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1.
Nature ; 582(7811): E5, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32461695

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Nature ; 576(7785): 91-95, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31802014

RESUMO

Additive manufacturing, often known as three-dimensional (3D) printing, is a process in which a part is built layer-by-layer and is a promising approach for creating components close to their final (net) shape. This process is challenging the dominance of conventional manufacturing processes for products with high complexity and low material waste1. Titanium alloys made by additive manufacturing have been used in applications in various industries. However, the intrinsic high cooling rates and high thermal gradient of the fusion-based metal additive manufacturing process often leads to a very fine microstructure and a tendency towards almost exclusively columnar grains, particularly in titanium-based alloys1. (Columnar grains in additively manufactured titanium components can result in anisotropic mechanical properties and are therefore undesirable2.) Attempts to optimize the processing parameters of additive manufacturing have shown that it is difficult to alter the conditions to promote equiaxed growth of titanium grains3. In contrast with other common engineering alloys such as aluminium, there is no commercial grain refiner for titanium that is able to effectively refine the microstructure. To address this challenge, here we report on the development of titanium-copper alloys that have a high constitutional supercooling capacity as a result of partitioning of the alloying element during solidification, which can override the negative effect of a high thermal gradient in the laser-melted region during additive manufacturing. Without any special process control or additional treatment, our as-printed titanium-copper alloy specimens have a fully equiaxed fine-grained microstructure. They also display promising mechanical properties, such as high yield strength and uniform elongation, compared to conventional alloys under similar processing conditions, owing to the formation of an ultrafine eutectoid microstructure that appears as a result of exploiting the high cooling rates and multiple thermal cycles of the manufacturing process. We anticipate that this approach will be applicable to other eutectoid-forming alloy systems, and that it will have applications in the aerospace and biomedical industries.

3.
Dev Dyn ; 253(2): 233-254, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37688792

RESUMO

BACKGROUND: Latent TGFß binding protein-2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFß, although it may interfere with the function of other LTBPs or interact with other signaling pathways. RESULTS: Here, we investigate mice lacking Ltbp2 (Ltbp2-/- ) and identify multiple phenotypes that impact bodyweight and fat mass, and affect bone and skin development. The alterations in skin and bone development are particularly noteworthy since the strength of these tissues is differentially affected by loss of Ltbp2. Interestingly, some tissues that express high levels of Ltbp2, such as the aorta and lung, do not have a developmental or homeostatic phenotype. CONCLUSIONS: Analysis of these mice show that LTBP2 has complex effects on development through direct effects on the extracellular matrix (ECM) or on signaling pathways that are known to regulate the ECM.


Assuntos
Proteínas de Transporte , Matriz Extracelular , Animais , Camundongos , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Matriz Extracelular/metabolismo , Fenótipo , Fator de Crescimento Transformador beta/metabolismo , Isoformas de Proteínas/metabolismo , Ligação Proteica
4.
J Occup Rehabil ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38286892

RESUMO

OBJECTIVE: A workers' compensation claim may have significant negative impacts on an injured worker's wellbeing. Wellbeing provides a good global measure of potential effects of a claim on an individual, and is important for contemporary economic modelling. The purpose of this study was to synthesize knowledge about the wellbeing of injured workers after the finalization of a workers' compensation claim and identify gaps in the current literature. METHODS: A systematic scoping review was conducted. RESULTS: 71 full-text articles were screened for inclusion, with 32 articles eligible for this review. None of the included articles evaluated overall wellbeing. Included articles did evaluate a variety of constructs inherent in wellbeing. Injured workers were generally disadvantaged in some manner following claim finalization. The literature recommends a focus on reducing negative impacts on injured workers after finalization of a compensation claim, with a need for regulatory bodies to review policy in this area. CONCLUSION: There appears to be potential for ongoing burden for individuals, employers, and society after finalization of a workers' compensation claim. A gap in knowledge exists regarding the specific evaluation of wellbeing of injured workers following finalization of a workers' compensation claim.

