to be anorexic or obese have different fat development patterns during the first 2 wk posthatch.
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Adipogenia , Tecido Adiposo/crescimento & desenvolvimento , Adiposidade , Galinhas/crescimento & desenvolvimento , Aumento de Peso , Acil-CoA Desidrogenase de Cadeia Longa/genética , Acil-CoA Desidrogenase de Cadeia Longa/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Animais Recém-Nascidos , Anorexia/genética , Anorexia/metabolismo , Anorexia/fisiopatologia , Anorexia/veterinária , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Galinhas/genética , Galinhas/metabolismo , Feminino , Regulação da Expressão Gênica , Masculino , Neuropeptídeo Y/genética , Neuropeptídeo Y/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade/veterinária , PPAR gama/genética , PPAR gama/metabolismo , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/fisiopatologia , Fatores de TempoRESUMO
Hepatitis E is an important global disease, causing outbreaks of acute hepatitis in many developing countries and sporadic cases in industrialized countries. Hepatitis E virus (HEV) infection typically causes self-limiting acute hepatitis but can also progress to chronic disease in immunocompromised individuals. The immune response necessary for the prevention of chronic infection is T cell-dependent; however, the arm of cellular immunity responsible for this protection is not currently known. To investigate the contribution of humoral immunity in control of HEV infection and prevention of chronicity, we experimentally infected 20 wild-type (WT) and 18 immunoglobulin knockout (JH-KO) chickens with a chicken strain of HEV (avian HEV). Four weeks postinfection (wpi) with avian HEV, JH-KO chickens were unable to elicit anti-HEV antibody but had statistically significantly lower liver lesion scores than the WT chickens. At 16 wpi, viral RNA in fecal material and liver, and severe liver lesions were undetectable in both groups. To determine the role of cytotoxic lymphocytes in the prevention of chronicity, we infected 20 WT and 20 cyclosporine and CD8+ antibody-treated chickens with the same strain of avian HEV. The CD8 + lymphocyte-depleted, HEV-infected chickens had higher incidences of prolonged fecal viral shedding and statistically significantly higher liver lesion scores than the untreated, HEV-infected birds at 16 wpi. The results indicate that CD8 + lymphocytes are required for viral clearance and reduction of liver lesions in HEV infection while antibodies are not necessary for viral clearance but may contribute to the development of liver lesions in acute HEV infection.
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Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Anticorpos Anti-Hepatite/sangue , Hepatite Viral Animal/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Infecções por Vírus de RNA/veterinária , Animais , Galinhas/imunologia , Fezes/virologia , Técnicas de Inativação de Genes , Hepatite Viral Animal/imunologia , Hepevirus , Imunidade Celular , Imunidade Humoral , Imunoglobulinas/genética , Fígado/patologia , Fígado/virologia , Depleção Linfocítica , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/prevenção & controle , RNA Viral/análise , Eliminação de Partículas ViraisRESUMO
Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in-house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta-analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in-house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.
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Alérgenos/imunologia , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/imunologia , Imunoensaio , Imunoglobulina E/imunologia , Indústrias , Exposição Ocupacional/efeitos adversos , Poluentes Ocupacionais do Ar/efeitos adversos , Alérgenos/química , Asma/diagnóstico , Asma/imunologia , Exposição Ambiental , Humanos , Hipersensibilidade Imediata/sangue , Imunoensaio/métodos , Imunoensaio/normas , Imunoglobulina E/sangue , Metanálise como Assunto , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Occupational exposure to the most widely used diisocyanate, 4,4'-methylene diphenyl diisocyanate (MDI), is a cause of occupational asthma (OA). Early recognition of MDI exposure and sensitization is essential for the prevention of MDI-OA. OBJECTIVE: Identify circulating microRNAs (miRs) as novel biomarkers for early detection of MDI exposure and prevention of MDI-OA. MATERIALS AND METHODS: Female BALB/c mice were exposed to one of three exposure regimens: dermal exposure to 1% MDI in acetone; nose-only exposure to 4580 ± 1497 µg/m3 MDI-aerosol for 60 minutes; or MDI dermal exposure/sensitization followed by MDI-aerosol inhalation challenge. Blood was collected and miRCURY™ miRs qPCR Profiling Service was used to profile circulate miRs from dermally exposed mice. Candidate miRs were identified and verified from mice exposed to three MDI-exposure regimens by TaqMan® miR assays. RESULTS: Up/down-regulation patterns of circulating mmu-miRs-183-5p, -206-3p and -381-3p were identified and verified. Circulating mmu-miR-183-5p was upregulated whereas mmu-miRs-206-3p and -381-3p were downregulated in mice exposed via all three MDI exposure regimens. DISCUSSION AND CONCLUSION: Upregulation of circulating miR-183-5p along with downregulation of circulating miRs-206-3p and -381-3p may serve as putative biomarkers of MDI exposure and may be considered as potential candidates for validation in exposed human worker populations.