5.
BMC Med ; 21(1): 128, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013595

RESUMO

BACKGROUND: Insomnia symptoms are widespread in the population and might have effects on many chronic conditions and their risk factors but previous research has focused on select hypothesised associations/effects rather than taking a systematic hypothesis-free approach across many health outcomes. METHODS: We performed a Mendelian randomisation (MR) phenome-wide association study (PheWAS) in 336,975 unrelated white-British UK Biobank participants. Self-reported insomnia symptoms were instrumented by a genetic risk score (GRS) created from 129 single-nucleotide polymorphisms (SNPs). A total of 11,409 outcomes from UK Biobank were extracted and processed by an automated pipeline (PHESANT) for the MR-PheWAS. Potential causal effects (those passing a Bonferroni-corrected significance threshold) were followed up with two-sample MR in MR-Base, where possible. RESULTS: Four hundred thirty-seven potential causal effects of insomnia symptoms were observed for a diverse range of outcomes, including anxiety, depression, pain, body composition, respiratory, musculoskeletal and cardiovascular traits. We were able to undertake two-sample MR for 71 of these 437 and found evidence of causal effects (with directionally concordant effect estimates across main and sensitivity analyses) for 30 of these. These included novel findings (by which we mean not extensively explored in conventional observational studies and not previously explored using MR based on a systematic search) of an adverse effect on risk of spondylosis (OR [95%CI] = 1.55 [1.33, 1.81]) and bronchitis (OR [95%CI] = 1.12 [1.03, 1.22]), among others. CONCLUSIONS: Insomnia symptoms potentially cause a wide range of adverse health-related outcomes and behaviours. This has implications for developing interventions to prevent and treat a number of diseases in order to reduce multimorbidity and associated polypharmacy.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/genética , Bancos de Espécimes Biológicos , Estudo de Associação Genômica Ampla , Fenótipo , Reino Unido/epidemiologia , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genética
6.
J Immunol ; 204(9): 2455-2463, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32213565

RESUMO

Cattle possess the most diverse repertoire of NK cell receptor genes among all mammals studied to date. Killer cell receptor genes encoded within the NK complex and killer cell Ig-like receptor genes encoded within the leukocyte receptor complex have both been expanded and diversified. Our previous studies identified two divergent and polymorphic KLRA alleles within the NK complex in the Holstein-Friesian breed of dairy cattle. By examining a much larger cohort and other ruminant species, we demonstrate the emergence and fixation of two KLRA allele lineages (KLRA*01 and -*02) at a single locus during ruminant speciation. Subsequent recombination events between these allele lineages have increased the frequency of KLRA*02 extracellular domains. KLRA*01 and KLRA*02 transcription levels contrasted in response to cytokine stimulation, whereas homozygous animals consistently transcribed higher levels of KLRA, regardless of the allele lineage. KLRA*02 mRNA levels were also generally higher than KLRA*01 Collectively, these data point toward alternative functional roles governed by KLRA genotype and allele lineage. On a background of high genetic diversity of NK cell receptor genes, this KLRA allele fixation points to fundamental and potentially differential function roles.


Assuntos
Subfamília A de Receptores Semelhantes a Lectina de Células NK/genética , Ruminantes/genética , Transcrição Gênica/genética , Alelos , Animais , Bovinos , Frequência do Gene/genética , Frequência do Gene/imunologia , Genótipo , Células Matadoras Naturais/imunologia , Subfamília A de Receptores Semelhantes a Lectina de Células NK/imunologia , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Ruminantes/imunologia , Transcrição Gênica/imunologia
7.
Int Q Community Health Educ ; 41(2): 173-187, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32276558

RESUMO

The purpose of this quasi-experimental, phenomenological study was to use embodied cognition in understanding learning experiences in skill development and performativity (e.g., storytelling and emotional expression) among 17 beginners in aerial practice (Mage = 20.59 ± 1.37 years old). Eight people were in the treatment-group class (skill development and performativity) and nine individuals participated in the control-group class (only skill development). Four themes emerged from the analysis: linking other exercises to aerial (e.g., cheerleading, dancing, and gymnastics) and uniqueness of aerial (e.g., artistic aspect while in the air); success in meeting aerial goals (at the posttest, performativity was valued more in the treatment group than the control group); exercise changes due to aerial, such as enhanced upper-body strengthening activities and stretches; and lessons learned, including importance of conditioning and small class size, switching Teaching Assistants (TAs), and silk awareness. Practitioners in community-based movement education programs like dancing and physical theater should recognize the need for embodied knowledge by emphasizing not only skill development but also performativity for enhanced learning experiences within supportive class settings. Although adding performative qualities to skill learning is more challenging than skill development alone, it can lead to enhanced performance, joy, and meaning of movement.

8.
Microsc Microanal ; 26(4): 741-749, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32406368

RESUMO

Accurate elemental quantification of materials by X-ray detection techniques in electron microscopes or microprobes can only be carried out if the appropriate mass absorption coefficients (MACs) are known. With continuous advancements in experimental techniques, databases of MACs must be expanded in order to account for new detection limits. Soft X-ray emission spectroscopy (SXES) is a characterization technique that can detect emitted X-rays whose energies are in the range of 10 eV to 2 keV by using a varied-line-spaced grating. Transitions producing soft X-rays can be detected and accurate MACs are required for use in quantification. This work uses Monte Carlo modeling coupled with multivoltage SXES measurements in an electron probe micro-analyzer (EPMA) to compute MACs for the L2,3-M and Li Kα transitions in a variety of aluminum alloys. Electron depth distribution curves obtained by the software MC X-ray are used in a parametrized fitting equation. The MACs are calculated using a least-squares regression analysis. It is shown that X-ray distribution cross-sections at such low energies need to take into account additional contributions, such as Coster­Kronig transitions, Auger yields, and wave function effects in order to be accurate.

9.
Nicotine Tob Res ; 21(6): 731-738, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30365022

RESUMO

INTRODUCTION: Cigarette smokers are at increased risk of poor sleep behaviors. However, it is largely unknown whether these associations are due to shared (genetic) risk factors and/or causal effects (which may be bidirectional). METHODS: We obtained summary-level data of genome-wide association studies of smoking (smoking initiation [n = 74 035], cigarettes per day [n = 38 181], and smoking cessation [n = 41 278]) and sleep behaviors (sleep duration and chronotype, or "morningness" [n = 128 266] and insomnia [n = 113 006]). Using linkage disequilibrium (LD) score regression, we calculated genetic correlations between smoking and sleep behaviors. To investigate causal effects, we employed Mendelian randomization (MR), both with summary-level data and individual-level data (n = 333 581 UK Biobank participants). For MR with summary-level data, individual genetic variants were combined with inverse variance-weighted meta-analysis, weighted median regression, MR-Robust Adjusted Profile Score, and MR Egger methods. RESULTS: We found negative genetic correlations between smoking initiation and sleep duration (rg = -.14, 95% CI = -0.26 to -0.01) and smoking cessation and chronotype (rg = -.18, 95% CI = -0.31 to -0.06), and positive genetic correlations between smoking initiation and insomnia (rg = .27, 95% CI = 0.06 to 0.49) and cigarettes per day and insomnia (rg = .15, 95% CI = 0.01 to 0.28). MR provided strong evidence that smoking more cigarettes causally decreases the odds of being a morning person, (RAPS) and weak evidence that insomnia causally increases smoking heaviness and decreases smoking cessation odds. CONCLUSIONS: Smoking and sleep behaviors show moderate genetic correlation. Heavier smoking seems to causally affect circadian rhythm and there is some indication that insomnia increases smoking heaviness and hampers cessation. Our findings point to sleep as a potentially interesting smoking treatment target. IMPLICATIONS: Using LD score regression, we found evidence that smoking and different sleep behaviors (sleep duration, chronotype (morningness), and insomnia) are moderately genetically correlated-genetic variants associated with less or poorer sleep also increased the odds of smoking (more heavily). MR analyses suggested that heavier smoking causally affects circadian rhythm (decreasing the odds of being a morning person) and there was some indication that insomnia increases smoking heaviness and hampers smoking cessation. Our findings indicate a complex, bidirectional relationship between smoking and sleep behaviors and point to sleep as a potentially interesting smoking treatment target.