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Asma Ocupacional/diagnóstico , MicroRNA Circulante/sangue , Isocianatos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Animais , Asma Ocupacional/induzido quimicamente , Biomarcadores/sangue , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , MicroRNAs/sangueRESUMO
BACKGROUND: Experimental intercrosses between outbred founder populations are powerful resources for mapping loci that contribute to complex traits i.e. quantitative trait loci (QTL). Here, we present an approach and its accompanying software for high-resolution reconstruction of founder mosaic genotypes in the intercross offspring from such populations using whole-genome high-coverage sequence data on founder individuals (~ 30×) and very low-coverage sequence data on intercross individuals (< 0.5×). Sets of founder-line informative markers were selected for each full-sib family and used to infer the founder mosaic genotypes of the intercross individuals. The application of this approach and the quality of the estimated genome-wide genotypes are illustrated in a large F2 pedigree between two divergently selected lines of chickens. RESULTS: We describe how we obtained whole-genome genotype data for hundreds of individuals in a cost- and time-efficient manner by using a Tn5-based library preparation protocol and an imputation algorithm that was optimized for this application. In total, 7.6 million markers segregated in this pedigree and, within each full-sib family, between 10.0 and 13.7% of these were fully informative, i.e. fixed for alternative alleles in the founders from the divergent lines, and were used for reconstruction of the offspring mosaic genotypes. The genotypes that were estimated based on the low-coverage sequence data were highly consistent (> 95% agreement) with those obtained using individual single nucleotide polymorphism (SNP) genotyping. The estimated resolution of the inferred recombination breakpoints was relatively high, with 50% of them being defined on regions shorter than 10 kb. CONCLUSIONS: A method and software for inferring founder mosaic genotypes in intercross offspring from low-coverage whole-genome sequencing in pedigrees from heterozygous founders are described. They provide high-quality, high-resolution genotypes in a time- and cost-efficient manner. The software is freely available at https://github.com/CarlborgGenomics/Stripes .
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Galinhas/genética , Técnicas de Genotipagem , Sequenciamento Completo do Genoma , Animais , Cruzamento , Custos e Análise de Custo , Cruzamentos Genéticos , Conjuntos de Dados como Assunto , Feminino , Efeito Fundador , Técnicas de Genotipagem/economia , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Software , Sequenciamento Completo do Genoma/economiaRESUMO
The body weight-selected lines of chickens are a model for understanding factors that predispose an individual to anorexia or obesity. The high body weight-selected (HWS) individuals are compulsive eaters that become obese whereas the low body weight-selected (LWS) are relatively lean and hypophagic. The objective of this study was to measure gene expression of various preadipocyte, proliferation, metabolic, and apoptotic markers in the stromal-vascular fraction and adipocytes from LWS and HWS adipose tissue. Although preadipocyte and proliferation markers were more highly expressed in the stromal-vascular fraction of LWS than HWS chicks, greater expression of granzyme-A and the presence of more annexin V-positive cells suggests that apoptosis may limit the adipogenic potential of adipocyte precursor cells and represent a novel mechanism that regulates the expansion of adipose tissue. Results provide insights on cellular mechanisms associated with adipose tissue development in the lean and obese state.