Assuntos
Marcadores Genéticos , Polimorfismo de Nucleotídeo Único , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Fumar/efeitos adversos , Fumar/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Prevalência , Reino Unido/epidemiologia
10.
Phonetica ; 76(6): 448-478, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31454798

RESUMO

We examined gestural coordination in C1C2 (C1 stop, C2 lateral or tap) word initial clusters using articulatory (electromagnetic articulometry) and acoustic data from six speakers of Standard Peninsular Spanish. We report on patterns of voice onset time (VOT), gestural plateau duration of C1, C2, and their overlap. For VOT, as expected, place of articulation is a major factor, with velars exhibiting longer VOTs than labials. Regarding C1 plateau duration, voice and place effects were found such that voiced consonants are significantly shorter than voiceless consonants, and velars show longer duration than labials. For C2 plateau duration, lateral duration was found to vary as a function of onset complexity (C vs. CC). As for overlap, unlike in French, where articulatory data for clusters have also been examined, clusters where both C1 and C2 are voiced show more overlap than where voicing differs. Further, overlap was affected by the C2 such that clusters where C2 is a tap show less overlap than clusters where C2 is a lateral. We discuss these results in the context of work aiming to uncover phonetic (e.g., articulatory or perceptual) and phonological forces (e.g., syllabic organization) on timing.


Assuntos
Idioma , Fonética , Percepção da Fala , Voz/fisiologia , Feminino , Humanos , Masculino , Estudos de Amostragem , Espanha
11.
J Sleep Res ; 27(5): e12695, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29682839

RESUMO

Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep.


Assuntos
Cafeína/efeitos adversos , Cafeína/genética , Estudo de Associação Genômica Ampla/métodos , Distúrbios do Início e da Manutenção do Sono/genética , Sono/efeitos dos fármacos , Sono/genética , Humanos , Análise da Randomização Mendeliana
12.
Environ Sci Technol ; 52(20): 11670-11681, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30215246

RESUMO

Exposure to ambient fine particulate matter (PM2.5) is a leading risk factor for the global burden of disease. However, uncertainty remains about PM2.5 sources. We use a global chemical transport model (GEOS-Chem) simulation for 2014, constrained by satellite-based estimates of PM2.5 to interpret globally dispersed PM2.5 mass and composition measurements from the ground-based surface particulate matter network (SPARTAN). Measured site mean PM2.5 composition varies substantially for secondary inorganic aerosols (2.4-19.7 µg/m3), mineral dust (1.9-14.7 µg/m3), residual/organic matter (2.1-40.2 µg/m3), and black carbon (1.0-7.3 µg/m3). Interpretation of these measurements with the GEOS-Chem model yields insight into sources affecting each site. Globally, combustion sectors such as residential energy use (7.9 µg/m3), industry (6.5 µg/m3), and power generation (5.6 µg/m3) are leading sources of outdoor global population-weighted PM2.5 concentrations. Global population-weighted organic mass is driven by the residential energy sector (64%) whereas population-weighted secondary inorganic concentrations arise primarily from industry (33%) and power generation (32%). Simulation-measurement biases for ammonium nitrate and dust identify uncertainty in agricultural and crustal sources. Interpretation of initial PM2.5 mass and composition measurements from SPARTAN with the GEOS-Chem model constrained by satellite-based PM2.5 provides insight into sources and processes that influence the global spatial variation in PM2.5 composition.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis , Poeira , Monitoramento Ambiental
13.
Ecotoxicol Environ Saf ; 161: 397-401, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29906758

RESUMO

Triphenyltin (TPT) is one of the most toxic chemicals artificially discharged into aquatic environment with human activities. Due to its intensive use in antifouling paints and adverse effects on non-target species, TPT has aroused wide concern in both saltwater and freshwater environment. Nevertheless, the water quality criteria (WQC) are not available in China, which impedes the risk assessment for this emerging pollutant. This study aims to establish the WQC of TPT for both freshwater and saltwater ecosystems. With the derived WQC, a four-level tiered ecological risk assessment (ERA) approach was employed to assess the ecological risks of this emerging pollutant in Chinese waters. Through the species sensitivity distribution (SSD) methodology, the freshwater criterion maximum concentration (CMC) and criterion continuous concentration (CCC) were derived as 396 ng Sn L-1 and 5.60 ng Sn L-1, respectively, whereas the saltwater CMC and CCC were 66.5 ng Sn L-1 and 4.11 ng Sn L-1, respectively. The ecological risk assessment for TPT demonstrated that the acute risk was negligible whereas the chronic risk was significant with HQ (Hazard Quotient) values of up to 5.669 and 57.1% of coastal waters in China facing clear risk. TPT contamination in coastal environment, therefore, warrants further concern.


Assuntos
Compostos Orgânicos de Estanho/toxicidade , Poluentes Químicos da Água/toxicidade , Qualidade da Água/normas , Animais , Organismos Aquáticos , China , Ecologia , Ecossistema , Monitoramento Ambiental , Água Doce , Humanos , Compostos Orgânicos de Estanho/normas , Medição de Risco/métodos , Poluentes Químicos da Água/normas
14.
Microsc Microanal ; 24(4): 325-341, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29911517

RESUMO

Electron and proton microprobes, along with electron backscatter diffraction (EBSD) analysis were used to study the microstructure of the contemporary Al-Cu-Li alloy AA2099-T8. In electron probe microanalysis, wavelength and energy dispersive X-ray spectrometry were used in parallel with soft X-ray emission spectroscopy (SXES) to characterize the microstructure of AA2099-T8. The electron microprobe was able to identify five unique compositions for constituent intermetallic (IM) particles containing combinations of Al, Cu, Fe, Mn, and Zn. A sixth IM type was found to be rich in Ti and B (suggesting TiB2), and a seventh IM type contained Si. EBSD patterns for the five constituent IM particles containing Al, Cu, Fe, Mn, and Zn indicated that they were isomorphous with four phases in the 2xxx series aluminium alloys including Al6(Fe, Mn), Al13(Fe, Mn)4 (two slightly different compositions), Al37Cu2Fe12 and Al7Cu2Fe. SXES revealed that Li was present in some constituent IM particles. Al SXES mapping revealed an Al-enriched (i.e., Cu, Li-depleted) zone in the grain boundary network. From the EBSD analysis, the kernel average misorientation map showed higher levels of localized misorientation in this region, suggesting greater deformation or stored energy. Proton-induced X-ray emission revealed banding of the TiB2 IM particles and Cu inter-band enrichment.

15.
Immunogenetics ; 69(4): 255-269, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28180967

RESUMO

Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ, and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination.


Assuntos
Evolução Molecular , Genoma , Mamíferos/genética , Anotação de Sequência Molecular , Polimorfismo Genético/genética , Receptores de Células Matadoras Naturais/genética , Análise de Sequência de DNA/métodos , Animais , Humanos , Células Matadoras Naturais/metabolismo , Lectinas Tipo C/genética , Filogenia , Seleção Genética/genética
16.
Int J Mol Sci ; 18(10)2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-28991210