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Adipogenia/genética , Tecido Adiposo/metabolismo , Anorexia/genética , Apoptose/genética , Biomarcadores/metabolismo , Galinhas/genética , Predisposição Genética para Doença , Obesidade/genética , Animais , Caspase 3/genética , Caspase 3/metabolismo , Granzimas/genética , Granzimas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Mesotocin (MT) decreases food intake and induces hyperthermia in chicks although hypothalamic mechanisms are unknown. The purpose of this study was thus to investigate effects of receptor antagonists and MT on feeding behavior and hypothalamic physiology. Intracerebroventricular injection of 2.5â¯nmol into broiler chicks was associated with decreased food intake for 180â¯min and water intake from 60 to 180â¯min. Cloacal temperatures were elevated in chicks injected with 0.156 and 0.625â¯nmol at 30 and 60â¯min, and up to 180â¯min in those injected with 2.5â¯nmol. MT also increased temperatures and decreased food and water intake in chicks from lines selected for low (LWS) or high (HWS) body weight with a higher dose threshold but longer food intake response in HWS chicks. An oxytocin receptor antagonist prevented MT-mediated changes in food intake but not water intake or temperature. Yohimbine, an α2-adrenergic receptor antagonist, did not affect food intake, temperature, or MT-mediated effects. MT increased c-Fos immunoreactivity in the paraventricular nucleus (PVN) and lateral hypothalamus (LH). Hypothalamic agouti-related peptide, corticotropin-releasing factor receptor sub-type 1, and melanocortin receptor 3 mRNAs increased in response to MT. There was increased MT mRNA in the LH and L-aromatic amino acid decarboxylase mRNA in the PVN of MT-injected chicks. In conclusion, MT induced anorexia and hyperthermia and reduced water intake. MT was associated with activation of the PVN and LH and differences in the mRNA abundance of some appetite-associated factors, thus implicating these nuclei and several signaling pathways in the effects observed.
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Anorexia/induzido quimicamente , Galinhas/genética , Região Hipotalâmica Lateral/efeitos dos fármacos , Ocitocina/análogos & derivados , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Animais , Descarboxilases de Aminoácido-L-Aromático/genética , Região Hipotalâmica Lateral/metabolismo , Ocitocina/farmacologia , RNA Mensageiro/metabolismoRESUMO
PURPOSE: Formaldehyde allergic contact dermatitis (ACD) may be due to products with free formaldehyde or formaldehyde-releasing agents; however, assessment of formaldehyde levels in such products is infrequently conducted. The present study quantifies total releasable formaldehyde from "in-use" products associated with formaldehyde ACD and tests the utility of commercially available formaldehyde spot test kits. MATERIALS AND METHODS: Personal care products from 2 patients with ACD to formaldehyde were initially screened at the clinic for formaldehyde using a formaldehyde spot test kit. Formaldehyde positive products were sent to the laboratory for confirmation by gas chromatography-mass spectrometry. In addition, 4 formaldehyde spot test kits were evaluated for potential utility in a clinical setting. RESULTS: Nine of the 10 formaldehyde spot test kit positive products obtained from formaldehyde allergic patients had formaldehyde with total releasable formaldehyde levels ranging from 5.4 to 269.4 µg/g. Of these, only two shampoos tested listed a formaldehyde-releasing agent in the ingredients or product literature. Subsequently, commercially available formaldehyde spot test kits were evaluated in the laboratory for ability to identify formaldehyde in personal care products. CONCLUSIONS: Chemical based formaldehyde spot test were more reliable than the enzymatic based test in identifying product releasable formaldehyde content. It is concluded that product labeled ingredient lists and available information are often inadequate to confirm the potential for formaldehyde exposure and chemical based spot test kits may have utility for identification of potential formaldehyde exposure from personal care products.
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Qualidade de Produtos para o Consumidor , Cosméticos/análise , Formaldeído/análise , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato , Formaldeído/efeitos adversos , Formaldeído/toxicidade , Humanos , Testes do EmplastroRESUMO
The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity.
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Galinhas/genética , Herança Multifatorial/genética , Aclimatação/genética , Adaptação Fisiológica/genética , Alelos , Animais , Peso Corporal/genética , Cruzamento , Mapeamento Cromossômico , Cruzamentos Genéticos , Epistasia Genética/genética , Loci Gênicos/genética , Variação Genética/genética , Genética Populacional/métodos , Polimorfismo Genético/genética , Locos de Características Quantitativas , Seleção Genética/genéticaRESUMO
1. Diisocyanates are highly reactive electrophiles utilized in the manufacture of a wide range of polyurethane products and have been identified as causative agents of occupational allergic respiratory disease. However, in spite of the significant occupational health burden associated with diisocyanate-induced asthma, the mechanism of disease pathogenesis remains largely unknown. 2. To better understand the fate of inhaled diisocyanates, a nose-only aerosol exposure system was constructed and utilized to expose a BALB/c mouse model to an aerosol generated from 4,4'-methylene diphenyl diisocyanate (MDI). Tissue and bronchoalveolar lavage samples were evaluated 4 and 24 h post-exposure for evidence of diisocyanate-protein haptenation, and a label-free quantitative proteomics strategy was employed to evaluate relative changes to the protein content of the cellular fraction of the lavage fluid. 3. Following MDI aerosol exposure, expression of the number of proteins with immunological or xenobiotic metabolism relevance is increased, including endoplasmin, cytochrome P450 and argininosuccinate synthase. Western blot analysis indicated MDI-conjugated protein in the lavage fluid, which was identified as serum albumin. 4. Tandem mass spectrometry analysis of MDI-albumin revealed MDI conjugation occurs at a dilysine motif at Lys525, as well as at a glutamine-lysine motif at Lys414, in good agreement with previously published in vitro data on diisocyanate-conjugated serum albumin.
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Argininossuccinato Sintase/metabolismo , Asma/metabolismo , Lavagem Broncoalveolar , Sistema Enzimático do Citocromo P-450/metabolismo , Isocianatos/toxicidade , Glicoproteínas de Membrana/metabolismo , Aerossóis , Animais , Asma/induzido quimicamente , Feminino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Scientific writing and publication are essential to advancing knowledge and practice in public health, but prospective authors face substantial challenges. Authors can overcome barriers, such as lack of understanding about scientific writing and the publishing process, with training and resources. The objective of this article is to provide guidance and practical recommendations to help both inexperienced and experienced authors working in public health settings to more efficiently publish the results of their work in the peer-reviewed literature. We include an overview of basic scientific writing principles, a detailed description of the sections of an original research article, and practical recommendations for selecting a journal and responding to peer review comments. The overall approach and strategies presented are intended to contribute to individual career development while also increasing the external validity of published literature and promoting quality public health science.
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Pesquisa Biomédica , Editoração/normas , Redação/normas , Guias como Assunto , HumanosRESUMO
Growth is a complex and dynamic process that may be measured at a specific point or over a period of time. Compared was the growth of male and female chickens over a three-generation period. Involved were red junglefowl (RJF; Gallus gallus), a line of White Plymouth Rock chickens (LWS; Gallus gallus domesticus) selected for low body weight, and their reciprocal F1 and F2 crosses. In both sexes, Gompertz's description of growth showed that RJF had significantly lower asymptotes, earlier inflection points, and faster growth rates than LWS. Heterosis for these measures was positive for asymptote and negative for growth rate and inflection point. The RJF commenced egg production at a significantly younger age and lower body weight than LWS. Although F1 and F2 reciprocal crosses were similar for body weight and for age at first egg, the F1 reciprocal crosses began lay at significantly younger ages than the F2 crosses and parental lines. When viewed on a physiological basis where age and body weight were simultaneously standardized, both parental lines and reciprocal F1 and F2 crosses had differing rapid and lag growth phases. Overall, sexual dimorphism increased in all populations from hatch to sexual maturity. The LWS males had a longer growth period consistent with their female counterparts who became sexually mature at older ages. Comprehensively, these results indicate additive and nonadditive genetic variation for distinct growth patterns and changes in resource allocation strategies over time.