RESUMO

Latent transforming growth factor-ß-1 binding protein-2 (LTBP-2) belongs to the LTBP-fibrillin superfamily of extracellular proteins. Unlike other LTBPs, LTBP-2 does not covalently bind transforming growth factor-ß1 (TGF-ß1) but appears to be implicated in the regulation of TGF-ß1 bioactivity, although the mechanisms are largely unknown. In experiments originally designed to study the displacement of latent TGF-ß1 complexes from matrix storage, we found that the addition of exogenous LTBP-2 to cultured human MSU-1.1 fibroblasts caused an increase in TGF-ß1 levels in the medium. However, the TGF-ß1 increase was due to an upregulation of TGF-ß1 expression and secretion rather than a displacement of matrix-stored TGF-ß1. The secreted TGF-ß1 was mainly in an inactive form, and its concentration peaked around 15 h after addition of LTBP-2. Using a series of recombinant LTBP-2 fragments, the bioactivity was identified to a small region of LTBP-2 consisting of an 8-Cys motif flanked by four epidermal growth factor (EGF)-like repeats. The LTBP-2 stimulation of TGF-ß expression involved the phosphorylation of both Akt and p38 mitogen-activated protein kinase (MAPK) signalling proteins, and specific inactivation of each protein individually blocked TGF-ß1 increase. The search for the cell surface receptor mediating this LTBP-2 activity proved inconclusive. Inhibitory antibodies to integrins ß1 and αVß5 showed no reduction of LTBP-2 stimulation of TGF-ß1. However, TGF-ß1 upregulation was partially inhibited by anti-αVß3 integrin antibodies, suggestive of a direct or indirect role for this integrin. Overall, the study indicates that LTBP-2 can directly upregulate cellular TGF-ß1 expression and secretion by interaction with cells via a short central bioactive region. This may be significant in connective tissue disorders involving aberrant TGF-ß1 signalling.


Assuntos
Fibroblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular , Fibrose/metabolismo , Humanos , Fosforilação , Reação em Cadeia da Polimerase
17.
Paediatr Perinat Epidemiol ; 30(4): 397-407, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27006293

RESUMO

BACKGROUND: Most cohort-based research for subfertility has been conducted in clinic-based cohorts, which may differ from population-based cohorts. METHODS: We retrospectively recruited parallel cohorts of subfertile women: one by sampling two specialty fertility clinics in Utah, and one by population-based sampling based on marriage and birth records. The index date (of first clinic visit or subfertility status) was between 2000 and 2009, and we linked the women recruited to subsequent birth certificate records through December 2010. RESULTS: We enrolled 459 women through clinic-based sampling and 501 women through population-based sampling. Clinic-based women were older, had higher annual household income and more likely to have had a most intensive treatment of intrauterine insemination (31%) or in vitro fertilisation (46%) than women from population recruitment (19% and 14% respectively). Conversely, they were less likely to have received no medical treatment (9%) compared to women from population recruitment (41%). For both types of sampling, prior to eligibility screening, non-responders were less likely to link to a live birth than responders: 51% vs. 58% for clinic-based, and 69% vs. 76% for the population-based with an index date in 2004. CONCLUSIONS: Population-based sampling for subfertility cohort research identifies women who were more likely to have had less intensive treatment or no treatment. However, in both clinic-based and population-based sampling, women who have had a live birth are more likely to respond to retrospective recruitment.


Assuntos
Infertilidade/epidemiologia , Cuidado Pré-Concepcional/métodos , Adulto , Coeficiente de Natalidade , Feminino , Fertilização in vitro , Humanos , Infertilidade/terapia , Masculino , Seleção de Pacientes , Gravidez , Projetos de Pesquisa , Estudos Retrospectivos , Inquéritos e Questionários , Utah/epidemiologia , Adulto Jovem
18.
Reprod Health ; 12: 62, 2015 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-26184507

RESUMO

BACKGROUND: Many women throughout the world have history of subfertility (resolved or unresolved), but much remains unknown about services and treatments chosen. METHODS: We developed a mixed-mode fertility experiences questionnaire (FEQ) in 2009 through literature review and iterative pilot work to optimize question format and mode of administration. The focus of the FEQ is to collect data retrospectively on time at risk for pregnancy, fertility treatments received and declined, pregnancy, time to pregnancy and pregnancy outcomes. We conducted a validation of key elements of the FEQ with comparison to medical records in 2009 and 2010. The validation sample was selected from women initially seen at a specialized fertility treatment center in Utah in 2004. RESULTS: The FEQ was optimized with two components: 1) written (paper or web-based), self-administered, followed by 2) telephone- administered questions. In 63 patients analyzed, high levels of correlation were identified between patient self-report and medical records for the use of intrauterine insemination and assisted reproductive technology, pregnancy and live birth histories, time at risk for pregnancy and time to pregnancy. There was low correlation between medical records and self-report for the use of oral ovulation drugs and injectable ovulation drugs. Compared to the medical record, the FEQ was over 90% sensitive for all elements, except injectable ovulation drugs (70% sensitivity). CONCLUSIONS: The FEQ accurately captured elements of fertility treatment history at 5-6 years after the first visit to a specialty clinic.