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BACKGROUND: Long-term selection experiments provide a powerful approach to gain empirical insights into adaptation, allowing researchers to uncover the targets of selection and infer their contributions to the mode and tempo of adaptation. Here we implement a pooled genome re-sequencing approach to investigate the consequences of 39 generations of bidirectional selection in White Leghorn chickens on a humoral immune trait: antibody response to sheep red blood cells. RESULTS: We observed wide genome involvement in response to this selection regime. Many genomic regions were highly differentiated resulting from this experimental selection regime, an involvement of up to 20% of the chicken genome (208.8 Mb). While genetic drift has certainly contributed to this, we implement gene ontology, association analysis and population simulations to increase our confidence in candidate selective sweeps. Three strong candidate genes, MHC, SEMA5A and TGFBR2, are also presented. CONCLUSIONS: The extensive genomic changes highlight the polygenic genetic architecture of antibody response in these chicken populations, which are derived from a common founder population, demonstrating the extent of standing immunogenetic variation available at the onset of selection.
Assuntos
Galinhas , Variação Genética , Genômica , Imunidade Humoral/genética , Seleção Genética , Alelos , Animais , Eritrócitos/imunologia , Evolução Molecular , Antígenos de Histocompatibilidade/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Ovinos/sangueRESUMO
Research on automatic processes in fear has emphasized the provocation of fear responses rather than their attenuation. We have previously shown that the repeated presentation of feared images without conscious awareness via backward masking reduces avoidance of a live tarantula in spider-phobic participants. Herein we investigated the neural basis for these adaptive effects of masked exposure. 21 spider-phobic and 21 control participants, identified by a psychiatric interview, fear questionnaire, and approaching a live tarantula, viewed stimuli in each of three conditions: (1) very brief exposure (VBE) to masked images of spiders, severely limited awareness; (2) clearly visible exposure (CVE) to spiders, full awareness; and (3) masked images of flowers (control), severely limited awareness. Only VBE to masked spiders generated neural activity more strongly in phobic than in control participants, within subcortical fear, attention, higher-order language, and vision systems. Moreover, VBE activated regions that support fear processing in phobic participants without causing them to experience fear consciously. Counter-intuitively, CVE to the same spiders generated stronger neural activity in control rather than phobic participants within these and other systems. CVE deactivated regions supporting fear regulation and caused phobic participants to experience fear. CVE-induced activations also correlated with measures of explicit fear ratings, whereas VBE-induced activations correlated with measures of implicit fear (color-naming interference of spider words). These multiple dissociations between the effects of VBE and CVE to spiders suggest that limiting awareness of exposure to phobic stimuli through visual masking paradoxically facilitates their processing, while simultaneously minimizing the experience of fear. Hum Brain Mapp 38:2466-2481, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Encéfalo/diagnóstico por imagem , Medo , Transtornos Fóbicos/patologia , Transtornos Fóbicos/psicologia , Estimulação Luminosa/efeitos adversos , Adolescente , Adulto , Análise de Variância , Animais , Conscientização , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imaginação , Imageamento por Ressonância Magnética , Aranhas , Estimulação Subliminar , Inquéritos e Questionários , Fatores de Tempo , Adulto JovemRESUMO
Recent global (1) and national (2,3) health equity initiatives conclude that the elimination of health disparities requires improved understanding of social context (4,5) and ability to measure social determinants of health, including food and housing security (3). Food and housing security reflect the availability of and access to essential resources needed to lead a healthy life. The 2013 Behavioral Risk Factor Surveillance System (BRFSS) included two questions to assess perceived food and housing security in 15 states.* Among 95,665 respondents, the proportion who answered "never or rarely" to the question "how often in the past 12 months would you say you were worried or stressed about having enough money to buy nutritious meals?" ranged from 68.5% to 82.4% by state. Among 90,291 respondents living in housing they either owned or rented, the proportion who answered "never or rarely" to the question, "how often in the past 12 months would you say you were worried or stressed about having enough money to pay your rent/mortgage?" ranged from 59.9% to 72.8% by state. Food security was reported less often among non-Hispanic blacks (blacks) (68.5%) and Hispanics (64.6%) than non-Hispanic whites (whites) (81.8%). These racial/ethnic disparities were present across all levels of education; housing security followed a similar pattern. These results highlight racial/ethnic disparities in two important social determinants of health, food and housing security, as well as a substantial prevalence of worry or stress about food or housing among all subgroups in the United States. The concise nature of the BRFSS Social Context Module's single-question format for food and housing security makes it possible to incorporate these questions into large health surveys so that social determinants can be monitored at the state and national levels and populations at risk can be identified.