Assuntos
Infertilidade/psicologia , Infertilidade/terapia , Inquéritos e Questionários , Adulto , Feminino , Fertilidade , Humanos , Projetos Piloto , Gravidez , Resultado da Gravidez/epidemiologia , Taxa de Gravidez , Técnicas de Reprodução Assistida/estatística & dados numéricos , Fatores Socioeconômicos , Tempo para Engravidar , Utah/epidemiologia
19.
Immunogenetics ; 66(7-8): 427-38, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24863340

RESUMO

The interleukin-1 gene family encodes a group of related proteins that exhibit a remarkable pleiotropy in the context of health and disease. The set of indispensable functions they control suggests that these genes should be found in all eukaryotic species. The ligands and receptors of this family have been primarily characterised in man and mouse. The genomes of most non-mammalian animal species sequenced so far possess all of the IL-1 receptor genes found in mammals. Yet, strikingly, very few of the ligands are identifiable in non-mammalian genomes. Our recent identification of two further IL-1 ligands in the chicken warranted a critical reappraisal of the evolution of this vitally important cytokine family. This review presents substantial data gathered across multiple, divergent metazoan genomes to unambiguously trace the origin of these genes. With the hypothesis that all of these genes, both ligands and receptors, were formed in a single ancient ancestor, extensive database mining revealed sufficient evidence to confirm this. It therefore suggests that the emergence of mammals is unrelated to the expansion of the IL-1 family. A thorough review of this cytokine family in the chicken, the most extensively studied amongst non-mammalian species, is also presented.


Assuntos
Proteínas Aviárias/genética , Galinhas/genética , Galinhas/imunologia , Interleucina-1/genética , Animais , Evolução Molecular , Humanos , Ligantes , Camundongos , Família Multigênica , Filogenia , Receptores de Interleucina-1/genética , Vertebrados/genética , Vertebrados/imunologia
20.
Environ Sci Technol ; 48(20): 12157-63, 2014 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-25247985

RESUMO

Residential wood combustion is an important source of ambient air pollution, accounting for over 25% of fine particulate matter (PM2.5) emissions in Canada. In addition to these ambient contributions, wood smoke pollutants can enter the indoor environment directly when loading or stoking stoves, resulting in a high potential for human exposure. A study of the effectiveness of air cleaners at reducing wood smoke-associated PM2.5 of indoor and outdoor origin was conducted in 31 homes during winter 2009-10. Day 1, the residents' wood burning appliance operated as usual with no air cleaner. Days 2 and 3, the wood burning appliance was not operational and the air cleaner was randomly chosen to operate in "filtration" or "placebo filtration" mode. When the air cleaner was operating, total indoor PM2.5 levels were significantly lower than on placebo filtration days (p = 0.0001) resulting in a median reduction of 52%. There was also a reduction in the median PM2.5 infiltration factor from 0.56 to 0.26 between these 2 days, suggesting the air cleaner was responsible for increased PM2.5 deposition on filtration days. Our findings suggest that the use of an air cleaner reduces exposure to indoor PM2.5 resulting from both indoor and ambient wood smoke sources.


Assuntos
Filtros de Ar/estatística & dados numéricos , Poluição do Ar em Ambientes Fechados/análise , Fumaça/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Canadá , Filtração/instrumentação , Glucose/análogos & derivados , Glucose/análise , Habitação/estatística & dados numéricos , Humanos , Material Particulado/análise , Estações do Ano , Poluição por Fumaça de Tabaco , Madeira/química
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